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1

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

ClinicalTrials.gov

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

2014-06-17

2

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

ClinicalTrials.gov

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

2015-02-09

3

Idiopathic thrombocytopenic purpura during pregnancy  

PubMed Central

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

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

2013-01-01

4

Idiopathic thrombocytopenic purpura  

PubMed Central

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

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

2014-01-01

5

Postoperative thrombotic thrombocytopenic purpura.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of thrombocytopenia and microangiopathic hemolytic anemia occurring due to platelet and von Willebrand factor deposition and hyaline thrombi formation in arterioles and capillaries throughout the body, which results in organ ischemia. TTP can be idiopathic or secondary, and there are several causes of secondary TTP. There is a clinical syndrome resembling TTP that occurs after surgical procedures, so-called "postoperative TTP" (pTTP). In this review, the differential diagnosis, pathogenesis and clinical and laboratory features of pTTP, together with the treatment modalities and outcomes of the patients, are discussed. The pTTP is a diagnosis of exclusion, and disseminated intravascular coagulation, heparin-induced thrombocytopenia and medication-induced effects should be ruled out. As in classical TTP, patients with pTTP should be diagnosed and treated with therapeutic plasma exchange (TPE) as early as possible to reduce their morbidity and mortality. Although rarely seen, surgeons and physicians of all specialties should be alert to the possibility of pTTP, and since pTTP is a life-threatening event that usually can be treated successfully with TPE, especially when diagnosed early in its course, it is critical to recognize and treat pTTP promptly. PMID:24374368

Eskazan, Ahmet Emre; Buyuktas, Deram; Soysal, Teoman

2015-01-01

6

Thrombotic Thrombocytopenic Purpura  

MedlinePLUS

... include infusions of fresh frozen plasma and plasma exchange, also called plasmapheresis (PLAZ-ma-feh-RE-sis). These treatments have greatly improved the outlook of the disorder. Rate This Content: Next >> March 21, 2014 Thrombotic Thrombocytopenic ...

7

How Is Thrombotic Thrombocytopenic Purpura Diagnosed?  

MedlinePLUS

... transplant . Take certain medicines, such as ticlopidine, clopidogrel, cyclosporine A, or hormone therapy and estrogens, or whether ... Next >> March 21, 2014 Thrombotic Thrombocytopenic Purpura Clinical Trials Clinical trials are research studies that explore whether ...

8

Genetics Home Reference: Thrombotic thrombocytopenic purpura  

MedlinePLUS

... causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious ... people with thrombotic thrombocytopenic purpura, clots develop in blood vessels even in the absence of injury. Blood clots ...

9

What Causes Thrombotic Thrombocytopenic Purpura?  

MedlinePLUS

... transplant Some medicines, such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone therapy and ... Purpura Clinical Trials Clinical trials are research studies that explore whether ...

10

Immune thrombocytopenic purpura associated with hepatitis A  

Microsoft Academic Search

A 23 year-old man developed thrombocytopenic purpura at the end of the second week of the clinical evolution of hepatitis A confirmed by viral markers. The bone marrow of this patient showed megakaryocytic hyperplasia. Circulating in his serum immune complexes were demonstrated by solid phase conglutinin enzymo-immunoassay. Platelet-reactive serum factors were also detected by an indirect immunofluorescence test using fresh

H. Ibarra; C. Zapata; J. Inostroza; S. Mezzano; S. Riedemann

1986-01-01

11

Management of Immune Thrombocytopenic Purpura: An Update  

PubMed Central

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

Warrier, Rajasekharan; Chauhan, Aman

2012-01-01

12

[Therapeutic approach in pregnant women with an autoimmune thrombocytopenic purpura].  

PubMed

The case presented herein aim to update the existing information about the common diagnostic problems and therapeutic approach in pregnant women that have autoimmune thrombocytopenic purpura (ATP). PMID:20225499

Christova, R; Lisichkov, T; Chernev, T

2009-01-01

13

[Chronic idiopathic thrombocytopenic purpura in childhood].  

PubMed

In 12 of 95 children with idiopathic thrombocytopenic purpura (ITP) admitted to the Department of Pediatrics of the University Hospital in Bern between January 1st and December 31st 1979, the disease became chronic. Sex and age distribution were similar in children with acute and chronic ITP. Neither the history nor the initial symptomatology were useful for early detection of chronic ITP. For this purpose the initial raise of the platelet count after initiation of prednisone treatment appeared to be a more reliable parameter. Five of the 12 children received only drugs while 7 were splenectomized. After an observation period of 4 years none of 4 children who had received only drugs but 2 of 3 splenectomized children required intensive treatment. Prednisone and azathioprine, vincristine or cyclophosphamide, used alone or in various combinations, induced impressive but only temporary remissions. PMID:7200968

Venetz, U; Willi, P; Hirt, A; Imbach, P; Wagner, H P

1982-01-01

14

Plasma exchange in thrombotic thrombocytopenic purpura.  

PubMed Central

Three patients were recently treated for thrombotic thrombocytopenic purpura (TTP). One presented with toxic shock syndrome; TTP developed but promptly responded to a regimen of antiplatelet agents, steroids and plasma exchange. In another the manifestations of TTP developed after presentation with hypertension and abdominal pain. This patient responded to a similar regimen but required extended treatment before remission could be maintained with medications alone. In the third patient the full TTP syndrome appeared after several days of plasma exchange treatment for hemolyticuremic syndrome. He did not respond. It is suggested that TTP may present in many forms initially, that microangiopathic hemolysis may be a late manifestation and that the optimal therapy is not known. PMID:6541965

Toffelmire, E B; Clark, W F; Cordy, P E; Linton, A L; Lohmann, R C

1984-01-01

15

The Kidney in Thrombotic Thrombocytopenic Purpura  

PubMed Central

Summary The kidney is commonly affected in thrombotic thrombocytopenic purpura (TTP), a multi-system disorder with microvascular thrombosis of the capillaries and arterioles. Nevertheless, due to difference in its diagnostic criteria, the frequency and severity of renal dysfunction in TTP remains controversial. With the recent studies indicating that severe deficiency of a VWF cleaving protease, ADAMTS13, is the main cause of platelet thrombosis in TTP, it is now possible to define TTP at the molecular level. Among patients with acquired TTP due to inhibitory antibodies of ADAMTS13, renal dysfunction is usually mild; oliguria, fluid overload, hypertension, and need of dialysis support are infrequent. When any of these complications occur, one must re-examine the diagnosis of TTP and consider the possibility that the patient has another cause for these complications. In a patient with hereditary TTP, acute renal failure may ensue. However, the renal dysfunction is mostly reversible if the patients are promptly treated with plasma to replenish ADAMTS13. Patients with TTP, particularly of the hereditary type, may develop chronic renal failure. This complication may be a consequence of repeated insults by overt or subclinical microvascular thrombosis to the kidney, or it may have a separate cause. Therapy of hereditary TTP should aim not only to prevent acute exacerbations but also to minimize the risk of irreversible renal injury. PMID:18299685

Tsai, Han-Mou

2008-01-01

16

Management of patients with refractory immune thrombocytopenic purpura  

Microsoft Academic Search

Summary. In immune thrombocytopenic purpura (ITP), thrombocytopenia is a result of both increased platelet destruction and insufficient platelet production. In adults, the course is commonly chronic, but most patients never experience serious bleeding even with severe thrombocytopenia. In case series of consecutive adult patients identified at the time of diagnosis, the frequency of death from bleeding is low, < 1%.

J. N. GEORGE

2006-01-01

17

Treatment of chronic immune thrombocytopenic purpura in adults  

Microsoft Academic Search

Until recently, the management of refractory immune thrombocytopenic purpura (ITP) was a real challenge as shown by the large\\u000a variety of treatments proposed in both American Society of Hematology and the British Committee for Standards in Haematology\\u000a guidelines published 10 and 6 years ago, respectively. However, as in the past 5 years, new therapeutic approaches including\\u000a eradication of Helicobacter pylori in infected

Bertrand Godeau; Marc Michel

2010-01-01

18

Management of Chronic Childhood Immune Thrombocytopenic Purpura: AIEOP Consensus Guidelines  

Microsoft Academic Search

Background\\/Objective: The management of chronic childhood idiopathic thrombocytopenic purpura (ITP) is distinct from acute ITP. Similar to the publication on acute ITP guidelines, the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) considered it appropriate to develop consensus guidelines for chronic childhood ITP to provide useful and shared information for physicians, healthcare professionals, parents and patients. Design\\/Methods: A preliminary, evidence-based

Domenico De Mattia; Giovanni Carlo Del Vecchio; Giovanna Russo; Attilio De Santis; Ugo Ramenghi; Lucia Notarangelo; Momcilo Jankovic; Angelo Claudio Molinari; Marco Zecca; Bruno Nobili; Paola Giordano

2010-01-01

19

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

PubMed Central

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

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

2014-01-01

20

Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy.  

PubMed

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

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

2014-01-01

21

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

PubMed

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

Gómez-Almaguer, David

2012-04-01

22

A Leptospirosis Case Presenting with Thrombotic Thrombocytopenic Purpura  

PubMed Central

Background: Leptospirosis is a zoonotic disease caused by spirochetes of the genus Leptospira. While the majority of leptospirosis cases occur in the tropics, some cases are also observed in temperate regions of developing countries. The disease has various clinical presentations ranging from a mild influenza-like form to a severe potentially fatal illness accompanied by multi-organ failure. However, atypical presentations of leptospirosis have occasionally been described. Here, a case of leptospirosis presenting as thrombotic thrombocytopenic purpura (TTP) is reported. Case Report: A 58-years-old male presented with fever, oliguria, darkening of urine, and visual hallucinations. Laboratory investigations revealed anaemia, severe thrombocytopaenia, elevated total bilirubin with indirect predominance, high lactate dehydrogenase, and increased urea (293 mg/dL) and creatinine (7.6 mg/dL) levels. He was diagnosed with TTP. Patient was thought leptospirosis due to atypical clinical manifestations. Leptospirosis was confirmed by strongly positive Microscopic Agglutination Test. Patient recovered completely with antibiotics and plasmapheresis. Conclusion: Leptospirosis may be accompanied by thrombotic thrombocytopenic purpura in particular subtropic regions. PMID:25207155

?ükran, Köse; Tatar, Bengü; Ersan, Gürsel; Topalo?lu, Selim

2013-01-01

23

Thrombotic Thrombocytopenic Purpura: Three Peripartum Cases and Diagnostic Challenges  

PubMed Central

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

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

2013-01-01

24

ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura.  

PubMed

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

Zheng, X Long

2015-01-14

25

Regression of idiopathic thrombocytopenic purpura after endoscopic mucosal resection of gastric mucosa associated lymphoid tissue lymphoma  

PubMed Central

Recent reports have suggested an association between Helicobacter pylori infection and both gastric mucosa associated lymphoid tissue (MALT) lymphoma and thrombocytopenic purpura. Although treatments eradicating H pylori lead to regression of these diseases in some cases, the exact mechanisms are still controversial. This case report describes a patient with thrombocytopenic purpura accompanied by an early stage gastric MALT lymphoma. Endoscopic mucosal resection of the lesion in this patient led to dramatic regression of thrombocytopenic purpura, and t(11;18)(q21;q21), which means resistance more likely to H pylori eradication therapy, was confirmed by fluorescence in situ hybridisation. There is no evidence of recurrence and his platelet count is within normal limits after 24 months of follow up. This is the first case report describing regression of thrombocytopenic purpura after mucosal resection of a gastric MALT lymphoma. We suggest that while some cases of thrombocytopenic purpura may be induced by H pylori, others may be due to an autoreactive antibody produced by MALT lymphoma B cells. PMID:15479694

Noda, M; Mori, N; Nomura, K; Kojima, K; Mitsufuji, S; Yamane, I; Misawa, S; Okanoue, T

2004-01-01

26

Treatment of immune thrombocytopenic purpura: focus on eltrombopag.  

PubMed

Immune thrombocytopenic purpura (ITP) is a relatively common autoimmune disorder in which antibodies are produced to circulating platelets. Symptoms can be mild, but for most patients the risk of severe bleeding is unacceptable and treatment is required. Glucocorticoids followed by splenectomy had been the mainstays of therapy. High dose intravenous immunoglobulin and anti-RhD therapy are available for patients with severe illness, but produce only temporary benefit. Rituximab may provide more durable responses, danazol may be underutilized, and immunosuppressants and cytotoxic agents are less often required. Recently the pathophysiology of ITP has been more clearly elucidated, particularly the importance of decreased production of platelets in most patients and the very blunted rise that occurs in serum thrombopoietin (TPO). The isolation of TPO and better understanding of its role in thrombopoiesis has led to the development of new highly effective treatments. TPO analogs had some successes in treating highly refractory ITP patients but were taken out of development due to TPO-antibody induction. Two second-generation TPO-mimetics, romiplostim and the orally available eltrombopag, have recently been licensed in some territories for the treatment of ITP. Approval of eltrombopag was based on results from Phase II and III placebo-controlled clinical trials and a long-term extension study. About 80% of patients achieve significant increases in platelet count (11% of placebo patients), with reduced bleeding and reduced use of concomitant medications; responses are often durable with no tachyphylaxis. The side effects of eltrombopag are generally mild and not worse than placebo, although there are concerns about hepatic dysfunction, and the potentials for thromboses, marrow reticulin fibrosis, rebound thrombocytopenia and cataracts. This is an important new option for highly refractory patients, and its niche in earlier treatment (and for other thrombocytopenic disorders) is yet to be defined. PMID:19707404

Rice, Lawrence

2009-01-01

27

Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias  

SciTech Connect

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.

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

1980-10-01

28

Interferon-? is not elevated in idiopathic thrombotic thrombocytopenic purpura patients.  

PubMed

Idiopathic thrombotic thrombocytopenic purpura (TTP) patients have ADAMTS13 deficiency, which is usually caused by ADAMTS13 autoantibodies. However, the triggering factors for the autoantibody production remain unclear. Interferon-? (IFN-?) is a cytokine involved with many autoimmune processes such as inducing the activation of peripheral dendritic cells and stimulating T cells and B cells. It also plays an important role in some autoimmune diseases. Elevated IFN-? levels have been observed in some TTP patients and previous case reports have shown the occurrence of TTP after IFN-? treatment. Thus, we hypothesized that high levels of IFN-? would correlate with presence of ADAMTS13 autoantibodies. However, we did not observe elevated IFN-? levels in 36 TTP patients (mean 5.29 pg/ml, standard deviation (SD) 26.56 pg/ml) compared to healthy controls (mean 0 pg/ml, SD 0 pg/ml), P?=?0.59. IFN-? levels of most patients (94%) were undetectable. Only two patients had increased IFN-? levels and ADAMTS13 autoantibodies were detected in these two patients. Interestingly, both the patients had an underlying autoimmune disease. Although there have been cases of secondary TTP following IFN-? treatment, no evidence supports a role of IFN-? in the development of idiopathic TTP in our patient population. J. Clin. Apheresis 29:336-338 2014. © 2014 Wiley Periodicals, Inc. PMID:24764259

Watanaboonyongcharoen, Phandee; Whinna, Herbert C; Park, Yara A

2014-12-01

29

Autosensitization and immune complexes in chronic idiopathic thrombocytopenic purpura.  

PubMed Central

Argument exists as to whether platelet damage in chronic idiopathic thrombocytopenic purpura (ITP) is mediated by an autoimmune response to platelet antigen or by immune complexes. We have studied thirty-nine patients with ITP for evidence of (i) sensitization to platelet antigen, using a macrophage migration inhibition factor (MIF) assay, (ii) circulating immune complexes, using a Clq deviation technique, and (iii) serum-induced platelet 'immunoinjury', using a 3H-serotonin release assay. Eighty-one per cent of the patient group had a migration index of less than 0.8 (normal range 0.8-1.3), while 91% of those tested had a serum factor (presumably immune complexes) which bound to labelled Clq. The serotonin release assay was abnormal in 32% of twenty-two patients, and the results of this test bore no clear relationship to either those of the Clq deviation test or the MIF results. We conclude that most patients with ITP are sensitized to platelet-associated antigen, and have circulating immune complexes. The contribution of these factors to platelet destruction and the nature of the antigen in the complexes remain to be demonstrated. The serotonin release assay is less sensitive, non-specific, and has limited value in the diagnosis of ITP. PMID:6993065

Clancy, R; Trent, R; Danis, V; Davidson, R

1980-01-01

30

Nonsteroidal Anti-inflammatory Drug Induced Thrombotic Thrombocytopenic Purpura  

PubMed Central

A 21-year-old male presented to the emergency department after a 5-day history of recurrent vomiting and decreased urine output. History revealed ingestion of ibuprofen. During the diagnostic workup, the following was identified: white blood cell count 13.4 (×10(3)/mcL), hemoglobin 11.9 (×10(6)/mcL) with an MCV of 73 fL, hematocrit 34% and platelets were 31,000/mcL, sodium of 130 mmol/L, potassium of 5.1 mmol/L, chloride of 83 mmol/L, bicarbonate of 21 mmol/L, blood urea nitrogen of 184 mg/dL and creatinine of 19.1 mg/dL. He was later diagnosed with thrombotic thrombocytopenic purpura (TTP) based on the fact that he presented with most components of the TTP pentad (except for fever), which included altered mental status, acute kidney injury, thrombocytopenia, and evidence of red cell fragmentation and his ADAMTS13 level was found to be less than 10% prior to therapy. The patient then received plasma exchange, oral corticosteroids, and hemodialysis, which led to a full recovery of platelet count and renal function. PMID:25512716

Oregel, Karlos Z; Ramdial, Jeremy; Glück, Stefan

2013-01-01

31

Natural history of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.  

PubMed

The differential diagnosis of thrombotic microangiopathy (TMA) has become clearer following the establishment of the relationships between (1) diarrhea-associated hemolytic uremic syndrome (HUS) and Shiga toxin-producing Escherichia coli-HUS (STEC-HUS), (2) a markedly reduced ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) level and typical thrombotic thrombocytopenic purpura (TTP), and (3) abnormalities in the complement regulatory system and atypical HUS (aHUS). These TMAs include typical TTP, other forms of TMA, STEC-HUS, and aHUS. The pathological mechanisms of TMA still overlap among several forms of TMA. With respect to the management of TMA, the use of plasma exchange (PE) for typical TTP, additional steroid therapy for TMA and rituximab for typical TTP with a high titer of the inhibitor of ADAMTS-13, as well as eculizumab for aHUS, have also been established. Although several issues remain in the pathophysiology and management of TMA, new findings will hopefully resolve these problems in the near future. PMID:25377323

Wada, Hideo; Matsumoto, Takeshi; Yamashita, Yoshiki

2014-11-01

32

Efficacy of rituximab in immune thrombocytopenic purpura: a retrospective survey.  

PubMed

We conducted a retrospective survey to assess prescription practice, response rates to rituximab, and the predictive indicators for a response to rituximab therapy in patients with primary or secondary immune thrombocytopenic purpura (ITP). Data were collected retrospectively from 40 consecutive patients with ITP attending our hospital: 29 (72.5%) had primary ITP and 11 (27.5%) had secondary ITP. Rituximab was given either as four weekly injections (375 mg/m(2)) or two injections of 1,000 mg given 2 weeks apart in 30 and 10 patients, respectively. The primary objective was to evaluate overall (OR) and complete response (CR) to rituximab therapy for ITP. OR was excellent and rapid and similar when secondary ITP was excluded from the analysis: OR was achieved in 28 (71.8%) patients and CR in 22 (56.4%). But, at >6 months, of the 28 responders, only 10 of 22 of the evaluable responses (45.5%) were sustained. In addition, except for the nonsignificant occurrence of antinuclear antibodies, no clinical or biological factors were predictive for OR or CR after the rituximab therapy. Twelve patients received a second course of rituximab. Overall, rituximab therapy achieved a response in two thirds of the patients, but the responders exhibited a high rate of early relapses, with no obvious difference according to the regimen of administration or rituximab dose. PMID:21710166

Brah, Souleymane; Chiche, Laurent; Fanciullino, Raphaelle; Bornet, Charléric; Mancini, Julien; Schleinitz, Nicolas; Jean, Rodolphe; Kaplanski, Gilles; Harlé, Jean-Robert; Durand, Jean-Marc

2012-02-01

33

ADAMTS13 mutations and polymorphisms in congenital thrombotic thrombocytopenic purpura.  

PubMed

Congenital thrombotic thrombocytopenic purpura (TTP) (also known as Upshaw-Schulman syndrome, USS) is a rare, life-threatening disease characterized by thrombocytopenia and microangiopathic hemolytic anemia, associated with the deficiency of the von Willebrand factor-cleaving protease (ADAMTS13) due to mutations in the corresponding gene. The spectrum of clinical phenotype in congenital TTP is wide, encompassing neonatal-onset disease and adult-onset disease, forms with a single disease episode and chronic-relapsing forms. We review ADAMTS13 gene variants associated with inherited ADAMTS13 deficiency and congenital TTP. To date, 76 mutations of ADAMTS13 are reported in the literature. Missense mutations, which constitute nearly 60% of ADAMTS13 mutations, preferentially localize in the 5'-half of the gene encoding the N-terminal half of the protein, where the domains that are indispensable for ADAMTS13 catalytic function are situated. In vitro expression studies in cell cultures have shown that defects in protein secretion and catalytic activity are the main mechanisms responsible for the deficiency of ADAMTS13 in congenital TTP patients. Even if data from the literature suggest the existence of genotype-phenotype correlations, a clear relationship between the type and the effect of ADAMTS13 genetic defects with disease manifestations remains to be established. PMID:19847791

Lotta, Luca A; Garagiola, Isabella; Palla, Roberta; Cairo, Andrea; Peyvandi, Flora

2010-01-01

34

Thrombopoietic growth factors in the treatment of immune thrombocytopenic purpura.  

PubMed

Immune thrombocytopenic purpura (ITP) is a relatively common blood disorder related to the production of anti-platelet antibodies. It is now clear that platelet production is also substantially impaired in most patients. After the cloning of TPO and analogs, there were reported therapeutic successes in a few refractory ITP patients, but neutralizing antibodies led to the withdrawal of first-generation thrombopoietic growth factor from development. Second-generation thrombopoietic growth factors are now available that stimulate c-mpl but share no homology with the native hormone. Second-generation thrombopoietic growth factors have shown responses in 50-80% of ITP patients with only modest toxicity, and thus they offer another therapeutic option. The first of these agents to enter clinical trials and to be approved by the FDA is romiplostim, a once weekly subcutaneous peptibody. Eltrombopag is the second FDA-approved thrombopoietic growth factor and has the advantage of oral formulation. Some concerns persist on the potential of these agents to cause increased thrombosis risk, rebound thrombocytopenia on drug withdrawal, reticulin fibrosis of the marrow, and induction of malignancy, but these have not emerged as major problems in clinical trials. PMID:20378370

Wang, Tingting; Wang, Zhao; Yang, Renchi

2011-03-01

35

[Childhood idiopathic thrombocytopenic purpura (the results of 20-year experience)].  

PubMed

Idiopathic thrombocytopenic purpura (ITP) of Childhood is a common hemorrhagic diathesis. The purpose of the present work is to summarize the results of 20-year observation over children suffering ITP, to record certain progress in diagnosing and treatment of this disease and to raise the problems still to be solved. The authors have been observing 181 ITP patients (girls 89, boys 92) at the age of 3 months up to 15 years. Childhood ITP mostly occurs at the age of 1 to 6 year i.e. in the so called "critical period" of immune system forming. Several peculiar cases were identified among infants and the children above 10 years old. Clinical manifestation of all the ITP patients was characterized with cutaneous hemorrhagic syndrome. 95% of childhood cases showed deep thrombocytopenia with the thrombocyte level <30X10 9/l. Most of the patients suffered acute form of ITP (87,9%). In the majority of cases illness took its normal predictable course after the glucocorticosteroid therapy. In heavy cases the combination of glucocorticosteroid and intravenous immunoglobulin is recommended. The indications of splenectomy were considered to be heavy, life -threatening, excessive bleeding, mainly in cases of chronic, steadily recurrent forms of ITP. Remissions were achieved in most of cases. PMID:19801732

Kvezereli-Kopadze, M A; Kvezereli-Kopadze, A N; Mtvarelidze, Z G

2009-09-01

36

Danazol in non-splenectomized patients with refractory idiopathic thrombocytopenic purpura.  

PubMed Central

Seven non-splenectomized patients with chronic refractory idiopathic thrombocytopenic purpura were treated with danazol 800 mg daily. All were glucocorticoid failures and four were refractory to all additional previous therapy. Five patients benefited from danazol and in two sustained normal platelet counts, for over 44 and 51 months, were observed. We conclude that danazol is useful for long term management of otherwise refractory idiopathic thrombocytopenic purpura. The advantage of danazol over splenectomy as a first line treatment in steroid failure is suggested. PMID:2099421

Edelmann, D. Z.; Knobel, B.; Virag, I.; Meytes, D.

1990-01-01

37

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

PubMed Central

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

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

2014-01-01

38

Improvement of thrombocytopenia after treatment for Helicobacter pylori in a patient with immunologic thrombocytopenic purpura  

PubMed Central

Immune thrombocytopenic purpura is the most common autoimmune hematologic disease, affecting individuals of different ages. Recently, the bacterium Helicobacter pylori entered the list of causes of immune thrombocytopenic purpura. Here we present the case of a 55-year-old female patient with low platelet counts initially attributed to chronic vaginal bleeding. As corticosteroid therapy was ineffective she was treated for H. pylori infection. Within four weeks the patient had a platelet count of 87.17 ×109/L accompanied by clinical improvement of the symptoms. PMID:24790544

Rocha, Aline Maia; Botelho, Luís Fábio Barbosa; Rocha, David Maia

2014-01-01

39

Novel Use of a Thrombopoietin Mimetic for Chronic Immune Thrombocytopenic Purpura in Pregnancy  

PubMed Central

BACKGROUND Thrombopoietin mimetic agents are a novel therapeutic option for patients with chronic immune thrombocytopenic purpura (ITP). We report on the use of romiplostim, a thrombopoietin mimetic, throughout pregnancy. CASE A 28 year old primigravida with chronic ITP initiated a planned pregnancy on romiplostim. The second and third trimesters were marked by a cyclic pattern of thrombocytopenia requiring supplemental corticosteroids or intravenous immunoglobulin and resultant thrombocytosis. Increased romiplostim doses and daily corticosteroids stabilized the platelet count prior to induction of labor. The delivery was uneventful, though the newborn manifested anemia and intraventricular hemorrhage. CONCLUSION The decreased efficacy of romiplostim monotherapy is attributed to increased target-mediated drug disposition and the physiologic changes of pregnancy. Safety concerns still exist for the developmental effects of romiplostim on the fetus. PMID:23884268

Patil, Avinash S.; Dotters-Katz, Sarah K.; Metjian, Ara D.; James, Andra H.; Swamy, Geeta

2014-01-01

40

Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura.  

PubMed

Complement dysregulation is key in the pathogenesis of atypical Haemolytic Uraemic Syndrome (aHUS), but no clear role for complement has been identified in Thrombotic Thrombocytopenic Purpura (TTP). We aimed to assess complement activation and cytokine response in acute antibody-mediated TTP. Complement C3a and C5a and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor, interferon-? and IL-17a) were measured in 20 acute TTP patients and 49 remission cases. Anti-ADAMTS13 immunoglobulin G (IgG) subtypes were measured in acute patients in order to study the association with complement activation. In acute TTP, median C3a and C5a were significantly elevated compared to remission, C3a 63·9 ng/ml vs. 38·2 ng/ml (P < 0·001) and C5a 16·4 ng/ml vs. 9·29 ng/ml (P < 0·001), respectively. Median IL-6 and IL-10 levels were significantly higher in the acute vs. remission groups, IL-6: 8 pg/ml vs. 2 pg/ml (P = 0·003), IL-10: 6 pg/ml vs. 2 pg/ml (P < 0·001). C3a levels correlated with both anti-ADAMTS13 IgG (rs = 0·604, P = 0·017) and IL-10 (rs = 0·692, P = 0·006). No anti-ADAMTS13 IgG subtype was associated with higher complement activation, but patients with the highest C3a levels had 3 or 4 IgG subtypes present. These results suggest complement anaphylatoxin levels are higher in acute TTP cases than in remission, and the complement response seen acutely may relate to anti-ADAMTS13 IgG antibody and IL-10 levels. PMID:24372446

Westwood, John-Paul; Langley, Kathryn; Heelas, Edward; Machin, Samuel J; Scully, Marie

2014-03-01

41

Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura  

PubMed Central

Complement dysregulation is key in the pathogenesis of atypical Haemolytic Uraemic Syndrome (aHUS), but no clear role for complement has been identified in Thrombotic Thrombocytopenic Purpura (TTP). We aimed to assess complement activation and cytokine response in acute antibody-mediated TTP. Complement C3a and C5a and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor, interferon-? and IL-17a) were measured in 20 acute TTP patients and 49 remission cases. Anti-ADAMTS13 immunoglobulin G (IgG) subtypes were measured in acute patients in order to study the association with complement activation. In acute TTP, median C3a and C5a were significantly elevated compared to remission, C3a 63·9 ng/ml vs. 38·2 ng/ml (P < 0·001) and C5a 16·4 ng/ml vs. 9·29 ng/ml (P < 0·001), respectively. Median IL-6 and IL-10 levels were significantly higher in the acute vs. remission groups, IL-6: 8 pg/ml vs. 2 pg/ml (P = 0·003), IL-10: 6 pg/ml vs. 2 pg/ml (P < 0·001). C3a levels correlated with both anti-ADAMTS13 IgG (rs = 0·604, P = 0·017) and IL-10 (rs = 0·692, P = 0·006). No anti-ADAMTS13 IgG subtype was associated with higher complement activation, but patients with the highest C3a levels had 3 or 4 IgG subtypes present. These results suggest complement anaphylatoxin levels are higher in acute TTP cases than in remission, and the complement response seen acutely may relate to anti-ADAMTS13 IgG antibody and IL-10 levels. PMID:24372446

Westwood, John-Paul; Langley, Kathryn; Heelas, Edward; Machin, Samuel J; Scully, Marie

2014-01-01

42

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura  

PubMed Central

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

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

2014-01-01

43

Sequential occurrence of thrombotic thrombocytopenic purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura in a 42-year-old African-American woman: a case report and review of the literature  

PubMed Central

Introduction Thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura are two well recognized syndromes that are characterized by low platelet counts. In contrast, essential thrombocythemia is a myeloproliferative disease characterized by abnormally high platelet numbers. The coexistence of thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura in a single patient has been reported in the literature on a few occasions. However, having essential thrombocythemia complicating the picture has never been reported before. Case presentation We present a case where thrombotic thrombocytopenic purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura were diagnosed in a 42-year-old African-American woman in the space of a few years; we are reporting this case with the aim of drawing attention to this undocumented occurrence, which remains under investigation. Conclusions As the three conditions have different natural histories and require different treatment modalities, it is important to recognize that these diseases may be seen sequentially. This case emphasizes the importance of reviewing peripheral blood smears for evaluation of thrombocytopenia and bone marrow aspirations for diagnosis of thrombocythemia in order to reach an accurate diagnosis and tailor therapy accordingly. Moreover, this case demonstrates the variability and complexity of platelet disorders. This occurrence of three different types of platelet disorders in one patient remains a pure observation on our part; regardless, this does raise the possibility of a common underlying, as yet undiscovered, pathophysiology that could explain the phenomenon. PMID:22472269

2012-01-01

44

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

PubMed

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

Liebman, Howard A

2009-01-01

45

Acute thrombotic thrombocytopenic purpura following doxycycline treatment of Chlamydia pneumoniae infection in a patient with dermatomyositis.  

PubMed

A 48-year-old white female who was suffering from dermatomyositis and Chlamydia pneumoniae infection, developed acute rapidly fatal thrombotic thrombocytopenic purpura (TTP) following treatment with steroids and doxycycline. As a relationship between TTP and the inflammatory myopathies is now probably well established, it is very likely that our patient's TTP became manifest in association with dermatomyositis. Nevertheless, C. pneumoniae infection and doxycycline therapy cannot be excluded entirely as cofactors responsible for triggering her thrombotic microangiopathy. PMID:15053810

Knox-Macaulay, H H M; Adil, S N; Ahmed, E M E

2004-04-01

46

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

Microsoft Academic Search

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

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

2001-01-01

47

[Thrombotic thrombocytopenic purpura in a child with low ADAMTS13 enzyme level.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is a rare condition, but important to consider in case of thrombocytopenia and haemolysis. It is imperative to proceed with the correct treatment, in order to ensure a satisfactory outcome. TTP is either acquired or idiopathic. This case report shows that a 14-year-old boy has acquired TTP due to an infection with Campylobacter jejuni and Samonella szentes. Plasma exchange plays an essential role in the treatment of TTP. PMID:25293573

Spangenberg, Katrine Bredsdorff; Clasen-Linde, Erik; Poulsen, Anja

2014-08-18

48

Recent Advances in the Treatment of Chronic Refractory Immune Thrombocytopenic Purpura  

Microsoft Academic Search

We define chronic refractory immune thrombocytopenic purpura (ITP) as ITP with persistent thrombocytopenia following treatment\\u000a with glucocorticoids and splenectomy. Chronic refractory ITP is uncommon, occurring in fewer than 10% of all adult patients\\u000a with ITP diagnoses.The goal of treatment is only to achieve a safe platelet count with minimal treatment-related risk. A safe\\u000a platelet count may be considered to be

Kiarash Kojouri; James N. George

2005-01-01

49

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

PubMed Central

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

2014-01-01

50

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

PubMed

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

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

2015-02-01

51

Expression of a structurally constrained von Willebrand factor variant triggers acute thrombotic thrombocytopenic purpura in mice.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that presents with thrombocytopenia, disseminated thrombosis, hemolytic anemia, and organ dysfunction. The etiology of TTP has revealed that patients share a deficiency in plasma protease a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), the enzyme responsible for cleaving ultra-large von Willebrand factor (VWF) multimers into nonthrombogenic fragments. Therefore, existing TTP mouse models were developed by targeted disruption of the ADAMTS13 gene. ADAMTS13(-/-) mice are mostly asymptomatic in the absence of a trigger, as redundant proteases appear to take on VWF processing. As an alternative approach to creating one such model, we devised a strategy based on the expression of a cleavage-resistant VWF mutant in mice. The creation of a disulfide bond within the A2 domain of VWF was found to render VWF multimers resistant to proteolysis by plasma proteases under flow. Furthermore, mice expressing the murine VWF/p.S1494C-p.A1534C mutant present with symptoms characteristics of acute TTP such as thrombocytopenia, red cell shredding, accumulation of VWF-rich thrombi in the microvasculature, and advanced TTP symptoms such as renal dysfunction and splenomegaly. Because this model appears to faithfully emulate the pathophysiology of TTP, it should prove most useful in the study of microangiopathic diseases and their treatment. PMID:24713928

Morioka, Yoko; Casari, Caterina; Wohner, Nikolett; Cho, Sungyun; Kurata, Sachiko; Kitano, Ayumi; Christophe, Olivier D; Lenting, Peter J; Li, Renhao; Denis, Cécile V; Prévost, Nicolas

2014-05-22

52

Coronary intervention for acute coronary syndrome in a 51-year-old man with immune thrombocytopenic purpura: a case report  

PubMed Central

Introduction Treatment of the rare cases of patients with chronic idiopathic thrombocytopenic purpura with acute coronary syndrome can be a significant problem. The patient in our case report was treated successfully with percutaneous coronary intervention. Case presentation A 51-year-old man of Turkish origin who had idiopathic thrombocytopenic purpura was admitted to our hospital with severe chest pain. His electrocardiography was normal on admission but dynamic ischemic changes were observed during follow-up. He underwent immediate coronary angiography. In his angiography, left anterior descending artery stenosis was 90% together with the diagonal ostium. Percutaneous coronary intervention was performed successfully. Bleeding complications were not observed after the procedure. Conclusions We report the presence of a rare case of chronic idiopathic thrombocytopenic purpura in a patient with acute coronary syndrome. In this situation a serious multidisciplinary approach is required before coronary intervention. PMID:24950596

2014-01-01

53

Revascularization for Patients with Idiopathic Thrombocytopenic Purpura and Coronary Artery Disease  

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder with a low platelet count characterized by premature platelet destruction and suppression of platelet production mediated by autoantibodies, which may predispose to bleeding. Although the prevalence of coronary artery disease (CAD) in ITP seems to be rare, their co-occurrence is not unusual. Patients with ITP have increased risks for thrombosis and atherosclerosis associated with hemostatic factors, endothelial damage, and the negative effects of steroid and immunoglobulin therapies. Thus, the coexistence of ITP and CAD presents complex problems requiring a balance between hemorrhagic risk and prevention of thrombosis. Here, the authors present two patients with ITP, who were revascularized in different ways for CAD. Although the optimal management of thrombocytopenic patients with CAD is uncertain, individualized treatment modalities can be useful in patients with ITP and CAD. PMID:25089139

Lee, Chan-Hee

2014-01-01

54

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

PubMed Central

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

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

2014-01-01

55

Immune thrombocytopenic purpura in ulcerative colitis: a case report and systematic review  

PubMed Central

Over 100 extraintestinal manifestations are reported in ulcerative colitis (UC). A commonly reported hematological manifestation is autoimmune hemolytic anemia. On rare occasions, immune thrombocytopenic purpura (ITP) has been reported with UC. The presence of thrombocytopenia can complicate the clinical scenario as the number of bloody bowel movements is an important indicator of disease activity in UC. A proposed theory for this association is antigenic mimicry between a platelet surface antigen and bacterial glycoprotein. We are reporting a case of UC and associated ITP managed successfully with anti-TNF therapy. We also performed a systemic review of case reports and a case series reporting this association. PMID:24765254

Chandra, Subhash; Finn, Sarah; Obah, Eugene

2014-01-01

56

Stroke due to typical thrombotic thrombocytopenic purpura treated successfully with intravenous thrombolysis and therapeutic plasma exchange  

PubMed Central

We report a case of a 39-year-old man with expressive aphasia due to occlusion of the temporal stem of the left middle cerebral artery. Laboratory tests showed microangiopathic haemolytic anaemia and thrombocytopenia. A thrombotic thrombocytopenic purpura (TTP) was diagnosed, and thrombolytic therapy (TT) with alteplase followed by therapeutic plasma exchange (TPE) were performed with complete resolution of symptoms. The gold standard TTP treatment is TPE, and its delay can be lethal. The use of TT in TTP is controversial and has potential risks. This case shows a successful TT in a patient with typical TTP presenting as a stroke due to a large cerebral artery occlusion. PMID:23362068

Boattini, Matteo; Procaccianti, Gaetano

2013-01-01

57

Changes in Follicular Helper T Cells in Idiopathic Thrombocytopenic Purpura Patients  

PubMed Central

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

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

2015-01-01

58

ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission  

Microsoft Academic Search

Background From 20 to 50% of patients who survive an acute episode of the acquired form of thrombotic thrombocytopenic purpura relapse but clinical and laborator y markers of recurrence are not well established. Design and Methods In 109 patients enrolled in an international registry we evaluated, in the frame of a retrospec- tive cohort stud y, the predictive role of

Flora Peyvandi; Silvia Lavoretano; Roberta Palla; Hendrik B. Feys; Karen Vanhoorelbeke; Tullia Battaglioli; Carla Valsecchi; Maria Teresa Canciani; Fabrizio Fabris; Samo Zver; Marienn Réti; Danijela Mikovic; Mehran Karimi; Gaetano Giuffrida; Luca Laurenti; Pier Mannuccio Mannucci; Angelo Bianchi; Marrow Transplantation; Vittorio Emanuele Ferrarotto-S

2008-01-01

59

Outcomes of platelet transfusion in patients with thrombotic thrombocytopenic purpura: a retrospective case series study.  

