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1

Idiopathic thrombocytopenic purpura (ITP)  

MedlinePLUS

Immune thrombocytopenic purpura; ITP; Immune thrombocytopenia ... Toltl LJ, et al. Diseases of platelet number: immune thrombocytopenia, neonatal alloimmune thrombocytopenia, and posttransfusion purpura. In: Hoffman ...

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.  

PubMed

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

2014-07-01

4

The history of idiopathic thrombocytopenic purpura (ITP).  

PubMed

Purpura, initially recognized in ancient times, was defined into clinical syndromes in the 16th, 17th and 18th centuries. With advances in microscope science in the nineteenth century, the platelet was identified, leading to the recognition of the thrombocytopenic component of idiopathic thrombocytopenic purpura (ITP). The 20th century brought recognition of the pathophysiology of the disorder and the clinical states were refined and treatments for ITP developed. The latter half of the 20th century has focused on the autoimmune components of ITP, attempting to develop diagnostic tests, apply new therapies, and elucidate the immune dysregulation associated with, and underlying, the disorder. PMID:10351134

Blanchette, M; Freedman, J

1998-09-01

5

Management of thrombotic thrombocytopenic purpura: current perspectives  

PubMed Central

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

Blombery, Piers; Scully, Marie

2014-01-01

6

Cytomegalovirus can make immune thrombocytopenic purpura refractory.  

PubMed

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

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

2009-06-01

7

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

8

Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy  

PubMed Central

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

9

Does hemolytic uremic syndrome differ from thrombotic thrombocytopenic purpura?  

PubMed

Both hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are characterized by thrombotic microangiopathy (TMA), affecting mainly the kidney and brain, respectively. Diagnosis of HUS or TTP has been complicated by the fact that these disorders share several clinical characteristics, and by the dearth of knowledge regarding the pathogenesis of TMA. Advances in the identification of pathogenic features--deficiency of the metalloprotease ADAMTS13 in TTP and association of mutated complement proteins with atypical HUS--have gone some way towards improving clinicians' ability to distinguish between the two diseases. Here, we pose the following question: is it important to patient management that HUS be distinguished from TTP? By discussing what is known about the pathogenesis, clinical features and treatment of these two conditions we address this question, and propose a new nomenclature for TMA. PMID:18033227

Fakhouri, Fadi; Frémeaux-Bacchi, Véronique

2007-12-01

10

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

2015-01-01

11

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

12

Refractory thrombotic thrombocytopenic purpura and membranoproliferative glomerulonephritis successfully treated with rituximab: a case associated with hepatitis C virus infection  

Microsoft Academic Search

Plasmapheresis remains the main treatment modality for patients with thrombotic thrombocytopenic purpura. We report a patient who had simultaneous onset of membranoproliferative glomerulonephritis and thrombotic thrombocytopenic purpura. She did not improve after 48 plasmapheresis sessions. A 6-week course of weekly intravenous doses of rituximab was then given. This achieved complete remission of her nephrotic syndrome and improvement in her renal

SF Chan; KC Lo; YY Wong; Gensy MW Tong; PN Wong; Edmond SK Ma; Andrew KM Wong

2009-01-01

13

Thrombotic thrombocytopenic purpura and cardiac papillary fibroelastoma: a 'unique coexistence'.  

PubMed

Thrombotic thrombocytopenic purpura (TTP), a complex thrombotic microangiopathy, remains an evolving enigma. A 49-year-old African-American woman presented with acute left hemiplegia, an ischemic cerebrovascular accident involving the right middle cerebral artery. Sequential appearance of thrombocytopenia and evidence of microangiopathic haemolysis led to the diagnosis of acquired idiopathic autoimmune TTP. This was managed with plasma exchange (PEX) and steroids. Early haematologic relapse within a month was managed with the addition of rituximab attaining sustained remission. The patient presented 3 years later with acute confusion and expressive aphasia due to multiple infarcts involving the left parieto-occipital cortex. Transoesophageal echocardiography demonstrated a pedunculated 6?mm mitral valvular mass consistent with a papillary fibroelastoma. Anticoagulation was instituted and the patient was continued on therapeutic oral warfarin. A haematologic relapse of TTP eventually emerged and was managed with PEX, steroids and rituximab. This vignette demonstrates several dilemmas in the clinical presentation, diagnosis and management of TTP in current day practice. Rituximab has adjuvant benefits to PEX and is being investigated as potential first-line therapy. Monitoring ADAMTS13 activity and inhibitor titre, as in our case, prove to have prognostic significance. Cardiac fibroelastomas are rare benign cardiac tumours usually arising from valvular endocardium with thromboembolic potential. One of the proposed mechanisms of origin of these masses is organizing thrombi in the setting of endocardial injury and inflammation questioning a possible link to thrombotic microangiopathy. To the best of our knowledge, this is the first report of this unique coexistence. PMID:24077148

Ramakrishnan Geethakumari, Praveen; Rubin, Alexander; Varadi, Gabor

2013-12-01

14

Pulmonary hyalinizing granuloma associated with idiopathic thrombocytopenic purpura.  

PubMed

Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

Coleman, Christopher; Nassar, Aziza; McComb, Barbara

2014-01-01

15

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

PubMed Central

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

Moake, Joel L.

2004-01-01

16

Pulmonary Hyalinizing Granuloma Associated with Idiopathic Thrombocytopenic Purpura  

PubMed Central

Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

Coleman, Christopher; Nassar, Aziza; McComb, Barbara

2014-01-01

17

Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura.  

PubMed

Several reports have defined nonfamilial thrombotic thrombocytopenic purpura (TTP) as an autoimmune disorder caused by antibodies to von Willebrand's factor-cleaving protease (vWF-CP). This raises the possibility that rituximab, a monoclonal antibody against CD20 present in B-lymphoid cells, may have utility in the treatment of TTP. We report five consecutively treated patients with relapsed TTP who responded rapidly to immune suppression by rituximab at our institution. These two male and three female patients had a median age of 37 years (27-70). The median time from diagnosis to therapy was 24 months (8-60). Prior therapies included plasma exchange and corticosteroids in all cases, splenectomy (4), vincristine and aspirin (3), and azathioprine (2). The median number of plasma exchanges received prior to therapy was 59 (21-158). The cohort had a median platelet count of 48 x 10(9)/l (23-110), median hemoglobin of 9 g/dl (8-11), and median lactate dehydrogenase of 632 IU/l (311-945) prior to administration of rituximab. Analysis of vWF-CP activity demonstrated absent or decreased activity with detectable inhibitors in four patients. All patients attained a complete response. The median time to response after the first dose of rituximab was 5 weeks. Responses are maintained in all patients from 10 to 21 months after treatment. This report adds to the evidence that rituximab has efficacy in nonfamilial TTP and warrants further study. PMID:15517266

Reddy, Pavan S; Deauna-Limayo, Delva; Cook, James D; Ganguly, Siddhartha S; Blecke, Carol; Bodensteiner, David C; Skikne, Barry S; Sahud, Mervin A

2005-04-01

18

Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura  

PubMed Central

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

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

2014-01-01

19

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

20

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

21

A case associated with comorbidities among cerebral infarction, idiopathic thrombocytopenic purpura, and triple x syndrome.  

PubMed

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

2014-06-01

22

Late Results After Splenectomy in Adult Idiopathic Thrombocytopenic Purpura  

PubMed Central

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

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

2015-01-01

23

Pregnancy outcomes in women with idiopathic thrombocytopenic purpura  

PubMed Central

Background: Idiopathic thrombocytopenic purpura (ITP) is a disease that commonly affects women of reproductive age and is associated with maternal and fetal complications. Objective: The aim of the present study was to report the perinatal outcome in pregnant women with ITP. Materials and Methods: Twenty one pregnant women with ITP admitted in a teaching hospital in Tehran, from October 2008 to February 2010, were enrolled in this prospective historical cohort study; course and perinatal outcome of pregnancies were studied. Results: Seven (33.3%) cases had been diagnosed before pregnancy, while the other fourteen (66.7%) were diagnosed during pregnancy. During hospitalization, thirteen (62%) patients required treatment, eight (61.5%) of them with steroids, two (15.3%) received intravenous immunoglobulin (IVIG), and three (23%) were treated with steroids and IVIG. Three babies were delivered vaginally (14.3%), seventeen (81%) through cesarean section and one patient aborted her fetus. Nine mothers (42.9%) had platelet counts <50000/ml at the time of delivery; but postpartum hemorrhage occurred in 4 (19%) women and one women received platelet transfusion during cesarean section. Six (28.6%) women developed gestational diabetes. Pregnancy was complicated by preeclampsia in one woman and by abruptio placenta in another. One pregnancy terminated in intrauterine fetal death. Seventeen infants (89.5%) had normal platelet counts, and two (10.5%) had moderate thrombocytopenia. No infant showed signs of hemorrhage, but 2 neonates (10.5%) were diagnosed with intrauterine growth restriction. Conclusion: Rate of gestational diabetes in pregnant women with ITP is higher than the general population. Rate of gestinational diabetes is 3-5% and postpartum hemorrhage is 5-7% in general. Postpartum hemorrhage is common in these women. Severe thrombocytopenia and bleeding in the newborns are uncommon. PMID:25246917

Yassaee, Fakhrolmolouk; Eskandari, Roghieh; Amiri, Zohreh

2012-01-01

24

Thrombotic Thrombocytopenic Purpura Associated with Bone Marrow Metastasis and Secondary Myelofibrosis in Cancer  

Microsoft Academic Search

To examine the relationship between cancer and development of thrombotic microangiopathy (TM), the medical records of patients with known TM were exam- ined in one institution from January 1981 to December 2002. Nine out of 93 patients with the established diagno- sis of TM had active cancer. All nine of those patients had thrombotic thrombocytopenic purpura (TTP). Among those patients,

JAE C. CHANG

2003-01-01

25

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

PubMed

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

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

2014-10-01

26

Complicated lower extremity wound caused by immune thrombocytopenic purpura leading to hypercoagulable state: a team approach for limb salvage.  

PubMed

This article describes a complicated lower extremity wound due to hypercoagulable state caused by immune thrombocytopenic purpura. A team approach was important to limb salvage. A literature review is included. PMID:24527141

Simman, Richard; Haluschak, John; Jackson, Sarah

2010-06-01

27

Thrombotic microangiopathies: thrombotic thrombocytopenic purpura / hemolytic uremic syndrome.  

PubMed

Thrombotic microangiopathies (TMAs) are pathological conditions characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic- uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Other disorders occasionally present with similar manifestations. Depending on whether renal or brain lesions prevail, two pathologically indistinguishable but somehow clinically different disorders have been described: HUS and TTP. Injury to the endothelial cell is the central and likely inciting factor in the sequence of events leading to TMA. Loss of physiological thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, abnormal von Willebrand factor release and fragmentation, and increased vascular shear stress may then sustain and amplify the microangiopathic process. Intrinsic abnormalities of the complement system and of the von Willebrand factor pathway may account for a genetic predisposition to the disease that may play a paramount role in particular in familial and recurrent forms. In the case of diarrhea-associated HUS (D+HUS), renal endothelial damage is mediated (at least in large part) by the bacterial agent Shigatoxin (Stx), which is actually a family of toxins elaborated by certain strains of Escherichia coli and Shigella dysenteriae. Outcome is usually good in childhood, Shiga toxin-associated HUS, whereas renal and neurological sequelae are more frequently reported in adult, atypical, and familial forms of HUS and in TTP. Recent studies have demonstrated that deficiency in the von Willebrand factor cleaving protease ADAMTS13, due to deficiency of ADAMTS13 can be genetic or more common, acquired, resulting from autoimmune production of inhibitory anti-ADAMTS13 antibodies, that causes TTP. During the last decade, atypical HUS (aHUS) has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Although TMAs are highly heterogeneous pathological conditions, one-third of TMA patients have severe deficiency of ADAMTS13. Platelet transfusions are contraindicated. Plasma infusion or exchange (PE) is the only treatment of proven efficacy. PMID:21103695

Polito, Maria Goretti; Kirsztajn, Gianna Mastroianni

2010-01-01

28

Hand-assisted laparoscopic splenectomy for idiopathic thrombocytopenic purpura during pregnancy.  

PubMed

A successful case of a hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum for autoimmune thrombocytopenic purpura in a patient at 23 weeks' gestation is reported. Preoperative splenic arterial embolization was performed on the same day as the operation using painless contour embolic material and super-absorbent polymer microspheres. The abdominal wall retraction method first was applied to avoid the effects of pneumoperitoneum on systemic hemodynamic alterations. However, a sufficient surgical view could not be obtained, as the intra-abdominal organs were elevated because of the enlarged uterus. A surgical view with 4 to 6-mm Hg pneumoperitoneum was available for the hand-assisted splenectomy. The postoperative course was uneventful, and the patient vaginally delivered a healthy infant. A hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum after splenic arterial embolization would be feasible for patients with autoimmune thrombocytopenic purpura during a relatively advanced pregnancy. PMID:11269558

Iwase, K; Higaki, J; Yoon, H E; Mikata, S; Tanaka, Y; Takahashi, T; Hatanaka, K; Tamaki, T; Hori, S; Mitsuda, N; Kamiike, W

2001-02-01

29

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

PubMed

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

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

2015-04-01

30

Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von Willebrand factor (VWF) observed in normal plasma is decreased in TTP patients. However, the identity of the responsible protease and its role in the pathophysiology of TTP remain unknown. We performed genome-wide linkage analysis in four pedigrees of humans

Gallia G. Levy; William C. Nichols; Eric C. Lian; Tatiana Foroud; Jeanette N. McClintick; Beth M. McGee; Angela Y. Yang; David R. Siemieniak; Kenneth R. Stark; Ralph Gruppo; Ravindra Sarode; Susan B. Shurin; Visalam Chandrasekaran; Sally P. Stabler; Hernan Sabio; Eric E. Bouhassira; Jefferson D. Upshaw; David Ginsburg; Han-Mou Tsai

2001-01-01

31

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

PubMed Central

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

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

2015-01-01

32

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

33

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

34

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

35

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

36

M-component with reactivity against actin associated with thrombotic thrombocytopenic purpura.  

PubMed

A patient with a monoclonal B-cell disorder producing an M-component with antiactin activity is described. After more than 3 years of observations, the final diagnosis is not completely established, but a malignant lymphoproliferative process is evidently under evolution. On three occasions, she has presented with symptoms compatible with a thrombotic thrombocytopenic purpura-like syndrome, concomitant with an increase in paraprotein. A relationship between this autoantibody and the patient's symptoms is proposed. Steroids have so far had a beneficial effect on the symptoms. PMID:1951388

Bäck, H; Nilsson, G; Hansson, G K; Rödjer, S; Tarkowski, A

1991-10-01

37

Difficult Management of Coronary Artery Disease in a Patient with Thrombotic Thrombocytopenic Purpura  

PubMed Central

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome affecting multiple organs. There is no sufficient evidence regarding the clinical cardiac manifestations of TTP. Nonetheless, pathologic cardiac involvement is quite frequent in acute TTP, which is predominantly manifested as myocardial necrosis due to coronary arteriolar microthrombosis. The present case report describes a 43-year-old man with long-standing remitted TTP, who suffered from a sequence of refractory thrombotic epicardial coronary events. Aggressive medical and interventional therapies, including long-term dual antiplatelets and coronary angioplasty, were finally successful in remitting the thrombotic events. During his two-year follow up, he has been asymptomatic.

Jorfi, Fatemeh; Sanati, Hamid Reza; Zahedmehr, Ali; Shakerian, Farshad; Zahedi, Lida; Firouzi, Ata; Kiani, Reza; Elmi, Ghazal

2014-01-01

38

Cardiac tuberculoma presenting as thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.  

PubMed

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a unique multisystem syndrome. It can present with either chronic or subacute infections. Tuberculosis (TB) is a chronic infection that has been reported to present with TTP-HUS as tuberculous endocarditis in the presence of immunodeficiency and implanted medical devices in regions where TB is endemic. Tuberculomas are space occupying lesions most commonly found in the brain in immunocompromised individuals. Herein, we present a rare association of tuberculosis with endocarditis manifesting as a tuberculoma and presenting as TTP-HUS in an immunocompetent patient and resident of the United States. PMID:24314749

Askari, Raza; Khouzam, Rami N

2014-01-01

39

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

40

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

41

Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature.  

PubMed

Thrombotic Thrombocytopenic Purpura (TTP) is a life threatening, multisystem disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological changes, renal failure, and fever. These signs and symptoms are thought to be caused by microthrombi, composed of agglutinated platelets and fibrin, which deposit in the arterioles and capillaries without mediation by an inflammatory process. TTP can occur in the first two weeks of initiation of Clopidogrel therapy. Early signs of TTP may be a skin reaction, which may precede the onset of TTP or it may be other type of purpura or neurological changes. We report the clinical and laboratory findings in a 67 years old female patient in whom TTP developed soon after treatment with 40 mg/day oral Clopidogrel after 8 days. She developed thrombocytopenia (platelets count 12000 /mm3). Her clinical signs and symptoms were fever (39.6C), bleeding from the nose and gum, large skin bruises (purpura and ecchymoses), neurological changes including hallucinations, bizarre behavior, altered mental status (fluctuating), headache, and renal dysfunction. Physicians should be aware of the possibility early onset of this syndrome when initiate Clopidogrel treatment. PMID:22091257

Azarm, Taleb; Sohrabi, Ayatollah; Mohajer, Hamid; Azarm, Arezou

2011-03-01

42

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

PubMed

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

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

2015-01-01

43

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

PubMed Central

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

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

2014-01-01

44

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

PubMed

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

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

2009-09-01

45

Cyclosporin A as an Immunosuppressive Treatment Modality for Patients with Refractory Autoimmune Thrombocytopenic Purpura after Splenectomy Failure  

Microsoft Academic Search

The treatment of autoimmune thrombocytopenic purpura (AITP) remains unsatisfactory in patients refractory to first-line management\\u000a such as corticosteroid therapy and\\/or splenectomy. Patients with refractory AITP usually require unacceptably high doses of\\u000a corticosteroids to maintain a safe platelet count. Immunosuppressive treatment with cyclosporin A (CsA) is a relatively new\\u000a treatment modality, and no large studies of this drug have been conducted.

Samo Zver; Irena Preloznik Zupan; Peter Cernelc

2006-01-01

46

An Experience of Oseltamivir Phosphate (Tamiflu™) in a Pediatric Patient with Chronic Idiopathic Thrombocytopenic Purpura: A Case Report  

Microsoft Academic Search

We report a pediatric patient with chronic idiopathic thrombocytopenic purpura who suffered from an influenza A (H1N1) virus infection. A 13-year-old girl presented with fever, coughing, and generalized petechiae. The influenza A antigen was positive in her pharyngeal aspirate. She was successfully treated with neuraminidase inhibitor oseltamivir phosphate. Her platelet counts progressively increased with oseltamivir phosphate without another blood product

Bulent Alioglu; Aysin Tasar; Cinar Ozen; Beray Selver; Yildiz Dallar

2011-01-01

47

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

48

Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients  

Microsoft Academic Search

Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet counts 9\\/l. They had received a median of five (2–13) previous treatments,

Francisco Javier Peñalver; Victor Jiménez-Yuste; Manuel Almagro; Alberto Alvarez-Larrán; Lluis Rodríguez; Marisol Casado; Laura Gallur; Pilar Giraldo; Roberto Hernández; Dolores Menor; Maria José Rodríguez; Dolores Caballero; Raúl González; José Mayans; Isabel Millán; José Rafael Cabrera

2006-01-01

49

Thrombotic Thrombocytopenic Purpura in a Patient with Brucella Infection Is Highly Responsive to Combined Plasma Infusion and Antimicrobial Therapy  

Microsoft Academic Search

Objective: To report a case of brucella infection presenting with thrombotic thrombocytopenic purpura (TTP) that responded well to plasma and antimicrobial treatment infusion. Case Presentation and Intervention: A 51-year-old man with moderate confusion, depressed mood and dysarthria was admitted. He was chronically ill, with fever (38.5°C), anemia, jaundice and petechial-purpuric skin lesions. Neurological examination revealed diminished consciousness with a Glasgow

Fuat Erdem; Hasan Kaya

2007-01-01

50

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

51

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

52

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

53

Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura.  

PubMed

Pregnancy may be complicated by a rare but life-threatening disease called thrombotic thrombocytopenic purpura (TTP). Most cases of TTP are due to an acquired autoimmune or hereditary (Upshaw-Schulman syndrome [USS]) severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). In the present study, we performed a cross-sectional analysis of the national registry of the French Reference Center for Thrombotic Microangiopathies from 2000-2010 to identify all women who were pregnant at their initial TTP presentation. Among 592 adulthood-onset TTP patients with a severe ADAMTS13 deficiency, 42 patients with a pregnancy-onset TTP were included. Surprisingly, the proportion of USS patients (n = 10 of 42 patients [24%]; confidence interval, 13%-39%) with pregnancy-onset TTP was much higher than that in adulthood-onset TTP in general (less than 5%) and was mostly related to a cluster of ADAMTS13 variants. In the present study, subsequent pregnancies in USS patients not given prophylaxis were associated with very high TTP relapse and abortion rates, whereas prophylactic plasmatherapy was beneficial for both the mother and the baby. Pregnancy-onset TTP defines a specific subgroup of patients with a strong genetic background. This study was registered at www.clinicaltrials.gov as number NCT00426686 and at the Health Authority, French Ministry of Health, as number P051064. PMID:22547583

Moatti-Cohen, Marie; Garrec, Céline; Wolf, Martine; Boisseau, Pierre; Galicier, Lionel; Azoulay, Elie; Stepanian, Alain; Delmas, Yahsou; Rondeau, Eric; Bezieau, Stéphane; Coppo, Paul; Veyradier, Agnès

2012-06-14

54

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

55

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

PubMed

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

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

2009-01-01

56

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

PubMed Central

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

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

2011-01-01

57

Reversible posterior leukoencephalopathy syndrome in a case of adult onset Still's disease with concurrent thrombotic thrombocytopenic purpura: response to high dose immunoglobulin infusions.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by a pentad consisting of thrombocytopenic, microangiopathic hemolytic anemia, renal dysfunction, neurological signs and fever. Coexistence of thrombotic thrombocytopenic purpura and Adult Onset Still's Disease (AOSD) is extremely rare. We report a case of 18 year old girl with AOSD who developed TTP. Neuroimaging of brain demonstrated white matter edema consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Complete recovery occurred with prompt anti-hypertensive treatment and high dose immunoglobulin infusions (IVIg). Plasma exchange is the standard of care and the first line treatment for patient with TTP. We used IVIg alone in our case and this showed a gratifying response. Use of IVIG before considering plasmapharesis is justifiable or not requires randomized control clinical trials. This should determine the optimal therapeutic strategies for TTP. PMID:23767207

Khobragade, A K; Chogle, A R; Ram, R P; Mascarenhas, Joanne; Kothari, Sweta; Kawadkar, Sneha; Deshpande, S S; Nair, Dipti; Makhija, Jhoomar

2012-11-01

58

[Evaluation of the efficacy of an Helicobacter pylori eradication treatment for idiopathic thrombocytopenic purpura patients].  

PubMed

The relationship between Helicobacter pylori (H. pylori) and gastric diseases (e.g. peptic ulcer, MALT lymphoma, and stomach cancer) has been widely accepted. Recent studies have also suggested an association between H. pylori infection and idiopathic thrombocytopenic purpura (ITP). In this study, an H. pylori eradication treatment was administered to 20 ITP patients and elucidated for its effectiveness. Among those 20 patients, H. pylori infection was confirmed in 17 (85%) through a C14 urea breath test, a rapid urease test, or a culture examination of a biopsied sample obtained by gastrointestinal endoscopy. Although the other 3 were negative to H. pylori, the H. pylori eradication treatment was also attempted because no other effective treatments had been established at the time of this study. In the H. pylori eradication treatment, lansoprazole (LPZ) 60 mg bid, amoxicillin (AMPC) 1500 mg bid, and clarithromycin (CAM) 400 mg bid were given to each patient for 7 days. For 4 cases, CAM was replaced with metronidazole (MNZ) 750 mg bid. The patients whose H. pylori infection was not eradicated after the first treatment received the re-eradication treatment with LPZ 60 mg bid, AMPC 1500 mg bid, and MNZ 750 mg bid for 7 days. After the treatments, the success of eradicating H. pylori was confirmed in all 17 H. pylori positive patients. In addition, platelet recovery was obtained in 11/20 patients (55%), which included 2 H. pylori negative patients and 2 patients whose H. pylori eradication was not successful after the first treatment. No relationship was found between the eradication effectiveness and the following clinical parameters: age, gender, previous therapies, disease duration, presence of anti-nucleus antibody, endoscopic atrophic change in the stomach, or kinds of antibiotics used for the treatment. These results support the efficacy of an H. pylori eradication treatment for ITP patients. A noteworthy result of this study was that an increase of platelet count was observed not only in H. pylori positive ITP patients, but also in 2 out of 3 H. pylori negative ITP patients after H. pylori eradication. Further studies are required to elucidate the efficacy of H. pylori eradication therapy in the patients negative for H. pylori. PMID:15570869

Kato, Atsunaga; Kato, Hideaki; Hirashima, Noboru; Sakamoto, Tomoyuki; Nukaya, Haruhiko; Ito, Kiyoaki; Matsunaga, Seijiro; Kondo, Hiromu; Tanaka, Yoshito; Sakakibara, Kenji

2004-11-01

59

Helicobacter pylori infection & immune thrombocytopenic purpura in children and adolescents: A randomized controlled trial.  

PubMed

Abstract Helicobacter pylori and immune thrombocytopenic purpura (ITP) association is not well established in chronic ITP (cITP) in children, although the cure of thrombocytopenia in approximately half of H. pylori eradicated adult patients has been described. The aim of this study was to investigate the effect of H. pylori eradication on platelet (PLT) recovery in cITP children and adolescents through a randomized, controlled trial. A total of 85 children (mean age 11.4 years) with cITP were prospectively enrolled. Diagnosis of H. pylori was established by two locally validated tests, (13)C-urea breath test and monoclonal stool antigen test. Twenty-two infected patients were identified, and randomly allocated into two groups: H. pylori treatment group (n?=?11) and the non-intervention control group (n?=?11). The control group was offered treatment if the thrombocytopenia persisted after the follow-up. At baseline, there were no differences regarding age, sex, duration of disease, and PLT count between groups. Sixty three of 85 patients were uninfected. PLT response was classified as complete response: PLT?>?150?×?10(9?)l(-1); partial response: PLT 50-150?×?10(9?)l(-1), or an increase of 20-30?×?10(9?)l(-1); no response: PLT?

