Kejadian Demam Neutropenia pada Anak dengan Keganasan

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Sarah Rafika Nursyirwan

2018-03-01

Kesimpulan. kejadian demam neutropenia lebih sering terjadi pada pasien dengan keganasan darah. Patogen ditemukan pada sebagian pasien dengan demam neutropenia. Penyebab terbanyak bakteremia adalah bakteri Gram positif. Sensitivitas antibiotik tertinggi didapatkan pada vankomisin. Data mengenai pola sensitivitas antibiotik terbaru diperlukan untuk pedoman tata laksana pasien demam neutropenia.

Serum endocan levels in children with febrile neutropenia

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Eylem Kiral

2016-03-01

Full Text Available Endocan is an endotelial cell specific molecule; previous studies have shown that serum endocan levels increased in cancer and sepsis and are also related to the severity of sepsis. There are no clinical study about serum endocan levels in children with febrile neutropenia. The aim of this study was to evaluate serum endocan levels in pediatric leukemia patients with febrile neutropenia (n=33 and compare them with children with leukemia without fever (n=33 and also with healthy children (n=24. The median serum endocan level in the first group (children with febrile neutropenia was statistically significantly higher compared to the leukemic children without febrile neutropenia and also control group (P<0.01 for both. No difference was determined between the serum endocan levels of the leukaemia patients without febrile neutropenia and the healthy control group (P>0.05. Serum endocan levels were also similar with febrile neutropenia due to bacterial causes comparing with the idiopathic febril neutropenia. The results of this study showed increased serum endocan in children with leukemia during the febrile neutropenia episode, and no changes of serum endocan levels in children without leukemia without infection/fever. The monitoring of a series of serum endocan levels would be helpful for the course of febrile neutropenia.

Drug induced neutropenia manifesting as oral ulcerations

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Rachna Kaul

2009-01-01

Full Text Available As dental practitioners, we often come across oral ulcerations of varied etiology. Among all the causes of oral ulcers, those due to neutropenia are significant. Neutropenia can occur in many systemic conditions and also in patients on long-term therapy of certain drugs like phenytoin. The diagnosis of neutropenia in time leads to early recognition of the cause of this fatal condition. Here, we report a case of a 50-year-old female patient who developed oral ulcerations secondary to phenytoin-induced neutropenia. Early diagnosis of the condition led to discontinuation of the offending drug and significant improvement in her blood picture and also prevented her from falling prey to many other systemic infections that neutropenia can cause.

Family caring strategies in neutropenia.

Science.gov (United States)

Eggenberger, Sandra K; Krumwiede, Norma; Meiers, Sonja J; Bliesmer, Mary; Earle, Patricia

2004-12-01

Aggressive chemotherapy protocols result in neutropenia in approximately half of all patients receiving chemotherapy. Thus, neutropenia continues to be a significant and potentially life-threatening side effect of treatment, even with use of colony-stimulating factors. Families of patients with neutropenia often provide the primary healing environment because most chemotherapy protocols are managed on an outpatient basis. To learn about the family's experience of managing chemotherapy-induced neutropenia (CIN), a grounded-theory methodology was used to analyze data from seven families. The central theme revealed by these families was "turbulent waiting with intensified connections." This meant that when families had a sense of greater vulnerability in response to the waiting after diagnosis of CIN, they connected intensely with each other and healthcare providers. Families reported that connections with nurses became more significant when neutropenia interrupted chemotherapy. Families also developed family caring strategies to manage this period of waiting for the chemotherapy to resume. These strategies included family inquiry, family vigilance, and family balancing. Nurses need to be aware of approaches to support the family's ability to manage CIN. Interventions and approaches constructed from the perspective of a family-professional partnership will enhance the family cancer experience as well as ongoing family growth and function.

Risperidone-induced reversible neutropenia.

Science.gov (United States)

Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

2017-01-01

This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance.

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Delgado, Asunción; Arco, Rocio; Ibarra-Molero, Beatriz; Sanchez-Ruiz, Jose M

2017-05-09

Proviral factors are host proteins hijacked by viruses for processes essential for virus propagation such as cellular entry and replication. Pathogens and their hosts co-evolve. It follows that replacing a proviral factor with a functional ancestral form of the same protein could prevent viral propagation without fatally compromising organismal fitness. Here, we provide proof of concept of this notion. Thioredoxins serve as general oxidoreductases in all known cells. We report that several laboratory resurrections of Precambrian thioredoxins display substantial levels of functionality within Escherichia coli. Unlike E. coli thioredoxin, however, these ancestral thioredoxins are not efficiently recruited by the bacteriophage T7 for its replisome and therefore prevent phage propagation in E. coli. These results suggest an approach to the engineering of virus resistance. Diseases caused by viruses may have a devastating effect in agriculture. We discuss how the suggested approach could be applied to the engineering of plant virus resistance. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Thickened cortical bones in congenital neutropenia

International Nuclear Information System (INIS)

Boechat, M.I.; Gormley, L.S.; O'Laughlin, B.J.

1987-01-01

Congenital neutropenia is an uncommon entity which may be familial and has a wide spectrum of clinical expression. Three sisters with the severe form of the disease, that suffered from recurrent infections which lead to their demise are described. Review of their radiographs revealed the presence of cortical thickening of the bones. Although several syndroms with different bone abnormalities have been reported associated with neutropenia, the radiographic finding of thickened cortex in children with congenital neutropenia has not been previously described. (orig.)

Thickened cortical bones in congenital neutropenia

Energy Technology Data Exchange (ETDEWEB)

Boechat, M.I.; Gormley, L.S.; O' Laughlin, B.J.

1987-02-01

Congenital neutropenia is an uncommon entity which may be familial and has a wide spectrum of clinical expression. Three sisters with the severe form of the disease, that suffered from recurrent infections which lead to their demise are described. Review of their radiographs revealed the presence of cortical thickening of the bones. Although several syndroms with different bone abnormalities have been reported associated with neutropenia, the radiographic finding of thickened cortex in children with congenital neutropenia has not been previously described.

Genetics Home Reference: severe congenital neutropenia

Science.gov (United States)

... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... Genetic Testing Registry: Severe congenital neutropenia 2, autosomal dominant Genetic Testing Registry: Severe congenital neutropenia 3, autosomal ...

Evaluasi Sensitivitas Antibiotik dengan Demam Neutropenia

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Sulaiman Hamid

2016-11-01

Kesimpulan. Bakteri Gram negatif merupakan penyebab utama demam neutropenia. Sensitivitas cefotaxime lebih rendah apabila dibandingkan dengan antibiotik yang lain. Cefpirome, cefepime dan ampicillin-sulbactam direkomendasikan untuk menggantikan cefotaxime sebagai obat yang dikombinasikan dengan gentamicin pada pengobatan demam neutropenia.

Febrile neutropenia in childhood cancer

African Journals Online (AJOL)

To classify and treat patients with febrile neutropenia adequately, one has to have a ... 48 hours.2,4,5. Approach. A child with possible febrile neutropenia should be viewed as a ... treating centre for information on the child's treatment if the family do not have a ... treatment, such as antimicrobial therapy, as well as the nature.

Prevalence, phenotype and inheritance of benign neutropenia in Arabs

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Nagelkerke Nicollas

2009-03-01

Full Text Available Abstract Background Benign neutropenia, i.e., neutropenia not associated with an increased risk of infection, may result in serious medical consequences when a 'standard' definition of neutropenia (absolute neutrophil count (ANC 9cells/L is universally applied to all races. The aims of this study were to determine the prevalence of benign neutropenia among healthy Arabs and evaluate its mode of inheritance. Methods ANCs were studied prospectively amongst a healthy indigenous population (n = 1032 from the United Arab Emirates undergoing a nation-wide sickle-cell and thalassemia screening program. The mean neutrophil count and the prevalence of benign neutropenia were compared by age, sex and amongst various tribes. Results The mean neutrophil count (× 109cells/L was 3.3 (range 0.95–7.6. Benign neutropenia was present in 110 (10.7% subjects of whom 24 (2.3% individuals had moderate neutropenia (ANC 0.5 – 1.0 × 109 cells/L. In the 22 tribe-family groups, the prevalence of benign neutropenia varied between 0% and 38%. Benign neutropenia showed no difference in the frequency amongst the sexes (p = 0.23 and it was independent of age (Spearman's rho = 0.05, p = 0.13. The age-related mean neutrophil count was the lowest in Arabs when compared with other ethnic groups (Blacks, Europeans and Mexicans. The inheritance of benign neutropenia was consistent with an autosomal dominant pattern; however, the diversity of observed phenotypes suggested the presence of more than one genetic variant for this trait. Conclusion Arabs have a high prevalence of benign neutropenia that may be inherited as an autosomal dominant trait.

Correlation Between Body Weight and Mitoxantrone-Associated Neutropenia in Dogs.

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Richardson, Danielle; Poirier, Valerie J; Matsuyama, Arata; Calvalido, Jerome

Thirty-seven dogs with histologically or cytologically confirmed malignant tumors treated with single-agent mitoxantrone at 5 mg/m 2 were evaluated in a retrospective study assessing the correlation between body weight and neutropenia associated with a single dose of mitoxantrone in dogs. Overall, eight dogs (21%) experienced grade 3 neutropenia and five dogs (14%) experienced grade 4 neutropenia on day 7 following mitoxantrone chemotherapy. Dogs ≤10 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (5.8 relative risk; 95% confidence interval, 2.6-12.9; P 10 kg. Dogs ≤15 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (8.1 relative risk; 95% confidence interval, 2.1-31.3; P 15 kg. Of the 13 patients who developed grade 3 or 4 neutropenia, 6 (46%) were hospitalized for clinical signs related to neutropenia. Based on the severity of neutropenia and the resulting hospitalization seen in dogs ≤10 kg, a dose reduction could be considered for the initial dose of mitoxantrone, and clinicians should be aware of the increased risk of neutropenia in patients 10.1 to ≤15 kg.

Mutations in Ovis aries TMEM154 are associated with lower small ruminant lentivirus proviral concentration in one sheep flock.

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Alshanbari, F A; Mousel, M R; Reynolds, J O; Herrmann-Hoesing, L M; Highland, M A; Lewis, G S; White, S N

2014-08-01

Small ruminant lentivirus (SRLV), also called ovine progressive pneumonia virus or maedi-visna, is present in 24% of US sheep. Like human immunodeficiency virus, SRLV is a macrophage-tropic lentivirus that causes lifelong infection. The production impacts from SRLV are due to a range of disease symptoms, including pneumonia, arthritis, mastitis, body condition wasting and encephalitis. There is no cure and no effective vaccine for preventing SRLV infection. However, breed differences in prevalence and proviral concentration indicate a genetic basis for susceptibility to SRLV. Animals with high blood proviral concentration show increased tissue lesion severity, so proviral concentration represents a live animal test for control post-infection in terms of proviral replication and disease severity. Recently, it was found that sheep with two copies of TMEM154 haplotype 1 (encoding lysine at position 35) had lower odds of SRLV infection. In this study, we examined the relationship between SRLV control post-infection and variants in two genes, TMEM154 and CCR5, in four flocks containing 1403 SRLV-positive sheep. We found two copies of TMEM154 haplotype 1 were associated with lower SRLV proviral concentration in one flock (P < 0.02). This identified the same favorable diplotype for SRLV control post-infection as for odds of infection. However, frequencies of haplotypes 2 and 3 were too low in the other three flocks to test. The CCR5 promoter deletion did not have consistent association with SRLV proviral concentration. Future work in flocks with more balanced allele frequencies is needed to confirm or refute TMEM154 association with control of SRLV post-infection. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

Neutropenia in infants with hemolytic disease of the newborn.

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Blanco, Esther; Johnston, Donna L

2012-06-01

This study examined the incidence, outcome and risk factors of neutropenia in infants with hemolytic disease of the newborn (HDN). A retrospective chart review was performed on infants with HDN. Of 69 evaluable infants, 45% developed neutropenia. Only one infectious complication was recorded. In most instances the neutropenia resolved spontaneously, but in seven infants it persisted for a median of 397 days. Males were at higher risk for developing neutropenia, but severity of HDN, antibody specificity, or therapy were not significant risk factors. Neutropenia is a common feature of HDN, regardless of severity of disease, treatment received, or antibody specificity. Copyright © 2011 Wiley Periodicals, Inc.

Four novel ELANE mutations in patients with congenital neutropenia.

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Kurnikova, Maria; Maschan, Michael; Dinova, Evgeniya; Shagina, Irina; Finogenova, Natalia; Mamedova, Elena; Polovtseva, Tatyana; Shagin, Dmitry; Shcherbina, Anna

2011-08-01

Congenital neutropenia is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoesis at the promyelocyte/myelocyte stage. Cyclic neutropenia (CyN) and severe congenital neutropenia (SCN) are two main forms of congenital neutropenia. Genetic analysis has shown that heterozygous mutations in the ELANE gene encoding the neutrophil elastase are the major cause of these disorders. We investigated the prevalence of ELANE mutations in a group of 16 patients from 14 families with congenital neutropenia. Five patients had typical manifestations of CyN, and 11 patients had SCN. Seven different heterozygous ELANE mutations were found, including four novel mutations. Copyright © 2011 Wiley-Liss, Inc.

Neutropenia in pediatric hematology/oncology practice

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E. A. Deordieva

2015-06-01

Full Text Available Acquired neutropenia is one of the most common conditions in pediatric hematology practice. These conditions usually are benign. In contrast, congenital neutropenia are rare conditions, but in the absence of pathogenic therapy can cause fatal complications. Approach to the differential diagnosis and management of these patients are discussed in this review.

Febrile neutropenia in haematological malignancies

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Sharma A

2005-01-01

Full Text Available Fever is the principle sign of infection in neutropenic patient and frequently may be the only evidence of infection. The pattern of fever in neutropenia is non-specific and not pathognomonic of any type of infections or non-infectious process and can be suppressed by the antipyretic effects of drugs such as corticosteroids. Neutropenia, resulting from cytotoxic chemotherapy is the most common risk factor for severe infections in hematological malignancies. The duration of neutropenia also contributes significantly to the risk of serious infections. This risk is significantly greater a lower neutrophil counts, such that 100% patients with ANC < 100 cells/µl lasting 3 weeks or more develop documented infections. The prompt initiation of empirical antibiotics in febrile neutropenia has been the most important advance in the management of the immunocompromised host. The initial empirical antibiotic regimen started at presentation of the febrile episode frequently requires modifications especially in high-risk febrile neutropenia. Neutropenic patients who remain febrile despite 4-7 days of broad spectrum antibacterial therapy are at a high risk of invasive fungal infection. Empirical antifungal therapy with Amphotericin B in persistently febrile neutropenic patients and other high risk patients has shown to reduce the risk of invasive fungal infection by 50-80% and the risk of fungal infection related mortality by 23-45% in 1980′s. The IDSA has recommended that amphotericin B at 0.5-0.7 mg/kg/day be administered till marrow recovery. This approach is limited however by the adverse effects caused by drug infusion (fever, chills, myalgias, nausea, hypotension and bronchospasm. Lipid formulations which improve the therapeutic ratio of the traditional formulation are available. The safety and efficacy of these formulations is well established. These formulations have comparable efficacy and are less nephrotoxic than conventional amphotericin B

Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load

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Sanabani Sabri Saeed

2012-12-01

Full Text Available Abstract Background The Interleukin 28B (IL28B rs12979860 polymorphisms was recently reported to be associated with the human T-cell leukemia virus type 1 (HTLV-1 proviral load (PvL and the development of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Methods In an attempt to examine this hypothesis, we assessed the association of the rs12979860 genotypes with HTLV-1 PvL levels and clinical status in 112 unrelated Brazilian subjects (81 HTLV-1 asymptomatic carriers, 24 individuals with HAM/TSP and 7 with Adult T cell Leukemia/Lymphoma (ATLL. Results All 112 samples were successfully genotyped and their PvLs compared. Neither the homozygote TT nor the heterozygote CT mutations nor the combination genotypes (TT/CT were associated with a greater PvL. We also observed no significant difference in allele distribution between asymptomatic carriers and patients with HTLV-1 associated HAM/TSP. Conclusions Our study failed to support the previously reported positive association between the IL28B rs12979860 polymorphisms and an increased risk of developing HAM/TSP in the Brazilian population.

Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy

International Nuclear Information System (INIS)

Dickie, Peter; Roberts, Amanda; Uwiera, Richard; Witmer, Jennifer; Sharma, Kirti; Kopp, Jeffrey B.

2004-01-01

Clinical and morphologic features of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN), such as proteinuria, sclerosing glomerulopathy, tubular degeneration, and interstitial disease, have been modeled in mice bearing an HIV proviral transgene rendered noninfectious through a deletion in gag/pol. Exploring the genetic basis of HIVAN, HIV transgenic mice bearing mutations in either or both of the accessory genes nef and vpr were created. Proteinuria and focal glomerulosclerosis (FGS) only developed in mice with an intact vpr gene. Transgenic mice bearing a simplified proviral DNA (encoding only Tat and Vpr) developed renal disease characterized by FGS in which Vpr protein was localized to glomerular and tubular epithelia by immunohistochemistry. The dual transgenic progeny of HIV[Tat/Vpr] mice bred to HIV[ΔVpr] proviral transgenic mice displayed a more severe nephropathy with no apparent increase in Vpr expression, implying that multiple viral genes contribute to HIVAN. However, the unique contribution of macrophage-specific Vpr expression in the development of glomerular disease was underscored by the induction of FGS in multiple murine lines bearing a c-fms/vpr transgene

Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega.

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Leal, Rodolfo O; Gil, Solange; Duarte, Ana; McGahie, David; Sepúlveda, Nuno; Niza, Maria M R E; Tavares, Luís

2015-04-01

This study assesses viremia, provirus and blood cytokine profile in naturally FIV-infected cats treated with two distinct protocols of interferon omega (rFeIFN-ω). Samples from FIV-cats previously submitted to two single-arm studies were used: 7/18 received the licensed/subcutaneous protocol (SC) while 11/18 were treated orally (PO). Viremia, provirus and blood mRNA expression of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12p40, Interferon-γ and Tumor Necrosis Factor-α were monitored by Real-Time qPCR. Concurrent plasma levels of IL-6, IL-12p40 and IL-4 were assessed by ELISA. IL-6 plasma levels decreased in the SC group (p = 0.031). IL-6 mRNA expression (p = 0.037) decreased in the PO group, albeit not sufficiently to change concurrent plasma levels. Neither viremia nor other measured cytokines changed with therapy. Proviral load increased in the SC group (p = 0.031), which can be justified by a clinically irrelevant increase of lymphocyte count. Independently of the protocol, rFeIFN-ω seems to act on innate immunity by reducing pro-inflammatory stimulus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months

DEFF Research Database (Denmark)

Katzenstein, T.; Ullum, H.; Røge, B.T.

2003-01-01

OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of

Investigating Signs of Recent Evolution in the Pool of Pro-viral DNA during Years of Successful HAART

DEFF Research Database (Denmark)

Mens, H.; Pedersen, Anders Gorm; Jørgensen, L. B.

2007-01-01

In order to shed light on the nature of the persistent reservoir of human immunodeficiency virus type 1 (HIV-1), we investigated signs of recent evolution in the pool of proviral DNA in patients on successful HAART. Pro-viral DNA, corresponding to the C2-V3-C3 region of the HIV-1 env gene...... there were temporal trends indicating ongoing replication and evolution. In summary, it was not possible to detect definitive signs of ongoing evolution in either the bulk-sequenced or the clonal data with the methods employed here, but our results could be consistent with localized expression of archival...

Water Extract of Deer Bones Activates Macrophages and Alleviates Neutropenia

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Han-Seok Choi

2013-01-01

Full Text Available Extracts from deer bones, called nok-gol in Korean, have long been used to invigorate Qi. While neutropenia is not well detected in normal physiological condition, it could be a cause of severe problems to develop diseases such as infectious and cancerous diseases. Thus, a prevention of neutropenia in normal physiology and pathophysiological states is important for maintaining Qi and preventing disease progress. In cell biological aspects, activated macrophages are known to prevent neutropenia. In this study, we demonstrate that water extract of deer bone (herein, NG prevents neutropenia by activating macrophages. In mouse neutropenia model system in vivo where ICR mice were treated with cyclophosphamide to immunosuppress, an oral administration of NG altered the number of blood cells including lymphocytes, neutrophils, basophils, and eosinophils. This in vivo effect of NG was relevant to that of granulocyte colony stimulating factor (G-CSF that was known to improve neutropenia. Our in vitro studies further showed that NG treatment increased intracellular reactive oxygen species (ROS and promoted macrophagic differentiation of mouse monocytic Raw264.7 cells in a dose-dependent manner. In addition, NG enhanced nitric oxide (NO synthesis and secretions of cytokines including IL-6 and TNF-α. Consistently, NG treatment induced phosphorylation of ERK, JNK, IKK, IκBα, and NF-κB in Raw264.7 cells. Thus, our data suggest that NG is helpful for alleviating neutropenia.

Re-challenge with Etanercept in patients with Etanercept-induced Neutropenia.

LENUS (Irish Health Repository)

Haroon, Muhammad

2011-08-05

TNF blockers have rarely been associated with haematological complications; however, there are scattered case reports of marked neutropenia with their use and necessitating in their withdrawal. We would like to report a series of five patients who developed neutropenia with etanercept use; however, all these patients were re-challenged with etanercept with a mean follow up of 30 months. These patients developed neutropenia within 2 months of starting etanercept. Two patients were eventually taken off etanercept; one of them needed switching to a different form of TNF blockers, and the second patient is in clinical remission with low-dose corticosteroids. All our patients continued to have mild-moderate degree of neutropenia; however, they are being monitored very closely and they are enjoying complete disease remission. It was interesting to note that none of our patients had increased infections during the re-challenge phase, even though they had grade 2 to grade 4 neutropenia. We have re-challenged these patients without any clinical complications, revealing that patients with mild to moderate neutropenia can be safely exposed to TNF blockers as long as they are monitored with regular cell count checks. Although largely noted to be clinically insignificant in our patient series, the potential of drug-induced neutropenia in causing higher rate of infections do exist. Careful clinical and hematologic monitoring is the best way to recognize this adverse event.

Severe congenital neutropenia

DEFF Research Database (Denmark)

Borregaard, Niels

2014-01-01

In this issue of Blood, Tidwell et al1 demonstrate that mutations in the start codon (protein synthesis is initiated at the codon ATG) of neutrophil elastase (ELANE) result in the production of N-terminally truncated elastase, which mislocates to the nucleus and results in severe congenital neutr...... neutropenia (SCN)....

Lipegfilgrastim in the management of chemotherapy-induced neutropenia of cancer patients

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Guariglia R

2016-01-01

Full Text Available Roberto Guariglia,1 Maria Carmen Martorelli,1 Rosa Lerose,2 Donatella Telesca,2 Maria Rita Milella,2 Pellegrino Musto3 1Unit of Hematology and Stem Cell Transplantation, 2Pharmacy Service, 3Scientific Direction, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, Potenza, Italy Abstract: Neutropenia and febrile neutropenia (FN are frequent and potentially fatal toxicities of myelosuppressive anticancer treatments. The introduction of granulocyte colony-stimulating factors (G-CSFs in clinical practice has remarkably reduced the duration and severity of neutropenia, as well as the incidence of FN, thus allowing the administration of chemotherapeutic agents at the optimal dose and time with lower risk. The current scenario of G-CSFs in Europe includes filgrastim, lenograstim, some G-CSF biosimilars, and pegfilgrastim. Recently, a novel long-acting G-CSF, lipegfilgrastim, became available. Lipegfilgrastim is a glycopegylated G-CSF, alternative to pegfilgrastim, and has shown in randomized trials, to be equivalent to pegfilgrastim in reducing the incidence of severe neutropenia and FN in patients with breast cancer receiving chemotherapy, with a similar safety profile. Furthermore, lipegfilgrastim was more effective than the placebo in reducing the incidence of severe neutropenia, its duration, and time to absolute neutrophil count recovery, in patients with non-small cell lung cancer receiving myelosuppressive therapy. Although the number of studies currently published is still limited, lipegfilgrastim seems to be a promising drug in the management of chemotherapy-induced neutropenia. Keywords: neutropenia, febrile neutropenia, granulocyte colony-stimulating factors, G-CSF, pegfilgrastim, lipegfilgrastim

Difference in Neutropenia due to Administration Schedule of TAS-102

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Yoichiro Yoshida

2017-03-01

Full Text Available TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102.

Tratamiento ambulatorio del paciente con neutropenia febril Outpatient therapy in patients with febrile neutropenia

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Andrés Londoño Gallo

2008-01-01

Full Text Available

El tratamiento de los pacientes con neoplasia y neutropenia febril plantea muchas dudas. Una de ellas, que genera ansiedad en el personal de la salud, el paciente y sus familiares, es la necesidad de hospitalización porque ésta implica exponer a gérmenes intrahospitalarios potencialmente resistentes a un paciente cuyo sistema inmune puede no estar en las mejores condiciones; incluso con un aislamiento óptimo existe el riesgo de adquirir una infección nosocomial. Muchos estudios han tratado de validar métodos para clasificar a los pacientes con fiebre y neutropenia en grupos de diferente riesgo, como fundamento para implementar estrategias de tratamiento selectivo; así se ha abierto la posibilidad de utilizar medidas más conservadoras para el tratamiento de los episodios de bajo riesgo, entre ellas la administración de regímenes orales ambulatorios de antibióticos de amplio espectro; ello sin demeritar la necesidad de aplicar un juicio clínico adecuado, hacer un buen seguimiento y tener acceso a la atención médica inmediata. La neutropenia es una de las consecuencias graves de la quimioterapia para el cáncer, y se ha demostrado que el tratamiento del paciente neutropénico febril con antibióticos intravenosos reduce la mortalidad. La terapia oral podría ser una alternativa aceptable para pacientes bien seleccionados. Ella puede mejorar la calidad de vida de los pacientes con cáncer, evitar las complicaciones asociadas con la terapia intravenosa y disminuir los costos del tratamiento.

Treatment of patients with neoplasia and febrile neutropenia, as a consequence of chemotherapy, poses many doubts, among them the need for hospitalization, since this implies exposure to potentially resistant nosocomial microorganisms. Even under the best isolation techniques, there may

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

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Rui-Rui Peng

2017-03-01

Full Text Available Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai.Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13% and 0.35% (95% CI: 0.06-1.39%, respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients, fatigue (2 patients, cough (1 patient, sore throat (1 patient, diarrhea (1 patient and erythematous rash (1 patient. The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05. Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia.Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for

Multiple proviral integration events after virological synapse-mediated HIV-1 spread

International Nuclear Information System (INIS)

Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

2013-01-01

HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes

Rationalizing the approach to children with fever in neutropenia

NARCIS (Netherlands)

Ammann, Roland A.; Tissing, Wim J. E.; Phillips, Bob

Purpose of review Fever in neutropenia is the most frequent potentially life-threatening complication of chemotherapy in children and adolescents with cancer. This review summarizes recent studies that refine our knowledge of how to manage pediatric fever in neutropenia, and their implications for

Periodontal disease in three siblings with familial neutropenia.

Science.gov (United States)

Kirstilä, V; Sewón, L; Laine, J

1993-06-01

The periodontal status and treatment of three teenagers in a Finnish family with familial neutropenia is described. The mother was also diagnosed with neutropenia. At initial examination, the 15-year-old male and the 10-year-old female had severe periodontitis, whereas the 13-year-old male had oral ulcerations but no significant periodontal disease. The two siblings with periodontitis were treated and followed approximately 5 years. It was concluded that periodontal therapy including scaling, surgery, and use of antimicrobial agents can be successful in patients with familial neutropenia, and that such patients are not necessarily candidates for full mouth extraction. The role of granulocyte colony-stimulating factor in which was used in the treatment of these patients remains to be established.

Kinetics of HIV-1 CTL epitopes recognized by HLA I alleles in HIV-infected individuals at times near primary infection: the Provir/Latitude45 study.

Directory of Open Access Journals (Sweden)

Jennifer Papuchon

Full Text Available In patients responding successfully to ART, the next therapeutic step is viral cure. An interesting strategy is antiviral vaccination, particularly involving CD8 T cell epitopes. However, attempts at vaccination are dependent on the immunogenetic background of individuals. The Provir/Latitude 45 project aims to investigate which CTL epitopes in proviral HIV-1 will be recognized by the immune system when HLA alleles are taken into consideration. A prior study (Papuchon et al, PLoS ONE 2013 showed that chronically-infected patients under successful ART exhibited variations of proviral CTL epitopes compared to a reference viral strain (HXB2 and that a generic vaccine may not be efficient. Here, we investigated viral and/or proviral CTL epitopes at different time points in recently infected individuals of the Canadian primary HIV infection cohort and assessed the affinity of these epitopes for HLA alleles during the study period. An analysis of the results confirms that it is not possible to fully predict which epitopes will be recognized by the HLA alleles of the patients if the reference sequences and epitopes are taken as the basis of simulation. Epitopes may be seen to vary in circulating RNA and proviral DNA. Despite this confirmation, the overall variability of the epitopes was low in these patients who are temporally close to primary infection.

Kinetics of HIV-1 CTL epitopes recognized by HLA I alleles in HIV-infected individuals at times near primary infection: the Provir/Latitude45 study.

Science.gov (United States)

Papuchon, Jennifer; Pinson, Patricia; Guidicelli, Gwenda-Line; Bellecave, Pantxika; Thomas, Réjean; LeBlanc, Roger; Reigadas, Sandrine; Taupin, Jean-Luc; Baril, Jean Guy; Routy, Jean Pierre; Wainberg, Mark; Fleury, Hervé

2014-01-01

In patients responding successfully to ART, the next therapeutic step is viral cure. An interesting strategy is antiviral vaccination, particularly involving CD8 T cell epitopes. However, attempts at vaccination are dependent on the immunogenetic background of individuals. The Provir/Latitude 45 project aims to investigate which CTL epitopes in proviral HIV-1 will be recognized by the immune system when HLA alleles are taken into consideration. A prior study (Papuchon et al, PLoS ONE 2013) showed that chronically-infected patients under successful ART exhibited variations of proviral CTL epitopes compared to a reference viral strain (HXB2) and that a generic vaccine may not be efficient. Here, we investigated viral and/or proviral CTL epitopes at different time points in recently infected individuals of the Canadian primary HIV infection cohort and assessed the affinity of these epitopes for HLA alleles during the study period. An analysis of the results confirms that it is not possible to fully predict which epitopes will be recognized by the HLA alleles of the patients if the reference sequences and epitopes are taken as the basis of simulation. Epitopes may be seen to vary in circulating RNA and proviral DNA. Despite this confirmation, the overall variability of the epitopes was low in these patients who are temporally close to primary infection.

Investigating signs of recent evolution in the pool of proviral HIV type 1 DNA during years of successful HAART

DEFF Research Database (Denmark)

Mens, Helene; Pedersen, Anders G; Jørgensen, Louise B

2007-01-01

In order to shed light on the nature of the persistent reservoir of human immunodeficiency virus type 1 (HIV-1), we investigated signs of recent evolution in the pool of proviral DNA in patients on successful HAART. Pro-viral DNA, corresponding to the C2-V3-C3 region of the HIV-1 env gene...... there were temporal trends indicating ongoing replication and evolution. In summary, it was not possible to detect definitive signs of ongoing evolution in either the bulk-sequenced or the clonal data with the methods employed here, but our results could be consistent with localized expression of archival...

Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

Science.gov (United States)

Klepfish, A; Rachmilevitch, E; Schattner, A

2006-11-01

A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

Indomethacin-associated neutropenia with subsequent Gram-negative sepsis in a preterm infant. Cause or coincidence?

Science.gov (United States)

Bengtsson, B-O S; Milstein, J M; Sherman, M P

2006-06-01

A preterm male infant with a patent ductus arteriosus developed neutropenia during treatment with indomethacin. Afterward, the mother described her own history of indomethacin-associated neutropenia. During the recovery from the neutropenia, the infant became septic with bacteremia caused by Enterobacter cloacae. Although indomethacin-related neutropenia has been described in adults, no case in a neonate has been reported. If neutropenia occurs after indomethacin therapy in a neonate, a familial history of indomethacin-associated neutropenia should be sought and the increased risk of infection should be considered.

REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

Directory of Open Access Journals (Sweden)

Emmanuel Gyan

2015-02-01

Full Text Available Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT, and refractory neutropenia (RN, characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS. Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS, and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008 are quite rare.These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.

Treatment of febrile neutropenia with cefepime monotherapy.

Science.gov (United States)

Jándula, B M; Martino, R; Gurgi, M; Manteiga, R; Sierra, J

2001-01-01

The empirical administration of a broad-spectrum beta-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be

Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy

Directory of Open Access Journals (Sweden)

Wayengera Misaki

2011-07-01

Full Text Available Abstract Background Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively. However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i to assemble and construct zinc finger arrays and nucleases (ZFN with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii to advance a model for pre-clinically testing lentiviral vectors (LV that deliver and transduce either ZFN genotype. Methods and Results First, we computationally generated the consensus sequences of (a 114 dsDNA-binding zinc finger (Zif arrays (ZFAs or ZifHIV-pol and (b two zinc-finger nucleases (ZFNs which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN. Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN. Second, a model for constructing lentiviral vectors (LVs that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively is proposed. Third, two preclinical models for controlled testing of

Proviral HIV-genome-wide and pol-gene specific zinc finger nucleases: usability for targeted HIV gene therapy.

Science.gov (United States)

Wayengera, Misaki

2011-07-22

Infection with HIV, which culminates in the establishment of a latent proviral reservoir, presents formidable challenges for ultimate cure. Building on the hypothesis that ex-vivo or even in-vivo abolition or disruption of HIV-gene/genome-action by target mutagenesis or excision can irreversibly abrogate HIV's innate fitness to replicate and survive, we previously identified the isoschizomeric bacteria restriction enzymes (REases) AcsI and ApoI as potent cleavers of the HIV-pol gene (11 and 9 times in HIV-1 and 2, respectively). However, both enzymes, along with others found to cleave across the entire HIV-1 genome, slice (SX) at palindromic sequences that are prevalent within the human genome and thereby pose the risk of host genome toxicity. A long-term goal in the field of R-M enzymatic therapeutics has thus been to generate synthetic restriction endonucleases with longer recognition sites limited in specificity to HIV. We aimed (i) to assemble and construct zinc finger arrays and nucleases (ZFN) with either proviral-HIV-pol gene or proviral-HIV-1 whole-genome specificity respectively, and (ii) to advance a model for pre-clinically testing lentiviral vectors (LV) that deliver and transduce either ZFN genotype. First, we computationally generated the consensus sequences of (a) 114 dsDNA-binding zinc finger (Zif) arrays (ZFAs or ZifHIV-pol) and (b) two zinc-finger nucleases (ZFNs) which, unlike the AcsI and ApoI homeodomains, possess specificity to >18 base-pair sequences uniquely present within the HIV-pol gene (ZifHIV-polFN). Another 15 ZFNs targeting >18 bp sequences within the complete HIV-1 proviral genome were constructed (ZifHIV-1FN). Second, a model for constructing lentiviral vectors (LVs) that deliver and transduce a diploid copy of either ZifHIV-polFN or ZifHIV-1FN chimeric genes (termed LV- 2xZifHIV-polFN and LV- 2xZifHIV-1FN, respectively) is proposed. Third, two preclinical models for controlled testing of the safety and efficacy of either of these

Intermittent chronic neutropenia in a patient with familial Mediterranean fever.

Science.gov (United States)

Ganiou Tidjani, K; Ailal, F; Najib, J; Bellanné-Chantelot, C; Donadieu, J; Bousfiha, A A

2008-11-01

A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia. No ELA2 gene mutations were found. At age 19 years she presented with edema of the limbs, proteinuria and renal failure. Renal amyloidosis AA was diagnosed by biopsy. Gene mutations associated with family Mediterranean fever (FMF) were sought, and a homozygous mutation (M694V) was found in the MFEV gene. This is the novel finding of FMF that masqueraded as cyclic neutropenia. (c) 2008 Wiley-Liss, Inc.

Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy.

Science.gov (United States)

Li, Wentao; Kwok, Carol Chi-Hei; Chan, Dominic Chun-Wan; Wang, Feng; Tse, Lap Ah

2018-04-01

Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study. We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters. Low levels of percent rhythm (HR:2.59, 95% CI 1.50-4.72), double amplitude (HR:2.70, 95% CI 1.51-4.85), and mesor (HR: 2.48, 95% CI 1.44-4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02-5.69) and double amplitude (HR:2.49, 95% CI 1.05-5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant. This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.

Severe neutropenia revealing a rare presentation of dengue fever: a case report.

Science.gov (United States)

Shourick, J; Dinh, A; Matt, M; Salomon, J; Davido, B

2017-08-17

Arboviruses are a common cause of fever in the returned traveler often associated with leucopenia, especially lymphopenia and thrombocytopenia. Transient neutropenia has been described in a few cases of arboviruses. However, prolonged and severe neutropenia (dengue fever, especially in the returned traveler in Europe. A 26-year-old healthy female without any medical past history, flying back from Thailand, presented a transient fever with severe neutropenia (dengue fever. Outcome was favorable without any antimicrobial therapy. Physicians should be wary of possible unusual presentation of dengue fever with prolonged neutropenia. Although such biological sign is more often associated with malaria or severe bacterial infection, it may be a sign of arbovirus.

Detection and quantification of proviral HIV-1 184 M/V in circulating CD4(+) T cells of patients on HAART with a viremia less than 1000 copies/ml

DEFF Research Database (Denmark)

Mohey, Rajesh; Jørgensen, Anne Louise; Møller, Bjarne K

2005-01-01

and incorporation of resistant forms in the long-lived CD4+ T cellular DNA compartment is not clear. Objective To investigate the relationship between lamivudine associated mutant-type 184V and the wild-type 184M proviral forms in the circulating CD4+ T cells of patients and low-level viremia. Study design Cross-sectional......Background Highly active anti-retroviral therapy (HAART) effectively reduces HIV replication but does not completely hinder it. Sub-optimal therapy leads to HIV resistance to the drugs administered. However, the role of low-level viremia (viral-load less than 1000 copies/ml) on mutation genesis...... study of 50 patients on long-term HAART, with a viremia of less than 1000 copies/ml. Patients were stratified into three groups; on lamivudine, group I (viral load

Febrile neutropenia and refeeding syndrome.

Science.gov (United States)

Jahn, H K; Barraclough, S; Currell, S; Tighe, M P

2016-12-01

We describe the management of a 4-year-old child with acute lymphoblastic leukaemia (ALL) who presented with febrile neutropenia, Cryptosporidium and subsequently developed refeeding syndrome. Febrile neutropenia is common and can be life-threatening and we highlight the identification of well low-risk neutropenic children with resolved febrile illnesses suitable for early discharge. We also discuss the potential management strategies for Cryptosporidium Refeeding syndrome is not common, but should be considered as a cause of acute inpatient deterioration and is a significant risk, with potential morbidity, in children who have undergone a period of catabolism. This article reviews the current literature and provides useful guidance on these issues. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Secondary Infections in Cancer Patients with Febrile Neutropenia

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Alpay Azap

2012-09-01

Full Text Available OBJECTIVE: Patients with neutropenia due to cancer chemotherapy are prone to severe infections. Cancer patients can experience >1 infectious episode during the same period of neutropenia. This study aimed to determine the etiological and clinical characteristics of secondary infectious episodes in cancer patients with febrile neutropenia and to identify the factors associated with the risk of secondary infectious episodes. METHODS: All cancer patients that received antineoplastic chemotherapy at Ankara University, School of Medicine, Department of Hematology between May 2004 and May 2005 and developed neutropenia were included in the study. Data were collected using survey forms that were completed during routine infectious diseases consultation visits. Categorical data were analyzed using the chi-square test, whereas Student’s t-test was used for continuous variables. Multivariate logistic regression analysis was performed to identify independent predictors of secondary infections (SIs. RESULTS: SIs were observed during 138 (53% of 259 febrile neutropenic episodes. Of the 138 episodes, 89 (64.5% occurred in male patients with a mean age of 40.9 years (range: 17-76 years. In total, 80% of the SIs were clinically or microbiologically documented. Factors on d 4 of the initial febrile episode were analyzed via a logistic regression model. The presence of a central intravenous catheter (OR: 3.01; P < 0.001, acute myeloid leukemia (AML as the underlying disease (OR: 2.12; P = 0.008, diarrhea (OR: 4.59; P = 0.005, and invasive aspergillosis (IA during the initial febrile episode (OR: 3.96; P = 0.009 were statistically significant risk factors for SIs. CONCLUSION: Among the cancer patients with neutropenia in the present study, AML as the underlying disease, the presence of a central venous catheter, diarrhea, and IA during the initial febrile episode were risk factors for the development of SIs.

Severe congenital neutropenia (Kostmann Syndrome)

African Journals Online (AJOL)

Severe congenital neutropenia (SCN), Kostmann syndrome is a heterogenous disorder of myelopoiesis characterized by severe chronic ... erogenous hematological disorders, characterized by extremely low circu- lating neutrophils and ..... tic activation of STAT5 and stimulate. G-CSF-induced cell proliferation.26, 27.

Appearance of febrile neutropenia episodes after cytostatic therapy on oncology patients

International Nuclear Information System (INIS)

Lami Casaus, Leonardo; Arbesu Michelena, Maria Antonieta; Sarmiento, Sofia Alsina; Brito Iglesia, Rosario

2009-01-01

Treatment of oncology patient using cytotoxic drugs has the neutropenia and its infectious complications as the commonest dose-limiting toxicity. Its appearance provokes dose delays and reduction during post-chemotherapy cycles, as well as the quality of life deterioration of patients. Oncology Medicine Group including the Pharmacy Service carried out a study to analyze the appearance of febrile neutropenia after cytotoxic therapy administration, and the presence of other factors that may to increase the risk to these reactions. A total of 42 patients were studied admitted with febrile neutropenia after above therapy from February to August, 2007. Biomedical variables from included patient group were achieved and the previously applied cytostatic therapy. The prevalent age-group was those patients aged over 50 and predominance of male sex and advanced stages with associated affections. The more frequent tumor locations were in breast, lung, and non-Hodgkin lymphoma. The cytostatic agent more used in cases of febrile neutropenia was Adriamycin (71.4 %) followed by Cyclophosphamide (52.4 %). The factors more associated with febrile neutropenia appearance were: Anthracycline chemotherapy, age over 50, advanced stages, and presence of associated diseases

Neutropenia and agranulocytosis in England and Wales: incidence and risk factors

NARCIS (Netherlands)

van Staa, T. P.; Boulton, F.; Cooper, C.; Hagenbeek, A.; Inskip, H.; Leufkens, H. G. M.

2003-01-01

The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes. The study was conducted using data from the General Practice Research Database. All cases of idiosyncratic neutropenia or

Biochemical characterization of cells transformed via transfection by feline sarcoma virus proviral DNA.

OpenAIRE

Rosenberg, Z F; Sahagan, B G; Snyder, H W; Worley, M B; Essex, M; Haseltine, W A

1981-01-01

Murine fibroblasts transformed by transfection with DNA from mink cells infected with the Snyder-Theilen strain of feline sarcoma virus and subgroup B feline leukemia virus were analyzed for the presence of integrated proviral DNA and the expression of feline leukemia virus- and feline sarcoma virus-specific proteins. The transformed murine cells harbored at least one intact feline sarcoma virus provirus, but did not contain feline leukemia virus provirus. The transformed murine cells express...

Neutropenia associated with osteomyelitis due to Hepatozoon canis infection in a dog.

Science.gov (United States)

Shimokawa Miyama, Takako; Umeki, Saori; Baba, Kenji; Sada, Kumiko; Hiraoka, Hiroko; Endo, Yasuyuki; Inokuma, Hisashi; Hisasue, Masaharu; Okuda, Masaru; Mizuno, Takuya

2011-10-01

A 4-year-old, intact male Shiba dog was referred to Yamaguchi University Animal Medical Center, Yamaguchi, Japan, for the following complaints: anorexia, lethargy, intermittent fever, gingival bleeding and abdominal purpura. The dog presented with persistent neutropenia. Histopathological examination of a bone marrow sample revealed round to oval structures that resembled Hepatozoon micromerozoites and formed a "wheel-spoke" pattern. Furthermore, mature neutrophils were observed around these structures. PCR and sequencing using bone marrow aspirate confirmed Hepatozoon canis (H. canis) infection. These findings suggest that the neutropenia observed in this case was associated with osteomyelitis due to H. canis infection. This is the first report of neutropenia associated with H. canis infection. H. canis infection can be included in the differential diagnosis in canine cases of neutropenia in areas where the disease is endemic.

Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy

Directory of Open Access Journals (Sweden)

Talita Garcia do Nascimento

2014-04-01

Full Text Available OBJECTIVES: to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer.METHODS: observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant.RESULTS: 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia.CONCLUSION: neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care.

Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

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Camila Cánepa

2015-10-01

Full Text Available Background: indeterminate Western blot (WB patterns are a major concern for diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1 infection, even in non-endemic areas. Objectives: (a to define the prevalence of indeterminate WB among different populations from Argentina; (b to evaluate if low proviral load (PVL is associated with indeterminate WB profiles; and (c to describe mutations in LTR and tax sequence of these cases. Results: Among 2031 samples, 294 were reactive by screening. Of them, 48 (16.3% were WB indeterminate and of those 15 (31.3% were PCR+. Quantitative real-time PCR (qPCR was performed to 52 HTLV-1+ samples, classified as Group 1 (G1: 25 WB+ samples from individuals with pathologies; Group 2 (G2: 18 WB+ samples from asymptomatic carriers (AC; and Group 3 (G3: 9 seroindeterminate samples from AC. Median PVL was 4.78, 2.38, and 0.15 HTLV-1 copies/100 PBMCs, respectively; a significant difference (p=0.003 was observed. Age and sex were associated with PVL in G1 and G2, respectively. Mutations in the distal and central regions of Tax Responsive Elements (TRE 1 and 2 of G3 were observed, though not associated with PVL.The 8403A>G mutation of the distal region, previously related to high PVL, was absent in G3 but present in 50% of WB+ samples (p = 0.03. Conclusions: indeterminateWBresults confirmed later as HTLV-1 positive may be associated with low PVL levels. Mutations in LTR and tax are described; their functional relevance remains to be determined.

Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases.

Science.gov (United States)

Weycker, Derek; Sofrygin, Oleg; Seefeld, Kim; Deeter, Robert G; Legg, Jason; Edelsberg, John

2013-02-13

Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive "gold standard" (ANC based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24-45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78-95) and sensitivity was 57% (46-68). For the definition including neutropenia in any position (n=71), PPV was 77% (68-87) and sensitivity was 67% (56-77). Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study

DEFF Research Database (Denmark)

Andersen, Christen Bertel L; Tesfa, D.; Siersma, Volkert Dirk

2016-01-01

BACKGROUND: Neutropenia, defined as an absolute blood neutrophil count (ANC) neutropenia detected in a routine complete blood cell count is poorly understood. METHODS: Using a primary care resource, comprising...... more than 370 000 individuals, we assessed the association with a number of previously recognized conditions as well as all-cause mortality in the 4 years following the identification of neutropenia. By matching laboratory data with Danish nationwide health registers, risk estimates were assessed....... RESULTS: Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality. Neutropenia was particularly associated with HIV, acute leukaemias...

Parental perspectives on inpatient versus outpatient management of pediatric febrile neutropenia.

Science.gov (United States)

Diorio, Caroline; Martino, Julia; Boydell, Katherine Mary; Ethier, Marie-Chantal; Mayo, Chris; Wing, Richard; Teuffel, Oliver; Sung, Lillian; Tomlinson, Deborah

2011-01-01

To describe parent preference for treatment of febrile neutropenia and the key drivers of parental decision making, structured face-to-face interviews were used to elicit parent preferences for inpatient versus outpatient management of pediatric febrile neutropenia. Parents were presented with 4 different scenarios and asked to indicate which treatment option they preferred and to describe reasons for this preference during the face-to-face interview. Comments were recorded in writing by research assistants. A consensus approach to thematic analysis was used to identify themes from the written comments of the research assistants. A total of 155 parents participated in the study. Of these, 80 (51.6%) parents identified hospital-based intravenous treatment as the most preferred treatment scenario for febrile neutropenia. The major themes identified included convenience/disruptiveness, physical health, emotional well-being, and modifiers of parental decision making. Most parents preferred hospital-based treatment for febrile neutropenia. An understanding of issues that influence parental decision making may assist health care workers in planning program implementation and further support families in their decision-making process.

Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update

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Paola Villafuerte-Gutierrez

2014-01-01

Full Text Available Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis.

A Case of Severe Neutropenia From Short-Term Exposure to Moxifloxacin

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Weihan Chen BS

2017-03-01

Full Text Available Moxifloxacin is commonly prescribed in the inpatient and outpatient management of community-acquired pneumonia and other common infections. We report a case of a 76-year-old man who developed severe neutropenia after several days of treatment for community-acquired pneumonia. The patient had a history of alcohol abuse; however, there were no other offending medications prescribed, and a thorough laboratory workup for other possible causes of neutropenia was negative. The patient’s neutrophils and white blood count responded quickly to cessation of fluoroquinolones. This case highlights the importance of identifying patients that might be at high risk for neutropenia that may need closer monitoring on this commonly prescribed medication.

Radiation-induced oesophagitis in lung cancer patients. Is susceptibility for neutropenia a risk factor?

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Ruysscher, D. de [MAASTRO Clinic, Maastricht (Netherlands). Dept. of Radiation Oncology; Meerbeeck, J. van [Ghent Univ. Hospital (Belgium). Dept. of Respiratory Medicine; Vandecasteele, K. [Ghent Univ. Hospital (BE). Dept. of Radiation Oncology] (and others)

2012-07-15

Background: Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. Methods and patients: A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. Results: Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). Conclusion: We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus

Radiation-induced oesophagitis in lung cancer patients. Is susceptibility for neutropenia a risk factor?

International Nuclear Information System (INIS)

Ruysscher, D. de; Meerbeeck, J. van; Vandecasteele, K.

2012-01-01

Background: Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. Methods and patients: A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. Results: Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). Conclusion: We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus

Results of high-risk neutropenia therapy of hematology-oncology patients in a university hospital in Uruguay

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Matilde Boada Burutaran

2015-02-01

Full Text Available Background: Febrile neutropenia is an important cause of mortality and morbidity in hematology-oncology patients undergoing chemotherapy. The management of febrile neutropenia is typically algorithm-driven. The aim of this study was to assess the results of a standardized protocol for the treatment of febrile neutropenia. Methods: A retrospective cohort study (2011-2012 was conducted of patients with high-risk neutropenia in a hematology-oncology service. Results: Forty-four episodes of 17 patients with a median age of 48 years (range: 18-78 years were included. The incidence of febrile neutropenia was 61.4%. The presence of febrile neutropenia was associated with both the duration and severity of neutropenia. Microbiological agents were isolated from different sources in 59.3% of the episodes with bacteremia iso- lated from blood being the most prevalent (81.3%. Multiple drug-resistant gram-negative bacilli were isolated in 62.5% of all microbiologically documented infections. Treatment of 63% of the episodes in which the initial treatment was piperacillin/tazobactam needed to be escalated to meropenem. The mortality rate due to febrile neutropenia episodes was 18.5%. Conclusion: The high rate of gram-negative bacilli resistant to piperacillin/tazobactam (frontline antibiotics in our protocol and the early need to escalate to carbapenems raises the question as to whether it is necessary to change the current protocol.