PubMed

Current guidelines advise against the transfusion of platelets in patients with thrombotic thrombocytopenic purpura (TTP) except in cases of life-threatening hemorrhage. We conducted a retrospective medical chart review to examine the outcomes of patients with TTP who received platelet transfusion at our institution from September 2002 to September 2012. A search for "thrombotic thrombocytopenic purpura" in the discharge summary identified 233 patients, out of which only 15 patients had TTP and received platelet transfusion. Primary outcomes were death due to any cause, myocardial infarction, ischemic stroke, coma, seizure, or worsening neurologic status within 24 h of platelet transfusion. Secondary outcomes included bleeding and worsening thrombocytopenia. No adverse outcomes occurred within 24 h of platelet transfusion. Two patients experienced bleeding following renal biopsy despite having platelet counts of greater than 50,000/?l and receiving one pack of pooled platelets prior to the procedures. The response to transfusion was variable. In general, platelet transfusion was not detrimental in this population; however, the efficacy is uncertain. PMID:25288377

Zhou, Amy; Mehta, Rohtesh S; Smith, Roy E

2015-03-01

60

Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes.  

PubMed

Pregnancy can precipitate thrombotic thrombocytopenic purpura (TTP). We present a prospective study of TTP cases from the United Kingdom Thrombotic Thrombocytopenic Purpura (UK TTP) Registry with clinical and laboratory data from the largest cohort of pregnancy-associated TTP and describe management through pregnancy, averting fetal loss and maternal complications. Thirty-five women presented with a first TTP episode during pregnancy: 23/47 with their first congenital TTP (cTTP) episode and 12/47 with acute acquired TTP in pregnancy. TTP presented primarily in the third trimester/postpartum, but fetal loss was highest in the second trimester. Fetal loss occurred in 16/38 pregnancies before cTTP was diagnosed, but in none of the 15 subsequent managed pregnancies. Seventeen of 23 congenital cases had a missense mutation, C3178T, within exon 24 (R1060W). There were 8 novel mutations. In acquired TTP presentations, fetal loss occurred in 5/18 pregnancies and 2 terminations because of disease. We also present data on 12 women with a history of nonpregnancy-associated TTP: 18 subsequent pregnancies have been successfully managed, guided by ADAMTS13 levels. cTTP presents more frequently than acquired TTP during pregnancy and must be differentiated by ADAMTS13 analysis. Careful diagnosis, monitoring, and treatment in congenital and acquired TTP have assisted in excellent pregnancy outcomes. PMID:24859360

Scully, Marie; Thomas, Mari; Underwood, Mary; Watson, Henry; Langley, Katherine; Camilleri, Raymond S; Clark, Amanda; Creagh, Desmond; Rayment, Rachel; Mcdonald, Vickie; Roy, Ashok; Evans, Gillian; McGuckin, Siobhan; Ni Ainle, Fionnuala; Maclean, Rhona; Lester, William; Nash, Michael; Scott, Rosemary; O Brien, Patrick

2014-07-10

61

Identification and Characterization of Anti-Platelet Antibodies in Idiopathic Thrombocytopenic Purpura Patients  

PubMed Central

Background: The autoimmune disease known as Idiopathic (immune thrombocytopenic purpura thrombocytopenic purpura (ITP) is clinically defined by a low numbers of platelets in the circulation blood. This study aimed to isolate autoantibodies made against the platelet glycoproteins using platelets from healthy volunteers, to determine their specificity and further elucidate their effects on platelet function. Methods: This study used a phage display system to recognize Fab anti-platelet antibodies. Anti-platelet After isolation, the anti-platelet Fab-expressing phage was characterized by ELISA and Western blotting. The Fab-bearing phage pool obtained from five rounds of panning was analysed in order to determine its anti-platelet reactivity. Of the phage colonies obtained, 100 colonies of different sizes were randomly selected for reaction with whole platelets, using M13 phage as a negative control. Results: Twelve colonies of them had strong reactions against the whole platelet preparation, but only four colonies showed substantial reactivity against the lysed platelet preparation (lysate). Three of the four colonies showed three bands representing proteins with different molecular weights. The fourth colony showed only a single band. The final experiment to characterise the protein isolated from the phage library was a DNA gel agarose test. Conclusion: Each colony showed a DNA band that corresponded with the molecular size marker for 5.4 kbase pairs, and this suggested the presence of heavy and light antibody chains in the phage. PMID:23113135

Aghabeigi, N; Lindsey, N; Zamani, A; Shishaeyan, B

2012-01-01

62

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

PubMed

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

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

63

THA in Patients with Idiopathic Thrombocytopenic Purpura (ITP): A Case Report  

PubMed Central

We report a case of idiopathic thrombocytopenic purpura (ITP) accompanied by steroid-induced avascular necrosis of the femoral head in a 68-year-old woman. Extremely low platelet counts of ITP patients prohibit any surgical interventions. Her platelet count was 25,000/?L. We performed a total hip arthroplasty with high-dose immunoglobulin therapy and transfusion of platelet concentrates. Her platelet count increased to 94,000/?L just before the operation. No hemostatic complications were encountered perioperatively, and the postoperative course was uneventful. She left the hospital 20 days after the operation with a T-cane. Her platelet count decreased to 34,000/?L on the day she left the hospital. Three years after the operation, she had no groin pain and could walk without ambulatory assistive devices. We did not observe implant loosening.

Suzuki, Koji; Kawachi, Sadaomi; Nanke, Hideki; Ito, Takayoshi

2011-01-01

64

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

PubMed Central

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

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

65

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

PubMed Central

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

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

2014-01-01

66

Triad of Idiopathic Thrombocytopenic Purpura, Preeclampsia, and HELLP Syndrome in a Parturient: A Rare Confrontation to the Anesthetist.  

PubMed

Idiopathic thrombocytopenic purpura (ITP) with HELLP represents a rare complication that requires combined care of obstetrician, anesthesiologist, hematologist, and neonatologist. At 37-week gestation a 35-year-old parturient (G2A1P0) a known case of chronic ITP presented with severe pregnancy induced hypertension (PIH), thrombocytopenia, and elevated liver enzymes. We describe successful anesthetic management of this patient who was taken for emergency caesarean section. PMID:25548684

Mehta, Tanu; Parikh, Geeta P; Shah, Veena R

2014-01-01

67

Triad of Idiopathic Thrombocytopenic Purpura, Preeclampsia, and HELLP Syndrome in a Parturient: A Rare Confrontation to the Anesthetist  

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) with HELLP represents a rare complication that requires combined care of obstetrician, anesthesiologist, hematologist, and neonatologist. At 37-week gestation a 35-year-old parturient (G2A1P0) a known case of chronic ITP presented with severe pregnancy induced hypertension (PIH), thrombocytopenia, and elevated liver enzymes. We describe successful anesthetic management of this patient who was taken for emergency caesarean section. PMID:25548684

Mehta, Tanu; Parikh, Geeta P.; Shah, Veena R.

2014-01-01

68

Sunitinib Induced Thrombotic Thrombocytopenic Purpura in addition to Severe Hypothyroidism: A Case Report and Review of the Literature.  

PubMed

Introduction. Sunitinib malate is an oral multitargeting tyrosine kinase inhibitor approved for the first line treatment of metastatic renal cell carcinoma. Sunitinib administration is associated with several adverse events including fatigue, diarrhea, skin toxicity, hypothyroidism, and cytopenia. Herein, we present a case of thrombotic thrombocytopenic purpura and clinical hypothyroidism presenting within 4 weeks of starting sunitinib therapy. Case Presentation. A 72-year-old woman with metastatic renal cell carcinoma presented with generalized fatigue 28 days after starting sunitinib 50?mg daily. She was found to have severe hypothyroidism, in addition to significant thrombocytopenia and anemia. The latter were explained by a clinical and laboratory diagnosis of thrombotic thrombocytopenic purpura. Sunitinib was stopped and she recovered completely after plasmapheresis. Conclusion. To our knowledge, this is the fourth case report of thrombotic thrombocytopenic purpura secondary to sunitinib. Oncologists should be aware of this rare but potentially fatal adverse event. We highly suggest to routinely test for platelet count and thyroid stimulating hormone level as early as two weeks after initiating sunitinib. PMID:25349620

El Dika, Imane; Mukherji, Deborah; Temraz, Sally; Assi, Rita; Shamseddine, Ali

2014-01-01

69

Sunitinib Induced Thrombotic Thrombocytopenic Purpura in addition to Severe Hypothyroidism: A Case Report and Review of the Literature  

PubMed Central

Introduction. Sunitinib malate is an oral multitargeting tyrosine kinase inhibitor approved for the first line treatment of metastatic renal cell carcinoma. Sunitinib administration is associated with several adverse events including fatigue, diarrhea, skin toxicity, hypothyroidism, and cytopenia. Herein, we present a case of thrombotic thrombocytopenic purpura and clinical hypothyroidism presenting within 4 weeks of starting sunitinib therapy. Case Presentation. A 72-year-old woman with metastatic renal cell carcinoma presented with generalized fatigue 28 days after starting sunitinib 50?mg daily. She was found to have severe hypothyroidism, in addition to significant thrombocytopenia and anemia. The latter were explained by a clinical and laboratory diagnosis of thrombotic thrombocytopenic purpura. Sunitinib was stopped and she recovered completely after plasmapheresis. Conclusion. To our knowledge, this is the fourth case report of thrombotic thrombocytopenic purpura secondary to sunitinib. Oncologists should be aware of this rare but potentially fatal adverse event. We highly suggest to routinely test for platelet count and thyroid stimulating hormone level as early as two weeks after initiating sunitinib. PMID:25349620

El Dika, Imane; Temraz, Sally

2014-01-01

70

Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases.  

PubMed

Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per ?l. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-? and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this. PMID:25427992

Perricone, Carlo; Ceccarelli, Fulvia; Nesher, Gideon; Borella, Elisabetta; Odeh, Qasim; Conti, Fabrizio; Shoenfeld, Yehuda; Valesini, Guido

2014-12-01

71

Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification.  

PubMed

Thrombotic microangiopathies (TMAs) include several diseases, most prominently are thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TMAs are characterized by profound thrombocytopenia, microangiopathic hemolytic anemia and organ ischemia. In most cases TTP results from deficiency of ADAMTS13, the von Willebrand factor-cleaving protease leading to increase of ultra-large von Willebrand factor (ULVWF) multimers. Congenital TTP is due to mutations in the gene of ADAMTS13 whereas acquired TTP is due to production of autoantibodies against ADAMTS13. In both cases severe deficiency of ADAMTS13 exists. However, the presence of ADAMTS13 activity does not rule out TTP. Diagnostic criteria of TTP are based on clinical features of neurologic and renal disfunction along with anemia and thrombocytopenia, low ADAMTS13 activity, and the presence of ULVWF. The standard treatment of TTP includes plasma exchange, protein A immunoabsobtion, immunosuppressive drugs, CD20 antibodies against B cells, and splenectomy. HUS is commonly caused by infection with Shiga-toxin produced by Escherichia coli. HUS is characterized by thrombocytopenia, anemia, renal impairment and diarrhea. Rarely, atypical HUS appears as a consequence of mutations related to the alternative pathway for the compliment system. Plasmapheresis in HUS is not efficient. Alternatively, plasma therapy and in some cases dialysis are used. TMA diseases may be associated with other infections, bone marrow transplantation, pregnancy, systemic vasculitis, and certain drugs. PMID:24418304

Shenkman, Boris; Einav, Yulia

2014-01-01

72

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

PubMed

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

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

1988-01-01

73

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

PubMed

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

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

2012-07-01

74

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

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10–15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×109/L) or partial (platelet count between 50 and 150×109/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients. PMID:21589818

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

2009-01-01

75

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

PubMed

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

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

2013-05-01

76

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

PubMed

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

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

2012-10-01

77

Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura.  

PubMed

In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe ADAMTS13 deficiency (<10%) during remission is associated with more relapse. Preemptive (ie, after remission) administration of rituximab in these patients to prevent relapses remains controversial. We performed a cross-sectional analysis of 12-year follow-up data to compare the relapse incidence with or without preemptive rituximab infusion. Among 48 patients who experienced at least one episode of acquired TTP followed by severe ADAMTS13 deficiency during remission, 30 received preemptive rituximab (group 1); the other 18 did not (group 2). After a median of 17 months (interquartile range [IQR], 11-29) following rituximab, the relapse incidence decreased from 0.57 episodes/year (IQR, 0.46-0.7) to 0 episodes/year (IQR, 0-0.81) (P < .01) in group 1. ADAMTS13 activity 3 months after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients required additional courses of rituximab. In 5 patients, ADAMTS13 activity failed to increase durably. Four patients experienced manageable adverse effects. In group 2, the relapse incidence was higher (0.5 relapses/year; IQR, 0.12-0.5; P < .01). Relapse-free survival was longer in group 1 (P = .049). A persistent severe ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses. PMID:24869941

Hie, Miguel; Gay, Julie; Galicier, Lionel; Provôt, François; Presne, Claire; Poullin, Pascale; Bonmarchand, Guy; Wynckel, Alain; Benhamou, Ygal; Vanhille, Philippe; Servais, Aude; Bordessoule, Dominique; Coindre, Jean-Philippe; Hamidou, Mohamed; Vernant, Jean-Paul; Veyradier, Agnès; Coppo, Paul

2014-07-10

78

A novel Wiskott-Aldrich syndrome protein mutation in an infant with thrombotic thrombocytopenic purpura.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) has not yet been reported to be associated with mutations in the Wiskott-Aldrich syndrome (WAS) gene. WAS is an X-linked recessive disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. A broad spectrum of mutations in the WAS protein (WASP) gene have been identified as causing the disease. In this study, we report on a 2-month-old Japanese boy who presented with cytomegalovirus (CMV) infection and TTP. The activity of von Willebrand factor cleaving metalloproteinase, ADAMTS13 was low and the antibody against ADAMTS13 was positive (3.6 Bethesda U/mL). Although TTP was improved by plasma exchange and steroid pulse therapy, thrombocytopenia persisted and regular transfusions of irradiated platelets were needed. Tiny platelets were found on a peripheral blood smear. CMV genome was positive in peripheral blood by polymerase chain reaction and the CMV viremia continued to persist despite intravenous gancyclovir therapy. Through direct sequencing of genomic DNA of the WASP gene in the patient, we identified a novel mutation of WASP gene: the seventh nucleotide in exon 11 (G) had been deleted (1345delG). This mutation causes a frameshift and a stop codon at amino acid 470. Western blotting demonstrated a truncated WAS protein. To our knowledge, this is the first report describing TTP in WAS patients with novel mutation in the WASP gene. PMID:23237501

Kawasaki, Yukako; Toyoda, Hidemi; Otsuki, Shoichiro; Iwasa, Tadashi; Iwamoto, Shotaro; Azuma, Eiichi; Itoh-Habe, Naomi; Wada, Hideo; Fujimura, Yoshihiro; Morio, Tomohiro; Imai, Kohsuke; Mitsuiki, Noriko; Ohara, Osamu; Komada, Yoshihiro

2013-02-01

79

Can thrombelastography be a new tool to assess bleeding risk in patients with idiopathic thrombocytopenic purpura?  

PubMed

Thrombelastography (TEG) analyses the status of blood coagulation including abnormalities associated with low platelet count. The aim of this study was to investigate the changes in TEG parameters in idiopathic thrombocytopenic purpura (ITP) patients. Thirty nine patients with ITP (platelet count?

Gunduz, Eren; Akay, Olga Meltem; Bal, Cengiz; Gulbas, Zafer

2011-01-01

80

Favorable Response of Chronic Refractory Immune Thrombocytopenic Purpura to Mesenchymal Stem Cells  

PubMed Central

Seven patients with chronic refractory immune thrombocytopenic purpura (ITP) received adipose tissue-derived mesenchymal stem cells (AMSC) from haplo-identical family donors. The AMSC dose was 2.0×106/kg. No side effects were noted after the AMSC infusions. Overall responses were reached in all patients and sustained response rate was 57.1% (4/7). The serum levels of transforming growth factor ?1 (TGF-?1), interleukin (IL)-4, and IL-10 were significantly elevated, whereas those of interferon-? (IFN-?) and IL-2 were significantly decreased after AMSC administration, compared with those in the patients with active ITP. During follow-up, the cytokine profiles in patients maintaining sustained response remained stable compared with the post-treatment level, but IFN-? and IL-2 levels were significantly increased, and those of TGF-?1, IL-4, and IL-10 were significantly reduced again in relapsed patients. AMSC therapy seems to represent reasonable salvage treatment in severe, chronic refractory ITP by causing a shift in the Th1/Th2 cytokine balance to the same levels as normal controls. PMID:21711157

Fang, Baijun; Mai, Ling; Li, Ning

2012-01-01

81

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

PubMed Central

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

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

2006-01-01

82

Learning from errors: when a low platelet count in neonate excludes immune thrombocytopenic purpura in mother.  

PubMed

This paper reviews the most common causes of thrombocytopenia in the newborn. It mentions few classification schemes that clearly characterize the most common causes, diagnosis and treatment approaches for neonatal thrombocytopenia. Particular attention is paid to inborn macrothrombocytopenia without congenital anomalies. They represent a rare group of diseases, often captured randomly or during routine examinations. An attention is paid on congenital macrothrombocytopenia variants with mutations in the MYH9 gene. If they are not associated with other disorders (deafness, presenile cataracts, nephritis or renal failure), they may be mistakenly diagnosed as the acquired immune thrombocytopenic purpura (ITP). This distinguishing is essential to avoid potentially harmful and unnecessary treatment. The listed case report points to a situation where a detection of the root causes of neonatal thrombocytopenia led to a review of misdiagnosed ITP in the mother. A platelet size evaluation by both an appropriate cell counter and blood film examination is useful for differentiating a heterogeneous group of rare inherited macrothrombocytopenias. A healthy twin supported autosomal dominant inheritance. The results of investigations of twins and mother confirmed the congenital/inherited macrothrombocytopenia from the group of MYH9-related diseases (Tab. 5, Fig. 2, Ref. 21). PMID:23514558

Gresikova, M

2013-01-01

83

A prospective study of protein-specific assays used to investigate idiopathic thrombocytopenic purpura.  

PubMed

Idiopathic thrombocytopenic purpura (ITP) is a disorder in which platelets, sensitized by autoantibodies, are destroyed by the reticuloendothelial system. The diagnosis of ITP has been a clinical one because assays measuring platelet-associated IgG (PAIgG) have low specificity. The recently introduced assays that measure antibodies against specific platelet glycoproteins (GP) offer the possibility of improved specificity. In this report we describe two prospective studies. In the first study we compared two protein-specific assays (AC and MAIPA) looking for the presence of autoantibodies against GP IIb/IIIa in 81 patient samples. These results were compared with an immunoradiometric assay for PAIgG. The second study investigated the enhanced sensitivity of measuring anti-GP Ib/IX autoantibodies in 76 patient samples. The protein-specific assays were able to differentiate immune from non-immune thrombocytopenia (specificity 91%, sensitivity 39%), whereas the PAIgG assay could not (specificity 19%, sensitivity 78%). The addition of the Ib/IX AC assay maintained a specificity of 92% while increasing the diagnostic sensitivity to 66%. In contrast to the PAIgG assay, there was no correlation between the platelet count and the likelihood or degree of positivity within the control samples using the glycoprotein assays. These studies confirm that glycoprotein assays can be used as diagnostic tests for ITP. PMID:10086776

Warner, M N; Moore, J C; Warkentin, T E; Santos, A V; Kelton, J G

1999-03-01

84

[Role of reticulated platelets and platelet-associated antibody in differential diagnosis of idiopathic thrombocytopenic purpura].  

PubMed

The objective of this study was to evaluate the role of reticulated platelets (RF) and platelet-associated antibody (PAIg) in differential diagnosis of idiopathic thrombocytopenic purpura (ITP). The immature platelet fraction (IPF) of 34 ITP patients, 36 non-ITP patients and 411 normal people were detected by Sysmex XE-5000 automated blood cell analyser and PAIgG content was detected by enzyme-linked immunosorbent assay. All results were analysed statistically. The results showed that IPF of ITP patients was significantly higher than that of non-ITP patients and normal people respectively (p < 0.05). For diagnosis of ITP, IPF positive rate of ITP patients was significantly higher than that of non-ITP patients (p < 0.05). There was no significant difference between the positive rate of PAIgG in ITP and non-ITP patients (p > 0.05). The sensibility, specificity and negative predictive value of IPF were higher than those of PAIgG, while the positive predictive value of IPF was a little lower than that of PAIgG. The area under receiver operating characteristic curve of IPF was larger than that of PAIgG. It is concluded that both IPF and PAIgG detection are valuable in differential diagnosis of ITP. The diagnostic value of IPF is better than that of PAIgG. PMID:21867628

Liu, Yan; Wang, Zhen; Yuan, Bai-Xiang; Wang, Xiao-Yan; Wu, Qiong; Yuan, Hong

2011-08-01

85

Evaluation of humoral immune function in patients with chronic idiopathic thrombocytopenic purpura.  

PubMed

Coincidence of autoimmune diseases such as immune thrombocytopenic purpura (ITP) with immunodeficiencies has been reported previously in patients who suffered from primary antibody deficiency (PAD). But there is no original study on immunological profiles of ITP patients to find out their probable immune deficiency. In this case-control study, ITP patients' humoral immunity was investigated for diagnosis of PAD in comparison with normal population. To evaluate the humoral immune system against polysaccharide antigens, patients' serum immunoglobulin levels were measured and a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) was administrated to evaluate the antibody response to vaccination. In this study, 14 out of 36 patients (39%) were diagnosed with antibody mediated immune deficiency including 2 patients (5.5%) with immunoglobulin class deficiency and 4 (11%) with IgG subclass deficiency. The remaining patients suffered from specific antibody deficiency. The most frequent deficiency in ITP patients was specific antibody deficiency.Therefore, immunological survey on ITP patients may be important especially for those who have undergone splenectomy. PMID:23454778

Rahiminejad, Mohammad Saeid; Mirmohammad Sadeghi, Mehrdad; Mohammadinejad, Payam; Sadeghi, Bamdad; Abolhassani, Hassan; Dehghani Firoozabadi, Mohammad Mehdi; Fathi, Seyed Mohammad; Rezvani, Hamid; Bahoush, Gholamreza; Ehsani, Mohammad Ali; Faranoush, Mohammad; Mehrvar, Azim; Torabi Sagvand, Babak; Ghadiani, Mojtaba; Rezaei, Nima; Aghamohammadi, Asghar

2013-03-01

86

Platelet Kinetics in Idiopathic Thrombocytopenic Purpura Patients Treated with Thrombopoietin Receptor Agonists  

PubMed Central

Aim Thrombopoietin receptor agonists (Tpo RA) increase platelet counts in the majority of chronic autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura; ITP) patients. It is unknown whether this treatment may also improve platelet survival (PS) in these patients. Methods In order to determine platelet survival (PS), autologous platelets were labeled with 111In oxine and retransfused in six patients under treatment with Tpo RA (romiplostim n = 3; eltrombopag n = 3). Results Stable platelet counts of greater than 100 × 103/?l were observed in all 6 patients. Platelet survival was decreased in all cases (mean 2.10 days; range 0.13–3.73 days). No correlation was found between platelet count and PS. Similarly, there was no significant relationship between platelet turnover and platelet count. However, a high platelet turnover, exceeding 25 or three times the norm was observed in 2 patients who presented the lowest PS (0.13 or 0.83 days). Two patients had a moderately shortened PS (1.91 or 2.42 days), and, correspondingly, a moderately increased platelet turnover rate (63,072 or 72,872 platelets/?l/day). Conclusion These results indicate that Tpo RA may not only overcompensate platelet destruction in ITP, but may interfere with other mechanisms, which, in some cases, results in a reduced platelet destruction rate. PMID:22896760

Meyer, Oliver; Herzig, Eric; Salama, Abdulgabar

2012-01-01

87

Vaccine administration and the development of immune thrombocytopenic purpura in children  

PubMed Central

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

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

2013-01-01

88

Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan  

PubMed Central

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed. PMID:22427934

Matsumoto, Masanori; Bennett, Charles L.; Isonishi, Ayami; Qureshi, Zaina; Hori, Yuji; Hayakawa, Masaki; Yoshida, Yoko; Yagi, Hideo; Fujimura, Yoshihiro

2012-01-01

89

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

PubMed Central

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

Torbey, Estelle; McCord, Donald; Lafferty, James

2013-01-01

90

[Embolizing aortic valve endocarditis in the differential diagnosis of thrombotic thrombocytopenic purpura].  

PubMed

A 50-year-old man complained of lumbar pains, lack of energy, dysarthria and ataxic gait. Investigation revealed progressive anaemia (haemoglobin initially 10.5 g/dl, later 6.8 g/dl) and thrombocytopenia (initially 67,000/microliters, later 25,000/microliters). In addition he had unexplained pyrexia of up to 39.8 degrees C. Lactate dehydrogenase was 780 U/l and fragmented red cells were noted in the blood film. Because of suspicion of thrombotic thrombocytopenic purpura, treatment with fresh plasma by infusion was immediately initiated. On the third day of treatment he developed left ventricular failure; auscultation revealed a blowing early diastolic murmur over Erb's point together with a spindle-shaped early diastolic murmur over the right second intercostal space. Computed tomography of the skull showed recent haemorrhage into the left half of the cerebellum and an older right posterior infarct. The abdominal ultrasound scan suggested a haemorrhagic spleen infarct. In view of these findings the diagnosis was revised to embolizing aortic endocarditis with aortic reflux (confirmed by colour Doppler echo-cardiography). Aortic valve replacement was performed immediately, and the patient was treated with gentamycin 80 mg/d and teicoplanin 400 mg/d for four weeks. Postoperatively he was given 12 units of platelet concentrate and the platelet count remained stable thereafter (greater than 100,000/microliters). Splenectomy became necessary because the splenic haematoma increased in size during oral anticoagulant therapy. After a 6 week hospital stay the patient was discharged in good condition. PMID:1533583

Thomas, M; Heyll, A; Meckenstock, G; Vogt, M; Aul, C

1992-05-01

91

Can we predict neonatal thrombocytopenia in offspring of women with idiopathic thrombocytopenic purpura?  

PubMed Central

Background We aimed to investigate which factors in the clinical profile of mothers with idiopathic thrombocytopenic purpura (ITP) can predict neonatal risk of thrombocytopenia. Methods Data was retrospectively collected from all pregnant women with ITP who presented to our institution between 2001 and 2013. Neonatal offspring of these women were classified into 2 groups based on the presence or absence of neonatal thrombocytopenia (platelet count <100×109/L). Several parameters were compared between the 2 groups, including maternal age, maternal platelet count, maternal treatment history, and thrombocytopenia in siblings. We further examined the correlation between maternal platelet count at the time of delivery and neonatal platelet count at birth; we also examined the correlation between the minimum platelet counts of other children born to multiparous women. Results Sixty-six neonates from 49 mothers were enrolled in the study. Thrombocytopenia was observed in 13 (19.7%) neonates. Maternal treatment for ITP such as splenectomy did not correlate with a risk of neonatal thrombocytopenia. Sibling thrombocytopenia was more frequently observed in neonates with thrombocytopenia than in those without (7/13 vs. 4/53, P<0.01). No association was observed between maternal and neonatal platelet counts. However, the nadir neonatal platelet counts of first- and second-born siblings were highly correlated (r=0.87). Conclusion Thrombocytopenia in neonates of women with ITP cannot be predicted by maternal treatment history or platelet count. However, the presence of an older sibling with neonatal thrombocytopenia is a reliable risk factor for neonatal thrombocytopenia in subsequent pregnancies. PMID:25548760

Hachisuga, Kazuhisa; Fujita, Yasuyuki; Fukushima, Kotaro; Kato, Kiyoko

2014-01-01

92

Ribosomal and Immune Transcripts Associate with Relapse in Acquired ADAMTS13-Deficient Thrombotic Thrombocytopenic Purpura  

PubMed Central

Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and immune transcripts with relapse history in acquired, ADAMTS13-deficient TTP. PMID:25671313

Edgar, Contessa E.; Terrell, Deirdra R.; Vesely, Sara K.; Wren, Jonathan D.; Dozmorov, Igor M.; Niewold, Timothy B.; Brown, Michael; Zhou, Fang; Frank, Mark Barton; Merrill, Joan T.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; James, Judith A.; George, James N.; Farris, A. Darise

2015-01-01

93

Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura  

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder characterized by auto antibody-mediated platelet destruction. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated. In recent years, many studies have demonstrated improvement of platelet counts in ITP patients after treating Helicobacter pylori infection. The aim of this study was to investigate the effects of H. pylori eradication on platelet count response in Iranian ITP patients. A total of 26 patients diagnosed with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts were less than 100×103/?L. These patients were tested for H. pylori infection by Urea Breath Test and serum H. pylori antibody. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. These patients followed for six months. Prevalence of H. pylori was 67.3%. H. pylori eradication achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete response (CR) and 11 (42.3%) were unresponsive. We did not find partial responders. There was a significant difference in the baseline platelet count of responders and non-responders patients (p<0.001). All responders had platelet count ?50×103/?L and all non-responders had platelet count <50×103/?L. Results of this study revealed that eradication therapy of H. pylori infection can improve platelet counts in ITP patients especially with mild thrombocytopenia and support routine detection and treatment of H. pylori infection in ITP patients in populations with a high prevalence of this infection. PMID:22973500

Payandeh, Mehrdad; Sohrabi, Nasrollah; Zare, Mohammad Erfan; Kansestani, Atefeh Nasir; Hashemian, Amir Hossein

2012-01-01

94

The role of PTPN22 gene polymorphism in childhood immune thrombocytopenic purpura.  

PubMed

Immune thrombocytopenia is an autoimmune disorder characterized by antibody-mediated platelet destruction. A protein tyrosine phosphatase (PTPN22) present in lymphocytes is an important negative regulator of signal transduction for the T-cell receptor-MHC complex and has been associated with autoimmune disorders that produce autoantibodies. The present study investigated the frequency of the 1858C>T single-nucleotide polymorphism (SNP) in the PTPN22 gene in idiopathic thrombocytopenic purpura (ITP) patients. This case series study included 50 children with ITP, 24 acute and 26 chronic cases, and 50 normal children as a control group. All were subjected to clinical history and laboratory investigations including complete blood count, genotyping of PTPN22 1858C/T SNP by polymerase chain reaction-restriction fragment length polymorphism and platelet antibodies using platelets suspension immunofluorescence test for the cases. Thirteen patients (26%) were positive for the PTPN22 1858C>T SNP. Three patients were homozygous for the mutation and 10 were heterozygous. Comparison of the 26% of the ITP patients who were positive for the PTPN22 1858C>T mutation with the 6% positive in the control group yielded a P value of 0.006. Antiplatelet antibodies were detected in five patients (20.8%) with acute ITP and in three patients (11.5%) with chronic ITP; no significant association between the presence of PTPN22 1858C>T mutation and the presence of antiplatelet antibodies was detected. The prevalence of PTPN22 gene mutation was higher in ITP patients, thus it may be considered as a genetic risk factor in the development of ITP in Egyptian children. PMID:21597364

Anis, Shahira K; Abdel Ghany, Eman A; Mostafa, Naglaa O; Ali, Aliaa A

2011-09-01

95

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

Microsoft Academic Search

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

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

2008-01-01

96

Evaluation of 143 Cases of Immune Thrombocytopenic Purpura With Regards to Clinical Course and Response to Treatment  

PubMed Central

Objective: Immune thrombocytopenic purpura (ITP) is also known as idiopathic thrombocytopenic purpura. Increased platelet destruction and insufficient platelet production are both responsible for its etiopathogenesis. ITP can be diagnosed after excluding other possible causes of thrombocytopenia. Materials and Methods: One hundred forty-three cases of chronic ITP that were monitored in a hematology clinic were retrospectively evaluated. All cases received first line treatment of 1 mg/kg/day prednisolone. Corticosteroid nonresponsive (CN) cases and corticosteroid-dependent (CD) cases underwent splenectomies. Results: The rate of CN/CD cases was found to be 53% (n=76). Sixty-six percent of these cases (n=50) underwent splenectomies. The ratio of non-responsive cases to relapse cases after splenectomy (SN/SR) was 30% (n=15). The total number of cases was 41, including those without splenectomy (n=26) and with SY/SR (n=15). Helicobacter pylori (Hp) eradication, immunosuppressive agents and danazol treatments were administered to patients (n=10, n=14 and n=4, respectively). Currently, 13 patients are being monitored without treatment. Fifteen patients who were non-responsive to Hp eradication treatment, immunosuppressive treatment or danazol treatment are still being monitored without any treatment. Conclusion: Optimal treatment is not available for splenectomy-resistant cases of ITP. The response rates for Hp eradication treatment, immunosuppressive treatments and anabolic agents are low. Therefore, larger studies with more patients are required using new agents, such as thrombopoietin (TPO) receptor agonists and anti-CD20 monoclonal antibodies.

Albayrak, Murat; Balcik, Ozlem Sahin; Aki, Sahika Zeynep; Gokmen, Ayla; Ceran, Funda; Yokus, Osman; Dagdas, Simten; Ayli, Meltem; Ozet, Gulsum

2010-01-01

97

Flow cytometric detection of platelet-associated immunoglobulin in patients with immune thrombocytopenic purpura and nonimmune thrombocytopenia.  

PubMed

We increased the specificity of flow cytometric detection of platelet-associated immunoglobulin (PAIg) by a combination of platelet gating and cutoff for positivity determined by the use of receiver operating characteristic (ROC) curve analysis, and we evaluated the significance of elevated PAIg in non-immune thrombocytopenic purpura (ITP) patients. Blood samples from 118 patients with a platelet count <100 x 10(9)/L were used in this study. Flow cytometric detection of PAIg was performed. To obtain the cutoff of the surface-bound immunoglobulin for the discrimination of ITP and non-ITP, ROC curve analysis was used. The sensitivity of a positive PAIgG and PAIgM test for ITP in thrombocytopenic patients was 74.6%; the specificity was 79.7%; the positive predictive value 78.6%; and the negative predictive value 75.8%. Among 3 patients with myelodysplastic syndrome, 2 showed increased PAIg. Six of 20 patients with benign disease showed positivity for PAIg. Among these patients, 4 with elevated PAIg were diagnosed with liver disease. This study demonstrates that flow cytometric detection of PAIg combined with ROC curve analysis is a convenient, sensitive, and specific test, compared to previous methods, and it is useful for the differential diagnosis of thrombocytopenic patients. PMID:19667413

Huh, Hee Jin; Park, Chan Jeoung; Kim, Sang We; Han, Sang Hee; Jang, Seongsoo; Chi, Hyun Sook

2009-01-01

98

Common variable immunodeficiency unmasked by treatment of immune thrombocytopenic purpura with Rituximab  

PubMed Central

Background Hypogammaglobulinemia may be part of several different immunological or malignant conditions, and its origin is not always obvious. Furthermore, although autoimmune cytopenias are known to be associated with common variable immunodeficiency (CVID) and even may precede signs of immunodeficiency, this is not always recognized. Despite novel insight into the molecular immunology of common variable immunodeficiency, several areas of uncertainty remain. In addition, the full spectrum of immunological effects of the B cell depleting anti-CD20 antibody Rituximab has not been fully explored. To our knowledge this is the first report of development of CVID in a patient with normal immunoglobulin prior to Rituximab treatment. Case presentation Here we describe the highly unusual clinical presentation of a 34-year old Caucasian male with treatment refractory immune thrombocytopenic purpura and persistent lymphadenopathy, who was splenectomized and received multiple courses of high-dose corticosteroid before treatment with Rituximab resulted in a sustained response. However, in the setting of severe pneumococcal meningitis, hypogammaglobulinemia was diagnosed. An extensive immunological investigation was performed in order to characterize his immune status, and to distinguish between a primary immunodeficiency and a side effect of Rituximab treatment. We provide an extensive presentation and discussion of the literature on the basic immunology of CVID, the mechanism of action of Rituximab, and the immunopathogenesis of hypogammaglobulinemia observed in this patient. Conclusions We suggest that CVID should be ruled out in any patient with immune cytopenias in order to avoid diagnostic delay. Likewise, we stress the importance of monitoring immunoglobulin levels before, during, and after Rituximab therapy to identify patients with hypogammaglobulinemia to ensure initiation of immunoglobulin replacement therapy in order to avoid life-threatening invasive bacterial infections. Recent reports indicate that Rituximab is not contra-indicated for the treatment of CVID-associated thrombocytopenia, however concomitant immunoglobulin substitution therapy is of fundamental importance to minimize the risk of infections. Therefore, lessons can be learned from this case report by clinicians caring for patients with immunodeficiencies, haematological diseases or other autoimmune disorders, particularly, when Rituximab treatment may be considered. PMID:24499503

2013-01-01

99

The feature of TRGV and TRDV repertoire distribution and clonality in patients with immune thrombocytopenic purpura.  

