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Sample records for antibiotic-induced severe neutropenia

  1. Severe congenital neutropenia

    DEFF Research Database (Denmark)

    Borregaard, Niels

    2014-01-01

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

  2. Severe congenital neutropenia (Kostmann Syndrome)

    African Journals Online (AJOL)

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

  3. Genetics Home Reference: severe congenital neutropenia

    Science.gov (United States)

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

  4. Differential antibiotic-induced endotoxin release in severe melioidosis

    NARCIS (Netherlands)

    Simpson, A. J.; Opal, S. M.; Angus, B. J.; Prins, J. M.; Palardy, J. E.; Parejo, N. A.; Chaowagul, W.; White, N. J.

    2000-01-01

    Severe melioidosis is a life-threatening, systemic bacterial infection caused by Burkholderia pseudomallei. A prospective, randomized treatment trial was conducted in northeast Thailand to compare ceftazidime (a penicillin-binding protein [PBP]-3-specific agent that causes release of large amounts

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

    OpenAIRE

    Cho, Hye-Kyung; Jeon, In Sang

    2014-01-01

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

  6. 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.

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

    Science.gov (United States)

    Cho, Hye-Kyung; Jeon, In Sang

    2014-03-01

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

  8. Severe neutropenia in children: a single institutional experience.

    Science.gov (United States)

    Yilmaz, Deniz; Ritchey, Arthur Kim

    2007-08-01

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

  9. Inherited biallelic CSF3R mutations in severe congenital neutropenia.

    Science.gov (United States)

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

    2014-06-12

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

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

    Science.gov (United States)

    Touw, Ivo P

    2015-01-01

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

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

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Weihan Chen BS

    2017-03-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

  15. 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 Copyright © 2011 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2003-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Marc Gregory Y. Yu

    2015-01-01

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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Farhoodi A

    2007-09-01

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

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

    Science.gov (United States)

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

    2010-03-01

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

  2. 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.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

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

    2017-01-01

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

  5. 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.

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

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

    2017-03-01

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

  7. 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

    Directory of Open Access Journals (Sweden)

    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

  8. Rare severe mycotic infections in children receiving empirical caspofungin treatment for febrile neutropenia

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    Deniz Yilmaz Karapinar

    2015-09-01

    Full Text Available Empirical antifungal therapy is most often given to patients with leukemia. However breakthrough fungal infections under antifungal therapy are not uncommon. Four children, with hematologic malignant disease developed mycotic breakthrough infections while on empirical caspofungin treatment for a median of 14 (range 11–19 days. Trichosporon asahii was detected in the blood culture of two patients and Geotrichum capitatum in the other two (one patient also had positive cerebrospinal fluid culture. Because the patients’ clinical situation worsened, voriconazole was empirically added for two patients three and five days before the agent was detected. The first sterile blood culture was obtained 3–7 days of voriconazole treatment. All patients reached clear cultures but one patient died. One patient with central nervous system infection with G. capitatum had severe neurological sequelae. Very severe fungal infections can occur during empirical caspofungin therapy. Therefore, patients should be followed closely.

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

    OpenAIRE

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

    2015-01-01

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

  10. Thickened cortical bones in congenital neutropenia

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  11. Thickened cortical bones in congenital neutropenia

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-02-01

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

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

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    Fernandez Bridget A

    2012-11-01

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

  13. 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.

  14. How I manage children with neutropenia.

    Science.gov (United States)

    Dale, David C

    2017-08-01

    Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 9 /l, is a common medical problem for children and adults. There are many causes for neutropenia, and at each stage in life the clinical pattern of causes and consequences differs significantly. I recommend utilizing the age of the child and clinical observations for the preliminary diagnosis and primary management. In premature infants, neutropenia is quite common and contributes to the risk of sepsis with necrotizing enterocolitis. At birth and for the first few months of life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and predisposes to the risk of severe bacterial infections. Thereafter when a child is discovered to have neutropenia, often associated with relatively minor symptoms, it is usually attributed to autoimmune disorder or viral infection. The congenital neutropenia syndromes are usually recognized when there are recurrent infections, the neutropenia is severe and there are congenital anomalies suggesting a genetic disorder. This review focuses on the key clinical finding and laboratory tests for diagnosis with commentaries on treatment, particularly the use of granulocyte colony-stimulating factor to treat childhood neutropenia. © 2017 John Wiley & Sons Ltd.

  15. Neutropenia in infants with hemolytic disease of the newborn.

    Science.gov (United States)

    Blanco, Esther; Johnston, Donna L

    2012-06-01

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

  16. Bactericidal antibiotics induce programmed metabolic toxicity

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    Aislinn D. Rowan

    2016-03-01

    Full Text Available The misuse of antibiotics has led to the development and spread of antibiotic resistance in clinically important pathogens. These resistant infections are having a significant impact on treatment outcomes and contribute to approximately 25,000 deaths in the U.S. annually. If additional therapeutic options are not identified, the number of annual deaths is predicted to rise to 317,000 in North America and 10,000,000 worldwide by 2050. Identifying therapeutic methodologies that utilize our antibiotic arsenal more effectively is one potential way to extend the useful lifespan of our current antibiotics. Recent studies have indicated that modulating metabolic activity is one possible strategy that can impact the efficacy of antibiotic therapy. In this review, we will address recent advances in our knowledge about the impacts of bacterial metabolism on antibiotic effectiveness and the impacts of antibiotics on bacterial metabolism. We will particularly focus on two studies, Lobritz, et al. (PNAS, 112(27: 8173-8180 and Belenky et al. (Cell Reports, 13(5: 968–980 that together demonstrate that bactericidal antibiotics induce metabolic perturbations that are linked to and required for bactericidal antibiotic toxicity.

  17. Four novel ELANE mutations in patients with congenital neutropenia.

    Science.gov (United States)

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

    2011-08-01

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

  18. Neutropenia in the Newborn

    Science.gov (United States)

    Maheshwari, Akhil

    2013-01-01

    PURPOSE OF REVIEW Review normal blood neutrophil concentrations and the clinical approach to neutropenia in the neonatal period. A literature search on neonatal neutropenia was performed using the databases PubMed, EMBASE, and Scopus and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RECENT FINDINGS This review summarizes current knowledge on the causes of neutropenia in premature and critically-ill neonates, focusing on common causes such as maternal hypertension, neonatal sepsis, twin-twin transfusion, alloimmunization, and hemolytic disease. The article provides a rational approach to diagnosis and treatment of neonatal neutropenia, including current evidence on the role of recombinant hematopoietic growth factors. SUMMARY Neutrophil counts should be carefully evaluated in premature and critically-ill neonates. Although neutropenia is usually benign and runs a self-limited course in most neonates, it can be prolonged and constitute a serious deficiency in antimicrobial defense in some infants. PMID:24322487

  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. Congenital neutropenia: diagnosis, molecular bases and patient management

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    Taaning, Ellen; Jensen, Lise; Varming, Kim

    2012-01-01

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

  2. Serum endocan levels in children with febrile neutropenia

    Directory of Open Access Journals (Sweden)

    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.

  3. {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.)

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

    Science.gov (United States)

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

    2001-11-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    Rui-Rui Peng

    2017-03-01

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

  7. Intermittent chronic neutropenia in a patient with familial Mediterranean fever.

    Science.gov (United States)

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

    2008-11-01

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

  8. Antibiotic-Induced Rash in Patients With Infectious Mononucleosis.

    Science.gov (United States)

    Thompson, Dennis F; Ramos, Carroll L

    2017-02-01

    To provide an extensive review of case reports, epidemiological data, and the underlying mechanism of antibiotic-induced skin rash in patients with concurrent infectious mononucleosis (IM). A MEDLINE literature search inclusive of the dates 1946 to June 2016 was performed using the search terms anti-bacterial agents and infectious mononucleosis. EMBASE (1980 to June 2016) was searched using the terms mononucleosis and antibiotic agent and drug eruption. References of all relevant articles were reviewed for additional citations and information. We selected English-language, primary literature, review articles, and mechanistic articles that addressed antibiotic-induced skin rash in patients with concurrent IM. We assessed all case reports available for causality utilizing a modified Naranjo nomogram specifically designed for this subject. We assembled the available epidemiological data into tables to identify trends in incidence rates over the years. We identified 17 case reports of antibiotic-associated rash in patients with IM. The median Naranjo score was 6 (range = 1 to 8). The top 3 reported drugs were ampicillin, azithromycin, and amoxicillin. Incidence of this adverse effect was higher in the 1960s (55.6%, 45%, and 33%) than in 2013 (33% and 15%). The mechanism most commonly proposed is a transient virus-mediated immune alteration that sets the stage for loss of antigenic tolerance and the development of a reversible, delayed-type hypersensitivity reaction to the antibiotic. A reassessment of the long-held belief of the high incidence (80%-100%) of antibiotic-induced skin rash in patients with IM seems prudent. Additional studies will be necessary to clarify this issue.

  9. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

    Directory of Open Access Journals (Sweden)

    Emmanuel Gyan

    2015-02-01

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

  10. Water Extract of Deer Bones Activates Macrophages and Alleviates Neutropenia

    Directory of Open Access Journals (Sweden)

    Han-Seok Choi

    2013-01-01

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

  11. Febrile neutropenia in childhood cancer

    African Journals Online (AJOL)

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

  12. Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

    Science.gov (United States)

    Klepfish, A; Rachmilevitch, E; Schattner, A

    2006-11-01

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

  13. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

    OpenAIRE

    Emmanuel Gyan; François Dreyfus; Pierre Fenaux

    2015-01-01

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

  14. Neutropenia, agranulocytosis and dipyrone

    Directory of Open Access Journals (Sweden)

    Nelson Hamerschlak

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

  15. Risperidone-induced reversible neutropenia.

    Science.gov (United States)

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

    2017-01-01

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

  16. [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.

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

    Science.gov (United States)

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

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

  18. Family caring strategies in neutropenia.

    Science.gov (United States)

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

    2004-12-01

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

  19. Treatment of febrile neutropenia with cefepime monotherapy.

    Science.gov (United States)

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

    2001-01-01

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

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

    NARCIS (Netherlands)

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

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

  1. Evaluasi Sensitivitas Antibiotik dengan Demam Neutropenia

    Directory of Open Access Journals (Sweden)

    Sulaiman Hamid

    2016-11-01

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

  2. Accelerate Genomic Aging in Congenital Neutropenia

    Science.gov (United States)

    2017-10-01

    reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...neutropenia; Shwachman Diamond syndrome; Cyclic neutropenia; Hematopoietic stem cells; Granulocyte colony- stimulating factor; Acute myeloid leukemia...high rate of leukemic transformation. For example, granulocyte colony stimulating factor (G-CSF) expression is induced by neutropenia and may increase

  3. Kejadian Demam Neutropenia pada Anak dengan Keganasan

    Directory of Open Access Journals (Sweden)

    Sarah Rafika Nursyirwan

    2018-03-01

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

  4. Periodontal disease in three siblings with familial neutropenia.

    Science.gov (United States)

    Kirstilä, V; Sewón, L; Laine, J

    1993-06-01

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

  5. Febrile neutropenia and refeeding syndrome.

    Science.gov (United States)

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

    2016-12-01

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

  6. 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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2013-02-13

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

  9. Neutropenia in pediatric hematology/oncology practice

    Directory of Open Access Journals (Sweden)

    E. A. Deordieva

    2015-06-01

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

  10. Secondary Infections in Cancer Patients with Febrile Neutropenia

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2018-04-01

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

  12. Drug induced neutropenia manifesting as oral ulcerations

    Directory of Open Access Journals (Sweden)

    Rachna Kaul

    2009-01-01

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

  13. 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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Jun Osugi

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-15

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  20. Management of Febrile Neutropenia in Patients receiving ...

    African Journals Online (AJOL)

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

  1. Viral findings in adult hematological patients with neutropenia.

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    Lars Ohrmalm

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

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

    Science.gov (United States)

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

    2004-02-01

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

  4. Ela2 mutations and clinical manifestations in familial congenital neutropenia.

    Science.gov (United States)

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

    2009-05-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  6. Difference in Neutropenia due to Administration Schedule of TAS-102

    Directory of Open Access Journals (Sweden)

    Yoichiro Yoshida

    2017-03-01

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

  7. Antibiotic-induced change of bacterial communities associated with the copepod Nitocra spinipes.

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    Anna Edlund

    Full Text Available Environmental pressures, such as physical factors, diet and contaminants may affect interactions between microbial symbionts and their multicellular hosts. Despite obvious relevance, effects of antimicrobial contaminants on host-symbiont relations in non-target aquatic organisms are largely unknown. We show that exposure to antibiotics had negative effects on survival and juvenile development of the copepod Nitocra spinipes and caused significant alterations in copepod-associated bacterial communities. The significant positive correlations between indices of copepod development and bacterial diversity indicate that disruption of the microflora was likely to be an important factor behind retarded juvenile development in the experimental animals. Moreover, as evidenced by ribotype distribution in the bacterial clone libraries, the exposure to antibiotics caused a shift in dominance from Betaproteobacteria to Cardinium bacteria; the latter have been shown to cause reproductive manipulations in various terrestrial arthropods. Thus, in addition to providing evidence that the antibiotic-induced perturbation of the microbial community associates with reductions in fitness-related traits of the host, this study is the first record of a copepod serving as a host for endosymbiotic Cardinium. Taken together, our results suggest that (1 antimicrobial substances and possibly other stressors can affect micobiome and symbiont-mediated interactions in copepods and other hosts, and (2 Cardinium endosymbionts may occur in other copepods and affect reproduction of their hosts.

  8. In silico analysis of antibiotic-induced Clostridium difficile infection: Remediation techniques and biological adaptations.

    Science.gov (United States)

    Jones, Eric W; Carlson, Jean M

    2018-02-01

    In this paper we study antibiotic-induced C. difficile infection (CDI), caused by the toxin-producing C. difficile (CD), and implement clinically-inspired simulated treatments in a computational framework that synthesizes a generalized Lotka-Volterra (gLV) model with SIR modeling techniques. The gLV model uses parameters derived from an experimental mouse model, in which the mice are administered antibiotics and subsequently dosed with CD. We numerically identify which of the experimentally measured initial conditions are vulnerable to CD colonization, then formalize the notion of CD susceptibility analytically. We simulate fecal transplantation, a clinically successful treatment for CDI, and discover that both the transplant timing and transplant donor are relevant to the the efficacy of the treatment, a result which has clinical implications. We incorporate two nongeneric yet dangerous attributes of CD into the gLV model, sporulation and antibiotic-resistant mutation, and for each identify relevant SIR techniques that describe the desired attribute. Finally, we rely on the results of our framework to analyze an experimental study of fecal transplants in mice, and are able to explain observed experimental results, validate our simulated results, and suggest model-motivated experiments.

  9. Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage

    Directory of Open Access Journals (Sweden)

    Peter Belenky

    2015-11-01

    Full Text Available Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (β-lactams, aminoglycosides, quinolones. These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products.

  10. Prevalence, phenotype and inheritance of benign neutropenia in Arabs

    Directory of Open Access Journals (Sweden)

    Nagelkerke Nicollas

    2009-03-01

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

  11. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. How we diagnose and treat neutropenia in adults.

    Science.gov (United States)

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

    2016-05-01

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

  15. Rationalizing the approach to children with fever in neutropenia

    NARCIS (Netherlands)

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

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

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

    Directory of Open Access Journals (Sweden)

    Ghidini M

    2016-06-01

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

  17. Lactobacillus GG and tributyrin supplementation reduce antibiotic-induced intestinal injury.

    Science.gov (United States)

    Cresci, Gail; Nagy, Laura E; Ganapathy, Vadivel

    2013-11-01

    Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or tributyrin would prevent these changes. C57BL/6 mice aged 6-8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate transport, and gut integrity via polymerase chain reaction and immunohistochemistry. Antibiotics decreased messenger RNA (mRNA) expression (butyrate transporter and receptor, Na(+)/H(+) exchanger, Cl(-)/HCO3 (-), and a water channel) and protein expression (butyrate transporter, Na(+)/H(+) exchanger, and tight junction proteins) in the intestinal tract. LGG and/or tributyrin supplementation maintained intestinal mRNA expression to that of the control animals, and tributyrin maintained intestinal protein intensity expression to that of control animals. Broad-spectrum antibiotics decrease expression of anion exchangers, butyrate transporter and receptor, and tight junction proteins in mouse intestine. Simultaneous oral supplementation with LGG and/or tributyrin minimizes these losses. Optimizing intestinal health with LGG and/or tributyrin may offer a preventative therapy for AAD.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Role of biosimilars in neutropenia prevention in cancer patients

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2014-01-01

    registered – all within the first chemotherapy cycle. Hospitalization due to FN was required in 3.5 % of patients, and none of these patients did require therapy in the Intensive Care Unit (ICU. Intravenous antibiotics received only 5.3 % of patients with FN. The average duration of severe neutropenia in first cycle in patients treated Zarsio® was 1.8 days compared with 7 days in the control group without the growth factors support. Expected side effects (musculoskeletal pain, leukocytosis, thrombocytopenia, and headache were of equal frequency in Zarsio® and Neypogen® groups. Serious adverse events were not observed, as well as deaths in all studies. Since 2009, the drug has been successfully used in oncology and hematology patients, which allowed within the expanded pharmacovigilance conduct a retrospective analysis of the effectiveness of neutropenia prevention after the change from the reference preparation filgrastim (GCSF – Neypogen® on G-CSF biosimilars Zarsio® in general oncology practice which showed comparable results at a lower treatment cost

  20. Role of biosimilars in neutropenia prevention in cancer patients

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2015-01-01

    registered – all within the first chemotherapy cycle. Hospitalization due to FN was required in 3.5 % of patients, and none of these patients did require therapy in the Intensive Care Unit (ICU. Intravenous antibiotics received only 5.3 % of patients with FN. The average duration of severe neutropenia in first cycle in patients treated Zarsio® was 1.8 days compared with 7 days in the control group without the growth factors support. Expected side effects (musculoskeletal pain, leukocytosis, thrombocytopenia, and headache were of equal frequency in Zarsio® and Neypogen® groups. Serious adverse events were not observed, as well as deaths in all studies. Since 2009, the drug has been successfully used in oncology and hematology patients, which allowed within the expanded pharmacovigilance conduct a retrospective analysis of the effectiveness of neutropenia prevention after the change from the reference preparation filgrastim (GCSF – Neypogen® on G-CSF biosimilars Zarsio® in general oncology practice which showed comparable results at a lower treatment cost

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

    OpenAIRE

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

    2013-01-01

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

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

    NARCIS (Netherlands)

    Mank, Arno; van der Lelie, Hans

    2003-01-01

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

  3. A mixture of Lactobacillus species isolated from traditional fermented foods promote recovery from antibiotic-induced intestinal disruption in mice.

    Science.gov (United States)

    Shi, Y; Zhao, X; Zhao, J; Zhang, H; Zhai, Q; Narbad, A; Chen, W

    2018-03-01

    This study evaluated the antibiotic-induced changes in microbial ecology, intestinal dysbiosis and low-grade inflammation; and the combined effect of four different Lactobacillus species on recovery of microbiota composition and improvement of gut barrier function in mice. Administration of the antibiotic ampicillin for 2 weeks decreased microbial community diversity, induced caecum tumefaction and increased gut permeability in mice. Application of a probiotic cocktail of four Lactobacillus species (JUP-Y4) modulated the microbiota community structure and promoted the abundance of potentially beneficial bacteria such as Akkermansia. Ampicillin administration led to a decline in Bacteroidetes from 46·6 ± 3·91% to 0·264 ± 0·0362%; the addition of JUP-Y4 restored this to 41·4 ± 2·87%. This probiotic supplementation was more effective than natural restoration, where the levels of Bacteroidetes were only restored to 29·3 ± 2·07%. Interestingly, JUP-Y4 treatment was more effective in the restoration of microbiota in faecal samples than in caecal samples. JUP-Y4 also significantly reduced the levels of d-lactate and endotoxin (lipopolysaccharide, LPS) in the serum of mice, and increased the expression of tight-junction proteins while reducing the production of inflammatory cytokines (TNF-α, IL-6, MCP-1, IFN-γ and IL-1β) in the ileum and the colon of antibiotic-treated mice. JUP-Y4 not only promoted recovery from antibiotic-induced gut dysbiosis, but also enhanced the function of the gut barrier, reduced inflammation and lowered levels of circulating endotoxin in mice. Consumption of a mixture of Lactobacillus species may encourage faster recovery from antibiotic-induced gut dysbiosis and gut microbiota-related immune disturbance. © 2018 The Society for Applied Microbiology.

  4. 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.

  5. Oral features of a family with benign familial neutropenia.

    Science.gov (United States)

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

    1994-05-01

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

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

    Science.gov (United States)

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

    2013-01-31

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

  7. 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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Young-In Kim

    1995-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Alberto Arencibia Núñez

    2009-08-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2015-02-05

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2006-04-01

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

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

    International Nuclear Information System (INIS)

    Saleem, L.; Zahid, N.A.

    2017-01-01

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

  17. Methimazole Associated Neutropenia in a Preterm Neonate Treated for Hyperthyroidism

    Directory of Open Access Journals (Sweden)

    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.

  18. Antibiotic-induced immediate type hypersensitivity is a risk factor for positive allergy skin tests for neuromuscular blocking agents.

    Science.gov (United States)

    Hagau, Natalia; Gherman, Nadia; Cocis, Mihaela; Petrisor, Cristina

    2016-01-01

    Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies. Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium. We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium). Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  19. Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Sven Geissler

    Full Text Available Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN. Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF or late (SPF+nonSPF pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.

  20. Biosimilars in the management of neutropenia: focus on filgrastim

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2017-05-01

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

  2. 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.

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

    Science.gov (United States)

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

    2006-06-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  5. 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.

  6. Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

    Science.gov (United States)

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

    2014-10-30

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

  7. Antibiotic-Induced Depletion of Anti-inflammatory Clostridia Is Associated with the Development of Graft-versus-Host Disease in Pediatric Stem Cell Transplantation Patients.