Brito, Helena Shino Hanai; Braga, Josefina Aparecida Pellegrini; Loggetto, Sandra Regina; Machado, Rodrigo Strehl; Granato, Celso Francisco Hernandes; Kawakami, Elisabete

2014-05-15

60

Purpura  

MedlinePLUS

Nonthrombocytopenic purpuras may be due to: Amyloidosis Blood clotting disorders Congenital cytomegalovirus Congenital rubella syndrome Drugs that affect platelet function Fragile blood vessels seen in older people (senile purpura) ...

61

Reticular erythematous mucinosis and thrombocytopenic purpura. Report of a case and review of the world literature, including plaquelike cutaneous mucinosis.  

PubMed

A case of reticular erythematous mucinosis associated with chronic idiopathic thrombocytopenic purpura and circulating immune complexes is described. We compare reticular erythematous mucinosis with the similar plaquelike cutaneous mucinosis. We discuss the apparent photosensitivity of reticular erythematous mucinosis and its possible relationship with altered states of immune function such as diabetes, thyroid disease, and neoplasia. The somewhat varied but characteristic histopathologic findings and staining are reviewed, including the characteristic perivascular and occasional perifollicular lymphocytic infiltrate and Alcian blue-positive dermal mucin. Treatment with antimalarial drugs still appears to be the most uniformly successful therapeutic approach to the management of this chronic dermatosis. Further research efforts should be directed at understanding its link with altered states of immune function. PMID:3056996

Braddock, S W; Davis, C S; Davis, R B

1988-11-01

62

Thrombotic thrombocytopenic purpura and deep vein thrombosis as the presenting manifestations of systemic lupus erythematosus: A case report and review of literature  

PubMed Central

Systemic lupus erythematosus (SLE), is sometimes complicated by the rare fatal syndrome, Thrombotic thrombocytopenic purpura (TTP), but the occurrence of TTP as the initial manifestation of SLE is very rare. Since they have similarities in some features, the differentiation of TTP from SLE may be missed. SLE patients are also more prone to thrombotic events. Here we report a case with TTP and deep vein thrombosis as the presenting symptoms of SLE. PMID:22279486

Mashhadi, Mohammad Ali; Bari, Zohreh

2011-01-01

63

Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience  

PubMed Central

Background Acquired thrombotic thrombocytopenic purpura is still associated with a 10–20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. Design and Methods The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. Results Non-survivors (11%) were older (P=10?6) and more frequently presented arterial hypertension (P=5.10?4) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. Conclusions A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis. PMID:22580997

Benhamou, Ygal; Assié, Cyrielle; Boelle, Pierre-Yves; Buffet, Marc; Grillberger, Rana; Malot, Sandrine; Wynckel, Alain; Presne, Claire; Choukroun, Gabriel; Poullin, Pascale; Provôt, François; Gruson, Didier; Hamidou, Mohamed; Bordessoule, Dominique; Pourrat, Jacques; Mira, Jean-Paul; Le Guern, Véronique; Pouteil-Noble, Claire; Daubin, Cédric; Vanhille, Philippe; Rondeau, Eric; Palcoux, Jean-Bernard; Mousson, Christiane; Vigneau, Cécile; Bonmarchand, Guy; Guidet, Bertrand; Galicier, Lionel; Azoulay, Elie; Rottensteiner, Hanspeter; Veyradier, Agnès; Coppo, Paul

2012-01-01

64

Dentoalveolar Trauma in a Patient With Chronic Idiopathic Thrombocytopenic Purpura: A Case Report  

Microsoft Academic Search

A case is presented of a 13-year-old boy with chronic idiopathic thrombocytopenic pur- pura (ITP) who sustained traumatic labial luxation of both lower central incisors, with partial alveolar fracture resulting in displacement of the labial alveolar plate. Intravenous immunoglobulin (Fleibogamma, 1 g\\/kg body weight · 2 days) was administered, re- sulting in the patient's platelet count rising from 15,000\\/mm 3

David Finucane; Padraig Fleming; Dublin Dental

2004-01-01

65

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

PubMed Central

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

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

2009-01-01

66

The effect of platelet autoantibodies on the course of the disease and clinical response of patients with idiopathic thrombocytopenic purpura.  

PubMed

In this study, we evaluated the response to treatment of 409 idiopathic thrombocytopenic purpura (ITP) patients who were tested for the presence of platelet-associated autoantibodies by direct-platelet immunofluorescence test (PIFT) and for the presence of plasma antibodies directed against the GPIIb/IIIa, GPIb and GPIa/IIa by monoclonal antibody immobilization of platelet antigens (MAIPA). In patients with platelet autoantibodies in comparison with patients without antibodies more frequently were observed the chronic form of disease (83.5%vs. 68.5%) and severe symptoms of haemorrhage diathesis (17.3%vs. 6.9%). Evaluation of the treatment response (to corticosteroids, immunosuppressive drugs and splenectomy) referred to patients with complete response, e.g. complete remission defined as platelet count of >100 x 10(9)/l for at least 2 years. The percentage of complete response in the whole population of ITP patients, both with and without autoantibodies regardless of the method of treatment, was similar (about 54%). However, the presence of platelet autoantibodies had effect on patients treated with corticosteroids: complete response approximately 71% (36/51) of patients with autoantibodies and in 60% (72/120) of patients without antibodies, as well as in patients treated with immunosuppressive drugs (cyclophosphamide, azathioprine, vincristin and vinblastin); complete response approximately 51% (11/21) of patients with autoantibodies and in 34.8% (6/17) of patients without autoantibodies. The presence of autoantibodies had no effect on the response of splenectomy patients. PMID:18190469

Sikorska, A; Konopka, L; Ma?lanka, K

2008-02-01

67

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

PubMed Central

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

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

2013-01-01

68

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

PubMed

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

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

2014-11-27

69

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

70

Presence of a platelet aggregating factor in the plasma of patients with thrombotic thrombocytopenic purpura (TTP) and its inhibition by normal plasma.  

PubMed

Three patients with thrombotic thrombocytopenic purpura (TTP) were treated by infusion of normal plasma with dramatic responses. The plasmas collected from these patients during relapse induced in vitro aggregation of washed platelets from both normal donors and the patients during remission. The platelet aggregating factor was not dialyzable or adsorbable by Al(OH)3 and was not inactivated by diisopropylfluorophosphate, hirudin, or heparin in the presence of normal amounts of antithrombin. In contrast to the platelet aggregation induced by platelet isoantibody, the platelet aggregating activity of TTP plasma diminished as a function of time when it was incubated with normal plasma at 37 degrees C. These observations suggest that at least some instances of TTP appear to be due to deficiency of a plasma inhibitor to counteract a platelet aggregating factor demonstrated to be present in the plasma of these patients. PMID:570069

Lian, E C; Harkness, D R; Byrnes, J J; Wallach, H; Nunez, R

1979-02-01

71

Thrombotic thrombocytopenic purpura  

MedlinePLUS

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

72

Thrombotic Thrombocytopenic Purpura  

MedlinePLUS

... procedures, such as surgery and blood and marrow stem cell transplant Some medicines, such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone therapy and estrogens Quinine, which is a substance often found in tonic water and nutritional health products If you have TTP, ...

73

Dieulafoy lesion in the ascending colon presenting with gastrointestinal bleeding and severe anemia complicated by a coexisting severe resistant chronic idiopathic thrombocytopenic purpura.  

PubMed

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

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

2014-01-01

74

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

PubMed Central

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

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

2014-01-01

75

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

PubMed Central

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

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

2014-01-01

76

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

PubMed

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

Radwan, Eman Roshdy; Goda, Rania L M

2015-05-01

77

FK506-binding protein 51 (FKBP5) gene polymorphism is not associated with glucocorticoid therapy outcome in patients with idiopathic thrombocytopenic purpura.  

PubMed

The FKBP5 gene codes for the FK506-binding protein 51 (FKBP5), a co-chaperone of hsp90, which regulates glucocorticoid (GC) receptor sensitivity. The FKBP5 gene single nucleotide polymorphisms (SNP), rs1360780, has been found to modulate GC sensitivity in stress-related psychiatric disorders. The aim of the present study was to examine the effects of rs1360780 on the treatment outcome of patients suffering from idiopathic thrombocytopenic purpura (ITP) administered with GC. The polymorphism of FKBP5, rs1360780, was genotyped in 55 GC-resistant ITP patients, 157 GC-sensitive ITP patients and 110 unrelated healthy individuals using real-time PCR and cycling probe technology with DNA extracted from peripheral blood. No significant differences in FKBP5 rs1360780 genotypes (P=0.51) and alleles (P=0.89) were observed between the GC-resistant ITP patients and the healthy controls. There were no significant differences observed between the GC-sensitive ITP patients and the healthy controls (P=0.40 for genotypes and P=0.62 for T allele), as well as between the GC-sensitive ITP patients and the GC-resistant patients (P=0.67 for genotypes and for T allele). The present study demonstrates that the FKBP5 polymorphism may not affect the response of ITP patients to GC treatment. PMID:22825419

Lao, Wansheng; Fang, Meiyun; Yang, Xifei

2012-10-01

78

Partial response to anti-CD20 monoclonal antibody treatment of severe immune thrombocytopenic purpura in a patient with common variable immunodeficiency.  

PubMed

Immune thrombocytopenic purpura (ITP), alone or in combination with autoimmune hemolytic anemia (Evans syndrome) and/or autoimmune neutropenia, is frequent in patients with common variable immunodeficiency (CVID). A 34-year-old man with CVID had long-standing unresponsive ITP. The patient had a 9-year history of CVID on substitutive therapy with intravenous immunoglobulin (IVIG). The clinical course of CVID was complicated with refractory fistulizing inflammatory bowel disease, nodular regenerative hyperplasia of the liver, splenomegaly, severe portal hypertension, and hypercatabolism of IgG. ITP was refractory to medical therapy, including different combinations of corticosteroids, high-dose IVIG, azathioprine, and vincristine. Splenectomy was not performed because of severe portal hypertension. He received a total five doses of rituximab, a monoclonal antibody directed against CD20 antigen, at a dose of 375 mg/m(2). After an initially slow response, his platelet count increased to more than 50,000/microL by the fourth week of infusion. Therapy was well tolerated, and B lymphocytes were effectively depleted from the peripheral blood. The patient was completely tapered off glucocorticoids and maintained platelets at above 40,000/microL. The patient has not taken immunosuppressive agents for 11 months. Early treatment with rituximab might be an option for patients with CVID and ITP that do not respond to other treatments or for patients for whom a splenectomy is contraindicated. PMID:16127007

Carbone, J; Escudero, A; Mayayo, M; Ballesteros, M; Perez-Corral, A; Sanchez-Ramon, S; Sarmiento, E; Micheloud, D; Fernandez-Cruz, E

2005-06-01

79

Intravenous Anti-D Treatment of Immune Thrombocytopenic Purpura: Analysis of Efficacy, Toxicity, and Mechanism of Effect  

Microsoft Academic Search

The efficacy, toxicity, and mechanism of effect of intravenous Anti-D (Winrho) were studied in 43 Rh' patients with immune thrombocytopenia purpura (ITP) who had not under- gone splenectomy and in three already splenectomized pa- tients. The mean platelet increase for the 43 nonsplenecto- mized patients was 95,OOO\\/pL (median 43,OOO\\/pL). Children had greater acute platelet responses than did adults. Human immunodeficiency

James B. Bussel; Joseph N. Graziano; Robert P. Kimberly; Savita Pahwa; Louis M. Aledort

1991-01-01

80

Plasma exchange as successful treatment of thrombotic thrombocytopenic purpura post autologous bone marrow transplant in a child.  

PubMed

We describe the case of a small child with stage IV neuroblastoma who developed thrombotic thromobocytopenic purpura (TTP) post autologous bone marrow transplant. Pneumococcal sepsis may have been the cause, a previously unreported association in transplant-associated TTP. Despite the child's size (10 kg) and the severity of the disease early intensive treatment with whole blood exchange and subsequently plasma exchange with cryosupernatant proved to be rapidly effective, in contrast to previous reports on its ineffectiveness in this setting. PMID:10734305

Plews, D E; Turner, M L; Wallace, W H

2000-03-01

81

The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use  

PubMed Central

On 11th March 2010, the European Commission issued a marketing authorization valid throughout the European Union for Revolade for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura. Revolade is an orphan medicinal product indicated for splenectomized patients with immune (idiopathic) thrombocytopenic purpura who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) and as second-line treatment for non-splenectomized patients where surgery is contraindicated. The active substance of Revolade is eltrombopag (ATC code B02BX05). Eltrombopag increases platelet production through activation of the thrombopoietin receptor. The recommended oral dose is 50 mg once daily to achieve and maintain a platelet count of the 50×109/L or more necessary to reduce or prevent the risk of bleeding. The benefit of Revolade is a durable response in maintaining platelet levels. The most common side effects include headache, nausea, hepatobiliary toxicity, diarrhea, fatigue, paresthesia, constipation, rash, pruritus, cataract, arthralgia and myalgia. The decision to grant the marketing authorization was based on the favorable recommendation of the Committee for Medicinal Products for Human Use of the European Medicines Agency. The objective of this paper is to describe the data submitted to the European Medicines Agency and to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (www.ema.europa.eu). PMID:21712542

Nieto, Maria; Calvo, Gonzalo; Hudson, Ian; Feldschreiber, Peter; Brown, David; Lee, Ching Cheng; Lay, Geoffrey; Valeri, Anna; Abadie, Eric; Thomas, Angela; Pignatti, Francesco

2011-01-01

82

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. PMID:25042026

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

2015-02-01

83

Living with Thrombotic Thrombocytopenic Purpura  

MedlinePLUS

... bleeding under the skin. Pinpoint-sized red or purple dots on the skin. These dots, called petechiae, often are found in groups and may look like a rash. Bleeding under the skin causes petechiae. Paleness or jaundice (a yellowish color of the skin or whites of the eyes). ...

84

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

PubMed Central

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

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

2015-01-01

85

How Is Thrombotic Thrombocytopenic Purpura Diagnosed?  

MedlinePLUS

... Also, your blood creatinine (kre-AT-ih-neen) level may be high. Creatinine is a blood product that's normally removed by the kidneys. Coombs Test This blood test is used to find out whether TTP is the cause of hemolytic anemia . For this test, a sample of blood is ...

86

How Is Thrombotic Thrombocytopenic Purpura Treated?  

MedlinePLUS

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

87

Genetics Home Reference: Thrombotic thrombocytopenic purpura  

MedlinePLUS

... clots can cause serious medical problems if they block vessels and restrict blood flow to organs such ... systems often produce specific proteins called autoantibodies that block the activity of the enzyme. A lack of ...

88

Psychogenic purpura  

PubMed Central

Psychogenic purpura, also known as Gardner-Diamond syndrome, is a rare, distinctive, localized cutaneous reaction pattern mostly affecting psychologically disturbed adult women. Repeated crops of tender, ill-defined ecchymotic lesions on the extremities and external bleeding from other sites characterize the condition. We report here a case of psychogenic purpura because of the rarity of the condition and to emphasize the importance of consideration of this entity during evaluation of a patient with recurrent ecchymoses. Early diagnosis of this condition will not only minimize the cost of the medical evaluation but will also benefit the patient. PMID:23825859

Sarkar, Sharmila; Ghosh, Sudip Kumar; Bandyopadhyay, Debabrata; Nath, Saswati

2013-01-01

89

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

90

Thrombotic thrombocytopenic purpura--possibilities of treatment and results.  

PubMed

Results of treatment of 13 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Eleven of 13 patients (84.6%) had conciousness disorder, and seven of 13 patients (53.8%) had renal impairment. Immunosuppressive therapy with plasmapheresis and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in statistically significant increase of platelet count (p = 0.0033), and significant improvement of consciousness as defined by increased Glasgow Coma Score (GCS) (p = 0.0524). In two patients, renal function recovered and, in one patient, hemodialysis was no longer needed. This improvement in a small patient group has no statistical significance. PMID:11345402

Gasparovi?, V; Meji?, S; Pisl, Z; Radoni?, R; Radman, I

2001-01-01

91

[Henoch-Schoenlein purpura and toxocarosis].  

PubMed

Henoch-Schoenlein purpura is a common vasculitic syndrome in childhood. Diagnosis is based on the presence of nonthrombocytopenic purpura arthritis or arthralgia, abdominal pain and glomerulonephritis. In our case report a causal relationship between toxocarosis and Henoch-Schoenlein purpura is suggested. PMID:9771003

Paw?owska-Kamieniak, A; Mroczkowska-Juchkiewicz, A; Papierkowski, A

1998-04-01

92

Platelets: an update on diagnosis and management of thrombocytopenic disorders.  

PubMed

Thrombocytopenia in the pregnant patient may result from a number of causes, most of which involve either immune-mediated platelet destruction or platelet consumption. Many of these disorders share clinical and laboratory features, making accurate diagnosis difficult. Moreover, uterine evacuation is indicated in the therapy of some disorders, while in others alternative interventions may allow the pregnancy to be carried to term. These and other issues are discussed as part of a comprehensive review of the differential diagnosis and management of thrombocytopenia in pregnancy. The term "refractory ITP" is used with reference to two distinct groups of patients: 1) patients in whom the platelet count cannot be easily increased, including those who are poorly responsive to initial single agent treatment, and 2) those with persistent thrombocytopenia despite the use of conventional therapies. An approach to management of the former group will be presented, followed by a discussion of patients with chronic refractory ITP. The latter will include presentation of new data on the role of Helicobacter pylori in ITP and whether its treatment ameliorates thrombocytopenia, as well as the use of rituximab and other modalities. Thrombotic microangiopathies such as thrombotic thrombocytopenic purpura (TTP) are rare, but life threatening causes of thrombocytopenia. Ultra-large multimers of von Willebrand factor (vWF) aggregate platelets intravascularly, and congenital or immune-mediated deficiencies of a metalloprotease that cleaves these ultra-large multimers may cause TTP. However, little information exists concerning the behavior of this protease in other physiological and pathological conditions. Levels of this protease have now been measured in healthy individuals of different ages, full-term newborns, pregnant women and a patients with variety of pathologic conditions, and these data will be reviewed herein. Heparin-induced thrombocytopenia/thrombosis (HIT/T) remains the most common antibody-mediated, drug-induced thrombocytopenic disorder, and a leading cause of morbidity and mortality. Based on clinical correlations and murine models, there is increasing evidence that antibodies to complexes between platelet factor 4 (PF4) and heparin cause HIT/T, and the molecular composition of the relevant antigen has also become better defined. However, the introduction of sensitive ELISAs to measure anti-PF4/heparin antibodies has complicated diagnosis in some settings in which the incidence of such antibodies in unaffected patients exceeds the incidence of the disease. In addition, the FDA approval of Lepirudin and Argatroban has expanded the repertoire of agents available for therapy of HIT/T and may change the approach to management of asymptomatic patients with thrombocytopenia. However, the optimal use of these drugs in commonly encountered settings remains in evolution, and a need for alternative approaches to prevention and treatment is evident. PMID:11722989

McCrae, K R; Bussel, J B; Mannucci, P M; Remuzzi, G; Cines, D B

2001-01-01

93

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

SciTech Connect

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

Levy, A.; Philip, N. [Hopital d`Enfants de la Timone, Marseilles (France)] [Hopital d`Enfants de la Timone, Marseilles (France); Michel, G. [Hopital d`Enfants de la Timone, Marseilles (France)] [and others] [Hopital d`Enfants de la Timone, Marseilles (France); and others

1997-04-14

94

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

PubMed Central

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

2012-01-01

95

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

96

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

97

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

98

Epidemiology of Schönlein-Henoch purpura.  

PubMed

The purpose of this study was to determine if Schönlein-Henoch purpura represents an abnormal host response to microorganisms. Among 1,222 cases, representing all new Danish cases in children during the years 1977-84, there was no tendency for the cases to cluster; this means that the disease is not caused by a single, contagious agent. In a smaller sample of 281 children examined in detail, a higher number than expected attended day nursery or nursery school and 17% had received antibiotic treatment during the week prior to admission. The latter findings, together with the seasonal variation of the incidence and the activation of the immune apparatus in many cases, suggest that Schönlein-Henoch purpura may be triggered by infection with several different microorganisms, but there is no evidence that a single one such as the streptococcus is the major offender. PMID:3369292

Nielsen, H E

1988-01-01

99

BULLOUS PRESENTATION OF HENOCH-SCHÖNLEIN PURPURA IN AN ADULT  

Microsoft Academic Search

Henoch-Schönlein purpura is a small vessel vasculitis occurring mainly in childhood and rarely in adulthood. Typical cutaneous eruption may begin as macular or urticarial erythematous lesions progressing to a palpable purpura. In adults, the dis - ease has a propensity to be more severe and chronic and affects mainly the ankles and feet. Bullae, vesi - cles and ulcers are

Fouad EL SAYED; Rola DHAYBI; Alfred AMMOURY

100

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

101

Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts.  

PubMed Central

Patients with human immunodeficiency virus type 1 (HIV-1) infection develop an immunologic thrombocytopenic purpura associated with markedly elevated platelet IgG, IgM, and C3C4 as well as serum immune complexes determined by the polyethylene glycol (PEG) method. Analysis of their serum PEG-precipitable immune complexes as well as platelet acid eluates revealed the presence of anti-HIV-1 antibody existing as a complex that eluted in the void volume of a Sephadex G-200 gel-filtration column. The complex binds to washed normal platelets, whereas affinity-purified anti-HIV-1 (gp120) antibody does not. HIV-1 antigen or proviral DNA was not detectable in the immune complexes or platelet extracts. However, anti-antibodies directed against anti-HIV-1 antibody were detectable in the immune complexes as well as platelet eluates. Approximately 50% of eluted platelet IgG contained anti-HIV-1 antibody. Thus the markedly elevated platelet immunoglobulin is partly due to the presence of anti-HIV-1 antibody complexes. This may be responsible for the enhanced platelet clearance and thrombocytopenia in patients with acquired immunodeficiency syndrome-related immunologic thrombocytopenia. Images PMID:3200854

Karpatkin, S; Nardi, M; Lennette, E T; Byrne, B; Poiesz, B

1988-01-01

102

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

2015-03-01

103

The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients.  

PubMed

Administration of vinca alkaloids (VA) to chronic corticosteroid refractory immune thrombocytopenia (ITP) patients results in a temporary increase of platelet count. The aim of the study was to evaluate the efficacy of vinca alkaloids in preparing adult corticosteroid refractory chronic ITP patients for splenectomy as well as to compare the costs of this method with costs of applying intravenous immunoglobulins. The study included 12 chronic ITP patients refractory to corticosteroids applied for 3-144 months. The patients were prepared for splenectomy with average 3.0 (from 1 to 4) 2-h intravenous infusions of vinca alkaloids at 7 day intervals. In eight patients, vincristin was used in a total dose of 6 mg (2 mg per infusion), in two patients, vinblastin was used in total dose of 30 mg (10 mg per infusion), and in two patients, vincristin and vinblastin infusions were administered alternatively. In nine of the 12 treated patients (75%) the platelet count increased to > or = 80 x 10(9)/l, which allowed safe splenectomy. Three patients unreactive to VA treatment were prepared for splenectomy with intravenous gammaglobulin infusions. Splenectomy was performed in 12 patients, in eight with laparoscopic method, in four with classic method. No complications during surgical intervention were observed. In none of the VA treated patients was myelosupression or liver or/and kidney dysfunction observed. Splenectomy resulted in normalization of platelet count in all patients after operation and in six of nine patients followed up for 10 months (on the average). Matching of VA costs with treatment efficacy and comparison with similar costs for intravenous immunoglobulin treatment revealed many fold lower costs of the former method. PMID:17824915

Szczepanik, A B; Sikorska, A; Slomkowski, M; Konopka, L

2007-10-01

104

[Hemolytic uremic syndrome (HUS): pathophysiology--with reference to the differentiation between HUS and thrombotic thrombocytopenic purpura].  

PubMed

HUS and TTP have the same fundamental pathologic lesion, thrombotic microangiopathy, induced by many possible causes, all of which initially induce endothelial cell damage. This damage triggers a cascade of biochemical events that ultimately leads to the formation of thrombi in the microcirculation. HUS and TTP share hematologic and vascular abnormalities and are sometimes similar in their clinical manifestations, some authors believe they should be considered a single condition and be termed HUS/TTP. On the contrary, others consider that HUS could be defined as a disorder marked by microvascular lesions limited to the kidney, whereas TTP has generalized lesions. The causative factor(s) resulting in either HUS or TTP have not been completely elucidated, and further studies are required for precise differentiation between HUS and TTP. PMID:8433517

Naruse, T

1993-01-01

105

TWO CASES OF SARCOMATOSIS WITH PURPURA HÆMORRHAGICA  

PubMed Central

The purpura accompanying the two foregoing cases of sarcoimatosis would seem to find its explanation in the coexistence of several factors, the main feature being an involvement of the vascular system by the sarcomatous elements. There existed in Case I a direct lesion of the vessel wall whereby the sarcoma cells invaded directly the various coats, and were found mainly between the intima and the adventitia, dissecting their way, as it were, along these tracts in the vessel walls. There was further an extensive involvement of the perivascular lymphatics, from which point, indeed, it would seem that the sarcoma cells had invaded the walls of the vessels themselves. In Case II, moreover, not only was there a definite invasion of the lymph spaces near the vessels, but, furthermore, there was undoubted evidence of the existence of emboli of sarcoma cells in the lumina of the blood vessels; and in the immediate vicinity of such conditions hæmorrhages were invariably found. While some vessels, and indeed a great many, were quite free from such emboli, in others the lumina were completely occluded by spindle cells, so as to preclude the possibility that these were merely a collection of desquamated endothelial cells, such as is frequently found as the result of post-mortem changes. That such an embolic condition can exist is by no means an unreasonable supposition, and, while it is generally recognised that multiple sarcomata are usually made up of small round cells, in this case we have an undoubted example of sarcomatosis of the spindle-celled variety. There are numerous instances of this " embolic purpura," as it may be called, especially in French and German literature, the condition being associated with rheumatism, valvular lesions of the heart, and other diseases which induce directly or indirectly the formation of emboli. Krauss, Gimard, Leloir, and others have insisted with considerable emphasis on the embolic origin of many purpuric conditions, and in some instances they have verified their observations by histological examination. Leloir assumes that, in addition to the presence of the ordinary emboli and the changes in the vessel walls with desquamative endarteritis, the blood itself may be much altered chemically, and that in the cachectic conditions clots may be thrown down from the circulating blood and be carried onward to form capillary emboli, with resulting hæmorrhagic infarctions. Krogerer, some ten years ago, in examining the skin removed from patients with symptomatic purpura, found definite thromboses in the smaller veins, and even in the arteries. According to his view, the alterations in the vessel walls gave rise to slowed circulation and tendency to thrombosis, bringing about a liability to hæmorrhages. His plates bear out his theories regarding the thrombi, many of which show considerable organization. But a careful examination of the purpuric areas shows further that a mere invasion of the vascular system by sarcoma cells can not explain all the various blood effusions present. On examining the skin, for instance, in those areas where large irregular hæmorrhages had occurred, there was but little evidence of vascular invasion, while the emboli, on the other hand, seemed to exist mainly in the localized smaller and more circumscribed patches. One must therefore conclude that in such instances a combination of factors will alone afford a rational explanation of the purpura, and that in the general condition of the patient we shall find another cause for the enormous effusions of blood. In both of our cases there were high fever, cachexia, and a rapid progressive asthenia, all being the results of a sarcomatosis, and implying also grave alterations in the composition of the blood. From this we may infer an altered condition of the vessel walls, and hence probably a combination of circumstances sufficient to explain the incidence of hæmorrhage. The raised cutaneous nodules in our second case, some of which were hæmorrhagic, can not be regarded as pure sarcomatous metastases

Martin, C. F.; Hamilton, W. F.