PubMed

Chronic idiopathic (immune) thrombocytopenic purpura (ITP) is an autoimmune disorder in which anti-platelet antibodies induce platelet destruction due to an imbalanced immune response. Recently, data indicated the gammadelta(+)T cells may play an important role in autoimmune disease. Our previous study has shown the restricted expression of TRBV subfamilies and the alteration of peripheral TRBV repertoire pattern in the majority of ITP patients. In the present study, we further analyze the feature of TRGV and TRDV repertoire distribution and clonality in patients with ITP. The CDR3 size of three TRGV and eight TRDV subfamily genes were analyzed in peripheral blood mononuclear cells (PBMCs) from 11 cases with ITP, using RT-PCR and GeneScan techniques. To determine the expression level of TRGV subfamily genes, quantitative analysis of TRGV I-III subfamilies was performed by real-time PCR. TRGV I-III subfamilies could be detected in the most samples from ITP as well as in healthy controls. However, clonal expansion of TRGV was identified in five cases with ITP, which displayed polyclonality in all of samples from healthy controls. The expression level of all TRGV I-III subfamilies in ITP was significantly lower than that from healthy controls (p=0.048, 0.001, 0.035, respectively). The expression pattern of TRGV I-III repertoire in ITP was TRGV I>TRGV III>TRGV II, in contrast, TRGV II>TRGV I>TRGV II was found in healthy controls. TRDV 1 and TRDV 2 could be detected in most samples from ITP as well as in healthy controls, whereas TRDV 3 could be detected in only two out of 11 cases with ITP, which could be found in 90% of healthy controls (p=0.02). Oligoclonally expanded TRDV 1 and TRDV 2 T cells could be identified in the half of the ITP samples, with similar results in healthy control. In conclusion, the alteration of peripheral TRGV and TRDV repertoire pattern might play a role in the pathogenesis of immune-mediated platelet destruction in some cases with ITP. PMID:19635188

Zhang, Xueli; Chen, Shaohua; Yang, Lijian; Li, Bo; Zhu, Kanger; Li, Yangqiu

2009-08-01

100

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

PubMed Central

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

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

2014-01-01

101

Predisposition to idiopathic thrombocytopenic purpura maps close to the major histocompatibility complex class I chain-related gene A.  

PubMed

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune condition with poorly known etiology, characterized by platelet destruction. Genetic association studies of this disease are scarce, discrepant, and restricted to major histocompatibility complex (MHC) polymorphisms. Hence, a case-control study was conducted with an aim to map the MHC to IPT susceptibility using HLA-B and nine microsatellite loci encompassing MHC class I, II, and III regions. We compared the allelic frequencies in samples of unrelated healthy controls and ITP patients. After correction for multiple tests, only allele MICA*183, also known as A5.1, demonstrated an association, resulting in the identification of a major predisposing region close to STR-MICA. This result may highlight the putative functional role of MICA in the immune response to ITP. PMID:19280715

Maia, Maria Helena Thomaz; Peixoto, Raquel de Lima; de Lima, Clayton Pereira Silva; Magalhães, Milena; Sena, Leonardo; Costa, Perpétua do Socorro Silva; Barbosa, Fabíola Brasil; de Oliveira, Layanna Freitas; Romero, Matilde; Silva, Christina Nogueira de Araujo; dos Santos, Eduardo José Melo

2009-03-01

102

[Expression of co-stimulatory molecules in peripheral blood of patients with idiopathic thrombocytopenic purpura in relation with platelet antibodies].  

PubMed

This study was aimed to detect the expression of co-stimulatory molecules CD80, CD86 and CD137 in peripheral blood of patients with idiopathic thrombocytopenic purpura (ITP), the content of platelet antibodies in serum (PAIgG), and to analyze the relationship between them and their correlation with the number of platelet in peripheral blood, so as to clarify the roles of co-stimulatory molecules in pathogenesis of idiopathic thrombocytopenic purpura and evaluation of disease status. The co-stimulatory molecules CD80, CD86 and CD137 in peripheral blood mononuclear cells (PBMNCs) of 48 ITP patients and 40 normal persons were detected by immunofluorescence and flow cytometry (FACS), PAIgG content in serum was detected by enzyme-linked immunosorbent assay (ELISA). The results showed that CD80, CD86 and CD137 expression levels in ITP patients were (4.92 +/- 2.02)%, (8.68 +/- 4.25)%, (5.32 +/- 2.67)% respectively, PAIgG content was 210 +/- 3.02 ng/10(7) PA, all these of which were significantly higher than these in normal control group (2.01 +/- 0.75)%, (4.56 +/- 2.06)%, (1.37 +/- 1.25)%, PAIgG 20 +/- 1.13 ng/10(7) PA (p < 0.01). Correlation of co-stimulatory molecule expression with PAIgG content were positive (r = 0.302, p < 0.05), but correlation of co-stimulatory molecule expression with platelet number was negative (r = -0.369, p < 0.05). It is concluded that the co-stimulatory molecules CD80, CD86 and CD137 are involved in immune response and the incidence of ITP. Their over-expression closely associates with the pathogenesis of ITP and clinical status, so that correcting the abnormal expression and regulating the immune status may be one therapeutic strategy and have important clinical significance. PMID:19379594

Ma, Xiao-Rong; Chen, Yin-Xia; Zhang, Wang-Gang; Tian, Wei; Liu, Jie; Cao, Xing-Mei; He, Ai-Li

2009-04-01

103

The Oklahoma thrombotic thrombocytopenic Purpura-Hemolytic uremic syndrome (TTP-HUS) registry: a community perspective of patients with clinically diagnosed TTP-HUS  

Microsoft Academic Search

The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry enrolls all consecutive patients for whom plasma exchange treatment is requested for clinically diagnosed TTP-HUS within a defined geographic region. During 14.5 years, from January 1, 1989 until June 30, 2003, 301 patients have been enrolled; follow-up is complete on 300 patients. Clinical categories have been designated based on associated conditions

James N George; Sara K Vesely; Deirdra R Terrell

2004-01-01

104

Human/BALB radiation chimera engrafted with splenocytes from patients with idiopathic thrombocytopenic purpura produce human platelet antibodies.  

PubMed Central

We have previously shown that lethally irradiated normal strains of mice, radioprotected with severe combined immunodeficient (SCID) bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC). The human/mouse radiation chimera can mount marked humoral and cellular responses to recall antigens, as well as primary responses. In the present study, we adoptively transferred splenocytes from patients with chronic immune thrombocytopenic purpura (ITP) into lethally irradiated BALB/c mice, radioprotected with SCID bone marrow. High titres of total human immunoglobulin appeared as early as 2 weeks post-transplant and declined after 6 weeks, while human anti-human platelet antibodies were detected 2-8 weeks after the transfer of splenocytes. The immunoglobulin G (IgG) fraction contained antibodies against glycoprotein (GP) IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibodies showed a low level of cross-reactivity with mouse platelets, and thrombocytopenia in the animals was not observed. Splenocytes from individual ITP patients differed in their capacity to produce either human platelet antibodies or total human immunoglobulin. Furthermore, antibodies produced in the murine system were not always identical to the original antibodies present in the serum of the patients. The study of the serological aspects of autoantibodies against human platelets in an animal model might be useful for the investigation of potential therapeutics in ITP. PMID:9767425

Dekel, B; Marcus, H; Shenkman, B; Shimoni, A; Shechter, Y; Canaan, A; Berrebi, A; Varon, D; Reisner, Y

1998-01-01

105

[H. pylori infection and extra-digestive disease--idiopathic thrombocytopenic purpura and iron deficiency anemia--review].  

PubMed

Although H. pylori infection has been shown to be associated with a wide variety of non-gastrointestinal tract conditions, the studies are conflicting regarding these associations. In addition, a biological rationale for the proposed association with H. pylori infection is often lacking. Recent systematic reviews have shown a beneficial effect of H. pylori eradication in idiopathic thrombocytopenic purpura. The weighted mean complete response (platelet count > or = 100 x 10(9)/L) and overall response (platelet count > or = 30 x 10(9)/L and at least doubling of the basal count) were 42.7% (95% confidence interval[CI], 31.8%-53.9%) and 50.3% (95% CI, 41.6%-59.0%), respectively. These recent reviews demonstrated that diagnosis and treatment of H. pylori infection should be considered; however, randomized controlled clinical trials and immunological investigations on the mechanism are still lacking and are required. The results of meta-analysis indicated a significant association between H. pylori infection and iron deficiency or iron deficiency anemia, especially in high-risk groups. Although some case studies, small patient series and non-randomized trials have shown a beneficial effect of eradication in children with iron deficiency anemia, negative findings have also been reported. Further evaluation of the improvement of iron stores by eradication in large and well-controlled trials are required and would allow further additional studies to understand its biological mechanisms. PMID:19860213

Shiotani, Akiko; Kamada, Tomoari; Imamura, Hiroshi; Kusunoki, Hiroaki; Hata, Jiro; Haruma, Ken

2009-09-01

106

R1933X mutation in the MYH9 gene in May-Hegglin anomaly mimicking idiopathic thrombocytopenic purpura.  

PubMed

May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. Recent evidence links MHA to mutations in the MYH9 gene. MHA has not been reported in Taiwan before. We report a 25-year-old Taiwanese man who presented with prolonged bleeding after dental extraction. Examination of peripheral blood smear revealed thrombocytopenia (platelet = 35,000/?L), giant platelets, and Döhle-like cytoplasmic inclusions in neutrophils. A strong family history of thrombocytopenia favored hereditary macrothrombocytopenia over idiopathic thrombocytopenic purpura (ITP). Electron microscopy revealed a spindle shape and parallel order of filaments in the inclusions, consistent with the diagnosis of MHA. We performed mutational analysis using polymerase chain reaction followed by direct sequence of the MYH9 gene for the patient, his maternal uncle and cousin, and all showed the same heterozygous R1933X mutation in exon 40. MHA should be considered when a young patient has thrombocytopenia, frequently misdiagnosed as ITP. Morphological examination of peripheral blood smear, family history tracing and genetic studies are required to make an accurate diagnosis and avoid unnecessary and even harmful therapies such as corticosteroids and splenectomy. PMID:23759689

Sung, Chih-Chien; Lin, Shih-Hua; Chao, Tai-Kuang; Chen, Yeu-Chin

2014-01-01

107

Fc?RIIa and Fc?RIIIa genetic polymorphisms in a group of pediatric immune thrombocytopenic purpura in Egypt.  

PubMed

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. The current case-control study aimed at detecting the frequency of Fc?RIIa-131H/R and Fc?RIIIa-158F/V genes polymorphism in Egyptian children with ITP as genetic markers for ITP risk, and to clear out their possible role in choosing the treatment protocols of ITP. To achieve this aim, Fc?RIIa genotyping was tested by PCR-restriction fragment length polymorphism (RFLP) technique, whereas Fc?RIIIa genotyping was tested by nested PCR followed RFLP analysis. The current case-control study was conducted on 92 children with ITP; 12 acute and 80 chronic cases and 90 controls. The V allele and Fc?RIIIa FV heterotype were significantly higher in ITP patients and conferred increased ITP risk [odds ratio (OR) = 1.96 and 2.55, respectively]. The frequency of Fc?RIIa H allele was significantly higher among chronic ITP patients. In conclusion, Fc?RIIIa gene polymorphism may contribute to susceptibility to ITP. Moreover, analysis of the Fc?R polymorphisms in ITP patients could influence the effectiveness of medications and selection of the line of treatment. PMID:22123287

Eyada, Tayseer K; Farawela, Hala M; Khorshied, Mervat M; Shaheen, Iman A; Selim, Neama M; Khalifa, Iman A S

2012-01-01

108

Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura - Therapeutic plasma exchange is the answer.  

PubMed

The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia-eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management. PMID:21814380

Nasa, Prashant; Dua, J M; Kansal, Sudha; Chadha, Geeta; Chawla, Rajesh; Manchanda, Manav

2011-04-01

109

Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura – Therapeutic plasma exchange is the answer  

PubMed Central

The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia–eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management. PMID:21814380

Nasa, Prashant; Dua, J. M.; Kansal, Sudha; Chadha, Geeta; Chawla, Rajesh; Manchanda, Manav

2011-01-01

110

FATAL OUTCOME OF INFECTION BY DENGUE 4 IN A PATIENT WITH THROMBOCYTOPENIC PURPURA AS A COMORBID CONDITION IN BRAZIL  

PubMed Central

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

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

111

An Optimized Fluorogenic ADAMTS13 Assay with Increased Sensitivity for the Investigation of Patients with Thrombotic Thrombocytopenic Purpura  

PubMed Central

Summary Background Most ADAMTS13 assays use non-physiological conditions (low ionic strength, low pH, barium chloride), are subject to interference from plasma proteins, hemoglobin and bilirubin, and have limited sensitivity, especially for inhibitors. Objectives We addressed these constraints by designing a substrate that can be used in undiluted plasma. Methods A polypeptide was expressed in E. coli that corresponds to von Willebrand factor Gln1599-Arg1668, with mutations N1610C and K1617R and an N-terminal Gly. Substrate FRETS-rVWF71 was prepared by modifying Cys1610 with DyLight 633 (abs 638 nm, em 658 nm) and the N-terminus with IRDye QC-1 (abs 500-800 nm). Assays were performed at pH 7.4 in 150 mM NaCl, 10 mM CaCl2. Results Serum and plasma anticoagulated with citrate or heparin had equivalent ADAMTS13 activity with FRETS-rVWF71. Neither bilirubin (?20 mg/dL) nor hemoglobin (?20 g/L) interfered with product detection. Assays with FRETS-rVWF71 and FRETS-VWF73 gave similar results (R2 = 0.95) for plasma from 80 subjects with thrombotic microangiopathy, 22 subjects with other causes of thrombocytopenia, and 20 healthy controls. The limit of detection with FRETS-rVWF71 for ADAMTS13 activity was ?0.3%. Inhibitor assays with FRETS-rVWF71 gave titers ~2.5-fold higher than with FRETS-VWF73 and clearly distinguished patients with and without inhibitors. Conclusions FRETS-rVWF71 is suitable for ADAMTS13 assays in minimally diluted plasma or serum without interference from proteins, bilirubin or free hemoglobin in plasma. Optimized detection of ADAMTS13 inhibitors will facilitate the monitoring of antibody responses during the treatment of thrombotic thrombocytopenic purpura. PMID:23773695

Muia, J.; Gao, W.; Haberichter, S. L.; Dolatshahi, L.; Zhu, J.; Westfield, L. A.; Covill, S. C.; Friedman, K. D.; Sadler, J. E.

2013-01-01

112

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

Microsoft Academic Search

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

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

2006-01-01

113

Idiopathic thrombocytopenic purpura (ITP)  

MedlinePLUS

... well your blood clots and to check your platelet count. A bone marrow aspiration or biopsy may also ... the spleen (splenectomy) is recommended. This increases the platelet count in about half of patients. However, other drug ...

114

Ticlopidine-, Clopidogrel-, and Prasugrel-Associated Thrombotic Thrombocytopenic Purpura: A 20-Year Review from the Southern Network on Adverse Reactions (SONAR)  

PubMed Central

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. PMID:23111862

Jacob, Sony; Dunn, Brianne L.; Qureshi, Zaina P.; Bandarenko, Nicholas; Kwaan, Hau C.; Pandey, Dilip K.; McKoy, June M.; Barnato, Sara E.; Winters, Jeffrey L.; Cursio, John F.; Weiss, Ivy; Raife, Thomas J.; Carey, Patricia M.; Sarode, Ravindra; Kiss, Joseph E.; Danielson, Constance; Ortel, Thomas L.; Clark, William F.; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X. Long; Chen, Hao; Chen, Fei; Armstrong, John M.; Raisch, Dennis W.; Bennett, Charles L.

2013-01-01

115

Portal vein thrombosis during eltrombopag treatment for immune thrombocytopenic purpura in a patient with liver cirrhosis due to hepatitis C viral infection.  

PubMed

Portal vein thrombosis is a rare, aggressive and life-threatening complication of liver cirrhosis (LC). Eltrombopag is effective for the treatment of chronic hepatitis with thrombocytopenia, and portal vein thrombosis at this time has rarely been reported. We describe the case of a 78-year-old woman who suffered from LC due to hepatitis C viral infection. The patient developed immune thrombocytopenic purpura (ITP) that was diagnosed on the basis of nasal bleeding, progressive severe thrombocytopenia, elevation of platelet-associated IgG (PAIgG), no response to the transfusion of platelets and no abnormal findings on bone marrow biopsy. Although we first administered prednisolone (0.5 mg/kg/day), there was no recovery of platelet function and the nasal bleeding persisted. Subsequently, we administered eltrombopag for refractory ITP at a dose of 12.5 mg/day, and the thrombocytopenia gradually improved. Fifty-four days after the start of eltrombopag therapy, she developed portal vein thrombosis. Eltrombopag was stopped immediately, and antithrombin III was administered for prophylaxis against further portal vein thrombosis. Despite these treatments, there were subsequent deep vein and pulmonary artery thromboses. We then administered heparin for recanalization of the thrombi. One month after the initiation of heparin, there was recanalization as well as improvements of the portal vein, deep vein and pulmonary artery thromboses. There was no further thrombosis progression after switching from heparin to warfarin therapy. Our case suggests that eltrombopag may increase the risk of portal vein thrombosis ; therefore, this drug must be used carefully in the treatment of ITP in patients with LC due to hepatitis C viral infection. PMID:23995112

Kawano, Noriaki; Hasuike, Satoru; Iwakiri, Hisayoshi; Nakamura, Kenichi; Ozono, Yoshinori; Kusumoto, Hisanori; Nagata, Kenji; Kikuchi, Ikuko; Yoshida, Shuro; Kuriyama, Takuro; Yamashita, Kiyoshi; Muranaka, Takahiro; Kawaguchi, Takumi; Sata, Michio; Okamura, Takashi; Ueda, Akira; Shimoda, Kazuya

2013-01-01

116

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): treatment outcome, relapses, prognostic factors. A single-center experience of 48 cases.  

PubMed

The thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome (TTP/HUS) is a rare disorder characterized by microangiopathic hemolysis and thrombocytopenia. We have undertaken a retrospective analysis of the clinical characteristics, treatment outcome, and prognosis of 48 patients diagnosed and treated in our institution during a 13-year period. Among our patients 22 (46%) had fever, 35 (73%) neurological abnormalities, and 22 (46%) renal impairment at presentation of the syndrome. All patients were treated with a multimodality regimen including plasma exchange, steroids, antiplatelet agents, and IgG infusion. Of the 48 patients, 41 achieved complete remission, two had a partial response, and five had no response and died of progressive disease. Within a median follow-up period of 40 months, ten of the 41 patients who had achieved remission relapsed, most of them within the first 2 years, and nine of these responded promptly to plasma exchange therapy. Eight deaths were observed, seven of refractory disease and one in fourth relapse. The analysis of prognostic factors revealed advanced age and severe renal impairment (creatinine levels above 2 mg%) as the only parameters associated with treatment failure and poor outcome. However, none of the pretreatment characteristics proved to be of prognostic value regarding the probability of relapse. In conclusion, TTP/HUS represent a syndrome of variable clinical expression and aggressiveness. The use of a multimodality regimen in our series produced a high response rate. Nevertheless, the early identification, based on clinical characteristics, of poor-prognosis cases that probably need more or alternative forms of treatment is an issue that remains to be elucidated in prospective trials. PMID:10741917

Dervenoulas, J; Tsirigotis, P; Bollas, G; Pappa, V; Xiros, N; Economopoulos, T; Pappa, M; Mellou, S; Kostourou, A; Papageorgiou, E; Raptis, S A

2000-02-01

117

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

PubMed

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

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

2010-01-01

118

Alteration in frequency and function of CD4?CD25?FOXP3? regulatory T cells in patients with immune thrombocytopenic purpura.  

PubMed

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterized by production of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs) have a major role in controlling immune homeostasis and preventing autoimmunity.To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age- and sex-matched healthy controls were recruited. The peripheral blood mononuclear cells were isolated and the proportion of Tregs was defined by flow cytometry method. The expression of immune-regulatory markers, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and glucocorticoid induced tumor necrosis factor receptor (GITR) were also assessed by quantitative Real-time PCR TaqMan method. For evaluation of Treg function, Tregs were enriched and their ability to inhibit proliferation of T cells was measured and levels of immune-regulatory cytokines IL-10 and TGF-? were also measured.Results showed that the frequency of Tregs and the mean fluorescence intensity of FOXP3 protein significantly decreased in ITP patients compared to those in healthy controls. In addition, there was a significant reduction in relative expression of both CTLA-4 and GITR mRNA in ITP patients (P=0.02 and P=0.006, respectively). The suppressive function of Tregs also diminished in ITP patients compared to that in controls. Both IL-10 and TGF-? cytokines were produced in lower amounts in ITP patients than controls.It could be concluded that alteration in Treg frequency and functional characteristics might be responsible for loss of self-tolerance and subsequently destructive immune responses observed in ITP patients. PMID:24338252

Arandi, Nargess; Mirshafiey, Abbas; Jeddi-Tehrani, Mahmood; Shaghaghi, Mohammadreza; Sadeghi, Bamdad; Abolhassani, Hassan; Sharifian, Ramazan Ali; Rahiminejad, Mohammad Saeid; Aghamohammadi, Asghar

2014-04-01

119

Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura  

PubMed Central

Thrombotic thrombocytopenic purpura (TTP) is primarily caused by immunoglobulin G (IgG) autoantibodies against A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats, 13 (ADAMTS13). Nearly all adult idiopathic TTP patients harbor IgGs, which bind the spacer domain of ADAMTS13, a region critical for recognition and proteolysis of von Willebrand factor (VWF). We hypothesize that a modification of an exosite in the spacer domain may generate ADAMTS13 variants with reduced autoantibody binding while preserving or enhancing specific activity. Site-directed mutagenesis was used to generate a series of ADAMTS13 variants, and their functional properties were assessed. Of 24 novel ADAMTS13 variants, 2 (ie, M4, R660K/F592Y/R568K/Y661F and M5, R660K/F592Y/R568K/Y661F/Y665F) exhibited increased specific activity approximately 4- to 5-fold and approximately 10- to 12-fold cleaving a peptide VWF73 substrate and multimeric VWF, respectively. More interestingly, the gain-of-function ADAMTS13 variants were more resistant to inhibition by anti-ADAMTS13 autoantibodies from patients with acquired idiopathic TTP because of reduced binding by anti-ADAMTS13 IgGs. These results shed more light on the critical role of the exosite in the spacer domain in substrate recognition. Our findings also help understand the pathogenesis of acquired autoimmune TTP. The autoantibody-resistant ADAMTS13 variants may be further developed as a novel therapeutic for acquired TTP with inhibitors. PMID:22289888

Jian, Cui; Xiao, Juan; Gong, Lingjie; Skipwith, Christopher G.; Jin, Sheng-Yu; Kwaan, Hau C.

2012-01-01

120

[Characterization of unusual macro CK1 of IgG3kappa-cK-MM type detected in the serum of a patient with idiopathic thrombocytopenic purpura].  

PubMed

An unusual creatine kinase (CK) band detected in the serum of a patient with idiopathic thrombocytopenic purpura (ITP) was studied. The number of platelets of the patient decreased to 2.3 x 10(4)/microL, and serum CK and CK-MB activities increased to 899 and 62.7 U/L, respectively. The unusual CK band with a molecular size of 320,000 migrated to the cathodal side of CK-MM through electrophoresis, and the position was similar to that of octameric mitochondrial CK(Mi-CK). However, the cathodal band did not react with anti ubiquitous or anti-sarcomeric Mi-CK antibodies; instead, a reaction of the band occurred with anti-CK-M subunit antibodies and CK activity was inhibited. In addition to the cathodal band of CK-MM, an atypical CK band was simultaneously detected on the anodal side of CK-MM. It was found that the cathodal and anodal bands were macro CK1 of IgG3kappa-CK-MM and IgG1kappa-CK-MM, respectively, by immunofixation electrophoresis with anti-IgG subclass antibodies. The number of platelets began to increase one week after the elimination of Helicobacter pylori. The cathodal band activity showed an opposite migration one to two weeks following the platelet count change. Change of the anodal band began one month or longer following the platelet count change. One year following the first medical examination, the level of IgG3 in the serum of the patient decreased to 45%, and the percentage was lower than those of the other IgG subclasses. These results suggest that changes in the cathodal band are associated with those of the number of platelets and reflect the disease state of the patient. In conclusion, the cathodal band of CK-MM in the serum of an ITP affected patient was macro CK1 of IgG3kappa-CK-MM type, it migrated to the opposite sides of the platelet count change, and reflected the disease state of the patient. PMID:23157112

Kanemitsu, Fusae; Kageoka, Takeshi

2012-09-01

121

Congenital amegakaryocytic thrombocytopenic purpura (CAMT).  

PubMed

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

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

2014-04-01

122

A multi-centre, single-arm, open-label study evaluating the safety and efficacy of fixed dose rituximab in patients with refractory, relapsed or chronic idiopathic thrombocytopenic purpura (R-ITP1000 study).  

PubMed

The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refractory, relapsed or chronic (platelet count >10 × 10(9) /l and ?50 × 10(9) /l) idiopathic thrombocytopenic purpura (ITP). Patients received two doses of rituximab (1000 mg) on days 1 and 15 and were followed-up on weeks 1-8, 12, 26, 39 and 52. A total of 122 patients were included in the safety population; efficacy was analysed in 108 patients. Overall response rate (ORR) at week 8, defined as the proportion of patients achieving complete response (CR; platelet count >150 × 10(9) /l) or partial response (PR; platelet count >50 × 10(9) /l) was 44%. Therapeutic response, defined as achieving a response at week 8, with at least a minor response (MR; platelet count >30 × 10(9) /l), sustained up to weeks 26 and 52 and accompanied by a reduction in ITP medications, was achieved in 44% (week 26) and 35% (week 52) of patients, respectively. Treatment was well tolerated with no safety concerns. While this study failed to meet its primary endpoint of an ORR of 50%, the efficacy of two fixed doses of rituximab appear to provide similar efficacy to the standard 375 mg/m(2) four-dose schedule in relapsed/chronic ITP. PMID:25041261

Tran, Huyen; Brighton, Tim; Grigg, Andrew; McRae, Simon; Dixon, Joanna; Thurley, Daniel; Gandhi, Maher K; Truman, Matt; Marlton, Paula; Catalano, John

2014-10-01

123

Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc. PMID:25042026

Pandey, Soumya; Nakagawa, Mayumi; Rosenbaum, Eric R; Arnaoutakis, Konstantinos; Hutchins, Laura F; Makhoul, Issam; Milojkovic, Natasha; Cottler-Fox, Michele

2014-07-17

124

How Is Thrombotic Thrombocytopenic Purpura Treated?  

MedlinePLUS

... plasma for people who have inherited TTP Plasma exchange for people who have acquired TTP Plasma therapy ... replace the missing or changed ADAMTS13 enzyme. Plasma exchange (also called plasmapheresis) is used to treat acquired ...

125

[Idiopathic thrombocytopenic purpura (ITP) in children].  

PubMed

Thrombocytopenia associated with ITP in children usually returns to normal within a couple of months. Drug therapies are required to treat hemorrhages in approximately one fifth of the patients. Intravenously infused immunoglobulin is effective more rapidly than corticosteroid therapy, but the treatment response is mostly temporary. Thrombocytopenia is alleviated by splenectomy in approx. 70% of chronic ITP patients. In the absence of primary disease causing thrombocytopenia, splenectomy has to be contemplated, if thrombocytopenia impairs the quality of life for more than one year. New drug therapies such as rituximab and growth factor products increasing thrombopoiesis may decrease the number of splenectomies. PMID:22073540

Rajantie, Jukka

2011-01-01

126

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

PubMed Central

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

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

2012-01-01

127

Henoch-Schonlein purpura  

MedlinePLUS

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

128

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

ClinicalTrials.gov

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

2014-10-16

129

[Autoimmune thrombocitopenic purpura in pregnancy].  

PubMed

The author deals with haematologists' and obstetricians' current views on acquired ATP in children and adults, characterised by a transient, acute or chronic decrease in platelets count (<50.109/l) due to premature destruction by the reticuloendothelial system. The most common questions arising in connection with this disease are: what is autoimmune thrombocytopenic purpura; is there any correlation between pregnancy and ATP; what are its symptoms; does pregnancy itself affect the autoimmune disease. If is of utter importance for women with ATP to be aware of the risks these symptoms pose both on the health of the mother and the foetus. Obstetricians and gynaecologists seldom object to pregnancy in women with ATP. Nevertheless, it is essential to point out that additional monitoring and therapy are needed. There is no medical evidence that supports the notion of terminating pregnancy due to ATP. Assessment is made only by an obstetrician, haematologist and pediatrician working in close collaboration. This collaborative work must be present throughout the whole pregnancy, delivery and puerperium. The treatment necessary for women with ATP aims to establish platelet count over 50.000 ppm when approaching the end of pregnancy, preferably between 80.000 ppm - 100.000 ppm taking into account vagina or surgical delivery as well as the administration of anaesthetic. Delivery management must be decided entirely on obstetrics consideration, but not on ATP ones. Pregnant women with ATP must be monitored and treated with caution by a highly specialised medical team. PMID:20225496

Christova, R; Lisichkov, T; Chernev, T

2009-01-01

130

[Rosette forming lymphocytes as prognostic indices in idiopathic thrombocytopenic purpura].  

PubMed

The study included 12 patients with acute ITP to whom subpopulations of rosette forming lymphocytes were determined in peripheral blood and in serial form, the number of platelets to establish a correlation as prognostic index in the evolution of the disease. No correlation was found between the progressive increment of platelets in the evolution of the disease. However, in patients with a tendency to remission, the percentage of E(T) rosette forming lymphocytes was low and normal that of EAC (B) lymphocytes. Dissimilarly, it was seen that in patients without tendency to remission, the percentage of T and B rosette forming lymphocytes was within normal limits. This seems to show that determination of the subpopulations of lymphocytes may be useful as a prognostic index in this stage of the disease. PMID:306255

Martínez Cairo, S; Farfán Canto, J M; Alanís, F; Gaitán Ramírez, F

1978-01-01

131

Assessment of Regulatory T Cells in Childhood Immune Thrombocytopenic Purpura  

PubMed Central

This study had the objective to assess the frequency of Tregs in children newly diagnosed with ITP and ascertain whether an association exists between Tregs and platelet counts, by means of a comparison with healthy controls. This case-control study included 19 patients newly diagnosed with ITP—whose blood samples were collected at four points in time: before any therapy and 1, 3, and 6 months after diagnosis—and 19 healthy controls. Tregs (CD4+ CD25+Foxp3 T cells) were evaluated by flow cytometry. There was a statistically significant difference in platelet count between the case and control groups. There were no significant differences in Treg counts between cases and controls at any point during the course of the study and no difference in Treg counts between the chronic and nonchronic groups and no significant correlation between Tregs and platelet counts in the case and control groups. The findings of this study did not show any statistically significant correlation between Tregs and number of platelets in the case and control groups. Treg cells did not play a role in the regulation of autoimmunity in children with ITP. PMID:24298390

Mazzucco, Karina L. M.; Junior, Lauro M.; Lemos, Natália E.; Wieck, Andréa; Pezzi, Annelise; Laureano, Alvaro M.; Amorin, Bruna; Valim, Vanessa; Silla, Lucia; Daudt, Liane E.; Marostica, Paulo J. C.

2013-01-01

132

Henoch-Schonlein Purpura  

MedlinePLUS

... sometimes progressing to serious kidney involvement. Who gets Henoch-Schönlein Purpura (the “typical” patient)? Usually, HSP affects a child ... with HSP is 5.9 years. What causes Henoch-Schönlein Purpura? In two-thirds of the cases, the disease ...

133

Progressive pigmentary purpura.  

PubMed

A 58-year-old man presented for evaluation and treatment of non-tender, non-pruritic, annular patches on the right temple and frontal aspect of the scalp that reddened with exercise. A biopsy specimen showed a purpuric dermatitis with features of lymphocytic vasculitis; a diagnosis of exercise-induced progressive pigmentary purpura was made. Whereas progressive pigmentary purpura is purported to be caused by exercise, other similar appearing entities are associated with exercise, namely exercise-induced vasculitis (EIV). EIV may be considered as an acute microcirculatory deficiency and thermoregulation decompensation that occurs after episodes of exhaustive major muscular activity or after unusual or excessive exercise. The combination of age greater than 50 years, heat, and prolonged exercise are the most potent contributing factors. This is the first report of exercise-induced progressive pigmentary purpura. PMID:22031640

Brauer, Jeremy A; Mundi, Jyoti; Chu, Julie; Patel, Rishi; Meehan, Shane; Greenspan, Alan H; Stein, Jennifer

2011-01-01

134

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

ClinicalTrials.gov

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

2014-07-18

135

Relationships of Mean Platelet Volume and Plasma Thrombopoietin with Glycocalicin Levels in Thrombocytopenic Patients.  

PubMed

Backgrounds/Aims: Relationships of mean platelet volume (MPV) and thrombopoietin (TPO) with platelet turnover assessed by glycocalicin measurement were evaluated in thrombocytopenic patients. Methods: MPV, glycocalicin and platelet-associated IgG (PA-IgG) were measured in 107 patients with idiopathic thrombocytopenic purpura (ITP) and 19 patients with hypoproductive thrombocytopenia (HPT; aplastic anemia or leukemia), and TPO was measured in 53 ITP and 12 HPT patients. All the included ITP patients had PA-IgG ?300% and glycocalicin ?50% of control values, and HPT patients had PA-IgG <300% and glycocalicin <50% of control values. Results and Conclusions: MPV was higher in ITP than in HPT patients: 9.56 ± 1.69 and 7.59 ± 0.90 fl (p < 0.001). In the ITP group a direct correlation was detected between MPV and glycocalicin (r = 0.344, p < 0.001). This interaction was essentially expressed in patients with normal/increased glycocalicin (?100% of control; r = 0.470, p < 0.001, n = 64). TPO was greatly enhanced in HPT in comparison with ITP patients (958 ± 659 and 11 ± 27 pg/ml, p < 0.001). In the ITP group a reverse correlation was detected between TPO and glycocalicin (r = -0.373, p = 0.006). © 2014 S. Karger AG, Basel. PMID:25472766

Khaspekova, Svetlana G; Shustova, Olga N; Golubeva, Nina V; Vasiliev, Sergey A; Mazurov, Alexey V

2014-12-01

136

The efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura.  

PubMed

The most difficult problem a physician encounters is the management of patients with idiopathic thrombocytopenic purpura (ITP), who has persistent severe thrombocytopenia after failure of initial treatment with glucocorticoids and splenectomy. Most of the patients refractory to corticosteroids and splenectomy will become refractory to other available agents, such as intravenous immunoglobulin (IVIg), danazol or chemotherapy. In this study, we investigated the effect of rituximab on 17 splenectomized refractory chronic ITP patients. Here, we showed that the anti-CD20 antibody, rituximab, induces a clinically significant response in severe chronic ITP patients, who are unresponsive to other therapeutic options. After sixth month, 10 out of 14 responders were still maintaining their durable and significant platelet responses (platelet counts >50 x 10(9)/l), without requirement to any other ITP medication. Therefore, we suggest that, rituximab is an effective treatment option in splenectomized refractory or relapsed ITP patients. Rituximab was well tolerated without severe side effects. PMID:18311541

Pasa, Semir; Altintas, Abdullah; Cil, Timucin; Danis, Ramazan; Ayyildiz, Orhan

2009-04-01

137

Refractory immune thrombocytopenic purpura in pregnancy, managed with multiple courses of high dose immunoglobulin  

Microsoft Academic Search

pleased with her pregnancy and was only mildly concerned by the seriousness of her condition. Ultrasound examination at 15 weeks showed a normal fetus of appropriate size. Serial scans were performed. IVIgG was administered as an infusion of 400 mg. perkilogram body weight per day, during the pregnancy. The first course was for two days and three further courses, each

G. Burke; C. Casey; P. Chamberlain; E. Egan; F. P. Meehan

1989-01-01

138

Poor platelet Count Response to Helicobacter Pylori Eradication in Patients with Severe Idiopathic Thrombocytopenic Purpura  

PubMed Central

Introduction ITP is an autoimmune blood disorder in which platelet destruction is mediated by anti-platelet antibodies. The mechanisms of anti-platelet antibodies development are still a little known. The rate of some bacterial or viral agents in cause of ITP is well known. Recently, some study proposed that H pylori infection may be associated with ITP and H pylori eradication can improves platelet counts in infected ITP patients. Materials and Method A baseline platelet count <50×103 µL for 4 weeks prior to study entry were required. These patients were tested for H. pylori infection by urea breath. All positive H pylori patients received triple therapy for 7 or 14 days to eradicate H pylori infection. These patients followed for six months. Results Of 92 patients with ITP, H pylori infection was found in 59.7% (55/92). After excluding patients with confounding factors, 41 patients were remained. After H pylori eradication, CR wasn't obtained in any patients. Partial response were obtained only in 3 (7.3%) of the 41 patients and no response in 38 (92.6%) patients. There is a significant difference between the platelet counts of PR and NR groups (P < 0.001). Conclusion The results of this study and our previously study showed H pylori eradication therapy has beneficial effect for patients with mild thrombocytopenia but the chance of obtaining a response by H pylori treatment is lower in patients with severe thrombocytopenia. PMID:24505529

Payandeh, Mehrdad; Raeisi, Dariyush; Sohrabi, Nasrollah; Zare, Mohammad Erfan; Kansestani, Atefeh Nasir; Keshavarz, Nazanin; Gholami, Samira; Hashemian, Amir Hossein

2013-01-01

139

Long-term management of acquired thrombotic thrombocytopenic purpura using serial plasma ADAMTS13 measurements.  

