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  1. Quantification of HTLV-I proviral load in experimentally infected rabbits

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    Kindt Thomas J

    2005-05-01

    Full Text Available Abstract Background Levels of proviral load in HTLV-1 infected patients correlate with clinical outcome and are reasonably prognostic. Adaptation of proviral load measurement techniques is examined here for use in an experimental rabbit model of HTLV-1 infection. Initial efforts sought to correlate proviral load with route and dose of inoculation and with clinical outcome in this model. These methods contribute to our continuing goal of using the model to test treatments that alleviate virus infection. Results A real-time PCR assay was used to measure proviral load in blood and tissue samples from a series of rabbits infected using HTLV-1 inocula prepared as either cell-free virus particles, infected cells or blood, or by naked DNA injection. Proviral loads from asymptomatically infected rabbits showed levels corresponding to those reported for human patients with clinically silent HTLV-1 infections. Proviral load was comparably increased in 50% of experimentally infected rabbits that developed either spontaneous benign or malignant tumors while infected. Similarly elevated provirus was found in organs of rabbits with experimentally induced acute leukemia/lymphoma-like disease. Levels of provirus in organs taken at necropsy varied widely suggesting that reservoirs of infections exist in non-lymphoid organs not traditionally thought to be targets for HTLV-1. Conclusion Proviral load measurement is a valuable enhancement to the rabbit model for HTLV-1 infection providing a metric to monitor clinical status of the infected animals as well as a means for the testing of treatment to combat infection. In some cases proviral load in blood did not reflect organ proviral levels, revealing a limitation of this method for monitoring health status of HTLV-1 infected individuals.

  2. Increased proviral load in HTLV-1-infected patients with rheumatoid arthritis or connective tissue disease

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    Olindo Stéphane

    2005-02-01

    Full Text Available Abstract Background Human T-lymphotropic virus type 1 (HTLV-1 proviral load is related to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP and has also been shown to be elevated in the peripheral blood in HTLV-1-infected patients with uveitis or alveolitis. Increased proliferation of HTLV-1-infected cells in, or migration of such cells into, the central nervous system is also seen in HAM/TSP. In the present study, we evaluated the proviral load in a cohort of HTLV-1-infected patients with arthritic conditions. Results HTLV-1 proviral load in the peripheral blood from 12 patients with RA and 6 patients with connective tissue disease was significantly higher than that in matched asymptomatic HTLV-1 carriers, but similar to that in matched HAM/TSP controls. HAM/TSP was seen in one-third of the HTLV-1-infected patients with RA or connective tissue disease, but did not account for the higher proviral load compared to the asymptomatic carrier group. The proviral load was increased in the synovial fluid and tissue from an HTLV-1-infected patient with RA, the values suggesting that the majority of infiltrated cells were HTLV-1-infected. In the peripheral blood from HTLV-1-infected patients with RA or connective tissue disease, HTLV-1 proviral load correlated with the percentages of memory CD4+ T cells and activated T cells, and these percentages were shown to be markedly higher in the synovial fluid than in the peripheral blood in an HTLV-1-infected patient with RA. Conclusions These biological findings are consistent with a role of the retrovirus in the development of arthritis in HTLV-1-infected patients. A high level of HTLV-1-infected lymphocytes in the peripheral blood and their accumulation in situ might play a central role in the pathogenesis of HTLV-1-associated inflammatory disorders. Alternatively, the autoimmune arthritis, its etiological factors or treatments might secondarily enhance HTLV-1 proviral load.

  3. Risk factors associated with increased bovine leukemia virus proviral load in infected cattle in Japan from 2012 to 2014.

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    Ohno, Ayumu; Takeshima, Shin-nosuke; Matsumoto, Yuki; Aida, Yoko

    2015-12-02

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, a malignant B cell lymphoma. BLV has spread worldwide and causes serious problems. After infection, the BLV genome is integrated into the host DNA and can be amplified during periods of latency. We previously designed degenerate primers using the Coordination of Common Motifs (CoCoMo) algorithm to establish a new quantitative real-time PCR method (BLV-CoCoMo-qPCR-2) of measuring the proviral load of both known and novel BLV variants. Here, we aimed to examine the correlation between proviral load and risk factors for BLV infection, such as breeding systems, parousity, and colostrum feeding. Blood and serum samples were collected from 83 BLV-positive farms in 22 prefectures of Japan, and the BLV proviral load and anti-BLV antibody levels were measured. BLV was detected in 73.3% (1039/1,417) of cattle by BLV-CoCoMo-qPCR-2 and the provirus was detected in 93 of 1039 antibody-negative samples. The results showed that the proviral load increased with progression of lymphocytosis. Next, the risk factors associated with increasing BLV infection rate were examined along with any association with proviral load. The proviral load was higher in cattle with lymphocytosis than in healthy cattle, and higher in multiparous cows than in nulliparous cows. Finally, proviral loads were higher in contact breeding systems than in non-contact breeding systems. Taken together, these findings may help to formulate a plan for eliminating BLV from contaminated farms. This is the first nationwide study to estimate BLV proviral load in Japanese cattle.

  4. Evolution of HTLV-1 proviral load in patients from Salvador, Brazil

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    Viviana Nilla Olavarria

    Full Text Available INTRODUCTION: Variations in human T cell lymphotropic virus type 1 (HTLV-1 proviral load (PVL in infected individuals over time are not well understood. Objective: To evaluate the evolution of proviral load in asymptomatic individuals and HAM/TSP patients in order to help determine periodicity for measuring proviral load. METHODS: A group of 104 HTLV-1 infected patients, followed at the HTLV reference center in Salvador, Brazil, were included in the study (70 asymptomatic and 34 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients. HTLV-1 PVL was measured using real-time polymerase chain reaction (PCR at baseline and again at another point, either 24 months. RESULTS: HAM/TSP patients had higher PVL (ranging from 11,041 to 317,009 copies/10(6 PBMC when compared to asymptomatic individuals (ranging from 0 to 68,228 copies/10(6 PBMC. No statistically significant differences were observed in the medians of PVL in HAM/TSP patients or asymptomatic individuals over time. However, in asymptomatic individuals with a PVL below 50,000 copies/10(6 PBMC, a statistically significant two-fold increase was observed over time. CONCLUSION: HTLV-1-PVL remained stable in both asymptomatic individuals and HAM/TSP patients over time. Frequent monitoring of asymptomatic individuals with low PVLs is recommended and further studies should be conducted to assess the course of PVL in these patients over extended periods of time.

  5. Cattle with the BoLA class II DRB3*0902 allele have significantly lower bovine leukemia proviral loads.

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    Hayashi, Takumi; Mekata, Hirohisa; Sekiguchi, Satoshi; Kirino, Yumi; Mitoma, Shuya; Honkawa, Kazuyuki; Horii, Yoichiro; Norimine, Junzo

    2017-09-12

    The bovine MHC (BoLA) class II DRB3 alleles are associated with polyclonal expansion of lymphocytes caused by bovine leukemia virus (BLV) infection in cattle. To examine whether the DRB3*0902 allele, one of the resistance-associated alleles, is associated with the proviral load, we measured BLV proviral load of BLV-infected cattle and clarified their DRB3 alleles. Fifty-seven animals with DRB3*0902 were identified out of 835 BLV-infected cattle and had significantly lower proviral load (PBoLA class II DRA/DRB3*0902 molecule plays an important immunological role in suppressing viral replication, resulting in resistance to the disease progression.

  6. Association of Sicca Syndrome with Proviral Load and Proinflammatory Cytokines in HTLV-1 Infection

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    Clara Mônica Lima

    2016-01-01

    Full Text Available The Sjögren syndrome has been diagnosed in patients with HTLV-1 associated myelopathy and dry mouth and dry eyes are documented in HTLV-1 carriers. However the diagnosis of Sjögren syndrome in these subjects has been contested. In this cross-sectional study, we evaluated the role of immunological factors and proviral load, in sicca syndrome associated with HTLV-1 in patients without myelopathy. Subjects were recruited in the HTLV-1 Clinic, from 2009 to 2011. The proviral load and cytokine levels (IFN-γ, TNF-α, IL-5, and IL-10 were obtained from a database containing the values presented by the subjects at admission in the clinic. Of the 272 participants, 59 (21.7% had sicca syndrome and in all of them anti-Sjögren syndrome related antigen A (SSA and antigen B (SSB were negatives. The production of TNF-α and IFN-γ was higher in the group with sicca syndrome (P<0.05 than in HTLV-1 infected subjects without sicca syndrome. Our data indicates that patients with sicca syndrome associated with HTLV-1 do not have Sjögren syndrome. However the increased production of TNF-α and IFN-γ in this group of patients may contribute to the pathogenesis of sicca syndrome associated with HTLV-1.

  7. Evaluation of HTLV-1 activity in HAM/TSP patients using proviral load and Tax mRNA expression after In Vitro lymphocyte activation

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    Atefeh Yari

    2014-07-01

    Conclusion: Although proviral load had been addressed as a valuable index for monitoring HTLV-1 infected subjects, the results of this study demonstrated that Tax expression in activated PBMCs along with proviral load assessment in HAM/TSP patients are a more reliable factor for determining the prognosis and monitoring healthy carriers and HAM/TSP patients.

  8. Telomere Length, Proviral Load and Neurologic Impairment in HTLV-1 and HTLV-2-Infected Subjects

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    Benjamin Usadi

    2016-08-01

    Full Text Available Short or damaged telomeres have been implicated in degenerative conditions. We hypothesized that analysis of telomere length (TL in human T-cell lymphotropic virus (HTLV infection and HTLV-associated neuropathy might provide clues to the etiology of HTLV-associated disease and viral dynamics. A subset of 45 human T-cell lymphotropic virus type 1 (HTLV-1, 45 human T-cell lymphotropic virus type 2 (HTLV-2, and 45 seronegative subjects was selected from the larger HTLV Outcomes Study (HOST cohort, matched on age, sex and race/ethnicity. Telomere-to-single-copy gene (T/S ratio (a measure of TL and HTLV-1 and HTLV-2 proviral loads were measured in peripheral blood mononuclear cells (PBMCs using quantitative PCR (qPCR. Vibration sensation measured by tuning fork during neurologic examinations performed as part of the HOST study allowed for an assessment of peripheral neuropathy. TL was compared between groups using t-tests, linear and logistic regression. Mean T/S ratio was 1.02 ± 0.16 in HTLV-1, 1.03 ± 0.17 in HTLV-2 and 0.99 ± 0.18 in HTLV seronegative subjects (p = 0.322. TL was not associated with HTLV-1 or -2 proviral load. Shorter TL was significantly associated with impaired vibration sense in the HTLV-2 positive group only. Overall, we found no evidence that telomere length was affected by chronic HTLV-1 and HTLV-2 infection. That TL was only associated with peripheral neuropathy in the HTLV-2-positive group is intriguing, but should be interpreted cautiously. Studies with larger sample size and telomere length measurement in lymphocyte subsets may clarify the relationship between TL and HTLV-infection.

  9. Carga proviral do HTLV-1 e HTLV-2: um método simples através da PCR quantitativa em tempo real HTLV-1 and HTLV-2 proviral load: a simple method using quantitative real-time PCR

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    Bruna Pedroso Tamegão-Lopes

    2006-12-01

    Full Text Available Os vírus linfotrópicos de células T humanas, quando integrados ao genoma da célula hospedeira, provírus, têm como marcador de replicação seu DNA proviral. A carga proviral parece ser um importante fator no desenvolvimento de patologias associadas a estes retrovírus. Neste estudo foi desenvolvida uma metodologia para quantificação absoluta da carga proviral dos HTLV-1 e HTLV-2 através da PCR em tempo real. Cinqüenta e três amostras de doadores de sangue com teste de ELISA reagente foram submetidas à metodologia, que utilizou o sistema TaqMan® para três seqüências alvo: HTLV-1, HTLV-2 e albumina. A quantificação proviral absoluta foi determinada através da proporção relativa entre o genoma do HTLV e o genoma da célula hospedeira, levando em consideração o número de leucócitos. O método apresentado é sensível (215 cópias/mL, prático e simples para quantificação proviral, além de eficiente e adequado para confirmação e discriminação da infecção pelos tipos virais.When the human T cell lymphotropic virus (HTLV is integrated with the host cell genome (provirus, its proviral DNA is a replication marker. Proviral load appears to be an important factor in the development of diseases related to these retroviruses. In this study, a methodology for absolute quantification of the HTLV-1 and HTLV-2 proviral load using real-time PCR was developed. Fifty-three blood donor samples with positive ELISA test result were subjected to this methodology, which utilized the TaqMan® system for three target sequences: HTLV-1, HTLV-2 and albumin. The absolute proviral load was quantified using the relative ratio between the HTLV genome and the host cell genome, taking into consideration the white blood cell count. The method presented is sensitive (215 copies/ml, practical and simple for proviral quantification, and is efficient and appropriate for confirming and discriminating infections according to viral type.

  10. Validation of a quantitative real-time PCR assay for HTLV-1 proviral load in peripheral blood mononuclear cells.

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    Rosadas, Carolina; Cabral-Castro, Mauro Jorge; Vicente, Ana Carolina Paulo; Peralta, José Mauro; Puccioni-Sohler, Marzia

    2013-11-01

    The objective of this study was to validate a TaqMan real-time PCR assay for HTLV-1 proviral load detection in peripheral blood mononuclear cells. TARL-2 cells were used to generate a standard curve. Peripheral blood mononuclear cell gDNA from 27 seropositive and 23 seronegative samples was analyzed. The sensitivity, specificity, accuracy, precision, dynamic range of the standard curve and qPCR efficiency were evaluated. All of the positive samples amplified the target gene. All of the negative samples amplified only the control gene (β-actin). The assay presented 100% specificity and sensibility. The intra- and inter-assay variability was 2.4% and 2.2%, respectively. The qPCR efficiency, slope and correlation coefficients (r2) were all acceptable. The limit of detection was 1 copy/rxn. This assay can reliably quantify HTLV-1 proviral load.

  11. Identification of bovine leukocyte antigen class II haplotypes associated with variations in bovine leukemia virus proviral load in Japanese Black cattle.

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    Miyasaka, T; Takeshima, S-n; Jimba, M; Matsumoto, Y; Kobayashi, N; Matsuhashi, T; Sentsui, H; Aida, Y

    2013-02-01

    Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle. Bovine leukocyte antigen (BoLA) is strongly involved in the subclinical progression of BLV infections. Recent studies show that the BoLA-DRB3 gene might play a direct role in controlling the number of BLV-infected peripheral B lymphocytes in vivo in Holstein cattle. However, the specific BoLA class II allele and DRB3-DQA1 haplotypes determining the BLV proviral load in Japanese Black cattle are yet to be identified. In this study, we focused on the association of BLV proviral load and polymorphism of BoLA class II in Japanese Black cattle. We genotyped 186 BLV-infected, clinically normal cattle for BoLA-DRB3 and BoLA-DQA1 using a polymerase chain reaction-sequence-based typing method. BoLA-DRB3*0902 and BoLA-DRB3*1101 were associated with a low proviral load (LPVL), and BoLA-DRB3*1601 was associated with a high proviral load (HPVL). Furthermore, BoLA-DQA1*0204 and BoLA-DQA1*10012 were related to LPVL and HPVL, respectively. Furthermore, we confirmed the correlation between the DRB3-DQA1 haplotype and BLV proviral load. Two haplotypes, namely 0902B or C (DRB3*0902-DQA1*0204) and 1101A (DRB3*1101-DQA1*10011), were associated with a low BLV proviral load, whereas one haplotype 1601B (DRB3*1601-DQA1*10012) was associated with a high BLV proviral load. We conclude that resistance is a dominant trait and susceptibility is a recessive trait. Additionally, resistant alleles were common between Japanese Black and Holstein cattle, and susceptible alleles differed. This is the first report to identify an association between the DRB3-DQA1 haplotype and variations in BLV proviral load.

  12. High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1

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    J. Primo

    2009-08-01

    Full Text Available Salvador (BA, Brazil is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1. The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP and infective dermatitis associated with HTLV-1 (IDH. IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.

  13. Association of TNF-α gene promoter region polymorphisms in bovine leukemia virus (BLV)-infected cattle with different proviral loads.

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    Lendez, Pamela Anahi; Passucci, Juan Antonio; Poli, Mario Andres; Gutierrez, Silvina Elena; Dolcini, Guillermina Laura; Ceriani, Maria Carolina

    2015-08-01

    Tumor necrosis factor alpha (TNF-α) is a pleiotropic cytokine involved in the immune response against viral and other infections. Its expression levels are affected by a polymorphism in the promoter region of the gene. Bovine leukemia virus is a retrovirus that infects cattle and develops two different infection profiles in the host. One profile is characterized by a high number of proviral copies integrated into the host genome and a strong immune response against the virus, while the most relevant property of the other profile is that the number of copies integrated into the host genome is almost undetectable and the immune response is very weak. We selected a population of cattle sufficiently large for statistical analysis and classified them according to whether they had a high or low proviral load (HPL or LPL). Polymorphisms in the promoter region were identified by PCR-RFLP. The results indicated that, in the HPL group, the three possible genotypes were normally distributed and that, in the LPL group, there was a significant association between the proviral load and a low frequency of the G/G genotype at position -824.

  14. Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients.

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    Akbarin, Mohammad Mehdi; Shirdel, Abbas; Bari, Alireza; Mohaddes, Seyedeh Tahereh; Rafatpanah, Houshang; Karimani, Ehsan Ghayour; Etminani, Kobra; Golabpour, Amin; Torshizi, Reza

    2017-06-01

    Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL. Forty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR. Significant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P=0.014 and P=0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC (P=0.000). There was a significant negative relationship between PVL and survival among all study groups (P=0.047). The HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.

  15. BLV-CoCoMo-qPCR: Quantitation of bovine leukemia virus proviral load using the CoCoMo algorithm

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    Matoba Kazuhiro

    2010-11-01

    Full Text Available Abstract Background Bovine leukemia virus (BLV is closely related to human T-cell leukemia virus (HTLV and is the etiological agent of enzootic bovine leukosis, a disease characterized by a highly extended course that often involves persistent lymphocytosis and culminates in B-cell lymphomas. BLV provirus remains integrated in cellular genomes, even in the absence of detectable BLV antibodies. Therefore, to understand the mechanism of BLV-induced leukemogenesis and carry out the selection of BLV-infected animals, a detailed evaluation of changes in proviral load throughout the course of disease in BLV-infected cattle is required. The aim of this study was to develop 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 clinical animals. Results Degenerate primers were designed from 52 individual BLV long terminal repeat (LTR sequences identified from 356 BLV sequences in GenBank using the CoCoMo algorithm, which has been developed specifically for the detection of multiple virus species. Among 72 primer sets from 49 candidate primers, the most specific primer set was selected for detection of BLV LTR by melting curve analysis after real-time PCR amplification. An internal BLV TaqMan probe was used to enhance the specificity and sensitivity of the assay, and a parallel amplification of a single-copy host gene (the bovine leukocyte antigen DRA gene was used to normalize genomic DNA. The assay is highly specific, sensitive, quantitative and reproducible, and was able to detect BLV in a number of samples that were negative using the previously developed nested PCR assay. The assay was also highly effective in detecting BLV in cattle from a range of international locations. Finally, this assay enabled us to demonstrate that proviral load correlates not only with BLV infection capacity as assessed by syncytium formation, but

  16. Evaluation of HTLV-1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP.

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    Mozhgani, Sayed-Hamidreza; Jaberi, Najmeh; Rezaee, Seyed Abdolrahim; Bustani, Reza; Jazayeri, Seyed Mohammad; Akbarin, Mohammad Mehdi; Milani, Saeideh; Tarokhian, Hanieh; Norouzi, Mehdi

    2017-06-01

    Human T-cell lymphotropic virus 1 (HTLV-1) is associated with two progressive diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although HTLV-1 proviral load (PVL) has been introduced as a risk factor for these diseases' progression, it is not sufficient on its own to yield an accurate estimation of the outcome of the infection. In the present study, PVL and HTLV-1 basic leucine zipper factor (HBZ) expression level as viral factors, and IFN λ3 as a host factor, were evaluated in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs). During 2014-2015, 12 HAM/TSP patients and 18 ACs who had been referred to the HTLV-1 Clinic, Ghaem Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and the DNA and mRNA were extracted for quantification of HBZ, IFN λ3 expression, and PVL using real-time PCR (TaqMan method). Although the PVL was higher in the HAM/TSP group, with a 94% confidence interval, there were no considerable differences in terms of HBZ mRNA and PVL between ACs and HAM patients. IFN λ3 expression in the HAM/TSP group was significantly higher than in the ACs (P = 0.02). To the best of our knowledge, no study has evaluated the expression level of IFN λ3 in HTLV-1 positive patients. The immune response against HTLV-1 viral antigens and virulent factors will therefore further refine our knowledge of interactions between the virus and host in the pathogenesis of HTLV-1-related disorders. The virus PVL and the host IFN λ3 can be used as pathogenic factors of HTLV-1 infected patients at risk of HAM/TSP manifestation. J. Med. Virol. 89:1102-1107, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Assessment of HTLV-I proviral load, HIV viral load and CD4 T cell count in infected subjects; with an emphasis on viral replication in co-infection

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    Hossein Rahimi

    2014-01-01

    The mean viral load of HIV infected subjects and HTLV-I infected individuals were 134626.07±60031.07 copies/ml and 373.6±143.3 copies/104 cells, respectively. The mean HIV viral load in co-infected group was 158947±78203.59 copies/ml which is higher than HIV infected group. The mean proviral load of HTLV-I in co-infected group was 222.33±82.56 copies/ml which is lower than HTLV-I infected group (P

  18. 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.

  19. Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats.

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    Webb, Craig B; Lehman, Tracy L; McCord, Kelly W

    2008-10-01

    This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (> or =16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66-0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.

  20. Quantitation of HTLV-I proviral load by a real-time PCR assay using SYBR Green: comparison of two methods for DNA isolation.

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    Altamirano, Natalia Andrea; Rocco, Carlos; Aulicino, Paula; Sen, Luisa; Mangano, Andrea

    2010-12-01

    A real-time quantitative PCR (qPCR) assay using SYBR Green was developed to determine HTLV-I proviral load (pVL) in peripheral blood mononuclear cells (PBMCs), and its performance was evaluated with samples processed as cell lysates and DNA isolated by salting out. Primers targeting the pol region were standardized against the MT2 cell line and HTLV-I copy number was normalized to the amount of cellular DNA by quantitation of the albumin gene. The sensitivity, specificity and reproducibility of the qPCR were assessed in the two methods used for DNA processing. The assay had a limit of detection of 400 HTLV-I copies/10(6) PBMCs for both methods, with a broad range of quantitation (2.6log(10) to >5log(10)), and without cross-reactivity with HTLV-II or with HIV-1. The inter- and intra-assay coefficients of variation were less than 2.4%. HTLV-I pVL quantitation in seven blood donor samples processed as either cell lysates or isolated DNA by salting out showed a strong linear correlation and no difference in the calculated pVL (Fisher's exact test, p>0.05). The assay was found to be a low cost, robust and reproducible assay for quantifying HTLV-I pVL in samples processed as cell lysates or as isolated DNA.

  1. 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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    Cánepa, Camila; Salido, Jimena; Ruggieri, Matías; Fraile, Sindy; Pataccini, Gabriela; Berini, Carolina; Biglione, Mirna

    2015-10-28

    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. (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. 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). indeterminate WB results 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.

  2. HTLV-1 Tax-Specific CTL Epitope-Pulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with Immune Tolerance against Tax.

    Science.gov (United States)

    Ando, Satomi; Hasegawa, Atsuhiko; Murakami, Yuji; Zeng, Na; Takatsuka, Natsuko; Maeda, Yasuhiro; Masuda, Takao; Suehiro, Youko; Kannagi, Mari

    2017-02-01

    Adult T cell leukemia/lymphoma (ATL), a CD4(+) T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1-specific CTL responses may be involved in the elevation of PVL. Our previous animal studies indicated that oral HTLV-1 infection, the major route of infection, caused persistent infection with higher PVL in rats compared with other routes. In this study, we found that Tax-specific CD8(+) T cells were present, but not functional, in orally infected rats as observed in some human asymptomatic carriers. Even in the infected rats with immune unresponsiveness against Tax, Tax-specific CTL epitope-pulsed dendritic cell (DC) therapy reduced the PVL and induced Tax-specific CD8(+) T cells capable of proliferating and producing IFN-γ. Furthermore, we found that monocyte-derived DCs from most infected individuals still had the capacity to stimulate CMV-specific autologous CTLs in vitro, indicating that DC therapy may be applicable to most infected individuals. These data suggest that peptide-pulsed DC immunotherapy will be useful to induce functional HTLV-1-specific CTLs and decrease PVL in infected individuals with high PVL and impaired HTLV-1-specific CTL responses, thereby reducing the risk of the development of ATL. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma.

    Science.gov (United States)

    Ramezani, Samaneh; Shirdel, Abbas; Rafatpanah, Houshang; Akbarin, Mohammad Mehdi; Tarokhian, Hanieh; Rahimi, Hossein; Bari, Alireza; Jahantigh, Hamid Reza; Rezaee, Seyed Abdolrahim

    2017-08-01

    Adult T cell leukemia/lymphoma (ATLL) is a life-threatening malignancy of HTLV-1 infected Th lymphocytes. In the present study host-virus interactions were investigated by assessment of HTLV-1 proviral load (PVL) and host gene expression. A cross-sectional study was carried out on 18 ATLL, 10 HAM/TSP patients and 18 HTLV-1 asymptomatic carriers (ACs). DNA and mRNA of the peripheral blood mononuclear cells were extracted for PVL and LAT, BIM, c-FOS and RAD51 gene expression measurement using qRT-PCR. The mean PVL in ATLL patients was 11,430 ± 3770 copies/10(4) which was statistically higher than ACs, 530 ± 119 copies/10(4), (p < 0.001). The expression of BIM, and c-FOS in ATLL patients were higher than HTLV-1 ACs; however, there were no statistically significant differences. The expression of RAD51 as an essential player on DNA repair showed around 160 times increase in ATLL group (166 ± 95) compared to ACs (1.04 ± 0.34) which is statistically significant (p < 0.001). Interestingly, there was a positive correlation between RAD51 expression and HTLV-PVL. The expression of LAT as a central adaptor in TCR signaling interestingly was around 36 times higher in ATLL group than ACs (ATLL; 41.33 ± 19.91 vs. ACs; 1.15 ± 0.22, p < 0.001). This finding showed that TCR signaling pathway mainly provides the growth factors for transformed cells. Furthermore, the overexpression of RAD51 which has been induced in HTLV-1 infected cells as a consequence of virus replication is not able to overcome the DNA damage toward cell transformation.

  4. 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?

    Directory of Open Access Journals (Sweden)

    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.

  5. Correlation between LTR point mutations and proviral load levels among Human T cell Lymphotropic Virus type 1 (HTLV-1 asymptomatic carriers

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    Neto Walter K

    2011-12-01

    Full Text Available Abstract Background In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE of the genuine human T-cell leukemia virus type I (HTLV-1 viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1i nfected cells and alter the proviral load (PvL. To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden. Methods A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared. Results Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31, 27.5% (8/29, and 61.8% (21/34 of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p p > 0.05. This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p p > 0. 05. Conclusions The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.

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

    Science.gov (United States)

    Domingos, João Américo; Soares, Luana Silva; Bandeira, Larissa M; Bonin, Camila Mareti; Vicente, Ana C P; Zanella, Louise; Puga, Marco Antonio Moreira; Tozetti, Inês Aparecida; Motta-Castro, Ana Rita Coimbra; da Cunha, Rivaldo Venâncio

    2017-01-01

    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 genetic

  7. Analysis of HTLV-1 proviral load (PVL) and antibody detected with various kinds of tests in Japanese blood donors to understand the relationship between PVL and antibody level and to gain insights toward better antibody testing.

    Science.gov (United States)

    Matsumoto, Chieko; Sagara, Yasuko; Sobata, Rieko; Inoue, Yukiko; Morita, Maiko; Uchida, Shigeharu; Kiyokawa, Hiroyuki; Satake, Masahiro; Tadokoro, Kenji

    2017-08-01

    Adult T-cell leukemia/lymphoma (ATL) occurs in approximately 5% of individuals infected with human T-cell leukemia virus type 1 (HTLV-1). A high proviral load (PVL; more than four copies per 100 peripheral blood mononuclear cells (PBMCs) or 1.6 copies per 100 blood leukocytes) and being male are risk factors for ATL development. Whether anti-HTLV-1 antibody level is related to such risk is unknown. Here, PVL and antibody levels were examined using real-time PCR and other tests in 600 HTLV-1 positive screened Japanese blood donors to understand the relationship between PVL and antibody level in asymptomatic carriers and to gain insights toward better antibody testing for HTLV-1 infection. The 430 donors in whom proviral DNA was detected were considered as true positives for HTLV-1 infection. Among donors aged 40 years or older, more males than females had a PVL corresponding to more than 1.6% infected leukocytes, and an antibody titer below the median (P = 0.0018). In antibody tests using an HTLV-1 positive cell line or Env antigens there was a large discrepancy in antibody titer among 13 provirus-positive samples, probably suggesting that antibody-based screening tests should incorporate multiple HTLV-1 antigens, such as Gag and Env antigens. © 2017 Wiley Periodicals, Inc.

  8. Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

    National Research Council Canada - National Science Library

    Boostani, Reza; Vakili, Rosita; Hosseiny, Samane Sadat; Shoeibi, Ali; Fazeli, Bahare; Etemadi, Mohammad Mehdi; Sabet, Faeze; Valizade, Narges; Rezaee, Seyed Abdolrahim

    2015-01-01

    .... HTLV-1 proviral load (PVL), and HBZ and Tax mRNA expression levels were measured in peripheral blood mononuclear cells of 13 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis before and after treatment with 180 μ...

  9. Human T-lymphotropic virus type 1 (HTLV-1 prevalence and quantitative detection of DNA proviral load in individuals with indeterminate/positive serological results

    Directory of Open Access Journals (Sweden)

    Bon Isabella

    2006-03-01

    Full Text Available Abstract Background HTLV-1 infection is currently restricted to endemic areas. To define the prevalence of HTLV-1 infection in patients living in Italy, we first carried out a retrospective serological analysis in a group of people originating from African countries referred to our hospital from January 2003 to February 2005. We subsequently applied a real time PCR on peripheral blood mononuclear cells from subjects with positive or indeterminate serological results. Methods All the sera were first analysed by serological methods (ELISA and/or Western Blotting and then the peripheral blood mononuclear cells from subjects with positive or inconclusive serological results were analyzed for the presence of proviral DNA by a sensitive SYBR Green real time PCR. In addition, twenty HTLV-I ELISA negative samples were assayed by real time PCR approach as negative controls. Results Serological results disclosed serum reactivity by ELISA (absorbance values equal or greater than the cut-off value in 9 out of 3408 individuals attending the Sexually Transmitted Diseases Clinic and/or Oncology Department, and 2 out 534 blood donors enrolled as a control population. Irrespective of positive or inconclusive serological results, all these subjects were analyzed for the presence of proviral DNA in peripheral blood mononuclear cells by SYBR real time PCR. A clear-cut positive result for the presence of HTLV-1 DNA was obtained in two subjects from endemic areas. Conclusion SYBR real time PCR cut short inconclusive serological results. This rapid and inexpensive assay showed an excellent linear dynamic range, specificity and reproducibility readily revealing and quantifying the presence of virus in PBMCs. Our results highlight the need to monitor the presence of HTLV-1 in countries which have seen a large influx of immigrants in recent years. Epidemiological surveillance and correct diagnosis are recommended to verify the prevalence and incidence of a new

  10. Long-term follow-up of HTLV-1 proviral load in asymptomatic carriers and in incident cases of HAM/TSP: what is its relevance as a prognostic marker for neurologic disease?

    Science.gov (United States)

    Martins, Marina Lobato; Guimarães, Jacqueline Cronemberger; Ribas, João Gabriel; Romanelli, Luiz Cláudio Ferreira; de Freitas Carneiro-Proietti, Anna Bárbara

    2017-02-01

    HTLV-1 proviral load (pvl) is an important risk marker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its value as prognostic marker is not well defined. Long-term prospective cohort studies are necessary to clarify this question. Here, we analyzed HTLV-1 pvl in the peripheral blood of 82 asymptomatic carriers (AC; 351 samples), 12 HAM/TSP patients (HAM; 46 samples), and six incident cases of HAM/TSP (iHAM), with serial samples collected before (n = 10) and after (n = 20) the disease onset. The mean interval of follow-up was 10 years in the AC group and 8 years in HAM and iHAM groups. pvl was not significantly different between the first and last measurements in the three groups, but there was a trend to decrease over time. Coefficient of variation of pvl was significantly lower in the AC group than in HAM (p = 0.015) and iHAM (p = 0.022) patients. AC and HAM individuals showed a significant and strong positive correlation between the first and last measurements of pvl, but not iHAM subjects. All individuals who developed HAM/TSP during the follow-up had high pvl level (>1 %) before the onset of disease, but a typical increase in pvl was not observed in that period. The data suggest that there is a trend to reach an equilibrium plateau of pvl over time, characteristic of each individual. A significant rate of AC keeps high pvl levels for a long time without developing clinical symptoms associated to HTLV-1 infection. Thus, serial quantification of pvl in the peripheral blood does not seem to be a good prognostic marker for HAM/TSP.

  11. HTLV-1 integration into transcriptionally active genomic regions is associated with proviral expression and with HAM/TSP.

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    Kiran N Meekings

    2008-03-01

    Full Text Available Human T-lymphotropic virus type 1 (HTLV-1 causes leukaemia or chronic inflammatory disease in approximately 5% of infected hosts. The level of proviral expression of HTLV-1 differs significantly among infected people, even at the same proviral load (proportion of infected mononuclear cells in the circulation. A high level of expression of the HTLV-1 provirus is associated with a high proviral load and a high risk of the inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. But the factors that control the rate of HTLV-1 proviral expression remain unknown. Here we show that proviral integration sites of HTLV-1 in vivo are not randomly distributed within the human genome but are associated with transcriptionally active regions. Comparison of proviral integration sites between individuals with high and low levels of proviral expression, and between provirus-expressing and provirus non-expressing cells from within an individual, demonstrated that frequent integration into transcription units was associated with an increased rate of proviral expression. An increased frequency of integration sites in transcription units in individuals with high proviral expression was also associated with the inflammatory disease HAM/TSP. By comparing the distribution of integration sites in human lymphocytes infected in short-term cell culture with those from persistent infection in vivo, we infer the action of two selective forces that shape the distribution of integration sites in vivo: positive selection for cells containing proviral integration sites in transcriptionally active regions of the genome, and negative selection against cells with proviral integration sites within transcription units.

  12. Administration of a Toll-like receptor 9 agonist decreases the proviral reservoir in virologically suppressed HIV-infected patients.

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    Anni A Winckelmann

    Full Text Available Toll-like receptor (TLR agonists can reactivate HIV from latently infected cells in vitro. We aimed to investigate the TLR-9 agonist, CPG 7909's in vivo effect on the proviral HIV reservoir and HIV-specific immunity. This was a post-hoc analysis of a double-blind randomized controlled vaccine trial. HIV-infected adults were randomized 1:1 to receive pneumococcal vaccines with or without 1 mg CPG 7909 as adjuvant at 0, 3 and 9 months. In patients on suppressive antiretroviral therapy we quantified proviral DNA at 0, 3, 4, 9, and 10 months (31 subjects in the CPG group and 37 in the placebo-adjuvant group. Furthermore, we measured HIV-specific antibodies, characterized T cell phenotypes and HIV-specific T cell immunity. We observed a mean reduction in proviral DNA in the CPG group of 12.6% (95% CI: -23.6-0.0 following each immunization whereas proviral DNA in the placebo-adjuvant group remained largely unchanged (6.7% increase; 95% CI: -4.2-19.0 after each immunization, p = 0.02. Among participants with additional cryo-preserved PBMCs, HIV-specific CD8+ T cell immunity as indicated by increased expression of degranulation marker CD107a and macrophage inflammatory protein 1β (MIP1β tended to be up-regulated following immunization with CPG 7909 compared with placebo as adjuvant. Further, increasing proportion of HIV-specific CD107a and MIP1β-expressing CD8+ T cells were strongly correlated with decreasing proviral load. No changes were observed in T cell phenotype distribution, HIV-specific CD4+ T cell immunity, or HIV-specific antibodies. TLR9-adjuvanted pneumococcal vaccination decreased proviral load. Reductions in proviral load correlated with increasing levels of HIV specific CD8+ T cells. Further investigation into the potential effect of TLR9 agonists on HIV latency is warranted.

  13. Administration of a Toll-like receptor 9 agonist decreases the proviral reservoir in virologically suppressed HIV-infected patients.

    Science.gov (United States)

    Winckelmann, Anni A; Munk-Petersen, Lærke V; Rasmussen, Thomas A; Melchjorsen, Jesper; Hjelholt, Thomas J; Montefiori, David; Østergaard, Lars; Søgaard, Ole S; Tolstrup, Martin

    2013-01-01

    Toll-like receptor (TLR) agonists can reactivate HIV from latently infected cells in vitro. We aimed to investigate the TLR-9 agonist, CPG 7909's in vivo effect on the proviral HIV reservoir and HIV-specific immunity. This was a post-hoc analysis of a double-blind randomized controlled vaccine trial. HIV-infected adults were randomized 1:1 to receive pneumococcal vaccines with or without 1 mg CPG 7909 as adjuvant at 0, 3 and 9 months. In patients on suppressive antiretroviral therapy we quantified proviral DNA at 0, 3, 4, 9, and 10 months (31 subjects in the CPG group and 37 in the placebo-adjuvant group). Furthermore, we measured HIV-specific antibodies, characterized T cell phenotypes and HIV-specific T cell immunity. We observed a mean reduction in proviral DNA in the CPG group of 12.6% (95% CI: -23.6-0.0) following each immunization whereas proviral DNA in the placebo-adjuvant group remained largely unchanged (6.7% increase; 95% CI: -4.2-19.0 after each immunization, p = 0.02). Among participants with additional cryo-preserved PBMCs, HIV-specific CD8+ T cell immunity as indicated by increased expression of degranulation marker CD107a and macrophage inflammatory protein 1β (MIP1β) tended to be up-regulated following immunization with CPG 7909 compared with placebo as adjuvant. Further, increasing proportion of HIV-specific CD107a and MIP1β-expressing CD8+ T cells were strongly correlated with decreasing proviral load. No changes were observed in T cell phenotype distribution, HIV-specific CD4+ T cell immunity, or HIV-specific antibodies. TLR9-adjuvanted pneumococcal vaccination decreased proviral load. Reductions in proviral load correlated with increasing levels of HIV specific CD8+ T cells. Further investigation into the potential effect of TLR9 agonists on HIV latency is warranted.

  14. Damaging the Integrated HIV Proviral DNA with TALENs.

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    Christy L Strong

    Full Text Available HIV-1 integrates its proviral DNA genome into the host genome, presenting barriers for virus eradication. Several new gene-editing technologies have emerged that could potentially be used to damage integrated proviral DNA. In this study, we use transcription activator-like effector nucleases (TALENs to target a highly conserved sequence in the transactivation response element (TAR of the HIV-1 proviral DNA. We demonstrated that TALENs cleave a DNA template with the HIV-1 proviral target site in vitro. A GFP reporter, under control of HIV-1 TAR, was efficiently inactivated by mutations introduced by transfection of TALEN plasmids. When infected cells containing the full-length integrated HIV-1 proviral DNA were transfected with TALENs, the TAR region accumulated indels. When one of these mutants was tested, the mutated HIV-1 proviral DNA was incapable of producing detectable Gag expression. TALEN variants engineered for degenerate recognition of select nucleotide positions also cleaved proviral DNA in vitro and the full-length integrated proviral DNA genome in living cells. These results suggest a possible design strategy for the therapeutic considerations of incomplete target sequence conservation and acquired resistance mutations. We have established a new strategy for damaging integrated HIV proviral DNA that may have future potential for HIV-1 proviral DNA eradication.

  15. [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.

  16. Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa

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    Jochen Bodem

    2012-09-01

    Full Text Available The Human Immunodeficiency Virus type 1 (HIV-1 subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC, replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317.

  17. Severe congenital neutropenia (Kostmann Syndrome)

    African Journals Online (AJOL)

    This is not thought to be the direct result of G-CSF therapy but related to the underlying .... phage progenitor cell is defective, with few colonies formed .... In the study of Rosenberg, et al.29, the hazard of .... neutropenia. A report from the French.

  18. 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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy.

    Science.gov (United States)

    Hashiguchi, Yasunori; Kasai, Mari; Fukuda, Takeshi; Ichimura, Tomoyuki; Yasui, Tomoyo; Sumi, Toshiyuki

    2015-11-01

    Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24-84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1-12 days) and 3.4 days (range 1-9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (PFebrile neutropenia was associated with poor performance status (Pneutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy-induced neutropenia may be possible in patients with gynecologic malignancy.

  1. In vivo expression of the HBZ gene of HTLV-1 correlates with proviral load, inflammatory markers and disease severity in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP

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    Saito Kousuke

    2009-02-01

    Full Text Available Abstract Background Recently, human T-cell leukemia virus type 1 (HTLV-1 basic leucine zipper factor (HBZ, encoded from a minus strand mRNA was discovered and was suggested to play an important role in adult T cell leukemia (ATL development. However, there have been no reports on the role of HBZ in patients with HTLV-1 associated inflammatory diseases. Results We quantified the HBZ and tax mRNA expression levels in peripheral blood from 56 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients, 10 ATL patients, 38 healthy asymptomatic carriers (HCs and 20 normal uninfected controls, as well as human leukemic T-cell lines and HTLV-1-infected T-cell lines, and the data were correlated with clinical parameters. The spliced HBZ gene was transcribed in all HTLV-1-infected individuals examined, whereas tax mRNA was not transcribed in significant numbers of subjects in the same groups. Although the amount of HBZ mRNA expression was highest in ATL, medium in HAM/TSP, and lowest in HCs, with statistical significance, neither tax nor the HBZ mRNA expression per HTLV-1-infected cell differed significantly between each clinical group. The HTLV-1 HBZ, but not tax mRNA load, positively correlated with disease severity and with neopterin concentration in the cerebrospinal fluid of HAM/TSP patients. Furthermore, HBZ mRNA expression per HTLV-1-infected cell was decreased after successful immunomodulatory treatment for HAM/TSP. Conclusion These findings suggest that in vivo expression of HBZ plays a role in HAM/TSP pathogenesis.

  2. Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis

    Science.gov (United States)

    Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.

    2011-01-01

    Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. PMID:21507463

  3. Severe congenital cyclic neutropenia: A case report

    Science.gov (United States)

    Patil, Vidyavathi H; Hugar, Shivayogi M; Balikai, Girish; Patil, Sudha

    2016-01-01

    Congenital cyclic neutropenia syndrome is a constitutional genetic disorder which is characterized by very low number of neutrophils (neutropenia). Patients suffering from this disorder clinically present with neutropenia at early age, history of recurrent fever, ulcerations in the oral cavity, gingivitis, and other recurrent infections. This paper describes a case report of a child with recurrent mouth ulcers, fever, and later diagnosed with severe congenital cyclic neutropenia. This also emphasizes the importance of identification of rare causes of immunosuppressive conditions in children presenting with recurrent oral ulcers and poor dental hygiene, to prevent long-term complications of oral cavity and also morbidity and mortality secondary to neutropenic sepsis. PMID:27857902

  4. Neutropenia Associated with X-Linked Agammaglobulinemia

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    Aghamohammadi Asghar

    2009-03-01

    Full Text Available X-linked Agammaglobulinemia (XLA is a hereditary immunodeficiency, characterized by an early onset of recurrent bacterial infections, hypogammaglobulinemia and markedly reduced B lymphocytes number. In order to determine the association of neutropenia among Iranian patients with XLA, hospital records of 30 patients with confirmed XLA in Children Medical Center Hospital, were reviewed. Eight out of 30 XLA patients (26.7% developed neutropenia during the course of the disease. In two patients, episodes of neutropenia were identified before or at the time of diagnosis of XLA. Other six patients whom were not visited regularly and did not receive periodical immunoglobulin replacement therapy experienced neutropenia after diagnosis of XLA. Neutropenia in XLA is mainly associated with infection and is resolved with intravenous immunoglobulin replacement and antibiotics therapy.