    Science.gov (United States)

    Simms-Waldrip, Tiffany R; Sunkersett, Gauri; Coughlin, Laura A; Savani, Milan R; Arana, Carlos; Kim, Jiwoong; Kim, Minsoo; Zhan, Xiaowei; Greenberg, David E; Xie, Yang; Davies, Stella M; Koh, Andrew Y

    2017-05-01

    Adult stem cell transplantation (SCT) patients with graft-versus-host-disease (GVHD) exhibit significant disruptions in gut microbial communities. These changes are associated with higher overall mortality and appear to be driven by specific antibiotic therapies. It is unclear whether pediatric SCT patients who develop GVHD exhibit similar antibiotic-induced gut microbiota community changes. Here, we show that pediatric SCT patients (from Children's Medical Center Dallas, n = 8, and Cincinnati Children's Hospital, n = 7) who developed GVHD showed a significant decline, up to 10-log fold, in gut anti-inflammatory Clostridia (AIC) compared with those without GVHD. In fact, the development of GVHD is significantly associated with this AIC decline and with cumulative antibiotic exposure, particularly antibiotics effective against anaerobic bacteria (P = .003, Firth logistic regression analysis). Using metagenomic shotgun sequencing analysis, we were able to identify specific commensal bacterial species, including AIC, that were significantly depleted in GVHD patients. We then used a preclinical GVHD model to verify our clinical observations. Clindamycin depleted AIC and exacerbated GVHD in mice, whereas oral AIC supplementation increased gut AIC levels and mitigated GVHD in mice. Together, these data suggest that an antibiotic-induced AIC depletion in the gut microbiota is associated with the development of GVHD in pediatric SCT patients. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Michael Wiesmeier

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

  10. 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.

  11. 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

  12. 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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  14. 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.

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

    Science.gov (United States)

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

    2011-10-01

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

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

    Science.gov (United States)

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

    2004-03-01

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

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

    Science.gov (United States)

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

    1980-04-01

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

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

    Science.gov (United States)

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

    2018-05-23

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

  19. 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.

  20. 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.

  1. Appearance of febrile neutropenia episodes after cytostatic therapy on oncology patients

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  2. 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.

  3. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    Science.gov (United States)

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

    2010-07-01

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

  4. Sleep and the gut microbiome: antibiotic-induced depletion of the gut microbiota reduces nocturnal sleep in mice

    OpenAIRE

    Seebach, Bradley; Lendrum, Jonathan; Liu, Sumei; Klein, Barrett

    2017-01-01

    Several bacterial cell wall components such as peptidoglycan and muramyl peptide are potent inducers of mammalian slow-wave sleep when exogenously administered to freely behaving animals. It has been proposed that the native gut microflora may serve as a quasi-endogenous pool of somnogenic bacterial cell wall products given their quantity and close proximity to the intestinal portal. This proposal suggests that deliberate manipulation of the host's intestinal flora may elicit changes in host ...

  5. Outcome of severe infections in afebrile neutropenic cancer patients

    Science.gov (United States)

    Mahkovic-Hergouth, Ksenija; Novakovic, Barbara Jezersek; Seruga, Bostjan

    2016-01-01

    Abstract Background In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia. Patients and methods We retrospectively analyzed all adult cancer patients with chemotherapy-induced neutropenia and severe infection, who were admitted to the Intensive Care Unit at our cancer center between 2000 and 2011. The outcome of interest was 30-day in-hospital mortality rate. Association between the febrile status and in-hospital mortality rate was evaluated by the Fisher’s exact test. Results We identified 69 episodes of severe neutropenic infections in 65 cancer patients. Among these, 9 (13%) episodes were afebrile. Patients with afebrile neutropenic infection presented with hypotension, severe fatigue with inappetence, shaking chills, altered mental state or cough and all of them eventually deteriorated to severe sepsis or septic shock. Overall 30-day in-hospital mortality rate was 55.1%. Patients with afebrile neutropenic infection had a trend for a higher 30-day in-hospital mortality rate as compared to patients with febrile neutropenic infection (78% vs. 52%, p = 0.17). Conclusions Afebrile cancer patients with chemotherapy-induced neutropenia and severe infections might have worse outcome as compared to cancer patients with febrile neutropenia. Patients should be informed that severe neutropenic infection without fever can occasionally occur during cancer treatment with chemotherapy. PMID:27904453

  6. 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.)

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Carstensen, M.; Sørensen, Jens Benn

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Mindy M. Sampson

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    V. A. Shuvaev

    2014-07-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2010-02-01

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

  17. Antibiotics induce mitonuclear protein imbalance but fail to inhibit respiration and nutrient activation in pancreatic β-cells.

    Science.gov (United States)

    Santo-Domingo, Jaime; Chareyron, Isabelle; Broenimann, Charlotte; Lassueur, Steve; Wiederkehr, Andreas

    2017-08-15

    Chloramphenicol and several other antibiotics targeting bacterial ribosomes inhibit mitochondrial protein translation. Inhibition of mitochondrial protein synthesis leads to mitonuclear protein imbalance and reduced respiratory rates as confirmed here in HeLa and PC12 cells. Unexpectedly, respiration in INS-1E insulinoma cells and primary human islets was unaltered in the presence of chloramphenicol. Resting respiratory rates and glucose stimulated acceleration of respiration were also not lowered when a range of antibiotics including, thiamphenicol, streptomycin, gentamycin and doxycycline known to interfere with bacterial protein synthesis were tested. However, chloramphenicol efficiently reduced mitochondrial protein synthesis in INS-1E cells, lowering expression of the mtDNA encoded COX1 subunit of the respiratory chain but not the nuclear encoded ATP-synthase subunit ATP5A. Despite a marked reduction of the essential respiratory chain subunit COX1, normal respiratory rates were maintained in INS-1E cells. ATP-synthase dependent respiration was even elevated in chloramphenicol treated INS-1E cells. Consistent with these findings, glucose-dependent calcium signaling reflecting metabolism-secretion coupling in beta-cells, was augmented. We conclude that antibiotics targeting mitochondria are able to cause mitonuclear protein imbalance in insulin secreting cells. We hypothesize that in contrast to other cell types, compensatory mechanisms are sufficiently strong to maintain normal respiratory rates and surprisingly even result in augmented ATP-synthase dependent respiration and calcium signaling following glucose stimulation. The result suggests that in insulin secreting cells only lowering COX1 below a threshold level may result in a measurable impairment of respiration. When focusing on mitochondrial function, care should be taken when including antibiotics targeting translation for long-term cell culture as depending on the sensitivity of the cell type analyzed

  18. 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

  19. 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...

  20. 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

    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...

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

    NARCIS (Netherlands)

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

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

  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

  3. 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.

  4. 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.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  6. 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

  7. 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.

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

    Science.gov (United States)

    Abbott, Iain J; Roberts, Jason A

    2012-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Alberto Arencibia Núñez

    2009-08-01

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

  10. Outcome of severe infections in afebrile neutropenic cancer patients

    Directory of Open Access Journals (Sweden)

    Strojnik Ksenija

    2016-12-01

    Full Text Available In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia.

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

    Science.gov (United States)

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

    2011-03-01

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

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Juliana Nunes Ferreira

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

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

    OpenAIRE

    Holmes, J A; Thompson, P W

    1988-01-01

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

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

    OpenAIRE

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2005-07-01

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

  18. A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

    Science.gov (United States)

    Tamary, H; Yaniv, I; Stein, J; Dgany, O; Shalev, Z; Shechter, T; Resnitzky, P; Shaft, D; Zoldan, M; Kornreich, L; Levy, R; Cohen, A; Moser, R A; Kapelushnik, J; Shalev, H

    2003-09-01

    Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Science.gov (United States)

    Tandeter, Howard; Glick, Karina; Moser, Asher

    2016-12-01

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

  1. 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.

  2. 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

    precoce são fundamentais para a melhora da sobrevida.OBJECTIVES: To provide a foundation for the diagnostic, prophylactic and therapeutic management of febrile neutropenia and sepsis in children with oncological diseases, with special attention to new protocols and guidelines. SOURCES: A review of the scientific literature utilizing an electronic bibliographic search on MEDLINE, Medscape, SciELO, Google, Cochrane and PubMED using the keywords febrile, neutropenic, cancer, children, sepsis, intensive, care. Articles published between 1987 and 2007 were selected, with preference given to review articles, protocols, systematic reviews, epidemiological studies, task force recommendations and phase III clinical trials. Consensus documents published by the Infectious Diseases Society of America, the Center for Diseases Control and the Infectious Diseases Working Party of the German Society of Hematology and Oncology, in addition to the recommendations of the World Federation of Pediatric Intensive and Critical Care Societies and Society of Critical Care Medicine, were also reviewed. SUMMARY OF THE FINDINGS: The use of aggressive chemotherapy regimens, bone marrow transplantation and intensive care resources have increased the survival rates of children with cancer and also their infectious morbidity, with septic complications as the principal cause of mortality. Several risk factors have been identified, such as neutropenia, oncology type, clinical signs and inflammatory response markers (polymerase chain reaction, procalcitonin and also increased resistance to antimicrobials and antifungal agents. Protocols for risk classification, diagnosis and treatment should be established at each service, taking into account the microbiological flora of each population. Pediatric intensive care has increased the short and long-term survival of these patients. CONCLUSIONS: Oncology patients are particularly vulnerable to infectious complications. Early identification and treatment are

  3. 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...

  4. 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.

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

    Science.gov (United States)

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

    2017-11-01

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

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Fátima Caeiro

    2009-08-01

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

  8. 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.


  9. 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.

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

    Science.gov (United States)

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

    2018-02-01

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

  11. 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. © 2011 Blackwell Verlag GmbH.

  12. 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.

  13. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Leonardo Lami Casaus

    2009-12-01

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

  17. 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.

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

    Hakim, R M; Lowrie, E G

    1982-01-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

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    Renno Hidayat

    2016-11-01

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

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

    Science.gov (United States)

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

    2016-05-26

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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    M. V. Peshikova

    2005-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    DEFF Research Database (Denmark)

    Rautiola, Juhana; Donskov, Frede; Peltola, Katriina

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

    Lyman, Gary H; Poniewierski, Marek S

    2017-12-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  12. 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

    Directory of Open Access Journals (Sweden)

    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

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-01

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

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

    Science.gov (United States)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2016-11-03

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

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

    Science.gov (United States)

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

    2016-05-24

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

  18. 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

  19. 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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

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

    2013-12-01

    Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary pegfilgrastim prophylaxis. Our economic evaluation used a health care perspective and was based on a randomized study in patients with breast cancer with increased risk of FN, comparing primary G-CSF prophylaxis throughout all chemotherapy cycles (G-CSF 1-6 cycles) with prophylaxis during the first two cycles only (G-CSF 1-2 cycles). Primary outcome was cost effectiveness expressed as costs per patient with episodes of FN prevented. The incidence of FN increased from 10% in the G-CSF 1 to 6 cycles study arm (eight of 84 patients) to 36% in the G-CSF 1 to 2 cycles study arm (30 of 83 patients), whereas the mean total costs decreased from € 20,658 (95% CI, € 20,049 to € 21,247) to € 17,168 (95% CI € 16,239 to € 18,029) per patient, respectively. Chemotherapy and G-CSF determined 80% of the total costs. As expected, FN-related costs were higher in the G-CSF 1 to 2 cycles arm. The incremental cost effectiveness ratio for the G-CSF 1 to 6 cycles arm compared with the G-CSF 1 to 2 cycles arm was € 13,112 per patient with episodes of FN prevented. We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of FN prevented.

  2. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    1998-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-02-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    M G Gerritsen

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2018-04-24

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    NARCIS (Netherlands)

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

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

  18. 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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2013-01-01

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

  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

  3. 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

  4. 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

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

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    J Mebis

    2010-07-01

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

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

    Science.gov (United States)

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

    2015-02-10

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

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

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    Wilfried Tröger

    2009-01-01

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

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

    Science.gov (United States)

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

    2001-12-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: results of monotherapy and combination therapy trials

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    Alecu I

    2018-02-01

    Full Text Available Iulian Alecu, Tsveta Milenkova, Simon R Turner Research and Development, AstraZeneca UK Limited, Cambridge, UKThe tolerability profile of PARP inhibitors often includes hematologic toxicities, and the characterization of these adverse events is important to allow effective management by clinicians. Zhou et al1 recently carried out a meta-analysis of the incidence and relative risks of severe neutropenia, thrombocytopenia, and anemia events in 12 randomized controlled trials of PARP inhibitors, either as monotherapy or in combination with chemotherapy or radiotherapy. The authors concluded that olaparib resulted in a higher incidence of severe (common terminology criteria for adverse events [CTCAE] grade $3 neutropenia when compared with niraparib and veliparib; however, these conclusions are based on inappropriate and incomplete comparisons of hematologic toxicity with olaparib or veliparib in combination with myelotoxic chemotherapy versus niraparib monotherapy. While both monotherapy and combination therapy olaparib studies are discussed in the paper, the neutropenia analysis is based on olaparib data solely from studies in combination with paclitaxel or paclitaxel plus carboplatin. In order to inform the practicing clinician of the relative risk of hematologic toxicity associated with different PARP inhibitors, direct comparison needs to be conducted based on monotherapy, where applicable, as per the approved drug indication, otherwise the reader is given misleading information.View the original paper by Zhou et al.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

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    S. Aliberti

    2009-07-01

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

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

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    Petrilli Antonio Sérgio

    2003-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-08-01

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

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  17. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours.

    Science.gov (United States)

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

    2011-01-01

    Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention

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

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    I. G. Bakulin

    2016-01-01

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

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

    Science.gov (United States)

    Mavroudi, Irene; Papadaki, Helen A.

    2012-01-01

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

  20. Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

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    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.

  1. Anemia of chronic disease is the more frequent type of anemia seen in patients with chronic idiopathic neutropenia of adults.

    Science.gov (United States)

    Papadaki, H A; Eliopoulos, D G; Valatas, V; Eliopoulos, G D

    2001-04-01

    This study describes the frequency and the type of anemia seen in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). We found that NI-CINA patients had low hemoglobin levels and increased serum concentrations of erythropoietin (EPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). The hemoglobin levels correlated positively with the number of circulating neutrophils and inversely with the levels of EPO and TNF-alpha but not of IL-1beta. Anemia, defined as the reduction of the hemoglobin below 12.0 g/dl for women and 13.3 g/dl for men, was found in 23 out of 148 patients studied, a proportion of 15.5%. Two of the anemic patients had iron deficiency anemia (8.7%), 11 had anemia of chronic disease (ACD; 47.8%) presenting with normal or slightly reduced erythrocytic indices, low serum iron, and increased serum ferritin, and the remaining ten had anemia of undefined pathogenesis (AUP; 43.5%) with normal or slightly decreased erythrocytic indices, serum iron ranging from 43 to 88 microg/dl, and ferritin values ranging from 12 to 50 ng/ml. We conclude that ACD is the more frequent type of anemia seen in patients with NI-CINA, and that pro-inflammatory cytokines, notably TNF-alpha, may be involved in the pathogenesis of both ACD and AUP, given that serum levels of the cytokine were significantly increased and that the EPO response to anemia was blunted in these patients. These findings further support our previously reported suggestion for the possible existence, in NI-CINA patients, of an unrecognized low-grade chronic inflammatory process that may be involved in the pathogenesis of the disorder.

  2. Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

    Science.gov (United States)

    Skedgel, Chris; Rayson, Daniel; Younis, Tallal

    2016-01-01

    Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

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

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    Desh Deepak

    2011-01-01

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

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

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    Zapata Ana X

    2006-03-01

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

  5. Antifungal prophylaxis in chemotherapy-associated neutropenia: a retrospective, observational study

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    Martin Thomas

    2007-07-01

    Full Text Available Abstract Background In August 2002, the antifungal prophylaxis algorithm for neutropenic hematology/oncology (NHO patients at the Medical Center was changed from conventional amphotericin (AMB to an azole (AZ based regimen (fluconazole [FLU] in low-risk and voriconazole [VOR] in high-risk patients. The aim of our study was to compare outcomes associated with the two regimens, including breakthrough fungal infection, adverse drug events, and costs. Methods Adult, non-febrile, NHO patients who received prophylactic AMB from 8/01/01-7/30/02 or AZ from 8/01/02-7/30/03 were retrospectively evaluated. Results A total of 370 patients (AMB: n = 181; AZ: n = 216 associated with 580 hospitalizations (AMB: n = 259; AZ: n = 321 were included. The incidence of probable/definite breakthrough Aspergillus infections was similar among regimens (AMB: 1.9% vs AZ: 0.6%; p=0.19. A greater incidence of mild/moderate (24.7% vs. 5.3%; p $9,000 increase in mean total costs/hospitalization, the mean acquisition cost associated with AZ was only $947/hospitalization more than AMB. Conclusion While an AZ-based regimen is associated with increased cost, the reduced rate of nephrotoxicity and availability of oral dosage forms, suggests that azoles be used preferentially over AMB. However, an increased rate of severe hepatic toxicity may be associated with VOR.

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

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    Norma E. Riera

    2006-10-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

  9. Congenital Neutropenia Syndromes

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  10. 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

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    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.

  11. [Association of atypical pulmonary TB, polyserositis, severe leukopenia and panniculitis. Case report].

    Science.gov (United States)

    Mihălţan, F; Lupu, A; Ungureanu, D; Halic, G; Badea, C; Marcu, C

    2001-01-01

    Many reports have associated tuberculosis with haematological abnormalities. These reports suggest that severe pulmonary tuberculosis, if associated with reduced tissue cellular reaction, may cause blood discrasias. Anemia was present in 32 percent of patients. Leucopenia with neutropenia and lymphopenia was observed in 15 percent in patients with very severe clinical tuberculosis. Active tuberculosis was associated with significant reductions in absolute numbers of total T, T4 and B lymphocytes, but there were no significant differences in total T8 counts. T4 lymphopenia causes reversal of T4/T8 ratio. Also, many histopathologic diagnosis of panniculitis have been reported in tuberculosis patients--the incidence of panniculitis caused by tuberculosis was 8.2%. We present a case of secondary pulmonary tuberculosis with atypically Rx changes, associated with polyserositis and severe leucopenia, which debuted with a panniculitis.

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

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    Lucy Johanna Hinojosa-Andía

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  14. Expression, purification, crystallization, and preliminary X-ray crystallographic analysis of OXA-17, an extended-spectrum {beta}-lactamase conferring severe antibiotic resistance

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H., E-mail: msgjhlee@mju.ac.kr; Sohn, S. G., E-mail: sgsohn@mju.ac.kr; Jung, H. I., E-mail: jhinumber1@hanmail.net; An, Y. J., E-mail: anyj0120@hanmail.net; Lee, S. H., E-mail: sangheelee@mju.ac.kr [Myongji University, Drug Resistance Proteomics Laboratory, Department of Biological Sciences (Korea, Republic of)

    2013-07-15

    OXA-17, an extended-spectrum {beta}-lactamase (ESBL) conferring severe antibiotic resistance, hydrolytically inactivates {beta}-lactam antibiotics, inducing a lack of eradication of pathogenic bacteria by oxyimino {beta}-lactams and not helping hospital infection control. Thus, the enzyme is a potential target for developing antimicrobial agents against pathogens producing ESBLs. OXA-17 was purified and crystallized at 298 K. X-ray diffraction data from OXA-17 crystal have been collected to 1.85 A resolution using synchrotron radiation. The crystal of OXA-17 belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 48.37, b = 101.12, and c = 126.07 A. Analysis of the packing density shows that the asymmetric unit probably contains two molecules with a solvent content of 54.6%.

  15. Expression, purification, crystallization, and preliminary X-ray crystallographic analysis of OXA-17, an extended-spectrum β-lactamase conferring severe antibiotic resistance

    International Nuclear Information System (INIS)

    Lee, J. H.; Sohn, S. G.; Jung, H. I.; An, Y. J.; Lee, S. H.

    2013-01-01

    OXA-17, an extended-spectrum β-lactamase (ESBL) conferring severe antibiotic resistance, hydrolytically inactivates β-lactam antibiotics, inducing a lack of eradication of pathogenic bacteria by oxyimino β-lactams and not helping hospital infection control. Thus, the enzyme is a potential target for developing antimicrobial agents against pathogens producing ESBLs. OXA-17 was purified and crystallized at 298 K. X-ray diffraction data from OXA-17 crystal have been collected to 1.85 Å resolution using synchrotron radiation. The crystal of OXA-17 belongs to space group P2 1 2 1 2 1 , with unit-cell parameters a = 48.37, b = 101.12, and c = 126.07 Å. Analysis of the packing density shows that the asymmetric unit probably contains two molecules with a solvent content of 54.6%

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Ritin Mohindra

    2017-01-01

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

  18. 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.

  19. Beneficial antimicrobial effect of the addition of an aminoglycoside to a β-lactam antibiotic in an E. coli porcine intensive care severe sepsis model.

    Science.gov (United States)

    Skorup, Paul; Maudsdotter, Lisa; Lipcsey, Miklós; Castegren, Markus; Larsson, Anders; Jonsson, Ann-Beth; Sjölin, Jan

    2014-01-01

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (pantibiotic groups compared with the controls (pantibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (pantibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  20. Antibiotic-Induced Anomalous Statistics of Collective Bacterial Swarming

    Science.gov (United States)

    Benisty, Sivan; Ben-Jacob, Eshel; Ariel, Gil; Be'er, Avraham

    2015-01-01

    Under sublethal antibiotics concentrations, the statistics of collectively swarming Bacillus subtilis transitions from normal to anomalous, with a heavy-tailed speed distribution and a two-step temporal correlation of velocities. The transition is due to changes in the properties of the bacterial motion and the formation of a motility-defective subpopulation that self-segregates into regions. As a result, both the colonial expansion and the growth rate are not affected by antibiotics. This phenomenon suggests a new strategy bacteria employ to fight antibiotic stress.

  1. Antibiotic-Induced Changes in the Intestinal Microbiota and Disease

    Science.gov (United States)

    Becattini, Simone; Taur, Ying; Pamer, Eric G.

    2016-01-01

    The gut microbiota is a key player in many physiological and pathological processes occurring in humans. Recent investigations suggest that the efficacy of some clinical approaches depends on the action of commensal bacteria. Antibiotics are invaluable weapons to fight infectious diseases. However, by altering the composition and functions of the microbiota, they can also produce long-lasting deleterious effects for the host. The emergence of multidrug-resistant pathogens raises concerns about the common, and at times inappropriate, use of antimicrobial agents. Here we review the most recently discovered connections between host pathophysiology, microbiota, and antibiotics highlighting technological platforms, mechanistic insights, and clinical strategies to enhance resistance to diseases by preserving the beneficial functions of the microbiota. PMID:27178527

  2. Antibiotic-Induced Changes in the Intestinal Microbiota and Disease.

    Science.gov (United States)

    Becattini, Simone; Taur, Ying; Pamer, Eric G

    2016-06-01

    The gut microbiota is a key player in many physiological and pathological processes occurring in humans. Recent investigations suggest that the efficacy of some clinical approaches depends on the action of commensal bacteria. Antibiotics are invaluable weapons to fight infectious diseases. However, by altering the composition and functions of the microbiota, they can also produce long-lasting deleterious effects for the host. The emergence of multidrug-resistant pathogens raises concerns about the common, and at times inappropriate, use of antimicrobial agents. Here we review the most recently discovered connections between host pathophysiology, microbiota, and antibiotics highlighting technological platforms, mechanistic insights, and clinical strategies to enhance resistance to diseases by preserving the beneficial functions of the microbiota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Benefits of Reiki therapy for a severely neutropenic patient with associated influences on a true random number generator.