O papel da neutropenia no prognóstico do doente oncológico com pneumonia adquirida na comunidade The role of neutropenia on outcomes of cancer patients with community-acquired pneumonia

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Fátima Caeiro

2009-08-01

Full Text Available A doença infecciosa contribui para uma elevada morbilidade e mortalidade no doente oncológico, representando a pneumonia adquirida na comunidade a mais frequente. O desenvolvimento de PAC no doente neoplásico parece advir da modificação de mecanismos de defesa imunitária resultante, quer da patologia maligna, quer do tratamento oncológico. O risco de infecção relacionada com o tipo de neoplasia pode associar-se ao défice de imunidade humoral, celular ou do número de neutrófilos. As doenças hematológicas malignas podem predispor o doente às infecções devido à substituição da medula por células neoplásicas. Consequentemente, estes doentes têm neutropenia funcional, apesar de apresentarem, muitas vezes, um número normal ou aumentado de neutrófilos. Por outro lado, estes doentes podem ter neutropenia como efeito secundário da quimioterapia e/ou radioterapia (neutropenia absoluta. A gravidade da neutropenia foi considerada como principal factor de risco isolado no doente neoplásico, com particular relevância se o número de neutrófilos ≤500cel/mm³. A mortalidade global atribuída à neutropenia febril no doente neoplásico é de 30-50%. Nas últimas décadas, o tratamento das infecções na população oncológica foi direccionado, primariamente, para o manuseamento da neutropenia febril, devido ao facto de o local da infecção não ser determinado em 50-80% dos casos. As guidelines da American Thoracic Society de 2001 utilizavam a neutropenia para identificar os quadros mais graves de PAC nos doentes oncológicos. Os doen tes com patologia hematológica e neutropenia funcional ou indivíduos com qualquer tipo de neoplasia e neutropenia absoluta foram excluídos das referidas guidelines. A decisão de incluir doentes com tumores sólidos não neutropénicos foi baseada, apenas, na opinião de especialistas. Assim, os clínicos podiam sentir-se confiantes e tratar a PAC no doente oncológico não neutropénico como na

Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases

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Weycker Derek

2013-02-01

Full Text Available Abstract Background Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Methods Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive “gold standard” (ANC 9/L, and body temperature ≥38.3°C or receipt of antibiotics and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection. Accuracy was evaluated principally based on positive predictive value (PPV and sensitivity. Results Among 357 study subjects, 82 (23% met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28, PPV was 100% and sensitivity was 34% (95% CI: 24–45. For the definition including neutropenia in the primary position (n=54, PPV was 87% (78–95 and sensitivity was 57% (46–68. For the definition including neutropenia in any position (n=71, PPV was 77% (68–87 and sensitivity was 67% (56–77. Conclusions Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

A brucellosis case presenting with vesicular and maculopapular rash and febrile neutropenia

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Selmin Dirgen Çaylak

2014-03-01

Full Text Available Brucellosis is a systemic disease in which all kind of tissues and organs can be affected. Brucellosis may present with different symptoms and symptoms are non-specific. A broad spectrum of clinical manifestations can be seen, therefore diagnosis can be difficult. Cutaneous complications and febrile neutropenia have been rarely reported. Here, a rare brucellosis case was reported that he applied with fever, skin eruption and neutropenia. We emphasized that especially in endemic areas brucellosis should always be kept on mind in the differential diagnosis of patient with skin eruption and febril neutropenia.J Microbiol Infect Dis 2014;4(1: 39-41

Aparición de episodios de neutropenia febril tras la quimioterapia citostática en el paciente oncológico Appearance of febrile neutropenia episodes after cytostatic therapy on Oncology patients

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Leonardo Lami Casaus

2009-12-01

Full Text Available El tratamiento con drogas citotóxicas en el paciente oncológico, tiene como toxicidad limitante de dosis más común la neutropenia y sus complicaciones infecciosas. Su aparición provoca retrasos y reducción de dosis en los ciclos posteriores de quimioterapia, así como deterioro en la calidad de vida de los pacientes. El colectivo de Medicina Oncológica, que incluye el Servicio de Farmacia, decidió realizar un estudio, con el objetivo de analizar la aparición de neutropenia febril tras la administración de la terapia citotóxica y la presencia de otros factores que pueden incrementar el riesgo de estas reacciones. Se estudiaron los 42 pacientes que ingresaron con neutropenia febril tras el tratamiento citotóxico en el periodo comprendido entre febrero y agosto del 2007. Se recogieron variables biomédicas del grupo de pacientes incluidos y se analizó el tratamiento citostático empleado previamente. El grupo de edad que prevaleció fue el de los pacientes mayores de 50 años, con un predomino del sexo masculino y los estadios avanzados con afecciones asociadas. Las localizaciones tumorales más frecuentes radicaron en mama, pulmón y linfoma no Hodgkin. El citostático más señalado en casos de neutropenia febril resultó la adriamicina con un 71,4 %, seguido de la ciclofosfamida con 52,4 %. Los factores que más se asociaron con la aparición de neutropenia febril fueron: quimioterapia con antraciclinas, la edad mayor de 50 años, estadios avanzados y presencia de enfermedades asociadas.Treatment of oncology patient using cytotoxic drugs has the neutropenia and its infectious complications as the commonest dose-limiting toxicity. Its appearance provokes dose delays and reduction during post-chemotherapy cycles, as well as the quality of life deterioration of patients. Oncology Medicine Group including the Pharmacy Service carried out a study to analyze the appearance of febrile neutropenia after cytotoxic therapy administration, and

Concise classification of the genomic porcine endogenous retroviral gamma1 load to defined lineages.

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Klymiuk, Nikolai; Wolf, Eckhard; Aigner, Bernhard

2008-02-05

We investigated the infection history of porcine endogenous retroviruses (PERV) gamma1 by analyzing published env and LTR sequences. PERV sequences from various breeds, porcine cell lines and infected human primary cells were included in the study. We identified a considerable number of retroviral lineages indicating multiple independent colonization events of the porcine genome. A recent boost of the proviral load in an isolated pig herd and exclusive occurrence of distinct lineages in single studies indicated the ongoing colonization of the porcine genome with endogenous retroviruses. Retroviral recombination between co-packaged genomes was a general factor for PERV gamma1 diversity which indicated the simultaneous expression of different proviral loci over a period of time. In total, our detailed description of endogenous retroviral lineages is the prerequisite for breeding approaches to minimize the infectious potential of porcine tissues for the subsequent use in xenotransplantation.

Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome.

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Guffroy, Aurélien; Mourot-Cottet, Rachel; Gérard, Laurence; Gies, Vincent; Lagresle, Chantal; Pouliet, Aurore; Nitschké, Patrick; Hanein, Sylvain; Bienvenu, Boris; Chanet, Valérie; Donadieu, Jean; Gardembas, Martine; Karmochkine, Marina; Nove-Josserand, Raphaele; Martin, Thierry; Poindron, Vincent; Soulas-Sprauel, Pauline; Rieux-Laucat, Fréderic; Fieschi, Claire; Oksenhendler, Eric; André-Schmutz, Isabelle; Korganow, Anne-Sophie

2017-10-01

Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID. The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed. Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0-1400]*10 6 /L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35-4.4]. Most patients presented increased numbers of CD21 low CD38 low B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process. Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an "alarm bell" considering patients' presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.

The Icsbp locus is a common proviral insertion site in mature B-cell lymphomas/plasmacytomas induced by exogenous murine leukemia virus

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Ma Shiliang; Sorensen, Annette Balle; Kunder, Sandra; Sorensen, Karina Dalsgaard; Quintanilla-Martinez, Leticia; Morris, David W.; Schmidt, Joerg; Pedersen, Finn Skou

2006-01-01

ICSBP (interferon consensus sequence binding protein)/IRF8 (interferon regulatory factor 8) is an interferon gamma-inducible transcription factor expressed predominantly in hematopoietic cells, and down-regulation of this factor has been observed in chronic myelogenous leukemia and acute myeloid leukemia in man. By screening about 1200 murine leukemia virus (MLV)-induced lymphomas, we found proviral insertions at the Icsbp locus in 14 tumors, 13 of which were mature B-cell lymphomas or plasmacytomas. Only one was a T-cell lymphoma, although such tumors constituted about half of the samples screened. This indicates that the Icsbp locus can play a specific role in the development of mature B-lineage malignancies. Two proviral insertions in the last Icsbp exon were found to act by a poly(A)-insertion mechanism. The remaining insertions were found within or outside Icsbp. Since our results showed expression of Icsbp RNA and protein in all end-stage tumor samples, a simple tumor suppressor function of ICSBP is not likely. Interestingly, proviral insertions at Icsbp have not been reported from previous extensive screenings of mature B-cell lymphomas induced by endogenous MLVs. We propose that ICSBP might be involved in an early modulation of an immune response to exogenous MLVs that might also play a role in proliferation of the mature B-cell lymphomas

Outpatient management of febrile neutropenia: time to revise the present treatment strategy

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Carstensen, M.; Sørensen, Jens Benn

2008-01-01

We reviewed medical literature on the efficacy and safety of outpatient versus hospital-based therapy of low-risk febrile neutropenia in adult cancer patients. A PubMed search for all studies evaluating the outpatient treatment of adults diagnosed with solid tumors who suffered from low......-risk febrile neutropenia was completed; reference lists from identified articles also were used. In all, 10 trials were included in the analysis, which showed no significant difference in clinical failure rates and mortality for ambulatory regimens and standard hospital-based therapy. Subgroup analysis...... treatment failure (P febrile neutropenia is safe, effective, and comparable to standard hospital-based therapy. Patients at low risk are outpatients and are hemodynamically...

Quantification of bovine leukemia virus proviral DNA using a low-cost real-time polymerase chain reaction.

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Petersen, M I; Alvarez, I; Trono, K G; Jaworski, J P

2018-04-11

The detection of bovine leukemia virus (BLV) proviral DNA is an important tool to address whether an animal is infected with BLV. Compared with serological assays, real-time PCR accounts for greater sensitivity and can serve as a confirmatory test for the clarification of inconclusive or discordant serological test results. However, the high cost related to real-time PCR assays has limited their systematic inclusion in BLV surveillance and eradication programs. The aim of the present study was to validate a low-cost quantitative real-time PCR. Interestingly, by using SYBR Green detection dye, we were able to reduce the cost of a single reaction by a factor of 5 compared with most common assays based on the use of fluorogenic probes (i.e., TaqMan technology). This approach allowed a highly sensitive and specific detection and quantification of BLV proviral DNA from purified peripheral blood leukocytes and a milk matrix. Due to its simplicity and low cost, our in-house BLV SYBR quantitative real-time PCR might be used either as a screening or as a confirmatory test in BLV control programs. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dental findings and treatment in consanguinity associated congenital chronic familial neutropenia.

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Buduneli, Nurcan; Cogulu, Dilsah; Kardesler, Levent; Kütükçüler, Necil

2006-01-01

The purpose of this report is to describe dental findings and treatment of an 11-year old male patient and a 5-year old female patient, children of first cousins, suffering from severe benign congenital chronic familial neutropenia. This case report emphazises the importance of differential diagnosis of immunodeficiencies including congenital chronic familial neutropenia in the background of severe periodontal diseases and/or diffuse carious lesions in children.

CHEMOTHERAPY-INDUCED NEUTROPENIA IN HIV POSITIVE PATIENTS WITH LYMPHOMA: COMPARISON OF PEGFILGRASTIM WITH DAILY FILGRASTIM ADMINISTRATION.

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Luciana Teofili

2012-01-01

Full Text Available

We retrospectively compared the incidence of neutropenia  in two groups of  HIV patients with lymphoma,  who underwent chemotherapy supported by once-per-cycle administration of pegfilgrastim or by daily subcutaneous injection of filgrastim, respectively. Our findings indicate that pegfilgrastim and filgastrim produce similar results in preventing both neutropenia and febrile neutropenia.

CHEMOTHERAPY-INDUCED NEUTROPENIA IN HIV POSITIVE PATIENTS WITH LYMPHOMA: COMPARISON OF PEGFILGRASTIM WITH DAILY FILGRASTIM ADMINISTRATION.

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Luciana Teofili

2012-10-01

Full Text Available We retrospectively compared the incidence of neutropenia  in two groups of  HIV patients with lymphoma,  who underwent chemotherapy supported by once-per-cycle administration of pegfilgrastim or by daily subcutaneous injection of filgrastim, respectively. Our findings indicate that pegfilgrastim and filgastrim produce similar results in preventing both neutropenia and febrile neutropenia.

G-CSF in solid tumor chemotherapy: a tailored regimen reduces febrile neutropenia, treatment delays and direct costs.

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Tsavaris, Nicolas; Kosmas, Christos; Gouveris, Panagiotis; Vadiak, Maria; Dimitrakopoulos, Antonis; Karadima, Dimitra; Pagouni, Efterpi; Panagiotakopoulos, George; Tzima, Evanthia; Ispoglou, Sevasti; Sakelariou, Dimitris; Koufos, Christos

2004-02-01

Current guidelines do not recommend G-CSF for patients with risk factors for neutropenia. One-hundred patients undergoing chemotherapy were randomized to treatment with G-CSF at 5 Kg/kg for established febrile neutropenia (ANC <1000/microl) (Group A) or G-CSF at 263 Kg/day if ANC was 1500/microl or less on the day of the expected nadir, with the duration of treatment determined by the severity of neutropenia (Group B). The number of doses of G-CSF was similar in the two groups. There were 34 cases of febrile neutropenia in Group A, but none in Group B (p=0.0001). Hospital admission for febrile neutropenia, antibiotic use and delays in chemotherapy were all significantly more common in Group A. Total direct costs were estimated to be 66, 646 for Group A and 47, 119 for Group B. Tailoring treatment does not increase G-CSF use, but significantly reduces febrile neutropenia and treatment delays and lowers direct costs.

Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil.

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João Américo Domingos

Full Text Available The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs. The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs and 18 healthy controls (HCs in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host

Infusional β-lactam antibiotics in febrile neutropenia: has the time come?

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Abbott, Iain J; Roberts, Jason A

2012-12-01

Febrile neutropenia presents a clinical challenge in which timely and appropriate antibiotic exposure is crucial. In the context of altered pharmacokinetics and rising bacterial resistance, standard antibiotic doses are unlikely to be sufficient. This review explores the potential utility of altered dosing approaches of β-lactam antibiotics to optimize treatment in febrile neutropenia. There is a dynamic relationship between the antibiotic, the infecting pathogen, and the host. Great advancements have been made in the understanding of the pharmacokinetic changes in critical illness and the pharmacodynamic relationships of antibiotics in these settings. Antibiotic treatment in febrile neutropenia is becoming increasingly difficult. Patients are of higher acuity, receive more intensive chemotherapy regimens leading to prolonged neutropenia, and are often exposed to multiple antibiotic courses. These patients display significant variability in antibiotic clearances and increases in volume of distribution compared with standard ward-based patients. Rising antibiotic resistance and a lack of new antibiotics in production have prompted alternative dosing strategies based on pharmacokinetic/pharmacodynamic data, such as extended or continuous infusions of β-lactam antibiotics, to maximize the likelihood of treatment success. A definitive study that describes a mortality benefit of such dosing regimens remains elusive and the theoretical advantages require testing in well designed clinical trials.

Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

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Mhaskar, Rahul; Clark, Otavio Augusto Camara; Lyman, Gary; Engel Ayer Botrel, Tobias; Morganti Paladini, Luciano; Djulbegovic, Benjamin

2014-10-30

Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897

Design and implementation of an external quality assessment program for HIV viral load measurements using dried blood spots.

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Prach, Lisa M; Puren, Adrian; Lippman, Sheri A; Carmona, Sergio; Stephenson, Sophie; Cutler, Ewalde; Barnhart, Scott; Liegler, Teri

2015-03-01

An external quality assurance program was developed for HIV-1 RNA viral load measurements taken from dried blood spots using a reference panel and field-collected specimens. The program demonstrated that accurate and reproducible quantitation can be obtained from field-collected specimens. Residual proviral DNA may confound interpretation in virologically suppressed subjects. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Different clinical phenotypes in familial severe congenital neutropenia cases with same mutation of the ELANE gene.

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Cho, Hye-Kyung; Jeon, In Sang

2014-03-01

Severe congenital neutropenia (SCN) is a heterogeneous group of disorders with a defect in granulopoiesis causing marked neutropenia and severe bacterial infections. A 17-month-old girl (patient 1) was admitted due to cervical lymphadenitis caused by methicillin-resistant Staphylococcus aureus, with neutropenia. She had Pseudomonas aeruginosa sepsis and peritonitis with perforated appendicitis at 8-month of age. Her sister, a 37-month-old girl (patient 2), had recurrent stomatitis with profound neutropenia, and her mother, a 32-yr-old woman (patient 3), had had recurrent stomatitis until her early 20s with neutropenia. We found an ELANE gene mutation (c.597+1G > A) from them in direct DNA sequencing analysis. Patients 1 and 2 did not respond to granulocyte colony stimulating factor and patient 1 was treated with prolonged antibiotics and excision. We demonstrated inherited SCN cases showing different severity even with the same mutation of the ELANE gene in a family.

Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves' disease.

Science.gov (United States)

Aggarwal, N; Tee, S A; Saqib, W; Fretwell, T; Summerfield, G P; Razvi, S

2016-12-01

Neutropenia secondary to antithyroid drug (ATD) therapy in Graves' disease (GD) is well recognized. However, the effect of hyperthyroidism, prior to and after ATD therapy, on neutrophil counts in patients with GD is unclear. To study the prevalence of neutropenia in newly diagnosed untreated GD and the effect of ATD on the neutrophil count. Prospective study from August 2010 to December 2014. Endocrinology outpatient clinic in a single centre. Consecutive patients (n = 206) with newly diagnosed GD. ATD therapy. Prevalence and factors predicting neutropenia (treatment with ATD and are related to reduction in thyroid hormone concentrations. It is therefore important to check neutrophil levels in newly diagnosed patients with GD prior to commencing ATD therapy as otherwise low levels may incorrectly be attributed to ATD therapy. © 2016 John Wiley & Sons Ltd.

Management of Febrile Neutropenia in Patients receiving ...

African Journals Online (AJOL)

BACKGROUND: One in ten patients on anticancer medication will develop febrile neutropenia irrespective of tumour type. There is need to protect our patients from this fatal condition while optimising chemotherapy. This may be difficult for a poor country. OBJECTIVE: To assess the management of cancer patients with

Different Clinical Phenotypes in Familial Severe Congenital Neutropenia Cases with Same Mutation of the ELANE Gene

OpenAIRE

Cho, Hye-Kyung; Jeon, In Sang

2014-01-01

Severe congenital neutropenia (SCN) is a heterogeneous group of disorders with a defect in granulopoiesis causing marked neutropenia and severe bacterial infections. A 17-month-old girl (patient 1) was admitted due to cervical lymphadenitis caused by methicillin-resistant Staphylococcus aureus, with neutropenia. She had Pseudomonas aeruginosa sepsis and peritonitis with perforated appendicitis at 8-month of age. Her sister, a 37-month-old girl (patient 2), had recurrent stomatitis with profou...

Cost Minimization Analysis of the Use of Meropenem and Ceftazidime in Febrile Neutropenia Therapy

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Rizky Abdulah

2016-06-01

Full Text Available Use of antibiotics is required in febrile neutropenia therapy. The variety choice on the use of antibiotics has increased the role of pharmacoeconomics study to determine the most effective and efficient antibiotic in a specific area. The purpose of this study was to investigate the lowest cost antibiotic between meropenem and ceftazidime that were used as one of febrile neutropenia treatments at one of referral hospitals in West Java province during 2011–2013. This study was a retrospective, observational and analytical study that was performed on February 2014 by collecting medical record data related to febrile neutropenia inpatient who received meropenem or ceftazidime therapy. The result showed that although it was not statistically significant, the total cost for ceftazidime therapy was IDR7,082,523, which was lower than meropenem therapy (IDR11,094,147. Hopefully, this result can assist the health professionals in the management of febrile neutropenia therapy.

Excision of HIV-1 proviral DNA by recombinant cell permeable tre-recombinase.

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Lakshmikanth Mariyanna

Full Text Available Over the previous years, comprehensive studies on antiretroviral drugs resulted in the successful introduction of highly active antiretroviral therapy (HAART into clinical practice for treatment of HIV/AIDS. However, there is still need for new therapeutic approaches, since HAART cannot eradicate HIV-1 from the infected organism and, unfortunately, can be associated with long-term toxicity and the development of drug resistance. In contrast, novel gene therapy strategies may have the potential to reverse the infection by eradicating HIV-1. For example, expression of long terminal repeat (LTR-specific recombinase (Tre-recombinase has been shown to result in chromosomal excision of proviral DNA and, in consequence, in the eradication of HIV-1 from infected cell cultures. However, the delivery of Tre-recombinase currently depends on the genetic manipulation of target cells, a process that is complicating such therapeutic approaches and, thus, might be undesirable in a clinical setting. In this report we demonstrate that E.coli expressed Tre-recombinases, tagged either with the protein transduction domain (PTD from the HIV-1 Tat trans-activator or the translocation motif (TLM of the Hepatitis B virus PreS2 protein, were able to translocate efficiently into cells and showed significant recombination activity on HIV-1 LTR sequences. Tre activity was observed using episomal and stable integrated reporter constructs in transfected HeLa cells. Furthermore, the TLM-tagged enzyme was able to excise the full-length proviral DNA from chromosomal integration sites of HIV-1-infected HeLa and CEM-SS cells. The presented data confirm Tre-recombinase activity on integrated HIV-1 and provide the basis for the non-genetic transient application of engineered recombinases, which may be a valuable component of future HIV eradication strategies.

Poikiloderma with Neutropenia in Morocco: a Report of Four Cases.

Science.gov (United States)

Aglaguel, Ayoub; Abdelghaffar, Houria; Ailal, Fatima; Habti, Norddine; Hesse, Sebastian; Kohistani, Naschla; Klein, Christoph; Bousfiha, Ahmed Aziz

2017-05-01

Poikiloderma with Neutropenia (PN) is inherited genodermatosis which results from a biallelic mutation in the USB1 gene (U Six Biogenesis 1). PN, first described in Navajo Native Americans, is characterized by early onset poikiloderma, pachyonychia, palmo-plantar hyperkeratosis, and permanent neutropenia. This condition results in frequent respiratory tract infections during infancy and childhood. From 2011 to 2013, four cases of PN were diagnosed in Morocco. In this paper, we report the first four cases of PN diagnosed in Morocco, out of three unrelated consanguinous families. We investigated the genetic, immunological, and clinical features of four Moroccan patients with PN from three unrelated consanguinous families. Mean age at onset was 3 months and mean age at diagnosis was 7.5 years. The diagnosis of these PN patients was made based on clinical features and confirmed by molecular analysis for three cases. We identified two undescribed homozygous mutations in the USB1 gene: c.609 + 1G>A in two siblings and c.518 T>G(p.(Leu173Arg)) in the other case. This report confirms the clinical and genetic identity of Poikiloderma with Neutropenia syndrome.

Oral features of a family with benign familial neutropenia.

Science.gov (United States)

Porter, S R; Luker, J; Scully, C; Oakhill, A

1994-05-01

The oral features of three members of a family with familial benign neutropenia (a mother and two children) are detailed. Prepubertal periodontitis, oral ulceration, and angular stomatitis were the principal features.

Specific Destruction of HIV Proviral p17 Gene in T Lymphoid Cells Achieved by the Genome Editing Technology.

Science.gov (United States)

Kishida, Tsunao; Ejima, Akika; Mazda, Osam

2016-01-01

Recent development in genome editing technologies has enabled site-directed deprivation of a nucleotide sequence in the chromosome in mammalian cells. Human immunodeficiency (HIV) infection causes integration of proviral DNA into the chromosome, which potentially leads to re-emergence of the virus, but conventional treatment cannot delete the proviral DNA sequence from the cells infected with HIV. In the present study, the transcription activator-like effector nucleases (TALENs) specific for the HIV p17 gene were constructed, and their activities to destroy the target sequence were evaluated. SSA assay showed a high activity of a pair of p17-specific TALENs. A human T lymphoid cell line, Jurkat, was infected with a lentivirus vector followed by transfection with the TALEN-HIV by electroporation. The target sequence was destructed in approximately 10-95% of the p17 polymerase chain reaction clones, and the efficiencies depended on the Jurkat-HIV clones. Because p17 plays essential roles for assembly and budding of HIV, and this gene has relatively low nucleotide sequence diversity, genome editing procedures targeting p17 may provide a therapeutic benefit for HIV infection.

Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients

DEFF Research Database (Denmark)

Donskov, Frede; Michaelson, M Dror; Puzanov, Igor

2015-01-01

), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand-foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. RESULTS: On-treatment neutropenia and hypertension were associated with longer...... PFS (P=0.0276 and Pneutropenia was significantly associated...... with longer PFS and OS (P=0.013 and P=0.0122, respectively) and hypertension or hand-foot syndrome with longer OS (P=0.0036 and P=0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63-0.67) for IMDC classification alone and 0.72 (95% CI: 0.70-0.74) when combined with hypertension and neutropenia...

Clinical profile of high-risk febrile neutropenia in a tertiary care hospital

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Mohan V Bhojaraja

2016-06-01

Full Text Available Background Infection in the immunocompromised host has been a reason of concern in the clinical setting and a topic of debate for decades. In this study, the aim was to analyse the clinical profile of high-risk febrile neutropenic patients. Aims To study the clinical profile of high risk febrile neutropenia patients with the objective of identifying the most common associated malignancy, most common associated pathogen, the source of infection, to correlate the treatment and management with that of the Infectious Diseases Society of America (IDSA 2010 guidelines and to assess the clinical outcome. Methods A cross-sectional time bound study was carried out and a total of 80 episodes of high-risk febrile neutropenia were recorded among patients with malignancies from September 2011 to July 2013 with each episode being taken as a new case. Results Non-Hodgkin’s lymphoma (30 per cent was the most common malignancy associated, commonest source of infection was due to central venous catheters, the commonest pathogens were gram negative (52 per cent the treatment and management of each episode of high risk febrile neutropenia correlated with that of IDSA 2010 guidelines and the mortality rate was 13.75 per cent. Conclusion Febrile neutropenia is one of the major complications and cause of mortality in patients with malignancy and hence understanding its entire spectrum can help us reduce morbidity and mortality.

Biosimilars in the management of neutropenia: focus on filgrastim

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Caselli D

2016-02-01

Full Text Available Désirée Caselli,1 Simone Cesaro,2 Maurizio Aricò1 1Medical Department, Pediatric Unit, Azienda Sanitaria Provinciale Ragusa, Ragusa, 2Department of Pediatrics, Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy Abstract: Advances in chemotherapy and surgery allows the majority of patients to survive cancer diseases. Yet, the price may be a proportion of patients dying of complications due to treatment-induced infectious complications, such as neutropenia. With the aim of decreasing morbidity and mortality related to infectious complications, recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia. A biosimilar is a copy of an approved original biologic medicine whose data protection has expired. The patent for filgrastim expired in Europe in 2006 and in the US in 2013. This review analyses the available evidence to be considered in order to design a strategy of use of G-CSF and its biosimilars. The clinical and safety outcomes of biosimilars are well within the range of historically reported data for originator filgrastim. This underscores the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice. Biosimilars can play an important role by offering the opportunity to reduce costs, thus contributing to the financial sustainability of treatment programs. Keywords: neutropenia, filgrastim, biosimilars, G-CSF, fever, prophylaxis

The proviral genome of radiation leukemia virus (RadLV): molecular cloning, restriction analysis and integration sites in tumor cell DNA

International Nuclear Information System (INIS)

Janowski, M.; Merregaert, J.; Nuyten, J.M.; Maisin, J.R.

1984-01-01

An infectious clone of the linear, unintegrated RadLV provirus was obtained by insertion in the plasmid pBR322. Its restriction map was indistinguishable from that of the majority of the multiple proviral copies, which are found apparently at random sites in the DNA of RadLV-induced rat thymic lymphomas [fr

Possible roles of HIV-1 nucleocapsid protein in the specificity of proviral DNA synthesis and in its variability.

Science.gov (United States)

Lapadat-Tapolsky, M; Gabus, C; Rau, M; Darlix, J L

1997-05-02

Retroviral nucleocapsid (NC) protein is an integral part of the virion nucleocapsid where it coats the dimeric RNA genome. Due to its nucleic acid binding and annealing activities, NC protein directs the annealing of the tRNA primer to the primer binding site and greatly facilitates minus strand DNA elongation and transfer while protecting the nucleic acids against nuclease degradation. To understand the role of NCp7 in viral DNA synthesis, we examined the influence of NCp7 on self-primed versus primer-specific reverse transcription. The results show that HIV-1 NCp7 can extensively inhibit self-primed reverse transcription of viral and cellular RNAs while promoting primer-specific synthesis of proviral DNA. The role of NCp7 vis-a-vis the presence of mutations in the viral DNA during minus strand elongation was examined. NCp7 maximized the annealing between a cDNA(-) primer containing one to five consecutive errors and an RNA representing the 3' end of the genome. The ability of reverse transcriptase (RT) in the presence of NCp7 to subsequently extend the mutated primers depended upon the position of the mismatch within the primer:template complex. When the mutations were at the polymerisation site, primer extension by RT in the presence of NCp7 was very high, about 40% for one mismatch and 3% for five consecutive mismatches. Mutations within the DNA primer or at its 5' end had little effect on the extension of viral DNA by RT. Taken together these results indicate that NCp7 plays major roles in proviral DNA synthesis within the virion core due to its ability to promote prime-specific proviral DNA synthesis while concurrently inhibiting non-specific reverse transcription of viral and cellular RNAs. Moreover, the observation that NCp7 enhances the incorporation of mutations during minus strand DNA elongation favours the notion that NCp7 is a factor contributing to the high mutation rate of HIV-1.

Simultaneous occurrence of fetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

DEFF Research Database (Denmark)

Taaning, Ellen; Jensen, Lise; Varming, Kim

2012-01-01

Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia...

Microbiology of destructive periodontal disease in adolescent patients with congenital neutropenia - A report of 3 cases

NARCIS (Netherlands)

van Winkelhoff, AJ; Schouten-van Meeteren, AYN; Baart, JA; Vandenbroucke-Grauls, CMJE

Background, aims: Congenital neutropenia is one condition that may predispose for destructive periodontal disease at a young age. In this report, we describe the microbiology of 3 adolescent patients with congenital neutropenia two of whom suffered from severe periodontitis. Method: Microbiological

The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies

DEFF Research Database (Denmark)

Ye, Ying; Carlsson, Göran; Karlsson-Sjöberg, Jenny M T

2015-01-01

The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels...... in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic...... diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low...

Effects of Traditional Chinese Medicine on Chemotherapy-Induced Myelosuppression and Febrile Neutropenia in Breast Cancer Patients

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Huan Tian

2015-01-01

Full Text Available Title. Chemotherapy-induced myelosuppression lowers the quality of life in breast cancer patients and causes many complications. Traditional Chinese Medicine (TCM is a widely used complementary and alternative medicine therapies. Objective. To study whether TCM can reduce the incidence of chemotherapy-induced leukopenia, neutropenia, and febrile neutropenia (FN in breast cancer patients. Methods. The data were analyzed retrospectively between patients who received TCM treatment (group 1, n=453 and patients who did not receive TCM treatment (group 2, n=359. Significant risk factors associated with the occurrence of chemotherapy-induced leukopenia, neutropenia, and FN were identified using multivariate analysis. Propensity score-matched patients were analyzed to adjust for any baseline differences. Results. Group 1 patients had a significantly lower rate of chemotherapy-induced severe leukopenia, neutropenia, and FN, compared with group 2 (43% versus 71%, P<0.0001, 72% versus 78%, P=0.005, 6% versus 24%, P<0.0001, resp.. Multivariate analysis revealed that chemotherapy regimens containing anthracyclines combined with paclitaxel or docetaxel were the most significant predictor. Subgroup analysis indicated that TCM treatment showed benefit in relieving chemotherapy-induced leukopenia and FN in most chemotherapy regimens. Conclusions. TCM treatment could lower the risk of severe chemotherapy-induced leukopenia, neutropenia, and FN in breast cancer patients.

Neutropenia febril: convertir el bajo riesgo en cero riesgo To convert the low risk in zero risk in patients with febrile neutropenia

Directory of Open Access Journals (Sweden)

Alberto Arencibia Núñez

2009-08-01

Full Text Available La neutropenia febril constituye una de las principales causas de morbiletalidad en los pacientes con hemopatías malignas; sin embargo, la presentación clínica y evolución de esta complicación varía considerablemente de un paciente a otro. El primer modelo de estratificación de riesgo fue desarrollado por Talcot a partir de elementos clínicos y diferenciaba a los pacientes según el riesgo de presentar complicaciones letales. No obstante, cerca del 10 % de los pacientes catalogados como de bajo riesgo de complicaciones graves requieren tratamiento intrahospitalario. La determinación de algunos reactantes de fase aguda como la proteína C reactiva, las interleucinas 6 y 8 y la procalcitonina, aumentan notablemente la sensibilidad y especificidad de los modelos pronósticos. Las nuevas técnicas imagenológicas y de biología molecular facilitarán el diagnóstico precoz y certero de las infecciones en un futuro cercano. Sin embargo, es necesario desarrollar modelos pronósticos que combinen elementos clínicos y humorales adaptados a las condiciones epidemiológicas de cada centro, para optimizar el tratamiento diferenciado de los enfermos con neutropenia febril.Febrile neutropenia is one of the main causes of mortality in patients presenting with malignant hemopathic disorders; however the clinical and course presentation of this condition differ notably between patients. The first risk stratification model was developed by Talcot from clinical elements and differentiated the patients according the risk of lethal complications. However, around the 10% of patients classed as low risk of severe complications required intrahospital treatment. The determination of some acute phase reactants e.g. reactive C protein, 6 and 8 interleukins, and procalcitonin, increases remarkably the sensitivity and specificity of prognostic model. The new imaging techniques and of molecular biology allow an early and accurate diagnosis of infections in a near

Viral findings in adult hematological patients with neutropenia.

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Lars Ohrmalm

Full Text Available BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159 were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22% and NPA (18% with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL (p<0.01 and patients with fever (p<0.001 were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia.

Neutropenia and eosinophilia among Ethiopian immigrants to Israel: Familial or environmental?

Science.gov (United States)

Tandeter, Howard; Glick, Karina; Moser, Asher

2016-12-01

Due to trends of population movements, Israeli family physicians are treating increasing numbers of African immigrants from Ethiopia. These immigrants were found to have complete blood counts (CBC) that are different from other ethnic groups, with a higher prevalence of eosinophilia and neutropenia. To evaluate haematological findings in an attempt to define whether they behave as familial (genetic) or environmental. Retrospective chart review of 300 patients from a primary care clinic: 100 individuals of Ethiopian heritage born in Ethiopia (EE); 100 individuals of Ethiopian heritage born in Israel, whose parents were born in Ethiopia (EI), and a control group of 100 patients who were not of Ethiopian heritage (C). Absolute eosinophilia (greater than 500/dl) was found in 13% of the EE study group significantly higher than the two other groups (P neutropenia (defined as less than 1500/dl) was found in 32% of EE group, 20% of EI, and 1% of C (P familial-genetic nature is probably the reason for the higher prevalence of neutropenia in this population, although some environmental influence may play a role. The knowledge of these findings may be useful for physicians treating people migrating from Africa.

New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim

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Ghidini M

2016-06-01

Full Text Available Michele Ghidini,1 Jens Claus Hahne,2 Francesco Trevisani,3 Stefano Panni,1 Margherita Ratti,1 Laura Toppo,1 Gianluca Tomasello1 1Medical Department, Division of Oncology, ASST di Cremona, Ospedale di Cremona, Cremona, Italy; 2Division of Molecular Pathology, The Institute of Cancer Research, London and Sutton, UK; 3Department of Urology, Unit of Urology/Division of Oncology, IRCCS Ospedale San Raffaele, URI, Milan, Italy Abstract: Neutropenia and febrile neutropenia are two major complications of chemotherapy. Dose reductions, delays in treatment administration, and the use of granulocyte colony-stimulating factors are equally recommended options to preserve absolute neutrophil count in case of chemotherapy regimens bringing a risk of febrile neutropenia of 20% or higher. Recombinant granulocyte colony-stimulating factors, such as filgrastim and lenograstim, have a short elimination half-life (t1/2 and need to be used daily, while others, like pegfilgrastim and lipegfilgrastim, are characterized by a long t1/2 requiring only a single administration per cycle. Balugrastim is a novel long-acting recombinant granulocyte colony-stimulating factor obtained by means of a genetic fusion between recombinant human serum albumin and granulocyte colony-stimulating factor. Albumin binding increases the molecular weight and determines a high plasmatic stability leading to a t1/2 of ~19 days. Balugrastim’s efficacy, safety, and tolerability have been assessed in four different clinical trials involving breast cancer patients treated with doxorubicin and docetaxel. Pegfilgrastim was chosen as a comparator. Balugrastim was noninferior to pegfilgrastim with regard to the reduction of mean duration of severe neutropenia during cycle 1. Moreover, both treatments were comparable in terms of efficacy and safety profile. Balugrastim was well tolerated, with the only related adverse event being mild to moderate bone pain. The aim of this review is to summarize the

[A pilot study of antibiotic cycling for the treatment of febrile neutropenia patients with hematological diseases].

Science.gov (United States)

Ikegaya, Satoshi; Iwasaki, Hiromichi; Kinoshita, Keiichi; Urasaki, Yoshimasa; Tsutani, Hiroshi; Ueda, Takanori

2004-03-01

Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.

Improved detection of CXCR4-using HIV by V3 genotyping: application of population-based and "deep" sequencing to plasma RNA and proviral DNA.

Science.gov (United States)

Swenson, Luke C; Moores, Andrew; Low, Andrew J; Thielen, Alexander; Dong, Winnie; Woods, Conan; Jensen, Mark A; Wynhoven, Brian; Chan, Dennison; Glascock, Christopher; Harrigan, P Richard

2010-08-01

Tropism testing should rule out CXCR4-using HIV before treatment with CCR5 antagonists. Currently, the recombinant phenotypic Trofile assay (Monogram) is most widely utilized; however, genotypic tests may represent alternative methods. Independent triplicate amplifications of the HIV gp120 V3 region were made from either plasma HIV RNA or proviral DNA. These underwent standard, population-based sequencing with an ABI3730 (RNA n = 63; DNA n = 40), or "deep" sequencing with a Roche/454 Genome Sequencer-FLX (RNA n = 12; DNA n = 12). Position-specific scoring matrices (PSSMX4/R5) (-6.96 cutoff) and geno2pheno[coreceptor] (5% false-positive rate) inferred tropism from V3 sequence. These methods were then independently validated with a separate, blinded dataset (n = 278) of screening samples from the maraviroc MOTIVATE trials. Standard sequencing of HIV RNA with PSSM yielded 69% sensitivity and 91% specificity, relative to Trofile. The validation dataset gave 75% sensitivity and 83% specificity. Proviral DNA plus PSSM gave 77% sensitivity and 71% specificity. "Deep" sequencing of HIV RNA detected >2% inferred-CXCR4-using virus in 8/8 samples called non-R5 by Trofile, and <2% in 4/4 samples called R5. Triplicate analyses of V3 standard sequence data detect greater proportions of CXCR4-using samples than previously achieved. Sequencing proviral DNA and "deep" V3 sequencing may also be useful tools for assessing tropism.

Very early discharge versus early discharge versus non-early discharge in children with cancer and febrile neutropenia

NARCIS (Netherlands)

Loeffen, Erik A. H.; te Poele, Esther M.; Tissing, Wim J. E.; Boezen, H. Marike; de Bont, Eveline S. J. M.

2016-01-01

Background Chemotherapy-induced neutropenia is a common adverse effect in children with cancer. Due to the high relative risk of infections and infectious complications, standard care for children with cancer and febrile neutropenia consists of routine hospitalization and parenteral administration

Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability.

Science.gov (United States)

Gauthier-Vasserot, Alexandra; Thauvin-Robinet, Christel; Bruel, Ange-Line; Duffourd, Yannis; St-Onge, Judith; Jouan, Thibaud; Rivière, Jean-Baptiste; Heron, Delphine; Donadieu, Jean; Bellanné-Chantelot, Christine; Briandet, Claire; Huet, Frédéric; Kuentz, Paul; Lehalle, Daphné; Duplomb-Jego, Laurence; Gautier, Elodie; Maystadt, Isabelle; Pinson, Lucile; Amram, Daniel; El Chehadeh, Salima; Melki, Judith; Julia, Sophia; Faivre, Laurence; Thevenon, Julien

2017-01-01

Neutropenia can be qualified as congenital when of neonatal onset or when associated with extra-hematopoietic manifestations. Overall, 30% of patients with congenital neutropenia (CN) remain without a molecular diagnosis after a multidisciplinary consultation and tedious diagnostic strategy. In the rare situations when neutropenia is identified and associated with intellectual disability (ID), there are few diagnostic hypotheses to test. This retrospective multicenter study reports on a clinically heterogeneous cohort of 10 unrelated patients with CN associated with ID and no molecular diagnosis prior to whole-exome sequencing (WES). WES provided a diagnostic yield of 40% (4/10). The results suggested that in many cases neutropenia and syndromic manifestations could not be assigned to the same molecular alteration. Three sub-groups of patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected early in life, and related to a known mutation in the CN spectrum (ELANE); (ii) mild to moderate benign intermittent neutropenia, detected later, and associated with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1); and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed feature of a newly reported syndrome (KAT6A). Unlike KAT6A, which seems to be associated with a syndromic form of CN, the other reported mutations may not explain the entire clinical picture. Although targeted gene sequencing can be discussed for the primary diagnosis of severe CN, we suggest that performing WES for the diagnosis of disorders associating CN with ID will not only provide the etiological diagnosis but will also pave the way towards personalized care and follow-up. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

OpenAIRE

Emmanuel Gyan; François Dreyfus; Pierre Fenaux

2015-01-01

Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medi...

Tyrosine kinase inhibitors therapy related neutropenia and thrombocythopenia correction in CML patients

Directory of Open Access Journals (Sweden)

V. A. Shuvaev

2014-07-01

Full Text Available At present, introduction of target therapy to chronic myelogenous leukemia (CML treatment made CML not life-limiting disorder. The main condition of treatment efficacy is its continuity. The most common causes of dose reduction and CML therapy interruption is hematologic toxicities such as neutropenia and thrombocytopenia. The adverse events correction in these circumstances is vital. Recommendations for neutropenia and thrombocytopenia correction are proposed in this article. The basement and results of the use of granulocyte colony stimulating factor (G-CSF and thrombopoietine receptor agonist for hematologic toxicities correction with clinical case are presented.

The use of rhG-CSF in chronic autoimmune neutropenia: reversal of autoimmune phenomena, a case history

NARCIS (Netherlands)

Kuijpers, T. W.; de Haas, M.; de Groot, C. J.; von dem Borne, A. E.; Weening, R. S.

1996-01-01

An 8-year-old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high-dose steroids and intravenous (either low-or high-dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of

Medical visits for chemotherapy and chemotherapy-induced neutropenia: a survey of the impact on patient time and activities

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Moore Kelley

2004-05-01

Full Text Available Abstract Background Patients with cancer must make frequent visits to the clinic not only for chemotherapy but also for the management of treatment-related adverse effects. Neutropenia, the most common dose-limiting toxicity of myelosuppressive chemotherapy, has substantial clinical and economic consequences. Colony-stimulating factors such as filgrastim and pegfilgrastim can reduce the incidence of neutropenia, but the clinic visits for these treatments can disrupt patients' routines and activities. Methods We surveyed patients to assess how clinic visits for treatment with chemotherapy and the management of neutropenia affect their time and activities. Results The mean amounts of time affected by these visits ranged from approximately 109 hours (hospitalization for neutropenia and 8 hours (physician and chemotherapy to less than 3 hours (laboratory and treatment with filgrastim or pegfilgrastim. The visits for filgrastim or pegfilgrastim were comparable in length, but treatment with filgrastim requires several visits per chemotherapy cycle and treatment with pegfilgrastim requires only 1 visit. Conclusions This study provides useful information for future modelling of additional factors such as disease status and chemotherapy schedule and provides information that should be considered in managing chemotherapy-induced neutropenia.

Immune-Mediated Neutropenia and Thrombocytopenia in a Patient with Ulcerative Colitis: An Unusual Hematological Association with IBD

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Young-In Kim

1995-01-01

Full Text Available Hematological manifestations of inflammatory bowel disease (IBD are well described in the literature. However, the combination of immune-mediated neutropenia and thrombocytopenia has only been reported once in association with IBD. A case is reported of immune-mediated neutropenia and thrombocytopenia in a patient with ulcerative colitis during a relapse. No obvious causes of these hematological abnormalities were found in the patient despite an exhaustive search. An immune-mediated process was confirmed by positive antineutrophil antibody and platelet-associated antibody in the patient’s serum, and the demonstration of binding of the patient’s immunoglobulin G to autologous neutrophils. The patient was treated with high-dose steroid, intravenous gamma-globulin and eventually splenectomy. The platelet count subsequently normalized; although the severe neutropenia recurred, it has subsequently improved without further treatment. Although a definitive cause-effect relationship cannot be established, the immune-mediated neutropenia and thrombocytopenia may be an unusual hematological manifestation associated with ulcerative colitis.

Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia.

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Setty, Bhuvana A; Yeager, Nicholas D; Bajwa, Rajinder P

2011-09-01

Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count ELA-2 have been described. We report the case of a premature male infant with congenital neutropenia, associated with multiple infections, refractory to treatment with granulocyte colony stimulating factor who subsequently underwent matched sibling donor stem-cell transplant. He was found to be heterozygous for the M1V variant of the ELA-2 gene that we postulate to be causative for his severe neutropenia Copyright © 2011 Wiley-Liss, Inc.

Successful Management of Crizotinib-Induced Neutropenia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Case Report

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Jun Osugi

2016-01-01

Full Text Available Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK gene rearrangement, is generally well tolerated. In contrast, neutropenia induced by crizotinib is a commonly reported grade 3 or 4 adverse event. In such cases, interruption and dose reduction of crizotinib might be necessary for some patients with severe neutropenia. However, information concerning clinical experience and management of severe neutropenia is currently limited. In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described.

Alloimmune neonatal neutropenia in Croatia during the 1998-2008 period.

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Tomicic, Maja; Starcevic, Mirta; Ribicic, Rebeka; Golubic-Cepulic, Branka; Hundric-Haspl, Zeljka; Jukic, Irena

2014-05-01

The aim of this study was to estimate the incidence of the disease and to analyze laboratory data of 23 newborns undergoing serologic testing for alloimmune neonatal neutropenia (ANN) during the 1998-2008 period in Croatia. Laboratory data on 23 newborns undergoing serologic testing for ANN during the 1998-2008 period and epidemiologic data on the number of live births in Croatia were analyzed. Laboratory testing for ANN included serologic screening of maternal and neonatal sera and granulocytes (neutrophils) by immunofluorescence (IF) method. The monoclonal antibody immobilization of neutrophil antigens (MAINA) was employed to determine anti-HNA antibody specificity. Anti-HNA antibodies were detected in seven (54%) of 13 cases of serologically positive ANN. Only anti-HLA class I antibodies were demonstrated in four (31%) of 13 cases In the 2007-2008 period of prospective data collection, the number of serologically verified ANN cases was one case per 17,323 live births. Results of the prospective study conducted at Maternity Ward, Department of Gynecology and Obstetrics, Sestre milosrdnice University Hospital Center yielded the ANN incidence of one case per 2843 live births. Monitoring of neutrophil count in neonatal blood and serologic testing for ANN in case of isolated neutropenia in the newborn contributed considerably to timely detection of ANN. Neonatal alloimmune neutropenia-incidence, serologic diagnosis, antineutrophil antibodies, anti-HNA, anti-HLA class I, Croatia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history.

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Donadieu, Jean; Beaupain, Blandine; Fenneteau, Odile; Bellanné-Chantelot, Christine

2017-11-01

This review focuses on the classification, diagnosis and natural history of congenital neutropenia (CN). CN encompasses a number of genetic disorders with chronic neutropenia and, for some, affecting other organ systems, such as the pancreas, central nervous system, heart, bone and skin. To date, 24 distinct genes have been associated with CN. The number of genes involved makes gene screening difficult. This can be solved by next-generation sequencing (NGS) of targeted gene panels. One of the major complications of CN is spontaneous leukaemia, which is preceded by clonal somatic evolution, and can be screened by a targeted NGS panel focused on somatic events. © 2017 John Wiley & Sons Ltd.

Familial benign chronic neutropenia associated with periodontal disease. A case report.

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Deasy, M J; Vogel, R I; Macedo-Sobrinho, B; Gertzman, G; Simon, B

1980-04-01

A rare case report of periodontal disease associated with familial benign chronic neutropenia is presented. The medical, dental and family histories as well as clinical and histologic observations are described and discussed.

CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo.

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Nadia T Sebastian

2017-07-01

Full Text Available Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells.

CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo.

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Sebastian, Nadia T; Zaikos, Thomas D; Terry, Valeri; Taschuk, Frances; McNamara, Lucy A; Onafuwa-Nuga, Adewunmi; Yucha, Ryan; Signer, Robert A J; Riddell, James; Bixby, Dale; Markowitz, Norman; Morrison, Sean J; Collins, Kathleen L

2017-07-01

Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells.

Neutropenia, agranulocytosis and dipyrone

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Nelson Hamerschlak

Full Text Available CONTEXT: Neutropenia and agranulocytosis may be defined as granulocyte counts of less than 1,500/mm³ and 500/mm³, respectively. Agranulocytosis is a rare and serious disease often caused by drugs. Its mortality rate is around 10%. The most common manifestations are infections such as tonsillitis, pharyngitis, stomatitis or pneumonia. Although dipyrone is one of the drugs known to be associated with agranulocytosis, the strength of the association has been a matter of much debate. Moreover, alternative analgesic and antipyretic agents are not devoid of serious side effects. CONCLUSIONS: It is therefore necessary to establish the incidence of agranulocytosis in Latin America and the role of dipyrone. The ongoing LATIN Study is a multicenter international case-control study that will provide answers for these questions.

Neutropenia febril em pacientes com câncer de mama submetidas à quimioterapia: experiência de 12 anos Febrile neutropenia in patients with breast cancer submitted to chemotherapy: a 12 year experience

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Omero Benedicto Poli Neto

2004-12-01

Full Text Available OBJETIVOS: Identificar as características das pacientes com câncer de mama que desenvolveram neutropenia febril, estabelecer fatores de risco para a sua ocorrência e indicadores de evolução desfavorável. MÉTODOS: Realizamos um estudo caso-controle com 65 pacientes. Foram incluídas 13 pacientes que desenvolveram neutropenia febril e quatro controles por caso pareados por data e número de ciclos de quimioterapia prévios, drogas e doses empregadas. Os dados clínicos e laboratoriais foram obtidos dos prontuários médicos. Utilizamos odds ratio (OR e intervalo de confiança (IC de 95% para estimar a significância dos fatores de risco. RESULTADOS: Identificamos dois fatores de risco associados à ocorrência de neutropenia febril: a realização de quimioterapia nas primeiras 24 horas após a cirurgia (OR: 159,9 IC 95%: 9,5 a 2699 e a realização concomitante de quimioterapia e radioterapia da mama (OR: 108,3 IC 95%: 4,9 a 2391. Não observamos diferenças significativas entre casos e controles quanto à idade, índice de massa corporal e contagem de neutrófilos e monócitos antes da quimioterapia. Três pacientes foram a óbito (23,1%. Duas delas tinham idade superior a 60 anos, não apresentavam comorbidades, tinham recebido o primeiro ciclo de CMF nas primeiras 24 horas após a cirurgia e tiveram infecção de sítio cirúrgico. CONCLUSÕES: Os principais fatores de risco associados a neutropenia febril em pacientes com câncer de mama foram quimioterapia nas primeiras 24 horas após a cirurgia, e uso concomitante de quimioterapia e radioterapia da mama. Nosso estudo mostra, portanto, que estas situações devem ser evitadas.PURPOSE: To identify the characteristis of patients with breast cancer who developed febrile neutropenia and to establish risk factors for its incidence and parameters for an unfavorable evolution. PATIENTS AND METHODS: A case-control study was performed and included 65 patients: 13 patients presented febrile

Methimazole Associated Neutropenia in a Preterm Neonate Treated for Hyperthyroidism

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Dimitrios Angelis

2015-01-01

Full Text Available Maternal Graves’ disease is relatively uncommon with an estimated incidence of 0.4%–1% of all pregnancies, but only 1–5% of newborns delivered to mothers with Graves’ disease develop overt clinical signs and symptoms of hyperthyroidism. Here, we describe a case of a 1380-gram female neonate who was born at 30-week gestation to a mother with Graves’ disease. Our patient presented with hyperthyroidism followed by transient hypothyroidism requiring treatment with levothyroxine. While hyperthyroid, she was treated with methimazole, iodine, and a beta-blocker. 20 days after the initiation of methimazole, she developed neutropenia. The neutrophil counts started to improve immediately after the initiation of the weaning of methimazole. To the best of our knowledge, this is the first case reported in the literature of methimazole induced neutropenia in a preterm infant being treated for neonatal Graves’ disease.