  5. Proviral HIV-1 DNA in gingival crevicular fluid of HIV-1-infected patients in various stages of HIV disease.

    Science.gov (United States)

    Maticic, M; Poljak, M; Kramar, B; Tomazic, J; Vidmar, L; Zakotnik, B; Skaleric, U

    2000-07-01

    The oral cavity is rarely reported to be a site of human immunodeficiency virus (HIV) transmission, despite detectable virus in saliva and relatively frequent prevalence of periodontal disease in HIV-infected persons yielding increased excretion of mononuclear-cell-enriched gingival fluid. To search for possible sources of HIV in saliva, and using the polymerase chain-reaction technique, we sought the presence and shedding patterns of proviral HIV-1 DNA in gingival crevicular fluid in a group of patients previously determined as HIV-1-seropositive. Periodontal status at the collection sites was monitored by several clinical parameters, including Plaque Index, Gingival Index, probing depth, and clinical attachment loss. Gingival crevicular fluid samples were collected by means of paper points. Proviral HIV-1 DNA was detected in the gingival fluid of 17 out of 35 HIV-1-infected patients. Its detection correlated significantly with higher plasma HIV-1 RNA viral load (p = 0.03) and not with peripheral blood CD4+ cell count, the presence of blood in gingival fluid, or oral lesions. There was a significant correlation between clinical attachment loss at the sites of fluid collection and plasma HIV-1 RNA viral load (p = 0.002), and borderline correlation between the latter and probing depth (p = 0.54) in the group of patients harboring proviral HIV-1 DNA in gingival crevicular fluid. The results of our study suggest that mononuclear cells present in gingival crevicular fluid and harboring proviral HIV-1 DNA could represent a potential source of HIV-1 in the presence or absence of local bleeding, especially in persons with advanced HIV infection and increased loss of clinical attachment.

  6. Autoimmune neutropenia after kidney transplantation: a disregarded entity of posttransplant neutropenia.

    Science.gov (United States)

    Aubert, Olivier; Sberro-Soussan, Rebecca; Scemla, Anne; Casadevall, Nicole; Teyssandier, Irène; Martinez, Frank; Hermine, Olivier; Legendre, Christophe; Varet, Bruno; De Fontbrune, Flore Sicre

    2014-04-15

    Neutropenia is common after kidney transplantation and is associated with an increased incidence of infections. Drug toxicities are the main causes of posttransplant neutropenia (PTN), mainly related to immunosuppressive drugs as mycophenolic acid (MPA) and anti-infectious agents, but some PTN remain unexplained. Between January 2012 and January 2013, cultures of autologous granulocytic progenitors from bone marrow aspirate were performed in two patients with unexplained severe neutropenia. Both patients' serum inhibited granulocytic differentiation while granulocytic differentiation was normal with the control serum. Similar inhibition of differentiation of granulocytic progenitors from a control marrow was observed with the patients' serum as compared with the control serum. Moreover, in both cases intravenous immunoglobulins allowed full neutrophil count recovery. Other usual etiologies of acquired neutropenia including systemic drug toxicity, infection, and autoimmune disease were excluded. As frequently observed in adult immune neutropenia, granulocyte autoantibodies were absent in both cases. Owing to biological and clinical results, we concluded that an autoimmune mechanism was responsible for neutropenia. The levels of MPA, which is known to interact with tacrolimus, were not measured in our patients. However, the persistence of neutropenia more than 70 days after withdrawal of MPA did not support this hypothesis. Autoimmune neutropenia should be considered in kidney transplant recipients in case of persistent unexplained neutropenia as it allows effective treatment and avoids the withdrawal of important immunosuppressive and anti-infectious treatments.

  7. Neutropenia in Congenital and Adult Babesiosis.

    Science.gov (United States)

    Wormser, Gary P; Villafuerte, Patrick; Nolan, Sheila M; Wang, Guiqing; Lerner, Robert G; Saetre, Kirsten L; Maria, Mazen H; Branda, John A

    2015-07-01

    Anemia and thrombocytopenia are expected hematologic abnormalities in patients with acute babesiosis, whereas neutropenia (defined as an absolute neutrophil count of ≤1,800 neutrophils/μL for adults and babesiosis. The frequency of neutropenia in cases of congenital babesiosis was determined based on a literature review and on the findings in an unreported case. The frequency of neutropenia in adult patients was assessed based on a review of the medical records of 51 patients who were diagnosed with babesiosis between 2010 and 2013 at two medical centers in the Northeastern United States. Four (80%; 95% confidence interval [CI], 36%-98%) of five infants with congenital babesiosis whose neutrophil count was reported were neutropenic. Among 51 adult cases with babesiosis, 11 (22%; 95% CI, 12%-35%) were neutropenic on clinical presentation, and seven others developed neutropenia over the next 1 to 21 days. Thus, a total of 18 (35%; 95% CI, 24%-49%) of the adult patients with babesiosis had neutropenia. Neutropenia appears to be a common finding in infants with congenital babesiosis and is also observed not infrequently in adults with this infection. Copyright© by the American Society for Clinical Pathology.

  8. Clozapine Rechallenge After Neutropenia or Leucopenia.

    Science.gov (United States)

    Prokopez, Cintia R; Armesto, Arnaldo R; Gil Aguer, María F; Balda, María V; Papale, Rosa M; Bignone, Inés M; Daray, Federico M

    2016-08-01

    To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia.

  9. Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance

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    Asunción Delgado

    2017-05-01

    Full Text Available 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.

  10. Delayed umbilical cord separation in alloimmune neutropenia.

    OpenAIRE

    Kemp, A S; Lubitz, L

    1993-01-01

    Delayed umbilical cord separation in association with neonatal alloimmune neutropenia is reported. Delayed umbilical cord separation has been described in association with defects in neutrophil function. The present case indicates that deficiency in neutrophil number should also be considered as a cause of delayed cord separation.

  11. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

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    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.

  12. Triagem para o tratamento ambulatorial da neutropenia febril Screening for the outpatient treatment of febrile neutropenia

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    Marcelo Bellesso

    2010-01-01

    Full Text Available A neutropenia febril (NF é uma complicação frequente e potencialmente fatal nos pacientes em tratamento quimioterápico. Entendemos hoje que a neutropenia febril é considerada uma emergência clínica e que a administração de antibióticos de amplo espectro diminui drasticamente a mortalidade. Estudos sugerem que a neutropenia febril compreende um grupo extremamente heterogêneo e que dados clínicos como febre domiciliar, ausência de hipotensão, ausência de desidratação, ausência de doença pulmonar obstrutiva crônica, ausência de outros sintomas, ausência de infecção fúngica prévia e idade Febrile neutropenia is a frequent and potentially fatal adverse event of chemotherapy. Nowadays, febrile neutropenia is considered an emergency and it is known that prompt infusion of antibiotics decreases mortality. Several studies demonstrated that febrile neutropenia is a heterogeneous group of diseases and that factors such as outpatient status, no hypotension, no dehydration, no chronic obstructive pulmonary disease, no symptoms, no previous fungal infection and age < 60 years are protective factors against serious complications as demonstrated by the Multinational Association for Supportive Care in Cancer (MASCC. These data show that outpatient treatment and early discharge is safer and much research has shown lower costs for outpatient treatment in low-risk patients with febrile neutropenia. The aim of this work is to review and discuss tools (in particular the MASCC index for safe screening of febrile neutropenia for outpatient treatment in addition to demonstrate results of research.

  13. Simultaneous detection and subtyping of porcine endogenous retroviruses proviral DNA using the dual priming oligonucleotide system.

    Science.gov (United States)

    Moon, Hyoung Joon; Park, Seong Jun; Kim, Hye Kwon; Ann, Soo Kyung; Rho, Semi; Keum, Hyun Ok; Park, Bong Kyun

    2010-09-01

    The purpose of this study was to develop a multiplex PCR that can detect porcine endogenous retrovirus (PERV) proviral genes (pol, envA, envB, envC) and porcine mitochondrial DNA, using a dual priming oligonucleotide (DPO) system. The primer specifically detected the PERV proviral genes pol, envA, envB, envC, and porcine mitochondrial DNA only in samples of pig origin. The sensitivity of the primer was demonstrated by simultaneous amplification of all 5 target genes in as little as 10 pg of pig DNA containing PERV proviral genes and mitochondrial DNA. The multiplex PCR, when applied to field samples, simultaneously and successfully amplified PERV proviral genes from liver, blood and hair root samples. Thus, the multiplex PCR developed in the current study using DPO-based primers is a rapid, sensitive and specific assay for the detection and subtyping of PERV proviral genes.

  14. IMPORTANCE OF SERUM PROCALCITONIN IN FEBRILE NEUTROPENIA

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    Mohd. Riyaz

    2014-07-01

    Full Text Available Febrile neutropenia is defined as a fever >101°F for 1 hour, with an absolute neutrophil count of ≤500 cells/microliter, or an ANC of ≤1000 cells/microliter with a projected nadir of ≤500 cells/microliter. In haematological malignancies it is the common complication and requires broad-spectrum antibacterial therapy. Clinical examination and cultures fail to detect a pathogen or an infectious focus in 25–50%, which are classified as pyrexia of unknown origin (PUO. Patient with pyrexia of unknown origin may receive long duration of antibiotic treatment as the cause is unclear of being infective or not. Febrile neutropenia is a common complication of many chemotherapeutic regimens for all types of cancers. Mortality and Morbidity is high particularly in elderly, immuno-compromised. Approximately 20- 40 % of patients with severe sepsis and 45-60% patients with septic shock die within 15-20 days. This study was done to know the sources of infection and to assess the diagnostic value of serum Procalcitonin and its relation with mortality in various stages of sepsis. Sepsis incidence was more in patient age more than 55yrs. the most common source of sepsis was respiratory tract infection. Serum PCT proved to be an indicator of sepsis in ill patients, with sensitivity of 91%. Presence of both persistent and profound neutropenia was associated with a much higher mortality. The occurrence of infection is directly proportional to the degree of neutropenia, at the onset of fever the PCT levels will not be helpful for the decision to start or stop the antibacterial therapy, and a PCT value higher than 0.5ng/ml in pyrexia of unknown origin might suggest a possibility of occult infection, i.e. with lacking microbiological and clinical documentation. A delayed PCT peak higher than0.5ng/ml contributes to the early diagnosis of fungal disease.

  15. [An unusual cause of febrile neutropenia: brucellosis].

    Science.gov (United States)

    Solmaz, Soner; Asma, Süheyl; Ozdoğu, Hakan; Yeral, Mahmut; Turunç, Tuba

    2014-10-01

    Febrile neutropenia which is a common complication of cancer treatment, is one of the major causes of morbidity and mortality. Several gram-negative and gram-positive bacteria are responsible for infections in neutropenic patients, however the most common microorganisms are Escherichia coli and coagulase-negative staphylococci, in decreasing order. Although Brucella spp. infections are endemic in Turkey, brucellosis-related febrile neutropenia has only rarely been reported. In this report, a case of brucellosis-related febrile neutropenia in a patient with acute myeloblastic leukemia (AML) was presented. A 56-year-old male patient presenting with fever, petechiae/purpura, leukocytosis, thrombocytopenia, and anemia was admitted to our hospital. Laboratory studies revealed a hemoglobin level of 8.27 g/dl, leukocyte count of 77.100 k/ml, absolute neutrophil count of 200 k/ml, and platelets at 94.200 k/ml. The patient was diagnosed as AML-M1 and piperacillin/tazobactam was started as the first-line antibiotic therapy due to the febrile neutropenia. On admission, blood and urine cultures were negative. Once the fever was controlled, remission/induction chemotherapy was initiated. However, fever developed again on the eight day, and vancomycin was added to the therapy. Since the fever persisted, the antibiotic therapy was gradually replaced with meropenem and linezolid. However, fever continued and the patient's general condition deteriorated. Subsequently performed Brucella tube agglutination test revealed positivity at 1/320 titer and the microorganism grown in blood culture (Bactec 9050; BD, USA) was identified as B.melitensis by conventional methods. Rifampicin and doxycycline therapy was started immediately, however, the patient died due to septic shock. If the tests for brucellosis were performed earlier when response to second step antibiotic therapy lacked in this patient, it was assumed that mortality could be prevented by the prompt initiation of the

  16. 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

    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...... proviral HIV-1 was detected and quantified by a specific and sensitive assay combining a TaqMan real-time PCR analysis with the amplification-refractory mutation system (ARMS) principle. Results Fifty-six percent of patients with low-level viremia had 184V in the CD4+ T cellular DNA compartment as compared...... a median viral load of 498 copies/ml (P = 0.006). No significant differences between the groups were observed in proviral HIV-1 DNA load. Conclusions The frequency of the 184V mutation was significantly lower, in the CD4+ T cellular compartment of patients with a viral load of less than 20 copies...

  17. Congenital neutropenia: diagnosis, molecular bases and patient management

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    Chantelot Christine

    2011-05-01

    Full Text Available Abstract The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe ( When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency and glycogen storage disease type Ib (associated with a glycogen storage syndrome. So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF. G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.

  18. Serum Endocan Levels in Children with Febrile Neutropenia.

    Science.gov (United States)

    Kiral, Eylem; Dinleyici, Ener Cagri; Bozkurt-Turhan, Ayse; Bor, Ozcan; Akgun, Yurdanur; Akgun, Necat Akdeniz

    2016-03-17

    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 (Pfebrile 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.

  19. 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.

  20. Intensified prophylaxis of febrile neutropenia with ofloxacin plus rifampin during severe short-duration neutropenia in patients with lymphoma.

    Science.gov (United States)

    Muñoz, L; Martino, R; Subirà, M; Brunet, S; Sureda, A; Sierra, J

    1999-08-01

    To analyse the impact of intensified prophylaxis with ofloxacin plus rifampin (O+R) in neutropenic patients we used this combination in 40 consecutive cycles of ifosfamide, cytarabine, prednisolone and etoposide (IAPVP-16). This salvage chemotherapy regimen for lymphoma usually produces four to six days of severe neutropenia without significant extrahematologic toxicities. We compared the infectious morbidity during neutropenia under O+R with 58 consecutives cycles using either norfloxacin or no prophylaxis (control group). Fifty-three percent of control group patients and 20% of the O+R group developed febrile neutropenia that required hospital admission (pfebril neutropenia was 42 days and 158 days, respectively (pfebrile neutropenia and GPC bacteremia in patients with short and severe neutropenia, which translates into a reduction in the need for hospitalization.

  1. Approach to the patient with neutropenia in childhood.

    Science.gov (United States)

    Celkan, Tiraje; Koç, Begüm Şirin

    2015-09-01

    Neutrophils have an important role in host defense and acute inflammation. It is well known that susceptibility to infection increases when the neutrophil count is low. Neutropenia were classified as mild, moderate and severe according to the neutrophil counts, or acute and chronic depending on the duration of neutropenia, or congenital and acquired according to the mechanism. The patients with neutropenia are clinically different due to underlying mechanism, they have life- threatening infections or no infection may be observed. The most common cause of acquired neutropenia is viral infection, followed by drugs and autoimmune neutropenia. Congenital neutropenia are usually diagnosed by acute and life- threatening invasive bacterial and fungal infections. Immune system disorders and other systemic abnormalities may be accompanied or not. Recent years, novel single gen defects causing congenital neutropenia were defined through advanced genetic techniques. Molecular diagnosis is useful for risk stratification, choice of therapy and prognosis on follow- up. This review was prepared for pediatricians as a guide focused on approach neutropenia, which tests should be performed and when should be referred to a specialist.

  2. Neutropenia in Patients with Primary Antibody Deficiency Disorders

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    "Nima Rezaei

    2004-06-01

    Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.

  3. Rationalizing the approach to children with fever in neutropenia

    NARCIS (Netherlands)

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

    2012-01-01

    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 c

  4. Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG's.

    Science.gov (United States)

    Weber, Stefanie; Weiser, Barbara; Kemal, Kimdar S; Burger, Harold; Ramirez, Christina M; Korn, Klaus; Anastos, Kathryn; Kaul, Rupert; Kovacs, Colin; Doerfler, Walter

    2014-01-20

    Efforts to cure HIV-1 infections aim at eliminating proviral DNA. Integrated DNA from various viruses often becomes methylated de novo and transcriptionally inactivated. We therefore investigated CpG methylation profiles of 55 of 94 CpG's (58.5%) in HIV-1 proviral genomes including ten CpG's in each LTR and additional CpG's in portions of gag, env, nef, rev, and tat genes. We analyzed 33 DNA samples from PBMC's of 23 subjects representing a broad spectrum of HIV-1 disease. In 22 of 23 HIV-1-infected individuals, there were only unmethylated CpG's regardless of infection status. In one long term nonprogressor, however, methylation of proviral DNA varied between 0 and 75% over an 11-year period although the CD4+ counts remained stable. Hence levels of proviral DNA methylation can fluctuate. The preponderance of unmethylated CpG's suggests that proviral methylation is not a major factor in regulating HIV-1 proviral activity in PBMC's. Unmethylated CpG's may play a role in HIV-1 immunopathogenesis. © 2013 Elsevier Inc. All rights reserved.

  5. Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results.

    Science.gov (United States)

    Kuramitsu, Madoka; Sekizuka, Tsuyoshi; Yamochi, Tadanori; Firouzi, Sanaz; Sato, Tomoo; Umeki, Kazumi; Sasaki, Daisuke; Hasegawa, Hiroo; Kubota, Ryuji; Sobata, Rieko; Matsumoto, Chieko; Kaneko, Noriaki; Momose, Haruka; Araki, Kumiko; Saito, Masumichi; Nosaka, Kisato; Utsunomiya, Atae; Koh, Ki-Ryang; Ogata, Masao; Uchimaru, Kaoru; Iwanaga, Masako; Sagara, Yasuko; Yamano, Yoshihisa; Okayama, Akihiko; Miura, Kiyonori; Satake, Masahiro; Saito, Shigeru; Itabashi, Kazuo; Yamaguchi, Kazunari; Kuroda, Makoto; Watanabe, Toshiki; Okuma, Kazu; Hamaguchi, Isao

    2017-09-01

    Western blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%), and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens because of a combination of a low proviral load and mutations in the provirus, which may interfere with host recognition of HTLV-1 antigens. Copyright © 2017 American Society for Microbiology.

  6. Risk factors of Ganciclovir-related neutropenia after allogeneic stem cell transplantation: a retrospective monocentre study on 547 patients.

    Science.gov (United States)

    Venton, G; Crocchiolo, R; Fürst, S; Granata, A; Oudin, C; Faucher, C; Coso, D; Bouabdallah, R; Berger, P; Vey, N; Ladaique, P; Chabannon, C; le Merlin, M; Blaise, D; El-Cheikh, J

    2014-02-01

    Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p 2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  7. Experiencing neutropenia: Quality of life interviews with adult cancer patients

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    Okon Ted

    2005-07-01

    Full Text Available Abstract Background Neutropenia is a common toxicity in chemotherapy but detailed information about how neutropenia is associated with changes in patients' quality of life is not readily available. This prospective study interviewed patients with grade 4 neutropenia to provide qualitative information on patients' experience of developing and coping with grade 4 neutropenia during a cycle of chemotherapy. Methods A sample of 34 patients who developed grade 4 neutropenia during the first cycle of chemotherapy completed a total of 100 structured clinical interviews. Interviews were transcribed, and 2 raters inductively developed 5 broad categories comprising 80 specific complaint domains nominated by patients. Thirty-five patient-nominated problems were mentioned in 5% or more of the interviews. Results Fatigue was the most common physical symptom. Interference in daily routine, negative self-evaluation, negative emotion, and social isolation were other common complaints associated with neutropenia. Conclusion Neutropenia is associated with a number of negative experiences among cancer patients undergoing chemotherapy, and these negative experiences have an adverse effect on the patient's quality of life. Oncology nurses can play a key role in helping patients manage adverse effects to maintain their quality of life.

  8. Role of myeloid growth factors in chemotherapy induced neutropenia

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    Ravinutala Srinath Bharadwaj

    2016-10-01

    Full Text Available Neutropenia is a major dose limiting toxicity of many chemo therapeutic regimens. Haemopoietic colony - stimulating factors (CSFs have been shown to reduce the duration and severity of chemotherapy induced neutropenia (CIN and risk of febrile neutropenia. Supportive care with myeloid growth factors improve chemotherapy delivery by minimizing chemotherapy dose reductions or treatment delays by enabling the delivery of full dose chemotherapy (dose dense in short time intervals. The goal of this article is to give comprehensive review of current literature regarding medical practice guidelines and risk assessment models for appropriate use of myeloid growth factors and management of febrile neutropenia. [Int J Basic Clin Pharmacol 2016; 5(5.000: 1715-1721

  9. Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection.

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    Nicolas A Gillet

    Full Text Available Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1 and bovine leukemia virus (BLV induce a persistent infection that remains generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle or via clonal expansion of the infected cells (mitotic cycle. The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone. We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1 initial integration inside genes or promoters and (2 host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in

  10. Refractory Adult Primary Autoimmune Neutropenia that Responded to Alemtuzumab.

    Science.gov (United States)

    Neerukonda, Anu R; Lan, Fengshuo; Gabig, Theodore; Saraya, Takeshi

    2016-01-01

    Primary autoimmune neutropenia (P-AIN) is an extremely rare disease. The most effective treatment for primary P-AIN is a granulocyte colony-stimulating factor; however, no curative treatment has been reported. We herein report a case of an adult P-AIN patient with a relatively mild medical history (irrespective of the severe neutropenia) who showed a sustained hematological response over seventeen months after the initiation of treatment with subcutaneous Alemtuzumab.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Febrile neutropenia in children treated for malignancy.

    Science.gov (United States)

    Barton, Chris D; Waugh, Lucy K; Nielsen, Maryke J; Paulus, Stéphane

    2015-06-01

    Febrile neutropenia (FN) in children treated for malignancy is a common and direct sequela of chemotherapy. Episodes of FN can be life-threatening, and demand prompt recognition, assessment and treatment with broad spectrum antibiotics. While in the majority of episodes no causal infection is identified, 10-20% are secondary to a bloodstream infection (BSI). A reduction in episodes of BSI could be achieved through robust infection prevention strategies, such as CVL care bundles. Alongside good antimicrobial stewardship, these strategies could reduce the risk of emergent, multi-drug resistant (MDR) infections. Emerging bacterial pathogens in BSI include Viridans Group Streptococci (VGS) and Enterobacteriaceae such as Klebsiella spp. which are known for their ability to carry MDR genes. There is also increased recognition of the role of invasive fungal infection (IFI) in FN, in particular with Aspergillus spp. Novel diagnostics, including multiplex blood and respiratory polymerase chain reaction assays can identify infections early in FN, facilitating targeted therapy, and reducing unnecessary antimicrobial exposure. Given appropriate, and sensitive rapid diagnostics, potential also exists to safely inform the risk assessment of patients with FN, identifying those at low risk of complication, who could be treated in the out-patient setting. Several clinical decision rules (CDR) have now been developed and validated in defined populations, for the risk assessment of children being treated for cancer. Future research is needed to develop a universal CDR to improve the management of children with FN.

  13. Predicting neutropenia risk in patients with cancer using electronic data.

    Science.gov (United States)

    Pawloski, Pamala A; Thomas, Avis J; Kane, Sheryl; Vazquez-Benitez, Gabriela; Shapiro, Gary R; Lyman, Gary H

    2017-04-01

    Clinical guidelines recommending the use of myeloid growth factors are largely based on the prescribed chemotherapy regimen. The guidelines suggest that oncologists consider patient-specific characteristics when prescribing granulocyte-colony stimulating factor (G-CSF) prophylaxis; however, a mechanism to quantify individual patient risk is lacking. Readily available electronic health record (EHR) data can provide patient-specific information needed for individualized neutropenia risk estimation. An evidence-based, individualized neutropenia risk estimation algorithm has been developed. This study evaluated the automated extraction of EHR chemotherapy treatment data and externally validated the neutropenia risk prediction model. A retrospective cohort of adult patients with newly diagnosed breast, colorectal, lung, lymphoid, or ovarian cancer who received the first cycle of a cytotoxic chemotherapy regimen from 2008 to 2013 were recruited from a single cancer clinic. Electronically extracted EHR chemotherapy treatment data were validated by chart review. Neutropenia risk stratification was conducted and risk model performance was assessed using calibration and discrimination. Chemotherapy treatment data electronically extracted from the EHR were verified by chart review. The neutropenia risk prediction tool classified 126 patients (57%) as being low risk for febrile neutropenia, 44 (20%) as intermediate risk, and 51 (23%) as high risk. The model was well calibrated (Hosmer-Lemeshow goodness-of-fit test = 0.24). Discrimination was adequate and slightly less than in the original internal validation (c-statistic 0.75 vs 0.81). Chemotherapy treatment data were electronically extracted from the EHR successfully. The individualized neutropenia risk prediction model performed well in our retrospective external cohort.

  14. Neutropenia in chronic hepatitis C during Interferon and Ribavirin Therapy.

    Directory of Open Access Journals (Sweden)

    Saadia Farid, Hala Morad and Samya Sweilam.

    2011-10-01

    Full Text Available Background: Neutropenia is a condition characterized by an abnormally low number of a type of white blood cells called Neutrophils, up to 25 % of people who take pegylated interferon, ribavirin and an HCV protease inhibitor experience Neutropenia. Aim of the work: The study will be intended to analyze neutrophil counts and associated conditions of the liver and spleen , platelet count, liver enzymes and infections, during Interferon and Ribavirin therapy. Patients and methods: One hundred forty two patients with chronic hepatitis C virus infection, their age between (18-59 years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during Interferon and Ribavirin therapy. All the patients were subjected to the following history, through clinical examination, abdominal ultrasonography and collection of blood samples for routine investigations, CBCs and serological assay for ALT, Bilirubin. Resuls: Our results revealed presence of 32.4 % anaemia, 18.3 % Thrombocytopenia, 16.9 % elevated ALT, 2.8 % elevated bilirubine, 16.9 % coarse liver, 25.4 % hepatomegaly, 16.2 % splenomegaly, and 16.9 % of cases complained different shapes of infection, associated with Neutropenia in patients of chronic hepatitis C during interferon and ribavirin therapy. Conclusion: Our study concluded that the prevalence of Neutropenia in chronic hepatitis C virus infection patients 23.8 % during interferon and ribavirin therapy but it is not usually associated with infection. Recommendations: Neutropenia is a complicated process that requires expert guidance from a medical provider.

  15. Electroporation of proviral RCAS DNA alters gene expression in the embryonic chick hindbrain.

    Science.gov (United States)

    Hermann, Petra M; Logan, C Cairine

    2003-11-01

    Gene transfer by means of electroporation is an effective method for delivering DNA into cells. Expression vectors encoding green fluorescent protein (GFP) are routinely used as a control for this technique and are also regularly used to indirectly or directly monitor the expression of introduced transgenes. However, recent studies suggest that GFP may have nonspecific and/or cytotoxic side effects. In this study, we investigated the effects of enhanced GFP (EGFP) expression delivered by means of electroporation of proviral RCASBP(B)-EGFP DNA on gene expression in the hindbrain of chick embryos. We examined, via whole-mount in situ hybridization, the expression of a number of transcription factors. We found that Tlx-1 was ectopically expressed following electroporation of proviral RCASBP(B)-EGFP DNA. In contrast, the number of cells expressing Tlx-3, Phox2a, and Phox2b were reduced. Intriguingly, these effects could be mimicked by electroporation of wild-type proviral RCASBP(B) DNA (i.e., lacking the GFP insert). However, neither delivery of the EGFP transgene by means of viral infection nor electroporation alone yielded aberrant expression patterns. Together our data indicate that alterations of gene expression patterns are not directly due to the expression of EGFP but instead reflect a confounding effect of electroporating proviral DNA.

  16. CEREBRITIS AND NEUTROPENIA IN A CHILD WITH ANA NEGATIVE LUPUS

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    J. Akhoondian

    2009-04-01

    Full Text Available ObjectiveSystemic lupus erythematosus (SLE, an autoimmune systemic disease with unknown etiology, affects virtually every part of the body; involvement of the central nervous system (CNS is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE patients and is the least understood aspect of the disease. neutropenia is very uncommon in childhood lupus. True negative anti nuclear antibody (ANA tests in patients with lupus are now very rare. The patient reported here was a 12-year-old girl with ANA negative lupus cerebritis who presented with left hemiparesia after a generalized seizure, with neutropenia observed during its course.Key words:lupus cerebritis, neutropenia, ANA negative lupus, children

  17. 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...

  18. Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update.

    Science.gov (United States)

    Villafuerte-Gutierrez, Paola; Villalon, Lucia; Losa, Juan E; Henriquez-Camacho, Cesar

    2014-01-01

    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.

  19. Clinical manifestations and outcomes of pediatric chronic neutropenia

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    Chuan Wan

    2012-04-01

    Conclusion: It is difficult and risky to draw any conclusion from such a small-scale study; however, we believe that promptly diagnosing underlying diseases and administering appropriate disease-oriented therapy would be crucial for the treatment of patients with chronic neutropenia, particularly with regard to CNSs.

  20. 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.

  1. Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription.

    Science.gov (United States)

    Qi, Shiqian; Li, Zichong; Schulze-Gahmen, Ursula; Stjepanovic, Goran; Zhou, Qiang; Hurley, James H

    2017-01-30

    The intrinsically disordered scaffold proteins AFF1/4 and the transcription elongation factors ELL1/2 are core components of the super elongation complex required for HIV-1 proviral transcription. Here we report the 2.0-Å resolution crystal structure of the human ELL2 C-terminal domain bound to its 50-residue binding site on AFF4, the ELLBow. The ELL2 domain has the same arch-shaped fold as the tight junction protein occludin. The ELLBow consists of an N-terminal helix followed by an extended hairpin that we refer to as the elbow joint, and occupies most of the concave surface of ELL2. This surface is important for the ability of ELL2 to promote HIV-1 Tat-mediated proviral transcription. The AFF4-ELL2 interface is imperfectly packed, leaving a cavity suggestive of a potential binding site for transcription-promoting small molecules.

  2. Epigenetic analysis of HIV-1 proviral genomes from infected individuals: Predominance of unmethylated CpG’s

    Science.gov (United States)

    Weber, Stefanie; Weiser, Barbara; Kemal, Kimdar S.; Burger, Harold; Ramirez, Christina M.; Korn, Klaus; Anastos, Kathryn; Kaul, Rupert; Kovacs, Colin; Doerfler, Walter

    2014-01-01

    Efforts to cure HIV-1 infections aim at eliminating proviral DNA. Integrated DNA from various viruses often becomes methylated de novo and transcriptionally inactivated. We therefore investigated CpG methylation profiles of 55 of 94 CpG’s (58.5%) in HIV-1 proviral genomes including ten CpG’s in each LTR and additional CpG’s in portions of gag, env, nef, rev, and tat genes. We analyzed 33 DNA samples from PBMC’s of 23 subjects representing a broad spectrum of HIV-1 disease. In 22 of 23 HIV-1-infected individuals, there were only unmethylated CpG’s regardless of infection status. In one long term nonprogressor, however, methylation of proviral DNA varied between 0 and 75% over an 11-year period although the CD4+ counts remained stable. Hence levels of proviral DNA methylation can fluctuate. The preponderance of unmethylated CpG’s suggests that proviral methylation is not a major factor in regulating HIV-1 proviral activity in PBMC’s. Unmethylated CpG’s may play a role in HIV-1 immunopathogenesis. PMID:24418551

  3. Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica).

    Science.gov (United States)

    Fioredda, Francesca; Calvillo, Michaela; Bonanomi, Sonia; Coliva, Tiziana; Tucci, Fabio; Farruggia, Piero; Pillon, Marta; Martire, Baldassarre; Ghilardi, Roberta; Ramenghi, Ugo; Renga, Daniela; Menna, Giuseppe; Barone, Angelica; Lanciotti, Marina; Dufour, Carlo

    2011-07-15

    Congenital and acquired neutropenia are rare disorders whose frequency in pediatric age may be underestimated due to remarkable differences in definition or misdiagnosed because of the lack of common practice guidelines. Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document which includes a classification of neutropenia and a comprehensive guideline on diagnosis of neutropenia. Copyright © 2011 Wiley-Liss, Inc.

  4. Hijos de madre toxémica: neutropenia y trombocitopenia.

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    Fabio D. Pereira

    2009-09-01

    Full Text Available La enfermedad hipertensiva del embarazo, particulamente la toxemia, se ha asociado con neutropenia y trombocitopenia en el recién nacido. En un estudio previo se había encontrado muy poca asociación con estos eventos. En la presente investigación, mediante métodos hematológicos, se estudiaron 70 hijos de madres con toxemia severa los días 1 y 5 de vida; sólo 44 niños asistieron a control el día 5. Se encontró que la trombocitopenia en la práctica era inexistente y que la neutropenia fue más escasa de lo informado en la literatura.

  5. Hijos de madre toxémica: neutropenia y trombocitopenia.

    OpenAIRE

    Fabio D. Pereira; Reynaldo Miranda; Carmen de Rosero; Jorge Estupiñán

    2009-01-01

    La enfermedad hipertensiva del embarazo, particulamente la toxemia, se ha asociado con neutropenia y trombocitopenia en el recién nacido. En un estudio previo se había encontrado muy poca asociación con estos eventos. En la presente investigación, mediante métodos hematológicos, se estudiaron 70 hijos de madres con toxemia severa los días 1 y 5 de vida; sólo 44 niños asistieron a control el día 5. Se encontró que la trombocitopenia en la práctica era inexistente y que la neutropenia fue más e...

  6. 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.

  7. Primary immunodeficiencies appearing as combined lymphopenia, neutropenia, and monocytopenia.

    Science.gov (United States)

    Dotta, Laura; Badolato, Raffaele

    2014-10-01

    Recurrent or prolonged severe infections associated to panleukopenia strongly suggest primary immune disorders. In recent years, new immunodeficiency syndromes turned up: besides the importance of continuous clinical characterization throughout added reports, the phenotype can easily lead to diagnosis of known rare entities. Our purpose is to review main emerging genetic syndromes featuring lymphopenia combined to neutropenia and/or monocytopenia in order to facilitate diagnosis of rare primary immune deficiencies.

  8. 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

  9. Distinctive Drug-resistant Mutation Profiles and Interpretations of HIV-1 Proviral DNA Revealed by Deep Sequencing in Reverse Transcriptase

    Institute of Scientific and Technical Information of China (English)

    YIN Qian Qian; SHAO Yi Ming; MA Li Ying; LI Zhen Peng; ZHAO Hai; PAN Dong; WANG Yan; XU Wei Si; XING Hui; FENGYi; JIANG Shi Bo

    2016-01-01

    ObjectiveTo investigate distinctive features in drug-resistant mutations(DRMs) and interpretations for reverse transcriptase inhibitors (RTIs) between proviral DNA and paired viral RNA in HIV-1-infected patients. MethodsForty-three HIV-1-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA. ResultsCompared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher’s exact test,P ConclusionCompared with viral RNA, the distinctive information of DRMsand drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Febrile neutropenia in children with acute lymphoblastic leukemia: single center experience

    Science.gov (United States)

    Özdemir, Nihal; Tüysüz, Gülen; Çelik, Nigar; Yantri, Leman; Erginöz, Ethem; Apak, Hilmi; Özkan, Alp; Yıldız, İnci; Celkan, Tiraje

    2016-01-01

    Aim: An important life-threatening complication of intensive chemotherapy administered in children with leukemia is febrile neutropenia. The objective of this study was to evaluate the clinical features and consequences of febrile neutropenia attacks in children who were treated for acute lymphoblastic leukemia. Material and Methods: Nighty-six children who received chemotherapy for acute lymphoblastic leukemia in our center between January 1995 and December 2010 were included in the study. The data related to demographic characteristics, treatment features, relapse and febrile neutropenia incidences, risk factors, culture results and prognosis were retrospectively evaluated from the patients’ files. Results: A total of two hundred-ninety nine febrile neutropenia attacks observed in the patients during initial treatment and relapse treatment were evaluated. When the incidence of febrile neutropenia was evaluated by years, it was observed that the patients treated after year 2000 had statistically significantly more febrile neutopenia attacks compared to the patients treated before year 2000. When the incidences of febrile neutropenia during initial treatment and during relapse treatment were compared, it was observed that more febrile neutropenia attacks occured during relapse treatment. Fifty-nine percent of all febrile neutropenia attacks were fever of unknown origin. Eighty microorganisms grew in cultures during febrile neutropenia throughout treatment in 75 patients; 86% were bacterial infections (50% gram positive and 50% gram negative), 8% were viral infections and 6% were fungal infections. Coagulase negative staphylococcus (n=17) was the most frequent gram positive pathogen; E. Coli (n=17) was the most commonly grown gram negative pathogen. Conclusions: In this study, it was found that an increase in the incidence of febrile neutropenia occured in years. Increments in treatment intensities increase the incidence of febrile neutropenia while improving

  12. 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.

  13. 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) 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...... for severe neutropenia corresponded to absolute risks of haematological malignancies and mortality from any cause of 40% and >50%, respectively. CONCLUSIONS: Neutropenia is an ominous sign necessitating careful follow-up. The risk estimates presented here support focusing attention to viral diseases...

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

    Science.gov (United States)

    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.

  15. 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......, was collected from PBMCs isolated from 57 patients. Both "consensus" (57 patients) and clonal (7 patients) sequences were obtained from five time points spanning a 24-month period. The main computational strategy was to use maximum likelihood to fit a set of alternative phylogenetic models to the clonal data...

  16. 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......, and then determine the support for models that imply evolution between time points. Model fit and model-selection uncertainty was assessed using the Akaike information criterion (AIC) and Akaike weights. The consensus sequence data was also analyzed using a range of phylogenetic techniques to determine whether...

  17. 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......, and then determine the support for models that imply evolution between time points. Model fit and model-selection uncertainty was assessed using the Akaike information criterion (AIC) and Akaike weights. The consensus sequence data was also analyzed using a range of phylogenetic techniques to determine whether...

  18. 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......, was collected from PBMCs isolated from 57 patients. Both "consensus" (57 patients) and clonal (7 patients) sequences were obtained from five time points spanning a 24-month period. The main computational strategy was to use maximum likelihood to fit a set of alternative phylogenetic models to the clonal data...

  19. Prevention of neutropenia during chemotherapy by prolonged myelostimulatory preparations

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2015-01-01

    Full Text Available Neutropenia and associated infection, resulting in hospitalization and use of antibiotics, has a negative effect on chemotherapy. The need to reduce the dose of cytotoxic drugs during neutropenia leads to lower survival rates in patients with hematological malignancies and solid tumors. Since 1990s myelocytokines – proteins that accelerate neutrophil recovery after cytostatic chemotherapy and reduce the risk of infection – is widely used in the clinical practice. The use of these drugs can support the planned dose intensity of chemotherapy and improves the treatment efficacy. The disadvantages of these drugs include the need for their daily parenteral administration for 7–10 days. The development of long-acting forms (pegfilgrastim and lipegfilgrastim has solved this problem. Self-regulating clearance of prolonged forms allowed to use them only once on a chemotherapy course. Results of pegfilgrastim administration in 25 patients with hematological malignancies (8 patients and solid tumors (17 patients included in our analysis. Prolonged preparation showed high efficacy in secondary prophylaxis of neutropenia and infection decreasing the risk by 82 %. The single administration of pegfilgrastim allowed safe dose intensity chemotherapy with shorter intervals between courses (AC-14 in 8 patients with breast cancer. Tolerability was good; cases of hyperleukocytosis have notbeen reported. Recently in Europe and the Russian Federation a new drug from prolonged myelocytokine group – lipegfilgrastim – has been registered. The results of two controlled trials in patients with breast cancer (n = 410 receiving doxorubicin/docetaxel showed high efficacy of the drug as the pegfilgrastim with comparable tolerability.

  20. Identification and Clinical Characterization of Children With Benign Ethnic Neutropenia.

    Science.gov (United States)

    Ortiz, Michael V; Meier, Emily R; Hsieh, Matthew M

    2016-04-01

    Benign ethnic neutropenia (BEN) is an asymptomatic condition reported in adults of African and Middle Eastern descent. The clinical description in children is currently lacking. In our urban outpatient pediatric hematology clinic, the median neutrophil count of children with BEN was lower than previous reports in adults at 893×10 cells/L, but increased with older age. There was an equal male to female ratio and 24% of our BEN children reported ethnicities other than African or Middle Eastern. Children with BEN had a clinical course comparable with other healthy children including otherwise normal blood counts, except for mild anemia.

  1. Full-Arch Rehabilitation of a Patient With Cyclic Neutropenia.

    Science.gov (United States)

    Block, Michael S; Brindis, Marco; Block, Celeste A; Berron, Joaquin M

    2015-09-01

    The purpose of this report is to discuss the treatment of a patient with cyclic neutropenia. This patient presented with flared teeth, thin alveolar bone, and mobile teeth. A staged approach was used to remove her teeth, augment the bone, use immediate fixed provisional to determine the type of final prostheses, and ultimately to use cone-shaped overdenture attachments to retain her final prostheses. The result was rehabilitation of the patient with esthetic full-arch fixed-removable dentures with no adverse sequelae in this patient with this systemic disease.

  2. Sequence analysis for the complete proviral genome of reticuloendotheliosis virus Chinese strain HA9901

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The genomic DNA extracted from chicken embryo fibroblast (CEF) infected with a Chinese field isolate HA9901 of reticuloendotheliosis virus (REV) was used as the template to amplify the REV proviral genomic cDNA by PCR with 6 pairs of primers according to published sequences. Six overlapping fragments were amplified, cloned into the TA vector and sequenced, including a fragment which was amplified from the circular proviral cDNA and covering both 5'- and 3'-ends. The complete sequence of the whole genome was established and analyzed with a DNAstar software. Comparisons of the sequence with two other strains demonstrated that the genomes of REV were relatively conservative, the homogenecity for all genes or LTR fragments of the 3 strains was over 92%, no matter whether they were isolated from different species and regions in different years. But, the homology of Chinese strain HA9901 to a fowl pox virus-associated strain from Chickens was higher than that to strain SNV isolated from ducks.

  3. Neutropenia Due to Very Long Time Propylthiouracil Usage in Toxic Multinodular Goiter

    Directory of Open Access Journals (Sweden)

    Ahmet Kaya

    2016-03-01

    Full Text Available Thyrotoxicosis affects hematopoiesis in several ways and thioamides may cause myelosuppression. We report a case of febrile neutropenia in a patient with hyperthyroidism who was using propylthiouracil for nearly 20 years for the treatment of toxic multinodular goitre. After surgery, the patient was euthyroid and neutropenia resolved. Postoperative pathology was evaluated as micropapillary thyroid carcinoma.

  4. 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

    2000-01-01

    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

  5. The use of FDG-PET/CT in patients with febrile neutropenia

    NARCIS (Netherlands)

    Vos, F.J.; Bleeker-Rovers, C.P.; Oyen, W.J.G.

    2013-01-01

    Fever is a frequent complication of neutropenia induced by the treatment of various neoplasms. This is referred to as febrile neutropenia, which is considered to be a sign of a potentially life-threatening infectious complication until proven otherwise. However, most infectious foci do not have loca

  6. Neutropenia associated with X-linked Agammaglobulinemia in an Iranian referral center.

    Science.gov (United States)

    Aghamohammadi, Asghar; Cheraghi, Taher; Rezaei, Nima; Kanegane, Hirokazu; Abdollahzede, Sina; Talaei-Khoei, Mojtaba; Heidari, Golnaz; Zandieh, Fariborz; Moin, Mostafa; Miyawaki, Toshio

    2009-03-01

    X-linked Agammaglobulinemia (XLA) is a hereditary immunodeficiency, characterized by an early onset of recurrent bacterial infections, hypogammaglobulinemia and markedly reduced B lymphocytes number. In order to determine the association of neutropenia among Iranian patients with XLA, hospital records of 30 patients with confirmed XLA in Children Medical Center Hospital, were reviewed. Eight out of 30 XLA patients (26.7%) developed neutropenia during the course of the disease. In two patients, episodes of neutropenia were identified before or at the time of diagnosis of XLA. Other six patients whom were not visited regularly and did not receive periodical immunoglobulin replacement therapy experienced neutropenia after diagnosis of XLA. Neutropenia in XLA is mainly associated with infection and is resolved with intravenous immunoglobulin replacement and antibiotics therapy.

  7. Generation of poikiloderma with neutropenia (PN) induced pluripotent stem cells (iPSCs).

    Science.gov (United States)

    Mills, Jason A; Hudock, Kristin M; Sullivan, Spencer K; Herrera, Pamela; Sullivan, Lisa M; Gadue, Paul; French, Deborah L

    2015-11-01

    Poikiloderma with neutropenia (PN, Clericuzio-type poikiloderma with neutropenia) is a rare autosomal recessive disorder caused by biallelic mutations in the USB1 gene (Alias C16orf57 and MPN1). To date, there have been only 37 reported cases worldwide of this disorder that presents with neutropenia, early onset poikiloderma, respiratory infections, palmo-plantar hyperkeratosis, and skeletal defects. Here we described the generation of human induced pluripotent stem cell lines (PN1 and PN2) from the peripheral blood of a 1-year-old patient using the dox-inducible STEMCCA vector. This patient presented with bacteremia, pneumonia, and neutropenia. Analysis of bone marrow demonstrated normal cellularity with trilineage hematopoiesis and neutropenia.

  8. Generation of poikiloderma with neutropenia (PN induced pluripotent stem cells (iPSCs

    Directory of Open Access Journals (Sweden)

    Jason A. Mills

    2015-11-01

    Full Text Available Poikiloderma with neutropenia (PN, Clericuzio-type poikiloderma with neutropenia is a rare autosomal recessive disorder caused by biallelic mutations in the USB1 gene (Alias C16orf57 and MPN1. To date, there have been only 37 reported cases worldwide of this disorder that presents with neutropenia, early onset poikiloderma, respiratory infections, palmo-plantar hyperkeratosis, and skeletal defects. Here we described the generation of human induced pluripotent stem cell lines (PN1 and PN2 from the peripheral blood of a 1-year-old patient using the dox-inducible STEMCCA vector. This patient presented with bacteremia, pneumonia, and neutropenia. Analysis of bone marrow demonstrated normal cellularity with trilineage hematopoiesis and neutropenia.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Detection of Bovine Leukaemia Virus Antibodies and Proviral DNA in Colostrum Replacers.