PubMed

Although significant advances in the understanding of TTP pathophysiology have been made in the last 15 yr, none have yet impacted the empiric treatment paradigm for this disease for which plasmapheresis is the mainstay. Laboratory assays for ADAMTS13 activity and inhibitors can be used to confirm a clinical diagnosis, but the assays are not routinely used to guide treatment. The routine availability of ADAMTS13 testing has allowed our group to tailor plasmapheresis and immunosuppressive therapy in patients under active treatment for TTP. In addition, the concept of establishing immune tolerance, similar to the eradication of a factor VIII inhibitor in patients with congenital or acquired hemophilia, has emerged as an important strategy to prevent early relapse of TTP. With the expected incorporation of recombinant ADAMTS13 into the treatment algorithm over the next several years, we anticipate that readily available ADAMTS13 testing will play an important role in individualized therapy that incorporates enzyme replacement and establishment of immune tolerance. PMID:22324373

Knovich, Mary Ann; Farland, Andrew; Owen, John

2012-06-01

140

Efficacy of amifostine in treating patients with idiopathic thrombocytopenia purpura.  

PubMed

Idiopathic Thrombocytopenic Purpura (ITP) is an autoimmune disease characterized by the production of antibodies against platelet surface antigens, resulting in platelet destruction. ITP is generally treated using glucocorticoids, splenectomy, immunosuppressants, platelet transfusions, and also rituxan and rituximab. However, as these treatments are not effective in some refractory ITP patients, especially the elderly, who are also at greater risk of cerebral hemorrhage, we have undertaken this study to find a safe and effective way of treating these patients. In a clinical protocol, we have examined the efficacy of the cytoprotective adjuvant, amifostine, on 24 ITP patients, consisting of 21 Chinese (age: 13-92 years), and 3 Caucasians (age: 46-73 years). In order to prevent the side effects associated with amifostine treatment, an alternative dosing and anti-emetic regimen was developed as part of this protocol, which significantly improved patient acceptance. The protocol consisted of daily intravenous infusions of amifostine 5 × 400 mg per week, for a total of 4-5 weeks. All the patients experienced a long-lasting and continuing remission, defined as platelet counts greater than 100,000. Two patients relapsed: one after an upper respiratory tract infection, and another due to Helicobacter pylori. However, both these patients had complete remission, after they were treated again with amifostine. In this clinical study, we report for the first time, the successful use of amifostine for ITP treatment in refractory patients. In conclusion, amifostine may have good therapeutic effect on ITP patients, especially in refractory and/or elderly. The long-term clinical outcome and the mechanism of action of this drug still need further investigation. PMID:21104159

Fan, Hui; Zhu, Hong-Li; Li, Su-Xia; Lu, Xue-Chun; Zhai, Bing; Guo, Bo; Yao, Shan-Qian; Liu, Yang

2011-01-01

141

Granulomatous pigmented purpura: an unusual histological variant.  

PubMed

Pigmented purpuric dermatoses (PPDs) tend to vary clinically, yet share a similar histology. Granulomas are only rarely seen, with 4 prior reported cases, designated granulomatous pigmented purpura. Historically, granulomatous pigmented purpura has been seen in Asians. In this article, we report the case of a 42-year-old, white female with granulomatous pigmented purpura, the fifth such reported case in the literature. Histopathological examination revealed a granulomatous dermatitis with eosinophils, extravasated erythrocytes, melanophages, and vascular proliferation. These findings were consistently reported on subsequent biopsy 6 months later. This case illustrates a rare histological finding in PPDs. Medications associated with PPD are reviewed and the patient's use of mesalamine and balsalazide for ulcerative colitis are deemed potential triggers, given their relative similarity to aspirin, a known trigger of PPD. Although other granulomatous processes must be excluded in such patients, one must consider the possibility of granulomatous pigmented purpura in the appropriate setting. PMID:19155731

Kerns, Mary Jo J; Mallatt, Bruce Douglas; Shamma, H Nicholas

2009-02-01

142

Indian tick typhus presenting as Purpura fulminans  

PubMed Central

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

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

2014-01-01

143

Indian tick typhus presenting as Purpura fulminans.  

PubMed

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

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

2014-07-01

144

Henoch-Schönlein purpura in children  

PubMed Central

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

Bluman, Joel; Goldman, Ran D.

2014-01-01

145

Henoch-Schönlein purpura nephritis.  

PubMed

Henoch-Schönlein purpura (HSP) is the one of most common types of systemic vasculitis in childhood. Glomerulonephritis (HSPN) occurs in 30-50 % of HSP patients, mostly in a mild form but a small percentage of patients present with nephrotic syndrome or renal failure. HSPN is caused by the glomerular deposition of immunoglobulin A1 (IgA1)-containing immune complexes in the mesangium, the subepithelial and the subendothelial space. Formation of the IgA1 immune complex is thought to be the consequence of aberrantly glycosylated IgA1 molecules secreted into the circulation and their subsequent recognition by IgG specific for galactose-deficient IgA1. Mesangial proliferation and renal damage are triggered by the deposited immune complexes, which likely require activation of the complement system. Whereas other organ manifestations of HSP are mostly benign and self-limiting, HSPN might lead to chronic renal disease and end stage renal failure, thereby justifying immunosuppressive treatment. Long-term renal outcome correlates to the severity of the initial clinical presentation and the extent of renal biopsy changes, both of which are used to decide upon a possible treatment. As there are no evidence-based treatment options for severe HSPN, a large variety of therapeutic regimens are used. Prospective randomized controlled treatment studies are needed, but the low incidence of severe HSPN renders such studies difficult. PMID:24733586

Pohl, Martin

2015-02-01

146

Post-Transfusion Purpura Following Cardiac Surgery.  

PubMed

Post-transfusion purpura (PTP) is a rare disorder characterized by severe thrombocytopenia developing after a blood component transfusion. Ninety percent of the reported cases are women. In this article, we present a case of PTP in a male patient who underwent coronary artery bypass grafting and discuss its management. PMID:25327777

Demir, Tolga; Sahin, Mazlum; El, Helin; Sezer, Husnu

2014-10-17

147

Treatment of purpura with lasers and light sources.  

PubMed

The potential for bruising is a frequent concern for patients undergoing minimally invasive procedures, particularly injection-based soft tissue fillers and botulinum toxin type A. Decreasing the risk of this side effect with good technique and careful patient selection is key, but interventions that quicken the resolution of bruising are also helpful. Many practitioners have employed the theory of selective photothermolysis, using laser and light devices, to target hemoglobin and its breakdown products to speed time to bruise resolution. 585-595 nm pulsed dye, pulsed 532 nm and 1064 nm long-pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers and intense pulsed light may be utilized with best results achieved when treatment is performed 1-2 days after the appearance of purpura. Specific therapy recommendations, side effects and contraindications will be addressed in this review. PMID:24196329

Morton, Laurel M; Smith, Kevin C; Dover, Jeffrey S; Arndt, Kenneth A

2013-11-01

148

Henoch–Schonlein purpura in mesothelioma  

PubMed Central

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

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

2014-01-01

149

Henoch-Schonlein purpura in mesothelioma.  

PubMed

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

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

2014-12-01

150

Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial  

Microsoft Academic Search

Methods In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30×10?\\/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain

David J Kuter; James B Bussel; Roger M Lyons; Vinod Pullarkat; Terry B Gernsheimer; Francis M Senecal; Louis M Aledort; James N George; Craig M Kessler; Miguel A Sanz; Howard A Liebman; Frank T Slovick; J Th M de Wolf; Emmanuelle Bourgeois; Troy H Guthrie; Adrian Newland; Jeffrey S Wasser; Solomon I Hamburg; Carlos Grande; François Lefrère; Alan Eli Lichtin; Michael D Tarantino; Howard R Terebelo; Jean-François Viallard; Francis J Cuevas; Ronald S Go; David H Henry; Robert L Redner; Lawrence Rice; Martin R Schipperus; D Matthew Guo; Janet L Nichol

2008-01-01

151

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

PubMed

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

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

2014-02-19

152

Idiopathic Seidlmayer's Purpura: A Case Report.  

PubMed

Acute hemorrhagic edema of infancy (AHEI) was considered a rare form of Henoch-Schönlein purpura; however, it is now regarded as an independent disease typically involving patients aged 4-24 months. The authors describe the clinical case of a toddler aged 8 months, with skin erythematous pomphoid lesions, treated at home with topical steroids without benefits. The appearance of new lesions and the worsening of the previous skin signs induced the parents to drive the child to the hospital. The medical history revealed the administration of a vaccine dose 2 months before. PMID:24932170

Maggio, Maria Cristina; Ferraro, Fabrizia; Ragusa, Saveria Sabrina; Corpora, Umberto; Corsello, Giovanni

2014-05-01

153

Idiopathic Seidlmayer's Purpura: A Case Report  

PubMed Central

Acute hemorrhagic edema of infancy (AHEI) was considered a rare form of Henoch-Schönlein purpura; however, it is now regarded as an independent disease typically involving patients aged 4–24 months. The authors describe the clinical case of a toddler aged 8 months, with skin erythematous pomphoid lesions, treated at home with topical steroids without benefits. The appearance of new lesions and the worsening of the previous skin signs induced the parents to drive the child to the hospital. The medical history revealed the administration of a vaccine dose 2 months before. PMID:24932170

Maggio, Maria Cristina; Ferraro, Fabrizia; Ragusa, Saveria Sabrina; Corpora, Umberto; Corsello, Giovanni

2014-01-01

154

Acute infectious purpura fulminans due to probable spotted fever.  

PubMed

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

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

2014-01-01

155

Gene Expression Profiling Identifies HOXB4 as a Direct Downstream Target of GATA-2 in Human CD34+ Hematopoietic Cells  

PubMed Central

Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n?=?10) and idiopathic thrombocytopenic purpura (n?=?13), and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r?=?0.6573, p<0.01). Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia. PMID:23028422

Fujiwara, Tohru; Yokoyama, Hisayuki; Okitsu, Yoko; Kamata, Mayumi; Fukuhara, Noriko; Onishi, Yasushi; Fujimaki, Shinichi; Takahashi, Shinichiro; Ishizawa, Kenichi; Bresnick, Emery H.; Harigae, Hideo

2012-01-01

156

[Scrotal pain and Henoch-Schönlein purpura].  

PubMed

An acute scrotum is a potential urologic emergency and requires urgent evaluation in order to rule out conditions that need immediate surgical management. The most important condition to rule out is torsion of the testis. In cases of less emergency, a wide variety of differentials may be considered. Scrotal pain or swelling may occur in 10 to 15% of boys with Henoch-Schönlein purpura. We present the case of a 19-year-old boy who had intermittent scrotal pain of two weeks' duration with acute exacerbation prior to admission. The clinical examination gave no specific results. A regular and Doppler sonographic scan showed no evidence of testicular affection. The patient was observed in hospital. Two years earlier he had present with abdominal cramps, rectal bleeding, duodenitis, proteinuria and a purpuric rash, suggestive of Henoch-Schönlein purpura; IgA-nephritis was proven after a renal biopsy. As all other differentials had been ruled out, we concluded that Henoch-Schönlein syndrome was the cause of the recurrent scrotal pain in our patient. PMID:14963505

Søreide, Kjetil; Ansorge, Christoph; Øgreid, Per

2004-02-01

157

Identification of Differentially Expressed Serum Proteins in Infectious Purpura Fulminans  

PubMed Central

Purpura fulminans (PF) is a life-threatening hemorrhagic condition. Because of the rarity and randomness of the disease, no improvement in treatment has been made for a long time. In this study, we assessed the serum proteome response to PF by comparing serum proteins between healthy controls and PF patient. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach was used after depleting 6 abundant proteins of serum. In total, 262 proteins were confidently identified with 2 unique peptides, and 38 proteins were identified significantly up- (?2) or downregulated (?0.5) based on spectral counting ratios (SpCPF/N). In the 38 proteins with significant abundance changes, 11 proteins were previously known to be associated with burn or sepsis response, but 27 potentially novel proteins may be specifically associated with PF process. Two differentially expressed proteins, alpha-1-antitrypsin (SERPINA1) and alpha-2 antiplasmin (SERPINF2), were validated by Western blot. This is the first study where PF patient and healthy controls are compared in a proteomic study to elucidate proteins involved in the response to PF. This study provides an initial basis for future studies of PF, and the differentially expressed proteins might provide new therapeutic targets to decrease the mortality of PF. PMID:24659849

Hu, Jiong-yu; Han, Jian; Zhang, Dong-xia; Jiang, Xu-pin; Chen, Bing; Huang, Yue-sheng

2014-01-01

158

Sepsis-induced purpura fulminans caused by Pasteurella multocida.  

PubMed

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

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

2014-01-01

159

[Henoch-Schönlein purpura in the adult].  

PubMed

Henoch-Schönlein purpura is a systemic vasculitis of the small vessels characterized by perivascular leucocyte infiltrates. It is an immunoglobulin A-related immune complex-mediated disease involving the skin, the joints and the gastrointestinal system. Renal disease may sometimes be associated to these clinical manifestations. Prevalence of the nephritis is highly variable, depending on the series. More rarely, other organs such as the lungs, the heart or the nervous system may be involved. The clinical diagnosis is confirmed by histopathology of the skin (leukocytoclastic vasculitis) and kidney (endo-capillary proliferative glomerulonephritis), showing IgA deposits in these tissues. Short-term prognosis depends on the severity of digestive involvement, but long-term prognosis depends on the renal disease. Recent publications of pediatric and adult series show that the chronic renal failure may progress, sometimes more than ten years after the initial flare. Treatment is usually supportive. The benefit of more specific treatments (corticosteroids or immunosuppressive drugs) in severe visceral forms (usually abdominal or kidney) has not yet been established. PMID:24657040

Pillebout, E; Verine, J

2014-06-01

160

Gastrointestinal bleeding in adult patients with Henoch-Schönlein purpura.  

PubMed

We investigated the clinical and endoscopic features of gastrointestinal lesions in adults with Henoch-Schönlein purpura (HSP) causing gastrointestinal bleeding. The study included 24 adult HSP patients with gastrointestinal hemorrhage who underwent both upper gastrointestinal endoscopy and colonoscopy. The controls were 27 adult HSP patients without gastrointestinal hemorrhage. Patients with gastrointestinal bleeding showed higher frequencies of purpura on the upper extremities and trunk, and of elevated serum C-reactive protein (CRP). The rate of concurrent lesions in both the upper and lower gastrointestinal tracts was 91.7 %. The second portion of duodenum and terminal ileum were most frequently and severely involved. Leukocytoclastic vasculitis was detected in severe lesions and was significantly associated with mucosal ischemic changes. Most lesions (95.7 %) dramatically improved after corticosteroid therapy. This study suggests that both upper and lower gastrointestinal examinations are necessary for proper evaluation of gastrointestinal bleeding in patients with HSP. PMID:25321618

Nam, Eon Jeong; Kim, Gun Woo; Kang, Jong Wan; Im, Churl Hyun; Jeon, Seong Woo; Cho, Chang-Min; Jeong, Ji Yun; Park, Ji Young; Jang, Yun Jin; Kang, Young Mo

2014-11-01

161

Purpura caused by Emla is of toxic origin.  

PubMed

Emla cream has been widely used as a local anaesthetic for superficial procedures. Blanching and redness are commonly observed side-effects. We observed purpura in 5 patients after application of Emla. Other authors have not reported this before. In 4 patients, purpura was observed after 30 min Emla application before the treatment of mollusca contagiosa. In 1 patient, Emla was used for 60 min before taking a lip biopsy. In these patients, patch tests were performed with the individual ingredients of Emla cream, Emla cream itself, placebo cream, and Tegaderm plaster. All tests were negative at an early reading after 30 min as well as after 2 and 3 days. We concluded that the purpuric reaction was not of an allergic nature. Possibly, it was caused by a toxic effect on the capillary endothelium. PMID:9034681

de Waard-van der Spek, F B; Oranje, A P

1997-01-01

162

[Acute scrotum: unusual presentation of Schönlein-Henoch purpura].  

PubMed

Being a systemic vasculitis, Schöenlein-Henoch purpura may affect the scrotum and its content. According to the series studied, this occurs in about 10% patients (2-38%) and sometimes requires a differential diagnosis with the spermatic cord torsion. An isotopic study with 99Tc may avoid a surgical procedure quite often unnecessary. In the case reported here, vasculitis presented as an acute scrotum, which is highly infrequent in the literature and makes a correct presumption diagnosis extraordinary difficult. PMID:9182455

Suarez González, J A; Pello Fonseca, J M; Rivas del Fresno, M; Cuervo Calvo, F J; Castaño González-Coto, D; Alonso Ordoñez, M A; Herrero Alvarez, M C; Muruamendiaraz Fernández, V

1997-01-01

163

Thrombocytopenia-adapted in vitro bleeding test assesses platelet function in thrombocytopenic patients.  

PubMed

Platelet counts do not always reflect the true bleeding risk in chronically thrombocytopenic patients, and the posttransfusion platelet increments do not necessarily demonstrate that therapeutic efficacy. There are no easy and reliable tests yet permitting the determination of platelet function in thrombocytopenic patients. The in-vitro bleeding test (IVBT) with the Thrombostat 4000 proved to be a very sensitive and specific test for the detection of platelet disorders. In order to become suitable for the investigation of thrombocytopenic blood with platelet count between 5 x 10(9)/L and 50 x 10(9)/L, special modifications were necessary. We report on the evaluation of two thrombocytopenia-adapted modifications (TP-IVBT 150/120), first with blood of healthy donors made thrombocytopenic (three experiments with six blood samples each of different platelet concentrations and identical hematocrit) and then in a clinical study on 77 thrombocytopenic patients (69 with bone marrow hypoplasia, eight with autoimmune thrombocytopenia) receiving 267 platelet transfusions. The patients were followed over 15 days on average (1-67 days) by daily examinations (total 1,285 observation days). Most TP-IVBT measurements were carried out in triplicate, using the modification with the 120-microns filter (TP-IVBT 120) because it proved to be superior to the other modification. Additionally, cell counts, hematocrit, body temperature, platelet volume, platelet distribution width, expression of CD 36, 41a, 42b on platelets, Simplate bleeding time, and detailed analysis of bleeding signs were performed for the calculation of a bleeding score. There was a close correlation between TP-IVBT and platelet counts with thrombocytopenic normal blood (r2 = 0.81-0.94). This indicated the suitability of this test modification to examine platelet function in thrombocytopenic patients. The clinical study showed that the TP-IVBT helped at least to determine the platelet-related bleeding risk in thrombocytopenic patients. It allowed differentiation between hypoplastic and autoimmune thrombocytopenia in most cases. In addition, significant differences in platelet function of various diseases and of different bone marrow regeneration could be demonstrated. The TP-IVBT is well-suited for the control of platelet transfusion efficacy and may replace the in-vivo bleeding time in most cases. On the other hand, the test still shows too much of a variation and involves too much labor and cost for routine application. PMID:7660163

Kretschmer, V; Huss, B; Bonacker, G; Hoffmann, J; Bewarder, S; Weber, S; Schulzki, T; Köppler, H; Heimanns, J

1995-01-01

164

An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients.  

PubMed

Thrombocytopenia is associated with bleeding risk. However, in thrombocytopenic patients, platelet count does not correlate with bleeding risk and other factors are thus likely to contribute to this risk. This review presents currently available platelet-related markers available on automated haematology analysers and commonly used methods for testing platelet function. The test principles, advantages and disadvantages of each test are described. We also evaluate the current literature regarding the clinical utility of the test for prediction of bleeding in thrombocytopenia in haematological and oncological diseases. We find that several platelet-related markers are available, but information about the clinical utility in thrombocytopenia is limited. Studies support that mean platelet volume (MPV) can aid diagnosing the cause of thrombocytopenia and low MPV may be associated with bleeding in thrombocytopenia. Flow cytometry, platelet aggregometry and platelet secretion tests are used to diagnose specific platelet function defects. The flow cytometric activation marker P-selectin and surface coverage by the Cone-and-Plate[let] analyser predict bleeding in selected thrombocytopenic populations. To fully uncover the clinical utility of platelet-related tests, information about the prevalence of platelet function defects in thrombocytopenic conditions is required. Finally, knowledge of the performance in thrombocytopenic samples from patients is essential. PMID:24400878

Vinholt, Pernille J; Hvas, Anne-Mette; Nybo, Mads

2014-01-01

165

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

PubMed Central

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

2014-01-01

166

Childhood Immune Thrombocytopenia: Long-term Follow-up Data Evaluated by the Criteria of the International Working Group on Immune Thrombocytopenic Purpura  

PubMed Central

Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood, characterized by isolated thrombocytopenia. The International Working Group (IWG) on ITP recently published a consensus report about the standardization of terminology, definitions, and outcome criteria in ITP to overcome the difficulties in these areas. Materials and Methods: The records of patients were retrospectively collected from January 2000 to December 2009 to evaluate the data of children with ITP by using the new definitions of the IWG. Results: The data of 201 children were included in the study. The median follow-up period was 22 months (range: 12-131 months). The median age and platelet count at presentation were 69 months (range: 7-208 months) and 19x109/L (range: 1x109/L to 93x109/L), respectively. We found 2 risk factors for chronic course of ITP: female sex (OR=2.55, CI=1.31-4.95) and age being more than 10 years (OR=3.0, CI=1.5-5.98). Life-threatening bleeding occurred in 5% (n=9) of the patients. Splenectomy was required in 7 (3%) cases. When we excluded 2 splenectomized cases, complete remission at 1 year was achieved in 70% (n=139/199). The disease was resolved in 9 more children between 12 and 90 months. Conclusion: Female sex and age above 10 years old significantly influenced chronicity. Therefore, long-term follow-up is necessary in these children. PMID:24764727

Evim, Melike Sezgin; Baytan, Birol; Güne?, Adalet Meral

2014-01-01

167

Organism-specific platelet response and factors affecting survival in thrombocytopenic very low birth weight babies with sepsis  

Microsoft Academic Search

Objective:To study organism-specific platelet response and factors affecting survival in thrombocytopenic very low birth weight (VLBW) babies with sepsis.Study Design:Very low birth weight babies (birth weight <1500 g) admitted to a single level-three intensive care unit from January 2000 to December 2005 were prospectively evaluated for sepsis by rapid screen test, blood counts and blood culture. In thrombocytopenic babies, organism-specific

M A Bhat; J I Bhat; M S Kawoosa; S M Ahmad; S W Ali

2009-01-01

168

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

PubMed

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

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

2013-09-01

169

Determination of bleeding risk in thrombocytopenic patients with platelet transfusion therapy.  

PubMed

In a clinical study (50 thrombocytopenic patients) we determined the bleeding risk and the platelet transfusion efficacy by a special modification of the in vitro bleeding test (IVBT, Thrombostat 4000). Additionally, cell count, hematocrit, body temperature, platelet volume and distribution width, Simplate bleeding time and a bleeding score were investigated. The use of the modified IVBT proved to be promising to find a clearer indication of platelet transfusion and to estimate its efficacy. PMID:9422122

Kretschmer, V; Huss, B; Weber, S; Bewarder, S; Schulzki, T; Köppler, H; Heimanns, J

1994-01-01

170

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

PubMed

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

Kulshrestha, Mudit; Sola-Visner, Martha; Widness, John A; Veng-Pedersen, Peter; Mager, Donald E

2015-01-01

171

Management of Pregnancy-Associated Thrombotic Thrombocytopenia Purpura  

PubMed Central

Thrombotic thrombocytopenia purpura (TTP) is an infrequent but serious disease. Pregnancy is a known risk factor for presentation or relapse of TTP. Difficulties in differentiating TTP from preeclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, and current treatment recommendations are discussed in this case report. A woman with previously treated and stable TTP had a relapse at 36 weeks' gestation. Careful surveillance led to an early diagnosis. Severe disease in the peripartum period was treated successfully with cryosupernatant plasma-based plasmapheresis and platelet transfusion, with good maternal and neonatal outcomes. Cryosupernatant plasma is a viable alternative to fresh frozen plasma for plasmapheresis for TTP and may offer some therapeutic and logistical advantages. Platelet transfusion can be undertaken safely if needed to prevent or treat significant hemorrhage. PMID:23943710

Fyfe-Brown, Ashley; Clarke, Gwen; Nerenberg, Kara; Chandra, Sujata; Jain, Venu

2012-01-01

172

Retiform purpura in plaques: a morphological approach to diagnosis.  

PubMed

Retiform purpura (RPP) is a livedoid pattern of cutaneous haemorrhage that may result from vasculitis, occlusion or altered coagulation. When this pattern presents as palpable plaques, vascular inflammation is present, and the differential diagnosis includes calciphylaxis, warfarin-induced skin necrosis, antiphospholipid antibody syndrome and heparin-induced skin necrosis. These diseases are clinically aggressive and may result in significant morbidity and mortality. Early recognition is essential to make the necessary medication changes and to begin intervention. Our morphological approach to diagnosis differs from traditional methods and can expedite management. Biopsy results and laboratory findings are then used to verify the diagnosis and determine the specific cause. This approach may allow the development of a treatment plan prior to availability of all ancillary data. Clinical and histological cases are presented for these four syndromes presenting as RPP. PMID:17489989

Jones, A; Walling, H

2007-09-01

173

Atypical Henoch-Schonlein purpura? Consider polyarteritis nodosa!  

PubMed

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

Braungart, Sarah; Campbell, Alison; Besarovic, Sanja

2014-01-01

174

Management of the oral manifestations of senile purpura in an edentulous patient: a case report.  

PubMed

Senile purpura occurs because of a weakness of the vascular supporting tissues mainly caused by aging and is most often seen on the dorsal surface of the hands and the extensor surfaces of the forearms, and has also been observed in the oral mucosa of elderly patients. These red lesions present as sharply margined subcutaneous hemorrhagic spots and are due to trauma, such as damage to the endothelium of small blood vessels, or a coagulation defect. They can also be due to reduced perivascular support, or capillary fragility and permeability, or a combination of all of these factors. Oral manifestation of senile purpura can also be induced by long periods of medication use leading to fragile areas of the mucosa. The presence of senile purpura requires continuous follow-up since drug-induced purpura may cause plaque function alterations. An accurate diagnosis in elderly complete denture wearers can minimize bleeding and prevent possible development of ulcerations under the dentures, especially during the adaptation period to the prosthesis. This case report, presents the care and 3-year follow-up of a 66-year-old woman with complete dentures who presented with the oral manifestations of senile purpura caused by the continued use of several medications. PMID:21592165

da Rosa, Rosena Santos; Garcia, Renata C M R; Cury, Altair A D B; Faot, Fernanda

2011-01-01

175

Is there a crossroad between infections, genetics, and Henoch-Schönlein purpura?  

PubMed

Henoch-Schönlein purpura is the most common systemic vasculitis in childhood, characterized by the presence of immunoglobulin A deposits in the small vessels of skin, gastrointestinal tube, joints and kidneys. Although there have been great efforts made in elucidating its pathogenic mechanisms, Henoch-Schönlein purpura etiology remains unknown: the basic scene comes across an abnormal inflammatory process deriving from immune reactions to various antigenic stimuli, which might be bacterial, viral, or parasitic agents, in a genetically prone individual. Then, a peculiar immune complex deposition in the vascular walls and overproduction of different proinflammatory molecules elicit different clinical signs, which might be differentiated according to either a specific trigger or a specific genetic make-up. The aim of this review is to make a critical appraisal of the last 15years' medical literature concerning the relationship between infections, genetics, and Henoch-Schönlein purpura in pediatrics. PMID:23684700

Rigante, Donato; Castellazzi, Luca; Bosco, Annalisa; Esposito, Susanna

2013-08-01

176

Establishing hospital admission criteria of pediatric Henoch-Schonlein purpura.  

PubMed

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

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

2014-11-01

177

Pneumatosis intestinalis associated with Henoch-Schönlein purpura.  

PubMed

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

Fatima, Ayesha; Gibson, Donald Paul

2014-09-01

178

Immunoregulation in glomerulonephritis, Henoch--Schonlein purpura and lupus nephritis.  

PubMed Central

Immunoregulation was examined in normal controls and in patients with immune complex glomerulonephritis and lupus nephritis (SLE) using OKT monoclonal anti-bodies against helper (OKT4) and suppressor (OKT8) T cell subsets. Functional studies assessed T cell control of in vitro immunoglobulin synthesis by cultured peripheral blood mononuclear cells (PBMC). IgG and IgA synthesis was measured in unstimulated, pokeweed mitogen (PWM) stimulated and PWM + concanavalin A (Con A) stimulated cultures. Patients with primary membranous nephropathy (MN) and mesangial IgA nephropathy (IgA GN) were found to have elevated T4/T8 ratios secondary to a deficiency of the T8+ subset. Patients with SLE had low T4/T8 ratios. B cell activation with high spontaneous immunoglobulin synthesis was present in cell cultures from patients with SLE, IgA GN and Henoch-Schonlein purpura (HSP). Defective Con A inducible suppression of in vitro immunoglobulin synthesis was found in SLE, HSP and to a lesser extent, primary MN. Functional Con A inducible suppressor defects correlated with elevated T4/T8 ratios only in patients with MN. All four disorders appear to share disturbances of cellular immune response with various degrees of defective immune suppression; however, it is not clear from these studies whether the defects are primary or secondary phenomena. PMID:6224610

Bannister, K M; Drew, P A; Clarkson, A R; Woodroffe, A J

1983-01-01

179

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

PubMed Central

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

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

2013-01-01

180

Predictive role of neutrophil to lymphocyte ratio in Henoch-Schonlein purpura related gastrointestinal bleeding.  

PubMed

We read with interest the recent article 'The relationship of neutrophil-to-lymphocyte ratio with gastrointestinal bleeding in Henoch-Schonlein purpura' by Makay et al. (Rheumatol Int. doi: 10.1007/s00296-014-2986-2 , 2014). In their study, researchers aimed to evaluate the relationship between blood neutrophil to lymphocyte ratio (NLR) and gastrointestinal bleeding in children with Henoch-Schonlein purpura (HSP). In discussion part, the authors concluded that blood NLR may be considered as a useful marker for predicting gastrointestinal bleeding in HSP. We would like to thank Makay et al. for their valuable contribution. PMID:24777779

Tanoglu, Alpaslan; Karagoz, Ergenekon

2014-09-01

181

The diagnosis and classification of Henoch-Schönlein purpura: an updated review.  

PubMed

Henoch-Schönlein purpura (HSP) is a common childhood systemic vasculitis with clinical characteristics of cutaneous palpable purpura, arthralgia/arthritis, bowel angina, and hematuria/proteinuria. HSP is identified mainly based on the above presentations. Combined with pathohistological findings of leukocytoclastic vasculitis (LCV) and IgA-immune deposits in vessel walls and/or glomeruli increase the diagnostic sensitivity and specificity. However, considering the accessibility of biopsy and some patients with atypical presentations, there are still medical unmet needs in HSP diagnosis. This article reviews the diagnosis of HSP including the aspects of classification criteria, differential diagnosis, and some laboratory findings as the biomarkers with diagnostic potential. PMID:24424188

Yang, Yao-Hsu; Yu, Hsin-Hui; Chiang, Bor-Luen

2014-01-01

182

Central venous catheter infection-induced Henoch-Schönlein purpura in a patient on hemodialysis.  

PubMed

A 69-year-old man, who had been dialyzed using a permanent central venous catheter for 2 years, presented with Henoch-Schönlein purpura and positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). He was diagnosed with catheter-related infection by Staphylococcus aureus. After administration of antibiotic and steroid therapy, purpura disappeared and p-ANCA gradually became negative. This case supports the conclusion that infection can be pathogenesis of the vasculitis, including ANCA-positive HSP. Additionally, impregnation of catheters with antibiotics can be an effective treatment for catheter infections. PMID:24845224

Gao, Jian Jun; Wei, Jia Mei; Gao, Yue Hua; Li, Shuang; Na, Yu

2014-08-01

183

Platelet Activation Test in Unprocessed Blood (Pac-t-UB) to Monitor Platelet Concentrates and Whole Blood of Thrombocytopenic Patients  

PubMed Central

Summary Background Platelet concentrate transfusion is the standard treatment for hemato-oncology patients to compensate for thrombocytopenia. We have developed a novel platelet activation test in anticoagulated unprocessed blood (pac-t-UB) to determine platelet function in platelet concentrates and in blood of thrombocytopenic patients. Methods We have measured platelet activity in a platelet concentrate and in anticoagulated unprocessed blood of a post-transfusion thrombocytopenic patient. Results Our data show time-dependent platelet activation by GPVI agonist (collagen related peptide; CRP), PAR-1 agonist (SFLLRN), P2Y12 agonist (ADP), and thromboxane receptor agonist (U46619) in a platelet concentrate. Furthermore, pac-t-UB showed time-dependent platelet activation in unprocessed blood of a post-transfusion patient with thrombocytopenia. Testing platelet function by different agonists in relation to storage show that 3-day-old platelet concentrates are still reactive to the studied agonists. This reactivity rapidly drops for each agonists during longer storage. Discussion Pac-t-UB is a novel tool to estimate platelet function by different agonists in platelet concentrates and in unprocessed blood of thrombocytopenic patients. In the near future, we will validate whether pac-t-UB is an adequate test to monitor the quality of platelet concentrates and whether pac-t-UB predicts the bleeding risk of transfused thrombocytopenic patients. PMID:23652405

Roest, Mark; van Holten, Thijs C.; Fleurke, Ger-Jan; Remijn, Jasper A.

2013-01-01

184

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

PubMed

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

Hogendorf, Anna; M?ynarski, Wojciech

2014-01-01

185

HLA-DRB1 association with Henoch-Schonlein purpura.  

PubMed

Objective: Henoch-Schönlein purpura (HSP) is the most common vasculitis in children but it is not exceptional in adults. Increased familial occurrence supports a genetic predisposition for HSP. In this context, an association with the human leukocyte antigen-HLA-DRB1*01 phenotype has been suggested in Caucasian individuals with HSP. However, data on the potential association of HSP with HLA-DRB1*01 were based on small case series. To further investigate this issue, we performed HLA-DRB1 genotyping of the largest series of HSP patients ever assessed for genetic studies in Caucasians. Methods: 342 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al classification criteria, and 303 sex and ethnically matched controls were assessed. HLA-DRB1 alleles were determined using a PCR-Sequence-Specific-Oligonucleotide Probe (PCR-SSOP) method. Results: A statistically significant increase of HLA-DRB1*01 in HSP patients when compared with controls was found (43% vs 7%, respectively; p<0.001; odds ratio-OR=2.03 [1.43-2.87]). It was due to the increased frequency of HLA-DRB1*0103 phenotype in HSP (14% vs 2%; p<0.001; OR=8.27 [3.46-23.9]). These results remained statistically significant after adjusting for Bonferroni correction. In contrast, a statistically significant decreased frequency of the HLA-DRB1*0301 phenotype was observed in patients compared to controls (5.6% vs 18.1%, respectively; p<0.001, OR=0.26 [0.14-0.47]), even after adjustment for Bonferroni correction. No HLA-DRB1 association with specific features of the disease was found. Conclusion: Our study confirms an association of HSP with HLA-DRB1*01 in Caucasians. Also, a protective effect against the development of HSP appears to exist in Caucasians carrying the HLA-DRB1*03 phenotype. This article is protected by copyright. All rights reserved. PMID:25470797

López-Mejías, Raquel; Genre, Fernanda; Pérez, Belén Sevilla; Castañeda, Santos; Ortego-Centeno, Norberto; Llorca, Javier; Ubilla, Begoña; Remuzgo-Martínez, Sara; Mijares, Verónica; Pina, Trinitario; Calvo-Río, Vanesa; Márquez, Ana; Sala-Icardo, Luis; Miranda-Filloy, José A; Conde-Jaldón, Marta; Ortiz-Fernández, Lourdes; Rubio, Esteban; León Luque, Manuel; Blanco-Madrigal, Juan M; Galíndez-Aguirregoikoa, Eva; González-Vela, M Carmen; Ocejo-Vinyals, J Gonzalo; González Escribano, Francisca; Martín, Javier; Blanco, Ricardo; González-Gay, Miguel A

2014-12-01

186

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

PubMed

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

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

2013-01-01

187

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura  

PubMed Central

We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria. PMID:16603444

Root-Bernstein, Robert; Couturier, Jacob

2006-01-01

188

Diffuse pulmonary hemorrhage as a fatal complication of Schönlein-Henoch purpura.  

PubMed

We report a case of a 69-year-old man with Schönlein-Henoch purpura who developed diffuse pulmonary hemorrhage. He complained of dyspnea and hemoptysis while he was treated with steroids for gastroenteropathy associated with Schönlein-Henoch purpura. The drop in his hemoglobin levels and diffuse ground-glass opacity at all levels of the lung fields on chest computed tomography were a significant clue to diagnosis. Despite pulse therapy, no clinical improvement of the lung was achieved, and he died on the 36th day after the admission. Although the combination of the corticosteroid and immunosuppressive agents is normally recommended, diffuse pulmonary hemorrhage could become a fatal complication in elderly Schönlein-Henoch patients. PMID:17908143

Usui, Keiko; Ochiai, Toyoko; Muto, Ritsuko; Abe, Ikuko; Aikawa, Miwa; Kikushima, Kimio; Nagao, Ken

2007-10-01

189

Terminal ileitis induced by henoch-schonlein purpura that presented as acute appendicitis: a case report.  

PubMed

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

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

2015-02-01

190

Henoch-Schönlein purpura presenting as terminal ileitis and complicated by thrombotic microangiopathy.  

PubMed

We report here on a 40-year-old woman with abdominal pain, low-grade fever, and diarrhea in whom the cutaneous features of Henoch-Schönlein purpura (HSP) appeared only a few days after acute abdominal symptoms. Endoscopy showed terminal ileitis, and histopathological examination of a biopsy of the ileum showed a picture of IgA vasculitis. The clinical course was further complicated by the development of microangiopathic hemolytic anemia, thrombocytopenia, and severe renal failure. PMID:16275547

Al-Toma, Abdulbaqi A; Brink, Menno A; Hagen, E C

2005-11-01

191

Sirolimus for Autoimmune Disease of Blood Cells  

ClinicalTrials.gov

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

2014-10-17

192

Effects of Increased Von Willebrand Factor Levels on Primary Hemostasis in Thrombocytopenic Patients with Liver Cirrhosis  

PubMed Central

In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ?165 s) or collagen and ADP (Col-ADP, upper limit of normal ?118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180±62 s with Col-Epi and 160±70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P?=?0.027) and vWF-antigen levels (P?=?0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ?150/nL and hematocrit ?27.0%, pathological PFA-100 results were found. In thrombocytopenic (<150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3±235.9% vs. 338.7±151.6%, P?=?0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future. PMID:25397410

Wannhoff, Andreas; Müller, Oliver J.; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A.; Gotthardt, Daniel N.