The relationship between periodontal status and peripheral levels of neutrophils in two consanguineous siblings with severe congenital neutropenia: case reports.

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Tözüm, Tolga Fikret; Berker, Ezel; Ersoy, Fügen; Tezcan, Iihan; Sanal, Ozden

2003-03-01

Congenital neutropenia is characterized by a severe reduction in absolute neutrophil counts, resulting in an almost total absence of neutrophils. It is well known that severe neutropenia affects periodontal status. Oral manifestations include ulcerations, gingival desquamation, gingival inflammation, attachment loss, and alveolar bone loss which may result in tooth loss. Treatment with granulocyte-colony stimulating factor (G-CSF) may improve this periodontal condition. This article reports the relationship between periodontal disease status and peripheral neutrophil levels in two consanguineous siblings with severe congenital neutropenia who did not receive routine G-CSF for 2 years prior to examination. Both siblings were given scaling, root planing, and periodontal prophylaxis in regular follow-up visits. This report demonstrates that periodontal therapy supported by adequate oral hygiene may result in restoration of neutrophil counts in siblings with congenital neutropenia.

Impact of chemotherapy-induced neutropenia on quality of life: a prospective pilot investigation.

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Fortner, Barry V; Schwartzberg, Lee; Tauer, Kurt; Houts, Arthur C; Hackett, James; Stolshek, Brad S

2005-07-01

In this exploratory, prospective study evaluated quality of life (QoL) changes in patients with diverse cancers during the first cycle of myelosuppressive chemotherapy. Of 80 patients enrolled, 71 were observed during one of five chemotherapy regimens: docetaxel; CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone); carboplatin-paclitaxel; carboplatin-docetaxel; and carboplatin-gemcitabine. Complete blood counts were taken weekly. QoL and symptom burden measures were administered at baseline and throughout the cycle, and included SF-36, Cancer Care Monitor (CCM), Hospital Anxiety and Depression Scale (HADS), and Psychosocial Adjustment to Illness Scale (PAIS). Using generalized estimating equations, we modeled the change in each measure from baseline to the end of each week using the following covariates: baseline QoL measure, baseline SF-36 Physical and Mental Health Summary scores, sex, age, cycle week, grade 4 neutropenia any time in the past 7 days (yes/no), and the interaction of the latter two covariates. Of the 71 patients observed, 33 developed grade 4 neutropenia during the first 2 weeks. Changes from baseline in SF-36 Bodily Pain, HADS Anxiety, and PAIS Social Environment scores were significantly less favorable (P<0.05) when patients experienced grade 4 neutropenia any time in the past 7 days compared to when they did not (grade 0-3). A similar, but non-significant, trend was also observed for 12 other QoL measures. QoL may be adversely affected up to 7 days after patients experience grade 4 (versus grade 0-3) neutropenia. Such findings need to be examined further in studies with adequate statistical power to test a priori hypotheses regarding specific QoL measures.

Detection of anti-neutrophil antibodies in autoimmune neutropenia of infancy: a multicenter study.

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Sella, Ruti; Flomenblit, Lena; Goldstein, Itamar; Kaplinsky, Chaim

2010-02-01

Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN is characterized by neutrophil count familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded. Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods. The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective tool for clinical decision making.

La neutropenia severa febril en niños con cáncer: Estudio descriptivo en el Hospital Universitario de Santander Severe febrile neutropenia in children with cancer: A descriptive study at the Hospital Universitario de Santander

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Ernesto Rueda

2010-08-01

Full Text Available Objetivos: Describir una población oncológica afectada por neutropenia severa febril, sus características demográficas, nutricionales, microbiológicas, de tratamiento y severidad de la enfermedad. Materiales y métodos: Esta es una serie de casos prospectiva de los pacientes atendidos en el Hospital Universitario de Santander entre enero/2007 y enero/2008. Resultados: Veintiun (21 pacientes aportaron 35 episodios de neutropenia febril; 65,7% eran hombres, la edad promedio 5,6 años; 38,3% vivían en el Área Metropolitana de Bucaramanga y 91,4% en estrato socioeconómico bajo. El diagnóstico oncológico más frecuente fue leucemia linfocítica aguda. Ninguno presentó dolor abdominal o síntomas neurológicos. La neutropenia se detectó 8,5 días en promedio posterior a la última quimioterapia. El 31,4% no tuvieron neutrófilos absolutos, 54,2% plaquetas Objective: To describe an oncological population affected with severe febrile neutropenia, its demographic, nutritional, and microbiological features, their treatment and severity of the illness. Materials and methods: A descriptive-prospective clinical chart review from attended patients at the Hospital Universitario de Santander, from January/2007 to January/2008. Results: Twenty (21 patients contributed with 35 febrile neutropenia episodes; 65.7% were male; they aged average was 5.6-years; 38.37% lived in Bucaramanga Metropolitan Area; 91.4% had low economic status. The most frequent oncological diagnosis was acute lumphocytic leukemia. No one presented abdominal pain or neurological symptoms. The neutropenia was detected 8.5 days after the last chemotherapy cycle. 31.4% patients had no absolute neutrophils; 54.2% blood platelets <50,000/mm3, 45.7% had reactive C protein <90 mg|/dL. The bloodculture was positive only in 7 patients. It was found the infection focus in 88.6% of the episodes and the most frequently diagnosis were related with the gastrointestinal tract. The most used

Lithium carbonate as a treatment for paliperidone extended-release-induced leukopenia and neutropenia in a patient with schizoaffective disorder; a case report.

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Matsuura, Hiroki; Kimoto, Sohei; Harada, Izumi; Naemura, Satoshi; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2016-05-26

Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia.

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

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Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; Larochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean; Delabesse, Eric

2013-01-31

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. Mutations of key transcription factor in myeloid malignancies.

Factores de mal pronóstico en pacientes internados con Neutropenia al inicio del episodio febril Prognostic risk factors for serious complications in an inpatient population with neutropenia at the onset of a febrile episode

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Carlos Gómez Roca

2006-10-01

Full Text Available Los pacientes con neutropenia y fiebre constituyen una población heterogénea con riesgo variable para el desarrollo de complicaciones serias y mortalidad. El objetivo de este trabajo es identificar factores que, presentes al ingreso, estuvieran asociados a mayor riesgo de complicaciones graves en pacientes que se internan por neutropenia y fiebre. Se trata de un estudio de seguimiento de una cohorte de 238 episodios de neutropenia y fiebre (neutrófilos 38.3 °C en 167 pacientes internados en sala general en nuestra institución desde 1997 a 2004. Ochenta y dos por ciento de los pacientes tenían enfermedad hematológica, 14% tumores sólidos y 4% no asociados a quimioterapia. Se registraron 67 eventos adversos (46% de insuficiencia renal, 27% de hipotensión refractaria, 15% de insuficiencia respiratoria y 12% con sangrado mayor. Se hallaron diferencias significativas en presencia de comorbilidades previas, temperatura mayor a 39 °C, frecuencia cardíaca mayor a 120 latidos por minuto, frecuencia respiratoria mayor a 24 por minuto, tensión arterial sistólica menor a 90 mm Hg, presencia de 3 o más valores de laboratorio alterados al ingreso, presencia de foco clínico y hemocultivos positivos. En el análisis multivariado de regresión logística mantuvieron asociación independiente con mayor riesgo de eventos graves: hipotensión arterial sistólica (OR=7, pPatients with neutropenia and fever conform a heterogeneous population with a variable risk of serious complications and mortality. The goal of this study was to identify prognostic risk factors present at the beginning of the episode, for adverse events and serious complications in patients admitted in a general ward with fever and neutropenia. A cohort of 238 episodes with neutropenia and fever (neutrophils 38.3 °C in 167 patients admitted to our general hospital between 1997 and 2004 was followed. Eighty two percent of the patients had hematologic malignancies, 14% solid tumors

Different patterns of HIV-1 DNA after therapy discontinuation

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Ghinelli Florio

2005-09-01

Full Text Available Abstract Background By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16 – 24 weeks to study the possible relationship between DNA and RNA viral load. Methods The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load. Results Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA. Conclusion Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects.

Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles.

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Su, Fang-Yi; Chuang, Er-Yuan; Lin, Po-Yen; Chou, Yi-Chun; Chen, Chiung-Tong; Mi, Fwu-Long; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Lin, Kun-Ju; Sung, Hsing-Wen

2014-04-01

Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia

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Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Dalbøge, Christina S

2014-01-01

and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia. SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were...

Mucositis and oral infections secondary to gram negative rods in patients with prolonged neutropenia

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Mindy M. Sampson

2017-01-01

Full Text Available Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

Role of biosimilars in neutropenia prevention in cancer patients

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V. V. Ptushkin

2014-01-01

Full Text Available Decreasing the neutrophils count in peripheral blood after intensive chemotherapy (CT dramatically increases the risk of infectious complications.As a consequence, treatment costs significantly increased and patients quality of life reduced. Correction of neutropenia is possible with granulocyte colony stimulating factor (G-CSF – a human protein produced by recombinant technology and is able to support the survival and proliferation of hematopoietic stem cells. Pharmacoeconomic studies have shown that G-CSF reduces the frequency of hospitalization and antibiotics using, which can reduce the treatment cost. The use of G-CSF allows to reduce early and infection mortality after chemotherapy, providing background to prolonging life especially for the elderly (over 65 years and debilitated patients. The drug is included in all international recommendations. However, its use in Russia is limited due to high cost.Part of the policy aimed to reducing protein drugs cost and increase their availability is the creation of biosimilars protein drugs with proven effective. At the same time biosimilars as the original protein molecules are living cells products, causing serious difficulties in achieving their identity. To eliminate the risk of reducing the effectiveness or increase the toxicity, the European Union established regulations for the determination the bioproducts quality, a detailed description of the requirements for pre-clinical and clinical research, as well as the requirements for pharmacovigilance. Registered in the EEC countries G-CSF biosimilars have been first studied in healthy volunteers, and then in controlled clinical trials in comparison with the reference drug. High efficacy of one such G-CSF biosimilars (Zarsio® was shown in controlled clinical trials of 170 patients with breast cancer receiving intensive chemotherapy with Docetaxel and Doxorubicin. Total in the study only 6 % cases of febrile neutropenia (FN was

Role of biosimilars in neutropenia prevention in cancer patients

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V. V. Ptushkin

2015-01-01

Full Text Available Decreasing the neutrophils count in peripheral blood after intensive chemotherapy (CT dramatically increases the risk of infectious complications.As a consequence, treatment costs significantly increased and patients quality of life reduced. Correction of neutropenia is possible with granulocyte colony stimulating factor (G-CSF – a human protein produced by recombinant technology and is able to support the survival and proliferation of hematopoietic stem cells. Pharmacoeconomic studies have shown that G-CSF reduces the frequency of hospitalization and antibiotics using, which can reduce the treatment cost. The use of G-CSF allows to reduce early and infection mortality after chemotherapy, providing background to prolonging life especially for the elderly (over 65 years and debilitated patients. The drug is included in all international recommendations. However, its use in Russia is limited due to high cost.Part of the policy aimed to reducing protein drugs cost and increase their availability is the creation of biosimilars protein drugs with proven effective. At the same time biosimilars as the original protein molecules are living cells products, causing serious difficulties in achieving their identity. To eliminate the risk of reducing the effectiveness or increase the toxicity, the European Union established regulations for the determination the bioproducts quality, a detailed description of the requirements for pre-clinical and clinical research, as well as the requirements for pharmacovigilance. Registered in the EEC countries G-CSF biosimilars have been first studied in healthy volunteers, and then in controlled clinical trials in comparison with the reference drug. High efficacy of one such G-CSF biosimilars (Zarsio® was shown in controlled clinical trials of 170 patients with breast cancer receiving intensive chemotherapy with Docetaxel and Doxorubicin. Total in the study only 6 % cases of febrile neutropenia (FN was

O papel da neutropenia no prognóstico do doente oncológico com pneumonia adquirida na comunidade

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S. Aliberti

2009-07-01

Full Text Available Resumo: A doença infecciosa contribui para uma elevada morbilidade e mortalidade no doente oncológico, representando a pneumonia adquirida na comunidade a mais frequente.O desenvolvimento de PAC no doente neoplásico parece advir da modificação de mecanismos de defesa imunitária resultante, quer da patologia maligna, quer do tratamento oncológico. O risco de infecção relacionada com o tipo de neoplasia pode associar-se ao défice de imunidade humoral, celular ou do número de neutrófilos. As doenças hematológicas malignas podem predispor o doente às infecções devido à substituição da medula por células neoplásicas. Consequentemente, estes doentes têm neutropenia funcional, apesar de apresentarem, muitas vezes, um número normal ou aumentado de neutrófilos. Por outro lado, estes doentes podem ter neutropenia como efeito secundário da quimioterapia e/ou radioterapia (neutropenia absoluta.A gravidade da neutropenia foi considerada como principal factor de risco isolado no doente neoplásico, com particular relevância se o número de neutrófilos ≤500cel/mm3.A mortalidade global atribuída à neutropenia febril no doente neoplásico é de 30–50%. Nas últimas décadas, o tratamento das infecções na população oncológica foi direccionado, primariamente, para o manuseamento da neutropenia febril, devido ao facto de o local da infecção não ser determinado em 50–80% dos casos.As guidelines da American Thoracic Society de 2001 utilizavam a neutropenia para identificar os quadros mais graves de PAC nos doentes oncológicos. Os doen tes com patologia hematológica e neutropenia funcional ou indivíduos com qualquer tipo de neoplasia e neutropenia absoluta foram excluídos das referidas guidelines. A decisão de incluir doentes com tumores sólidos não neutropénicos foi baseada, apenas, na opinião de

Case report of a family with benign familial neutropenia and the implications for the general dental practitioner.

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Casey, Christine; Brooke, Tony; Davies, Rebecca; Franklin, Deborah

2011-03-01

Benign familial neutropenia (BFN) is a condition where there is a decrease in circulating neutrophils in the blood and patients suffer from oral manifestations which include: persistant periodontal disease, recurrent neutropenic ulceration and candidal infections. This report discusses a family affected by BFN and the effects on their oral health. Benign familial neutropenia is a rare condition and this article aims to raise awareness among general dental practitioners so that prompt referral and management in secondary care can be arranged.

Hepatic expression of proteasome subunit alpha type-6 is upregulated during viral hepatitis and putatively regulates the expression of ISG15 ubiquitin-like modifier, a proviral host gene in hepatitis C virus infection.

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Broering, R; Trippler, M; Werner, M; Real, C I; Megger, D A; Bracht, T; Schweinsberg, V; Sitek, B; Eisenacher, M; Meyer, H E; Baba, H A; Weber, F; Hoffmann, A-C; Gerken, G; Schlaak, J F

2016-05-01

The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infection. Transcriptomic and proteomic analyses were performed using liver samples of HCV-infected (n = 54) and uninfected (n = 10) or HBV-infected controls (n = 23). Primary human hepatocytes (PHH) were treated with Toll-like receptor ligands, interferons and kinase inhibitors. Expression of ISG15 and proteasome subunit alpha type-6 (PSMA6) was suppressed in subgenomic HCV replicon cell lines using specific siRNAs. Comparison of hepatic expression patterns revealed significantly increased signals for ISG15, IFIT1, HNRNPK and PSMA6 on the protein level as well as ISG15, IFIT1 and PSMA6 on the mRNA level in HCV-infected patients. In contrast to interferon-stimulated genes, PSMA6 expression occurred independent of HCV load and genotype. In PHH, the expression of ISG15 and PSMA6 was distinctly induced by poly(I:C), depending on IRF3 activation or PI3K/AKT signalling, respectively. Suppression of PSMA6 in HCV replicon cells led to significant induction of ISG15 expression, thus combined knock-down of both genes abrogated the antiviral effect induced by the separate suppression of ISG15. These data indicate that hepatic expression of PSMA6, which is upregulated during viral hepatitis, likely depends on TLR3 activation. PSMA6 affects the expression of immunoregulatory ISG15, a proviral factor in the pathogenesis of HCV infection. Therefore, the proteasome might be involved in the enigmatic interaction between ISG15 and HCV. © 2016 John Wiley & Sons Ltd.

Familial severe congenital neutropenia associated with infantile osteoporosis: a new entity.

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Elhasid, R; Hofbauer, L C; Ish-Shalom, S; Ben-Arush, M; Koc, O; Rowe, J M; Etzioni, A

2003-01-01

A new entity manifested by severe congenital neutropenia associated with osteoporosis and recurrent bone fracture is described in a family. A possible role for a new recognized cytokine system involved in bone remodeling, the osteoprotegerin/receptor activator of nuclear factor-kappa B ligand, is suggested. Copyright 2002 Wiley-Liss, Inc.

Concomitant Use of Topiramate Inducing Neutropenia in a Schizophrenic Male Stabilized on Clozapine

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Pravesh Sharma

2016-01-01

Full Text Available This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient’s psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient’s laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner.

Prior Virus Exposure Alters the Long-Term Landscape of Viral Replication during Feline Lentiviral Infection

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Sue VandeWoude

2011-10-01

Full Text Available We developed a feline model of lentiviral cross-species transmission using a puma lentivirus (PLV or FIVPco which infects domestic cats but does not cause disease. Infection with PLV protects cats from CD4+ T-cell decline caused by subsequent infection with virulent feline immunodeficiency virus (FIV. Previous studies implicate innate immune and/or cellular restriction mechanisms for FIV disease attenuation in PLV-infected cats. In this study, we evaluated viral infection and cytokine mRNA transcription in 12 different tissue reservoirs approximately five months post infection. We quantitated tissue proviral load, viral mRNA load and relative transcription of IL-10, IL-12p40 and IFNγ from tissues of cats exposed to FIV, PLV or both viruses and analyzed these parameters using a multivariate statistical approach. The distribution and intensity of FIV infection and IFNγ transcription differed between single and co-infected cats, characterized by higher FIV proviral loads and IFNγ expression in co-infected cat tissues. Variability in FIV mRNA load and IFNγ was significantly more constrained in co-infected versus singly infected cat tissues. Single-infected:co-infected ratios of FIV mRNA load compared to FIV proviral load indicated that active viral transcription was apparently inhibited during co-infection. These results indicate that previous PLV infection increases activation of tissue innate immunity and constrains the ability of FIV to productively infect tissue reservoirs of infection for months, independent of FIV proviral load, supporting a model in which innate immunity and/or modulation of target cell susceptibility play a key role in PLV-induced protection from FIV disease.

Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia

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Peterson Josh F

2006-12-01

Full Text Available Abstract Background Several clinical trials have demonstrated the efficacy of fluconazole as empiric antifungal therapy in cancer patients with fever and neutropenia. Our objective was to assess the frequency and resource utilization associated with treatment failure in cancer patients given empiric fluconazole antifungal therapy in routine inpatient care. Methods We performed a retrospective cohort study of cancer patients treated with oral or intravenous fluconazole between 7/97 and 6/01 in a tertiary care hospital. The final study cohort included cancer patients with neutropenia (an absolute neutrophil count below 500 cells/mm3 and fever (a temperature above 38°C or 100.4°F, who were receiving at least 96 hours of parenteral antibacterial therapy prior to initiating fluconazole. Patients' responses to empiric therapy were assessed by reviewing patient charts. Results Among 103 cancer admissions with fever and neutropenia, treatment failure after initiating empiric fluconazole antifungal therapy occurred in 41% (95% confidence interval (CI 31% – 50% of admissions. Patients with a diagnosis of hematological malignancy had increased risk of treatment failure (OR = 4.6, 95% CI 1.5 – 14.8. When treatment failure occurred the mean adjusted increases in length of stay and total costs were 7.4 days (95% CI 3.3 – 11.5 and $18,925 (95% CI 3,289 – 34,563, respectively. Conclusion Treatment failure occurred in more than one-third of neutropenic cancer patients on fluconazole as empiric antifungal treatment for fever in routine clinical treatment. The increase in costs when treatment failure occurs is substantial.

Relato de um caso de neutropenia congênita grave em um lactente jovem A case report of severe congenital neutropenia in a young infant

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Lucas Fadel M. dos Santos

2011-12-01

Full Text Available OBJETIVO: Relatar um caso de neutropenia congênita grave e alertar os pediatras sobre tal diagnóstico em pacientes jovens, com infecções recorrentes. DESCRIÇÃO DO CASO: Lactente jovem com 45 dias de vida, com história de febre alta, letargia, recusa alimentar e hemogramas repetidos com leucopenia importante à custa de polimorfonucleares. A hipótese diagnóstica foi confirmada pelo aspirado de medula óssea, que mostrou hipoplasia de série granulocítica e completa ausência de neutrófilos maduros. Foi introduzida antibioticoterapia de largo espectro e estimulador da formação de colônias de granulócitos. O paciente evoluiu para óbito em decorrência de complicações infecciosas após 21 dias de internação. COMENTÁRIOS: Trata-se de um lactente jovem, portador de uma rara desordem congênita que leva à intensa neutropenia, deixando-o vulnerável a infecções graves e potencialmente fatais. À internação, o paciente apresentava sinais e sintomas sugestivos de sepse, sendo introduzido antibioticoterapia de amplo espectro, necessária por se tratar de lactente jovem, neutropênico e febril. A hipótese diagnóstica se baseou na história clínica e nos leucogramas alterados, sendo posteriormente confirmada pelo aspirado de medula óssea. Foi introduzido o estimulador da formação de colônias de granulócitos, que geralmente é efetivo, porém, nesse caso, não houve sucesso e o paciente evoluiu para óbito devido à grave infecção.OBJECTIVE: To report a case of severe congenital neutropenia and alert pediatricians about its diagnosis in young patients with recurrent infectious diseases. CASE DESCRIPTION: Young infant with 45 days of life, with a history of high fever, lethargy, poor feeding and repeated blood counts showing significant leucopenia due to a significant decrease of polymorphonuclear cells. The diagnosis was confirmed by bone marrow aspirate showing hypoplasia of the granulocytic series and complete absence of

Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

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Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

2017-01-01

Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

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Chaudhuri, Jasodhara; Biswas, Tamoghna; Datta, Jyotishka; Sabui, Tapas Kumar; Chatterjee, Sukanta; Ray, Somosri; Raychaudhuri, Dibyendu; Mandal, Kalyanbrata; Chatterjee, Kaushani; Chakraborty, Swapna

2016-07-01

Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2)  = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged malnutrition was not. Malnutrition may be a potential predictor of mortality in febrile neutropenia. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders

International Nuclear Information System (INIS)

Reddy, E.P.; Mettus, R.V.; DeFreitas, E.; Wroblewska, Z.; Cisco, M.; Koprowski, H.

1988-01-01

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, the authors have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. They have clones the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome

Predictors of Outcome and Severity in Adult Filipino Patients with Febrile Neutropenia

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Marc Gregory Y. Yu

2015-01-01

Full Text Available Aim. The study aimed to describe the profile of Filipino febrile neutropenia patients and to determine parameters associated with severe outcomes. Methods. This is a retrospective study of Filipino febrile neutropenia patients admitted to the Philippine General Hospital. Patients were described in terms of clinical presentation and stratified according to the presence or absence of severe outcomes. Prognostic factors were then identified using regression analysis. Results. 115 febrile episodes in 102 patients were identified. Regression analysis yielded prolonged fever >7 days prior to admission (OR 2.43; 95% CI, 0.77–7.74, isolation of a pathogen on cultures (OR 2.69; 95% CI, 1.04–6.98, and nadir absolute neutrophil count (ANC 7 days prior to admission, positive pathogen on cultures, and nadir ANC < 100 during admission predicted severe outcomes, whereas G-CSF use and complete antibiotic therapy were associated with better outcomes. These prognostic variables might be useful in identifying patients that need more intensive treatment and monitoring.

Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

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Groner, B; Hynes, N E

1980-01-01

The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

Efficacy and safety of ior® LeukoCIM (G-CSF in patients with neutropenia after chemotherapy Eficacia y seguridad del ior® LeukoCIM (FEC-G en pacientes con neutropenia posquimioterapia

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Leslie Pérez Ruiz

2011-03-01

Full Text Available Neutropenia and infections are the most restrictive side effects during chemotherapy application. The granulocytic colonies stimulating factor activates the neutrophils, shortens the neutropenic period and can be effective against the potential risk of infection. The purpose of this study was to evaluate the efficacy and safety of LeukoCIM® (CIMAB, Havana. A retrospective observational study was carried out with data from the patients with neutropenic episodes enrolled in the open-label, non-randomized, multicenter, phase IV clinical trial. These patients were from Gustavo Aldereguía Lima hospital. They had been evaluated for one year. Demographic information, clinical data and side effects were analyzed. As prophylaxis indication LeukoCIM® was administrated 24-72 h after the last chemotherapy dose and as treatment when neutropenia was diagnosed. In both cases, a daily single 300 µg dose was administrated subcutaneously. The application of the next chemotherapy cycle on time was the main variable of response and the product safety was assessed by measuring the side effects. Forty seven patients with 95 neutropenic episodes were enrolled. The 82.1 % of episodes received their next chemotherapy cycle on time. The most frequent side effects were: bone pain and fever (11.2 % respectively, hyperuricemia (9.2 %, leukocytosis and neutrophilia (7.1 % and increased LDH (6.1 %. LeukoCIM® was effective in patients receiving chemotherapy, because it accelerated neutrophil recovery, decreased the incidence of febrile neutropenia and improved delivery of protocol doses of chemotherapy on time. Additionally, this product was considered safe for the studied patients since just known adverse events were reported.La neutropenia y las infecciones constituyen los eventos adversos más limitantes en la aplicación de quimioterapia. Los factores estimulantes de colonias de granulocitos activan los neutrófilos, acortan el periodo neutropénico y pueden ser

Benign chronic neutropenia with abnormalities involving 16q22, affecting mother and daughter.

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Glasser, Lewis; Meloni-Ehrig, Aurelia; Joseph, Plakyil; Mendiola, Jennifer

2006-04-01

We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) x 10(9)/L with a median value of 1.02 x 10(9)/L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others. Copyright 2006

Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA

International Nuclear Information System (INIS)

Buckley, Kathleen A.; Li Peilin; Khimani, Anis H.; Hofmann-Lehmann, Regina; Liska, Vladimir; Anderson, Daniel C.; McClure, Harold M.; Ruprecht, Ruth M.

2003-01-01

The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVΔ3 (the live attenuated vaccine strain derived from SIVmac239), or SIVΔ3+ (a pathogenic progeny virus that had evolved from SIVΔ3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVΔ3, and SIVΔ3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression

Managing febrile neutropenia in adult cancer patients: an integrative review of the literature

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Juliana Nunes Ferreira

Full Text Available ABSTRACT Objective: To analyze the interventions performed by health professionals with a view to managing chemotherapy-induced febrile neutropenia. Method: Integrative literature review, the sample of 12 primary articles was selected from the following databases: LILACS, SciELO, BVS, PubMed, CINAHL and Web of Science. Results: There was a prevalence of studies, realized by doctors, focused on pharmacological treatment and on the association of methods for greater diagnostic accuracy of febrile neutropenia. A study was found on pharmaceutical management regarding antibiotic dosing efficacy and a study indicating that nurses could contribute to the identification of elderly patients who would benefit from prophylactic use of growth factor. Conclusion: There was a shortage of studies involving the participation of other health professionals, besides the doctors, and a knowledge gap regarding interprofessional practice in the management of interventions specific to their area of specialism, joint interventions and non-pharmacological interventions.

The frequency of CD127low expressing CD4+CD25high T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1 proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

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Chieia Marco

2008-07-01

Full Text Available Abstract Background CD4+CD25high regulatory T (TReg cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of TReg cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of TReg cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP patients, and to correlate with measures of T cell activation. Results We were able to confirm that HTLV-I drives activation, spontaneous IFNγ production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4+ TReg cells (CD4+CD25high T cells in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4+ TReg cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127low TReg cells in healthy control subjects. Finally, the proportion of CD127low TReg cells correlated inversely with HTLV-1 proviral load. Conclusion Taken together, the results suggest that TReg cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4+ T cells, in particular those expressing the CD25highCD127low phenotype. TReg cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events

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Okolo, Onyemaechi N.; Katsanis, Emmanuel; Yun, Seongseok; Reveles, Candace Y.; Anwer, Faiz

2017-01-01

Objective and Importance. Cyclic neutropenia (CyN) is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk o...

Prevention of chemotherapy-induced neutropenia with pegfilgrastim: pharmacokinetics and patient outcomes.

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Yang, Bing-Bing; Savin, Michael A; Green, Michael

2012-01-01

Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF) that stimulates the proliferation, differentiation and function of neutrophils, is approved for the prevention of CIN. To eliminate the burden of daily filgrastim injection, pegfilgrastim, a long-acting form of filgrastim, was developed by covalently attaching a 20-kDa polyethylene glycol molecule to filgrastim to increase molecular size and thus reduce renal elimination. Consequently, neutrophil-mediated clearance is the primary mechanism for pegfilgrastim elimination. Therefore, after a single pegfilgrastim injection following chemotherapy treatment, pegfilgrastim concentration is sustained during neutropenia and decreases with neutrophil recovery. Pegfilgrastim has received marketing authorization approval from many regions to reduce the incidence of CIN based on the similar efficacy and safety of a single injection of 6 mg of pegfilgrastim administered once per chemotherapy cycle and 10 to 11 daily injections of filgrastim at 5 µg/kg. The efficient self-regulating clearance of pegfilgrastim allows administration once per chemotherapy cycle, thereby providing a more convenient treatment regimen than filgrastim. Copyright © 2012 S. Karger AG, Basel.

Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia

DEFF Research Database (Denmark)

Johansen, Helle Krogh; Gøtzsche, Peter C

2014-01-01

a fever. OBJECTIVES: To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA...

[A multicenter, randomized, controlled, phase Ⅳ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

Science.gov (United States)

Jiang, Z F; Xu, F R; Fan, J; Li, B J; Gao, J N; Hu, J W; Wang, X J; Zhang, Y Q; Wang, J H; Li, F; Liu, Q; Liu, Y H; Wang, S; Wang, Y S; Ouyang, Q C; Hu, B; Sun, G P; Zhang, Y; Zang, A M; Fan, P Z; Wu, C P; Liu, J; Zhang, H W; Wang, W; Hu, X C; Tang, L L; Zhang, J; Bao, Y Y; Geng, C Z; Sun, Q; Zhang, F; Yin, Y M; Jiang, H C; An, Y H

2018-04-24

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences ( P =0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference ( P =0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

NARCIS (Netherlands)

Miedema, Karin G. E.; de Bont, Eveline S. J. M.; Elferink, Rob F. M. Oude; van Vliet, Michel J.; Nijhuis, Claudi S. M. Oude; Kamps, Willem A.; Tissing, Wim J. E.

2011-01-01

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced

Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

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Lorand-Metze Irene

2010-05-01

Full Text Available Abstract Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang - are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10 presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31. These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.

Risk assessment in fever and neutropenia in children with cancer : What did we learn?

NARCIS (Netherlands)

Poele, Esther M. te; Tissing, Wim J. E.; Kamps, Willem A.; de Bont, Eveline S. J. M.

2009-01-01

Children with cancer treated with chemotherapy are susceptible to bacterial infections and serious infectious complications. However, fever and neutropenia can also result from other causes, for which no antibiotic treatment is needed. In the past decades attempts have been made to stratify the

MATHEMATICAL MODELS PREDICTING LEUKOPENIA AND NEUTROPENIA IN PATIENTS WITH CHRONIC HEPATITIS C IN THE BACKGROUND INTERFERONCONTAINING SCHEMES

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I. G. Bakulin

2016-01-01

Full Text Available Currently in the Russian Federation or chronic hepatitis C (CHC are still relevant Interferon-based regimens. The purpose of this study is to investigate the influence of baseline characteristics and prognosis of the patient HCV genotype 1 for the development  of leukopenia (LP and neutropenia  (NP. We investigated  factors such as sex, age, body mass index (BMI, viral load, genotype  of Interleukin-28 B (IL-28B,  the initial level of leukocytes and neutrophils,  alanine aminotransferase (ALT, fibrosis, duration  of infection, presence  of previous therapy.  Absolute values of leukocytes  and neutrophils  were analyzed on 4, 12, 24, 48 weeks of therapy,  and at 4, 12, 24 weeks after antiviral treatment with protease  inhibitors (PI 1 and 2 generation. Prognostic criteria were identified, indicating the possible development  of the LP and NP expressed during treatment with interferon: female  gender,  low initial load, TT-genotype of IL-28B, the  initial level of white  blood cells and neutrophils  below 5,7×109/L and 3,4×109/L, respectively. Mathematical  models predicting the onset of LP and NP, formalized in the form of decision trees were also constructed. These models have shown the greatest potential for practical use in view of highest accuracy and reliability.

Febrile Neutropenia Risk Assessment and Granulocyte-Colony Stimulating Factor Support in Patients with Diffuse Large B Cell Lymphoma Receiving R-CHOP Regimens

DEFF Research Database (Denmark)

Salar, Antonio; Haioun, Corinne; Rossi, Francesca Gaia

2009-01-01

BACKGROUND: ASCO and EORTC guidelines recommend granulocyte colony-stimulating factor (G-CSF) primary prophylaxis for cancer patients with a ≥20% overall risk of febrile neutropenia (FN), and to support delivery of dose-dense regimens. CHOP-like regimens (with rituximab [R]) are the current...... standard of care for the management of aggressive non-Hodgkin lymphoma (NHL), but they are often associated with significant myelosuppression. Neutropenic events, particularly febrile neutropenia (FN), can be life-threatening and may lead to dose delays or reductions that compromise the efficacy......-CSF primary prophylaxis. Across all cycles, 29% of R-CHOP-21 patients had an unplanned hospitalization, with neutropenia/FN being the main reason. Subsequently, 67% of patients achieved a relative dose intensity (RDI) of ≥90% of their planned treatment (with respect to cyclophosphamide, doxorubicin...

Is there still an indication for nursing patients with prolonged neutropenia in protective isolation? An evidence-based nursing and medical study of 4 years experience for nursing patients with neutropenia without isolation

NARCIS (Netherlands)

Mank, Arno; van der Lelie, Hans

2003-01-01

Patients with severe neutropenia due to high-dose chemotherapy and/or total-body irradiation are at risk of serious infections and are frequently nursed in strict protective isolation. This is a costly procedure and results in a psychological burden for the patient and its significance has been

Chemotherapy-induced neutropenia and the prognosis of colorectal cancer: a meta-analysis of cohort studies.

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Tan, XiangZhou; Wen, QiaoCheng; Wang, Ran; Chen, ZhiKang

2017-11-01

Recently, there has been a controversial discussion about the prognostic value of chemotherapy-induced neutropenia (CIN) in colorectal cancer patients. Thus, a meta-analysis was conducted to determine the relationship between CIN and the prognosis of colorectal cancer patients. We searched the PubMed, EMBASE, and Cochrane library databases to identify studies evaluating the association between CIN and colorectal cancer prognosis. Pooled random/fixed effect models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association. Eight studies were selected for the meta-analysis, for a total of 2,745 patients. There was significant improved survival among colorectal cancer patients with CIN (HR = 0.62, 95% CI = 0.47-0.76). However, significant heterogeneity was found (p = 0.000, Ι 2  = 75.0%). Through subgroup analysis, we could greatly eliminate the heterogeneity and found that neutropenia was associated with better survival in stage IV colorectal cancer patients, no matter the HR calculated by overall survival (OS) or progression-free survival (PFS). Meanwhile, the prognostic value of neutropenia in stage II/III colorectal cancer can be found when the HR is calculated by disease-free survival (DFS). Additionally, we observed significant differences after stratification according to various tumor stages, endpoints, and the use of G-CSF. Our results which, based on a cohort study, indicate that CIN is associated with improved survival in patients with colorectal cancer. However, further randomized controlled trials are warranted.

Severe neutropenia at time of port insertion is not a risk factor for catheter-associated infections in children with acute lymphoblastic leukemia.

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Junqueira, Beatriz L P; Connolly, Bairbre; Abla, Oussama; Tomlinson, George; Amaral, Joao G

2010-09-15

The objective of this study was to determine whether severe neutropenia on the day of port-a-catheter (PORT) insertion was a risk factor for catheter-associated infection (CAI) in children with acute lymphoblastic leukemia (ALL). This was a retrospective study of children with ALL who had a PORT insertion between January 2005 and August 2008. Early (≤ 30 days) and late (>30 days) postprocedure complications were reviewed. The length of follow-up ranged between 7 months and 42 months. In total, 192 PORTs were inserted in 179 children. There were 43 CAIs (22%), and the infection rate was 0.35 per 1000 catheter-days. The CAI rate (15%) in children who had severe neutropenia on the day of the procedure did not differ statistically from the CAI rate (24%) in children who did not have severe neutropenia (P = .137). Conversely, patients with severe neutropenia who had a CAI were more likely to have their PORT removed (P = .019). The most common organisms to cause catheter removal were coagulase-negative Staphylococcus and Staphylococcus aureus. Patients with high-risk ALL had a statistically significant higher incidence of late CAI than patients with standard-risk ALL (P = .012). Age (P = .272), positive blood culture preprocedure (P = 1.0), and dexamethasone use (P = .201) were not risk factors for CAI. Patients who had an early CAI did not have a greater chance of having a late CAI. The catheter infection-free survival rate at 1 year was 88.6%. The current results indicated that severe neutropenia on the day of PORT insertion does not increase the risk of CAI in children with ALL. © 2010 American Cancer Society.

How we diagnose and treat neutropenia in adults.

Science.gov (United States)

Palmblad, Jan; Nilsson, Christer C; Höglund, Petter; Papadaki, Helen A

2016-05-01

Neutropenias (NPs), being acute and often transient, or chronic, range from life-threatening conditions with very low absolute neutrophil blood counts (ANC) to disorders characterized by only mild NP and of no obvious significance for health. Many are caused by genetic variations/mutations, e.g. the benign familial NP and the chronic severe NPs (e.g. Kostmann disease). Some of the latter are associated with various bodily malformations. Many of the mild-to-moderate NPs are signs of underlying disorders that need specialized treatments (e.g. HIV, hepatitis, autoimmune disorders, the large granular lymphocyte syndrome). We provide here means for the evaluation of a previously unknown NP, suggest a triage and treatments.

EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours.

NARCIS (Netherlands)

Aapro, M.S.; Cameron, D.; Pettengell, R.; Bohlius, J.; Crawford, J.; Ellis, M.; Kearney, N.; Lyman, G.H.; Tjan-Heijnen, V.C.; Walewski, J.A.; Weber, D.C.; Zielinski, C.

2006-01-01

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose

High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors.

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Rodrigo Pessôa

Full Text Available An improved understanding of the prevalence of low-abundance transmitted drug-resistance mutations (TDRM in therapy-naïve HIV-1-infected patients may help determine which patients are the best candidates for therapy. In this study, we aimed to obtain a comprehensive picture of the evolving HIV-1 TDRM across the massive parallel sequences (MPS of the viral entire proviral genome in a well-characterized Brazilian blood donor naïve to antiretroviral drugs.The MPS data from 128 samples used in the analysis were sourced from Brazilian blood donors and were previously classified by less-sensitive (LS or "detuned" enzyme immunoassay as non-recent or longstanding HIV-1 infections. The Stanford HIV Resistance Database (HIVDBv 6.2 and IAS-USA mutation lists were used to interpret the pattern of drug resistance. The minority variants with TDRM were identified using a threshold of ≥ 1.0% and ≤ 20% of the reads sequenced. The rate of TDRM in the MPS data of the proviral genome were compared with the corresponding published consensus sequences of their plasma viruses.No TDRM were detected in the integrase or envelope regions. The overall prevalence of TDRM in the protease (PR and reverse transcriptase (RT regions of the HIV-1 pol gene was 44.5% (57/128, including any mutations to the nucleoside analogue reverse transcriptase inhibitors (NRTI and non-nucleoside analogue reverse transcriptase inhibitors (NNRTI. Of the 57 subjects, 43 (75.4% harbored a minority variant containing at least one clinically relevant TDRM. Among the 43 subjects, 33 (76.7% had detectable minority resistant variants to NRTIs, 6 (13.9% to NNRTIs, and 16 (37.2% to PR inhibitors. The comparison of viral sequences in both sources, plasma and cells, would have detected 48 DNA provirus disclosed TDRM by MPS previously missed by plasma bulk analysis.Our findings revealed a high prevalence of TDRM found in this group, as the use of MPS drastically increased the detection of these

Aplicación de un modelo pronóstico para predecir la evolución de la neutropenia febril en niños con leucemias agudas A new model applied in prediction of febrile neutropenia in children with acute leukemias

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Alberto Arencibia Núñez

2009-08-01

Full Text Available Se realizó estudio analítico retrospectivo de casos controles en 62 episodios de neutropenia febril presentados por pacientes con hemopatías malignas admitidos en el Instituto de Hematología e Inmunología durante los años 2005 y 2006. Los episodios de neutropenia febril se dividieron en 2 grupos a partir de su evolución favorable (56 % o desfavorable (44 % y se compilaron los parámetros clínicos y de laboratorio en ambos grupos. Los factores que mayor asociación mostraron con la evolución desfavorable fueron la presencia de comorbilidad (sepsis, deshidratación, hipoxia, hipovolemia, mucositis severa, el diagnóstico de leucemia aguda no linfoblástica, el uso de quimioterapia en los 7 días previos al inicio de la fiebre, el compromiso del estado general, y el conteo absoluto de neutrófilos menor de 100 x mm³. Los pacientes con neutropenia febril de evolución desfavorable presentaron entre 3 y 5 factores de riesgo, mientras que los de evolución satisfactoria tuvieron menos de 2 factores de mal pronóstico. El valor predictivo positivo del modelo pronóstico fue del 91,4 % y el negativo del 92,6 %, con una sensibilidad y especificidad del 94,1 % y 89,3 %, respectivamente.A retrospective and analytical control cases study was carried out in 62 episodes of febrile neutropenia present in patients with malignant blood disease admitted in Hematology and Immunology Institute during 2005 and 2006. Above episodes were divided in 2 groups from its favorable course (56% or unfavorable (44% as well as the laboratory and clinical parameters compiled in both groups. Factors with higher association related to unfavorable course were the comorbidities presence (sepsis, dehydration, hypoxia, hypovolemia and severe mucositis, diagnosis of non-lymphoblastic, use of chemotherapy during the 7 previous days to fever onset, general status involvement, and the neutrophil absolute count lower than 100 x mm³. Patients presenting with a unfavorable course

CLPB Variants Associated with Autosomal-Recessive Mitochondrial Disorder with Cataract, Neutropenia, Epilepsy, and Methylglutaconic Aciduria

DEFF Research Database (Denmark)

Saunders, Carol; Smith, Laurie; Wibrand, Flemming

2015-01-01

of type IV 3-MGA-uria characterized by cataracts, severe psychomotor regression during febrile episodes, epilepsy, neutropenia with frequent infections, and death in early childhood. Four of the individuals were of Greenlandic descent, and one was North American, of Northern European and Asian descent...

A patient with common glycogen storage disease type Ib mutations without neutropenia or neutrophil dysfunction

NARCIS (Netherlands)

Martens, DHJ; Kuijpers, TW; Maianski, NA; Rake, JP; Smit, GPA; Visser, G

We describe a 16-year old boy with glycogen storage disease type Ib, homozygous for the common 1211-1212delCT mutation, who never experienced neutropenia, and did not suffer from frequent infections or inflammatory bowel disease. In addition, neutrophil function tests showed no abnormalities.

Piperacillin-tazobactam vs. imipenem-cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia.

Science.gov (United States)

Jing, Yu; Li, Jian; Yuan, Lei; Zhao, Xiaoli; Wang, Quanshun; Yu, Li; Zhou, Daobin; Huang, Wenrong

2016-03-01

This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Asthma and cyclic neutropenia].

Science.gov (United States)

Salazar Cabrera, A N; Berrón Pérez, R; Ortega Martell, J A; Onuma Takane, E

1996-01-01

We report a male with history of recurrent infections (recurrent oral aphtous disease [ROAD], middle ear infections and pharyngo amigdalitis) every 3 weeks since he was 7 months old. At the age of 3 years cyclic neutropenia was diagnosed with cyclic fall in the total neutrophil count in blood smear every 21 days and prophylactic antimicrobial therapy was indicated. Episodic events every 3 weeks of acute asthma and allergic rhinitis were detected at the age of 6 years old and specific immunotherapy to Bermuda grass was given during 3 years with markedly improvement in his allergic condition but not in the ROAD. He came back until the age of 16 with episodic acute asthma and ROAD. The total neutrophil count failed to 0 every 21 days and surprisingly the total eosinophil count increased up to 2,000 at the same time, with elevation of serum IgE (412 Ul/mL). Specific immunotherapy to D.pt. and Aller.a. and therapy with timomodulin was indicated. After 3 months we observed clinical improvement in the asthmatic condition and the ROAD disappeared, but the total neutrophil count did not improve. We present this case as a rare association between 2 diseases with probably no etiological relationship but may be physiopatological that could help to understand more the pathogenesis of asthma.

Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report

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Miguel E. Pinto

2012-06-01

Full Text Available Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.A 48-year old woman with a recent diagnosis of Graves’ disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf. After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.

Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

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Valeria Contreras

2016-03-01

Full Text Available En pacientes con cáncer que se presentan con neutropenia febril existe controversia sobre si es mejor utilizar una combinación de antibióticos betalactámicos y aminoglicósidos o si bastaría la monoterapia con betalactámicos de amplio espectro como tratamiento empírico inicial. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen 14 estudios aleatorizados pertinentes a esta pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que adicionar aminoglicósidos a los betalactámicos en el tratamiento de la neutropenia febril en pacientes con cáncer aumenta la nefrotoxicidad y podría aumentar la mortalidad en comparación con la monoterapia con betalactámicos.

Neutropenia Inmune - Aloinmune neonatal: IgG sérica reactiva y fenotipo específico de los neutrófilos evaluados por citometría de flujo Autoimmune-alloimmune neonatal neutropenia: Serum reactive IgG and neutrophil-specific phenotype detected by flow cytometry

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Norma E. Riera

2006-10-01

Full Text Available La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con los neutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna a los antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20 en reacción autóloga (suero y células de un mismo individuo y heteróloga (suero y células de diferentes individuos. Los resultados se expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilución del suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune.Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4

Is preemptive antifungal therapy a good alternative to empirical treatment in prolonged febrile neutropenia?

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Erica Koch

2016-06-01

Full Text Available La neutropenia febril prolongada conlleva un alto riesgo de desarrollar infecciones fúngicas invasoras, por lo que habitualmente se administra terapia antifúngica empírica en estos casos. Sin embargo, esta se asocia a importantes efectos adversos, por lo que se ha propuesto como alternativa la estrategia "preemptive" o anticipada, es decir, la indicación de antifúngicos sólo ante la evidencia indirecta de infección fúngica invasora. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen doce estudios. Cuatro estudios aleatorizados evaluaron la pregunta abordada en este artículo. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro si la estrategia "preemptive" tiene algún efecto sobre la mortalidad porque la certeza de la evidencia es muy baja, pero podría disminuir levemente el uso de antifúngicos en pacientes con neutropenia febril prolongada.

Ela2 mutations and clinical manifestations in familial congenital neutropenia.

Science.gov (United States)

Shiohara, Masaaki; Shigemura, Tomonari; Saito, Shoji; Tanaka, Miyuki; Yanagisawa, Ryu; Sakashita, Kazuo; Asada, Hiroshi; Ishii, Eizaburo; Koike, Kazutoshi; Chin, Motoaki; Kobayashi, Masao; Koike, Kenichi

2009-05-01

Three familial cases of each of severe congenital neutropenia (SCN) and cyclic neutropenia (CN) in addition to 3 sporadic cases of SCN were analyzed for neutrophil elastase (Ela2) gene mutation. The contents of the neutrophil-specific granule proteins cathelicidin antimicrobial peptide and neutrophil gelatinase-associated lipocalin were also analyzed in SCN. Genomic DNA was extracted from the patients' peripheral blood or bone marrow, and the coding sequence of the Ela2 gene was amplified by polymerase chain reaction and subjected to direct sequencing. The contents of antimicrobial peptides were analyzed by flow cytometry. Three cases of familial SCN (P13L, R52P, and S97L), 2 of familial CN (W212stop and P110L), and 1 of sporadic SCN (V72M) were shown to have heterozygous mutations in the Ela2 gene. W212stop found in a familial CN case was a novel mutation of Ela2. Prophylactic treatment for growth factors or antibiotic prophylaxis against bacterial infection was useful for lowering the frequency of infectious episodes. Adult patients tended to have less frequent infections compared with minors in the same family. The contents of both cathelicidin antimicrobial peptide and neutrophil gelatinase-associated lipocalin were significantly reduced in SCN compared with healthy controls. Prophylaxis by growth factor or antibiotics is useful for decreasing risks of bacterial infections in SCN and CN. Adults were likely to have less frequent infections than children in familial cases of SCN and CN with the same mutation of Ela2.

Severe Neutropenia at the Time of Implantable Subcutaneous Chest Port Insertion Is Not a Risk Factor for Port Removal at a Tertiary Pediatric Center.

Science.gov (United States)

Hoss, Daniel R; Bedros, Antranik A; Mesipam, Avinash; Criddle, Jared; Smith, Jason C

2017-03-01

To determine if severe neutropenia at the time of chest port insertion is a risk factor for port removal and central catheter-associated bloodstream infection (CCABSI) in pediatric patients. From May 2007 to June 2015, 183 consecutive patients (mean age, 9.9 y; range, 0.75-21 y) had a port inserted at a single tertiary pediatric center. Seventy-two had severe neutropenia at the time of port insertion (absolute neutrophil count [ANC] range, 0-500/mm 3 ; mean, 185/mm 3 ). Follow-up until port removal or death and CCABSI events were recorded. Within the first 30 days, similar incidences of CCABSI (12.5% of patients with severe neutropenia [n = 9] vs 4.5% of patients without [n = 5]), port removal for infection (2.8% [n = 2] vs 2.7% [n = 3]), and local port infection (2.8% [n = 2] vs 0.9% [n = 1]) were observed in both groups (P > .05), but the rate of CCABSI per 1,000 catheter-days was higher for patients with severe neutropenia (P = .045). Overall, similar incidences of CCABSI (18.1% [n = 13] vs 16.2% [n = 18]), port removal for infection (2.8% [n = 2] vs 7.2% [n = 8]), local port infection (2.8% [n = 2] vs 2.7% [n = 3]), and CCABSIs per 1,000 catheter-days (0.332 vs 0.400) were observed in both groups (P > .05). Port placement in patients with severe neutropenia can be performed without an increased incidence of port removal for infection. The majority of CCABSIs were successfully treated without port removal. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Cost Effectiveness of Primary Pegfilgrastim Prophylaxis in Patients With Breast Cancer at Risk of Febrile Neutropenia

NARCIS (Netherlands)

Aarts, Maureen J.; Grutters, Janneke P.; Peters, Frank P.; Mandigers, Caroline M.; Dercksen, M. Wouter; Stouthard, Jacqueline M.; Nortier, Hans J.; van Laarhoven, Hanneke W.; van Warmerdam, Laurence J.; van de Wouw, Agnes J.; Jacobs, Esther M.; Mattijssen, Vera; van der Rijt, Carin C.; Smilde, Tineke J.; van der Velden, Annette W.; Temizkan, Mehmet; Batman, Erdogan; Muller, Erik W.; van Gastel, Saskia M.; Joore, Manuela A.; Borm, George F.; Tjan-Heijnen, Vivianne C.

2013-01-01

Purpose Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary

Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia

NARCIS (Netherlands)

Aarts, M.J.; Grutters, J.P.C.; Peters, F.P.; Mandigers, C.M.P.W.; Dercksen, M.W.; Stouthard, J.M.; Nortier, H.J.; Laarhoven, H.W.M. van; Warmerdam, L.J. van; Wouw, A.J. van de; Jacobs, E.M.G.; Mattijssen, V.; Rijt, C.C. van der; Smilde, T.J.; Velden, A.W. van der; Temizkan, M.; Batman, E.; Muller, E.W.; Gastel, S.M. van; Joore, M.A.; Borm, G.F.; Tjan-Heijnen, V.C.