    Science.gov (United States)

    Choudhury, B; Finnegan, C; Phillips, A; Horigan, M; Pollard, T; Steinbach, F

    2015-10-01

    Great Britain has been bovine leukaemia virus (BLV) disease free since 1999. We recently reported three separate incidents of BLV seropositivity on farms with home-reared cattle due to the use of colostrum replacer rather than infection with BLV (Emerg. Infect. Dis., 19, 2013, 1027). These cases were all linked via the use of the same brand of colostrum replacer. Here, we investigate further by examining multiple brands of colostrum replacer for proviral DNA and BLV antibodies. BLV antibodies were detected in 7 of the colostrum replacers tested, with PCR concurring in two cases. Thus, the use of these BLV antibody-positive colostrum replacers may also lead to false-positive serological diagnostics.

  11. Role of biosimilars in neutropenia prevention in cancer patients

    Directory of Open Access Journals (Sweden)

    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

  12. Neutropenia, fever, and infection in children with acute lymphocytic leukemia.

    Science.gov (United States)

    Wolk, J A; Stuart, M J; Stockman, J A; Oski, F A

    1977-02-01

    In an attempt to determine the relationship between neutropenia (absolute granulocyte count less than 1,000/cu mm), infection, and disease status, 20 patients with acute lymphoblastic leukemia were observed for a total of 34 patient-years. Febrile episodes occurred with much greater frequency in patients during the course of treatment induction (0.9/mo), or while in relapse (2.46/mo) than while in remission (0.19/mo). A cause for fever was identified much more frequently in patients in remission, both when neutropenic and nonneutropenic. When absolute granulocyte counts fell below 200/cu mm, a cause for fever was generally identified regardless of disease status. We propose that the majority of febrile episodes in patients at the time of induction of treatment or in relapse with neutrophil counts of more than 200/cu mm are caused by the disease process rather than secondary to a diagnosable infection.

  13. The Importance of Serum Cytokine Levels in Febrile Neutropenia

    Directory of Open Access Journals (Sweden)

    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

  14. Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle.

    Science.gov (United States)

    Li, Xiaoyan; Luthra, Rakesh; Morrow, Phuong K; Fisher, Maxine D; Reiner, Maureen; Barron, Richard L; Langeberg, Wendy J

    2016-10-01

    Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle. This case-control study used administrative claims from adult patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who received chemotherapy between 2007 and 2012. Each patient who developed febrile neutropenia (case) was matched with up to four patients without febrile neutropenia (controls) by cancer type, metastasis, chemotherapy regimen, age group, and sex. For each comorbidity (identified in the year before chemotherapy began), the adjusted odds ratio (aOR) for febrile neutropenia by cancer type was evaluated using conditional logistic regression models adjusted for potential confounding factors. Of 31,331 eligible patients, 672 developed febrile neutropenia in the first chemotherapy cycle. A total of 3312 febrile neutropenia cases and matched controls were analyzed. Across tumor types, comorbidity prevalence was higher in patients who developed febrile neutropenia than in those without febrile neutropenia. Among patients with breast cancer, osteoarthritis was more prevalent in patients with febrile neutropenia (aOR, 1.85; 95% CI, 1.07 to 3.18). Among patients with non-Hodgkin lymphoma, renal disease was more prevalent in patients with febrile neutropenia (aOR, 2.25; 95% CI, 1.23 to 4.11). Patients who developed febrile neutropenia in the first chemotherapy cycle presented with comorbidities more often than otherwise similar patients who did not develop febrile neutropenia. These findings warrant further investigation and support the inclusion of comorbidities into febrile neutropenia risk models.

  15. Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions.

    Science.gov (United States)

    Kanagasegar, Sivalingam; Cimaz, Rolando; Kurien, Biji T; Brucato, Antonio; Scofield, R Hal

    2002-01-01

    Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.

  16. 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.

  17. XLA-associated neutropenia treatment: a case report and review of the literature.

    Science.gov (United States)

    Jacobs, Zachary David; Guajardo, Jesus Ramon; Anderson, Katherine Marie

    2008-08-01

    X-linked agammaglobulinemia (XLA) is a primary B-cell deficiency syndrome with an incidence of 5 to 10 cases per million. The current treatment approach includes intravenous immunoglobulin and aggressive antibiotic regimens for infections. Besides recurrent infections, XLA patients may present with other manifestations, such as alopecia, enteropathy, amyloidosis, and neutropenia. Neutropenia, which has been shown in up to 25% of affected patients, might also contribute to the degree of severity of bacterial infections that have been reported in these cases. Here we present our experience with the granulocyte colony-stimulant factor, filgrastim (Neupogen), in the treatment of neutropenia in a 14-month-old child with XLA.

  18. Recurrent febrile neutropenia and thrombocytopenia in a chronic cocaine user: a case of levamisole induced complications.

    Science.gov (United States)

    Martinez, Eduardo; Alvi, Raza; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda

    2015-01-01

    Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.

  19. Recurrent Febrile Neutropenia and Thrombocytopenia in a Chronic Cocaine User: A Case of Levamisole Induced Complications

    Directory of Open Access Journals (Sweden)

    Eduardo Martinez

    2015-01-01

    Full Text Available Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Patterns of neutropenia and risk factors for febrile neutropenia of diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

    Science.gov (United States)

    Choi, Yong Won; Jeong, Seong Hyun; Ahn, Mi Sun; Lee, Hyun Woo; Kang, Seok Yun; Choi, Jin-Hyuk; Jin, U Ram; Park, Joon Seong

    2014-11-01

    Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age ≥65 yr, comorbidities, bone marrow involvement, and baseline serum albumin ≤3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.

  2. 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......, and then determine the support for models that imply evolution between time points. Model fit and model-selection uncertainty was assessed using the Akaike information criterion (AIC) and Akaike weights. The consensus sequence data was also analyzed using a range of phylogenetic techniques to determine whether...... 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...

  3. Fever and neutropenia in cancer patients : the diagnostic role of cytokines in risk assessment strategies

    NARCIS (Netherlands)

    Nijhuis, CSMO; Daenen, SMGJ; Vellenga, E; van der Graaf, WTA; Gietema, JA; Groen, HJM; Kamps, WA; de Bont, ESJM

    2002-01-01

    Cancer patients treated with chemotherapy are susceptible to bacterial infections. Therefore, all neutropenic cancer patients with fever receive standard therapy consisting of broad-spectrum antibiotics and hospitalization. However, febrile neutropenia in cancer patients is often due to other causes

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Moxifloxacin Compared With Ciprofloxacin/Amoxicillin in Treating Fever and Neutropenia in Patients With Cancer

    Science.gov (United States)

    2012-09-20

    Chronic Myeloproliferative Disorders; Fever, Sweats, and Hot Flashes; Infection; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neutropenia; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  6. Fever and neutropenia in cancer patients : the diagnostic role of cytokines in risk assessment strategies

    NARCIS (Netherlands)

    Nijhuis, CSMO; Daenen, SMGJ; Vellenga, E; van der Graaf, WTA; Gietema, JA; Groen, HJM; Kamps, WA; de Bont, ESJM

    2002-01-01

    Cancer patients treated with chemotherapy are susceptible to bacterial infections. Therefore, all neutropenic cancer patients with fever receive standard therapy consisting of broad-spectrum antibiotics and hospitalization. However, febrile neutropenia in cancer patients is often due to other causes

  7. Evaluation of ior ® Leukocim efficacy on patients with Neutropenia.

    Directory of Open Access Journals (Sweden)

    Ana María Ramos Cedeño

    2007-12-01

    Full Text Available Bakground: Neutropenia and infections are the most restrictive side effects in chemotherapy application. The granulocytic colonies stimulating factor activates the neutrophils, shortens the neutropenic period and can be effective against the potential risk of infection. There is a need of studies for its commercialization to endorse their effectiveness and security. Objective: To evaluate the impact of the G-CSF in primary and secondary prevention and neutropenia episodes, in onco-haematological patients in Cienfuegos. Method: 95 neutropenic episodes were studied, picked up in clinical histories and data collection notebooks belonging to 47 patients treated in the University Hospital ¨Dr. Gustavo Aldereguía Lima¨ in Cienfuegos and happened during one year (2005-2006. It was analyzed: demographic data, absolute neutrophils count values, number of administered doses, treatment regime and possible treatment interruptions Results: 50, 5% received treatment in an ambulatory way. There was treatment interruption in 9 episodes, 9,5% and the mean dose number administered to obtain the recovery of neutrophils absolute count was 6,69. Conclusions: The product was effective, sine the decrease of neutropenic episodes could be verified, as the elevation of neutrophil values in approximately one week, what allowed a better pursuit of chemotherapy to patients of the studied series.AbstractTo demonstrate the effectiveness of Leukocim an open, phase IV clinical trial was designed, 39 patients from Cienfuegos were evaluated with 73 neutropenic episodes in primary or secondary prophylaxis or treatment, the demographic parameters behaved with an age 49.86 year old average, the predominant sex was the feminine 64.38%, 73.97% belonged to the white race, when the effectiveness was analyzed we obtained that 46.5% received the treatment in an ambulatory way, whereas 52.1% was hospitalized; one patient abandoned before beginning the treatment, the 12,3% of patients

  8. Complete Sequence of Proviral DNA of Equine Infectious Anemia Virus Strain L

    Institute of Scientific and Technical Information of China (English)

    LIU Hong-quan; WANG Liu; YANG Zhi-biao; KONG Xian-gang; TONG Guang-Zhi

    2002-01-01

    Equine infectious anemia virus strain L (EIAV-L) is the parental virulent virus of equine infectious anemia donkey leukocyte attenuated vaccine (DLA EIAV ). In this study, peripheral blood leukocytes(PBL) were collected from a horse infected with EIAV-L. The PBL DNAs were extracted. The EIAV-L proviral DNA was amplified in four parts covering the entire proviral genomic sequence by polymerase chain reaction (PCR). Each of the four parts was cloned into the plasmid pBluescript SK, and the recombinant plasmids were designated as p2.8, p2.4, p3.1, and p1.2 respectively. After identification with restriction digestion, the inserts within the four plasmids were sequenced. The complete nucleotide sequence of EIAV-L provirus was determined by analyzing each of the four parts and connecting them as a whole. The genome of EIAV-L is 8235 bp in length, and G + C content is 38%. The comparison analysis by the computer software DNASIS showed that the sequence of EIAV-L shares 98.4% and 96.9% identities with that of D-A EIAV and DLA EIAV respectively. The high homology between these strains showed that they were genetically related.The homology between EIAV-L and D-A EIAV is higher than that between EIAV-L and DLA EIAV, and this is consistent with the derivation progress of DLA EIAV. At both ends of EIAV-L provirus, there is an identical long terminal repeat (LTR) sequence of 316bp in length. The LTR consists of U3, R, and U5 regions. The genome of EIAV-L provirus has three long open reading frames(ORF) corresponding to gag, pol and env genes respectively. The gag gene is 1200bp and located at position 613-1912nt. The pol gene is 3402bp and located at position 1708-5109nt. There is a termination codon within the env dividing it into two parts,env1 of 699bp (position 5305-6003nt)and env2 of 1827bp (position 6073-7899nt). The provirus has three additional small ORFs: S1, S2 and S3 with sizes of 153bp (position 5113-5265nt), 204bp (position 5279-5482nt) and 402bp ( position 7245

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

    Directory of Open Access Journals (Sweden)

    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

  10. Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA.

    Science.gov (United States)

    Lorenzi, Julio C C; Cohen, Yehuda Z; Cohn, Lillian B; Kreider, Edward F; Barton, John P; Learn, Gerald H; Oliveira, Thiago; Lavine, Christy L; Horwitz, Joshua A; Settler, Allison; Jankovic, Mila; Seaman, Michael S; Chakraborty, Arup K; Hahn, Beatrice H; Caskey, Marina; Nussenzweig, Michel C

    2016-12-06

    HIV-1-infected individuals harbor a latent reservoir of infected CD4(+) T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses. Leukapheresis samples from four fully ART-suppressed, chronically infected individuals were assayed at two time points separated by a 4- to 6-mo interval. Overall, 54% of the viruses emerging from the latent reservoir showed gp160 env sequences that were identical to at least one other virus. Moreover, 43% of the env sequences from viruses emerging from the reservoir were part of identical groups at the two time points. Groups of identical expanded sequences made up 54% of proviral DNA, and, as might be expected, the sequences of replication-competent viruses in the active reservoir showed limited overlap with integrated proviral DNA, most of which is known to represent defective viruses. Finally, there was an inverse correlation between proviral DNA clone size and the probability of reactivation, suggesting that replication-competent viruses are less likely to be found among highly expanded provirus-containing cell clones.

  11. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study.

    Science.gov (United States)

    Ishikawa, Takashi; Sakamaki, Kentaro; Narui, Kazutaka; Kaise, Hiroshi; Tsugawa, Koichiro; Ichikawa, Yasushi; Mukai, Hirofumi

    2016-07-01

    With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests.

  12. Mucosal damage and neutropenia are required for Candida albicans dissemination.

    Directory of Open Access Journals (Sweden)

    Andrew Y Koh

    2008-02-01

    Full Text Available Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections.

  13. [Efficacy of Levofloxacin Hydrate in Febrile Neutropenia for Outpatient Chemotherapy].

    Science.gov (United States)

    Inagaki, Manato; Sato, Junya; Nihei, Satoru; Kashiwaba, Masahiro; Kudo, Kenzo

    2016-05-01

    Management of febrile neutropenia (FN) is important for the safety of patients undergoing outpatient chemotherapy. Oral antimicrobials are usually prescribed as the initial treatment for FN, and outpatients are instructed to begin medication prior to chemotherapy. However, the effectiveness and safety of the use of these oral antibiotics have not yet been established. In this study, we investigated the effectiveness and safety of levofloxacin hydrate (LVFX) for breast cancer patients with FN, and the factors associated with the onset of FN in 134 breast cancer patients who underwent chemotherapy including the anticancer drug anthracycline (total, 513 courses), in an outpatient chemotherapy department. The effectiveness and safety of LVFX were defined respectively as defervescence within 5 days, and the appearance of side effects such as diarrhea and rashes. Fever was observed in 89 (66%) of the 134 patients, and during 164 (32%) of 513 courses. Defervescence was observed with the LVFX medication in 149 (93%) of 160 courses. The primary side effect was the development of rashes, and only 2 (1%) of the 160 courses were discontinued. Onset of stomatitis during chemotherapy was observed as a factor of FN (odds ratio: 1.36, p<0.05). Our results suggest that the use of LVFX according to the patients' discretion might be an effective and safe option for the management of FN during outpatient chemotherapy.

  14. Neutropenia y fiebre en el paciente con cáncer Neutropenia and fever in the patient with cancer

    Directory of Open Access Journals (Sweden)

    A. Manterola

    2004-01-01

    Full Text Available La infección en el huésped inmunocomprometido supone una situación clínica de gravedad por su alta morbi-mortalidad y es una de las complicaciones más frecuentes del paciente con cáncer. En los pacientes tratados con quimioterapia, el riesgo de infección depende fundamentalmente de la duración e intensidad de la neutropenia. Es fundamental evaluar cuál es el patógeno involucrado con mayor probabilidad para iniciar el tratamiento, a priori, más adecuado, así como la situación clínica general del paciente, que nos obligará a realizar un tratamiento más o menos agresivo desde el inicio, teniendo en cuenta que es posible el manejo domiciliario en aquel grupo de pacientes considerado de "bajo riesgo" de complicaciones. Estas cuestiones las podremos conocer evaluando los antecedentes y la historia clínica del paciente, la exploración física y los datos de exploraciones de laboratorio y radiológicas. El inicio precoz de la antibioterapia de amplio espectro es crucial, y revisaremos en este capítulo, las recomendaciones terapéuticas más recientes.Infection in the immunocompromised host is a serious clinical situation due to its high morbi-mortality and is one of the most frequent complications in the patient with cancer. In patients treated with chemotherapy, the risk of infection basically depends on the duration and intensity of the neutropenia. It is essential to evaluate, the most probable pathogen involved to initiate, a priori, the most suitable treatment, and also to evaluate the general clinical situation of the patient, because from the very beginning the treatment is quite aggressive. Outpatient care is possible for patients at "low risk" of complications. By evaluating the antecedents and clinical history of the patient, through physical exploration and from the data of laboratory and radiological explorations these points can be acknowledged. The early start of broad spectrum antibiotherapy is crucial, and in this

  15. Proviral Silencing in Embryonic Cells Is Regulated by Yin Yang 1

    Directory of Open Access Journals (Sweden)

    Sharon Schlesinger

    2013-07-01

    Full Text Available Embryonic cells transcriptionally repress the expression of endogenous and exogenous retroelements. Trim28, a key player in this silencing, is known to act in a large DNA-bound complex, but the other components of the complex are not fully characterized. Here, we show that the zinc finger protein Yin Yang 1 (YY1 is one such component. YY1 binds to the long terminal repeat (LTR region of both exogenous and endogenous retroviruses (ERVs. Deletion of the YY1-binding site from the retroviral genome leads to a major loss of silencing in embryonic cells and a coordinated loss of repressive histone marks from the proviral chromatin. Depletion of YY1 protein results in marked upregulation of expression of exogenous viruses and of selected ERVs. Finally, we report an embryonic cell-specific interaction between YY1 and Trim28. Our results suggest a major role for YY1 in the silencing of both exogenous retroviruses and ERVs in embryonic cells.

  16. Existence of proviral porcine endogenous retrovirus in fresh and decellularised porcine tissues

    Directory of Open Access Journals (Sweden)

    Prabha S

    2008-01-01

    Full Text Available Purpose: Swine are expected to be utilized as xenograft donors for both whole organ and cellular transplantation. A major concern in using porcine organs for transplantation is the potential of transmission of porcine endogenous retrovirus (PERV. Tissue-engineered or decellularised heart valves have already been implanted in humans and have been marketed by certain companies after Food and Drug Administration (FDA approval. The aim of this study was to examine the existence of porcine endogenous retrovirus (PERV in fresh and decellularised porcine tissues. Methods: Porcine tissues (both fresh and decellularised were analysed using validated assays specific for PERV: polymerase chain reaction (PCR, reverse transcriptase polymerase chain reaction (RT-PCR. Results: PERV specific GAG sequences were found in the porcine heart tissue samples using PCR for DNA and RT- PCR for RNA. All tissue samples (both fresh and treated tissues like aortic valve, pulmonary valve and heart muscle showed the presence of PERV DNA. RT PCR for PERV was positive in all fresh tissues and was found to be negative in decellularised treated tissues. Conclusions: PCR is a rapid, specific test for the detection of PERV virus in xenografts. These findings have demonstrated that the presence of proviral DNA form of PERV in porcine tissues needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Microbiology and mortality of pediatric febrile neutropenia in El Salvador.

    Science.gov (United States)

    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.

  20. Management of autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus.

    Science.gov (United States)

    Newman, Kam A; Akhtari, Mojtaba

    2011-05-01

    Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. Neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose.

  1. HIV Excision Utilizing CRISPR/Cas9 Technology: Attacking the Proviral Quasispecies in Reservoirs to Achieve a Cure.

    Science.gov (United States)

    Dampier, Will; Nonnemacher, Michael R; Sullivan, Neil T; Jacobson, Jeffrey M; Wigdahl, Brian

    2014-10-17

    Recently several gene-editing technologies developed are being explored for their potential utility in providing new and unique treatments for HIV. One of these technologies is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)9 system. This system is being explored for its utility against host genes important to HIV infection, namely the HIV coreceptor CCR5, and for excision of the integrated genome from infected cells by targeting selected genes or genomic regions, especially the HIV-1 promoter or long terminal repeat (LTR). One of the major hurdles with the development of this technology for use in patients is defining the LTR sequence spectrum within the viral quasispecies present in the integrated virus and how that effects the number of guide RNAs (gRNAs) required to completely excise all proviral genomes. In this study, the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort was utilized to demonstrate that [1] the predominant sequence of the integrated proviral LTR within the PBMC compartment shows a decrease in the amount of variation per year regardless of the type of therapy; [2] predominant HIV-1 LTR sequence undergoes continued genetic change with respect to the predominant genotype in these cells for at least 6 years while on effective suppressive ART; [3] using next generation sequencing (NGS), to demonstrate that 4 of the 8 patient samples examined could have a complete gRNA regimen designed to target all known quasispecies; and [4] length of HAART therapy may reduce the number of gRNA required to eradicate provirus as shown by NGS and gRNA design for longitudinal samples of patient A0017 in the CARES cohort. Overall, these studies demonstrate the feasibility of addressing at least one of the major technological challenges of CRISPR/Cas9-mediated HIV-1 proviral genome eradication involving the effective targeting of all viral quasispecies in a given patient sample.

  2. Detection of HTLV-I proviral sequences in CD30-positive large cell cutaneous T-cell lymphomas.

    OpenAIRE

    Anagnostopoulos, I.; Hummel, M.; Kaudewitz, P.; Herbst, H; Braun-Falco, O.; Stein, H

    1990-01-01

    To investigate the possibility that cutaneous T-cell lymphomas of large cell type may be associated with human T-cell leukemia/lymphoma virus type I infection in nonendemic regions, tissue samples from six cases of large cell cutaneous T-cell lymphoma and four cases of small cell cutaneous T-cell lymphoma were screened for the presence of integrated proviral human T-cell leukemia/lymphoma virus type I DNA. Combined use of Southern blot hybridization and enzymatic DNA amplification revealed hu...

  3. Detección proviral de HTLV-1 mediante reacción en cadena de la polimerasa (PCR)

    OpenAIRE

    Sevilla, Carlos; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Alarcón, Jorge; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Huiza, Alina; D. A. Microbiología Médica, Facultad de Medicina, UNMSM; Centro de Biotecnología, Universidad Iberoamericana de Ciencias y Tecnología; Laboratorio Entomología Médica, Sección Parasitología, Instituto de Salud Pública; Laboratorio de Entomología Médica, Laboratorio de Referencia Regional, Gerencia Regional de Salud La Libertad; Dirección Ejecutiva de Salud Ambiental, Sub Región de Salud “Luciano Castillo Colonna”, DIRESA Piura.; Gutiérrez, César; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Ñavincopa, Marcos; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Cornejo, William; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Cáceres, Abraham; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Tejada, Abelardo; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Romaní, Franco; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Mori, Nicanor; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Wong, Paolo; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Huamán, Víctor; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Vásquez, Rubén; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Tejada, Romina; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Flores, Alitza; D.A. Microbiología Médica, Facultad de Medicina, UNMSM

    2013-01-01

    Objetivos: Detectar el genoma proviral de HTLV-1 mediante el desarrollo de reacción en cadena de la polimerasa (PCR). Diseño: Descriptivo. Institución: D.A. Microbiología Médica, Facultad de Medicina, UNMSM. Participantes: Personas con y sin sospecha de HTLV-I. Principales medidas de resultados: detección de HTLV-1 mediante PCR. Resultados: El 71,4% de los pacientes con sospecha clínica de HTLV-I fue reactivo por métodos Inmunológico. Elisa HTLV I-II Biokit detectó 5 casos reactivos (X=2,359 ...

  4. Detección proviral de HTLV-1 mediante reacción en cadena de la polimerasa (PCR)

    OpenAIRE

    Sevilla, Carlos; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Alarcón, Jorge; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Huiza, Alina; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Gutiérrez, César; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Ñavincopa, Marcos; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Cornejo, William; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Cáceres, Abraham; D. A. Microbiología Médica, Facultad de Medicina, UNMSM; Centro de Biotecnología, Universidad Iberoamericana de Ciencias y Tecnología; Laboratorio Entomología Médica, Sección Parasitología, Instituto de Salud Pública; Laboratorio de Entomología Médica, Laboratorio de Referencia Regional, Gerencia Regional de Salud La Libertad; Dirección Ejecutiva de Salud Ambiental, Sub Región de Salud “Luciano Castillo Colonna”, DIRESA Piura.; Tejada, Abelardo; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Romaní, Franco; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Mori, Nicanor; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Wong, Paolo; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Huamán, Víctor; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Vásquez, Rubén; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Tejada, Romina; D.A. Microbiología Médica, Facultad de Medicina, UNMSM; Flores, Alitza; D.A. Microbiología Médica, Facultad de Medicina, UNMSM

    2013-01-01

    Objetivos: Detectar el genoma proviral de HTLV-1 mediante el desarrollo de reacción en cadena de la polimerasa (PCR). Diseño: Descriptivo. Institución: D.A. Microbiología Médica, Facultad de Medicina, UNMSM. Participantes: Personas con y sin sospecha de HTLV-I. Principales medidas de resultados: detección de HTLV-1 mediante PCR. Resultados: El 71,4% de los pacientes con sospecha clínica de HTLV-I fue reactivo por métodos Inmunológico. Elisa HTLV I-II Biokit detectó 5 casos reactivos (X=2,359 ...

  5. [Serum lactate as a biomarker of severe sepsis in children with cancer, neutropenia and fever].

    Science.gov (United States)

    Pacheco-Rosas, Daniel Octavio; Huelgas-Plaza, Ana Celia; Miranda-Novales, María Guadalupe

    2014-01-01

    INTRODUCCIÓN: la neutropenia es una complicación frecuente secundaria a la quimioterapia en los pacientes con cáncer, en quienes la prevalencia de sepsis es de 12.9 a 17.4 % y la letalidad es de 16 %. El objetivo de este estudio fue determinar la utilidad del lactato como biomarcador de sepsis grave en niños con cáncer, fiebre y neutropenia. MÉTODOS: se realizó un estudio de prueba diagnóstica fase II. Se midieron los niveles del lactato al ingreso. Los episodios de neutropenia se clasificaron en tres grupos: I, con sepsis II, sin sepsis; III, pacientes neutropénicos sin fiebre (controles). Se calculó sensibilidad, especificidad, valores predictivos positivo y negativo e índices de verosimilitud. El estándar de oro fue el diagnóstico clínico de sepsis grave.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Critical appraisal of biosimilar filgrastim (Nivestim™ for febrile and chemotherapy-induced neutropenia

    Directory of Open Access Journals (Sweden)

    Waller CF

    2012-08-01

    Full Text Available Cornelius F WallerFreiburg University Medical Center, Department of Hematology/Oncology, Freiburg, GermanyAbstract: Recombinant granulocyte colony-stimulating factor (filgrastim stimulates the proliferation and differentiation of hematopoietic stem and progenitor cells committed to neutrophil and granulocyte lineages. Filgrastim has been used as an adjunct to chemotherapy for ameliorating neutropenia, one of the major side effects of chemotherapy in cancer patients. Its use has led to reduction of infections and hospital admissions for patients with cancer undergoing chemotherapy. In addition, filgrastim has multiple other indications in hematology and oncology. Following the European Union patent expiry of Neupogen® (filgrastim; Amgen Inc in 2006, a biosimilar filgrastim has been developed (Nivestim™; Hospira. In accordance with the requirements of the European Medicines Agency, Nivestim has been studied in a development program that included preclinical studies, two Phase I clinical trials, and one Phase III clinical study. Preclinical studies showed pharmacodynamic as well as pharmacokinetic bioequivalence with the original product, Neupogen. Two randomized, single-center, Phase I trials compared both the pharmacokinetic, pharmacodynamic, and safety profiles of Nivestim and Neupogen in healthy volunteers. In both studies, 90% confidence intervals for the primary endpoints were within the predefined range (0.80–1.25 necessary to demonstrate bioequivalence. Nivestim was well tolerated, with no additional safety concerns over Neupogen. Bioequivalence was demonstrated in a randomized, double-blind multicenter Phase III trial of 279 patients with breast cancer receiving myelosuppressive chemotherapy. The mean duration of severe neutropenia in cycle 1, the primary endpoint, was similar between Nivestim (1.6 days, n = 165 and Neupogen (1.3 days, n = 85, meeting predefined criteria for bioequivalence. Secondary endpoints supporting

  8. Levamisole-induced occlusive necrotising vasculitis in cocaine abusers: An unusual cause of skin necrosis and neutropenia

    Science.gov (United States)

    Belfonte, Cassius Diego; Shanmugam, Victoria Kate; Kieffer, Nicole; Coker, Shodeinde; Boucree, Suelyn; Kerr, Gail

    2013-01-01

    We present three cases describing the various skin manifestations of presumed levamisole-contaminated cocaine use. Antibody-mediated vasculitis and neutropenia were consistent findings in these cases and repeat exposure resulted in distinct dermatologic complications. This phenomenon of levamisole-induced vasculitis and neutropenia is being increasingly described and has characteristic wound manifestations that must be recognised and treated early. PMID:22716045

  9. 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 o

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

    Science.gov (United States)

    Boada Burutaran, Matilde; Guadagna, Regina; Grille, Sofia; Stevenazzi, Mariana; Guillermo, Cecilia; Diaz, Lilian

    2014-01-01

    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 isolated 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 (front-line 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. PMID:25638764

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    NARCIS (Netherlands)

    F. Dong (Fan); R.K. Brynes; N. Tidow; K. Welte (Karl); B. Löwenberg (Bob); I.P. Touw (Ivo)

    1995-01-01

    textabstractBACKGROUND. In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction

  13. 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.

  14. Is aripiprazole the only choice of treatment of the patients who developed anti-psychotic agents-induced leucopenia and neutropenia? A case report.

    Science.gov (United States)

    Yalcin, Demet Ozen; Goka, Erol; Aydemir, M Cigdem; Kisa, Cebrail

    2008-05-01

    Leucopenia and neutropenia could be side effects of anti-psychotic drugs, especially clozapine. However, there is evidence that other anti-psychotics can cause leucopenia and neutropenia. We present the clinical follow-up and treatment process of a patient, who had initially developed quetiapine and amisulpride related neutropenia, but not with aripiprazole.

  15. 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

  16. [Esophageal aspergillosis in a patient with acute myelogenous leukemia and febrile neutropenia].

    Science.gov (United States)

    Besa, Santiago; Kattan, Eduardo; Cid, Ximena; Claro, Juan C

    2014-04-01

    Aspergillosis usually compromises the respiratory system, but can also affect others. We report a 46 yo female with acute myeloid leukemia, developed febrile neutropenia and dysphagia. Endoscopy revealed esophageal cytomegalovirus-like ulcers, but biopsies showed Aspergillus spp. It's important to consider aspergillosis in the differential diagnosis of esophageal lesions in high-risk patients.

  17. Successful Management of Neutropenia in a Patient with CD40 Ligand Deficiency by Immunoglobulin Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Lida Atarod

    2007-03-01

    Full Text Available Hyper-IgM syndromes are characterized by profound reduction of serum IgG, IgA, and IgE levels with normal or increased concentrations of serum IgM. CD40 ligand deficiency is X-linked form of the disease, which results in a lack of immunoglobulin class switching from IgM to IgG in B cells. In addition to the recurrent infections, a number of patients suffer from neutropenia. There are some evidences indicating the effect of G-CSF in combination with intravenous immunoglobulin (IVIG in improvement of neutrophil counts, which has become the most common procedure to control neutropenia.In this report we present a 6 year-old patient of CD40 ligand deficiency, who suffered from chronic, severe neutropenia. Administration of IVIG was started for him when the diagnosis was made at the age of 1.5 years and he was on the regular IVIG therapy after that time untill now for a period of 4.5 years. IVIG and prophylactic antibiotic therapy, despite cessation of granulocyte colony-stimulating factor, injection after one month, corrected the severe neutropenic state of this patient. It seems that regular administration of sufficient doses of IVIG can be useful in the management of neutropenia in CD40 ligand deficiency, which results in better quality of life with decreasing occurrence of infection.

  18. G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence

    Institute of Scientific and Technical Information of China (English)

    Francesca Lodato; Francesco Azzaroli; Maria Rosa Tamè; Maria Di Girolamo; Federica Buonfiglioli; Natalia Mazzella; Paolo Cecinato; Enrico Roda; Giuseppe Mazzella

    2009-01-01

    AIM: To evaluate the efficacy of granulocyte colony stimulating factors (G-CSF) in liver transplanted patients with hepatitis C (HCV) recurrence and Pegylated-IFN α-2b induced neutropenia, and to evaluate the impact of G-CSF administration on virological response.METHODS: Sixty-eight patients undergoing antiviral treatment for post-liver transplantation (OLT) HCV recurrence were enrolled.All patients developing neutropenia received G-CSF.RESULTS: Twenty three (34%) received G-CSF.Mean neutrophil count at the onset of neutropenia was 700/mmc (range 400-750/mmc); after 1 mo of G-CSF it increased to 1210/mmc (range 300-5590/mmc) ( P < 0.0001).Three patients did not respond to G-CSF.Treatment duration was similar in neutropenic and non-neutropenic patients.No differences in the rate of discontinuation, infections or virological response were observed between the two groups.G-CSF was protective for the onset of de novo autoimmune hepatitis ( P < 0.003).CONCLUSION: G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasing neutrophil count, prolonging treatment and leading to sustained virological response (SVR) rates comparable to non-neutropenic patients.It prevents the occurrence of de novo autoimmune hepatitis.

  19. Interleukin 6 blockage-induced neutropenia in a patient with rheumatoid arthritis and resolved hepatitis B.

    Science.gov (United States)

    Chmielińska, Magdalena; Olesińska, Marzena; Felis-Giemza, Anna

    2015-01-01

    The authors present a case report of a 59-year-old woman with rheumatoid arthritis after documented recovery from hepatitis C (HCV) infection and with resolved HBV infection who has been undergoing successful tocilizumab treatment. The patient experienced moderate to severe neutropenia after consecutive tocilizumab administrations. However, no serious infections or HBV reactivation was recorded during that period.

  20. 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.

  1. 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.

  2. 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 hete

  3. The role of mannose-binding lectin (MBL) in paediatric oncology patients with febrile neutropenia

    NARCIS (Netherlands)

    F.N.J. Frakking; M.D. van de Wetering; N. Brouwer; K.M. Dolman; J. Geissler; B. Lemkes; H.N. Caron; T.W. Kuijpers

    2006-01-01

    Children with cancer often have fever during chemotherapy-induced neutropenia, but only some develop serious infectious complications. Mannose-binding lectin (MBL) deficiency might increase infection susceptibility in these children. MBL genotype and phenotype were prospectively determined in 110 pa

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia

    Science.gov (United States)

    2009-01-01

    Background Five cases of severe neutropenia (neutrophil counts < 0.5 per 109 cells/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. Methods Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. Results We compare cases of severe neutropenia associated with tainted cocaine (NATC) identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55%) were from Alberta; 19(45%) were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used); 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%). Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA). Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in Alberta Interpretation Our findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness of the

  6. Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia

    Directory of Open Access Journals (Sweden)

    Fan Shihe

    2009-11-01

    Full Text Available Abstract Background Five cases of severe neutropenia (neutrophil counts 9 cells/L associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. Methods Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. Results We compare cases of severe neutropenia associated with tainted cocaine (NATC identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55% were from Alberta; 19(45% were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used; 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%. Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA. Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in Alberta Interpretation Our findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness

  7. Single genome amplification of proviral HIV-1 DNA from dried blood spot specimens collected during early infant screening programs in Lusaka, Zambia.

    Science.gov (United States)

    Seu, Lillian; Mwape, Innocent; Guffey, M Bradford

    2014-07-01

    The ability to evaluate individual HIV-1 virions from the quasispecies of vertically infected infants was evaluated in a field setting at the Centre for Infectious Disease Research in Zambia. Infant heel-prick blood specimens were spotted onto dried blood spot (DBS) filter paper cards at government health clinics. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA detection by a commercial Amplicor HIV-1 PCR test (Roche, version 1.5). On samples that tested positive by commercial diagnostic assay, amplification of DNA was performed using an in-house assay of the 5' and 3' region of the HIV-1 genome. Additionally, fragments covering 1200 nucleotides within pol (full length protease and partial reverse transcriptase) and 1400 nucleotides within env (variable 1-variable 5 region) were further analyzed by single genome amplification (SGA). In summary, we have demonstrated an in-house assay for amplifying the 5' and 3' proviral HIV-1 DNA as well as pol and env proviral DNA fragments from DBS cards collected and analyzed entirely in Zambia. In conclusion, this study shows the feasibility of utilizing DBS cards to amplify the whole proviral HIV-1 genome as well as perform SGA on key HIV-1 genes.

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

    Science.gov (United States)

    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

  9. Mutations in the Primer Grip of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Impair Proviral DNA Synthesis and Virion Maturation

    Science.gov (United States)

    Yu, Qiang; Ottmann, Michele; Pechoux, Christine; Le Grice, Stuart; Darlix, Jean-Luc

    1998-01-01

    This report describes the effects of mutating highly conserved residues in the primer grip domain of human immunodeficiency virus type 1 reverse transcriptase (RT) on virus formation and infectivity. Among a series of RT mutant viruses, three (M230A, L234D, and W239A) were found to be noninfectious or very poorly infectious. Our data indicate that these mutations in RT caused severe defects in proviral DNA synthesis. Interestingly, assembly and maturation of mutant virus M230A were similar to those of the wild type, while mutants L234D and W239A showed impaired maturation. The immature morphology of RT mutants L234D and W239A is due at least in part to premature cleavage of the gag-pol precursor, prior to virion budding, indicating that intracellular stability of Pr160gag-pol is of key importance during virus assembly. PMID:9696874

  10. Development of a nested PCR assay to detect equine infectious anemia proviral DNA from peripheral blood of naturally infected horses.

    Science.gov (United States)

    Dong, Jian-Bao; Zhu, Wei; Cook, Frank R; Goto, Yoshitaka; Horii, Yoichiro; Haga, Takeshi

    2012-11-01

    Equine infectious anemia (EIA) has posed a major challenge and caused significant losses to the equine industry worldwide. PCR detection methods have considerable potential as an adjunct to conventional serological diagnostic techniques. However, most published PCR methods, including that recommended by the OIE, were designed using laboratory-adapted virus strains and do not function with field isolates of EIA virus (EIAV). In the present study, a nested PCR assay for detection of EIAV proviral DNA in peripheral blood cells of naturally infected horses was developed. Primer sets were designed based on conserved 5' regions of the viral genome extending from the LTR to the tat gene. Preliminary studies demonstrated that the method has a detection limit of 10 genomic copies and, when applied to a naturally EIAV-infected feral horse population, shows 100 % correlation with conventional serological diagnostic techniques. This assay provides a powerful new tool in the control of EIAV.

  11. Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia.

    Science.gov (United States)

    Nagy, K; Marschalkó, Márta; Kemény, B; Horváth, A

    2005-01-01

    The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

  12. Proviral genomic sequence analysis of Chinese donkey leukocyte attenuated equine infectious anemia virus vaccine and its parental virus strain Liaoning

    Institute of Scientific and Technical Information of China (English)

    王柳; 童光志; 刘红全; 杨志彪; 仇华吉; 孔宪刚; 王玫

    2002-01-01

    Proviral DNA was extracted from donkey leukocyte infected with Chinese donkey leukocyte attenuated equine infectious anemia virus(DLA-EIAV), and peripheral blood lymphocytes(PBL) from a horse infected with the virulent EIAV strain Liaoning(EIAV L). The entire proviral DNA from both viruses was cloned and sequenced. The lengths of complete genomic sequences of DLA-EIAV and EIAV L provirus were 8266 bp and 8235 bp, respectively. Sequence comparison indicated that DLA-EIAV shares 97.0% and 97.5% in sequence homology with EIAV L and donkey-adapted EIAV(DA-EIAV), respectively. Lots of variations occurred in long terminal repeat(LTR, consisting of U3, R, U5), ORF S2, and env regions between DLA-EIAV and EIAV L. The nucleotide sequence differences of the two viruses in U3, R, U5, ORF S2, and env are 13.2%, 7.5%, 5.1%, 3.9%, and 2.7%, respectively, and predicted amino acid sequence differences in env and S2 coding regions are 4.4% and 8.8%, respectively. Six conserved regions are characterized in Gp90. There is a cis-activating GATA motif in ENH of DLA-EIAV and EIAV L. Two N-linked glycosylation sites disappeared in DLA-EIAV Gp90 in comparison with that of EIAV L. A bHLH transcription factor binding consensus sequence was found in LTR of DLA-EIAV but not in EIAV L. Furthermore, there is a mutation in the stem of DLA-EIAV TAR resulting in formation of a uridine tuber. Further study is needed to uncover the relationship between sequence changes and their biological functions of DLA-EIAV and L.

  13. Evolution of Specific Antibodies and Proviral DNA in Milk of Small Ruminants Infected by Small Ruminant Lentivirus

    Directory of Open Access Journals (Sweden)

    Ana Domenech

    2013-10-01

    Full Text Available The diagnosis of Small Ruminant Lentivirus (SRLV is based on clinical signs, pathological lesions and laboratory testing. No standard reference test for the diagnosis of maedi visna has been validated up to the present, and it is puzzling that tests which detect antibodies against the virus and tests which detect the proviral genome may render opposite results. The aim of this study was to evaluate the presence in milk throughout a lactation period of specific antibodies by ELISA and of SRLV proviral DNA by a PCR of the highly conserved pol region. A six-month study was conducted with the milk of 28 ewes and 31 goats intensively reared. The percentage of animals with antibodies against SRLV increased throughout the study period. Seroprevalence in sheep was 28% at the beginning of the study and by the end it had increased up to 52.4%. In goats, initial seroprevalence of 5.6% increased to 16%. The percentage of PCR positive ewes was stable throughout the study period. Of the positive sheep, 21.4% were PCR-positive before antibodies could be detected and most of them became PCR-negative shortly after the first detection of antibodies. This might suggest that antibodies have a neutralizing effect. In addition, an equal percentage of sheep were always PCR-negative but either became ELISA-positive or was always ELISA-positive, which might support this hypothesis. On the other hand, the PCR results in goats did not follow any pattern and oscillated between 35.3% and 55.6% depending on the month. Most goats positive by PCR failed to develop antibodies in the 6 months tested. We may conclude that the infection and the antibody response to it follow a different trend in sheep and goats.

  14. Potential of a COX-2 inhibitor in lowering chemotherapy-induced neutropenia%Potential of a COX-2 inhibitor in lowering chemotherapy induced neutropenia

    Institute of Scientific and Technical Information of China (English)

    Louis Wing-Cheong Chow; Adrian Yun-San Yip; Eleanor Yuen-Yuen Ong; Chi-Kei Lam; Masakazu Toi

    2010-01-01

    Objective This study was initially designed to evaluate the effect of celecoxib on the regimen of 5 fluorouracil, epirubicin, and cyclophosphamide (FEC) combination, followed by docetaxel (T) in neoadjuvant setting. An unplanned preliminary review on safety was conducted after a halt of the study due to the concerned potential cardiovascular risk of using COX 2 inhibitors.Methods We studied 23 consecutive cases of operable breast cancer having received four cycles of FEC(500 mg/m2, 100 mg/m2, 500 mg/m2) followed by four cycles of T(100 mg/m2) with concurrent celecoxib (400 mg twice daily) (group A) or same chemotherapy regimen but without concurrent celecoxib (group B). These combined chemotherapies were administered every 3 weeks. The Chi square test or Fisher's exact test were used to assess the difference in incidence of limiting hematological toxicites between groups. Results 23 patients (group A: n=12; group B, n=11) received a total of 183 out of 184 planned treatment cycles; one (4%, 1/23) of them omitted the fourth cycle of FEC owing to repeated incidences of febrile neutropenia. Received dose intensity (RDI) for FEC in group A (90%±11%) was higher than that in group B (80%±8%) while RDI for T was similar between group A (93%±8%) and group B (96%±9%). Of the first 91 treatment cycles of FEC, limiting hematological toxicity, severe neutropenia including febrile neutropenia, was significantly different between group A and B [(10.4%, 5/48) vs.( 32.6%, 14/43), P=0.009]. Other toxicities commonly observed in chemotherapy receiving patients were manageable. Conclusions Neoadjuvant use of FEC followed by T with concurrent celecoxib appeared to be safe for treatment of operable invasive breast cancer. The observed lower incidence of chemotherapy induced neutropenia is possibly contributed by the administration of COX inhibitor. We believe that further investigation might provide more evidence on the use of COX 2 inhibitors in breast cancer.

  15. Congenital and acquired neutropenias consensus guidelines on therapy and follow-up in childhood from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica).

    Science.gov (United States)

    Fioredda, Francesca; Calvillo, Michaela; Bonanomi, Sonia; Coliva, Tiziana; Tucci, Fabio; Farruggia, Piero; Pillon, Marta; Martire, Baldassarre; Ghilardi, Roberta; Ramenghi, Ugo; Renga, Daniela; Menna, Giuseppe; Pusiol, Anna; Barone, Angelica; Gambineri, Eleonora; Palazzi, Giovanni; Casazza, Gabriella; Lanciotti, Marina; Dufour, Carlo

    2012-02-01

    The management of congenital and acquired neutropenias presents some differences according to the type of the disease. Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is not standardized and scanty data are available on the best schedule to apply. The frequency and the type of longitudinal controls in patients affected with neutropenias are not usually discussed in the literature. The Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document that includes recommendations on neutropenia treatment and timing of follow-up.