1896-01-01

106

Meningococcal interaction to microvasculature triggers the tissular lesions of purpura fulminans.  

PubMed

Neisseria meningitidis is a strict human pathogen that closely interacts with human endothelial cells via type IV pili in vitro. To decipher whether this interaction plays a role in vivo, we set up an experimental model of fulminant meningococcemia in human skin grafted SCID mice using the wild-type strain 2C4.3. Human skin and mouse tissues were sampled 24 hours after bacterial challenge for histopathology, immunohistochemistry and ultrastructural analysis. In all infected mice, N. meningitidis targeted the human vasculature, leading to bacterial and blood thrombi, infectious vasculitis and vascular leakage. Mouse vessels, including brain vessels, remained unaffected by the infectious and thrombotic process, and a nonpiliated ? pilE derivative of 2C4.3 failed to target human graft vessels and to induce vascular damages. These data demonstrate that N. meningitidis targets human endothelial cells in vivo and that this interaction triggers the vascular damages that characterize purpura fulminans. PMID:23840047

Join-Lambert, Olivier; Lecuyer, Hervé; Miller, Florence; Lelievre, Lucie; Jamet, Anne; Furio, Laetitia; Schmitt, Alain; Pelissier, Philippe; Fraitag, Sylvie; Coureuil, Mathieu; Nassif, Xavier

2013-11-15

107

The protective effect of brachial plexus palsy in purpura fulminans.  

PubMed

Acute infectious purpura fulminans is reported in a 16-month-old male with a history of posttraumatic asplenia and complete left brachial plexus palsy. This patient developed peripheral necrosis of both lower extremities and the right upper extremity, whereas the left upper extremity was completely spared from ischemia and tissue damage. Amputation of four digits on the right hand and debridement of both lower extremities were required. This patient demonstrated the protective effect of a traumatic sympathectomy, which suggests the requirement of an intact sympathetic reflex in the development of purpura fulminans. PMID:11516614

Willis, T M; Hopp, R J; Romero, J R; Larsen, P D

2001-05-01

108

Purpura Fulminans with Transient Protein C and Protein S Deficiency  

Microsoft Academic Search

Summary Purpura Fulminans is a rare but devastating disease. The acute infectious type is the commonly encounte- red form of the disease and is responsible for about 90% of the cases. The most common etiologic factors are Neisseria Menengitidis and ? hemolytic Strepto- coccus among bacterial agents, and Varicella Zoster among viral infections. We present the case of a previously

M. Tayyip Aslan; Hüseyin Onay

109

Henoch - Schönlein Purpura, a Rare Disease in Pregnancy  

Microsoft Academic Search

Introduction: Henoch-Schönlein purpura is an IgA-mediated small vessel vasculitis involving mainly skin, gastrointestinal system and kidneys. It is predominantly a disease of young children. Most common symptoms are rash (95-100%), sometimes necrotizing involving specially the legs, subcutaneous oedema (20-50%), abdominal pain and vomiting(85%), bloody stool and joint pain (60-80%) involving mainly the knees and ankles. Diagnosis is clinical and not

TABASSUM PARVEEN; FIROZA BEGUM

2008-01-01

110

[A case of Anaphylactoid purpura suggested to Empedobacter (flavobacterium) brevis infection concerned].  

PubMed

The patient was an 83 Year-old woman with purpura on her right foot and on both crura starting from the end of November 2005. First, she took medical advice from a nearby doctor, but it did not improve. Since blisters were formed besides purpura, she visited Nagoya City Midori Municipal Hospital. When she visited, she had many purpura on her both legs, her right lower crus and her right foot was swelling with redness, blisters and erosion. Histopathological finding showed leukocytoclastic vasculitis, deposit of fibrin and hemorrhage. Only Empedobacter brevis was cultured from right feet lesion. This strain was sensitive to minocycline hydrochloride. Her purpura and right foot swelling were improved just after internal use of minocycline hydrochloride, so Empedobacter brevis infection was speculated to be a trigger, or at least concerned to this Anaphylactoid purpura. PMID:20502105

Nishio, Eiichi

2010-05-01

111

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

PubMed

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

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

2013-05-01

112

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

113

Connective tissue disease following hepatitis B vaccination; topiramate-associated fatal heat stroke; ramelteon-induced autoimmune hepatitis; acute oxaliplatin-induced thrombotic thrombocytopenic purpura.  

PubMed

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

Mancano, Michael A

2014-03-01

114

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

115

Renal involvement in Henoch-Schönlein purpura: A multivariate analysis of prognostic factors  

Microsoft Academic Search

Renal involvement in Henoch-Schönlein purpura: A multivariate analysis of prognostic factors. This study is the first report in which the relationship between the progression of renal involvement in Henoch-Schönlein purpura (HSP) and various factors was evaluated using a multivariate analysis. Sixty-five (33.5%) of 194 patients with HSP developed renal involvement from three days to 17 months after the onset of

Yoshitsugu Kaku; Kaoru Nohara; Sunao Honda

1998-01-01

116

Schönlein-Henoch purpura during pregnancy with successful outcome for mother and newborn  

Microsoft Academic Search

ABSTRAC: BACKGROUND: Schönlein-Henoch purpura is a systemic vasculitis that affects vessels of a small caliber and rarely reported in the literature. CASE PRESENTATION: We report on a 35-year-old woman who developed palpable purpura with necrotizing cutaneous lesions on the lower limbs at 27 weeks of gestation. She also complained of epigastric pain and arthralgias. Histologic examination of a skin biopsy

Robert Feldmann; Walter Rieger; Paul G Sator; Friedrich Gschnait; Friedrich Breier

2002-01-01

117

Massive lower gastrointestinal haemorrhage, successfully treated with corticosteroids, as main symptom of Schönlein-Henoch purpura  

Microsoft Academic Search

Schönlein-Henoch purpura is a small vessel disease that affects mainly skin and kidney, although several gastrointestinal\\u000a symptoms may occur including abdominal pain, intussusception, perforation or bleeding. Massive lower gastrointestinal haemorrhage\\u000a is rare and even more as the main symptom of the disease. We present a case of a 2-year-old boy with Schönlein-Henoch purpura\\u000a who developed a massive lower gastrointestinal bleeding

F. Álvarez-Caro; J. A. Concha-Torre; I. García-Hernández; S. Menéndez-Cuervo; M. los Arcos-Solas; J. Santos-Juanes; E. Ramos-Polo

2009-01-01

118

Henoch-Schonlein purpura: ultrasonography of scrotal and penile involvement  

PubMed Central

Testicular or scrotal involvement has been reported in children with Henoch-Schonlein purpura (HSP), but there are very few reports on penile involvement. We report the initial and follow-up ultrasonographic findings of scrotal and penile involvement of HSP in a 5-year-old boy. On ultrasonography, scrotal soft tissue thickening and epididymal swelling with increased vascularity were noted, and on the penis, a focal mass-like lesion appeared on the dorsal surface of the distal penis, having a hypoechoic mass-like appearance without visible vascular flow on a Doppler study. After 2 days of treatment, follow-up ultrasonography showed normal scrotum and penis with a resolved soft tissue mass-like lesion. Therefore, we think that HSP ultrasonographic findings involving the scrotum and penis might help to diagnose scrotal and penile involvement in a case of HSP and to avoid unnecessary medication and/or surgical procedures. PMID:25541068

2015-01-01

119

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

120

Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.  

PubMed

Human immunodeficiency virus 1-related idiopathic thrombocytopenic purpura (HIV-1-ITP) patients have a 4-fold increased percentage of CD5+ B cells and a 4.8-fold increased percentage of serum immune complexes precipitated by polyethylene glycol (PEG-ICs) compared to control subjects, as reported previously. Since CD5+ B cells produce predominantly IgM rheumatoid factor (RF) vs. Fc of IgG and PEG-ICs contain high levels of IgM, we looked for the presence of RF in the immune complexes of HIV-1-ITP patients. PEG-ICs were adsorbed to protein A and dissociated with acid, and IgM and IgG were purified by gel filtration and affinity chromatography. Solid-phase ELISA was used to measure antibody specificity vs. platelets, Fc, and HIV-1 gp120, p24, and CD4. Dissociated IgG antibody reacted with platelets, HIV-1 gp120, p24, and CD4, but not with Fc. Serum IgG did not react with platelets or Fc but did react with HIV-1 gp120, p24, and CD4. Both PEG-IC IgM and serum IgM reacted with Fc as well as the other four antigens. Control IgM and IgG were unreactive. Isolated IgM from PEG-ICs relocated approximately 50% of the IgG preincubated with IgM to the Vo region of a G200 gel-filtration column. Anti-platelet IgG but not IgM could be affinity-purified from fixed platelets. Both F(ab')2 fragments of anti-platelet IgG and the total PEG-IC bound to platelets in a saturation-dependent manner. F(ab')2 of anti-platelet IgG inhibited 50% binding of PEG-IC to platelets at an F(ab')2/complex ratio of 3:1 (wt/wt). Scatchard analysis revealed two classes of binding sites: high-affinity Kd values of 0.8-1.8 nM and lower-affinity Kd values of 6.6-12.3 nM with respective numbers of binding sites of 44,000-57,000 and 122,000-256,000 (n = 4). Anti-platelet IgG of 6/6 patients precipitated GPIIIa from platelet lysates of surface 125I-labeled platelets. Platelet count correlated inversely with anti-platelet IgG (r = -0.73; P < 0.01; n = 27). Thus, PEG-ICs of HIV-1-ITP patients contain IgM RF, which sequesters serum anti-platelet IgG containing anti-GPIIIa. Anti-platelet IgG contributes to binding of immune complexes to platelets and correlates with thrombocytopenia. PMID:7892259

Karpatkin, S; Nardi, M A; Hymes, K B

1995-03-14

121

In vitro propagation of Dioscorea alata var. purpurae.  

PubMed

Dioscorea alata var. purpurae (Indian purple yam) is an important source of diosgenin, a triterpenoid that is used as a raw material in the synthesis of corticosteroid hormones. These drugs are used for the treatment of pharmacological conditions such as arthritis. This paper reports in vitro propagation of explants of various parts of Dioscorea-tuber, leaves, and nodes. Murashige and Skoog media supplemented with hormones and additives was used to get maximum callus initiation and shoot/root induction. All the cultures were maintained at 25?±?2 °C under cool-white fluorescent tubes with 16-h photoperiod. Callus initiation was observed from 8th to 11th day of inoculation, and subsequent root/shoot was initiated in nodal callus after 21 days. Hormones such as kinetin, indole-3-acetic acid, indole-3-butyric acid, ?-naphthalene acetic acid, and thiadizuron did not show significant enhancement. Also, there was no need for supplementing additives (silver nitrate, glutamine, L-: asparagine monohydrate, polyethylene glycol). Combination of 6-benzylaminopurine (0.2 ppm) and 2,4-dichlorophenoxyacetic acid (2 ppm) hormones gave the best results, and all parts of the plants gave similar callus induction. PMID:22476929

Shah, Heena J; Lele, S S

2012-07-01

122

Henoch–Schönlein purpura: a clinical case with dramatic presentation  

PubMed Central

A case study involving a 55-year-old Caucasian male with end-stage glomerulosclerosis is presented here. Kidney biopsies showed no deposits on imunofluorescent microscopy. Relapsing massive haemoptysis and suspected bronchovascular malformation required lung lobectomy which revealed malformative and tortuous small blood vessels, with no vasculitis. Blood antinuclear antibodies, antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were undetectable. Seric immunoglobulins and complement levels were normal. Three months later, arthralgia and joint oedema first appeared. Skin biopsy revealed vasculitis immune-reactive to immunoglobulin A. Systemic corticotherapy was then started. Two weeks later, the patient presented with abdominal pain melena and rectal bleeding (haematoquesia). Endoscopic study showed diffuse gastrointestinal haemorrhage. Angiographic study revealed diffuse lesions compatible with vasculitis and haemorrhage from multiple spots. Cyclophosphamide and then intravenous immunoglobulin were associated to treatment without response. Increasing blood loss occurred, with massive gastrointestinal haemorrhage and haemorrhagic ascitis. Death occurred due to uncontrolled diffuse bleeding. Necropsy findings showed generalised small vessels vasculitis compatible with Henoch–Schönlein purpura. PMID:22778211

Bento, João; Magalhães, Adriana; Moura, Conceição Souto; Hespanhol, Venceslau

2010-01-01

123

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

124

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

PubMed Central

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

Prathiba Rajalakshmi, Parameswaran; Srinivasan, Kalyanasundaram

2015-01-01

125

Endothelin 1 levels in relation to clinical presentation and outcome of Henoch Schonlein purpura  

Microsoft Academic Search

BACKGROUND: Henoch Schonlein purpura (HSP) is a common vasculitis of small vessels whereas endothelin-1 (ET-1) is usually reported elevated in vasculities and systematic inflammation. The aim of the present study was to investigate whether ET-1 levels are correlated with the clinical presentation and the outcome of HSP. METHODS: The study sample consisted of thirty consecutive patients with HSP. An equal

S Fessatou; P Nicolaidou; D Gourgiotis; H Georgouli; K Douros; M Moustaki; A Fretzayas

2008-01-01

126

Laparoscopic splenectomy and the treatment outcomes for idiopathic thrombocytopaenic purpura at North Shore Hospital  

Microsoft Academic Search

Aim Firstly, the demographics of laparoscopic splenectomy cases at North Shore Hospital (Takapuna, Auckland, New Zealand), the outcomes of operative technique, and perioperative complications by a single surgeon were reviewed. Secondly, analysis was performed on patients with idiopathic thrombocytopaenic purpura (ITP) with regard to platelet response and detection of preoperative predictors. Methods Laparoscopic splenectomy patients from 1998 to 2007 were

Shalvin Prasad; Richard Harman; Ross Henderson; Sanjeev Chunnilal; David Simpson

127

Schönlein-Henoch purpura during pregnancy with successful outcome for mother and newborn  

PubMed Central

Background Schönlein-Henoch purpura is a systemic vasculitis that affects vessels of a small caliber and rarely reported in the literature. Case presentation We report on a 35-year-old woman who developed palpable purpura with necrotizing cutaneous lesions on the lower limbs at 27 weeks of gestation. She also complained of epigastric pain and arthralgias. Histologic examination of a skin biopsy showed leukocytoclastic vasculitis with intravascular fibrin thrombi. The direct immunofluorescence analysis evidenced vascular deposits of IgA and C3 in the upper and mid-dermis. These findings were consistent with Schönlein-Henoch purpura. There was no evidence of renal involvement or placental dysfunction. The patient was treated with low-dose oral corticosteroids and a healthy infant was delivered by cesarean section. Examination of the placenta and the navel string disclosed no signs of vasculitis or infarction. Conclusions Schönlein-Henoch purpura is rarely reported in pregnancy. Treatment with orally administred corticosteroids may lead to a beneficial outcome for mother and newborn. PMID:11866865

Feldmann, Robert; Rieger, Walter; Sator, Paul G; Gschnait, Friedrich; Breier, Friedrich

2002-01-01

128

Multiple small-intestine intussusceptions: a complication of purpura haemorrhagica in a horse.  

PubMed

A Belgian draft horse stallion presented with classical signs of purpura haemorrhagica: oedema of the distal limbs, ventral abdomen and head, ecchymotic haemorrhage of mucous membranes, epistaxis, fever, lethargy, reluctance to move, and anorexia. Serum chemistry revealed a highly elevated gamma-globulin fraction. Streptococcal lymphadenitis (strangles) had been present on a neighbouring farm in the past few months. After an initial positive response to therapy with benzylpenicillin, flunixin and dexamethasone, the horse's condition deteriorated suddenly on day 4 of hospitalization, with signs of severe endotoxaemia and small-intestine obstruction. The horse was euthanized because of its poor prognosis and because of economic considerations. On necropsy, large serosal haemorrhages in the small and large intestine and multiple jejunojejunal intussusceptions were found. Intussusception is a well-known complication in children with Henoch-Schonlein purpura, a human autoimmune disease resembling purpura haemorrhagica in horses. To the author's knowledge, this is the first report to describe intussusception as a complication of purpura haemorrhagica in a horse. PMID:21699093

Dujardin, C L L

2011-06-01

129

Purpura fulminans in a Child as a Complication of Chickenpox Infection  

Microsoft Academic Search

Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation or in the context of an acquired or congenital protein C or S deficiency. Here we report the case of a 4-year-old child who developed, 5 days after a chickenpox infection, large painful ecchymotic, necrotizing and retiform plaques on the lower extremities. Laboratory analyses revealed very

Alexandre Campanelli; Gürkan Kaya; Ayse Hulya Ozsahin; Giorgio La Scala; Cédric Jacquier; Mélanie Stauffer; Françoise Boehlen; Philippe de Moerloose; Jean-Hilaire Saurat

2004-01-01

130

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

131

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

PubMed Central

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

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

2014-01-01

132

Purpura fulminans in a child as a complication of chickenpox infection.  

PubMed

Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation or in the context of an acquired or congenital protein C or S deficiency. Here we report the case of a 4-year-old child who developed, 5 days after a chickenpox infection, large painful ecchymotic, necrotizing and retiform plaques on the lower extremities. Laboratory analyses revealed very low protein S levels as well as anticardiolipin antibodies. Aggressive treatment by low-molecular-weight heparin, steroids, intravenous immunoglobulins and fresh frozen plasma was able to prevent the extension of the lesions and to correct the coagulation abnormalities. No lesions required skin grafting. As in our patient, an acquired protein S deficiency is probably responsible for most cases of purpura fulminans occurring after varicella, but the concomitant presence of antiphospholipid antibodies may also play a role. PMID:15118384

Campanelli, Alexandre; Kaya, Gürkan; Ozsahin, Ayse Hulya; La Scala, Giorgio; Jacquier, Cédric; Stauffer, Mélanie; Boehlen, Françoise; de Moerloose, Philippe; Saurat, Jean-Hilaire

2004-01-01

133

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

PubMed Central

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

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

2013-01-01

134

An adult patient with Kabuki syndrome presenting with Henoch-Schönlein purpura complicated with pulmonary hemorrhage  

Microsoft Academic Search

We present a case of a 33-year-old woman with Kabuki syndrome (KS) presenting with Henoch-Schönlein purpura (HSP). She was\\u000a admitted to our hospital with a brain abscess in the lateral ventricle and meningitis. She had been diagnosed with KS. Skin\\u000a eruptions had appeared on her lower extremities, with arthralgia, cough, and hemoptysis. She suddenly developed pulmonary\\u000a hemorrhage and respiratory failure.

Jun Oto; Akiko Mano; Emiko Nakataki; Harutaka Yamaguchi; Daisuke Inui; Hideaki Imanaka; Masaji Nishimura

2008-01-01

135

Ataxia and peripheral neuropathy: rare manifestations in Henoch-Schönlein purpura  

Microsoft Academic Search

.   Henoch-Schönlein purpura (HSP) is a multisystemic vasculitis. Nervous system involvement is usually underestimated. Headaches,\\u000a mental status changes and seizures are the most frequent neurologic symptoms. Ataxia and mononeuropathy are both very rare.\\u000a We present an 11-year-old boy with HSP who suffered from ataxia during the initial presentation and peripheral neuropathy\\u000a at the time of a relapse. Brainstem vasculitic involvement

A. Bulun; R. Topaloglu; A. Duzova; I. Saatci; N. Besbas; A. Bakkaloglu

2001-01-01

136

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

137

Hemoglobinuria test  

MedlinePLUS

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

138

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

PubMed Central

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

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

2015-01-01

139

[Videocapsule endoscopy used for diagnosis of Henoch-Schönlein purpura with gastrointestinal complications.  

PubMed

Henoch-Schönlein purpura (HSP) is primarily a childhood disease and is less common in adults where the incidence varies from 3.4 to 14.3 cases per million. We describe a case of adult HSP and discuss the role of videocapsule endoscopy, which is a non-invasive and safe method to evaluate the typical mucosa changes in especially small bowel. Medical doctors should be aware of HSP in adults and pay attention to the fact that in an unusual presentation with gastrointestinal manifestation videocapsule endoscopy may play a safe diagnostic role. PMID:24044543

Sivayogajeyam, Sivakaran; Christensen, Kent Dencker

2013-09-16

140

Atypical Henoch-Schonlein purpura: a forerunner of familial Mediterranean fever.  

PubMed

Insuception is the most common cause of intestinal obstruction in early childhood. The cause of most intussusceptions is unknown but it can complicate the course of Henoch-Schonlein purpura (HSP) as a result of the vasculitic process. Familial Mediterranean fever (FMF), a common disease in Israel, is also associated with HSP. In a few patients, particularly in children, HSP has been reported to precede the diagnosis of FMF. We describe two patients with an unusual clinical course of severe abdominal pain as a result of intusucception. The correlation between intusucception, HSP and FMF are discussed. PMID:21598807

Adiv, Orly Eshach; Butbul, Yonathan; Nutenko, Igor; Brik, Riva

2011-04-01

141

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

142

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

143

Single donor, HL-A matched platelet transfusions for thrombocytopenic patients undergoing surgery.  

PubMed

Thrombocytopenic patients, who displayed hemostatic disorders and had been previously sensitized by repeated blood transfusions and/or pregnancies, were supported for surgical procedures by platelet transfusions obtained from a single ABO and HL-A matched donor by the use of continuous collection centrifugation. Because of the low incidence of HL-A identical donors, compatibility was assessed by known serological cross-reactivity of the HL-A determinants. In three cases repeated platelet transfusions had excellent in vivo survival, and sensitization could not be detected by a battery of immunological assays. In one case there was immune sensitization and refractoriness to repeated platelet transfusion, as documented by accelerated in vivo destruction of donor and third-party platelets bearing the disparate factor HL-A8. Although serologic tests for lymphocytotoxic and leukoagglutinating antibodies were negative, the patient displayed cellular immunity in leukocyte aggregation and cell-mediated plateletolysis tests. The single donor, continuous collection technique appears to have the technical advantage of rapid, efficient collection and the immunological benefit of a restricted spectrum of allosensitization. PMID:124097

Kahan, B D; Green, D; Ruder, A; Ranney, D F; Hartz, W H; Mittal, K K

1975-02-01

144

The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals.  

PubMed

Neuraxial anaesthesia is increasingly performed in thrombocytopenic patients at the time of delivery of pregnancy. There is a lack of data regarding the optimum platelet count at which spinal procedures can be safely performed. Reports are often confounded by the presence of other risk factors for spinal haematomata, such as anticoagulants, antiplatelet agents and other acquired or congenital coagulopathies/platelet function defects or rapidly falling platelet counts. In the absence of these additional risk factors, a platelet count of 80 x 10(9)/l is a 'safe' count for placing an epidural or spinal anaesthetic and 40 x 10(9)/l is a 'safe' count for lumbar puncture. It is likely that lower platelet counts may also be safe but there is insufficient published evidence to make recommendations for lower levels at this stage. For patients with platelet counts of 50-80 x 10(9)/l requiring epidural or spinal anaesthesia and patients with a platelet count 20-40 x 10(9)/l requiring a lumbar puncture, an individual decision based on assessment of risks and benefits should be made. PMID:19775301

van Veen, Joost J; Nokes, Timothy J; Makris, Mike

2010-01-01

145

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

146

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

147

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

148

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

PubMed

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

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

2015-01-01

149

The incidence and severity of Henoch-Schönlein purpura nephritis over a 22-year period in Fukushima Prefecture, Japan  

Microsoft Academic Search

Background  Recently, there have been a few reports on the decrease in the incidence of severe Henoch-Schönlein purpura nephritis (HSPN)\\u000a in Japan. To evaluate the incidence and the severity of HSPN, we examined the epidemiology and clinical manifestations of\\u000a HSPN in Fukushima Prefecture over a 22-year period.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We enrolled 61 patients (Group 1) diagnosed with HSPN between 1987 and 1997 and

Yukihiko Kawasaki; Kazuhide Suyama; Eichi Yugeta; Masahiko Katayose; Shigeo Suzuki; Hiroko Sakuma; Kenji Nemoto; Akira Tsukagoshi; Katsutoshi Nagasawa; Mitsuaki Hosoya

2010-01-01

150

Laboratory Markers Indicating Gastrointestinal Involvement of Henoch-Schönlein Purpura in Children  

PubMed Central

Purpose To determine clinically useful biochemical markers reflecting disease activity and/or gastrointestinal (GI) tract involvement in Henoch-Schönlein purpura (HSP). Methods A total of 185 children with HSP and 130 controls were included. Laboratory data indicating inflammation, standard coagulation, and activated coagulation were analyzed for the HSP patients, including measurements of the hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, prothrombin time, activated partial thromboplastin time, and fibrinogen, D-dimer, and fibrin degradation product (FDP) levels. The clinical scores of the skin, joints, abdomen, and kidneys were assessed during the acute and convalescence phases of HSP. Results The WBC count, ANC, ESR, and CRP, fibrinogen, D-dimer, and FDP levels were significantly higher in the acute phase compared with the convalescent phase of HSP (p<0.05). The total clinical scores were more strongly correlated with the D-dimer (r=0.371, p<0.001) and FDP (r=0.369, p<0.001) levels than with inflammatory markers, such as the WBC count (r=0.241, p=0.001), ANC (r=0.261, p<0.001), and CRP (r=0.260, p<0.001) levels. The patients with GI symptoms had significantly higher ANC (median [interquartile range], 7,138.0 [4,446.4-9,470.0] vs. 5,534.1 [3,263.0-8,153.5], p<0.05) and CRP (0.49 [0.15-1.38] vs. 0.23 [0.01-0.67], p<0.05), D-dimer (2.63 [1.20-4.09] vs. 1.75 [0.62-3.39]), and FDP (7.10 [0.01-13.65] vs. 0.10 [0.01-7.90], p<0.05) levels than those without GI symptoms. Conclusion D-dimer and FDPs are more strongly associated with disease activity and more consistently reflect GI involvement than inflammatory markers during the acute phase of HSP.