    Science.gov (United States)

    Morse, Melvin L; Beem, Lance W

    2011-12-01

    Reiki therapy is documented for relief of pain and stress. Energetic healing has been documented to alter biologic markers of illness such as hematocrit. True random number generators are reported to be affected by energy healers and spiritually oriented conscious awareness. The patient was a then 54-year-old severely ill man who had hepatitis C types 1 and 2 and who did not improve with conventional therapy. He also suffered from obesity, the metabolic syndrome, asthma, and hypertension. He was treated with experimental high-dose interferon/riboviron therapy with resultant profound anemia and neutropenia. Energetic healing and Reiki therapy was administered initially to enhance the patient's sense of well-being and to relieve anxiety. Possible effects on the patient's absolute neutrophil count and hematocrit were incidentally noted. Reiki therapy was then initiated at times of profound neutropenia to assess its possible effect on the patient's absolute neutrophil count (ANC). Reiki and other energetic healing sessions were monitored with a true random number generator (RNG). Statistically significant relationships were documented between Reiki therapy, a quieting of the electronically created white noise of the RNG during healing sessions, and improvement in the patient's ANC. The immediate clinical result was that the patient could tolerate the high-dose interferon regimen without missing doses because of absolute neutropenia. The patient was initially a late responder to interferon and had been given a 5% chance of clearing the virus. He remains clear of the virus 1 year after treatment. The association between changes in the RNG, Reiki therapy, and a patient's ANC is the first to the authors' knowledge in the medical literature. Future studies assessing the effects of energetic healing on specific biologic markers of disease are anticipated. Concurrent use of a true RNG may prove to correlate with the effectiveness of energetic therapy.

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

    Directory of Open Access Journals (Sweden)

    S. Aliberti

    2009-07-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Stéphanie Wagner

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

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

    Science.gov (United States)

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

    2018-01-01

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

  8. Severe Aplastic Anemia (SAA)

    Science.gov (United States)

    ... page Print this page My Cart Severe aplastic anemia (SAA) Severe aplastic anemia (SAA) is a disease ... leukemia (ALL) Other diseases What is severe aplastic anemia (SAA)? SAA is a bone marrow disease. The ...

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

    Science.gov (United States)

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

    2017-10-01

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

  10. No contribution of GSTM1 and GSTT1 null genotypes to the risk of neutropenia due to benzene exposure in Southeastern Brazil

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    Carmen Silvia Passos Lima

    2009-01-01

    Full Text Available Exposure to benzene has been associated with haematological diseases such as neutropenia (NEB and acute myeloid leukaemia (AML. We tested whether the null genotypes of the GSTM1 and GSTT1 genes, involved in benzene inactivation, altered the risk for NEB in southeastern Brazil. Genomic DNA from 55 NEB patients and 330 controls was analysed by multiplex-polymerase chain reaction. The frequency of the GSTM1, GSTT1 and combined null genotypes was similar in patients and controls (GSTM1, 27.3% vs. 38.8%, p = 0.16; GSTT1, 25.5% vs. 19.7%, p = 0.24; GSTM1/GSTT1, 12.7% vs. 6.7%, p = 0.26; respectively. The distribution of genotype classes in NEB patients was similar to normal controls, suggesting that GSTM1 and GSTT1 null genotypes make no specific contribution to the risk of NEB. As the GSTM1 and GSTT1 null genotypes were previously associated with increased risk for AML in Brazil and elsewhere, we hypothesise that different thresholds of chemical exposure relative to distinct GSTM1 and GSTT1 genotypes may determine whether AML or NEB manifests in benzene exposed individuals from southeastern Brazil. Although indicative, our results still require support by prospective and large scale epidemiological studies, with rigorous assessment of daily chemical exposures and control of the possible contribution of other polymorphic genes involved in benzene metabolism.

  11. Mpn1, Mutated in Poikiloderma with Neutropenia Protein 1, Is a Conserved 3′-to-5′ RNA Exonuclease Processing U6 Small Nuclear RNA

    Directory of Open Access Journals (Sweden)

    Vadim Shchepachev

    2012-10-01

    Full Text Available Clericuzio-type poikiloderma with neutropenia (PN is a rare genodermatosis associated with mutations in the C16orf57 gene, which codes for the uncharacterized protein hMpn1. We show here that, in both fission yeasts and humans, Mpn1 processes the spliceosomal U6 small nuclear RNA (snRNA posttranscriptionally. In Mpn1-deficient cells, U6 molecules carry 3′ end polyuridine tails that are longer than those in normal cells and lack a terminal 2′,3′ cyclic phosphate group. In mpn1Δ yeast cells, U6 snRNA and U4/U6 di-small nuclear RNA protein complex levels are diminished, leading to precursor messenger RNA splicing defects, which are reverted by expression of either yeast or human Mpn1 and by overexpression of U6. Recombinant hMpn1 is a 3′-to-5′ RNA exonuclease that removes uridines from U6 3′ ends, generating terminal 2′,3′ cyclic phosphates in vitro. Finally, U6 degradation rates increase in mpn1Δ yeasts and in lymphoblasts established from individuals affected by PN. Our data indicate that Mpn1 promotes U6 stability through 3′ end posttranscriptional processing and implicate altered U6 metabolism as a potential mechanism for PN pathogenesis.

  12. [Severe rhabdomyolysis secondary to severe hypernatraemic dehydration].

    Science.gov (United States)

    Mastro-Martínez, Ignacio; Montes-Arjona, Ana María; Escudero-Lirio, Margarita; Hernández-García, Bárbara; Fernández-Cantalejo Padial, José

    2015-01-01

    Rhabdomyolysis is a rare paediatric condition. The case is presented of a patient in whom this developed secondary to severe hypernatraemic dehydration following acute diarrhoea. Infant 11 months of age who presented with vomiting, fever, diarrhoea and anuria for 15 hours. Parents reported adequate preparation of artificial formula and oral rehydration solution. He was admitted with malaise, severe dehydration signs and symptoms, cyanosis, and low reactivity. The laboratory tests highlighted severe metabolic acidosis, hypernatraemia and pre-renal kidney failure (Sodium [Na] plasma 181 mEq/L, urine density> 1030). He was managed in Intensive Care Unit with gradual clinical and renal function improvement. On the third day, slight axial hypotonia and elevated cell lysis enzymes (creatine phosphokinase 75,076 IU/L) were observed, interpreted as rhabdomyolysis. He was treated with intravenous rehydration up to 1.5 times the basal requirements, and he showed a good clinical and biochemical response, being discharged 12 days after admission without motor sequelae. Severe hypernatraemia is described as a rare cause of rhabdomyolysis and renal failure. In critically ill patients, it is important to have a high index of suspicion for rhabdomyolysis and performing serial determinations of creatine phosphokinase for early detection and treatment. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Palmer Drought Severity Index

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — PDSI from the Dai dataset. The Palmer Drought Severity Index (PDSI) is devised by Palmer (1965) to represent the severity of dry and wet spells over the U.S. based...

  14. 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.

  15. 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.

    Science.gov (United States)

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

    2013-12-01

    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 during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy. In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm. After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis). In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.

  16. 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

    2018-02-01

    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.

  17. Severe accident phenomena

    International Nuclear Information System (INIS)

    Jokiniemi, J.; Kilpi, K.; Lindholm, I.; Maekynen, J.; Pekkarinen, E.; Sairanen, R.; Silde, A.

    1995-02-01

    Severe accidents are nuclear reactor accidents in which the reactor core is substantially damaged. The report describes severe reactor accident phenomena and their significance for the safety of nuclear power plants. A comprehensive set of phenomena ranging from accident initiation to containment behaviour and containment integrity questions are covered. The report is based on expertise gained in the severe accident assessment projects conducted at the Technical Research Centre of Finland (VTT). (49 refs., 32 figs., 12 tabs.)

  18. De-severing distance

    DEFF Research Database (Denmark)

    Jensen, Hanne Louise; de Neergaard, Maja

    2016-01-01

    De-severing Distance This paper draws on the growing body of mobility literature that shows how mobility can be viewed as meaningful everyday practices (Freudendal –Pedersen 2007, Cresswell 2006) this paper examines how Heidegger’s term de-severing can help us understand the everyday coping with ...

  19. Severe Bleeding: First Aid

    Science.gov (United States)

    ... 12, 2017. Jevon P, et al. Part 5 — First-aid treatment for severe bleeding. Nursing Times. 2008;104:26. Oct. 19, 2017 Original article: http://www.mayoclinic.org/first-aid/first-aid-severe-bleeding/basics/ART-20056661 . Mayo ...

  20. Allergy in severe asthma

    NARCIS (Netherlands)

    Del Giacco, Stefano R.; Bakirtas, A.; Bel, E.; Custovic, A.; Diamant, Z.; Hamelmann, E.; Heffler, E.; Kalayci, O.; Saglani, S.; Sergejeva, S.; Seys, S.; Simpson, A.; Bjermer, Leif

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps

  1. Currency flaw severity. [Banknotes

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, C.; Burnett, M.; Goodman, C.; Sherrod, R.; Schmoyer, R.; Harrison, C.; Uppuluri, R.

    1986-01-01

    A survey of currency flaw severity was carried out using 300 banknotes and 37 judges. Each judge assigned each note to one of five flaw severity categories. These categories correspond to severity grades of 1 to 5 with 1 equivalent to ''always accepted'' and 5 ''never accepted.'' An average flaw severity grade for each note was obtained by taking the mean of the severity grades assigned to that note by the 37 judges. Thus, each note has a single numerical real-number flaw grade between 1 and 5. Mathematical modeling of the currency flaw survey results is continuing with some very promising initial results. Our present model handles common excess ink and missing ink flaw types quite well. We plan to extend the model to ink level, mash, setoff and blanket impression flaw types.

  2. 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.

     

     

  3. Severe childhood malnutrition

    DEFF Research Database (Denmark)

    Bhutta, Zulfiqar A; Berkley, James A; Bandsma, Robert H J

    2017-01-01

    The main forms of childhood malnutrition occur predominantly in children malnutrition. Here, we use...... the term 'severe malnutrition' to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal...... nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide...

  4. Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent fever?

    Directory of Open Access Journals (Sweden)

    James Owen Robinson

    Full Text Available BACKGROUND: Management of febrile neutropenic episodes (FE is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT in FE for initial diagnosis of infection and reassessment in persistent fever. METHODS: PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples: 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS, 68 clinically documented infections (CDI, 35%; 39 deep-seated, and 61 fever of unexplained origin (FUO, 31.5%. RESULTS: At fever onset median PCT was 190 pg/mL (range 30-26'800, without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350 vs. FUO (205, 33-771; p500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570-771. A PCT peak >500 pg/mL (1196, 524-11950 occurred beyond 3 days of persistent fever in 17/21 (81% invasive fungal diseases (IFD. This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1-23 vs. 10 (3-22; p = 0.026, respectively. CONCLUSION: While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses.

  5. Several complex variables

    International Nuclear Information System (INIS)

    Field, M.J.

    1976-01-01

    Topics discussed include the elementary of holomorphic functions of several complex variables; the Weierstrass preparation theorem; meromorphic functions, holomorphic line bundles and divisors; elliptic operators on compact manifolds; hermitian connections; the Hodge decomposition theorem. ( author)

  6. Severe malaria in Europe

    DEFF Research Database (Denmark)

    Kurth, Florian; Develoux, Michel; Mechain, Matthieu

    2017-01-01

    BACKGROUND: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. METHODS: The European Network for Tropical Medicine and Travel Health (Trop......Net) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre...... for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. RESULTS: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections...

  7. Severe accident management guidelines

    International Nuclear Information System (INIS)

    Uhle, Jennifer

    2014-01-01

    The events at Fukushima Daiichi have highlighted the importance of Severe Accident Management Guidelines (SAMGs). As the world has learned from the catastrophe and countries are considering changes to their nuclear regulatory programs, the content of SAMGs and their regulatory control are being evaluated. This presentation highlights several factors that are being addressed in the United States as rulemaking is underway pertaining to SAMGs. The question of how to be prepared for the unexpected is discussed with specific insights gleaned from Fukushima. (author)

  8. Allergy in severe asthma.

    Science.gov (United States)

    Del Giacco, S R; Bakirtas, A; Bel, E; Custovic, A; Diamant, Z; Hamelmann, E; Heffler, E; Kalayci, Ö; Saglani, S; Sergejeva, S; Seys, S; Simpson, A; Bjermer, L

    2017-02-01

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Severe childhood malnutrition.

    Science.gov (United States)

    Bhutta, Zulfiqar A; Berkley, James A; Bandsma, Robert H J; Kerac, Marko; Trehan, Indi; Briend, André

    2017-09-21

    The main forms of childhood malnutrition occur predominantly in children malnutrition. Here, we use the term 'severe malnutrition' to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide therapeutic end points. The early detection of severe wasting and kwashiorkor and outpatient therapy for these conditions using ready-to-use therapeutic foods form the cornerstone of modern therapy, and only a small percentage of children require inpatient care. However, the normalization of physiological and metabolic functions in children with malnutrition is challenging, and children remain at high risk of relapse and death. Further research is urgently needed to improve our understanding of the pathophysiology of severe malnutrition, especially the mechanisms causing kwashiorkor, and to develop new interventions for prevention and treatment.

  10. 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

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

    Science.gov (United States)

    Fung, Monica; Kim, Jane; Marty, Francisco M; Schwarzinger, Michaël; Koo, Sophia

    2015-01-01

    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. We

  13. Severe accident behavior

    International Nuclear Information System (INIS)

    Denning, R.S.

    1986-01-01

    The purpose of this paper is to provide an overview of severe accident behavior. The term source term is defined and a brief history of the regulatory use of source term is presented. The processes in severe accidents in light water reactors are described with particular emphasis on the relationships between accident thermal-hydraulics and chemistry. Those factors which have the greatest impact on predicted source terms are identified. Design differences between plants that affect source term estimation are also described. The principal unresolved issues are identified that are the focus of ongoing research and debate in the technical community

  14. Severe asthma in childhood

    International Nuclear Information System (INIS)

    Ciznar, P.

    2013-01-01

    Patients with severe asthma are clinically, physiologically and biologically a heterogeneous group. About half of children referred for medical examination for severe asthma have true severe, therapy resistant asthma. The rest of referred patients have difficult to treat asthma. Symptoms persist mostly due to drug non-compliance, inappropriate inhalation technique, persistent environmental exposures or co-morbid conditions. Compared with adults have children more frequently atopic form of severe asthma. This is associated with eosinophilia in peripheral blood and sensitization to inhaled allergens. The IgE levels are high. Therapy of co-morbidities and improvement of treatment compliance lead in most cases to full asthma control. Proportion of children will benefit from biologics like anti-IgE monoclonal antibody, administered by subcutaneous injections in 2 to 4 week intervals. By this therapy it is not only possible to suppress symptoms, but also decrease the total steroid dose and the risk of adverse effects associated with its long-term administration. By achieving a full asthma control we lower future risk of exacerbations and probably improve long-term prognosis of disease, frequently persisting for the rest of life. (author)

  15. [Severe depression : psychoanalysis].

    Science.gov (United States)

    Bouvet de la Maisonneuve, O

    2009-12-01

    The indication for psychoanalysis in severe depression is not clear. And yet, demands for this type of intervention are increasing, despite the absence of any form of consensus on the subject. Freud considered depression as a failure of analytical efforts and, based on this observation, revised his theory, in particular to include the notions of narcissism and the death drive. Many analysts have been reluctant to follow his teachings on this last point and provide depressed patients with analytical-type therapies aimed at restoring narcissism. Melanie Klein pushed Freud's ideas about depression even further and brought such therapies back to the heart of analytical practice. Jacques Lacan took the debate to another level by proposing an overhaul of the principles on which analysis has been based. Today, while following certain precautionary rules, true psychoanalyses can be proposed to patients with severe depression, whether of the bipolar, recurring or even neurotic type that can reach this level of severity. Copyright 2009 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  16. Management of severe accidents

    International Nuclear Information System (INIS)

    Jankowski, M.W.

    1987-01-01

    The definition and the multidimensionality aspects of accident management have been reviewed. The suggested elements in the development of a programme for severe accident management have been identified and discussed. The strategies concentrate on the two tiered approaches. Operative management utilizes the plant's equipment and operators capabilities. The recovery managment concevtrates on preserving the containment, or delaying its failure, inhibiting the release, and on strategies once there has been a release. The inspiration for this paper was an excellent overview report on perspectives on managing severe accidents in commercial nuclear power plants and extending plant operating procedures into the severe accident regime; and by the most recent publication of the International Nuclear Safety Advisory Group (INSAG) considering the question of risk reduction and source term reduction through accident prevention, management and mitigation. The latter document concludes that 'active development of accident management measures by plant personnel can lead to very large reductions in source terms and risk', and goes further in considering and formulating the key issue: 'The most fruitful path to follow in reducing risk even further is through the planning of accident management.' (author)

  17. Several real variables

    CERN Document Server

    Kantorovitz, Shmuel

    2016-01-01

    This undergraduate textbook is based on lectures given by the author on the differential and integral calculus of functions of several real variables. The book has a modern approach and includes topics such as: •The p-norms on vector space and their equivalence •The Weierstrass and Stone-Weierstrass approximation theorems •The differential as a linear functional; Jacobians, Hessians, and Taylor's theorem in several variables •The Implicit Function Theorem for a system of equations, proved via Banach’s Fixed Point Theorem •Applications to Ordinary Differential Equations •Line integrals and an introduction to surface integrals This book features numerous examples, detailed proofs, as well as exercises at the end of sections. Many of the exercises have detailed solutions, making the book suitable for self-study. Several Real Variables will be useful for undergraduate students in mathematics who have completed first courses in linear algebra and analysis of one real variable.

  18. Epidemiology of severe trauma.

    Science.gov (United States)

    Alberdi, F; García, I; Atutxa, L; Zabarte, M

    2014-12-01

    Major injury is the sixth leading cause of death worldwide. Among those under 35 years of age, it is the leading cause of death and disability. Traffic accidents alone are the main cause, fundamentally in low- and middle-income countries. Patients over 65 years of age are an increasingly affected group. For similar levels of injury, these patients have twice the mortality rate of young individuals, due to the existence of important comorbidities and associated treatments, and are more likely to die of medical complications late during hospital admission. No worldwide, standardized definitions exist for documenting, reporting and comparing data on severely injured trauma patients. The most common trauma scores are the Abbreviated Injury Scale (AIS), the Injury Severity Score (ISS) and the Trauma and Injury severity Score (TRISS). Documenting the burden of injury also requires evaluation of the impact of post-trauma impairments, disabilities and handicaps. Trauma epidemiology helps define health service and research priorities, contributes to identify disadvantaged groups, and also facilitates the elaboration of comparable measures for outcome predictions. Copyright © 2014 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  19. Management of severe accidents

    International Nuclear Information System (INIS)

    Jankowski, M.W.

    1988-01-01

    The definition and the multidimensionality aspects of accident management have been reviewed. The suggested elements in the development of a programme for severe accident management have been identified and discussed. The strategies concentrate on the two tiered approaches. Operative management utilizes the plant's equipment and operators capabilities. The recovery management concentrates on preserving the containment, or delaying its failure, inhibiting the release, and on strategies once there has been a release. The inspiration for this paper was an excellent overview report on perspectives on managing severe accidents in commercial nuclear power plants and extending plant operating procedures into the severe accident regime; and by the most recent publication of the International Nuclear Safety Advisory Group (INSAG) considering the question of risk reduction and source term reduction through accident prevention, management and mitigation. The latter document concludes that active development of accident management measures by plant personnel can lead to very large reductions in source terms and risk, and goes further in considering and formulating the key issue: The most fruitful path to follow in reducing risk even further is through the planning of accident management

  20. Severe fuel damage projects

    International Nuclear Information System (INIS)

    Sdouz, G.

    1987-10-01

    After the descriptions of the generation of a Severe Fuel Damage Accident in a LWR the hypothetical course of such an accident is explained. Then the most significant projects are described. At each project the experimental facility, the most important results and the concluding models and codes are discussed. The selection of the projects is concentrated on the German Projekt Nukleare Sicherheit (PNS), tests performed at the Idaho National Engineering Laboratory (INEL) and smaller projects in France and Great Britain. 25 refs., 26 figs. (Author)

  1. One reason, several logics

    Directory of Open Access Journals (Sweden)

    Evandro Agazzi

    2011-06-01

    Full Text Available Humans have used arguments for defending or refuting statements long before the creation of logic as a specialized discipline. This can be interpreted as the fact that an intuitive notion of "logical consequence" or a psychic disposition to articulate reasoning according to this pattern is present in common sense, and logic simply aims at describing and codifying the features of this spontaneous capacity of human reason. It is well known, however, that several arguments easily accepted by common sense are actually "logical fallacies", and this indicates that logic is not just a descriptive, but also a prescriptive or normative enterprise, in which the notion of logical consequence is defined in a precise way and then certain rules are established in order to maintain the discourse in keeping with this notion. Yet in the justification of the correctness and adequacy of these rules commonsense reasoning must necessarily be used, and in such a way its foundational role is recognized. Moreover, it remains also true that several branches and forms of logic have been elaborated precisely in order to reflect the structural features of correct argument used in different fields of human reasoning and yet insufficiently mirrored by the most familiar logical formalisms.

  2. Several crimes solved

    CERN Multimedia

    Relations with the Host States Service

    2007-01-01

    A member of a contractor's personnel suspected of having committed several thefts in and around Building 180 has recently been questioned by the French police. He was immediately tried by the court in Bourg-en-Bresse and sentenced to six months in prison, with a requirement to serve at least three months. His arrest was facilitated, among other things, by a video recording, fast and detailed statements to the CERN Fire Brigade and close collaboration between the members of the personnel concerned, the Reception and Access Control Service and the police. Several laptops and other items of electronic equipment were seized during a search of the culprit's home. A stolen digital camera has yet to be returned to its owner as he has not reported the theft to the CERN Fire Brigade and the police. The person concerned is therefore requested to go to the Gendarmerie in Saint-Genis-Pouilly with the necessary proof of ownership. In addition, the French authorities have informed CERN that the presumed authors of the a...

  3. Severe service sealing solutions

    International Nuclear Information System (INIS)

    Metcalfe, R.; Wensel, R.