2014-01-01

193

A rare presentation of seizures in a not-so-rare disease: Henoch-Schönlein purpura presenting with repeated seizures.  

PubMed

Henoch-Schönlein purpura represents the most common form of systemic vasculitis in children. Although a very common cause of vasculitis, seizures are a very rare complication of this disorder. We report a 5-year-old boy who presents with no other clinical symptoms of the disorder other than a seizure. By presenting this case, we hope to expand the differential diagnosis of repeated seizures to include diseases in which the pathogenesis of diseases with small vessel vasculitis such as Henoch-Schönlein purpura is considered. PMID:24892684

Camacho, Christina; Leva, Ernest G

2014-06-01

194

Age of onset as a risk factor of renal involvement in Henoch-Schönlein purpura  

PubMed Central

Background Henoch-Schönlein purpura (HSP) is the most common vasculitis in children, characterized by triad of symptoms; palpable purpura without thrombocytopenia, abdominal pain, and arthritis. Renal involvement often occur in children with HSP. No data on the renal involvement of children with HSP in Indonesia, especially West Java. Objective To evaluate renal involvement in children with HSP. Methods Retrospective study was conducted in children with HSP in Department of Child Health, Hasan Sadikin Hospital, from 2006 to 2011. Characteristics and clinical manifestations was reviewed from medical record. HSP was diagnosed by American College of Rheumatology 1990 criteria or European League Against Rheumatism/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society 2008. Results There were 128 patients, consisting of 82 male (64.9%) and 46 female (35.1%) with ratio 1.8:1. Mean age was 7.9 ± 2.9 years old which range from 6 month to 15 years. Peak morbidity was between 5-10 years old. Prevalence of HSP in Hasan Sadikin Hospital tend to raise from 2.7/100,000 in 2008 to 5.2/100,000 in 2010. In most patients (71%) purpura was the first symptom. Seventy-one patients (44.5%) had arthritis and 89 patients (69.5%) had abdominal pain, while renal involvement was in 28 patients (21.8%). Gastrointestinal manifestations tend to manifest in patients less than 5 years old (p = 0.267), while renal involvement tend to manifest in age group 11-15 years old (p = 0.015) with odds ratio 3.1 (95% confidence interval, 1.2-8.1). Conclusion Renal involvement in children with HSP is more common in age group 11 to 15 years old. PMID:24527410

Ledika, Masayu Amanda; Sapartini, Gartika; Setiabudiawan, Budi

2014-01-01

195

A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura, and elevated IgA level  

PubMed Central

Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed “lupus-like feature” glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding. PMID:25120835

Yang, Jihyun; Seo, Min Young; Kim, Ki Tae; Lee, Jun Yong; Kim, Sun-Chul; Kim, Myung-gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu; Won, Nam Hee; Cha, Ran-Hui; Cho, Eunjung

2014-01-01

196

Brazilian purpuric fever: epidemic purpura fulminans associated with antecedent purulent conjunctivitis. Brazilian Purpuric Fever Study Group.  

PubMed

In late 1984, 10 children in a small, rural town in Brazil had high fever associated with vomiting and abdominal pain. Within 12-48 h of the onset of fever, purpura developed associated with vascular collapse and peripheral necrosis. All 10 children died. Cerebrospinal fluid examinations did not suggest meningitis and, when done, tests were negative for Neisseria meningitidis. Other culture, serological, and necropsy examinations did not reveal a cause. Case-finding uncovered another cluster of similar illness in children in a second town and sporadic cases in five other cities. Two case-control studies demonstrated that children who became ill were significantly more likely than control children to have had conjunctivitis during the month before illness. This conjunctivitis was purulent, preceded the onset of more severe disease by 3-15 days, and had resolved before fever began. Although no conjunctival cultures were obtained from case-children, Haemophilus aegyptius was the most common pathogen isolated from other conjunctival cultures during the epidemic. This organism was also isolated from a non-aseptic skin scraping from 1 case child. A 25-megadalton plasmid distinguished the H aegyptius isolates epidemiologically associated with illness from other Brazilian conjunctival isolates. Brazilian purpuric fever is a newly recognized syndrome of epidemic purpura fulminans associated with antecedent purulent conjunctivitis, possibly caused by H aegyptius. PMID:2888985

1987-10-01

197

A purple rash: a case study of Henoch-Schönlein purpura.  

PubMed

Rashes are one of the most common presenting symptoms in the emergency department setting; they may be a primary diagnosis or a symptom of systemic disease. Accurate diagnosis of a rash may be challenging and requires clinical acumen, systematic history and physical examination, and judicious use of diagnostic testing. This case study reviews Henoch-Schönlein purpura (HSP) or IgA vasculitis, a common vasculitis of childhood. Although typically a self-limited disease, HSP may cause serious complications in a small subset of patients and requires monitoring. In addition, there are several differential diagnoses that may mimic HSP that are more serious. This article reviews the case of a 6-year-old boy who presented to a community emergency department and had a nontypical clinical course. PMID:25076400

Contino, Christopher; Bradbury-Golas, Kathleen

2014-01-01

198

Treatment of severe henoch-schonlein purpura nephritis with mycophenolate mofetil.  

PubMed

Henoch-Schonlein purpura (HSP) is the most common childhood vasculitis. Renal involvement in HSP is one of the major causes of chronic renal failure in children. It is important to start effective and relatively safe medication to prevent end-stage renal disease (ESRD). Mycophenolate mofetil (MMF) appears to be a promising therapeutic agent in many autoimmune diseases such as lupus nephritis and vasculitis. Herein, we describe the treatment with MMF of three patients with HSP nephritis. In two cases with rapidly progressive glomerulonephritis without response to steroid, after treatment with MMF, significant improvement in kidney function and proteinuria were observed. In another patient with HSP nephritic-nephrotic syndrome who showed resistance to steroid, MMF offered a favorable effect. MMF seems to be a promising therapeutic agent in the treatment of the severe HSP nephritis. PMID:24969202

Nikibakhsh, Ahmad Ali; Mahmoodzadeh, Hashem; Karamyyar, Mohamad; Hejazi, Sasan; Noroozi, Mehran; Macooie, Ali Agayar

2014-07-01

199

Self-limiting recurrent bullous Henoch-Schonlein purpura with lupus anticoagulant.  

PubMed

Henoch-Schonlein purpura (HSP) is the most common acute systemic vasculitis of childhood with an incidence of approximately 1:10?000. It commonly presents with skin, gastrointestinal tract, joints and renal system signs and symptoms. We present a case of recurrent self-limiting HSP with lupus anticoagulant presenting with haemorrhagic bullous skin lesions and scrotal swelling. The initial presentation resolved within 4?weeks but over the next 6?months, a few self-limiting but milder skin lesions occurred. Some institutions have advocated the use of steroids in these cases but our case showed that the use of steroids may not be required. This atypical presentation of HSP led to unnecessary investigations that this case report aims to prevent in the future by raising its awareness. PMID:25604501

Gration, Betty; Osakwe, Edwin

2015-01-01

200

Abnormality of regulatory T-cells in remission and non-remission idiopathic thrombocytopaenic purpura patients.  

PubMed

Primer immunologic defect in patients with idiopathic thrombocytopaenic purpura (ITP) result from autoreactive B-lymphocytes secreting antiplatelet antibodies. Dysfunctional cellular immunity has also great importance in ITP pathogenesis. CD4(+)CD25(+) regulatory T-cells have immunoregulatory features and it is able to inhibit CD4(+)CD25(-) and CD8(+) responses. ITP is also an autoimmune disease; the CD4(+)CD25(+) T-cell levels of the patients decrease during the active state. According to our findings, immunosuppressive treatments increase the CD4(+)CD25(+) Treg cell levels in the non-remission ITP patients. However, this level is not enough to overcome the resistance. CD4(+)CD25(-)Foxp3(+) and CD4(+)Foxp3(+) Treg cells are responsible for the pathogenesis of the non-remission ITP patients and other factors exist, which are responsible for the resistance of ITP treatment. PMID:23215839

Teke, Hava Üsküdar; Gündüz, Eren; Akay, Olga Meltem; Gülbas, Zafer

2013-01-01

201

[Clinical research on effectiveness of 2 110 patients with Henoch Schonlein purpura from 19 comprehensive hospitals in real world].  

PubMed

Nineteen comprehensive hospital information system (HIS) data are collected. Cleaning up the database, then analysis the patients' information. Using the basic description method and association rules to analysis the data. Analysis the data come from HIS database, we found that in 2 110 patients, main five complications are Henoch Schonlein purpura nephritis, upper respiratory tract infections, renal insufficiency, virus infection and glomerulonephritis (chronic), treatment of chemical drugs with sugar cortical hormone and anti infection drugs, such as intravenous input cephalosporin drugs. Traditional Chinese medicine with blood-activating and stasis-resolving medicine, heat clearing and detoxifying medicine. Combination scheme with blood-activating and stasis-resolving medicine joint glucocorticoid, followed by blood-activating and stasis-resolving medicine combined antiallergic drugs, heat-clearing and detoxifying medicine combined antiallergic drugs. Promoting blood circulation and removing blood stasis is an important part of traditional Chinese medicine treatment in patients with Henoch Schonlein purpura. PMID:25532391

Yan, Li; Wang, Lian-Xin; Xie, Yan-Ming; Yang, Wei; Wang, Zhuo-Yue; Zhuang, Yan; Wang, Yong-Yan

2014-09-01

202

Fifteen-year experience of children with Henoch-Schönlein purpura in southern Taiwan, 1991-2005  

Microsoft Academic Search

Background and Purpose: Although Henoch-Schönlein purpura (HSP) is the most common cause of systemic vasculitis in children, long-term and large-scale Taiwanese studies on HSP are rare. We reviewed the records of 107 Taiwanese pediatric patients diagnosed with HSP at our institution between 1991 and 2005. Methods: The first clinical manifestations, laboratory findings, and outcome evaluations of the patients were analyzed.

Bao-Ren Nong; Yung-Feng Huang; Chih-Ming Chuang; Chia-Chia Liu; Kai-Sheng Hsieh

2007-01-01

203

Plasmapheresis therapy in an elderly patient with rapidly progressive Henoch-Schönlein purpura with disseminated organ involvement  

Microsoft Academic Search

Henoch-Schönlein purpura (HSP) frequently occurs in children below the age of 15 years and is rare with increasing age. Prognosis\\u000a and therapy largely depend on the clinical presentation. The disease may be preceded by an upper respiratory tract infection,\\u000a and drugs have also been implicated in the pathogenesis of the disease. Most children recover from the illness, whereas 40%\\u000a of adults

J. Rech; F. Fuchs; S. Kallert; A. J. Hueber; C. Requadt; B. Manger; J. R. Kalden; K. Amann; R. Strauss; H. Schulze-Koops

2007-01-01

204

A case report suggesting a common pathogenesis for IgA nephropathy and Henoch-Schönlein purpura  

Microsoft Academic Search

A 7-year-old boy who had been followed for asymptomatic haematuria and elevated serum IgA levels developed Henoch-Schönlein purpura (HSP) after a streptococcal infection of the tonsils. Findings on renal biopsy were compatible with mild IgA nephropathy (IgAN); tonsillectomy was also performed as he had chronic tonsillitis. This case suggests that there is a common pathogenesis for IgAN and HSP, at

Kazunari Kaneko; Yoshiharu Suzuki; Keiichi Kiya; Yutaka Fukuda; Keijirou Yabuta

1994-01-01

205

Anesthetic management of a patient with Henoch-Schonlein purpura for drainage of cervical lymphadenitis: A case report.  

PubMed

Henoch-Schonlein purpura (HSP) is a multisystem disease and immunoglobulin A-mediated vasculitis with a self-limited course affecting the skin, joints, gastrointestinal tract, and kidneys. Severe renal and central nervous system disease may lead to life-threatening conditions, and immunosuppressive agents and plasmapheresis may be needed. We report successful management of a 6-year-old patient with HSP for drainage of cervical lymphadenitis. PMID:24843348

Hasija, Neha; Taxak, Susheela; Bhardwaj, Mamta; Vashist, Kirti

2014-04-01

206

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

PubMed

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

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

2014-05-01

207

[Immunogenetics of mesangial IgA glomerulonephritis and Schönlein- Henoch purpura].  

PubMed

We have recently examined polymorphisms of immunoglobuline heavy chain genes at S mu and S alpha 1 switch region loci by RFLP technique and described differences of genotype frequencies between healthy controls and patients with IgA-nephritis and Henoch-Schönlein-Purpura respectively. In the present study we further characterized the heavy chain constant region of IgG2 and IgG3 and, in addition, a hypervariable region (D 14 S 1) of unknown function localized downstream. In the present larger patient cohort we confirmed a higher frequency of S alpha 1 7.4 kb homozygotes in patients with IgA-nephritis (but not SHP), i.e. 62.0% vs 38.8% in controls, p less than 0.001. Compared to controls RFLP-frequencies of the constant region of IgG2 were also different in patients with IgA-nephritis, but not RFLP frequencies of D 14 S 1 or of the constant region of IgG3. Patients with IgA-nephritis homozygote for 7.4 kb in S alpha 1 had more adverse renal outcome and hypertension and more severe histological lesions (i.e. interstitial fibrosis, p less than 0.005). PMID:2482596

Rambausek, M; Waldherr, R; Jünger, E; Krupp, G; Demaine, A; Ritz, E

1989-01-01

208

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

PubMed Central

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

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

2014-01-01

209

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

PubMed Central

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

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

2014-01-01

210

The relationship of neutrophil-to-lymphocyte ratio with gastrointestinal bleeding in Henoch-Schonlein purpura.  

PubMed

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis of childhood. Gastrointestinal (GI) bleeding is one of the major complications of HSP. The blood neutrophil-to-lymphocyte ratio (NLR) is identified as a potentially useful marker of clinical outcome in inflammatory diseases. NLR may be a useful biomarker of GI bleeding in children with HSP, which has a neutrophil-dominated inflammation. The aim of this study was to evaluate NLR in patients with HSP and to investigate the relationship with GI bleeding. The study consisted of 63 HSP patients and 38 age- and sex-matched healthy children. C-reactive protein, white blood cell count, platelet count, mean platelet volume (MPV), hemoglobin level, and NLR were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used to determine the variables associated with GI bleeding. NLR and MPV were the only two indicators associated with GI bleeding in HSP in logistic regression analysis. The area under the ROC curve analysis indicated that NLR could be a more efficient potential predictor of GI bleeding in HSP when compared to MPV. This study suggested that higher NLR might predict GI bleeding in HSP. PMID:24647793

Makay, Balahan; Gücenmez, Özge Altu?; Duman, Murat; Ünsal, Erbil

2014-09-01

211

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

PubMed Central

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

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

2014-01-01

212

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

NASA Astrophysics Data System (ADS)

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.

Ailioaie, Laura; Ailioaie, C.

2001-06-01

213

Two cases of eczematid-like purpura of Doucas and Kapetanakis responsive to narrow band ultraviolet B treatment.  

PubMed

Eczematid-like purpura of Doucas and Kapetanakis is a type of pigmented purpuric dermatoses (PPDs) with eczematous changes in the purpuric surface. A 10-year-old male and a 44-year-old male patients were admitted to our clinics for itching and flaking of the skin rashes. Based on the clinical and histopathological evaluations, the rashes were identified as eczematid-like PPDs of Doucas and Kapetanakis. Both patients were treated with narrow band ultraviolet B. The lesions were remarkably regressed following the treatment. These cases reported due its rarity and good response to narrow band ultraviolet B. PMID:23458394

Karadag, Ayse Serap; Bilgili, Serap Gunes; Onder, Sevda; Calka, Omer

2013-04-01

214

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

PubMed

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

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

2014-01-01

215

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

PubMed

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

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

2014-01-01

216

Increased serum HMGB1 levels in patients with Henoch-Schönlein purpura.  

PubMed

High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC-1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF-? and IL-6 release in cultured supernatant. Furthermore, by real-time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC-1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of ?B-? (I?B?) and the nuclear translocation of nuclear factor-?B (NF-?B) p65 in HMEC-1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF-? and IL-6 production and may play a crucial role in the pathogenesis of HSP. PMID:24758390

Chen, Tao; Guo, Zai-Pei; Wang, Wen-Ju; Qin, Sha; Cao, Na; Li, Meng-Meng

2014-06-01

217

Effect of platelet count on the DDAVP-induced shortening of the bleeding time in thrombocytopenic Gaucher's patients.  

PubMed

As part of an investigative protocol requiring serial liver biopsies in patients with Type I Gaucher's disease who were receiving enzyme replacement therapy, we gave 11 patients a total of 15 infusions of DDAVP (0.3 micrograms/kg IV) and measured the Simplate bleeding time pre- and postin-fusion. All patients were thrombocytopenic (one patient 100-150,000; seven 66-99,000; and three 50-65,000/microliters). Nine of 15 infusions resulted in at least a 2-min shortening of the bleeding time; in 6/11 infusions in which the platelet count was greater than 65,000, the bleeding time shortened to less than or equal to 10 min, in 1/11 it shortened greater than or equal to 2 min but not to less than or equal to 10 min. In only 2/4 infusions given to patients with platelet counts less than 65,000 did the bleeding time demonstrate any significant shortening. None of the six liver biopsies performed in the patients whose bleeding time shortened to less than or equal to 10 min resulted in any significant bleeding; blood products were not transfused either pre- or postprocedure. These limited data demonstrate that a high percentage of patients with platelet counts of 65-100,000/microliters can manifest a significant shortening of bleeding time following a standard infusion of DDAVP, and that in approximately half of these patients the bleeding time will shorten enough to safely allow the performance of a liver biopsy without the need for prophylactic transfusion of blood products. PMID:1550261

Parker, R I; Grewal, R P; McKeown, L P; Barton, N W

1992-01-01

218

MASKER MASKER TARGET TARGET TARGET  

E-print Network

from a large speech database (Ives et al,2005). The original speech is from one speaker Probabilitycorrect -6 dB 0 dB Listeners were presented with two phrases of concurrent speech syllables. The masker syllables coincided with the second and third target syllables. The speech syllables were taken

Ives, D. Timothy

219

A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity  

PubMed Central

Thrombotic thrombocytopenia purpura (TTP) caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA). Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE). In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation. PMID:21776377

Yamada, Risa; Nozawa, Kazuhisa; Yoshimine, Takashi; Takasaki, Yoshinari; Ogawa, Hideoki; Takamori, Kenji; Sekigawa, Iwao

2011-01-01

220

Henoch-Schönlein purpura associated with solid-organ malignancies: three case reports and a literature review.  

PubMed

Adult Henoch-Schönlein purpura (HSP) is rarely associated with solid-organ malignancies. We describe here three adult patients with HSP diagnosed within 3 months of the diagnosis of associated solid-organ malignancies, including pulmonary, prostate, and renal carcinomas. Two patients had complete remission with a combination of immunosuppressive therapies and treatment of the associated malignancy. The third patient had partial remission with immunosuppressive therapies, but never received treatment for the associated malignancy and did not achieve complete remission before his death 10 months after diagnosis of HSP. These cases suggest that HSP associated with solid-organ malignancies may be resistant to immunosuppressive therapies without treatment of the associated malignancy. Therefore, evaluation for solid-organ malignancies should be considered in adult patients without an identifiable cause of HSP, especially if the disease is not self-limited or does not respond appropriately to treatment. PMID:22293661

Podjasek, Joshua O; Wetter, David A; Pittelkow, Mark R; Wada, David A

2012-07-01

221

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

PubMed

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

Ilyas, Shahid; Salim, Sumera

2014-12-01

222

Haematology and neurology  

PubMed Central

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

Austin, Steven; Cohen, Hannah; Losseff, Nick

2007-01-01

223

Romiplostim Injection  

MedlinePLUS

... clot) in order to decrease the risk of bleeding in people who have chronic idiopathic thrombocytopenic purpura ( ... ongoing condition that may cause easy bruising or bleeding due to an abnormally low number of platelets ...

224

76 FR 36367 - National Vaccine Injury Compensation Program: Revisions to the Vaccine Injury Table  

Federal Register 2010, 2011, 2012, 2013

...prescribed. III. Measles, mumps, and A...hours. rubella vaccine or any of its anaphylactic...prescribed. V. Vaccines containing measles A. Thrombocytopenic...purpura. B. Vaccine-Strain 6 months. Measles Viral...

2011-06-22

225

Refractory Evans' syndrome treated with allogeneic SCT followed by DLI. Demonstration of a graft-versus-autoimmunity effect  

Microsoft Academic Search

Evans' syndrome, a combination of autoimmune haemolytic anaemia and autoimmune (idiopathic) thrombocytopenic purpura, is generally harder to treat and more refractory than the single entities. In a male patient with refractory disease, predominantly thrombocytopenic, an allogeneic reduced intensity BMT from his human leukocyte antigen (HLA)-identical sister was followed by a dramatic platelet peak while he was still experiencing initial engraftment

A M Marmont; F Gualandi; M T van Lint; A Bacigalupo

2003-01-01

226

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

ClinicalTrials.gov

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

2005-06-23

227

Circulating adhesion molecules ICAM-1, E-selectin, and von Willebrand factor in Henoch-Schönlein purpura.  

PubMed Central

Adhesion molecules play an important part in leucocyte transendothelial migration and thus may provide a useful marker of surface expression at inflammatory sites. In 20 patients with Henoch-Schönlein purpura serum intercellular adhesion molecule 1 (ICAM-1), E-selectin, and plasma von Willebrand factor (vWF) were determined by ELISA during the active and inactive phase of the disease. Twelve healthy children were studied as a control group. Serum ICAM-1 concentrations increased during the active phase of the disease and differed significantly compared with the inactive phase (p < 0.05). However ICAM-1 in the active phase did not differ significantly compared with controls (p = 0.08). Serum E-selectin concentrations did not differ in the active and inactive phase of the disease. By contrast, vWF increased in the active phase of the disease and differed significantly compared with inactive disease and control groups (p < 0.01). Considering the adhesion molecules and vWF, only vWF correlated well with the C reactive protein measurement in the active phase, which is considered a good marker of disease activity. These data suggest that plasma vWF is a good marker of vascular inflammation and endothelial damage. Circulating ICAM-1 might be an additional parameter in some of the patients. PMID:9014604

Söylemezoglu, O; Sultan, N; Gursel, T; Buyan, N; Hasanoglu, E

1996-01-01

228

Using the Oxford classification of IgA nephropathy to predict long-term outcomes of Henoch-Schönlein purpura nephritis in adults.  

PubMed

Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60?ml/min per 1.73?m(2) with ?30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ?50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis. PMID:24390221

Kim, Chan Ho; Lim, Beom Jin; Bae, Yoon Sung; Kwon, Young Eun; Kim, Yung Ly; Nam, Ki Heon; Park, Kyoung Sook; An, Seong Yeong; Koo, Hyang Mo; Doh, Fa Mee; Lee, Mi Jung; Oh, Hyung Jung; Yoo, Tae-Hyun; Kang, Shin-Wook; Choi, Kyu Hun; Jeong, Hyun Joo; Han, Seung Hyeok

2014-07-01

229

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

SciTech Connect

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.

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

1982-01-01

230

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

PubMed

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

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

2015-03-01

231

Interferon-gamma gene polymorphism +874 (a/t) in Chinese children with Henoch-Schonlein purpura.  

PubMed

The aim of this study was to investigate the possible influence of Interferon-gamma (IFN-?) gene polymorphism +874 (A/T) (rs2430561) in the susceptibility and renal complications of patients with Henoch-Schonlein purpura (HSP). We also studied the effects of IFN-? allelic variation on serum levels of pro-and anti-inflammatory cytokines in HSP patients. The study population comprised 97 patients suffering from HSP and 97 control participants. Patients and controls were genotyped for a single nucleotide polymorphism +874 (A/T) in the first intron of the IFN-? gene by the TaqMan PCR method. Frequencies of individuals with IFN-? +874 AA, AT and TT genotypes were 77.3%, 21.6% and 1% in HSP patients and 79.4%, 17.5% and 3.1% in controls, respectively. The frequency of the AA genotype in HSP patients with nephritis was slightly higher (83.3%) than in HSP patients without nephritis (73.8%). The allele A occurred more commonly in HSP patients with nephritis (92%) than in HSP patients without nephritis (86%), but these differences were not statistically significant (p= 0.469 and p= 0.244, respectively). In addition, significant difference in serum IL-10 levels between IFN-? +874 different genotype groups was found. Our results do not support a role for IFN-? gene polymorphism +874 (A/T) in the susceptibility to HSP and allelic variation at IFN-? +874 locus had no effect on serum levels of cytokines in patients with HSP except for IL-10. PMID:24659122

Xu, Hui; Li, Wei; Fu, Haidong; Jiang, Guizheng

2014-06-01

232

Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders  

PubMed Central

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

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

2012-01-01

233

Sputter target  

DOEpatents

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.

Gates, Willard G. (Kansas City, MO); Hale, Gerald J. (Overland Park, KS)

1980-01-01

234

Targeting adenovirus  

Microsoft Academic Search

The use of targeted viral vectors to localize gene transfer to specific cell types holds many advantages over conventional, non-targeted vectors currently used in gene therapy. The resulting improvements in gene localization from targeted adenovirus vectors are likely to reduce immunogenicity and toxicity, increase safety, and enable the systemic administration of these vectors for multiple indications including cancer, cardiovascular disease,

T J Wickham

2000-01-01

235

Target discovery  

Microsoft Academic Search

Target discovery, which involves the identification and early validation of disease-modifying targets, is an essential first step in the drug discovery pipeline. Indeed, the drive to determine protein function has been stimulated, both in industry and academia, by the completion of the human genome project. In this article, we critically examine the strategies and methodologies used for both the identification

Mark A. Lindsay

2003-01-01

236

Evaluation of serum procalcitonin and C-reactive protein levels as biomarkers of Henoch-Schönlein purpura in pediatric patients.  

PubMed

Henoch-Schönlein purpura (HSP) is a vasculitic disorder resulting from autoinflammatory-mediated tissue injury. Procalcitonin (PCT) and C-reactive protein (CRP) are two biomarkers of the immune response that recognize bacterial infection and inflammation, respectively. This study tested whether levels of PCT and CRP were associated with selected clinical features, disease severity, and organ damage in HSP. Eighty-nine pediatric patients with HSP were analyzed for clinical manifestations and organ damage. Serum CRP, PCT, and occult blood in the urine and stool (prior to steroid therapy) were measured. Disease severity was classified according to previously established clinical classifications. Sixty patients (67.4 %) had a low clinical score (LCS) of <4 (group A) while 29 patients (32.5 %) had a high clinical score (HCS) of ?4 (group B). When patients were then classified by the presence of gastrointestinal bleeding, 66 (74.2 %) cases lacked alimentary tract hemorrhage (group C) while 23 (25.8 %) cases presented with gastrointestinal bleeding (group D). There were no significant differences in CRP (group A: median?=?5.26, range?=?1.00-77.60 vs. group B: median?=?8.59, range?=?1.00-144.00 mg/l; u?=?1.397) or PCT levels (group A: median?=?0.05, range?=?0.05-0.24 vs. group B: median?=?0.08, range?=?0.05-1.02 ng/ml; u?=?1.709) between groups A and B. When serum PCT levels were examined in relation to gastrointestinal bleeding, the levels of serum PCT were higher in group D than group C patients (group D: median?=?0.09, range?=?0.05-1.02 vs. group C: median?=?0.05, range?=?0.05-0.32 ng/ml; u?=?2.849). It is important to note that the average PCT level was below the threshold for a systemic bacterial infection (0.5 ng/ml). We did not observe a correlation between CRP levels and the absence or presence of GI bleeding in groups C or D (group C: median?=?4.66, range?=?1.00-144.00 vs. group D: median?=?9.44, range?=?1.06-124.00 mg/l; u?=?1.783), respectively. In all patients, there was a significant correlation between the concentrations of PCT and CRP (r?=?0.721, p?=?0.002). In patients with HSP, inflammatory markers are not uniformly associated with the disease and instead, show variable association depending on the clinical severity and level of organ damage. In patients with severe HSP, elevated serum PCT was significantly associated with gastrointestinal bleeding. In contrast, CRP was not a specific predictor for different clinical classifications of HSP, despite a similar pattern of concentration changes to PCT. PMID:25273597

Teng, Xu; Wang, Yang; Lin, Nan; Sun, Mei; Wu, Jie

2014-10-01

237

EULAR\\/PRINTO\\/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation  

Microsoft Academic Search

ObjectivesTo report methodology and overall clinical, laboratory and radiographic characteristics for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria.MethodsThe preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR\\/PRINTO\\/PRES - supported validation project divided into three main steps. Step 1: retrospective\\/prospective web-data collection for HSP,

Nicolino Ruperto; Seza Ozen; Angela Pistorio; Pavla Dolezalova; Paul Brogan; David A Cabral; Ruben Cuttica; Raju Khubchandani; Daniel J Lovell; Kathleen M ONeil; Pierre Quartier; Angelo Ravelli; Silvia M Iusan; Giovanni Filocamo; Claudia Saad Magalhães; Erbil Unsal; Sheila Oliveira; Claudia Bracaglia; Arvind Bagga; Valda Stanevicha; Silvia Magni Manzoni; Polyxeni Pratsidou; Loredana Lepore; Graciela Espada; Isabelle Kone Paut; Francesco Zulian; Patrizia Barone; Zelal Bircan; Maria del Rocio Maldonado; Ricardo Russo; Iris Vilca; Kjell Tullus; Rolando Cimaz; Gerd Horneff; Jordi Anton; Stella Garay; Susan Nielsen; Giancarlo Barbano; Alberto Martini

2010-01-01

238

Progressive Pigmentary Purpura  

MedlinePLUS

... the skin. The blood leaking through the damaged walls forms the little red dots. The iron from ... in your area. Contact Us 2902 North Baltimore Street Kirksville, Missouri 63501 Phone: 660-665-2184 1- ...

239

Henoch-Schönlein Purpura  

MedlinePLUS

... 738–4929 Email: nkudic@info.niddk.nih.gov Internet: www.kidney.niddk.nih.gov NIH...Turning Discovery Into Health ® Privacy Statement | Disclaimers | Accessibility | PDF versions require the free ...

240

Targeted ?-Therapy  

PubMed Central

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

Brechbiel, Martin W.

2008-01-01

241

Targeted Training.  

ERIC Educational Resources Information Center

Describes the use of data on student achievement to create more effective professional development programs for teachers. Profiles the Pella Community School District, Pella, Iowa, and the Glendale Union High School District, Glendale, Arizona. Includes questions and answers on initial targets and first steps in planning professional development…

Sanborn, Jane

2002-01-01

242

Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience  

PubMed Central

Background Plasma exchange (PEX) is a life-saving therapeutic procedure in patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic microangiopathic anaemias (TMAs). However, it may be associated with significant complications, exacerbating the morbidity and mortality in this patient group. Study Design and Methods We reviewed all PEX procedures over a 72-month period, following the exclusive introduction of solvent–detergent double viral-inactivated plasma in high-volume users, such as TTP, in the United Kingdom (UK). We documented allergic reactions to plasma, citrate reactions, complications relating to central venous access insertion and venous thrombotic events (VTE) in 155 patient episodes and >2000 PEX procedures. Results The overall complication rate was low. Allergic plasma reactions occurred in 6·45% of the cohort with only one episode of acute anaphylaxis. Similarly, VTEs were 6·45%, not significantly greater than in medical patients receiving thromboprophylaxis, despite added potential risk factors in TTP. Citrate reactions were the most frequent complication documented, but toxicity was significantly reduced by administration of further calcium infusions during the PEX procedure. There were no serious central line infections and no catheter thrombosis. Conclusion Our data confirms that PEX continues to be a life-saving procedure in the acute TTP setting and, the procedure was not associated with an increased mortality and limited morbidity. PMID:24117855

McGuckin, S; Westwood, J-P; Webster, H; Collier, D; Leverett, D; Scully, M

2014-01-01

243

Elevated Urinary Levels of Cystatin C and Neutrophil Gelatinase-Associated Lipocalin in Henoch-Schönlein Purpura Patients with Renal Involvement  

PubMed Central

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis in childhood. The long-term prognosis of HSP is determined by the degree of renal involvement. The aim of this study is to search novel clinically applicable biomarkers to evaluate renal involvement in HSP patients. 20 bio-indexes in urine samples were simultaneously screened by antibody array assay. We indicated that urinary levels of cystatin C (Cys C) and neutrophil gelatinase-associated lipocalin (NGAL) in HSP patients with renal involvement were significantly higher than those without renal involvement and healthy controls. Furthermore, ELISA was used to analyze urinary Cys C and NGAL levels in HSP patients with or without renal involvement, atopic dermatitis (AD) patients and healthy controls. Our results demonstrated that urinary Cys C and NGAL levels in HSP patients with renal involvement were significantly elevated, when compared with those without renal involvement, AD patients and control subjects. In addition, by receiver operating characteristic (ROC) curve analysis, we demonstrated that the area under the ROC curve of NGAL (0.789) was larger than that of Cys C (0.692). Taken together, we show firstly that urinary Cys C and NGAL levels is abnormally elevated in HSP patients with renal involvement. We suggest that urinary Cys C and NGAL are novel useful biomarkers of renal involvement in HSP patients. PMID:24963810

Chen, Tao; Lu, Yong-hong; Wang, Wen-ju; Bian, Cai-yun; Cheng, Xiao-yun; Su, Yu; Zhou, Pei-mei

2014-01-01

244

Target assembly  

DOEpatents

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.

Lewis, Richard A. (Falls Church, VA)

1980-01-01

245

On Target  

NSDL National Science Digital Library

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

Wgbh

2010-01-01

246

Accelerator target  

DOEpatents

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.

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

1999-06-29

247

Targeting mitochondria.  

PubMed

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are closely linked to degenerative diseases such as Alzheimer's disease, Parkinson's, neuronal death including ischemic and hemorrhagic stroke, acute and chronic degenerative cardiac myocyte death, and cancer. As a byproduct of oxidative phosphorylation, a steady stream of reactive species emerge from our cellular energy plants, the mitochondria. ROS and RNS potentially cause damage to all cellular components. Structure alteration, biomolecule fragmentation, and oxidation of side chains are trade-offs of cellular energy production. ROS and RNS escape results in the activation of cytosolic stress pathways, DNA damage, and the upregulation of JNK, p38, and p53. Incomplete scavenging of ROS and RNS particularly affects the mitochondrial lipid cardiolipin (CL), triggers the release of mitochondrial cytochrome c, and activates the intrinsic death pathway. Due to the active redox environment and the excess of NADH and ATP at the inner mitochondrial membrane, a broad range of agents including electron acceptors, electron donors, and hydride acceptors can be used to influence the biochemical pathways. The key to therapeutic value is to enrich selective redox modulators at the target sites. Our approach is based on conjugating nitroxides to segments of natural products with relatively high affinity for mitochondrial membranes. For example, a modified gramicidin S segment was successfully used for this purpose and proven to be effective in preventing superoxide production in cells and CL oxidation in mitochondria and in protecting cells against a range of pro-apoptotic triggers such as actinomycin D, radiation, and staurosporine. More importantly, these mitochondria-targeted nitroxide/gramicidin conjugates were able to protect against apoptosis in vivo by preventing CL oxidation induced by intestinal hemorrhagic shock. Optimization of nitroxide carriers could lead to a new generation of effective antiapoptotic agents acting at an early mitochondrial stage. Alternative chemistry-based approaches to targeting mitochondria include the use of proteins and peptides, as well as the attachment of payloads to lipophilic cationic compounds, sulfonylureas, anthracyclines, and other agents with proven or hypothetical affinities for mitochondria. Manganese superoxide dismutase (MnSOD), SS tetrapeptides with 2',6'-dimethyltyrosine (Dmt) residues, rhodamine, triphenylphosphonium salts, nonopioid analgesics, adriamycin, and diverse electron-rich aromatics and stilbenes were used to influence mitochondrial biochemistry and the biology of aging. Some general structural principles for effective therapeutic agents are now emerging. Among these are the presence of basic or positively charged functional groups, hydrophobic substructures, and, most promising for future selective strategies, classes of compounds that are actively shuttled into mitochondria, bind to mitochondria-specific proteins, or show preferential affinity to mitochondria-specific lipids. PMID:18193822

Hoye, Adam T; Davoren, Jennifer E; Wipf, Peter; Fink, Mitchell P; Kagan, Valerian E

2008-01-01

248

[Targeted therapy].  

PubMed

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

Niitsu, Nozomi

2014-03-01

249

Clinical significance of TLR3 and TLR4 in peripheral blood mononuclear cells from children with Henoch-Schönlein purpura nephritis.  

PubMed

The aim of the present study was to investigate the expression levels and clinical significance of Toll-like receptor (TLR) 3 and 4 in peripheral blood mononuclear cells (PBMCs) collected from children with Henoch-Schönlein purpura (HSP) nephritis. The randomized controlled trial was conducted between August 2011 and March 2013, and 105 children with a clinical diagnosis of HSP were enrolled in the study. According to the 24-h urinary protein measurements and the presence of renal damage, the 105 cases were divided into groups A, B and C as follows: Group A, children with HSP but without renal damage; group B, children with HSP nephritis but without proteinuria; group C, children with HSP nephritis and proteinuria. A total of 30 healthy children were enrolled in the normal control group (group N). The primary endpoints were the detection of TLR3 and 4 mRNA and protein expression levels in PBMCs by flow cytometry and quantitative polymerase chain reaction. The mRNA and protein expression levels of TLR4 in the PBMCs were significantly higher in groups A, B and C when compared with group N. In addition, the mRNA and protein expression levels of TLR4 in group C were much higher when compared with groups A and B. A positive correlation was identified between TLR4 protein expression and 24-h urinary protein levels in group C. The expression levels of TLR3 did not significantly differ among the groups. Protein and mRNA expression levels of TLR4 in PBMCs significantly increased and exhibited a positive correlation with urinary protein excretion. These results indicate that aberrant activation of TLR4 may be relevant to the development of HSP nephritis. PMID:24926370

Chang, Hong; Yu, Dong-Sheng; Liu, Xiu-Qin; Zhang, Qiu-Ye; Cheng, Na; Zhang, Shou-Qing; Qu, Zheng-Hai

2014-06-01

250

Renal neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 expression in children with acute kidney injury and Henoch-Schönlein purpura nephritis.  