  16. Incidence of Severe Neutropenia in HIV-Infected People Starting Antiretroviral Therapy in West Africa

    Science.gov (United States)

    Leroi, Charline; Balestre, Eric; Messou, Eugene; Minga, Albert; Sawadogo, Adrien; Drabo, Joseph; Maiga, Moussa; Zannou, Marcel; Seydi, Moussa; Dabis, Francois; Jaquet, Antoine

    2017-01-01

    Background In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. Methods A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). Results Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6–9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8–2.6), ≥6–12 months (aHR = 2.1; 95% CI: 1.6–2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2–2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1–1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0–1.4). Conclusion The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation. PMID:28122041

  17. [Chemotherapy-induced febrile neutropenia: about 200 episodes. Clinical, microbiological and therapeutic characteristics].

    Science.gov (United States)

    Gharbi, O; Ben Hadj Hassen, S; Kaabia, N; Limam, S; Hadj Amor, M; Ben Fatma, L; Landolsi, A; Hochlef, M; Letaief, A; Boukadida, J; Ben Ahmed, S

    2008-05-01

    Cytotoxic chemotherapy suppresses the haematopoietic system, febrile neutropenia is the most serious haematological toxicity associated with the risk of life-threatening infections. We present a retrospective study of 200 episodes of febrile neutropenia in 128 patients treated in department of medical oncology. The aim of this study was to determinate the clinical, therapeutic and evolutive characteristics in patients treated essentially for solid tumors. Among these patients, 72% of them have at least two episodes, the median age was 34 years with extremes six and 75 years. It has been noticed that 26.3% of patients have diabetes, the dominate neoplasm was solid tumors in 79.7%, 65% of patients have received preventive colony-stimulating factors, 83% have received preventive buccal disinfection with antifungic. The median duration of hospitalisation was 12 days, the median delay of febrile neutropenia was 10 days with extremes two and 31 days, median duration of febrile neutropenia was 5.45 days with extremes one and 24 days. Among these cases, 9.45% of them have nadir zero, 68% of patients have clinical documented infections, ORL in 47% of cases. According to the study, 12% of cases have documented microbiological fever, the sites was urinary in 33% of cases, blood in 33% of cases, derm in 30% of cases. The microbe was staphylococcus negative coagulase in 37.5% essentially in blood and derm, the Escherichia coli in 20.8% essentially in urinary and blood. First line antibiotherapy was cefotaxim associated with amikacine in 93.5%, second line antibiotherapy was association of imipenam and amikacine in 82% of cases. Among these cases,7% of them have received anti-staphylococcus, and antifungic treatment in 50% of cases. The thermic defervescence was obtained in median delay of 2.8 days. We have noted nine deaths (22% of cases). Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality and costs. The colony

  18. Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

    Science.gov (United States)

    Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert

    2016-12-12

    Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm(3)). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm(3) of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Antifungal prophylaxis with posaconazole vs. fluconazole or itraconazole in pediatric patients with neutropenia.

    Science.gov (United States)

    Döring, M; Eikemeier, M; Cabanillas Stanchi, K M; Hartmann, U; Ebinger, M; Schwarze, C-P; Schulz, A; Handgretinger, R; Müller, I

    2015-06-01

    Pediatric patients with hemato-oncological malignancies and neutropenia resulting from chemotherapy have a high risk of acquiring invasive fungal infections. Oral antifungal prophylaxis with azoles, such as fluconazole or itraconazole, is preferentially used in pediatric patients after chemotherapy. During this retrospective analysis, posaconazole was administered based on favorable results from studies in adult patients with neutropenia and after allogeneic hematopoietic stem cell transplantation. Retrospectively, safety, feasibility, and initial data on the efficacy of posaconazole were compared to fluconazole and itraconazole in pediatric and adolescent patients during neutropenia. Ninety-three pediatric patients with hemato-oncological malignancies with a median age of 12 years (range 9 months to 17.7 years) that had prolonged neutropenia (>5 days) after chemotherapy or due to their underlying disease, and who received fluconazole, itraconazole, or posaconazole as antifungal prophylaxis, were analyzed in this retrospective single-center survey. The incidence of invasive fungal infections in pediatric patients was low under each of the azoles. One case of proven aspergillosis occurred in each group. In addition, there were a few cases of possible invasive fungal infection under fluconazole (n = 1) and itraconazole (n = 2). However, no such cases were observed under posaconazole. The rates of potentially clinical drug-related adverse events were higher in the fluconazole (n = 4) and itraconazole (n = 5) groups compared to patients receiving posaconazole (n = 3). Posaconazole, fluconazole, and itraconazole are comparably effective in preventing invasive fungal infections in pediatric patients. Defining dose recommendations in these patients requires larger studies.

  1. Pharmacokinetic and pharmacodynamic analysis of hyperthermic intraperitoneal oxaliplatin-induced neutropenia in subjects with peritoneal carcinomatosis.

    Science.gov (United States)

    Valenzuela, Belén; Nalda-Molina, Ricardo; Bretcha-Boix, Pere; Escudero-Ortíz, Vanesa; Duart, Maria José; Carbonell, Vicente; Sureda, Manuel; Rebollo, José Pascual; Farré, Josep; Brugarolas, Antonio; Pérez-Ruixo, Juan José

    2011-03-01

    The objective of this study was to characterize the pharmacokinetics and the time course of the neutropenia-induced by hyperthermic intraperitoneal oxaliplatin (HIO) after cytoreductive surgery in cancer patients with peritoneal carcinomatosis. Data from 30 patients who received 360 mg/m(2) of HIO following cytoreductive surgery were used for pharmacokinetic-pharmacodynamic (PK/PD) analysis. The oxaliplatin plasma concentrations were characterized by an open two-compartment pharmacokinetic model after first-order absorption from peritoneum to plasma. An oxaliplatin-sensitive progenitor cell compartment was used to describe the absolute neutrophil counts in blood. The reduction of the proliferation rate of the progenitor cells was modeled by a linear function of the oxaliplatin plasma concentrations. The typical values of oxaliplatin absorption and terminal half-lives were estimated to be 2.2 and 40 h, with moderate interindividual variability. Oxaliplatin reduced the proliferation rate of the progenitor cells by 18.2% per mg/L. No patient's covariates were related to oxaliplatin PK/PD parameters. Bootstrap and visual predictive check evidenced the model was deemed appropriate to describe oxaliplatin pharmacokinetics and the incidence and severity of neutropenia. A peritoneum oxaliplatin exposure of 65 and 120 mg·L/h was associated with a 20% and 33% incidence of neutropenia grade 4. The time course of neutropenia following HIO administration was well described by the semiphysiological PK/PD model. The maximum tolerated peritoneum oxaliplatin exposure is 120 mg L/h and higher exposures should be avoided in future studies. We suggest the prophylactic use of granulocyte colony stimulating factor for patients treated with HIO exposure higher than 65 mg L/h.

  2. Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.

    Science.gov (United States)

    Demirkaya, Metin; Tugcu, Deniz; Akcay, Arzu; Aydogan, Gönül; Akıcı, Ferhan; Salcioglu, Zafer; Ekmekci, Hakan; Sevinir, Betül; Balci Ekmekci, Ozlem

    2015-01-01

    In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

  3. Practices of infectious control management during neutropenia: A survey from 149 French hospitals.

    Science.gov (United States)

    Lequilliec, N; Raymond, R; Vanjak, D; Baghdadi, N; Boulestreau, H; Zahar, J-R; Gangneux, J-P

    2017-06-01

    Neutropenic patients represent a growing and fragile population in our hospitals. Numerous treatments induce neutropenia in haematology wards and elsewhere. Although strict isolation is recommended during post-haematopoietic stem cell transplantation neutropenia, this may not be the current practice in other situations. In this study, our objective was to analyse what protective measures are applied in neutropenic patients in a French survey. A questionnaire was sent out to infection control teams of 400 public and private French hospitals to enquire about their local recommendations regarding infection prevention in neutropenic patients. Among the 166 (41%) responders, 134 (81%) managed neutropenic patients. All of the centres recommended protective isolation for neutropenic patients. However, only 46 (34%) had clearly defined patients warranting specific isolation measures in terms of the level of neutropenia. All of the centres recommended several barrier measures, but these were highly variable according to the type of air treatment in the wards (note that only 72% of haematology wards are equipped with air treatment). Gowns, gloves, masks, hats and shoe covers were respectively recommended in 128 (95%), 79 (59%), 132 (98%), 87 (65%), and 34 (25%) of the establishments. Surprisingly, the recommendations vary both among hospitals and within the same hospital among different clinical wards. In conclusion, protective measures for neutropenic patients are applied variably and urgently require a consensus to homogenize practices. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

    Science.gov (United States)

    Legge, Sophie E; Hamshere, Marian L; Ripke, Stephan; Pardinas, Antonio F; Goldstein, Jacqueline I; Rees, Elliott; Richards, Alexander L; Leonenko, Ganna; Jorskog, L Fredrik; Chambert, Kimberly D; Collier, David A; Genovese, Giulio; Giegling, Ina; Holmans, Peter; Jonasdottir, Adalbjorg; Kirov, George; McCarroll, Steven A; MacCabe, James H; Mantripragada, Kiran; Moran, Jennifer L; Neale, Benjamin M; Stefansson, Hreinn; Rujescu, Dan; Daly, Mark J; Sullivan, Patrick F; Owen, Michael J; O’Donovan, Michael C; Walters, James T R

    2016-01-01

    The antipsychotic clozapine is uniquely effective in the management of schizophrenia, but its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown although genetic factors play an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed HLA alleles, exome array, and copy number variation analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (OR=4.32, P=1.79×10-8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P = 0.015, positive predictive value = 35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect. PMID:27400856

  5. Dengue fever causing febrile neutropenia in children with acute lymphoblastic leukemia: an unknown entity.

    Science.gov (United States)

    Ramzan, Mohammed; Yadav, Satya Prakash; Dinand, Veronique; Sachdeva, Anupam

    2013-06-01

    Dengue fever is endemic in many parts of the world but it has not been described as a cause of febrile neutropenia. We describe here clinical features, laboratory values and outcome in 10 children with acute lymphoblastic leukemia (ALL) and with dengue fever as a cause of febrile neutropenia. These data are compared to an age-matched control population of 22 children with proven dengue infection without ALL. Except for fever in all patients and plethoric face in one patient, typical symptoms of dengue such as abdominal pain, myalgias, and headaches, were absent. Mean duration of hospital stay was 6.3±2.0 days in ALL patients vs. 5.0±2.0 in controls (p=0.096). Median platelet count was 13,000/cmm (range 1000-28,000) in cases vs. 31,500 (range 13,000-150,000) in controls (p=0.018). Mean time for recovery for platelet was 6.0±1.3days in ALL patients vs. 2.5±0.9days in controls (pfebrile neutropenia although typical symptoms may be lacking. Platelet recovery may be significantly delayed.

  6. Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study

    Directory of Open Access Journals (Sweden)

    Federico Garcia

    2014-11-01

    Full Text Available Introduction: In a previous interim 24-week virological safety analysis of the PROTEST study (1, initiation of Maraviroc (MVC plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. Methods: PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910 carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL 10% in a singleton, initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week*100. Results: Tropism results were available from 141/175 (80.6% subjects screened: 87/141 (60% were R5 and 74/87 (85% were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm3 at screening, and median nadir CD4+ counts were 143 cells/mm3. Previous ART included PIs in 46 (62% subjects, NNRTIs in 27 (36% and integrase inhibitors (INIs in 1 (2%. The main reasons for treatment change were dyslipidemia (42%, gastrointestinal symptoms (22%, and liver toxicity (15%. MVC was given alongside TDF/FTC in 40 (54% subjects, ABC/3TC in 30 (40%, AZT/3TC in 2 (3% and ABC/TDF in 2 (3%. Sixty-two (84% subjects maintained VL<50 c/mL through week 48, whereas 12 (16% discontinued treatment: two (3% withdrew informed consent, one (1% had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1% was lost to follow-up, one (1% developed an ART-related adverse event (rash, two (3% died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36, and five (7% developed protocol

  7. Neutropenia crónica e infección por el virus de la inmunodeficiencia humana Chronic neutropenia and human immunodeficiency virus infection

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    Ronald A Noguera-Valverde

    2008-09-01

    Full Text Available Se presenta el caso de un paciente masculino con neutropenia crónica e infección por el virus de inmunodeficiencia humana, con una revisión de los posibles mecanismos patogénicos. Las alteraciones hematológicas como anemia, trombocitopenia y leucopenia se presentan asociadas con frecuencia a la infección aguda por el virus de inmunodeficiencia humana. Al establecer la terapia antirretroviral y disminuir la actividad del virus, estas alteraciones tienden a mejorar. Sin embargo, algunos fármacos antirretrovirales, como la zidovudina, poseen toxicidad medular y pueden producir o empeorar las alteraciones hematológicas en estos pacientes, lo cual lleva a cambios en los esquemas de tratamiento. Los citotóxicos y antimetabolitos empleados en el tratamiento de neoplasias asociadas tienen conocida actividad depresora sobre la médula ósea. Algunos antimicrobianos utilizados en la profilaxis de infecciones poseen también toxicidad hematológica conocida, como el trimetoprim-sulfametoxazol, por lo que deben ser utilizados con precaución en pacientes con infección por el virus de inmunodeficiencia humana. Por otro lado, se plantean mecanismos alternativos que causan neutropenia en estos pacientes, como la formación de anticuerpos antineutrófilos, daño primario del progenitor granulocítico, por desbalance en la producción de neutrófilos, por anticuerpos contra la glicoproteína gp120 de la cápside viral del VIH, y deficiencias vitamínicas. En el caso del paciente neutropénico febril, en quien se sospecha infección bacteriana grave, se pueden utilizar los factores estimulantes de las colonias de granulocitos para aumentar los conteos absolutos de neutrófilos y mejorar la recuperación clínica.A case of a male with chronic neutropenia and human immunodeficiency virus infection is presented along, with a review of possible pathogenic mechanisms. Hematological abnormalities as anemia, thrombocytopenia and leucopenia are frequently

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Proviral amplification of the Gypsy endogenous retrovirus of Drosophila melanogaster involves env-independent invasion of the female germline.

    Science.gov (United States)

    Chalvet, F; Teysset, L; Terzian, C; Prud'homme, N; Santamaria, P; Bucheton, A; Pélisson, A

    1999-05-04

    Gypsy is an infectious endogenous retrovirus of Drosophila melanogaster. The gypsy proviruses replicate very efficiently in the genome of the progeny of females homozygous for permissive alleles of the flamenco gene. This replicative transposition is correlated with derepression of gypsy expression, specifically in the somatic cells of the ovaries of the permissive mothers. The determinism of this amplification was studied further by making chimeric mothers containing different permissive/restrictive and somatic/germinal lineages. We show here that the derepression of active proviruses in the permissive soma is necessary and sufficient to induce proviral insertions in the progeny, even if the F1 flies derive from restrictive germ cells devoid of active proviruses. Therefore, gypsy endogenous multiplication results from the transfer of some gypsy-encoded genetic material from the soma towards the germen of the mother and its subsequent insertion into the chromosomes of the progeny. This transfer, however, is not likely to result from retroviral infection of the germline. Indeed, we also show here that the insertion of a tagged gypsy element, mutant for the env gene, occurs at high frequency, independently of the production of gypsy Env proteins by any transcomplementing helper. The possible role of the env gene for horizontal transfer to new hosts is discussed.

  11. Quantification of HIV-1 proviral DNA from peripheral blood mononuclear cells using a high throughput four-competitor competitive PCR.

    Science.gov (United States)

    Comandini, U V; Sönnerborg, A; Vahlne, A; Yun, Z

    1997-12-01

    A multiple competitor PCR (mcPCR) was developed to quantify HIV-1 proviral DNA from peripheral blood mononuclear cells (PBMC). DNA extracted from a mixture of HIV infected PBMC and four size-mutated DNA competitors were co-amplified. The Cy5-fluorescence labelled PCR products were denatured by heating, separated using an automated DNA sequencer and quantified by a fragment analysis computer software. An internal standard was generated by plotting the peak areas of the four competitors against their inputs. Based on the internal standard, HIV sample DNA was quantified by extrapolating the corresponding signal. The linear range of the mcPCR was three log wide and the quantitation limit was about 20 copies of HIV DNA/10(6) PBMC. Using the mcPCR, HIV DNA was quantified from 14 long-term non progressors (LTNP) and 14 patients with advanced disease. A significantly lower copy number of HIV DNA was obtained in the LTNP (p = 0.018). These data suggest that the mcPCR is sensitive, reliable and especially useful for HIV DNA quantification of a large number of clinical samples.

  12. The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.

    Science.gov (United States)

    Cavignac, Yolaine; Lieber, Diana; Laib Sampaio, Kerstin; Madlung, Johannes; Lamkemeyer, Tobias; Jahn, Gerhard; Nordheim, Alfred; Sinzger, Christian

    2015-01-01

    While it is well established that human cytomegalovirus (HCMV) upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.

  13. The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.

    Directory of Open Access Journals (Sweden)

    Yolaine Cavignac

    Full Text Available While it is well established that human cytomegalovirus (HCMV upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.

  14. 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.

  15. 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.

  16. ANA-Negative Presentation of SLE in Man with Severe Autoimmune Neutropenia

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    Melissa Zhao

    2016-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a chronic, inflammatory, connective tissue disease that commonly affects the joints and a variety of organs due to an overactivation of the body’s immune system. There is wide heterogeneity in presentation of SLE patients, including lung, central nervous system, skin, kidney, and hematologic manifestations. Case Presentation. We report a case of atypical manifestation of SLE in a 53-year-old man who presented with neutropenic fever. Physical findings of interest included oral ulcers on the lower lip, a malar-like rash across the bridge of the nose, and a discoid-like rash on extensor surfaces of the elbows and knees. Labs include ANC <100, weakly positive anti-dsDNA, negative ANA, ferritin 1237 ng/mL, low C3/C4, and positive direct Coombs’ test. A thorough workup for infection and hematologic malignancy was negative. Two days after initiation of therapy with 25 mg IV solumedrol twice a day, the patient’s daily fevers resolved. ANC drastically improved to 2000 after two weeks of steroid treatment. He was later found to have a high titer of anti-neutrophil antibodies. Discussion. Autoimmune leukopenia is a common presentation in SLE, occurring in 50–60% of patients. Severe autoimmune neutropenia is uncommon and may correlate with high anti-neutrophil antibody activity despite a negative ANA. As neutropenia is usually mild, there are currently no guidelines for therapy. For our patient, we started him on low dose IV solumedrol and found that he responded drastically to treatment. Given strongly positive nonspecific anti-neutrophil antibodies in the setting of a negative ANA noted in our patient, it is likely that there are other currently unknown antibodies associated with SLE which may correlate strongly with autoimmune neutropenia.

  17. 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.

  18. ANA-Negative Presentation of SLE in Man with Severe Autoimmune Neutropenia.

    Science.gov (United States)

    Zhao, Melissa

    2016-01-01

    Background. Systemic lupus erythematosus (SLE) is a chronic, inflammatory, connective tissue disease that commonly affects the joints and a variety of organs due to an overactivation of the body's immune system. There is wide heterogeneity in presentation of SLE patients, including lung, central nervous system, skin, kidney, and hematologic manifestations. Case Presentation. We report a case of atypical manifestation of SLE in a 53-year-old man who presented with neutropenic fever. Physical findings of interest included oral ulcers on the lower lip, a malar-like rash across the bridge of the nose, and a discoid-like rash on extensor surfaces of the elbows and knees. Labs include ANC ANA, ferritin 1237 ng/mL, low C3/C4, and positive direct Coombs' test. A thorough workup for infection and hematologic malignancy was negative. Two days after initiation of therapy with 25 mg IV solumedrol twice a day, the patient's daily fevers resolved. ANC drastically improved to 2000 after two weeks of steroid treatment. He was later found to have a high titer of anti-neutrophil antibodies. Discussion. Autoimmune leukopenia is a common presentation in SLE, occurring in 50-60% of patients. Severe autoimmune neutropenia is uncommon and may correlate with high anti-neutrophil antibody activity despite a negative ANA. As neutropenia is usually mild, there are currently no guidelines for therapy. For our patient, we started him on low dose IV solumedrol and found that he responded drastically to treatment. Given strongly positive nonspecific anti-neutrophil antibodies in the setting of a negative ANA noted in our patient, it is likely that there are other currently unknown antibodies associated with SLE which may correlate strongly with autoimmune neutropenia.

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

    Science.gov (United States)

    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.

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

    OpenAIRE

    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...

  1. 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......3-methylglutaconic aciduria (3-MGA-uria) is a nonspecific finding associated with mitochondrial dysfunction, including defects of oxidative phosphorylation. 3-MGA-uria is classified into five groups, of which one, type IV, is genetically heterogeneous. Here we report five children with a form...

  2. Fluoroquinolone Prophylaxis Against Febrile Neutropenia in Areas With High Fluoroquinolone Resistance—An Asian Perspective

    Directory of Open Access Journals (Sweden)

    Esther Shu-Ting Ng

    2010-09-01

    Full Text Available Febrile neutropenia remains a major cause of morbidity and mortality in patients receiving chemotherapy. Major prophylactic strategies include granulocyte colony-stimulating factor and antibiotics, the most widely used of which are fluoroquinolones. While fluoroquinolone prophylaxis has been shown to be effective in areas where fluoroquinolone resistance is low, this same efficacy has not been proven in areas where resistance is high, such as in Asia. Given the increase in antimicrobial resistance with the use of prophylaxis, the risks and benefits of this strategy need to be carefully considered. This review presents the evidence for and against fluoroquinolone prophylaxis in areas of high fluoroquinolone resistance.

  3. Fluoroquinolone prophylaxis against febrile neutropenia in areas with high fluoroquinolone resistance--an Asian perspective.

    Science.gov (United States)

    Ng, Esther Shu-Ting; Liew, Yixin; Koh, Liang Piu; Hsu, Li Yang

    2010-09-01

    Febrile neutropenia remains a major cause of morbidity and mortality in patients receiving chemotherapy. Major prophylactic strategies include granulocyte colony-stimulating factor and antibiotics, the most widely used of which are fluoroquinolones. While fluoroquinolone prophylaxis has been shown to be effective in areas where fluoroquinolone resistance is low, this same efficacy has not been proven in areas where resistance is high, such as in Asia. Given the increase in antimicrobial resistance with the use of prophylaxis, the risks and benefits of this strategy need to be carefully considered. This review presents the evidence for and against fluoroquinolone prophylaxis in areas of high fluoroquinolone resistance.

  4. [Septic shock following platelet transfusion contaminated with Citrobacter koseri in a child with postchemotherapy febrile neutropenia].

    Science.gov (United States)

    Tichit, R; Saumet, L; Marchandin, H; Haouy, S; Latry, P; Sirvent, N

    2016-01-01

    The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers.

  5. Uso do estimulante de colônia de granulócitos nas neutropenias em cães e gatos Granulocyte colony-stimulating factor use in neutropenias in dogs and cats

    Directory of Open Access Journals (Sweden)

    Cynthia de Assumpção Lucidi

    2007-06-01

    Full Text Available As neutropenias persistentes podem ser decorrentes de alterações na granulopoiese, causadas por efeitos supressivos ou tóxicos à medula óssea, predispõem o paciente a infecções comprometendo sua sobrevida. As neutropenias intensas decorrentes de toxicidade por quimioterápicos podem requerer a suspensão temporária ou permanente do medicamento, podendo gerar resistência das células neoplásicas ao tratamento. O uso de fatores de crescimento hematopoiético recombinantes em animais tem aumentado muito nos últimos anos, devido a sua crescente disponibilidade na medicina humana. O fator estimulante de colônia para granulócitos recombinante humano (rhG-CSF age aumentando o número de neutrófilos circulantes e possui grande potencial para amenizar ou reverter quadros de neutropenia associada a condições de mielotoxicidade e mielosupressão em cães e gatos.Persistent neutropenias can occur after granulopoiesis disturbances caused by myelosupressive or myelotoxic effects, and predispose patients to infections and impairs their survival. Furthermore, severe chemotherapy-induced neutropenias must require temporary or definitive treatment interruption, what may lead to drug-resistance of neoplastic cells. The use of recombinant stem cell factors in animals has been increasing due to its bigger disponibility for human beings. The human recombinant granulocyte colony-stimulating factor (rhG-CSF increases neutrophil numbers in peripheral blood and has great potential to alleviate or revert myelotoxic or myelosupression neutropenias in dogs and cats.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Posaconazole plasma concentrations in pediatric patients receiving antifungal prophylaxis during neutropenia.

    Science.gov (United States)

    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Klinker, Hartwig; Eikemeier, Melinda; Feucht, Judith; Blaeschke, Franziska; Schwarze, Carl-Philipp; Ebinger, Martin; Feuchtinger, Tobias; Handgretinger, Rupert; Heinz, Werner J

    2016-10-04

    Invasive fungal infections are one of the major complications in pediatric patients during prolonged neutropenia after chemotherapy. Evaluation of the efficacy and safety of the triazole posaconazole in these patients is missing. This multicenter survey analyzed trough concentrations of 33 pediatric patients with a median age of 8 years during 108 neutropenic episodes who received prophylactic posaconazole oral suspension. A total of 172 posaconazole trough levels were determined to median 438 ng/ml (range 111-2011 ng/ml; mean 468 ± 244 ng/ml). Age and gender had no influence on posaconazole plasma levels. Posaconazole was not discontinued due to adverse events in any of the patients. Only hepatic parameters significantly increased beyond the upper normal limit to median values of ALT of 87 U/l (P posaconazole trough concentration of 306 ng/ml experienced an invasive fungal infection. In conclusion, posaconazole was effective, safe and feasible in 33 pediatric patients with neutropenia ≥5 days after chemotherapy. Median posaconazole plasma concentrations were approximately 1.6-fold lower than the recommended plasma level of 700 ng/ml. Larger patient cohorts are needed to evaluate these findings.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.


  11. Which Variables Are Useful for Predicting Severe Infection in Children With Febrile Neutropenia?

    Science.gov (United States)

    Delebarre, Mathilde; Garnier, Nathalie; Macher, Emilie; Thebaud, Estelle; Mazingue, Françoise; Leblond, Pierre; Duhamel, Alain; Martinot, Alain; Dubos, François

    2015-11-01

    To distinguish children with chemotherapy-induced febrile neutropenia (FN) at low risk of severe infection, the variables that are significant risk factors must be identified. Our objective was to identify them by applying evidence-based standards. This retrospective 2-center cohort study included all episodes of chemotherapy-induced FN in children in 2005 and 2006. The medical history, clinical, and laboratory data available at admission were collected. Severe infection was defined by bacteremia, a positive culture of a normally sterile body fluid, invasive fungal infection, or localized infection at high risk of extension. Univariate analysis identified potential predictive variables. A generalized mixed model was used to determine the adjusted variables that predict severe infection. We analyzed 372 FN episodes. Severe infections occurred in 16.1% of them. Variables predictive of severe infection at admission were: disease with high risk of prolonged neutropenia (adjusted odds ratio [aOR]=2.5), blood cancer (aOR=1.9), fever ≥38.5°C (aOR=3.7), and C-reactive protein level ≥90 mg/L (aOR=4.5). Now that we have identified these variables significantly associated with the risk of severe infection, they must be validated prospectively before combining the best predictive variables in a decision rule that can be used to distinguish children at low risk.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Flow cytometric detection of neutrophil-associated immunoglobulin in patients with or without neutropenia and establishment of the reference interval.

    Science.gov (United States)

    Hwang, Keumrock; Park, Chan-Jeoung; Huh, Hee Jin; Han, Sang Hee; Jang, Seongsoo; Chi, Hyun-Sook

    2011-01-01

    We measured neutrophil-associated immunoglobulin (NAIg) levels using flow cytometry to establish the reference interval for NAIg and to estimate NAIg in patients with or without neutropenia. Peripheral blood from 152 individuals was analyzed for NAIg detection by flow cytometry. Using fluorescescent-conjugated anti-CD10 monoclonal antibody and anti-human immunoglobulins, proportions of NAIgG, NAIgA, and NAIgM bound to neutrophils were measured. Reference intervals for NAIg were set as NAIgG reference intervals defined herein, patients with neutropenia or adverse transfusion reactions may be evaluated in a clinically relevant manner.

  14. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    NARCIS (Netherlands)

    F. Dong (Fan); R.K. Brynes; N. Tidow; K. Welte (Karl); B. Löwenberg (Bob); I.P. Touw (Ivo)

    1995-01-01

    textabstractIn severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction pathways for granulocyte colony-stimulati

  15. 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

  16. Ocorrência de neutropenia em mulheres com câncer de mama durante tratamento quimioterápico Ocurrencia de neutropenia en mujeres con cáncer de mama durante el tratamiento quimioterápico Occurrence of neutropenia in women with breast cancer during chemotherapy treatment

    Directory of Open Access Journals (Sweden)

    Thaís de Oliveira Gozzo

    2011-01-01

    Full Text Available OBJETIVO: Analisar a ocorrência de neutropenia induzida por drogas utilizadas no tratamento quimioterápico de mulheres com câncer de mama. MÉTODOS: Estudo retrospectivo, com avaliação de 72 prontuários, durante 2003-2006. RESULTADOS: Dos 558 ciclos de quimioterapia realizados, foram registrados 152 eventos adversos nos períodos de neoadjuvância e adjuvância, totalizando 43 casos por toxicidade hematológica. Quanto à ocorrência de neutropenia, 43% apresentaram, pelo menos, um episódio durante o tratamento. Testes de hipótese para comparar as médias dos valores de glóbulos brancos entre as mulheres que apresentaram ou não neutropenia apontaram para valores estatisticamente significantes, nos ciclos dois e três da neoadjuvância e nos ciclos dois, três e quatro da adjuvância. CONCLUSÃO: A neutropenia, tanto na neoadjuvância como na adjuvância ocorreu a partir do segundo ciclo e manteve-se durante o tratamento e foi estatisticamente significante quando foram compadas as mulheres que tiveram ou não esta ocorrência.OBJETIVO: Analizar la ocurrencia de neutropenia inducida por drogas utilizadas en el tratamiento quimioterápico de mujeres con cáncer de mama. MÉTODOS: Estudio retrospectivo, realizado con la evaluación de 72 historias clínicas, durante loa años 2003-2006. RESULTADOS: De los 558 ciclos de quimioterapia realizados, fueron registrados 152 eventos adversos en los períodos de neoadyuvante y adyuvante, totalizando 43 casos por toxicidad hematológica. En cuanto a la ocurrencia de neutropenia, el 43% presentaron, por lo menos, un episodio durante el tratamiento. Las pruebas de hipótesis para comparar los promedios de los valores de glóbulos blancos entre las mujeres que presentaron o no neutropenia apuntaron hacia valores estadísticamente significativos, en los ciclos dos y tres de la neoadyuvancia y en los ciclos dos, tres y cuatro de la adyuvancia. CONCLUSIÓN: La neutropenia, tanto en la neoadyuvancia como

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Evaluation of ior ® Leukocim efficacy on patients with Neutropenia. Evaluación de la eficacia del ior® Leukocim en pacientes con neutropenia.

    Directory of Open Access Journals (Sweden)

    Hailen Bobillo López

    2007-02-01

    Full Text Available

    Bakground: Neutropenia and infections are the most restrictive side effects in chemotherapy application. The granulocytic colonies stimulating factor activates the neutrophils, shortens the neutropenic period and can be effective against the potential risk of infection. There is a need of studies for its commercialization to endorse their effectiveness and security. Objective: To evaluate the impact of the G-CSF in primary and secondary prevention and neutropenia episodes, in onco-haematological patients in Cienfuegos. Method: 95 neutropenic episodes were studied, picked up in clinical histories and data collection notebooks belonging to 47 patients treated in the University Hospital ¨Dr. Gustavo Aldereguía Lima¨ in Cienfuegos and happened during one year (2005-2006. It was analyzed: demographic data, absolute neutrophils count values, number of administered doses, treatment regime and possible treatment interruptions Results: 50, 5% received treatment in an ambulatory way. There was treatment interruption in 9 episodes, 9,5% and the mean dose number administered to obtain the recovery of neutrophils absolute count was 6,69. Conclusions: The product was effective, sine the decrease of neutropenic episodes could be verified, as the elevation of neutrophil values in approximately one week, what allowed a better pursuit of chemotherapy to patients of the studied series.

    Abstract

    To demonstrate the effectiveness of Leukocim an open, phase IV clinical trial was designed, 39 patients from Cienfuegos were evaluated with 73 neutropenic episodes in primary or secondary prophylaxis or treatment, the demographic parameters behaved with an age 49.86 year old average, the predominant sex was the feminine 64.38%, 73.97% belonged to the white race, when the effectiveness was analyzed we obtained that 46.5% received the treatment in an

  19. Detection of monoclonal integration of bovine leukemia virus proviral DNA as a malignant marker in two enzootic bovine leukosis cases with difficult clinical diagnosis

    OpenAIRE

    Miura, Saori; HORIUCHI, Noriyuki; Matsumoto, Kotaro; KOBAYASHI, Yoshiyasu; Kawazu, Shin-ichiro; INOKUMA, Hisashi

    2015-01-01

    Monoclonal integration of bovine leukemia virus (BLV) proviral DNA into bovine genomes was detected in peripheral blood from two clinical cases of enzootic bovine leukosis (EBL) without enlargement of superficial lymph nodes. A BLV-specific probe hybridized with 1 to 3 EcoRI and HindIII fragments in these 2 atypical EBL cattle by Southern blotting and hybridization, as well as in 3 typical EBL cattle. The probe also hybridized to a large number of EcoRI and HindIII fragments in 5 cattle with ...

  20. Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene.

    NARCIS (Netherlands)

    Volpi, L.; Roversi, G.; Colombo, E.A.; Leijsten, N.; Concolino, D.; Calabria, A.; Mencarelli, M.A.; Fimiani, M.; Macciardi, F.; Pfundt, R.; Schoenmakers, E.F.P.M.; Larizza, L.

    2010-01-01

    Next-generation sequencing is a straightforward tool for the identification of disease genes in extended genomic regions. Autozygosity mapping was performed on a five-generation inbred Italian family with three siblings affected with Clericuzio-type poikiloderma with neutropenia (PN [MIM %604173]),

  1. G-CSF receptor (CSF3R) mutations in X-linked neutropenia evolving to acute myeloid leukemia or myelodysplasia

    OpenAIRE

    2009-01-01

    This paper shows for the first time that patients with X-linked neutropenia, caused by mutations in the Wiskott Aldrich syndrome gene, developed myelodysplasia/acute myeloid leukemia with acquisition of mutations in the CSF3R gene and loss of chromosome 7. See related perspective article on page 1333.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

    Gerritsen, M G; Willemink, M J; Pompe, E; van der Bruggen, T; van Rhenen, A; Lammers, J W J|info:eu-repo/dai/nl/071697624; Wessels, F; Sprengers, R W; de Jong, Pim|info:eu-repo/dai/nl/287955672; Minnema, M C|info:eu-repo/dai/nl/171618149

    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

  4. Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia-species distribution and susceptibility patterns

    NARCIS (Netherlands)

    Miedema, Karin G. E.; Winter, Rik H. L. J.; Ammann, Roland A.; Droz, Sara; Spanjaard, Lodewijk; de Bont, Eveline S. J. M.; Kamps, Willem A.; van de Wetering, Marianne D.; Tissing, Wim J. E.

    2013-01-01

    Infections are a major cause of morbidity and mortality in pediatric cancer patients. The aim of this study was to establish the microbiological spectrum and the susceptibility patterns of bacteremia-causing bacteria in pediatric cancer patients with febrile neutropenia in relation to the use of pro

  5. Mannose-Binding Lectin (MBL) and the Risk for Febrile Neutropenia and Infection in Pediatric Oncology Patients With Chemotherapy

    NARCIS (Netherlands)

    F.N.J. Frakking; J. Israëls; L.C.M. Kremer; T.W. Kuijpers; H.N. Caron; M.D. van de Wetering

    2011-01-01

    Background. We determined whether mannose-binding lectin (MBL) deficiency is associated with an increased risk of febrile neutropenia (FN) and/or infection in pediatric oncology patients. Procedure. We systematically searched and reviewed all the literature on MBL and infections in children with can

  6. Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia-species distribution and susceptibility patterns

    NARCIS (Netherlands)

    Miedema, Karin G. E.; Winter, Rik H. L. J.; Ammann, Roland A.; Droz, Sara; Spanjaard, Lodewijk; de Bont, Eveline S. J. M.; Kamps, Willem A.; van de Wetering, Marianne D.; Tissing, Wim J. E.

    2013-01-01

    Infections are a major cause of morbidity and mortality in pediatric cancer patients. The aim of this study was to establish the microbiological spectrum and the susceptibility patterns of bacteremia-causing bacteria in pediatric cancer patients with febrile neutropenia in relation to the use of pro

  7. Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports

    Science.gov (United States)

    Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

    2016-01-01

    Objective: Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. Methods: We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia Results: We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Conclusion: Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine. PMID:26913176

  8. 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.

  9. Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene.

    NARCIS (Netherlands)

    Volpi, L.; Roversi, G.; Colombo, E.A.; Leijsten, N.; Concolino, D.; Calabria, A.; Mencarelli, M.A.; Fimiani, M.; Macciardi, F.; Pfundt, R.; Schoenmakers, E.F.P.M.; Larizza, L.

    2010-01-01

    Next-generation sequencing is a straightforward tool for the identification of disease genes in extended genomic regions. Autozygosity mapping was performed on a five-generation inbred Italian family with three siblings affected with Clericuzio-type poikiloderma with neutropenia (PN [MIM %604173]),

  10. Caracterización de pacientes pediátricos con neutropenia enviados a un hospital de referencia

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Lazo-Páez

    2010-06-01

    Full Text Available Objetivo: La neutropenia es un motivo relativamente frecuente de referencia al Servicio de Inmunología y Reumatología Pediátrica del Hospital Nacional de Niños; el estudio pretende caracterizar los casos de neutropenia referidos a este Servicio en el periodo comprendido entre noviembre de 1988 y junio de 2008. Métodos: Se estudiaron 84 pacientes entre 0 y 12 años de edad, referidos entre el 6 de noviembre de 1988 y el 1 de junio de 2008. Se efectuó un análisis descriptivo global de las características presentadas por estos pacientes en términos de evolución clínica, patrón de infección, gérmenes más frecuentes causantes de infección, complicaciones y tratamiento. Resultados: El 52.2% de los pacientes analizados resolvieron su neutropenia espontáneamente, por lo que fueron catalogados como neutropenia transitoria; el 21.7% de los casos evolucionó como neutropenia cíclica; el 13% de los pacientes fueron catalogados como neutropenia crónica benigna; el 7.2% evolucionaron como neutropenia crónica grave sintomática; el 2.9% tuvieron neutropenia asociada a glucogenosis tipo 1B, y el 2.9% de los casos no fueron clasificables en las categorías propuestas. El 56.5% de los casos se asoció a un patrón de infección anormal, sea por incremento en la frecuencia, mayor gravedad, compromiso multisistémico o presencia de microorganismos oportunistas. El sistema más afectado por infección fue la vía respiratoria superior. El 39.1% de los casos de neutropenia evaluados ameritaron uso de antibióticos profilácticos, y el 11.6% de los casos requirieron usar factor estimulante de colonias granulocíticas, en algún momento de su evolución. Los gérmenes más frecuentemente involucrados en infección fueron Pseudomona aeruginosa, Staphylococcus spp y E. coli. Conclusión: La gran mayoría de los pacientes neutropénicos estudiados tiene un curso clínico benigno caracterizado por pocas hospitalizaciones y una intervención farmacol

  11. Paternal Somatic Mosaicism of a Novel Frameshift Mutation in ELANE Causing Severe Congenital Neutropenia.

    Science.gov (United States)

    Kim, Hee-Jung; Song, Min-Jung; Lee, Ki-O; Kim, Sun-Hee; Kim, Hee-Jin

    2015-12-01

    Severe congenital neutropenia (SCN) is a bone marrow failure disease with an autosomal dominant inheritance from mutations in ELANE. Here, we report a 7-week-old Korean male with SCN. His elder sister died from pneumonia at 2 years. Direct sequencing of ELANE in the proband identified a heterozygous novel frameshift mutation: c.658delC (p.Arg220Glyfs20*). Family study involving his asymptomatic parents with normal cell counts revealed that his father had the same mutation, but at a lower burden than expected in a typical heterozygous state. Further molecular investigation demonstrated somatic mosaicism with ~18% mutant alleles. We concluded the proband inherited the mutation from his somatic mosaic father.

  12. Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and therapeutically in these patients. OBJECTIVES: To compare the benefits and harms of voriconazole with those of amphotericin B...... 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...... and adverse effects leading to discontinuation of therapy were extracted independently by two review authors. MAIN RESULTS: Three trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infection) in neutropenic...

  13. Management of infection and febrile neutropenia in patients with solid cancer.

    Science.gov (United States)

    Virizuela, J A; Carratalà, J; Aguado, J M; Vicente, D; Salavert, M; Ruiz, M; Ruiz, I; Marco, F; Lizasoain, M; Jiménez-Fonseca, P; Gudiol, C; Cassinello, J; Carmona-Bayonas, A; Aguilar, M; Cruz, J J

    2016-06-01

    An expert group from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, for its acronym in Spanish) and the Spanish Society of Medical Oncology (SEOM, for its acronym in Spanish) have reviewed the main aspects to be considered when evaluating patients with solid cancer and infectious complications contained in this article. Recommendations have, therefore, been put forth regarding the prophylaxis of the most prevalent infections in these patients, the use of vaccines, measures to control infection through vascular catheters, and preventing infection in light of certain surgical maneuvers. The following is a revision of the criteria for febrile neutropenia management and the use of colony-stimulating factors and closes with several guidelines for treating the cancer patient with serious infection. The document concludes with a series of measures to control hospital infection.

  14. Splenic tuberculosis presenting as fever of unknown origin with severe neutropenia.

    Science.gov (United States)

    Azzam, Nahla A

    2013-06-18

    Fever of undetermined origin always poses a challenging problem to the physician. Tuberculosis is an important health problem in developing countries. It is mostly seen in immune-compromised patients. And it is one of the common causes of fever of unknown origin. I am reporting a case of a splenic tuberculosis in 48 years old male who is not known of any immune deficiency state, he was presented with 3 weeks history of fever and found to have severe neutropenia and with negative work up for all hematological, rheumatological and malignant causes. A computerized tomography scan of the abdomen confirmed splenic enlargement with multiples hypo dense lesions consist with either splenic infection or splenic lymphoma so exploratory splenectomy was performed. Histological examination revealed granulomatouse inflammation with numerous acid fast bacilli consist with tuberculosis. He was started on four anti-tuberculouse drugs. in less than one week his fever subside with normalization of his neutrophilic count.

  15. Chronic Refractory Uveitis in a Patient with Childhood-Onset Cyclic Neutropenia

    Directory of Open Access Journals (Sweden)

    Li-Li Chen

    2011-05-01

    Full Text Available We report a rare case of chronic refractory uveitis in a patient with childhood-onset cyclic neutropenia (CN. A 19-year-old woman, who had a history of CN beginning at age 2, presented with bilateral chronic nongranulomatous uveitis, complicated cataract, retinal vasculitis, cystoids macular edema, and vitreous hemorrhage. She had recurrent episodes of oral ulcers, tonsillitis, genital ulcers, and folliculitis during neutropenic nadir. After the resumption of granulocyte colony-stimulating factor therapy for her CN, vitreous hemorrhage in both eyes followed. Her eyes were treated with topical corticosteroids, retinal photocoagulation, and cataract surgery. Blood and bone marrow test results confirmed the diagnosis of CN. She also fulfilled the diagnostic criteria of Behçet’s disease, though clinical features of her uveitis were dissimilar to those found in that disease.

  16. Role of Early Onset Neutropenia in Development of Candidemia in Premature Infants.

    Science.gov (United States)

    Ramy, Nermin; Hashim, Mohamed; Abou Hussein, Heba; Sawires, Happy; Gaafar, Maha; El Maghraby, Ayat

    2017-04-24

    The aim of the study was to assess the effect of early-onset neutropenia (EON) on the development of candidemia in premature infants and evaluate other risk factors. This prospective study was carried out in a neonatal intensive care unit of Cairo University Hospital. Fifty neutropenic premature infants were matched to 50 non-neutropenics. Subjects were then regrouped into candidemics and non-candidemics to study other risk factors such as central venous catheters, mechanical ventilation, parenteral nutrition, drugs as corticosteroids and others. Candidemia was assessed by Bactec and then seminested polymerase chain reaction for culture negatives. Candidemia developed in 28 neutropenic preterms and in 8 non-neutropenics (odds ratio  = 6.68, 95% confidence interval = 2.61-17.1, p  candidemia in multivariate regression analysis included EON, mechanical ventilation and steroid therapy. EON is an independent risk factor for candidemia in premature infants.