    1994-09-01

    Successful sealing usually requires much more than initial leak-tightness. Friction and wear must also be acceptable, requiring a good understanding of tribology at the sealing interface. This paper describes various sealing solutions for severe service conditions. The CAN2A and CAN8 rotary face seals use tungsten carbide against carbon-graphite to achieve low leakage and long lifetime in nuclear main coolant pumps. The smaller CAN6 seal successfully uses tungsten carbide against silicon carbide in reactor water cleanup pump service. Where friction in CANDU fuelling machine rams must be essentially zero, a hydrostatic seal using two silicon carbide faces is the solution. In the NRU reactor moderator pumps, where pressure is much lower, eccentric seals that prevent boiling at the seal faces are giving excellent service. All these rotary face seals rely on supplementary elastomer seals between their parts. An integrated engineering approach to high performance sealing with O-rings is described. This is epitomized in critical Space Shuttle applications, but is increasingly being applied in CANDU plants. It includes gland design, selection and qualification of material, quality assurance, detection of defects and the effects of lubrication, surface finish, squeeze, stretch and volume constraints. In conclusion, for the severe service applications described, customized solutions have more than paid for themselves by higher reliability, lower maintenance requirements and reduced outage time. (author)

  4. Leukopenia and neutropenia caused by sertraline%舍曲林致白细胞和中性粒细胞减少

    Institute of Scientific and Technical Information of China (English)

    庄红艳; 刘珊珊; 杜海霞; 崔永华

    2016-01-01

    1例11岁女性患儿因童年情绪障碍服用舍曲林25 mg、喹硫平25 mg,1次/ d。2 d 后实验室检查:WBC 4.6×109/ L,中性粒细胞计数(NEUT)1.8×109/ L。诊断:中性粒细胞减少。停用喹硫平,继续服用舍曲林,给予盐酸小檗胺84 mg、利可君20 mg,3次/ d 口服。6 d 后为改善病情,舍曲林剂量增至50 mg,1次/ d。同时加用维生素 B610 mg,3次/ d 口服。舍曲林治疗第13天,患儿 WBC 3.5×109/ L ,NEUT 1.4×109/ L,诊断为白细胞减少。舍曲林治疗第24天,患儿 WBC 3.3×109/ L, NEUT 1.4×109/ L。加用安多霖胶囊0.64 g,2次/ d 口服。次日舍曲林减量至25 mg,1次/ d,2 d 后停用。5 d 后复查,患儿 WBC 4.4×109/ L,NEUT 2.0×109/ L。给予氟伏沙明改善情绪。7 d 后,患儿WBC 4.6×109/ L,NEUT 2.3×109/ L。%An 11-year-old female patient was given sertraline 25 mg once daily and quetiapine 25 mg once daily for childhood emotional disorders. The patient's white blood cells count(WBC)was 4. 6 ×109 / L and neutrophil count( NEUT)was 1. 8 ×109 / L two days later. The patient was diagnosed as neutropenia. Quetiapine was stopped and sertraline was given continually. At the same time berbamine hydrochloride 84 mg thrice daily and leucogen 20 mg thrice daily were given. Six days later,the dosage of sertraline was increased to 50 mg once daily to improve the symptoms and vitamin B6 10 mg thrice daily was given. On day 13 of sertraline therapy,the WBC was 3. 5 ×109 / L and the NEUT was 1.4×109 / L. Leukopenia was diagnosed. On day 24 of sertraline therapy,the WBC was 3. 3 ×109 / L and the NEUT was 1.4×109 / L. Anduolin(安多霖)capsules 0. 64 g twice daily were added to her regimen. Sertraline dose was reduced to 25 mg once daily the next day and was stopped 2 days later. Five days later,the patient's WBC was 4.4×109 / L and NEUT was 2. 0 ×109 / L. Then,fluvoxamine was given to improve mood. Seven days later,the patient's WBC was 4. 6

  5. Measurement by phase severance

    International Nuclear Information System (INIS)

    Noyes, H.P.

    1987-03-01

    It is claimed that the measurement process is more accurately described by ''quasi-local phase severance'' than by ''wave function collapse''. The approach starts from the observation that the usual route to quantum mechanics starting from the Hamilton-Jacobi equations throws away half the degrees of freedom, namely, the classical initial state parameters. To overcome this difficulty, the full set of Hamilton-Jacobi equations is interpreted as operator equations acting on a state vector. The measurement theory presented is based on the conventional S-matrix boundary condition of N/sub A/ free particles in the distant past and N/sub B/ free particles in the distant future and taking the usual free particle wave functions, multiplied by phase factors

  6. CANDU severe accident analysis

    International Nuclear Information System (INIS)

    Negut, Gheorghe; Catana, Alexandru; Prisecaru, Ilie; Dupleac, Daniel

    2007-01-01

    Romania is a EU member since January first 2007. This country faces now new challenges which imply also the nuclear power reactors now in operation. Romania operates since 1996 a CANDU nuclear power reactor and soon will start up a second unit. In EU PWR reactors are mostly operated, so that the Romania's reactors have to meet EU standards. Safety analysis guidelines require to model severe accidents for reactors of this type. Starting from previous studies a thermal-hydraulic model for a degraded CANDU core was developed. The initiating event is assumed to be a LOCA with simultaneous loss of moderator and coolant and the failure of emergency core cooling system (ECCS). This type of accident is likely to modify the reactor geometry and will lead to a severe accident development. When the coolant temperatures inside a pressure tube reaches 1000 deg. C, a contact between pressure tube and calandria tube occurs and the decay heat is transferred to the moderator. Due to the lack of cooling, the moderator eventually begins to boil and is expelled, through the calandria vessel relief ducts, into the containment. Therefore the calandria tubes (fuel channels) uncover, then disintegrate and fall down to the calandria vessel bottom. All the quantity of calandria moderator is vaporized and expelled, the debris will heat up and eventually boil. The heat accumulated in the molten debris will be transferred through the calandria vessel wall to the shield water tank surrounding the calandria vessel. The thermal hydraulics phenomena described above are modeled, analyzed and compared with the existing data. (authors)

  7. Methodology for clinical trials involving patients with cancer who have febrile neutropenia: updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies.

    Science.gov (United States)

    Feld, Ronald; Paesmans, Marianne; Freifeld, Alison G; Klastersky, Jean; Pizzo, Philip A; Rolston, Kenneth V I; Rubenstein, Edward; Talcott, James A; Walsh, Thomas J

    2002-12-15

    Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy.

  8. Treatment of severe tinnitus.

    Science.gov (United States)

    Laurikainen, E; Johansson, R; Akaan-Penttilä, E; Haapaniemi, J

    2000-01-01

    In 1995-96 we selected a group of 26 patients who were suffering from severe invalidating idiopathic tinnitus (IT) in order to evaluate the efficacy of rehabilitation and some alternative therapies. All patients were assessed thoroughly by means of audiology and radiology regarding any objective cause for the symptom. In order to help patients control their symptom by increasing knowledge and adding supportive elements, they were given basic education (presentations of the anatomy and physiology of the ear and hearing system, psychological and social aspects of IT, guided and non-guided group discussions, relaxation therapy, physiotherapy, music therapy) for 4 months, comprising one 2-h session bi-weekly. This type of group therapy was found to be extremely helpful, although no objective evaluation revealed effects on IT sensation (VAS) or psychometric measures (SLC-90). In a second limb of the study, the same patients attended a 6-day intensive course in a spa. The purpose was to evaluate the possible usefulness of the widely recommended alternative therapies for IT. All patients had an opportunity to sample the treatments. Six months later only a few had tried any of these treatments, but all reported that the lessons were the most helpful in association with supportive group discussions. The results indicated that none of these therapies can be recommended, based on rational medical practise.

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

    Science.gov (United States)

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

    2012-12-01

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

  10. 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

  11. Morbidity of severe obesity.

    Science.gov (United States)

    Kral, J G

    2001-10-01

    Although obesity is an easy diagnosis to make, its etiologies, pathophysiology, and symptomatology are extraordinarily complex. Progress in surgical technique and anesthesiological management has substantially improved the safety of performing operations on the severely obese in the last 20 years. These improvements have occurred more or less empirically, without a full understanding of etiology or pathophysiology, although this has advanced concomitantly with improvements in practice. This review has attempted to provide a framework to facilitate progress in the neglected areas of patient selection and choice of operation, in an effort to improve long-term outcome. Despite the disparate etiologies of obesity and its diverse comorbidities and complications, there are unifying interdependent pathogenetic mechanisms of great relevance to the practice of antiobesity surgery. The rate of eating, whether driven by HPA dysfunction, ambient stress, or related hereditary susceptibility factors including the increased energy demands of an expanded body fat mass, participates in a cycle that results in disordered satiety (see Fig. 3). This leads to substrate overload, causing extensive metabolic abnormalities such as atherogenesis, insulin resistance, thrombogenesis, and carcinogenesis. This interpretation of the pathophysiology of obesity ironically accords with the original meaning of the word obesity: "to overeat." The ultimate solution to the problem of obesity--preventing it--will not be forthcoming until the food industry is forced to lower production and change its marketing strategies, as the liquor and tobacco industries in the United States were compelled to do. This cannot occur until the large and fast-growing populations of industrialized nations become educated in the personal implications of the energy principle. Regardless of whether school curricula are modified to prioritize health education, the larger problems of cultural and economic change remain for

  12. SEVERE (GRADE III-IV ACUTE GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Irena Preložnik-Zupan

    2002-09-01

    Full Text Available Background. Beside greater susceptibility to infections, acute graft host disease is a consequence of the activation of donor T-cells against host antigens. Most common target organs are skin, liver and intestinal mucosis.Methods. In the 6-year period between January 1995 and December 2000, 49 patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT in Transplant unit, Department of Hematology, Clinical Centre Ljubljana. The standard GVHD prophylaxis regimen consisted of cyclosporine and short-course methotrexate. Severe, grade III-IV aGVHD with skin and/or gastrointestinal and/or liver involvement appeared in 16 (32% of the 49 patients.Results. Among the 16 patients with severe aGVHD, 14 had liver involvement, ten gastrointestinal and eight skin involvement. One patient had skin involvement only, the rest of them had combined involvement of two or three organ systems. Routine first-line treatment for aGVHD, given to all 16 pts with severe forms of the disease, was methylprednisolone (MP 2mg/ kg. Six patients with predominant skin involvement responded to MP. Other ten patients with mainly liver and gastrointestinal involvement needed second or even third line aGVHD treatment. These were anti-thymocyte globulin (ATG and/or monoclonal antibodies (OKT3 and/or mycophenolate mofetil (MMF and/or FK506 (tacrolimus. Seven patients died of advanced aGVHD and treatment related infection.Conclusions. Based on our experiences, we conclude that in critically ill patients with severe aGVHD, neutropenia and high risk for opportunistic infection, each day of ineffective MP therapy may have fatal consequences. Simultaneous institution of a combination of corticosteroids and a second-line drug might prove more appropriate for patients with a severe form of aGVHD.

  13. Severity parameters for steam cracking

    NARCIS (Netherlands)

    Golombok, M.; Bijl, J.L.M.; Kornegoor, M.

    2001-01-01

    There are several ways to measure severity in steam cracking which are all a function of residence time, temperature, and pressure. Many measures of severity are not practicable for experimental purposes. Our experimental study shows that methane make is the best measure of severity because it is an

  14. Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections.

    Science.gov (United States)

    DeVoe, P W; Buckley, R H; Shirley, L R; Darby, C P; Ward, F E; Mickey, G H; Raab-Traub, N; Vandenbark, G R

    1985-01-01

    Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.

  15. TREATMENT OF SEVERE AUTOIMMUNE CYTOPENIAS AFTER ALLOGENEIC STEM CELL TRANSPLANTATION – REPORT OF TWO CASES

    Directory of Open Access Journals (Sweden)

    Irena Preložnik Zupan

    2004-12-01

    Full Text Available Background. Autoimmune cytopenias, thrombocytopenia, anemia and neutropenia, are rare but serious complications after stem cell transplantation (SCT. There are only a few reports concerning their treatment. We performed splenectomy in two patients with severe autoimmune cytopenias after allogeneic SCT resistant to immunosuppressive treatment.Patients, methods and results. First patient had unrelated alloSCT at Royal Free Hospital London for chronic granulocytic leukemia (CGL in July 2000. Post-transplant period was complicated with cytomegalovirus reactivation and septicemia. Seven months later RBC and platelet counts went down. Direct Coomb’s test was intermittently positive. She was resistant to steroids and high dose immunoglobulin. Splenectomy was performed in February 2001. After splenectomy hemoglobin concentration and platelet count improved. Her blood counts remained stable with hemoglobin about 110 g/L and platelets over 100 x109/L. She continued therapy with Itraconazol, Valacyclovir and Penicillin. Three months later she was readmitted for E. Coli fulminated septic infection with fatal outcome.Second patient had related alloSCT at University Medical Centre Ljubljana for CGL in January 2003. Post-transplant course was uneventful. Seven months later he was readmitted for retinal bleeding with severe thrombocytopenia with positive anti-platelet antibodies. He was resistant to steroids and high dose immunoglobulin. Splenectomy was performed in September 2003. His platelet count normalized and remains stable so far. He continues therapy with Itraconazol, Valacyclovir and Penicillin and didn’t experience any serious infection.Conclusions. We assume that splenectomy is an efficient treatment for resistant immune cytopenias after alloSCT. However, severe late infections may compromise the outcome.

  16. Gene polymorphisms and febrile neutropenia in acute leukemia--no association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 are associated with the disease in Turkish patients: a preliminary study.

    Science.gov (United States)

    Pehlivan, Mustafa; Sahin, Handan Haydaroğlu; Ozdilli, Kurşat; Onay, Hüseyin; Ozcan, Ali; Ozkinay, Ferda; Pehlivan, Sacide

    2014-07-01

    The aim of this study was to investigate the mannose-binding lectin 2 (MBL-2), interleukin (IL)-4, Toll-like receptor 4 (TLR-4), angiotensin converting enzyme (ACE), chemokine receptor 5 (CCR-5), and IL-1 receptor antagonist (RA) gene polymorphisms (GPs) in acute leukemias (ALs) and to evaluate their roles in febrile neutropenia (FN) resulting from chemotherapy. The study included 60 AL patients hospitalized between the period of July 2001 and August 2006. Polymorphisms for the genes ACE(I/D), CCR-5, IL-1RA, MBL-2, TLR-4, and IL-4 were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymerase. Genotype frequencies for these genes were compared in the patient and control groups. The relationships between the genotypes and the body distribution of infections, pathogens, the duration of neutropenia, and febrile episodes in AL patients were evaluated. No significant differences in either the genotype distribution or the allelic frequencies of TLR-4, IL-4, CCR-5, IL-1RN GPs were observed between patients and healthy controls. The AB/BB genotype (53.3%) in the MBL-2 gene was found to be significantly higher in the AL patients compared with control groups. There were correlations between the presence of MBL-2, TLR-4, and ACE polymorphisms and clinical parameters due to FN. Overall, bacteremia was more common in MBL BB and ACE DD. Gram-positive bacteremia was more common in ACE for ID versus DD genotype. Gram-negative bacteremia was more common for both the MBL-2 AB/BB genotype and TLR-4 AG genotype. Median durations of febrile episodes were significantly shorter in ACE DD and MBL AB/BB. Although TLR-4, ACE, and MBL-2 GPs have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of FN in patients with ALs. As a conclusion, TLR-4, ACE, and MBL-2 genes might play roles in the genetic etiopathogenesis of FN in patients with ALs.

  17. Severe Weather Data Inventory (SWDI)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Severe Weather Data Inventory (SWDI) is an integrated database of severe weather records for the United States. SWDI enables a user to search through a variety...

  18. Severe rosacea: A case report

    Directory of Open Access Journals (Sweden)

    Ebrahim Shirzadeh

    2017-01-01

    Conclusion: Rosacea can be extremely severe and disfiguring, and it can be misdiagnosed as the pathognomonic butterfly rash of LE. Demodex carriage in rosacea is consistent and may play a significant role in the severe forms.

  19. Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.

    Science.gov (United States)

    Huizing, Marjan; Scher, Charles D; Strovel, Erin; Fitzpatrick, Diana L; Hartnell, Lisa M; Anikster, Yair; Gahl, William A

    2002-02-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disease consisting of oculocutaneous albinism and a storage pool deficiency resulting from absent platelet dense bodies. The disorder is genetically heterogeneous. The majority of patients, including members of a large genetic isolate in northwest Puerto Rico, have mutations in HPS1. Another gene, ADTB3A, was shown to cause HPS-2 in two brothers having compound heterozygous mutations that allowed for residual production of the gene product, the beta3A subunit of adaptor complex-3 (AP-3). This heterotetrameric complex serves as a coat protein-mediating formation of intracellular vesicles, e.g. the melanosome and platelet dense body, from membranes of the trans-Golgi network. We determined the genomic organization of the human ADTB3A gene, with intron/exon boundaries, and describe a third patient with beta3A deficiency. This 5-y-old boy has two nonsense mutations, C1578T (R-->X) and G2028T (E-->X), which produce no ADTB3A mRNA and no beta3A protein. The associated mu3 subunit of AP-3 is also entirely absent. In fibroblasts, the cell biologic concomitant of this deficiency is robust and aberrant trafficking through the plasma membrane of LAMP-3, an integral lysosomal membrane protein normally carried directly to the lysosome. The clinical concomitant is a severe, G-CSF-responsive neutropenia in addition to oculocutaneous albinism and platelet storage pool deficiency. Our findings expand the molecular, cellular, and clinical spectrum of HPS-2 and call for an increased index of suspicion for this diagnosis among patients with features of albinism, bleeding, and neutropenia.

  20. Severe acute hepatitis and cold agglutinin-related hemolytic anemia secondary to prime infection with Epstein-Barr virus

    Directory of Open Access Journals (Sweden)

    Guillermo Ontanilla-Clavijo

    Full Text Available Epstein-Barr virus, a member of the Herpesviridae family, is responsible for the infectious mononucleosis clinical syndrome, which mainly includes the pharyngitis, fever, and lymphadenopathy triad after incubation for 30-50 days. The liver is involved in 80-90% of patients in a self-limiting transient manner, with jaundice being much more uncommon (5%. From a hematological standpoint it may manifest aplastic anemia, neutropenia, and thrombocytopenia. We report a case of infectious mononucleosis that included severe acute hepatitis and was associated with severe hemolytic anemia secondary to cold agglutinins. After exclusion of other etiologies, and given the clinical suspicion of the above association, which was later confirmed by lab tests, empiric therapy was initiated with antiviral agents (aciclovir + valganciclovir and corticoids, which resulted in a progressive clinical improvement until complete remission. Therefore, we believe that this case report will reinforce the clinical evidence in support of the above combined therapy for serious infectious mononucleosis as a step prior to liver transplantation.

  1. Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system.

    Science.gov (United States)

    Wen, Tsun-Jen; Wen, Yu-Wen; Chien, Chun-Ru; Chiang, Shao-Chin; Hsu, William Wei-Yuan; Shen, Li-Jiuan; Hsiao, Fei-Yuan

    2017-04-01

    The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system. © 2016 John Wiley & Sons, Ltd.

  2. Chronic obstructive pulmonary disease severity is associated with severe pneumonia

    Directory of Open Access Journals (Sweden)

    Jung Seop Eom

    2015-01-01

    Full Text Available CONTEXT: Chronic obstructive pulmonary disease (COPD is a heterogeneous disorder, and various aspects of COPD may be associated with the severity of pneumonia in such patients. AIMS: We examined the risk factors associated with severe pneumonia in a COPD population. MATERIALS AND METHODS: We performed a retrospective observational study using a prospectively collected database of pneumonia patients who were admitted to our hospital through emergency department between 2008 and 2012. Patients with hospital-acquired pneumonia and those with an immunocompromised status were excluded. RESULTS: Of 148 pneumonia patients with COPD for whom chest computed tomography (CT scans were available, 106 (71.6% and 42 (28.4% were classified as non-severe and severe pneumonia, respectively. Multivariate logistic regression analysis revealed that the severity of airflow limitation [odds ratio (OR, 2.751; 95% confidence interval (CI, 1.074-7.050; P = 0.035] and the presence of emphysema on a chest CT scan (OR, 3.366; 95% CI, 1.104-10.265; P = 0.033 were independently associated with severe pneumonia in patients with COPD. CONCLUSIONS: The severity of COPD including the airflow limitation grade and the presence of pulmonary emphysema were independently associated with the development of severe pneumonia.

  3. Current concepts of severe asthma

    Science.gov (United States)

    Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

    2016-01-01

    The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

  4. Accident management for severe accidents

    International Nuclear Information System (INIS)

    Bari, R.A.; Pratt, W.T.; Lehner, J.; Leonard, M.; Disalvo, R.; Sheron, B.

    1988-01-01

    The management of severe accidents in light water reactors is receiving much attention in several countries. The reduction of risk by measures and/or actions that would affect the behavior of a severe accident is discussed. The research program that is being conducted by the US Nuclear Regulatory Commission focuses on both in-vessel accident management and containment and release accident management. The key issues and approaches taken in this program are summarized. 6 refs

  5. Statistics of severe tornadoes and severe tornado outbreaks

    Directory of Open Access Journals (Sweden)

    B. D. Malamud

    2012-09-01

    Full Text Available The standard measures of the intensity of a tornado in the USA and many other countries are the Fujita and Enhanced Fujita scales. These scales are based on the damage that a tornado causes. Another measure of the strength of a tornado is its path length of touchdown, L. In this study we consider severe tornadoes, which we define as L≥10 km, in the continental USA (USA Storm Prediction Center Severe Weather Database. We find that for the period 1982–2011, for individual severe tornadoes (L≥10 km: (i There is a strong linear scaling between the number of severe tornadoes in a year and their total path length in that year. (ii The cumulative frequency path length data suggests that, not taking into account any changing trends over time, we would expect in a given year (on average one severe tornado with a path length L≥115 km and in a decade (on average one severe tornado with a path length L≥215 km. (iii The noncumulative frequency-length statistics of severe tornado touchdown path lengths, 20<L<200 km, is well approximated by an inverse power-law relationship with exponent near 3. We then take the total path length of severe tornadoes in a convective day (12:00–12:00 UTC, LD, as a measure of the strength of a 24-h USA tornado outbreak. We find that: (i For 1982–2011, the number of severe tornadoes in a USA convective day outbreak has a strong power-law relationship (exponent 0.80 on the convective day total path length, LD. (ii For 1952–2011, the cumulative frequency path length data for severe tornado outbreaks suggests that we would expect in a given year (on average one daily severe tornado outbreak with total path length LD≥480 km and in a decade (on average one daily severe tornado outbreak with a total path length LD≥1200 km. (iii For 1982–2011, the noncumulative frequency-length statistics of tornado

  6. Functional Limitations in Severe Haemophilia

    NARCIS (Netherlands)

    Genderen, F.R. van

    2006-01-01

    This thesis aims to describe the Disablement Process (DP) in Dutch adult patients with severe haemophilia, with specific focus on the domain of “Functional Limitations”. Four main questions underlie this thesis: How can Functional Limitations in severe haemophilia be investigated? Can the

  7. Severe anemia in Malawian children

    NARCIS (Netherlands)

    Calis, Job C. J.; Phiri, Kamija S.; Faragher, E. Brian; Brabin, Bernard J.; Bates, Imelda; Cuevas, Luis E.; de Haan, Rob J.; Phiri, Ajib I.; Malange, Pelani; Khoka, Mirriam; Hulshof, Paul J. M.; van Lieshout, Lisette; Beld, Marcel G. H. M.; teo, Yik Y.; Rockett, Kirk A.; Richardson, Anna; Kwiatkowski, Dominic P.; Molyneux, Malcolm E.; Boele van Hensbroek, Michael

    2008-01-01

    Background Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. Methods We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and

  8. Severe anemia in Malawian children

    NARCIS (Netherlands)

    Calis, Job Cj; Phiri, Kamija S.; Faragher, E. Brian; Brabin, Bernard J.; Bates, Imelda; Cuevas, Luis E.; de Haan, Rob J.; Phiri, Ajib I.; Malange, Pelani; Khoka, Mirriam; Hulshof, Paul Jm; van Lieshout, Lisette; Beld, Marcel Ghm; teo, Yik Y.; Rockett, Kirk A.; Richardson, Anna; Kwiatkowski, Dominic P.; Molyneux, Malcolm E.; van Hensbroek, Michaël Boele

    2016-01-01

    Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool

  9. Severe Anemia in Malawian Children

    NARCIS (Netherlands)

    Calis, J.C.J.; Kamija, S.P.; Faragher, E.B.; Brabin, B.J.; Bates, I.; Cuevas, L.E.; Haan, de R.J.; Phiri, A.I.; Malange, P.; Khoka, M.; Hulshof, P.J.M.; Lieshout, L.; Beld, M.G.H.M.; Teo, Y.Y.; Rockett, K.A.; Richardson, A.; Kwiatkowski, D.P.; Molyneux, M.E.; Hensbroek, van M.B.