2013-01-01

PURPOSE: Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary

O papel da neutropenia no prognóstico do doente oncológico com pneumonia adquirida na comunidade** Eur Respir J 2009; 33:142-147

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S. Aliberti

2009-07-01

Full Text Available Resumo: A doença infecciosa contribui para uma elevada morbilidade e mortalidade no doente oncológico, representando a pneumonia adquirida na comunidade a mais frequente.O desenvolvimento de PAC no doente neoplásico pa-rece advir da modificação de mecanismos de defesa imunitária resultante, quer da patologia maligna, quer do tratamento oncológico. O risco de infecção relacionada com o tipo de neoplasia pode associarse ao défice de imunidade humoral, celular ou do número de neutrófilos. As doenças hematológicas malignas podem predispor o doente às infecções devido à substituição da medula por células neoplásicas. Consequentemente, estes doentes têm neutropenia funcional, apesar de apresentarem, muitas vezes, um número normal ou aumentado de neutrófilos. Por outro lado, estes doentes podem ter neutropenia como efeito secundário da quimioterapia e/ou radioterapia (neutropenia absoluta.A gravidade da neutropenia foi considerada como principal factor de risco isolado no doente neoplásico, com particular relevância se o número de neutrófilos ≤500cel/mm3.A mortalidade global atribuída à neutropenia febril no doente neoplásico é de 30-50%. Nas últimas décadas, o tratamento das infecções na população oncológica foi direccionado, primariamente, para o manuseamento da neutropenia febril, devido ao facto de o local da infecção não ser determinado em 50-80% dos casos. As guidelines da American Thoracic Society de 2001 utilizavam a neutropenia para identificar os quadros mais graves de PAC nos doentes oncológicos. Os doentes com patologia hematológica e neutropenia funcional ou indivíduos com qualquer tipo de neoplasia e neutropenia absoluta foram excluídos das referidas guidelines. A decisão de incluir doentes com tumores sólidos não neutropénicos foi baseada, apenas, na opinião de especialistas

A Patient Risk Model of Chemotherapy-Induced Febrile Neutropenia: Lessons Learned From the ANC Study Group.

Science.gov (United States)

Lyman, Gary H; Poniewierski, Marek S

2017-12-01

Neutropenia and its complications, including febrile neutropenia (FN), represent major toxicities associated with cancer chemotherapy, resulting in considerable morbidity, mortality, and costs. The myeloid growth factors such as granulocyte colony-stimulating factor (G-CSF) have been shown to reduce the risk of neutropenia complications while enabling safe and effective chemotherapy dose intensity. Concerns about the high costs of these agents along with limited physician adherence to clinical practice guidelines, resulting in both overuse and underuse, has stimulated interest in models for individual patient risk assessment to guide appropriate use of G-CSF. In a model developed and validated by the ANC Study Group, half of patients were classified as high risk and half as low risk based on patient-, disease-, and treatment-related factors. This model has been further validated in an independent patient population. Physician-assessed risk of FN, as well as the decision to use prophylactic CSF, has been shown to correlate poorly with the FN risk estimated by the model. Additional modeling efforts in both adults and children receiving cancer treatment have been reported. Identification of patients at a high individual risk for FN and its consequences may offer the potential for optimal chemotherapy delivery and patient outcomes. Likewise, identification of patients at low risk for neutropenic events may reduce costs when such supportive care is not warranted. This article reviews and summarizes FN modeling studies and the opportunities for personalizing supportive care in patients receiving chemotherapy. Copyright © 2017 by the National Comprehensive Cancer Network.

Efficacy and safety of ior® LeukoCIM (G-CSF in patients with neutropenia after chemotherapy

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Leslie Pérez Ruiz

2011-03-01

Full Text Available Neutropenia and infections are the most restrictive side effects during chemotherapy application. The granulocytic colonies stimulating factor activates the neutrophils, shortens the neutropenic period and can be effective against the potential risk of infection. The purpose of this study was to evaluate the efficacy and safety of LeukoCIM® (CIMAB, Havana. A retrospective observational study was carried out with data from the patients with neutropenic episodes enrolled in the open-label, non-randomized, multicenter, phase IV clinical trial. These patients were from Gustavo Aldereguía Lima hospital. They had been evaluated for one year. Demographic information, clinical data and side effects were analyzed. As prophylaxis indication LeukoCIM® was administrated 24-72 h after the last chemotherapy dose and as treatment when neutropenia was diagnosed. In both cases, a daily single 300 µg dose was administrated subcutaneously. The application of the next chemotherapy cycle on time was the main variable of response and the product safety was assessed by measuring the side effects. Forty seven patients with 95 neutropenic episodes were enrolled. The 82.1 % of episodes received their next chemotherapy cycle on time. The most frequent side effects were: bone pain and fever (11.2 % respectively, hyperuricemia (9.2 %, leukocytosis and neutrophilia (7.1 % and increased LDH (6.1 %. LeukoCIM® was effective in patients receiving chemotherapy, because it accelerated neutrophil recovery, decreased the incidence of febrile neutropenia and improved delivery of protocol doses of chemotherapy on time. Additionally, this product was considered safe for the studied patients since just known adverse events were reported.

CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder.

Science.gov (United States)

Wortmann, Saskia B; Ziętkiewicz, Szymon; Kousi, Maria; Szklarczyk, Radek; Haack, Tobias B; Gersting, Søren W; Muntau, Ania C; Rakovic, Aleksandar; Renkema, G Herma; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Rubio-Gozalbo, M Estela; Chrusciel, Elzbieta; Distelmaier, Felix; Golzio, Christelle; Jansen, Joop H; van Karnebeek, Clara; Lillquist, Yolanda; Lücke, Thomas; Õunap, Katrin; Zordania, Riina; Yaplito-Lee, Joy; van Bokhoven, Hans; Spelbrink, Johannes N; Vaz, Frédéric M; Pras-Raves, Mia; Ploski, Rafal; Pronicka, Ewa; Klein, Christine; Willemsen, Michel A A P; de Brouwer, Arjan P M; Prokisch, Holger; Katsanis, Nicholas; Wevers, Ron A

2015-02-05

We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Emergence of MRSA in positive blood cultures from patients with febrile neutropenia--a cause for concern.

LENUS (Irish Health Repository)

Morris, Patrick G

2008-09-01

Febrile neutropenia (FN) causes considerable morbidity in patients on cytotoxic chemotherapy. Recently, there has been a trend towards fewer Gram-negative and more Gram-positive infections with increasing antibiotic resistance. To assess these patterns, data from a supra-regional cancer centre in Ireland were reviewed.

Evaluation of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation.

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Shahideh Amini

2014-01-01

Full Text Available The aim of this study was to determine the incidence and causes of fever as a major problem contributing to transplantation related mortality among patients undergoing hematopoietic stem cell transplantation (HSCT and evaluation of antibiotic use, according to reliable guidelines.We retrospectively reviewed hospital records of 195 adult patients who underwent HSCT between 2009-2011 at hematology-oncology and bone marrow transplantation research center. Baseline information and also data related to fever and neutropenia, patient's outcomes, duration of hospitalization and antibiotic use pattern were documented.A total of 195 patients were analyzed and a total of 268 febrile episodes in 180 patients were recorded (mean 1.5 episodes per patient. About 222 episodes (82% were associated with neutropenia which one-fourth of them were without any documented infection sources. Microbiologic documents showed that the relative frequencies of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively. The hospital stay duration was directly related to the numbers of fever episodes (P<0.0001.The rate of febrile episodes in autologous stem cell transplantation was significantly higher compared to allogeneic type (P<0.05.It is necessary to determine not only the local profile of microbiologic pattern, but also antibiotic sensitivities in febrile neutropenic patients following hematopoietic stem cell transplantation, and reassess response to antibiotic treatment to establish any necessity for modifications to treatment guidelines in order to prevent any fatal complications from infection.

Is serum albumin an independent predictor of post chemotherapy febrile neutropenia?

International Nuclear Information System (INIS)

Saleem, L.; Zahid, N.A.

2017-01-01

Objective: To evaluate the association between serum albumin and risk of post chemotherapy febrile neutropenia. Study Design: Cross sectional study. Place and Duration of Study: Department of oncology, Liaquat National Hospital, from 1st Jan 2015 to 31st Dec 2016. Material and Method: One hundred and sixty-six biopsy proven cancer patients with Eastern cooperative oncology group (ECOG) performance status <2 and without significant co-morbidities received first cycle of chemotherapy during two years study period. Different chemotherapies with moderate to severe risk of FN were used. Patient's pre-treatment serum albumin was measured and patients followed for occurrence of FN. Association between serum albumin and post chemotherapy FN was analyzed. Results: Data of 166 patients was available for final analysis. Post chemotherapy FN was observed in 19.9% (33/166) patients. Pre-chemotherapy serum albumin level was <3.5 mg/dl in (35/166) 21.1% of patients, out of which (15/35) 42.9% developed FN. Serum albumin (p=0.0005) was highly significantly associated with a risk of FN. On analysis of other factors age, gender, body surface area (BSA) and pre-chemotherapy hemoglobin level were not significantly associated with a risk of FN while body mass index (p=0.0005) was found to be associated with risk of FN. Conclusion: Pre-chemotherapy serum albumin levels were found to be statistically significant predictor of postchemotherapy febrile neutropenia.

Utilization of a DNA enzyme immunoassay for the detection of proviral DNA of human immunodeficiency virus type 1 by polymerase chain reaction.

Science.gov (United States)

Zella, D; Cavicchini, A; Cattaneo, E; Cimarelli, A; Bertazzoni, U

1995-02-01

The detection of proviral DNA by Polymerase Chain Reaction (PCR) is regarded as an important tool in the diagnosis of HIV-1 infection, specially among adults at risk of AIDS and children born to seropositive mothers. However, application of PCR in routine testing is hampered by the need to use radioactive probes. In this study, a non-radioactive test based on a microtiter plate (DNA Enzyme ImmunoAssay, DEIA) was used for the detection of proviral sequences of HIV-1 in peripheral blood cells of different patients. The results of the PCR-DEIA assay were compared to those obtained by liquid hybridization (PCR-LH), virus isolation (VI) and Western blot (WB). The study population included 92 patients belonging to three different groups: seropositive subjects with a well-defined clinical status and WB profile; adults at risk of infection with negative or indeterminate WB; children born to seropositive mothers with still unestablished HIV-1 infection. In the seropositive subjects, both PCR-LH and PCR-DEIA confirmed infection and gave the same results as WB. In adults at risk of infection, PCR with both methods anticipated the seroconversion in one patient with indeterminate WB and confirmed the absence of infection among seronegative and other indeterminate patients. In children born to seropositive mothers, both PCR systems as well as VI permitted an early diagnosis of infection, as confirmed by the clinical follow-up. This study has shown that in subjects at risk of AIDS and in children born to seropositive mothers, the non-isotopic DEIA method presents the same sensitivity and specificity for the detection of HIV-1 infection as the radioactive procedure. The DEIA method appears to be particularly useful for the detection of PCR products in routine diagnostic analyses.

Distribution of pathogens in central line-associated bloodstream infections among patients with and without neutropenia following chemotherapy: evidence for a proposed modification to the current surveillance definition.

Science.gov (United States)

Steinberg, James P; Robichaux, Chad; Tejedor, Sheri Chernetsky; Reyes, Mary Dent; Jacob, Jesse T

2013-02-01

Many bloodstream infections (BSIs) occurring in patients with febrile neutropenia following cytotoxic chemotherapy are due to translocation of intestinal microbiota. However, these infections meet the National Healthcare Safety Network (NHSN) definition of central line-associated BSIs (CLABSIs). We sought to determine the differences in the microbiology of NHSN-defined CLABSIs in patients with and without neutropenia and, using these data, to propose a modification of the CLABSI definition. Retrospective review. Two large university hospitals over 18 months. All hospital-acquired BSIs occurring in patients with central venous catheters in place were classified using the NHSN CLABSI definition. Patients with postchemotherapy neutropenia (500 neutrophils/mm(3) or lower) at the time of blood culture were considered neutropenic. Pathogens overrepresented in the neutropenic group were identified to inform development of a modified CLABSI definition. Organisms that were more commonly observed in the neutropenic group compared with the nonneutropenic group included Escherichia coli (22.7% vs 2.5%; P definition (removing BSI with enterococci, streptococci, or E. coli) excluded 33 of 66 neutropenic CLABSIs and decreased the CLABSI rate in one study hospital with large transplant and oncology populations from 2.12 to 1.79 cases per 1,000 line-days. Common gastrointestinal organisms were more common in the neutropenia group, suggesting that many BSIs meeting the NHSN criteria for CLABSI in the setting of neutropenia may represent translocation of gut organisms. These findings support modification of the NHSN CLABSI definition.

Canadian supportive care recommendations for the management of neutropenia in patients with cancer

OpenAIRE

Kouroukis, C.T.; Chia, S.; Verma, S.; Robson, D.; Desbiens, C.; Cripps, C.; Mikhael, J.

2008-01-01

Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest...

Quality of Life and Neutropenia in Patients with Early Stage Breast Cancer: A Randomized Pilot Study Comparing Additional Treatment with Mistletoe Extract to Chemotherapy Alone

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Wilfried Tröger

2009-01-01

Full Text Available Background: Chemotherapy for breast cancer often deteriorates quality of life, augments fatigue, and induces neutropenia. Mistletoe preparations are frequently used by cancer patients in Central Europe. Physicians have reported better quality of life in breast cancer patients additionally treated with mistletoe preparations during chemotherapy. Mistletoe preparations also have immunostimulant properties and might therefore have protective effects against chemotherapy-induced neutropenia.Patients and Methods: We conducted a prospective randomized open label pilot study with 95 patients randomized into three groups. Two groups received Iscador® M special (IMS or a different mistletoe preparation, respectively, additionally to chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluoro-uracil (CAF. A control group received CAF with no additional therapy. Here we report the comparison IMS (n = 30 vs. control (n = 31. Quality of life including fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30. Neutropenia was defined as neutrophil counts <1,000/µl and assessed at baseline and one day before each CAF cycle.Results: In the descriptive analysis all 15 scores of the EORTC-QLQ-C30 showed better quality of life in the IMS group compared to the control group. In 12 scores the differences were significant (p < 0.02 and nine scores showed a clinically relevant and significant difference of at least 5 points. Neutropenia occurred in 3/30 IMS patients and in 8/31 control patients (p = 0.182.Conclusions: This pilot study showed an improvement of quality of life by treating breast cancer patients with IMS additionally to CAF. CAF-induced neutropenia showed a trend to lower frequency in the IMS group.

Prophylaxis against febrile neutropenia with pegfilgrastim in Italy: a budget impact analysis

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Giovanni Rosti

2011-09-01

Full Text Available Introduction: prophylaxis with granulocyte colony-stimulating factors (G-CSF is indicated for reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy for malignancy.
Objective: to evaluate the budgetary impact for the Italian NHS.
Design: a decision-analytic model has been developed to analyze the budget impact from the national health care system perspective. Costs include direct healthcare costs to the public payer of G-CSFs as well as their administration costs and costs of FN-related events. The comparison has been done using prophylaxis with G‑CSF (filgrastim for 11 days, pegfilgrastim, lenograstim for 11 days and antibiotics.
Patients and participants: The population of interest for the analysis were patients with breast cancer in stage II and III and patients with non-Hodgkin’s lymphoma (NHL.
Main outcome measures and results: for all the three patients group (NHL, Breast II and III, and for all the chemotherapy regimens (CHOP 21 and R-CHOP 21 for NHL, AC-T, TAC and TC for Breast stage II and III the budget impact analyses shows a cost reduction for the Italian NHS, as a result of an increase of the use of pegfilgrastim.
Conclusions: in Italy, a treatment strategy including pegfilgrastim as either primary or secondary prophylaxis provides value for money.


Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

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Jordana Grazziela Alves Coelho-dos-Reis

Full Text Available In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+HLA-DR(+, CD8(+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

Evaluation of ticarcillin/clavulanic acid versus ceftriaxone plus amikacin for fever and neutropenia in pediatric patients with leukemia and lymphoma

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Petrilli Antonio Sérgio

2003-01-01

Full Text Available BACKGROUND: The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia. Intravenous monotherapy, with broad spectrum antibiotics, of patients with a high risk of complications is a possible alternative. METHODS: We conducted a prospective open-label, randomized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients received either monotherapy with ticarcillin/clavulanic acid (T or ceftriaxone plus amikacin (C+A. RESULTS: Seventy patients who presented 136 episodes were evaluated, 68 in each arm of the study. The mean neutrophil counts at admission were 217cells/mm³ (T and 201cells/mm³ (C+A. The mean duration of neutropenia was 8.7 days (T and 7.6 days (C+A. Treatment was successful without the need for modifications in 71% of the episodes in the T group and 81% in the C+A group (p=0.23. Treatment was considered to have failed because of death in two episodes (3% in the T group and three episodes (4% in the C+A group, and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group. Overall success was 96% (T and 93% (C+A. Adverse events that occurred in group T were not related to the drugs used in this study. CONCLUSION: In pediatric and adolescent patients with leukemia or lymphoma, who presented with fever and neutropenia, during chemotherapy, ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin. It should be considered an appropriate option for this group of patients at high risk for infections.

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

NARCIS (Netherlands)

Aapro, M.S.; Bohlius, J.; Cameron, D.A.; Dal Lago, L.; Donnelly, J.P.; Kearney, N.; Lyman, G.H.; Pettengell, R.; Tjan-Heijnen, V.C.; Walewski, J.; Weber, D.C.; Zielinski, C.

2011-01-01

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or

Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, A.F. Tibúrcio; Nobre, V.; Neuenschwander, L.C. [Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, A.L. [Laboratório de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Xavier, S.G.; Paula, F.D.F. [Departamento de Propedêutica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, M.M. [Laboratório de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, J.C.A.; Bittencourt, H. [Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

2013-02-01

Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α), soluble TNF-α I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1α (MIP-1α or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

Use of inflammatory molecules to predict the occurrence of fever in onco-hematological patients with neutropenia

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A.F. Tiburcio Ribeiro

2013-02-01

Full Text Available Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-α, soluble TNF-α I and II receptors (sTNFRI and sTNFRII, monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif ligand 2 (CCL2], macrophage inflammatory protein-1α (MIP-1α or CCL3, eotaxin (CCL11, interleukin-8 (IL-8 or CXCL8, and interferon-inducible protein-10 (IP-10 or CXCL10 in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24 h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15 before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02. Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients.

[Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

Science.gov (United States)

Uchiyama, Kimio; Yamada, Manabu; Tamate, Shusuke; Iwasaki, Konomi; Mitomo, Keisuke; Nakayama, Seiichi

2015-09-01

The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy).

Identifying patient- and family-centered outcomes relevant to inpatient versus at-home management of neutropenia in children with acute myeloid leukemia.

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Szymczak, Julia E; Getz, Kelly D; Madding, Rachel; Fisher, Brian; Raetz, Elizabeth; Hijiya, Nobuko; Gramatges, Maria M; Henry, Meret; Mian, Amir; Arnold, Staci D; Aftandilian, Catherine; Collier, Anderson B; Aplenc, Richard

2018-04-01

Efficacy of therapeutic strategies relative to patient- and family-centered outcomes in pediatric oncology must be assessed. We sought to identify outcomes important to children with acute myeloid leukemia and their families related to inpatient versus at-home management of neutropenia. We conducted qualitative interviews with 32 children ≥8 years old and 54 parents. Analysis revealed the impact of neutropenia management strategy on siblings, parent anxiety, and child sleep quality as being outcomes of concern across respondents. These themes were used to inform the design of a questionnaire that is currently being used in a prospective, multiinstitutional comparative effectiveness trial. © 2017 Wiley Periodicals, Inc.

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

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M G Gerritsen

Full Text Available We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4% had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197. Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

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Gerritsen, M G; Willemink, M J; Pompe, E; van der Bruggen, T; van Rhenen, A; Lammers, J W J; Wessels, F; Sprengers, R W; de Jong, P A; Minnema, M C

2017-01-01

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases

OpenAIRE

Weycker Derek; Sofrygin Oleg; Seefeld Kim; Deeter Robert G; Legg Jason; Edelsberg John

2013-01-01

Abstract Background Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Methods Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classifie...

The Importance of Serum Cytokine Levels in Febrile Neutropenia

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Nuray Buyukberber

2003-02-01

Full Text Available The most important evaluation of the neutropenic patients is to determine the risk group. The desired approach to patients with low risks should be either not to hospitalize or to hospitalize for a short period of time which both decreases the cost and exposure to the resistant flora. The early diagnosis of sepsis in patients with high risk may be life saving. Recently, the determination of low and high-risk groups only by the clinical variables is not found to be a reliable method. The laboratory parameters supported by the clinical variables may be more practical. The determination of serum cytokines levels in febrile neutropenia may be helpful for the early risk diagnosis, new treatment approaches, and prognosis. [Archives Medical Review Journal 2003; 12(1.000: 12-19

Febrile neutropenia in paediatric peripheral blood stem cell transplantation, in vitro sensitivity data and clinical response to empirical antibiotic therapy

International Nuclear Information System (INIS)

Ansari, S.H.; Nasim, S.; Ahmed, A.; Irfan, M.; Ishaque, A.; Farzana, T.; Panjwani, V.K.; Taj, M.; Shamsi, T.S.

2006-01-01

To find the in-vitro sensitivity data and clinical response in order to determine the changes required in empiric antibiotic therapy for management of febrile neutropenia in paediatric patients undergoing peripheral blood stem cell transplantation. All patients were treated according to institutional protocol for febrile neutropenia. Empirical antibiotics include Ceftriaxone and Amikacin. In non-responders, changes made included Imipenem and Amikacin, Piperacillin Tazobactum/Tiecoplanin or Vancomycin/Cloxacilin/Ceftazidime. In non-responders, amphotaracin was added until recovery. Out of 52 patients, 5 did not develop any fever; in the remaining 47 patients there were 57 episodes of febrile neutropenia. The mean days of febrile episodes were 4.71 (range 3-8). Fever of unknown origin (FUO) occurred in 31 (54.3%) episodes. Microbiologically documented infection (MDI) occurred in 17 (29.8%) episodes of fever. Clinically documented infection (CDI) occurred in 9 (15.7%) episodes. Gram-negative organisms were isolated in 10 while gram-positive organisms in 7. Klebseilla, S. aureus were the most common isolates. Empirical therapy was effective in 12 of the 33 (36%) episodes. Out of 28, 26 (92%) responded to Imipenem/Amikacin as second line therapy while those who received any other second line combination, only 11 out of 22 (50%) showed response. Systemic Amphotericin was used in 4 patients, 2 responded. Infection related mortality rate was 4%. (author)

ELANE mutant-specific activation of different UPR pathways in congenital neutropenia.

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Nustede, Rainer; Klimiankou, Maksim; Klimenkova, Olga; Kuznetsova, Inna; Zeidler, Cornelia; Welte, Karl; Skokowa, Julia

2016-01-01

A number of studies have demonstrated induction of the unfolded protein response (UPR) in patients with severe congenital neutropenia (CN) harbouring mutations of ELANE, encoding neutrophil elastase. Why UPR is not activated in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations is unclear. We evaluated the effects of ELANE mutants on UPR induction in myeloid cells from CN and CyN patients, and analysed whether additional CN-specific defects contribute to the differences in UPR induction between CN and CyN patients harbouring identical ELANE mutations. We investigated CN-specific p.C71R and p.V174_C181del (NP_001963.1) and CN/CyN-shared p.S126L (NP_001963.1) ELANE mutants. We found that transduction of haematopoietic cells with p.C71R, but not with p.V174_C181del or p.S126L ELANE mutants induced expression of ATF6, and the ATF6 target genes PPP1R15A, DDIT3 and HSPA5. Recently, we found that levels of secretory leucocyte protease inhibitor (SLPI), a natural ELANE inhibitor, are diminished in myeloid cells from CN patients, but not CyN patients. Combined knockdown of SLPI by shRNA and transduction of ELANE p.S126L in myeloid cells led to elevated levels of ATF6, PPP1R15A and HSPA5 RNA, suggesting that normal levels of SLPI in CyN patients might protect them from the UPR induced by mutant ELANE. In summary, different ELANE mutants have different effects on UPR activation, and SLPI regulates the extent of ELANE-triggered UPR. © 2015 John Wiley & Sons Ltd.

Detection of the BLV provirus from nasal secretion and saliva samples using BLV-CoCoMo-qPCR-2: Comparison with blood samples from the same cattle.

Science.gov (United States)

Yuan, Yuan; Kitamura-Muramatsu, Yuri; Saito, Susumu; Ishizaki, Hiroshi; Nakano, Miwa; Haga, Satoshi; Matoba, Kazuhiro; Ohno, Ayumu; Murakami, Hironobu; Takeshima, Shin-Nosuke; Aida, Yoko

2015-12-02

Bovine leukemia virus (BLV) induces enzootic bovine leukosis, which is the most common neoplastic disease in cattle. Sero-epidemiological studies show that BLV infection occurs worldwide. Direct contact between infected and uninfected cattle is thought to be one of the risk factors for BLV transmission. Contact transmission occurs via a mixture of natural sources, blood, and exudates. To confirm that BLV provirus is detectable in these samples, matched blood, nasal secretion, and saliva samples were collected from 50 cattle, and genomic DNA was extracted. BLV-CoCoMo-qPCR-2, an assay developed for the highly sensitive detection of BLV, was then used to measure the proviral load in blood (n=50), nasal secretions (n=48), and saliva (n=47) samples. The results showed that 35 blood samples, 14 nasal secretion samples, and 6 saliva samples were positive for the BLV provirus. Matched blood samples from cattle that were positive for the BLV provirus (either in nasal secretion or saliva samples) were also positive in their blood. The proviral load in the positive blood samples was >14,000 (copies/1×10(5) cells). Thus, even though the proviral load in the nasal secretion and saliva samples was much lower (blood, prolonged direct contact between infected and healthy cattle may be considered as a risk factor for BLV transmission. Copyright © 2015 Elsevier B.V. All rights reserved.

Association of oesophageal radiation dose volume metrics, neutropenia and acute radiation oesophagitis in patients receiving chemoradiotherapy for non-small cell lung cancer

International Nuclear Information System (INIS)

Everitt, Sarah; Duffy, Mary; Bressel, Mathias; McInnes, Belinda; Russell, Christine; Sevitt, Tim; Ball, David

2016-01-01

The relationship between oesophageal radiation dose volume metrics and dysphagia in patients having chemoradiation (CRT) for non-small cell lung cancer (NSCLC) is well established. There is also some evidence that neutropenia is a factor contributing to the severity of oesophagitis. We retrospectively analysed acute radiation oesophagitis (ARO) rates and severity in patients with NSCLC who received concurrent chemotherapy and high dose radiation therapy (CRT). We investigated if there was an association between grade of ARO, neutropenia and radiation dose volume metrics. Patients with NSCLC having concurrent CRT who had RT dose and toxicity data available were eligible. Exclusion criteria included previous thoracic RT, treatment interruptions and non-standard dose regimens. RT dosimetrics included maximum and mean oesophageal dose, oesophagus dose volume and length data. Fifty four patients were eligible for analysis. 42 (78 %) patients received 60 Gy. Forty four (81 %) patients received carboplatin based chemotherapy. Forty eight (89 %) patients experienced ARO ≥ grade 1 (95 % CI: 78 % to 95 %). ARO grade was associated with mean dose (r s = 0.27, p = 0.049), V20 (r s = 0.31, p = 0.024) and whole oesophageal circumference receiving 20 Gy (r s = 0.32 p = 0.019). In patients who received these doses, V20 (n = 51, r s = 0.36, p = 0.011), V35 (n = 43, r s = 0.34, p = 0.027) and V60 (n = 25, r s = 0.59, P = 0.002) were associated with RO grade. Eleven of 25 (44 %) patients with ARO ≥ grade 2 also had ≥ grade 2 acute neutropenia compared with 5 of 29 (17 %) patients with RO grade 0 or 1 (p = 0.035). In addition to oesophageal dose-volume metrics, neutropenia may also be a risk factor for higher grades of ARO

Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

International Nuclear Information System (INIS)

Yasui, K.; Yamazaki, M.; Miyagawa, Y.; Komiyama, A.; Akabane, T.

1987-01-01

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine ( 3 H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder

The proviral genome of radiation leukemia virus: Molecular cloning, nucleotide sequence of its long terminal repeat and integration in lymphoma cell DNA

International Nuclear Information System (INIS)

Janowski, M.; Merregaert, J.; Boniver, J.; Maisin, J.R.

1985-01-01

The proviral genome of a thymotropic and leukemogenic C57BL/Ka mouse retrovirus, RadLV/VL/sub 3/(T+L+), was cloned as a biologically active PstI insert in the bacterial plasmid pBR322. Its restriction map was compared to those, already known, of two nonthymotropic and nonleukemogenic viruses of the same mouse strain, the ecotropic BL/Ka(B) and the xenotropic constituent of the radiation leukemia virus complex (RadLV). Differences were observed in the pol gene and in the env gene. Moreover, the nucleotide sequence of the RadLV/VL/sub 3/(T+L+) long terminal repeat revealed the existence of two copies of a 42 bp long sequence, separated by 11 nucleotides and of which BL/Ka(B) possesses only one copy

CONTENTS OF LYMPHOCYTE SUB-POPULATIONS IN THE CHILDREN WITH ACUTE LEUKEMIA AND LYMPHOMAS DEPENDENT ON INFECTIOUS COMPLICATION AND NEUTROPENIA

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M. V. Peshikova

2005-01-01

Full Text Available Abstract. The aim of the present work was to evaluate the contents of some lymphocyte sub-populations in peripheral blood of the children with tumors of hematopoietic and lymphoid tissues, depending on infectious complication of cytostatic therapy and neutropenia. In all children undergoing cytostatic therapy for acute lympho-blastic leukemia and non-B cell non-Hodgkinґs lymphomas, we found significant decrease in the numbers of CD95 lymphocytes, absolute amounts of natural killer cells (CD16, CD56-lymphocytes and activated lymphocytes (СD11b, HLA-DR-cells, irrespective of neutrophile numbers in their blood and infectious complications. However, absolute number of CD25- lymphocytes was significantly decreased in the children with neutropenia. Relative contents of CD16, CD56, СD11b, HLA-DR, CD25-lymphocytes did not significantly differ from those in healthy children, or they were found to be significantly increased.

A prospective, randomized, double-blinded, placebo-controlled trial of empirical teicoplanin in febrile neutropenia with persistent fever after imipenem monotherapy

NARCIS (Netherlands)

Erjavec, Z; de Vries-Hospers, HG; Halie, RM; Daenen, S

Glycopeptide antibiotics are used extensively in the empirical treatment of febrile patients with neutropenia. To come to a more rational and restricted application of these expensive drugs and to reduce the risk of emergence of resistance, we carried out a prospective, double-blinded,

Validasi Sistem Skoring Rondinelli untuk Mendeteksi Komplikasi Infeksi Berat pada Pasien Leukemia Limfoblastik Akut L1 dengan Demam Neutropenia Selama Kemoterapi Fase Induksi

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Renno Hidayat

2016-11-01

Kesimpulan. Sistem skoring Rondinelli merupakan instrumen yang cukup baik untuk mendeteksi komplikasi infeksi berat pada anak dengan LLA-L1 yang mengalami demam neutropenia selama pemberian kemoterapi fase induksi.

Neurological aspects of HTLV-1 infection in Bahia: results from an 8-year cohort

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Davi Tanajura

2015-01-01

Full Text Available HTLV-1 is the causal agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a disease observed in up to 5% of individuals infected with HTLV-1. However, infected individuals without the disease can present neurological complaints relating to sensory, motor or urinary manifestations. The aim of this study was to investigate the incidence of neurological manifestations among patients with HTLV-1. Method HTLV-1 patients in Salvador, Bahia, Brazil, were enrolled into a cohort study. Results Among 414 subjects, 76 had definite and 87 had possible or probable HAM/TSP at the baseline, whereas 251 subjects had no neurological signs or symptoms. Definite HAM/TSP developed in 5 patients (1.74%. The asymptomatic subjects were selected for analysis. The incidence rate expressed per 1,000 persons-year was calculated. It was 206 for hand numbness, 129 for nocturia and 126 for urinary urgency. In the neurological examination, leg hyperreflexia presented an average incidence rate of 76; leg paraparesis, 52; and Babinski sign, 36. Kaplan-Meyer curves categorized according to gender and proviral load showed that females and patients with proviral load of more than 100,000 copies per 106 peripheral blood mononuclear cells (PBMCs presented higher risk. Conclusion Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up. Female gender and high proviral load were risk factors for neurological disease.

Expression of fra(10)(q25) in peripheral blood and bone marrow in familial neutropenia.

OpenAIRE

Holmes, J A; Thompson, P W

1988-01-01

We report on the expression of fra(10)(q25) in a mother and daughter with familial chronic neutropenia. Differences in expression of the fragile site in bone marrow cells compared with peripheral blood lymphocytes were observed. Short term bone marrow cultures in complete medium showed high levels of spontaneous expression, whereas in 72 hour stimulated blood cultures it was virtually absent. There were also differences in the types of lesions found; chromosome type lesions predominated in th...

Distribution and clinical determinants of time-to-positivity of blood cultures in patients with neutropenia.

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Lambregts, Merel M C; Warreman, Eva B; Bernards, Alexandra T; Veelken, Hendrik; von dem Borne, Peter A; Dekkers, Olaf M; Visser, Leo G; de Boer, Mark G

2018-02-01

Blood cultures (BCs) are essential in the evaluation of neutropenic fever. Modern BC systems have significantly reduced the time-to-positivity (TTP) of BC. This study explores the probability of bacteraemia when BCs have remained negative for different periods of time. All adult patients with neutropenia and bacteraemia were included (January 2012-February 2016). Predictive clinical factors for short (≤16 hours) and long (>24 hours) TTP were determined. The residual probability of bacteraemia was estimated for the scenario of negative BC 24 hours after collection. The cohort consisted of 154 patients, accounting for 190 episodes of bacteraemia. Median age of 61 years, 60.5% were male. In 123 (64.7%) episodes, BC yielded a single Gram-positive micro-organism and in 49 (25.8%) a Gram-negative micro-organism (median TTP 16.7, 14.5 hours respectively, P hours in 91.6% of episodes. Central line-associated bacteraemia was associated with long TTP. The probability of bacteraemia if BC had remained negative for 24 hours was 1%-3%. The expected TTP offers guidance in the management of patients with neutropenia and suspected bacteraemia. The knowledge of negative BC can support a change in working diagnosis, and impact clinical decisions as soon as 24 hours after BC collection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sunitinib-induced hypertension, neutropenia and thrombocytopenia as predictors of good prognosis in metastatic renal cell carcinoma patients

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Rautiola, Juhana; Donskov, Frede; Peltola, Katriina

2016-01-01

OBJECTIVES: To evaluate the clinical significance of hypertension, neutropenia and thrombocytopenia as possible new biomarkers of sunitinib efficacy in non-trial metastatic renal cell carcinoma (mRCC) patients. MATERIALS AND METHODS: 181 consecutive mRCC patients were treated with sunitinib. Thir...... of sunitinib efficacy patients with mRCC. Our results may help to individualize sunitinib dosing during therapy based on these common sunitinib-related AEs....

Incidence of chemotherapy-induced neutropenia in HIV-infected and uninfected patients with breast cancer receiving neoadjuvant chemotherapy

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Sithembile Ngidi

2017-07-01

Full Text Available Background. Chemotherapy-induced neutropenia (CIN can result in poor tolerance of chemotherapy, leading to dose reductions, delays in therapy schedules, morbidity and mortality. Actively identifying predisposing risk factors before treatment is of paramount importance. We hypothesised that chemotherapy is associated with a greater increase in CIN and its complications in HIV-infected patients than in those who are not infected. Objective. To establish the incidence of CIN in HIV-infected and uninfected patients undergoing chemotherapy. Methods. A retrospective chart review and analysis was conducted in the oncology departments at Inkosi Albert Luthuli Central Hospital and Addington Hospital, Durban, South Africa. The study population consisted of 65 previously untreated women of all ages with stage II - IV breast cancer and known HIV status treated with neoadjuvant chemotherapy from January 2012 to December 2015. Results. HIV-infected patients formed 32.3% of the group, and 95.2% of them were on antiretroviral therapy. The mean age (standard deviation (SD of the cohort was 48.5 (13.2 years (40.6 (9.6 years for the HIV-infected group v. 52.0 (13.1 years for the uninfected group; p<0.001. Ninety-five neutropenia episodes were observed (rate 0.85 per 1 year of follow-up time. Following multivariate adjustment, patients with HIV infection were almost two times more likely to develop CIN (hazard ratio (HR 1.76, 95% confidence interval (CI 1.06 - 2.92; p=0.029. A high baseline absolute neutrophil count (ANC (HR 0.80, 95% CI 0.68 - 0.95; p=0.005 remained significantly associated with protection against CIN. Conclusions. HIV-infected patients were younger than those who were not infected, and presented at a more locally advanced stage of disease. HIV infection was an independent predictor for CIN. HIV-infected patients had an almost two-fold increased risk of developing CIN and developed neutropenia at a much faster rate. A high baseline white cell

Characterisation of Neutropenia-Associated Neutrophil Elastase Mutations in a Murine Differentiation Model In Vitro and In Vivo.

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Michael Wiesmeier

Full Text Available Severe congenital neutropenia (SCN is characterised by a differentiation block in the bone marrow and low neutrophil numbers in the peripheral blood, which correlates with increased risk of bacterial infections. Several underlying gene defects have been identified in SCN patients. Mutations in the neutrophil elastase (ELANE gene are frequently found in SCN and cyclic neutropenia. Both mislocalization and misfolding of mutant neutrophil elastase protein resulting in ER stress and subsequent induction of the unfolded protein response (UPR have been proposed to be responsible for neutrophil survival and maturation defects. However, the detailed molecular mechanisms still remain unclear, in part due to the lack of appropriate in vitro and in vivo models. Here we used a system of neutrophil differentiation from immortalised progenitor lines by conditional expression of Hoxb8, permitting the generation of mature near-primary neutrophils in vitro and in vivo. NE-deficient Hoxb8 progenitors were reconstituted with murine and human forms of typical NE mutants representative of SCN and cyclic neutropenia, and differentiation of the cells was analysed in vitro and in vivo. ER stress induction by NE mutations could be recapitulated during neutrophil differentiation in all NE mutant-reconstituted Hoxb8 cells. Despite ER stress induction, no change in survival, maturation or function of differentiating cells expressing either murine or human NE mutants was observed. Further analysis of in vivo differentiation of Hoxb8 cells in a murine model of adoptive transfer did not reveal any defects in survival or differentiation in the mouse. Although the Hoxb8 system has been found to be useful for dissection of defects in neutrophil development, our findings indicate that the use of murine systems for analysis of NE-mutation-associated pathogenesis is complicated by differences between humans and mice in the physiology of granulopoiesis, which may go beyond possible

Zinc finger nuclease: a new approach for excising HIV-1 proviral DNA from infected human T cells.

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Qu, Xiying; Wang, Pengfei; Ding, Donglin; Wang, Xiaohui; Zhang, Gongmin; Zhou, Xin; Liu, Lin; Zhu, Xiaoli; Zeng, Hanxian; Zhu, Huanzhang

2014-09-01

A major reason that Acquired Immune Deficiency Syndrome (AIDS) cannot be completely cured is the human immunodeficiency virus 1 (HIV-1) provirus integrated into the human genome. Though existing therapies can inhibit replication of HIV-1, they cannot eradicate it. A molecular therapy gains popularity due to its specifically targeting to HIV-1 infected cells and effectively removing the HIV-1, regardless of viral genes being active or dormant. Now, we propose a new method which can excellently delete the HIV provirus from the infected human T cell genome. First, we designed zinc-finger nucleases (ZFNs) that target a sequence within the long terminal repeat (LTR) U3 region that is highly conserved in whole clade. Then, we screened out one pair of ZFN and named it as ZFN-U3. We discovered that ZFN-U3 can exactly target and eliminate the full-length HIV-1 proviral DNA after the infected human cell lines treated with it, and the frequency of its excision was about 30 % without cytotoxicity. These results prove that ZFN-U3 can efficiently excise integrated HIV-1 from the human genome in infected cells. This method to delete full length HIV-1 in human genome can therefore provide a novel approach to cure HIV-infected individuals in the future.

Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice

Energy Technology Data Exchange (ETDEWEB)

Kabaya, Koji; Watanabe, Masahiko; Kusaka, Masaru; Seki, Masatoshi (Kirin Brewery Co., Ltd., Gunma (Japan). Pharmaceutical Research Laboratory); Fushiki, Masato

1994-08-01

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 [mu]g/body/day from day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also reveals an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation. (author).

Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice

International Nuclear Information System (INIS)

Kabaya, Koji; Watanabe, Masahiko; Kusaka, Masaru; Seki, Masatoshi; Fushiki, Masato.

1994-01-01

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 μg/body/day from day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also reveals an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation. (author)

BLV-CoCoMo-qPCR: a useful tool for evaluating bovine leukemia virus infection status

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Jimba Mayuko

2012-09-01

Full Text Available Abstract Background Bovine leukemia virus (BLV is associated with enzootic bovine leukosis, which is the most common neoplastic disease of cattle. BLV infects cattle worldwide, imposing a severe economic impact on the dairy cattle industry. Recently, we developed a new quantitative real-time polymerase chain reaction (PCR method using Coordination of Common Motifs (CoCoMo primers to measure the proviral load of known and novel BLV variants in BLV-infected animals. Indeed, the assay was highly effective in detecting BLV in cattle from a range of international locations. This assay enabled us to demonstrate that proviral load correlates not only with BLV infection capacity as assessed by syncytium formation, but also with BLV disease progression. In this study, we compared the sensitivity of our BLV-CoCoMo-qPCR method for detecting BLV proviruses with the sensitivities of two real-time PCR systems, and also determined the differences of proviral load with serotests. Results BLV-CoCoMo-qPCR was found to be highly sensitive when compared with the real-time PCR-based TaqMan MGB assay developed by Lew et al. and the commercial TaKaRa cycleave PCR system. The BLV copy number determined by BLV-CoCoMo-qPCR was only partially correlated with the positive rate for anti-BLV antibody as determined by the enzyme-linked immunosorbent assay, passive hemagglutination reaction, or agar gel immunodiffusion. This result indicates that, although serotests are widely used for the diagnosis of BLV infection, it is difficult to detect BLV infection with confidence by using serological tests alone. Two cattle were experimentally infected with BLV. The kinetics of the provirus did not precisely correlate with the change in anti-BLV antibody production. Moreover, both reactions were different in cattle that carried different bovine leukocyte antigen (BoLA-DRB3 genotypes. Conclusions Our results suggest that the quantitative measurement of proviral load by BLV

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia.

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Qin, Yan; Han, Xiaohong; Wang, Lin; Du, Ping; Yao, Jiarui; Wu, Di; Song, Yuanyuan; Zhang, Shuxiang; Tang, Le; Shi, Yuankai

2017-10-01

The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated. A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0-2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment.

Mannose receptor may be involved in small ruminant lentivirus pathogenesis

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Crespo Helena

2012-05-01

Full Text Available Abstract Thirty-one sheep naturally infected with small ruminant lentiviruses (SRLV of known genotype (A or B, and clinically affected with neurological disease, pneumonia or arthritis were used to analyse mannose receptor (MR expression (transcript levels and proviral load in virus target tissues (lung, mammary gland, CNS and carpal joints. Control sheep were SRLV-seropositive asymptomatic (n = 3, seronegative (n = 3 or with chronic listeriosis, pseudotuberculosis or parasitic cysts (n = 1 in each case. MR expression and proviral load increased with the severity of lesions in most analyzed organs of the SRLV infected sheep and was detected in the affected tissue involved in the corresponding clinical disease (CNS, lung and carpal joint in neurological disease, pneumonia and arthritis animal groups, respectively. The increased MR expression appeared to be SRLV specific and may have a role in lentiviral pathogenesis.

Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases

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Zapata Ana X

2006-03-01

Full Text Available Abstract Background For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM to induce neutropenia. Although high doses (350–450 mg/kg are still used and their effects on mouse leukocytes have been described, a lower dose (250 mg/kg is widely preferred today, but the characteristics and applicability of this approach in outbred mice have not been determined. Methods Fifteen female ICR mice were injected intraperitoneally with 150 and 100 mg/kg of CPM on days 1 and 4, respectively. Blood samples (~160 μL were drawn from the retro-orbital sinus of each mouse on days 1, 4, 5, 6, 7 and 11. Leukocytes were counted manually and the number of granulocytes was based on microscopic examination of Wright-stained smears. The impact of neutropenia induced by this method was then determined with a variety of pathogens in three different murine models of human infections: pneumonia (Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, meningoencephalitis (S. pneumoniae, and the thigh model (S. aureus, Escherichia coli, Bacteroides fragilis. Results The basal count of leukocytes was within the normal range for outbred mice. On day 4, there was an 84% reduction in total white blood cells, and by day 5 the leukopenia reached its nadir (370 ± 84 cells/mm3. Profound neutropenia (≤10 neutrophils/mm3 was demonstrated at day 4 and persisted through days 5 and 6. Lymphocytes and monocytes had a 92% and 96% decline between days 1 and 5, respectively. Leukocytes recovered completely by day 11. Mice immunosupressed under this protocol displayed clinical and microbiological patterns of progressive and lethal infectious diseases after inoculation in different organs with diverse human pathogens. Conclusion A CPM total dose of 250 mg/kg is sufficient to induce

Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study.

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Carmona-Bayonas, Alberto; Jiménez-Fonseca, Paula; Virizuela Echaburu, Juan; Antonio, Maite; Font, Carme; Biosca, Mercè; Ramchandani, Avinash; Martínez, Jerónimo; Hernando Cubero, Jorge; Espinosa, Javier; Martínez de Castro, Eva; Ghanem, Ismael; Beato, Carmen; Blasco, Ana; Garrido, Marcelo; Bonilla, Yaiza; Mondéjar, Rebeca; Arcusa Lanza, María Ángeles; Aragón Manrique, Isabel; Manzano, Aránzazu; Sevillano, Elena; Castañón, Eduardo; Cardona, Mercé; Gallardo Martín, Elena; Pérez Armillas, Quionia; Sánchez Lasheras, Fernando; Ayala de la Peña, Francisco

2015-02-10

To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes. © 2015 by American Society of Clinical Oncology.

Pharmacoeconomic analysis of voriconazole vs. caspofungin in the empirical antifungal therapy of febrile neutropenia in Australia.

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Al-Badriyeh, Daoud; Liew, Danny; Stewart, Kay; Kong, David C M

2012-05-01

In two major clinical trials, voriconazole and caspofungin were recommended as alternatives to liposomal amphotericin B for empirical use in febrile neutropenia. This study investigated the health economic impact of using voriconazole vs. caspofungin in patients with febrile neutropenia. A decision analytic model was developed to measure downstream consequences of empirical antifungal therapy. Clinical outcomes measured were success, breakthrough infection, persistent base-line infection, persistent fever, premature discontinuation and death. Treatment transition probabilities and patterns were directly derived from data in two relevant randomised controlled trials. Resource use was estimated using an expert clinical panel. Cost inputs were obtained from latest Australian sources. The analysis adopted the perspective of the Australian hospital system. The use of caspofungin led to a lower expected mean cost per patient than voriconazole (AU$40,558 vs. AU$41,356), with a net cost saving of AU$798 (1.9%) per patient. Results were most sensitive to the duration of therapy and the alternative therapy used post-discontinuation. In uncertainty analysis, the cost associated with caspofungin is less than that with voriconazole in 65.5% of cases. This is the first economic evaluation of voriconazole vs. caspofungin for empirical therapy. Caspofungin appears to have a higher probability of having cost-savings than voriconazole for empirical therapy. The difference between the two medications does not seem to be statistically significant however. © 2011 Blackwell Verlag GmbH.

Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome.

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De Nicola, Beatrice; Lech, Christopher J; Heddi, Brahim; Regmi, Sagar; Frasson, Ilaria; Perrone, Rosalba; Richter, Sara N; Phan, Anh Tuân

2016-07-27

The long terminal repeat (LTR) of the proviral human immunodeficiency virus (HIV)-1 genome is integral to virus transcription and host cell infection. The guanine-rich U3 region within the LTR promoter, previously shown to form G-quadruplex structures, represents an attractive target to inhibit HIV transcription and replication. In this work, we report the structure of a biologically relevant G-quadruplex within the LTR promoter region of HIV-1. The guanine-rich sequence designated LTR-IV forms a well-defined structure in physiological cationic solution. The nuclear magnetic resonance (NMR) structure of this sequence reveals a parallel-stranded G-quadruplex containing a single-nucleotide thymine bulge, which participates in a conserved stacking interaction with a neighboring single-nucleotide adenine loop. Transcription analysis in a HIV-1 replication competent cell indicates that the LTR-IV region may act as a modulator of G-quadruplex formation in the LTR promoter. Consequently, the LTR-IV G-quadruplex structure presented within this work could represent a valuable target for the design of HIV therapeutics. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

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Valeria Contreras; Sebastián Sepúlveda; Ana Heredia

2016-01-01

En pacientes con cáncer que se presentan con neutropenia febril existe controversia sobre si es mejor utilizar una combinación de antibióticos betalactámicos y aminoglicósidos o si bastaría la monoterapia con betalactámicos de amplio espectro como tratamiento empírico inicial. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen 14 estudios aleatorizados pertinentes a esta p...

The time has come for new models in febrile neutropenia: a practical demonstration of the inadequacy of the MASCC score.

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Carmona-Bayonas, A; Jiménez-Fonseca, P; Virizuela Echaburu, J; Sánchez Cánovas, M; Ayala de la Peña, F

2017-09-01

Since its publication more than 15 years ago, the MASCC score has been internationally validated any number of times and recommended by most clinical practice guidelines for the management of febrile neutropenia (FN) around the world. We have used an empirical data-supported simulated scenario to demonstrate that, despite everything, the MASCC score is impractical as a basis for decision-making. A detailed analysis of reasons supporting the clinical irrelevance of this model is performed. First, seven of its eight variables are "innocent bystanders" that contribute little to selecting low-risk candidates for ambulatory management. Secondly, the training series was hardly representative of outpatients with solid tumors and low-risk FN. Finally, the simultaneous inclusion of key variables both in the model and in the outcome explains its successful validation in various series of patients. Alternative methods of prognostic classification, such as the Clinical Index of Stable Febrile Neutropenia, have been specifically validated for patients with solid tumors and should replace the MASCC model in situations of clinical uncertainty.

Hemodialysis-associated neutropenia and hypoxemia: the effect of dialyzer membrane materials.

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Hakim, R M; Lowrie, E G

1982-01-01

The fall in white blood cells (WBC) and arterial oxygen pressure that occurs during hemodialysis was investigated as a function of different dialysis membranes and different sterilization methods. 8 chronic hemodialysis patients were studied and each was dialyzed with three different membranes: cellulosic hollow fiber, polyacrylonitrile flat sheet and polymethylmethacrylate hollow fiber. Each dialyzer was studied with a dry sterilization method and after formalin treatment. Arterialized blood gas, bicarbonate and WBC were drawn at various intervals throughout dialysis. The effect of the sterilization method was minimal. Cellulosic membranes were shown to cause significantly more neutropenia (p less than 0.001) and hypoxemia (p less than 0.01) than the other two membranes. No significant differences was seen in pH, PCO2 and bicarbonate. The results indicate differences in biocompatibility between different membranes. Clinical implications are discussed.

High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy.

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Saravanan, Shanmugam; Gomathi, Selvamurthi; Delong, Allison; Kausalya, Bagavathi; Sivamalar, Sathasivam; Poongulali, Selvamuthu; Brooks, Katherine; Kumarasamy, Nagalingeswaran; Balakrishnan, Pachamuthu; Solomon, Sunil S; Cu-Uvin, Susan; Kantor, Rami

2018-05-24

Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ≥6 months; GVL when PVL >2000 copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000 copies/mL. Wilcoxon rank-sum and Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Inter-compartmental resistance discordance was evaluated using generalized estimating equations. Of 200 women, 37% had detectable (>400 copies/mL) PVL and 31% had PVL >1000 copies/mL. Of women with detectable PVL, 74% had PVL >2000 copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34 years, median ART duration of 33 months, median CD4 count of 217 cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10 copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.

Ciprofloxacin reduces occurrence of fever in children with acute leukemia who develop neutropenia during chemotherapy.