Hong, Jeana

2015-01-01

151

A case of IgG4-related tubulointerstitial nephritis concurrent with Henoch-Schönlein purpura nephritis  

PubMed Central

We describe a 72-year-old man, who had been suffered from Henoch-Schönlein purpura (HSP) several times, presented with hematoproteinuria with granular cast, and general lymphadenopathy. The immunological examination of the serum showed polyclonal hypergammagloburinemia with high value of IgG4. The renal biopsy revealed interstitial inflammatory cell infiltration, including infiltration of lymphocytes and plasma cells, and segmental glomerulonephritis. Direct immunofluorescence microscopy revealed apparent positive staining with anti-human IgA, and anti-human IgG in glomeruli, anti-human IgG4 antibody staining showed many positive plasma cells in the interstitium. The patient was diagnosed with HSP nephritis that was complicated by IgG4-related nephropathy. As a result of the treatment with 30mg prednisolone, the swelling of the LNs decreased, but the patient continued to have persistent hematoproteinuria. PMID:21450108

2011-01-01

152

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

153

Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies  

Microsoft Academic Search

INTRODUCTION: We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF\\/MEN\\/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials

Jean-Louis Vincent; Simon Nadel; Demetrios J Kutsogiannis; RT Noel Gibney; S Betty Yan; Virginia L Wyss; Joan E Bailey; Carol L Mitchell; Samiha Sarwat; Stephen M Shinall; Jonathan M Janes

2005-01-01

154

Efficacy of Beef Carcass Surface Trimming to Reduce or Eliminate Escherichia coli O157:H7 Surrogates from Subsequent Subprimals  

E-print Network

due to their level of immunity being 7 low. Clinical symptoms include watery diarrhea, hemorrhagic colitis, hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and death (4, 25, 30). Patients with E. coli O157:H7 infection...

Laster, Brittany Anise

2012-02-14

155

High dose gammaglobulin treatment for atopic dermatitis.  

PubMed Central

Patients with both severe atopic dermatitis and Kawasaki disease or idiopathic thrombocytopenic purpura were treated with high dose intravenous gammaglobulin. There was a marked improvement in the dermatitis. PMID:8185369

Kimata, H

1994-01-01

156

75 FR 32951 - Determination of Regulatory Review Period for Purposes of Patent Extension; PROMACTA  

Federal Register 2010, 2011, 2012, 2013, 2014

...the human drug product PROMACTA (eltrombopag olamine). PROMACTA is indicated the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to...

2010-06-10

157

Angioimmunoblastic T-Cell Lymphoma  

MedlinePLUS

... of autoimmune disorders, such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), in which the ... and red blood cells (in the case of AIHA). As with other types of NHL, diagnosing angioimmunoblastic ...

158

42 CFR 100.3 - Vaccine injury table.  

Code of Federal Regulations, 2010 CFR

...bradycardia, tachycardia, arrhythmia, edema of the pharynx and/or trachea and...lower respiratory tract obstruction, edema of the hypopharynx, epiglottis, larynx...include cases of immune (formerly called idiopathic) thrombocytopenic purpura...

2010-10-01

159

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

160

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

PubMed Central

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

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

2015-01-01

161

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

PubMed

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

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

2015-01-01

162

Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center.  

PubMed

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

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

2014-03-01

163

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

PubMed Central

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

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

2015-01-01

164

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

165

[Treatment of thoracic and abdominal cavity perforation complicated by Henoch-Schonlein purpura nephritis in a patient with high-voltage electric burn].  

PubMed

A 55-year-old male patient suffered from severe high-voltage electric burn with an area of 20%TBSA full-thickness injury. The injury involved the distal end of left upper limb, right trunk, and whole abdominal wall. Fracture of the 7th-10th ribs was found in the right side of chest, with perforation of abdominal cavity, and bilateral pleural effusion was found. Part of the small intestine was necrotic and exposed. At the early stage, xeno-acellular dermal matrix was grafted after debridement of abdominal wound; peritoneal lavage was performed; negative pressure drainage was performed in orificium fistula of intestine for promoting the adhesion between perforated intestine and abdominal scar. Two orificium fistulas formed after closure of abdominal granulation wound by autologous skin grafting. Eschar of chest wall and denatured ribs were retained. The risk of infection of thoracic cavity was decreased by promoting the adhesion between lung tissue and chest wall. During the treatment, the patient was diagnosed with Henoch-Schonlein purpura nephritis by renal biopsy, with the symptoms of purpura in the lower limbs, heavy proteinuria, severe hypoalbuminemia, edema, etc. After control of kidney damage by immunosuppressive treatment instead of glucocorticoid, alleviation of the levels of proteinuria and blood albumin, free latissimus dorsi myocutaneous flap was excised to repair chest wall, and free skin graft was excised to repair intestinal fistula. After all the wounds were successfully covered, the patient was treated with glucocorticoid combined with immunosuppressants for more than 1 year. The patient was followed up for 3 years, and his renal function was completely recovered with satisfactory clinical outcome. PMID:24360004

Zhang, Wei; Xie, Wei-guo; Min, Wei-xiong; Wang, De-yun; Zhang, Jia; Wan, Shi-yong

2013-10-01

166

A study of complement components C3, C5, C6, C7, C8 and C9 in chronic membranoproliferative glomerulonephritis, systemic lupus erythematosus, poststreptococcal nephritis, idiopathic nephrotic syndrome and anaphylactoid purpura  

Microsoft Academic Search

In a comparative study the hemolytic activity of C3, C5, C6, C7, C8, C9 and the C3 proactivator (C3PA) were measured in sera of 22 patients with chronic membrano-proliferative glomerulonephritis (CMPGN), 15 patients with idiopathic nephrotic syndrome, 10 patients with systemic lupus erythematosus, 7 patients with anaphylactoid purpura and 10 patients with acute poststreptococcal nephritis. In CMPGN, C3, C5, C6,

Hartmut Geiger; Robert A. Good; Noorbibi K. Day

1975-01-01

167

Progressive Pigmentary Purpura  

MedlinePLUS

... American Osteopathic College of Dermatology. Community Search Search » Sign In Remember Me Forgot your password? Haven't registered yet? more Calendar 4/23/2015 » 4/26/2015 2015 AOCD Spring Current Concepts in Dermatology Meeting 3/30/2016 » ...

168

Henoch-Schönlein Purpura  

MedlinePLUS

... aimed at preventing long-term kidney disease. [ Top ] Hope through Research Through its Division of Kidney, Urologic, ... co-chair); Steve Wassner, M.D. (co-chair); John Brandt, M.D.; Deepa Chand, M.D.; Ira ...

169

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

170

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

171

Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis.  

PubMed

Serum galactose-deficient immunoglobulin A1 (Gd-IgA1) is an inherited risk factor for adult IgA nephropathy (IgAN). In this paper, we determined the heritability of serum Gd-IgA1 levels in children with IgAN and Henoch-Schönlein purpura nephritis (HSPN), two disorders with clinical phenotypes sharing common pathogenic mechanisms. Serum Gd-IgA1 concentrations were quantified using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay. As a group, 34 children with either disorder (20 with HSPN and 14 with IgAN) had significantly higher Gd-IgA1 levels compared with 51 age- and ethnicity-matched pediatric controls. Serum levels of Gd-IgA1 were also elevated in a large fraction of 54 first-degree relatives of pediatric IgAN and HSPN patients compared with 141 unrelated healthy adult controls. A unilineal transmission of the trait was found in 17, bilineal transmission in 1, and sporadic occurrence in 5 of 23 families when both parents and the patient were analyzed. There was a significant age-, gender-, and household-adjusted heritability of serum galactose-deficient IgA1 estimated at 76% in pediatric IgAN and at 64% in HSPN patients. Thus, serum galactose-deficient IgA1 levels are highly inherited in pediatric patients with IgAN and HSPN, providing support for another shared pathogenic link between these disorders. PMID:21326171

Kiryluk, Krzysztof; Moldoveanu, Zina; Sanders, John T; Eison, T Matthew; Suzuki, Hitoshi; Julian, Bruce A; Novak, Jan; Gharavi, Ali G; Wyatt, Robert J

2011-07-01

172

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

173

Case of TTP with Cerebral Infarct Secondary to Platelet Transfusion  

Microsoft Academic Search

Background  Thrombotic thrombocytopenic purpura (TTP) is a rare disease in children with significant mortality in cases who do not receive\\u000a appropriate treatment.\\u000a \\u000a \\u000a \\u000a \\u000a Case  The author describe a 3-year-old child who presented with skin bleeds, microangiopathic anemia, thrombocytopenia and right\\u000a sided hemi paresis with aphasia and altered sensorium following platelet transfusion.\\u000a \\u000a \\u000a \\u000a \\u000a Conclusion  A diagnosis of thrombotic thrombocytopenic purpura was made and the child recovered

Sushil P. Tripathi; Anand S. Deshpande; Sandhya Khadse; Rajesh K. Kulkarni

2011-01-01

174

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

PubMed

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

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

2015-03-01

175

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

176

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

177

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

178

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.

Schlyer, David J. (Bellport, NY); Ferrieri, Richard A. (Patchogue, NY); Koehler, Conrad (Miller Place, NY)

1999-01-01

179

[Brain abscess caused by Nocardia sp in immunosuppressed patient].  

PubMed

Patient with autoimmune haemolytic anaemia and thrombocytopenic purpura (Evans Syndrome), treated with immunosuppressive therapy (prednisone and azathioprine) developed brain abscess unresponsive to antimicrobial therapy, in spite of its 23 days duration. Diagnosis could be possible after recover secretion of peribulbar abscess and maintenance of this material over seven days in incubation. PMID:11175594

Barata, C H; Oliveira, D A; Colombo, A L; Pereira, C A

2000-01-01

180

INVITED REVIEW Biology and physics of von Willebrand factor concatamers  

E-print Network

: biosynthesis, secretion, shear flow, thrombotic thrombocytopenic purpura, von Willebrand disease, weibel palade. Mutations in von Willebrand disease (VWD) both contribute to and are illuminated by understand- ing of VWFINVITED REVIEW Biology and physics of von Willebrand factor concatamers T. A. SPRINGER* *Immune

Springer, Timothy A.

181

Discovery of dual ZAP70 and Syk kinases inhibitors by docking into a rare C-helix-out conformation of Syk  

E-print Network

, is currently in clinical trials as an oral treatment of immune thrombocytopenic purpura (ITP). The majority in the ATP binding site and exposes an additional hydrophobic pocket. Inter- estingly, upon binding II inhibitors,3 the moiety occupying the hydrophobic pocket of the DFG-out conformation is (trifluoro

Caflisch, Amedeo

182

Presenting ADAMTS13 on a TTP-associated MHC.  

PubMed

In this issue of Blood, Sorvillo et al investigate possible molecular triggers leading to idiopathic, autoimmune thrombotic thrombocytopenic purpura (TTP) by identifying naturally processed A Disintegrin And Metalloprotease with ThromboSpondin type 1 motif 13 (ADAMTS13)-derived peptides presented on human dendritic cells. PMID:23620569

Pratt, Kathleen P

2013-04-25

183

Immune thrombocytopenia associated with consumption of tonic water  

PubMed Central

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

2015-01-01

184

Laparoscopic splenectomy  

Microsoft Academic Search

Summary Splenectomy has traditionally been done through a generous laparotomy incision, requiring complete mobilization of the spleen for removal. In selected cases, however, splenectomy may either be facilitated or performed entirely by laparoscopic means. Two patients with Hodgkin's disease in whom splenectomy was facilitated laparoscopically are described; in another patient with idiopathic thrombocytopenic purpura (ITP), the splenectomy was successfully performed

Brendan J. Carroll; Edward H. Phillips; Chester J. Semel; Moses Fallas; Leon Morgenstern

1992-01-01

185

Pulsed high dose dexamethasone treatment in chronic inflammatory demyelinating polyneuropathy: a pilot study  

Microsoft Academic Search

Six cycles of dexamethasone (40 mg per day for four sequential days) every 28 days induced remissions in 10 patients with idiopathic thrombocytopenic purpura (ITP). Whether the same results could be achieved in 10 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was investigated by comparing the Rivermead mobility index (RMI) before and after six cycles of treatment. Three patients discontinued

D. S. M. Molenaar; P A van Doorn; M. Vermeulen

1997-01-01

186

Chronic ITP: Analysis of various factors at presentation which predict failure to first line treatment and their response to second line therapy  

Microsoft Academic Search

Objective: To observe the significance of various factors in chronic idiopathic thrombocytopenic purpura (ITP) which predict the response of first line (corticosteroids) and second line therapy (splenectomy) and to evaluate their response to second line therapy. Methods: This was a descriptive, prospective study conducted from August 2004 till January 2006. Patients of all age groups and both genders with diagnosis

Naveen Naz Syed; Salman Naseem Adil; Raihan Sajid; Mohammad Usman; Bushra Moiz; Ghulam Nabi Kakepoto; Mohammad Khurshid

2007-01-01

187

Target: Terror  

NSDL National Science Digital Library

This week's In the News investigates the US military strike against targets linked to international terrorism. The eight resources discussed provide analysis, commentary, and recent news. On August 7, simultaneous bombings of US embassies in Nairobi, Kenya and Dar es Salaam, Tanzania, injured thousands of civilians and killed more than 250, including a dozen Americans. In a reprisal on August 20, based on "compelling evidence" from US intelligence agencies, President Clinton ordered a Tomahawk cruise missile attack on several sites suspected of being connected to the terrorist network responsible for the embassy bombings. The targets of the assault included six sites within the distributed Zhawar Kili al-Badr guerrilla camp near Khost, Afghanistan, and the El Shifa Pharmaceutical Plant near Khartoum, Sudan--assumed to be a manufacturing center for chemical weapons. Both locations are believed to be supported by Osama Bin Muhammad Bin Laden, who is, according to the Pentagon, linked to the embassy bombings and considered the "world's leading individual sponsor of terrorism against Americans." The transnational missile attack marks the most powerful military offensive against a private sponsor of confederate terrorist groups. The US called the assault a pre-emptive measure against terrorism and justified its use of force under Article 51 of the UN charter, which authorizes nations to act in self-defense if they anticipate aggression. US Defense Secretary William Cohen acknowledged that the military retaliation "will not eliminate the problem" of terrorism, but he believes the disruption and destruction of terrorist sanctuaries sends a clear message that the US will be steadfast in defense of its citizens "against these cowardly attacks."

Osmond, Andrew.

188

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

189

Electrically charged targets  

DOEpatents

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

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

1984-01-01

190

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

191

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

192

Magnetically attached sputter targets  

DOEpatents

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

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

1994-01-01

193

Human target acquisition performance  

NASA Astrophysics Data System (ADS)

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

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

2012-06-01

194

Magnetically attached sputter targets  

DOEpatents

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

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

1994-02-15

195

Monitoring production target thickness  

SciTech Connect

Pion and muon production targets at the Clinton P. Anderson Meson Physics Facility consist of rotating graphite wheels. The previous target thickness monitoring Procedure scanned the target across a reduced intensity beam to determine beam center. The fractional loss in current across the centered target gave a measure of target thickness. This procedure, however, required interruption of beam delivery to experiments and frequently indicated a different fractional loss than at normal beam currents. The new monitoring Procedure compares integrated ups and downs toroid current monitor readings. The current monitors are read once per minute and the integral of readings are logged once per eight-hour shift. Changes in the upstream to downstream fractional difference provide a nonintrusive continuous measurement of target thickness under nominal operational conditions. Target scans are now done only when new targets are installed or when unexplained changes in the current monitor data are observed.

Oothoudt, M.A.

1993-01-01

196

Monitoring production target thickness  

SciTech Connect

Pion and muon production targets at the Clinton P. Anderson Meson Physics Facility consist of rotating graphite wheels. The previous target thickness monitoring Procedure scanned the target across a reduced intensity beam to determine beam center. The fractional loss in current across the centered target gave a measure of target thickness. This procedure, however, required interruption of beam delivery to experiments and frequently indicated a different fractional loss than at normal beam currents. The new monitoring Procedure compares integrated ups and downs toroid current monitor readings. The current monitors are read once per minute and the integral of readings are logged once per eight-hour shift. Changes in the upstream to downstream fractional difference provide a nonintrusive continuous measurement of target thickness under nominal operational conditions. Target scans are now done only when new targets are installed or when unexplained changes in the current monitor data are observed.

Oothoudt, M.A.

1993-06-01

197

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

198

DTP - Molecular Targets  

Cancer.gov

Thousands of molecular targets have been measured in the NCI panel of 60 human tumor cell lines. Measurements include protein levels, RNA measurements, mutation status and enzyme activity levels. You can choose to search for a target of interest, or you may browse through a list of targets.

199

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

200

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

201

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

202

Bar coded retroreflective target  

DOEpatents

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

Vann, Charles S. (Fremont, CA)

2000-01-01

203

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

204

Effective neutron targets  

SciTech Connect

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

Gao, H.

1997-07-01

205

Targeting the tumor microenvironment  

PubMed Central

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. PMID:17485314

Kenny, Paraic A.; Lee, Genee Y.; Bissell, Mina J.

2010-01-01

206

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

207

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.

208

GWAS and drug targets  

PubMed Central

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

2014-01-01

209

Strategic Targeted Advertising  

Microsoft Academic Search

We present a strategic game of pricing and targeted-advertising. Firms can simultaneously target price advertisements to different groups of customers, or to the entire market. Pure strategy equilibria do not exist and thus market segmentation cannot occur surely. Equilibria exhibit random advertising --to induce an unequal distribution of information in the market-- and random pricing --to obtain profits from badly

Andrea Galeotti; José-Luis Moraga

2003-01-01

210

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

211

Tungsten Helium cooled Target  

E-print Network

Rotating Tungsten Helium cooled Target RoTHeTa Cyril Kharoua Daniela Ene, Ferenc Mezei, Etam Noah 2011 Some history >Granular Tungsten target helium cooled was first proposed by Peter Sievers for a MW a rotating wheel, fitted with tungsten rods and cooled with helium is a viable solution... #12;Page 4Cyril

McDonald, Kirk

212

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

213

Cellular Targets of Gefitinib  

Microsoft Academic Search

Targeted inhibition of protein kinases with small molecule drugs has evolved into a viable approach for anticancer therapy. However, the true selectivity of these therapeutic agents has remained unclear. Here, we used a proteomic method to profile the cellular targets of the clinical epidermal growth factor receptor kinase inhibitor gefitinib. Our data suggest alternative cellular modes of action for gefitinib

Dirk Brehmer; Klaus Godl; Stephanie Blencke; Alexander Kurtenbach; Martina Weber; Stefan Muller; Bert Klebl; Matt Cotten; Gyorgy Keri; Josef Wissing; Henrik Daub

2005-01-01

214

First SNS Target Replacement  

E-print Network

and Contamination · Target Change-out Operations · First Change-out Experience #12;3 Managed by UT several key functions: ­ Enclosure of the mercury process ­ Maintenance of the mercury process equipment, including the target ­ Processing and disposing of spent mercury processing equipment ­ Constructed using 1

McDonald, Kirk

215

Prioritising target markets  

Microsoft Academic Search

Target marketing is a key decision area for all businesses. Market size, growth rates, competitive forces, customer fit and profitability are just a few of the criteria which can be used by businesses assessing the attractiveness of their target markets. Yet despite the wealth of variables available to managers and the development of a range of decision tools to help

Lyndon Simkin; Sally Dibb

1998-01-01

216

Thyroid-associated autoimmune coagulation disorders  

Microsoft Academic Search

Abnormalities of blood coagulation are not rarely observed in patients with thyroid dysfunctions and may range from subclinical\\u000a laboratory abnormalities to clinically significant hemorrhagic or thrombotic complications. In this review, we summarize the\\u000a current knowledge on thyroid-associated autoimmune coagulation disorders (i.e., autoimmune thrombocytopenic purpura, antiphospholipid\\u000a syndrome, and autoantibodies against coagulation factor VIII) and discuss their laboratory characteristics, clinical impact,\\u000a and

Massimo Franchini; Giuseppe Lippi; Franco Manzato; Pier Paolo Vescovi

2010-01-01

217

Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy  

Microsoft Academic Search

A 16-year-old patient with steroid-dependent nephrotic syndrome with more than 35 relapses developed severe relapsing idiopathic thrombocytopenic purpura (ITP). At the age of 2 years, nephrotic syndrome was diagnosed and successfully treated with a standard prednisone regimen. Frequent relapses occurred. Treatment with oral cyclophosphamide followed by cyclosporine was successful, but several attempts to withdraw steroids failed and the patient suffered from

Kerstin Benz; Jörg Dötsch; Wolfgang Rascher; Daniel Stachel

2004-01-01

218

Evaluation of Alternative Cooking and Cooling Procedures for Large, Intact Meat Products to Achieve Lethality and Stabilization Microbiological Performance Standards  

E-print Network

will develop Hemolytic Uremic Syndrome (HUS). HUS usually affects children and has three components, hemolytic anemia, thrombocytopenia, and acute renal failure (13). In the elderly, thrombocytopenic purpura (TTP) can develop from the combination of HUS.... However, type A is the most common strain and is most frequently associated with foodborne illness. Type C has been reported to produce an enterotoxin that causes a more serious food-poisoning syndrome (13). The syndrome is known as necrotic enteritis...

Haneklaus, Ashley

2010-01-16

219

Validation of Hot Water and Lactic Acid Sprays for the Reduction of Enteric Pathogens on the Surface of Beef Carcasses  

E-print Network

% of cases can then become asymptomatic carriers. Death is highly unlikely among otherwise healthy individuals, resulting in a 0.1% death rate (25). Secondary disease syndromes and death from gastroenteritis, bacteremia, and subsequent focal infection... is differentiated from shigellosis by a lack of fever. Several clinical manifestations can result from infection including hemorrhagic colitis (HC), hemolytic uremic syndrome (HUS), and thrombotic thrombocytopenic purpura (TTP). Approximately 2-7% of E. coli O...

Wright, Kyle D.

2011-02-22

220

Factors contributing to the presence of Escherichia coli O157:H7 and O157:NM in feedlots and feedlot cattle.  

E-print Network

have increased since first reported in 1982. The infection can range from self-limited watery diarrhea to life-threatening manifestations including hemorrhagic colitis, and the diarrhea-associated form of the hemolytic-uremic syndrome. The increase...). The severity of infection with E. coli O157:H7 and O157: NM (nonmotile) can range from self-limited watery diarrhea to life-threatening manifestations, such as hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP) (62, 63). Children...

Ungkuraphinunt, Paphapit

2004-11-15

221

Intermittent cyclophosphamide treatment of autoimmune thrombocytopenia  

PubMed Central

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

Weinerman, Brian; Maxwell, Ian; Hryniuk, William

1974-01-01

222

Clopidogrel-Associated TTP An Update of Pharmacovigilance Efforts Conducted by Independent Researchers, Pharmaceutical Suppliers, and the Food and Drug Administration  

Microsoft Academic Search

Background and Purpose—Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n13), pharmaceutical suppliers

Anaadriana Zakarija; Nicholas Bandarenko; Dilip K. Pandey; Amy Auerbach; Dennis W. Raisch; Benjamin Kim; Hau C. Kwaan; June M. McKoy; Brian P. Schmitt; Charles J. Davidson; Paul R. Yarnold; Philip B. Gorelick; Charles L. Bennett

2010-01-01

223

Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS 13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP  

Microsoft Academic Search

Antibodies directed against ADAMTS13 have been detected in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). We have previously localized a major antigenic determinant within the spacer domain of ADAMTS13. To identify the amino acid residues of the spacer domain that are involved in binding of anti-ADAMTS13 antibodies, we constructed a series of fifteen hybrids (designated A-O) in

Brenda M. Luken; Ellen A. M. Turenhout; Paul H. P. Kaijen; Mascha J. Greuter; Wouter Pos; Mourik van J. A; Rob Fijnheer; Jan Voorberg

2006-01-01

224

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

225

A case of systemic lupus erythematosus expressing intractable thrombocytopenia remedied effectively by intermittent and continuous administrations of a small amount of immune globulin  

Microsoft Academic Search

We describe a case where intermittent and continuous administrations of a small amount of immune globulin were effective in\\u000a the treatment of refractory chronic immune thrombocytopenic purpura by systemic lupus erythematosus (SLE). Steroid pulse therapy\\u000a and cyclophosphamide pulse therapy were considered for thrombopenia. However, the patient had compressed fracture of the lumbar\\u000a vertebrae due to osteoporosis and right external malleolus

Etsuko Maeshima; Yohei Kida; Mikako Goda; Yoshinobu Minami

2006-01-01

226

A new method for active surveillance of adverse events from diphtheria\\/tetanus\\/pertussis and measles\\/mumps\\/rubella vaccines  

Microsoft Academic Search

We describe a new method for active post-marketing surveillance of vaccine safety based on patient records. We studied the association between diphtheria\\/ tetanus\\/pertussis (DTP) vaccination and febrile convulsion, and between measles\\/mumps\\/rubella (MMR) vaccination and febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in five district health authorities in England by linking vaccination records with computerised hospital admission records. We found an

P Farrington; M Rush; E Miller; S Pugh; A Colville; A Flower; J Nash; P Morgan-Capner

1995-01-01

227

Plasma Levels of ADAMTS13 Antigen Determined with an Enzyme Immunoassay Using a Neutralizing Monoclonal Antibody Parallel ADAMTS13 Activity Levels  

Microsoft Academic Search

Measurements of plasma ADAMTS13 activity (ADAMTS13: AC) have been used for the diagnosis of patients with thrombotic thrombocytopenic\\u000a purpura (TTP); however, the clinical usefulness of plasma ADAMTS13 antigen (ADAMTS13:AG) has been controversial, because antigen\\u000a values vary widely among patients with acquired idiopathic TTP (ai-TTP). We have developed a novel enzyme-linked immunosorbent\\u000a assay (ELISA) for the determination of plasma ADAMTS13:AG. This

Hideo Yagi; Shin Ito; Seiji Kato; Hisahide Hiura; Masanori Matsumoto; Yoshihiro Fujimura

2007-01-01

228

TTP presenting as refractory hypoglycemia in a patient with thromboangiitis obliterans.  