    2008-01-01

    Background Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. Methods We conducted a case¿control study of 381 preschool children with severe anemia (hemoglobin concentration,

  10. Severe accident management guidelines tool

    International Nuclear Information System (INIS)

    Gutierrez Varela, Javier; Tanarro Onrubia, Augustin; Martinez Fanegas, Rafael

    2014-01-01

    Severe Accident is addressed by means of a great number of documents such as guidelines, calculation aids and diagnostic trees. The response methodology often requires the use of several documents at the same time while Technical Support Centre members need to assess the appropriate set of equipment within the adequate mitigation strategies. In order to facilitate the response, TECNATOM has developed SAMG TOOL, initially named GGAS TOOL, which is an easy to use computer program that clearly improves and accelerates the severe accident management. The software is designed with powerful features that allow the users to focus on the decision-making process. Consequently, SAMG TOOL significantly improves the severe accident training, ensuring a better response under a real situation. The software is already installed in several Spanish Nuclear Power Plants and trainees claim that the methodology can be followed easier with it, especially because guidelines, calculation aids, equipment information and strategies availability can be accessed immediately (authors)

  11. Parthenium dermatitis severity score to assess clinical severity of disease

    Directory of Open Access Journals (Sweden)

    Kaushal K Verma

    2017-01-01

    Full Text Available Background: Parthenium dermatitis is the most common type of airborne contact dermatitis in India. It is a chronic disease of a remitting and relapsing course with significant morbidity and distress, but there is no scoring system to assess its severity. Aim: To design a scoring system for the assessment of clinical severity of disease in Parthenium dermatitis and to use this scoring system in various studies to determine its sensitivity, specificity, and reproducibility. Methods and Results: In our first few studies on Parthenium dermatitis, we designed and used a basic clinical severity scoring system based on itching, morphology of the lesions, and areas involved. However, in subsequent studies, we modified it to the present scoring system as Parthenium dermatitis severity score (PDSS. Our studies showed the high sensitivity of PDSS in characterization of the disease severity at the given point of time, as well as to determine the efficacy of a prescribed treatment modality which was reliable and reproducible. Conclusion: Thus, PDSS may be used by clinicians for appropriate scoring of the clinical severity of Parthenium dermatitis and in monitoring the disease response to therapy.

  12. Severe acute respiratory syndrome (SARS)

    Science.gov (United States)

    SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

  13. Severe heparin osteoporosis in pregnancy.

    OpenAIRE

    Griffiths, H. T.; Liu, D. T.

    1984-01-01

    A case of severe osteoporosis following administration of low dose subcutaneous heparin in pregnancy is reported. Possible reasons for the condition are suggested which caution against the indiscriminate use of subcutaneous heparin in pregnancy.

  14. Severe accidents in nuclear reactors

    International Nuclear Information System (INIS)

    Ohai, Dumitru; Dumitrescu, Iulia; Tunaru, Mariana

    2004-01-01

    The likelihood of accidents leading to core meltdown in nuclear reactors is low. The consequences of such an event are but so severe that developing and implementing of adequate measures for preventing or diminishing the consequences of such events are of paramount importance. The analysis of major accidents requires sophisticated computation codes but necessary are also relevant experiments for checking the accuracy of the predictions and capability of these codes. In this paper an overview of the severe accidents worldwide with definitions, computation codes and relating experiments is presented. The experimental research activity of severe accidents was conducted in INR Pitesti since 2003, when the Institute jointed the SARNET Excellence Network. The INR activity within SARNET consists in studying scenarios of severe accidents by means of ASTEC and RELAP/SCDAP codes and conducting bench-scale experiments

  15. Severe ASR damaged concrete bridges

    DEFF Research Database (Denmark)

    Antonio Barbosa, Ricardo; Gustenhoff Hansen, Søren

    2015-01-01

    Technical University of Denmark (DTU) and University of Southern Denmark (SDU) have conducted several full-scale experiments with severe ASR deteriorated bridges. This paper presents few and preliminary results from both the shear tests and the measuring of the material properties. The shear test...... show that the shear capacity is almost unaffected of ASR despite significant reduction in compressive concrete strength. Furthermore, measurements show a significant tensile reinforcement strain developed due to ASR expansion....

  16. Severe forms of food allergy.

    Science.gov (United States)

    Sarinho, Emanuel; Lins, Maria das Graças Moura

    To guide the diagnostic and therapeutic management of severe forms of food allergy. Search in the Medline database using the terms "severe food allergy," "anaphylaxis and food allergy," "generalized urticaria and food allergy," and "food protein-induced enterocolitis syndrome" in the last ten years, searching in the title, abstract, or keyword fields. Food allergy can be serious and life-threatening. Milk, eggs, peanuts, nuts, walnuts, wheat, sesame seeds, shrimp, fish, and fruit can precipitate allergic emergencies. The severity of reactions will depend on associated cofactors such as age, drug use at the onset of the reaction, history and persistence of asthma and/or severe allergic rhinitis, history of previous anaphylaxis, exercise, and associated diseases. For generalized urticaria and anaphylaxis, intramuscular epinephrine is the first and fundamental treatment line. For the treatment in acute phase of food-induced enterocolitis syndrome in the emergency setting, prompt hydroelectrolytic replacement, administration of methylprednisolone and ondansetron IV are necessary. It is important to recommend to the patient with food allergy to maintain the exclusion diet, seek specialized follow-up and, in those who have anaphylaxis, to emphasize the need to carry epinephrine. Severe food allergy may occur in the form of anaphylaxis and food-protein-induced enterocolitis syndrome, which are increasingly observed in the pediatric emergency room; hence, pediatricians must be alert so they can provide the immediate diagnosis and treatment. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  17. Cernavoda CANDU severe accident evaluation

    International Nuclear Information System (INIS)

    Negut, G.; Marin, A.

    1997-01-01

    The papers present the activities dedicated to Romania Cernavoda Nuclear Power Plant first CANDU Unit severe accident evaluation. This activity is part of more general PSA assessment activities. CANDU specific safety features are calandria moderator and calandria vault water capabilities to remove the residual heat in the case of severe accidents, when the conventional heat sinks are no more available. Severe accidents evaluation, that is a deterministic thermal hydraulic analysis, assesses the accidents progression and gives the milestones when important events take place. This kind of assessment is important to evaluate to recovery time for the reactor operators that can lead to the accident mitigation. The Cernavoda CANDU unit is modeled for the of all heat sinks accident and results compared with the AECL CANDU 600 assessment. (orig.)

  18. Severe anemia in Malawian children.

    Science.gov (United States)

    Calis, Job Cj; Phiri, Kamija S; Faragher, E Brian; Brabin, Bernard J; Bates, Imelda; Cuevas, Luis E; de Haan, Rob J; Phiri, Ajib I; Malange, Pelani; Khoka, Mirriam; Hulshof, Paul Jm; van Lieshout, Lisette; Beld, Marcel Ghm; Teo, Yik Y; Rockett, Kirk A; Richardson, Anna; Kwiatkowski, Dominic P; Molyneux, Malcolm E; van Hensbroek, Michaël Boele

    2016-09-01

    Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling. Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD -202/-376 genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B 12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age. There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.

  19. The treatment of severe malaria.

    Science.gov (United States)

    Dondorp, Arjen M; Day, Nick P J

    2007-07-01

    In the SEAQUAMAT trial, parenteral artesunate was shown to be associated with a considerably lower mortality than quinine, and is now the recommended treatment for severe malaria in low-transmission areas and in the second and third trimesters of pregnancy. A trial is underway to establish its role in African children. The development of artesunate suppositories may provide the means to treat patients with severe disease in remote rural settings, potentially buying the time needed to reach a health care facility. The increasing availability of basic intensive care facilities in developing countries also has the potential to further reduce mortality.

  20. Surgical Management of Severe Epistaxis.

    Science.gov (United States)

    Lin, Giant; Bleier, Benjamin

    2016-06-01

    Many patients with severe epistaxis benefit from endoscopic intervention for control of bleeding. Critical maneuvers to improve endoscopic visualization during surgery include head-of-bed elevation, application of topical vasoconstrictors, and local injection of vasonstrictors. Controlled, hypotensive anesthesia may also decrease intraoperative blood loss and improve visualization during surgery. Intractable posterior epistaxis can be controlled with high rates of success with endoscopic sphenopalatine artery ligation. Although less common, intractable anterior epistaxis may be controlled by anterior ethmoid artery ligation once this artery is identified as the primary source. Less common sources of severe epistaxis are also discussed in this article. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Restoration of severely weathered wood

    Science.gov (United States)

    R. Sam. Williams; Mark. Knaebe

    2000-01-01

    Severely weathered window units were used to test various restoration methods and pretreatments. Sanded and unsanded units were pretreated with a consolidant or water repellent preservative, finished with an oil- or latex-based paint system, and exposed outdoors near Madison, WI, for five years. Pretreatments were applied to both window sashes (stiles and rails) and...

  2. Newborn with severe epidermolysis bullosa

    DEFF Research Database (Denmark)

    Boesen, Martin Lehmann; Bygum, Anette; Hertz, Jens Michael

    2016-01-01

    of EB depends on the subtype, and therefore maximum treatment is necessary until the final diagnosis is known. In this case, it took 2 weeks before a final diagnosis was reached. In the meantime, we had several ethical discussions on the treatment level. The most important issues were management of pain...

  3. Severe forms of food allergy

    Directory of Open Access Journals (Sweden)

    Emanuel Sarinho

    2017-11-01

    Conclusion: Severe food allergy may occur in the form of anaphylaxis and food‐protein‐induced enterocolitis syndrome, which are increasingly observed in the pediatric emergency room; hence, pediatricians must be alert so they can provide the immediate diagnosis and treatment.

  4. Containment severe accident thermohydraulic phenomena

    International Nuclear Information System (INIS)

    Frid, W.

    1991-08-01

    This report describes and discusses the containment accident progression and the important severe accident containment thermohydraulic phenomena. The overall objective of the report is to provide a rather detailed presentation of the present status of phenomenological knowledge, including an account of relevant experimental investigations and to discuss, to some extent, the modelling approach used in the MAAP 3.0 computer code. The MAAP code has been used in Sweden as the main tool in the analysis of severe accidents. The dependence of the containment accident progression and containment phenomena on the initial conditions, which in turn are heavily dependent on the in-vessel accident progression and phenomena as well as associated uncertainties, is emphasized. The report is in three parts dealing with: * Swedish reactor containments, the severe accident mitigation programme in Sweden and containment accident progression in Swedish PWRs and BWRs as predicted by the MAAP 3.0 code. * Key non-energetic ex-vessel phenomena (melt fragmentation in water, melt quenching and coolability, core-concrete interaction and high temperature in containment). * Early containment threats due to energetic events (hydrogen combustion, high pressure melt ejection and direct containment heating, and ex-vessel steam explosions). The report concludes that our understanding of the containment severe accident progression and phenomena has improved very significantly over the parts ten years and, thereby, our ability to assess containment threats, to quantify uncertainties, and to interpret the results of experiments and computer code calculations have also increased. (au)

  5. Dyslexia and Severe Reading Disability.

    Science.gov (United States)

    Ngandu, Kathleen M.

    This handbook contains advice for the teacher in diagnosing dyslexia and developing an individualized program for overcoming severe reading problems. Observable characteristics of dyslexia are listed as an aid to the teacher's diagnosis, but it is emphasized that cooperation between the teacher and a reading specialist is of great importance in…

  6. Stuttering Severity and Educational Attainment

    Science.gov (United States)

    O'Brian, Sue; Jones, Mark; Packman, Ann; Menzies, Ross; Onslow, Mark

    2011-01-01

    Purpose: This study investigated the relationship between self-reported stuttering severity ratings and educational attainment. Method: Participants were 147 adults seeking treatment for stuttering. At pretreatment assessment, each participant reported the highest educational level they had attained and rated their typical and worst stuttering…

  7. Polyradiculopathy secondary to severe hypertriglyceridemia.

    Science.gov (United States)

    Nesbitt, Cassie; Wong, Daniel; Batchelor, Peter

    2015-05-08

    A 74-year-old man presented with a subacute severe thoracic polyradiculopathy affecting the T4-T8 dermatomes bilaterally. Extensive investigation demonstrated markedly raised triglyceride levels of 44 mmol/L (<1.7). The patient's unique presentation is discussed alongside a review of triglyceride-induced neurotoxicity and therapeutic management. 2015 BMJ Publishing Group Ltd.

  8. Bioimpedance in Severely Malnourished Children

    DEFF Research Database (Denmark)

    Girma Nigatu, Tsinuel

    Worldwide severe acute malnutrition (SAM) affects millions of children and considerably contributes to under-five mortality, mainly in low-income settings. Among children with SAM, deaths occur largely in those with oedema and during early phase of treatment often aggravated by infection. Treatment...

  9. Severe combined immune deficiency syndrome

    International Nuclear Information System (INIS)

    Saleem, A.F.; Khawaja, R.D.A.; Shaikh, A.S.; Ali, S.A.; Zaidi, A.K.M.

    2013-01-01

    To determine the clinico-demographic features and laboratory parameters of children with severe combined immunodeficiency (SCID). Study Design: Case series. Place and Duration of Study: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, from July 2006 to July 2011. Methodology: Thirteen infants who were discharged with a diagnosis of SCID were inducted in the study. Their clinicodemographic features and laboratory parameters were determined. Descriptive statistics has been used for computing frequency and percentage. Results: The median age at diagnosis was five months; 5 infants presented within 3 months of life. Three-fourth (77%) were males. Most of the infants were severely malnourished (85%) at the time of presentation. More than two-thirds (69%) were products of consanguineous marriages. All subjects had severe lymphopenia (absolute lymphocyte count (ALC) ranging between 170 – 2280) and low T and B lymphocyte counts. Conclusion: SCID should be considered in infants presenting with severe and recurrent infections. Low ALC (< 2500/mm3), is a reliable diagnostic feature of SCID. These infants should be promptly referred to a facility where stem cell transplant can be done. (author)

  10. Predicting severity of paranoid schizophrenia

    OpenAIRE

    Kolesnichenko Elena Vladimirovna

    2015-01-01

    Clinical symptoms, course and outcomes of paranoid schizophrenia are polymorphic. 206 cases of paranoid schizophrenia were investigated. Clinical predictors were collected from hospital records and interviews. Quantitative assessment of the severity of schizophrenia as special indexes was used. Schizoid, epileptoid, psychasthenic and conformal accentuation of personality in the premorbid, early onset of psychosis, paranoid and hallucinatory-paranoid variants of onset predicted more expressed ...

  11. Severe Malnutrition: A Global Approach.

    Science.gov (United States)

    Pelletier, Jean-Gerard

    1993-01-01

    This report examines the immediate and underlying causes of malnutrition in the developing world. The first section discusses the effects of malnutrition on childhood development and examines the efficacy of nutritional rehabilitation. The second section addresses the medical effects of severe malnutrition, including the onset of ponderostatural…

  12. Nuclear and cell division in Bacillus subtilis. Antibiotic-induced morphological changes

    NARCIS (Netherlands)

    van Iterson, W.; Aten, J. A.

    1976-01-01

    Incubation of Bacillus subtilis after outgrowth from spores in the presence of four different antibiotics in two different concentrations, showed that septation can occur without termination of nuclear division. Septation is then only partially uncoupled from the normal division cycle. Observations

  13. Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study.

    Science.gov (United States)

    Lankelma, Jacqueline M; Cranendonk, Duncan R; Belzer, Clara; de Vos, Alex F; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

    2017-09-01

    The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens. As such, the use of antibiotics may attribute to immunosuppression as seen in sepsis. We aimed to test whether disruption of the gut microbiota affects systemic innate immune responses during endotoxemia in healthy subjects. In this proof-of-principle intervention trial, 16 healthy young men received either no treatment or broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days, after which all were administered lipopolysaccharide intravenously to induce a transient sepsis-like syndrome. At various time points, blood and faeces were sampled. Gut microbiota diversity was significantly lowered by the antibiotic treatment in all subjects. Clinical parameters, neutrophil influx, cytokine production, coagulation activation and endothelial activation during endotoxemia were not different between antibiotic-pretreated and control individuals. Antibiotic treatment had no impact on blood leucocyte responsiveness to various Toll-like receptor ligands and clinically relevant causative agents of sepsis ( Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli ) during endotoxemia. These findings suggest that gut microbiota disruption by broad-spectrum antibiotics does not affect systemic innate immune responses in healthy subjects during endotoxemia in humans, disproving our hypothesis. Further research is needed to test this hypothesis in critically ill patients. These data underline the importance of translating findings in mice to humans. ClinicalTrials.gov (NCT02127749; Pre-results). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Single-cell tracking reveals antibiotic-induced changes in mycobacterial energy metabolism.

    Science.gov (United States)

    Maglica, Željka; Özdemir, Emre; McKinney, John D

    2015-02-17

    ATP is a key molecule of cell physiology, but despite its importance, there are currently no methods for monitoring single-cell ATP fluctuations in live bacteria. This is a major obstacle in studies of bacterial energy metabolism, because there is a growing awareness that bacteria respond to stressors such as antibiotics in a highly individualistic manner. Here, we present a method for long-term single-cell tracking of ATP levels in Mycobacterium smegmatis based on a combination of microfluidics, time-lapse microscopy, and Förster resonance energy transfer (FRET)-based ATP biosensors. Upon treating cells with antibiotics, we observed that individual cells undergo an abrupt and irreversible switch from high to low intracellular ATP levels. The kinetics and extent of ATP switching clearly discriminate between an inhibitor of ATP synthesis and other classes of antibiotics. Cells that resume growth after 24 h of antibiotic treatment maintain high ATP levels throughout the exposure period. In contrast, antibiotic-treated cells that switch from ATP-high to ATP-low states never resume growth after antibiotic washout. Surprisingly, only a subset of these nongrowing ATP-low cells stains with propidium iodide (PI), a widely used live/dead cell marker. These experiments also reveal a cryptic subset of cells that do not resume growth after antibiotic washout despite remaining ATP high and PI negative. We conclude that ATP tracking is a more dynamic, sensitive, reliable, and discriminating marker of cell viability than staining with PI. This method could be used in studies to evaluate antimicrobial effectiveness and mechanism of action, as well as for high-throughput screening. New antimicrobials are urgently needed to stem the rising tide of antibiotic-resistant bacteria. All antibiotics are expected to affect bacterial energy metabolism, directly or indirectly, yet tools to assess the impact of antibiotics on the ATP content of individual bacterial cells are lacking. The method described here for single-cell tracking of intracellular ATP in live bacteria has many advantages compared to conventional ensemble-averaged assays. It provides a continuous real-time readout of bacterial ATP content, cell vitality, and antimicrobial mechanism of action with high temporal resolution at the single-cell level. In combination with high-throughput microfluidic devices and automated microscopy, this method also has the potential to serve as a novel screening tool in antimicrobial drug discovery. Copyright © 2015 Maglica et al.

  15. 2H NMR evidence for antibiotic-induced cholesterol immobilization in biological model membranes

    International Nuclear Information System (INIS)

    Dufourc, E.J.; Smith, I.C.

    1985-01-01

    The interaction of the polyene antibiotic filipin with membrane sterols has been studied by deuterium nuclear magnetic resonance of the molecular probes [2,2,3,4,4,6- 2 H6]cholesterol and 1-myristoyl-2-[4',4',14',14',14'- 2 H5]myristoyl-sn-glycero-3-phospho- choline. At physiological temperatures, there is evidence of filipin-induced cholesterol immobilization in the membrane. The 2 H NMR spectra of cholesterol show two domains in which ordering and dynamics are very different. In one of these, cholesterol is static on the 2 H NMR time scale, whereas in the other it undergoes rapid axially symmetric motions similar to those it exhibits in the drug-free membrane; this indicates that the jumping frequency of cholesterol between the labile and immobilized domains is less than 10(5) s -1 . The distribution of cholesterol between these two sites is temperature dependent. In contrast to cholesterol, the phospholipids sense only one type of environment, at both the top and center of the bilayer, indicating that cholesterol acts as a screen, preventing the lipids from direct interaction with the antibiotic. At low temperature, the ordering of the lipid in the presence of cholesterol does not change upon filipin addition, whereas at elevated temperatures the local ordering of both the lipid and the labile cholesterol is significantly lower than that in the absence of the drug

  16. Variation in antibiotic-induced microbial recolonization impacts on the host metabolic phenotypes of rats.

    Science.gov (United States)

    Swann, Jonathan R; Tuohy, Kieran M; Lindfors, Peter; Brown, Duncan T; Gibson, Glenn R; Wilson, Ian D; Sidaway, James; Nicholson, Jeremy K; Holmes, Elaine

    2011-08-05

    The interaction between the gut microbiota and their mammalian host is known to have far-reaching consequences with respect to metabolism and health. We investigated the effects of eight days of oral antibiotic exposure (penicillin and streptomycin sulfate) on gut microbial composition and host metabolic phenotype in male Han-Wistar rats (n = 6) compared to matched controls. Early recolonization was assessed in a third group exposed to antibiotics for four days followed by four days recovery (n = 6). Fluorescence in situ hybridization analysis of the intestinal contents collected at eight days showed a significant reduction in all bacterial groups measured (control, 10(10.7) cells/g feces; antibiotic-treated, 10(8.4)). Bacterial suppression reduced the excretion of mammalian-microbial urinary cometabolites including hippurate, phenylpropionic acid, phenylacetylglycine and indoxyl-sulfate whereas taurine, glycine, citrate, 2-oxoglutarate, and fumarate excretion was elevated. While total bacterial counts remained notably lower in the recolonized animals (10(9.1) cells/g faeces) compared to the controls, two cage-dependent subgroups emerged with Lactobacillus/Enterococcus probe counts dominant in one subgroup. This dichotomous profile manifested in the metabolic phenotypes with subgroup differences in tricarboxylic acid cycle metabolites and indoxyl-sulfate excretion. Fecal short chain fatty acids were diminished in all treated animals. Antibiotic treatment induced a profound effect on the microbiome structure, which was reflected in the metabotype. Moreover, the recolonization process was sensitive to the microenvironment, which may impact on understanding downstream consequences of antibiotic consumption in human populations.