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Laoprasopwattana, Kamolwish; Khwanna, Thida; Suwankeeree, Pussayaban; Sujjanunt, Tipwan; Tunyapanit, Wanutsanun; Chelae, Sureerat

2013-03-01

Fluoroquinolones reduce occurrence of fever in adult cancer patients who develop neutropenia, but there has been no randomized controlled trial in children, and there are only a few studies considering resistance in intestinal floral after ciprofloxacin has been used. Children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before and at 1 and/or 2 weeks after the intervention. Of the total of 95 patients, 45 and 50 patients received ciprofloxacin and placebo, respectively. Of the 71 patients who developed neutropenia, the proportion of children who developed fever was significantly lower in the ciprofloxacin group than in the placebo group (17/34 [50.0%] versus 27/37 [73.0%]; absolute difference in risk, -23.0%; 95% confidence interval: -45.0% to -0.9%; P = 0.046). Ciprofloxacin significantly reduced the occurrence of febrile episodes in patients with acute lymphoblastic leukemia in the induction phase of chemotherapy, but not in patients with lymphoma or in the consolidation phase of chemotherapy. Adverse effects were not different between the groups. After intervention, the percentages of Escherichia coli and Klebsiella pneumoniae susceptible to ciprofloxacin were significantly lower in the ciprofloxacin group. Ciprofloxacin can prevent fever in neutropenic patients with acute lymphoblastic leukemia during the induction phase of chemotherapy with good tolerance and no serious side effects. Due to the selective pressure of intestinal flora resistance to ciprofloxacin, the long-term effectiveness needs further investigation.

Long-term epidemiology of bacterial susceptibility profiles in adults suffering from febrile neutropenia with hematologic malignancy after antibiotic change

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J Mebis

2010-07-01

Full Text Available J Mebis1,2, H Jansens3, G Minalu4, G Molenberghs4, WA Schroyens1, AP Gadisseur1, A van de Velde1, I Vrelust1, H Goossens3, ZN Berneman11Division of Hematology, Antwerp University Hospital, Edegem, 2Division of Medical Oncology, Jessa Hospital, Hasselt, 3Division of Microbiology, Antwerp University Hospital, Edegem, 4Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, BelgiumObjective: The aim of this study was to investigate the epidemiology and antibiotic ­susceptibility profiles of isolated bacterial organisms in relation to empiric treatment of neutropenic fever over a 15-year period.Methods: All patients with or at risk febrile neutropenia and treated in the hematology ward of the Antwerp University Hospital during 1994–2008 were prospectively included. Skin, blood, and urine cultures were taken. Oral quinolone prophylaxis was started in patients with neutropenia without fever. Empiric starting therapy consisted of amikacin in combination with cefepime.Results: A total of 3624 bacteria were isolated. The most common pathogens were coagulase-negative Staphylococci (46%, followed by Escherichia coli (25%, Enterobacteriaceae (15.6%, Staphylococcus aureus (7.2%, and Pseudomonas aeruginosa (3.8%. The balance between Gram-positive and Gram-negative bacteria remained stable, with a majority of Gram-positive bacteria. A shift from oxacillin-sensitive to oxacillin-resistant coagulase-negative Staphylococci was observed. Regarding susceptibility patterns, no vancomycin resistance was detected in coagulase-negative Staphylococci or in S. aureus. The E. coli susceptibility rates remained stable. However, 66% of bloodstream infections were ciprofloxacin-resistant. A reduced susceptibility of P. aeruginosa strains to meropenem was noticed.Conclusions: Improvement in antibiotic susceptibility of inducible Enterobacteriaceae ­following a switch of empiric antibiotic therapy was maintained 15 years

Severe neutropenia in children: a single institutional experience.

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Yilmaz, Deniz; Ritchey, Arthur Kim

2007-08-01

Severe neutropenia (SN) is a rare disorder in childhood. This study aimed to document the approach to diagnosis and treatment of children with SN in a single university-based children's hospital, determine the types of SN seen in a 4-year period, and determine outcomes of the subtypes of SN. Forty-five children with SN were identified between 2000 and 2004. Two patients had autoimmune, 3 congenital, 3 familial, 6 cyclic, and 31 idiopathic SN. The median age of the patients with idiopathic SN was 15 months (3 mo to 17 y). Thirteen patients with idiopathic SN received filgrastim and 18 were observed. The history of severe infection and hospitalization at presentation was significantly more common among the patients who received filgrastim than those observed, but was not different between the 2 groups during the follow-up period. SN resolved in 16 patients and persisted in 14 patients. One patient with idiopathic SN did not respond to filgrastim and died of sepsis while she was still neutropenic. In summary, the majority of patients with SN had idiopathic SN, the infection risk was variable, treatment was based on clinical judgment rather than absolute neutrophil count, and approximately half of the patients had complete recovery.

Absence of A3Z3-Related Hypermutations in the env and vif Proviral Genes in FIV Naturally Infected Cats

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Lucía Cano-Ortiz

2018-05-01

Full Text Available Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3 proteins comprise an important family of restriction factors that produce hypermutations on proviral DNA and are able to limit virus replication. Vif, an accessory protein present in almost all lentiviruses, counteracts the antiviral A3 activity. Seven haplotypes of APOBEC3Z3 (A3Z3 were described in domestic cats (hap I–VII, and in-vitro studies have demonstrated that these proteins reduce infectivity of vif-defective feline immunodeficiency virus (FIV. Moreover, hap V is resistant to vif-mediated degradation. However, studies on the effect of A3Z3 in FIV-infected cats have not been developed. Here, the correlation between APOBEC A3Z3 haplotypes in domestic cats and the frequency of hypermutations in the FIV vif and env genes were assessed in a retrospective cohort study with 30 blood samples collected between 2012 and 2016 from naturally FIV-infected cats in Brazil. The vif and env sequences were analyzed and displayed low or undetectable levels of hypermutations, and could not be associated with any specific A3Z3 haplotype.

Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4 phenotype

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Fernandez Bridget A

2012-11-01

Full Text Available Abstract Background Severe congenital neutropenia type 4 (SCN4 is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3. Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4 is caused by autosomal recessive mutations in SLC45A2. Methods We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature. Results The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood. Conclusions This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.

Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

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Contreras, Valeria; Sepúlveda, Sebastián; Heredia, Ana

2016-02-24

It is still controversial if the combined use of beta-lactam antibiotics and aminoglycosides has advantages over broad-spectrum beta-lactam monotherapy for the empirical treatment of cancer patients with febrile neutropenia. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including 14 pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the combination of beta-lactam antibiotics and aminoglycosides probably does not lead to a reduced mortality in febrile neutropenic cancer patients and it might increase nephrotoxicity.

Cytotoxic T cells in chronic idiopathic neutropenia express restricted antigen receptors.

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Mastrodemou, Semeli; Stalika, Evangelia; Vardi, Anna; Gemenetzi, Katerina; Spanoudakis, Michalis; Karypidou, Maria; Mavroudi, Irene; Hadzidimitriou, Anastasia; Stavropoulos-Giokas, Catherine; Papadaki, Helen A; Stamatopoulos, Kostas

2017-12-01

Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8 + cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV-TRBD-TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection. Cross-comparison of our sequence dataset with public TRB sequence databases revealed that CIN may rarely share common immunogenetic features with other entities, however, the CIN TRB repertoire is largely disease-biased. Overall, these findings suggest that CIN may be driven by long-term exposure to a restricted set of specific CIN-associated antigens.

Novas diretrizes na abordagem clínica da neutropenia febril e da sepse em oncologia pediátrica New guidelines for the clinical management of febrile neutropenia and sepsis in pediatric oncology patients

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Ana Verena Almeida Mendes

2007-05-01

Full Text Available OBJETIVOS: Fornecer subsídios à abordagem diagnóstica, profilática e terapêutica da neutropenia febril e da sepse em criança com doença oncológica, dando especial atenção aos novos protocolos e diretrizes. FONTES DE DADOS: Revisão de literatura científica utilizando uma busca bibliográfica eletrônica nas páginas do MEDLINE, Medscape, SciELO, Google, Cochrane e PubMED com as palavras-chave febrile, neutropenic, cancer, children, sepse, intensive, care. Foram selecionados artigos publicados entre 1987 e 2007, preferencialmente artigos de revisão, protocolos, revisões sistemáticas, estudos epidemiológicos, recomendações de força-tarefa e ensaios clínicos fase III. Foram revistos os consensos publicados pela Infectious Diseases Society of America, Center for Diseases Control e Infectious Diseases Working Party da German Society of Hematology and Oncology, além de recomendações da World Federation of Pediatric Intensive and Critical Care Societies e da Society of Critical Care Medicine. SÍNTESE DOS DADOS: A utilização de esquemas quimioterápicos agressivos, transplante de medula óssea e recursos de terapia intensiva aumentaram a sobrevida nas crianças com câncer e também a morbidade infecciosa, sendo as complicações sépticas a principal causa de mortalidade. Diversos fatores de risco têm sido identificados, como neutropenia, tipo oncológico, sinais clínicos e marcadores de resposta inflamatória (reação em cadeia da polimerase, procalcitonina, assim como a maior resistência aos antimicrobianos e antifúngicos. Protocolos de classificação de risco, de diagnóstico e tratamento devem ser estabelecidos em cada serviço, respeitando a flora microbiológica da população estudada. A terapia intensiva pediátrica tem aumentado a sobrevida a curto e longo prazo nestes pacientes. CONCLUSÕES: Pacientes oncológicos são particularmente vulneráveis a complicações infecciosas. A identificação e o tratamento

Could Neutrophil CD64 Expression Be Used as a Diagnostic Parameter of Bacteremia in Patients with Febrile Neutropenia?

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Nur Efe İris

2017-06-01

Full Text Available Objective: The aim of this study is to investigate if neutrophil CD64 expression in febrile neutropenia patients could be used as an early indicator of bacteremia. Materials and Methods: All consecutive patients older than 18 years of age who had developed febrile neutropenia episodes due to hematological malignancies were included in the study. Those patients who had significant growth in their blood cultures constituted the case group, while those who had febrile neutropenia without any growth in their cultures and who did not have any documented infections formed the control group. Blood culture bottles were incubated in the Bact ALERT 3D system (bioMerieux, France, identification and susceptibility testing were performed using an automated broth microdilution method (VITEK 2, bioMerieux, and CD64 expression analysis was performed by the flow cytometry method. C-reactive protein (CRP was measured by turbidimetric methods (Biosystems, Spain and erythrocyte sedimentation rate (ESR was measured by the Wintrobe method. Results: In total, we prospectively evaluated 31 febrile episodes. The case group consisted of 17 patients while the control group included 14 patients. CD64 was found on neutrophils of the case group patients with a mean count of 8006 molecules/cell and of control group with a mean count of 2786 molecules/cell. CD64 levels of the case group were significantly higher than those of the control group (p=0.005. In the differentiation of the case group from the control group, a 2500 cut-off value for CD64 had significant [AUC=0.792 (0.619-0.965] predictive value (p=0.001. In the prediction of patients with a 2500 cut-off value for CD64, sensitivity was 94.1%, positive predictive value was 76.2%, specificity was 64.3%, and negative predictive value was 90.0%. CRP levels and ESR values did not differ significantly between the groups (p=0.005. Conclusion: Neutrophil CD64 expression could be a good predictor as an immune parameter with

Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib : Results of the European Study on Glycogen Storage Disease Type I

NARCIS (Netherlands)

Visser, G; Rake, JP; Fernandes, J; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Smit, GPA

Objective: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. Method: As part of a collaborative European Study on GSD type I, a retrospective registry was established in

Assessment of intrafamilial clinical variability of poikiloderma with neutropenia by a 10-year follow-up of three affected siblings.

Science.gov (United States)

Concolino, Daniela; Sestito, Simona; Falvo, Francesca; Romano, Giusy; Ceravolo, Miriam; Anastasio, Elisa; Pensabene, Licia; Colombo, Elisa A; Larizza, Lidia

2018-05-23

Clericuzio-type poikiloderma with neutropenia is a well-defined nosological entity, but despite a remarkable number of clinical reports, no long term follow-up data has been presented to date regarding patients with this rare condition. Here we describe the results of clinical follow-up of three siblings, one male (Patient 1) and two females (Patients 2 and 3), subsequent to their first clinical and then molecular diagnosis of Clericuzio-type poikiloderma with neutropenia syndrome due to mutation of USB1gene. Patient 1 always expressed the most severe phenotype, while patients 2 and 3 showed an intermediate and mild phenotype, respectively, as observed since their first clinical evaluation. None of the patients developed skin cancer and/or myelodysplastic disorders considering the peripheral haematological findings. Lens opacity, never reported before, was found in two of the three patients. The long term follow-up observations confirm the stability over time of the pronounced intra-familial heterogeneity of clinical manifestations observed prior to and upon molecular diagnosis. We conclude that prolonged follow-up is an adjunct tool to monitor intra-familial variability of PN clinical spectrum which may favour surveillance of more serious complications of the disease among siblings, when a patient-specific clinical expressivity is present. Copyright © 2018. Published by Elsevier Masson SAS.

Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events

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Onyemaechi N. Okolo

2017-01-01

Full Text Available Objective and Importance. Cyclic neutropenia (CyN is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk of infection. Case. A 25-year-old male diagnosed with CyN, on G-CSF but worsening quality of life. Pretransplant investigations revealed ELANE mutation positive severe CyN along with familial Mediterranean fever (MEFV mutation. Intervention. Bone marrow transplantation as treatment for dual mutation (ELANE and MEFV mutation positive severe CyN. Conclusion. BMT may be considered as an alternative treatment for severe CyN in patients who are refractory to G-CSF. It is postulated that in our patient the combined mutations (CyN and MEFV may have contributed to the severity of this individual’s symptoms. We suggest CyN patients who present with severe symptoms have evaluation with ELANE mutation testing, Periodic Fever Syndromes Panel, and routine marrow assessment with FISH, conventional cytogenetics, and morphological evaluation for MDS/AML.

Management of Infection and Febrile Neutropenia in Patients with Solid Cancer.

Science.gov (United States)

Aguado, José María; Cruz, Juan Jesús; Virizuela, Juan Antonio; Aguilar, Manuela; Carmona, Alberto; Cassinello, Javier; Gudiol, Carlota; Jiménez Fonseca, Paula; Lizasoain, Manuel; Marco, Francesc; Ruiz, Isabel; Ruiz, Maribel; Salavert, Miguel; Vicente, David; Carratalà, Jordi

A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Farmacocinética y farmacodinamia de antimicrobianos: a propósito de pacientes con neutropenia y fiebre

OpenAIRE

Garzón, Javier R; Cuervo M, Sonia; Gómez R, Julio; Cortés, Jorge A

2011-01-01

La neutropenia febril es una complicación grave de la terapia antineoplásica que se presenta más frecuentemente en pacientes con neoplasias hematológicas, asociada a tasas elevadas de mortalidad. Uno de los factores descritos como causa de fracasos terapéuticos de la terapia antimicrobiana es la inadecuada concentración tisular de los antimicrobianos que a su vez se correlaciona con bajas concentraciones en el líquido intersticial en el caso de los fármacos hidrofílicos. En pacientes críticam...

Tax secretion from peripheral blood mononuclear cells and Tax detection in plasma of patients with human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis and asymptomatic carriers.

Science.gov (United States)

Medina, Fernando; Quintremil, Sebastián; Alberti, Carolina; Godoy, Fabián; Pando, María E; Bustamante, Andrés; Barriga, Andrés; Cartier, Luis; Puente, Javier; Tanaka, Yuetsu; Valenzuela, María A; Ramírez, Eugenio

2016-03-01

Human T-lymphotropic virus-type 1 (HTLV-1) is the etiologic agent of the neurologic disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax viral protein plays a critical role in viral pathogenesis. Previous studies suggested that extracellular Tax might involve cytokine-like extracellular effects. We evaluated Tax secretion in 18 h-ex vivo peripheral blood mononuclear cells (PBMCs) cultures from 15 HAM/TSP patients and 15 asymptomatic carriers. Futhermore, Tax plasma level was evaluated from other 12 HAM/TSP patients and 10 asymptomatic carriers. Proviral load and mRNA encoding Tax were quantified by PCR and real-time RT-PCR, respectively. Intracellular Tax in CD4(+)CD25(+) cells occurred in 100% and 86.7% of HAM/TSP patients and asymptomatic carriers, respectively. Percentage of CD4(+)CD25(+) Tax+, proviral load and mRNA encoding Tax were significantly higher in HAM/TSP patients. Western blot analyses showed higher secretion levels of ubiquitinated Tax in HAM/TSP patients than in asymptomatic carriers. In HTLV-1-infected subjects, Western blot of plasma Tax showed higher levels in HAM/TSP patients than in asymptomatic carriers, whereas no Tax was found in non-infected subjects. Immunoprecipitated plasma Tax resolved on SDS-PAGE gave two major bands of 57 and 48 kDa allowing identification of Tax and Ubiquitin peptides by mass spectrometry. Relative percentage of either CD4(+)CD25(+) Tax+ cells, or Tax protein released from PBMCs, or plasma Tax, correlates neither with tax mRNA nor with proviral load. This fact could be explained by a complex regulation of Tax expression. Tax secreted from PBMCs or present in plasma could potentially become a biomarker to distinguish between HAM/TSP patients and asymptomatic carriers. © 2015 Wiley Periodicals, Inc.

Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients

International Nuclear Information System (INIS)

Guy, Stephen D.; Tramontana, Adrian R.; Worth, Leon J.; Thursky, Karin A.; Slavin, Monica A.; Lau, Eddie; Hicks, Rodney J.; Seymour, John F.

2012-01-01

Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [ 18 F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38 C and neutrophil count <500 cells/μl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/μl (range 0-730 cells/μl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as ''true positives'' by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required. (orig.)

Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients

Energy Technology Data Exchange (ETDEWEB)

Guy, Stephen D.; Tramontana, Adrian R. [Western Health, Department of Infectious Diseases, Private Bag, Footscray, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia); Worth, Leon J.; Thursky, Karin A.; Slavin, Monica A. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Department of Infectious Diseases, Melbourne, Victoria (Australia); Lau, Eddie; Hicks, Rodney J. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, Victoria (Australia); Seymour, John F. [University of Melbourne, Parkville, Victoria (Australia); Peter MacCallum Cancer Centre, Department of Haematology, Melbourne, Victoria (Australia)

2012-08-15

Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [{sup 18} F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature {>=}38 C and neutrophil count <500 cells/{mu}l for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/{mu}l (range 0-730 cells/{mu}l). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as ''true positives'' by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required. (orig.)

Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

NARCIS (Netherlands)

de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma

Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

NARCIS (Netherlands)

de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

1999-01-01

The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma

The Effect of Recombinant Granulocyte Colony-Stimulating Factor on Oral and Periodontal Manifestations in a Patient with Cyclic Neutropenia: A Case Report

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Sergio Matarasso

2009-01-01

Full Text Available Cyclic Neutropenia (CN is characterized by recurrent infections, fever, oral ulcerations, and severe periodontitis as result of the reduced host defences. The previous studies have established the effectiveness of recombinant granulocyte colony-stimulating factor (GCSF to increase the number and the function of neutrophils in the peripheral blood in this disease. In a 20-year-old Caucasian female with a diagnosis of cyclic neutropenia, oral clinical examination revealed multiple painful ulcerations of the oral mucosa, poor oral hygiene conditions, marginal gingivitis, and moderate periodontitis. The patient received a treatment with G-CSF (Pegfilgrastim, 6 mg/month in order to improve her immunological status. Once a month nonsurgical periodontal treatment was carefully performed when absolute neutrophil count (ANC was ≥500/L. The treatment with G-CSF resulted in a rapid increase of circulating neutrophils that, despite its short duration, leaded to a reduction in infection related events and the resolution of the multiple oral ulcerations. The disappearance of oral pain allowed an efficacy nonsurgical treatment and a normal tooth brushing that determined a reduction of probing depth (PD≤4 mm and an improvement of the oral hygiene conditions recorded at 6-month follow-up.

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer

OpenAIRE

Burton, J.H.; Stanley, S.D.; Knych, H.K.; Rodriguez, C.O.; Skorupski, K.A.; Rebhun, R.B.

2015-01-01

Background Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)?approved products. Hypothesis/Objectives The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA?approved formulations of lomustine. Subsequent analyses aimed t...

Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia

NARCIS (Netherlands)

Aarts, M.J.; Peters, F.P.; Mandigers, C.M.P.W.; Dercksen, M.W.; Stouthard, J.M.; Nortier, H.J.; Laarhoven, H.W.M. van; Warmerdam, L.J. van; Wouw, A.J. van de; Jacobs, E.M.G.; Mattijssen, V.; Rijt, C.C. van der; Smilde, T.J.; Velden, A.W. van der; Temizkan, M.; Batman, E.; Muller, E.W.; Gastel, S.M. van; Borm, G.F.; Tjan-Heijnen, V.C.

2013-01-01

PURPOSE: Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF

Primary Granulocyte Colony-Stimulating Factor Prophylaxis During the First Two Cycles Only or Throughout All Chemotherapy Cycles in Patients With Breast Cancer at Risk for Febrile Neutropenia

NARCIS (Netherlands)

Aarts, Maureen J.; Peters, Frank P.; Mandigers, Caroline M.; Dercksen, M. Wouter; Stouthard, Jacqueline M.; Nortier, Hans J.; van Laarhoven, Hanneke W.; van Warmerdam, Laurence J.; van de Wouw, Agnes J.; Jacobs, Esther M.; Mattijssen, Vera; van der Rijt, Carin C.; Smilde, Tineke J.; van der Velden, Annette W.; Temizkan, Mehmet; Batman, Erdogan; Muller, Erik W.; van Gastel, Saskia M.; Borm, George F.; Tjan-Heijnen, Vivianne C. G.

2013-01-01

Purpose Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF

Prime-boost vaccination using DNA and whole inactivated virus vaccines provides limited protection against virulent feline immunodeficiency virus.

Science.gov (United States)

Dunham, Stephen P; Bruce, Jennifer; Klein, Dieter; Flynn, J Norman; Golder, Matthew C; MacDonald, Susan; Jarrett, Oswald; Neil, James C

2006-11-30

Protection against feline immunodeficiency virus (FIV) has been achieved using a variety of vaccines notably whole inactivated virus (WIV) and DNA. However protection against more virulent isolates, typical of those encountered in natural infections, has been difficult to achieve. In an attempt to improve protection against virulent FIV(GL8), we combined both DNA and WIV vaccines in a "prime-boost" approach. Thirty cats were divided into four groups receiving vaccinations and one unvaccinated control group. Following viral challenge, two vaccinated animals, one receiving DNA alone and one the prime-boost vaccine remained free of viraemia, whilst all controls became viraemic. Animals vaccinated with WIV showed apparent early enhancement of infection at 2 weeks post challenge (pc) with higher plasma viral RNA loads than control animals or cats immunised with DNA alone. Despite this, animals vaccinated with WIV or DNA alone showed significantly lower proviral loads in peripheral blood mononuclear cells and mesenteric lymph node cells, whilst those receiving the DNA-WIV prime-boost vaccine showed significantly lower proviral loads in PBMC, than control animals, at 35 weeks pc. Therefore both DNA and WIV vaccines conferred limited protection against viral challenge but the combination of WIV and DNA in a prime-boost approach appeared to offer no significant advantage over either vaccine alone.

Tratamiento antibiótico oral versus intravenosopara la neutropenia febril en pacientes con cáncer

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2014-05-01

Conclusiones de los autores: Según los datos actuales, el tratamiento oral es una opción aceptable al tratamiento con antibióticos intravenosos en los pacientes con cáncer con neutropenia febril (se excluye a los pacientes con leucemia aguda hemodinámicamente estables, sin insuficiencia orgánica y sin neumonía, infección de una vía central o infección grave de partes blandas. El IC amplio en la mortalidad permite el uso actual del tratamiento oral en grupos de pacientes con bajo riesgo de mortalidad esperado y los estudios de investigación adicionales deben tener como objetivo aclarar la definición de pacientes con bajo riesgo.

{sup 18}F-FDG PET/CT for diagnosing infectious complications in patients with severe neutropenia after intensive chemotherapy for haematological malignancy or stem cell transplantation

Energy Technology Data Exchange (ETDEWEB)

Vos, Fidel J.; Kullberg, Bart-Jan; Bleeker-Rovers, Chantal P. [Radboud University Nijmegen Medical Centre, Department of Internal Medicine, PO Box 9101, Nijmegen (Netherlands); Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Donnelly, J.P.; Blijlevens, Nicole M.A. [Radboud University Nijmegen Medical Centre, Department of Hematology, Nijmegen (Netherlands); Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

2012-01-15

Between 30 and 50% of febrile neutropenic episodes are accounted for by infection. C-reactive protein (CRP) is a nonspecific parameter for infection and inflammation but might be employed as a trigger for diagnosis. The aim of the study was to evaluate whether {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT can be used to detect inflammatory foci in neutropenic patients with elevated CRP and whether it helps to direct treatment. Twenty-eight consecutive patients with neutropenia as a result of intensive chemotherapy for haematological malignancies or myeloablative therapy for haematopoietic stem cell transplantation were prospectively included. {sup 18}F-FDG PET/CT was added to the regular diagnostic workup once the CRP level rose above 50 mg/l. Pathological FDG uptake was found in 26 of 28 cases despite peripheral neutrophil counts less than 0.1 x 10{sup -9}/l in 26 patients: in the digestive tract in 18 cases, around the tract of the central venous catheter (CVC) in 9 and in the lungs in 7 cases. FDG uptake in the CVC tract was associated with coagulase-negative staphylococcal bacteraemia (p < 0.001) and deep venous thrombosis (p = 0.002). The number of patients having Streptococcus mitis bacteraemia appeared to be higher in patients with grade 3 oesophageal FDG uptake (p = 0.08). Pulmonary FDG uptake was associated with the presence of invasive fungal disease (p = 0.04). {sup 18}F-FDG PET/CT scanning during chemotherapy-induced febrile neutropenia and increased CRP is able to detect localized foci of infection and inflammation despite the absence of circulating neutrophils. Besides its potential role in detecting CVC-related infection during febrile neutropenia, the high negative predictive value of {sup 18}F-FDG PET/CT is important for avoiding unnecessary diagnostic tests and therapy. (orig.)

Bacteriemia asociada a neutropenia febril en pacientes hemato-oncológicos, su espectro bacteriano y patrón de susceptibilidad antibiótica

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Lucy Johanna Hinojosa-Andía

2014-01-01

Full Text Available La neutropenia febril es una de las complicaciones más frecuentes y de mayor morbilidad y mortalidad en los pacientes hematológicos. Su documentación microbiológica es una herramienta invaluable para el manejo; sin embargo, la cambiante tendencia en etiología de la bacteriemia y el patrón de susceptibilidad antimicrobiana comprometen la tasa de respuesta a los esquemas de tratamiento empírico. Objetivo: Determinar la etiología de bacteriemia en pacientes con neoplasias hematológicas y neutropenia febril, su patrón de susceptibilidad antimicrobiana y el grado de resistencia vigente a los medicamentos comúnmente utilizados en esquemas empíricos de manejo. Material y métodos: Se revisaron datos microbiológicos de las historias clínicas de pacientes hematológicos, hospitalizados en el HNERM entre diciembre 2010 y marzo 2012; que habían presentado neutropenia febril y bacteriemia concurrente. La información se analizó con el paquete estadístico STATA v. 10 y se empleó estadística descriptiva. Resultados: La bacteriemia fue predominantemente por bacterias gram negativas (75,9% y post consolidación de LMA con Ara-C por gram positivas (63,6%. La mortalidad de pacientes post reinducción con bacteriemia fue 75% y se asoció a Klebsiella pneumoniae BLEE+ en 31,2%. Conclusiones: Gérmenes gram negativos fueron la etiología más frecuente de bacteriemia en la población estudiada, particularmente en pacientes que recibieron quimioterapia de reinducción, donde se vio la mayor frecuencia de bacteriemia con mayor resistencia y asociados a mayor mortalidad. Posterior a quimioterapia de consolidación con Citarabina en altas dosis para LMA, resultó más frecuente la bacteriemia a gram positivos. Carbapenems y Amoxicilina/Clavulánico mostraron considerable menor resistencia que cefalosporinas y fluoroquinolonas.

Inherited biallelic CSF3R mutations in severe congenital neutropenia.

Science.gov (United States)

Triot, Alexa; Järvinen, Päivi M; Arostegui, Juan I; Murugan, Dhaarini; Kohistani, Naschla; Dapena Díaz, José Luis; Racek, Tomas; Puchałka, Jacek; Gertz, E Michael; Schäffer, Alejandro A; Kotlarz, Daniel; Pfeifer, Dietmar; Díaz de Heredia Rubio, Cristina; Ozdemir, Mehmet Akif; Patiroglu, Turkan; Karakukcu, Musa; Sánchez de Toledo Codina, José; Yagüe, Jordi; Touw, Ivo P; Unal, Ekrem; Klein, Christoph

2014-06-12

Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frameshifts and premature stop codons (NM_000760.3:c.948_963del, NP_000751.1:p.Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis. © 2014 by The American Society of Hematology.

Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.

Science.gov (United States)

Freeman, Joshua T; Elinder-Camburn, Anna; McClymont, Catherine; Anderson, Deverick J; Bilkey, Mary; Williamson, Deborah A; Berkahn, Leanne; Roberts, Sally A

2013-01-01

We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.

MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.

Science.gov (United States)

Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G

2016-11-03

Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

Genetic modelling of PIM proteins in cancer: proviral tagging, cooperation with oncogenes, tumor suppressor genes and carcinogens.

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Enara eAguirre

2014-05-01

Full Text Available The PIM proteins, which were initially discovered as proviral insertion sites in Moloney murine leukemia virus infection, are a family of highly homologous serine/threonine kinases that have been reported to be overexpressed in hematological malignancies and solid tumors. The PIM proteins have also been associated with metastasis and overall treatment responses and implicated in the regulation of apoptosis, metabolism, the cell cycle, and homing and migration, which makes these proteins interesting targets for anticancer drug discovery. The use of retroviral insertional mutagenesis and refined approaches such as complementation tagging has allowed the identification of myc, pim and a third group of genes (including bmi1 and gfi1 as complementing genes in lymphomagenesis. Moreover, mouse modeling of human cancer has provided an understanding of the molecular pathways that are involved in tumor initiation and progression at the physiological level. In particular, genetically modified mice have allowed researchers to further elucidate the role of each of the Pim isoforms in various tumor types. PIM kinases have been identified as weak oncogenes because experimental overexpression in lymphoid tissue, prostate and liver induces tumors at a relatively low incidence and with a long latency. However, very strong synergistic tumorigenicity between Pim1/2 and c-Myc and other oncogenes has been observed in lymphoid tissues. Mouse models have also been used to study whether the inhibition of specific PIM isoforms is required to prevent carcinogen-induced sarcomas, indicating that the absence of Pim2 and Pim3 greatly reduces sarcoma growth and bone invasion; the extent of this effect is similar to that observed in the absence of all 3 isoforms. This review will summarize some of the animal models that have been used to understand the isoform-specific contribution of PIM kinases to tumorigenesis.

The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

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Hamadah, Aziz; Schreiber, Yoko; Toye, Baldwin; McDiarmid, Sheryl; Huebsch, Lothar; Bredeson, Christopher; Tay, Jason

2012-01-01

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program. PMID:23029441

Complication-related removal of totally implantable venous access port systems: Does the interval between placement and first use and the neutropenia-inducing potential of chemotherapy regimens influence their incidence? A four-year prospective study of 4045 patients.

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Kakkos, A; Bresson, L; Hudry, D; Cousin, S; Lervat, C; Bogart, E; Meurant, J P; El Bedoui, S; Decanter, G; Hannebicque, K; Regis, C; Hamdani, A; Penel, N; Tresch-Bruneel, E; Narducci, F

2017-04-01

Totally implantable venous access port systems are widely used in oncology, with frequent complications that sometimes necessitate device removal. The aim of this study is to investigate the impact of the time interval between port placement and initiation of chemotherapy and the neutropenia-inducing potential of the chemotherapy administered upon complication-related port removal. Between January 2010 and December 2013, 4045 consecutive patients were included in this observational, single-center prospective study. The chemotherapy regimens were classified as having a low (20%) risk for inducing neutropenia. The overall removal rate due to complications was 7.2%. Among them, port-related infection (2.5%) and port expulsion (1%) were the most frequent. The interval between port insertion and its first use was shown to be a predictive factor for complication-related removal rates. A cut-off of 6 days was statistically significant (p = 0.008), as the removal rate for complications was 9.4% when this interval was 0-5 days and 5.7% when it was ≥6 days. Another factor associated with port complication rate was the neutropenia-inducing potential of the chemotherapy regimens used, with removal for complications involved in 5.5% of low-risk regimens versus 9.4% for the intermediate- and high-risk regimens (p = 0.003). An interval of 6 days between placement and first use of the port reduces the removal rate from complications. The intermediate- and high-risk for neutropenia chemotherapy regimens are related to higher port removal rates from complications than low-risk regimens. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Comparative Efficacy of Feline Leukemia Virus (FeLV) Inactivated Whole-Virus Vaccine and Canarypox Virus-Vectored Vaccine during Virulent FeLV Challenge and Immunosuppression.

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Patel, M; Carritt, K; Lane, J; Jayappa, H; Stahl, M; Bourgeois, M

2015-07-01

Four vaccines for feline leukemia virus (FeLV) are available in the United States. This study's purpose was to compare the efficacy of Nobivac feline 2-FeLV (an inactivated, adjuvanted whole-virus vaccine) and PureVax recombinant FeLV (a live, canarypox virus-vectored vaccine) following FeLV challenge. Cats were vaccinated at 9 and 12 weeks with Nobivac feline 2-FeLV (group A, n = 11) or PureVax recombinant FeLV (group B, n = 10). Group C (n = 11) comprised unvaccinated controls. At 3 months postvaccination, cats were immunosuppressed and challenged with FeLV-A/61E. The outcomes measured were persistent antigenemia at 12 weeks postchallenge (PC) and proviral DNA and viral RNA at 3 to 9 weeks PC. Persistent antigenemia was observed in 0 of 11 cats in group A, 5 of 10 cats in group B, and 10 of 11 cats in group C. Group A was significantly protected compared to those in groups B (P 0.063). The preventable fraction was 100% for group A and 45% for group B. At 9 weeks PC, proviral DNA and viral RNA were detected 1 of 11 cats in group A, 6 of 10 cats in group B, and 9 of 11 cats in group C. Nucleic acid loads were significantly lower in group A than in group C (P feline 2-FeLV-vaccinated cats were fully protected against persistent antigenemia and had significantly smaller amounts of proviral DNA and plasma viral RNA loads than PureVax recombinant FeLV-vaccinated cats and unvaccinated controls. Copyright © 2015, Patel et al.

Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

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Kontny Udo

2008-03-01

Full Text Available Abstract Background Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90% and specificity (85%. Conclusion These findings may have clinical implications for risk-based antimicrobial treatment strategies.

Effect of benign familial neutropenia on the periodontium of Yemenite Jews.

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Stabholz, A; Soskolne, V; Machtei, E; Or, R; Soskolne, W A

1990-01-01

The purpose of this study was to compare the periodontal status of Yemenite Jews with and without benign familial neutropenia (BFN). Thirty-four volunteers were examined at baseline and after 3 years. Plaque index (PlI), bleeding index (BI) probing depth (PD), and attachment levels (AL) were recorded. Differential blood counts were done on at least three occasions during the study. Volunteers with at least one count of less than 2000 neutrophils were considered neutropenic. The majority of patients received oral hygiene instructions and scaling at the initial visit. During the study there was a significant drop in PlI (P less than 0.01) and BI (P less than 0.05). At baseline the BFN and non-BFN volunteers had similar PlI, but the BI was significantly greater in the BFN group. At follow-up, there was a significantly greater number of teeth with pockets greater than or equal to 6 mm in the BFN group (P less than 0.05). These results indicate that volunteers with BFN, a phenomenon that has not previously been associated with any pathology, are more susceptible to gingival inflammation and attachment loss than unaffected volunteers and that they respond more favorably to an improvement in oral hygiene.

Loads and loads and loads: The influence of prospective load, retrospective load, and ongoing task load in prospective memory

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Beat eMeier

2015-06-01

Full Text Available In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load can affect prospective memory performance. The existence of multiple target events increases prospective load and adding complexity to the to-be-remembered action increases retrospective load. In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of prospective load on costs in the ongoing task for categorical targets (Experiment 2, but not for specific targets (Experiment 1. Retrospective load and ongoing task load both affected remembering the retrospective component of the prospective memory task. We suggest that prospective load can enhance costs in the ongoing task due to additional monitoring requirements. Retrospective load and ongoing task load seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.

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Castagnola, Elio; Caviglia, Ilaria; Pescetto, Luisa; Bagnasco, Francesca; Haupt, Riccardo; Bandettini, Roberto

2015-01-01

Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each β-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to β-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to β-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.

Analisi Costo-Efficacia di Amfotericina B Liposomiale (L-AmB versus Amfotericina B Complesso Lipidico (ABLC nel trattamento empirico della neutropenia febbrile

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Mario Eandi

2005-12-01

Full Text Available Current international guidelines for the management of immuno-compromised patients with febrile neutropenia recommend a systemic antimicrobial therapy if fever hasn’t receded after three days of antibiotic treatment. Amphotericin B remains the gold standard because of its broad spectrum fungicidal action and minimal resistance development risk. Nonetheless, therapeutic use of the standard formulation, Amphotericin B deoxycholate, is limited by its toxicity, especially on the kidneys. To counteract this, amphotericin B has been encapsulated in liposomes, a process which reduces its toxicity and allows higher doses to be given. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD, amB lipid complex (ABLC, and liposomal amB (L-AmB. These lipid formulations differ in pharmacodynamics and pharmacokinetics, and can’t therefore be considered interchangeable. Besides, they are more expensive than Amphotericin B deoxycholate. Aim of the study is to perform a cost/effectiveness analysis (CEA comparing L-AmB (3mg/kg/die or 5mg/kg/ die and ABLC (5mg/kg/die as first-line antimicrobial empirical treatments in immuno-compromised patients with febrile neutropenia resistant to broad spectrum antibiotics. Secondly, we present a cost-minimization analysis (CMA of the considered alternatives, assuming the same efficacy for all treatments. At the end we value the principal cost items from the point of view of the Italian Health Service, with a particular focus on the economic burden caused by adverse reactions.

Prevalidation of a model for predicting acute neutropenia by colony forming unit granulocyte/macrophage (CFU-GM) assay.

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Pessina, A; Albella, B; Bueren, J; Brantom, P; Casati, S; Gribaldo, L; Croera, C; Gagliardi, G; Foti, P; Parchment, R; Parent-Massin, D; Sibiril, Y; Van Den Heuvel, R

2001-12-01

This report describes an international prevalidation study conducted to optimise the Standard Operating Procedure (SOP) for detecting myelosuppressive agents by CFU-GM assay and to study a model for predicting (by means of this in vitro hematopoietic assay) the acute xenobiotic exposure levels that cause maximum tolerated decreases in absolute neutrophil counts (ANC). In the first phase of the study (Protocol Refinement), two SOPs were assessed, by using two cell culture media (Test A, containing GM-CSF; and Test B, containing G-CSF, GM-CSF, IL-3, IL-6 and SCF), and the two tests were applied to cells from both human (bone marrow and umbilical cord blood) and mouse (bone marrow) CFU-GM. In the second phase (Protocol Transfer), the SOPs were transferred to four laboratories to verify the linearity of the assay response and its interlaboratory reproducibility. After a further phase (Protocol Performance), dedicated to a training set of six anticancer drugs (adriamycin, flavopindol, morpholino-doxorubicin, pyrazoloacridine, taxol and topotecan), a model for predicting neutropenia was verified. Results showed that the assay is linear under SOP conditions, and that the in vitro endpoints used by the clinical prediction model of neutropenia are highly reproducible within and between laboratories. Valid tests represented 95% of all tests attempted. The 90% inhibitory concentration values (IC(90)) from Test A and Test B accurately predicted the human maximum tolerated dose (MTD) for five of six and for four of six myelosuppressive anticancer drugs, respectively, that were selected as prototype xenobiotics. As expected, both tests failed to accurately predict the human MTD of a drug that is a likely protoxicant. It is concluded that Test A offers significant cost advantages compared to Test B, without any loss of performance or predictive accuracy. On the basis of these results, we proposed a formal Phase II validation study using the Test A SOP for 16-18 additional

Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease.

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Ancliff, P J; Gale, R E; Liesner, R; Hann, I M; Linch, D C

2001-11-01

Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Subsequently, autosomal dominant and sporadic forms of the disease have been recognized. All forms are manifest by persistent severe neutropenia and recurrent bacterial infection. In contrast, cyclical hematopoiesis is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, linkage analysis on 13 affected pedigrees identified chromosome 19p13.3 as the likely position for mutations in cyclical hematopoiesis. Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied. Further work also demonstrated mutations in ELA2 in sporadic and autosomal dominant SCN. However, all mutations described to date are heterozygous and thus appear to act in a dominant fashion, which is inconsistent with an autosomal recessive disease. Therefore, the current study investigated whether mutations in ELA2 could account for the disease phenotype in classical autosomal recessive SCN and in the sporadic and autosomal dominant types. All 5 exons of ELA2 and their flanking introns were studied in 18 patients (3 autosomal recessive, 5 autosomal dominant [from 3 kindreds], and 10 sporadic) using direct automated sequencing. No mutations were found in the autosomal recessive families. A point mutation was identified in 1 of 3 autosomal dominant families, and a base substitution was identified in 8 of 10 patients with the sporadic form, though 1 was subsequently shown to be a low-frequency polymorphism. These results suggest that mutations in ELA2 are not responsible for classical autosomal recessive Kostmann syndrome but provide further evidence for the role of ELA2 in SCN.

High-risk febrile neutropenia in Auckland 2003-2004: the influence of the microbiology laboratory on patient treatment and the use of pathogen-specific therapy.

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Ritchie, S; Palmer, S; Ellis-Pegler, R

2007-01-01

International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result. The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy. Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication

International Nuclear Information System (INIS)

Gabet, Anne-Sophie; Moules, Vincent; Sibon, David; Nass, Catharie C.; Mortreux, Franck; Mauclere, Philippe; Gessain, Antoine; Murphy, Edward L.; Wattel, Eric

2006-01-01

As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population

Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients

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Addai, Amma B.; Pandhare, Jui; Paromov, Victor; Mantri, Chinmay K.; Pratap, Siddharth; Dash, Chandravanu

2015-01-01

Epidemiologic studies suggest that cocaine abuse worsens HIV-1 disease progression. Increased viral load has been suggested to play a key role for the accelerated HIV disease among cocaine-abusing patients. The goal of this study was to investigate whether cocaine enhances proviral DNA integration as a mechanism to increase viral load. We infected CD4+ T cells that are the primary targets of HIV-1 in vivo and treated the cells with physiologically relevant concentrations of cocaine (1 µM–100 µM). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated that cocaine from 1 µM through 50 µM increased HIV-1 integration in CD4+ T cells in a dose-dependent manner. As integration can be modulated by several early postentry steps of HIV-1 infection, we examined the direct effects of cocaine on viral integration by in vitro integration assays by use of HIV-1 PICs. Our data illustrated that cocaine directly increases viral DNA integration. Furthermore, our MS analysis showed that cocaine is able to enter CD4+ T cells and localize to the nucleus-. In summary, our data provide strong evidence that cocaine can increase HIV-1 integration in CD4+ T cells. Therefore, we hypothesize that increased HIV-1 integration is a novel mechanism by which cocaine enhances viral load and worsens disease progression in drug-abusing HIV-1 patients. PMID:25691383

Flow cytometric analysis of lymphocyte subset in patients with neutropenia among atomic bomb survivors

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Imamura, Nobutaka; Kimura, Akiro [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

1998-12-01

In 51 patients (atomic bomb survivors 50, unexposed persons 1) who have had neutropenia for two years or more under indistinct cause, cell surface antigen was analyzed by flow cytometry. Twenty-nine cases of survivors were diagnosed as NK cell leukemia or NK cell cytosis because analysis data showed CD3(-), CD56(+) and CD57(+/-). Six cases were diagnosed as NK like T cell hypercytosis because analysis data showed CD3(+), CD56(+/-) and CD57(+). As for 15 cases, CD56(+) cell number was in range of 15.96{+-}5.35 of a normal person, and no relation with NK cell was recognized. But, CD4/CD8 ratio was higher than 2.1, and gain of T helper cell was recognized. One unexposed persons was diagnosed as chronic NK cell leukemia because analysis data showed CD3(-), CD56(+) and CD57(+). Anti-neutrophil antibody wasn't recognized. Cytotoxic activity for K562 and Raji cell line showed high value compared with that of a normal person. Epstein Barr virus wasn't detected. (K.H.)

Study design: two long-term observational studies of the biosimilar filgrastim Nivestim™ (Hospira filgrastim) in the treatment and prevention of chemotherapy-induced neutropenia

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Kamioner, Didier; Fruehauf, Stefan; Maloisel, Fréderic; Cals, Laurent; Lepretre, Stéphane; Berthou, Christian

2013-01-01

Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen ® . Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world’ clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy. Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with

Suppression of HTLV-1 transcription by SIRT1 deacetylase

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Tang, HMV; Jin, D; Gao, W; Chan, CP; Iha, H; Yuen, KS

2015-01-01

Infection with HTLV-1 causes adult T-cell leukemia and tropical spastic paraparesis in different subsets of infected people. Treatments for HTLV-1-associated diseases are unspecific and unsatisfactory. Prophylactic measures have not been developed. Although HTLV-1 pathogenesis involves multiple stages and factors, high proviral load has been singled out as a major risk factor which predicts disease. HTLV-1 encodes Tax transactivator that potently activates transcription from viral long termin...

Microbiology and mortality of pediatric febrile neutropenia in El Salvador.

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Gupta, Sumit; Bonilla, Miguel; Gamero, Mario; Fuentes, Soad L; Caniza, Miguela; Sung, Lillian

2011-05-01

Febrile neutropenia (FN) and infection-related mortality are major problems for children with cancer in low-income countries. Identifying predictors for adverse outcome of FN in low-income countries permits targeted interventions. We describe the nature and predictors of microbiologically documented infection (MDI) and mortality of FN in children with cancer in El Salvador. We examined Salvadoran pediatric oncology patients admitted with FN over a 1-year period. Data were collected prospectively. Demographic, treatment, and admission-related variables were examined as predictors of outcomes. Hundred six FN episodes among 85 patients were included. Twenty-three of 106 episodes (22%) were microbiologically documented; 13 of 106 episodes (12%) resulted in death. Gram-positive and gram-negative organisms were isolated in 14 of 23 and 11 of 23 specimens; polymicrobial infections were common (11 of 23 episodes of MDI). Older age decreased the MDI risk [odds ratio (OR) per year=0.87, 95% confidence interval (CI), 0.75-0.99; P=0.04] while increasing number of days since the last chemotherapy increased the risk (OR=1.03 per day, 95% CI, 1.01-1.04; P=0.002). Pneumonia diagnosed either clinically (OR=6.6, 95% CI, 1.8-30.0; P=0.005) or radiographically (OR=5.5, 95% CI, 1.7-18.1; P=0.005) was the only predictor of mortality. In El Salvador, polymicrobial infections were common. Pneumonia at admission identified children with FN at high risk of death; these children may benefit from targeted interventions.

Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

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Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

2010-07-01

Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

Filgrastim as a Rescue Therapy for Persistent Neutropenia in a Case of Dengue Hemorrhagic Fever with Acute Respiratory Distress Syndrome and Myocarditis

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Desh Deepak

2011-01-01

Full Text Available Pathogenesis of dengue involves suppression of immune system leading to development of characteristic presentation of haematological picture of thrombocytopenia and leucopenia. Sometimes, this suppression in immune response is responsible for deterioration in clinical status of the patient in spite of all specific and supportive therapy. Certain drugs like steroids are used for rescue therapy in conditions like sepsis. We present a novel use of filgrastim as a rescue therapy in a patient with dengue hemorrhagic fever (DHF with acute respiratory distress syndrome (ARDS, myocarditis, and febrile neutropenia and not responding to standard management.

Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory

Science.gov (United States)

Meier, Beat; Zimmermann, Thomas D.

2015-01-01

In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially. PMID:26082709

Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory.

Science.gov (United States)

Meier, Beat; Zimmermann, Thomas D

2015-01-01

In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

Game of clones: the genomic evolution of severe congenital neutropenia.

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Touw, Ivo P

2015-01-01

Severe congenital neutropenia (SCN) is a genetically heterogeneous condition of bone marrow failure usually diagnosed in early childhood and characterized by a chronic and severe shortage of neutrophils. It is now well-established that mutations in HAX1 and ELANE (and more rarely in other genes) are the genetic cause of SCN. In contrast, it has remained unclear how these mutations affect neutrophil development. Innovative models based on induced pluripotent stem cell technology are being explored to address this issue. These days, most SCN patients receive life-long treatment with granulocyte colony-stimulating factor (G-CSF, CSF3). CSF3 therapy has greatly improved the life expectancy of SCN patients, but also unveiled a high frequency of progression toward myelodysplastic syndrome (MDS) and therapy refractory acute myeloid leukemia (AML). Expansion of hematopoietic clones with acquired mutations in the gene encoding the G-CSF receptor (CSF3R) is regularly seen in SCN patients and AML usually descends from one of these CSF3R mutant clones. These findings raised the questions how CSF3R mutations affect CSF3 responses of myeloid progenitors, how they contribute to the pre-leukemic state of SCN, and which additional events are responsible for progression to leukemia. The vast (sub)clonal heterogeneity of AML and the presence of AML-associated mutations in normally aged hematopoietic clones make it often difficult to determine which mutations are responsible for the leukemic process. Leukemia predisposition syndromes such as SCN are unique disease models to identify the sequential acquisition of these mutations and to interrogate how they contribute to clonal selection and leukemic evolution. © 2015 by The American Society of Hematology. All rights reserved.

Evaluation of serum galactomannan enzyme immunoassay at two different cut-offs for the diagnosis of invasive aspergillosis in patients with febrile neutropenia

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Ritin Mohindra

2017-01-01

Full Text Available Background: Invasive aspergillosis (IA is an increasingly common and fatal opportunistic fungal infection in patients with haematological diseases. Early diagnosis is difficult as mycological culture techniques have low sensitivity and the radiological tools have low specificity. Galactomannan enzyme immunoassay (GEI detects galactomannan in the human serum with a reported sensitivity and specificity between 30% and 100%. Aims: The aim of this study was to analyse the role of GEI in diagnosis of IA in patients with febrile neutropenia and to evaluate the role of GEI in the diagnosis of IA as per the revised (2008 European Organization for Research and Treatment of Cancer–Mycoses Study Group (EORTC–MSG criteria at two different optical density (OD cut-offs of 0.5 and 1.0. Setting: This prospective study was conducted in Safdarjung Hospital, New Delhi, India. Methods: GEI testing was performed in adult patients of febrile neutropenia with evidence of IA. Results at two different OD indices (ODIs of 0.5 and 1.0 were analysed. The evaluation of the diagnostic parameter, that is, GEI was measured in terms of sensitivity, specificity and positive and negative predictive value and was validated with the revised (2008 EORTC–MSG diagnostic criteria of IA. Results: One hundred and eleven patients had evidence of IA, of which 79 patients were GEI positive when cut-off ODI was 0.5, whereas with cut-off ODI 1.0, 55 patients were GEI positive. Conclusion: ODI of 1.0 should be considered as positive while in patients with OD between 0.5 and 1.0, repeat sampling from the patient is recommended.