PubMed

The aim of this study was to investigate the expression of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the serum, urine and renal tissues of children with acute kidney injury (AKI) and Henoch-Schönlein purpura nephritis (A-on-C). A prospective single-center evaluation of the serum, urine and renal NGAL and KIM-1 levels was performed in a cohort of children. Blood and 5-ml urine samples were collected from each patient for the analysis of NGAL and KIM-1 levels using an ELISA. In addition, the expression of NGAL and KIM-1 in the kidney was examined using immunohistochemistry in patients with A-on-C and HSPN. The expression of serum cystatin C, ?2-macroglobulin and serum creatinine (SCr), as well as urinary ?2-MG and SCr, in the patients with A-on-C was significantly higher than that of HSPN patients, and the expression of NGAL and KIM-1 in the serum and urine in the A-on-C patients was also significantly higher than that of HSPN patients. However, there were no significant differences in the urine protein levels between the two groups. NGAL and KIM-1 were expressed in renal tubular epithelial cells, and the expression of NGAL and KIM-1 in the A-on-C patients was significantly higher than that in HSPN patients. In addition, the urine NGAL and KIM-1 levels were negatively correlated with glomerular filtration rate, but there was no significant correlation between the urine NGAL/KIM-1 and urine protein levels. The changes in serum and urine NGAL and KIM-1 levels may be applied to the diagnosis of A-on-C. PMID:24940398

DU, Yue; Hou, Ling; Guo, Jinjie; Sun, Tingting; Wang, Xiuli; Wu, Yubin

2014-05-01

251

Pathogenic effects of anti-glycoprotein Ib antibodies on megakaryocytes and platelets.  

PubMed

Antibodies directed against the glycoprotein (GP) Ib have been identified as the potential cause of various platelet disorders: Immune thrombocytopenic purpura (ITP) may be caused by such autoantibodies; Anti-thrombotic drugs targeting GPIb also induce thrombocytopenia. In order to elucidate the potential mechanism(s) of the anti-GPIb effects, we have examined by electron microscopy (EM) the effect of several antibodies directed against GPIb and GPIIb-IIIa on human culture megakaryocytes (MK). Virtually all antibodies to GPIb enhanced the interaction of newly formed platelets with MK when compared to other antibodies. These effects were retrieved when antibodies were tested on platelets. We conclude that antibodies to GPIb can potentially inhibit platelet release by MK, and can also induce homotypic platelet adhesion. These results may have implications in the pathophysiology of thrombocytopenia and platelet recovery in ITP, and shed light on the pathological effect of anti-GPIb antibodies used as antithrombotic drugs. PMID:12529757

Alimardani, Gulie; Guichard, Josette; Fichelson, Serge; Cramer, Elisabeth M

2002-12-01

252

Synthesis and effects of novel thiazole derivatives against thrombocytopenia  

Microsoft Academic Search

5-(2-Pyridylsulfonyl)-2-thiazolamine (2) was effective both in mitomycin C (MMC)-induced thrombocytopenia and in an animal model of idiopathic thrombocytopenic purpura (ITP). It also suppressed the increase of autoantibodies against platelets in the ITP model and showed no blood toxicity. Chemical modification of 2 led to the discovery of more potent compounds against MMC-induced thrombocytopenia.

Kiyoshi Tsuji; Takashi Ogino; Nobuo Seki; Masae Sawada; Yu Sudo; Fusako Nishigaki; Toshitaka Manda; Massaki Matsuo

1998-01-01

253

Therapeutic Strategies for Hepatitis and Other Infection-Related Immune Thrombocytopenias  

Microsoft Academic Search

Secondary thrombocytopenia may result from autoimmune diseases, lymphoproliferative disorders, infections, myelodysplastic syndromes, common variable immunodeficiency, agammaglobuline- mia, hypogammaglobulinemia, immunoglobulin A deficiency, and drugs. The presence of throm- bocytopenia may result from chronic infections with hepatitis C virus (HCV), human immunode- ficiency virus (HIV), and Helicobacter pylori and should be considered in the differential diagnosis of immune thrombocytopenic purpura (ITP). Studies

Roberto Stasi

2009-01-01

254

Pathogenesis of Thrombotic Microangiopathy: Insights from Animal Models  

Microsoft Academic Search

Animal models are important experimental tools for investigating the molecular mechanisms, environmental and genetic susceptibilities underlying the development of thrombotic microangiopathies. Large mammal, small animal models, knockout, transgenic and conditional knockout mouse models are available to investigate haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura and vascular endothelial growth factor-associated thrombotic microangiopathy. These models have shown that it is possible to model

Anna Richards; David Kavanagh

2009-01-01

255

HUS AND TTP  

PubMed Central

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

Trachtman, Howard

2013-01-01

256

Increasing platelets without transfusion: is it time to introduce novel thrombopoietic agents in neonatal care?  

Microsoft Academic Search

The Food and Drug Administration recently approved two novel thrombopoiesis-stimulating agents, Romiplostim (AMG-531, Nplate) and Eltrombopag (Promacta), for the treatment of adults with immune thrombocytopenic purpura. For physicians taking care of critically ill neonates, this offers the opportunity of decreasing platelet transfusions and potentially improving the outcomes of neonates with severe and prolonged thrombocytopenia. However, several developmental factors need to

H Sallmon; R K Gutti; F Ferrer-Marin; Z-J Liu; M C Sola-Visner

2010-01-01

257

Polarized internal target apparatus  

DOEpatents

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.

Holt, Roy J. (Downers Grove, IL)

1986-01-01

258

Polarized internal target apparatus  

DOEpatents

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.

Holt, R.J.

1984-10-10

259

Organelle targeting: third level of drug targeting  

PubMed Central

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

Sakhrani, Niraj M; Padh, Harish

2013-01-01

260

FLIR target screening  

NASA Technical Reports Server (NTRS)

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.

Aggarwal, R.

1982-01-01

261

The Targeting of Advertising  

Microsoft Academic Search

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

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

2005-01-01

262

Targets for Precision Measurements  

E-print Network

The general properties needed in targets (sources) for high precision, high accuracy measurements are reviewed. The application of these principles to the problem of developing targets for the Fission TPC is described. Longer term issues, such as the availability of actinide materials, improved knowledge of energy losses and straggling and the stability of targets during irradiation are also discussed.

Loveland, W; Asner, David M; Baker, R G; Bundgaard, J; Burgett, E; Cunningham, M; Deaven, J; Duke, D L; Greife, U; Grimes, S; Heffer, M; Hill, T; Isenhower, D; Klay, J L; Kleinrath, V; Kornilov, N; Laptev, A B; Massey, T N; Meharchand, R; Qu, H; Ruz, J; Sangiorgio, S; Selhan, B; Snyder, L; Stave, S; Tatishvili, G; Thornton, R T; Tovesson, F; Towell, D; Towell, R S; Watson, S; Wendt, B; Wood, L

2013-01-01

263

Targets for Precision Measurements  

NASA Astrophysics Data System (ADS)

The general properties needed in targets (sources) for high precision, high accuracy measurements are reviewed. The application of these principles to the problem of developing targets for the Fission TPC is described. Longer term issues, such as the availability of actinide materials, improved knowledge of energy losses and straggling and the stability of targets during irradiation are also discussed.

Loveland, W.; Yao, L.; Asner, D. M.; Baker, R. G.; Bundgaard, J.; Burgett, E.; Cunningham, M.; Deaven, J.; Duke, D. L.; Greife, U.; Grimes, S.; Heffner, M.; Hill, T.; Isenhower, D.; Klay, J. L.; Kleinrath, V.; Kornilov, N.; Laptev, A. B.; Massey, T. N.; Meharchand, R.; Qu, H.; Ruz, J.; Sangiorgio, S.; Selhan, B.; Snyder, L.; Stave, S.; Tatishvili, G.; Thornton, R. T.; Tovesson, F.; Towell, D.; Towell, R. S.; Watson, S.; Wendt, B.; Wood, L.

2014-05-01

264

Targets for Precision Measurements  

E-print Network

The general properties needed in targets (sources) for high precision, high accuracy measurements are reviewed. The application of these principles to the problem of developing targets for the Fission TPC is described. Longer term issues, such as the availability of actinide materials, improved knowledge of energy losses and straggling and the stability of targets during irradiation are also discussed.

W. Loveland; L. Yao; David M. Asner; R. G. Baker; J. Bundgaard; E. Burgett; M. Cunningham; J. Deaven; D. L. Duke; U. Greife; S. Grimes; M. Heffer; T. Hill; D. Isenhower; J. L. Klay; V. Kleinrath; N. Kornilov; A. B. Laptev; T. N. Massey; R. Meharchand; H. Qu; J. Ruz; S. Sangiorgio; B. Selhan; L. Snyder; S. Stave; G. Tatishvili; R. T. Thornton; F. Tovesson; D. Towell; R. S. Towell; S. Watson; B. Wendt; L. Wood

2013-03-09

265

High Power Cryogenic Targets  

SciTech Connect

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.

Gregory Smith

2011-08-01

266

Inflation Forecast Targeting: Implementing and Monitoring Inflation Targets  

Microsoft Academic Search

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

Lars E. O. Svensson

1997-01-01

267

Polarized gas targets  

NASA Astrophysics Data System (ADS)

This review describes the development and present performance of nuclear polarized gas targets in nuclear or particle physics experiments. After a brief account of the various development steps, the design principles for the relevant light nucleon targets, hydrogen, deuterium and 3He, for storage rings, are discussed. Most of these targets make use of so-called storage cells in order to enhance the target thickness. The performance of targets used in medium and high-energy ion and electron storage rings is reviewed. Finally, future trends and possible improvements are discussed.

Steffens, Erhard; Haeberli, Willy

2003-11-01

268

In planta gene targeting  

PubMed Central

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

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

2012-01-01

269

Integrin Targeted MR Imaging  

PubMed Central

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

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

270

Future Directions: New Targets  

Microsoft Academic Search

The biology of endometrial cancer is providing new therapeutic targets. In this chapter we review (a) how the integration\\u000a of chemotherapy has been taking place; (b) new targeted therapies and immunotherapies being tested in the treatment of these\\u000a malignancies; (c) new targets worthy of consideration based on the biology of uterine cancers; (d) other consequences such\\u000a as of these advances

Franco Muggia; Leslie I. Gold; John Curtin

271

Inertial Confinement fusion targets  

NASA Technical Reports Server (NTRS)

Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were 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.

Hendricks, C. D.

1982-01-01

272

Targeting the tumor microenvironment  

SciTech Connect

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.

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

2006-11-07

273

Precision Medicine and Targeted Therapy  

Cancer.gov

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

274

Thrombotic microangiopathies (TTP, HUS, HELLP).  

PubMed

Thrombocytopenia, strictly defined as a platelet count less than 150,000, is common in the emergency department. Recognition, diagnostic investigation, and proper disposition of a thrombocytopenic patient are imperative. One group of disorders leading to thrombocytopenia is the thrombotic microangiopathies, hallmarked by platelet destruction. These thrombotic microangiopathies include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and hemolysis, elevated liver enzyme levels, low platelet count (HELLP), which should be distinguished from similar disease processes such as immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC) and heparin induced thrombocytopenia (HIT). In this article, clinical presentations, pathophysiology, diagnostic workup, management plans, complications, and dispositions are addressed for this complex group of platelet disorders. PMID:25060255

Kappler, Shane; Ronan-Bentle, Sarah; Graham, Autumn

2014-08-01

275

Moving target exploitation  

NASA Astrophysics Data System (ADS)

The understanding of maneuvering forces is invaluable to the warfighter, as it enhances understanding of enemy force structure and disposition, provides cues to potential enemy actions, and expedites targeting of time critical targets. Airborne ground moving target indicator (GMTI) radars are a class of highly-effective, all-weather, wide-area senors that aid in the surveillance of these moving ground vehicles. Unfortunately conventional GMTI radars are incapable of identifying individual vehicles, and techniques for exploiting information imbedded within GMTI radar reports are limited. The Defense Advanced Research Projects Agency (DARPA) Moving Target Exploitation (MTE) program is working to mitigate these deficiencies by developing, integrating, and evaluating a suite of automated and semi-automated technologies to classify moving targets and units, and to provide indications of their activities. These techniques include: aid in the interpretation of GMTI data to provide moving force structure analysis, automatic tracking of thousands of moving ground vehicles, 1-D target classification based upon high-range- resolution (HRR) radar profiles, and 2-D target classification based upon moving target imaging (MTIm) synthetic aperture radar (SAR). This paper shall present the MTE concept and motivation and provide an overview of results to date.

Johnson, Bruce L.; Grayson, Timothy P.

1998-08-01

276

Inflation Targeting: Some Extensions  

Microsoft Academic Search

Previous analyses of the implementation of inflation targeting are extended to monetary policy responses to different shocks, consequences of model uncertainty, and effects of interest rate smoothing and stabilization. Model uncertainty, output stabilization, and interest rate stabilization or smoothing all call for a more gradual adjustment of the conditional inflation forecast toward the inflation target. The conditional inflation forecast is

Lars E. o. Svensson

1998-01-01

277

Targets for Muon Colliders  

NASA Astrophysics Data System (ADS)

Efficient production and collection of pions is vital in achieving high luminosity in muon colliders. Results of extensive simulations with the MARS13(97) code are reported for 8 to 30 GeV proton beams (10^14 ppp at 15 Hz) on various targets. Validity of the low-energy pion production model is demonstrated. Circulated liquids (gallium or lead in a pipe, and an open jet of platinum oxide) and solid targets of various composition and shape are considered for pion production and collection in a 15-20 T hybrid solenoid. Beam, target and solenoid parameters are optimized with respect to target and superconducting coil behavior and pion yield. These parameters include beam energy and spot size, target material, composition, shape, longitudinal and transverse dimensions and tilt angle with respect to the solenoid axis, solenoid dimensions, aperture and field.

Mokhov, N. V.

1998-04-01

278

Dynamic tactical targeting  

NASA Astrophysics Data System (ADS)

Today's Warfighter requires new capabilities that reduce the kill chain timeline. The capability to maintain track on mobile Time Sensitive Targets (TSTs) throughout the entire targeting cycle is a step towards that goal. Continuous tracking provides strike assets with high confident, actionable, targeting information, which reduces the time it takes to reacquire the target prior to prosecution. The Defense Advanced Research Program Agency (DARPA) Dynamic Tactical Targeting (DTT) program is developing new sensor resource management and data fusion technologies for continuous coordination of tactical sensor resources to detect and identify mobile ground targets and maintain track on these known high-value targets. An essential concept of the DTT approach is the need for the fusion system and the resource manager to operate as part of a closed loop process that produces optimum collection plans against the designated high value TSTs. In this paper, we describe this closed loop approach used within the DTT system. The paper also describes other aspects of the DTT program, including overall program status, the DTT distributed architecture, details of the fusion and dynamic sensor management components, and concludes with current evaluation results.

Hanselman, Phillip B.; Lawrence, Craig; Fortunato, Evan; Tenney, Robert R.; Blasch, Erik P.

2004-07-01

279

Immunogenicity of targeted lentivectors  

PubMed Central

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

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

280

USGS aerial resolution targets.  

USGS Publications Warehouse

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

Salamonowicz, P.H.

1982-01-01

281

Ampliseq Targeted Resequencing  

Cancer.gov

Exome Sequencing frequently identifies regions of interest for further exploration or validation of variants. Targeted resequencing, either as a follow-up to exome sequencing, or as a stand-alone project, can be done using Life Technologies' Ion Ampliseq

282

Target-detection strategies  

NASA Astrophysics Data System (ADS)

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.

Schachter, Bruce J.

2013-04-01

283

Fractional-targeted phototherapy.  

PubMed

Targeted ultraviolet B phototherapy is used in the treatment for localized variants of psoriasis. We present two cases in which we compared the efficacy of lite spot and lite brush in the treatment of psoriasis and vitiligo. PMID:25593795

Shanmuga, Sekar C; Srinivas, C R

2014-12-01

284

Fractional-targeted phototherapy  

PubMed Central

Targeted ultraviolet B phototherapy is used in the treatment for localized variants of psoriasis. We present two cases in which we compared the efficacy of lite spot and lite brush in the treatment of psoriasis and vitiligo. PMID:25593795

Shanmuga, Sekar C.; Srinivas, C.R.

2014-01-01

285

CDRP - Target Populations  

Cancer.gov

Home About CDRP Background The Challenge Ahead Health Disparities Cooperative Planning Grant Objective and Scope U56 Award Mechanism Target Populations Funded Institutions Funded Institutions Programs' Presentations CDRP Symposium Presentations Clinical

286

Dimensional Automatic Target Classification  

NASA Astrophysics Data System (ADS)

High resolution electro-optical sensors are emerging from technology, offering a capability to remotely determine geometric shape of objects. In terms of military reconnaissance and surveilance needs, this capability enhances the potential to detect, classify, and identify enemy targets automatically, and record or report only their type and location. The objective of this paper is to outline the general nature of an automatic classifier for processing high resolution, active electro-optical sensor data on the basis of target dimensional features. A simple geometric analysis is used to demonstrate the predominant features of the data, and to suggest approaches for cueing potential targets by masking out extraneous background data. The goal is to provide an early data reduction so that potential target subframes can be processed in the classification processor at lower data rates. Both line-scan and raster-scan data formats are considered, in forward- and down-looking configurations.

Rose, Harold W.; Rachal, James C.

1981-11-01

287

High pressure gas target  

NASA Astrophysics Data System (ADS)

Compact, high pressure, high current gas target features all metal construction and semi-automatic window assembly change. The unique aspect of this target is the domed-shaped window. The Havar alloy window is electron beam welded to a metal ring, thus forming one, interchangeable assembly. The window assembly is sealed by knife-edges locked by a pneumatic toggle allowing a quick, in situ window change.

Gelbart, W.; Johnson, R. R.; Abeysekera, B.

2012-12-01

288

Combining Targeted Therapies  

Microsoft Academic Search

Many new agents have emerged in the drug development pipeline that target the mechanisms driving the development and progression\\u000a of specific cancers. Ultimately, the goal is to create personalized treatment plans for each patient’s tumor(s). Despite promising\\u000a early preclinical data, only a handful of the targeted molecules developed thus far have shown benefit when used as single\\u000a agents. The need

David Hong; Lakshmi Chintala

289

Target activated frame capture  

NASA Astrophysics Data System (ADS)

Over the past decade, technological advances have enabled the use of increasingly intelligent systems for battlefield surveillance. These systems are triggered by a combination of external devices including acoustic and seismic sensors. Such products are mainly used to detect vehicles and personnel. These systems often use infra-red imagery to record environmental information, but Textron Defense Systems' Terrain Commander is one of a small number of systems which analyze these images for the presence of targets. The Terrain Commander combines acoustic, infrared, magnetic, seismic, and visible spectrum sensors to detect nearby targets in military scenarios. When targets are detected by these sensors, the cameras are triggered and images are captured in the infrared and visible spectrum. In this paper we discuss a method through which such systems can perform target tracking in order to record and transmit only the most pertinent surveillance images. This saves bandwidth which is crucial because these systems often use communication systems with throughputs below 2400bps. This method is expected to be executable on low-power processors at frame rates exceeding 10HZ. We accomplish this by applying target activated frame capture algorithms to infra-red video data. The target activated frame capture algorithms combine edge detection and motion detection to determine the best frames to be transmitted to the end user. This keeps power consumption and bandwidth requirements low. Finally, the results of the algorithm are analyzed.

Roberts, G. Marlon; Fitzgerald, James; McCormack, Michael; Steadman, Robert

2008-04-01

290

Inflation Forecast Targeting: Implementing and Monitoring Inflation Targets  

E-print Network

Inflation targeting is shown to imply inflation forecast targeting: the central bank's inflation forecast becomes an explicit intermediate target. Inflation forecast targeting simplifies both implementation and monitoring of monetary policy. The weight on output stabilization determines how quickly the inflation forecast is adjusted towards the inflation target. Money growth or exchange rate targeting is generally inferior than inflation targeting and leads to higher inflation variability. Commitment to `target rules' may be better than commitment to `instrument rules'.

Lars E. O. Svensson; Hans Dillén; Neil Ericsson; Jon Faust; Stanley Fischer; Marvin Goodfriend; Andrew Haldane; Hans Lindberg; David Mayes; Stefan Mellin; Frederic Mishkin; Stefan Palmqvist; Torsten Persson

1996-01-01

291

Targeted Therapies for Kidney Cancer  

MedlinePLUS

... cause cancer, they have developed newer drugs that target some of these changes. These targeted drugs are ... It attacks both blood vessel growth and other targets that help cancer cells grow. This drug is ...

292

Targeted assets risk analysis.  

PubMed

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

Bouwsema, Barry

2013-01-01

293

High power density targets  

NASA Astrophysics Data System (ADS)

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.

Pellemoine, Frederique

2013-12-01

294

Penetration of concrete targets  

SciTech Connect

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.

Forrestal, M.J. [Sandia National Labs., Albuquerque, NM (United States); Cargile, J.D. [Corps of Engineers, Vicksburg, MS (United States). Waterways Experiment Station; Tzou, R.D.Y. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Mechanical Engineering

1993-08-01

295

Setting reference targets  

SciTech Connect

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.

Ruland, R.E.

1997-04-01

296

Mesothelin targeted cancer immunotherapy.  

PubMed

Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. It is, however, highly expressed in several human cancers including malignant mesothelioma, pancreatic, ovarian and lung adenocarcinoma. The normal biologic function of mesothelin is unknown but recent studies have shown that it binds to CA-125 and may play a role in the peritoneal spread of ovarian cancer. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. Three mesothelin targeted agents are in various stages of clinical evaluation in patients. These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy. PMID:17945478

Hassan, Raffit; Ho, Mitchell

2008-01-01

297

Targeted polypeptide degradation  

DOEpatents

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.

Church, George M. (Brookline, MA); Janse, Daniel M. (Brookline, MA)

2008-05-13

298

Targeting the tumor microenvironment  

PubMed Central

Persistent JAK-STAT3 signaling is implicated in many aspects of tumorigenesis. Apart from its tumor-intrinsic effects, STAT3 also exerts tumor-extrinsic effects, supporting tumor survival and metastasis. These involve the regulation of paracrine cytokine signaling, alterations in metastatic sites rendering these permissive for the growth of cancer cells and subversion of host immune responses to create an immunosuppressive environment. Targeting this signaling pathway is considered a novel promising therapeutic approach, especially in the context of tumor immunity. In this article, we will review to what extent JAK-STAT3-targeted therapies affect the tumor microenvironment and whether the observed effects underlie responsiveness to therapy. PMID:24058812

Bournazou, Eirini; Bromberg, Jacqueline

2013-01-01

299

Targets, backgrounds, and discrimination  

NASA Astrophysics Data System (ADS)

The present volume discusses a model-based aircraft identification technique, target intensity and angle scintillations, spatiotemporal nonstationary scene generation, an overview of the Strategic Scene Generation Model (SSGM), nuclear backgrounds for SSGM, and an atmospheric and transmittance code for 50-300 km altitudes. Also discussed are a data base for airborne target signatures, the auroral module of the Strategic High Altitude Radiance Code, and the 3D characteristics of underexpanded and overexpanded rectangular jets. (No individual items are abstracted in this volume)

Accetta, J. S.; Kelley, G. H.

300

Integrin Targeted Therapeutics  

PubMed Central

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

Millard, Melissa; Odde, Srinivas; Neamati, Nouri

2011-01-01

301

Foam encapsulated targets  

DOEpatents

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.

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

1983-01-01

302

Comet and Target Ghost: Techniques for Selecting Moving Targets  

E-print Network

Comet and Target Ghost: Techniques for Selecting Moving Targets Khalad Hasan1 , Tovi Grossman2 that assist in selecting moving targets. We present Comet, a technique that enhances tar- gets based of the target, while leaving the motion uninterrupted. We found a speed benefit for the Comet in a 1D selection

303

Laparoscopic Splenectomy for Malignant Diseases  

Microsoft Academic Search

\\u000a Since Delaitre and Maignien [1] reported the first laparoscopic splenectomy in 1991, the utility of laparoscopic splenectomy\\u000a in the treatment of hematologic diseases such as hereditary spherocytosis, immune thrombocytopenic purpura, and autoimmune\\u000a hemolytic anemia has been well established. Thousands of cases in the surgical literature have documented laparoscopic splenectomy\\u000a as safe and effective in the management of these benign hematologic

R. Matthew Walsh; B. Todd Heniford

304

A Girl with Autoimmune Cytopenias, Nonmalignant Lymphadenopathy, and Recurrent Infections  

PubMed Central

We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent infections, and autoimmune hemolytic anemia. Her symptoms partly fit the definitions of both autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency disorders (CVIDs). Genetic analysis showed no abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI gene showed a homozygous polymorphism (Pro251Leu), which is found also in healthy controls. PMID:25379303

Mattheij, Marjolein A. C.; Schatorjé, Ellen J. H.; Gemen, Eugenie F. A.; van de Corput, Lisette; Nooijen, Peet T. G. A.; van der Burg, Mirjam; de Vries, Esther

2012-01-01

305

Rituximab Off Label Use for Difficult-To-Treat AutoImmune Diseases: Reappraisal of Benefits and Risks  

Microsoft Academic Search

Rituximab is increasingly used off label for difficult-to-treat auto-immune diseases. We reviewed the main case series or\\u000a clinical studies to identify the best indications of rituximab and the situations at substantial risks for adverse events.\\u000a Refractory immune thrombocytopenic purpura was the main indication. However, the long term benefit-to-risk ratio of rituximab\\u000a treatment before or after splenectomy is unknown. A single

Laurent Sailler

2008-01-01

306

Crystal Structures of Human ADAMTS-1 Reveal a Conserved Catalytic Domain and a Disintegrin-like Domain with a Fold Homologous to Cysteine-Rich Domains  

Microsoft Academic Search

The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type I motifs) family of proteases plays a role in pathological conditions including arthritis, cancer, thrombotic thrombocytopenic purpura and the Ehlers–Danlos type VIIC and Weill–Marchesani genetic syndromes. Here, we report the first crystal structures for a member of the ADAMTS family, ADAMTS-1. Originally cloned as an inflammation-associated gene, ADAMTS-1 has been

Stefan Gerhardt; Giles Hassall; Paul Hawtin; Eileen McCall; Liz Flavell; Claire Minshull; David Hargreaves; Attilla Ting; Richard A. Pauptit; Andrew E. Parker; W. Mark Abbott

2007-01-01

307

47,XXX in an Adolescent with Premature Ovarian Failure and Autoimmune Disease  

Microsoft Academic Search

Background: Premature ovarian failure (POF) may be idiopathic or may be associated with genetic or autoimmune disorders. The 47,XXX karyotype has been associated with POF and other genitourinary anomalies.Case: A 17-year-old woman with a history of immune thrombocytopenic purpura was referred to the adolescent medicine clinic for evaluation of oligomenorrhea with secondary amenorrhea. Evaluation revealed hypergonadotrophic premature ovarian failure, a

C. M Holland

2001-01-01

308

Cloning, expression, and functional characterization of the von Willebrand factor-cleaving protease (ADAMTS13)  

Microsoft Academic Search

Deficient von Willebrand factor (VWF) deg- radation has been associated with throm- botic thrombocytopenic purpura (TTP). In hereditary TTP, the specific VWF-cleaving protease (VWF-cp) is absent or function- ally defective, whereas in the nonfamilial, acquired form of TTP, an autoantibody inhibiting VWF-cp activity is found tran- siently in most patients. The gene encod- ing for VWF-cp has recently been identi-

Barbara Plaimauer; Klaus Zimmermann; Dirk Volkel; Gerhard Antoine; Randolf Kerschbaumer; Pegah Jenab; Miha Furlan; Helen Gerritsen; Bernhard Lammle; Hans Peter Schwarz; Friedrich Scheiflinger

2002-01-01

309

Mutation analysis and clinical implications of von Willebrand factor–cleaving protease deficiency  

Microsoft Academic Search

Mutation analysis and clinical implications of von Willebrand factor–cleaving protease deficiency.BackgroundThe pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an acquired form but a congenital form in children has also been described. In the latter case, the initial presentation is often

Karin Assink; Rikke Schiphorst; Sarah Allford; Diana Karpman; Amos Etzioni; Bénédicte Brichard; Nicole Van De Kar; Leo Monnens; Lambertus Van Den Heuvel

2003-01-01

310

Target fragmentation in radiobiology  

NASA Technical Reports Server (NTRS)

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.

Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.; Townsend, Lawrence W.

1993-01-01

311

Target fragmentation in radiobiology  

SciTech Connect

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.

Wilson, J.W.; Cucinotta, F.A.; Shinn, J.L.; Townsend, L.W.

1993-02-01

312

Active Target Simulation  

NASA Astrophysics Data System (ADS)

We have simulated an existing experimental design to determine the resolution improvement upon energy measurements of neutron unbound nuclei. A number of experiments of this type have been performed at the National Superconducting Cyclotron Laboratory (NSCL), located at Michigan State University. An excited nucleus is typically produced with a radioactive beam interacting with a passive Beryllium target. Many different nuclei are produced in experiment, each of which immediately decays into a charged particle and neutron. The charged particles are detected and the neutrons interact in scintillation detectors such as the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). In our simulation, we have constructed an active target that provides additional information such that the point of nuclear interaction within the target may be determined. This information improves the resolution in decay energy measurements of neutron unbound isotopes. This presentation will cover some aspects of the simulation process, as well as showing some of the results that demonstrate the simulated improvement over a passive target.

Smith, Nathan; Draznik, Peter; Frank, Nathan

2012-10-01

313

AKAPs as Antiarrhythmic Targets?  

Microsoft Academic Search

Phosphorylation of ion channels plays a critical role in the modulation and amplification of biophysical signals. Kinases and phosphatases have broad substrate recognition sequences. Therefore, the targeting of kinases and phosphatases to specific sites enhances the regulation of diverse signaling events. Ion channel macromolecular complexes can be formed by the association of A-kinase anchoring proteins(AKAPs) or other adaptor proteins directly

S. O. Marx; J. Kurokawa

314

Tungsten Helium cooled Target  

E-print Network

characteristics >Rotating seal >Maintenance >Lifetime >Conclusion #12;Page 3Cyril Kharoua ­ 4th HPTW ­ Malmö ­ May metal technology Avoid Water cooling / corrosion issue related to tungsten target and therefore avoid!) Rotating seals to be adapted from existing solutions Heavy assembly #12;Page 7Cyril Kharoua ­ 4th HPTW

McDonald, Kirk

315

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...

316

Targets of curcumin  

PubMed Central

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-?B), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

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

2010-01-01

317

Targeting the RAS oncogene  

PubMed Central

Introduction The Ras proteins (K-Ras, N-Ras, H-Ras) are GTPases that function as molecular switches for a variety of critical cellular activities and their function is tightly and temporally regulated in normal cells. Oncogenic mutations in the RAS genes, which create constitutively-active Ras proteins, can result in uncontrolled proliferation or survival in tumor cells. Areas covered The paper discusses three therapeutic approaches targeting the Ras pathway in cancer: 1) Ras itself, 2) Ras downstream pathways, and 3) synthetic lethality. The most adopted approach is targeting Ras downstream signaling, and specifically the PI3K-AKT-mTOR and Raf-MEK pathways, as they are frequently major oncogenic drivers in cancers with high Ras signaling. Although direct targeting of Ras has not been successful clinically, newer approaches being investigated in preclinical studies, such as RNA interference-based and synthetic lethal approaches, promise great potential for clinical application. Expert opinion The challenges of current and emerging therapeutics include the lack of “tumor specificity” and their limitation to those cancers which are “dependent” upon aberrant Ras signaling for survival. While the newer approaches have the potential to overcome these limitations, they also highlight the importance of robust preclinical studies and bidirectional translational research for successful clinical development of Ras-related targeted therapies. PMID:23360111

Takashima, Asami

2013-01-01

318

Inflation targeting in Brazil  

Microsoft Academic Search

The purpose of this paper is to examine the Inflation Targeting (IT) framework as it is applied in the case of Brazil since its adoption in June 1999. For this purpose we first summarize the macroeconometric model utilized by the Central Bank of Brazil (BCB) in its pursuit of the IT framework. While the focus of this paper is on

Philip Arestis; Luiz Fernando de Paula

2011-01-01

319

Tumour vascular targeting  

Microsoft Academic Search

It is now accepted that the growth of solid tumours is dependent on their capacity to acquire a blood supply, and much effort has been directed towards the development of agents (known as anti-angiogenics) that disrupt this process. More recently, it has become apparent that targeted destruction of the established tumour vasculature is another avenue for exciting therapeutic opportunities. In

Dario Neri; Roy Bicknell

2005-01-01

320

MECO Production Target Developments  

E-print Network

MECO Production Target Developments James L. Popp University of California, Irvine NuFact'03. Hebert, T. J. Liu, W. Molzon, J. Popp, V. Tumakov University of Houston E. V. Hungerford, K. A. Lan, L. S UCI: A. Arjad, W.Molzon, M.Hebert, V.Tumakov, J.Popp Radiation-cooled R = 3 mm, L = 16 cm #12;June

McDonald, Kirk

321

Targeting nanoparticles to cancer.  

PubMed

Nanotechnology applications in medicine, termed as nanomedicine, have introduced a number of nanoparticles of variable chemistry and architecture for cancer imaging and treatment. Nanotechnology involves engineering multifunctional devices with dimensions at the nanoscale, similar dimensions as those of large biological vesicles or molecules in our body. These devices typically have features just tens to hundred nanometers across and they can carry one or two detection signals and/or therapeutic cargo(s). One unique class of nanoparticles is designed to do both, providing this way the theragnostic nanoparticles (therapy and diagnosis). Being inspired by physiologically existing nanomachines, nanoparticles are designed to safely reach their target and specifically release their cargo at the site of the disease, this way increasing the drug's tissue bioavailability. Nanoparticles have the advantage of targeting cancer by simply being accumulated and entrapped in tumours (passive targeting). The phenomenon is called the enhanced permeation and retention effect, caused by leaky angiogenetic vessels and poor lymphatic drainage and has been used to explain why macromolecules and nanoparticles are found at higher ratios in tumours compared to normal tissues. Although accumulation in tumours is observed cell uptake and intracellular drug release have been questioned. Polyethyleneglycol (PEG) is used to protect the nanoparticles from the Reticulo-Endothelial System (RES), however, it prevents cell uptake and the required intracellular drug release. Grafting biorecognition molecules (ligands) onto the nanoparticles refers to active targeting and aims to increase specific cell uptake. Nanoparticles bearing these ligands are recognised by cell surface receptors and this leads to receptor-mediated endocytosis. Several materials are suggested for the design of nanoparticles for cancer. Polymers, linear and dendrimers, are associated with the drug in a covalent or non-covalent way and have been used with or without a targeting ligand. Stealth liposomes are suggested to carry the drug in the aqueous core, and they are usually decorated by recognition molecules, being widely studied and applied. Inorganic nanoparticles such as gold and iron oxide are usually coupled to the drug, PEG and the targeting ligand. It appears that the PEG coating and ligand decoration are common constituents in most types of nanoparticles for cancer. There are several examples of successful cancer diagnostic and therapeutic nanoparticles and many of them have rapidly moved to clinical trials. Nevertheless there is still a room for optimisation in the area of the nanoparticle kinetics such as improving their plasma circulation and tumour bioavailability and understanding the effect of targeting ligands on their efficiency to treat cancer. The need to develop novel and efficient ligands has never been greater, and the use of proper conjugation chemistry is mandatory. PMID:20380880

Wang, M; Thanou, M

2010-08-01

322

Targeting HER2 Epitopes.  

PubMed

Variable expression of the HER2 receptor has been implicated in the pathogenesis of a number of malignancies. Many therapeutic modalities have been devised that target the receptor and downstream molecular pathways. The humanized monoclonal antibodies trastuzumab and pertuzumab bind epitopes on the extracellular domain, resulting in cell growth inhibition though a number of proposed mechanisms. Peptidomimetic agents represent short amino acid sequences containing structural features of the antibody complementarity determining regions (CDRs), and appear to have similar inhibitory properties in experimental models. RNA aptamers are ribonucleotide sequences that also exhibit complementarity with extracellular epitopes and lead to growth inhibition. Recent data suggest a synergistic interaction of HER2 epitope-targeting agents when used in combination. PMID:16890794

Pal, Sumanta Kumar; Pegram, Mark

2006-08-01

323

Targeted adenoviral vectors  

NASA Astrophysics Data System (ADS)

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

Douglas, Joanne T.

324

Mitochondria-targeting particles.  

PubMed

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

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

2014-11-01

325

Cellular Targeting in Autoimmunity  

PubMed Central

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

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

2012-01-01

326

Optimal discriminating multispectral target detection and optical correlation target tracking  

NASA Astrophysics Data System (ADS)

This paper presents feasibility studies of a multispectral moving target detection (MTD) system designed to detect and track low-signature moving targets. The system performs multispectral detection based on linear and nonlinear optimal discriminating features (ODF) for low-signature target detection and correlation tracking of slowly moving targets in clutter. Multispectral detection was tested against multispectral data from an acousto-optic tunable filter in the visible and near infrared. Optical Joint Transform Correlator for target tracking was designed and manufactured. The feasibility of correlation target tracking was demonstrated with actual Army MICOM FLIR long wavelength infrared (LWIR: 8 to 12 ?m) images of moving vehicles and tanks in clutter.

Kostrzewski, Andrew A.; Savant, Gajendra; Shnitser, Paul; Piliavin, Michael; Sandomirsky, Sergey; Vasiliev, Anatoly A.; Casasent, David P.

2003-09-01

327

CDTI target selection criteria  

NASA Technical Reports Server (NTRS)

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

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

1984-01-01

328

Nanocrystal targeting in vivo  

NASA Astrophysics Data System (ADS)

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.