  17. Rituximab-induced neutropenia in a patient with inflammatory myopathy and systemic sclerosis overlap disease.

    Science.gov (United States)

    Akram, Qasim; Roberts, Mark; Oddis, Chester; Herrick, Arianne; Chinoy, Hector

    2016-01-01

    Rituximab (RTX) is a monoclonal chimeric antibody directed against the CD20 antigen of B lymphocytes. Late onset neutropenia (LON) is a recognised complication of rituximab usually occurring 4 weeks after the last dose and is reported in both haematological and rheumatological conditions. However, it has never been described in a patient with myositis and systemic sclerosis overlap disease. We describe a case of LON in a 54-year-old man who was diagnosed with myositis and then systemic sclerosis overlap disease. It resolved within 7 days, and the patient did not suffer neutropenic sepsis or any other complications. We propose similar mechanisms for LON as described in other conditions and routine blood monitoring in such patients.

  18. 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......: Randomised clinical trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B. DATA COLLECTION AND ANALYSIS: The two review authors independently assessed trial eligibility and risk of bias and abstracted data. MAIN RESULTS: We found 13 trials (1960 patients). Lipid...... fungal infection (RR 0.63; 95% CI 0.39 to 1.01, P value 0.053).AmBisome, amphotericin B in Intralipid (6 trials, 379 patients), amphotericin B colloidal dispersion (ABCD) (2 trials, 262 patients), and amphotericin B lipid complex (ABLC) (1 trial, 105 patients) all decreased the occurrence...

  19. Prolonged or Standard Infusion of Cefepime Hydrochloride in Treating Patients With Febrile Neutropenia

    Science.gov (United States)

    2013-07-10

    Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Burkitt Lymphoma; Adult Diffuse Large Cell Lymphoma; Adult Diffuse Mixed Cell Lymphoma; Adult Diffuse Small Cleaved Cell Lymphoma; Adult Hodgkin Lymphoma; Adult Immunoblastic Large Cell Lymphoma; Adult Lymphoblastic Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Breast Cancer; Chronic Eosinophilic Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Cutaneous T-cell Non-Hodgkin Lymphoma; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Malignant Testicular Germ Cell Tumor; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Multiple Myeloma; Mycosis Fungoides/Sezary Syndrome; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neutropenia; Nodal Marginal Zone B-cell Lymphoma; Ovarian Epithelial Cancer; Ovarian Germ Cell Tumor; Plasma Cell Neoplasm; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Primary Myelofibrosis; Prolymphocytic Leukemia; Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  20. Economic burden of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review.

    Science.gov (United States)

    Wang, Xiao Jun; Lopez, Shaun Eric; Chan, Alexandre

    2015-05-01

    The primary objective of this review was to identify the cost components that were most frequently associated with the economic burden of febrile neutropenia (FN) among patients with lymphoma. The secondary objective was to identify any parameter associated with higher FN cost. Ten cost of illness (COI) studies were identified. General characteristics on study design, country, perspective, and patient population were extracted and systematically reported. It was observed that majority (70%) of the studies employed the perspective of healthcare provider. 20% of the studies considered long-term costs. Estimated costs were adjusted to 2013 US dollars and ranged from US$5819 to US$34,756. The cost components that were most frequently associated with economic burden were ward and medication costs. Inpatient management, male gender, discharged dead, and comorbidity were positively associated with higher FN costs. Future COI studies on FN should focus on the accurate estimation on ward and medication costs.

  1. [Consensus: Rational approach towards the patient with cancer, fever and neutropenia].

    Science.gov (United States)

    Santolaya, María Elena; Rabagliati, Ricardo; Bidart, Teresa; Payá, Ernesto; Guzmán, Ana M; Morales, Ricardo; Braun, Stephanie; Bronfman, Lucía; Ferrés, Marcela; Flores, Claudio; García, Patricia; Letelier, Luz M; Puga, Bárbara; Salgado, Carmen; Thompson, Luis; Tordecilla, Juan; Zubieta, Marcela

    2005-01-01

    The severity and duration of post chemotherapy neutropenia were recognized during the 1960s as main predisposing factors for infections in cancer patients. At the beginning of the 70's a standard management approach for all febrile neutropenia (FN) episodes was proposed, based on hospitalization and intravenous empirical broad spectrum antibiotic therapy. Widespread use of this approach resulted in a significant reduction in mortality attributable to bacterial infections. During the last 10 to 15 years, reappraisal of this standard approach has been done by several research groups who question the benefit of treating all FN patients similarly without taking in to consideration differences in severity of the FN episodes. This reappraisal has led during the 1990s to the development of the concept of high and low risk FN episodes that has been the base for the adoption of selective therapies based on the risk categorization of the individual patient. The Chilean Infectious Diseases Society called upon two government National Programs responsible for the appropriate distribution of chemotherapeutic drugs to all pediatric and adults cancer patients within the public health system, and upon the Chilean Hematology Society for the development of a Consensus on Diagnosis, Treatment and Prevention of Infections during FN Episodes in Cancer patients. The need for this Consensus is based on two main aspects: the new approaches proposed during the past year for management of these episodes, and the increasing population of cancer patients receiving improved chemotherapeutic agents that has increased there survival possibilities as well as there possibility to suffer a FN episode. The topics discussed in this document are based on an updated systematic and analytic review of the medical literature including epidemiology, laboratory diagnostics, risk categorization, treatment and prophylaxis. National data was included when available in order to provide the healthcare personnel

  2. The Value of C-Reactive Protein and Procalcitonin in Febrile Neutropenia

    Directory of Open Access Journals (Sweden)

    Solmaz Çelebi

    2009-06-01

    Full Text Available Aim: Febrile neutropenia is the major cause of mortality and morbidity in cancer patients. For this reason, early diagnosis of severe infections and appropriate antimicrobial therapy are very important. The aim of this study was to investigate the difference between C-reactive protein (CRP and procalcitonin in determining the sepsis and its severity. Materials and Method: A total of 30 children (35 episodes with febrile neutropenia who were hospitalized in the Uludag University, Pediatric Hematology and Oncology Unit were included in this prospective study. The blood samples for CRP and procalcitonin were collected daily between 0 to 5th days. Serum CRP and procalcitonin levels were compared with culture positivity, prolonged fever, mucositis and absolute granulosit count (AGC. Results: A total of 16 patients (56% diagnosed with acute leukemia and, 14 patients (46% having solid tumours were evaluated. In sequential analysis of febrile episodes, both the median of procalcitonin and the CRP concentrations showed the same tendency and there was no significant correlation between them (r=0.2, p>0.05. There was no significant association between CRP and procalcitonin among those having positive culture and mucositis. However, CRP values at the 3rd, 4th and 5th days were significantly higher in the patients with AGC100/mm3. Similarly, CRP values were significantly higher at the 1st, 2nd, 3rd and 4th days among the patients having prolonged fever. Conclusion: Our study suggests that there is no difference between CRP and procalcitonin in determining sepsis and its severity. Although procalcitonin is a valuable acute phase reactant in non-neutropenic patients, larger prospective investigations are needed to show the prognostic value of procalcitonin in neutropenic patients. (Journal of Current Pediatrics 2009; 7: 7-12

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

    DEFF Research Database (Denmark)

    Katzenstein, T L; Ullum, H; Røge, Birgit 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

  4. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Roberto Hegg

    Full Text Available OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI for the rate of neutropenia between the two groups (12.61% was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯.

  5. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Science.gov (United States)

    Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

    2016-01-01

    OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

  6. A simple and rapid DNA extraction method from whole blood for highly sensitive detection and quantitation of HIV-1 proviral DNA by real-time PCR.

    Science.gov (United States)

    McFall, Sally M; Wagner, Robin L; Jangam, Sujit R; Yamada, Douglas H; Hardie, Diana; Kelso, David M

    2015-03-01

    Early diagnosis and access to treatment for infants with human immunodeficiency virus-1 (HIV-1) is critical to reduce infant mortality. The lack of simple point-of-care tests impedes the timely initiation of antiretroviral therapy. The development of FINA, filtration isolation of nucleic acids, a novel DNA extraction method that can be performed by clinic personnel in less than 2 min has been reported previously. In this report, significant improvements in the DNA extraction and amplification methods are detailed that allow sensitive quantitation of as little as 10 copies of HIV-1 proviral DNA and detection of 3 copies extracted from 100 μl of whole blood. An internal control to detect PCR inhibition was also incorporated. In a preliminary field evaluation of 61 South African infants, the FINA test demonstrated 100% sensitivity and specificity. The proviral copy number of the infant specimens was quantified, and it was established that 100 microliters of whole blood is required for sensitive diagnosis of infants.

  7. Efficacy of Adenine in the Treatment of Leukopenia and Neutropenia Associated with an Overdose of Antipsychotics or Discontinuation of Lithium Carbonate Administration: Three Case Studies

    Science.gov (United States)

    Tomita, Takashi; Goto, Hidekazu; Sumiya, Kenji; Yoshida, Tadashi; Tanaka, Katsuya; Kohda, Yukinao

    2016-01-01

    Because adenine is effective for managing cases of radiation-induced and drug-induced leukopenia, it may be effective in cases of antipsychotic-induced leukopenia and neutropenia. Here, we report our experience with patients with leukopenia and neutropenia caused by an antipsychotic overdose or discontinuation of lithium carbonate, in whom adenine administration ameliorated the white blood cell and neutrophil counts. The progress of patients suggests that adenine is effective in cases of leukopenia and neutropenia associated with lithium carbonate discontinuation and an antipsychotic overdose. PMID:27776394

  8. Virus load as a marker of disease progression in HIV-infected children.

    Science.gov (United States)

    Tetali, S; Abrams, E; Bakshi, S; Paul, M; Oyaizu, N; Pahwa, S

    1996-05-20

    The relationship of virus load to clinical disease progression in HIV-infected children remains to be elucidated. In this study, HIV-1 proviral DNA load was determined in peripheral blood mononuclear cells (PBMCs) by the quantitative competitive DNA polymerase chain reaction assay (QC-PCR) in 47 HIV-infected children subdivided by age (group I, or = 5 years), who were further categorized to include 12 rapid progressors (RP, age or = 5 years, excluding CDC categories C and/or immune category 3). Significantly higher mean proviral copies/10(3) PBMCs were detected in group I versus group II (75.4 +/- 104.3 and 13.0 +/- 17.8 respectively, p < 0.0001) and in RP (158.0 +/- 118.2) as compared to either SP (11.8 +/- 18.8, p < 0.0001) or other age-matched infected children (20.3 +/- 38.8, p < 0.0001). Thus HIV-infected children appear to have a higher cell-associated virus load early in life, especially in association with rapid disease progression.

  9. 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

    Directory of Open Access Journals (Sweden)

    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

  10. Load Measurements

    DEFF Research Database (Denmark)

    Kock, Carsten Weber; Vesth, Allan

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regarding...... the fatigue loads, the rotor, blades and tower moments are presented. The fatigue loads are evaluated using rainflow counting described in detail in Ref. [1]. The 1Hz equivalent load ranges are calculated at different wind speeds. All information regarding the instrumentation is collected in [ref 4] and [ref...

  11. Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors.

    Science.gov (United States)

    Oguz, Aynur; Karadeniz, Ceyda; Citak, Elvan Caglar; Cil, Visal; Eldes, Nilufer

    2006-01-01

    A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.

  12. Rapid lung MRI - paradigm shift in evaluation of febrile neutropenia in children with leukemia: a pilot study.

    Science.gov (United States)

    Sodhi, Kushaljit Singh; Khandelwal, Niranjan; Saxena, Akshay Kumar; Bhatia, Anmol; Bansal, Deepak; Trehan, Amita; Singh, Meenu; Agarwal, Ritesh

    2016-01-01

    Immunocompromised children with hematological malignancies are at increased risk of developing potentially fatal pulmonary infections. Early detection and prompt treatment is critical to combat morbidity and mortality in these children. Twenty-six children with leukemia (age range: 5-13years) presenting with fever and neutropenia were included in this prospective study, which was approved by the institutional ethics committee. All patients underwent HRCT and MRI of the chest on the same day. The findings of HRCT and MRI were compared, with HRCT as the standard of reference. There was perfect agreement between MRI and CT examinations findings by kappa test (κ = 1). No significant difference was observed between the two modalities by the McNemar test (p > 0.05). Rapid lung MRI is technically feasible; has a high correlation, sensitivity and specificity to CT scan; and can emerge as the first line modality for the detection of pulmonary nodules in children with leukemia and persistent febrile neutropenia.

  13. 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.

    Science.gov (United States)

    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.

  14. Detection of bacteria, fungi, and viruses by a real-time PCR assay using universal primers and probes from blood in patients with febrile neutropenia.

    OpenAIRE

    TERANISHI, Hideto; OUCHI, Kazunobu

    2014-01-01

    Febrile neutropenia is the main treatment-related cause of mortality in cancer patients. During June 2012 to April 2013, 76 blood culture samples from patients receiving chemotherapy for hematological malignancy and cancer with febrile neutropenia episodes (FNEs) were examined for the presence of bacteria and fungi based on 16S rRNA gene and 18S rRNA combined with real-time PCR amplification and sequencing. Furthermore, we used a loopmediatedisothermal amplification (LAMP) assay for the detec...

  15. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    OpenAIRE

    1995-01-01

    textabstractBACKGROUND. In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction pathways for granulocyte colony-stimulating factor (G-CSF) may play a part in the progression to acute myeloid leukemia. METHODS. We isolated genomic DNA and RNA from hematopoietic cells obtained from two patients with acute m...

  16. C-reactive protein and the MASCC risk index identify high-risk patients with febrile neutropenia and hematologic neoplasms.

    Science.gov (United States)

    Combariza, Juan F; Lombana, Milton; Pino, Luis E; Arango, Marcos

    2015-04-01

    The objective of this study is to assess the prognostic usefulness of the Multinational Association of Supportive Care in Cancer (MASCC) risk score in association with the value of C-reactive protein (CRP) to identify high-risk patients with febrile neutropenia and hematologic neoplasms. A retrospective cohort study in which the MASCC score and the CRP values were used to assess the mortality risk at 30 days among patients with febrile neutropenia and hematologic malignancies was performed. Two hundred thiry-seven patients with febrile neutropenia were analyzed; the mortality rate within 30 days was 9 %. High-risk patients according to the MASCC score were significantly more likely to experience adverse outcomes, such as being transferred to the intensive care unit (RR 3.55; CI 95 % 2.73-6.62, p risk group identified by the MASCC score (HR 3.0; CI 95 % 1.12-13.54, p = 0.032) and the mean levels of CRP (HR 17; CI 95 % 2.21-136.48, p = 0.007) and survival. The survival rate within 30 days was 100 % for the patients with a low-risk MASCC score and a mean CRP less than 15 mg/dL. This rate was only 64 % for high-risk patients with a mean CRP greater than 15 mg/dL. The MASCC risk score combined with the mean CRP value successfully identifies patients with febrile neutropenia and hematological malignancies and a high risk of death.

  17. A Case of Neonatal Neutropenia Due to Anti-Fc Gamma Receptor IIIb Isoantibodies Treated with Recombinant Human Granulocyte Colony Stimulating Factor

    Directory of Open Access Journals (Sweden)

    Maja Tomicic

    2009-01-01

    Full Text Available Alloimmunization to granulocyte-specific antigens can occur during pregnancy. Maternal antibodies of IgG class can cross the placenta to result in alloimmune neonatal neutropenia. Antibodies to human neutrophil antigens anti-HNA-1a, HNA-1b, and HNA-2a have been most commonly reported to cause alloimmune neonatal neutropenia. Isoantibodies to Fc gamma RIIIb (CD16 if mother is a HNA-null phenotype are rarely involved in neonatal neutropenia. We report on a case of severe neutropenia (440 neutrophils/μL due to anti-Fc gamma RIIIb (CD16 isoimmunization. On day 14 severe omphalitis developed, which was treated for 7 days by an antibiotic (ceftriaxone in a dose of 80 mg/kg/d according to umbilical swab finding. Omphalitis persisted for 10 days in spite of antibiotic therapy and only resolved upon the introduction of rhG-CSF therapy. Therapy with rh-GCSF proved efficient and led to neutrophil count increase to 1970/μL and cure of omphalitis. However, therapeutic effect on granulocyte count was of transient nature, as granulocyte count fell to 760 n/μL on day 4 of therapy discontinuation. Neutropenia persisted for 2 months. The newborn was discharged from the hospital on day 26 with normal clinical status with clinical and laboratory control examinations at 2-week intervals. No additional infections were observed during the course of neutropenia.

  18. Neutropenia relacionada con la quimioterapia en tumores sólidos. Hospital General Universitario Camilo Cienfuegos Enero 2009- 2013

    Directory of Open Access Journals (Sweden)

    Yania Luisa Jiménez Madrigal

    2015-09-01

    Full Text Available Se realizó un estudio descriptivo de corte transversal y retrospectivo referente al comportamiento de la neutropenia relacionada con la quimioterapia en tumores sólidos en el período comprendido Enero 2009- 2013 atendido en el servicio de oncología del Hospital General Universitario Camilo Cienfuegos de la provincia Sancti-Spíritus. La población la conformaron 230 enfermos neutropénicos relacionados con la quimioterapia. La investigación describe de forma general la relación existente entre la neutropenia con la quimioterapia, localización tumoral, entidades nosológicas asociadas, edad, sexo, tratamientos quimioterapéuticos y antibióticos más utilizados. Pudo observarse que existe alta incidencia de neutropenia relacionada con la quimioterapia en pacientes con cáncer de pulmón, el grupo más afectado fue el de 50-59 años predominando el sexo femenino con un alto índice de hipertensos asociados. Los tratamientos más utilizados fueron Etopóxido-Platino y Ceftrixone-Amikacina.

  19. Detection of monoclonal integration of bovine leukemia virus proviral DNA as a malignant marker in two enzootic bovine leukosis cases with difficult clinical diagnosis.

    Science.gov (United States)

    Miura, Saori; Horiuchi, Noriyuki; Matsumoto, Kotaro; Kobayashi, Yoshiyasu; Kawazu, Shin-Ichiro; Inokuma, Hisashi

    2015-07-01

    Monoclonal integration of bovine leukemia virus (BLV) proviral DNA into bovine genomes was detected in peripheral blood from two clinical cases of enzootic bovine leukosis (EBL) without enlargement of superficial lymph nodes. A BLV-specific probe hybridized with 1 to 3 EcoRI and HindIII fragments in these 2 atypical EBL cattle by Southern blotting and hybridization, as well as in 3 typical EBL cattle. The probe also hybridized to a large number of EcoRI and HindIII fragments in 5 cattle with persistent leukosis. These results suggest that the detection of monoclonal integration of BLV provirus into the host genome may serve as a marker of monoclonal proliferation and malignancy in difficult to diagnose EBL cattle.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Early discontinuation of intravenous antimicrobial therapy in pediatric oncology patients with febrile neutropenia

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    Grundy Paul E

    2005-05-01

    Full Text Available Abstract Background There are no standard criteria for when to discontinue intravenous antimicrobial therapy (IVAMT in children with febrile neutropenia (FN, but it is now common to discontinue IVAMT and discharge patients with an absolute neutrophil count (ANC ≤ 500 /mm3. The purpose of this study was to evaluate the outcome of a large cohort of children with FN who had IVAMT discontinued with an ANC ≤ 500 /mm3 Methods A retrospective chart review was completed of patients in the Northern Alberta Children's Cancer Program with FN and no apparent clinical source of fever from June 1, 1997 to July 1, 2002. Results Out of a total of 275 patients, 127 (46% had at least one episode of FN, with FN occurring in patients with sarcomas more commonly than in those with leukemia/ lymphoma and least in those with other solid tumors. In 59 of 276 episodes of FN (21% patients had a microbiologically defined infection at admission. Of the 217 remaining episodes, 112 of 199 patients (56% with known neutrophil counts had IVAMT discontinued before their absolute neutrophil count (ANC reached 500 /mm3 at the discretion of the clinician. Fever recurred in only two of these patients after discharge, and there were no bacterial infections diagnosed after parenteral antibiotics were discontinued. Conclusion Even without use of standard criteria for early discharge, clinicians appear to be skilled at selecting children with FN who can safely have IVAMT discontinued with an ANC ≤ 500 /mm3.

  2. 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.

  3. Dopamine is a safe antiangiogenic drug which can also prevent 5-fluorouracil induced neutropenia.

    Science.gov (United States)

    Sarkar, Chandrani; Chakroborty, Debanjan; Dasgupta, Partha Sarathi; Basu, Sujit

    2015-08-01

    The role of vascular endothelial growth factor A (VEGFA) in tumor angiogenesis is well established and accordingly, molecules targeting VEGFA or its receptors are being presently used in the clinics for treatment of several types of cancer. However, these antiangiogenic agents are expensive and have serious side effects. Thus identification of newer drugs with manageable systemic side effects or toxicities is of immense clinical importance. Since we have reported earlier that dopamine (DA) inhibits VEGFA induced angiogenesis in experimental tumor models, we therefore sought to investigate whether DA treatment results in similar toxicities like other antiangiogenic agents. Our results indicated that unlike sunitinib, another commonly used antiangiogenic agent in the clinics which targets VEGF receptors, DA [50 mg/kg/days × 7days intraperitoneally (i.p.)] not only could inhibit tumor angiogenesis and growth of HT29 human colon cancer and LLC (Lewis lung carcinoma) in mice, it also did not cause hypertension, hematological, renal and hepatic toxicities in normal, HT29 and LLC tumor bearing animals. Furthermore and interestingly, in contrast to the currently used antiangiogenic agents, DA also prevented 5-fluorouracil (5FU) induced neutropenia in HT29 colon cancer bearing mice. This action of DA was through inhibition of 5FU mediated suppression of colony forming unit-granulocyte macrophage colony forming units in the bone marrow. Thus our results indicate that DA may be safely used as an antiangiogenic drug for the treatment of malignant tumors.

  4. Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012).

    Science.gov (United States)

    Balda, María V; Garay, Osvaldo U; Papale, Rosa M; Bignone, Inés; Bologna, Viviana G; Brandolini, Andrés; Prokopez, Cintia R; Balasini, Juan I; Baldessarini, Ross J; Daray, Federico M

    2015-03-01

    The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.

  5. Load Measurements

    DEFF Research Database (Denmark)

    Vesth, Allan; Kock, Carsten Weber

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regardi...

  6. Load Measurements

    DEFF Research Database (Denmark)

    Kock, Carsten Weber; Vesth, Allan

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regarding...

  7. 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

  8. 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

  9. Proviral integrations and expression of endogenous Avian leucosis virus during long term selection for high and low body weight in two chicken lines

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    Bornold Lina

    2009-07-01

    Full Text Available Abstract Background Long-term selection (> 45 generations for low or high juvenile body weight from a common founder population of White Plymouth Rock chickens has generated two extremely divergent lines, the LWS and HWS lines. In addition to a > 9-fold difference between lines for the selected trait, large behavioural and metabolic differences between the two lines evolved during the course of the selection. We recently compared gene expression in brain tissue from birds representing these lines using a global cDNA array analysis and the results showed multiple but small expression differences in protein coding genes. The main differentially expressed transcripts were endogenous retroviral sequences identified as avian leucosis virus subgroup-E (ALVE. Results In this work we confirm the differential ALVE expression and analysed expression and number of proviral integrations in the two parental lines as well as in F9 individuals from an advanced intercross of the lines. Correlation analysis between expression, proviral integrations and body weight showed that high ALVE levels in the LWS line were inherited and that more ALVE integrations were detected in LWS than HWS birds. Conclusion We conclude that only a few of the integrations contribute to the high expression levels seen in the LWS line and that high ALVE expression was significantly correlated with lower body weights for the females but not males. The conserved correlation between high expression and low body weight in females after 9 generations of intercrosses, indicated that ALVE loci conferring high expression directly affects growth or are very closely linked to loci regulating growth.

  10. 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.

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

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    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.

  12. Impact of multiplex PCR on antimicrobial treatment in febrile neutropenia: a randomized controlled study.

    Science.gov (United States)

    Idelevich, Evgeny A; Silling, Gerda; Niederbracht, Yvonne; Penner, Hanna; Sauerland, Maria Cristina; Tafelski, Sascha; Nachtigall, Irit; Berdel, Wolfgang E; Peters, Georg; Becker, Karsten

    2015-10-01

    Multiplex PCR (mPCR) directly from blood has been suggested as a promising method for rapid identification of pathogens causing sepsis. This study aimed to investigate whether mPCR has any impact on antimicrobial treatment. Hematological patients with febrile neutropenia were randomized into two groups. In the study group, mPCR was performed as an addition to standard diagnostics, and PCR finding was immediately communicated to the clinicians, thus being available for decision making. In the control group, clinicians were not aware of PCR result. PCR samples were collected simultaneously with clinically indicated blood culture specimens from peripheral vein and/or central venous catheter at fever onset and once again if fever persisted up to 72 h. Overall, 74 patients of the study group and 76 patients of the control group were enrolled and 253 samples collected. Therapy was changed to targeted antimicrobial therapy (AMT) in 12 patients (16.2%) in the study group and in 12 patients (15.8%) in the control group. For patients with changes, the median time to change to the targeted AMT was 21.4 h in the study group and 47.5 h in the control group (p = 0.018). In the study group, 57.1% (8/14) of changes to targeted AMT was due to PCR finding. PCR led to AMT change in 9.5% (7/74) of study group patients, i.e., in 33.3% (7/21) of patients who had positive PCR finding. There were no significant differences in patient outcomes (secondary endpoints). In conclusion, PCR method accelerates change to the targeted AMT in febrile neutropenic patients.

  13. 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

  14. 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.

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

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    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.

  16. Clinical impact of fluoroquinolone-resistant Escherichia coli in the fecal flora of hematological patients with neutropenia and levofloxacin prophylaxis.

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    Yong Chong

    Full Text Available BACKGROUND: Fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated. METHODS: We prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times. RESULTS: In this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P = 0.65. Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum β-lactamase (ESBL producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis. CONCLUSIONS: Levofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis.

  17. Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery

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    Schwenkglenks Matthias

    2010-08-01

    Full Text Available Abstract Background In newly diagnosed patients with Hodgkin lymphoma (HL the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN on ABVD chemotherapy delivery in HL patients. Study design Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events. Results Chemotherapy delivery was suboptimal (with a relative dose intensity ≤ 85% in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%. Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%. Use of primary colony-stimulating factor (CSF prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively. The relative risk (RR of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036 for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046 for patients with vs. without primary CSF prophylaxis. Conclusions In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.

  18. Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.

    Science.gov (United States)

    Craig, Morgan; Humphries, Antony R; Nekka, Fahima; Bélair, Jacques; Li, Jun; Mackey, Michael C

    2015-11-21

    The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy.

  19. Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections.

    Science.gov (United States)

    Moen, Marit D; Lyseng-Williamson, Katherine A; Scott, Lesley J

    2009-01-01

    Liposomal amphotericin B (AmBisome) is a lipid-associated formulation of the broad-spectrum polyene antifungal agent amphotericin B. It is active against clinically relevant yeasts and moulds, including Candida spp., Aspergillus spp. and filamentous moulds such as Zygomycetes, and is approved for the treatment of invasive fungal infections in many countries worldwide. It was developed to improve the tolerability profile of amphotericin B deoxycholate, which was for many decades considered the gold standard of antifungal treatment, despite being associated with infusion-related events and nephrotoxicity. In well controlled trials, liposomal amphotericin B had similar efficacy to amphotericin B deoxycholate and amphotericin B lipid complex as empirical therapy in adult and paediatric patients with febrile neutropenia. In addition, caspofungin was noninferior to liposomal amphotericin B as empirical therapy in adult patients with febrile neutropenia. For the treatment of confirmed invasive fungal infections, liposomal amphotericin B was more effective than amphotericin B deoxycholate treatment in patients with disseminated histoplasmosis and AIDS, and was noninferior to amphotericin B deoxycholate in patients with acute cryptococcal meningitis and AIDS. In adults, micafungin was shown to be noninferior to liposomal amphotericin B for the treatment of candidaemia and invasive candidiasis. Data from animal studies suggested that higher dosages of liposomal amphotericin B might improve efficacy; however, in the AmBiLoad trial in patients with invasive mould infection, there was no statistical difference in efficacy between the standard dosage of liposomal amphotericin B 3 mg/kg/day and a higher 10 mg/kg/day dosage, although the standard dosage was better tolerated. Despite being associated with fewer infusion-related adverse events and less nephrotoxicity than amphotericin B deoxycholate and amphotericin B lipid complex, liposomal amphotericin B use is still limited to

  20. Caracterización de pacientes pediátricos con neutropenia enviados a un hospital de referencia Characterization of neutropenic pediatric patients sent to a referral centre

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Lazo-Páez

    2010-06-01

    Full Text Available Objetivo: La neutropenia es un motivo relativamente frecuente de referencia al Servicio de Inmunología y Reumatología Pediátrica del Hospital Nacional de Niños; el estudio pretende caracterizar los casos de neutropenia referidos a este Servicio en el periodo comprendido entre noviembre de 1988 y junio de 2008. Métodos: Se estudiaron 84 pacientes entre 0 y 12 años de edad, referidos entre el 6 de noviembre de 1988 y el 1 de junio de 2008. Se efectuó un análisis descriptivo global de las características presentadas por estos pacientes en términos de evolución clínica, patrón de infección, gérmenes más frecuentes causantes de infección, complicaciones y tratamiento. Resultados: El 52.2% de los pacientes analizados resolvieron su neutropenia espontáneamente, por lo que fueron catalogados como neutropenia transitoria; el 21.7% de los casos evolucionó como neutropenia cíclica; el 13% de los pacientes fueron catalogados como neutropenia crónica benigna; el 7.2% evolucionaron como neutropenia crónica grave sintomática; el 2.9% tuvieron neutropenia asociada a glucogenosis tipo 1B, y el 2.9% de los casos no fueron clasificables en las categorías propuestas. El 56.5% de los casos se asoció a un patrón de infección anormal, sea por incremento en la frecuencia, mayor gravedad, compromiso multisistémico o presencia de microorganismos oportunistas. El sistema más afectado por infección fue la vía respiratoria superior. El 39.1% de los casos de neutropenia evaluados ameritaron uso de antibióticos profilácticos, y el 11.6% de los casos requirieron usar factor estimulante de colonias granulocíticas, en algún momento de su evolución. Los gérmenes más frecuentemente involucrados en infección fueron Pseudomona aeruginosa, Staphylococcus spp y E. coli. Conclusión: La gran mayoría de los pacientes neutropénicos estudiados tiene un curso clínico benigno caracterizado por pocas hospitalizaciones y una intervención farmacol

  1. Early lymphopenia as a risk factor for chemotherapy-induced febrile neutropenia.

    Science.gov (United States)

    Choi, Chul Won; Sung, Hwa Jung; Park, Kyong Hwa; Yoon, So Young; Kim, Seok Jin; Oh, Sang Cheul; Seo, Jae Hong; Kim, Byung Soo; Shin, Sang Won; Kim, Yeul Hong; Kim, Jun Suk

    2003-08-01

    Febrile neutropenia (FN) is a frequent complication of cancer chemotherapy, which causes death in 4-21% of patients and worsens the quality of life of patients. As a simple and accurate way of identifying patients who are at risk of FN, a lymphocyte count on post-chemotherapy day 5 was suggested. To confirm the feasibility of this method and to define the incidence of FN among our own patient group, we conducted this prospective study. From September 2001 to February 2002, patients who received cytotoxic chemotherapy at Guro Hospital, Korea University, were enrolled. Blood sampling for a complete blood count was done on the starting day of chemotherapy and on day 3 and day 5 post-chemotherapy. The prospective results of the CBC were compared between the FN group and non-FN group. During the study period, 82 patients were enrolled. The male to female ratio was 52:30, and the median age was 56 years old (range: 14-78). Underlying malignancies were non-Hodgkin's lymphoma (14 patients), stomach cancer (17), breast cancer (11), NSCLC (7), hepatobiliary cancer (10), sarcoma (3), colorectal cancer (3), and others (17). The incidence of FN was 18% (15/82 patients), and ANC at the time of FN was 275 +/- 327/ micro l. Duration of fever was 3.9 +/- 3.5 days. The incidence of FN was significantly higher in patients with lymphocyte counts at day 3 < or = 500/micro l (P = 0.06), day 5 < or = 500/micro l (P = 0.023), day 3 < or = 700/micro l (P = 0.01), and day 5 < or = 700/micro l (P = 0.0001). As a result of a logistic regression test, a day-5 lymphocyte count < or = 700/ micro l was identified as an independent risk factor for FN. In conclusion, a day-5 lymphocyte count <700/micro l was a risk factor for FN. To strengthen our result, we are planning to validate in a larger patient group.

  2. Clinical study on immune neutropenia%免疫性中性粒细胞减少症临床研究

    Institute of Scientific and Technical Information of China (English)

    银广悦; 王文红; 龚庆辉; 张继领

    2012-01-01

    Objective To explore the diagnosis and of immune neutopenia.Methods Clinical data of 150 patients with immune neutropenia were collected and analyzed.Results Of 150 patients with immune neutropenia,35 cases went male(23.3%),115 cases were female(76.7%),and male to female ratio was 1 ∶ 3.3.Based on the difference produced way of granulocytes associated antibody,all patients could be divided into alloimmune neonatal neutropenia 9 cases (6.0%),drug-induced immune neutropenia 28 cases (18.7 %),primary autoimmune neutropenia 22 cases(14.6%),and secondary autoimmune neutropenia 91 cases (60.7%).Secondary autoimmune neutropenia included 39 cases of systemic lupus erythematous,21 cases of rheumatoid arthritis,2 cases of immune hemolytic anemia accompany with neutropenia,6 cases of immune thrombocytopenia accompany with neutropenia,3 cases of autoimmune hepatitis,16 cases of autoimmune thyroiditis,and 4 cases of Sjogren's syndrome.Conclusion The majority of primary immune neutropenia are female,which is usually secondary to autoimmune diseases.The diagnosis of primary immune neutropenia is very complicated,which requires a long period of clinical observation and follow-up.The majority of granulocytes associated antibody is IgG in the autoimmune neutropenia patients.Yet sometimes two or three kinds of antibodies were increased as well.%目的 探讨免疫性粒细胞减少症的诊断及治疗.方法 收集150例住院及门诊免疫性中性粒细胞减少症患者临床资料.利用SPSS 13.0进行数据的统计分析.结果 150例患者中,男性35例(23.3%),女性115例(76.7%),男女之比为1∶3.3.依据中性粒细胞抗体产生方式不同分为新生儿同种免疫性中性粒细胞减少症9例(6.0%);药物性免疫粒细胞减少症28例(18.7%);原发性自身免疫性中性粒细胞减少症22例(14.6%);继发性免疫性粒细胞减少症91例(60.7%):包括系统性红斑狼疮39例、类风湿关节炎21例、免

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

    Science.gov (United States)

    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 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Variation in Management of Fever and Neutropenia Among Pediatric Patients With Cancer: A Survey of Providers in Michigan.

    Science.gov (United States)

    Mueller, Emily L; Walkovich, Kelly J; Yanik, Gregory A; Clark, Sarah J

    2015-01-01

    Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An online survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for "Decreased" and "Increased" risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%); the majority defined a febrile event as temperature >38.3°C and/or 2 events >38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) 2 hours away. Respondents were significantly more likely to have a "Decreased Risk" patient travel over 2 hours if they rated the local ED as "Poor to Fair" on ability to access Port-a-caths (P = .048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL; 40% preferred discharge on oral antibiotics when the ANC febrile pediatric patients with cancer is significantly influenced by the providers' perceptions of local EDs. Future investigation of local hospitals' ability to provide urgent evaluation, combined with parental perspectives, could lead to improvements in timely and effective management.

  6. The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febrile neutropenia resulted from methotrexate toxicity.

    Science.gov (United States)

    Ozkol, Hatice Uce; Toptas, Tayfur; Calka, Omer; Akdeniz, Necmettin

    2015-01-01

    Methotrexate (MTX) remains one of the most frequently used anti-metabolite agents in dermatology. MTX is an analog of folate that competitively and irreversibly inhibits dihydrofolate reductase. Oral mucositis is a common side effect of chemotherapy drugs and is characterized by erythema, pain, poor oral intake, pseudomembranous destruction, open ulceration and hemorrhage of the oral mucosa. In this paper, we report a 32-year-old female with a case of mucositis due to MTX intoxication that resulted from an overdose for rheumatoid arthritis. The patient had abdominal pain, vomiting, and nausea. During follow-up, the patient's white blood cell count was found to be 0.9 × 10(9)/L (4-10 × 10(9)/L). The patient developed fever exceeding 40 °C. The patient was consulted to the hematology service. They suggested using granulocyte colony-stimulating factor for febrile neutropenia. On the fifth day of treatment, the white blood cell count reached 5.3 × 10(9)/L and the patient's fever and mucositis started to resolve. Here, we presented a case of hemorrhagic mucositis and febrile neutropenia resulted from high-dose MTX that responded very well to granulocyte colony-stimulating factor treatment and we reviewed the literature.

  7. Iron load

    Directory of Open Access Journals (Sweden)

    Filippo Cassarà

    2013-03-01

    Full Text Available Recent research addressed the main role of hepcidin in the regulation of iron metabolism. However, while this mechanism could be relevant in causing iron load in Thalassemia Intermedia and Sickle-Cell Anemia, its role in Thalassemia Major (TM is marginal. This is mainly due to the high impact of transfusional requirement into the severe increase of body iron. Moreover, the damage of iron load may be worsened by infections, as HCV hepatitis, or liver and endocrinological damage. One of the most relevant associations was found between splenectomy and increase of risk for mortality due,probably, to more severe iron load. These issues suggest as morbidity and mortality of this group of patients they do not depend only by our ability in controlling heart damage but even in preventing or treating particular infections and complications. This finding is supported by the impairment of survival curves in patients with complications different from heart damage. However, because, during recent years different direct and indirect methods to detect iron overload in patients affected by secondary hemochromatosis have been implemented, our ability to maintain under control iron load is significantly improved. Anyway, the future in iron load management remains to be able to have an iron load map of our body for targeting chelation and other medical treatment according to the single organ damage.

  8. Clinical and microbiological profile of children with febrile neutropenia following antineoplastic treatments in a hospital in Medellin (Colombia), 2009-2010: case series

    OpenAIRE

    Martínez Sánchez, Lina Maria; Universidad Pontificia Bolivariana; Palacio Mesa, María Juliana; Universidad pontificia bolivariana; Diosa Restrepo, Mariana; Universidad pontificia bolivariana; Ramírez Pulgarín, Sergio; Universidad Pontificia Bolivariana; Rodríguez Gázquez, María de los Angeles; Universidad pontificia bolivariana; Orozco Forero, Juan Pablo; Universidad pontificia bolivariana

    2015-01-01

    La neutropenia febril compromete la respuesta inmunológica, facilitando la invasión de microorganismos generando altas tasas de morbilidad y mortalidad. Objetivo: describir el perfil clínico y microbiológico de los niños con neutropenia febril sometidos a tratamientos antineoplásicos, en una institución hospitalaria de Medellín. Materiales y métodos: estudio descriptivo retrospectivo en el que se incluyeron las historias clínicas de 34 pacientes pediátricos con tratamiento antineoplásico, neu...

  9. [Effectiveness of Leukostim, a Russian preparation of granulocyte colony-stimulating factor, in the treatment of chemotherapy-induced neutropenia in patients with malignant tumors].

    Science.gov (United States)

    Korman, D B; Boronovskaia, L E; Maslova, I A; Andreeva, E V; Seregina, G V

    2008-01-01

    Recombinant preparation of human G-CSF-Leukostim (Russia)--(filgrastim; analog of Neupogen)--was administered in 31 patients (breast cancer--28; ovarian carcinoma--3) to treat or prevent chemotherapy-induced neutropenia. The latter was aborted after 2-6 injections. Due to use of Leukostim, another course of chemotherapy (10 cycles) was successfully used in 5 breast cancer patients: no inhibition of hemopoiesis followed although the patients had suffered acute and persistent neutropenia from previous chemotherapy. No adverse side-effects of Leukostim administration were reported.

  10. Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins

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    Daniel Sauter

    2015-02-01

    Full Text Available NF-κB is essential for effective transcription of primate lentiviral genomes and also activates antiviral host genes. Here, we show that the early protein Nef of most primate lentiviruses enhances NF-κB activation. In contrast, the late protein Vpu of HIV-1 and its simian precursors inhibits activation of NF-κB, even in the presence of Nef. Although this effect of Vpu did not correlate with its ability to interact with β-TrCP, it involved the stabilization of IκB and reduced nuclear translocation of p65. Interestingly, however, Vpu did not affect casein kinase II-mediated phosphorylation of p65. Lack of Vpu was associated with increased NF-κB activation and induction of interferon and interferon-stimulated genes (ISGs in HIV-1-infected T cells. Thus, HIV-1 and its simian precursors employ Nef to boost NF-κB activation early during the viral life cycle to initiate proviral transcription, while Vpu is used to downmodulate NF-κB-dependent expression of ISGs at later stages.

  11. Sphingosine kinase 1 serves as a pro-viral factor by regulating viral RNA synthesis and nuclear export of viral ribonucleoprotein complex upon influenza virus infection.

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    Young-Jin Seo

    Full Text Available Influenza continues to pose a threat to humans by causing significant morbidity and mortality. Thus, it is imperative to investigate mechanisms by which influenza virus manipulates the function of host factors and cellular signal pathways. In this study, we demonstrate that influenza virus increases the expression and activation of sphingosine kinase (SK 1, which in turn regulates diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF-κB activation and markedly reduced the synthesis of viral RNAs and proteins. Further, SK blockade interfered with activation of Ran-binding protein 3 (RanBP3, a cofactor of chromosome region maintenance 1 (CRM1, to inhibit CRM1-mediated nuclear export of the influenza viral ribonucleoprotein complex. In support of this observation, SK inhibition altered the phosphorylation of ERK, p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation. Collectively, these results indicate that SK is a key pro-viral factor regulating multiple cellular signal pathways triggered by influenza virus infection.

  12. Insights into HIV-1 proviral transcription from integrative structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex

    Science.gov (United States)

    Schulze-Gahmen, Ursula; Echeverria, Ignacia; Stjepanovic, Goran; Bai, Yun; Lu, Huasong; Schneidman-Duhovny, Dina; Doudna, Jennifer A; Zhou, Qiang; Sali, Andrej; Hurley, James H

    2016-01-01

    HIV-1 Tat hijacks the human superelongation complex (SEC) to promote proviral transcription. Here we report the 5.9 Å structure of HIV-1 TAR in complex with HIV-1 Tat and human AFF4, CDK9, and CycT1. The TAR central loop contacts the CycT1 Tat-TAR recognition motif (TRM) and the second Tat Zn2+-binding loop. Hydrogen-deuterium exchange (HDX) shows that AFF4 helix 2 is stabilized in the TAR complex despite not touching the RNA, explaining how it enhances TAR binding to the SEC 50-fold. RNA SHAPE and SAXS data were used to help model the extended (Tat Arginine-Rich Motif) ARM, which enters the TAR major groove between the bulge and the central loop. The structure and functional assays collectively support an integrative structure and a bipartite binding model, wherein the TAR central loop engages the CycT1 TRM and compact core of Tat, while the TAR major groove interacts with the extended Tat ARM. DOI: http://dx.doi.org/10.7554/eLife.15910.001 PMID:27731797

  13. The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus.

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    Thomas von Hahn

    Full Text Available The pan-protein kinase C (PKC inhibitor sotrastaurin (AEB071 is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV and hepatitis C virus (HCV, major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients.

  14. The novel immunosuppressive protein kinase C inhibitor sotrastaurin has no pro-viral effects on the replication cycle of hepatitis B or C virus.

    Science.gov (United States)

    von Hahn, Thomas; Schulze, Andreas; Chicano Wust, Ivan; Heidrich, Benjamin; Becker, Thomas; Steinmann, Eike; Helfritz, Fabian A; Rohrmann, Katrin; Urban, Stephan; Manns, Michael P; Pietschmann, Thomas; Ciesek, Sandra

    2011-01-01

    The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients.

  15. 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.

  16. Fever and neutropenia due to cytomegalovirus infection in a breast cancer patient under chemotherapy: a case report

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    Ahmadinejad Z

    2010-06-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Fever in neutropenic patients is a medical emergency which may happen in patients undergoing chemotherapy. The definition of neutropenia varies from institution to institution but is usually defined as an absolute neutrophil count (ANC    < 500 cells/ml or < 1,000 cells/ml with a predicted nadir of < 500 cells/ml. Bacterial and fungal infections are the most important in neutropenic patients. Viral infections with agents such as herpes simplex virus and cytomegalovirus are common but less than other pathogens."n"nCase presentation: We report a patient with fever & neutropenia following cytomegalovirus infection during chemotherapy course for breast cancer."n"nConclusion: Although fever and neutropenia after cytomegalovirus infection is not very common but prompt diagnosis and treatment of this disease reduces the mortality and morbidity associated with cytomegalovirus. For this reason, screen testing for CMV infection in high risk patients including patients with cancer and preemptive therapy in patients with viremia, for prevention of CMV disease could be considered as a strategy for prevention of CMV infection.