Relationship between ELA2 gene mutations, clinical and laboratory parameters in severe congenital and cyclic neutropenia

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Farhoodi A

2007-09-01

Full Text Available   Background: Mutations of ELA2, the gene encoding neutrophil elastase (NE are known to be associated with cyclic neutropenia (CN and severe congenital neutropenia (SCN. However, high variability of these mutations has been reported. This study was designed to describe the analysis of the ELA2 gene, clinical manifestations and demographic characteristics in patients with CN and SCN.Methods: A series of 21 patients with CN or SCN were selected, based on SCINR criteria, from the immunology ward of the Pediatric Medicine Center, Tehran, Iran, from March 2004 to August 2005. The ELA2 gene, isolated from blood samples, was analyzed using RT-PCR and automated capillary sequencing. Informed consent was obtained under the tenets of the Helsinki Declaration and the Ethical Committee of the Tehran University of Medical Sciences.Results: Kostmann's syndrome and CN was diagnosed in three and 18 patients respectively. Of all the patients, one or two mutations were found in 18 cases (85.7%, including all three patients with SCN and 15 of the patients with CN. Exons two and four had the most mutations (eight and seven cases, respectively. Seven patients had double mutations in two distinct exons. Overall, 16 different mutations were found. At the time of presentation, the mean age of patients was 13.4 ±17.6 months, ranging from one month to seven years. Overall, 61.9% of patients had consanguineous parents. The mean absolute neutrophil count was 830.5 ±419.4 (150-2000/mm3. On average, each patient had been admitted to the hospital 2.2 ±1.6 times. The neutrophil counts of the SCN patients were significantly higher than those of the CN patients. However, there was no significant difference in the neutrophil counts between patients with mutations and those without mutations. All patients with SCN had two or more infectious complications, although the prevalence of infectious or non-infectious complications did not correlate with ELA2 mutations or the

Determinación de la profundidad y duración de la neutropenia inducida por ciclofosfamida en ratones hembras MPF de la cepa Udea: ICR(cd-1

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Omar Vesga

2004-02-01

Full Text Available

El modelo murino de infección del muslo emplea animales neutropénicos para poder determinar la eficacia intrínseca de los antibióticos in vivo. Sin embargo, no se ha definido el número de neutrófilos y la duración de la neutropenia inducida por ciclofosfamida (CFM intraperitoneal (IP, información fundamental
para valorar la reproducibilidad y confiabilidad del modelo.

Neutropenia Prediction Based on First-Cycle Blood Counts Using a FOS-3NN Classifier

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Elize A. Shirdel

2011-01-01

Full Text Available Background. Delivery of full doses of adjuvant chemotherapy on schedule is key to optimal breast cancer outcomes. Neutropenia is a serious complication of chemotherapy and a common barrier to this goal, leading to dose reductions or delays in treatment. While past research has observed correlations between complete blood count data and neutropenic events, a reliable method of classifying breast cancer patients into low- and high-risk groups remains elusive. Patients and Methods. Thirty-five patients receiving adjuvant chemotherapy for early-stage breast cancer under the care of a single oncologist are examined in this study. FOS-3NN stratifies patient risk based on complete blood count data after the first cycle of treatment. All classifications are independent of breast cancer subtype and clinical markers, with risk level determined by the kinetics of patient blood count response to the first cycle of treatment. Results. In an independent test set of patients unseen by FOS-3NN, 19 out of 21 patients were correctly classified (Fisher’s exact test probability P<0.00023 [2 tailed], Matthews’ correlation coefficient +0.83. Conclusions. We have developed a model that accurately predicts neutropenic events in a population treated with adjuvant chemotherapy in the first cycle of a 6-cycle treatment.

Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia.

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Malcov, Mira; Reches, Adi; Ben-Yosef, Dalit; Cohen, Tania; Amit, Ami; Dgany, Orly; Tamary, Hannah; Yaron, Yuval

2010-03-01

Severe congenital neutropenia is an inherited disease characterized by low peripheral blood neutrophils, amenable to bone marrow transplantation. Genetic analysis in the family here described detected a ELA2 splice-site mutation in the affected child and also in his asymptomatic father. The parents requested preimplantation genetic diagnosis (PGD), coupled with HLA matching, to obtain a suitable bone marrow donor for the affected child. A PGD protocol was developed, based on multiplex nested PCR for direct analysis of the ELA2 mutation, flanking polymorphic markers and HLA typing. The amplification efficiency of the mutation was > 90% in single leukocytes from the affected child but only 67% in the father. Analysis of single haploid sperm cells from the father demonstrated three different sperm-cell populations: (1) sperm cells harboring the ELA2 mutation on the 'affected' haplotype, (2) sperm cells without the ELA2 mutation on the 'normal' haplotype, and (3) sperm cells without the ELA2 mutation on the 'affected' haplotype. These data demonstrate that the ELA2 mutation in the father occurred de novo during his embryonic development, resulting in somatic as well as germ-line mosaicism. This conclusion was also taken into consideration when PGD was performed. Copyright (c) 2010 John Wiley & Sons, Ltd.

A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial.

Science.gov (United States)

Blackwell, Kimberly; Donskih, Roman; Jones, C Michael; Nixon, Allen; Vidal, Maria J; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

2016-07-01

Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2)) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count prevention of neutropenia in patients with early-stage breast cancer receiving TAC. The granulocyte colony-stimulating factor pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. Biosimilars are biologics with similar quality, safety, and efficacy to a reference product that may increase the affordability of treatment compared with their reference compounds. There are currently no approved biosimilars of pegfilgrastim in highly regulated markets. No previous phase III studies have been performed with LA-EP2006. PROTECT-2 was conducted to confirm the similarity of the proposed biosimilar LA-EP2006 to pegfilgrastim. Biosimilar pegfilgrastim (LA-EP2006) may benefit oncology patients by offering increased access to biological treatments that may improve clinical outcomes. This means that patients could potentially be treated prophylactically with biologics rather than only after complications have occurred. ©AlphaMed Press.

Neutropenia febril en el trópico: una descripción de los hallazgos clínicos y microbiológicos y el impacto de la terapia inapropiada que utilizan en un centro de referencia oncológica en Colombia

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Jorge A. Cortés

2013-03-01

Full Text Available Introducción. La neutropenia febril es una complicación frecuente de la quimioterapia para las neoplasias hematológicas. Se dispone de escasa información de sus complicaciones infecciosas en nuestro medio. Objetivo. Evaluar las características clínicas y microbiológicas de pacientes con neutropenia febril, así como su resultado clínico en una institución de referencia oncológica en Colombia. Materiales y métodos. Se conformó prospectivamente una serie de casos con pacientes con enfermedad oncológica confirmada, que consultaron o presentaron neutropenia febril durante la hospitalización. Se excluyeron aquellos con enfermedad hematológica benigna. Se recolectaron datos sobre variables demográficas, microbiológicas, clínicas, de tratamiento y de resultado de los pacientes. Se llevaron a cabo un análisis univariado y uno multivariado, con la mortalidad como resultado. Resultados. Se identificaron 130 episodios de neutropenia febril en 104 pacientes, con una edad media de 19 años y 53 % masculinos. El 86 % de los episodios ocurrieron en pacientes con alteraciones hematológicas. Se demostró infección en 65 % de los casos: 41 % con un foco infeccioso localizado y 27,7 % con bacteriemia. Los principales focos infecciosos se localizaron en el torrente sanguíneo, el aparato urinario, el sistema gastrointestinal, la piel y los tejidos blandos. De los aislamientos microbiológicos, 46,4 % fueron bacilos Gram negativos, 38,4 %, cocos Gram positivos, 9 %, hongos y, 7,1%, parásitos. La mortalidad global fue de 7,7 %. En el análisis multivariado la utilización de un tratamiento empírico apropiado se correlacionó con una menor mortalidad, de forma independiente (OR=0,17; IC95% 0,034-0,9; p=0,037. Conclusiones. La tasa de mortalidad fue relativamente baja y fue comparable con lo reportado en países desarrollados. El tratamiento antimicrobiano inapropiado fue el principal factor asociado con mortalidad.   doi: http://dx.doi.org/10

[The recent advances of HAM/TSP research].

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Osame, M

1999-12-01

The ninth international conference on HTLVs and related disorders was held on April 5-9, 1999 at Kagoshima, Japan under the conference chairperson, Dr. Mitsuhiro Osame. In this meeting, world-wide epidemiological data on HTLV-I carriers, ATL patients, and HAM/TSP patients were summarized as shown in the table. The total number of them was supposed to be more than 2.2 millions, 1,200, and 3,000, respectively. To elucidate the localization of HTLV-I proviral DNA directly, double staining using immunohistochemistry and PCR in situ hybridization in the spinal cords of HAM/TSP patients were performed. HTLV-I proviral DNA was localized only to OPD 4-positive cells (Matsuoka et al, 1998). The localization of HTLV-I messenger RNA was the same (Moritoyo et al, 1996). A novel technique to detect HTLV-I tax protein was also developed. In HAM/TSP patients, 0.04-1.16% of the CSF cells and 0.02-0.54% of PBMCs were positive for HTLV-I tax protein (Moritoyo et al, 1999). It was also hypothesized that HLA alleles control HTLV-I proviral load and thus influence susceptibility to HAM/TSP. Two hundred and thirty-two cases of HAM/TSP were compared with 201 randomly selected HTLV-I seropositive asymptomatic blood donors. It was shown that, after infection with HTLV-I, the class I allele HLA-A*02 halves the odds of HAM/TSP (p doubled the odds of HAM/TSP in the absence of the protective effect of HLA-A*02 (Jeffery and Usuku et al, 1999).

Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

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Mavroudi, Irene; Papadaki, Helen A.

2012-01-01

Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA) molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients. PMID:22956967

Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.

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Esbenshade, Adam J; Zhao, Zhiguo; Aftandilian, Catherine; Saab, Raya; Wattier, Rachel L; Beauchemin, Melissa; Miller, Tamara P; Wilkes, Jennifer J; Kelly, Michael J; Fernbach, Alison; Jeng, Michael; Schwartz, Cindy L; Dvorak, Christopher C; Shyr, Yu; Moons, Karl G M; Sulis, Maria-Luisa; Friedman, Debra L

2017-10-01

Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness. A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables. From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI. The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781-3790. © 2017 American Cancer Society. © 2017 American Cancer Society.

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control.

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Ruiz-Riol, M; Berdnik, D; Llano, A; Mothe, B; Gálvez, C; Pérez-Álvarez, S; Oriol-Tordera, B; Olvera, A; Silva-Arrieta, S; Meulbroek, M; Pujol, F; Coll, J; Martinez-Picado, J; Ganoza, C; Sanchez, J; Gómez, G; Wyss-Coray, T; Brander, C

2017-08-15

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia ( P HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/β-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor ( IL27RA ) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC. IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and

The Role Of Multidetector Computed Tomography In The Early Diagnosis Of Invasive Pulmonary Aspergıllosis In Patients With Febrile Neutropenia Undergoing Hematopoietic Stem Cell Transplantation

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Nazan Çiledağ

2012-03-01

Full Text Available OBJECTIVE: To evaluate the vessel involvement and the role of multidedector computed tomograpy (MDCT in the early diagnosis of invasive pulmonary aspergillosis (IPA at MDCT in autologous bone morrow transplantation patients with febrile neutropenia and antibiotic-resistant fever of unknown origin with clinically suspected IPA. METHODS: 74 pulmonary MDCT examinations of 37 consecutive hematopoietic stem cell transplantation patients with febrile neutropenia with clinically suspected IPA were retrospectively evaluated. RESULTS: The diagnosis of IPA was made according to according to the Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Consensus Group criteria and 0, 14, 11 patients were diagnosed as proven, probable, possible IPA, respectively. Among 25 cases accepted as probable and possible IPA, all patients had pulmonary MDCT findings consistent with IPA. Remaining 12 patients were accepted as having fever of unknown origin (FUO and in these 12, MDCT showed patent vessel. In patients with probable/possible IPA, 72 focal pulmonary lesions were detected. In 41 of 72 (57%, vascular occlusion was detected. The CT halo sign was present in 25 of 41 (61% lesions. A clinical improvement, resolution of fever was observed following antifungal therapy in 19 (76% of 25 patients with probable/possible IPA. Six (25% patients diagnosed as IPA died during follow-up. Transplant related mortality at day 100 in patients with IPA and FUO were found to be 24% and 0%, respectively. CONCLUSION: In conclusion, MDCT has a potential role in early diagnosis of IPA by detection of vessel occlusion.

HTLV-1 modulates the frequency and phenotype of FoxP3+CD4+ T cells in virus-infected individuals

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Satou Yorifumi

2012-05-01

Full Text Available Abstract Background HTLV-1 utilizes CD4 T cells as the main host cell and maintains the proviral load via clonal proliferation of infected CD4+ T cells. Infection of CD4+ T cells by HTLV-1 is therefore thought to play a pivotal role in HTLV-1-related pathogenicity, including leukemia/lymphoma of CD4+ T cells and chronic inflammatory diseases. Recently, it has been reported that a proportion of HTLV-1 infected CD4+ T cells express FoxP3, a master molecule of regulatory T cells. However, crucial questions remain unanswered on the relationship between HTLV-1 infection and FoxP3 expression. Results To investigate the effect of HTLV-1 infection on CD4+ T-cell subsets, we used flow cytometry to analyze the T-cell phenotype and HTLV-1 infection in peripheral mononuclear cells (PBMCs of four groups of subjects, including 23 HTLV-1-infected asymptomatic carriers (AC, 10 patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP, 10 patients with adult T-cell leukemia (ATL, and 10 healthy donors. The frequency of FoxP3+ cells in CD4+ T cells in AC with high proviral load and patients with HAM/TSP or ATL was higher than that in uninfected individuals. The proviral load was positively correlated with the percentage of CD4+ T cells that were FoxP3+. The CD4+FoxP3+ T cells, themselves, were frequently infected with HTLV-1. We conclude that FoxP3+ T- cells are disproportionately infected with HTLV-1 during chronic infection. We next focused on PBMCs of HAM/TSP patients. The expression levels of the Treg associated molecules CTLA-4 and GITR were decreased in CD4+FoxP3+ T cells. Further we characterized FoxP3+CD4+ T-cell subsets by staining CD45RA and FoxP3, which revealed an increase in CD45RA−FoxP3low non-suppressive T-cells. These findings can reconcile the inflammatory phenotype of HAM/TSP with the observed increase in frequency of FoxP3+ cells. Finally, we analyzed ATL cells and observed not only a high frequency of FoxP3 expression

Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple sheep flocks

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White, S N; Mousel, M R; Reynolds, J O; Herrmann-Hoesing, L M; Knowles, D P

2014-01-01

Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infection and control of OvLV post-infection. Although variants in TMEM154 have consistent association with odds of infection, no variant in any gene has been associated with host control of OvLV post-infection in multiple animal sets. Proviral concentration is a live-animal diagnostic measure of OvLV control post-infection related to severity of OvLV-induced lesions. A recent genome-wide association study identified a region including four zinc finger genes associated with proviral concentration in one Rambouillet flock. To refine this region, we tested additional variants and identified a small insertion/deletion variant near ZNF389 that showed consistent association with proviral concentration in three animal sets (P sheep from multiple locations and management conditions. Strikingly, one flock had exceptionally high prevalence (>87%, including yearlings) and mean proviral concentration (>950 copies/μg), possibly due to needle sharing. The best estimate of proviral concentration by genotype, obtained from all 1310 OvLV-positive animals tested, showed insertion homozygotes had less than half the proviral concentration of other genotypes (P sheep flocks. PMID:24303974

Load research manual. Volume 1. Load research procedures

Energy Technology Data Exchange (ETDEWEB)

Brandenburg, L.; Clarkson, G.; Grund, Jr., C.; Leo, J.; Asbury, J.; Brandon-Brown, F.; Derderian, H.; Mueller, R.; Swaroop, R.

1980-11-01

This three-volume manual presents technical guidelines for electric utility load research. Special attention is given to issues raised by the load data reporting requirements of the Public Utility Regulatory Policies Act of 1978 and to problems faced by smaller utilities that are initiating load research programs. In Volumes 1 and 2, procedures are suggested for determining data requirements for load research, establishing the size and customer composition of a load survey sample, selecting and using equipment to record customer electricity usage, processing data tapes from the recording equipment, and analyzing the data. Statistical techniques used in customer sampling are discussed in detail. The costs of load research also are estimated, and ongoing load research programs at three utilities are described. The manual includes guides to load research literature and glossaries of load research and statistical terms.

Transcriptional regulation of latent feline immunodeficiency virus in peripheral CD4+ T-lymphocytes.

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McDonnel, Samantha J; Sparger, Ellen E; Luciw, Paul A; Murphy, Brian G

2012-05-01

Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

Load power device, system and method of load control and management employing load identification

Science.gov (United States)

Yang, Yi; Luebke, Charles John; Schoepf, Thomas J.

2018-01-09

A load power device includes a power input, at least one power output for at least one load, a plurality of sensors structured to sense voltage and current at the at least one power output, and a processor. The processor provides: (a) load identification based upon the sensed voltage and current, and (b) load control and management based upon the load identification.

Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia.

Science.gov (United States)

Freire, M P; de Oliveira Garcia, D; Garcia, C P; Campagnari Bueno, M F; Camargo, C H; Kono Magri, A S G; Francisco, G R; Reghini, R; Vieira, M F; Ibrahim, K Y; Rossi, F; Hajjar, L; Levin, A S; Hoff, P M; Pierrotti, L C; Abdala, E

2016-04-01

This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Anti-human neutrophil antigen-1a, -1b, and -2 antibodies in neonates and children with immune neutropenias analyzed by extracted granulocyte antigen immunofluorescence assay.

Science.gov (United States)

Onodera, Rie; Kurita, Emi; Taniguchi, Kikuyo; Karakawa, Shuhei; Okada, Satoshi; Kihara, Hirotaka; Fujii, Teruhisa; Kobayashi, Masao

2017-11-01

Anti-human neutrophil antigen (HNA) antibodies have been implicated in the development of neonatal alloimmune neutropenia (NAN) and autoimmune neutropenia (AIN). There are many conventional assay methods that detect anti-HNA antibodies. However, a method to measure multiple samples and detect several anti-HNA antibodies simultaneously is needed. We developed a new method, the extracted granulocyte antigen immunofluorescence assay (EGIFA), to analyze anti-HNA-1a, -1b, and -2 antibodies in sera. The results obtained by EGIFA were evaluated in comparison with those from several standard assay methods. Anti-HNA antibodies in serum samples from nine familial cases with suspected NAN (n = 19) and children with suspected AIN (n = 88) were also measured by EGIFA. The evaluation of nine serum samples with anti-HNA antibodies suggested that EGIFA demonstrated equivalent specificity and superior sensitivity to monoclonal antibody-specific immobilization of granulocyte antigens and had comparable sensitivity to the granulocyte indirect immunofluorescence test. EGIFA successfully detected anti-HNA-1a or -1b antibodies in seven of nine familial cases with suspected NAN. EGIFA detected anti-HNA antibodies in 40.9% of children with suspected AIN. Among them, isolated anti-HNA-1a or -1b antibody was detected in 4.5 or 12.5% of children, respectively, and anti-HNA-2 antibody was identified in 3.4% of children. The 30.8% (16 of 52) of children negative for anti-HNA antibody by EGIFA were positive for anti-HLA antibody. EGIFA facilitated the measurement of anti-HNA-1a, -1b, and/or -2 antibodies in sera. The prompt measurement of anti-HNA antibodies will improve the diagnosis and clinical management of patients with suspected NAN or AIN. © 2017 AABB.

Análisis de Costo Efectividad de Estrategias de Tratamiento Antimicótico en Pacientes con Neutropenia Febril Persistente y Tratamiento Antibiótico de Amplio Espectro.

Science.gov (United States)

Gamboa Garay, Oscar Andrés; Fuentes Pachón, Juan Camilo; Cuervo Maldonado, Sonia Isabel; Gómez Rincón, Julio Cesar; Castillo Londoño, Juan Sebastian

2012-12-01

To assess cost-effectiveness of antifungal treatment on patients with persistent fever neutropenia: empiric antifungal therapy (EAT) vs. anticipated antifungal therapy (AAT). A decision model was performed to evaluate the cost-effectiveness of antifungal treatment strategies in patients with febrile neutropenia not responding to a broad spectrum antibiotic treatment. The strategies included were: 1) EAT with amphotericin B deoxycholate; 2) EAT with liposomal amphotericin B; 3) EAT with caspofungin; and 4) AAT with voriconazole and amphotericin B deoxycholate or liposomal amphotericin B or caspofungin in patients who initiate treatment despite having negative CT scan and galactomannan or fail to voriconazole. Effectiveness was measured as the number of deaths averted. Cost-effectiveness and incremental cost-effectiveness ratios were calculated. Deterministic and probabilistic sensitivity analyzes were performed. EAT with Amphotericin B deoxycholate was the least expensive and least effective strategy. The EAT with caspofungin was the most effective. The cost per death averted for caspofungin when compared with amphotericin B deoxycholate was $17,011,073.83, which would indicate that this strategy would be cost-effective for the country if the willingness to pay per death averted is equal to or greater than this value. EAT with liposomal amphotericin B and AAT with voriconazole were dominated by AET with caspofungin, which is less costly and more effective. EAT with caspofungin would be cost-effective for Colombia if the threshold per death averted is greater to $18.000.000. If the threshold is lesser the EAT with amphotericin B deoxycholate would be the election. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Subgingival microflora and treatment in prepubertal periodontitis associated with chronic idiopathic neutropenia.

Science.gov (United States)

Kamma, J J; Lygidakis, N A; Nakou, M

1998-09-01

Prepubertal periodontitis affects both primary and permanent dentition. The purpose of this study was to examine the composition of subgingival microflora of the permanent dentition in an 11-year-old Caucasian female, who had premature exfoliation of her deciduous teeth on her 5th year of age, and the response of this condition to the antibiotic therapy and supportive periodontal care. Gingival tissues were highly inflamed and alveolar bone loss was detected radiographically. The girl had experienced frequent upper respiratory tract infections, tonsilitis and recurrent otitis media. Her mother had history of early onset periodontitis associated with chronic idiopathic neutropenia. Blood chemistry tests and immunological examinations were also performed. Subgingival plaque samples were collected from the proximal sites of permanent molars, incisors, canines and maxillary premolars. 27 different microbial species were isolated from the subgingival microflora. Among the predominant species were Porphyromonas gingivalis (17.6%-7.3%), Prevotella intermedia (12.4%-4.7%), Capnocytophaga sputigena (14.4%-10.4%), Capnocytophaga ochracea (13.2%-6.9%) and Actinobacillus actinomycetemcomitans (9.3%-5.5%). Periodontal treatment consisted of scaling, root planing in conjunction with antibiotic administration of Augmentin 312.5 mg and Flagyl 200 mg, each t.i.d. for 10 days. 3 weeks after the antibiotic therapy, bacterial samples were collected from the same sites. All the periodontal pathogens were recovered in lower levels and A.actinomycetemcomitans was almost eliminated in the 3-week period. The evaluation of clinical indices at 3, 6 and 12 months showed that periodontal treatment in conjunction with antibiotics was effective and rapidly followed by marked clinical improvement. The microbiological monitoring at 3, 6 and 12 months after antibiotic treatment and each time prior to supportive periodontal care, revealed that the periodontal pathogens fluctuated in low levels even

Distribution load forecast with interactive correction of horizon loads

International Nuclear Information System (INIS)

Glamochanin, V.; Andonov, D.; Gagovski, I.

1994-01-01

This paper presents the interactive distribution load forecast application that performs the distribution load forecast with interactive correction of horizon loads. It consists of two major parts implemented in Fortran and Visual Basic. The Fortran part is used for the forecasts computations. It consists of two methods: Load Transfer Coupling Curve Fitting (LTCCF) and load Forecast Using Curve Shape Clustering (FUCSC). LTCCF is used to 'correct' the contaminated data because of load transfer among neighboring distribution areas. FUCSC uses curve shape clustering to forecast the distribution loads of small areas. The forecast for each small area is achieved by using the shape of corresponding cluster curve. The comparison of forecasted loads of the area with historical data will be used as a tool for the correction of the estimated horizon load. The Visual Basic part is used to provide flexible interactive user-friendly environment. (author). 5 refs., 3 figs

The influence of different fever definitions on diagnostics and treatment after diagnosis of fever in chemotherapy-induced neutropenia in children with cancer.

Directory of Open Access Journals (Sweden)

Stéphanie Wagner

Full Text Available There is no evidence-based definition of the temperature limit defining fever (TLDF in children with neutropenia. Lowering the TLDF is known to increase the number of episodes of fever in neutropenia (FN. This study aimed to investigate the influence of a lower versus standard TLDF on diagnostics and therapy.In a single pediatric cancer center using a high standard TLDF (39°C tympanic-temperature patients were observed prospectively (NCT01683370. The effect of applying lower TLDFs (range 37.5°C to 38.9°C versus 39.0°C on these measures was simulated in silicon.In reality, 45 FN episodes were diagnosed. Of 3391 temperatures measured, 193 were ≥39.0°C, and 937 ≥38.0°C. For persisting fever ≥24 hours, additional blood cultures were taken in 31 (69% episodes in reality. This number decreased to 22 (49% when applying 39.0°C, and increased to 33 for 38.0°C (73%; plus 11 episodes; plus 24%. For persisting fever ≥48 hours, i.v.-antibiotics were escalated in 25 (56% episodes. This number decreased to 15 (33% when applying 39.0°C, and increased to 26 for 38.0°C (58%; plus 11 episodes; plus 24%. For persisting fever ≥120 hours, i.v.-antifungals were added in 4 (9% episodes. This number increased to 6 (13% by virtually applying 39.0°C, and to 11 for 38.0°C (24%; plus 5 episodes; plus 11%. The median length of stay was 5.7 days (range, 0.8 to 43.4. In 43 episodes with hospital discharge beyond 24 hours, applying 38.0°C led to discharge delay by ≥12 hours in 24 episodes (56%; 95% CI, 40 to 71, with a median delay of 13 hours, and a cumulative delay of 68 days.Applying a low versus standard TLDF led to relevant increases of diagnostics, antimicrobial therapy, and length of stay. The differences between management in reality versus simply applying 39.0° as TLDF reflect the important impact of clinical assessment.

The influence of different fever definitions on diagnostics and treatment after diagnosis of fever in chemotherapy-induced neutropenia in children with cancer.

Science.gov (United States)

Wagner, Stéphanie; Brack, Eva K; Stutz-Grunder, Eveline; Agyeman, Philipp; Leibundgut, Kurt; Teuffel, Oliver; Ammann, Roland A

2018-01-01

There is no evidence-based definition of the temperature limit defining fever (TLDF) in children with neutropenia. Lowering the TLDF is known to increase the number of episodes of fever in neutropenia (FN). This study aimed to investigate the influence of a lower versus standard TLDF on diagnostics and therapy. In a single pediatric cancer center using a high standard TLDF (39°C tympanic-temperature) patients were observed prospectively (NCT01683370). The effect of applying lower TLDFs (range 37.5°C to 38.9°C) versus 39.0°C on these measures was simulated in silicon. In reality, 45 FN episodes were diagnosed. Of 3391 temperatures measured, 193 were ≥39.0°C, and 937 ≥38.0°C. For persisting fever ≥24 hours, additional blood cultures were taken in 31 (69%) episodes in reality. This number decreased to 22 (49%) when applying 39.0°C, and increased to 33 for 38.0°C (73%; plus 11 episodes; plus 24%). For persisting fever ≥48 hours, i.v.-antibiotics were escalated in 25 (56%) episodes. This number decreased to 15 (33%) when applying 39.0°C, and increased to 26 for 38.0°C (58%; plus 11 episodes; plus 24%). For persisting fever ≥120 hours, i.v.-antifungals were added in 4 (9%) episodes. This number increased to 6 (13%) by virtually applying 39.0°C, and to 11 for 38.0°C (24%; plus 5 episodes; plus 11%). The median length of stay was 5.7 days (range, 0.8 to 43.4). In 43 episodes with hospital discharge beyond 24 hours, applying 38.0°C led to discharge delay by ≥12 hours in 24 episodes (56%; 95% CI, 40 to 71), with a median delay of 13 hours, and a cumulative delay of 68 days. Applying a low versus standard TLDF led to relevant increases of diagnostics, antimicrobial therapy, and length of stay. The differences between management in reality versus simply applying 39.0° as TLDF reflect the important impact of clinical assessment.

Load theory behind the wheel; perceptual and cognitive load effects.

Science.gov (United States)

Murphy, Gillian; Greene, Ciara M

2017-09-01

Perceptual Load Theory has been proposed as a resolution to the longstanding early versus late selection debate in cognitive psychology. There is much evidence in support of Load Theory but very few applied studies, despite the potential for the model to shed light on everyday attention and distraction. Using a driving simulator, the effect of perceptual and cognitive load on drivers' visual search was assessed. The findings were largely in line with Load Theory, with reduced distractor processing under high perceptual load, but increased distractor processing under high cognitive load. The effect of load on driving behaviour was also analysed, with significant differences in driving behaviour under perceptual and cognitive load. In addition, the effect of perceptual load on drivers' levels of awareness was investigated. High perceptual load significantly increased inattentional blindness and deafness, for stimuli that were both relevant and irrelevant to driving. High perceptual load also increased RTs to hazards. The current study helps to advance Load Theory by illustrating its usefulness outside of traditional paradigms. There are also applied implications for driver safety and roadway design, as the current study suggests that perceptual and cognitive load are important factors in driver attention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Development of neurologic diseases in a patient with primate T lymphotropic virus type 1 (PTLV-1).

Science.gov (United States)

Enose-Akahata, Yoshimi; Caruso, Breanna; Haner, Benjamin; Charlip, Emily; Nair, Govind; Massoud, Raya; Billioux, Bridgette J; Ohayon, Joan; Switzer, William M; Jacobson, Steven

2016-08-12

Virus transmission from various wild and domestic animals contributes to an increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 originated from ancient zoonotic transmission from nonhuman primates, although cases of zoonotic infections continue to occur. Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys, and combined are called primate T-lymphotropic viruses (PTLV-1). However, other clinical syndromes typically seen in humans such as a chronic progressive myelopathy have not been observed in nonhuman primates. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following nonhuman primate exposure. We performed detailed laboratory analyses on an HTLV-1 seropositive patient with typical HAM/TSP who was born in Liberia and now resides in the United States. Using a novel droplet digital PCR for the detection of the HTLV-1 tax gene, the proviral load in PBMC and cerebrospinal fluid cells was 12.98 and 51.68 %, respectively; however, we observed a distinct difference in fluorescence amplitude of the positive droplet population suggesting possible mutations in proviral DNA. A complete PTLV-1 proviral genome was amplified from the patient's PBMC DNA using an overlapping PCR strategy. Phylogenetic analysis of the envelope and LTR sequences showed the virus was highly related to PTLV-1 from sooty mangabey monkeys (smm) and humans exposed via nonhuman primates in West Africa. These results demonstrate the patient is infected with a simian variant of PTLV-1, suggesting for the first time that PTLV-1smm infection in humans may be associated with a chronic progressive neurologic disease.

Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.

Science.gov (United States)

Teranishi, Hideto; Koga, Yuhki; Nishio, Hisanori; Kato, Wakako; Ono, Hiroaki; Kanno, Shunsuke; Nakashima, Kentaro; Takada, Hidetoshi

2017-07-01

Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged ≥13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered. The detection rates for extended-spectrum β-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p = 0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Plastic limit loads for cylindrical shell intersections under combined loading

International Nuclear Information System (INIS)

Skopinsky, V.N.; Berkov, N.A.; Vogov, R.A.

2015-01-01

In this research, applied methods of nonlinear analysis and results of determining the plastic limit loads for shell intersection configurations under combined internal pressure, in-plane moment and out-plane moment loadings are presented. The numerical analysis of shell intersections is performed using the finite element method, geometrically nonlinear shell theory in quadratic approximation and plasticity theory. For determining the load parameter of proportional combined loading, the developed maximum criterion of rate of change of relative plastic work is employed. The graphical results for model of cylindrical shell intersection under different two-parameter combined loadings (as generalized plastic limit load curves) and three-parameter combined loading (as generalized plastic limit load surface) are presented on the assumption that the internal pressure, in-plane moment and out-plane moment loads were applied in a proportional manner. - Highlights: • This paper presents nonlinear two-dimensional FE analysis for shell intersections. • Determining the plastic limit loads under combined loading is considered. • Developed maximum criterion of rate of change of relative plastic work is employed. • Plastic deformation mechanism in shell intersections is discussed. • Results for generalized plastic limit load curves of branch intersection are presented

Opposite effects of capacity load and resolution load on distractor processing.

Science.gov (United States)

Zhang, Weiwei; Luck, Steven J

2015-02-01

According to the load theory of attention, an increased perceptual load reduces distractor processing whereas an increased working memory load facilitates distractor processing. Here we raise the possibility that the critical distinction may instead be between an emphasis on resolution and an emphasis on capacity. That is, perceptual load manipulations typically emphasize resolution (fine-grained discriminations), whereas working memory load manipulations typically emphasize capacity (simultaneous processing of multiple relevant stimuli). To test the plausibility of this hypothesis, we used a visual working memory task that emphasized either the number of items to be stored (capacity load, retaining 2 vs. 4 colors) or the precision of the representations (resolution load, detecting small vs. large color changes). We found that an increased capacity load led to increased flanker interference (a measure of distractor processing), whereas an increased resolution load led to reduced flanker interference. These opposite effects of capacity load and resolution load on distractor processing mirror the previously described opposite effects of perceptual load and working memory load.

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia.

Science.gov (United States)

Fonseca, Paula Jiménez; Carmona-Bayonas, Alberto; García, Ignacio Matos; Marcos, Rosana; Castañón, Eduardo; Antonio, Maite; Font, Carme; Biosca, Mercè; Blasco, Ana; Lozano, Rebeca; Ramchandani, Avinash; Beato, Carmen; de Castro, Eva Martínez; Espinosa, Javier; Martínez-García, Jerónimo; Ghanem, Ismael; Cubero, Jorge Hernando; Manrique, Isabel Aragón; Navalón, Francisco García; Sevillano, Elena; Manzano, Aránzazu; Virizuela, Juan; Garrido, Marcelo; Mondéjar, Rebeca; Arcusa, María Ángeles; Bonilla, Yaiza; Pérez, Quionia; Gallardo, Elena; Del Carmen Soriano, Maria; Cardona, Mercè; Lasheras, Fernando Sánchez; Cruz, Juan Jesús; Ayala, Francisco

2016-05-24

We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes 0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN.

Load testing circuit

DEFF Research Database (Denmark)

2009-01-01

A load testing circuit a circuit tests the load impedance of a load connected to an amplifier. The load impedance includes a first terminal and a second terminal, the load testing circuit comprising a signal generator providing a test signal of a defined bandwidth to the first terminal of the load...

46 CFR 154.1730 - Ethylene oxide: Loading and off loading.

Science.gov (United States)

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Ethylene oxide: Loading and off loading. 154.1730... Operating Requirements § 154.1730 Ethylene oxide: Loading and off loading. (a) The master shall ensure that before ethylene oxide is loaded into a cargo tank: (1) The tank is thoroughly clean, dry, and free of...

Peak load-impulse characterization of critical pulse loads in structural dynamics

International Nuclear Information System (INIS)

Abrahamson, G.R.; Lindberg, H.E.

1975-01-01

In presenting the characterization scheme, some general features are described first. A detailed analysis is given for the rigid-plastic system of one degree of freedom to illustrate the calculation of critical load curves in terms of peak load and impulse. This is followed by the presentation of critical load curves for uniformly loaded rigid-plastic beams and plates and for dynamic buckling of cylindrical shells under uniform lateral loads. The peak load-impulse characterization of critical pulse loads is compared with the dynamic load factor characterization, and some aspects of the history of the peak load-pulse scheme are presented. (orig./HP) [de

Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-β (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation.

Science.gov (United States)

Gautam, S; Kirschnek, S; Gentle, I E; Kopiniok, C; Henneke, P; Häcker, H; Malleret, L; Belaaouaj, A; Häcker, G

2013-08-01

Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation

Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes

Directory of Open Access Journals (Sweden)

Brian G. Murphy

2012-05-01

Full Text Available Feline immunodeficiency virus (FIV, the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10³ CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.

System and method employing a minimum distance and a load feature database to identify electric load types of different electric loads

Science.gov (United States)

Lu, Bin; Yang, Yi; Sharma, Santosh K; Zambare, Prachi; Madane, Mayura A

2014-12-23

A method identifies electric load types of a plurality of different electric loads. The method includes providing a load feature database of a plurality of different electric load types, each of the different electric load types including a first load feature vector having at least four different load features; sensing a voltage signal and a current signal for each of the different electric loads; determining a second load feature vector comprising at least four different load features from the sensed voltage signal and the sensed current signal for a corresponding one of the different electric loads; and identifying by a processor one of the different electric load types by determining a minimum distance of the second load feature vector to the first load feature vector of the different electric load types of the load feature database.

System and method employing a self-organizing map load feature database to identify electric load types of different electric loads

Science.gov (United States)

Lu, Bin; Harley, Ronald G.; Du, Liang; Yang, Yi; Sharma, Santosh K.; Zambare, Prachi; Madane, Mayura A.

2014-06-17

A method identifies electric load types of a plurality of different electric loads. The method includes providing a self-organizing map load feature database of a plurality of different electric load types and a plurality of neurons, each of the load types corresponding to a number of the neurons; employing a weight vector for each of the neurons; sensing a voltage signal and a current signal for each of the loads; determining a load feature vector including at least four different load features from the sensed voltage signal and the sensed current signal for a corresponding one of the loads; and identifying by a processor one of the load types by relating the load feature vector to the neurons of the database by identifying the weight vector of one of the neurons corresponding to the one of the load types that is a minimal distance to the load feature vector.

Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study.

Science.gov (United States)

Porter, Danielle P; Toma, Jonathan; Tan, Yuping; Solberg, Owen; Cai, Suqin; Kulkarni, Rima; Andreatta, Kristen; Lie, Yolanda; Chuck, Susan K; Palella, Frank; Miller, Michael D; White, Kirsten L

2016-02-01

Antiretroviral regimen switching may be considered for HIV-1-infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre-existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48. Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance-associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance

Demand Response Load Following of Source and Load Systems

DEFF Research Database (Denmark)

Hu, Jianqiang; Cao, Jinde; Yong, Taiyou

2017-01-01

This paper presents a demand response load following strategy for an interconnected source and load system, in which we utilize traditional units and population of cooling thermostatically controlled loads (TCLs) to follow the mismatched power caused by the load activities and the renewable power...... injection in real time. In the demand side of power systems, these TCLs are often affiliated to a bus load agent and can be aggregated to multiple TCL aggregators. Firstly, aggregate evaluation of the TCL aggregator is carried out based on a bilinear aggregate model so as to derive the available regulation...

Cognitive Load Theory: How Many Types of Load Does It Really Need?

Science.gov (United States)

Kalyuga, Slava

2011-01-01

Cognitive load theory has been traditionally described as involving three separate and additive types of load. Germane load is considered as a learning-relevant load complementing extraneous and intrinsic load. This article argues that, in its traditional treatment, germane load is essentially indistinguishable from intrinsic load, and therefore…

Chromosomal locations of members of a family of novel endogenous human retroviral genomes

International Nuclear Information System (INIS)

Horn, T.M.; Huebner, K.; Croce, C.; Callahan, R.

1986-01-01

Human cellular DNA contains two distinguishable families of retroviral related sequences. One family shares extensive nucleotide sequence homology with infectious mammalian type C retroviral genomes. The other family contains major regions of homology with the pol genes of infectious type A and B and avian type C and D retroviral genomes. Analysis of the human recombinant clone HLM-2 has shown that the pol gene in the latter family is located within an endogenous proviral genome. The authors show that the proviral genome in HLM-2 and the related recombinant clone HLM-25 are located, respectively, on human chromosomes 1 and 5. Other related proviral genomes are located on chromosomes 7, 8, 11, 14, and 17

PROCALCITONIN AND INTERLEUKIN-6 AS MARKERS OF SEVERE INFECTION IN CHILDREN WITH FEBRILE NEUTROPENIA

Directory of Open Access Journals (Sweden)

Lidija Kitanovski

2004-12-01

Full Text Available Background. The results of the study conducted to determine whether procalcitonin (PCT and interleukin-6 (IL-6 are more sensitive and specific markers of severe infection in children with febrile neutropenia (FN than routinelly used C-reactive protein (CRP are presented in the article. 68 episodes of FN experienced by 32 patients were divided into three groups according to the site of infection. Group 1: episodes of bacteraemia and/or clinical sepsis (n = 16, group 2: episodes of focal infection (n = 16 and group 3: episodes of fever of unknown origin (FUO (n = 36. Blood samples for further PCT and IL-6 determination were collected on three consecutive days. CRP concentrations were measured daily in each patient until the resolution of fever. PCT, IL-6 and CRP concentrations were measured on one occassion in each of the 18 afebrile patients with malignant disase forming the reference group. Serum PCT and IL-6 concentrations were measured by immunochemiluminometric and immunoenzymatic assay. Receiver Operating Characteristic (ROC curves were used to determine optimum sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of the studied parameters.Conclusions. PCT and IL-6 were found to be earlier and more sensitive markers of severe infection in neutropenic patients than CRP. The erliest one was IL-6, followed by PCT and CRP. Sequential determination of PCT up to 72 hours improved its diagnostic value, which was not the case for IL-6.In patients with gramnegative bacteraemias PCT concentracions were 3–5 times higher comparing to grampositive, whereas IL-6 concentrations were comparable in both groups.

Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor

International Nuclear Information System (INIS)

Hwang, Jun-Eul; Yoon, Ju-Young; Bae, Woo-Kyun; Shim, Hyun-Jeong; Cho, Sang-Hee; Chung, Ik-Joo

2010-01-01

Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST. A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities. The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug

Dynamical load factor of impact loaded shell structures

International Nuclear Information System (INIS)

Hammel, J.

1977-01-01

Dynamical loaded structures can be analysed by spectral representations, which usually lead to an enormous computational effort. If it is possible to find a fitting dynamical load factor, the dynamical problem can be reduced to a statical one. The computation of this statical problem is much simpler. The disadvantage is that the dynamical load factor usually leads to a very rough approximation. In this paper it will be shown, that by combination of these two methods, the approximation of the dynamical load factor can be improved and the consumption of computation time can be enormously reduced. (Auth.)

Research of Impact Load in Large Electrohydraulic Load Simulator

Directory of Open Access Journals (Sweden)

Yongguang Liu

2014-01-01

Full Text Available The stronger impact load will appear in the initial phase when the large electric cylinder is tested in the hardware-in-loop simulation. In this paper, the mathematical model is built based on AMESim, and then the reason of the impact load is investigated through analyzing the changing tendency of parameters in the simulation results. The inhibition methods of impact load are presented according to the structural invariability principle and applied to the actual system. The final experimental result indicates that the impact load is inhibited, which provides a good experimental condition for the electric cylinder and promotes the study of large load simulator.

Evidence of a higher prevalence of HPV infection in HTLV-1-infected women: a cross-sectional study

Directory of Open Access Journals (Sweden)

Sônia Sampaio Lôpo

2012-06-01

Full Text Available INTRODUCTION:HTLV-1 infection increases susceptibility to other infections. Few studies have addressed the co-infection between HPV and HTLV-1 and the immune response involved in this interaction. The aim of this study was to determine the prevalence of cervical HPV infection in HTLV-1-infected women and to establish the risk factors involved in this co-infection. METHODS: A cross-sectional study was carried out in Salvador, Brazil, between September 2005 and December 2008, involving 50 HTLV-1-infected women from the HTLV Reference Center and 40 uninfected patients from gynecological clinic, both at the Bahiana School of Medicine. HPV infection was assessed using hybrid capture. HTLV-1 proviral load was quantified using real-time polymerase chain reaction (PCR. RESULTS: The mean age of HTLV-1-infected women (38 ± 10 years was similar to that of the control group (36 ± 13 years. The prevalence of HPV infection was 44% in the HTLV-1-infected group and 22.5% in uninfected women (p = 0.03. HTLV-1-infected women had lower mean age at onset of sexual life (17 ± 3 years versus 19 ± 3 years; p = 0.03 and greater number of lifetime partners compared with the control group (4 ± 3 versus 2 ± 1; p < 0.01. In the group of HTLV-1-infected patients, there was neither difference in HTLV-1 proviral load between HPV-infected women and the uninfected. CONCLUSIONS: The prevalence of HPV infection was higher in HTLV-1-infected women. Further studies should be performed to evaluate the progression of this co-infection.

Load research manual. Volume 2. Fundamentals of implementing load research procedures

Energy Technology Data Exchange (ETDEWEB)

Brandenburg, L.; Clarkson, G.; Grund, Jr., C.; Leo, J.; Asbury, J.; Brandon-Brown, F.; Derderian, H.; Mueller, R.; Swaroop, R.

1980-11-01

This three-volume manual presents technical guidelines for electric utility load research. Special attention is given to issues raised by the load data reporting requirements of the Public Utility Regulatory Policies Act of 1978 and to problems faced by smaller utilities that are initiating load research programs. In Volumes 1 and 2, procedures are suggested for determining data requirements for load research, establishing the size and customer composition of a load survey sample, selecting and using equipment to record customer electricity usage, processing data tapes from the recording equipment, and analyzing the data. Statistical techniques used in customer sampling are discussed in detail. The costs of load research also are estimated, and ongoing load research programs at three utilities are described. The manual includes guides to load research literature and glossaries of load research and statistical terms.

Effect of ripple loads on sustained-load cracking in titanium alloys

International Nuclear Information System (INIS)

Pao, P.S.; Meyn, D.A.; Bayles, R.A.; Feng, C.R.; Yoder, G.R.

1995-01-01

In the present paper, the authors have extended their study on the effect of the ripple loads on the sustained-load cracking (SLC) behavior of two titanium alloys, Ti-6Al-4V (an α-β alloy) and Ti-15V-3Cr-3Al-3Sn (a β-α alloy), in an ambient air environment. The methodology which has been used successfully to treat ripple effects on stress-corrosion cracking (SCC) is employed again to address the influence of ripple loads on sustained-load cracking. Ripple loads can significantly reduce the apparent sustained load cracking resistance of titanium alloys in a relatively benign environment such as ambient air. For a ripple-load amplitude equal to 5% of the sustained load, the ripple-load cracking thresholds (K IRLC ) of beta-annealed Ti-6Al-4V and Ti-15V-3Cr-3al-3Sn are less than half of the respective sustained-load cracking thresholds (K ISLC ). The extent of ripple-load degradation for these alloys in ambient air -- relative to K ISLC , were found comparable to those observed in a much more aggressive 3.5% NaCl aqueous solution

Low cognitive load strengthens distractor interference while high load attenuates when cognitive load and distractor possess similar visual characteristics.

Science.gov (United States)

Minamoto, Takehiro; Shipstead, Zach; Osaka, Naoyuki; Engle, Randall W

2015-07-01

Studies on visual cognitive load have reported inconsistent effects of distractor interference when distractors have visual characteristic that are similar to the cognitive load. Some studies have shown that the cognitive load enhances distractor interference, while others reported an attenuating effect. We attribute these inconsistencies to the amount of cognitive load that a person is required to maintain. Lower amounts of cognitive load increase distractor interference by orienting attention toward visually similar distractors. Higher amounts of cognitive load attenuate distractor interference by depleting attentional resources needed to process distractors. In the present study, cognitive load consisted of faces (Experiments 1-3) or scenes (Experiment 2). Participants performed a selective attention task in which they ignored face distractors while judging a color of a target dot presented nearby, under differing amounts of load. Across these experiments distractor interference was greater in the low-load condition and smaller in the high-load condition when the content of the cognitive load had similar visual characteristic to the distractors. We also found that when a series of judgments needed to be made, the effect was apparent for the first trial but not for the second. We further tested an involvement of working memory capacity (WMC) in the load effect (Experiment 3). Interestingly, both high and low WMC groups received an equivalent effect of the cognitive load in the first distractor, suggesting these effects are fairly automatic.

Modelling the role of Tax expression in HTLV-I persistence in vivo.

Science.gov (United States)

Li, Michael Y; Lim, Aaron G

2011-12-01

Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.

Distribution load estimation (DLE)

Energy Technology Data Exchange (ETDEWEB)

Seppaelae, A; Lehtonen, M [VTT Energy, Espoo (Finland)

1998-08-01

The load research has produced customer class load models to convert the customers` annual energy consumption to hourly load values. The reliability of load models applied from a nation-wide sample is limited in any specific network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to find improvements to the load models or, in general, improvements to the load estimates. In Distribution Load Estimation (DLE) the measurements from the network are utilized to improve the customer class load models. The results of DLE will be new load models that better correspond to the loading of the distribution network but are still close to the original load models obtained by load research. The principal data flow of DLE is presented

Residential Load Manageability Factor Analyses by Load Sensitivity Affected by Temperature

Directory of Open Access Journals (Sweden)

N. Eskandari

2016-12-01

Full Text Available Load side management is the basic and significant principle to keeping the balance between generation side and consumption side of electrical power energy. Load side management on typical medium voltage feeder is the power energy consumption control of connected loads with variation of essential parameters that loads do reaction to their variation. Knowing amount of load's reaction to each parameters variation in typical medium voltage feeder during the day, leads to gain Load Manageability Factor (LMF for that specific feeder that helps power utilities to manage their connected loads. Calculating this LMF needs to find out each types of load with unique inherent features behavior to each parameters variation. This paper results and future work results will help us to catch mentioned LMF. In this paper analysis of residential load behavior due to temperature variation with training artificial neural network will be done. Load behavior due to other essential parameters variations like energy pricing variation, major event happening, and power utility announcing to the customers, and etc will study in future works. Collecting all related works results in a unit mathematical equation or an artificial neural network will gain LMF.

Opposite Effects of Capacity Load and Resolution Load on Distractor Processing

OpenAIRE

Zhang, Weiwei; Luck, Steven J.

2014-01-01

According to the load theory of attention, an increased perceptual load reduces distractor processing whereas an increased working memory load facilitates distractor processing. Here we raise the possibility that the critical distinction may instead be between an emphasis on resolution and an emphasis on capacity. That is, perceptual load manipulations typically emphasize resolution (fine-grained discriminations), whereas working memory load manipulations typically emphasize capacity (simulta...

Pay for load demand - electricity pricing with load demand component

International Nuclear Information System (INIS)

Pyrko, Jurek; Sernhed, Kerstin; Abaravicius, Juozas

2003-01-01

This publication is part of a project called Direct and Indirect Load Control in Buildings. Peak load problems have attracted considerable attention in Sweden during last three winters, caused by a significant decrease in available reserve power, which is a consequence of political decisions and liberalisation of the electricity market. A possible way to lower peak loads, avoiding electricity shortages and reducing electricity costs both for users and utilities, is to make customers experience the price difference during peak load periods and, in this way, become more aware of their energy consumption pattern and load demand. As of January 1st 2001, one of the Swedish energy utilities - Sollentuna Energi - operating in the Stockholm area, introduced a new electricity tariff with differentiated grid fees based on a mean value of the peak load every month. This tariff was introduced for all residential customers in the service area. The objective of this study is to investigate the extent to which a Load Demand Component, included in electricity pricing, can influence energy use and load demand in residential buildings. What are the benefits and disadvantages for customers and utilities? This paper investigates the impact of the new tariff on the utility and different types of typical residential customers, making comparisons with previous tariff. Keywords Load demand, electricity pricing, tariff, residential customers, energy behaviour

Frequent and recent human acquisition of simian foamy viruses through apes' bites in central Africa.

Directory of Open Access Journals (Sweden)

Edouard Betsem

2011-10-01

Full Text Available Human infection by simian foamy viruses (SFV can be acquired by persons occupationally exposed to non-human primates (NHP or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (proviral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436 or Bantus (1085 live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2% persons were found to be infected. In the second group, 37/198 (18.6% persons were SFV positive. They were mostly infected by apes (37/39 FV (mainly gorilla. Infection by monkey FV was less frequent (2/39. The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83% are aged 20 to 40 years and acquired the infection during the last twenty years. The (proviral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 10(5 cells in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question.

Prediction of Febrile Neutropenia after Chemotherapy Based on Pretreatment Risk Factors among Cancer Patients

Science.gov (United States)

Aagaard, Theis; Roen, Ashley; Daugaard, Gedske; Brown, Peter; Sengeløv, Henrik; Mocroft, Amanda; Lundgren, Jens; Helleberg, Marie

2017-01-01

Abstract Background Febrile neutropenia (FN) is a common complication to chemotherapy associated with a high burden of morbidity and mortality. Reliable prediction of individual risk based on pretreatment risk factors allows for stratification of preventive interventions. We aimed to develop such a risk stratification model to predict FN in the 30 days after initiation of chemotherapy. Methods We included consecutive treatment-naïve patients with solid cancers and diffuse large B-cell lymphomas at Copenhagen University Hospital, 2010–2015. Data were obtained from the PERSIMUNE repository of electronic health records. FN was defined as neutrophils ≤0.5 × 10E9/L ​at the time of either a blood culture sample or death. Time from initiation of chemotherapy to FN was analyzed using Fine-Gray models with death as a competing event. Risk factors investigated were: age, sex, body surface area, haemoglobin, albumin, neutrophil-to-lymphocyte ratio, Charlson Comorbidity Index (CCI) and chemotherapy drugs. Parameter estimates were scaled and summed to create the risk score. The scores were grouped into four: low, intermediate, high and very high risk. Results Among 8,585 patients, 467 experienced FN, incidence rate/30 person-days 0.05 (95% CI, 0.05–0.06). Age (1 point if > 65 years), albumin (1 point if 2) and chemotherapy (range -5 to 6 points/drug) predicted FN. Median score at inclusion was 2 points (range –5 to 9). The cumulative incidence and the incidence rates and hazard ratios of FN are shown in Figure 1 and Table 1, respectively. Conclusion We developed a risk score to predict FN the first month after initiation of chemotherapy. The score is easy to use and provides good differentiation of risk groups; the score needs independent validation before routine use. Disclosures All authors: No reported disclosures.