PubMed

Thrombotic thrombocytopenic purpura (TTP) is a challenging diagnosis to make in the emergency department. We present a case of TTP initially presenting with refractory hypoglycemia in a woman with thromboangiitis obliterans (Buerger's disease). To our knowledge, this is the first description of the association of hypoglycemia and thromboangiitis obliterans with TTP. We briefly review key aspects of the acute diagnosis and management of hypoglycemia and TTP pertinent to the emergency physician. PMID:24929773

Strobel, Ashley; Gingold, Daniel B; Calvello, Emilie J B

2014-12-01

229

Anti-Factor H Autoantibodies Associated with Atypical Hemolytic Uremic Syndrome  

Microsoft Academic Search

Several studies have demonstrated genetic predisposition in non-shigatoxin-associated hemolytic uremic syndrome (HUS), involving regulatory proteins of the complement alternative pathway: Factor H (FH) and membrane co-factor protein (CD46). Regarding the observations of thrombotic thrombocytopenic purpura patients, in whom a von Willebrand factor protease (ADAMST-13) deficiency may be inherited or acquired secondary to IgG antibodies, it was speculated that HUS might

Marie-Agnes Dragon-Durey; Chantal Loirat; Sylvie Cloarec; Marie-Alice Macher; Jacques Blouin; Hubert Nivet; Laurence Weiss; Wolf Herman Fridman; Veronique Fremeaux-Bacchi

2005-01-01

230

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

231

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

232

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

233

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

234

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

235

[Desperately seeking targets].  

PubMed

In clinical oncology, obtaining sequence data from tumour samples has become practical in terms of logistics, turnover time and costs. The major issue now is the interpretation of this sequence to define actionable targets, i.e. genome changes that are involved in tumorogenesis and that predict the efficacy of existing and available targeted treatments. This is the focus of major efforts from public clinical centres and from companies that see it as a promising commercial activity. PMID:25744270

Jordan, Bertrand

2015-02-01

236

Solid Target Options S. Childress  

E-print Network

Solid Target Options NuFACT'00 S. Childress Solid Target Options · The choice of a primary beam to demonstrate basic feasibility #12;Solid Target Options NuFACT'00 S. Childress Case for a Solid Target power is higher than for existing solid target designs - but not by a large factor. · NuMI graphite

McDonald, Kirk

237

Burglar Target Selection  

PubMed Central

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

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

2015-01-01

238

Quantum state targeting  

E-print Network

We introduce a new primitive for quantum communication that we term "state targeting" wherein the goal is to pass a test for a target state even though the system upon which the test is performed is submitted prior to learning the target state's identity. Success in state targeting can be described as having some control over the outcome of the test. We show that increasing one's control above a minimum amount implies an unavoidable increase in the probability of failing the test. 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 provide some applications of the results to the security analysis of 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 on a novel notion of security that arises only in the quantum context, that of cheat-sensitivity. Finally, our analysis of state targeting leads to some interesting secondary results, for instance, a generalization of Uhlmann's theorem and an operational interpretation of the fidelity between two mixed states.

Terry Rudolph; Robert W. Spekkens

2003-10-09

239

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

240

Phoenix Color Targets  

NASA Technical Reports Server (NTRS)

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

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

2008-01-01

241

LANSCE target calculations  

SciTech Connect

The LANSCE target operates at a beam current of 30 microamps. We present here the results of the finite-element calculations for the temperatures and stresses in the present target operated at 100 microamps. The calculations were run using the ABAQUS finite-element code. All finite-element codes require as input both the boundary conditions for the material being heated, and such material properties as the thermal conductivity, specific heat, and the elastic modulus. For the LANSCE target, the boundary conditions involve knowing the power deposition from the beam, and the heat transfer coefficients between the tungsten-alloy cylinder and the cooling water. We believe that these numbers are quite well established. 5 refs., 6 figs.

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

1989-01-01

242

Cooled particle accelerator target  

DOEpatents

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

Degtiarenko, Pavel V.

2005-06-14

243

Targeted antithrombotic protein micelles.  

PubMed

Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site-specific delivery of a variety of therapeutic agents. Multifunctional protein micelles bearing targeting and therapeutic proteins were now obtained by one-pot transpeptidation using an evolved sortase?A. Conjugation to the corona of a single-chain antibody (scFv), which binds to the ligand-induced binding site (LIBS) of activated GPIIb/IIIa receptors, enabled the efficient detection of thrombi. The inhibition of thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for the local generation of activated protein?C, which inhibits the formation of thrombin. An effective strategy has been developed for the preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events. PMID:25504546

Kim, Wookhyun; Haller, Carolyn; Dai, Erbin; Wang, Xiowei; Hagemeyer, Christoph E; Liu, David R; Peter, Karlheinz; Chaikof, Elliot L

2015-01-26

244

Nonglycemic targets in diabetes.  

PubMed

In conclusion, targets for patients with diabetes have actually become simpler with the release of new guidelines. The targets discussed in this article are summarized in Box 3. Finally, as clinicians and patients with diabetes struggle with the overwhelming burden of care, clinicians should consider the increasingly codified ethic of minimally disruptive medicine, which considers not just what patients and doctors can do but what patients' priorities, wishes, and needs are rather than the many specialist tests and treatment options available. Finding the balance may be easier with the new evidence-based and more straightforward guidelines. PMID:25456650

DeWitt, Dawn; Dugdale, David C; Adam, William R

2015-01-01

245

Emerging bacterial enzyme targets.  

PubMed

The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents, as well as by the emergence of new pathogens with the potential for rapid global spread. Thus, there is a critical need for novel antibacterial agents and new strategies to advance the drug discovery process. In the post-genomic era, comparative genomics, functional genomics and proteomics will play important roles in identifying new enzyme targets for the discovery of novel antibacterial agents. This review will discuss bacterial enzyme targets, specifically focusing on enzymes involved in fatty acid and cell wall biosynthesis. PMID:17328230

Su, Zhengding; Honek, John F

2007-02-01

246

Target Heart Rate  

NSDL National Science Digital Library

Students will practice how to calculate their Target Heart Rate to use during exercise routines. This will help students monitor the intensity of their workouts, and ultimately help them achieve results from their workout. Standard 2: Objective 2: a,b,c Before we discuss what the Target Heart Range is and how we can us it, we must first have some basic knowledge of the heart and it's functions. Click the "habits of the heart" to learn the basics of the heart and how it circulates blood throughout the body. Habits of the Heart The hearts ...

Mr. Peterson

2011-09-18

247

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

248

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

249

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

250

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

251

Targeted radionuclide therapy  

PubMed Central

Targeted radionuclide therapy (TRT) seeks molecular and functional targets within patient tumor sites. A number of agents have been constructed and labeled with beta, alpha, and Auger emitters. Radionuclide carriers spanning a broad range of sizes; e.g., antibodies, liposomes, and constructs such as nanoparticles have been used in these studies. Uptake, in percent-injected dose per gram of malignant tissue, is used to evaluate the specificity of the targeting vehicle. Lymphoma (B-cell) has been the primary clinical application. Extension to solid tumors will require raising the macroscopic absorbed dose by several-fold over values found in present technology. Methods that may effect such changes include multistep targeting, simultaneous chemotherapy, and external sequestration of the agent. Toxicity has primarily involved red marrow so that marrow replacement can also be used to enhance future TRT treatments. Correlation of toxicities and treatment efficiency has been limited by relatively poor absorbed dose estimates partly because of using standard (phantom) organ sizes. These associations will be improved in the future by obtaining patient-specific organ size and activity data with hybrid SPECT?CT and PET?CT scanners. PMID:18697529

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

2008-01-01

252

Laser-target interactions  

Microsoft Academic Search

Metallographic and microscopic techniques have been applied to the study of laser targets of various materials. Optical microscopy and scanning electron microscopy of foils and wires that had been irradiated by a 10-J laser (wavelength 1.06 ?m) were followed by sectioning through the holes both longitudinally and transversely. Foils of gold and titanium show considerable melting and splatter on the

C. G. Hoffman

1974-01-01

253

Laser-target interactions  

Microsoft Academic Search

Metallographic and microscopic techniques have been applied to the study of laser targets of various materials. Optical microscopy and scanning electron microscopy of foils and wires that had been irradiated by a 10-J laser (wavelength 1.06 mum) were followed by sectioning through the holes both longitudinally and transversely. Foils of gold and titanium show considerable melting and splatter on the

C. G. Hoffman

1974-01-01

254

Costly Targeted Persuasive Advertising  

Microsoft Academic Search

Traditionally, advertising has been thought of as an informative message displayed by firms to a large number of potential consumers in order to educate them about their product's characteristics. Recently, other aspects of advertising have moved to the forefront. Improvements in technology allow for the targeting of specific consumers with messages, and for collecting enough data on individuals so that

Christopher Willmore

255

Target-Rich Environment  

ERIC Educational Resources Information Center

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

Perna, Mark C.

2005-01-01

256

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

257

Targeted radionuclide therapy  

SciTech Connect

Targeted radionuclide therapy (TRT) seeks molecular and functional targets within patient tumor sites. A number of agents have been constructed and labeled with beta, alpha, and Auger emitters. Radionuclide carriers spanning a broad range of sizes; e.g., antibodies, liposomes, and constructs such as nanoparticles have been used in these studies. Uptake, in percent-injected dose per gram of malignant tissue, is used to evaluate the specificity of the targeting vehicle. Lymphoma (B-cell) has been the primary clinical application. Extension to solid tumors will require raising the macroscopic absorbed dose by several-fold over values found in present technology. Methods that may effect such changes include multistep targeting, simultaneous chemotherapy, and external sequestration of the agent. Toxicity has primarily involved red marrow so that marrow replacement can also be used to enhance future TRT treatments. Correlation of toxicities and treatment efficiency has been limited by relatively poor absorbed dose estimates partly because of using standard (phantom) organ sizes. These associations will be improved in the future by obtaining patient-specific organ size and activity data with hybrid SPECT/CT and PET/CT scanners.

Williams, Lawrence E.; DeNardo, Gerald L.; Meredith, Ruby F. [Radiology Division, City of Hope National Medical Center, Duarte, California 91010 (United States); Internal Medicine, University of California Davis Medical Center, 1508 Alhambra Boulevard, Suite 3100, Sacramento, California 95816 (United States); Department of Radiation Oncology, Wallace Tumor Institute WTI No. 117, University of Alabama at Birmingham, Birmingham, Alabama 35294 (United States)

2008-07-15

258

High purity tungsten targets  

NASA Technical Reports Server (NTRS)

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

1975-01-01

259

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

260

Future Fixed Target Facilities  

SciTech Connect

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

Melnitchouk, Wolodymyr

2009-01-01

261

Target Heart Rate Calculator  

MedlinePLUS

... workout Enter your age to find a target heart rate during exercise. You'll get the most out of your activities by staying within this range of heartbeats/minute. What is your age? years. How to Check Your Heart Rate Right after you stop exercising, take your pulse: ...

262

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

263

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...

264

How effective is targeted advertising?  

Microsoft Academic Search

Advertisers are demanding more accurate estimates of the impact of targeted advertisements, yet no study proposes an appropriate methodology to analyze the effectiveness of a targeted advertising campaign, and there is a dearth of empirical evidence on the effectiveness of targeted advertising as a whole. The targeted population is more likely to convert from advertising so the response lift between

Ayman Farahat; Michael C. Bailey

2012-01-01

265

Air target algorithm development (ATAD)  

Microsoft Academic Search

The Combat Air Forces have invested heavily in a sensor and weapon capability to detect and attack air targets at long ranges. Unfortunately, the ability to identify these targets lags behind these capabilities. Under the Air Force sponsored Air Target Algorithm Development (ATAD) program, model-based reasoning (MBR) fusion algorithms have been developed and demonstrated for improved air target identification (ID).

B. Overfield; J. Thomas; M. Cohen; V. Sylvester; R. Rogers; D. Morgan

1998-01-01

266

Interferometric moving ground target imaging  

Microsoft Academic Search

This paper describes an interferometric synthetic aperture radar (SAR) processing technique, interferometric moving target focusing (IMTF), which is capable of creating clutter suppressed moving ground target images. One-meter range resolution data has been processed and is presented. The potential benefit of a moving ground target imaging system, the IMTF processing approach, differences between IMTF and other moving ground target imaging

E. F. Stockburger; D. N. Held

1995-01-01

267

Media Exposure in Target Markets  

Microsoft Academic Search

In spite of the fact that nearly all advertising campaigns target specific target markets, no models exist for estimating the exposure of a media schedule to a target market, given commonly available data. We propose such a model, based on an approximate log-linear model approach. We tested the model against available models for estimating pairwise duplications within target markets, for

Peter J. Danaher; Roland T. Rust

1993-01-01

268

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.

269

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.

270

Solvent recovery targeting  

SciTech Connect

One of the environmental challenges faced by the pharmaceutical and specialty chemical industries is the widespread use of organic solvents. With a solvent-based chemistry, the solvent necessarily has to be separated from the product. Chemical species in waste-solvent streams typically form multicomponent azeotropic mixtures, and this often complicates separation and, hence, recovery of solvents. A design approach is presented whereby process modifications proposed by the engineer to reduce the formation of waste-solvent streams can be evaluated systematically. This approach, called solvent recovery targeting, exploits a recently developed algorithm for elucidating the separation alternatives achievable when applying batch distillation to homogeneous multicomponent mixtures. The approach places the composition of the waste-solvent mixture correctly in the relevant residue curve map and computes the maximum amount of pure material that can be recovered via batch distillation. Solvent recovery targeting is applied to two case studies derived from real industrial processes.

Ahmad, B.S.; Barton, P.I. [Massachusetts Inst. of Tech., Cambridge, MA (United States)] [Massachusetts Inst. of Tech., Cambridge, MA (United States)

1999-02-01

271

Complement-targeted therapeutics  

PubMed Central

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

Ricklin, Daniel; Lambris, John D

2010-01-01

272

Targeting and Informal Insurance  

Microsoft Academic Search

The standard method of testing for e-cient risk-sharing in village economies (Townsend, 1994) doesn't allow one to identify vulnerable households, only to make state- ments about the average risk in the village, or of sub-groups identiflable on the basis of observables. Here,byworkingdirectlywithinter-householdconsumptioncorrelationswe're abletoidentifyhouseholdswhichareprobablyexposedtounusuallyhighamountsofidiosyn- cratic risk. An obvious use for this identifying information involves targeted interventions to help those households. However,

Ethan Ligon

2002-01-01

273

Targeting fragile X  

PubMed Central

Ten years after the identification of the gene responsible for fragile X syndrome, recent studies have revealed a list of mRNAs bound by the fragile X gene product and have identified specific sequences required for the interaction between the fragile X protein and its targets. These results are a breakthrough in understanding why absence of the fragile X protein leads to mental retardation. PMID:12049671

Gantois, Ilse; Kooy, R Frank

2002-01-01

274

SETI target selection.  

PubMed

The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. In this paper we propose strategies for target selection. We have two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites. For the main Targeted Search survey of approximately 1000 nearby solar-type stars, we argue that the selection criteria should be heavily biased by what we know about the origin and evolution of life here on Earth. We propose that observations of stars with stellar companions orbiting near the habitable zone should be de-emphasized, because such companions would prevent the formation of habitable planets. We also propose that observations of stars younger than about three billion years should be de-emphasized in favor of older stars, because our own technical civilization took longer than three billion years to evolve here on Earth. To provide the information needed for the preparation of specific target lists, we have undertaken an inventory of a large sample of solar-type stars out to a distance of 60 pc, with the goal of characterizing the relevant astrophysical properties of these stars, especially their ages and companionship. To complement the main survey, we propose that a modest sample of the nearest stars should be observed without any selection biases whatsoever. Finally, we argue that efforts to identify stars with planetary systems should be expanded. If found, such systems should receive intensive scrutiny. PMID:11540737

Latham, D W; Soderblom, D R

1995-01-01

275

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

276

New targets for DBS.  

PubMed

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

Benabid, Alim Louis; Torres, Napoleon

2012-01-01

277

Bromodomains as therapeutic targets  

PubMed Central

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

Muller, Susanne; Filippakopoulos, Panagis; Knapp, Stefan

2011-01-01

278

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

279

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

280

Target Asteroids! Observing Targets for 2014 October through December  

NASA Astrophysics Data System (ADS)

Asteroids to be observed by the Target Asteroids! program during the period of October to December 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

2014-10-01

281

SNS Target Systems Operational  

E-print Network

.8 80 800 1.1x10141.5x1014 80 4.8 1.02 #12;5 Managed by UT-Battelle for the U.S. Department of Energy.8 27.9 RF 226.4 20.3 Ion Source 101.8 9.1 Controls 90.4 8.1 E-MagPS 68.1 6.1 E-choppers 58.3 5.2 E · Proton Beam Window Replacement · Target Imaging System · Mercury System Development · Power Upgrade

McDonald, Kirk

282

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)

2004-02-17

283

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

284

Targeted advertising as a signal  

Microsoft Academic Search

This study presents a signaling model of advertising for horizontally differentiated products. The central ingredients of\\u000a the model are two important characteristics of advertising—targeting, and noisy information content. The theory yields interesting\\u000a results about the informational role of targeted advertising, and its consequences. First, targeting can itself serve as a\\u000a signal on product attributes. Second, the effectiveness of targeting depends

Bharat N. Anand; Ron Shachar

2009-01-01

285

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

286

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

287

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. PMID:25538966

Guan, Yong-Song; Hu, Ying

2014-01-01

288

Marasmius oreades lectin induces renal thrombotic microangiopathic lesions.  

PubMed

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

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

2004-10-01

289

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

290

Role of Siglec-7 in Apoptosis in Human Platelets  

PubMed Central

Background Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis. Methodology/Principal Findings We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on ? granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (??m) depolarization; (ii) elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii) phosphatidylserine exposure and (iv), microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis. Conclusions/Significance The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions), Siglec-7 might be a molecular target for therapeutic intervention/prevention. PMID:25230315

Nguyen, Kim Anh; Hamzeh-Cognasse, Hind; Palle, Sabine; Anselme-Bertrand, Isabelle; Arthaud, Charles-Antoine; Chavarin, Patricia; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

2014-01-01

291

Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options.  

PubMed

Abstract Adult-onset Still's disease (AOSD), a systemic inflammatory disorder, is often considered a part of the spectrum of the better-known systemic-onset juvenile idiopathic arthritis, with later age onset. The diagnosis is primarily clinical and necessitates the exclusion of a wide range of mimicking disorders. AOSD is a heterogeneous entity, usually presenting with high fever, arthralgia, skin rash, lymphadenopathy, and hepatosplenomegaly accompanied by systemic manifestations. The diagnosis is clinical and empirical, where patients are required to meet inclusion and exclusion criteria with negative immunoserological results. There are no clear-cut diagnostic radiological or laboratory signs. Complications of AOSD include transient pulmonary hypertension, macrophage activation syndrome, diffuse alveolar hemorrhage, thrombotic thrombocytopenic purpura and amyloidosis. Common laboratory abnormalities include neutrophilic leukocytosis, abnormal liver function tests, and elevated acute-phase reactants (ESR, CRP, ferritin). Treatment consists of anti-inflammatory medications. Non-steroidal anti-inflammatory drugs have limited efficacy, and corticosteroid therapy and disease-modifying anti-rheumatic drugs are usually required. Recent advances have revealed a pivotal role of proinflammatory cytokines such as tumor necrosis factor-? (TNF-?), interleukin (IL)-1, IL-6, IL-8, and IL-18 in disease pathogenesis, giving rise to the development of novel targeted therapies aiming at optimal disease control. The review aims to summarize recent advances in pathophysiology and potential therapeutic strategies in AOSD. PMID:25613167

Kadavath, Sabeeda; Efthimiou, Petros

2015-02-01

292

Life-threatening complications of adult-onset Still's disease.  

PubMed

Adult-onset Still's Disease (AOSD) since its description in 1971 has proven to be a very complex and challenging disease entity. This rare auto-inflammatory disease is classically described by the "Still's triad" of fever, rash, and arthritis, although the atypical cases frequently outnumber the typical ones. The exact pathogenesis and etiologic factors responsible for the clinical features remain largely obscure, despite recent suggestive cytokine biology findings. Diagnosis is made on clinical grounds, following the exclusion of mimickers of infectious, autoimmune or neoplastic etiology, with the additional consideration of non-specific laboratory abnormalities such as peripheral leukocytosis and elevation of serum ferritin and other acute phase reactants. The disease manifestations are protean and can include diverse complications, affecting multiple organ systems. Moreover, the severity of the organ involvement can vary considerably, representing a wide spectrum from the self-limited to severe. The mainstay of therapy has evolved from the traditional use of corticosteroids and oral immunosupressants to the newer targeted treatments with biologic agents. The scope of this review is to alert the clinician to the existence of life-threatening AOSD complications, namely the macrophage activation syndrome, disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura, diffuse alveolar hemorrhage, and pulmonary arterial hypertension. Such knowledge may lead in earlier recognition, prompt treatment, and, ideally, improved patient outcomes. PMID:24435354

Efthimiou, Petros; Kadavath, Sabeeda; Mehta, Bella

2014-03-01

293

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

294

Liquid Hydrogen: Target, Detector  

NASA Astrophysics Data System (ADS)

In 1952 D. Glaser demonstrated that a radioactive source's radiation could boil 135°C superheated-diethyl ether in a 3-mm Ø glass vessel and recorded bubble track growth on high-speed film in a 2-cm3 chamber. This Bubble Chamber (BC) promised improved particle track time and spatial resolution and cycling rate. Hildebrand and Nagle, U of Chicago, reported Liquid Hydrogen minimum ionizing particle boiling in August 1953. John Wood created the 3.7-cm Ø Liquid Hydrogen BC at LBL in January 1954. By 1959 the Lawrence Berkley Laboratory (LBL) Alvarez group's "72-inch" BC had tracks in liquid hydrogen. Within 10 years bubble chamber volumes increased by a factor of a million and spread to every laboratory with a substantial high-energy physics program. The BC, particle accelerators and special separated particle beams created a new era of High Energy Physics (HEP) experimentation. The BC became the largest most complex cryogenic installation at the world's HEP laboratories for decades. The invention and worldwide development, deployment and characteristics of these cryogenic dynamic target/detectors and related hydrogen targets are described.

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

2004-06-01

295

Liquid Hydrogen: Target, Detector  

SciTech Connect

In 1952 D. Glaser demonstrated that a radioactive source's radiation could boil 135 deg. C superheated-diethyl ether in a 3-mm O glass vessel and recorded bubble track growth on high-speed film in a 2-cm3 chamber. This Bubble Chamber (BC) promised improved particle track time and spatial resolution and cycling rate. Hildebrand and Nagle, U of Chicago, reported Liquid Hydrogen minimum ionizing particle boiling in August 1953. John Wood created the 3.7-cm O Liquid Hydrogen BC at LBL in January 1954. By 1959 the Lawrence Berkley Laboratory (LBL) Alvarez group's '72-inch' BC had tracks in liquid hydrogen. Within 10 years bubble chamber volumes increased by a factor of a million and spread to every laboratory with a substantial high-energy physics program. The BC, particle accelerators and special separated particle beams created a new era of High Energy Physics (HEP) experimentation. The BC became the largest most complex cryogenic installation at the world's HEP laboratories for decades. The invention and worldwide development, deployment and characteristics of these cryogenic dynamic target/detectors and related hydrogen targets are described.

Mulholland, G.T. [Applied Cryogenics Technology, Ovilla TX 75154 (United States); Harigel, G.G. [CERN, European Organization for Nuclear Research, 1211 Geneva 23 (Switzerland)

2004-06-23

296

Targeted therapy for sarcomas  

PubMed Central

Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing’s sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing’s sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. PMID:24669185

Forscher, Charles; Mita, Monica; Figlin, Robert

2014-01-01

297

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

298

Old Drug, New Target  

PubMed Central

Transcription by RNA polymerase I (Pol-I) is the main driving force behind ribosome biogenesis, a fundamental cellular process that requires the coordinated transcription of all three nuclear polymerases. Increased Pol-I transcription and the concurrent increase in ribosome biogenesis has been linked to the high rates of proliferation in cancers. The ellipticine family contains a number of potent anticancer therapeutic agents, some having progressed to stage I and II clinical trials; however, the mechanism by which many of the compounds work remains unclear. It has long been thought that inhibition of Top2 is the main reason behind the drugs antiproliferative effects. Here we report that a number of the ellipticines, including 9-hydroxyellipticine, are potent and specific inhibitors of Pol-I transcription, with IC50 in vitro and in cells in the nanomolar range. Essentially, the drugs did not affect Pol-II and Pol-III transcription, demonstrating a high selectivity. We have shown that Pol-I inhibition occurs by a p53-, ATM/ATR-, and Top2-independent mechanism. We discovered that the drug influences the assembly and stability of preinitiation complexes by targeting the interaction between promoter recognition factor SL1 and the rRNA promoter. Our findings will have an impact on the design and development of novel therapeutic agents specifically targeting ribosome biogenesis. PMID:23293027

Andrews, William J.; Panova, Tatiana; Normand, Christophe; Gadal, Olivier; Tikhonova, Irina G.; Panov, Konstantin I.