  17. Combined treatment of UVA irradiation and antibiotics induces greater bactericidal effects on Vibrio parahaemolyticus.

    Science.gov (United States)

    Hou, Yanfei; Nakahashi, Mutsumi; Mawatari, Kazuaki; Shimohata, Takaaki; Uebanso, Takashi; Harada, Yumi; Tsunedomi, Akari; Emoto, Takahiro; Akutagawa, Masatake; Kinouchi, Yohsuke; Takahashi, Akira

    2016-01-01

    The presence of antibiotics in the environment and their subsequent impact on the development of multi-antibiotic resistant bacteria has raised concerns globally. Consequently, much research is focused on a method to produce a better disinfectant. We have established a disinfectant system using UVA-LED that inactivates pathogenic bacteria. We assessed the bactericidal efficiency of a combination of UVA-LED and antibiotics against Vibrio parahaemolyticus. Combined use of antibiotic drugs and UVA irradiation was more bactericidal than UVA irradiation or antibacterial drugs alone. The bactericidal synergy was observed at low concentrations of each drug that are normally unable to kill the bacteria. This combination has the potential to become a sterilization technology.

  18. Combined treatment of UVA irradiation and antibiotics induces greater bactericidal effects on Vibrio parahaemolyticus

    OpenAIRE

    Hou, Yanfei; Nakahashi, Mutsumi; Mawatari, Kazuaki; Shimohata, Takaaki; Uebanso, Takashi; Harada, Yumi; Tsunedomi, Akari; Emoto, Takahiro; Akutagawa, Masatake; Kinouchi, Yohsuke; Takahashi, Akira

    2016-01-01

    The presence of antibiotics in the environment and their subsequent impact on the development of multi-antibiotic resistant bacteria has raised concerns globally. Consequently, much research is focused on a method to produce a better disinfectant. We have established a disinfectant system using UVA-LED that inactivates pathogenic bacteria. We assessed the bactericidal efficiency of a combination of UVA-LED and antibiotics against Vibrio parahaemolyticus. Combined use of antibiotic drugs and U...

  19. Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function

    DEFF Research Database (Denmark)

    Yang, Jason H.; Bhargava, Prerna; McCloskey, Douglas

    2017-01-01

    Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect eithe...

  20. Severe forms of food allergy

    Directory of Open Access Journals (Sweden)

    Emanuel Sarinho

    Full Text Available Abstract Objectives: To guide the diagnostic and therapeutic management of severe forms of food allergy. Data sources: Search in the Medline database using the terms “severe food allergy,” “anaphylaxis and food allergy,” “generalized urticaria and food allergy,” and “food protein-induced enterocolitis syndrome” in the last ten years, searching in the title, abstract, or keyword fields. Summary of data: Food allergy can be serious and life-threatening. Milk, eggs, peanuts, nuts, walnuts, wheat, sesame seeds, shrimp, fish, and fruit can precipitate allergic emergencies. The severity of reactions will depend on associated cofactors such as age, drug use at the onset of the reaction, history and persistence of asthma and/or severe allergic rhinitis, history of previous anaphylaxis, exercise, and associated diseases. For generalized urticaria and anaphylaxis, intramuscular epinephrine is the first and fundamental treatment line. For the treatment in acute phase of food-induced enterocolitis syndrome in the emergency setting, prompt hydroelectrolytic replacement, administration of methylprednisolone and ondansetron IV are necessary. It is important to recommend to the patient with food allergy to maintain the exclusion diet, seek specialized follow-up and, in those who have anaphylaxis, to emphasize the need to carry epinephrine. Conclusion: Severe food allergy may occur in the form of anaphylaxis and food-protein-induced enterocolitis syndrome, which are increasingly observed in the pediatric emergency room; hence, pediatricians must be alert so they can provide the immediate diagnosis and treatment.

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

    Directory of Open Access Journals (Sweden)

    Jorge A. Cortés

    2013-03-01

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

  2. Neutropenia restores virulence to an attenuated Cu,Zn superoxide dismutase-deficient Haemophilus ducreyi strain in the swine model of chancroid.

    Science.gov (United States)

    San Mateo, L R; Toffer, K L; Orndorff, P E; Kawula, T H

    1999-10-01

    Haemophilus ducreyi causes chancroid, a sexually transmitted cutaneous genital ulcer disease associated with increased heterosexual transmission of human immunodeficiency virus. H. ducreyi expresses a periplasmic copper-zinc superoxide dismutase (Cu, Zn SOD) that protects the bacterium from killing by exogenous superoxide in vitro. We hypothesized that the Cu,Zn SOD would protect H. ducreyi from immune cell killing, enhance survival, and affect ulcer development in vivo. In order to test this hypothesis and study the role of the Cu,Zn SOD in H. ducreyi pathogenesis, we compared a Cu,Zn SOD-deficient H. ducreyi strain to its isogenic wild-type parent with respect to survival and ulcer development in immunocompetent and immunosuppressed pigs. The Cu,Zn SOD-deficient strain was recovered from significantly fewer inoculated sites and in significantly lower numbers than the wild-type parent strain or a merodiploid (sodC+ sodC) strain after infection of immunocompetent pigs. In contrast, survival of the wild-type and Cu,Zn SOD-deficient strains was not significantly different in pigs that were rendered neutropenic by treatment with cyclophosphamide. Ulcer severity in pigs was not significantly different between sites inoculated with wild type and sites inoculated with Cu,Zn SOD-deficient H. ducreyi. Our data suggest that the periplasmic Cu,Zn SOD is an important virulence determinant in H. ducreyi, protecting the bacterium from host immune cell killing and contributing to survival and persistence in the host.

  3. Large errors and severe conditions

    CERN Document Server

    Smith, D L; Van Wormer, L A

    2002-01-01

    Physical parameters that can assume real-number values over a continuous range are generally represented by inherently positive random variables. However, if the uncertainties in these parameters are significant (large errors), conventional means of representing and manipulating the associated variables can lead to erroneous results. Instead, all analyses involving them must be conducted in a probabilistic framework. Several issues must be considered: First, non-linear functional relations between primary and derived variables may lead to significant 'error amplification' (severe conditions). Second, the commonly used normal (Gaussian) probability distribution must be replaced by a more appropriate function that avoids the occurrence of negative sampling results. Third, both primary random variables and those derived through well-defined functions must be dealt with entirely in terms of their probability distributions. Parameter 'values' and 'errors' should be interpreted as specific moments of these probabil...

  4. Severe acute malnutrition and infection

    Science.gov (United States)

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  5. A CANDU Severe Accident Analysis

    International Nuclear Information System (INIS)

    Negut, Gheorghe; Catana, Alexandru; Prisecaru, Ilie

    2006-01-01

    As interest in severe accident studies has increased in the last years, we have developed a set of simple models to analyze severe accidents for CANDU reactors that should be integrated in the EU codes. The CANDU600 reactor uses natural uranium fuel and heavy water (D2O) as both moderator and coolant, with the moderator and coolant in separate systems. We chose to analyze accident development for a LOCA with simultaneous loss of moderator cooling and the loss of emergency core cooling system (ECCS). This type of accident is likely to modify the reactor geometry and will lead to a severe accident development. When the coolant temperatures inside a pressure tube reaches 10000 deg C, a contact between pressure tube and calandria tube occurs and the residual heat is transferred to the moderator. Due to the lack of cooling, the moderator eventually begins to boil and is expelled, through the calandria vessel relief ducts, into the containment. Therefore the calandria tubes (fuel channels) will be uncovered, then will disintegrate and fall down to the calandria vessel bottom. After all the quantity of moderator is vaporized and expelled, the debris will heat up and eventually boil. The heat accumulated in the molten debris will be transferred through the calandria vessel wall to the shield tank water, which normally surrounds the calandria vessel. The phenomena described above are modelled, analyzed and compared with the existing data. The results are encouraging. (authors)

  6. Gender differences in addiction severity.

    Science.gov (United States)

    Díaz-Mesa, Eva M; García-Portilla, Paz; Fernández-Artamendi, Sergio; Sáiz, Pilar A; Bobes Bascarán, Teresa; Casares, María José; Fonseca, Eduardo; Al-Halabí, Susana; Bobes, Julio

    2016-06-14

    Gender has been associated with substance use disorders (SUD). However, there are few studies that have evaluated gender differences in a global and a standardized way, and with a large sample of patients with SUD. Our goal is to analyze the role of gender in addiction severity throughout multiple life domains, using the Addiction Severity Index-6 (ASI-6). A naturalistic, multicenter and prospective study was conducted. A total of 221 patients with SUD (80.1% men) were interviewed with the ASI-6. Our results indicate that the Recent Summary Scores (RSSs) of men and women are similar, with the exception of Psychiatric and Partner- Problems, where women showed higher severity (p = .017 and p = .013, respectively). Statistically significant gender differences were found in certain aspects of the ASI-6 domains: men have more problems of physical health, legal issues, and alcohol and other substance use; and woman score higher in problems of mental health, social network, subjective evaluations of SUD consequences, and treatment needs. These results should be taken into account to improve the identification, prevention, and treatment of SUD.

  7. CANDU safety under severe accidents

    International Nuclear Information System (INIS)

    Snell, V.G.; Howieson, J.Q.; Alikhan, S.; Frescura, G.M.; King, F.; Rogers, J.T.; Tamm, H.

    1996-01-01

    The characteristics of the CANDU reactor relevant to severe accidents are set first by the inherent properties of the design, and second by the Canadian safety/licensing approach. The pressure-tube concept allows the separate, low-pressure, heavy-water moderator to act as a backup heat sink even if there is no water in the fuel channels. Should this also fail, the calandria shell itself can contain the debris, with heat being transferred to the water-filled shield tank around the core. Should the severe core damage sequence progress further, the shield tank and the concrete reactor vault significantly delay the challenge to containment. Furthermore, should core melt lead to containment overpressure, the containment behaviour is such that leaks through the concrete containment wall reduce the possibility of catastrophic structural failure. The Canadian licensing philosophy requires that each accident, together with failure of each safety system in turn, be assessed (and specified dose limits met) as part of the design and licensing basis. In response, designers have provided CANDUs with two independent dedicated shutdown systems, and the likelihood of Anticipated Transients Without Scram is negligible. Probabilistic safety assessment studies have been performed on operating CANDU plants, and on the 4 x 880 MW(e) Darlington station now under construction; furthermore a scoping risk assessment has been done for a CANDU 600 plant. They indicate that the summed severe core damage frequency is of the order of 5 x 10 -6 /year. 95 refs, 3 tabs

  8. CANDU safety under severe accidents

    Energy Technology Data Exchange (ETDEWEB)

    Snell, V G; Howieson, J Q [Atomic Energy of Canada Ltd. (Canada); Alikhan, S [New Brunswick Electric Power Commission (Canada); Frescura, G M; King, F [Ontario Hydro (Canada); Rogers, J T [Carleton Univ., Ottawa, ON (Canada); Tamm, H [Atomic Energy of Canada Ltd. (Canada). Whiteshell Research Lab.

    1996-12-01

    The characteristics of the CANDU reactor relevant to severe accidents are set first by the inherent properties of the design, and second by the Canadian safety/licensing approach. The pressure-tube concept allows the separate, low-pressure, heavy-water moderator to act as a backup heat sink even if there is no water in the fuel channels. Should this also fail, the calandria shell itself can contain the debris, with heat being transferred to the water-filled shield tank around the core. Should the severe core damage sequence progress further, the shield tank and the concrete reactor vault significantly delay the challenge to containment. Furthermore, should core melt lead to containment overpressure, the containment behaviour is such that leaks through the concrete containment wall reduce the possibility of catastrophic structural failure. The Canadian licensing philosophy requires that each accident, together with failure of each safety system in turn, be assessed (and specified dose limits met) as part of the design and licensing basis. In response, designers have provided CANDUs with two independent dedicated shutdown systems, and the likelihood of Anticipated Transients Without Scram is negligible. Probabilistic safety assessment studies have been performed on operating CANDU plants, and on the 4 x 880 MW(e) Darlington station now under construction; furthermore a scoping risk assessment has been done for a CANDU 600 plant. They indicate that the summed severe core damage frequency is of the order of 5 x 10{sup -6}/year. 95 refs, 3 tabs.

  9. Treatment of severe acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Praznik Ivan

    2014-01-01

    Full Text Available Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or other organ systems. The severe form of the disease occurs in 10-20% of cases, and usually requires prolonged hospitalization due to a frequent local and systemic complications. Additionally, considerable mortality despite diagnostic and therapeutic advances, makes this disease a serious health problem nowadays. The aim of this study was to conduct a review of randomized controlled trials to determine differences in the efficiency between standard methods of treatment for severe acute pancreatitis and new treatment ways in terms of decreased mortality. Search of the 'Medline' database of original scientific papers and systematic review articles was made, using a combination of the following keywords: acute pancreatitis, treatment, mortality. In total 914 papers were found, published in the last 13 years; 14 of 64 randomized controlled clinical trials met the selection criteria and were eligible for inclusion. From a total of 16 papers, the conservative treatment was related to 11, which includes some of the new treatment methods, while the effects of new methods of treatment have been the subject of research in the four studies. Combined endoscopic and surgical treatment was applied in only one study. The largest sample of 290 patients was included in the study with platelet activation factor antagonist, while the smallest sample of 22 patients was used in the study that compared total parenteral with enteral nutrition. Continuous regional arterial infusion of protease inhibitors in combination with antibiotics, intravenous supplementation of alanyl-glutamine dipeptide and the early, high-volume continuous veno-venous hemofiltration showed the best results in the treatment of patients with severe acute pancreatitis. Also, the use of low molecular weight heparin and enteral nutrition significantly reduced mortality.

  10. Severe accident source term reassessment

    International Nuclear Information System (INIS)

    Hazzan, M.J.; Gardner, R.; Warman, E.A.; Jacobs, S.B.

    1987-01-01

    This paper summarizes the status of the reassessment of severe reactor accident source terms, which are defined as the quantity, type, and timing of fission product releases from such accidents. Concentration is on the major results and conclusions of analyses with modern methods for both pressurized water reactors (PWRs) and boiling water reactors (BWRs), and the special case of containment bypass. Some distinctions are drawn between analyses for PWRs and BWRs. In general, the more the matter is examined, the consequences, or probability of serious consequences, seem to be less. (author)

  11. Nuclear reactor with several cores

    International Nuclear Information System (INIS)

    Swars, H.

    1977-01-01

    Several sodium-cooled cores in separate vessels with removable closures are placed in a common reactor tank. Each individual vessel is protected against the consequences of an accident in the relevant core. Maintenance devices and inlet and outlet pipes for the coolant are also arranged within the reactor tank. The individual vessels are all enclosed by coolant in a way that in case of emergency cooling or refuelling each core can be continued to be cooled by means of the coolant loops of the other cores. (HP) [de

  12. Severe hyponatremia associated with escitalopram

    Directory of Open Access Journals (Sweden)

    Gautam Rawal

    2017-01-01

    Full Text Available Hyponatremia is a rare but potentially fatal complication of selective serotonin reuptake inhibitor (SSRI therapy with only limited cases of escitalopram as the causative drug. We report the case of a 54-year-old hypertensive female who was admitted to the hospital with seizure episode and subsequently diagnosed to have severe hyponatremia due to SSRI-induced syndrome of inappropriate antidiuretic hormone (SIADH with the cause attributed to the short history of intake of escitalopram for depression. All SSRIs, including escitalopram, can cause SIADH and should be used with caution in the depressive patients with regular monitoring of electrolytes, especially in the elderly.

  13. [Severe candidiasis in heroin addicts].

    Science.gov (United States)

    Badillet, G; Puissant, A; Colliard, H

    1984-01-01

    Seven cases of severe candida infection in heroin addicts are reported. The principal features of this condition which arose in 1980, apparently due to a particular quality of heroin, are described, Candida albicans was the only pathogenic agent isolated from mainly scalp nodular and pustular lesions. These cutaneous lesions were associated in half the cases with ocular lesions, which sometimes had a poor prognosis despite active therapy. Osteo-articular complications were less common. Ketoconazole therapy alone gave good results in this series. The precise reasons for this dissemination of Candida albicans and for these localisations are still not clearly understood.

  14. Towards a Flood Severity Index

    Science.gov (United States)

    Kettner, A.; Chong, A.; Prades, L.; Brakenridge, G. R.; Muir, S.; Amparore, A.; Slayback, D. A.; Poungprom, R.

    2017-12-01

    Flooding is the most common natural hazard worldwide, affecting 21 million people every year. In the immediate moments following a flood event, humanitarian actors like the World Food Program need to make rapid decisions ( 72 hrs) on how to prioritize affected areas impacted by such an event. For other natural disasters like hurricanes/cyclones and earthquakes, there are industry-recognized standards on how the impacted areas are to be classified. Shake maps, quantifying peak ground motion, from for example the US Geological Survey are widely used for assessing earthquakes. Similarly, cyclones are tracked by Joint Typhoon Warning Center (JTWC) and Global Disaster Alert and Coordination System (GDACS) who release storm nodes and tracks (forecasted and actual), with wind buffers and classify the event according to the Saffir-Simpson Hurricane Wind Scale. For floods, the community is usually able to acquire unclassified data of the flood extent as identified from satellite imagery. Most often no water discharge hydrograph is available to classify the event into recurrence intervals simply because there is no gauging station, or the gauging station was unable to record the maximum discharge due to overtopping or flood damage. So, the question remains: How do we methodically turn a flooded area into classified areas of different gradations of impact? Here, we present a first approach towards developing a global applicable flood severity index. The flood severity index is set up such that it considers relatively easily obtainable physical parameters in a short period of time like: flood frequency (relating the current flood to historical events) and magnitude, as well as land cover, slope, and where available pre-event simulated flood depth. The scale includes categories ranging from very minor flooding to catastrophic flooding. We test and evaluate the postulated classification scheme against a set of past flood events. Once a severity category is determined, socio

  15. The severity of an earthquake

    Science.gov (United States)

    ,

    1997-01-01

    The severity of an earthquake can be expressed in terms of both intensity and magnitude. However, the two terms are quite different, and they are often confused. Intensity is based on the observed effects of ground shaking on people, buildings, and natural features. It varies from place to place within the disturbed region depending on the location of the observer with respect to the earthquake epicenter. Magnitude is related to the amount of seismic energy released at the hypocenter of the earthquake. It is based on the amplitude of the earthquake waves recorded on instruments

  16. Pneumothorax in severe thoracic traumas

    International Nuclear Information System (INIS)

    Camassa, N.W.; Boccuzzi, F.; Diettorre, E.; Troilo, A.

    1988-01-01

    The authors reviewed CT scans and supine chest X-ray of 47 patients affected by severe thoracic trauma, examined in 1985-86. The sensibility of the two methodologies in the assessment of pneumothorax was compared. CT detected 25 pneumothorax, whereas supine chest X-ray allowed a diagnosis in 18 cases only. In 8 of the latter (44.4%) the diagnosis was made possible by the presence of indirect signs of pneumothorax only - the most frequent being the deep sulcus sign. The characterization of pneumothorax is important especially in the patients who need to be treated with mechanical ventilation therapy, or who are to undergo surgery in total anaesthesia

  17. CANDU safety under severe accidents

    International Nuclear Information System (INIS)

    Snell, V.G.; Howieson, J.Q.; Frescura, G.M.; King, F.; Rogers, J.T.; Tamm, H.

    1988-01-01

    The characteristics of the CANDU reactor relevant to severe accidents are set first by the inherent properties of the design, and second by the Canadian safety/licensing approach. Probabilistic safety assessment studies have been performed on operating CANDU plants, and on the 4 x 880 MW(e) Darlington station now under construction; furthermore a scoping risk assessment has been done for a CANDU 600 plant. They indicate that the summed severe core damage frequency is of the order of 5 x 10 -6 /year. CANDU nuclear plant designers and owner/operators share information and operational experience nationally and internationally through the CANDU Owners' Group (COG). The research program generally emphasizes the unique aspects of the CANDU concept, such as heat removal through the moderator, but it has also contributed significantly to areas generic to most power reactors such as hydrogen combustion, containment failure modes, fission product chemistry, and high temperature fuel behaviour. Abnormal plant operating procedures are aimed at first using event-specific emergency operating procedures, in cases where the event can be diagnosed. If this is not possible, generic procedures are followed to control Critical Safety Parameters and manage the accident. Similarly, the on-site contingency plans include a generic plan covering overall plant response strategy, and a specific plan covering each category of contingency

  18. [Management of severe alcoholic hepatitis].

    Science.gov (United States)

    Wieser, Verena; Tilg, Herbert

    2014-01-01

    Severe alcoholic hepatitis is still associated with high mortality and presence of liver failure manifested by jaundice, coagulopathy and encephalopathy is a poor prognostic indicator. The management of these patients includes at first hand several supportive measures as treatment of alcohol withdrawal, administration of fluid and vitamins and admission to an intensive care unit in the unstable patient. Glucocorticoids have been since decades the most intensively studied therapy in alcoholic hepatitis and are effective in certain subgroups. Indication for such a therapy is usually defined on a Maddrey Discriminant Function > 32. The Lille score at day 7 is used to decide whether corticosteroid therapy should be stopped or continued for a 1 month course. Nutritional supplementation is also likely to be beneficial. The main progress in better understanding its pathophysiology has come from cytokine studies. Various proinflammatory cytokines such as tumor necrosis factor-alpha (TNFα) or interleukin-1 (IL-1) have been proposed to play a role in this disease. This advancement has recently led to pilot studies investigating anti-TNF drugs such as pentoxifylline, infliximab (anti-TNF antibody) or etanercept in the treatment of this disease. These studies revealed besides for pentoxifylline rather negative results. Despite this fact, targeting of certain cytokines such as IL-1 remains an attractive treatment concept for this devastating disorder in the future.