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

2002-10-01

329

Novel diuretic targets  

PubMed Central

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

Pao, Alan C.; Maduke, Merritt

2013-01-01

330

Targeted therapy in gastrointestinal malignancies  

PubMed Central

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

Chhatrala, Ravi; Thanavala, Yasmin; Iyer, Renuka

2014-01-01

331

Target Asteroids! Observing Targets for 2014 April through June  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of 2014 April through June are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to 101955 Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2014-04-01

332

Target Asteroids! Observing Targets for 2014 July through September  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of July to September 2014 are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

Hergenrother, Carl; Hill, Dolores

2014-07-01

333

Target Mass Corrections Revisited  

SciTech Connect

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}.

W. Melnitchouk; F. Steffens

2006-03-07

334

Targeting the androgen receptor.  

PubMed

Androgen receptor (AR)-mediated signaling is critical to the growth and survival of prostate cancer. Although medical castration and antiandrogen therapy can decrease AR activity and lower PSA, castration resistance eventually develops. Recent work exploring the molecular structure and evolution of AR in response to hormonal therapies has revealed novel mechanisms of progression of castration-resistant prostate cancer and yielded new targets for drug development. This review focuses on understanding the mechanisms of persistent AR signaling in the castrate environment, and highlights new therapies either currently available or in clinical trials, including androgen synthesis inhibitors and novel direct AR inhibitors. PMID:23084523

Friedlander, Terence W; Ryan, Charles J

2012-11-01

335

TARGETing "When" and "Where"  

NSDL National Science Digital Library

In Drosophila, the cyclic adenosine monophosphate (cAMP) pathway has been shown to be crucial for learning and memory, but whether this represents a developmental or a specific effect has not been resolved. Research with a new targeting system that allows both spatial and temporal control of gene expression shows that expression of rutabaga-encoded adenylyl cyclase, a component of the cAMP signaling pathway, in the mushroom bodies of adult flies is necessary and sufficient to rescue the learning defect of rutabaga mutant. This demonstrates an acute role for Rutabaga in learning and memory.

Yalin Wang (Cold Spring Harbor Laboratory; REV); Yi Zhong (Cold Spring Harbor Laboratory; REV)

2004-02-17

336

A Note on Inflation Targeting.  

ERIC Educational Resources Information Center

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)

Lai, Ching-chong; Chang, Juin-jen

2001-01-01

337

Open-Economy Inflation Targeting  

Microsoft Academic Search

The paper examines inflation targeting in a small open economy with forward-looking aggregate supply and demand with microfoundations, and with stylised realistic lags in the different monetary-policy transmission channels. The paper compares strict and flexible targeting of CPI and domestic inflation and inflation-targeting reaction functions and the Taylor rule. Flexible CPI-inflation targeting does not only limit the variability of CPI

Lars E. O. Svensson

1998-01-01

338

Open-economy inflation targeting  

Microsoft Academic Search

The paper examines inflation targeting in a small open economy with forward-looking aggregate supply and demand with microfoundations, and with stylized realistic lags in the different monetary-policy transmission channels. The paper compares strict and flexible targeting of CPI and domestic inflation, and inflation-targeting reaction functions and the Taylor rule. Flexible CPI-inflation targeting does not limit the variability of CPI inflation

Lars E. O. Svensson

2000-01-01

339

Magnetized Target Fusion  

NASA Technical Reports Server (NTRS)

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.

Griffin, Steven T.

2002-01-01

340

Quantum state targeting  

NASA Astrophysics Data System (ADS)

We introduce a primitive for quantum cryptography that we term “state targeting.” We show that increasing one’s probability of success in this task above a minimum amount implies an unavoidable increase in the probability of a particular kind of failure. This is analogous to the unavoidable disturbance to a quantum state that results from gaining information about its identity, and can be shown to be a purely quantum effect. We solve various optimization problems for state targeting that are useful for the security analysis of two-party cryptographic tasks implemented between remote antagonistic parties. Although we focus on weak coin flipping, the results are significant for other two-party protocols, such as strong coin flipping, partially binding and concealing bit commitment, and bit escrow. Furthermore, the results have significance not only for the traditional notion of security in cryptography, that of restricting a cheater’s ability to bias the outcome of the protocol, but also for a different notion of security that arises only in the quantum context, that of cheat sensitivity. Finally, our analysis leads to some interesting secondary results, namely, a generalization of Uhlmann’s theorem and an operational interpretation of the fidelity between two mixed states.

Rudolph, Terry; Spekkens, Robert W.

2004-11-01

341

Quantum state targeting  

SciTech Connect

We introduce a primitive for quantum cryptography that we term 'state targeting'. We show that increasing one's probability of success in this task above a minimum amount implies an unavoidable increase in the probability of a particular kind of failure. This is analogous to the unavoidable disturbance to a quantum state that results from gaining information about its identity, and can be shown to be a purely quantum effect. We solve various optimization problems for state targeting that are useful for the security analysis of two-party cryptographic tasks implemented between remote antagonistic parties. Although we focus on weak coin flipping, the results are significant for other two-party protocols, such as strong coin flipping, partially binding and concealing bit commitment, and bit escrow. Furthermore, the results have significance not only for the traditional notion of security in cryptography, that of restricting a cheater's ability to bias the outcome of the protocol, but also for a different notion of security that arises only in the quantum context, that of cheat sensitivity. Finally, our analysis leads to some interesting secondary results, namely, a generalization of Uhlmann's theorem and an operational interpretation of the fidelity between two mixed states.

Rudolph, Terry [Bell Labs, 600-700 Mountain Avenue, Murray Hill, New Jersey 07974 (United States); Spekkens, Robert W. [Perimeter Institute for Theoretical Physics, 31 Caroline Street North, Waterloo, Ontario, N2L 2Y5 (Canada)

2004-11-01

342

Policy Rules for Inflation Targeting  

Microsoft Academic Search

Policy rules that are consistent with inflation targeting are examined in a small macroeconomic model of the US economy. We compare the properties and outcomes of explicit instrument rules' as well as targeting rules.' The latter, which imply implicit instrument rules, may be closer to actual operating procedures of inflation-targeting central banks. We find that inflation forecasts are central for

Glenn D. Rudebusch; Lars E. O. Svensson

1998-01-01

343

Robotic Target-Tracking Subsystem  

NASA Technical Reports Server (NTRS)

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.

Shawaga, Lawrence M.

1989-01-01

344

Target noise in overlay metrology  

NASA Astrophysics Data System (ADS)

We have developed a method for calculating the statistical effects of spatial noise on the overlay measurement extracted from a given overlay target. The method has been applied to two kinds of overlay targets on three process layers, and the new metric, Target Noise, has been shown to correlate well to the random component of Overlay Mark Fidelity. A significant difference in terms of robustness has been observed between AIM targets and conventional Frame-in-Frame targets. The results fit well into the spatial noise hierarchy presented in this paper.

Seligson, Joel L.; Adel, Mike E.; Izikson, Pavel; Levinski, Vladimir; Yaffe, Dan

2004-05-01

345

Target control of complex networks  

NASA Astrophysics Data System (ADS)

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.

Gao, Jianxi; Liu, Yang-Yu; D'Souza, Raissa M.; Barabási, Albert-László

2014-11-01

346

ORION laser target diagnostics  

SciTech Connect

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.

Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K. [Plasma Physics Department, Atomic Weapons Establishment, Aldermaston, Reading, Berkshire RG7 4PR (United Kingdom); and others

2012-10-15

347

Targeting neutrophils in sepsis.  

PubMed

Sepsis continues to have a high mortality rate worldwide. The multi-step effects of this syndrome make it difficult to develop a comprehensive understanding of its pathophysiology and to identify a direct treatment. Neutrophils play a major role in controlling infection. Interestingly, the recruitment of these cells to an infection site is markedly reduced in severe sepsis. The systemic activation of Toll-like receptors and high levels of TNF-? and nitric oxide are involved in the reduction of neutrophil recruitment due to down-regulation of CXCR2 in neutrophils. By contrast, CCR2 is expressed in neutrophils after sepsis induction and contributes to their recruitment to organs far from the infection site, which contributes to organ damage. This review provides an overview of the recent advances in the understanding of the role of neutrophils in sepsis, highlighting their potential as a therapeutic target. PMID:24867165

Sônego, Fabiane; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

2014-08-01

348

TARGETING SURVIVIN IN CANCER  

PubMed Central

With almost 4,000 citations in Medline in a little over ten years, survivin has certainly kept scores of investigators busy worldwide. Tangible progress has been made in revealing the multiple functions of survivin, uncovering their wirings as integrated cellular networks, and mapping their exploitation in virtually every human tumor, in vivo. Considering the normally long and excruciating timeline of oncology drug discovery, it is clearly a resounding success that a better understanding of survivin biology has led to several clinical trials of survivin-based therapeutics in cancer patients. However, the portfolio of survivin antagonists available in the clinic remains small, pressing the need for a less rigid drug development approach to fully unlock the potential of this unique, albeit unconventional oncology drug target. PMID:22410464

Altieri, Dario C.

2012-01-01

349

Target detection portal  

SciTech Connect

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.

Linker, Kevin L. (Albuquerque, NM); Brusseau, Charles A. (Tijeras, NM)

2002-01-01

350

Stroke Neuroprotection: Targeting Mitochondria  

PubMed Central

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

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

2013-01-01

351

Epilepsy: Novel therapeutic targets  

PubMed Central

Despite of established and effective therapy for epilepsy, 20–25% patients develop therapeutic failure; this encourages finding newer drugs. Novel approaches target receptors which remain unaffected by conventional therapy or inhibit epileptogenesis. AMPA receptor antagonists have shown faster and complete protection compared to diazepam. Protein kinase (PK) plays an important role in the development of epilepsy. PK inhibitors such as K252a, VID-82925, and Herbimycin A have been found effective in inhibition of spread of epileptiform activity and epileptogenesis. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors classified into three groups. Group 1 mGluRs antagonist and Groups 2 and 3 mGluRs agonists inhibited pentylenetetrazole-induced kindled seizures. Combined use of these agents has also shown favorable results. Mammalian target of rapamycin (mTOR) plays a central role in multiple mechanisms of epileptogenesis. mTOR causes transcription, induction of proapoptotic proteins, and autophagy inhibition. Rapamycin was effective in suppression of recurrent seizures as well as in tuberous sclerosis and acute brain injury model. 5% CO2 showed potent effects on cortical epileptiform activity and convulsions in animal epilepsy models and in humans with drug-resistant partial epilepsy. It is found to be rapidly acting, safe and cheap, thus it can be a good option in emergency for suppression of seizure. Neurosteroids are considered as fourth generation neuromessengers, they act as positive allosteric modulators of ?-aminobutyric acid (GABAA) receptors. Clinical trial of ganaxolone, an allopregnanolone analogue, has shown a beneficial role in pharmacoresistant epilepsy. However, most of these drugs are tested in early phases of development and the possible use and safety in epilepsy has to be proven in clinical trials. PMID:22629084

Anovadiya, Ashish P.; Sanmukhani, Jayesh J.; Tripathi, C. B.

2012-01-01

352

Immunotherapy Targets in Pediatric Cancer  

PubMed Central

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

Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

2011-01-01

353

Tumor Targeting-Retargeted Adenovirus  

Microsoft Academic Search

Adenovirus (Ad) has been applied for gene therapy in various applications. The current Ad vector system has two critical problems;\\u000a low transduction of the target cancer cells and high transduction of nontarget normal organs. To address these issues, we\\u000a have been working on “retargeting” of Ad vectors via transductional or transcriptional targeting. Transductional targeting\\u000a has been achieved with application of

Masato Yamamoto; David T. Curiel

354

Multiple target laser ablation system  

DOEpatents

A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film.

Mashburn, Douglas N. (Knoxville, TN)

1996-01-01

355

Accountability, Transparency, and Inflation Targeting  

E-print Network

Inflation targeting regimes define a performance measure for the central bank. A regime that places a large (small) weight on achieving the target is analogous to a high (low) power incentive scheme. High powered incentive structures promote accountability but may distort stabilization policy. The optimal power under inflation targeting is derived under perfect and imperfect information. The fundamental trade off between accountability and stabilization depends on the degree of transparency, defined as the ability to monitor the central banks performance. Multiplicative uncertainty increases the optimal weight to place on achieving an inflation target.

Carl E. Walsh

2001-01-01

356

Targeting targeted agents: open issues for clinical trial design  

Microsoft Academic Search

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced

Emilio Bria; Massimo Di Maio; Paolo Carlini; Federica Cuppone; Diana Giannarelli; Francesco Cognetti; Michele Milella

2009-01-01

357

Progress on Field Reversed Configuration target for Magnetized Target Fusion  

Microsoft Academic Search

We overview the experimental high density Field Reversed Configuration (FRC) approach for a LANL AFRL collaborative physics demonstration of Magnetized Target Fusion (MTF). We show some initial translation data from the Los Alamos FRC experiment FRXL that characterize the MTF translated target plasma. The conical theta coil is expected to generate toroidal magnetic field, helicity, and good curvature field lines,

T. Intrator; G. A. Wurden; P. E. Sieck; W. J. Waganaar; R. Oberto; T. D. Olson; D. Sutherland; J. H. Degnan; E. L. Ruden; M. Domonkos; P. Adamson; C. Grabowski; D. G. Gale; W. Sommars; M. Kostora; M. H. Frese; S. D. Frese; J. F. Camacho; S. K. Coffey; N. F. Roderick; D. J. Amdahl; P. Parks; R. E. Siemon; T. Awe; A. G. Lynn

2009-01-01

358

An autoantibody epitope comprising residues R660, Y661, and Y665 in the ADAMTS13 spacer domain identifies a binding site for the A2 domain of VWF  

PubMed Central

In the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP), antibodies are directed toward the spacer domain of ADAMTS13. We have previously shown that region Y658-Y665 is involved. We now show that replacement of R660, Y661, or Y665 with alanine in ADAMTS13 reduced/abolished the binding of 2 previously isolated human monoclonal antibodies and polyclonal antibodies derived from plasma of 6 patients with acquired TTP. We investigated whether these residues also influenced cleavage of short von Willebrand factor (VWF) fragment substrate VWF115. An ADAMTS13 variant (R660A/Y661A/Y665A, ADAMTS13-RYY) showed a 12-fold reduced catalytic efficiency (kcat/Km) arising from greatly reduced (> 25-fold) binding, demonstrated by surface plasmon resonance. The influence of these residue changes on full-length VWF was determined with denaturing and flow assays. ADAMTS13-RYY had reduced activity in both, with proteolysis of VWF unaffected by autoantibody. Binding of ADAMTS13-RYY mutant to VWF was, however, similar to normal. Our results demonstrate that residues within Y658-Y665 of the ADAMTS13 spacer domain that are targeted by autoantibodies in TTP directly interact with a complementary exosite (E1660-R1668) within the VWF A2 domain. Residues R660, Y661, and Y665 are critical for proteolysis of short VWF substrates, but wider domain interactions also make important contributions to cleavage of full-length VWF. PMID:20032502

Pos, Wouter; Crawley, James T. B.; Fijnheer, Rob; Voorberg, Jan; Lane, David A.

2010-01-01

359

Fecal microbiota transplantation broadening its application beyond intestinal disorders  

PubMed Central

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

Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao

2015-01-01

360

Clinical Application of Partial Splenic Embolization  

PubMed Central

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.

Guan, Yong-Song; Hu, Ying

2014-01-01

361

Peptibodies  

PubMed Central

Peptibodies or peptide-Fc fusions are an attractive alternative therapeutic format to monoclonal antibodies. They consist of biologically active peptides grafted onto an Fc domain. This approach retains certain desirable features of antibodies, notably an increased apparent affinity through the avidity conferred by the dimerization of two Fcs and a long plasma residency time. Peptibodies can be made in E. coli using recombinant technology. The manufacturing process involves fermentation and downstream processing, including refolding and multiple column chromatographic steps, that result in overall yields and quality suitable for commercial development. Romiplostim, marketed under the brand name Nplate®, is the first peptibody to be approved by the United States Food and Drug Administration and the European Medicines Agency and is indicated for the treatment of immune thrombocytopenic purpura. AMG 386, a peptibody antagonist to angiopoietins 1 and 2, is being evaluated in Phase 3 clinical testing in combination with chemotherapy in women with ovarian cancer. AMG 819, a peptibody targeting nerve growth factor for pain has also progressed to clinical trials. These peptibodies illustrate the versatility of the modality. PMID:22820181

Shimamoto, Grant; Gegg, Colin; Boone, Tom; Quéva, Christophe

2012-01-01

362

Pathology Case Study: Fever, Purpura and Hypotension  

NSDL National Science Digital Library

The Department of Pathology at the University of Pittsburgh Medical Center has compiled a wide range of pathology case studies to aid students and instructors in the medical/health science field. In this case, a 20 year old male college student is admitted to the emergency room with "general malaise, low-grade fever, and purplish discoloration on his face. Using the information provided, which includes patient and social history, images and descriptions from his physical exam, the hospital course and microscopic images, students are encouraged to test their knowledge of pathology and diagnose the patient's medical condition. You can check your diagnosis against the official conclusions in the "Final Diagnosis" section. This is an excellent resource for providing students experience with patient history, lab results and diagnostics.

Anhalt, John P.; Aronica, Patricia; Pasculle, A. W.; Richert, Charles A.

2007-11-22

363

Modeling and TARGET: Transportability Analysis Reports Generator  

E-print Network

Modeling and Simulation TARGET: Transportability Analysis Reports Generator What Is TARGET loading Air Loading Model (ALM): aircraft loading What Does TARGET Do? TARGET provides detailed cargo and rail assets, and aircraft to analyze: Deployability of alternative force structures, Changes

364

Mimosine targets serine hydroxymethyltransferase.  

PubMed

The plant amino acid, mimosine, is an extremely effective inhibitor of DNA replication in mammalian cells (Mosca, P. J., Dijkwel, P. A., and Hamlin, J. L. (1992) Mol. Cell. Biol. 12, 4375-4383). Mimosine appears to prevent the formation of replication forks at early-firing origins when delivered to mammalian cells approaching the G1/S boundary, and blocks DNA replication when added to S phase cells after a lag of approximately 2.5 h. We have shown previously that [3H]mimosine can be specifically photocross-linked both in vivo and in vitro to a 50-kDa polypeptide (p50) in Chinese hamster ovary (CHO) cells. In the present study, six tryptic peptides (58 residues total) from p50 were sequenced by tandem mass spectrometry and their sequences were found to be at least 77.5% identical and 96.5% similar to sequences in rabbit mitochondrial serine hydroxymethyltransferase (mSHMT). This assignment was verified by precipitating the [3H]mimosine-p50 complex with a polyclonal antibody to rabbit cSHMT. The 50-kDa cross-linked product was almost undetectable in a mimosine-resistant CHO cell line and in a CHO gly- cell line that lacks mitochondrial, but not cytosolic, SHMT activity. The gly- cell line is still sensitive to mimosine, suggesting that the drug may inhibit both the mitochondrial and the cytosolic forms. SHMT is involved in the penultimate step of thymidylate biosynthesis in mammalian cells and, as such, is a potential target for chemotherapy in the treatment of cancer. PMID:8576220

Lin, H B; Falchetto, R; Mosca, P J; Shabanowitz, J; Hunt, D F; Hamlin, J L

1996-02-01

365

Target-directed catalytic metallodrugs  

PubMed Central

Most drugs function by binding reversibly to specific biological targets, and therapeutic effects generally require saturation of these targets. One means of decreasing required drug concentrations is incorporation of reactive metal centers that elicit irreversible modification of targets. A common approach has been the design of artificial proteases/nucleases containing metal centers capable of hydrolyzing targeted proteins or nucleic acids. However, these hydrolytic catalysts typically provide relatively low rate constants for target inactivation. Recently, various catalysts were synthesized that use oxidative mechanisms to selectively cleave/inactivate therapeutic targets, including HIV RRE RNA or angiotensin converting enzyme (ACE). These oxidative mechanisms, which typically involve reactive oxygen species (ROS), provide access to comparatively high rate constants for target inactivation. Target-binding affinity, co-reactant selectivity, reduction potential, coordination unsaturation, ROS products (metal-associated vs metal-dissociated; hydroxyl vs superoxide), and multiple-turnover redox chemistry were studied for each catalyst, and these parameters were related to the efficiency, selectivity, and mechanism(s) of inactivation/cleavage of the corresponding target for each catalyst. Important factors for future oxidative catalyst development are 1) positioning of catalyst reduction potential and redox reactivity to match the physiological environment of use, 2) maintenance of catalyst stability by use of chelates with either high denticity or other means of stabilization, such as the square planar geometric stabilization of Ni- and Cu-ATCUN complexes, 3) optimal rate of inactivation of targets relative to the rate of generation of diffusible ROS, 4) targeting and linker domains that afford better control of catalyst orientation, and 5) general bio-availability and drug delivery requirements. PMID:23828584

Joyner, J.C.; Cowan, J.A.

2013-01-01

366

Dual targeting of peroxisomal proteins  

PubMed Central

Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed. PMID:24151469

Ast, Julia; Stiebler, Alina C.; Freitag, Johannes; Bölker, Michael

2013-01-01

367

Targeted Marketing and Public Health  

Microsoft Academic Search

Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as

Sonya A. Grier; Shiriki Kumanyika

2010-01-01

368

Inflation Targeting in Latin America  

Microsoft Academic Search

This paper analyzes Latin America’s recent experience with the use of inflation targeting (IT) while the region has made substantial progress toward eradicating high inflation. The paper assesses the implementation and results of inflation targeting in Latin America from a broad perspective. It starts by reviewing the issues relevant for the choice of exchange-rate regimes and monetary frameworks, documenting the

Vittorio Corbo; Klaus Schmidt-Hebbel

2001-01-01

369

Inflation Targeting in Latin America  

Microsoft Academic Search

This paper analyzes Latin America’s recent experience with the use of inflation targeting (IT) while the region has made substantial progress toward eradicating high inflation. The paper assesses the implementation and results of inflation targeting in Latin America from a broad perspective. It starts by reviewing the issues relevant for the choice of exchange-rate regimes and monetary frameworks, documenting the

Vittorio Corbo; Klaus Schmidt-Hebbel

2002-01-01

370

RTE with Li vapor target  

Microsoft Academic Search

High resolution projectile Auger electron spectroscopy is being used to measure cross sections for resonant transfer and excitation (RTE) as a function of projectile energy, in collisions of highly charged ions with a lithium vapor target. Previously H2 and He have been used [4] as targets for RTE studies via high resolution projectile Auger electron spectroscopy. With Li as a

R. Parameswaran; W. J. Axmann; T. J. M. Zouros; B. D. Depaola

1989-01-01

371

Killing cells by targeting mitosis  

Microsoft Academic Search

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

E Manchado; M Guillamot; M Malumbres

2012-01-01

372

Recent progress in targeting cancer  

PubMed Central

In recent years, numerous new targets have been identified and new experimental therapeutics have been developed. Importantly, existing non-cancer drugs found novel use in cancer therapy. And even more importantly, new original therapeutic strategies to increase potency, selectivity and decrease detrimental side effects have been evaluated. Here we review some recent advances in targeting cancer. PMID:22228887

Demidenko, Zoya N.; McCubrey, James A.

2011-01-01

373

Molecular Targeting in Pancreatic Cancer  

Microsoft Academic Search

The mortality and morbidity of tumors of the upper GI tract are formidable with incidence and mortality nearly the same. Therefore, better therapies are necessary, and these are generally molecularly targeted therapies. This chapter focuses on the treatment of pancreatic cancer with targeted therapy. Important cellular pathways are reviewed, including signal transduction, proteasome inhibition, cell cycle, anti-angiogenesis pathways, immunologic therapies,

Scott Wadler

2007-01-01

374

Target migration path morphology of moving targets in spotlight SAR  

NASA Astrophysics Data System (ADS)

This paper examines the signature characteristics of moving targets in spotlight synthetic aperture radar (SAR) image data. This analysis considers the special case in which the radar sensor is assumed to move with constant speed and heading on a level flight path with broadside imaging geometry. It is shown that the resulting defocused smear signature in the spotlight SAR image exhibits range migration effects, as has been shown previously for strip map SAR analysis. In particular, cases of uniform target motion exhibit simply curved range migration paths, whereas non-uniform target motion can cause complicated smear shapes.

Garren, David A.; Scrofani, James W.; Tummala, Murali; McEachen, John C.

2013-05-01

375

Aided targeting system simulation evaluation  

NASA Technical Reports Server (NTRS)

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.

Demaio, Joe; Becker, Curtis

1994-01-01

376

Targeted Therapies for Lung Cancer  

PubMed Central

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

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

2012-01-01

377

A variable optical target simulator  

NASA Technical Reports Server (NTRS)

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.

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

1979-01-01

378

Target Article Epigenetic Perspectives on  

E-print Network

Target Article Epigenetic Perspectives on Development: Evolving Insights on the Origins of the meeting: ``Epigenetics and Behavioral Development Within and Across Generations'' included discussion. The contributions to this special section highlight the importance of the epigenetic regulation of gene expression

Champagne, Frances A.

379

Tumor targeting, trifunctional dendritic wedge.  

PubMed

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

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

2015-01-21

380

Target detection through quantum illumination  

E-print Network

Classical target detection can suffer large error probabilities in noisy and lossy environments when noise photons are mistaken for signal photons reflected from an object. It has been shown theoretically that the correlation ...

Mouradian, Sara L

2012-01-01

381

Cavitation in a Mercury Target  

SciTech Connect

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.

West, C.D.

2000-09-01

382

"Cavitation in a Mercury Target"  

SciTech Connect

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.

West, C.D.

2000-09-06

383

The JLab Frozen Spin Target  

SciTech Connect

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.

Keith, C. D. [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States)

2009-08-04

384

Riboswitches as antibacterial drug targets  

Microsoft Academic Search

New validated cellular targets are needed to reinvigorate antibacterial drug discovery. This need could potentially be filled by riboswitches—messenger RNA (mRNA) structures that regulate gene expression in bacteria. Riboswitches are unique among RNAs that serve as drug targets in that they have evolved to form structured and highly selective receptors for small drug-like metabolites. In most cases, metabolite binding to

Kenneth F Blount; Ronald R Breaker

2006-01-01

385

Ion beam inertial confinement target  

DOEpatents

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.

Bangerter, Roger O. (Danville, CA); Meeker, Donald J. (Livermore, CA)

1985-01-01

386

Passive detection of moving targets  

NASA Astrophysics Data System (ADS)

The paper presents the concept of passive detection of moving targets based on thermal radiation in microwave region. Up to now the passive detection of moving targets, especially airplanes and ground vehicles is performed using infrared sensor. The microwave radiometric methods are now widely used in many other fields of applications, such as radio astronomy, remote sensing, medicine, pollution control, mine detection and other. All these methods are based on measurement of power of thermal noise radiated by hot surface. The usage of power-only information is usually not sufficient to discriminate between moving and stationary target. To sense the target movement different phenomena can be applied. The most fundamental one is Doppler shift of the spectrum of radiating thermal noise. To perform this task complex envelope of received signal must be recorded and Doppler processing must be applied. The Doppler and time correlations are widely used in radio astronomy, for sensing the weather and for high-resolution image creation, but up to now was not exploited for moving target indication, so important in ATC applications. The fundamental problem - distinction between stationary and moving targets is performed by calculating range-Doppler correlation between thermal signals obtained from different localization in multi-static radiometric antenna constellation. Further more, using correlation principles, it is possible to obtain high resolution images of the detected objects.

Kulpa, Krzysztof S.

2005-09-01

387

Molecular Imaging and Targeted Therapies  

PubMed Central

Targeted therapeutic and imaging agents are becoming more prevalent, and are used to treat increasingly smaller segments of the patient population. This has lead to dramatic increases in the costs for clinical trials. Biomarkers have great potential to reduce the numbers of patients needed to test novel targeted agents by predicting or identifying non-response early-on and thus enriching the clinical trial population with patients more likely to respond. Biomarkers are characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers can be used to predict response to specific therapies, predict response regardless of therapy, or to monitor response once a therapy has begun. In terms of drug development, predictive biomarkers have the greatest impact, as they can be used as inclusion criteria for patient segmentation. Prognostic markers are used routinely in clinical practice but do not provide direction for the use of targeted therapies. Imaging biomarkers have distinct advantages over those that require a biopsy sample in that they are “non-invasive” and can be monitored longitudinally at multiple time points in the same patient. This review will examine the role of functional and molecular imaging in predicting response to specific therapies; will explore the advantages and disadvantages of targeting intracellular or extracellular markers; and will discuss the attributes of useful targets and methods for target identification and validation. PMID:20399197

Morse, David L.; Gillies, Robert J.

2010-01-01

388

Ground target tracking-a historical perspective  

Microsoft Academic Search

Airborne sensor platforms such as Joint STARS provide a capability for ground surveillance and monitoring target movements. Because of the high target density and maneuverability, high clutter, low visibility due to terrain masking, etc., ground target tracking presents unique challenges not present in tracking other types of targets. This paper reviews major developments in multi-target tracking over the past four

Chee-Yee Chong; David Garren; Timothy P. Grayson

2000-01-01

389

Inflation targeting as a monetary policy rule  

Microsoft Academic Search

The purpose of the paper is to survey and discuss inflation targeting in the context of monetary policy rules. The paper provides a general conceptual discussion of monetary policy rules, attempts to clarify the essential characteristics of inflation targeting, compares inflation targeting to monetary targeting and nominal-GDP targeting, and draws some conclusions for the monetary policy of the European System

Lars E. O. Svensson

1999-01-01

390

Chemical Structural Novelty: On-Targets and Off-Targets  

PubMed Central

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

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

2011-01-01

391

Targets and methods for target preparation for radionuclide production  

DOEpatents

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.

Zhuikov, Boris L; Konyakhin, Nicolai A; Kokhanyuk, Vladimir M; Srivastava, Suresh C

2012-10-16

392

Optimum Polarization for Foliage Camouflaged Target Discrimination  

E-print Network

Optimum Polarization for Foliage Camouflaged Target Discrimination Using a Genetic Algorithm camouflaged target detection at low microwave frequencies is investigated, using a powerful foliage and hard. Based on fully polarimetric simulation results of a foliage camouflaged metallic target a polarization

Sarabandi, Kamal

393

Novel targets for antidepressant therapies.  

PubMed

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

Holtzheimer, Paul E; Nemeroff, Charles B

2008-12-01

394

Myc proteins as therapeutic targets  

PubMed Central

Myc proteins (c-myc, Mycn and Mycl) target proliferative and apoptotic pathways vital for progression in cancer. Amplification of the MYCN gene has emerged as one of the clearest indicators of aggressive and chemotherapy-refractory disease in children with neuroblastoma, the most common extracranial solid tumor of childhood. Phosphorylation and ubiquitin-mediated modulation of Myc protein influence stability and represent potential targets for therapeutic intervention. Phosphorylation of Myc proteins is controlled in-part by the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt/mTOR signaling, with additional contributions from Aurora A kinase. Myc proteins regulate apoptosis in part through interactions with the p53/Mdm2/Arf signaling pathway. Mutation in p53 is commonly observed in patients with relapsed neuroblastoma, contributing to both biology and therapeutic resistance. This review examines Myc function and regulation in neuroblastoma, and discusses emerging therapies that target Mycn. PMID:20101214

Gustafson, WC; Weiss, WA

2010-01-01

395

A cryogenic infrared calibration target  

NASA Astrophysics Data System (ADS)

A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R ? 0.003, from 800 to 4800 cm-1 (12 - 2 ?m). Upon expanding the spectral range under consideration to 400-10 000 cm-1 (25 - 1 ?m) the observed performance gracefully degrades to R ? 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to ˜4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials—Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder—are characterized and presented.

Wollack, E. J.; Kinzer, R. E.; Rinehart, S. A.

2014-04-01

396

High-efficiency target-ion sources for RIB generation  

SciTech Connect

A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory.

Alton, G.D.

1993-12-31

397

Observations of Spacecraft Targets, Unusual Asteroids, and Targets of Opportunity  

NASA Technical Reports Server (NTRS)

Obtain physical and astrometric observations of: (1) spacecraft targets to support mission operations; (2) known asteroids with unusual orbits to help determine their origin; and (3) newly discovered minor planets (including both asteroids and comets) that represent a particular opportunity to add significant new knowledge of the Solar System.

Tholen, David J.

1998-01-01

398

The Smart Targeting of Nanoparticles  

PubMed Central

One major challenge in nanomedicine is how to selectively deliver nanoparticles to diseased tissues. Nanoparticle delivery system requires targeting for specific delivery to pathogenic sites when enhanced permeability and retention (EPR) is not suitable or inefficient. Functionalizing nanoparticles is a widely-used technique that allows for conjugation with targeting ligands, which possess inherent ability to direct selective binding to cell types or states and, therefore, confer “smartness” to nanoparticles. This review illustrates methods of ligand-nanoparticle functionalization, provides a cross-section of various ligand classes, including small molecules, peptides, antibodies, engineered proteins, or nucleic acid aptamers, and discusses some unconventional approaches currently under investigation. PMID:23470005

Friedman, Adam D.; Claypool, Sarah E.; Liu, Rihe

2014-01-01

399

Targeting cancer using cholesterol conjugates  

PubMed Central

Conjugation of cholesterol moiety to active compounds for either cancer treatment or diagnosis is an attractive approach. Cholesterol derivatives are widely studied as cancer diagnostic agents and as anticancer derivatives either in vitro or in vivo using animal models. In largely growing studies, anticancer agents have been chemically conjugated to cholesterol molecules, to enhance their pharmacokinetic behavior, cellular uptake, target specificity, and safety. To efficiently deliver anticancer agents to the target cells and tissues, many different cholesterol–anticancer conjugates were synthesized and characterized, and their anticancer efficiencies were tested in vitro and in vivo. PMID:24493968

Radwan, Awwad A.; Alanazi, Fares K.

2013-01-01

400

Targeting antibodies to the cytoplasm  

PubMed Central

A growing number of research consortia are now focused on generating antibodies and recombinant antibody fragments that target the human proteome. A particularly valuable application for these binding molecules would be their use inside a living cell, e.g., for imaging or functional intervention. Animal-derived antibodies must be brought into the cell through the membrane, whereas the availability of the antibody genes from phage display systems allows intracellular expression. Here, the various technologies to target intracellular proteins with antibodies are reviewed. PMID:21099369

Marschall, Andrea L J; Frenzel, André; Schirrmann, Thomas; Schüngel, Manuela

2011-01-01

401

Tumor Targeting via Integrin Ligands  

PubMed Central

Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side-effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability, and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor-specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug-delivery systems, and discuss the prospects of such therapies to specifically target tumor cells. PMID:24010121

Marelli, Udaya Kiran; Rechenmacher, Florian; Sobahi, Tariq Rashad Ali; Mas-Moruno, Carlos; Kessler, Horst

2013-01-01

402

Mercury Intense Target (MERIT) Update  

E-print Network

Profile · 15 Tesla peak field has a 1-sec flat top at t = 9.5 s Peak Field Stray field profile #12;9 OAK, supports, sump tank, instruments, filtered vent, supply line, laser optic windows, and beam windows/TTF - Characterize operating parameters of the target equipment and the laser diagnostic (pictures of Hg jet) - Ship

McDonald, Kirk

403

Substrate-targeting ?-secretase modulators  

PubMed Central

Selective lowering of A?42 levels (the 42-residue isoform of the amyloid-? peptide) with small-molecule ?-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer’s disease1. To identify the target of these agents we developed biotinylated photo-activatable GSMs. GSM photoprobes did not label the core proteins of the ?-secretase complex, but instead labelled the ?-amyloid precursor protein (APP), APP carboxy-terminal fragments and amyloid-? peptide in human neuroglioma H4 cells. Substrate labelling was competed by other GSMs, and labelling of an APP ?-secretase substrate was more efficient than a Notch substrate. GSM interaction was localized to residues 28–36 of amyloid-?, a region critical for aggregation. We also demonstrate that compounds known to interact with this region of amyloid-? act as GSMs, and some GSMs alter the production of cell-derived amyloid-? oligomers. Furthermore, mutation of the GSM binding site in the APP alters the sensitivity of the substrate to GSMs. These findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in A?42 production and inhibition of amyloid-? aggregation, which may synergistically reduce amyloid-? deposition in Alzheimer’s disease. These data also demonstrate the existence and feasibility of ‘substrate targeting’ by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of ‘druggable’ targets2. PMID:18548070

Kukar, Thomas L.; Ladd, Thomas B.; Bann, Maralyssa A.; Fraering, Patrick C.; Narlawar, Rajeshwar; Maharvi, Ghulam M.; Healy, Brent; Chapman, Robert; Welzel, Alfred T.; Price, Robert W.; Moore, Brenda; Rangachari, Vijayaraghavan; Cusack, Bernadette; Eriksen, Jason; Jansen-West, Karen; Verbeeck, Christophe; Yager, Debra; Eckman, Christopher; Ye, Wenjuan; Sagi, Sarah; Cottrell, Barbara A.; Torpey, Justin; Rosenberry, Terrone L.; Fauq, Abdul; Wolfe, Michael S.; Schmidt, Boris; Walsh, Dominic M.; Koo, Edward H.; Golde, Todd E.

2009-01-01

404

Targeting lipophilic cations to mitochondria  

Microsoft Academic Search

Mitochondrial function and dysfunction contributes to a range of important aspects of biomedical research. Consequently there is considerable interest in developing approaches to modify and report on mitochondria in cells and in vivo. One approach has been to target bioactive molecules to mitochondria by conjugating them to lipophilic cations. Due to the large mitochondrial membrane potential, the cations are accumulated

Michael P. Murphy

2008-01-01

405

Polarimetric imaging of underwater targets  

NASA Astrophysics Data System (ADS)

Underwater imaging is challenging because of the significant attenuation of light due to absorption and scattering of light in water. Using polarization properties of light is one of the options for improving image quality. We present results of imaging of a polarized target in open ocean (Curacao) and coastal (NY Bight) waters. The target in the shape of a square is divided into several smaller squares, each of which is covered with a polarizing film with different polarization orientations or transmission coefficients was placed on a mirror and imaged under water by a green-band full-Stokes polarimetric video camera at the full range of azimuth angles against the Sun. The values of the Stokes vector components from the images are compared with the modeled image of the target using radiative transfer code for the atmosphere-ocean system combined with the simple imaging model. It is shown that even in clear water the impact of the water body on the polarized underwater image is very significant and retrieval of target polarization characteristics from the image is extremely challenging.