2013-01-01

299

Gelina neutron target optimisation.  

PubMed

A study is being performed on the properties of the Geel Electron Linear Accelerator (GELINA), a powerful white neutron source, designed for the high-energy resolution time-of-flight measurements. The main aim of this study is to reduce the time spread of neutrons of the given energy without compromising the neutron yield. Both time spread and neutron intensity influence the experimental accuracy of high-resolution neutron cross section measurements, which are particularly important in the resonance region. The quantities of interest have been simulated with coupled electron-photon-neutron steady state and transient MCNP4C3 calculations. Following benchmarking of the code to the properties of the existing target, neutron yield, energy spectra, resolution functions, and neutron and heat spatial distributions have been determined for various alternative geometries and materials. At a fixed accelerator power, actinides deliver the highest neutron yield and a small target provides the best time resolution. The resulting high-power density requires a joint optimisation of the thermal hydraulics and neutronics properties. PMID:16381756

Flaska, M; Plompen, A J M; Mondelaers, W; Lathouwers, D; van der Hagen, T H J J; van Dam, H

2005-01-01

300

Projectile penetration into representative targets  

Microsoft Academic Search

The differential equation representing the penetration of a 'hard' projectile into semi-infinite, homogeneous target materials is solved for several generic combinations of the target material\\/projectile characteristics. A 'hard' projectile is defined as one that does not change size or shape and does not lose mass during the penetration process. The target materials evaluated range from the structurally 'soft' materials (liquids)

George W. Stone

1994-01-01

301

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

302

Cancer Cell Targeting Androgen Receptor  

E-print Network

Cancer Cell Article Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer Min Ni therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%­30% of cases in the development of endo- crine therapies targeting estrogen production or ER for both breast cancer treatment

Liu, Xiaole Shirley

303

Target fabrication activities in Japan  

Microsoft Academic Search

Some of the recent achievements in fabrication technologies for laser fusion targets are reviewed. Fabrications of hollow glass and plastic microspheres, development of cryogenic targets, control of density and effective atomic number in coatings on microspheres, fabrication of complicated multishell target, and new characterization technique by electrostatic handling are described.

Y. Izawa; T. Norimatsu; C. Yamanaka

1985-01-01

304

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

305

Foveal target repetitions reduce crowding.  

PubMed

Crowding is the limitation of peripheral vision by clutter. Objects that are easily identified when presented in isolation are hard to identify when presented flanked by similar close-by objects. It is often assumed that the signal of a crowded target is irretrievably lost because it is combined with the signals of the flankers. Here, we asked whether a target signal can be enhanced (or retrieved) by items presented far outside the crowding region. We investigated whether remote items matching a peripheral, crowded target enhanced discrimination compared to remote items not matching the target. In Experiment 1, we presented the remote item at different locations in the visual field and found that, when presented in the fovea, a matching remote item improved target discrimination compared to a nonmatching remote item. In Experiment 2, we varied stimulus onset asynchronies between target and remote items and found a strong effect when the remote item was presented simultaneously with the target. The effect diminished (or was absent) with increasing temporal separation. In Experiment 3, we asked whether semantic knowledge of a target was sufficient to improve target discrimination and found that this was not the case. We conclude that crowded target signals are not irretrievably lost. Rather, their accurate recognition is facilitated in the presence of remote items that match the target. We suggest that long-range grouping mechanisms underlie this "uncrowding" effect. PMID:25294741

Sayim, Bilge; Greenwood, John A; Cavanagh, Patrick

2014-01-01

306

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

307

PDFs for nuclear targets  

E-print Network

Understanding nuclear effects in parton distribution functions (PDF) is an essential component needed to determine the strange and anti-strange quark contributions in the proton. In addition Nuclear Parton Distribution Functions (NPDF) are critically important for any collider experiment with nuclei (e.g. RHIC, ALICE). Here two next-to-leading order chi^2-analyses of NPDF are presented. The first uses neutral current charged-lepton Deeply Inelastic Scattering (DIS) and Drell-Yan data for several nuclear targets and the second uses neutrino-nucleon DIS data. We compare the nuclear corrections factors (F_2^Fe/F_2^D) for the charged-lepton data with other results from the literature. In particular, we compare and contrast fits based upon the charged-lepton DIS data with those using neutrino-nucleon DIS data.

Karol Kovarik

2010-06-25

308

Novel astrocyte targets  

PubMed Central

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

Carmignoto, Giorgio; Steinhäuser, Christian

2015-01-01

309

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

310

ORION laser target diagnosticsa)  

NASA Astrophysics Data System (ADS)

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

2012-10-01

311

ORION laser target diagnostics.  

PubMed

The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics. PMID:23126904

Bentley, C D; Edwards, R D; Andrew, J E; James, S F; Gardner, M D; Comley, A J; Vaughan, K; Horsfield, C J; Rubery, M S; Rothman, S D; Daykin, S; Masoero, S J; Palmer, J B; Meadowcroft, A L; Williams, B M; Gumbrell, E T; Fyrth, J D; Brown, C R D; Hill, M P; Oades, K; Wright, M J; Hood, B A; Kemshall, P

2012-10-01

312

Target detection portal  

DOEpatents

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

313

Targeting TRAIL death receptors.  

PubMed

The natural occurring tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis following binding to the two TRAIL death receptors (DRs). Its recombinant form and monoclonal antibodies against the TRAIL DRs induce cell death in a wide variety of tumor cell lines and xenografts without causing toxicity to normal cells and are therefore potential attractive anticancer agents. These agents are currently in early clinical development. The phase 1 and 2 studies showed until now limited toxicity and tumor responses have been observed. Ongoing studies focus especially on combination of these agents with other targeted therapies or cytotoxic therapies. In this review, we summarize current knowledge on these agents and highlight their potential role in the intrinsically chemotherapy-resistant glioblastomas. In addition, we discuss the mechanisms to sensitize tumors cells to rhTRAIL by combination with the proteasome inhibitor bortezomib. PMID:18625341

Oldenhuis, C N A M; Stegehuis, J H; Walenkamp, A M E; de Jong, S; de Vries, E G E

2008-08-01

314

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

315

Target control of complex networks  

PubMed Central

Controlling large natural and technological networks is an outstanding challenge. It is typically neither feasible nor necessary to control the entire network, prompting us to explore target control: the efficient control of a preselected subset of nodes. We show that the structural controllability approach used for full control overestimates the minimum number of driver nodes needed for target control. Here we develop an alternate ‘k-walk’ theory for directed tree networks, and we rigorously prove that one node can control a set of target nodes if the path length to each target node is unique. For more general cases, we develop a greedy algorithm to approximate the minimum set of driver nodes sufficient for target control. We find that degree heterogeneous networks are target controllable with higher efficiency than homogeneous networks and that the structure of many real-world networks are suitable for efficient target control. PMID:25388503

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

2014-01-01

316

Behavioural Targeting & Law 1 March 2013  

E-print Network

profiles (iii) Targeted advertising #12;4 Example - Tracking #12;5 Tracking #12;6 Targeting #12;7 Targeting) Tracking people online (ii) Building profiles (iii) Targeted advertising #12;Profiles Facebook data centre Targeting (i) Tracking people online (ii) Building profiles (iii) Targeted advertising #12;23 Targeting

Hoepman, Jaap-Henk

317

Using the Nova target chamber for high-yield targets  

SciTech Connect

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

Pitts, J.H.

1987-09-28

318

Automatic target recognition of slow moving ground targets using stap  

Microsoft Academic Search

A new approach is proposed which will allow air-to-ground target identification of slow moving vehicles in clutter. A wideband space-time adaptive (STAP) filter for clutter suppression is developed which preserves the target amplitude integrity of returns from multiple range bins within the automatic target recognition (ATR) high range resolution (HRR) approach. The wideband STAP processor utilizes narrowband STAP principles to

John A. Malas; Krishna M. Pasala; John J. Westerkamp

2003-01-01

319

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

PubMed

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

Jouin, A; Pourel, N

2013-10-01

320

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

321

Neuropathy target esterase.  

PubMed Central

Neuropathy target esterase (NTE) is an integral membrane protein present in all neurons and in some non-neural-cell types of vertebrates. Recent data indicate that NTE is involved in a cell-signalling pathway controlling interactions between neurons and accessory glial cells in the developing nervous system. NTE has serine esterase activity and efficiently catalyses the hydrolysis of phenyl valerate (PV) in vitro, but its physiological substrate is unknown. By sequence analysis NTE has been found to be related neither to the major serine esterase family, which includes acetylcholinesterase, nor to any other known serine hydrolases. NTE comprises at least two functional domains: an N-terminal putative regulatory domain and a C-terminal effector domain which contains the esterase activity and is, in part, conserved in proteins found in bacteria, yeast, nematodes and insects. NTE's effector domain contains three predicted transmembrane segments, and the active-site serine residue lies at the centre of one of these segments. The isolated recombinant domain shows PV hydrolase activity only when incorporated into phospholipid liposomes. NTE's esterase activity appears to be largely redundant in adult vertebrates, but organophosphates which react with NTE in vivo initiate unknown events which lead, after a delay of 1-3 weeks, to a neuropathy with degeneration of long axons. These neuropathic organophosphates leave a negatively charged group covalently attached to the active-site serine residue, and it is suggested that this may cause a toxic gain of function in NTE. PMID:10585848

Glynn, P

1999-01-01

322

Targeting Cancer Metabolism  

PubMed Central

The understanding that oncogenes can have profound effects on cellular metabolism and the discovery of mutations and alterations in several metabolism-related enzymes (IDH1, IDH2, SDH, FH, PKM2) has renewed interest in cancer metabolism and renewed hope of taking therapeutic advantage of cancer metabolism. Otto Warburg observed that aerobic glycolysis was a characteristic of cancer cells. More than 50-years later, we understand that aerobic glycolysis and uptake of glutamine and glycine allow cancer cells to produce energy (ATP) and the nucleotides, amino acids and lipids required for proliferation. Expression of the MYC oncogene drives the increase in cellular biomass facilitating proliferation. PKM2 expression in cancer cells stimulates aerobic glycolysis. Amongst intermediary metabolism enzyme, mutations in succinate dehydrogenase (SDH) occur in gastointestinal stromal tumors and result in a pseudohypoxic metabolic milieu. Fumarate hydratase (FH) mutations lead to a characteristic renal cell carcinoma. Isocitrate dehydrogenase (IDH1/2) mutations have been found in leukemias, gliomas, prostate cancer, colon cancer, thyroid cancer and sarcomas. These recently recognized oncogenic metabolic lesions may be selective targets for new anticancer therapeutics. PMID:23071355

Teicher, Beverly A.; Linehan, W. Marston; Helman, Lee J.

2012-01-01

323

Therapeutic targets in subependymoma.  

PubMed

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

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

2014-12-15

324

The OLYMPUS internal hydrogen target  

NASA Astrophysics Data System (ADS)

An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

Bernauer, J. C.; Carassiti, V.; Ciullo, G.; Henderson, B. S.; Ihloff, E.; Kelsey, J.; Lenisa, P.; Milner, R.; Schmidt, A.; Statera, M.

2014-08-01

325

Targeted Therapy in Hepatocellular Carcinoma  

PubMed Central

Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, as well as a common cause of cancer-related death. HCC frequently occurs in the setting of a diseased cirrhotic liver and many patients present at an advanced stage of disease. Together with a poor functional status, this often precludes the use of systemic therapy, especially conventional cytotoxic drugs. Moreover, HCC is known to be a relatively chemo-refractory tumor. There have been many targeted drugs that have shown potential in the treatment of HCC. Many clinical trials have been carried out with many more in progress. They include trials evaluating a single targeted therapy alone, two or more targeted therapy in tandem or a combination of targeted therapy and conventional chemotherapy. In this article, we seek to review some of the more important trials examining the use of targeted therapy in HCC and to look into what the future holds in terms of targeted treatment of HCC. PMID:21994852

Chua, Clarinda W. L.; Choo, Su Pin

2011-01-01

326

The OLYMPUS Internal Hydrogen Target  

E-print Network

An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

J. C. Bernauer; V. Carassiti; G. Ciullo; B. S. Henderson; E. Ihloff; J. Kelsey; P. Lenisa; R. Milner; A. Schmidt; M. Statera

2014-04-02

327

Target repurposing for neglected diseases  

PubMed Central

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

Pollastri, Michael P; Campbell, Robert K

2011-01-01

328

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

329

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. 3 figs.

Mashburn, D.N.

1996-01-09

330

Inertial-confinement-fusion targets  

SciTech Connect

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

Hendricks, C.D.

1981-11-16

331

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

332

Consensus on demographic targets.  

PubMed

In an interview, Dr. Nibhon Debavalya of the Population Division, Economic and Social commission for Asia and the Pacific (ESCAP), explained the significance of the Bali Conference as well as other population-related issues in the region. ESCAP's Population Division receives its mandate from the Committee on Population and Social Development. ESCAP's population concerns are handled under the Committee on Poverty Alleviation through Economic Growth and Social Development which will have its 1st meeting in 1993. The Population Division carries out 1) collaborative research, 2) technical assistance and advisory services 3) human resources development, and 4) population information and dissemination. In collaborative research, studies are carried out on aging of the population, consequences of population change, planning of small towns and rural human resources development, the accessibility of contraceptives and improving family planning and maternal and child health, and management information systems. The Bali Declaration on Population and Sustainable Development provides practical guidelines for developing the infrastructure for sustainable development within the region. It will be the basis of related policies and their implementation. The countries of the ESCAP region have set population goals: to reduce rates of population growth, countries should adopt strategies to attain replacement level fertility of 2.2 children per woman by the year 2010. The Declaration also encourages countries to reduce the level of infant mortality to 40 per 1000 live births or less during the same period. It states that in countries with high maternal mortality efforts should be made to reduce it by at least half by the year 2010. Major concerns also relate to the low level of male involvement in contraceptive usage, the high fertility in some countries, the issue of aging East Asia, and international migration. So far, the Asia-Pacific region is the only region that has come up with a consensus on its demographic targets. PMID:12286377

Seewald, M

1993-03-01

333

Targeted chemical nucleases  

SciTech Connect

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

Sigman, D.S.; Bruice, T.W.; Mazumder, A.; Sutton, C.L. (Univ. of California, Los Angeles (United States))

1993-03-01

334

Detection of multidimensional targets in visual search  

Microsoft Academic Search

Search performance for targets defined along multiple dimensions was investigated with an accuracy visual search task. Initially, threshold was measured for targets that differed from homogeneous distractors along a single dimension (e.g., a reddish target among achromatic distractors, or a right-tilted target among vertically oriented distractors). Threshold was then measured for a multidimension- al target (a redundant target) that differed

Patrick Monnier

2006-01-01

335

Targeted chromosome elimination from ES-  

E-print Network

Targeted chromosome elimination from ES- somatic hybrid cells Hiroyuki Matsumura1,6, Masako Tada1 cell genome, we developed a technology for targeted elimination of chromosomes from mouse embryonic stem (ES)­somatic hybrid cells. Here we demonstrate the use of a universal chromosome elimination

Cai, Long

336

Visual motion shifts saccade targets.  

PubMed

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

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

2014-08-01

337

Is targeted advertising always beneficial?  

Microsoft Academic Search

In this paper, we study a simple model in which two horizontally differentiated firms compete in prices and targeted advertising on an initially uninformed market. First, the Nash equilibrium is fully characterized. We prove that when the advertising cost is low, firms target only their “natural markets”, while they cross-advertise when this cost is high. Second, the outcome at equilibrium

Nada Ben Elhadj-Ben Brahim; Rim Lahmandi-Ayed; Didier Laussel

2011-01-01

338

Plasma Window for SNS Target  

Microsoft Academic Search

Proton beam loss between the vacuum window and the target in the SNS ring to target beam transport can be completely eliminated, if Plasma Windows replace solid vacuum windows. Consequently, all problems associated with proton solid-window interaction will no longer exist. The Plasma Window is a novel apparatus, which utilized a short plasma arc to provide a vacuum -atmosphere interface

Deepak Raparia; Ady Hershcovitch

339

Windowless targets for intense beams  

Microsoft Academic Search

Earlier results have shown that a plasma window can effectively separate vacuum from a pressure of close to 3atm. Present results indicate that a plasma window enhanced by a venturi facilitates a rather effective vacuum separation from a 9atm gas target. Utilization of the plasma arc as the window for gas targets removes all of the limitations on beam current,

D. Salerno; B. T. Pinkoski; A. Hershcovitch; E. Johnson

2001-01-01

340

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

341

COLON TARGETED DRUG DELIVERY SYSTEMS  

Microsoft Academic Search

Colon targeted drug delivery systems have the potential to deliver drugs for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. In recent years, various pharmaceutical approaches have been developed for targeting the drugs to the colon include, formation of prodrugs, coating of pH-sensitive polymers, use of colon

Ceyda Tuba

342

Bacterial cytotoxins: targeting eukaryotic switches  

Microsoft Academic Search

Many bacterial cytotoxins act on eukaryotic cells by targeting the regulators that are involved in controlling the cytoskeleton or by directly modifying actin, with members of the Rho GTPase family being particularly important targets. The actin cytoskeleton, and especially the GTPase 'molecular switches' that are involved in its control, have crucial functions in innate and adaptive immunity, and have pivotal

Joseph T. Barbieri; Klaus Aktories

2005-01-01

343

Projectile penetration into representative targets  

NASA Astrophysics Data System (ADS)

The differential equation representing the penetration of a 'hard' projectile into semi-infinite, homogeneous target materials is solved for several generic combinations of the target material/projectile characteristics. A 'hard' projectile is defined as one that does not change size or shape and does not lose mass during the penetration process. The target materials evaluated range from the structurally 'soft' materials (liquids) to structurally 'hard' materials (armor plate) with viscous and fluid dynamic drag considered. The solutions to the differential equation(s) are expanded in series form to demonstrate the underlying parameters governing projectile penetration and the way they interact to limit penetration in a given target material. It is shown that the fundamental parameter governing projectile penetration into structurally 'firm' materials is the initial kinetic energy of the projectile divided by the frontal area of the projectile and the inherent structural characteristic of the target. Experimental data on the penetration of steel spheres into ballistic gelatin and for armor piercing bullets into armor plate materials are used to verify the characteristics of the solutions to the equation of motion for the projectile and to demonstrate how penetration can vary with projectile size and target characteristics. The penetration equation for a single 'hard' target material is used to develop a solution for the penetration of multilayered 'hard' target materials.

Stone, George W.

1994-10-01

344

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

345

Wearout effects in target marketing  

Microsoft Academic Search

Given that most advertising campaigns attempt to target advertisements to a specified demographic or product usage group, it seems reasonable to demand a high correlation between exposure to the media and membership of the target group. A surprising result of this research is that this correlation peaks and then declines as the number of insertions or spots in the campaign

Peter J. Danaher

1996-01-01

346

RESEARCH COMMUNICATION Targeting genes for  

E-print Network

of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112 USA A procedure; revised version accepted May 3, 1999. The paradigm for targeted germ-line modification of a mammalian into a cloned gene is transferred by homologous recombination to its chromosomal target in a pluripo- tent

Capecchi, Mario R.

347

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

348

Targeted Advertising Strategies on Television  

Microsoft Academic Search

The personal video recorder (PVR) facilitates the use of targeted advertising by allowing companies to monitor television viewing behavior and to build demographic profiles of viewers from the data that are collected. Our research explores the extent to which an advertiser should allocate resources to increase the quality of its targeting. We present a game-theoretic model that extends the conventional

Esther Gal-Or; Mordechai Gal-Or; Jerrold H. May; William E. Spangler

2006-01-01

349

Spinning targets for laser fusion  

SciTech Connect

Several techniques for spinning the ICF targets up prior to or in the course of their compression are suggested. Interference of the rotational shear flow with Rayleigh-Taylor instability is briefly discussed and possible consequences for the target performance are pointed out.

Baldwin, D.E.; Ryutov, D.D.

1995-09-01

350

A high yield neutron target  

NASA Technical Reports Server (NTRS)

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

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

1974-01-01

351

Targeted marketing and public health.  

PubMed

Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies. PMID:20070196

Grier, Sonya A; Kumanyika, Shiriki

2010-01-01

352

Human MicroRNA Targets  

PubMed Central

MicroRNAs (miRNAs) interact with target mRNAs at specific sites to induce cleavage of the message or inhibit translation. The specific function of most mammalian miRNAs is unknown. We have predicted target sites on the 3? untranslated regions of human gene transcripts for all currently known 218 mammalian miRNAs to facilitate focused experiments. We report about 2,000 human genes with miRNA target sites conserved in mammals and about 250 human genes conserved as targets between mammals and fish. The prediction algorithm optimizes sequence complementarity using position-specific rules and relies on strict requirements of interspecies conservation. Experimental support for the validity of the method comes from known targets and from strong enrichment of predicted targets in mRNAs associated with the fragile X mental retardation protein in mammals. This is consistent with the hypothesis that miRNAs act as sequence-specific adaptors in the interaction of ribonuclear particles with translationally regulated messages. Overrepresented groups of targets include mRNAs coding for transcription factors, components of the miRNA machinery, and other proteins involved in translational regulation, as well as components of the ubiquitin machinery, representing novel feedback loops in gene regulation. Detailed information about target genes, target processes, and open-source software for target prediction (miRanda) is available at http://www.microrna.org. Our analysis suggests that miRNA genes, which are about 1% of all human genes, regulate protein production for 10% or more of all human genes. PMID:15502875

2004-01-01

353

Spallation source neutron target systems  

SciTech Connect

This is the final report for a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The project sought to design a next-generation spallation source neutron target system for the Manuel Lujan, Jr., Neutron Scattering Center (LANSCE) at Los Alamos. It has been recognized for some time that new advanced neutron sources are needed in the US if the country is to maintain a competitive position in several important scientific and technological areas. A recent DOE panel concluded that the proposed Advanced Neutron Source (a nuclear reactor at Oak Ridge National Laboratory) and a high-power pulsed spallation source are both needed in the near future. One of the most technically challenging designs for a spallation source is the target station itself and, more specifically, the target-moderator-reflector arrangement. Los Alamos has demonstrated capabilities in designing, building, and operating high-power spallation-neutron-source target stations. Most of the new design ideas proposed worldwide for target system design for the next generation pulsed spallation source have either been conceived and implemented at LANSCE or proposed by LANSCE target system designers. These concepts include split targets, flux-trap moderators, back scattering and composite moderators, and composite reflectors.

Russell, G.; Brown, R.; Collier, M.; Donahue, J. [and others

1996-07-01

354

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

355

Behavioral Targeting—Consumer Tracking  

NASA Astrophysics Data System (ADS)

Behavioral targeting is an online marketing method that collects data on the browsing activities of consumers, in order to `target' more relevant online advertising. Behavioral targeting enables marketers to reach in-market consumers and increases the value of publisher inventory. At the heart of behavioral targeting is a learning-based investigation of consumer behaviors. It helps marketers understand consumers' purchase patterns over time, mapping out a customer's activities based not only on a single purchase but also on an annual or even lifetime basis. As marketers increasingly appreciate the importance of customer lifetime value, behavioral targeting can be a foundation for creating a continuous analytical study of consumer trends and patterns. But as behavioural-targeting systems become more sophisticated and invasive, it is vital that the companies behind them are open with users about what is going on, and give them control over their personal information. The aim of this paper is to explore the various tools and techniques of behavioral targeting and its benefits to online marketing. A multiple—case study approach was used for exploring the effectiveness and acceptance of online marketing in the area of the online marketing.

Srimani, P. K.; Srinivas, A.

2011-12-01

356

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

357

Integrated precision SAR targeting: a SAR targeting simulation  

Microsoft Academic Search

Operational deficiencies exist in the current ability to perform high resolution synthetic aperture radar (SAR) targeting for precision strike missions in difficult electronic countermeasure (ECM) and anti-aircraft environments. Increasingly sophisticated enemy defenses require that fire control information be derived from highly maneuverable aircraft trajectories rather than traditional straight-and-level flight. In addition, target area, aspect information is needed to determine optimal

D. Martinsek; J. Toussaint

1998-01-01

358

Integrated precision SAR targeting: a SAR targeting simulation  

Microsoft Academic Search

Operational deficiencies exist in the current ability to perform high resolution synthetic aperture radar (SAR) targeting for precision strike missions in difficult electronic countermeasure (ECM) and anti-aircraft environments. Increasingly sophisticated enemy defenses require that fire control information be derived from highly maneuverable aircraft trajectories rather than traditional straight-and-level flight. In addition, target area aspect information is needed to determine optimal

J. A. Toussaint; D. M. Martinsek

1999-01-01

359

Targeted biopharmaceuticals for cancer treatment.  

PubMed

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

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

2014-10-01

360

Nanoparticles for Targeted Drug Delivery  

E-print Network

Nanoparticles were synthesized and modified for target drug delivery. The research involved the aqueous synthesis of near infrared (NIR) sensitive Au-Au2S nanoparticles. An anti-cancer drug (cis-platin) ...

Chow, Gan-Moog

361

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

362

Gene targeting with retroviral vectors  

SciTech Connect

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

Ellis, J.; Bernstein, A. (Toronto Univ., ON (Canada))

1989-04-01

363

"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

364

Target Groups Allundergraduatestudents,witha  

E-print Network

Target Groups · Allundergraduatestudents,witha formaloffertostudyatEdinburghNapierlooksforwardtoabrightfutureIhopethatyou willjoinmebyinvestingyourfinancialsupportinthenextgeneration ofproductdesigners,filmmakers,marketeers,accountants,nurses, entrepreneursandmore the chance to experience a new culture. Ka Wing BA(Hons)Communications, Advertising&PublicRelations Donor

Maizels, Rick

365

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

366

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

367

Inertial-confinement-fusion targets  

SciTech Connect

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

Hendricks, C.D.