Structural load combinations

International Nuclear Information System (INIS)

Hwang, H.; Reich, M.; Ellingwood, B.; Shinozuka, M.

1985-01-01

This paper presents the latest results of the program entitled, ''Probability Based Load Combinations For Design of Category I Structures''. In FY 85, a probability-based reliability analysis method has been developed to evaluate safety of shear wall structures. The shear walls are analyzed using stick models with beam elements and may be subjected to dead load, live load and in-plane eqrthquake. Both shear and flexure limit states are defined analytically. The limit state probabilities can be evaluated on the basis of these limit states. Utilizing the reliability analysis method mentioned above, load combinations for the design of shear wall structures have been established. The proposed design criteria are in the load and resistance factor design (LRFD) format. In this study, the resistance factors for shear and flexure and load factors for dead and live loads are preassigned, while the load factor for SSE is determined for a specified target limit state probability of 1.0 x 10 -6 or 1.0 x 10 -5 during a lifetime of 40 years. 23 refs., 9 tabs

Structural load combinations

International Nuclear Information System (INIS)

Hwang, H.; Reich, M.; Ellingwood, B.; Shinozuka, M.

1986-01-01

This paper presents the latest results of the program entitled, ''Probability Based Load Combinations For Design of Category I Structures''. In FY 85, a probability-based reliability analysis method has been developed to evaluate safety of shear wall structures. The shear walls are analyzed using stick models with beam elements and may be subjected to dead load, live load and in-plane earthquake. Both shear and flexure limit states are defined analytically. The limit state probabilities can be evaluated on the basis of these limit states. Utilizing the reliability analysis method mentioned above, load combinations for the design of shear wall structures have been established. The proposed design criteria are in the load and resistance factor design (LRFD) format. In this study, the resistance factors for shear and flexure and load factors for dead and live loads are preassigned, while the load factor for SSE is determined for a specified target limit state probability of 1.0 x 10 -6 or 1.0 x 10 -5 during a lifetime of 40 years

Distribution load estimation - DLE

Energy Technology Data Exchange (ETDEWEB)

Seppaelae, A. [VTT Energy, Espoo (Finland)

1996-12-31

The load research project has produced statistical information in the form of load models to convert the figures of annual energy consumption to hourly load values. The reliability of load models is limited to a certain network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to make improvements in the load models. Distribution load estimation (DLE) is the method developed here to improve load estimates from the load models. The method is also quite cheap to apply as it utilises information that is already available in SCADA systems

Distribution load estimation - DLE

Energy Technology Data Exchange (ETDEWEB)

Seppaelae, A [VTT Energy, Espoo (Finland)

1997-12-31

The load research project has produced statistical information in the form of load models to convert the figures of annual energy consumption to hourly load values. The reliability of load models is limited to a certain network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to make improvements in the load models. Distribution load estimation (DLE) is the method developed here to improve load estimates from the load models. The method is also quite cheap to apply as it utilises information that is already available in SCADA systems

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Stevenson Matt D

2011-09-01

Full Text Available Abstract Background Febrile neutropenia (FN occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65 for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69 for filgrastim, and 0.62 (95% CI: 0.44 to 0.88 for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62. In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98. Conclusions Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.

Maternal Proviral Load and Vertical Transmission of Human T Cell Lymphotropic Virus Type 1 in Guinea-Bissau

NARCIS (Netherlands)

van Tienen, Carla; McConkey, Samuel J.; de Silva, Thushan I.; Cotten, Matthew; Kaye, Steve; Sarge-Njie, Ramu; da Costa, Carlos; Gonçalves, Nato; Parker, Julia; Vincent, Tim; Jaye, Assan; Aaby, Peter; Whittle, Hilton; Schim van der Loeff, Maarten

2012-01-01

The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and

Load forecasting

International Nuclear Information System (INIS)

Mak, H.

1995-01-01

Slides used in a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about the changing needs for load forecasting were presented. Technological innovations and population increase were said to be the prime driving forces behind the changing needs in load forecasting. Structural changes, market place changes, electricity supply planning changes, and changes in planning objectives were other factors discussed. It was concluded that load forecasting was a form of information gathering, that provided important market intelligence

Wind Loads on Structures

DEFF Research Database (Denmark)

Dyrbye, Claes; Hansen, Svend Ole

Wind loads have to be taken into account when designing civil engineering structures. The wind load on structures can be systematised by means of the wind load chain: wind climate (global), terrain (wind at low height), aerodynamic response (wind load to pressure), mechanical response (wind...... pressure to structural response) and design criteria. Starting with an introduction of the wind load chain, the book moves on to meteorological considerations, atmospheric boundary layer, static wind load, dynamic wind load and scaling laws used in wind-tunnel tests. The dynamic wind load covers vibrations...... induced by wind turbulence, vortex shedding, flutter and galloping. The book gives a comprehensive treatment of wind effects on structures and it will be useful for consulting engineers designing wind-sensitive structures. It will also be valuable for students of civil engineering as textbook...

Limit load assessment of centre cracked plates under biaxial loading

International Nuclear Information System (INIS)

Meek, C.; Ainsworth, R.A.

2015-01-01

Fitness-for-service of equipment and components containing defects is generally assessed using procedures such as BS 7910, API 579 and R6. There is currently little detailed advice in these procedures on the effects of biaxial and triaxial loading on fracture. This poster shows some theoretical bounding solutions of the plastic limit load for centre cracked plates under a variety of biaxial loading ratios and compares the estimates with those found by numerical methods using finite element (FE) analysis using Abacus CAE modelling software. The limit load of a structure is the maximum load that it can carry before plastic collapse occurs; this is often when the plastic zone has become large enough to spread from the crack tip to a remote boundary. For an elastic-perfectly plastic material, the irreversible deformation will continue at stresses no higher than the yield stress. The model for these limit load solutions is a bi-axially loaded plate of width 2W and height 2H, a centre crack of width 2a, acted on by remotely applied uniform stresses σ 2 perpendicular to the crack and Bσ 2 parallel to the crack, where B is the biaxial loading ratio, it means the ratio of the parallel to the perpendicular stress. A quarter plate of an elastic-perfectly plastic material has been modelled. The results show that an exact solution has been found for negative and low positive values of B. For B > 1, the lower bound solution is conservative for all values of a/W and B

Torque and Axial Loading Physics for Measuring Atmospheric Icing Load and Icing Rate

OpenAIRE

Mughal, Umair Najeeb; Virk, Muhammad Shakeel

2015-01-01

Measuring icing load and icing rate are important parameters for an atmospheric icing sensor. A new icing sensor has recently been designed and developed at Narvik University College for measuring atmospheric icing rate, icing load and icing type. Unlike the existing atmospheric icing sensors commercially available in market, which uses the axial loading for measuring icing load and icing rate, this new sensory system measures icing load and icing rate using the torque loading physics. The pe...

Low-back loading in lifting two loads beside the body compared to lifting one load in front of the body

NARCIS (Netherlands)

Faber, G.S.; Kingma, I.; Bakker, A.J.; van Dieen, J.H.

2009-01-01

Low-back load during manual lifting is considered an important risk factor for the occurrence of low-back pain. Splitting a load, so it can be lifted beside the body (one load in each hand), instead of in front of the body, can be expected to reduce low-back load. Twelve healthy young men lifted 10

Probabilistic Load Models for Simulating the Impact of Load Management

DEFF Research Database (Denmark)

Chen, Peiyuan; Bak-Jensen, Birgitte; Chen, Zhe

2009-01-01

. It is concluded that the AR(12) model is favored with limited measurement data and that the joint-normal model may provide better results with a large data set. Both models can be applied in general to model load time series and used in time-sequential simulation of distribution system planning.......This paper analyzes a distribution system load time series through autocorrelation coefficient, power spectral density, probabilistic distribution and quantile value. Two probabilistic load models, i.e. the joint-normal model and the autoregressive model of order 12 (AR(12)), are proposed...... to simulate the impact of load management. The joint-normal model is superior in modeling the tail region of the hourly load distribution and implementing the change of hourly standard deviation. Whereas the AR(12) model requires much less parameter and is superior in modeling the autocorrelation...

Concurrent Working Memory Load Can Facilitate Selective Attention: Evidence for Specialized Load

Science.gov (United States)

Park, Soojin; Kim, Min-Shik; Chun, Marvin M.

2007-01-01

Load theory predicts that concurrent working memory load impairs selective attention and increases distractor interference (N. Lavie, A. Hirst, J. W. de Fockert, & E. Viding, see record 2004-17825-003). Here, the authors present new evidence that the type of concurrent working memory load determines whether load impairs selective attention or not.…

Using bench press load to predict upper body exercise loads in physically active individuals.

Science.gov (United States)

Wong, Del P; Ngo, Kwan-Lung; Tse, Michael A; Smith, Andrew W

2013-01-01

This study investigated whether loads for assistance exercises of the upper body can be predicted from the loads of the bench press exercise. Twenty-nine physically active collegiate students (age: 22.6 ± 2.5; weight training experience: 2.9 ± 2.1 years; estimated 1RM bench press: 54.31 ± 14.60 kg; 1RM: body weight ratio: 0.80 ± 0.22; BMI: 22.7 ± 2.1 kg·m(-2)) were recruited. The 6RM loads for bench press, barbell bicep curl, overhead dumbbell triceps extension, hammer curl and dumbbell shoulder press were measured. Test-retest reliability for the 5 exercises as determined by Pearson product moment correlation coefficient was very high to nearly perfect (0.82-0.98, p bench press load was significantly correlated with the loads of the 4 assistance exercises (r ranged from 0.80 to 0.93, p bench press load was a significant (R(2) range from 0.64 to 0.86, p Bench press load (0.28) + 6.30 kg, (b) Barbell biceps curl = Bench press load (0.33) + 6.20 kg, (c) Overhead triceps extension = Bench press load (0.33) - 0.60 kg, and (d) Dumbbell shoulder press = Bench press load (0.42) + 5.84 kg. The difference between the actual load and the predicted load using the four equations ranged between 6.52% and 8.54%, such difference was not significant. Fitness professionals can use the 6RM bench press load as a time effective and accurate method to predict training loads for upper body assistance exercises. Key pointsThe bench press load was significantly correlated with the loads of the 4 assistance exercises.No significant differences were found between the actual load and the predicted load in the four equations.6RM bench press load can be a time effective and accurate method to predict training loads for upper body assistance exercises.

The duration perception of loading applications in smartphone: Effects of different loading types.

Science.gov (United States)

Zhao, Wenguo; Ge, Yan; Qu, Weina; Zhang, Kan; Sun, Xianghong

2017-11-01

The loading time of a smartphone application is an important issue, which affects the satisfaction of phone users. This study evaluated the effects of black loading screen (BLS) and animation loading screen (ALS) during application loading on users' duration perception and satisfaction. A total of 43 volunteers were enrolled. They were asked to complete several tasks by clicking the icons of each application, such as camera or message. The duration of loading time for each application was manipulated. The participants were asked to estimate the duration, evaluate the loading speed and their satisfaction. The results showed that the estimated duration increased and the satisfaction for loading period declined along with the loading time increased. Compared with the BLS, the ALS prolonged the estimated duration, and lowered the evaluation of speed and satisfaction. We also discussed the tendency and key inflection points of the curves involving the estimated duration, speed evaluation and satisfaction with the loading time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrical load modeling

Energy Technology Data Exchange (ETDEWEB)

Valgas, Helio Moreira; Pinto, Roberto del Giudice R.; Franca, Carlos [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil); Lambert-Torres, Germano; Silva, Alexandre P. Alves da; Pires, Robson Celso; Costa, Junior, Roberto Affonso [Escola Federal de Engenharia de Itajuba, MG (Brazil)

1994-12-31

Accurate dynamic load models allow more precise calculations of power system controls and stability limits, which are critical mainly in the operation planning of power systems. This paper describes the development of a computer program (software) for static and dynamic load model studies using the measurement approach for the CEMIG system. Two dynamic load model structures are developed and tested. A procedure for applying a set of measured data from an on-line transient recording system to develop load models is described. (author) 6 refs., 17 figs.

Spatial electric load forecasting

CERN Document Server

Willis, H Lee

2002-01-01

Spatial Electric Load Forecasting Consumer Demand for Power and ReliabilityCoincidence and Load BehaviorLoad Curve and End-Use ModelingWeather and Electric LoadWeather Design Criteria and Forecast NormalizationSpatial Load Growth BehaviorSpatial Forecast Accuracy and Error MeasuresTrending MethodsSimulation Method: Basic ConceptsA Detailed Look at the Simulation MethodBasics of Computerized SimulationAnalytical Building Blocks for Spatial SimulationAdvanced Elements of Computerized SimulationHybrid Trending-Simulation MethodsAdvanced

Shot loading platform analysis

International Nuclear Information System (INIS)

Norman, B.F.

1994-01-01

This document provides the wind/seismic analysis and evaluation for the shot loading platform. Hand calculations were used for the analysis. AISC and UBC load factors were used in this evaluation. The results show that the actual loads are under the allowable loads and all requirements are met

Evaluación del desenlace y características clínicas de una serie de niños con neutropenia febril sin foco en el Hospital Universitario San Vicente de Paúl, Medellín, Colombia, 2000-2005

Directory of Open Access Journals (Sweden)

María Adelaida Aristizábal Gil

2008-11-01

Full Text Available Introducción: la neutropenia febril (NF se asocia a infección en 48-60% de los casos y es la segunda causa de ingreso hospitalario al servicio de oncología pediátrica. El objetivo del estudio fue evaluar el desenlace de una serie de niños, que recibían tratamiento para neutropenia febril sin foco aparente, según un protocolo preestablecido en el Servicio de Hematooncología infantil del Hospital Universitario San Vicente de Paúl. MATERIALES Y MÉTODOS: se incluyeron retrospectivamente historias clínicas de pacientes menores de 15 años con diagnóstico nuevo de neoplasia maligna y neutropenia febril sin foco, hospitalizados en un lapso de 5 años. Los datos se registraron en un formato preestablecido. RESULTADOS: se incluyeron 103 historias clínicas con 182 episodios de NF; 34,1% fueron pacientes con leucemia linfoblástica riesgo estándar (LLA, 19,8% LLA de alto riesgo y 13,7%, linfoma no Hodking. 68,1% tuvieron NF grave y en 94,5% se había aplicado quimioterapia previa (79,7% intensiva. La infección se documentó clínicamente en 38,4% y microbiológicamente en 25,2% de los episodios; hubo bacteriemia en 15,4% de los episodios, 3,3% con urocultivo positivo y 6,5% con aislamiento del invasor en otros sitios. Los microorganismos más frecuentes fueron Escherichia coli (24% y Pseudomonas aeruginosa (13%. Hubo mayor resistencia a ceftriazona y cefatzidime tanto de gérmenes grampositivos como de gramnegativos y producción de betalactamasas en 9% durante un año de evaluación; 50% de los aislamientos de S. aureus coagulasa negativo fueron resistentes a oxacilina. En 37 episodios hubo complicaciones (20,2%, la más frecuente de las cuales fue la afectación cardiopulmonar; en 25,2% fracasó el tratamiento, en 21,4% hubo respuesta parcial y 7 pacientes (3,8% fallecieron. CONCLUSIONES: los hallazgos son similares a los reportados por otros autores; predominan en nuestra unidad los microorganismos gramnegativos como causa importante de

Mosaicism of an ELANE mutation in an asymptomatic mother in a familial case of cyclic neutropenia.

Science.gov (United States)

Hirata, Osamu; Okada, Satoshi; Tsumura, Miyuki; Karakawa, Shuhei; Matsumura, Itaru; Kimura, Yujiro; Maihara, Toshiro; Yasunaga, Shin'ichiro; Takihara, Yoshihiro; Ohara, Osamu; Kobayashi, Masao

2015-07-01

To confirm and characterize mosaicism of the cyclic neutropenia (CyN)-related mutation in the ELANE gene identified in the asymptomatic mother of patients with CyN. We identified sibling cases with CyN due to a novel heterozygous splicing site mutation, IVS4 +5SD G>T, in the ELANE gene, resulting in an internal in-frame deletion of 30 nucleotides (corresponding to a ten amino acid deletion, V161-F170). The mutated allele was also detected in their asymptomatic mother but at low frequency. We measured the frequency of the mutant allele from peripheral blood leukocytes (PBLs) by subcloning, and confirmed the allelic frequency of mosaicism in various cell types by massively parallel DNA sequencing (MPS) analysis. In the subcloning analysis, the mutant allele was identified in 21.36 % of PBLs from the asymptomatic mother, compared with 54.72 % of PBLs from the CyN patient. In the MPS analysis, the mutant allele was observed in approximately 30 % of mononuclear cells, CD3(+) T cells, CD14(+) monocytes and the buccal mucosa. Conversely, it was detected in low frequency in polymorphonuclear leukocytes (PLMLs) (3-4 %) and CD16(+) granulocytes (2-3 %). Mosaicism of the ELANE mutation has only previously been identified in one confirmed and one unconfirmed case of SCN. This is the first report of mosaicism of the ELANE mutation in a case of CyN. The MPS results suggest that this de novo mutation occurred during the two-cell stage of embryogenesis. PLMLs expressing the ELANE mutation were found to be actively undergoing apoptosis.

Optimisation of load control

International Nuclear Information System (INIS)

Koponen, P.

1998-01-01

Electricity cannot be stored in large quantities. That is why the electricity supply and consumption are always almost equal in large power supply systems. If this balance were disturbed beyond stability, the system or a part of it would collapse until a new stable equilibrium is reached. The balance between supply and consumption is mainly maintained by controlling the power production, but also the electricity consumption or, in other words, the load is controlled. Controlling the load of the power supply system is important, if easily controllable power production capacity is limited. Temporary shortage of capacity causes high peaks in the energy price in the electricity market. Load control either reduces the electricity consumption during peak consumption and peak price or moves electricity consumption to some other time. The project Optimisation of Load Control is a part of the EDISON research program for distribution automation. The following areas were studied: Optimization of space heating and ventilation, when electricity price is time variable, load control model in power purchase optimization, optimization of direct load control sequences, interaction between load control optimization and power purchase optimization, literature on load control, optimization methods and field tests and response models of direct load control and the effects of the electricity market deregulation on load control. An overview of the main results is given in this chapter

Optimisation of load control

Energy Technology Data Exchange (ETDEWEB)

Koponen, P [VTT Energy, Espoo (Finland)

1998-08-01

Electricity cannot be stored in large quantities. That is why the electricity supply and consumption are always almost equal in large power supply systems. If this balance were disturbed beyond stability, the system or a part of it would collapse until a new stable equilibrium is reached. The balance between supply and consumption is mainly maintained by controlling the power production, but also the electricity consumption or, in other words, the load is controlled. Controlling the load of the power supply system is important, if easily controllable power production capacity is limited. Temporary shortage of capacity causes high peaks in the energy price in the electricity market. Load control either reduces the electricity consumption during peak consumption and peak price or moves electricity consumption to some other time. The project Optimisation of Load Control is a part of the EDISON research program for distribution automation. The following areas were studied: Optimization of space heating and ventilation, when electricity price is time variable, load control model in power purchase optimization, optimization of direct load control sequences, interaction between load control optimization and power purchase optimization, literature on load control, optimization methods and field tests and response models of direct load control and the effects of the electricity market deregulation on load control. An overview of the main results is given in this chapter

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours.

Science.gov (United States)

Aapro, M S; Bohlius, J; Cameron, D A; Dal Lago, Lissandra; Donnelly, J Peter; Kearney, N; Lyman, G H; Pettengell, R; Tjan-Heijnen, V C; Walewski, J; Weber, Damien C; Zielinski, C

2011-01-01

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention

Finite element-based limit load of piping branch junctions under combined loadings

International Nuclear Information System (INIS)

Xuan Fuzhen; Li Peining

2004-01-01

The limit load is an important input parameter in engineering defect-assessment procedures and strength design. In the present work, a total of 100 different piping branch junction models for the limit load calculation were performed under combined internal pressure and moments in use of non-linear finite element (FE) method. Three different existing accumulation rules for limit load, i.e., linear equation, parabolic equation and quadratic equation were discussed on the basis of FE results. A novel limit load solution was developed based on detailed three-dimensional FE limit analyses which accommodated the geometrical parameter influence, together with analytical solutions based on equilibrium stress fields. Finally, six experimental results were provided to justify the presented equation. According to the FE limit analysis, limit load interaction of the piping tees under combined pressure and moments has a relationship with the geometrical parameters, especially with the diameter ratio d/D. The predicted limit loads from the presented formula are very close to the experimental data. The resulting limit load solution is given in a closed form, and thus can be easily used in practice

Short term load forecasting of anomalous load using hybrid soft computing methods

Science.gov (United States)

Rasyid, S. A.; Abdullah, A. G.; Mulyadi, Y.

2016-04-01

Load forecast accuracy will have an impact on the generation cost is more economical. The use of electrical energy by consumers on holiday, show the tendency of the load patterns are not identical, it is different from the pattern of the load on a normal day. It is then defined as a anomalous load. In this paper, the method of hybrid ANN-Particle Swarm proposed to improve the accuracy of anomalous load forecasting that often occur on holidays. The proposed methodology has been used to forecast the half-hourly electricity demand for power systems in the Indonesia National Electricity Market in West Java region. Experiments were conducted by testing various of learning rate and learning data input. Performance of this methodology will be validated with real data from the national of electricity company. The result of observations show that the proposed formula is very effective to short-term load forecasting in the case of anomalous load. Hybrid ANN-Swarm Particle relatively simple and easy as a analysis tool by engineers.

Load-redistribution strategy based on time-varying load against cascading failure of complex network

International Nuclear Information System (INIS)

Liu Jun; Shi Xin; Wang Kai; Shi Wei-Ren; Xiong Qing-Yu

2015-01-01

Cascading failure can cause great damage to complex networks, so it is of great significance to improve the network robustness against cascading failure. Many previous existing works on load-redistribution strategies require global information, which is not suitable for large scale networks, and some strategies based on local information assume that the load of a node is always its initial load before the network is attacked, and the load of the failure node is redistributed to its neighbors according to their initial load or initial residual capacity. This paper proposes a new load-redistribution strategy based on local information considering an ever-changing load. It redistributes the loads of the failure node to its nearest neighbors according to their current residual capacity, which makes full use of the residual capacity of the network. Experiments are conducted on two typical networks and two real networks, and the experimental results show that the new load-redistribution strategy can reduce the size of cascading failure efficiently. (paper)

Laterally loaded masonry

DEFF Research Database (Denmark)

Raun Gottfredsen, F.

In this thesis results from experiments on mortar joints and masonry as well as methods of calculation of strength and deformation of laterally loaded masonry are presented. The strength and deformation capacity of mortar joints have been determined from experiments involving a constant compressive...... stress and increasing shear. The results show a transition to pure friction as the cohesion is gradually destroyed. An interface model of a mortar joint that can take into account this aspect has been developed. Laterally loaded masonry panels have also been tested and it is found to be characteristic...... that laterally loaded masonry exhibits a non-linear load-displacement behaviour with some ductility....

Critical Axial Load

Directory of Open Access Journals (Sweden)

Walt Wells

2008-01-01

Full Text Available Our objective in this paper is to solve a second order differential equation for a long, simply supported column member subjected to a lateral axial load using Heun's numerical method. We will use the solution to find the critical load at which the column member will fail due to buckling. We will calculate this load using Euler's derived analytical approach for an exact solution, as well as Euler's Numerical Method. We will then compare the three calculated values to see how much they deviate from one another. During the critical load calculation, it will be necessary to calculate the moment of inertia for the column member.

Cognitive Load of Learner Control: Extraneous or Germane Load?

Directory of Open Access Journals (Sweden)

Mieke Vandewaetere

2013-01-01

Full Text Available Computer-based learning environments become more tailored when learners can exert control over one or more parts of the learning process. Learner control (LC demands additional efforts of learners because, in addition to learning, they also have to monitor that learning. As a consequence, LC may cause additional cognitive load and even cognitive overload. The central question in this study is what type of cognitive load is induced by LC and whether the experienced load is related to learning outcomes. For this study, half of the students had control over task selection, while the other half had not. Within each condition, students were assigned to a single treatment, with the primary task to solely focus on the learning content, and a dual treatment, comprising a primary task and a secondary task. The results indicate that LC did not impose higher cognitive load as measured by secondary task scores and mental effort ratings.

Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation.

Science.gov (United States)

Leal, Fabio E; Menezes, Soraya Maria; Costa, Emanuela A S; Brailey, Phillip M; Gama, Lucio; Segurado, Aluisio C; Kallas, Esper G; Nixon, Douglas F; Dierckx, Tim; Khouri, Ricardo; Vercauteren, Jurgen; Galvão-Castro, Bernardo; Saraiva Raposo, Rui Andre; Van Weyenbergh, Johan

2018-01-01

HTLV-1-Associated Myelopathy (HAM/TSP) is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β) in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this "IFN paradox" in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4 + T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax), proviral load and 42 host genes with known antiretroviral (anti-HIV) activity in purified CD4 + T cells. This revealed two major clusters ("antiviral/protective" vs. "proviral/deleterious"), as evidenced by significant negative (TRIM5/TRIM22/BST2) vs. positive correlation (ISG15/PAF1/CDKN1A) with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H), underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2) were significantly up-regulated by IFN

Lateral loadings on snubber assemblies

International Nuclear Information System (INIS)

Raphael, L.S.

1981-01-01

This paper examines the installation of snubber assemblies in power plants with respect to transverse or lateral loads as well as axial loads. Evaluation of the effects of low level, lateral loads was performed by analytical means. At higher loadings, the snubber assembly could no longer be treated as a column; therefore, the effects of lateral loadings was determined by test. The test consisted of applying both lateral and axial loads simultaneously. Results of both the analysis and the test showed that the application of lateral loads had a considerable effect on the snubber assemblies

Cognitive Load and Cooperation

DEFF Research Database (Denmark)

Døssing, Felix Sebastian; Piovesan, Marco; Wengström, Erik Roland

2017-01-01

We study the effect of intuitive and reflective processes on cooperation using cognitive load. Compared with time constraint, which has been used in the previous literature, cognitive load is a more direct way to block reflective processes, and thus a more suitable way to study the link between...... intuition and cooperation. Using a repeated public goods game, we study the effect of different levels of cognitive load on contributions. We show that a higher cognitive load increases the initial level of cooperation. In particular, subjects are significantly less likely to fully free ride under high...... cognitive load....

Limit loads in nozzles

International Nuclear Information System (INIS)

Zouain, N.

1983-01-01

The static method for the evaluation of the limit loads of a perfectly elasto-plastic structure is presented. Using the static theorem of Limit Analysis and the Finite Element Method, a lower bound for the colapso load can be obtained through a linear programming problem. This formulation if then applied to symmetrically loaded shells of revolution and some numerical results of limit loads in nozzles are also presented. (Author) [pt

Diluting the Burden of Load: Perceptual Load Effects Are Simply Dilution Effects

Science.gov (United States)

Tsal, Yehoshua; Benoni, Hanna

2010-01-01

The substantial distractor interference obtained for small displays when the target appears alone is reduced in large displays when the target is embedded among neutral letters. This finding has been interpreted as reflecting low-load and high-load processing, respectively, thereby supporting the theory of perceptual load (Lavie & Tsal, 1994).…

Perceptual load affects exogenous spatial orienting while working memory load does not.

Science.gov (United States)

Santangelo, Valerio; Finoia, Paola; Raffone, Antonino; Belardinelli, Marta Olivetti; Spence, Charles

2008-01-01

We examined whether or not increasing visual perceptual load or visual working memory (WM) load would affect the exogenous orienting of visuo-spatial attention, in order to assess whether or not exogenous orienting is genuinely automatic. In Experiment 1, we manipulated visual perceptual load by means of a central morphing shape that in some trials morphed into a particular target shape (a rectangle) that participants had to detect. In Experiment 2, the possibility that the presentation of any changing stimulus at fixation would eliminate exogenous orienting was ruled out, by presenting two alternating letters at fixation. In Experiment 3, we manipulated visual WM load by means of arrays consisting of three (low-load) or five (high-load) randomly located coloured squares. The participants had to remember these items in order to judge whether a cued square had been presented in the same or different colour at the end of each trial. In all the experiments, exogenous visuo-spatial attentional orienting was measured by means of an orthogonal spatial cuing task, in which the participants had to discriminate the elevation (up vs. down) of a visual target previously cued by a spatially nonpredictive visual cue. The results showed that increasing the perceptual load of the task eliminated the exogenous orienting of visuo-spatial attention. By contrast, increasing the WM load had no effect on spatial orienting. These results are discussed in terms of the light that they shed on claims regarding the automaticity of visuo-spatial exogenous orienting.

Load Balancing in Hypergraphs

Science.gov (United States)

Delgosha, Payam; Anantharam, Venkat

2018-03-01

Consider a simple locally finite hypergraph on a countable vertex set, where each edge represents one unit of load which should be distributed among the vertices defining the edge. An allocation of load is called balanced if load cannot be moved from a vertex to another that is carrying less load. We analyze the properties of balanced allocations of load. We extend the concept of balancedness from finite hypergraphs to their local weak limits in the sense of Benjamini and Schramm (Electron J Probab 6(23):13, 2001) and Aldous and Steele (in: Probability on discrete structures. Springer, Berlin, pp 1-72, 2004). To do this, we define a notion of unimodularity for hypergraphs which could be considered an extension of unimodularity in graphs. We give a variational formula for the balanced load distribution and, in particular, we characterize it in the special case of unimodular hypergraph Galton-Watson processes. Moreover, we prove the convergence of the maximum load under some conditions. Our work is an extension to hypergraphs of Anantharam and Salez (Ann Appl Probab 26(1):305-327, 2016), which considered load balancing in graphs, and is aimed at more comprehensively resolving conjectures of Hajek (IEEE Trans Inf Theory 36(6):1398-1414, 1990).

Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia.

Science.gov (United States)

Aarts, Maureen J; Grutters, Janneke P; Peters, Frank P; Mandigers, Caroline M; Dercksen, M Wouter; Stouthard, Jacqueline M; Nortier, Hans J; van Laarhoven, Hanneke W; van Warmerdam, Laurence J; van de Wouw, Agnes J; Jacobs, Esther M; Mattijssen, Vera; van der Rijt, Carin C; Smilde, Tineke J; van der Velden, Annette W; Temizkan, Mehmet; Batman, Erdogan; Muller, Erik W; van Gastel, Saskia M; Joore, Manuela A; Borm, George F; Tjan-Heijnen, Vivianne C

2013-12-01

Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary pegfilgrastim prophylaxis. Our economic evaluation used a health care perspective and was based on a randomized study in patients with breast cancer with increased risk of FN, comparing primary G-CSF prophylaxis throughout all chemotherapy cycles (G-CSF 1-6 cycles) with prophylaxis during the first two cycles only (G-CSF 1-2 cycles). Primary outcome was cost effectiveness expressed as costs per patient with episodes of FN prevented. The incidence of FN increased from 10% in the G-CSF 1 to 6 cycles study arm (eight of 84 patients) to 36% in the G-CSF 1 to 2 cycles study arm (30 of 83 patients), whereas the mean total costs decreased from € 20,658 (95% CI, € 20,049 to € 21,247) to € 17,168 (95% CI € 16,239 to € 18,029) per patient, respectively. Chemotherapy and G-CSF determined 80% of the total costs. As expected, FN-related costs were higher in the G-CSF 1 to 2 cycles arm. The incremental cost effectiveness ratio for the G-CSF 1 to 6 cycles arm compared with the G-CSF 1 to 2 cycles arm was € 13,112 per patient with episodes of FN prevented. We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of FN prevented.

Impact of measurement uncertainty from experimental load distribution factors on bridge load rating

Science.gov (United States)

Gangone, Michael V.; Whelan, Matthew J.

2018-03-01

Load rating and testing of highway bridges is important in determining the capacity of the structure. Experimental load rating utilizes strain transducers placed at critical locations of the superstructure to measure normal strains. These strains are then used in computing diagnostic performance measures (neutral axis of bending, load distribution factor) and ultimately a load rating. However, it has been shown that experimentally obtained strain measurements contain uncertainties associated with the accuracy and precision of the sensor and sensing system. These uncertainties propagate through to the diagnostic indicators that in turn transmit into the load rating calculation. This paper will analyze the effect that measurement uncertainties have on the experimental load rating results of a 3 span multi-girder/stringer steel and concrete bridge. The focus of this paper will be limited to the uncertainty associated with the experimental distribution factor estimate. For the testing discussed, strain readings were gathered at the midspan of each span of both exterior girders and the center girder. Test vehicles of known weight were positioned at specified locations on each span to generate maximum strain response for each of the five girders. The strain uncertainties were used in conjunction with a propagation formula developed by the authors to determine the standard uncertainty in the distribution factor estimates. This distribution factor uncertainty is then introduced into the load rating computation to determine the possible range of the load rating. The results show the importance of understanding measurement uncertainty in experimental load testing.

Blinded by the load: attention, awareness and the role of perceptual load.

Science.gov (United States)

Lavie, Nilli; Beck, Diane M; Konstantinou, Nikos

2014-05-05

What is the relationship between attention and conscious awareness? Awareness sometimes appears to be restricted to the contents of focused attention, yet at other times irrelevant distractors will dominate awareness. This contradictory relationship has also been reflected in an abundance of discrepant research findings leading to an enduring controversy in cognitive psychology. Lavie's load theory of attention suggests that the puzzle can be solved by considering the role of perceptual load. Although distractors will intrude upon awareness in conditions of low load, awareness will be restricted to the content of focused attention when the attended information involves high perceptual load. Here, we review recent evidence for this proposal with an emphasis on the various subjective blindness phenomena, and their neural correlates, induced by conditions of high perceptual load. We also present novel findings that clarify the role of attention in the response to stimulus contrast. Overall, this article demonstrates a critical role for perceptual load across the spectrum of perceptual processes leading to awareness, from the very early sensory responses related to contrast detection to explicit recognition of semantic content.

A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

Science.gov (United States)

Tamary, H; Yaniv, I; Stein, J; Dgany, O; Shalev, Z; Shechter, T; Resnitzky, P; Shaft, D; Zoldan, M; Kornreich, L; Levy, R; Cohen, A; Moser, R A; Kapelushnik, J; Shalev, H

2003-09-01

Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

Design loads, loading combinations and structural acceptance criteria for BWR containments in the United States

International Nuclear Information System (INIS)

Edwards, N.W.

1979-01-01

The definition of loads, loading combinations, and structural acceptance criteria used for the design and evaluation of BWR containments in the Unites States has become much more comprehensive over the past decade. The Mark I pressure suppression containment vessels were designed for a static design pressure, a design temperature, dead load and static equivalent earthquake. The current Mark III containments are being designed to accommodate many more loads such as safety relief valve discharge loads, and suppression pool hydrodynamic loadings associated with the steam condensation phenomena as well as pressure and temperature transients for a range of pipe break sizes. Consistent with the more comprehensive definition of loads and loading combinations, the ASME Code presently establishes structural acceptance criteria with different margins of safety by the definition of Service Level Assignments A, B, C and D. Acting in a responsible manner, United States utilities are currently evaluating and modifying existing containment vessels to account for the more detailed load definition and structural acceptance criteria. (orig.)

Carbohydrate-Loading Diet

Science.gov (United States)

... Grape juice (12 ounces) 55 225 Lunch Milk, chocolate, reduced fat (12 ounces) 45 285 4 slices ... usual during carbohydrate loading to get the same benefits as a man does. Despite carbohydrate loading, you ...

ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

Science.gov (United States)

Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

2017-10-01

Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

Science.gov (United States)

Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

2016-05-12

Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

Survey of feline leukemia virus and feline coronaviruses in captive neotropical wild felids from Southern Brazil.

Science.gov (United States)

Guimaraes, Ana M S; Brandão, Paulo E; de Moraes, Wanderlei; Cubas, Zalmir S; Santos, Leonilda C; Villarreal, Laura Y B; Robes, Rogério R; Coelho, Fabiana M; Resende, Mauricio; Santos, Renata C F; Oliveira, Rosangela C; Yamaguti, Mauricio; Marques, Lucas M; Neto, Renata L; Buzinhani, Melissa; Marques, Regina; Messick, Joanne B; Biondo, Alexander W; Timenetsky, Jorge

2009-06-01

A total of 57 captive neotropical felids (one Leopardus geoffroyi, 14 Leopardus pardalis, 17 Leopardus wiedii, 22 Leopardus tigrinus, and three Puma yagouaroundi) from the Itaipu Binacional Wildlife Research Center (Refúgio Bela Vista, Southern Brazil) were anesthetized for blood collection. Feces samples were available for 44 animals, including one L. geoffroyi, eight L. pardalis, 14 L. wiedii, 20 L. tigrinus, and one P. yagouaroundi. Total DNA and RNA were extracted from blood and feces, respectively, using commercial kits. Blood DNA samples were evaluated by polymerase chain reaction (PCR) for feline leukemia virus (FeLV) proviral DNA, whereas reverse transcriptase-PCR was run on fecal samples for detection of coronavirus RNA. None of the samples were positive for coronaviruses. A male L. pardalis and a female L. tigrinus were positive for FeLV proviral DNA, and identities of PCR products were confirmed by sequencing. This is the first evidence of FeLV proviral DNA in these species in Southern Brazil.

Miliaria-rash after neutropenic fever and induction chemotherapy for acute myelogenous leukemia Miliária 'rash' após neutropenia febril e quimioterapia de indução para a leucemia mielóide aguda

Directory of Open Access Journals (Sweden)

Tuyet A Nguyen

2011-08-01

Full Text Available Miliaria is a disorder of the eccrine sweat glands which occurs in conditions of increased heat and humidity. It can be associated with persistent febrile states as well as with certain drugs. We presented a 40 year-old female with myelodysplastic syndrome and progression to acute myelogenous leukemia who was admitted to the hospital for chemotherapy induction. The patient was treated with idarubicin and cytarabine. She became pancytopenic and developed neutropenic fever and was started on vancomycin and cefepime, but was persistently febrile with night sweats. Five days into her fevers, she developed diffuse, nonpruritic and fragile vesicles together with drenching nightsweats. The patient's exanthem was diagnosed as Miliaria crystallina, most probably induced by neutropenic fever and idarubucin exposureMiliária é uma desordem das glândulas sudoríparas écrinas, que ocorre em condições de aumento de calor e umidade. Miliária pode ser associada com estados febris persistentes bem como com certos medicamentos. Apresentamos o caso de uma mulher de 40 anos com síndrome mielodisplásica e progressão para leucemia mielóide aguda que foi admitida no hospital para quimioterapia de indução. A paciente foi tratada com idarrubicina e citarabina. Ela se tornou pancitopênica e desenvolveu neutropenia febril. Iniciou tratamento com vancomicina e cefepime, mas a febre com sudorese noturna continou. Cinco dias depois a paciente desenvolveu vesículas difusas, não pruríticas e frágeis juntamente com a persistência de sudorese noturna. O exantema do paciente foi diagnosticado como Miliária cristalina, provavelmente induzida por neutropenia febril e exposição a idarubucin

Load power device and system for real-time execution of hierarchical load identification algorithms

Science.gov (United States)

Yang, Yi; Madane, Mayura Arun; Zambare, Prachi Suresh

2017-11-14

A load power device includes a power input; at least one power output for at least one load; and a plurality of sensors structured to sense voltage and current at the at least one power output. A processor is structured to provide real-time execution of: (a) a plurality of load identification algorithms, and (b) event detection and operating mode detection for the at least one load.

On load paths and load bearing topology from finite element analysis

International Nuclear Information System (INIS)

Kelly, D; Reidsema, C; Lee, M

2010-01-01

Load paths can be mapped from vector plots of 'pointing stress vectors'. They define a path along which a component of load remains constant as it traverses the solution domain. In this paper the theory for the paths is first defined. Properties of the plots that enable a designer to interpret the structural behavior from the contours are then identified. Because stress is a second order tensor defined on an orthogonal set of axes, the vector plots define separate paths for load transfer in each direction of the set of axes. An algorithm is therefore presented that combines the vectors to define a topology to carry the loads. The algorithm is shown to straighten the paths reducing bending moments and removing stress concentration. Application to a bolted joint, a racing car body and a yacht hull demonstrate the usefulness of the plots.

Concentrated loads on concrete

DEFF Research Database (Denmark)

Lorenzen, Karen Grøndahl; Nielsen, Mogens Peter

1997-01-01

This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas are devel......This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas...

The effect of load-controlled bending load on the failure pressure of wall-thinned pipe elbows

International Nuclear Information System (INIS)

Kim, Jin Weon; Yoon, Min Soo; Park, Chi Yong

2013-01-01

Highlights: • We evaluated bending load effect on the failure pressure of wall-thinned pipe elbows. • Burst tests were conducted on real-scale elbow specimens with local wall thinning. • The tests were performed under combined pressure and load-controlled bending. • Load-controlled bending reduced the failure pressure of wall-thinned elbows. • Bending load effect was significant for opening-mode and intrados wall-thinning case. - Abstract: In this research, burst tests were conducted on real-scale elbow specimens, each with an artificial local wall-thinning defect, under combined internal pressure and constant in-plane bending load, as well as under simple internal pressure, to evaluate the effect of load-controlled bending load on the failure pressure of locally wall-thinned pipe elbows. Ninety-degree, 65A Schedule 80 elbows, with wall-thinning defects in the intrados and extrados, were used as specimens. The bending loads were in-plane opening- and closing-mode bending, applied in load-control mode. The results clearly indicated that a load-controlled in-plane bending load reduced the failure pressure of wall-thinned pipe elbows, in contrast to observations previously made under displacement-controlled bending conditions. The effect of the bending load was more significant for opening-mode than for closing-mode bending, regardless of the wall-thinning location in the elbow. Also, the effect was greater when the wall-thinning defect was located in the intrados region of the elbow, rather than the extrados region. Existing models that have been proposed to evaluate the failure of wall-thinned elbows under simple internal pressure conservatively predicted the failure pressure of elbows subjected to a combined internal pressure and load-controlled bending load

Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes.

Science.gov (United States)

Kannan, Vinayagam; Balabathula, Pavan; Divi, Murali K; Thoma, Laura A; Wood, George C

2015-01-01

The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.

Reduced design load basis for ultimate blade loads estimation in multidisciplinary design optimization frameworks

DEFF Research Database (Denmark)

Pavese, Christian; Tibaldi, Carlo; Larsen, Torben J.

2016-01-01

The aim is to provide a fast and reliable approach to estimate ultimate blade loads for a multidisciplinary design optimization (MDO) framework. For blade design purposes, the standards require a large amount of computationally expensive simulations, which cannot be efficiently run each cost...... function evaluation of an MDO process. This work describes a method that allows integrating the calculation of the blade load envelopes inside an MDO loop. Ultimate blade load envelopes are calculated for a baseline design and a design obtained after an iteration of an MDO. These envelopes are computed...... for a full standard design load basis (DLB) and a deterministic reduced DLB. Ultimate loads extracted from the two DLBs with the two blade designs each are compared and analyzed. Although the reduced DLB supplies ultimate loads of different magnitude, the shape of the estimated envelopes are similar...

Probabilistic model of bridge vehicle loads in port area based on in-situ load testing

Science.gov (United States)

Deng, Ming; Wang, Lei; Zhang, Jianren; Wang, Rei; Yan, Yanhong

2017-11-01

Vehicle load is an important factor affecting the safety and usability of bridges. An statistical analysis is carried out in this paper to investigate the vehicle load data of Tianjin Haibin highway in Tianjin port of China, which are collected by the Weigh-in- Motion (WIM) system. Following this, the effect of the vehicle load on test bridge is calculated, and then compared with the calculation result according to HL-93(AASHTO LRFD). Results show that the overall vehicle load follows a distribution with a weighted sum of four normal distributions. The maximum vehicle load during the design reference period follows a type I extremum distribution. The vehicle load effect also follows a weighted sum of four normal distributions, and the standard value of the vehicle load is recommended as 1.8 times that of the calculated value according to HL-93.

Load Balancing Scientific Applications

Energy Technology Data Exchange (ETDEWEB)

Pearce, Olga Tkachyshyn [Texas A & M Univ., College Station, TX (United States)

2014-12-01

The largest supercomputers have millions of independent processors, and concurrency levels are rapidly increasing. For ideal efficiency, developers of the simulations that run on these machines must ensure that computational work is evenly balanced among processors. Assigning work evenly is challenging because many large modern parallel codes simulate behavior of physical systems that evolve over time, and their workloads change over time. Furthermore, the cost of imbalanced load increases with scale because most large-scale scientific simulations today use a Single Program Multiple Data (SPMD) parallel programming model, and an increasing number of processors will wait for the slowest one at the synchronization points. To address load imbalance, many large-scale parallel applications use dynamic load balance algorithms to redistribute work evenly. The research objective of this dissertation is to develop methods to decide when and how to load balance the application, and to balance it effectively and affordably. We measure and evaluate the computational load of the application, and develop strategies to decide when and how to correct the imbalance. Depending on the simulation, a fast, local load balance algorithm may be suitable, or a more sophisticated and expensive algorithm may be required. We developed a model for comparison of load balance algorithms for a specific state of the simulation that enables the selection of a balancing algorithm that will minimize overall runtime.

Status of load management

Energy Technology Data Exchange (ETDEWEB)

Juchymenko, A

1983-08-01

A summary is presented of the status of load management, defined as any activity by an electric utility to affect the size and characteristics of its load. Load management is currently viewed by electric utilities as an important tool for marketing electricity in a competitive fuel situation. A major aim of the National Energy Program is to reduce Canada's dependence on oil by 1990 to 10% of the energy used by all markets. As a result, electricity may play a greater role in the supply of primary energy. Research in load management has been directed mostly towards the residential market, especially direct control of domestic hot water heaters and air conditioners. Studies conducted in Canada and the U.S. to determine user's receptiveness to direct control of loads and thermal energy storage systems indicate that these load management techniques are in most cases not acceptable to customers, who prefer voluntary reduction in demand. The potential exists in the industrial market to use load management to assist in electrifying many of the fossil fuel-fired processes at competitive energy prices. Some of the more important applications include an industrial heat pump to heat liquids to 120{degree}C, induction heating for melting and heat treating of metals, and mechanical vapor recompression equipment to produce proces steam. 21 refs., 2 figs., 2 tabs.

Strategies for Controlling Plug Loads. A Tool for Reducing Plug Loads in Commercial Buildings

Energy Technology Data Exchange (ETDEWEB)

Torcellini, Paul [National Renewable Energy Lab. (NREL), Golden, CO (United States); Bonnema, Eric [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sheppy, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Pless, Shanti [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2015-09-01

Plug loads are often not considered as part of the energy savings measures in Commercial Buildings; however, they can account for up to 50% of the energy used in the building. These loads are numerous and often scattered throughout a building. Some of these loads are purchased by the owner and some designed into the building or the tenant finishes for a space. This document provides a strategy and a tool for minimizing these loads.

Cognitive load measurement as a means to advance cognitive load theory

NARCIS (Netherlands)

Paas, F.; Tuovinen, J.E.; Tabbers, H.; van Gerven, P.W.M.

2003-01-01

This paper discusses cognitive load measurement techniques with regard to their contribution to cognitive load theory (CLT). CLT is concerned with the design of instructional methods that efficiently use people's limited cognitive processing capacity to apply acquired knowledge and skills to new

Evaluation of self-assembled HCPT-loaded PEG-b-PLA nanoparticles by comparing with HCPT-loaded PLA nanoparticles.

Science.gov (United States)

Yang, Xiangrui; Wu, Shichao; Wang, Yange; Li, Yang; Chang, Di; Luo, Yin; Ye, Shefang; Hou, Zhenqing

2014-12-01

We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(D,L-lactide) (PEG-b-PLA) and PLA, respectively. Both HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of -31.2 and -45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG-b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG-b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG-b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

Beam loading

OpenAIRE

Boussard, Daniel

1987-01-01

We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superco...

Load regulating expansion fixture

International Nuclear Information System (INIS)

Wagner, L.M.; Strum, M.J.

1998-01-01

A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

Dorzolamide Loaded Niosomal Vesicles: Comparison of Passive and Remote Loading Methods.

Science.gov (United States)

Hashemi Dehaghi, Mohadeseh; Haeri, Azadeh; Keshvari, Hamid; Abbasian, Zahra; Dadashzadeh, Simin

2017-01-01

Glaucoma is a common progressive eye disorder and the treatment strategies will benefit from nanoparticulate delivery systems with high drug loading and sustained delivery of intraocular pressure lowering agents. Niosomes have been reported as a novel approach to improve drug low corneal penetration and bioavailability characteristics. Along with this, poor entrapment efficiency of hydrophilic drug in niosomal formulation remains as a major formulation challenge. Taking this perspective into consideration, dorzolamide niosomes were prepared employing two different loading methodologies (passive and remote loading methods) and the effects of various formulation variables (lipid to drug ratio, cholesterol percentage, drug concentration, freeze/thaw cycles, TPGS content, and external and internal buffer molarity and pH) on encapsulation efficiency were assessed. Encapsulation of dorzolamide within niosomes increased remarkably by the incorporation of higher cholesterol percentage as well as increasing the total lipid concentration. Remote loading method showed higher efficacy for drug entrapment compared to passive loading technique. Incorporation of TPGS in bilayer led to decrease in EE; however, retarded drug release rate. Scanning electron microscopy (SEM) studies confirmed homogeneous particle distribution, and spherical shape with smooth surface. In conclusion, the highest encapsulation can be obtained using phosphate gradient method and 50% cholesterol in Span 60 niosomal formulation.

Multi-Capacity Load Cell Concept

Directory of Open Access Journals (Sweden)

Seif. M. OSMAN

2014-09-01

Full Text Available Force measuring systems are usually used to calibrate force generated systems, it is not preferable to use load cells to measure forces less than 10 % of its nominal capacity. Several load cells are required to offer calibration facilities at sites to cover different ranges, this lead to difficulties in handling procedures, through the need for several carrying cases to carry this overweight in addition to the over cost of purchasing several load cells. This article concerns with introducing a new concept for designing a multi-capacity load cell as a new force standard in the field of measuring the force. This multi-capacity load cell will replace a set of load cells and reflects economically on the total cost and on easiness of handling procedures.

What does germane load mean? An empirical contribution to the cognitive load theory.

Science.gov (United States)

Debue, Nicolas; van de Leemput, Cécile

2014-01-01

While over the last decades, much attention has been paid to the mental workload in the field of human computer interactions, there is still a lack of consensus concerning the factors that generate it as well as the measurement methods that could reflect workload variations. Based on the multifactorial Cognitive Load Theory (CLT), our study aims to provide some food for thought about the subjective and objective measurement that can be used to disentangle the intrinsic, extraneous, and germane load. The purpose is to provide insight into the way cognitive load can explain how users' cognitive resources are allocated in the use of hypermedia, such as an online newspaper. A two-phase experiment has been conducted on the information retention from online news stories. Phase 1 (92 participants) examined the influence of multimedia content on performance as well as the relationships between cognitive loads and cognitive absorption. In Phase 2 (36 participants), eye-tracking data were collected in order to provide reliable and objective measures. Results confirmed that performance in information retention was impacted by the presence of multimedia content such as animations and pictures. The higher number of fixations on these animations suggests that users' attention could have been attracted by them. Results showed the expected opposite relationships between germane and extraneous load, a positive association between germane load and cognitive absorption and a non-linear association between intrinsic and germane load. The trends based on eye-tracking data analysis provide some interesting findings about the relationship between longer fixations, shorter saccades and cognitive load. Some issues are raised about the respective contribution of mean pupil diameter and Index of Cognitive Activity.