  19. Mechanical ventilation for severe asthma.

    Science.gov (United States)

    Leatherman, James

    2015-06-01

    Acute exacerbations of asthma can lead to respiratory failure requiring ventilatory assistance. Noninvasive ventilation may prevent the need for endotracheal intubation in selected patients. For patients who are intubated and undergo mechanical ventilation, a strategy that prioritizes avoidance of ventilator-related complications over correction of hypercapnia was first proposed 30 years ago and has become the preferred approach. Excessive pulmonary hyperinflation is a major cause of hypotension and barotrauma. An appreciation of the key determinants of hyperinflation is essential to rational ventilator management. Standard therapy for patients with asthma undergoing mechanical ventilation consists of inhaled bronchodilators, corticosteroids, and drugs used to facilitate controlled hypoventilation. Nonconventional interventions such as heliox, general anesthesia, bronchoscopy, and extracorporeal life support have also been advocated for patients with fulminant asthma but are rarely necessary. Immediate mortality for patients who are mechanically ventilated for acute severe asthma is very low and is often associated with out-of-hospital cardiorespiratory arrest before intubation. However, patients who have been intubated for severe asthma are at increased risk for death from subsequent exacerbations and must be managed accordingly in the outpatient setting.

  20. The management of severe accidents

    International Nuclear Information System (INIS)

    Pelce, J.; Brignon, P.

    1987-01-01

    In considering severe accidents in water power reactors, a major problem that arises is how to manage them in such a way that the situation can be controlled as well as possible, from the aspects both of preventing serious damage to the core of limiting the discharge of radioactivity. A number of countries have announced provisions in the field of accident management, some already set up, others planned, but these mainly apply to preventing damage to the core. Part of this report deals with this aspect, to show that there is a fairly wide consensus on how problems should be approached. Attitudes vary, on the other hand, in the approach to mitigate radioactive release. In fact, few countries have proposed concrete steps to manage severe accidents in the final stages when the core is seriously damaged. Since it is difficult to compare different approaches, only the French approach is described. This description is however very brief, because in the five or six years since it was defined, the approach has been presented many times. The stress is placed more on the comments which this type of approach suggests, to make the subsequent general discussion easier

  1. Common paths to ASD severity and PTSD severity

    DEFF Research Database (Denmark)

    Hansen, Maj; Armour, Cherie; Wittmann, Lutz

    Numerous studies have identified risk factors for acute and long term posttraumatic symptoms following traumatic exposure. However, little is known about possible common pathways to the development of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD). Research suggests that a c......Numerous studies have identified risk factors for acute and long term posttraumatic symptoms following traumatic exposure. However, little is known about possible common pathways to the development of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD). Research suggests...... that a common pathway to ASD and PTSD may lie in peritraumatic responses and cognitions. Using structural equation modeling we examined the role of three peritraumatic factors (tonic immobility, panic and dissociation) and three cognitive factors (anxiety sensitivity, negative cognitions about the world......, and negative cognitions about self ) on the development of ASD and PTSD severity in a national study of Danish bank robbery victims (N = 450). Peritraumatic panic, anxiety sensitivity, and negative cognitions about self were found to be significant common risk factors, whereas peritraumatic dissociation...

  2. Convective behaviour in severe accidents

    International Nuclear Information System (INIS)

    Clement, C.F.

    1988-01-01

    The nature and magnitude of the hazard from radioactivity posed by a possible nuclear accident depend strongly on convective behaviour within and immediately adjacent to the plant in question. This behaviour depends upon the nature of the vapour-gas-aerosol mixture concerned, and can show unusual properties such as 'upside-down' convection in which hot mixtures fall and cold mixtures rise. Predictions and criteria as to the types of behaviour which could possibly occur are summarised. Possible applications to present reactors are considered, and ways in which presently expected convection could be drastically modified are described. In some circumstances these could be used to suppress the radioactive source term or to switch its effect between distant dilute contamination and severe local contamination. (author). 8 refs, 2 figs, 2 tabs

  3. Severe accident recriticality analyses (SARA)

    DEFF Research Database (Denmark)

    Frid, W.; Højerup, C.F.; Lindholm, I.

    2001-01-01

    with all three codes. The core initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality-both super-prompt power bursts and quasi steady-state power......Recriticality in a BWR during reflooding of an overheated partly degraded core, i.e. with relocated control rods, has been studied for a total loss of electric power accident scenario. In order to assess the impact of recriticality on reactor safety, including accident management strategies......, which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal g(-1), was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding rate of 2000 kg s(-1). In most cases, however, the predicted energy deposition was smaller, below...

  4. Severe accident simulation at Olkiuoto

    Energy Technology Data Exchange (ETDEWEB)

    Tirkkonen, H.; Saarenpaeae, T. [Teollisuuden Voima Oy (TVO), Olkiluoto (Finland); Cliff Po, L.C. [Micro-Simulation Technology, Montville, NJ (United States)

    1995-09-01

    A personal computer-based simulator was developed for the Olkiluoto nuclear plant in Finland for training in severe accident management. The generic software PCTRAN was expanded to model the plant-specific features of the ABB Atom designed BWR including its containment over-pressure protection and filtered vent systems. Scenarios including core heat-up, hydrogen generation, core melt and vessel penetration were developed in this work. Radiation leakage paths and dose rate distribution are presented graphically for operator use in diagnosis and mitigation of accidents. Operating on an graphically for operator use in diagnosis and mitigation of accidents. Operating on an 486 DX2-66, PCTRAN-TVO achieves a speed about 15 times faster than real-time. A convenient and user-friendly graphic interface allows full interactive control. In this paper a review of the component models and verification runs are presented.

  5. Severe Urticaria Following Erythromycin Therapy

    Directory of Open Access Journals (Sweden)

    Anada S. Prasad

    1960-01-01

    Full Text Available Enythromycin is believed to cause no serlous reactions after large doses, nausea, rarely vomiting and occasionally abdominal pain and diarrhea may occur, (Herrell, 1954. According to' Kagan and Faller (1955 no allergic reaction to' erythromycin has been reported. Phlebitis and thrombosis have been observed, (Shoe maker & Yow, 1954. In a report by Solomon and Johnson, (1955 toxic reactions were recorded as being uncommon. In a large series of cases, only one patient had a rash, another had fever possibly due to the drug, nne had nausea and vomiting and 4 had loose bowel movements while under therapy. Among the 122 patients treated with erythromcin, therapy was stopped owing to side effects in only one. My patient had severe urticaria within 24 hours of beginning therapy with erythromycin and a positive skin test was observed. It was believed to be an allergic reaction caused by the drug.

  6. [Tracheobronchoplasty for Severe Diffuse Tracheomalacia].

    Science.gov (United States)

    Hoffmann, H; Gompelmann, D; Heußel, C P; Dienemann, H; Eberhardt, R

    2016-09-01

    Patients with diffuse airway instability due to tracheobronchomalacia or excessive dynamic airway collapse are typically highly symptomatic, with marked dyspnoea, recurrent bronchopulmonary infections and excruciating intractable cough. Silicone stents achieve immediate symptom control, but are - due to the typical complications associated with stent treatment - usually not an option for long-term treatment. The aim of surgical intervention is definitive stabilisation of the trachea and of both main bronchi by posterior splinting of the Paries membranaceus with a polypropylene mesh. This operation is an appropriate treatment option for patients with documented severe tracheobronchomalacia or excessive dynamic airway collapse and is ultimately the only therapy that can achieve permanent symptom control. The success of the operation, however, depends on many factors and requires close interdisciplinary collaboration. Georg Thieme Verlag KG Stuttgart · New York.

  7. Severe rhabdomyolysis after excessive bodybuilding.

    Science.gov (United States)

    Finsterer, J; Zuntner, G; Fuchs, M; Weinberger, A

    2007-12-01

    A 46-year-old male subject performed excessive physical exertion during 4-6 h in a studio for body builders during 5 days. He was not practicing sport prior to this training and denied the use of any aiding substances. Despite muscle aching already after 1 day, he continued the exercises. After the last day, he recognized tiredness and cessation of urine production. Two days after discontinuation of the training, a Herpes simplex infection occurred. Because of acute renal failure, he required hemodialysis. There were absent tendon reflexes and creatine kinase (CK) values up to 208 274 U/L (normal: <170 U/L). After 2 weeks, CK had almost normalized and, after 4 weeks, hemodialysis was discontinued. Excessive muscle training may result in severe, hemodialysis-dependent rhabdomyolysis. Triggering factors may be prior low fitness level, viral infection, or subclinical metabolic myopathy.

  8. Diarrhea in severely burned children.

    Science.gov (United States)

    Thakkar, Kalpesh; Kien, C Lawrence; Rosenblatt, Judah I; Herndon, David N

    2005-01-01

    Diarrhea is a common problem in critically ill patients. Our patients are fed a high-carbohydrate enteral formula. We hypothesized that diarrhea in our patients may be related to the osmotic effects of unabsorbed carbohydrate in the small intestine and colon. We studied 19 patients, 3 months to 17 years, with burns >40% total body surface area. Each subject was studied weekly for up to 4 weeks postburn. Breath H2 concentration was measured. For the 24-hour period before the breath H2 measurement, the enteral carbohydrate intake, stool volume, and total enteral fluid volume were recorded. At each of several weekly intervals for each subject, the times when stool volume and enteral carbohydrate intake were each maximal were noted. Maximal stool volume ranged from 12 to 69 mL/kg/d. At the time point of maximal carbohydrate intake, diarrhea (stool volume >10 mL/kg/d) occurred in 18 of 19 patients, and maximal stool volume occurred in 10 of 19. Breath H2 concentration (ppm/5% CO2; mean +/- SEM) was 5.5 +/- 3.5 at the time of maximal carbohydrate intake, and was 25 +/- 20 at maximal stool volume. There were no correlations among breath H2 concentration, stool volume, enteral fluid intake, and enteral carbohydrate intake. Almost all the subjects had diarrhea over several weeks postburn. The lack of correlation of either carbohydrate intake or breath H2 with stool volume suggests that diarrhea in these patients may be caused by factors other than carbohydrate malabsorption. These data do not support altering nutrition support because of watery diarrhea.

  9. Therapeutic interventions in severe asthma.

    Science.gov (United States)

    Canonica, Giorgio Walter; Senna, Gianenrico; Mitchell, Patrick D; O'Byrne, Paul M; Passalacqua, Giovanni; Varricchi, Gilda

    2016-01-01

    The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospitalizations and Emergency Department accesses as well as expensive treatments. The recent identification of different endotypes of asthma, based on the inflammatory pattern, has led to the development of tailored treatments that target different inflammatory mediators. These are major achievements in the perspective of Precision Medicine: a leading approach to the modern treatment strategy. Omalizumab, an anti-IgE antibody, has been the only biologic treatment available on the market for severe asthma during the last decade. It prevents the linkage of the IgE and the receptors, thereby inhibiting mast cell degranulation. In clinical practice omalizumab significantly reduced the asthma exacerbations as well as the concomitant use of oral glucocorticoids. In the "Th2-high asthma" phenotype, the hallmarks are increased levels of eosinophils and other markers (such as periostin). Because anti-IL-5 in this condition plays a crucial role in driving eosinophil inflammation, this cytokine or its receptors on the eosinophil surface has been studied as a potential target for therapy. Two different anti-IL-5 humanized monoclonal antibodies, mepolizumab and reslizumab, have been proven effective in this phenotype of asthma (recently they both came on the market in the United States), as well as an anti-IL-5 receptor alpha (IL5Rα), benralizumab. Other monoclonal antibodies, targeting different cytokines (IL-13, IL-4, IL-17 and TSLP) are still under evaluation, though the preliminary results are encouraging. Finally, AIT, Allergen Immunotherapy, a prototype of Precision Medicine, is considered, also in light of the recent evidences of Sublingual Immunotherapy (SLIT) tablet efficacy and safety in mite allergic asthma patients. Given the high costs of these therapies

  10. Colposacrosuspension for severe genital prolapse.

    Science.gov (United States)

    Cronjé, H S

    2004-04-01

    A descriptive study of 140 patients with severe genital prolapse managed by colposacrosuspension with mesh interposition and a modified Burch colposuspension. A laparotomy was performed with mobilization of the rectum and exploration of the rectovaginal septum. Vaginally, a longitudinal incision was made in the posterior vaginal wall which was completely separated from the rectum. A perineal repair was done, whereafter a strip of Vypro (Johnson & Johnson, Brussels, Belgium) mesh was inserted from the perineum to the sacrum at S1. It was fixated to the perineum and vagina while the rectum was elevated and attached to the mesh. Where a perineal repair was deemed not necessary, the mesh extended from the mid-vagina to the sacrum. A second mesh strip was placed anteriorly of the vagina, covering the upper third of the vagina and extending to the sacrum. After closure of the pelvic peritoneum, covering the mesh, a modified Burch colposuspension was performed. Follow-up was done at 6 weeks, 6 months and yearly thereafter. The median age was 61 years with a median parity of 3. All patients presented with grade 2 (extending to the vaginal introitus) or 3 (outside the vaginal introitus) prolapse. Approximately one-third had urinary incontinence and a similar proportion complained of difficulty in defecation. All the patients underwent colposacrosuspension with the mesh extending to the perineum in 67% of the patients. A Burch colposuspension was performed in 79% of the women. Postoperatively, 97% of the patients were followed for 1-29 months with a median of 8.5 months (mean 10.2 months). Recurrent prolapse, grade 2 or 3, developed in 11 patients (8%) and 17 patients (12%) developed urinary incontinence, needing a transvaginal tape procedure. Removal of the mesh was necessary in one patient (0.7%). Colposacrosuspension for severe genital prolapse delivered satisfactory short-term results. It is, however, a major surgical procedure and elderly or compromised patients may

  11. Severe accident research in France

    International Nuclear Information System (INIS)

    Duco, J.; Reocreux, M.; Tattegrain, A.

    1988-01-01

    French PWR power plant design relies basically on a deterministic approach. Nevertheless, an overall safety objective was issued in 1977 by the safety authority which set an upper probability limit for having unacceptable consequences; this resulted, in particular, in the elaboration of the ''H'' procedures, aimed at reducing significantly the risk of core uncovery subsequent to the loss of redunbant safety-related systems. The U1 symptom-oriented procedure, based on the nuclear steam supply system ''cooling states'', was introduced later, in order to prevent core melting in situations where the operating crew was confused by multiple failures and/or inappropriate previous actions. In the event that a core-melt should occur, the ultimate procedures U2, U4 and U5 - the latter providing a venting of the containment through a filtration system - should enable the radioactive releases to be limited to characteristics compatible with the feasibility of the off-site emergency plans. Such emergency management procedures necessitate a significant study effort in order to be elaborated and qualified; this also presupposes that an adequate level of scientific knowledge has been gained as regards the response of specific components of a PWR under beyond-design conditions. The purpose of severe accident research in France is to attain a level of basic knowledge such that emergency procedures may be conceived and ultimately tested

  12. Pregnancy-associated severe sepsis.

    Science.gov (United States)

    Oud, Lavi

    2016-04-01

    This article examines the contemporary knowledge and uncertainties about the burden of pregnancy-associated severe sepsis (PASS), and its manifestations, management, and outcomes. There are relatively sparse data on PASS, related in part to infrequent reports and varying use of terminology and case definitions. PASS remains rare, although its incidence appears to be rapidly rising in some high-resource countries, affecting especially women with limited resources, minorities, and those with chronic illness. High level of clinician vigilance and rapid initiation of appropriate antimicrobial therapy, coupled with effective systemic support for organ dysfunction and correction of occult and overt hypoperfusion are the keys to limit adverse outcomes. However, timely diagnosis and provision of effective care remain a challenge, with reported prevalent delay in recognition and delivery of time-sensitive care interventions among maternal decedents. The mortality rate of PASS has been rising and its case fatality, although relatively low, has remained unchanged, in contrast to the outcome gains in the general population. The long-term sequelae of PASS remain unknown. The relatively limited contemporary data on PASS suggest a rising public health hazard in the obstetric population in high-resource countries, with ongoing challenges in assuring consistent provision of time-sensitive care.

  13. Severe Anaemia during Late Pregnancy

    Directory of Open Access Journals (Sweden)

    Mahenaz Akhtar

    2012-01-01

    Full Text Available Vitamin B12 deficiency is uncommon in pregnancy, it occurs in 10–28% of uncomplicated pregnancies, and is associated with a few complications. We present a case report of a 21-year-old patient with severe anaemia during late pregnancy caused by vitamin B12 deficiency. At 38 weeks gestation and with a BMI of 48.9, a history of rupture of membranes was given but not confirmed. On examination, she appeared pale and therefore full blood counts were done. Interestingly her haemoglobin (Hb levels were 3.7 g/dL. Folate and vitamin B12 levels were also found to be low, and the diagnosis of anaemia caused by vitamin B12 deficiency was made. After treatment with vitamin B12 injections, folic acid and blood transfusions, the patient’s haemoglobin levels improved from 3.7 g/dL to 10.7 g/dL. The conclusion is that effective history taking, diagnosis, and management can prevent many complications that are usually associated with vitamin B12 deficiency anaemia.

  14. Antibodies to Actin in Autoimmune Neutropenia

    Science.gov (United States)

    1990-02-01

    S) 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Dept of Hematology (If applicable) Div of Medicine ...ceph- standard deviations above the mean value for 20 normal serum alosporins, phenothiazines, antithyroid drugs, antiarrythmic controls reflecting

  15. Iodine behaviour in severe accidents

    Energy Technology Data Exchange (ETDEWEB)

    Dutton, L M.C.; Grindon, E; Handy, B J; Sutherland, L [NNC Ltd., Knutsford (United Kingdom); Bruns, W G; Sims, H E [AEA Technology, Harwell (United Kingdom); Dickinson, S [AEA Technology, Winfrith (United Kingdom); Hueber, C; Jacquemain, D [IPSN/CEA, Cadarache, Saint Paul-Lez-Durance (France)

    1996-12-01

    A description is given of analyses which identify which aspects of the modelling and data are most important in evaluating the release of radioactive iodine to the environment following a potential severe accident at a PWR and which identify the major uncertainties which affect that release. Three iodine codes are used namely INSPECT, IODE and IMPAIR, and their predictions are compared with those of the PSA code MAAP. INSPECT is a mechanistic code which models iodine behaviour in the aqueous aerosol, spray water and sump water, and the partitioning of volatile species between the aqueous phases and containment gas space. Organic iodine is not modelled. IODE and IMPAIR are semi-empirical codes which do not model iodine behaviour in the aqueous aerosol, but model organic iodine. The fault sequences addressed are based on analyses for the Sizewell `B` design. Two types of sequence have been analysed.: (a) those in which a major release of fission products from the primary circuit to the containment occur, e.g. a large LOCAS, (b) those where the release by-passes the containment, e.g. a leak into the auxiliary building. In the analysis of the LOCA sequences where the pH of the sump is controlled to be a value of 8 or greater, all three codes predict that the oxidation of iodine to produce gas phase species does not make a significant contribution to the source term due to leakage from the reactor building and that the latter is dominated by iodide in the aerosol. In the case where the pH of the sump is not controlled, it is found that the proportion of gas phase iodine increases significantly, although the cumulative leakage predicted by all three codes is not significantly different from that predicted by MAAP. The radiolytic production of nitric acid could be a major factor in determining the pH, and if the pH were reduced, the codes predict an increase in gas phase iodine species leaked from the containment. (author) 4 figs., 7 tabs., 13 refs.

  16. Severe Accident Recriticality Analyses (SARA)

    Energy Technology Data Exchange (ETDEWEB)

    Frid, W. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden); Hoejerup, F. [Risoe National Lab. (Denmark); Lindholm, I.; Miettinen, J.; Puska, E.K. [VTT Energy, Helsinki (Finland); Nilsson, Lars [Studsvik Eco and Safety AB, Nykoeping (Sweden); Sjoevall, H. [Teoliisuuden Voima Oy (Finland)

    1999-11-01

    Recriticality in a BWR has been studied for a total loss of electric power accident scenario. In a BWR, the B{sub 4}C control rods would melt and relocate from the core before the fuel during core uncovery and heat-up. If electric power returns during this time-window unborated water from ECCS systems will start to reflood the partly control rod free core. Recriticality might take place for which the only mitigating mechanisms are the Doppler effect and void formation. In order to assess the impact of recriticality on reactor safety, including accident management measures, the following issues have been investigated in the SARA project: 1. the energy deposition in the fuel during super-prompt power burst, 2. the quasi steady-state reactor power following the initial power burst and 3. containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core state initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality - both superprompt power bursts and quasi steady-state power generation - for the studied range of parameters, i. e. with core uncovery and heat-up to maximum core temperatures around 1800 K and water flow rates of 45 kg/s to 2000 kg/s injected into the downcomer. Since the recriticality takes place in a small fraction of the core the power densities are high which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal/g, was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding

  17. Severe accident recriticality analyses (SARA)

    Energy Technology Data Exchange (ETDEWEB)

    Frid, W. E-mail: wiktor.frid@ski.se; Hoejerup, F.; Lindholm, I.; Miettinen, J.; Nilsson, L.; Puska, E.K.; Sjoevall, H

    2001-11-01

    Recriticality in a BWR during reflooding of an overheated partly degraded core, i.e. with relocated control rods, has been studied for a total loss of electric power accident scenario. In order to assess the impact of recriticality on reactor safety, including accident management strategies, the following issues have been investigated in the SARA project: (1) the energy deposition in the fuel during super-prompt power burst; (2) the quasi steady-state reactor power following the initial power burst; and (3) containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality--both super-prompt power bursts and quasi steady-state power generation--for the range of parameters studied, i.e. with core uncovering and heat-up to maximum core temperatures of approximately 1800 K, and water flow rates of 45-2000 kg s{sup -1} injected into the downcomer. Since recriticality takes place in a small fraction of the core, the power densities are high, which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal g{sup -1}, was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding rate of 2000 kg s{sup -1}. In most cases, however, the predicted energy deposition was smaller, below the regulatory limits for fuel failure, but close to or above recently observed thresholds for fragmentation and dispersion of high burn-up fuel. The highest calculated

  18. Severe accident recriticality analyses (SARA)

    International Nuclear Information System (INIS)

    Frid, W.; Hoejerup, F.; Lindholm, I.; Miettinen, J.; Nilsson, L.; Puska, E.K.; Sjoevall, H.