1982-08-10

368

Target identification using laser imaging  

SciTech Connect

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

Jennings, J.; Baker, M.; Barrett, J.; Ellis, B.N.; Kacerek, J.; Yee, J. [AlliedSignal Aerospace Co., Teterboro, NJ (United States)

1994-12-31

369

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

370

Ethical Implications of Target Market Selection  

Microsoft Academic Search

Marketers have been criticized recently for the selection of target markets, especially for targeting disadvantaged segments of a society with harmful products. Very little has been done, however, to provide guidelines for marketers developing target market strategies. This article examines the ethical dimensions of target market selection. The proposed model for analyzing target markets allows for differences in both the

Terri L. Rittenburg; Madhavan Parthasarathy

1997-01-01

371

Unification of automatic target tracking and automatic target recognition  

NASA Astrophysics Data System (ADS)

The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT?ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

Schachter, Bruce J.

2014-06-01

372

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

373

75 FR 73987 - Target Date Disclosure  

Federal Register 2010, 2011, 2012, 2013, 2014

...Andrew. Testimony Concerning Target Date Funds. Before the United...The financial market downturn that started in 2008...Financial Advisory Services LLP, Target Date Funds: Historical Volatility...Deloitte also found that funds with target date 2010 were more...

2010-11-30

374

Microsurgical reconstruction of the mandible in a patient with evans syndrome: a case report and review of the literature.  

PubMed

In this report, we describe the first successful case of microvascular free tissue transfer in a patient with Evans Syndrome (ES), a rare form of idiopathic thrombocytopenic purpura (ITP) and associated autoimmune hemolytic anemia (AIHA). Microvascular surgery in the setting of ES is likely to have higher complication rates because of the increased risk of postoperative bleeding and free flap thrombosis. The case presented here opens up to the feasibility of microvascular reconstruction of patients with coagulation disorders like ES. Every effort should be made to control for hemolytic, thrombocytopenic, and thrombophilic states associated with ES. In the absence of evidence-based treatment guidelines for ES, personalized treatment protocols with high-dose corticosteroids, immunoglobulin, and postoperative anticoagulation regimen are highly recommended. PMID:23804021

Bedogni, Alberto; Anesi, Alexandre; Fior, Andrea; Bettini, Giordana; Nocini, Pier Francesco

2013-10-01

375

Manifold knowledge extraction and target recognition  

NASA Astrophysics Data System (ADS)

Advanced mammalian target identification derived from the perception of target's manifold and measurement manifolddistance. It does not rely on object's segmented accuracy, not depend on target's variety model, and adapt to a range of changes on targets. In this paper, based on the existed manifold learning algorithm, set up a new bionic automatic target recognition model, discussed the targets manifold knowledge acquisition and the knowledge expression architecture, gave a manifold knowledge-based new method for automatic target recognition. Experiments show that the new method has a strong adaptability to targets various transform, and has a very high correctly identification probability.

Chao, Cai; Hua, Zhou

2009-10-01

376

STIS Target Acquisitions During SMOV  

NASA Astrophysics Data System (ADS)

We summarize the first results on the analysis of in-flight STIS target acquisition (ACQ and ACQ/PEAK). These results show that the STIS target acquisition (ACQ) is working very accurately for point sources (within 0.5 pixels = 0.025 arcseconds), about 4 times better than specified in the Instrument Handbook. As a result of the accuracy of the ACQ algorithm, we are no longer recommending to perform ACQ/PEAKs for the 0.2 arcsecond wide slits. For diffuse acquisitions the accuracy varies with target size. Although analysis of ACQ/PEAK data is hampered by a flight software problem, we anticipate that peakups will be accurate to roughly ±5% of the slit width (instead of the ±15% pr eviously advertised). We are implementing several enhancements to the flight software that will take effect by mid- August to improve the quality of the acquisitions.

Katsanis, Rocio M.; Downes, Ron; Hartig, George; Kraemer, Steve

1997-07-01

377

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

378

Thermal Targets for Satellite Calibration  

SciTech Connect

The Savannah River Technology Center (SRTC) is currently calibrating the Multispectral Thermal Imager (MTI) satellite sponsored by the Department of Energy. The MTI imager is a research and development project with 15 wavebands in the visible, near-infrared, short-wave infrared, mid-wave infrared and long-wave infrared spectral regions. A plethora of targets with known temperatures such as power plant heated lakes, volcano lava vents, desert playas and aluminized Mylar tarps are being used in the validation of the five thermal bands of the MTI satellite. SRTC efforts in the production of ''cold targets'' with aluminized Mylar tarps will be described. Visible and thermal imagery and wavelength dependent radiance measurements of the calibration targets will be presented.

Villa-Aleman, E.

2001-01-10

379

A cryogenic infrared calibration target.  

PubMed

A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R ? 0.003, from 800?to?4800?cm(-1) (12 - 2??m). Upon expanding the spectral range under consideration to 400-10,000?cm(-1) (25 - 1??m) the observed performance gracefully degrades to R ? 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to ?4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials-Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder-are characterized and presented. PMID:24784638

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

2014-04-01

380

Ethnically targeted advertising: views of those not targeted  

Microsoft Academic Search

Purpose – This paper sets out to extend current knowledge on advertising effects on those not targeted by noting unintended consequences on attitudinal, emotional, and behavioral reactions. Design\\/methodology\\/approach – This paper tests these effects based on relevant theories in the communication and advertising literature on two distinct ethnic groups (Malay and Chinese) in Kuala Lumpur, Malaysia utilizing questionnaires based on

Ernest Cyril de Run

2007-01-01

381

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

382

Progress with developing a target for magnetized target fusion  

SciTech Connect

Magnetized Target Fusion (MTF) is an approach to fusion where a preheated and magnetized plasma is adiabatically compressed to fusion conditions. Successful MTF requires a suitable initial target plasma with an embedded magnetic field of at least 5 T in a closed-field-line topology, a density of roughly 10{sup 18} cm{sup {minus}3}, a temperature of at least 50 eV, and must be free of impurities which would raise radiation losses. Target plasma generation experiments are underway at Los Alamos National Laboratory using the Colt facility; a 0.25 MJ, 2--3 {micro}s rise-time capacitor bank. The goal of these experiments is to demonstrate plasma conditions meeting the minimum requirements for a MTF initial target plasma. In the first experiments, a Z-pinch is produced in a 2 cm radius by 2 cm high conducting wall using a static gas-fill of hydrogen or deuterium gas in the range of 0.5 to 2 torr. Thus far, the diagnostics include an array of 12 B-dot probes, framing camera, gated OMA visible spectrometer, time-resolved monochrometer, filtered silicon photodiodes, neutron yield, and plasma-density interferometer. These diagnostics show that a plasma is produced in the containment region that lasts roughly 10 to 20 {micro}s with a maximum plasma density exceeding 10{sup 18} cm{sup {minus}3}. The experimental design and data are presented.

Wysocki, F.J.; Chrien, R.E.; Idzorek, G.; Oona, H.; Whiteson, D.O.; Kirkpatrick, R.C.; Lindemuth, I.R.; Sheehey, P.T.

1997-09-01

383

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

384

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

385

Gastrohepatology: tools, targets, and trajectories.  

PubMed

Gastrointestinal (GI) and hepatic conditions are a leading source of health-care utilization today. A significant segment of the over-the-counter and prescription drug market comprises drugs used to alleviate symptoms localized to the alimentary tract. The discovery of new mechanisms of disease pathogenesis will inform the future development of targeted therapeutics for conditions managed by gastroenterologists and hepatologists. Newly approved drugs and evolving mechanistic targets offer a promising trajectory to both clinicians and patients with GI and liver disorders. PMID:22910480

James, L P; Senior, J

2012-09-01

386

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

387

Modulation domain infrared target models  

Microsoft Academic Search

We compute joint AM-FM models that characterize infrared targets and backgrounds in the modulation domain. We consider spatially localized structures within an IR image as sums of nonstationary, quasi-sinusoidal functions admitting locally narrowband amplitude and frequency modulations. By quantitatively estimating the modulations that dominate the signal spectrum on a spatially local basis, we obtain a new modulation domain feature vector

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

2006-01-01

388

Targeted advertising in magazine markets  

Microsoft Academic Search

We examine the scope and value of targeted advertising in the magazine industry. We use data on reader characteristics at individual media, in contrast to previous work that has needed to infer this information from aggregate data. Our results show a strong relationship between subscriber characteristics and advertising prices. Advertisers clearly value more homogenous groups of readers, measured according to

Ambarish Chandra; Ulrich Kaiser

2010-01-01

389

Targeted Advertising and Social Status  

Microsoft Academic Search

This paper shows how a firm can use non-targeted advertising to exploit consumers' desire for social status. A monopolist sells multiple varieties of a good to consumers who each care about what others believe about his wealth. Advertising allows consumers both to buy different varieties and to recognize them when others buy. In equilibrium, the firm advertises each variety to

N. Vikander

2010-01-01

390

Targeted Advertising in Magazine Markets  

Microsoft Academic Search

We examine the scope and value of targeted advertising in the magazine industry. We use data on reader characteristics at individual media, in contrast to previous work that has needed to infer this information from aggregate data. Our results show a strong relationship between subscriber characteristics and advertising prices. Advertisers clearly value more homogenous groups of readers, measured according to

Ambarish Chandra; Ulrich Kaiser

2010-01-01

391

Targeted Advertising and Advertising Avoidance  

Microsoft Academic Search

I examine how the increasing ability of firms to target their advertise- ments to particular individuals influences market outcomes when consumers have access to advertising avoidance tools. Today firms possess an unprecedented and rapidly improving ability to discover details about individuals and reach them with advertising based on this information. For instance, as many readers know, an individual's web browsing

Justin P. Johnson

392

Treatment targets in intracerebral hemorrhage.  

PubMed

Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than ischemic stroke. The therapeutic interventions that are currently available focus mainly on supportive care and secondary prevention. There is a paucity of evidence to support any one acute intervention that improves functional outcome. This chapter highlights current treatment targets for ICH based on the pathophysiology of the disease. PMID:21732225

Sangha, Navdeep; Gonzales, Nicole R

2011-07-01

393

Molecular targets in pituitary tumours  

Microsoft Academic Search

Pituitary tumours are associated with unrestrained secretion and subsequent action of trophic hormones. One approach to therapy involves suppressing pituitary-hormone hypersecretion without compromising endogenous pituitary function. Identification of novel neuroendocrine-receptor targets has enabled the development of safe and effective receptor ligands that can be used to treat pituitary tumours and associated hormonal excess. Some of these agents, such as somatostatin

Anthony P. Heaney; Shlomo Melmed

2004-01-01

394

Therapeutic targets for premature ejaculation.  

PubMed

Premature ejaculation (PE) is the most common male sexual complaint, and may exert a profound negative impact on the man's life and partnership. Using currently available treatment alternatives (e.g., selective serotonin uptake inhibitor, agents acting locally on the penis), PE can be treated in most, but not all patients. However, since long term success rates have been disappointing, and the only approved treatment so far is the short-acting selective serotonin re-uptake inhibitor dapoxetine, there is currently an intensive search for new treatment modalities. Selection of the most promising therapeutic targets from a host of current and potential candidates depends heavily on their roles in the pathophysiology of PE. Possible central nervous targets that will be discussed are serotonin transporters, and CNS receptors for 5-HT(IA) and 5-HT(1B), dopamine, oxytocin, opioids, neurokinin-1, and glutamate. Putative peripheral targets include ?(1)-adrenoceptors, phosphodiestrase enzymes, Rho kinases, purinergic (P2X) receptors, and penile sensory nerves. It is clear that exploiting the full therapeutic potential of these targets will require additional basic and clinical research. PMID:21816550

Andersson, Karl-Erik; Abdel-Hamid, Ibrahim A

2011-09-01

395

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

396

Targeted imaging of myocardial damage  

Microsoft Academic Search

Molecular imaging agents can be targeted to a specific receptor or protein on the cardiomyocyte surface, or to enzymes released into the interstitial space, such as cathepsins, matrix metalloproteinases and myeloperoxidase. Molecular imaging of the myocardium, however, requires the imaging agent to be small, sensitive (nanomolar levels or better), and able to gain access to the interstitial space. Several novel

Matthias Nahrendorf; Ralph Weissleder; David E Sosnovik

2008-01-01

397

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

398

Targeting Control of Chaotic Systems  

Microsoft Academic Search

Targeting control of chaos is concerned with taking advantage of sen- sitive dependence to initial conditions to coax a dynamical system to following a desirable trajectory. In other words, it is taking advantage of the butterfly effect so that the rich spectrum of possible trajectories embedded within a chaotic attractor can be selected with extremely small energy input. We review

Erik M. Bollt

399

Targeting Src in breast cancer  

Microsoft Academic Search

The clinical benefit of blocking oncogenic pathways in breast cancer and other malignancies has validated this approach and ushered in the era of molecularly targeted therapeutics. Src and its family members make up the largest group of nonreceptor tyrosine kinases. In laboratory models, these proteins have been shown to play a critical role in cellular growth and proliferation, angiogenesis, and

R. S. Finn

2008-01-01

400

Biofuels : markets, targets and impacts  

Microsoft Academic Search

This paper reviews recent developments in biofuel markets and their economic, social and environmental impacts. Several countries have introduced mandates and targets for biofuel expansion. Production, international trade and investment have increased sharply in the past few years. However, several existing studies have blamed biofuels as one of the key factors behind the 2007-2008 global food crisis, although the magnitudes

Govinda R. Timilsina; Ashish Shrestha

2010-01-01

401

National Ignition Facility Target Chamber  

Microsoft Academic Search

On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at

R W Wavrik; J R Cox; P J Fleming

2000-01-01

402

Is money supply targeting obsolete?  

Microsoft Academic Search

Money supply targeting has come out of fashion. The large changes in velocity in some countries and the fact that inflation is still low in spite of the strong monetary expansion in most industrial economies since 1985 have undermined the formerly accepted notion of a stable relationship between money and economic activity. In this paper, the most important objections to

Enno Langfeldt; Joachim Scheide; Peter Trapp

1988-01-01

403

TARGETED DELIVERY OF INHALED PROTEINS  

EPA Science Inventory

ETD-02-047 (Martonen) GPRA # 10108 TARGETED DELIVERY OF INHALED PROTEINS T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5 1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

404

Targeting Resources for Local Growth.  

ERIC Educational Resources Information Center

Focusing state and federal dollars on targeted areas, the Kentucky Appalachian Community Development Initiative helps communities in eastern Kentucky fund their own strategies for economic growth. In Hindman, the project focuses on creating the Kentucky School of Crafts, to train master artisans; supporting the Kentucky Appalachian Artisan Center;…

Casto, James E.

2001-01-01

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

Targeting multidrug resistance in cancer  

Microsoft Academic Search

Effective treatment of metastatic cancers usually requires the use of toxic chemotherapy. In most cases, multiple drugs are used, as resistance to single agents occurs almost universally. For this reason, elucidation of mechanisms that confer simultaneous resistance to different drugs with different targets and chemical structures — multidrug resistance — has been a major goal of cancer biologists during the

Gergely Szakács; Jill K. Paterson; Joseph A. Ludwig; Catherine Booth-Genthe; Michael M. Gottesman

2006-01-01

407

RADIATION ONCOLOGY TARGET YOUR FUTURE  

E-print Network

RADIATION ONCOLOGY TARGET YOUR FUTURE #12;A Career in Radiation Oncology YOUR CHOICE SAVE LIVES Take the first step towards a career in Radiation Oncology Visit www.acareerinradiationoncology.com.au 2 What is Radiation Oncology? Radiation Oncology is made up of three unique medical specialties

Tobar, Michael

408

Novel targets in prostate cancer.  

PubMed

Despite recent advances in the understanding of the cellular and molecular biology of prostate cancer, new options for the treatment of prostate cancer remain elusive. Targeted therapies have shown promising activities in many solid tumours and the growing number of targets and targeted agents is creating numerous opportunities for clinical research in advanced prostate cancer. At ASCO 2006 in Atlanta, a clinical science symposium on novel targets in prostate cancer was presented. It consisted of three abstracts, each of which was followed by a discussant who reviewed the work and placed it in the overall context of current approaches to treating prostate cancer. The three abstracts were a discussion of a new method for quantification of the androgen receptor; the impact of high-dose vitamin D plus chemotherapy on hormone refractory disease and on the risk of thromboembolic disease; and the paradoxical effects seen with the raf-kinase and vascular endothelial growth factor inhibitor sorafenib, which produced improvement in bone scans in the absence of any prostate-specific antigen responses. PMID:16981834

Berthold, Dominik R; Moore, Malcolm J

2006-10-01

409

Antibodies against the CUB1-2 domains of ADAMTS13 in a patient with benign monoclonal gammopathy: no causal relationship.  

PubMed

We present a patient with a history of benign monoclonal gammopathy, who developed thrombotic thrombocytopenic purpura (TTP), initially presenting as bilateral serous retinal detachment. Plasma of the patient contained high titers of anti ADAMTS13 antibodies that were directed towards the disintegrin/TSR1/cysteine-rich/spacer and CUB1-2 domains. ADAMTS13 activity was undetectable. Total IgG purified from plasma of the patient partially inhibited ADAMTS13 activity. In contrast, the isolated M-protein did neither bind to, nor inhibit activity of ADAMTS13. We conclude that in this patient the monoclonal gammopathy and TTP co-existed as distinct pathological entities. PMID:17650455

Riksen, Niels P; Luken, Brenda M; Klasen, Ina S; Voorberg, Jan; Crama, Niels; van Deuren, Marcel

2007-07-01

410

[Severe thrombocytopenia after diagnosis of deep venous thrombosis].  

PubMed

A patient presented with erysipelas and developed deep venous thrombosis (DVT) and later idiopatic thrombocytopenic purpura (ITP). In the literature we find no reports of ITP following DVT. It is well known that patients can develop HIT after DVT or DVT after ITP, both caused by the medicine used for treatment. Patients have developed ITP after heparin-induced thrombocytopenia (HIT). Cases are also described in which heparin antibodies are found, but in which the final diagnosis was ITP. The diagnosis of the patient in our case story could be ITP based on DVT, but with no history of HIT. Alternatively, he could have developed two complications to an infection. PMID:23937877

Frøslev-Friis, Christina; Kliment, Herbert; Andersen, Johnny Dohn Holmgren

2013-08-12

411

Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source.  

PubMed Central

A summer outbreak of severe gastroenteritis followed by haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura in a nursery school and kindergarten is described. Sandwiches prepared with green butter made with contaminated parsley were the likely vehicle of infection. The parsley originated from an organic garden in which manure of pig origin was used instead of artificial fertilizers. Clonally identical verotoxinogenic Citrobacter freundii were found as causative agents of HUS and gastroenteritis and were also detected on the parsley. Images Fig. 1 Fig. 2 PMID:7781732

Tschape, H.; Prager, R.; Streckel, W.; Fruth, A.; Tietze, E.; Böhme, G.

1995-01-01

412

Breast cancer presenting as paraneoplastic erythroderma: an extremely rare case.  

PubMed

The skin may exhibit the first clinical evidence of a systemic disease and may provide the first clues to a diagnosis in malignancies. Erythroderma is defined as generalized redness and scaling and it is a clinical manifestation of a variety of underlying diseases including, rarely, solid tumors. Breast cancer is associated with a variety of skin paraneoplastic manifestations like acanthosis nigricans, erythromelalgia, thrombotic thrombocytopenic purpura, acrokeratosis paraneoplastica, dermatomyositis, systemic sclerosis, and scleroderma. However, in the literature, the correlation of erythroderma with breast cancer is quite infrequent. Here, we describe a case of a 76-year-old woman who presented with a paraneoplastic manifestation of erythroderma due to breast cancer. PMID:25295062

Protopsaltis, Ioannis; Drossou, Aspasia; Katsantonis, Ioannis; Roussos, Nikolaos; Manoludaki, Kassiani; Arvanitis, Miltiadis; Papazafiropoulou, Athanasia; Antonopoulos, Stavros

2014-01-01

413

Breast Cancer Presenting as Paraneoplastic Erythroderma: An Extremely Rare Case  

PubMed Central

The skin may exhibit the first clinical evidence of a systemic disease and may provide the first clues to a diagnosis in malignancies. Erythroderma is defined as generalized redness and scaling and it is a clinical manifestation of a variety of underlying diseases including, rarely, solid tumors. Breast cancer is associated with a variety of skin paraneoplastic manifestations like acanthosis nigricans, erythromelalgia, thrombotic thrombocytopenic purpura, acrokeratosis paraneoplastica, dermatomyositis, systemic sclerosis, and scleroderma. However, in the literature, the correlation of erythroderma with breast cancer is quite infrequent. Here, we describe a case of a 76-year-old woman who presented with a paraneoplastic manifestation of erythroderma due to breast cancer. PMID:25295062

Katsantonis, Ioannis; Roussos, Nikolaos; Manoludaki, Kassiani; Antonopoulos, Stavros

2014-01-01

414

Extragastric manifestations of Helicobacter pylori infection.  

PubMed

The role of Helicobacter pylori (HP) in some digestive diseases (gastritis, ulcer, gastric cancer, MALT lymphoma) is well known. It has been suggested relatively recently that infection with HP can be involved in various extra-digestive conditions: respiratory disorders (chronic obstructive pulmonary disease, bronchiectasis, lung cancer, pulmonary tuberculosis, bronchial asthma); vascular disorders (ischaemic heart disease, stroke, primary Raynaud phenomena, primary headache); autoimmune disorders (Sjogren syndrome, Henoch-Schonlein purpura, autoimmune thrombocytopenia, autoimmune thyroiditis, Parkinson's disease, idiopathic chronic urticaria, rosacea, alopecia areata); other disorders (iron deficiency anaemia, growth retardations, liver cirrhosis). Case studies, small patient series and non-randomized trials that have shown a beneficial effect of HP eradication in different conditions are not convincing. According to Mastricht III the only conditions where HP eradication is indicated are immune thrombocytopenic purpura and iron deficiency anaemia. PMID:18293684

Prelipcean, Cristina Cijevschi; Mihai, C?t?lina; Gog?lniceanu, P; Mitric?, Dana; Drug, V L; Stanciu, C

2007-01-01

415

Polarized Sources, Targets and Polarimetry  

NASA Astrophysics Data System (ADS)

Remarks on the history of workshops on "spin tools" / E. Steffens -- Polarized proton beams in RHIC / A. Zelenski -- The COSY/Julich polarized H[symbol] and D[symbol] ion source / O. Felden -- The new source of polarized ions for the JINR accelerator complex / V. V. Fimushkin -- Resonance effects in nuclear dichroism - an inexpensive source of tensor-polarized deuterons / H. Seyfarth -- Polarized electrons and positrons at the MESA accelerator / K. Aulenbacher -- Status report of the Darmstadt polarized electron injector / Y. Poltoratska -- The Mott polarimeter at MAMI / V. Tioukine -- Proton polarimetry at the relativistic heavy ion collider / Y. Makdisi -- Polarisation and polarimetry at HERA / B. Sobloher -- Polarisation measurement at the ILC with a Compton polarimeter / C. Bartels -- Time evolution of ground motion-dependent depolarisation at linear colliders / A. Hartin -- Electron beam polarimetry at low energies and its applications / R. Barday -- Polarized solid targets: recent progress and future prospects / C. D. Keith -- HD gas distillation and analysis for HD frozen spin targets / A. D'Angelo -- Electron spin resonance study of hydrogen and alkyl free radicals trapped in solid hydrogen aimed for dynamic nuclear polarization of solid HD / T. Kumada -- Change of ultrafast nuclear-spin polarization upon photoionization by a short laser pulse / T. Nakajima -- Radiation damage and recovery in polarized [symbol]NH[symbol] ammonia targets at Jefferson lab / J. D. Maxwell.Polarized solid proton target in low magnetic field and at high temperature / T. Uesaka -- Pulse structure dependence of the proton spin polarization rate / T. Kawahara -- Proton NMR in the large COMPASS [symbol]NH[symbol] target / J. Koivuniemi -- DNP with TEMPO and trityl radicals in deuterated polystyrene / L. Wang -- The CLIC electron and positron polarized sources / L. Rinolfi -- Status of high intensity polarized electron gun at MIT-Bates / E. Tsentalovich -- Target section for spin filtering studies at COSY and CERN/AD / C. Barschel -- First experiments with the polarized internal gas target at ANKE/COSY / M. Mikirtychyants -- Extra physics with an ABS and a Lamb-shift polarimeter / R. Engels -- Systematic studies for the development of high-intensity ABS / L. Barion -- Upgrade of the 50 keV GaAs source of polarized electrons at ELSA / D. Heiliger -- Lifetime measurements of DBR and nonDBR photocathodes at high laser intensities / E. Riehn -- Polarized electron source based on FZD SRF gun / R. Xiang -- Major advances in SEOP of [symbol]He targets / P. Dolph -- A study of polarized metastable [symbol]He beam production / Yu. A. Plis -- Polarized [symbol]He targets for real and virtual photons / J. Krimmer -- Spin-filtering studies at COSY and AD / F. Rathmann -- Experimental setup for spin-filtering studies at COSY and AD / A. Nass -- Polarizing a stored proton beam by spin-flip? - A reanalysis / D. Oellers -- Tracking studies of spin coherence in COSY in view of EDM polarization measurements / A. U. Luccio -- Summary of the XIII international workshop on polarized sources, targets and polarimetry / F. Rathmann.

Ciullo, Guiseppe; Contalbrigo, Marco; Lenisa, P.