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

Science.gov (United States)

Skedgel, Chris; Rayson, Daniel; Younis, Tallal

2016-01-01

Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

A comparison of measured wind park load histories with the WISPER and WISPERX load spectra

Science.gov (United States)

Kelley, N. D.

1995-01-01

The blade-loading histories from two adjacent Micon 65/13 wind turbines are compared with the variable-amplitude test-loading histories known as the WISPER and WISPERX spectra. These standardized loading sequences were developed from blade flapwise load histories taken from nine different horizontal-axis wind turbines operating under a wide range of conditions in Europe. The subject turbines covered a broad spectrum of rotor diameters, materials, and operating environments. The final loading sequences were developed as a joint effort of thirteen different European organizations. The goal was to develop a meaningful loading standard for horizontal-axis wind turbine blades that represents common interaction effects seen in service. In 1990, NREL made extensive load measurements on two adjacent Micon 65/13 wind turbines in simultaneous operation in the very turbulent environment of a large wind park. Further, before and during the collection of the loads data, comprehensive measurements of the statistics of the turbulent environment were obtained at both the turbines under test and at two other locations within the park. The trend to larger but lighter wind turbine structures has made an understanding of the expected lifetime loading history of paramount importance. Experience in the US has shown that the turbulence-induced loads associated with multi-row wind parks in general are much more severe than for turbines operating individually or within widely spaced environments. Multi-row wind parks are much more common in the US than in Europe. In this paper we report on our results in applying the methodology utilized to develop the WISPER and WISPERX standardized loading sequences using the available data from the Micon turbines. While the intended purpose of the WISPER sequences were not to represent a specific operating environment, we believe the exercise is useful, especially when a turbine design is likely to be installed in a multi-row wind park.

A combined loading system integrated with portable winch and polyethylene chutes for loading of timber products

Directory of Open Access Journals (Sweden)

H. Hulusi Acar

2016-01-01

Full Text Available Truck loading operation is an important task during timber production operations in forestry. In Turkey, approximately 50 million timbers/logs are being produced per year, and then they are loaded into the logging trucks. The timber/logs are transported over the forest roads with an average of one million roundtrips. However, the traditional loading methods using manpower are mostly performed while some part is done by using loading machines which can be very costly and risky. This study aims developing a combined loading system in which heavy logs are loaded into logging trucks by pulling them by a log-line powered by a portable crane within the chute system. The slope of the log-line from ground to logging truck varied between 1% and 25%. Within the each work cycle of loading operation, only one log was loaded by pulling with portable crane. The average loading time was found as 161.8 seconds per cycle, in which 67% of the time was spent on pulling the log into the logging truck. The results indicated that the average pulling speed with crane power was 840.4 m/hr and productivity was calculated as 4.94 m3/hr. The result on system speed and productivity indicated close relations with results from previous studies. The hydraulic grapple loader or cranes are widely used and common loading machines, but they cannot be efficiently used in forestry operations, especially ones having a low timber productivity rate or having low economic value timber. In these conditions, loading methods that are cost efficient and do not require higher production rate should be employed. Therefore, a combined loading system introduced in this study can be a feasible solution for loading operations in those cases. Furthermore, it is believed that this loading system integrated with a portable crane can be cost efficient and time saving solution, as well as ergonomic and safe method in the field.

Optimal Control Allocation with Load Sensor Feedback for Active Load Suppression

Science.gov (United States)

Miller, Christopher

2017-01-01

These slide sets describe the OCLA formulation and associated algorithms as a set of new technologies in the first practical application of load limiting flight control utilizing load feedback as a primary control measurement. Slide set one describes Experiment Development and slide set two describes Flight-Test Performance.

The Atlas load protection switch

CERN Document Server

Davis, H A; Dorr, G; Martínez, M; Gribble, R F; Nielsen, K E; Pierce, D; Parsons, W M

1999-01-01

Atlas is a high-energy pulsed-power facility under development to study materials properties and hydrodynamics experiments under extreme conditions. Atlas will implode heavy liner loads (m~45 gm) with a peak current of 27-32 MA delivered in 4 mu s, and is energized by 96, 240 kV Marx generators storing a total of 23 MJ. A key design requirement for Atlas is obtaining useful data for 95601130f all loads installed on the machine. Materials response calculations show current from a prefire can damage the load requiring expensive and time consuming replacement. Therefore, we have incorporated a set of fast-acting mechanical switches in the Atlas design to reduce the probability of a prefire damaging the load. These switches, referred to as the load protection switches, short the load through a very low inductance path during system charge. Once the capacitors have reached full charge, the switches open on a time scale short compared to the bank charge time, allowing current to flow to the load when the trigger pu...

Dynamic stability under sudden loads

International Nuclear Information System (INIS)

Simitses, G.J.

1998-01-01

The concept of dynamic stability of elastic structures subjected to sudden (step) loads is discussed. The various criteria and related methodologies for estimating critical conditions are presented with the emphasis on their similarities and differences. These are demonstrated by employing a simple mechanical model. Several structural configurations are analyzed, for demonstration purposes, with the intention of comparing critical dynamic loads to critical static loads. These configurations include shallow arches and shallow spherical caps, two bar frames, and imperfect cylindrical shells of metallic as well as laminated composite construction. In the demonstration examples, the effect of static pre loading on the dynamic critical load is presented

Damage Accumulation in Vertical Breakwaters due to Combined Impact Loading and Pulsating Wave Loads

DEFF Research Database (Denmark)

Sørensen, John Dalsgaard; Nielsen, Søren R. K.

1999-01-01

Vertical wall breakwaters used to protect for example an harbour from large waves usually consist of large concrete caissons placed on the seabed. The wave loads can be divided in two types, pulsating and impact loads. For some types of breakwaters especially the impact wave loads can be very large...

Load Induced Blindness

Science.gov (United States)

Macdonald, James S. P.; Lavie, Nilli

2008-01-01

Although the perceptual load theory of attention has stimulated a great deal of research, evidence for the role of perceptual load in determining perception has typically relied on indirect measures that infer perception from distractor effects on reaction times or neural activity (see N. Lavie, 2005, for a review). Here we varied the level of…

Characteristic expression of HTLV-1 basic zipper factor (HBZ transcripts in HTLV-1 provirus-positive cells

Directory of Open Access Journals (Sweden)

Yamada Yasuaki

2008-04-01

Full Text Available Abstract Background HTLV-1 causes adult T-cell leukemia (ATL. Although there have been many studies on the oncogenesis of the viral protein Tax, the precise oncogenic mechanism remains to be elucidated. Recently, a new viral factor, HTLV-1 basic Zip factor (HBZ, encoded from the minus strand mRNA was discovered and the current models of Tax-centered ATL cell pathogenesis are in conflict with this discovery. HBZs consisting of non-spliced and spliced isoforms (HBZ-SI are thought to be implicated in viral replication and T-cell proliferation but there is little evidence on the HBZ expression profile on a large scale. Results To investigate the role of HBZ-SI in HTLV-1 provirus-positive cells, the HBZ-SI and Tax mRNA loads in samples with a mixture of infected and non-infected cells were measured and then adjusted by dividing by the HTLV-I proviral load. We show here that the HBZ-SI mRNA level is 4-fold higher than non-spliced HBZ and is expressed by almost all cells harboring HTLV-1 provirus with variable intensity. The proviral-adjusted HBZ-SI and Tax quantification revealed a characteristic imbalanced expression feature of high HBZ and low Tax expression levels in primary ATL cells or high HBZ and very high Tax levels in HTLV-1-related cell lines (cell lines compared with a standard expression profile of low HBZ and low Tax in infected cells. Interestingly, according to the mutual Tax and HBZ expression status, HTLV-1-related cell lines were subcategorized into two groups, an ATL cell type with high HBZ and low Tax levels and another type with high Tax and either high or low HBZ, which was closely related to its cell origin. Conclusion This is the first comprehensive study to evaluate the mutual expression profile of HBZ and Tax in provirus-positive cells, revealing that there are quantitative and relative characteristic features among infected cells, primary ATL cells, and cell lines.

Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

Directory of Open Access Journals (Sweden)

Feuer Gerold

2004-11-01

Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

Strongyloidiasis and infective dermatitis alter human T lymphotropic virus-1 clonality in vivo.

Directory of Open Access Journals (Sweden)

Nicolas A Gillet

Full Text Available Human T-lymphotropic Virus-1 (HTLV-1 is a retrovirus that persists lifelong by driving clonal proliferation of infected T-cells. HTLV-1 causes a neuroinflammatory disease and adult T-cell leukemia/lymphoma. Strongyloidiasis, a gastrointestinal infection by the helminth Strongyloides stercoralis, and Infective Dermatitis associated with HTLV-1 (IDH, appear to be risk factors for the development of HTLV-1 related diseases. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the HTLV-1-infected T-cell population (i.e. the number of distinct clones and abundance of each clone. A newly developed biodiversity estimator called "DivE" was used to estimate the total number of clones in the blood. We found that the major determinant of proviral load in all subjects without leukemia/lymphoma was the total number of HTLV-1-infected clones. Nevertheless, the significantly higher proviral load in patients with strongyloidiasis or IDH was due to an increase in the mean clone abundance, not to an increase in the number of infected clones. These patients appear to be less capable of restricting clone abundance than those with HTLV-1 alone. In patients co-infected with Strongyloides there was an increased degree of oligoclonal expansion and a higher rate of turnover (i.e. appearance and disappearance of HTLV-1-infected clones. In Strongyloides co-infected patients and those with IDH, proliferation of the most abundant HTLV-1⁺ T-cell clones is independent of the genomic environment of the provirus, in sharp contrast to patients with HTLV-1 infection alone. This implies that new selection forces are driving oligoclonal proliferation in Strongyloides co-infection and IDH. We conclude that strongyloidiasis and IDH increase the risk of development of HTLV-1-associated diseases by increasing the rate of infection of new clones and the abundance of existing HTLV-1⁺ clones.

Effect of density and weight of load on the energy cost of carrying loads by donkeys and ponies.

Science.gov (United States)

Pearson, R A; Dijkman, J T; Krecek, R C; Wright, P

1998-02-01

Two experiments were designed to compare the energy used in carrying loads by donkeys and ponies. In the first experiment 3 donkeys and 3 ponies were compared on treadmills in the UK. Density of load (lead shot or straw) had no significant effect on the energy cost of carrying loads; however, the energy cost of carrying a load decreased significantly (p < 0.001) as the weight of the load increased (in donkeys 6.44, 4.35 and 3.03 J/kg load/m, in ponies 5.82, 3.75 and 3.68 J/kg load/m, for loads of 13, 20 and 27 kg/100 kg liveweight (M) respectively). Differences between species were not significant. In the second experiment energy expenditures were determined in 3 donkeys carrying loads equivalent to 40 kg/100 kg M over gently undulating gravel tracks in Tunisia. Energy costs of carrying the load were 2.34 (SE 0.07) J/kg load/m. The results of both experiments showed that provided the load is balanced, density does not significantly affect the energy cost of carrying; however, as the load increased then the unit energy cost of carrying it decreased. This suggest that it is more efficient in terms of energy used to carry loads equivalent to 27 to 40 kg/100 kg M than it is to carry lighter loads to less than 20 kg/100 kg M.

Wound healing in immediately loaded implants.

Science.gov (United States)

Romanos, Georgios E

2015-06-01

The orthopedic field has accumulated ample evidence that bone formation is related to functional loading and in general to physical activity. However, despite evidence that immediately loaded implants can be predictably successful, many clinicians still use the classical (delayed loading) treatment protocol. This paper examines the effects of loading on dental implants and discusses the advantages of immediate loading. The role of loading on augmented alveolar ridges is also addressed and provides evidence that early bone resorption may be controlled when bone is functionally loaded. Similar data are emerging for advanced augmentation techniques in order to control crestal bone loss. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autonomous Propellant Loading Project

Data.gov (United States)

National Aeronautics and Space Administration — The AES Autonomous Propellant Loading (APL) project consists of three activities. The first is to develop software that will automatically control loading of...

Loading nature of the interfacial cracks in a joint component under fusion-relevant thermal loads

International Nuclear Information System (INIS)

You, J.H.

1998-01-01

One of the standard design concepts for divertor components in a fusion reactor is the bonded joint structure. Understanding the loading nature of interfacial cracks are significant for the assessment of structural integrity of divertor joint components. In this paper, the thermomechanical loading nature of interfacial cracks is discussed. A bi-material joint element consisting of the CFC/TZM system is considered. A typical fusion operation condition is simulated assuming a pulsed high heat flux loading. Stress singularities near the interfacial crack tips are characterized quantitatively in terms of the fracture mechanical parameters. The evolution of the stress intensity factors and the energy release rate during the given transient thermal load are determined. The difference in loading characteristics between the edge crack and the center crack is discussed. High heat flux cycling tests are performed on brazed CFC/TZM divertor elements in an electron beam test facility. The microstructures of the damaged interface agree with the predicted fracture modes. The loading nature and possible failure mechanisms are discussed for a fusion-relevant thermal loading. (orig.)

Resident Load Influence Analysis Method for Price Based on Non-intrusive Load Monitoring and Decomposition Data

Science.gov (United States)

Jiang, Wenqian; Zeng, Bo; Yang, Zhou; Li, Gang

2018-01-01

In the non-invasive load monitoring mode, the load decomposition can reflect the running state of each load, which will help the user reduce unnecessary energy costs. With the demand side management measures of time of using price, a resident load influence analysis method for time of using price (TOU) based on non-intrusive load monitoring data are proposed in the paper. Relying on the current signal of the resident load classification, the user equipment type, and different time series of self-elasticity and cross-elasticity of the situation could be obtained. Through the actual household load data test with the impact of TOU, part of the equipment will be transferred to the working hours, and users in the peak price of electricity has been reduced, and in the electricity at the time of the increase Electrical equipment, with a certain regularity.

Cognitive Load and Strategic Sophistication

OpenAIRE

Allred, Sarah; Duffy, Sean; Smith, John

2013-01-01

We study the relationship between the cognitive load manipulation and strategic sophistication. The cognitive load manipulation is designed to reduce the subject's cognitive resources that are available for deliberation on a choice. In our experiment, subjects are placed under a large cognitive load (given a difficult number to remember) or a low cognitive load (given a number which is not difficult to remember). Subsequently, the subjects play a one-shot game then they are asked to recall...

+Gz load and executive functions.

Science.gov (United States)

Biernacki, Marcin P; Tarnowski, Adam; Lengsfeld, Kamila; Lewkowicz, Rafał; Kowalczuk, Krzysztof; Dereń, Miroslaw

2013-05-01

Pilots are constantly exposed to a number of environmental factors, which include +Gz load. Physiological changes evoked by +Gz stimuli have already been well investigated in aviation medicine. However, the influence of +Gz stimulation on executive functions in pilots has not yet been thoroughly explored. There were 20 pilot cadets between the ages of 19 and 22 yr who volunteered to participate in the experiment. The subjects were divided into two groups: the G-load group, which was exposed to accelerations in the centrifuge, and the control group, which did not undergo this stimulation. Executive functions were assessed by means of the Schulte tables and the Rey-Osterrieth complex figure test. +Gz load exposure significantly improved attention switching. This relationship was valid for performance speed (M = 268.09 s in the pretest in the G-load group; M = 228.09 s in the posttest in the G-load group) and for the cumulative time of mistakes (M = 26.73 s in the pretest in the G-load group; M = 12 s in the posttest in the G-load group), whereas reproduction of visuospatial stimuli from memory deteriorated significantly under the influence of +Gz stimulation (M = 17.18 points in the posttest in the G-load group; M = 28.18 points in the posttest in the control group). These results suggest that the impact of +Gz load is not homogenous and unidirectional, since it improves attention switching but visuospatial working memory decreases under its influence. These aspects are particularly important for understanding the mechanisms responsible for maintaining situational awareness during the flight.

A Microstructural Study of Load Distribution in Cartilage: A Comparison of Stress Relaxation versus Creep Loading

Directory of Open Access Journals (Sweden)

Ashvin Thambyah

2015-01-01

Full Text Available The compressive response of articular cartilage has been extensively investigated and most studies have focussed largely on the directly loaded matrix. However, especially in relation to the tissue microstructure, less is known about load distribution mechanisms operating outside the directly loaded region. We have addressed this issue by using channel indentation and DIC microscopy techniques that provide visualisation of the matrix microstructural response across the regions of both direct and nondirect loading. We hypothesise that, by comparing the microstructural response following stress relaxation and creep compression, new insights can be revealed concerning the complex mechanisms of load bearing. Our results indicate that, with stress relaxation, the initial mode of stress decay appears to primarily involve relaxation of the surface layer. In the creep loading protocol, the main mode of stress release is a lateral distribution of load via the mid matrix. While these two modes of stress redistribution have a complex relationship with the zonally differentiated tissue microstructure and the depth of strain, four mechanostructural mechanisms are proposed to describe succinctly the load responses observed.

Fuel pellet loading apparatus

International Nuclear Information System (INIS)

1980-01-01

Apparatus is described for loading a predetermined amount of nuclear fuel pellets into nuclear fuel elements and particularly for the automatic loading of fuel pellets from within a sealed compartment. (author)

Beam loading

CERN Document Server

Gamp, Alexander

2013-01-01

We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superconducting cavities are also given. Finally, a dedicated phase loop for damping synchrotron oscillations is discussed.

Beam loading

International Nuclear Information System (INIS)

Gamp, Alexander

2013-01-01

We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superconducting cavities are also given. Finally, a dedicated phase loop for damping synchrotron oscillations is discussed. (author)

77 FR 53884 - Automatic Underfrequency Load Shedding and Load Shedding Plans Reliability Standards; Notice of...

Science.gov (United States)

2012-09-04

... Underfrequency Load Shedding and Load Shedding Plans Reliability Standards; Notice of Compliance Filing Take notice that on August 9, 2012, North American Electric Reliability Corporation submitted a compliance... Load Shedding Plans Reliability Standards, 139 FERC ] 61,098, (Order No. 763) (2012). Any person...

Load bearing and deformation behaviour of dynamically loaded wide plate specimens

International Nuclear Information System (INIS)

Julisch, P.; Haedrich, H.J.; Stadtmueller, W.; Sturm, D.

1989-01-01

For the testing of large-scale specimens, a 12 MN-High Loading Rate Tensile Testing Machine was designed and built at MPA Stuttgart. The aim was to determine the influence of high loading rates on the stress and strain behaviour of unwelded and welded components of ferritic and austenitic materials. This new generation of testing machines is driven by a propellant charge, and generates a maximum tensile force of 12 MN with a piston velocity of 25 m/s after a stroke of 20 mm, or a maximum velocity of 60 m/s after a stroke of 400 mm. In a first test programme, welded and unwelded wide plate specimens made of material X 6 CrNi 18 11 were tested at room temperature with different strain rates from 10 -3 /s to 63/s. In addition to a description of the 12 MN-High Loading Rate Tensile Testing Machine, the results of the high loading rate tensile tests performed will be presented and compared with quasistatically tested wide plate specimens. (orig.)

Auditory working memory load impairs visual ventral stream processing: toward a unified model of attentional load.

Science.gov (United States)

Klemen, Jane; Büchel, Christian; Bühler, Mira; Menz, Mareike M; Rose, Michael

2010-03-01

Attentional interference between tasks performed in parallel is known to have strong and often undesired effects. As yet, however, the mechanisms by which interference operates remain elusive. A better knowledge of these processes may facilitate our understanding of the effects of attention on human performance and the debilitating consequences that disruptions to attention can have. According to the load theory of cognitive control, processing of task-irrelevant stimuli is increased by attending in parallel to a relevant task with high cognitive demands. This is due to the relevant task engaging cognitive control resources that are, hence, unavailable to inhibit the processing of task-irrelevant stimuli. However, it has also been demonstrated that a variety of types of load (perceptual and emotional) can result in a reduction of the processing of task-irrelevant stimuli, suggesting a uniform effect of increased load irrespective of the type of load. In the present study, we concurrently presented a relevant auditory matching task [n-back working memory (WM)] of low or high cognitive load (1-back or 2-back WM) and task-irrelevant images at one of three object visibility levels (0%, 50%, or 100%). fMRI activation during the processing of the task-irrelevant visual stimuli was measured in the lateral occipital cortex and found to be reduced under high, compared to low, WM load. In combination with previous findings, this result is suggestive of a more generalized load theory, whereby cognitive load, as well as other types of load (e.g., perceptual), can result in a reduction of the processing of task-irrelevant stimuli, in line with a uniform effect of increased load irrespective of the type of load.

Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation

Directory of Open Access Journals (Sweden)

Fabio E. Leal

2018-05-01

Full Text Available HTLV-1-Associated Myelopathy (HAM/TSP is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this “IFN paradox” in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4+ T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax, proviral load and 42 host genes with known antiretroviral (anti-HIV activity in purified CD4+ T cells. This revealed two major clusters (“antiviral/protective” vs. “proviral/deleterious”, as evidenced by significant negative (TRIM5/TRIM22/BST2 vs. positive correlation (ISG15/PAF1/CDKN1A with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H, underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2 were significantly

Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

Science.gov (United States)

Dobón, Albor; Canet, Juan Vicente; García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

2015-04-01

Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

Directory of Open Access Journals (Sweden)

Albor Dobón

2015-04-01

Full Text Available Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

Procedures for Calculating Residential Dehumidification Loads

Energy Technology Data Exchange (ETDEWEB)

Winkler, Jon [National Renewable Energy Lab. (NREL), Golden, CO (United States); Booten, Chuck [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2016-06-01

Residential building codes and voluntary labeling programs are continually increasing the energy efficiency requirements of residential buildings. Improving a building's thermal enclosure and installing energy-efficient appliances and lighting can result in significant reductions in sensible cooling loads leading to smaller air conditioners and shorter cooling seasons. However due to fresh air ventilation requirements and internal gains, latent cooling loads are not reduced by the same proportion. Thus, it's becoming more challenging for conventional cooling equipment to control indoor humidity at part-load cooling conditions and using conventional cooling equipment in a non-conventional building poses the potential risk of high indoor humidity. The objective of this project was to investigate the impact the chosen design condition has on the calculated part-load cooling moisture load, and compare calculated moisture loads and the required dehumidification capacity to whole-building simulations. Procedures for sizing whole-house supplemental dehumidification equipment have yet to be formalized; however minor modifications to current Air-Conditioner Contractors of America (ACCA) Manual J load calculation procedures are appropriate for calculating residential part-load cooling moisture loads. Though ASHRAE 1% DP design conditions are commonly used to determine the dehumidification requirements for commercial buildings, an appropriate DP design condition for residential buildings has not been investigated. Two methods for sizing supplemental dehumidification equipment were developed and tested. The first method closely followed Manual J cooling load calculations; whereas the second method made more conservative assumptions impacting both sensible and latent loads.

Load Estimation from Modal Parameters

DEFF Research Database (Denmark)

Aenlle, Manuel López; Brincker, Rune; Fernández, Pelayo Fernández

2007-01-01

In Natural Input Modal Analysis the modal parameters are estimated just from the responses while the loading is not recorded. However, engineers are sometimes interested in knowing some features of the loading acting on a structure. In this paper, a procedure to determine the loading from a FRF m...

The effects of load drop, uniform load and concentrated loads on waste tanks

International Nuclear Information System (INIS)

Marusich, R.M. Westinghouse Hanford

1996-01-01

This document provides the supporting calculations performed by others specifically for the TWRS FSAR and more detailed summaries of the important references issued in the past regarding the effects of various loads

Load proportional safety brake

Science.gov (United States)

Cacciola, M. J.

1979-01-01

This brake is a self-energizing mechanical friction brake and is intended for use in a rotary drive system. It incorporates a torque sensor which cuts power to the power unit on any overload condition. The brake is capable of driving against an opposing load or driving, paying-out, an aiding load in either direction of rotation. The brake also acts as a no-back device when torque is applied to the output shaft. The advantages of using this type of device are: (1) low frictional drag when driving; (2) smooth paying-out of an aiding load with no runaway danger; (3) energy absorption proportional to load; (4) no-back activates within a few degrees of output shaft rotation and resets automatically; and (5) built-in overload protection.

Loading capacities and failure modes of various reinforced concrete slabs subjected to high-speed loading

International Nuclear Information System (INIS)

Saito, H.; Imamura, A.; Takeuchi, M.; Okamoto, S.; Kasai, Y.; Tsubota, H.; Yoshimura, M.

1993-01-01

The objective of this study was to clarify experimentally and analytically the loading capacities, deformations and failure modes of various types of reinforced concrete structures subjected to loads applied at various loading rates. Flat slabs, slabs with beams and cylindrical walls were tested under static, low-speed and high-speed loading. Analysis was applied to estimate the test results by the finite element method using a layered shell element. The analysis closely simulated the experimental results until punching shear failure occurred. (author)

Working memory load modulates microsaccadic rate.

Science.gov (United States)

Dalmaso, Mario; Castelli, Luigi; Scatturin, Pietro; Galfano, Giovanni

2017-03-01

Microsaccades are tiny eye movements that individuals perform unconsciously during fixation. Despite that the nature and the functions of microsaccades are still lively debated, recent evidence has shown an association between these micro eye movements and higher order cognitive processes. Here, in two experiments, we specifically focused on working memory and addressed whether differential memory load could be reflected in a modulation of microsaccade dynamics. In Experiment 1, participants memorized a numerical sequence composed of either two (low-load condition) or five digits (high-load condition), appearing at fixation. The results showed a reduction in the microsaccadic rate in the high-load compared to the low-load condition. In Experiment 2, five red or green digits were always presented at fixation. Participants either memorized the color (low-load condition) or the five digits (high-load condition). Hence, visual stimuli were exactly the same in both conditions. Consistent with Experiment 1, microsaccadic rate was lower in the high-load than in the low-load condition. Overall, these findings reveal that an engagement of working memory can have an impact on microsaccadic rate, consistent with the view that microsaccade generation is pervious to top-down processes.

Application of PSAT to Load Flow Analysis with STATCOM under Load Increase Scenario and Line Contingencies

Science.gov (United States)

Telang, Aparna S.; Bedekar, P. P.

2017-09-01

Load flow analysis is the initial and essential step for any power system computation. It is required for choosing better options for power system expansion to meet with ever increasing load demand. Implementation of Flexible AC Transmission System (FACTS) device like STATCOM, in the load flow, which is having fast and very flexible control, is one of the important tasks for power system researchers. This paper presents a simple and systematic approach for steady state power flow calculations with FACTS controller, static synchronous compensator (STATCOM) using command line usage of MATLAB tool-power system analysis toolbox (PSAT). The complexity of MATLAB language programming increases due to incorporation of STATCOM in an existing Newton-Raphson load flow algorithm. Thus, the main contribution of this paper is to show how command line usage of user friendly MATLAB tool, PSAT, can extensively be used for quicker and wider interpretation of the results of load flow with STATCOM. The novelty of this paper lies in the method of applying the load increase pattern, where the active and reactive loads have been changed simultaneously at all the load buses under consideration for creating stressed conditions for load flow analysis with STATCOM. The performance have been evaluated on many standard IEEE test systems and the results for standard IEEE-30 bus system, IEEE-57 bus system, and IEEE-118 bus system are presented.

Methodology for clinical trials involving patients with cancer who have febrile neutropenia: updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies.

Science.gov (United States)

Feld, Ronald; Paesmans, Marianne; Freifeld, Alison G; Klastersky, Jean; Pizzo, Philip A; Rolston, Kenneth V I; Rubenstein, Edward; Talcott, James A; Walsh, Thomas J

2002-12-15

Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy.

What does germane load mean? An empirical contribution to the cognitive load theory

Directory of Open Access Journals (Sweden)

Nicolas eDebue

2014-10-01

Full Text Available While over the last decades, much attention has been paid to the mental workload in the field of human computer interactions, there is still a lack of consensus concerning the factors that generate it as well as the measurement methods that could reflect workload variations. Based on the multifactorial Cognitive Load Theory, our study aims to provide some food for thought about the subjective and objective measurement that can be used to disentangle the intrinsic, extraneous and germane load. The purpose is to provide insight into the way cognitive load can explain how users’ cognitive resources are allocated in the use of hypermedia, such as an online newspaper. A two-phase experiment has been conducted on the information retention from online news stories. Phase 1 (92 participants examined the influence of multimedia content on performance as well as the relationships between cognitive loads and cognitive absorption. In Phase 2 (36 participants, eye-tracking data were collected in order to provide reliable and objective measures. Results confirmed that performance in information retention was impacted by the presence of multimedia content such as animations and pictures. The higher number of fixations on these animations suggests that users’ attention could have been attracted by them. Results showed the expected opposite relationships between Germane and Extraneous Load, a positive association between GL and cognitive absorption and a nonlinear association between Intrinsic and Germane Load. The trends based on eye-tracking data analysis provide some interesting findings about the relationships between longer fixations, shorter saccades and cognitive load. Some issues are raised about the respective contribution of mean pupil diameter and Index of Cognitive Activity.

SLUDGE TREATMENT PROJECT COST COMPARISON BETWEEN HYDRAULIC LOADING AND SMALL CANISTER LOADING CONCEPTS

Energy Technology Data Exchange (ETDEWEB)

GEUTHER J; CONRAD EA; RHOADARMER D

2009-08-24

The Sludge Treatment Project (STP) is considering two different concepts for the retrieval, loading, transport and interim storage of the K Basin sludge. The two design concepts under consideration are: (1) Hydraulic Loading Concept - In the hydraulic loading concept, the sludge is retrieved from the Engineered Containers directly into the Sludge Transport and Storage Container (STSC) while located in the STS cask in the modified KW Basin Annex. The sludge is loaded via a series of transfer, settle, decant, and filtration return steps until the STSC sludge transportation limits are met. The STSC is then transported to T Plant and placed in storage arrays in the T Plant canyon cells for interim storage. (2) Small Canister Concept - In the small canister concept, the sludge is transferred from the Engineered Containers (ECs) into a settling vessel. After settling and decanting, the sludge is loaded underwater into small canisters. The small canisters are then transferred to the existing Fuel Transport System (FTS) where they are loaded underwater into the FTS Shielded Transfer Cask (STC). The STC is raised from the basin and placed into the Cask Transfer Overpack (CTO), loaded onto the trailer in the KW Basin Annex for transport to T Plant. At T Plant, the CTO is removed from the transport trailer and placed on the canyon deck. The CTO and STC are opened and the small canisters are removed using the canyon crane and placed into an STSC. The STSC is closed, and placed in storage arrays in the T Plant canyon cells for interim storage. The purpose of the cost estimate is to provide a comparison of the two concepts described.

SLUDGE TREATMENT PROJECT COST COMPARISON BETWEEN HYDRAULIC LOADING AND SMALL CANISTER LOADING CONCEPTS

International Nuclear Information System (INIS)

Geuther, J.; Conrad, E.A.; Rhoadarmer, D.

2009-01-01

The Sludge Treatment Project (STP) is considering two different concepts for the retrieval, loading, transport and interim storage of the K Basin sludge. The two design concepts under consideration are: (1) Hydraulic Loading Concept - In the hydraulic loading concept, the sludge is retrieved from the Engineered Containers directly into the Sludge Transport and Storage Container (STSC) while located in the STS cask in the modified KW Basin Annex. The sludge is loaded via a series of transfer, settle, decant, and filtration return steps until the STSC sludge transportation limits are met. The STSC is then transported to T Plant and placed in storage arrays in the T Plant canyon cells for interim storage. (2) Small Canister Concept - In the small canister concept, the sludge is transferred from the Engineered Containers (ECs) into a settling vessel. After settling and decanting, the sludge is loaded underwater into small canisters. The small canisters are then transferred to the existing Fuel Transport System (FTS) where they are loaded underwater into the FTS Shielded Transfer Cask (STC). The STC is raised from the basin and placed into the Cask Transfer Overpack (CTO), loaded onto the trailer in the KW Basin Annex for transport to T Plant. At T Plant, the CTO is removed from the transport trailer and placed on the canyon deck. The CTO and STC are opened and the small canisters are removed using the canyon crane and placed into an STSC. The STSC is closed, and placed in storage arrays in the T Plant canyon cells for interim storage. The purpose of the cost estimate is to provide a comparison of the two concepts described

Load forecasting for supermarket refrigeration

DEFF Research Database (Denmark)

Bacher, Peder; Madsen, Henrik; Aalborg Nielsen, Henrik

This report presents a study of models for forecasting the load for supermarket refrigeration. The data used for building the forecasting models consists of load measurements, local climate measurements and weather forecasts. The load measurements are from a supermarket located in a village...... in Denmark. The load for refrigeration is the sum of all cabinets in the supermarket, both low and medium temperature cabinets, and spans a period of one year. As input to the forecasting models the ambient temperature observed near the supermarket together with weather forecasts are used. Every hour...

Formulation of Forming Load in V-Bending

Directory of Open Access Journals (Sweden)

Koumura Yuki

2016-01-01

Full Text Available A novel method is described to calculate the forming load in V-bending by a press brake. The data of forming load are collected by FEM analysis. With an increase of the punch stroke in V-bending, the forming load increases gradually after the elastic limit, and then decreases after showing the maximum value. The proposal formulation to trace the variations in the forming load curve includes the calculating method of the load of the elastic limit, the maximum load in air bending and the variations of the forming load before/after the bending stroke of the maximum load. The calculated precision is confirmed by comparing with the measured load-stroke curves in V-bending with a press brake.

Fuel loading and homogeneity analysis of HFIR design fuel plates loaded with uranium silicide fuel

International Nuclear Information System (INIS)

Blumenfeld, P.E.

1995-08-01

Twelve nuclear reactor fuel plates were analyzed for fuel loading and fuel loading homogeneity by measuring the attenuation of a collimated X-ray beam as it passed through the plates. The plates were identical to those used by the High Flux Isotope Reactor (HFIR) but were loaded with uranium silicide rather than with HFIR's uranium oxide fuel. Systematic deviations from nominal fuel loading were observed as higher loading near the center of the plates and underloading near the radial edges. These deviations were within those allowed by HFIR specifications. The report begins with a brief background on the thermal-hydraulic uncertainty analysis for the Advanced Neutron Source (ANS) Reactor that motivated a statistical description of fuel loading and homogeneity. The body of the report addresses the homogeneity measurement techniques employed, the numerical correction required to account for a difference in fuel types, and the statistical analysis of the resulting data. This statistical analysis pertains to local variation in fuel loading, as well as to ''hot segment'' analysis of narrow axial regions along the plate and ''hot streak'' analysis, the cumulative effect of hot segment loading variation. The data for all twelve plates were compiled and divided into 20 regions for analysis, with each region represented by a mean and a standard deviation to report percent deviation from nominal fuel loading. The central regions of the plates showed mean values of about +3% deviation, while the edge regions showed mean values of about -7% deviation. The data within these regions roughly approximated random samplings from normal distributions, although the chi-square (χ 2 ) test for goodness of fit to normal distributions was not satisfied

46 CFR 169.689 - Demand loads.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Demand loads. 169.689 Section 169.689 Shipping COAST... Electrical Electrical Installations on Vessels of 100 Gross Tons and Over § 169.689 Demand loads. Demand loads must meet § 111.60-7 of this chapter except that smaller demand loads for motor feeders are...

Environmental Aspects of Load Management

International Nuclear Information System (INIS)

Abaravicius, Juozas

2004-02-01

This study approaches load management from an environmental perspective. It identifies and discusses the possible environmental benefits of load management and evaluates their significance, primary focusing on CO 2 emissions reduction. The analysis is carried out on two levels: national - the Swedish electricity market, and local - one electric utility in southern Sweden. Our results show the importance of considering the influence of site-specific or level-specific conditions on the environmental effects of load management. On the national level, load management measures can hardly provide significant environmental benefits, due to the high hydropower production in Sweden, which is the demand following production source. Emission reductions will rather be the result of energy efficiency measures, which will cut the load demand as well as the energy demand. However, when it comes to a local (utility) level, where load management is considered as an alternative to an installation of peak diesel power plant, the benefits are clear. It is demonstrated that significant CO 2 emissions savings can be achieved due to avoided peak diesel power production

Estimation of structural reliability under combined loads

International Nuclear Information System (INIS)

Shinozuka, M.; Kako, T.; Hwang, H.; Brown, P.; Reich, M.

1983-01-01

For the overall safety evaluation of seismic category I structures subjected to various load combinations, a quantitative measure of the structural reliability in terms of a limit state probability can be conveniently used. For this purpose, the reliability analysis method for dynamic loads, which has recently been developed by the authors, was combined with the existing standard reliability analysis procedure for static and quasi-static loads. The significant parameters that enter into the analysis are: the rate at which each load (dead load, accidental internal pressure, earthquake, etc.) will occur, its duration and intensity. All these parameters are basically random variables for most of the loads to be considered. For dynamic loads, the overall intensity is usually characterized not only by their dynamic components but also by their static components. The structure considered in the present paper is a reinforced concrete containment structure subjected to various static and dynamic loads such as dead loads, accidental pressure, earthquake acceleration, etc. Computations are performed to evaluate the limit state probabilities under each load combination separately and also under all possible combinations of such loads

Climate control loads prediction of electric vehicles

International Nuclear Information System (INIS)

Zhang, Ziqi; Li, Wanyong; Zhang, Chengquan; Chen, Jiangping

2017-01-01

Highlights: • A model of vehicle climate control loads is proposed based on experiments. • Main climate control loads of the modeled vehicle are quantitatively analyzed. • Range reductions of the modeled vehicle under different conditions are simulated. - Abstract: A new model of electric vehicle climate control loads is provided in this paper. The mathematical formulations of the major climate control loads are developed, and the coefficients of the formulations are experimentally determined. Then, the detailed climate control loads are analyzed, and the New European Driving Cycle (NEDC) range reductions due to these loads are calculated under different conditions. It is found that in an electric vehicle, the total climate control loads vary with the vehicle speed, HVAC mode and blower level. The ventilation load is the largest climate control load, followed by the solar radiation load. These two add up to more than 80% of total climate control load in summer. The ventilation load accounts for 70.7–83.9% of total heating load under the winter condition. The climate control loads will cause a 17.2–37.1% reduction of NEDC range in summer, and a 17.1–54.1% reduction in winter, compared to the AC off condition. The heat pump system has an advantage in range extension. A heat pump system with an average heating COP of 1.7 will extend the range by 7.6–21.1% based on the simulation conditions.

Bone healing response in cyclically loaded implants: Comparing zero, one, and two loading sessions per day.

Science.gov (United States)

de Barros E Lima Bueno, Renan; Dias, Ana Paula; Ponce, Katia J; Wazen, Rima; Brunski, John B; Nanci, Antonio

2018-05-31

When bone implants are loaded, they are inevitably subjected to displacement relative to bone. Such micromotion generates stress/strain states at the interface that can cause beneficial or detrimental sequels. The objective of this study is to better understand the mechanobiology of bone healing at the tissue-implant interface during repeated loading. Machined screw shaped Ti implants were placed in rat tibiae in a hole slightly bigger than the implant diameter. Implants were held stable by a specially-designed bone plate that permits controlled loading. Three loading regimens were applied, (a) zero loading, (b) one daily loading session of 60 cycles with an axial force of 1.5 N/cycle for 7 days, and (c) two such daily sessions with the same axial force also for 7 days. Finite element analysis was used to characterize the mechanobiological conditions produced by the loading sessions. After 7 days, the implants with surrounding interfacial tissue were harvested and processed for histological, histomorphometric and DNA microarray analyses. Histomorphometric analyses revealed that the group subjected to repeated loading sessions exhibited a significant decrease in bone-implant contact and increase in bone-implant distance, as compared to unloaded implants and those subjected to only one loading session. Gene expression profiles differed during osseointegration between all groups mainly with respect to inflammatory and unidentified gene categories. The results indicate that increasing the daily cyclic loading of implants induces deleterious changes in the bone healing response, most likely due to the accumulation of tissue damage and associated inflammatory reaction at the bone-implant interface. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Predictive equations for lumbar spine loads in load-dependent asymmetric one- and two-handed lifting activities.

Science.gov (United States)

Arjmand, N; Plamondon, A; Shirazi-Adl, A; Parnianpour, M; Larivière, C

2012-07-01

Asymmetric lifting activities are associated with low back pain. A finite element biomechanical model is used to estimate spinal loads during one- and two-handed asymmetric static lifting activities. Model input variables are thorax flexion angle, load magnitude as well as load sagittal and lateral positions while response variables are L4-L5 and L5-S1 disc compression and shear forces. A number of levels are considered for each input variable and all their possible combinations are introduced into the model. Robust yet user-friendly predictive equations that relate model responses to its inputs are established. Predictive equations with adequate goodness-of-fit (R(2) ranged from ~94% to 99%, P≤0.001) that relate spinal loads to task (input) variables are established. Contour plots are used to identify combinations of task variable levels that yield spine loads beyond the recommended limits. The effect of uncertainties in the measurements of asymmetry-related inputs on spinal loads is studied. A number of issues regarding the NIOSH asymmetry multiplier are discussed and it is concluded that this multiplier should depend on the trunk posture and be defined in terms of the load vertical and horizontal positions. Due to an imprecise adjustment of the handled load magnitude this multiplier inadequately controls the biomechanical loading of the spine. Ergonomists and bioengineers, faced with the dilemma of using either complex but more accurate models on one hand or less accurate but simple models on the other hand, have hereby easy-to-use predictive equations that quantify spinal loads under various occupational tasks. Copyright © 2011 Elsevier Ltd. All rights reserved.

A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Seymour, J F; Kim, D W; Rubin, E

2014-01-01

achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK-0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected...

Comparative Study of Load Testing Tools: Apache JMeter, HP LoadRunner, Microsoft Visual Studio (TFS, Siege

Directory of Open Access Journals (Sweden)

Rabiya Abbas

2017-12-01

Full Text Available Software testing is the process of verifying and validating the user’s requirements. Testing is ongoing process during whole software development. Software testing is characterized into three main types. That is, in Black box testing, user doesn’t know domestic knowledge, internal logics and design of system. In white box testing, Tester knows the domestic logic of code. In Grey box testing, Tester has little bit knowledge about the internal structure and working of the system. It is commonly used in case of Integration testing.Load testing helps us to analyze the performance of the system under heavy load or under Zero load. This is achieved with the help of a Load Testing Tool. The intention for writing this research is to carry out a comparison of four load testing tools i.e. Apache JMeter, LoadRunner, Microsoft Visual Studio (TFS, Siege based on certain criteria  i.e. test scripts generation , result reports, application support, plug-in supports, and cost . The main focus is to study these load testing tools and identify which tool is better and more efficient . We assume this comparison can help in selecting the most appropriate tool and motivates the use of open source load testing tools.

Inexpensive Bolt-Load Gage

Science.gov (United States)

Long, M. J.

1983-01-01

"Built-in" gage determines whether large bolt or stud has been torqued to desired load and provides for continuous inspection to ensure proper load is being maintained. Gage detects longitudinal stress/strain bolt; requires no electronic or sonic test equipment.

Load and resistance factor design of drilled shafts in shale for lateral loading.

Science.gov (United States)

2014-04-01

A research project involving 32 drilled shaft load tests was undertaken to establish LRFD procedures for : design of drilled shafts subjected to lateral loads. Tests were performed at two Missouri Department of : Transportation (MoDOT) geotechnical r...

Economic costs of chemotherapy-induced febrile neutropenia among patients with non-Hodgkin’s lymphoma in European and Australian clinical practice

Directory of Open Access Journals (Sweden)

Weycker Derek

2012-08-01

Full Text Available Abstract Background Economic implications of chemotherapy-induced febrile neutropenia (FN in European and Australian clinical practice are largely unknown. Methods Data were obtained from a European (97% and Australian (3% observational study of patients with non-Hodgkin’s lymphoma (NHL receiving CHOP (±rituximab chemotherapy. For each patient, each cycle of chemotherapy within the course, and each occurrence of FN within cycles, was identified. Patients developing FN in a given cycle (“FN patients”, starting with the first, were matched to those who did not develop FN in that cycle (“comparison patients”, irrespective of subsequent FN events. FN-related healthcare costs (£2010 were tallied for the initial FN event as well as follow-on care and FN events in subsequent cycles. Results Mean total cost was £5776 (95%CI £4928-£6713 higher for FN patients (n = 295 versus comparison patients, comprising £4051 (£3633-£4485 for the initial event and a difference of £1725 (£978-£2498 in subsequent cycles. Among FN patients requiring inpatient care (76% of all FN patients, mean total cost was higher by £7259 (£6327-£8205, comprising £5281 (£4810-£5774 for the initial hospitalization and a difference of £1978 (£1262-£2801 in subsequent cycles. Conclusions Cost of chemotherapy-induced FN among NHL patients in European and Australian clinical practice is substantial; a sizable percentage is attributable to follow-on care and subsequent FN events.

The concept of target and critical loads

International Nuclear Information System (INIS)

Grigal, D.F.

1991-09-01

Target and critical loads were initially developed for assessment and control of acidic deposition, but are being considered for other air pollutants such as ozone and air-borne toxic compounds. These loads are based on thresholds, with damage assumed to occur above some defined level of deposition. Many of the historically proposed targets for acidic deposition were based on arbitrary interpretations of data. The concept of critical loads has recently separated from that of target loads. A critical load is the amount of pollutant deposition, determined by technical analysis, above which there is a specific deleterious ecological effect. A target load is the deposition, determined by political agreement, above which unacceptable ecological damage occurs; it may be greater than the critical load because of political or economic considerations, or less to conservatively account for uncertainty in the estimation of the critical load. Recent definitions of critical loads include recognition that each kind of ecosystem and effect may require a different load. Geographic regions contain a mosaic of aquatic and terrestrial resources. If precise knowledge leads to different critical loads for each system, then how is the regional target load established? For better or worse, target and critical loads are likely to be used to regulate air pollutants. The philosophy of their establishment as thresholds, their quantitative validity, and their application in regulation all require careful examination. 36 refs., 3 figs

Comparison between simplified load spectra in accordance with Germanische Lloyd guidelines, and load spectra derived from time domain simulations

Energy Technology Data Exchange (ETDEWEB)

Rees, M [Aerodyn Energiesysteme gmbH, Rendsburg (Germany)

1996-09-01

The Germanische Lloyd guideline allows calculations of load spectra in two fundamentally different ways. In the case of the so-called `simplified load spectra` the maximum amplitude of fluctuation of a load component is formed as {+-}75% of the average value of the purely aerodynamic loads of this component at rated wind conditions, together with an overlay of mass-related loads. The second method allowed in the GL guideline is the calculation of load spectra from simulation results in the time domain. For a number of average wind speeds the time-dependent characteristics of the load components are calculated taking account of the natural spatial turbulence of the wind. These are converted into load spectra using the rainflow method. In a parametric study the load spectra are calculated according to both methods and compared. The calculations are performed for turbines with rated powers of 100 kW to 2000 kW, with two and three blades, and also for stall-controlled and pitch-controlled turbines. The calculated load spectra are compared with each by means of 1 P fatigue equivalent load spectra. The influence of individual parameters is presented, as is the validity of the simplified load spectra. (au)

Alaska Village Electric Load Calculator

Energy Technology Data Exchange (ETDEWEB)

Devine, M.; Baring-Gould, E. I.

2004-10-01

As part of designing a village electric power system, the present and future electric loads must be defined, including both seasonal and daily usage patterns. However, in many cases, detailed electric load information is not readily available. NREL developed the Alaska Village Electric Load Calculator to help estimate the electricity requirements in a village given basic information about the types of facilities located within the community. The purpose of this report is to explain how the load calculator was developed and to provide instructions on its use so that organizations can then use this model to calculate expected electrical energy usage.

Future residential loads profiles : scenario-based analysis of high penetration of heavy loads and distributed generation

NARCIS (Netherlands)

Asare-Bediako, B.; Kling, W.L.; Ribeiro, P.F.

2014-01-01

Electric load profiles are useful for accurate load forecasting, network planning and optimal generation capacity. They represent electricity demand patterns and are to a large extent predictable. However, new and heavier loads (heat pumps and electric vehicles), distributed generation, and home

Static Load Distribution in Ball Bearings

Science.gov (United States)

Ricci, Mario

2010-01-01

A numerical procedure for computing the internal loading distribution in statically loaded, single-row, angular-contact ball bearings when subjected to a known combined radial and thrust load is presented. The combined radial and thrust load must be applied in order to avoid tilting between inner and outer rings. The numerical procedure requires the iterative solution of Z + 2 simultaneous nonlinear equations - where Z is the number of the balls - to yield an exact solution for axial and radial deflections, and contact angles. Numerical results for a 218 angular-contact ball bearing have been compared with those from the literature and show significant differences in the magnitudes of the ball loads, contact angles, and the extent of the loading zone.

Power Load Prediction Based on Fractal Theory

OpenAIRE

Jian-Kai, Liang; Cattani, Carlo; Wan-Qing, Song

2015-01-01

The basic theories of load forecasting on the power system are summarized. Fractal theory, which is a new algorithm applied to load forecasting, is introduced. Based on the fractal dimension and fractal interpolation function theories, the correlation algorithms are applied to the model of short-term load forecasting. According to the process of load forecasting, the steps of every process are designed, including load data preprocessing, similar day selecting, short-term load forecasting, and...

Estimation of structural reliability under combined loads

International Nuclear Information System (INIS)

Shinozuka, M.; Kako, T.; Hwang, H.; Brown, P.; Reich, M.

1983-01-01

For the overall safety evaluation of seismic category I structures subjected to various load combinations, a quantitative measure of the structural reliability in terms of a limit state probability can be conveniently used. For this purpose, the reliability analysis method for dynamic loads, which has recently been developed by the authors, was combined with the existing standard reliability analysis procedure for static and quasi-static loads. The significant parameters that enter into the analysis are: the rate at which each load (dead load, accidental internal pressure, earthquake, etc.) will occur, its duration and intensity. All these parameters are basically random variables for most of the loads to be considered. For dynamic loads, the overall intensity is usually characterized not only by their dynamic components but also by their static components. The structure considered in the present paper is a reinforced concrete containment structure subjected to various static and dynamic loads such as dead loads, accidental pressure, earthquake acceleration, etc. Computations are performed to evaluate the limit state probabilities under each load combination separately and also under all possible combinations of such loads. Indeed, depending on the limit state condition to be specified, these limit state probabilities can indicate which particular load combination provides the dominant contribution to the overall limit state probability. On the other hand, some of the load combinations contribute very little to the overall limit state probability. These observations provide insight into the complex problem of which load combinations must be considered for design, for which limit states and at what level of limit state probabilities. (orig.)

Visual perceptual load induces inattentional deafness.

Science.gov (United States)

Macdonald, James S P; Lavie, Nilli

2011-08-01

In this article, we establish a new phenomenon of "inattentional deafness" and highlight the level of load on visual attention as a critical determinant of this phenomenon. In three experiments, we modified an inattentional blindness paradigm to assess inattentional deafness. Participants made either a low- or high-load visual discrimination concerning a cross shape (respectively, a discrimination of line color or of line length with a subtle length difference). A brief pure tone was presented simultaneously with the visual task display on a final trial. Failures to notice the presence of this tone (i.e., inattentional deafness) reached a rate of 79% in the high-visual-load condition, significantly more than in the low-load condition. These findings establish the phenomenon of inattentional deafness under visual load, thereby extending the load theory of attention (e.g., Lavie, Journal of Experimental Psychology. Human Perception and Performance, 25, 596-616, 1995) to address the cross-modal effects of visual perceptual load.

The load structure of electro boilers

International Nuclear Information System (INIS)

Feilberg, N.; Livik, K.

1995-01-01

Load measurements have been performed on 24 electro boilers with a time resolution of one hour throughout a period of one year. The boilers are used for space heating and heating of tap water in office buildings, shopping centres and apartment buildings. All boilers have tariffs with disconnection agreements. This report presents load analyses of the measurements from each boiler, and typical load profiles are calculated and presented. It also analyses how boilers are used in relation to the outdoor temperature and the power price on the spot market. All the measurements are performed in Bergen, Norway, in the period August 1993 - August 1994. Typical load profiles are shown, both annual and daily, as well as specific load parameters in addition to key figures used in calculating the total power load on the distribution network. The climate impact on energy and power load is evaluated. The report also shows examples of how the results may be applied in various special fields. 8 figs., 9 tabs

Hood River Conservation Project load analysis

Energy Technology Data Exchange (ETDEWEB)