  17. 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

  18. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry

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    Beaussant Cohen Sarah

    2012-09-01

    Full Text Available Abstract Background WHIM syndrome (WS, a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the light of the recent development of new CXCR4 inhibitors. Objective This study aims to describe the natural history of WS based on a French cohort of 8 patients. Methods We have reviewed the clinical, biological and immunological features of patients with WS enrolled into the French Severe Chronic Neutropenia Registry. Results We identified four pedigrees with WS comprised of eight patients and one foetus. Estimated incidence for WS was of 0.23 per million births. Median age at the last visit was 29 years. Three pedigrees encompassing seven patients and the fetus displayed autosomal dominant heterozygous mutations of the CXCR4 gene, while one patient presented a wild-type CXCR4 gene. Two subjects exhibited congenital conotruncal heart malformations. In addition to neutropenia and myelokathexis, all patients presented deep monocytopenia and lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well as severe bacterial infections that were curable with antibiotics. Four patients with late onset prophylaxis developed chronic obstructive pulmonary disease (COPD. Two patients reported atypical mycobacteria infections which in one case may have been responsible for one patient’s death due to liver failure at the age of 40.6 years. HPV-related disease manifested in five subjects and progressed as invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5 years. In addition, two patients developed T cell lymphoma skin cancer and basal cell carcinoma at the age of 38 and 65 years. Conclusions

  19. 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

  20. 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

  1. 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 d

  2. 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 interleukin

  3. Cefepime Monotherapy is as Effective as Ceftriaxone Plus Amikacin in Pediatric Patients with Cancer and High-Risk Febrile Neutropenia: A Randomized Comparison

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Pires Pereira

    2008-01-01

    Full Text Available The empirical use of antibiotic therapies is widely accepted in patients with fever and neutropenia during cancer chemotherapy. The use of intravenous monotherapy with broad-spectrum antibiotics in patients with high-risk of complications is an appropriate alternative. However, few data are available in pediatric patients. We conducted a prospective, randomized, open study in patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients were randomized to receive cefepime (CFP or ceftriaxone plus amikacin (CFT+AK. A total of 57 patients with 125 episodes of fever and neutropenia were evaluated (CFP, 62 and CFT + AK, 63 episodes. The mean neutrophil count at admission was 118.6 cells mm-3 (CFP and 107 cells mm-3 (CFT+AK. The mean duration of neutropenia was 9.0 days (CFP and 8.0 days (CFT+AK. Analyzing only the first episodes of each patient, CFP treatment was successful in 65.5% of the episodes and CFT+AK were successful in 64.3%. Overall rates of success with modification were 90% (CFP and 89% (CFT+AK. No major treatment-emergent toxicity was reported. Monotherapy with CFP seems to be as effective and safe as the combination of CFT+AK for initial empirical therapy in children and adolescents with NF.

  4. Carbohydrate Loading.

    Science.gov (United States)

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  5. Load sensor

    NARCIS (Netherlands)

    Van den Ende, D.; Almeida, P.M.R.; Dingemans, T.J.; Van der Zwaag, S.

    2007-01-01

    The invention relates to a load sensor comprising a polymer matrix and a piezo-ceramic material such as PZT, em not bedded in the polymer matrix, which together form a compos not ite, wherein the polymer matrix is a liquid crystalline resin, and wherein the piezo-ceramic material is a PZT powder for

  6. Carbohydrate Loading.

    Science.gov (United States)

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  7. [A case of pseudomembranous colitis with febrile neutropenia induced by chemotherapy and effectively treated by vancomycin enemas].

    Science.gov (United States)

    Tsuchida, Kazuhito; Hayashi, Tsutomu; Hayashi, Shigeya; Sawazaki, Sho; Jin, Yasuyuki; Hasuo, Kimiatsu; Suzuki, Hiroharu; Rino, Yasushi; Masuda, Munetaka

    2010-09-01

    Pseudomembranous colitis, an antibiotic-associated diarrhea, needs early diagnosis and treatment for the high fatality rate in severe cases. We report a case of pseudomembranous colitis following the use of antibiotics in febrile neutropenia (FN). A 74-year-old man with non-curative resected sigmoid colon cancer was treated with cefepime in FN induced by chemotherapy. Complications of diarrhea were seen on day 2. Paralytic ileus and disseminated intravascular coagulation were also complications. He was diagnosed as pseudomembranous colitis for Clostridium difficile toxin-positive. Vancomycin enemas were administered because oral administrations were impossible, and the effect was provided. Vancomycin enemas are an effective therapy for patients with severe pseudomembranous colitis unable to tolerate oral medications because of ileus.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  12. Ciprofloxacin versus colistin prophylaxis during neutropenia in acute myeloid leukemia: two parallel patient cohorts treated in a single center

    Science.gov (United States)

    Pohlen, Michele; Marx, Julia; Mellmann, Alexander; Becker, Karsten; Mesters, Rolf M.; Mikesch, Jan-Henrik; Schliemann, Christoph; Lenz, Georg; Müller-Tidow, Carsten; Büchner, Thomas; Krug, Utz; Stelljes, Matthias; Karch, Helge; Peters, Georg; Gerth, Hans U.; Görlich, Dennis; Berdel, Wolfgang E.

    2016-01-01

    Patients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapy-related neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. We report a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of more than seven days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematologic services at our hospital, as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs. without prophylaxis; P=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs. 79.5% in the colistin group; P=0.07), as determined by univariate analysis. This result was confirmed through multivariate analysis (OR: 0.475, 95%CI: 0.236–0.958; P=0.041). The prophylactic agents did not differ with regard to the microbiological findings (P=0.6, not significant). Of note, the use of ciprofloxacin was significantly associated with an increased rate of infections with pathogens that are resistant to the antibiotic used for prophylaxis (79.5% vs. 9.5% in the colistin group; P<0.0001). The risk factors for higher infection rates were the presence of a central venous catheter (P<0.0001), mucositis grade III/IV (P=0.0039), and induction/relapse courses (vs. consolidation; P<0.0001). In conclusion, ciprofloxacin prophylaxis appears to be of particular benefit during induction and relapse chemotherapy for acute myeloid leukemia. To prevent and control drug resistance, it may be safely replaced by colistin during consolidation cycles of acute myeloid leukemia therapy. PMID:27470601

  13. 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.)

  14. The use of intravenous antibiotics at the onset of neutropenia in patients receiving outpatient-based hematopoietic stem cell transplants.

    Directory of Open Access Journals (Sweden)

    Aziz Hamadah

    Full Text Available 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.

  15. Neutropenia crónica e infección por el virus de la inmunodeficiencia humana

    Directory of Open Access Journals (Sweden)

    Ronald A Noguera-Valverde

    2008-09-01

    Full Text Available Se presenta el caso de un paciente masculino con neutropenia crónica e infección por el virus de inmunodeficiencia humana, con una revisión de los posibles mecanismos patogénicos. Las alteraciones hematológicas como anemia, trombocitopenia y leucopenia se presentan asociadas con frecuencia a la infección aguda por el virus de inmunodeficiencia humana. Al establecer la terapia antirretroviral y disminuir la actividad del virus, estas alteraciones tienden a mejorar. Sin embargo, algunos fármacos antirretrovirales, como la zidovudina, poseen toxicidad medular y pueden producir o empeorar las alteraciones hematológicas en estos pacientes, lo cual lleva a cambios en los esquemas de tratamiento. Los citotóxicos y antimetabolitos empleados en el tratamiento de neoplasias asociadas tienen conocida actividad depresora sobre la médula ósea. Algunos antimicrobianos utilizados en la profilaxis de infecciones poseen también toxicidad hematológica conocida, como el trimetoprim-sulfametoxazol, por lo que deben ser utilizados con precaución en pacientes con infección por el virus de inmunodeficiencia humana. Por otro lado, se plantean mecanismos alternativos que causan neutropenia en estos pacientes, como la formación de anticuerpos antineutrófilos, daño primario del progenitor granulocítico, por desbalance en la producción de neutrófilos, por anticuerpos contra la glicoproteína gp120 de la cápside viral del VIH, y deficiencias vitamínicas. En el caso del paciente neutropénico febril, en quien se sospecha infección bacteriana grave, se pueden utilizar los factores estimulantes de las colonias de granulocitos para aumentar los conteos absolutos de neutrófilos y mejorar la recuperación clínica.

  16. Assessing patients' risk of febrile neutropenia: is there a correlation between physician-assessed risk and model-predicted risk?

    Science.gov (United States)

    Lyman, Gary H; Dale, David C; Legg, Jason C; Abella, Esteban; Morrow, Phuong Khanh; Whittaker, Sadie; Crawford, Jeffrey

    2015-08-01

    This study evaluated the correlation between the risk of febrile neutropenia (FN) estimated by physicians and the risk of severe neutropenia or FN predicted by a validated multivariate model in patients with nonmyeloid malignancies receiving chemotherapy. Before patient enrollment, physician and site characteristics were recorded, and physicians self-reported the FN risk at which they would typically consider granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (FN risk intervention threshold). For each patient, physicians electronically recorded their estimated FN risk, orders for G-CSF primary prophylaxis (yes/no), and patient characteristics for model predictions. Correlations between physician-assessed FN risk and model-predicted risk (primary endpoints) and between physician-assessed FN risk and G-CSF orders were calculated. Overall, 124 community-based oncologists registered; 944 patients initiating chemotherapy with intermediate FN risk enrolled. Median physician-assessed FN risk over all chemotherapy cycles was 20.0%, and median model-predicted risk was 17.9%; the correlation was 0.249 (95% CI, 0.179-0.316). The correlation between physician-assessed FN risk and subsequent orders for G-CSF primary prophylaxis (n = 634) was 0.313 (95% CI, 0.135-0.472). Among patients with a physician-assessed FN risk ≥ 20%, 14% did not receive G-CSF orders. G-CSF was not ordered for 16% of patients at or above their physician's self-reported FN risk intervention threshold (median, 20.0%) and was ordered for 21% below the threshold. Physician-assessed FN risk and model-predicted risk correlated weakly; however, there was moderate correlation between physician-assessed FN risk and orders for G-CSF primary prophylaxis. Further research and education on FN risk factors and appropriate G-CSF use are needed.

  17. Load, and Modifies the Immune Response in a Patient with HAM/TSP

    Directory of Open Access Journals (Sweden)

    Davi Tanajura Costa

    2012-01-01

    Full Text Available The human T-cell lymphotropic virus type 1 (HTLV-1 is the known causative agent of a chronic neurologic condition known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Although several therapies have been evaluated for HAM/TSP, none have been approved for use in humans. In this paper, we describe a 55-year-old female patient with HAM/TSP who was treated with interferon beta-1a. This patient, in comparison to 20 female patients with HAM/TSP who were not treated, showed improvement in urinary symptoms over four years of therapy, as well as a reduction in HTLV-1 proviral load and serum cytokine levels typically observed in HAM/TSP. This improved outcome merits further controlled studies on the use and efficacy of interferon beta-1a as a therapy for HAM/TSP.

  18. 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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2016-01-01

    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. 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 to determine the potency of lomustine obtained from several compounding pharmacies. Thirty-seven dogs treated with FDA-approved or compounded lomustine. Dogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Twenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration. These data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. 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

    at lower risk), and only around two-thirds of patients received optimal chemotherapy RDI. Our data suggest that improvements in neutropenia management are required. More consistent use of G-CSF primary prophylaxis may further reduce FN and assist in optimal chemotherapy delivery. Sponsored by Amgen...... Disclosures: Salar: Amgen: Honoraria. Haioun: Roche: Research Funding; Amgen: Other, Research Funding; Celgene: Other, Research Funding; Mundipharma: Research Funding. Pettengell: Amgen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Bayer: Honoraria, Speakers Bureau. Jaeger: Amgen: Research...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Efficacy and safety of tazobactam/piperacillin as an empirical treatment for the patients of adult and child with febrile neutropenia in Japan.

    Science.gov (United States)

    Tamura, Kazuo; Akiyama, Nobu; Kanda, Yoshinobu; Saito, Masahiro

    2015-09-01

    Tazobactam/piperacillin (4.5 g for adults and 90 mg/kg body weight for children, every 6 h) was administered to Japanese patients with febrile neutropenia to evaluate its defervescence and clinical efficacy and safety. The pharmacokinetics in children were also examined. Defervescence efficacy at day 4 of the treatment was achieved in 50.0% of 94 adult and 62.5% of 8 pediatric patients, respectively. The defervescence efficacy rate in relation to the neutrophil count in adults was 37.5% for the patients with a neutrophil count of less than 100/μL and 62.5% for that between 100 and 500/μL. The clinical efficacy rate at day 7 and at the end or discontinuation of the treatment was 79.6% and 59.1% in adult patients, respectively, and 57.1% and 75.0% in pediatric patients, respectively. Fifteen strains of causative bacteria were isolated in 13 adult patients at baseline. All strains were eradicated within 4 days of the treatment. The side effects that occurred in adult and pediatric patients during the treatment were all known and not specific to febrile neutropenia patients. The pharmacokinetics profiles of tazobactam/piperacillin in children with febrile neutropenia are unlikely to be different from those in children with a common bacterial infection and without any immunosuppressive conditions. The study results in Japanese patients with febrile neutropenia demonstrate that tazobactam/piperacillin treatment is efficacious and safe in adults. As for pediatric patients, given the limited number of cases studied, further investigation is needed (Clinical trial number: Japic CTI-121728).

  3. The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy.

    Science.gov (United States)

    Stepensky, Polina; Saada, Ann; Cowan, Marianne; Tabib, Adi; Fischer, Ute; Berkun, Yackov; Saleh, Hani; Simanovsky, Natalia; Kogot-Levin, Aviram; Weintraub, Michael; Ganaiem, Hamam; Shaag, Avraham; Zenvirt, Shamir; Borkhardt, Arndt; Elpeleg, Orly; Bryant, Nia J; Mevorach, Dror

    2013-06-20

    Severe congenital neutropenia as well as primary myelofibrosis are rare in infancy. Elucidation of the underlying mechanism is important because it extends our understanding of the more common adult forms of these disorders. Using homozygosity mapping followed by exome sequencing, we identified a Thr224Asn mutation in the VPS45 gene in infants from consanguineous families who suffered from life-threatening neutropenia, which was refractory to granulocyte CSF, from defective platelet aggregation and myelofibrosis. The mutation segregated in the families, was not present in controls, affected a highly conserved codon, and apparently destabilized the Vps45 protein, which was reduced in the patients' leukocytes. Introduction of the corresponding mutation into yeast resulted in reduced cellular levels of Vps45 and also of the cognate syntaxin Tlg2, which is required for membrane traffic through the endosomal system. A defect in the endosomal-lysosomal pathway, the homologous system in humans, was suggested by the absence of lysosomes in the patients' fibroblasts and by the depletion of α granules in their platelets. Importantly, accelerated apoptosis was observed in the patients' neutrophils and bone marrow. This is the first report of a Vps45-related disease in humans, manifesting by neutropenia, thrombasthenia, myelofibrosis, and progressive bone marrow failure.

  4. The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia.

    Science.gov (United States)

    Sirinoglu, Melis; Soysal, Ahmet; Karaaslan, Ayşe; Kepenekli Kadayifci, Eda; Cinel, Ismail; Koç, Ahmet; Tokuç, Gülnur; Yaman, Ali; Haklar, Goncagül; Şirikçi, Önder; Turan, Serap; Altınkanat Gelmez, Gülşen; Söyletir, Güner; Bakır, Mustafa

    2016-04-01

    The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

  5. 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...

  6. A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children.

    Science.gov (United States)

    Caselli, Désirée; Cesaro, Simone; Ziino, Ottavio; Ragusa, Pietro; Pontillo, Alfredo; Pegoraro, Anna; Santoro, Nicola; Zanazzo, Giulio; Poggi, Vincenzo; Giacchino, Mareva; Livadiotti, Susanna; Melchionda, Fraia; Chiodi, Marcello; Aricò, Maurizio

    2012-07-01

    Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8-15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.

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

    Directory of Open Access Journals (Sweden)

    Irene Mavroudi

    2012-01-01

    Full Text Available 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.

  8. Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.

    Science.gov (United States)

    Low, Siew-Kee; Chung, Suyoun; Takahashi, Atsushi; Zembutsu, Hitoshi; Mushiroda, Taisei; Kubo, Michiaki; Nakamura, Yusuke

    2013-08-01

    Chemotherapeutic agents are notoriously known to have a narrow therapeutic range that often results in life-threatening toxicity. Hence, it is clinically important to identify the patients who are at high risk for severe toxicity to certain chemotherapy through a pharmacogenomics approach. In this study, we carried out multiple genome-wide association studies (GWAS) of 13 122 cancer patients who received different chemotherapy regimens, including cyclophosphamide- and platinum-based (cisplatin and carboplatin), anthracycline-based (doxorubicin and epirubicin), and antimetabolite-based (5-fluorouracil and gemcitabine) treatment, antimicrotubule agents (paclitaxel and docetaxel), and topoisomerase inhibitors (camptothecin and etoposide), as well as combination therapy with paclitaxel and carboplatin, to identify genetic variants that are associated with the risk of severe neutropenia/leucopenia in the Japanese population. In addition, we used a weighted genetic risk scoring system to evaluate the cumulative effects of the suggestive genetic variants identified from GWAS in order to predict the risk levels of individuals who carry multiple risk alleles. Although we failed to identify genetic variants that surpassed the genome-wide significance level (P < 5.0 × 10(-8) ) through GWAS, probably due to insufficient statistical power and complex clinical features, we were able to shortlist some of the suggestive associated loci. The current study is at the relatively preliminary stage, but does highlight the complexity and problematic issues associated with retrospective pharmacogenomics studies. However, we hope that verification of these genetic variants through local and international collaborations could improve the clinical outcome for cancer patients.

  9. Neutropenia predicts better prognosis in patients with metastatic gastric cancer on a combined epirubicin, oxaliplatin and 5-fluorouracil regimen

    Science.gov (United States)

    Zhao, Xiaoying; Peng, Wei; Sun, Si; Cao, Jun; Ji, Dongmei; Wang, Chenchen; Guo, Weijian; Li, Jin; Yin, Jiliang; Zhu, Xiaodong

    2015-01-01

    Chemotherapy-induced neutropenia (CIN) reportedly indicated better prognosis for some cancers. We retrospectively analyzed 150 evaluable metastatic gastric cancer (MGC) patients who had received first-line EOF5 (combination regimen of epirubicin, oxaliplatin and 5-day continuous infusion of 5-fluorouracil) treatment. We divided patients into three groups according to the worst grade of CIN: absent group (grade 0), moderate group (grade 1–2) and severe group (grade 3–4). Multivariate analyses of overall survival (OS) proved moderate and severe CIN were important prognostic factors whether regarding CIN as a time-varying covariate (TVC) or not. Compared with absent CIN, hazard ratio (HR) for moderate and severe CIN were 0.31 (95% confidential interval (CI): 0.17–0.55; P CIN showed similar results. In the landmark group (n = 122 patients) analyses with TVC, moderate and severe CIN remained prognostic factors for PFS, while only moderate CIN was prognostic factor for OS. CIN predicted longer OS and PFS in MGC patients treated with first-line EOF5 chemotherapy. PMID:26528696

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Electrical load detection aparatus

    DEFF Research Database (Denmark)

    2010-01-01

    A load detection technique for a load comprising multiple frequency-dependant sub-loads comprises measuring a representation of the impedance characteristic of the load; providing stored representations of a multiplicity of impedance characteristics of the load; each one of the stored representat...

  12. Micro-organisms Associated with Febrile Neutropenia in Patients with Haematological Malignancies in a Tertiary Care Hospital in Eastern India.

    Science.gov (United States)

    Mandal, Prakas Kumar; Maji, Suman Kumar; Dolai, Tuphan Kanti; De, Rajib; Dutta, Shyamali; Saha, Sandeep; Bhattacharyya, Maitreyee

    2015-03-01

    There is paucity of information from eastern India with regard to observed dominant micro-organisms causing febrile neutropenia (FN) in patients with haematological malignancies. To identify the prevalence of pathogenic microorganisms associated with FN. A total number of 268 episodes of FN were analysed from September'2010 to October'2013. The blood samples were inoculated into brain heart infusion broth, glucose broth, Hicombi dual performance media (Himedia, LQ-12) at 37° C for 168 h and Bactec method was also performed for these samples. Blood agar, chocolate agar, MacConkey's agar and cystine lactose electrolyte deficient agar were used for isolation of the microorganisms. A total number of 78 (29.10 %) episodes revealed positive growths. Gram negative bacilli and Gram positive cocci were isolated in 61.53 and 34.61 % cases respectively. The eight commonest isolates were Pseudomonas aeruginosa (14.10 %), methicillin resistant Staphylococcus aureus (MRSA-12.82 %), Acinetobacter sps (11.53 %), coagulase negative Staphylococcus (10.25 %), Klebsiella pneumoniae (8.97 %), Escherichia coli (8.97 %), ESBL E. coli (6.41 %), methicillin sensitive S. aureus (MSSA-6.41 %). Amongst other less common isolates were Citrobacter kosseri (3.84 %), Citrobacter freundii (2.56 %), Ralstonia paucula (2.56 %), Cedecia neteri (1.28 %), methicillin resistant coagulase negative Staphylococcus (2.56 %). Candida spp. including two cases of Candida non-albicans was isolated in 3.84 % of cases. P. aeruginosa was the commonest pathogenic isolates in FN patients associated with haematological malignancies in this study. Gram negative bacteria were the commonest isolates in FN including significant numbers of rare opportunistic micro-organisms.

  13. Acupuncture for Chemotherapy-Induced Neutropenia in Patients with Gynecologic Malignancies: A Pilot Randomized, Sham-Controlled Clinical Trial

    Science.gov (United States)

    Lu, Weidong; Matulonis, Ursula A.; Doherty-Gilman, Anne; Lee, Hang; Dean-Clower, Elizabeth; Rosulek, Andrew; Gibson, Carolyn; Goodman, Annekathryn; Davis, Roger B.; Buring, Julie E.; Wayne, Peter M.; Rosenthal, David S.; Penson, Richard T.

    2009-01-01

    Abstract Objectives The objective of this study was to investigate the effect of acupuncture administered during myelosuppressive chemotherapy on white blood cell (WBC) count and absolute neutrophil count (ANC) in patients with ovarian cancer. Design This study is a pilot, randomized, sham-controlled clinical trial. Patients received active acupuncture versus sham acupuncture while undergoing chemotherapy. A standardized acupuncture protocol was employed with manual and electrostimulation. The frequency of treatment was 2–3 times per week for a total of 10 sessions, starting 1 week before the second cycle of chemotherapy. Setting The setting was two outpatient academic centers for patients with cancer. Subjects Twenty-one (21) newly diagnosed and recurrent ovarian cancer patients were the subjects. Outcome measures WBC count, ANC, and plasma granulocyte colony-stimulating factor (G-CSF) were assessed weekly. Results The median leukocyte value in the acupuncture arm at the first day of the third cycle of chemotherapy was significantly higher than in the control arm after adjusting for baseline value (8600 cells/μL, range: 4800–12,000 versus 4400 cell/μL, range: 2300–10,000) (p = 0.046). The incidence of grade 2–4 leukopenia was less in the acupuncture arm than in the sham arm (30% versus 90%; p = 0.02). However, the median leukocyte nadir, neutrophil nadir, and recovering ANC were all higher but not statistically significantly different (p = 0.116–0.16), after adjusting for baseline differences. There were no statistically significant differences in plasma G-CSF between the two groups. Conclusions We observed clinically relevant trends of higher WBC values during one cycle of chemotherapy in patients with ovarian cancer, which suggests a potential myeloprotective effect of acupuncture. A larger trial is warranted to more definitively determine the efficacy of acupuncture on clinically important outcomes of chemotherapy-induced neutropenia. PMID:19552597

  14. Procalcitonin and quantitative C-reactive protein role in the early diagnosis of sepsis in patients with febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Mohsen Meidani

    2013-01-01

    Full Text Available Background: Neutropenia with fever is a common syndrome in patients with hematologic malignancies who have a high risk of infectious diseases. As early diagnosis of infection in such patients is really important, the aim of this study was to investigate the sensitivity and specificity of procalcitonin (PCT and C-reactive protein (CRP in the diagnosis of sepsis in febrile neutropenic patients in a referral malignant care center of Isfahan in 2010-2011. Materials and Methods: In this analytical cross-sectional study, all the febrile neutropenic patients who were admitted in the referral malignant care center in 2010-2011 were evaluated. The data from every individual, including sex, age, admission time, and duration of fever before taking antibiotics were collected. Sixty-four subjects were involved in the study. Blood samples of the subjects were obtained and the levels of PCT, CRP, Absolute neutrophil count (ANC, and white blood cell count were measured, and blood cultures were obtained. According to the test results, the 64 subjects were divided into two groups including patients with sepsis and without sepsis. Results: Mean value of PCT in the sepsis group was 28.65 ± 2.68 and in the non-sepsis group was 2.48 ± 0.66, with a P value of 0.000. In case of CRP, the sepsis group had a mean of 159.48 ± 9.73 and the non-sepsis group had a mean of 126.17 ± 10.63 (P = 0.015. Sensitivity and specificity were analyzed by using receiver operating characteristic (ROC curve and were found to be 92.5% and 97.3%, respectively, for PCT and 70.5% and 42.1%, respectively, for CRP. Conclusion: PCT can be considered as a predictive factor and a diagnostic marker for the diagnosis of sepsis in febrile neutropenic patients.

  15. 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.

  16. Sequence analysis for the complete proviral genome of subgroup J Avian Leukosis virus associated with hemangioma: a special 11 bp deletion was observed in U3 region of 3'UTR

    Directory of Open Access Journals (Sweden)

    Zou Nianli

    2011-04-01

    Full Text Available Abstract Background Avian Leukosis virus (ALV of subgroup J (ALV-J belong to retroviruses, which could induce tumors in domestic and wild birds. Myelocytomatosis was the most common neoplasma observed in infected flocks; however, few cases of hemangioma caused by ALV-J were reported in recent year. Results An ALV-J strain SCDY1 associated with hemangioma was isolated and its proviral genomic sequences were determined. The full proviral sequence of SCDY1 was 7489 nt long. Homology analysis of the env, pol and gag gene between SCDY1 and other strains in GenBank were 90.3-94.2%, 96.6-97.6%, and 94.3-96.5% at nucleotide level, respectively; while 85.1-90.7%, 97.4-98.7%, and 96.2-98.4% at amino acid level, respectively. Alignment analysis of the genomic sequence of ALV-J strains by using HPRS-103 as reference showed that a special 11 bp deletion was observed in U3 region of 3'UTR of SCDY1 and another ALV-J strain NHH isolated from case of hemangioma, and the non-functional TM and E element were absent in the genome of SCDY1, but the transcriptional regulatory elements including C/EBP, E2BP, NFAP-1, CArG box and Y box were highly conserved. Phylogenetic analysis revealed that all analyzed ALV-J strains could be separated into four groups, and SCDY1 as well as another strain NHH were included in the same cluster. Conclusion The variation in envelope glycoprotein was higher than other genes. The genome sequence of SCDY1 has a close relationship with that of another ALV-J strain NHH isolated from case of hemangioma. A 11 bp deletion observed in U3 region of 3'UTR of genome of ALV-J isolated from case of hemangioma is interesting, which may be associated with the occurrence of hemangioma.

  17. 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

  18. Wind Loads on Structures

    DEFF Research Database (Denmark)

    Dyrbye, Claes; Hansen, Svend Ole

    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......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...

  19. 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

  20. Wind Loads on Structures

    DEFF Research Database (Denmark)

    Dyrbye, Claes; Hansen, Svend Ole

    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......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...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. {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.)

  3. Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato-oncological patients: randomized controlled trial.

    Science.gov (United States)

    Paul, Mical; Ram, Ron; Kugler, Eitan; Farbman, Laura; Peck, Anat; Leibovici, Leonard; Lahav, Meir; Yeshurun, Moshe; Shpilberg, Ofer; Herscovici, Corina; Wolach, Ofir; Itchaki, Gilad; Bar-Natan, Michal; Vidal, Liat; Gafter-Gvili, Anat; Raanani, Pia

    2014-03-01

    Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato-oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/µL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6-9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6-6.2), log-rank P = 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P = 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study)

    Science.gov (United States)

    Aapro, M.; Ludwig, H.; Bokemeyer, C.; Gascón, P.; Boccadoro, M.; Denhaerynck, K.; Krendyukov, A.; Gorray, M.; MacDonald, K.; Abraham, I.

    2016-01-01

    Background Risk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle. Design We applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at the patient (‘ever’ during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being ‘nested’ under patients was managed using generalized estimation equations. Predictive performance of each model was evaluated using bootstrapped c concordance statistics. Results Static patient-level risk models of ‘ever’ experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history, risk factors, and prophylaxis initiation and intensity. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics. Conclusion(s) These ‘real-world evidence’ models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically

  7. Chemotherapy-induced Neutropenia

    Directory of Open Access Journals (Sweden)

    A. Catherine Casey

    1995-01-01

    Full Text Available Background:Pasteurella multocida is a commensal organism found in the saliva and oropharynx of domestic animals. It causes a variety of human infections ranging from cellulitis to bacteremia and sepsis. The severity of infection is somewhat related to the immunocompetency of the infected host. An immunocompromised host is more likely to suffer a disseminated infection as a result of contact with this organism than an immunocompetent host. This case report and review of the literature are presented to further evaluate the types of infections caused by this organism in oncology patients.

  8. Congenital Neutropenia Syndromes

    Science.gov (United States)

    ... of Award Clinical Terms of Award Restriction for China Clinical Terms Guidance Compliance Sample Letter Inclusion Codes ... Division of AIDS Division of Allergy, Immunology, and Transplantation Division of Microbiology and Infectious Diseases Division of ...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Detection of bacteria and fungi in blood of patients with febrile neutropenia by real-time PCR with universal primers and probes.

    Science.gov (United States)

    Teranishi, Hideto; Ohzono, Nanae; Inamura, Norikazu; Kato, Atsushi; Wakabayashi, Tokio; Akaike, Hiroto; Terada, Kihei; Ouchi, Kazunobu

    2015-03-01

    Febrile neutropenia is the main treatment-related cause of mortality in cancer patients. During June 2012 to April 2014, 97 blood culture samples were collected from patients receiving chemotherapy for hematological malignancy and cancer with febrile neutropenia episodes (FNEs). The samples were examined for the presence of bacteria and fungi using real-time PCR amplification and sequencing of 16S and 18S rRNA genes. Bacteria were identified in 20 of 97 samples (20.6%) by the real-time PCR assay and in 10 of 97 (10.3%) samples by blood culture. In 6 blood culture-positive samples, the real-time PCR assay detected the same type of bacteria. No fungi were detected by the real-time PCR assay or blood culture. During antibiotic therapy, all samples were negative by blood culture, but the real-time PCR assay yielded a positive result in 2 cases of 2 (100%). The bacterial DNA copy number was not well correlated with the serum C-reactive protein titer of patients with FNEs. We conclude that a real-time PCR assay could provide better detection of causative microbes' in a shorter time, and with a smaller blood sample than blood culture. Using a real-time PCR assay in combination with blood culture could improve microbiological documentation of FNEs.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. The role of ¹⁸F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia.

    Science.gov (United States)

    Gafter-Gvili, Anat; Paul, Mical; Bernstine, Hanna; Vidal, Liat; Ram, Ron; Raanani, Pia; Yeshurun, Moshe; Tadmor, Boaz; Leibovici, Leonard; Shpilberg, Ofer; Groshar, David

    2013-09-01

    We assessed the performance of PET/CT for diagnosis and management of infections in high-risk hematological cancer patients with persistent febrile neutropenia in a prospective study. (18)F-FDG PET/CT with contrast-enhanced CT was performed on day 5-7 of persistent fever. Between 2008 and 2011, 91 PET/CT examinations were performed for different episodes in 79 patients, resulting in 117 diagnoses. The sensitivity of the PET/CT was 79.8% (71/89) compared to 51.7% (46/89) with chest/sinus CT alone. Specificities were 32.14% (9/28) vs. 42.85% (12/28), respectively. PET/CT resulted in a change from the pre-test diagnosis in 63/91 (69%) of episodes and in modification of patients' management in 46/91 (55%). PET/CT was beneficial in diagnosing abdominal infections. PET/CT has a potential role in the diagnostic evaluation of patients with persistent febrile neutropenia.

  13. Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated with Streptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis

    Directory of Open Access Journals (Sweden)

    Christina Voulgari

    2015-01-01

    Full Text Available Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated by Streptococcus pneumonia and sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy.

  14. 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

    Directory of Open Access Journals (Sweden)

    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

  15. High Power Disk Loaded Guide Load

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, Z.D.; /SLAC

    2006-02-22

    A method to design a matching section from a smooth guide to a disk-loaded guide, using a variation of broadband matching, [1, 2] is described. Using this method, we show how to design high power loads. The load consists of a disk-loaded coaxial guide operating in the TE{sub 01}-mode. We use this mode because it has no electric field terminating on a conductor, has no axial currents, and has no current at the cylinder-disk interface. A high power load design that has -35 dB reflection and a 200 MHz, -20 dB bandwidth, is presented. It is expected that it will carry the 600 MW output peak power of the pulse compression network. We use coaxial geometry and stainless steel material to increase the attenuation per cell.

  16. Plasma virus load evaluation in relation to disease progression in HIV-infected children.

    Science.gov (United States)

    Tetali, S; Bakshi, S; Than, S; Pahwa, S; Abrams, E; Romano, J; Pahwa, S G

    1998-05-01

    The objective of this study was to investigate the relationship of plasma HIV RNA load with survival and disease progression in HIV-infected children and to determine its correlation with cellular HIV DNA. Virus load (VL, HIV RNA copies/ml) was determined retrospectively by nucleic acid sequence-based amplification (NASBA) assay in 144 stored plasma samples between birth and 48 months in 50 children of whom 40 are alive (age range, 2-13 years). On the basis of clinical and immunologic status children were classified as rapid progressors (RPs), or nonrapid progressors (NRPs). Proviral HIV DNA quantitated by QC-PCR (quantitative competitive polymerase chain reaction) in 24 children was compared with plasma HIV RNA. At age 2 years (p or =750,000 copies/ml. Increasing mortality was observed with increasing plasma HIV RNA levels at ages 3-24 months and baseline VL of infants who died before age 24 months was significantly higher (p = 0.004) than baseline VL of those who survived beyond 24 months. Although baseline VL in infants classified as RPs was higher than that of NRPs, the difference was not statistically significant. Among surviving children 2-13 years of age, the baseline VL obtained at 80%. We conclude that high plasma HIV RNA in infancy is associated with increased mortality.

  17. Lightening the Load

    OpenAIRE

    Remington, Anna M.; Swettenham, John G.; Lavie, Nilli

    2012-01-01

    Autism spectrum disorder (ASD) research portrays a mixed picture of attentional abilities with demonstrations of enhancements (e.g., superior visual search) and deficits (e.g., higher distractibility). Here we test a potential resolution derived from the Load Theory of Attention (e.g., Lavie, 2005). In Load Theory, distractor processing depends on the perceptual load of the task and as such can only be eliminated under high load that engages full capacity. We hypothesize that ASD involves enh...

  18. Prevalence of Resistant Gram-Negative Bacilli in Bloodstream Infection in Febrile Neutropenia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Single Center Retrospective Cohort Study.

    Science.gov (United States)

    Wang, Ling; Wang, Ying; Fan, Xing; Tang, Wei; Hu, Jiong

    2015-11-01

    Bloodstream infection (BSI) is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the causative bacteria and identify risk factors for BSI associated mortality in febrile neutropenia patients undergoing HSCT, we collected the clinical and microbiological data from patients underwent HSCT between 2008 and 2014 and performed a retrospective analysis. Throughout the study period, among 348 episodes of neutropenic fever in patients underwent HSCT, 89 episodes in 85 patients had microbiological defined BSI with a total of 108 isolates. Gram-negative bacteria (GNB) were the most common isolates (76, 70.3%) followed by gram-positive bacteria (GPB, 29, 26.9%) and fungus (3, 2.8%). As to the drug resistance, 26 multiple drug resistance (MDR) isolates were identified. Resistant isolates (n = 23) were more common documented in GNB, mostly Escherichia coli (9/36, 25%) and Klebsiella pneumonia (6/24, 25%). A total of 12 isolated were resistant to carbapenem including 4 K pneumoniae (4/24, 16.7%), 3 Stenotrophomonas maltophilia, and 1 Pseudomonas aeruginosa and other 4 GNB isolates (Citrobacter freumdii, Pseudomonas stutzeri, Acinetobacter baumanii, and Chryseobacterium indologenes). As to the GPB, only 3 resistant isolates were documented including 2 methicillin-resistant isolates (Staphylococcus hominis and Arcanobacterium hemolysis) and 1 vancomycin-resistant Enterococcus faecium. Among these 85 patients with documented BSI, 11 patients died of BSI as primary or associated cause with a BSI-related mortality of 13.1 ± 3.7% and 90-day overall survival after transplantation at 80.0 ± 4.3%. Patients with high-risk disease undergoing allo-HSCT, prolonged neutropenia (≥15 days) and infection with carbapenem-resistant GNB were associated with BSI associated mortality in univariate and multivariate analyses. Our report revealed a prevalence of GNB in BSI of neutropenic patients undergoing

  19. Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study.

    Science.gov (United States)

    Kasi, Pashtoon M; Kotani, Daisuke; Cecchini, Michael; Shitara, Kohei; Ohtsu, Atsushi; Ramanathan, Ramesh K; Hochster, Howard S; Grothey, Axel; Yoshino, Takayuki

    2016-07-13

    TAS-102 (trifluridine and tipiracil hydrochloride; a novel combination oral nucleoside anti-tumor agent) has recently received regulatory approval for patients with refractory metastatic colorectal cancer (mCRC). Internal review of data at a single-institution showed a trend towards better overall survival (OS) for patients who experienced chemotherapy-induced neutropenia at 1-month (CIN-1-month). To explore this finding further, a cohort study was designed based on outcome data from three centers in United States and one from Japan. CIN-1-month after starting TAS-102 was defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 as a neutrophil count decrease of ≥ grade 2 (absolute neutrophil count < 1500/mm(3)). Patients had confirmed mCRC that was refractory to standard therapies. Patient demographics and clinical characteristics were compared between patients with CIN-1-month (CIN-1-month positive) versus those who did not have CIN-1-month (CIN-1-month negative); with the median progression-free survival (PFS) and OS were calculated using the Kaplan-Meier method, and differences evaluated using the Log-rank test. Our cohort study had a total of 149 patients with data regarding their neutrophil assessment at 1-month mark. Patients who developed ≥ grade 2 CIN-1-month had a both longer PFS (median 3.0 months versus 2.4 months; Log-rank P-value = 0.01), as well as OS (14.0 versus 5.6 months; Log-rank P-value < 0.0001). Only CIN-1-month (adjusted HR: 0.21 (95 % CI: 0.11-0.38) and higher baseline CEA levels (adjusted HR: 2.00 (95 % CI: 1.22-3.35) were noted to be independent predictors of OS. Furthermore, the CIN-1-month was noted to be a statistically significantly predictor of OS over a wide range of cutoffs. Our observations are novel and hypothesis generating. Neutropenia after starting TAS-102 was associated with better prognosis in patients with refractory mCRC. It can be postulated that the dosage of TAS

  20. Taking a Load Off.

    Science.gov (United States)

    Kenny, John

    1995-01-01

    Discusses the snow -load capacity of school roofs and how understanding this data aids in planning preventive measures and easing fear of roof collapse. Describes how to determine snow-load capacity, and explains the load-bearing behavior of flat versus sloped roofs. Collapse prevention measures are highlighted. (GR)

  1. The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia.

    Science.gov (United States)

    Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

    2013-04-01

    Prediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients. A total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups. Median of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently. PCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Jaagsiekte sheep retrovirus proviral clone JSRV(JS7), derived from the JS7 lung tumor cell line, induces ovine pulmonary carcinoma and is integrated into the surfactant protein A gene.

    Science.gov (United States)

    DeMartini, J C; Bishop, J V; Allen, T E; Jassim, F A; Sharp, J M; de las Heras, M; Voelker, D R; Carlson, J O

    2001-05-01

    Ovine pulmonary carcinoma (OPC) is a contagious neoplasm of alveolar epithelial type II (ATII) or Clara cells caused by a type D/B chimeric retrovirus, jaagsiekte sheep retrovirus (JSRV). Here we report the isolation, sequencing, pathogenicity, and integration site of a JSRV provirus isolated from a sheep lung tumor cell line (JS7). The sequence of the virus was 93 to 99% identical to other JSRV isolates and contained all of the expected open reading frames. To produce virions and test its infectivity, the JS7 provirus (JSRV(JS7)) was cloned into a plasmid containing a cytomegalovirus promoter and transfected into 293T cells. After intratracheal inoculation with virions from concentrated supernatant fluid, JSRV-associated OPC lesions were found in one of four lambs, confirming that JSRV(JS7) is pathogenic. In JS7-cell DNA, the viral genome was inserted in the protein-coding region for the surfactant protein A (SP-A) gene, which is highly expressed in ATII cells, in an orientation opposite to the direction of transcription of the SP-A gene. No significant transcription was detected from either the viral or the SP-A gene promoter in the JS7 cell line at passage level 170. The oncogenic significance of the JSRV proviral insertion involving the SP-A locus in the JS7 tumor cell line is unknown.

  3. 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

  4. Outcomes in adult critically Ill cancer patients with and without neutropenia: a systematic review and meta-analysis of the Groupe de Recherche en Réanimation Respiratoire du patient d'Onco-Hématologie (GRRR-OH)

    Science.gov (United States)

    Bourmaud, Aurélie; Azoulay, Elie; Mokart, Djamel; Darmon, Michael

    2017-01-01

    PURPOSE Whether neutropenia has an impact on the mortality of critically ill cancer patients remains controversial, yet it is widely used as an admission criterion and prognostic factor. METHODS Systematic review and meta-analysis. Studies on adult cancer patients and intensive care units were searched on PubMed and Cochrane databases (2005-2015). Summary estimates of mortality risk differences were calculated using the random-effects model. RESULTS Among the 1,528 citations identified, 38 studies reporting on 6,054 patients (2,097 neutropenic patients) were included. Median mortality across the studies was 54% [45–64], with unadjusted mortality in neutropenic and non-neutropenic critically ill patients of 60% [53–74] and 47% [41–68], respectively. Overall, neutropenia was associated with a 10% increased mortality risk (6%-14%; I2 = 50%). The admission period was not associated with how neutropenia affected mortality. Mortality significantly dropped throughout the study decade [−11% (−13.5 to −8.4)]. This mortality drop was observed in non-neutropenic patients [−12.1% (−15.2 to −9.0)] but not in neutropenic patients [−3.8% (−8.1 to +5.6)]. Sensitivity analyses disclosed no differences in underlying malignancy, mechanical ventilation use, or Granulocyte-colony stimulating factor use. Seven studies allowed the adjustment of severity results (1,350 patients). Although pooled risk difference estimates were similar to non-adjusted results, there was no significant impact of neutropenia on mortality (risk difference of mortality, 9%; 95% CI, −15 to +33) CONCLUSION Although the unadjusted mortality of neutropenic patients was 11% higher, this effect disappeared when adjusted for severity. Therefore, when cancer patients become critically ill, neutropenia cannot be considered as a decision-making criterion. PMID:27661125

  5. Duration of load revisited

    DEFF Research Database (Denmark)

    Hoffmeyer, Preben; Sørensen, John Dalsgaard

    2007-01-01

    were formed. Four groups were subjected to short-term strength tests, and four groups were subjected to long-term tests. Creep and time to failure were moni-tored. Time to failure as a function of stress level was established and the reliability of stress level assessment was discussed. A significant...... mechanosorptive effect was demonstrated both in terms of increased creep and shortening of time to failure. The test results were employed for the calibration of four existing duration of load models. The effect of long-term loading was expressed as the stress level SL50 to cause failure after 50 years of loading...... and of the short-term and long-term strengths. For permanent and imposed library loads, reliability-based estimation of the load duration factor gave almost the same results as direct, deterministic calibration. Keywords: Creep, damage models, duration of load, equal rank assumption, load duration factor, matched...

  6. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. Anchor Loads on Pipelines

    OpenAIRE

    Wei, Ying

    2015-01-01

    Anchor hooking on a subsea pipeline has been investigated in this thesis. Anchor loads on pipelines is in general a rarely occurring event, however, the severity when it occurs could easily jeopardize the integrity of any pipeline. It is considered as an accidental load in the design of pipelines. Pipeline Loads, limit state criteria and anchor categories are defined by the DNV standards. For pipeline, DNV-OS-F101 (08.2012), Submarine Pipeline Systems is adopted. Offshore standard DNV-RP...

  12. Load induced blindness

    OpenAIRE

    Macdonald, J. S. P.; Lavie, N.

    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 oil 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 perceptual load in a letter-search task and assessed its effect oil the conscious perception of a search-irrelevant shape stimulus appearing in the pe...

  13. 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...

  14. 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...

  15. 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.

  16. 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.