2011-01-01

416

Endoglin-Targeted Cancer Therapy  

PubMed Central

Vascular-targeting antiangiogenic therapy (VTAT) of cancer can be advantageous over conventional tumor cell targeted cancer therapy if an appropriate target is found. Our hypothesis is that endoglin (ENG; CD105) is an excellent target in VTAT. ENG is selectively expressed on vascular and lymphatic endothelium in tumors. This allows us to target both tumor-associated vasculature and lymphatic vessels to suppress tumor growth and metastasis. ENG is essential for angiogenesis/vascular development and a co-receptor of TGF-?. Our studies of selected anti-ENG monoclonal antibodies (mAbs) in several animal models and in vitro studies support our hypothesis. These mAbs and/or their immunoconjugates (immunotoxins and radioimmunoconjugates) induced regression of preformed tumors as well as inhibited formation of new tumors. In addition, they suppressed metastasis. Several mechanisms were involved in the suppressive activity of the naked (unconjugated) anti-ENG mAbs. These include direct growth suppression of proliferating endothelial cells, induction of apoptosis, ADCC (antibody-dependent cell-mediated cytotoxicity) and induction of T cell immunity. To facilitate clinical application, we generated a human/mouse chimeric anti-ENG mAb termed c-SN6j and performed studies of pharmacokinetics, toxicology and immunogenicity of c-SN6j in nonhuman primates. No significant toxicity was detected by several criteria and minimal immune response to the murine part of c-SN6j was detected after multiple i.v. injections. The results support our hypothesis that c-SN6j can be safely administered in cancer patients. This hypothesis is supported by the ongoing phase 1 clinical trial of c-SN6j (also known as TRC105) in patients with advanced or metastatic solid cancer in collaboration with Tracon Pharma and several oncologists (NCT00582985). PMID:21034418

Seon, Ben K.; Haba, Akinao; Matsuno, Fumihiko; Takahashi, Norihiko; Tsujie, Masanori; She, Xinwei; Harada, Naoko; Uneda, Shima; Tsujie, Tomoko; Toi, Hirofumi; Tsai, Hilda; Haruta, Yuro

2015-01-01

417

Ballistic target discrimination based on polarimetric entropy  

Microsoft Academic Search

Polarimetric entropy derived from the Cloude-Pottier decomposition is widely applied to fully polarimetric SAR images for target unsupervised discrimination and classification. In this paper, an algorithm for discriminating ballistic targets based on polarimetric entropy is studied. Using the fully polarimetric narrowband target echoes, polarimetric entropy is extracted to represent the randomness of target scattering characteristic in temporal domain. Based on

Xu Cheng; Yong Liu; Yongzhen Li; Xuesong Wang

2011-01-01

418

Civilian Target Detection using Hierarchical Fusion  

Microsoft Academic Search

Automatic Target Recognition (ATR) is the process of aided or unaided target detection and recognition using data from different sensors. Fusion techniques are used to improve ATR since this reduces system dependence on a single sensor and increases noise tolerance. In this work, ATR is performed on civilian targets which are considered more difficult to classify than military targets. The

Balasubramanian Lakshminarayanan; Hairong Qi

2005-01-01

419

The HERMES Polarized Hydrogen Internal Gas Target  

E-print Network

nuclei, and a windowless storage cell design. A windowless cell design is required for an internal target gas target using the storage cell technique. It was installed in the HERA ring at DESY during the 1996 with some studies of the target cell surface. Evidence suggests that the effective HERMES target cell

420

Coherent accumulation technology for space target exploration  

NASA Astrophysics Data System (ADS)

In the space target exploration with narrowband radar, targets with high-speed go through several range cells in the observation period which makes it more difficult to get each target's power coherently accumulated for target detection. In addition, for multi-target detection with different velocity, the range migration amount will not be equal. This is another problem for small target detection. In this study, novel multi-target detection with narrowband radar system is proposed. The Keystone transform firstly be used for correcting the range migration in a pulse repetition frequency (PRF). Then the fold factor of the strongest target can be estimated through Sparse Radon transform and compensates the corresponding phase term, following a quadratic phase term be compensated and at last the energy of the strongest target can be accumulated effectively by Fourier transform. The Clean technique is applied to the case of multi-target detection. The proposed algorithm is verified by simulation results.

Su, Jun-hai

2011-08-01

421

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

422

Effects of target typicality on categorical search.  

PubMed

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

423

Reticulocytes: Plasmodium vivax target cells.  

PubMed

Reticulocytes represent the main invasion target for Plasmodium vivax, the second most prevalent parasite species around the world causing malaria in humans. In spite of these cells' importance in research into malaria, biological knowledge related to the nature of the host has been limited, given the technical difficulties present in working with them in the laboratory. Poor reticulocyte recovery from total blood, by different techniques, has hampered continuous in vitro P. vivax cultures being developed, thereby delaying basic investigation in this parasite species. Intense research during the last few years has led to advances being made in developing methodologies orientated towards obtaining enriched reticulocytes from differing sources, thereby providing invaluable information for developing new strategies aimed at preventing infection caused by malaria. This review describes the most recent studies related to obtaining reticulocytes and discusses approaches which could contribute towards knowledge regarding molecular interactions between target cell proteins and their main infective agent, P. vivax. PMID:23458497

Moreno-Pérez, Darwin A; Ruíz, Jhenniffer A; Patarroyo, Manuel A

2013-06-01

424

Targeted Therapy in Ewing Sarcoma  

PubMed Central

Despite marked improvement in the prognosis of patients with nonmetastatic Ewing sarcoma (ES), the outcome for patients with recurrent or metastatic disease remains poor. Insight into key biologic processes in ES could provide new therapeutic targets. The particular biologic feature of ES, the fusion of the EWS gene with a member of the ETS family of genes, is present in >95% of cases. The EWS-ETS chimeric protein leads to aberrant transcription that promotes tumor initiation and propagation via prosurvival and antiapoptotic pathways. Recent research has identified cooperating mutations important for ES tumorigenesis. This paper provides a summary of the latest research in ES and discusses potential novel targets for therapy. PMID:22690342

Lissat, A.; Chao, M. M.; Kontny, U.

2012-01-01

425

Search for Basonuclin Target Genes  

PubMed Central

Basonuclin (Bnc 1) is a transcription factor that has an unusual ability to interact with promoters of both RNA polymerases I and II. The action of basonuclin is mediated through three pairs of evolutionarily conserved zinc fingers, which produce three DNase I footprints on the promoters of rDNA and the basonuclin gene. Using these DNase footprints, we built a computational model for the basonuclin DNA-binding module, which was used to identify in silico potential RNA polymerase II target genes in the human and mouse promoter databases. The target genes of basonuclin show that it regulates the expression of proteins involved in chromatin structure, transcription/DNA-binding, ion-channels, adhesion/cell-cell junction, signal transduction and intracellular transport. Our results suggest that basonuclin, like MYC, may coordinate transcriptional activities among the three RNA polymerases. But basonuclin regulates a distinctive set of pathways, which differ from that regulated by MYC. PMID:16919236

Wang, Junwen; Zhang, Shengliang; Schultz, Richard M.; Tseng, Hung

2006-01-01

426

Jet Perturbation by HE target  

SciTech Connect

We have previously reported the degree of attenuation and perturbation by a Cu jet passing through Comp B explosive. Similar tests have now been performed with high explosive (HE) targets having CJ pressures higher than and lower than the CJ pressure of Comp B. The explosives were LX-14 and TNT, respectively. We found that the measured exit velocity of the jet where it transitions from perturbed to solid did not vary significantly as a function of HE type for each HE thickness. The radial momentum imparted to the perturbed jet segment did vary as a function of HE type, however, and we report the radial spreading of the jet and the penetration of a downstream target as a function of HE type and thickness.

Poulsen, P; Kuklo, R M

2001-03-01

427

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

428

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

429

Targeted therapies for bone sarcomas  

PubMed Central

Bone sarcomas include a very large number of tumour subtypes, which originate form bone and more particularly from mesenchymal stem cell lineage. Osteosarcoma, Ewing's sarcoma and chondrosarcoma, the three main bone sarcoma entities develop in a favourable microenvironment composed by bone cells, blood vessels, immune cells, based on the ‘seed and soil theory'. Current therapy associates surgery and chemotherapy, however, bone sarcomas remain diseases with high morbidity and mortality especially in children and adolescents. In the past decade, various new therapeutic approaches emerged and target the tumour niche or/and directly the tumour cells by acting on signalling/metabolic pathways involved in cell proliferation, apoptosis or drug resistance. The present review gives a brief overview from basic to clinical assessment of the main targeted therapies of bone sarcoma cells. PMID:24422100

Heymann, Dominique; Rédini, Françoise

2013-01-01

430

Targeted therapies for bone sarcomas.  

PubMed

Bone sarcomas include a very large number of tumour subtypes, which originate form bone and more particularly from mesenchymal stem cell lineage. Osteosarcoma, Ewing's sarcoma and chondrosarcoma, the three main bone sarcoma entities develop in a favourable microenvironment composed by bone cells, blood vessels, immune cells, based on the 'seed and soil theory'. Current therapy associates surgery and chemotherapy, however, bone sarcomas remain diseases with high morbidity and mortality especially in children and adolescents. In the past decade, various new therapeutic approaches emerged and target the tumour niche or/and directly the tumour cells by acting on signalling/metabolic pathways involved in cell proliferation, apoptosis or drug resistance. The present review gives a brief overview from basic to clinical assessment of the main targeted therapies of bone sarcoma cells. PMID:24422100

Heymann, Dominique; Rédini, Françoise

2013-01-01

431

Chloride channels as drug targets  

PubMed Central

Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABAA (?-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery. PMID:19153558

Verkman, Alan S.; Galietta, Luis J. V.

2013-01-01

432

Targeting molecular addictions in cancer  

PubMed Central

Cancer cells depend on a finite number of critical signals for their survival. Oncogene addiction, that is, the acquired dependence of a cancer cell on the activity of a single oncogenic gene product, has been the basis for the targeted therapy paradigm, and operationally defines such signals. Additionally, cancer cells have altered metabolic requirements that create addictions to specific nutrients such as glucose and glutamine. In this review, I will discuss the therapeutic opportunities that these two types of molecular addictions offer, focusing on lessons learned from targeting members of the epidermal growth factor receptor family of kinases, and components of MAPK pathway. I will also discuss the challenges in simultaneously harnessing two types of molecular addictions for therapeutic benefit, and the importance of understanding not only the effects of oncogenic signal transduction on metabolism, but also the impact of metabolic states on signal transduction. PMID:25268375

Vivanco, I

2014-01-01

433

Remote moving target indication assessment  

SciTech Connect

The objective of this project was to design and test key components of a sensor to be used on remotely piloted vehicles, aircraft, or satellites for the detection of moving vehicles in cluttered backgrounds. The proposed sensor uses modern large-array focal planes to provide multiple infrared observations of moving targets and capable on-board computers to integrate multiple observations to detect moving targets in background clutter. This combination reduces the size, weight, and cost of the sensor to levels that can be flown on many small unmanned platforms. This effort selected the actual components, integrated them into a test bed, tested the performance of the sensor against realistic generated scenes, and designed a proof-of-concept prototype.

Canavan, G.H.

1996-10-01

434

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

435

Targeting immunosuppression for cancer therapy  

PubMed Central

Failing immunity has been acknowledged for its contribution to cancer development and progression. Recent clinical findings have provided payoffs for significant preclinical evaluation and refinement over the last 20 years, but many questions remain to be answered. In this issue of the JCI, Marabelle et al. describe a novel method for targeting the Tregs that infiltrate tumors, demonstrating that dampening the tumor immunosuppressive environment while activating innate antitumor immunity may be an effective approach to cancer treatment. PMID:23728169

Ghirelli, Cristina; Hagemann, Thorsten

2013-01-01

436

Drug Targeting to the Brain  

Microsoft Academic Search

The goal of brain drug targeting technology is the delivery of therapeutics across the blood–brain barrier (BBB), including\\u000a the human BBB. This is accomplished by re-engineering pharmaceuticals to cross the BBB via specific endogenous transporters\\u000a localized within the brain capillary endothelium. Certain endogenous peptides, such as insulin or transferrin, undergo receptor-mediated\\u000a transport (RMT) across the BBB in vivo. In addition,

William M. Pardridge; P. J. Gaillard

2007-01-01

437

Targeted Advertising ... And Privacy Too  

Microsoft Academic Search

The Web presents a rich and powerful tool for aggregation of consumer information. A flurry of recent articles in the popular\\u000a press has documented aggressive manipulation of such information by some companies for the purposes of targeted advertising.\\u000a While advertisers tout the economic and social benefits of such advertising, consumer privacy groups have expressed grave\\u000a concerns about its potential abuses,

Ari Juels

2001-01-01

438

Preparation of thick molybdenum targets  

NASA Technical Reports Server (NTRS)

Thick natural molybdenum deposits on nickel plated copper substrates were prepared by thermal decomposition of molybdenum hexacarbonyl vapors on a heated surface in an inert gas atmosphere. The molybdenum metal atoms are firmly bonded to the substrate atoms, thus providing an excellent thermal contact across the junction. Molybdenum targets thus prepared should be useful for internal bombardment in a cyclotron where thermal energy inputs can exceed 10 kW.

Singh, J. J.

1974-01-01

439

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

440

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

441

Target racking with glint noise  

Microsoft Academic Search

In tracking targets, there can be an uncertainty associated with the measurements in addition to their inaccuracy, which is usually modeled by aDditive Gaussian noise. However, the Gaussian modeling of the noise may not be true. Noise can be non-Gaussian. The non-Gaussian noise arising in a radar system is known as glint noise. The distribution of glint noise is long

Weng-Rong Wu

1993-01-01

442

Treatment Targets in Intracerebral Hemorrhage  

Microsoft Academic Search

Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than ischemic stroke. The therapeutic interventions\\u000a that are currently available focus mainly on supportive care and secondary prevention. There is a paucity of evidence to support\\u000a any one acute intervention that improves functional outcome. This chapter highlights current treatment targets for ICH based\\u000a on the pathophysiology of the disease.

Navdeep Sangha; Nicole R. Gonzales

2011-01-01

443

Radar detection of hidden targets  

Microsoft Academic Search

To counter long-standing reconnaissance deficiencies against target camouflage and concealment, the Radio Frequency (RF) Technology Division of Wright Laboratory has been supporting the development of Ultra-High Frequency (UHF) Synthetic-Aperture Radar (SAR) technology. The capability to detect and classify vehicles hidden under foliage and\\/or camouflage has been successfully demonstrated through significant airborne data collections from a 200-700 MHz, fully polarimetric SAR

Doug MacDonald; Jeff Isenman; J. Roman

1997-01-01

444

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

445

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

446

DNA Polymerases as Therapeutic Targets  

PubMed Central

Numerous pathological states including cancer, autoimmune diseases, and viral/bacterial infections are often attributed to uncontrollable DNA replication. Inhibiting this essential biological process provides an obvious therapeutic target against these diseases. A logical target is the DNA polymerase, the enzyme responsible for catalyzing the addition of mononucleotides into a growing polymer using a DNA or RNA template as a guide for directing each incorporation event. This review provides a summary of therapeutic agents that target polymerase activity. A discussion of the biological function and mechanism of polymerases is first provided to illustrate the strategy for therapeutic intervention as well as the rational design of various nucleoside analogs that inhibit various polymerases associated with viral infections and cancer. The development of nucleoside and non-nucleoside inhibitors as anti-viral agents is discussed with particular emphasis on their mechanism of action, structure-activity relationships, toxicity, and mechanism of resistance. In addition, commonly used anti-cancer agents are described to illustrate the similarities and differences associated with various nucleoside analogs as therapeutic agents. Finally, new therapeutic approaches are discussed that include the inhibition of selective polymerases involved in DNA repair and/or translesion DNA synthesis as anti-cancer agents. PMID:18642851

Berdis, Anthony J.

2009-01-01

447

Thomson scattering on inhomogeneous targets.  

PubMed

The introduction of brilliant free-electron lasers enables new pump-probe experiments to characterize warm dense matter states. For instance, a short-pulse optical laser irradiates a liquid hydrogen jet that is subsequently probed with brilliant soft x-ray radiation. The strongly inhomogeneous plasma prepared by the optical laser is characterized with particle-in-cell simulations. The interaction of the soft x-ray probe radiation for different time delays between pump and probe with the inhomogeneous plasma is also taken into account via radiative hydrodynamic simulations. We calculate the respective scattering spectrum based on the Born-Mermin approximation for the dynamic structure factor considering the full density and temperature-dependent Thomson scattering cross section throughout the target. We can identify plasmon modes that are generated in different target regions and monitor their temporal evolution. Therefore, such pump-probe experiments are promising tools not only to measure the important plasma parameters density and temperature but also to gain valuable information about their time-dependent profile through the target. The method described here can be applied to various pump-probe scenarios by combining optical lasers and soft x ray, as well as x-ray sources. PMID:21230599

Thiele, R; Sperling, P; Chen, M; Bornath, Th; Fäustlin, R R; Fortmann, C; Glenzer, S H; Kraeft, W-D; Pukhov, A; Toleikis, S; Tschentscher, Th; Redmer, R

2010-11-01

448

KRAS as a Therapeutic Target.  

PubMed

KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. Clin Cancer Res; 21(8); 1797-801. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers." PMID:25878360

McCormick, Frank

2015-04-15

449

A Cryogenic Infrared Calibration Target  

E-print Network

A compact cryogenic calibration target is presented that has a peak diffuse reflectance, $R \\le 0.003$, from $800-4,800\\,{\\rm cm}^{-1}$ $(12-2\\,\\mu$m). Upon expanding the spectral range under consideration to $400-10,000\\,{\\rm cm}^{-1}$ $(25-1\\,\\mu$m) the observed performance gracefully degrades to $R \\le 0.02$ 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 $\\sim4\\,$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 character...

Wollack, Edward J; Rinehart, Stephan A

2014-01-01

450

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

451

26 CFR 1.338-1 - General principles; status of old target and new target.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false General principles; status of old target and new target. 1.338-1... § 1.338-1 General principles; status of old target and new target. (a...10)-1.) Although target is a single corporation under...

2011-04-01

452

26 CFR 1.338-1 - General principles; status of old target and new target.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false General principles; status of old target and new target. 1.338-1... § 1.338-1 General principles; status of old target and new target. (a...6)(ii). Although target is a single corporation under corporate...

2014-04-01

453

26 CFR 1.338-1 - General principles; status of old target and new target.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false General principles; status of old target and new target. 1.338-1... § 1.338-1 General principles; status of old target and new target. (a...10)-1.) Although target is a single corporation under...

2012-04-01

454

26 CFR 1.338-1 - General principles; status of old target and new target.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false General principles; status of old target and new target. 1.338-1... § 1.338-1 General principles; status of old target and new target. (a...10)-1.) Although target is a single corporation under...

2013-04-01

455

LIFE Target Fabrication Research Plan Sept 2008  

SciTech Connect

The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

2008-11-10

456

Cryogenic Target Performance on OMEGA  

NASA Astrophysics Data System (ADS)

Ignition-relevant target physics is studied using direct-drive cryogenic D2 and DT implosions on the OMEGA Laser System. These experiments are designed to validate the performance of polar-drive ignition designs for the NIF using energy-scaled symmetric-drive designs on OMEGA. The focus of current experiments is on shell stability and preheat at ignition adiabats. Recent work with cryogenic cone-in-shell targets demonstrated the sensitivity of the baseline design to shock (mis)-timing and subsequent shock-induced preheating. Hot-electron preheat was shown to be mitigated by including high-Z dopants in the ablator that raise the temperature of the corona and increase the threshold for the two-plasmon decay. Nonlocal heat transport was found to be important in modeling laser absorption during the leading picket, and hydrodynamic growth of target modulations was experimentally shown to be stabilized at peak drive intensities by these nonlocal effects. Finally, much work has been done to prepare the cryogenic target systems for backlighting using the new high-energy, short-pulse beams provided by the recently completed OMEGA EP Facility. This work includes proof-of-principle demonstrations using OMEGA beams to backlight a cryogenic core. The status of short-pulse backlighting will be presented along with the latest fuel compression and target-performance results. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302. Contributors: R. Betti, R.S. Craxton, J.A. Delettrez, D.H. Edgell, V.Yu. Glebov, V.N. Goncharov, D.R. Harding, S.X. Hu, J.P. Knauer, F.J. Marshall, R.L. McCrory, P.W. McKenty, D.D. Meyerhofer, P.B. Radha, S.P. Regan, T.C. Sangster, W. Seka, R.W. Short, S. Skupsky, J.M. Soures, C. Stoeckl, B. Yaakobi, UR/LLE; J.A. Frenje, C.K. Li, R.D. Petrasso, F.H. S'eguin, PSFC MIT.

Smalyuk, V. A.

2008-11-01

457

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

458

Properties of Protein Drug Target Classes  

PubMed Central

Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein’s sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein’s sequence (e.g. secondary structure). Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins’ hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme. PMID:25822509

Bull, Simon C.; Doig, Andrew J.

2015-01-01

459

The Ursinus College Liquid Hydrogen Target  

NASA Astrophysics Data System (ADS)

The Ursinus College Liquid Hydrogen Target has been constructed at the National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University, for the purpose of eliminating unwanted gamma-rays from carbon in polyethylene or deuterated polyethylene targets that are commonly used in experiments requiring thick proton targets. Existing geant4 simulations of the Segmented Germanium Array (SeGA) and the CAESium iodide ARray (CAESAR) have been modified to incorporate the liquid hydrogen target. The impact of the target on gamma-ray detection efficiencies and the use of the simulations to plan experiments with the target are discussed.

Palardy, Jessica; Ferrante, Nicholas; Riley, Lewis; Zegers, Remco

2010-11-01

460

NLC Positron Target Heating(LCC-0065)  

SciTech Connect

The NLC requires an intense beam with a large number of positrons. These positrons are produced by a high energy electron beam impinging on a solid tungsten-rhenium alloy target. The particle shower that develops in the solid target deposits significant energy in the material, leading to target stresses and potentially to target damage. The stresses can be analyzed once the magnitude and extent of the energy deposition is known. This note details the modeling of the energy deposition using EGS, performed for the NLC and the SLC targets and for possible NLC targets made of copper or nickel instead of WRe.

Schultz, D

2003-10-07

461

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

462

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

Hnatowich, DJ

2008-10-28

463

Status of T2K Target 2nd Oxford-Princeton High-Power Target Workshop  

E-print Network

station ·Aims of target design ·Current target design ·CFD analysis ·Remote target exchange concept tube as a total source ­ TOTAL HEAT LOAD = 22kW Required flow rate #12;2nd Oxford-Princeton High, RAL #12;2nd Oxford-Princeton High-Power Target Workshop Mike Fitton Aims of Target Design · Target

McDonald, Kirk

464

Pinatubo global cooling on target  

SciTech Connect

When Pinatubo blasted millions of tons of debris into the stratosphere in June 1991, Hansen of NASA's Goddard Institute for Space Studies used his computer climate model to predict that the shade cost by the debris would cool the globe by about half a degree C. Year end temperature reports for 1992 are now showing that the prediction was on target-confirming the tentative belief that volcanos can temporarily cool the climate and validating at least one component of the computer models predicting a greenhouse warming.

Kerr, R.A.

1993-01-29

465

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

466

Combination therapy targeting cancer metabolism.  

PubMed

Cancer cells undergo significant metabolic adaptation. Cellular transformation enhances both glycolysis and mitochondrial respiration efficiency through the induction of HIF-1? and HIF-2?. In this process, energy production and synthesis of macromolecules are maximized with minimal ROS accumulation. Furthermore, a series of antioxidant enzymes are induced to mitigate the damaging effects of ROS. Examination of these metabolic changes provides rationale for a synergistic approach to combination anti-cancer therapy; targeted inhibition of HIF and inhibition of cellular defenses against oxidative stress. PMID:20947261

Wenger, Justin B; Chun, Sang Y; Dang, Duyen T; Luesch, Hendrik; Dang, Long H

2011-02-01

467

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.

468

Pfizer targets genomics through Pfizergen  

SciTech Connect

Recently, Pfizer (New York) formed Pfizergen to develop and commercialize genomics. For starters, Pfizergen involves investments by Pfizer of more than $115 million - excluding milestone payments and royalties on future products - in four biotech firms. Seeking a strong foothold in genomics, Pfizer is piecing together a multifaceted network of technologies. Through its alliance with Incyte, Pfizer has already accessed gene databases, high-throughput gene sequencing, and transcription analysis. Through Pfizergen, it will access expertise in microbial genetic engineering and combinatorial chemistry, as well as antiviral, antisense, and gene therapy capabilities. Future investments could target firms specializing in such products as positional cloning and bioinformatics.

Glaser, V.

1995-06-01

469

Electromagnetic Scattering from Realistic Targets  

NASA Technical Reports Server (NTRS)

The general goal of the project is to develop computational tools for calculating radar signature of realistic targets. A hybrid technique that combines the shooting-and-bouncing-ray (SBR) method and the finite-element method (FEM) for the radiation characterization of microstrip patch antennas in a complex geometry was developed. In addition, a hybridization procedure to combine moment method (MoM) solution and the SBR method to treat the scattering of waveguide slot arrays on an aircraft was developed. A list of journal articles and conference papers is included.

Lee, Shung- Wu; Jin, Jian-Ming

1997-01-01

470

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

471

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

472

Targeting Fatigue in Stroke Patients  

PubMed Central

Symptoms of fatigue are often reported by patients in both the acute and chronic stages of recovery following a stroke. It is commonly associated with low mood and sleep disturbances, but can arise in their absence. However, it has also been associated with poorer long-term outcome and, as such, its aetiology warrants a greater understanding. There is convincing evidence that inflammatory cascades and cytokine signalling precipitated by the infarct promote fatigue, and these pathways may harbour therapeutic targets in its management. PMID:22389829

Barritt, Andrew W.; Smithard, David G.

2011-01-01

473

Targeting to intestinal M cells.  

PubMed

The specialised, antigen-transporting, epithelial M cells in the follicle-associated epithelium (FAE) overlying gut-associated lymphoid tissues constitute the primary target for oral delivery of vaccines. Our studies have shown that polystyrene microspheres selectively bind to, and are efficiently transcytosed by, rabbit Peyer's patch M cells in closed intestinal loops. Binding of biodegradable poly(DL-lactide-co-glycolide) microspheres to rabbit Peyer's patch FAE is an order of magnitude lower than that of polystyrene microspheres. Although poly(DL-lactide-co-glycolide) microspheres are not selectively targeted to M cells, a high proportion of those which bind to M cells are transcytosed, supporting the potential of such microspheres as vehicles for oral vaccine delivery. Comparison of the binding of polystyrene microspheres by murine FAE revealed this to be markedly less extensive than by rabbit FAE. These data demonstrate that microsphere binding by M cells depends on the surface properties of both cells and microspheres and suggest that surface modification may enhance the efficacy of microsphere delivery vehicles. One such approach is the incorporation of molecules with inherent binding specificity for M cells. Lectin-binding studies have revealed that M cells exhibit pronounced regional and species variation in glycoconjugate expression. In murine intestine, certain lectins bind selectively to M cells either in Peyer's patches or caecum, or at both sites. Selective targeting to, and transcytosis of, lectin-conjugates by M cells in ligated segments of muri