Gilerson, Alex; Carrizo, Carlos; Tonizzo, Alberto; Ibrahim, Amir; El-Habashi, Ahmed; Foster, Robert; Ahmed, Samir

2013-06-01

406

Raw eggs-moving target  

NASA Astrophysics Data System (ADS)

High school physics students often have difficulty with understanding when and where to use an appropriate calculation to solve a problem. In this activity students have to solve a real problem using formulas they have seen before, but in a context with which they are unfamiliar; namely dropping a raw egg on a moving target-their instructor.

Forrest, Doug

1999-09-01

407

Aptamers for Targeted Drug Delivery  

PubMed Central

Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

Ray, Partha; White, Rebekah R.

2010-01-01

408

Target Audience: Health care professionals  

E-print Network

Target Audience: Health care professionals Workshop Facilitator: Valerie Spironello, MSW, RSW Valerie has been a social worker for over 20 years working in a variety of settings including health care provided workshops and presentations to health care providers on a variety of topics such as compassion

Hitchcock, Adam P.

409

Right on Target: Catapult Game  

NSDL National Science Digital Library

Students experience the engineering design process as they design and build accurate and precise catapults using common materials. They use their catapults to participate in a game in which they launch Ping-Pong balls to attempt to hit various targets.

Integrated Teaching and Learning Program,

410

Tumor Targeting via Integrin Ligands.  

PubMed

Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side-effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability, and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor-specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug-delivery systems, and discuss the prospects of such therapies to specifically target tumor cells. PMID:24010121

Marelli, Udaya Kiran; Rechenmacher, Florian; Sobahi, Tariq Rashad Ali; Mas-Moruno, Carlos; Kessler, Horst

2013-01-01

411

Targeted multi-pinhole SPECT  

PubMed Central

Purpose Small-animal single photon emission computed tomography (SPECT) with focused multi-pinhole collimation geometries allows scanning modes in which large amounts of photons can be collected from specific volumes of interest. Here we present new tools that improve targeted imaging of specific organs and tumours, and validate the effects of improved targeting of the pinhole focus. Methods A SPECT system with 75 pinholes and stationary detectors was used (U-SPECT-II). An XYZ stage automatically translates the animal bed with a specific sequence in order to scan a selected volume of interest. Prior to stepping the animal through the collimator, integrated webcams acquire images of the animal. Using sliders, the user designates the desired volume to be scanned (e.g. a xenograft or specific organ) on these optical images. Optionally projections of an atlas are overlaid semiautomatically to locate specific organs. In order to assess the effects of more targeted imaging, scans of a resolution phantom and a mouse myocardial phantom, as well as in vivo mouse cardiac and tumour scans, were acquired with increased levels of targeting. Differences were evaluated in terms of count yield, hot rod visibility and contrast-to-noise ratio. Results By restricting focused SPECT scans to a 1.13-ml resolution phantom, count yield was increased by a factor 3.6, and visibility of small structures was significantly enhanced. At equal noise levels, the small-lesion contrast measured in the myocardial phantom was increased by 42%. Noise in in vivo images of a tumour and the mouse heart was significantly reduced. Conclusion Targeted pinhole SPECT improves images and can be used to shorten scan times. Scan planning with optical cameras provides an effective tool to exploit this principle without the necessity for additional X-ray CT imaging. PMID:21063706

Vastenhouw, Brendan; van der Have, Frans; Blezer, Erwin L. A.; Bleeker, Wim K.; Beekman, Freek J.

2010-01-01

412

Behavioural Targeting & Law 1 March 2013  

E-print Network

for Information Law #12;2 Contents 1. Behavioural targeting 2. Audience buying 3. Right to privacy 4. Right;26 Campaigngrid.com #12;27 Targeting ­ Politics `Targeting fathers aged 35-44 in Texas who frequent gun enthusiast (i) Tracking people online (ii) Building profiles (iii) Targeted advertising #12;30 Audience Buying 1

Hoepman, Jaap-Henk

413

Toll-like receptors as pharmacological targets  

Microsoft Academic Search

TLRs represent attractive drug targets for the modulation of the immune response and hold promising applications for the treatment of infection and inflammation as well as for the development of vaccine adjuvants. Two main strategies for targeting TLRs seem to be promising for drug development: targeting TLRs with synthetic agonists or antagonists and targeting the protein-protein interaction involved in the

Bruno Conti; Christopher N. Davis; M. Margarita Behrens; Julius Rebek; Tamas Bartfai

414

Possible Target Options Michael A. Green  

E-print Network

are obvious medium Z target materials. A less obvious candidate is a titanium or niobium-titanium alloy target. These materials are strong and non- corrosive. The problem with niobium-titanium is its poor thermal conductivity are best for the target. #12;Possible Elemental Candidate Materials for Targets Element Z Density Melt

McDonald, Kirk

415

Nonsinusoidal radar signal design for stealth targets  

Microsoft Academic Search

The detection of stealth point targets challenges the design of conventional radars using sinusoidal carriers since the objective of stealth technology is to reduce the radar cross section (RCS) of targets to a level where the radar receiver cannot detect the target. While there are a number of techniques employing different technologies to reduce the RCS of targets, shaping and

Nasser J. Mohamed

1995-01-01

416

Proton beam targets shot on PBFA II  

SciTech Connect

In recent proton beam experiments on PBFA II, foam-filled gold targets and gas-filled spherical exploding pushers were shot as physics targets. Surrounding these targets were gold foils used to characterize the beam. The target fabrication and characterization are presented in this paper.

Derzon, D.K.; Aubert, J.H.; Schneider, D.A.; Assink, R.A. (Sandia National Labs., Albuquerque, NM (United States)); Sawyer, P.S. (Ktech Corp., Albuquerque, NM (United States)); McNamara, W.F. (L and M Technologies, Inc., Albuquerque, NM (United States))

1992-01-01

417

Proton beam targets shot on PBFA II  

SciTech Connect

In recent proton beam experiments on PBFA II, foam-filled gold targets and gas-filled spherical exploding pushers were shot as physics targets. Surrounding these targets were gold foils used to characterize the beam. The target fabrication and characterization are presented in this paper.

Derzon, D.K.; Aubert, J.H.; Schneider, D.A.; Assink, R.A. [Sandia National Labs., Albuquerque, NM (United States); Sawyer, P.S. [Ktech Corp., Albuquerque, NM (United States); McNamara, W.F. [L and M Technologies, Inc., Albuquerque, NM (United States)

1992-04-01

418

Gated viewing for target detection and target recognition  

NASA Astrophysics Data System (ADS)

Gated viewing using short pulse lasers and fast cameras offers many new possibilities in imaging compared with passive EO imaging. Among these we note ranging capability, large target-to-background contrast also in low visibility, good penetration capability trough obscurants and vegetation as well as through shadows in buildings, cars, etc. We also note that short wavelength laser systems have better angular resolution than long-wave infrared systems of the same aperture size. This gives an interesting potential of combined IR and laser systems for target detection and classification. Beside military applications civilian applications of gated viewing for search and rescue as well as vehicle enhanced vision and other applications are in progress. This presentation investigates the performance for gated viewing systems during different atmospheric conditions, including obscurants and gives examples of experimental data. The paper also deals with signal processing of gated viewing images for target detection. This is performed in two steps. First, image frames containing information of interest are found. In a second step those frames are investigated further to evaluate if man-made objects are present. In this step a sequence of images (video frames) are set up as a 3-D volume to incorporate spatial information. The object will then be detected using a set of quadrature filters operating on the volume.

Steinvall, Ove K.; Olsson, Hakan; Bolander, Goeran; Groenwall, Christina A.; Letalick, Dietmar

1999-05-01

419

Tyrosine kinase inhibitors: Multi-targeted or single-targeted?  

PubMed Central

Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients. PMID:21603317

Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

2011-01-01

420

Target explosion generated fireballs in the nitrogen filled target chamber of the light ion fusion target development facility  

SciTech Connect

Molecular nitrogen is a possible choice for the target chamber gas in the light ion beam driven target development facility. The response of a nitrogen target chamber gas to fusion target explosions is considered. Targets with yields of 200 MJ, 400 MJ and 800 MJ are considered for a target chamber 3 m in radius and 6 m high which is filled with nitrogen gas at a density of 7.07 X 10/sup 17/ molecules/cm/sup 3/. The soft x-rays and ions from the explosion of these targets are stopped in short distances in this gas and create a hot spherical fireball in the center of the target chamber. Heat fluxes and shock pressures on the target chamber first walls due to these fireballs are presented and nitrogen is shown to be an acceptable cavity gas from the point of view of first wall loading.

Peterson, R.R.; Moses, G.A.

1983-09-01

421

Effects of target typicality on categorical search  

PubMed Central

The role of target typicality in a categorical visual search task was investigated by cueing observers with a target name, followed by a five-item target present/absent search array in which the target images were rated in a pretest to be high, medium, or low in typicality with respect to the basic-level target cue. Contrary to previous work, we found that search guidance was better for high-typicality targets compared to low-typicality targets, as measured by both the proportion of immediate target fixations and the time to fixate the target. Consistent with previous work, we also found an effect of typicality on target verification times, the time between target fixation and the search judgment; as target typicality decreased, verification times increased. To model these typicality effects, we trained Support Vector Machine (SVM) classifiers on the target categories, and tested these on the corresponding specific targets used in the search task. This analysis revealed significant differences in classifier confidence between the high-, medium-, and low-typicality groups, paralleling the behavioral results. Collectively, these findings suggest that target typicality broadly affects both search guidance and verification, and that differences in typicality can be predicted by distance from an SVM classification boundary. PMID:25274990

Maxfield, Justin T.; Stalder, Westri D.; Zelinsky, Gregory J.

2014-01-01

422

Anticancer Agents Targeted to Sirtuins.  

PubMed

Sirtuins are nicotinamide adenine dinucleotide+-dependent deacetylases of which there are seven isoforms (SIRT1-7). Sirtuin activity is linked to gene expression, lifespan extension, neurodegeneration, and age-related disorders. Numerous studies have suggested that sirtuins could be of great significance with regard to both antiaging and tumorigenesis, depending on its targets in specific signaling pathways or in specific cancers. Recent studies have identified small chemical compounds that modulate sirtuins, and these modulators have enabled a greater understanding of the biological function and molecular mechanisms of sirtuins. This review highlights the possibility of sirtuins, especially SIRT1 and SIRT2, for cancer therapy targets, and focuses on the therapeutic potential of sirtuin modulators both in cancer prevention and treatment. PMID:25486244

Kozako, Tomohiro; Suzuki, Takayoshi; Yoshimitsu, Makoto; Arima, Naomichi; Honda, Shin-Ichiro; Soeda, Shinji

2014-01-01

423

Multishell inertial confinement fusion target  

DOEpatents

A method of fabricating multishell fuel targets for inertial confinement fusion usage. Sacrificial hemispherical molds encapsulate a concentric fuel pellet which is positioned by fiber nets stretched tautly across each hemispherical mold section. The fiber ends of the net protrude outwardly beyond the mold surfaces. The joint between the sacrificial hemispheres is smoothed. A ceramic or glass cover is then deposited about the finished mold surfaces to produce an inner spherical surface having continuously smooth surface configuration. The sacrificial mold is removed by gaseous reaction accomplished through the porous ceramic cover prior to enclosing of the outer sphere by addition of an outer coating. The multishell target comprises the inner fuel pellet concentrically arranged within a surrounding coated cover or shell by fiber nets imbedded within the cover material.

Holland, James R. (Butler, PA); Del Vecchio, Robert M. (Vandergrift, PA)

1984-01-01

424

Multishell inertial confinement fusion target  

DOEpatents

A method of fabricating multishell fuel targets for inertial confinement fusion usage. Sacrificial hemispherical molds encapsulate a concentric fuel pellet which is positioned by fiber nets stretched tautly across each hemispherical mold section. The fiber ends of the net protrude outwardly beyond the mold surfaces. The joint between the sacrificial hemispheres is smoothed. A ceramic or glass cover is then deposited about the finished mold surfaces to produce an inner spherical surface having continuously smooth surface configuration. The sacrificial mold is removed by gaseous reactions accomplished through the porous ceramic cover prior to enclosing of the outer sphere by addition of an outer coating. The multishell target comprises the inner fuel pellet concentrically arranged within a surrounding coated cover or shell by fiber nets imbedded within the cover material.

Holland, James R. (Butler, PA); Del Vecchio, Robert M. (Vandergrift, PA)

1987-01-01

425

Hox Targets and Cellular Functions  

PubMed Central

Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function. PMID:24490109

Sánchez-Herrero, Ernesto

2013-01-01

426

Novel targets for antidepressant therapies  

Microsoft Academic Search

Most depressed patients fail to achieve remission despite adequate antidepressant monotherapy, and a substantial minority\\u000a show minimal improvement despite optimal and aggressive therapy. However, major advances have taken place in elucidating the\\u000a neurobiology of depression, and several novel targets for antidepressant therapy have emerged. Three primary approaches are\\u000a currently being taken: 1) optimizing the pharmacologic modulation of monoaminergic neurotransmission, 2)

Paul E. Holtzheimer; Charles B. Nemeroff

2008-01-01

427

Fixed target flammable gas upgrades  

SciTech Connect

In the past, fixed target flammable gas systems were not supported in an organized fashion. The Research Division, Mechanical Support Department began to support these gas systems for the 1995 run. This technical memo describes the new approach being used to supply chamber gasses to fixed target experiments at Fermilab. It describes the engineering design features, system safety, system documentation and performance results. Gas mixtures provide the medium for electron detection in proportional and drift chambers. Usually a mixture of a noble gas and a polyatomic quenching gas is used. Sometimes a small amount of electronegative gas is added as well. The mixture required is a function of the specific chamber design, including working voltage, gain requirements, high rate capability, aging and others. For the 1995 fixed target run all the experiments requested once through gas systems. We obtained a summary of problems from the 1990 fixed target run and made a summary of the operations logbook entries from the 1991 run. These summaries primarily include problems involving flammable gas alarms, but also include incidents where Operations was involved or informed. Usually contamination issues were dealt with by the experimenters. The summaries are attached. We discussed past operational issues with the experimenters involved. There were numerous incidents of drift chamber failure where contaminated gas was suspect. However analyses of the gas at the time usually did not show any particular problems. This could have been because the analysis did not look for the troublesome component, the contaminant was concentrated in the gas over the liquid and vented before the sample was taken, or that contaminants were drawn into the chambers directly through leaks or sub-atmospheric pressures. After some study we were unable to determine specific causes of past contamination problems, although in argon-ethane systems the problems were due to the ethane only.

Schmitt, R.; Squires, B.; Gasteyer, T.; Richardson, R.

1996-12-01

428

Pharmaceutical Targeting of Chemokine Receptors  

Microsoft Academic Search

In this chapter, we will give a perspective of in vitro assays used in drug discovery when targeting chemokine receptors.\\u000a We outline the complexity of the chemokine system and give a historical perspective on the in vitro assays and types of assays\\u000a used at different stages of discovery, followed by several examples of successes and failures in clinical trials. Finally,

Sofia Ribeiro; Richard Horuk

429

Targeting telomerase for cancer therapeutics  

PubMed Central

One of the hallmarks of advanced malignancies is continuous cell growth and this almost universally correlates with the reactivation of telomerase. Although there is still much we do not understand about the regulation of telomerase, it remains a very attractive and novel target for cancer therapeutics. Several clinical trials have been initiated, and in this review we highlight some of the most promising approaches and conclude by speculating on the role of telomerase in cancer stem cells. PMID:18231105

Shay, J W; Keith, W N

2008-01-01

430

Novel anticancer therapeutics targeting telomerase.  

PubMed

Telomeres are protective caps at the ends of human chromosomes. Telomeres shorten with each successive cell division in normal human cells whereas, in tumors, they are continuously elongated by human telomerase reverse transcriptase (hTERT). Telomerase is overexpressed in 80-95% of cancers and is present in very low levels or is almost undetectable in normal cells. Because telomerase plays a pivotal role in cancer cell growth it may serve as an ideal target for anticancer therapeutics. Inhibition of telomerase may lead to a decrease of telomere length resulting in cell senescence and apoptosis in telomerase positive tumors. Several strategies of telomerase inhibition are reviewed, including small molecule inhibitors, antisense oligonucleotides, immunotherapies and gene therapies, targeting the hTERT or the ribonucleoprotein subunit hTER. G-quadruplex stabilizers, tankyrase and HSP90 inhibitors targeting telomere and telomerase assembly, and T-oligo approach are also covered. Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001). Most of these agents have entered phase I and II clinical trials in patients with various tumors, and have shown good response rates as evidenced by a reduction in tumor cell growth, increased overall disease survival, disease stabilization in advanced staged tumors and complete/partial responses. Most therapeutics have shown to be more effective when used in combination with standard therapies, resulting in concomitant telomere shortening and tumor mass shrinkage, as well as preventing tumor relapse and resistance to single agent therapy. PMID:22841437

Ruden, Maria; Puri, Neelu

2013-08-01

431

Coherent Communications, Imaging and Targeting  

SciTech Connect

Laboratory and field demonstration results obtained as part of the DARPA-sponsored Coherent Communications, Imaging and Targeting (CCIT) program are reviewed. The CCIT concept uses a Phase Conjugation Engine based on a quadrature receiver array, a hologram processor and a spatial light modulator (SLM) for high-speed, digital beam control. Progress on the enabling MEMS SLM, being developed by a consortium consisting of LLNL, academic institutions and small businesses, is presented.

Stappaerts, E; Baker, K; Gavel, D; Wilks, S; Olivier, S; Brase, J; Olivier, S; Brase, J

2003-10-03

432

Novel therapeutic targets for hypertension  

Microsoft Academic Search

Despite the existence of established, effective therapies for hypertension, new methods of blood pressure and cardiovascular risk reduction are still needed. Novel approaches are targeted towards treating resistant hypertension, improving blood-pressure control, and achieving further risk reduction beyond blood-pressure lowering. Modulation of the renin–angiotensin–aldosterone system (RAAS) provides the rationale for current antihypertensive therapies, including the relatively new agents eplerenone and

Ludovit Paulis; Thomas Unger

2010-01-01

433

Targeting a low carbon estate.  

PubMed

Sustainability specialists within global professional services consultancy Arup have developed a statistical model based on Carbon Trust-collated data that they believe will enable owners and occupiers of even large estates to identify the most cost-effective means of improving their buildings' sustainability both now and in the future. As senior engineer Thomas Briault explains, the model, developed to address the Climate Change Act's 2050 carbon reduction targets, will even factor in such uncertain aspects as future economic growth. PMID:19911557

Briault, Thomas

2009-10-01

434

Promising therapeutic targets in neuroblastoma  

PubMed Central

Neuroblastoma, the most common extra- cranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease, and have 5-year EFS of less than 50%. New approaches with targeted therapy may improve efficacy without increased toxicity. The current review will evaluate three promising targeted therapies, including 131I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical taken up by the human norepinephrine transporter expressed in 90% of neuroblastomas, immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, expressed on 98% of neuroblastoma cells, and inhibitors of ALK, a tyrosine kinase which is mutated or amplified in approximately 10% of neuroblastoma and expressed on the surface of most neuroblastoma cells. Early phase trials have confirmed the activity of 131I-MIBG in relapsed neuroblastoma, with response rates of about 30%, but the technical aspects of administration of large amounts of radioactivity in young children and the limited access have hindered incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also demonstrated activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small molecule inhibitor of ALK has promising pre-clinical activity for neuroblastoma, and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma. PMID:22589483

Matthay, Katherine K.; George, Rani E.; Yu, Alice L.

2012-01-01

435

HPM coupling into realistic targets  

SciTech Connect

High-Power Microwave coupling into targets of interest is extremely difficult to assess analytically or numerically. The practicalities of accurately modeling physical structures, as well as the subtlety of determining which simplifications are allowable for the accuracy needed, require that target interaction calculations be verified by careful laboratory measurements. In addition, the differences in construction techniques and tolerances on joints and seams make an experimental scan of the parameter space essential if we are to establish rules-of-thumb for coupling into systems. To meet this need for a benchmark for HPM coupling calculations, we have designed and constructed several RF shielding enclosures with generic but realistic joints and seams. We measured the coupling of RF into these enclosures over the frequency range of 45 MHz to 18 GHz, recording both amplitude and phase information. These data allow us to evaluate the response of various ports-of-entry to both continuous wave and pulsed sources. We can see trends with frequency for various port of entry types that relate to relatively simple geometric factors. This paper outlines what these results for generic targets imply for HPM coupling to real systems.

Bacon, L.D.; Aurand, J.F.; Toth, R.P.

1988-01-01

436

TARGETED THERAPIES FOR PANCREATIC CANCER  

PubMed Central

Introduction Pancreatic cancer is a devastating malignancy and a leading cause of cancer mortality. Furthermore, early diagnosis represents a serious hurdle for clinicians as symptoms are non-specific and usually manifest in advanced, treatment-resistant stages of the disease. Sources of data Here, we review the rationale and progress of targeted therapies currently under investigation. Areas of agreement At present, chemoradiation regimes are administered palliatively, and produce only marginal survival benefits, underscoring a desperate need for more effective treatment modalities. Areas of controversy Questions have been raised as to whether erlotinib, the only targeted therapy to attain a statistically significant increase in median survival, is cost-effective. Growing points The last decade of research has provided us with a wealth of information regarding the molecular nature of pancreatic cancer, leading to the identification of signalling pathways and their respective components which are critical for the maintenance of the malignant phenotype. Areas timely for developing research These proteins thus represent ideal targets for novel molecular therapies which embody an urgently needed novel treatment strategy. PMID:18753179

Danovi, S A; Wong, H H; Lemoine, N R

2010-01-01

437

Targeting TGF-? signaling in cancer  

PubMed Central

Introduction The transforming growth factor-? (TGF-?) signaling pathway has a pivotal role in tumor suppression and yet, paradoxically, in tumor promotion. Functional context dependent insights into the TGF-? pathway are crucial in developing TGF-?-based therapeutics for cancer. Areas covered This review discusses the molecular mechanism of the TGF-? pathway and describes the different ways of tumor suppression by TGF-?. It is then explained how tumors can evade these effects and how TGF-? contributes to further growing and spreading of some of the tumors. In the last part of the review, the data on targeting TGF-? pathway for cancer treatment is assessed. This review focuses on anti-TGF-? based treatment and other options targeting activated pathways in tumors where the TGF-? tumor suppressor pathway is lost. Pre-clinical as well up to date results of the most recent clinical trials are given. Expert opinion Targeting the TGF-? pathway can be a promising direction in cancer treatment. However, several challenges still exist, the most important are differentiating between the carcinogenic effects of TGF-? and its other physiological roles, and delineating the tumor suppressive versus the tumor promoting roles of TGF-? in each specific tumor. Future studies are needed in order to find safer and more effective TGF-?-based drugs. PMID:23651053

Katz, Lior H; Li, Ying; Chen, Jiun-Sheng; Muñoz, Nina M; Majumdar, Avijit; Chen, Jian; Mishra, Lopa

2013-01-01

438

The npdgamma liquid parahydrogen target  

NASA Astrophysics Data System (ADS)

The NPDGamma Experiment is measuring the parity-violating correlation Agamma between neutron spin and gamma momentum in the radiative capture of a polarized cold neutron beam on a cryogenic liquid parahydrogen target. This measurement is expected to give insight into theories that incorporate the weak interaction into what is primarily a strongly interacting system. This dissertation discusses the operation and characterization of the liquid hydrogen target, including the calibration of the instrumentation that monitors the state of the hydrogen. An important consideration is the fact that for safety reasons the instrumentation in direct contact with the hydrogen is limited, and so a detailed understanding of the target design and of the properties of hydrogen is required in order to interpret the state of the system. For this experiment, it is essential that the hydrogen be kept mostly in the para state in order to prevent the beam from being significantly depolarized before capture. Since the uncatalyzed conversion rate is slow, an ortho-para conversion loop is used to promote conversion from the room temperature orthohydrogen fraction to the fraction associated with the temperatures of the cryogenic vessel. In addition to the calibration and characterization studies, a method is introduced for placing an empirical limit on the deviation of the orthohydrogen fraction inside the vessel from the desired level associated with the temperature of the ortho-para conversion catalyst and vessel. This method, which does not require precise knowledge of the parahydrogen cross section, involves observing the transmission of the beam through the target while the rate of flow of hydrogen through the ortho-para conversion loop is changed. In addition to the studies of the hydrogen target, this dissertation discusses a calibration of some 3He ion chambers that monitor the flux of the neutron beam and that are used to perform beam transmission measurements. This calibration, which involves a study of the noise inherent in the signal due to neutron capture, does not involve comparison to a separate calibrated detector.

Gillis, Robert Chat

439

Interleukin-11 levels in healthy and thrombocytopenic neonates.  

PubMed

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. Although recombinant human (rh) thrombopoietin remains under therapeutic development, rhIL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, nothing is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis (NEC) with or without thrombocytopenia. At birth IL-11 was undetectable (<10 pg/mL) in healthy term neonates (n = 20) and 27 of 31 (87%) stable preterm neonates. Three stable preterm neonates with detectable IL-11 (mean+/-SD, 11.3 +/- 0.4 pg/mL; median, 11.6 pg/mL) suffered chorioamnionitis, the remaining neonate (IL-11, 14 pg/mL) being one of nine with early onset thrombocytopenia (present by <72 h of age). IL-11 was also measured in 58 preterm neonates with suspected sepsis or NEC. In 25 of 58, sepsis or NEC was unconfirmed and IL-11 was undetectable. By contrast, 14 of 33 with proven sepsis or NEC had elevated IL-11 (median, 14.9 pg/mL; range, 11.2-92.2 pg/mL). Of these 33 neonates, 19 developed thrombocytopenia: nine of 19 (47%) had detectable IL-11 and 10 of 19 (53%) did not (p > 0.05). Although its role in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response. PMID:12032273

McCloy, Mary P; Roberts, Irene A G; Howarth, Lucy J; Watts, Timothy L; Murray, Neil A

2002-06-01

440

Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms.  

PubMed

Alcoholism is a major public health problem and resembles, in many ways, other chronic relapsing medical conditions. At least 2 separate dimensions of its symptomatology offer targetable pathophysiological mechanisms. Systems that mediate positive reinforcement by alcohol are likely important targets in early stages of the disease, particularly in genetically susceptible individuals. In contrast, long term neuroadaptive changes caused by chronic alcohol use primarily appear to affect systems mediating negative affective states, and gain importance following a prolonged history of dependence. Feasibility of pharmacological treatment in alcoholism has been demonstrated by a first wave of drugs which consists of 3 currently approved medications, the aldehyde dehydrogenase blocker disulfiram, the opioid antagonist naltrexone (NTX) and the functional glutamate antagonist acamprosate (ACM). The treatment toolkit is likely to be expanded in the near future. This will improve overall efficacy and allow individualized treatment, ultimately taking in account the patient's genetic makeup. In a second wave, early human efficacy data are available for the 5HT3 antagonist ondansetron, the GABA-B agonist baclofen and the anticonvulsant topiramate. The third wave is comprised of compounds predicted to be effective based on a battery of animal models. Using such models, a short list of additional targets has accumulated sufficient preclinical validation to merit clinical development. These include the cannabinoid CB1 receptor, receptors modulating glutamatergic transmission (mGluR2, 3 and 5), and receptors for stress-related neuropeptides corticotropin releasing factor (CRF), neuropeptide Y (NPY) and nociceptin. Once novel treatments are developed, the field faces a major challenge to assure their delivery to patients. PMID:16545872

Heilig, Markus; Egli, Mark

2006-09-01

441

Towards large scale multi-target tracking  

NASA Astrophysics Data System (ADS)

Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

2014-06-01

442

HYPERSPECTRAL TARGET DETECTION FROM INCOHERENT PROJECTIONS: NONEQUIPROBABLE TARGETS AND INHOMOGENEOUS SNR  

E-print Network

, and the known a priori probabilities of the targets. Index Terms-- Hyperspectral imaging, Target detection, False Discovery Rate, Incoherent projections, Compressive sensing 1. HYPERSPECTRAL TARGET DETECTION Hyperspectral imaging combines spatial and spectral information, and thus enables one to characterize

Raginsky, Maxim

443

Adaptive optics to enhance target recognition  

NASA Astrophysics Data System (ADS)

Target recognition can be enhanced by reducing image degradation due to atmospheric turbulence. This is accomplished by an adaptive optic system. We discuss the forms of degradation when a target is viewed through the atmosphere1: scintillation from ground targets on a hot day in visible or infrared light; beam spreading and wavering around in time; atmospheric turbulence caused by motion of the target or by weather. In the case of targets we can use a beacon laser that reflects back from the target into a wavefront detector to measure the effects of turbulence on propagation to and from the target before imaging.1 A deformable mirror then corrects the wavefront shape of the transmitted, reflected or scattered data for enhanced imaging. Further, recognition of targets is enhanced by performing accurate distance measurements to localized parts of the target using lidar. Distance is obtained by sending a short pulse to the target and measuring the time for the pulse to return. There is inadequate time to scan the complete field of view so that the beam must be steered to regions of interest such as extremities of the image during image recognition. Distance is particularly valuable to recognize fine features in range along the target or when segmentation is required to separate a target from background or from other targets. We discuss the issues involved.

McAulay, Alastair D.

2012-06-01

444

Bioengineering Strategies for Designing Targeted Cancer Therapies  

PubMed Central

The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

Wen, Xuejun

2014-01-01

445

Targeting Cancer with Antisense Oligomers  

SciTech Connect

With financial assistance from the Department of Energy, we have shown definitively that radiolabeled antisense DNAs and other oligomers will accumulate in target cancer cells in vitro and in vivo by an antisense mechanism. We have also shown that the number of mRNA targets for our antisense oligomers in the cancer cell types that we have investigated so far is sufficient to provide and antisense image and/or radiotherapy of cancer in mice. These studies have been reported in about 10 publications. However our observation over the past several years has shown that radiolabeled antisense oligomers administered intravenously in their native and naked form will accumulate and be retained in target xenografts by an antisense mechanism but will also accumulate at high levels in normal organs such as liver, spleen and kidneys. We have investigated unsuccessfully several commercially available vectors. Thus the use of radiolabeled antisense oligomers for the imaging of cancer must await novel approaches to delivery. This laboratory has therefore pursued two new paths, optical imaging of tumor and Auger radiotherapy. We are developing a novel method of optical imaging tumor using antisense oligomers with a fluorophore is administered while hybridized with a shorter complementary oligomer with an inhibitor. In culture and in tumored mice that the duplex remains intact and thus nonfluorescent until it encounters its target mRNA at which time it dissociates and the antisense oligomer binds along with its fluorophore to the target. Simultaneous with the above, we have also observed, as have others, that antisense oligomers migrate rapidly and quantitatively to the nucleus upon crossing cell membranes. The Auger electron radiotherapy path results from this observation since the nuclear migration properties could be used effectively to bring and to retain in the nucleus an Auger emitting radionuclide such as 111In or 125I bound to the antisense oligomer. Since the object becomes radiotherapy rather than imaging, the delivery problem may be obviated by attaching the antisense oligomer to an antitumor antibody to improve delivery following intravenous administration. Since many antibodies are trapped in endosomes following internalization, a cell penetrating peptide such as tat will also be included to ensure transport of the complex without entrapment. Rather than covalent conjugation of the three entities, we are using streptavidin as linker after biotinylated each component. Our recent efforts have concentrated on establishing the influence of the streptavidin linker on the properties of each component within the delivery nanoparticle. Thus, we have shown that the Herceptin antibody, when linked to a labeled oligomer via streptavidin, remains capable of directing the label oligomer to Her2+ tumor cells in vitro and Her2+ tumor xenografts in mice. In addition, we have demonstrated that a labeled antisense oligomer within the nanoparticle remains capable of migrating to the nucleus and binding to its target mRNA in vitro and in vivo. We have shown that the tat peptide also preserves its properties of cell transport when incubated as one component of the nanoparticle. Most recently, we have addressed another of our concerns, namely whether the streptavidin would adversely effect the biodistribution of the antisense oligomer. We were pleased to find that the 99mTc-labeled antisense MORF within the Herceptin three component and two component nanoparticles accumulated and was retained in tumor in a manner suggestive of radiolabeled Herceptin itself. Thus the preserved properties within the streptavidin delivery nanoparticle of the Herceptin antibody, the tat peptide and the 111In labeled antisense MORF oligomer will explain why we have successfully demonstrated an Auger electron-mediated, antisense-mediated radiotherapy in cells in culture. One remaining concern is that the delivery nanoparticle may deliver the Auger electron emitting radionuclide to the nucleus of normal cells as well as tumor cells. We have now performed tumored mice stu

DJ Hnatowich

2008-10-28

446

Targeting inhibitory neurotransmission in tinnitus  

PubMed Central

Tinnitus perception depends on the presence of its neural correlates within the auditory neuraxis and associated structures. Targeting specific circuits and receptors within the central nervous system in an effort to relieve the perception of tinnitus and its impact on one’s emotional and mental state has become a focus of tinnitus research. One approach is to upregulate endogenous inhibitory neurotransmitter levels (e.g. glycine and GABA) and selectively target inhibitory receptors in key circuits to normalize tinnitus pathophysiology. Thus, the basic functional and molecular properties of two major ligand-gated inhibitory receptor systems, the GABAA receptor (GABAAR) and glycine receptor (GlyR) are described. Also reviewed is the rationale for targeting inhibition which stems from reported tinnitus-related homeostatic plasticity of inhibitory neurotransmitter systems and associated enhanced neuronal excitability throughout most central auditory structures. However, the putative role of the medial geniculate body (MGB) in tinnitus has not been previously addressed, specifically in terms of its inhibitory afferents from inferior colliculus and thalamic reticular nucleus and its GABAAR functional heterogeneity. This heterogeneous population of GABAARs, which may be altered in tinnitus pathology, and its key anatomical position in the auditory CNS make the MGB a compelling structure for tinnitus research. Finally, some selective compounds, which enhance tonic inhibition, have successfully ameliorated tinnitus in animal studies, suggesting that the MGB and, to a lesser degree, the auditory cortex may be their primary locus of action. These pharmacological interventions are examined, in terms of their mechanism of action and why these agents, may be effective in tinnitus treatment. PMID:22405692

Richardson, Ben D.; Brozoski, Thomas J.; Ling, Lynne L.; Caspary, Donald M.

2012-01-01

447

Cascaded target normal sheath acceleration  

SciTech Connect

A cascaded target normal sheath acceleration (TNSA) scheme is proposed to simultaneously increase energy and improve energy spread of a laser-produced mono-energetic proton beam. An optimum condition that uses the maximum sheath field to accelerate the center of the proton beam is theoretically found and verified by two-dimensional particle-in-cell simulations. An initial 10 MeV proton beam is accelerated to 21 MeV with energy spread decreased from 5% to 2% under the optimum condition during the process of the cascaded TNSA. The scheme opens a way to scale proton energy lineally with laser energy.

Wang, W. P.; Shen, B. F.; Zhang, X. M.; Wang, X. F.; Xu, J. C.; Zhao, X. Y.; Yu, Y. H.; Yi, L. Q.; Shi, Y.; Zhang, L. G.; Xu, T. J.; Xu, Z. Z. [State Key Laboratory of High Field Laser Physics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800 (China)] [State Key Laboratory of High Field Laser Physics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800 (China)

2013-11-15

448

Conotoxins: Molecular and Therapeutic Targets  

NASA Astrophysics Data System (ADS)

Marine molluscs known as cone snails produce beautiful shells and a complex array of over 50,000 venom peptides evolved for prey capture and defence. Many of these peptides selectively modulate ion channels and transporters, making them a valuable source of new ligands for studying the role these targets play in normal and disease physiology. A number of conopeptides reduce pain in animal models, and several are now in pre-clinical and clinical development for the treatment of severe pain often associated with diseases such as cancer. Less than 1% of cone snail venom peptides are pharmacologically characterised.

Lewis, Richard J.

449

Approaching Rock Target No. 1  

NASA Technical Reports Server (NTRS)

This 3-D stereo anaglyph image was taken by the Mars Exploration Rover Spirit front hazard-identification camera after the rover's first post-egress drive on Mars Sunday. Engineers drove the rover approximately 3 meters (10 feet) from the Columbia Memorial Station toward the first rock target, seen in the foreground. The football-sized rock was dubbed Adirondack because of its mountain-shaped appearance. Scientists plan to use instruments at the end of the rover's robotic arm to examine the rock and understand how it formed.

2004-01-01

450

Cascaded target normal sheath acceleration  

NASA Astrophysics Data System (ADS)

A cascaded target normal sheath acceleration (TNSA) scheme is proposed to simultaneously increase energy and improve energy spread of a laser-produced mono-energetic proton beam. An optimum condition that uses the maximum sheath field to accelerate the center of the proton beam is theoretically found and verified by two-dimensional particle-in-cell simulations. An initial 10 MeV proton beam is accelerated to 21 MeV with energy spread decreased from 5% to 2% under the optimum condition during the process of the cascaded TNSA. The scheme opens a way to scale proton energy lineally with laser energy.

Wang, W. P.; Shen, B. F.; Zhang, X. M.; Wang, X. F.; Xu, J. C.; Zhao, X. Y.; Yu, Y. H.; Yi, L. Q.; Shi, Y.; Zhang, L. G.; Xu, T. J.; Xu, Z. Z.

2013-11-01

451

Envisaging bacteria as phage targets  

PubMed Central

It can be difficult to appreciate just how small bacteria and phages are or how large, in comparison, the volumes that they occupy. A single milliliter, for example, can represent to a phage what would be, with proper scaling, an “ocean” to you and me. Here I illustrate, using more easily visualized macroscopic examples, the difficulties that a phage, as a randomly diffusing particle, can have in locating bacteria to infect. I conclude by restating the truism that the rate of phage adsorption to a given target bacterium is a function of phage density, that is, titer, in combination with the degree of bacterial susceptibility to adsorption by an encountering phage. PMID:23616932

Abedon, Stephen T.

2011-01-01