  17. A Live Attenuated Equine Infectious Anemia Virus Proviral Vaccine with a Modified S2 Gene Provides Protection from Detectable Infection by Intravenous Virulent Virus Challenge of Experimentally Inoculated Horses

    Science.gov (United States)

    Li, Feng; Craigo, Jodi K.; Howe, Laryssa; Steckbeck, Jonathan D.; Cook, Sheila; Issel, Charles; Montelaro, Ronald C.

    2003-01-01

    Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAVUKΔS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAVUKΔS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAVPV. This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAVPV by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID50], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID50. In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure. PMID:12805423

  18. Combination of external loads

    Energy Technology Data Exchange (ETDEWEB)

    Frandsen, S.; Tarp Johansen, N.J.; Joergensen, H. [Forskningscenter Risoe, Roskilde (Denmark); Gravesen, H.; Soerensen, S.L. [Carl Bro, Glostrup (Denmark); Pedersen, J. [Elsam Engineering, Fredericia (Denmark); Zorn, R.; Hvidberg Knudsen, M. [DHI Water and Environment, Hoersholm (Denmark); Voelund, P. [Energi E2, Koebenhavn (Denmark)

    2003-09-01

    The project onbectives have been: To improve and consequently opimise the basis for design of offshore wind turbines. This is done through 1) mapping the wind, wave ice and current as well as correlations of these, and 2) by clarifyring how these external conditions transform into loads. A comprehensive effort has been made to get a thorough understanding of the uncertainties that govern the reliability of wind turbines with respect to wind and wave loading. One of the conclusions is that the reliability of wind turbines is generally lower, than the average reliability of building structures that are subject not only to environmental loads, which are very uncertain, but also imposed loads and self weight, which are less uncertain than the environmental loads. The implication is that, at the moment lower load partial safety factors for onshore wind turbines cannot be recommended. For the combination of wind and wave design loads the problem is twofold: 1). A very conservative design will be generated by simply adding the individual wind and wave design loads disregarding the independence of the short-term fluctuations of wind and wave loads. 2). Characteristic values and partial safety factors for wind and wave loads are not defined similarly. This implies that the reliability levels of turbine support structures subject to purely aerodynamic loads and subject to purely hydrodynamic loads are not identical. For the problem of combining aerodynamic design loads and hydrodynamic design loads two results have been obtained in the project: 1). By simple means a site specific wave load safety factor rendering the same safety level for hydrodynamic loads as for aerodynamic loads is derived, and next, by direct square summation of extreme fluctuations, the wind and wave load safety factors are weighted. 2). Under the assumptions that a deep water site is considered and that the wave loading is a fifty-fifty mix of drag and inertia the same wind and wave load safety factor

  19. 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…

  20. Indentation load relaxation test

    Energy Technology Data Exchange (ETDEWEB)

    Hannula, S.P.; Stone, D.; Li, C.Y. (Cornell Univ., Ithaca, NY (USA))

    Most of the models that are used to describe the nonelastic behavior of materials utilize stress-strain rate relations which can be obtained by a load relaxation test. The conventional load relaxation test, however, cannot be performed if the volume of the material to be tested is very small. For such applications the indentation type of test offers an attractive means of obtaining data necessary for materials characterization. In this work the feasibility of the indentation load relaxation test is studied. Experimental techniques are described together with results on Al, Cu and 316 SS. These results are compared to those of conventional uniaxial load relaxation tests, and the conversion of the load-indentation rate data into the stress-strain rate data is discussed.

  1. 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

  2. 化疗后粒细胞缺乏与患者特异性危险因素的相关探讨%Research on the Correlation of Neutropenia after Chemotherapy and Patients’ Specific Risk Factors

    Institute of Scientific and Technical Information of China (English)

    彭群英

    2015-01-01

    目的:探讨白血病患者化疗后出现粒细胞缺乏的相关特异性危险因素。方法:随机抽选2014年1-12月本院收治的138例急性白血病患者作为研究对象。对其两次化疗后的粒细胞缺乏情况以及相应的特异性危险因素情况进行统计、分析和比较。结果:138例患者共276次化疗,粒细胞缺乏总发生率明显高于粒细胞缺乏总未发生率。年龄≥60岁、首次化疗有粒细胞缺乏、肿瘤分期Ⅲ~Ⅳ期以及食欲下降患者的粒细胞缺乏发生率均明显高于年龄<60岁、首次化疗无粒细胞缺乏、肿瘤分期Ⅰ~Ⅱ期以及食欲良好患者的粒细胞缺乏发生率,比较差异均有统计学意义(P<0.05)。结论:白血病患者经过化疗后出现粒细胞缺乏症与年龄、既往史、肿瘤分期及食欲下降有关。%Objective:To explore the specific risk factors related to neutropenia in leukemic patients after chemotherapy.Method:138 patients with acute leukemia in our hospital from January to December 2014 were randomly selected as the research objects.The situation of neutropenia and its related specific risk factors after chemotherapy were analyzed and compared.Result:138 patients finished 276 times of chemotherapy totally.The total occurrence rate of neutropenia was higher than the non-occurrence rate of neutropenia.The incidence rates of neutropenia in patients who were 60 years or more,with neutropenia for the first time,with tumor of Ⅲ to Ⅳ stage and with decreased appetite were higher than those in patients who were less than 60 years,without neutropenia for the first time,with tumor of Ⅰto Ⅱ stage and without decreased appetite,the differences were statistically significant(P<0.05).Conclusion:The occurrence of neutropenia in leukemic patients after chemotherapy has a correlation with patients’ age,previous history, tumor staging and loss of appetite.

  3. 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.

  4. Risk Factors for Neutropenia in Extremely Low Birth Weight Infants%极低出生体重儿中性粒细胞减少症的危险因素

    Institute of Scientific and Technical Information of China (English)

    王晨; 王丹华

    2014-01-01

    目的:研究极低出生体重儿中性粒细胞减少症的危险因素。方法回顾性纳入2011年1月至2013年12月在北京协和医院新生儿重症监护室住院治疗的极低出生体重儿。根据生后第一周内有无中性粒细胞减少症,分为早发中性粒细胞减少症和无早发中性粒细胞减少症病例;同时根据第一周后有无中性粒细胞减少症,分为晚发中性粒细胞减少症和无晚发中性粒细胞减少症病例。分别对其临床情况进行比较,对中性粒细胞减少症的危险因素进行分析。结果共108例患儿纳入本研究,平均胎龄(30.1±2.2)周,平均出生体重(1188±216) g。其中32例发生早发中性粒细胞减少症,53例发生晚发中性粒细胞减少症。早发中性粒细胞减少症患儿孕母妊娠期患高血压疾病发生率高于未发生早发中性粒细胞减少症患儿(59.4%比31.6%, P=0.007)。晚发中性粒细胞减少症患儿胎龄小于未发生晚发中性粒细胞减少症患儿[(29.5±2.3)周比(30.6±2.0)周, P=0.009];出生体重低于未发生晚发中性粒细胞减少症患儿[(1123±212) g比(1251±201) g, P=0.002];早发感染、晚发感染的发生率均高于未发生晚发中性粒细胞减少症患儿(50.9%比30.9%, P=0.034;100%比43.6%, P<0.001)。早发感染患儿中血小板减少症发生率高于中性粒细胞减少症发生率(45.5%比25.0%, P=0.045)。结论早发中性粒细胞减少症与晚发中性粒细胞减少症的危险因素不同。孕母妊娠期高血压疾病可能是早发中性粒细胞减少症的危险因素;小胎龄、低出生体重、早发感染和晚发感染可能是晚发中性粒细胞减少症的危险因素。%Objective To investigate the risk factors for neutropenia in extremely low birth weight ( EL-BW) infants.Methods We retrospectively studied the clinical data of ELBW infants treated in Neonatal

  5. Lumbriculus variegatus loading study

    Data.gov (United States)

    U.S. Environmental Protection Agency — Results from sediment bioaccumulation tests with Lumbriculus variegatus with evaluating the effects of organism loading density. This dataset is associated with the...

  6. Carbohydrate-Loading Diet

    Science.gov (United States)

    ... Grape juice (12 ounces) 55 225 Lunch Milk, chocolate, reduced fat (12 ounces) 45 285 4 slices ... of carb-loading for sports performance. Academy of Nutrition and Dietetics. http://www.eatright.org/resource/fitness/ ...

  7. LOADING SIMULATION PROGRAM C

    Data.gov (United States)

    U.S. Environmental Protection Agency — LSPC is the Loading Simulation Program in C++, a watershed modeling system that includes streamlined Hydrologic Simulation Program Fortran (HSPF) algorithms for...

  8. Cognitive load theory

    NARCIS (Netherlands)

    Kirschner, Paul A.; Kirschner, Femke; Paas, Fred

    2010-01-01

    Kirschner, P. A., Kirschner, F. C., & Paas, F. (2009). Cognitive load theory. In E. M. Anderman & L. H. Anderman (Eds.). Psychology of classroom learning: An encyclopedia, Volume 1, a-j (pp. 205-209). Detroit, MI: Macmillan Reference.

  9. Static Loads Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides the capability to perform large-scale structural loads testing on spacecraft and other structures. Results from these tests can be used to verify...

  10. Plug Load Data

    Data.gov (United States)

    National Aeronautics and Space Administration — We provide MATLAB binary files (.mat) and comma separated values files of data collected from a pilot study of a plug load management system that allows for the...

  11. Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X-linked neutropenia by exceeding Aurora B kinase error correction capacity.

    Science.gov (United States)

    Moulding, Dale A; Moeendarbary, Emad; Valon, Leo; Record, Julien; Charras, Guillaume T; Thrasher, Adrian J

    2012-11-01

    The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics because of increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased viscosity by up-regulating force applied to chromosomes and increased the density of microtubules at kinetochores. Mitotic abnormalities were because of overload of the aurora signaling pathway as subcritical inhibition of Aurora in CA-WASp cells caused increased cytokinesis failure, while overexpression reduced defects. These findings demonstrate that changes in cell mechanics can cause significant mitotic abnormalities leading to genomic instability, and highlight the importance of mechanical sensors such as Aurora B in maintaining the fidelity of hematopoietic cell division.

  12. Levamisole-induced leukocytoclastic vasculitis and neutropenia in a patient with cocaine use: An extensive case with necrosis of skin, soft tissue, and cartilage

    Science.gov (United States)

    2012-01-01

    Levamisole-induced vasculitis is a relatively new entity in people who use cocaine. We describe a 44-year-old woman with a history of cocaine use who presented with a complaint of a painful rash of 2-3 month’s duration on her extremities, cheeks, nose, and earlobes. She had not experienced fever, weight loss, alopecia, dry eyes, oral ulcers, photosensitivity, or arthralgia. Examination revealed tender purpuric eruptions with central necrosis on her nose, cheeks, earlobes, and extremities. Laboratory investigations revealed neutropenia, an elevated erythrocyte sedimentation rate (ESR), presence of lupus anticoagulant, low complement component 3 (C3), and presence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). A urine toxicology screen was positive for cocaine, and gas chromatography–mass spectrometry was positive for levamisole. Skin biopsy showed leukocytoclastic vasculitis and small vessel thrombosis. Necrotic lesions of the nose led to its self-amputation. Large bullae on the lower extremities ruptured, leading to wound infection and extensive necrosis that required multiple surgical debridements. When necrosis progressed despite debridement, bilateral above-knee amputation of the legs was performed. Once new lesions stopped appearing, the patient was discharged home. Two months later, she had a recurrence related to cocaine use. To the best of our knowledge, this is only the second reported case of levamisole-induced vasculitis that required above-knee amputation. PMID:23186390

  13. TE(01) High Power Disk Loaded Guide Load

    CERN Document Server

    Farkas, Zoltan D

    2005-01-01

    A method to design a matching section from a smooth guide to a disk loaded guide, using a variation of broadband matching* is described. Using this method, we show how to design high power loads, filters and attenuators. The load consists of a disk loaded coaxial guide, operating in the T01

  14. E-2C Loads Calibration in DFRC Flight Loads Lab

    Science.gov (United States)

    Schuster, Lawrence S.

    2008-01-01

    Objectives: a) Safely and efficiently perform structural load tests on NAVAIR E-2C aircraft to calibrate strain gage instrumentation installed by NAVAIR; b) Collect load test data and derive loads equations for use in NAVAIR flight tests; and c) Assist flight test team with use of loads equations measurements at PAX River.

  15. Dielectrically Loaded Biconical Antennas

    Science.gov (United States)

    Nusseibeh, Fouad Ahmed

    1995-01-01

    Biconical antennas are of great interest to those who deal with broadband applications including the transmission/reception of pulses. In particular, wide-angle conical antennas are an attractive choice in many applications including Electronic Support Measures (ESM) and the measurements of transient surface currents and charge densities on aircraft. Dielectric loading in the interior region of a conical antenna can be used to reduce the size of the antenna especially at low frequencies and/or for structural strength. Therefore, having an analytical solution for the input impedance and the frequency response is very helpful in optimizing the design and understanding the behavior of the antenna. From the quasi-analytical solution for the input impedance and the electric field of a wide-angle conical antenna, it can be seen that the dielectric loading in the antenna region improves the input impedance at low frequencies, but increases the number of resonance points and the magnitude of these peaks. When an inhomogeneous dielectric load is used, the magnitude of the resonance peaks is decreased (depending on the way the load is distributed), improving the input impedance of the antenna significantly. Introducing a dielectric load in the interior region of an electrically short receiving cone makes the antenna behave as an electrically longer antenna. However, this is not true for the case for electrical1y long antennas. For the case of pulse transmission, the dielectric load affects only the amplitude. Of course, if the dielectric fills the whole space, both transmitting and receiving antennas behave as electrically longer antennas.

  16. 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...

  17. Wave Loads on Cylinders

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Frigaard, Peter

    1989-01-01

    Wave loads may be defined as time varying forces on a body resulting from the wave induced flow fields which surrounds the body in whole or in part. Such unsteady fluid forces are the net result of pressure and shear forces integrated over the instantaneous wetted area.......Wave loads may be defined as time varying forces on a body resulting from the wave induced flow fields which surrounds the body in whole or in part. Such unsteady fluid forces are the net result of pressure and shear forces integrated over the instantaneous wetted area....

  18. Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

    Science.gov (United States)

    Younis, T; Rayson, D; Jovanovic, S; Skedgel, C

    2016-10-01

    The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold.

  19. Retrospective survey and evaluation of first-line antibiotics for chemotherapy-induced febrile neutropenia in patients with acute myeloid leukemia

    Science.gov (United States)

    Mukoyama, Naoki; Nakashima, Marie; Miyamura, Koichi; Yoshimi, Akira; Noda, Yukihiro; Mori, Kazuhiro

    2017-01-01

    ABSTRACT Patients with acute leukemia are susceptible to chemotherapy-induced severe myelosuppression, and therefore are at a high risk for febrile neutropenia (FN). In such cases, the use of broad-spectrum antibiotics such as fourth-generation cephalosporins and carbapenems is recommended as first-line antimicrobial treatment; however, the effectiveness of these agents in patients with acute myeloid leukemia (AML) has not been investigated in detail. We retrospectively examined and evaluated the effectiveness of first-line antibiotic treatment regimens for chemotherapy-induced FN in patients with AML in Japanese Red Cross Nagoya Daiichi Hospital. The evaluated first-line treatment regimens were as follows: cefozopran (CZOP) + amikacin (AMK) in 38 cases, cefepime (CFPM) alone in 2 cases, CFPM + AMK in 2 cases, piperacillin (PIPC) + AMK in 2 cases, and CZOP alone in 1 case. Additionally, prophylactic antifungal agents were administered in all cases. Markedly effective, effective, moderately effective, and ineffective responses occurred in 31.1%, 8.9%, 8.9%, and 51.1%, respectively, of the treated cases. The response rate, defined as the combination of markedly effective and effective outcomes, was 40.0%. In 11 cases, impairment of renal functions were observed, and they were associated with combination treatments including AMK; nine of these were associated with a glycopeptide. The combination of CZOP with AMK (84.4%) was the most commonly used first-line treatment for FN in patients with AML; carbapenem or tazobactam/PIPC has never been used for treatment of such cases. Our findings demonstrate that fourth-generation cephems will be an effective first-line treatment for FN in patients with AML in our hospital. PMID:28303057

  20. Time trends in utilization of G-CSF prophylaxis and risk of febrile neutropenia in a Medicare population receiving adjuvant chemotherapy for early-stage breast cancer.

    Science.gov (United States)

    Goyal, Ravi K; Tzivelekis, Spiros; Rothman, Kenneth J; Candrilli, Sean D; Kaye, James A

    2017-09-18

    The purpose of this study is to assess temporal trends in the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis and risk of febrile neutropenia (FN) among older women receiving adjuvant chemotherapy for early-stage breast cancer. Women aged ≥ 66 years with diagnosis of early-stage breast cancer who initiated selected adjuvant chemotherapy regimens were identified using the SEER-Medicare data from 2002 to 2012. Adjusted, calendar-year-specific proportions were estimated for use of G-CSF primary prophylaxis (PP) and secondary prophylaxis and FN risk in the first and the second/subsequent cycles during the first course of chemotherapy, using logistic regression models. calendar-year-specific mean probabilities were estimated with covariates set to modal values. Among 11,107 eligible patients (mean age 71.7 years), 74% received G-CSF in the first course of chemotherapy. Of all patients, 5819 (52%) received G-CSF PP, and among those not receiving G-CSF PP, only 5% received G-CSF secondary prophylaxis. The adjusted proportion using G-CSF PP increased from 6% in 2002 to 71% in 2012. During the same period, the adjusted risk of FN in the first cycle increased from 2% to 3%; the adjusted risk increased from 1.5% to 2.9% among those receiving G-CSF PP and from 2.3% to 3.5% among those not receiving G-CSF PP. The use of G-CSF PP increased substantially during the study period. Although channeling of higher-risk patients to treatment with G-CSF PP is expected, the adjusted risk of FN among patients treated with G-CSF PP tended to be lower than among those not receiving G-CSF PP.

  1. Incidence of Febrile Neutropenia in Korean Female Breast Cancer Patients Receiving Preoperative or Postoperative Doxorubicin/Cyclophosphamide Followed by Docetaxel Chemotherapy

    Science.gov (United States)

    Kim, Chang Gon; Sohn, Joohyuk; Chon, Hongjae; Kim, Joo Hoon; Heo, Su Jin; Cho, Hyunsoo; Kim, In Jung; Kim, Seung Il; Park, Seho; Park, Hyung Seok

    2016-01-01

    Purpose Doxorubicin/cyclophosphamide followed by docetaxel chemotherapy (AC-D) is an intermediate risk factor (incidence of 10%–20%) for febrile neutropenia (FN) in breast cancer. However, the reported incidence of FN while using this regimen was obtained mostly from Western breast cancer patients, with little data available from Asian patients. This study aimed to assess the incidence of FN in Korean breast cancer patients and to describe clinical variables related to FN. Methods From September 2010 to February 2013, data from the Yonsei Cancer Center registry of breast cancer patients who received neoadjuvant or adjuvant chemotherapy with four cycles of AC-D (60 mg/m2 doxorubicin, 600 mg/m2 cyclophosphamide every 3 weeks for four cycles followed by 75 mg/m2 or 100 mg/m2 docetaxel every 3 weeks for four cycles) were analyzed. The incidence of FN, FN associated complications, dose reduction/delays, and relative dose intensity (RDI) were investigated. Results Among the 254 patients reported to the registry, the FN incidence after AC-D chemotherapy was 29.5% (75/254), consisting of 25.2% (64/254) events during AC and 4.7% (12/254) during docetaxel chemotherapy. Dose reductions, delays, and RDI less than 85.0% during AC were observed in 16.5% (42/254), 19.5% (47/254), and 11.0% (28/254) of patients, respectively. Patients with FN events frequently experienced dose reduction/delays, which eventually led to a decreased RDI. Conclusion The incidence of FN during AC-D neoadjuvant or adjuvant chemotherapy was higher than expected in Korean breast cancer patients. Whether these patients should be classified as a high-risk group for FN warrants future prospective studies. PMID:27064666

  2. 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.

  3. Clinical Outcomes and Cost-effectiveness of Primary Prophylaxis of Febrile Neutropenia During Adjuvant Docetaxel and Cyclophosphamide Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Yu, Joanne L; Chan, Kelvin; Kurin, Michael; Pasetka, Mark; Kiss, Alex; Sridhar, Srikala S; Warner, Ellen

    2015-01-01

    Docetaxel and cyclophosphamide (TC) is a widely used breast cancer adjuvant regimen. We sought to compare the rates of febrile neutropenia (FN) between patients receiving no primary prophylaxis (PP) and those receiving PP with either granulocyte-colony stimulating factor (G-CSF) or antibiotics. We also analyzed cost-effectiveness of TC with and without either G-CSF or antibiotics. Charts were reviewed of all 340 patients who received adjuvant TC between January 2008 and December 2012 at two major cancer centers. Rates of FN in the three groups - no PP, PP with G-CSF and PP with antibiotics were compared. A Markov model was constructed comparing cost-effectiveness of PP with G-CSF, PP with antibiotics, and secondary prophylaxis (SP) with G-CSF after an episode of FN in a previous cycle. Costs were based on actual resource utilization and supplemented by the published literature, adjusted to 2012 Canadian dollars. Of the 73 (21%) patients who did not receive any PP, 23 (32%) of patients developed FN. Of the 192 (57%) patients receiving PP with G-CSF alone, only two (1%; p < 0.0001) developed FN; and of the 53 (16%) receiving PP with antibiotics alone, six (11%; p < 0.01) developed FN. From a cost-standpoint, PP with G-CSF was less cost-effective than PP with antibiotics. The rate of FN with TC chemotherapy exceeds 30%, and American Society of Clinical Oncology guidelines recommend PP with G-CSF in this situation. PP with antibiotics is more cost-effective, and is a reasonable option in resource-limited settings or for patients who decline or do not tolerate G-CSF.

  4. Load research and load estimation in electricity distribution

    Energy Technology Data Exchange (ETDEWEB)

    Seppaelae, A. [VTT Energy, Espoo (Finland). Energy Systems

    1996-12-31

    The topics introduced in this thesis are: the Finnish load research project, a simple form customer class load model, analysis of the origins of customers load distribution, a method for the estimation of the confidence interval of customer loads and Distribution Load Estimation (DLE) which utilises both the load models and measurements from distribution networks. The Finnish load research project started in 1983. The project was initially coordinated by the Association of Finnish Electric Utilities and 40 utilities joined the project. Now there are over 1000 customer hourly load recordings in a database. A simple form customer class load model is introduced. The model is designed to be practical for most utility applications and has been used by the Finnish utilities for several years. The only variable of the model is the customers annual energy consumption. The model gives the customers average hourly load and standard deviation for a selected month, day and hour. The statistical distribution of customer loads is studied and a model for customer electric load variation is developed. The model results in a lognormal distribution as an extreme case. Using the `simple form load model`, a method for estimating confidence intervals (confidence limits) of customer hourly load is developed. The two methods selected for final analysis are based on normal and lognormal distribution estimated in a simplified manner. The estimation of several cumulated customer class loads is also analysed. Customer class load estimation which combines the information from load models and distribution network load measurements is developed. This method, called Distribution Load Estimation (DLE), utilises information already available in the utilities databases and is thus easy to apply

  5. Probabilistic Load Flow

    DEFF Research Database (Denmark)

    Chen, Peiyuan; Chen, Zhe; Bak-Jensen, Birgitte

    2008-01-01

    This paper reviews the development of the probabilistic load flow (PLF) techniques. Applications of the PLF techniques in different areas of power system steady-state analysis are also discussed. The purpose of the review is to identify different available PLF techniques and their corresponding...

  6. Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis.

    Directory of Open Access Journals (Sweden)

    Pieter W Smit

    Full Text Available BACKGROUND: Dried blood spots (DBS have been used as alternative specimens to plasma to increase access to HIV viral load (VL monitoring and early infant diagnosis (EID in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. METHODS AND FINDINGS: Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52-100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78-100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. CONCLUSIONS: Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. TRIAL REGISTRATION: PROSPERO Registration #: CRD42013003621.

  7. Systematic Review of the Use of Dried Blood Spots for Monitoring HIV Viral Load and for Early Infant Diagnosis

    Science.gov (United States)

    Smit, Pieter W.; Sollis, Kimberly A.; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M.; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perriens, Joseph H.; Peeling, Rosanna W.

    2014-01-01

    Background Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. Methods and Findings Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52–100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78–100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. Conclusions Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. Trial Registration PROSPERO Registration #: CRD42013003621. PMID:24603442

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

    Directory of Open Access Journals (Sweden)

    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.

     

     

  9. daily nigerian nigerian nigerian peak load forec peak load forec ...

    African Journals Online (AJOL)

    User

    is generally needed for control and scheduling power system and also as inputs to load flo analysis .... Figure 1 Seasonal indices computing neural network ... Feedback paths are sometimes used. In applying a neural network to electric load ...

  10. Load flow analysis using decoupled fuzzy load flow under critical ...

    African Journals Online (AJOL)

    user

    of power system, reliable fuzzy load flow is developed to overcome the limitations of the ... of power mismatches are taken as two inputs for fuzzy logic controller. ..... Programming Based Load Flow Algorithm For Systems Containing Unified ...

  11. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

    Directory of Open Access Journals (Sweden)

    Monica Fung

    Full Text Available Invasive fungal disease (IFD causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN. These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates.Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85 and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87 or overall mortality (RR 0.95, 95% CI 0.46-1.99. The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing.Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality

  12. Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

    Directory of Open Access Journals (Sweden)

    Colombo Elisa A

    2012-01-01

    Full Text Available Abstract Background Poikiloderma with Neutropenia (PN is a rare autosomal recessive genodermatosis caused by C16orf57 mutations. To date 17 mutations have been identified in 31 PN patients. Results We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel C16orf57 mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain. Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase. According to bioinformatic prediction, all known C16orf57 mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding. Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect. Conclusions In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of C16orf57 gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance. The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the

  13. Nutrient and Coliform Loading (NCL)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is a database of available fecal coliform bacteria, fecal streptococci bacteria, and nutrient loading data. Loading for contaminants other than fecal coliform...

  14. The International Mass Loading Service

    CERN Document Server

    Petrov, Leonid

    2015-01-01

    The International Mass Loading Service computes four loadings: a) atmospheric pressure loading; b) land water storage loading; c) oceanic tidal loading; and d) non-tidal oceanic loading. The service provides to users the mass loading time series in three forms: 1) pre-computed time series for a list of 849 space geodesy stations; 2) pre-computed time series on the global 1deg x 1deg grid; and 3) on-demand Internet service for a list of stations and a time range specified by the user. The loading displacements are provided for the time period from 1979.01.01 through present, updated on an hourly basis, and have latencies 8-20 hours.

  15. Febrile neutropenia in childhood cancer

    African Journals Online (AJOL)

    Chemotherapy-induced immunosuppression renders children who receive treatment for cancer ... of the effect of chemotherapeutic agents and radiotherapy on the proliferation and ... negative organisms penetrate the mucosa frequently at the ...

  16. Android Fully Loaded

    CERN Document Server

    Huddleston, Rob

    2012-01-01

    Fully loaded with the latest tricks and tips on your new Android! Android smartphones are so hot, they're soaring past iPhones on the sales charts. And the second edition of this muscular little book is equally impressive--it's packed with tips and tricks for getting the very most out of your latest-generation Android device. Start Facebooking and tweeting with your Android mobile, scan barcodes to get pricing and product reviews, download your favorite TV shows--the book is positively bursting with practical and fun how-tos. Topics run the gamut from using speech recognition, location-based m

  17. 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

    OpenAIRE

    María Adelaida Aristizábal Gil; Isabel Cristina Valencia Montoya; Carolina Jaramillo Arango

    2008-01-01

    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 historia...

  18. 儿童恶性肿瘤化疗后中性粒细胞减少并发脓毒症的早期识别%Early identification of sepsis in cancer children with neutropenia after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    杨燕文; 王莹; 汤静燕; 李璧如

    2012-01-01

    目的 本研究通过对恶性肿瘤儿童化疗后粒细胞减少症并发发热时早期临床征象进行研究,探寻其和脓毒症发病的关系.方法 以恶性肿瘤化疗后粒细胞减少症并发发热的66例患儿为研究对象,进行前瞻性观察性研究.根据病情进展,将66例患儿分为脓毒症组26例,非脓毒症组40例.收集并比较两组患儿的临床资料和实验室指标.结果 脓毒症组和非脓毒症组患儿的初始体温、粒细胞减少天数、中性粒细胞绝对计数(absolute neutrophic count,ANC)、血清C反应蛋白水平、降钙素原水平和培养阳性率比较,差异有统计学意义(P<0.05).当体温>40℃、ANC<0.1×109/L、C反应蛋白升高、降钙素原升高、培养阳性提示可能并发脓毒症.体温< 39℃、粒细胞减少<5d、ANC >0.5×109/L提示并发脓毒症可能性很小.结论 初始体温高、粒细胞减少天数长、ANC严重减少、C反应蛋白及降钙素原升高和培养阳性与恶性肿瘤儿童并发脓毒症相关.%Objective To investigate the clinical manifestations of the febrile neutropenia cancer children,explore the relationship between the clinical data and sepsis.Methods A prospective observation study was employed,and 66 cancer children complicated with febrile and neutropenia after chemotherapy were enrolled.Sixty-six cases were divided into two groups:septic group ( n =26 ) and non-septic group ( n =40).Clinical and laboratory data were collected and compared.Results Body temperature,neutropenia duration,absolute neutrophic count ( ANC ),C-reactive protein ( CRP ),procalcitonin (PCT) and culture positive rate showed statistically differences between the septic and non-septic groups ( P < 0.05 ).Body temperature >40 ℃,ANC < 0.1 × 109/L,increases of serum CRP and PCT levels and positive culture were correlated with sepsis.Body temperature < 39 ℃,neutropenia duration < 5 ds,ANC > 0.5 × 109/L were less correlated with sepsis

  19. Load Control System Reliability

    Energy Technology Data Exchange (ETDEWEB)

    Trudnowski, Daniel [Montana Tech of the Univ. of Montana, Butte, MT (United States)

    2015-04-03

    This report summarizes the results of the Load Control System Reliability project (DOE Award DE-FC26-06NT42750). The original grant was awarded to Montana Tech April 2006. Follow-on DOE awards and expansions to the project scope occurred August 2007, January 2009, April 2011, and April 2013. In addition to the DOE monies, the project also consisted of matching funds from the states of Montana and Wyoming. Project participants included Montana Tech; the University of Wyoming; Montana State University; NorthWestern Energy, Inc., and MSE. Research focused on two areas: real-time power-system load control methodologies; and, power-system measurement-based stability-assessment operation and control tools. The majority of effort was focused on area 2. Results from the research includes: development of fundamental power-system dynamic concepts, control schemes, and signal-processing algorithms; many papers (including two prize papers) in leading journals and conferences and leadership of IEEE activities; one patent; participation in major actual-system testing in the western North American power system; prototype power-system operation and control software installed and tested at three major North American control centers; and, the incubation of a new commercial-grade operation and control software tool. Work under this grant certainly supported the DOE-OE goals in the area of “Real Time Grid Reliability Management.”

  20. 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...... the hourly load for refrigeration for the following 42 hours is forecasted. The forecast models are adaptive linear time-series models which are fitted with a computationally efficient recursive least squares scheme. The dynamic relations between the inputs and the load is modeled by simple transfer...

  1. Shear loading of costal cartilage

    CERN Document Server

    Subit, Damien

    2014-01-01

    A series of tests were performed on a single post-mortem human subject at various length scales. First, tabletop tests were performed. Next, the ribs and intercostal muscles were tested with the view to characterize the load transfer between the ribs. Finally, the costal cartilage was tested under shear loading, as it plays an important in the transfer of the load between the ribs and the sternum. This paper reports the results of dynamic shear loading tests performed on three samples of costal cartilage harvested from a single post-mortem human subject, as well as the quantification of the effective Young's modulus estimated from the amount of cartilage calcification.

  2. Metamaterial Loadings for Waveguide Miniaturization

    CERN Document Server

    Odabasi, H

    2013-01-01

    We show that a rectangular metallic waveguide loaded with metamaterial elements consisting of electric-field coupled (ELC) resonators placed at the side walls can operate well below the cutoff frequency of the respective unloaded waveguide. The dispersion diagrams indicate that propagating modes in ELC-loaded waveguides are of forward-type for both TE and TM modes. We also study the dispersion diagram and transmission characteristics of rectangular metallic waveguides simultaneously loaded with ELCs and split ring resonators (SRRs). Such doubly-loaded waveguides can support both forward wave and backward waves, and provide independent control of the propagation characteristics for the respective modes.

  3. Load forecasting of supermarket refrigeration

    DEFF Research Database (Denmark)

    Rasmussen, Lisa Buth; Bacher, Peder; Madsen, Henrik

    2016-01-01

    This paper presents a novel study of models for forecasting the electrical load for supermarket refrigeration. The data used for building the models consists of load measurements, local climate measurements and weather forecasts. The load measurements are from a supermarket located in a village...... in Denmark. Every hour the hourly electrical load for refrigeration is forecasted for the following 42 h. The forecast models are adaptive linear time series models. The model has two regimes; one for opening hours and one for closing hours, this is modeled by a regime switching model and two different...

  4. Load carriage by infantry soldiers

    Directory of Open Access Journals (Sweden)

    N. C. Majumdar

    1958-07-01

    Full Text Available At constant speed of marching, oxygen consumption has been found to increase linearly with the amount of load carried, indicating that there is no optimum load. However, an optimum speed of marching has been found, depending on the terrain condition. A different line of approach, involving a study of the relationship between stride-length, frequency of stepping and speed in normal walking and the effect of muscular fatigue on this relationship has also yielded similar results. Desirability of further studies on the effect of load on optimum speed of marching, effective reduction of weight of equipment and optimum distribution of load on the body has been stressed.

  5. Demand Response Load Following of Source and Load Systems

    DEFF Research Database (Denmark)

    Hu, Jianqiang; Cao, Jinde; Yong, Taiyou

    2017-01-01

    capacities and regulation rates of aggregators. Based on the evaluation results, the dispatch center optimizes the real time load following trajectories for the generating units and the flexible load agents via look-ahead optimization by considering the injection of renewable power. Furthermore, we mainly...

  6. TE_01 High Power Disk Loaded Guide Load

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, Z.D.; /SLAC

    2005-06-01

    A method to design a matching section from a smooth guide to a disk-loaded guide, using a variation of broadband matching, [1, 2] is described. Using this method, we show how to design high power loads, attenuators and filters. The load consists of a disk-loaded coaxial guide operating in the TE{sub 01}-mode. We use this mode because it has no electric field terminating on a conductor, has no axial currents, and has no current at the cylinder-disk interface. A high power load design that has -35 dB reflection and a 200 MHz, -20 dB bandwidth, is presented. It is expected that it will carry the 600 MW output peak power of the pulse compression network. We use coaxial geometry and stainless steel material to increase the attenuation per cell.

  7. Immediate Versus Early Loading and Conventional Loading in Implant Dentistry

    Directory of Open Access Journals (Sweden)

    Hassan Maghaireh

    2013-12-01

    Full Text Available To minimize the risk of implant failures after their placement, dental implants are traditionally kept load-free for 3 to 8 months to establish osseointegration before connecting the prosthetic super-structure (conventional loading. However, implant dentists are under continuous pressure from the media and patients to speed up the treatment and reduce number of visits during the implant therapy. Immediate implant loading can also reduce the cost and might also improve aesthetics as claimed by some surgeons. This pressure from the media, patients and dentists was behind introducing changes into the loading protocols and nowadays implants are loaded early and even immediately and it would be useful to know whether there is a difference in success rates between immediately and early loaded implants compared with conventionally loaded implants. It is well known that whenever a clinician is faced with a clinical question, the answer(s should be evidence based to avoid the risk of bias as opinion based answers can be misleading and can cause more failures in the dental practice. This mini-review aims to evaluate the effects of (1 immediate (within 1 week, (2 early (between 1 week and 2 months, and (3 conventional (after 2 months loading of osseointegrated dental implants. The review found no evidence that attaching artificial teeth either immediately, after 6 weeks (early or after at least 3 months (conventional led to any important differences in the failure of the implant or the artificial tooth, or to the amount of bone which surrounded the implant (any bone loss would be an undesirable consequence. However, we found a trend of more failures and complications with early loading when compared to immediate or conventional loading. More research is needed in this area. - See more at: http://smiledentaljournal.com/article.php?id=59#sthash.mniQLIcf.dpuf

  8. Optimal load shedding and restoration

    Science.gov (United States)

    Xu, Ding

    Load shedding is an emergency control action in power systems that can save systems from a wide-area blackout. Underfrequency load shedding, steady state load shedding, and voltage load shedding are widely used in power systems. These methods utilize either the steady state model or a simplified dynamic model to represent a power systems. In this dissertation, a general optimal load shedding method that considers both the dynamic process and load distribution is proposed. The unfavorable load shedding is then formulated as an optimization problem with the objective function of cost minimization. This objective function is subjected to system, security, and operation constraints. The entire problem becomes a question of optimization with differential and nonlinear equations as constraints. To solve this problem, discretization is used to change the differential equations into algebraic equations. The original problem is thus reformulated as an optimization problem and can be solved by a standard mathematical program. The general idea is then applied to traditional power systems, deregulated power systems, power systems with distributed generation, and load restoration. In the traditional power system, the method shows that governor action, generation dynamic, disturbance location, and economic factors can be taken into consideration. In the deregulated power system, two power market models are developed and incorporated into the load shedding scheme. In power systems with multiple distributed generations, the different cases of disturbances are analyzed and models of different distributed generation developed. The general idea is then applied. Finally, the load restoration problem is studied, and it is proposed that an optimization method be applied to it. This dissertation provides a comprehensive solution for load shedding problem in power systems. The models developed in this research can also be used to study other power system problems.

  9. Load identification during object handling

    NARCIS (Netherlands)

    Kortier, H.G.; Veltink, P.H.

    2011-01-01

    In this paper a new concept to identify environ- mental loads during the interaction with the human body by sensing interface forces and movement is proposed. Mass and spring loads were moved by hand over a fixed height difference. Kinematic and kinetic quantities were measured between the hand and

  10. Loading Conditions and Longitudinal Strength

    DEFF Research Database (Denmark)

    Sørensen, Herman

    1995-01-01

    Methods for the calculation of the lightweight of the ship.Loading conditions satisfying draught, trim and intact stability requirements and analysis of the corresponding stillwater longitudinal strength.......Methods for the calculation of the lightweight of the ship.Loading conditions satisfying draught, trim and intact stability requirements and analysis of the corresponding stillwater longitudinal strength....

  11. Loading Conditions and Longitudinal Strength

    DEFF Research Database (Denmark)

    Sørensen, Herman

    1995-01-01

    Methods for the calculation of the lightweight of the ship.Loading conditions satisfying draught, trim and intact stability requirements and analysis of the corresponding stillwater longitudinal strength.......Methods for the calculation of the lightweight of the ship.Loading conditions satisfying draught, trim and intact stability requirements and analysis of the corresponding stillwater longitudinal strength....

  12. LOAD MANAGEMENT IN CLOUD ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Esha Sarkar

    2014-09-01

    Full Text Available Cloud computing is an on demand service in which shared resources, information, software and other devices are provided to the end user as per their requirement at a specific time. A cloud consists of several elements such as clients, datacenters and distributed servers. There are n number of clients and end users involved in cloud environment. These clients may make requests to the cloud system simultaneously, making it difficult for the cloud to manage the entire load at a time. The load can be CPU load, memory load, delay or network load. This might cause inconvenience to the clients as there may be delay in the response time or it might affect the performance and efficiency of the cloud environment. So, the concept of load balancing is very important in cloud computing to improve the efficiency of the cloud. Good load balancing makes cloud computing more efficient and improves user satisfaction. This paper gives an approach to balance the incoming load in cloud environment by making partitions of the public cloud

  13. 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

  14. The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis.

    Science.gov (United States)

    Do, Tran; Medhekar, Rohan; Bhat, Raksha; Chen, Hua; Niravath, Polly; Trivedi, Meghana V

    2015-10-01

    The febrile neutropenia (FN) rates reported with the docetaxel 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) (TC) regimen given every 3 weeks vary from 4 to 69 % in early-stage breast cancer (ESBC) patients. This creates uncertainty as to whether patients receiving the TC regimen should also receive granulocyte colony-stimulating factor primary prophylaxis (G-CSFpp), which is recommended when chemotherapy regimens have ≥20 % FN rate. We conducted a meta-analysis of published studies to determine FN rate with the TC regimen, its dependence on patients' age, and the efficacy of G-CSFpp in reducing it in ESBC patients. We systematically searched the literature via PUBMED using the following terms: 'docetaxel', 'cyclophosphamide', 'febrile neutropenia', and 'breast cancer'. Inclusion criteria were full text peer-reviewed clinical studies in English reporting FN rates with TC regimen in relationship to G-CSFpp. Comprehensive meta-analysis software was used for all statistical analyses. Eight studies (N = 1542 patients) were included in our meta-analysis. The pooled mean FN rate was 23.2 % (95 % confidence interval (CI) 6.9-55.2 %; Q = 218.17, I (2) = 97.7). The FN risk in <65 years old patients was lower by 67.7 % compared to that in patients ≥65 years old (pooled odds ratio (OR) 0.323; 95 % CI 0.127-0.820; P = 0.017). The FN risk was reduced by 92.3 % with G-CSFpp (pooled OR 0.077; 95 % CI 0.013-0.460; P = 0.005). Our meta-analysis demonstrated that TC regimen was associated with ≥20 % FN risk, which was significantly higher in patients ≥65 years old and improved with G-CSFpp. G-CSFpp should be considered for all ESBC patients receiving TC regimen, especially those ≥65 years old.

  15. Umbilical Cable Recovery Load Analysis

    Institute of Scientific and Technical Information of China (English)

    YAN Shu-wang; JIA Zhao-lin; FENG Xiao-wei; LI Shi-tao

    2013-01-01

    Umbilical cable is a kind of integrated subsea cable widely used in the exploration and exploitation of oil and gas field.The severe ocean environment makes great challenges to umbilical maintenance and repair work.Damaged umbilical is usually recovered for the regular operation of the offshore production system.Analysis on cables in essence is a two-point boundary problem.The tension load at the mudline must be known first,and then the recovery load and recovery angle on the vessel can be solved by use of catenary equation.The recovery analysis also involves umbilicalsoil interaction and becomes more complicated.Calculation methods for recovery load of the exposed and buried umbilical are established and the relationship between the position of touch down point and the recovery load as well as the recovery angle and recovery load are analyzed.The analysis results provide a theoretical reference for offshore on-deck operation.

  16. Umbilical cable recovery load analysis

    Science.gov (United States)

    Yan, Shu-wang; Jia, Zhao-lin; Feng, Xiao-wei; Li, Shi-tao

    2013-06-01

    Umbilical cable is a kind of integrated subsea cable widely used in the exploration and exploitation of oil and gas field. The severe ocean environment makes great challenges to umbilical maintenance and repair work. Damaged umbilical is usually recovered for the regular operation of the offshore production system. Analysis on cables in essence is a two-point boundary problem. The tension load at the mudline must be known first, and then the recovery load and recovery angle on the vessel can be solved by use of catenary equation. The recovery analysis also involves umbilical-soil interaction and becomes more complicated. Calculation methods for recovery load of the exposed and buried umbilical are established and the relationship between the position of touch down point and the recovery load as well as the recovery angle and recovery load are analyzed. The analysis results provide a theoretical reference for offshore on-deck operation.

  17. Wind load reduction for heliostats

    Energy Technology Data Exchange (ETDEWEB)

    Peterka, J.A.; Hosoya, N.; Bienkiewicz, B.; Cermak, J.E.

    1986-05-01

    This report presents the results of wind-tunnel tests supported through the Solar Energy Research Institute (SERI) by the Office of Solar Thermal Technology of the US Department of Energy as part of the SERI research effort on innovative concentrators. As gravity loads on drive mechanisms are reduced through stretched-membrane technology, the wind-load contribution of the required drive capacity increases in percentage. Reduction of wind loads can provide economy in support structure and heliostat drive. Wind-tunnel tests have been directed at finding methods to reduce wind loads on heliostats. The tests investigated primarily the mean forces, moments, and the possibility of measuring fluctuating forces in anticipation of reducing those forces. A significant increase in ability to predict heliostat wind loads and their reduction within a heliostat field was achieved.

  18. Detection of HIV proviral DNA by a duplex fluorescence PCR for early diagnosis of HIV infection in infants%双重荧光PCR检测HIV前病毒DNA及其在婴幼儿HIV感染早期诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    张佳峰; 郭志宏; 黄晶晶; 丁晓贝; 黄蓓

    2013-01-01

    Objective To establish a duplex fluorescence PCR for detection of HIV proviral DNA and to evaluate its application for early diagnosis of HIV infection in infants .Methods A duplex fluores-cence PCR system was set up based on TaqMan technology for detection of human ribonuclease P ( RNase P) gene and long terminal repeat ( LTR) region of HIV.A recombinant plasmid containing the targeted gene fragment , pTG19-T, was constructed by TA cloning technique and used as the template for evaluation of sen -sitivity of the assay .Blood samples from 11 healthy individuals and 98 HIV-infected patients were collected and detected to validate the assay specificity .The assay of duplex fluorescence PCR was then carried out to detect 96 infant blood samples collected from several maternal and child health hospitals in Zhejiang province from January 2011 to September 2012 for early diagnosis of HIV infection .The results were compared with those by using the Roche HIV DNA qualitative detection kit .Results The established duplex fluorescence PCR could specifically detect HIV proviral DNA with a specificity of 100%and a detection sensitivity of 100 cps per reaction .The coincidence rate between the established assay and the Roche HIV DNA qualitative de -tection kit was 100%in the detection of 96 blood samples .Conclusion The duplex fluorescence PCR as-say showed advantages of cost-effectiveness , convenience , good specificity and accuracy with high sensitivi-ty.It could be used for early diagnosis of HIV infection in infants and also as a general technical platform for the detection of HIV proviral DNA .%  目的建立双重荧光PCR检测HIV前病毒DNA的方法,并应用于婴幼儿HIV感染的早期诊断。方法采用TaqMan技术,组建针对人类核糖核酸酶P( RNase P)和HIV的长末端重复序列( LTR)基因的双重荧光PCR体系;采用TA克隆技术构建pTG19-T重组质粒作为模板进行该方法灵敏度的评价;采用11

  19. Quasi monolithic silicon load cell for loads up to 1000 kg with insensitivity to non-homogeneous load distributions

    NARCIS (Netherlands)

    Wiegerink, Remco; Zwijze, Robert; Krijnen, Gijs; Lammerink, Theo; Elwenspoek, Miko

    2000-01-01

    In this paper, a micromachined silicon load cell (force sensor) is presented for measuring loads up to 1000 kg. The sensitive surface of 1 cm2 contains a matrix of capacitive sensing elements to make the load cell insensitive to non-homogeneous load distributions. The load cell has been realized and

  20. 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...

  1. Immediate loading of dental implants.

    Science.gov (United States)

    Henry, P J; Liddelow, G J

    2008-06-01

    The purpose of this review is to explore the concept of immediate loading as it pertains to dental implants and the indications for clinical practice. The definition of immediate loading will be considered together with a review of the relevant literature in an attempt to provide evidence-based guidelines for successful implementation into practice. A search of electronic databases including Medline, PubMed and the Cochrane Database of Systematic Reviews was undertaken using the terms "immediate loading'', "dental implants'', "immediate function'', "early loading'', "oral implants'', "immediate restoration'' and "systematic review''. This was supplemented by handsearching in peer-reviewed journals and cross-referenced with the articles accessed. Emphasis was given to systematic reviews and controlled clinical trials. A definition of immediate loading was suggested pertinent to the realities of logistics in clinical practice with respect to application and time frame. The literature was evaluated and shown to be limited with significant shortcomings. Guidelines and recommendations for clinical protocols were suggested and illustrated by examples of case types with a minimum of 1-3 years follow-up. A list of additional references for further reading was provided. Within the limitations of this review, there is evidence to suggest that immediate loading protocols have demonstrated high implant survival rates and may be cautiously recommended for certain clinical situations. However, more high level evidence studies, preferably randomized controlled trials (RCTs), over a long time frame are required to show a clear benefit over more conventional loading protocols.

  2. 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...... matrix assembled from modal parameters and the experimental responses recorded using standard sensors, is presented. The method implies the inversion of the FRF which, in general, is not full rank matrix due to the truncation of the modal space. Furthermore, some ecommendations are included to improve...

  3. Power Load Management as a Computational Market

    NARCIS (Netherlands)

    Ygge, Fredrik; Akkermans, Hans; Akkermans, J.M.

    1997-01-01

    Power load management enables energy utilities to reduce peak loads and thereby save money. Due to the large number of different loads, power load management is a complicated optimization problem. We present a new decentralized approach to this problem by modeling direct load management as a

  4. Probabilistic Meteorological Characterization for Turbine Loads

    DEFF Research Database (Denmark)

    Kelly, Mark C.; Larsen, Gunner Chr.; Dimitrov, Nikolay Krasimirov;

    2014-01-01

    Beyond the existing, limited IEC prescription to describe fatigue loads on wind turbines, we look towards probabilistic characterization of the loads via analogous characterization of the atmospheric flow, particularly for today's "taller" turbines with rotors well above the atmospheric surface....... These are used as input to loads calculation, and with a statistical loads output description, they allow for improved design and loads calculations....

  5. Power Load Management as a Computational Market

    NARCIS (Netherlands)

    Ygge, F.; Akkermans, J.M.

    1996-01-01

    Power load management enables energy utilities to reduce peak loads and thereby save money. Due to the large number of different loads, power load management is a complicated optimization problem. We present a new decentralized approach to this problem by modeling direct load management as a computa

  6. Power Load Management as a Computational Market

    NARCIS (Netherlands)

    Ygge, Fredrik; Akkermans, Hans

    1997-01-01

    Power load management enables energy utilities to reduce peak loads and thereby save money. Due to the large number of different loads, power load management is a complicated optimization problem. We present a new decentralized approach to this problem by modeling direct load management as a computa

  7. Essentials of filoviral load quantification.

    Science.gov (United States)

    Cnops, Lieselotte; van Griensven, Johan; Honko, Anna N; Bausch, Daniel G; Sprecher, Armand; Hill, Charles E; Colebunders, Robert; Johnson, Joshua C; Griffiths, Anthony; Palacios, Gustavo F; Kraft, Colleen S; Kobinger, Gary; Hewlett, Angela; Norwood, David A; Sabeti, Pardis; Jahrling, Peter B; Formenty, Pierre; Kuhn, Jens H; Ariën, Kevin K

    2016-07-01

    Quantitative measurement of viral load is an important parameter in the management of filovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of filovirus disease.

  8. Internet Load and Traffic Balancing

    Institute of Scientific and Technical Information of China (English)

    李文正; 郭巧; 郭为民

    2005-01-01

    Load and traffic balancing for the Internet are analyzed. An intelligent domain name system(DNS) policy for the control and management of content distribution networks (CDN) is presented. An CDNs network based Urtitech IntelliDNS is built, and performance of the network in realizing traffic and load balancing is measured. It is proved that CDNs provide a valuable service and the methods are feasible.

  9. Wind Structure and Wind Loading

    DEFF Research Database (Denmark)

    Brorsen, Michael

    The purpose of this note is to provide a short description of wind, i.e. of the flow in the atmosphere of the Earth and the loading caused by wind on structures. The description comprises: causes to the generation of windhe interaction between wind and the surface of the Earthhe stochastic nature...... of windhe interaction between wind and structures, where it is shown that wind loading depends strongly on this interaction...

  10. Environmental Aspects of Load Management

    Energy Technology Data Exchange (ETDEWEB)

    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{sub 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{sub 2} emissions savings can be achieved due to avoided peak diesel power production.

  11. 46 CFR 169.689 - Demand loads.

    Science.gov (United States)

    2010-10-01

    ... 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...

  12. [Structure of allostatic load in railway workers].

    Science.gov (United States)

    Gorokhova, S G; Pfaf, V F; Muraseyeva, E V; Akhsanova, E R; Prigorovskaya, T S; At'kov, O Yu

    2016-01-01

    The authors studied allostatic load in railway workers, as an indicator of stress effect. Analysis covered biomarkers that form allostatic load index, and their ratio for variable allostatic load index levels. Moderate allostatic load appeared to prevail in the examinees group. Findings are that systolic and diastolic blood pressure, general cholesterol and hemoglobin make major contribution into allostatic load index. Comparison covered models of allostatic load index calculation for variable biomarkers sets.

  13. Calibration set up for load cells

    Science.gov (United States)

    Rao, T. V. Govinda; Venkatesh, C. S.; Shivashankar, N.

    1989-05-01

    The planning, designing, fabrication, and calibration of 30, 50, and 100 ton tension load cells and 30 ton shear load cells are described. The tension load cells are for monitoring the force developed by earth moving vehicles and the shear load cells are for monitoring the load that tipplers unload form platform to ground. The shear load cells were incorporated into a rotary wagon tippler.

  14. The DEMO wall load challenge

    Science.gov (United States)

    Wenninger, R.; Albanese, R.; Ambrosino, R.; Arbeiter, F.; Aubert, J.; Bachmann, C.; Barbato, L.; Barrett, T.; Beckers, M.; Biel, W.; Boccaccini, L.; Carralero, D.; Coster, D.; Eich, T.; Fasoli, A.; Federici, G.; Firdaouss, M.; Graves, J.; Horacek, J.; Kovari, M.; Lanthaler, S.; Loschiavo, V.; Lowry, C.; Lux, H.; Maddaluno, G.; Maviglia, F.; Mitteau, R.; Neu, R.; Pfefferle, D.; Schmid, K.; Siccinio, M.; Sieglin, B.; Silva, C.; Snicker, A.; Subba, F.; Varje, J.; Zohm, H.

    2017-04-01

    For several reasons the challenge to keep the loads to the first wall within engineering limits is substantially higher in DEMO compared to ITER. Therefore the pre-conceptual design development for DEMO that is currently ongoing in Europe needs to be based on load estimates that are derived employing the most recent plasma edge physics knowledge. An initial assessment of the static wall heat load limit in DEMO infers that the steady state peak heat flux limit on the majority of the DEMO first wall should not be assumed to be higher than 1.0 MW m-2. This compares to an average wall heat load of 0.29 MW m-2 for the design {\\tt {EU}}{\\tt {~}}{\\tt {DEMO1}}{\\tt {~2015}} assuming a perfect homogeneous distribution. The main part of this publication concentrates on the development of first DEMO estimates for charged particle, radiation, fast particle (all static) and disruption heat loads. Employing an initial engineering wall design with clear optimization potential in combination with parameters for the flat-top phase (x-point configuration), loads up to 7 MW m-2 (penalty factor for tolerances etc not applied) have been calculated. Assuming a fraction of power radiated from the x-point region between 1/5 and 1/3, peaks of the total power flux density due to radiation of 0.6-0.8 MW m-2 are found in the outer baffle region. This first review of wall loads, and the associated limits in DEMO clearly underlines a significant challenge that necessitates substantial engineering efforts as well as a considerable consolidation of the associated physics basis.

  15. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.

    Science.gov (United States)

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes.

  16. Ultimate loading of wind turbines

    DEFF Research Database (Denmark)

    Larsen, Gunner Chr.; Ronold, K.; Ejsing Jørgensen, Hans

    1999-01-01

    An extreme loading study has been conducted comprising a general wind climate analysis as well as a wind turbine reliability study. In the wind climate analysis, the distribution of the (horizontal) turbulence standard deviation, conditioned on the meanwind speed, has been approximated by fitting......, a design turbulence intensity for off-shore application is proposed which, in the IEC code framework, is applicable for extreme as well as for fatigue loaddetermination. In order to establish a rational method to analyse wind turbine components with respect to failure in ultimate loading, and in addition...... to the event of failure in ultimate loading in flapwise bending in the normal operating condition of a site-specific turbine....

  17. Efficiency of Capacitively Loaded Converters

    DEFF Research Database (Denmark)

    Andersen, Thomas; Huang, Lina; Andersen, Michael A. E.;

    2012-01-01

    This paper explores the characteristic of capacitance versus voltage for dielectric electro active polymer (DEAP) actuator, 2kV polypropylene film capacitor as well as 3kV X7R multi layer ceramic capacitor (MLCC) at the beginning. An energy efficiency for capacitively loaded converters...... is introduced as a definition of efficiency. The calculated and measured efficiency curves for charging DEAP actuator, polypropylene film capacitor and X7R MLCC are provided and compared. The attention has to be paid for the voltage dependent capacitive load, like X7R MLCC, when evaluating the charging...... polypropylene film capacitor can be the equivalent capacitive load. Because of the voltage dependent characteristic, X7R MLCC cannot be used to replace the DEAP actuator. However, this type of capacitor can be used to substitute the capacitive actuator with voltage dependent property at the development phase....

  18. electrical load survey electrical load survey and forecast for a ...

    African Journals Online (AJOL)

    eobe

    1, 2NATIONAL CENTRE FOR HYDROPOWER RESEARCH AND DEV., UNIV. OF ILORIN ... be integrated to meet the present and future energy needs of this are ... paper reports the results of electrical load demand and forecast for Elebu rural community located in Kwara State, ... geothermal and ocean energies [5].

  19. RF Loads for Energy Recovery

    CERN Document Server

    Federmann, S; Caspers, F

    2012-01-01

    Different conceptional designs for RF high power loads are presented. One concept implies the use of solid state rectifier modules for direct RF to DC conversion with efficiencies beyond 80%. In addition, robust metallic low-Q resonant structures, capable of operating at high temperatures (>150 ◦C) are discussed. Another design deals with a very high temperature (up to 800 ◦C) air cooled load using a ceramic foam block inside a metal enclosure. This porous ceramic block is the microwave absorber and is not brazed to the metallic enclosure.

  20. Loading Rate for Modulus of Rupture Test

    Institute of Scientific and Technical Information of China (English)

    QUMing; ZHANGYong-fang

    1996-01-01

    Relationship among load rate,strain rate and stress rate for modulus of ruptue test,the way of applying load with stress rate using both hydraulic compression testing machine and nechanical compression testing machine have been described.The test results are identical with selected strain rate loading and stress rate loading.

  1. Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia.

    Science.gov (United States)

    Duarte, Rafael F; López-Jiménez, Javier; Cornely, Oliver A; Laverdiere, Michel; Helfgott, David; Haider, Shariq; Chandrasekar, Pranatharthi; Langston, Amelia; Perfect, John; Ma, Lei; van Iersel, Marlou L P S; Connelly, Nancy; Kartsonis, Nicholas; Waskin, Hetty

    2014-10-01

    Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).

  2. Fatigue Reliability under Random Loads

    DEFF Research Database (Denmark)

    Talreja, R.

    1979-01-01

    , with the application of random loads, the initial homogeneous distribution of strength changes to a two-component distribution, reflecting the two-stage fatigue damage. In the crack initiation stage, the strength increases initially and then decreases, while an abrupt decrease of strength is seen in the crack...... propagation stage. The consequences of this behaviour on the fatigue reliability are discussed....

  3. Diffusion Indexes with Sparse Loadings

    DEFF Research Database (Denmark)

    Kristensen, Johannes Tang

    to the problem by using the LASSO as a variable selection method to choose between the possible variables and thus obtain sparse loadings from which factors or diffusion indexes can be formed. This allows us to build a more parsimonious factor model which is better suited for forecasting compared...

  4. 中性粒细胞缺乏并细菌感染发热患儿的诊断与治疗%Diagnosis and treatment of bacterial infection in children with febrile neutropenia

    Institute of Scientific and Technical Information of China (English)

    孙立荣; 杨静

    2015-01-01

    Infection rate was high in children with hematologic cancers and febrile neutropenia,especially the number of drug-resistant bacteria showed an increasing trend.Because of defects of the immune function,the typical symptoms,pathogenic bacteria and infection was not clear in these children,the fever may be the only sign of serious underlying infection,mortality related with infection was high,so it was important to evalute the clinical risk accuratly and select antibiotic properly.%中性粒细胞缺乏的造血系统恶性肿瘤患儿感染发生率高,尤其是耐药菌的感染数量呈增加趋势.此类患儿免疫功能低下,炎症的症状、体征不具型,病原菌及感染灶也不明确,发热可能是严重潜在感染的唯一征象,感染相关病死率高,因此,准确地进行临床及风险度评估,并选用恰当的抗菌药物具有重要临床意义.

  5. The clinical value of procalcitonin in patients with chemotherapy-induced febrile neutropenia%降钙素原在化疗致粒细胞减少伴发热患者中的临床意义

    Institute of Scientific and Technical Information of China (English)

    张忠伟; 申丽华; 傅凤鸣; 王朋妹; 朱彪

    2016-01-01

    Background and purpose:Previous researches have shown that procalcitonin differentiates infec-tious from non-infectious fever and assesses the severity of infectious diseases. This study aimed to investigate the clin-ical value of procalcitonin in patients with chemotherapy-induced febrile neutropenia.Methods:A total of 147 patients with chemotherapy-induced febrile neutropenia admitted to intensive care unit from Jan. 2012 to Dec. 2014 were di-vided into infectious group and fever of unknown origin group according to clinical symptoms, signs and etiology. The infectious group was divided into sepsis, severe sepsis, and septic shock groups according to the severity of infection. The procalcitonin levels were compared between different groups.Results:A procalcitonin cut-off value>0.935 ng/mL provided a sensitivity of 90.0%, speciifcity of 90.0% and AUC=0.905. The procalcitonin level of the infectious group was signiifcantly higher than that of the fever of unknown origin group [1.805 (1.268-2.523) ng/mLvs 0.555 (0.398-0.818) ng/mL,P<0.001]. There is a signiifcant difference between the severe sepsis group and the sepsis group [13.885 (7.600-17.961) ng/mLvs 1.805 (1.268-2.563) ng/mL,P<0.001]. Compared with the severe sepsis group, the value of procalcitonin in the septic shock group was signiifcantly higher [23.800 (20.050-30.478) ng/mLvs 13.885 (4.955-19.133) ng/mL,P<0.001].Conclusion:Plasma procalcitonin is a useful marker for diagnosing neutropenia in patients with infection. Meanwhile, procalcitonin can be used to assess the severity of infection in patients with neutropenia.%背景与目的:以往研究显示血清降钙素原可用于发热性疾病的诊断及其严重程度的评估。该研究旨在探讨血清降钙素原在化疗致粒细胞减少伴发热患者中的临床意义。方法:回顾性分析2012年1月—2014年12月以化疗致粒细胞减少伴发热收入复旦大学附属肿瘤医院ICU治疗的147例患者的临床资料。根据患

  6. Experimental investigation of ultimate loads

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, S.M.; Larsen, G.C.; Antoniou, I.; Lind, S.O.; Courtney, M. [Risoe National Lab., Wind Energy and Atmospheric Physics, Roskilde (Denmark)

    1999-03-01

    Verification of the structural integrity of a wind turbine involves analysis of fatigue loading as well as ultimate loading. With the trend of persistently growing turbines, the ultimate loading seems to become relatively more important. For wind turbines designed according to the wind conditions prescribed in the IEC-61400 code, the ultimate load is often identified as the leading load parameter. Exemplified by the use of an extensive measurement campaign a procedure for evaluation of the extreme flap-wise bending moments, occurring during normal operating of a wind turbine, is presented. The structural measurements are made on a NEG Micon 650 kW wind turbine erected at a complex high wind site in Oak Creek, California. The turbine is located on the top of a ridge. The prevailing wind direction is perpendicular to the ridge, and the annual mean wind speed is 9.5 m/s. The associated wind field measurement, are taken from two instrumented masts erected less than one rotor diameter in front of the turbine in direction of the prevailing wind direction. Both masts are instrumented at different heights in order to gain insight of the 3D-wind speed structure over the entire rotor plane. Extreme distributions, associated with a recurrence period of 10 minutes, conditioned on the mean wind speed and the turbulence intensity are derived. Combined with the wind climate model proposed in the IEC standard, these distributions are used to predict extreme distributions with recurrence periods equal to one and fifty years, respectively. The synthesis of the conditioned PDF`s and the wind climate model is performed by means of Monte Carlo simulation. (au)

  7. 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...

  8. Use of Flexible Body Coupled Loads in Assessment of Day of Launch Flight Loads

    Science.gov (United States)

    Starr, Brett R.; Yunis, Isam; Olds, Aaron D.

    2011-01-01

    A Day of Launch flight loads assessment technique that determines running loads calculated from flexible body coupled loads was developed for the Ares I-X Flight Test Vehicle. The technique was developed to quantify DOL flight loads in terms of structural load components rather than the typically used q-alpha metric to provide more insight into the DOL loads. In this technique, running loads in the primary structure are determined from the combination of quasi-static aerodynamic loads and dynamic loads. The aerodynamic loads are calculated as a function of time using trajectory parameters passed from the DOL trajectory simulation and are combined with precalculated dynamic loads using a load combination equation. The potential change in aerodynamic load due to wind variability during the countdown is included in the load combination. In the event of a load limit exceedance, the technique allows the identification of what load component is exceeded, a quantification of how much the load limit is exceeded, and where on the vehicle the exceedance occurs. This technique was used to clear the Ares I-X FTV for launch on October 28, 2009. This paper describes the use of coupled loads in the Ares I-X flight loads assessment and summarizes the Ares I-X load assessment results.

  9. Thermal loading of natural streams

    Science.gov (United States)

    Jackman, Alan P.; Yotsukura, Nobuhiro

    1977-01-01

    The impact of thermal loading on the temperature regime of natural streams is investigated by mathematical models, which describe both transport (convection-diffusion) and decay (surface dissipation) of waste heat over 1-hour or shorter time intervals. The models are derived from the principle of conservation of thermal energy for application to one- and two-dimensional spaces. The basic concept in these models is to separate water temperature into two parts, (1) excess temperature due to thermal loading and (2) natural (ambient) temperature. This separation allows excess temperature to be calculated from the models without incoming radiation data. Natural temperature may either be measured in prototypes or calculated from the model. If use is made of the model, however, incoming radiation is required as input data. Comparison of observed and calculated temperatures in seven natural streams shows that the models are capable of predicting transient temperature regimes satisfactorily in most cases. (Woodard-USGS)

  10. Numerical prediction of slamming loads

    DEFF Research Database (Denmark)

    Seng, Sopheak; Jensen, Jørgen J; Pedersen, Preben T

    2012-01-01

    . The pressure distribution as well as the total force is then determined by integration over a pseudo-three-dimensional presentation of the hull geometry.In this paper the evaluation of the slamming load is taken one step further by performing direct three-dimensional, fully non-linear numerical calculations...... in a realistic wave environment.Both the global and the local slamming loads are assessed numerically using a finite-volume formulation with the free surface captured by a volume-of-fluid technique. This numerical procedure is justified by comprehensive validation studies where numerically evaluated slamming...... pressures are compared with experimentally measured results.To obtain an insight into the three-dimensional flow effects the next step is to apply the validated numerical procedure to evaluate and compare the accuracy and performance of the traditionally used two-dimensional formulations by a comparison...

  11. Auditory perceptual load: A review.

    Science.gov (United States)

    Murphy, Sandra; Spence, Charles; Dalton, Polly

    2017-02-08

    Selective attention is a crucial mechanism in everyday life, allowing us to focus on a portion of incoming sensory information at the expense of other less relevant stimuli. The circumstances under which irrelevant stimuli are successfully ignored have been a topic of scientific interest for several decades now. Over the last 20 years, the perceptual load theory (e.g. Lavie, 1995) has provided one robust framework for understanding these effects within the visual modality. The suggestion is that successful selection depends on the perceptual demands imposed by the task-relevant information. However, less research has addressed the question of whether the same principles hold in audition and, to date, the existing literature provides a mixed picture. Here, we review the evidence for and against the applicability of perceptual load theory in hearing, concluding that this question still awaits resolution.

  12. Trailer-loading of horses

    DEFF Research Database (Denmark)

    Hendriksen, Payana; Elmgreen, Katrine; Ladewig, Jan

    2011-01-01

    The traditional way to train horses is by the application of negative reinforcement (NR). In the past few years, however, the use of positive reinforcement (PR) has become more common. To evaluate the effectiveness and the possible stressor effect of the 2 training methods, 12 horses showing severe...... trailer-loading problems were selected and exposed to trailer-loading. They were randomly assigned to one of the 2 methods. NR consisted of various degrees of pressure (lead rope pulling, whip tapping). Pressure was removed as soon as the horse complied. PR horses were exposed to clicker training...... and taught to follow a target into the trailer. Heart rate (HR) was recorded every 5 seconds and behavior denoting discomfort was observed using one-zero sampling with 10 seconds sampling intervals. Training was completed when the horse could enter the trailer upon a signal, or was terminated after a maximum...

  13. Robust Multimodal Cognitive Load Measurement

    Science.gov (United States)

    2014-03-26

    b) q=0.1 with the load levels, for channel F7 of subject 1. On each box, the red mark is the median; the edges of the box are the 25th and the...channel F7 of subject 1, for two extreme values of q (entropic index); (a) q= 0.9, (b) q= 0.1, in the delta frequency band. As shown, the median of

  14. Polymer brushes under high load.

    Directory of Open Access Journals (Sweden)

    Suzanne M Balko

    Full Text Available Polymer coatings are frequently used to provide repulsive forces between surfaces in solution. After 25 years of design and study, a quantitative model to explain and predict repulsion under strong compression is still lacking. Here, we combine experiments, simulations, and theory to study polymer coatings under high loads and demonstrate a validated model for the repulsive forces, proposing that this universal behavior can be predicted from the polymer solution properties.

  15. PASSIVE DETECTION OF VEHICLE LOADING

    Energy Technology Data Exchange (ETDEWEB)

    Garrett, A.

    2012-01-03

    The Digital Imaging and Remote Sensing Laboratory (DIRS) at the Rochester Institute of Technology, along with the Savannah River National Laboratory is investigating passive methods to quantify vehicle loading. The research described in this paper investigates multiple vehicle indicators including brake temperature, tire temperature, engine temperature, acceleration and deceleration rates, engine acoustics, suspension response, tire deformation and vibrational response. Our investigation into these variables includes building and implementing a sensing system for data collection as well as multiple full-scale vehicle tests. The sensing system includes; infrared video cameras, triaxial accelerometers, microphones, video cameras and thermocouples. The full scale testing includes both a medium size dump truck and a tractor-trailer truck on closed courses with loads spanning the full range of the vehicle's capacity. Statistical analysis of the collected data is used to determine the effectiveness of each of the indicators for characterizing the weight of a vehicle. The final sensing system will monitor multiple load indicators and combine the results to achieve a more accurate measurement than any of the indicators could provide alone.

  16. High Temperature Radio Frequency Loads

    CERN Document Server

    Federmann, S; Grudiev, A; Montesinos, E; Syratchev, I

    2011-01-01

    In the context of energy saving and recovery requirements the design of reliable and robust RF power loads which permit a high outlet temperature and high pressure of the cooling water is desirable. Cooling water arriving at the outlet withmore than 150 ◦C and high pressure has a higher value than water with 50 ◦C under low pressure. Conventional RF power loads containing dielectric and magnetic materials as well as sensitive ceramic windows usually do not permit going much higher than 90 ◦C. Here we present and discuss several design concepts for "metal only" RF high power loads. One concept is the application of magnetic steel corrugated waveguides near cutoff – this concept could find practical use above several GHz. Another solution are resonant structures made of steel to be installed in large waveguides for frequencies of 500 MHz or lower. Similar resonant structures above 100 MHz taking advantage of the rather high losses of normal steel may also be used in coaxial line geometries with large di...

  17. Maximum holding endurance time: Effects of load and load's center of gravity height.

    Science.gov (United States)

    Lee, Tzu-Hsien

    2015-01-01

    Manual holding task is a potential risk to the development of musculoskeletal injuries since it is prone to induce localized muscle fatigue. Maximum holding endurance time is a significant parameter for the design of manual holding task. This study aimed to examine the effects of load and load's COG height on maximum holding endurance time. Fifteen young and healthy males were recruited as participants. A factorial design was used to examine the effects of load and load's COG height on maximum holding endurance time. Four levels of load (15% , 30% , 45% and 60% of the participant's maximum holding capacity) and two levels of load's COG height in box (0 cm and 40 cm high from the handle position) were examined. Maximum holding endurance time decreased with increasing load and/or increasing load's COG height. The effect of load's COG height on maximum holding endurance time decreased with increasing load. Load, load's COG height, and the interaction of load and load's COG height significantly affected maximum holding endurance time. Practitioners should realize the effects of load, load's COG height, and the interaction of load and load's COG height on maximum holding endurance time when setting the working conditions of holding tasks.

  18. Acid loading test (pH)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003615.htm Acid loading test (pH) To use the sharing features on this page, please enable JavaScript. The acid loading test (pH) measures the ability of the ...

  19. 30 CFR 57.9317 - Suspended loads.

    Science.gov (United States)

    2010-07-01

    ... SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Loading, Hauling, and Dumping Safety Devices, Provisions, and Procedures for Roadways, Railroads, and Loading and Dumping Sites...

  20. 四例氯吡格雷致白细胞和中性粒细胞减少患者的药学服务%Pharmaceutical care for four patients with clopidogrel-associated leukopenia and neutropenia

    Institute of Scientific and Technical Information of China (English)

    张青霞; 李博宇; 侯凯旋

    2016-01-01

    目的:探讨临床药师在氯吡格雷致白细胞和中性粒细胞减少患者中如何提供药学服务。方法临床药师通过参与4例氯吡格雷导致的白细胞和中性粒细胞减少患者的治疗,根据药学相关知识及阅读相关文献,及时判断导致白细胞减少的可疑药物,并提供替代药物及对症治疗药物,通过定期血常规检查结果逐步调整治疗方案,并积极治疗原发病与伴发的感染,参与并监护患者用药的全过程。结果在临床医生和临床药师的共同合作下,4例患者的白细胞逐渐回升至基线水平,伴发感染与原发疾病也得到合理的治疗,患者病情好转后全部安全出院。结论临床药师要充分发挥自己药学专业的优势,在临床工作中及时辨别药物的不良反应,协助临床医生更好地使用药物,为患者提供更好的药学监护。%Objective To explore the pharmaceutical care approaches for patients with clopidogrel-associated leukopenia and neutropenia by clinical pharmacists. Methods Clinical pharmacists participated in the treatment of 4 patients with clopidogrel-associated leukopenia and neutropenia,determined the suspected drug causing leukopenia and provided alternative drugs and symptomatic treatment by using pharmacy-related knowledge and reading literature. The treatment plan was adjusted gradually according to the periodic blood test results,then the medication of patients was monitored,and the primary disease and associated infection was treated aggressively. Results With the cooperation of clinical pharmacists and physicians,the white blood cells of four patients gradually rose to its baseline level,and the as-sociated infection and primary disease were treated reasonably. Patients′condition was improved after being discharged. Conclusion Clinical pharmacists should give full play to their own advantages of pharmacy,identify adverse drug re-actions timely in the clinical work,help clinicians make better

  1. Simulation of Stochastic Loads for Fatigue Experiments

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Brincker, Rune

    A simple direct simulation method for stochastic fatigue load generation is described in this paper. The simulation method is based on the assumption that only the peaks of the load process significantly affect the fatigue life. The method requires the conditional distribution functions of load...... second using an IBM PC. Finally the proposed simulation method for fatigue load generation is tested by comparing some fatigue damage measures obtained by the simulation methods....

  2. Plug Load Behavioral Change Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Metzger, I.; Kandt, A.; VanGeet, O.

    2011-08-01

    This report documents the methods and results of a plug load study of the Environmental Protection Agency's Region 8 Headquarters in Denver, Colorado, conducted by the National Renewable Energy Laboratory. The study quantified the effect of mechanical and behavioral change approaches on plug load energy reduction and identified effective ways to reduce plug load energy. Load reduction approaches included automated energy management systems and behavioral change strategies.

  3. Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim or Pegfilgrastim Is Cost Effective in Non-Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Xiao Jun Wang

    Full Text Available This study aims to compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP chemotherapy with curative intent.A Markov model was created to compare seven prophylaxis strategies: 1 primary prophylaxis (PP with nivestim (biosimilar filgrastim throughout all cycles of chemotherapy; 2 PP with nivestim during the first two cycles of chemotherapy; 3 secondary prophylaxis (SP with nivestim; 4 PP with pegfilgrastim throughout all cycles of chemotherapy; 5 PP with pegfilgrastim during the first two cycles of chemotherapy; 6 SP with pegfilgrastim; and 7 no prophylaxis (NP. The perspective of a hospital was taken and cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy. A probabilistic sensitivity analysis was conducted.Strategies 3, 6, and 7 were dominated in the base case analysis by strategy 5. The costs associated with strategies 2, 5, 1, and 4 were US$3,813, US$4,056, US$4,545, and US$5,331, respectively. The incremental cost-effectiveness ratios for strategy 5 vs. strategy 2, strategy 1 vs. strategy 5, and strategy 4 vs. strategy 1 were US$13,532, US$22,565, and US$30,452, respectively, per episode of FN avoided. Strategy 2 has the highest probability to be cost-effective (ranged from 48% to 60% when the willingness to pay (WTP threshold is lower than US$10,000 per FN episode prevented.In Singapore, routine PP with granulocyte colony-stimulating factor (nivestim or pegfilgrastim is cost-effective for reducing the risk of FN in patients receiving R-CHOP.

  4. Interleukin-5, interleukin-6, interleukin-8 and tumour necrosis factor-alpha levels obtained within 24-h of admission do not predict high-risk infection in children with febrile neutropenia

    Directory of Open Access Journals (Sweden)

    R Aggarwal

    2013-01-01

    Full Text Available Purpose: Biomarkers that can predict the severity of febrile neutropenia (FN are potential tools for clinical practice. Objective: The objective of this study is to evaluate the reliability of plasma interleukin (IL levels as indicators of high-risk FN. Materials and Methods: Children with haematological malignancies and FN were enrolled prospectively. A blood sample was obtained within 24-h of admission for estimation of IL-5, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-α level by the enzyme-linked immunosorbent assay. Patients were stratified into three groups. Group I (low-risk: No focus of infection; Group II: Clinical/radiological focus of infection; Group III: Microbiologically proven infection or FN related mortality. Groups II and III were analysed as high-risk. The cytokines were assessed at three different cut-off levels. Results: A total of 52 episodes of FN in 48 patients were evaluated. The mean age was 6 years (range: 2-13. Primary diagnosis included acute lymphoblastic leukaemia (82%, non-Hodgkin′s lymphoma (13% and acute myeloid leukaemia (5%. Absolute neutrophil count was < 200 cells/μl in half and 200-500 in 23%. Majority were categorised as Group I (69%, followed by Group II (16% and III (15%. The range of IL-5 was too narrow and similar in the two risk-groups to be of any relevance. The best sensitivity of TNF-α and IL-6 for high-risk group was 78% and 70%, respectively. The highest specificity observed was 35%. The negative predictive value of IL-6, IL-8 and TNF-α exceeded 80%. Conclusion: IL-5, IL-6, IL-8 and TNF-α failed as predictors of clinically localised or microbiologically documented infection in children with chemotherapy induced FN. However, IL-6, IL-8 and TNF-α could be useful in excluding the possibility of high-risk infection.

  5. The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review.

    Science.gov (United States)

    Lyman, Gary H; Allcott, Kim; Garcia, Jacob; Stryker, Scott; Li, Yanli; Reiner, Maureen T; Weycker, Derek

    2017-08-01

    Granulocyte colony-stimulating factors (G-CSF) are commonly used in clinical practice to prevent febrile neutropenia (FN). US and EU prescribing information and treatment guidelines from the NCCN, ASCO, and EORTC specify that pegfilgrastim, a long-acting (LA) G-CSF, should be administered at least 24 h after myelosuppressive chemotherapy. Nevertheless, many patients receive LA G-CSFs on the same day as chemotherapy. This systematic literature review evaluated the relative merits of same-day versus next-day dosing of LA G-CSFs. A broad Ovid MEDLINE® and Embase® literature search was conducted that examined all publications indexed before May 9, 2016 that compared same-day versus next-day LA G-CSF administration. A congress abstract literature search included congresses from January 1, 2011 to April 6, 2016. The parameters for this review were prospectively delineated in a research protocol and adhered to the PRISMA Guidelines. The first part of the systematic literature search identified 1736 publications. After elimination of duplicates, title/abstract screening was conducted on 1440 records, and full text review was conducted on 449 publications. Eleven publications met all criteria and are included in this systematic review; of these, four included data from randomized or single arm prospective studies, and seven were retrospective studies. In most studies included in this review and across a variety of tumor types, administration of pegfilgrastim at least 24 h after myelosuppressive chemotherapy resulted in improved patient outcomes. Data from multiple publications support administration of pegfilgrastim at least 1 day after chemotherapy.

  6. Wind loads on solar energy systems

    NARCIS (Netherlands)

    Kampen, B.J.M. van; Geurts, C.P.W.; Borsboom, W.A.; Blackmore, P.

    2005-01-01

    Wind loads on solar energy systems are not covered by current wind loading standards. This paper describes results of a parametric study into the wind loads 0on solar energy systems,. which are placed on flat roofs. Wind tunnel measurements have been carried out on a number of configurations. The

  7. Comparison of load parameters for stored materials

    DEFF Research Database (Denmark)

    Munch-Andersen, J.; Nielsen, J.

    1997-01-01

    that the wall friction measured in a silo might be significantly larger than the value obtained from shear tests. The load parameters depend on the load level, perhaps in a way not reflected by the internal friction angle. It is not necessarily on the safe side to determine the parameters for a high load level....

  8. Wind loads on solar energy systems

    NARCIS (Netherlands)

    Kampen, B.J.M. van; Geurts, C.P.W.; Borsboom, W.A.; Blackmore, P.

    2005-01-01

    Wind loads on solar energy systems are not covered by current wind loading standards. This paper describes results of a parametric study into the wind loads 0on solar energy systems,. which are placed on flat roofs. Wind tunnel measurements have been carried out on a number of configurations. The re

  9. Response of Rubble Foundation to Dynamic Loading

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Ibsen, Lars Bo

    1993-01-01

    The soil beneath vertical monolithic structures is subjected to a combination of static load due to the submerged weight of the structure and stochastic non-stationary loads as a result of the wave loads on the vertical wall. The stress conditions in the soil below a foundation exposed to both st...

  10. Response of Rubble Foundation to Dynamic Loading

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Ibsen, Lars Bo

    1994-01-01

    The soil beneath vertical monolithic structures is subjected to a combination of static load due to the submerged weight of the structure and stochastic non-stationary loads as a result of the wave loads on the vertical wall. The stress conditions in the soil below a foundation exposed to both st...

  11. Introduction to Single Piles under Lateral Loading

    DEFF Research Database (Denmark)

    Augustesen, Anders; Ibsen, Lars Bo

    The purpose of this chapter is to give a short introduction to single piles subjected to lateral loading. First, the observed behaviour of laterally loaded piles is described, i.e. the effects of loading conditions, installation procedure, pile type etc. on pile behaviour are presented (section 1...

  12. Load Characteristics Analysis of State Grid

    Institute of Scientific and Technical Information of China (English)

    Chen Wei; Zhou Feng; Han Xinyang; Shan Baoguo; Zhu Li

    2009-01-01

    @@ Introduction Analysis and forecast of load characteristics are important aspects in power market analysis and prediction.Correctly mastering grid load characteristics and its development trend is not only the vital basis for power planning,generation and operation,but also the important references for formulating the relevant policies.It is usually very hard to grasp the load characteristics of power grid.

  13. Load Bearing Equipment for Bone and Muscle

    Science.gov (United States)

    Shackelford, Linda; Griffith, Bryan

    2015-01-01

    Resistance exercise on ISS has proven effective in maintaining bone mineral density and muscle mass. Exploration missions require exercise with similar high loads using equipment with less mass and volume and greater safety and reliability than resistance exercise equipment used on ISS (iRED, ARED, FWED). Load Bearing Equipment (LBE) uses each exercising person to create and control the load to the partner.

  14. Plutonium Immobilization Can Loading Preliminary Specifications

    Energy Technology Data Exchange (ETDEWEB)

    Kriikku, E.

    1998-11-25

    This report discusses the Plutonium Immobilization can loading preliminary equipment specifications and includes a process block diagram, process description, equipment list, preliminary equipment specifications, plan and elevation sketches, and some commercial catalogs. This report identifies loading pucks into cans and backfilling cans with helium as the top priority can loading development areas.

  15. Wind loads on solar energy systems

    NARCIS (Netherlands)

    Kampen, B.J.M. van; Geurts, C.P.W.; Borsboom, W.A.; Blackmore, P.

    2005-01-01

    Wind loads on solar energy systems are not covered by current wind loading standards. This paper describes results of a parametric study into the wind loads 0on solar energy systems,. which are placed on flat roofs. Wind tunnel measurements have been carried out on a number of configurations. The re

  16. Local Dynamic Stability Associated with Load Carrying

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2013-03-01

    Conclusion: Current study confirmed the sensitivity of local dynamic stability measure in load carrying situation. It was concluded that load carrying tasks were associated with declined local dynamic stability, which may result in increased risk of fall accident. This finding has implications in preventing fall accidents associated with occupational load carrying.

  17. 感染相关性中性粒细胞减少症患儿的常见特点分析%Clinical study on features of children with infection related neutropenia

    Institute of Scientific and Technical Information of China (English)

    周立萍; 鞠秀丽

    2011-01-01

    目的:观察中性粒细胞减少症患儿的年龄分布、骨髓细胞学改变及血小板、肝功能、心肌酶和免疫功能的临床变化特点.方法:将60例中性粒细胞减少症患儿设为观察组,并分为婴儿组和儿童组,另选取58名健康儿童作为健康对照组,也分为婴儿组和儿童组.检测所有研究对象的血小板、ALT、磷酸肌酸激酶同工酶、细胞免疫、体液免疫指标,比较两组差异.结果与结论:① 1岁以下患儿占所有患儿的63%,其中又以6~8月龄最多,占35%;②骨髓常呈增生活跃或减低,易于见到异型淋巴细胞;③观察组的婴儿组血小板、ALT、磷酸肌酸激酶同工酶、IgM、CD8+高于健康对照组的同龄组;观察组婴儿组的IgG、CD3+、CD4+、CD4+/CD8+低于健康对照组的同龄组(P<0.05或0.01);④观察组的儿童组血小板、磷酸肌酸激酶同工酶、IgM、CD8+高于健康对照组的同龄组;观察组的儿童组IgG、CD3+、CD4+、CD4+/CD8+低于对照组的同龄组(P<0.05或0.01);⑤中性粒细胞减少症患儿血小板、肝功能、心肌酶和免疫功能的改变可能与病毒感染以及体内细胞免疫功能紊乱有关.%Objective: To observe age distribution, laboratory parameter characteristics (bone marrow cytology, platelet count, liver function, myocardial enzyme and immune function) and the possible causes of neutropenia in children.Methods: Sixty children diagnosed as neutropenia were included in observation group and were divided into two subgroups, infant observation group ( aged between 1 month and 1 year old, n = 37) and child observation group (aged between 1 year and 12 years old, n =23).At the same period, fifty-eight healthy children were selected into control group, who were divided into two subgroups according to the same age standard.Platelet count, alanine aminotransferase (ALT) level, MB isoenzyme of creatine kinase (CK-MB) , cellular and humoral immunity function were examined in both

  18. High Human T Cell Leukemia Virus Type-1(HTLV-1 Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders

    Directory of Open Access Journals (Sweden)

    Yamada Yasuaki

    2010-04-01

    Full Text Available Abstract Background To address the clinical and virological significance of a high HTLV-1 proviral load (VL in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR quantification (infected cell % of peripheral mononuclear cells and Southern blotting hybridization (SBH methods. Results The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2% of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells. In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL. Conclusion The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by

  19. Critical loads - assessment of uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Barkman, A.

    1998-10-01

    The effects of data uncertainty in applications of the critical loads concept were investigated on different spatial resolutions in Sweden and northern Czech Republic. Critical loads of acidity (CL) were calculated for Sweden using the biogeochemical model PROFILE. Three methods with different structural complexity were used to estimate the adverse effects of S0{sub 2} concentrations in northern Czech Republic. Data uncertainties in the calculated critical loads/levels and exceedances (EX) were assessed using Monte Carlo simulations. Uncertainties within cumulative distribution functions (CDF) were aggregated by accounting for the overlap between site specific confidence intervals. Aggregation of data uncertainties within CDFs resulted in lower CL and higher EX best estimates in comparison with percentiles represented by individual sites. Data uncertainties were consequently found to advocate larger deposition reductions to achieve non-exceedance based on low critical loads estimates on 150 x 150 km resolution. Input data were found to impair the level of differentiation between geographical units at all investigated resolutions. Aggregation of data uncertainty within CDFs involved more constrained confidence intervals for a given percentile. Differentiation as well as identification of grid cells on 150 x 150 km resolution subjected to EX was generally improved. Calculation of the probability of EX was shown to preserve the possibility to differentiate between geographical units. Re-aggregation of the 95%-ile EX on 50 x 50 km resolution generally increased the confidence interval for each percentile. Significant relationships were found between forest decline and the three methods addressing risks induced by S0{sub 2} concentrations. Modifying S0{sub 2} concentrations by accounting for the length of the vegetation period was found to constitute the most useful trade-off between structural complexity, data availability and effects of data uncertainty. Data

  20. Automated Loads Analysis System (ATLAS)

    Science.gov (United States)

    Gardner, Stephen; Frere, Scot; O’Reilly, Patrick

    2013-01-01

    ATLAS is a generalized solution that can be used for launch vehicles. ATLAS is used to produce modal transient analysis and quasi-static analysis results (i.e., accelerations, displacements, and forces) for the payload math models on a specific Shuttle Transport System (STS) flight using the shuttle math model and associated forcing functions. This innovation solves the problem of coupling of payload math models into a shuttle math model. It performs a transient loads analysis simulating liftoff, landing, and all flight events between liftoff and landing. ATLAS utilizes efficient and numerically stable algorithms available in MSC/NASTRAN.