    2001-01-01

    Recriticality in a BWR during reflooding of an overheated partly degraded core, i.e. with relocated control rods, has been studied for a total loss of electric power accident scenario. In order to assess the impact of recriticality on reactor safety, including accident management strategies, the following issues have been investigated in the SARA project: (1) the energy deposition in the fuel during super-prompt power burst; (2) the quasi steady-state reactor power following the initial power burst; and (3) containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality--both super-prompt power bursts and quasi steady-state power generation--for the range of parameters studied, i.e. with core uncovering and heat-up to maximum core temperatures of approximately 1800 K, and water flow rates of 45-2000 kg s -1 injected into the downcomer. Since recriticality takes place in a small fraction of the core, the power densities are high, which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal g -1 , was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding rate of 2000 kg s -1 . In most cases, however, the predicted energy deposition was smaller, below the regulatory limits for fuel failure, but close to or above recently observed thresholds for fragmentation and dispersion of high burn-up fuel. The highest calculated quasi steady

  19. Severe Accident Recriticality Analyses (SARA)

    International Nuclear Information System (INIS)

    Frid, W.; Hoejerup, F.; Lindholm, I.; Miettinen, J.; Puska, E.K.; Nilsson, Lars; Sjoevall, H.

    1999-11-01

    Recriticality in a BWR has been studied for a total loss of electric power accident scenario. In a BWR, the B 4 C control rods would melt and relocate from the core before the fuel during core uncovery and heat-up. If electric power returns during this time-window unborated water from ECCS systems will start to reflood the partly control rod free core. Recriticality might take place for which the only mitigating mechanisms are the Doppler effect and void formation. In order to assess the impact of recriticality on reactor safety, including accident management measures, the following issues have been investigated in the SARA project: 1. the energy deposition in the fuel during super-prompt power burst, 2. the quasi steady-state reactor power following the initial power burst and 3. containment response to elevated quasi steady-state reactor power. The approach was to use three computer codes and to further develop and adapt them for the task. The codes were SIMULATE-3K, APROS and RECRIT. Recriticality analyses were carried out for a number of selected reflooding transients for the Oskarshamn 3 plant in Sweden with SIMULATE-3K and for the Olkiluoto 1 plant in Finland with all three codes. The core state initial and boundary conditions prior to recriticality have been studied with the severe accident codes SCDAP/RELAP5, MELCOR and MAAP4. The results of the analyses show that all three codes predict recriticality - both superprompt power bursts and quasi steady-state power generation - for the studied range of parameters, i. e. with core uncovery and heat-up to maximum core temperatures around 1800 K and water flow rates of 45 kg/s to 2000 kg/s injected into the downcomer. Since the recriticality takes place in a small fraction of the core the power densities are high which results in large energy deposition in the fuel during power burst in some accident scenarios. The highest value, 418 cal/g, was obtained with SIMULATE-3K for an Oskarshamn 3 case with reflooding

  20. Evaluación del desenlace y características clínicas de una serie de niños con neutropenia febril sin foco en el Hospital Universitario San Vicente de Paúl, Medellín, Colombia, 2000-2005

    Directory of Open Access Journals (Sweden)

    María Adelaida Aristizábal Gil

    2008-11-01

    Full Text Available Introducción: la neutropenia febril (NF se asocia a infección en 48-60% de los casos y es la segunda causa de ingreso hospitalario al servicio de oncología pediátrica. El objetivo del estudio fue evaluar el desenlace de una serie de niños, que recibían tratamiento para neutropenia febril sin foco aparente, según un protocolo preestablecido en el Servicio de Hematooncología infantil del Hospital Universitario San Vicente de Paúl. MATERIALES Y MÉTODOS: se incluyeron retrospectivamente historias clínicas de pacientes menores de 15 años con diagnóstico nuevo de neoplasia maligna y neutropenia febril sin foco, hospitalizados en un lapso de 5 años. Los datos se registraron en un formato preestablecido. RESULTADOS: se incluyeron 103 historias clínicas con 182 episodios de NF; 34,1% fueron pacientes con leucemia linfoblástica riesgo estándar (LLA, 19,8% LLA de alto riesgo y 13,7%, linfoma no Hodking. 68,1% tuvieron NF grave y en 94,5% se había aplicado quimioterapia previa (79,7% intensiva. La infección se documentó clínicamente en 38,4% y microbiológicamente en 25,2% de los episodios; hubo bacteriemia en 15,4% de los episodios, 3,3% con urocultivo positivo y 6,5% con aislamiento del invasor en otros sitios. Los microorganismos más frecuentes fueron Escherichia coli (24% y Pseudomonas aeruginosa (13%. Hubo mayor resistencia a ceftriazona y cefatzidime tanto de gérmenes grampositivos como de gramnegativos y producción de betalactamasas en 9% durante un año de evaluación; 50% de los aislamientos de S. aureus coagulasa negativo fueron resistentes a oxacilina. En 37 episodios hubo complicaciones (20,2%, la más frecuente de las cuales fue la afectación cardiopulmonar; en 25,2% fracasó el tratamiento, en 21,4% hubo respuesta parcial y 7 pacientes (3,8% fallecieron. CONCLUSIONES: los hallazgos son similares a los reportados por otros autores; predominan en nuestra unidad los microorganismos gramnegativos como causa importante de

  1. Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial.

    Science.gov (United States)

    Cambau, Emmanuelle; Durand-Zaleski, Isabelle; Bretagne, Stéphane; Brun-Buisson, Christian; Cordonnier, Catherine; Duval, Xavier; Herwegh, Stéphanie; Pottecher, Julien; Courcol, René; Bastuji-Garin, Sylvie

    2017-11-01

    Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE). Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler ® SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE). A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients. Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.

  2. [Results of immunosupressive therapy in children with severe aplastic anaemia. Report of the Polish Paediatric Haematology Group].

    Science.gov (United States)

    Pawelec, Katarzyna; Matysiak, Michał; Niewiadomska, Edyta; Rokicka-Milewska, Roma; Kowalczyk, Jerzy; Stefaniak, Jolanta; Balwierz, Walentyna; Załecka-Czerpko, Ewa; Chybicka, Alicja; Szmyd, Krzysztof; Sońta-Jakimczyk, Danuta; Bubała, Halina; Krauze, Agnieszka; Wysocki, Mariusz; Kurylak, Andrzej; Wachowiak, Jacek; Grund, Grzegorz; Młynarski, Wojciech; Bulas, Monika; Krawczuk-Rybak, Maryna; Leszczyńska, Elzbieta; Urasiński, Tomasz; Peregud-Pogorzelski, Jarosław; Balcerska, Anna; Włazłowski, Marek

    2008-01-01

    Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When there is no donor available, combined immunosuppressive therapy is given. evaluation of results of immunosupressive therapy in children with severe aplastic anaemia. SAA was diagnosed in 105 children (42 girls, 73 boys), aged 2-18 years, in the eleven haematological centres in Poland, between 1993-2007. All patients received the Severe Aplastic Anaemia Working Party of the EBMT protocol which included: antilymphocyte globulin or antithymocyte globulin, cyclosporin A, prednisolone. Granulocyto- or granulocytomacrophagic-cell stimulation factor was additionally administered during deep neutropenia. Haematological response was evaluated on day 84 or 112 and 180 of the therapy. complete remission occurred in 53 patients (51.5%), partial remission in 27 (24.7%), no response was obtained in 25 children (23.8%) on day 180, of the therapy. Period of observation was from 12 months to 12.5 years. During this time relapse occurred in 10 patients (9.5%). We observed 22 deaths: 8 early, during the first 3 months of IS and 14 after the first 3 months of immunosuppresive therapy (IS). At present 70 children (66.6%) are in first remission with lasts from 12 months to 12.5 years. The survival at 12.5-years is 78.6%. During the 12.5 years of follow-up we had two cases with a late clonal complication (PNH and MDS). Transformation to acute nonlymphoblastic leukaemia was observed in two of our patients. 1. Immunosuppresive therapy (IS) in children with SAA, without bone marrow family donors, is more effective after introduction of combined IS (12.5 years survival in this study was 80% for children with very severe aplastic anaemia (v SAA). 2. In our studies among the children followed up after IS therapy, there were: 1 case of periodic nocturnal haemoglobinuria (PNH), 1 case of myelodysplastic syndrome (MDS) and 2 cases of myeloid leukaemia

  3. Targeted treatment of severe head injury

    African Journals Online (AJOL)

    injury is not a homogeneous concept and is poorly classified for the purposes of treatment.1 The separation of patients into 3 categories of severity (mild, moderate and severe) remains a blunt measure used to guide therapy in individual patients. Patients with severe traumatic brain injury (TBI), i.e. a Glasgow Coma Score ...

  4. Computed tomography in severe protein energy malnutrition.

    OpenAIRE

    Househam, K C; de Villiers, J F

    1987-01-01

    Computed tomography of the brain was performed on eight children aged 1 to 4 years with severe protein energy malnutrition. Clinical features typical of kwashiorkor were present in all the children studied. Severe cerebral atrophy or brain shrinkage according to standard radiological criteria was present in every case. The findings of this study suggest considerable cerebral insult associated with severe protein energy malnutrition.

  5. Asthma Is More Severe in Older Adults

    Science.gov (United States)

    Dweik, Raed A.; Comhair, Suzy A.; Bleecker, Eugene R.; Moore, Wendy C.; Peters, Stephen P.; Busse, William W.; Jarjour, Nizar N.; Calhoun, William J.; Castro, Mario; Chung, K. Fan; Fitzpatrick, Anne; Israel, Elliot; Teague, W. Gerald; Wenzel, Sally E.; Love, Thomas E.; Gaston, Benjamin M.

    2015-01-01

    Background Severe asthma occurs more often in older adult patients. We hypothesized that the greater risk for severe asthma in older individuals is due to aging, and is independent of asthma duration. Methods This is a cross-sectional study of prospectively collected data from adult participants (N=1130; 454 with severe asthma) enrolled from 2002 – 2011 in the Severe Asthma Research Program. Results The association between age and the probability of severe asthma, which was performed by applying a Locally Weighted Scatterplot Smoother, revealed an inflection point at age 45 for risk of severe asthma. The probability of severe asthma increased with each year of life until 45 years and thereafter increased at a much slower rate. Asthma duration also increased the probability of severe asthma but had less effect than aging. After adjustment for most comorbidities of aging and for asthma duration using logistic regression, asthmatics older than 45 maintained the greater probability of severe asthma [OR: 2.73 (95 CI: 1.96; 3.81)]. After 45, the age-related risk of severe asthma continued to increase in men, but not in women. Conclusions Overall, the impact of age and asthma duration on risk for asthma severity in men and women is greatest over times of 18-45 years of age; age has a greater effect than asthma duration on risk of severe asthma. PMID:26200463

  6. Surviving severe traumatic brain injury in Denmark

    DEFF Research Database (Denmark)

    Odgaard, Lene; Poulsen, Ingrid; Kammersgaard, Lars Peter

    2015-01-01

    PURPOSE: To identify all hospitalized patients surviving severe traumatic brain injury (TBI) in Denmark and to compare these patients to TBI patients admitted to highly specialized rehabilitation (HS-rehabilitation). PATIENTS AND METHODS: Patients surviving severe TBI were identified from...... severe TBI were admitted to HS-rehabilitation. Female sex, older age, and non-working status pre-injury were independent predictors of no HS-rehabilitation among patients surviving severe TBI. CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI was stable in Denmark...

  7. SEVERITY CLASSIFICATION OF MICROANEURYSMS USING NEURAL NETWORK

    Directory of Open Access Journals (Sweden)

    Shree Divya R

    2014-01-01

    Full Text Available Diabetic Retinopathy is one of the most common causes of blindness that leads to the loss of vision to the human eye. Several methods have been proposed to detect several defects of the human eye like hemorrhages, exudates etc. which are to be considered as the major symptoms. Among them, Microaneurysms should be considered as one of the severe condition for the early blindness. Several techniques have been proposed based on this, but they have certain drawbacks. A new technique called neural network taken for presentation, helps to detect and determine the severity of Microaneurysms which would be able to give a better performance than the existing techniques.

  8. Reporting Severe Hypoglycemia in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2017-01-01

    PURPOSE OF REVIEW: To describe potential factors influencing reporting of severe hypoglycemia in adult patients with type 1 diabetes and to analyze their effect on reported rates of severe hypoglycemia. RECENT FINDINGS: Reported rates of severe hypoglycemia defined as need for third party...... by partners report higher rates of severe hypoglycemia. There is a large variation between studies reporting incidence and prevalence of severe hypoglycemia in patients with type 1 diabetes, mainly explained by definition of severity, methods of reporting, and patient selection. These findings call...... hypoglycemia are 0.02-0.5 events per patient-year and 1-29%, respectively. When subjects with recurrent severe hypoglycemia in the past or suffering from impaired hypoglycemia awareness are excluded from participation in studies, lower rates are reported. Studies applying anonymous reporting or reporting...

  9. State energy severance taxes, 1985-1993

    International Nuclear Information System (INIS)

    1995-09-01

    This report analyzes changes in aggregate and State-level energy severance taxes for 1985 through 1993. Data are presented for crude oil, natural gas, and coal. The report highlights trends in severance tax receipts relative to energy prices and production, using severance tax data published by the Bureau of the Census of the US Department of Commerce and production data published by the Energy Information Administration

  10. Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

    OpenAIRE

    Gupta, Natasha; Ahmed, Seema; Shaffer, Lemuel; Cavens, Paula; Blankstein, Josef

    2014-01-01

    Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term an...

  11. Severe Accident Research Program plan update

    International Nuclear Information System (INIS)

    1992-12-01

    In August 1989, the staff published NUREG-1365, ''Revised Severe Accident Research Program Plan.'' Since 1989, significant progress has been made in severe accident research to warrant an update to NUREG-1365. The staff has prepared this SARP Plan Update to: (1) Identify those issues that have been closed or are near completion, (2) Describe the progress in our understanding of important severe accident phenomena, (3) Define the long-term research that is directed at improving our understanding of severe accident phenomena and developing improved methods for assessing core melt progression, direct containment heating, and fuel-coolant interactions, and (4) Reflect the growing emphasis in two additional areas--advanced light water reactors, and support for the assessment of criteria for containment performance during severe accidents. The report describes recent major accomplishments in understanding the underlying phenomena that can occur during a severe accident. These include Mark I liner failure, severe accident scaling methodology, source term issues, core-concrete interactions, hydrogen transport and combustion, TMI-2 Vessel Investigation Project, and direct containment heating. The report also describes the major planned activities under the SARP over the next several years. These activities will focus on two phenomenological issues (core melt progression, and fuel-coolant interactions and debris coolability) that have significant uncertainties that impact our understanding and ability to predict severe accident phenomena and their effect on containment performance SARP will also focus on severe accident code development, assessment and validation. As the staff completes the research on severe accident issues that relate to current generation reactors, continued research will focus on efforts to independently evaluate the capability of new advanced light water reactor designs to withstand severe accidents

  12. Screening for severe combined immunodeficiency in neonates

    OpenAIRE

    Kelly, Brian T; Tam, Jonathan S; Verbsky, James W; Routes, John M

    2013-01-01

    Brian T Kelly,1 Jonathan S Tam,1 James W Verbsky,1,2 John M Routes1,2 1Department of Pediatrics, 2Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA Abstract: Severe combined immunodeficiency (SCID) is a rare disease that severely affects the cellular and humoral immune systems. Patients with SCID present with recurrent or severe infections and often with chronic diarrhea and failure to thrive. The disease is uniformly fatal, making early diag...

  13. SAMEX: A severe accident management support expert

    International Nuclear Information System (INIS)

    Park, Soo-Yong; Ahn, Kwang-Il

    2010-01-01

    A decision support system for use in a severe accident management following an incident at a nuclear power plant is being developed which is aided by a severe accident risk database module and a severe accident management simulation module. The severe accident management support expert (SAMEX) system can provide the various types of diagnostic and predictive assistance based on the real-time plant specific safety parameters. It consists of four major modules as sub-systems: (a) severe accident risk data base module (SARDB), (b) risk-informed severe accident risk data base management module (RI-SARD), (c) severe accident management simulation module (SAMS), and (d) on-line severe accident management guidance module (on-line SAMG). The modules are integrated into a code package that executes within a WINDOWS XP operating environment, using extensive user friendly graphics control. In Korea, the integrated approach of the decision support system is being carried out under the nuclear R and D program planned by the Korean Ministry of Education, Science and Technology (MEST). An objective of the project is to develop the support system which can show a theoretical possibility. If the system is feasible, the project team will recommend the radiation protection technical support center of a national regulatory body to implement a plant specific system, which is applicable to a real accident, for the purpose of immediate and various diagnosis based on the given plant status information and of prediction of an expected accident progression under a severe accident situation.

  14. Severe accidents: in nuclear power plants

    International Nuclear Information System (INIS)

    1986-01-01

    A ''severe'' nuclear accident refers to a reactor accident that could exceed reactor design specifications to such a degree as to prevent cooling of the reactor's core by normal means. This report summarizes the work of a NEA Senior Group of Experts who have studied the potential response of existing light-water reactors to severe accidents and have found that current designs of reactors are far more capable of coping with severe accidents than design specifications would suggest. The report emphasises the specific knowledge and means that can be used for diagnosing a severe accident and for managing its progression in order to prevent or mitigate its consequences

  15. Association between severity of chronic obstructive pulmonary ...

    African Journals Online (AJOL)

    The statistical analysis was performed by SPSS software and the Kendall's tau-b correlation test. Results: The mean age (±standard deviation) was 64.3 ± 11.3 years. Twelve percent were female and 88 percent were male. The COPD severity, according to the ATS criteria, was mild in 16%, moderate in 48%, severe in 32% ...

  16. Euthanasia of Severely Handicapped Infants: Ethical Issues.

    Science.gov (United States)

    Cohen, Libby

    Ethical decisions are involved in life and death decisions for severely handicapped infants. Although it has become common practice for physicians not to treat severely handicapped infants, the ethical considerations involved in euthanasia are complex. A review of the literature reveals that concerns center around the quality of life of the…

  17. Prevalence of exchange blood transfusion in severe ...

    African Journals Online (AJOL)

    Background: Exchange blood transfusion (EBT) is carried out for the treatment of conditions presenting with severe hyperbilirubinaemia and anaemia, such as ABO incompatibility, sepsis, prematurity and birth trauma among others. While it is fast being abandoned as treatment modality for severe neonatal jaundice in the ...

  18. Personality dimensions and service failure severity

    African Journals Online (AJOL)

    kirstam

    Dr L. Kruger is a senior lecturer in the Department of Marketing Management ... severity rather than possible individual consumer effects on service failure severity. ... When service failures occur, there is an imbalance in the relationship, because ... service recovery strategies may result in a successful recovery experience ( ...

  19. Fire severity classification: Uses and abuses

    Science.gov (United States)

    Theresa B. Jain; Russell T. Graham

    2003-01-01

    Burn severity (also referred to as fire severity) is not a single definition, but rather a concept and its classification is a function of the measured units unique to the system of interest. The systems include: flora and fauna, soil microbiology and hydrologic processes, atmospheric inputs, fire management, and society. Depending on the particular system of interest...

  20. Severe accident training simulator APROS SA

    International Nuclear Information System (INIS)

    Raiko, Eerikki; Salminen, Kai; Lundstroem, Petra; Harti, Mika; Routamo, Tomi

    2003-01-01

    APROS SA is a severe accident training simulator based on the APROS simulation environment. APROS SA has been developed in Fortum Nuclear Services Ltd to serve as a training tool for the personnel of the Loviisa NPP. Training with APROS SA gives the personnel a deeper understanding of the severe accident phenomena and thus it is an important part of the implementation of the severe accident management strategy. APROS SA consists of two parts, a comprehensive Loviisa plant model and an external severe accident model. The external model is an extension to the Loviisa plant model, which allows the simulation to proceed into the severe accident phase. The severe accident model has three submodels: the core melting and relocation model, corium pool model and fission product model. In addition to these, a new thermal-hydraulic solver is introduced to the core region of the Loviisa plant model to replace the more limited APROS thermal-hydraulic solver. The full APROS SA training simulator has a graphical user interface with visualizations of both severe accident management panels at the operator room and the important physical phenomena during the accident. This paper describes the background of the APROS SA training simulator, the severe accident submodels and the graphical user interface. A short description how APROS SA will be used as a training tool at the Loviisa NPP is also given

  1. Severe interpersonal violence against children in sport

    NARCIS (Netherlands)

    Vertommen, Tine; Kampen, Jarl; Schipper-van Veldhoven, Nicolette; Uzieblo, Kasia; Eede, Van Den Filip

    2018-01-01

    In a recent large-scale prevalence study of interpersonal violence (IV) against child athletes in the Netherlands and Belgium we found that 9% of adult respondents who participated in organized sports before the age of 18 had experienced severe psychological violence, 8% severe physical violence,

  2. Severe hypothyroidism masquerading as renal impairment

    DEFF Research Database (Denmark)

    Bistrup, C; Jensen, Dorte Møller; Kvetny, J

    1996-01-01

    A case of severe hypothyroidism in a 51-year old male is presented. The patient was especially complaining of weakness, stiffness and moderate pain in the proximal muscle groups together with rhinorrhea and nasal stenosis. Because of severely elevated S-creatine-kinase combined with reduced...

  3. Nutrition of patients with severe neurologic impairment

    Directory of Open Access Journals (Sweden)

    Orel Anija

    2017-12-01

    Full Text Available Commercial enteral formulas are generally recommended for gastrostomy feeding in patients with severe neurologic impairment. However, pureed food diets are still widely used and even gaining popularity among certain groups. We tried to compare the effectiveness of gastrostomy feeding for treatment of severe malnutrition with either enteral formulas or pureed feeds.

  4. Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

    Directory of Open Access Journals (Sweden)

    Natasha Gupta

    2014-01-01

    Full Text Available Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term and was successfully treated with postpartum therapeutic plasma exchange. Patient also developed several other complications related to her substantial hypertriglyceridemia including preeclampsia, chylous ascites, retinal detachment, pleural effusion, and chronic pericarditis. This patient had no previous family or personal history of lipid abnormality and had four successful prior pregnancies without developing gestational hypertriglyceridemia. Such a severe hypertriglyceridemia is usually seen in patients with familial chylomicronemia syndromes where hypertriglyceridemia is exacerbated by the pregnancy, leading to fatal complications such as acute pancreatitis.

  5. Air pollution and asthma severity in adults

    Science.gov (United States)

    Rage, Estelle; Siroux, Valérie; Künzli, Nino; Pin, Isabelle; Kauffmann, Francine

    2009-01-01

    Objectives There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. Methods Asthma severity over the last 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The 4-class severity score integrated clinical events and type of treatment. The 5-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991–1995. The second consisted in spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). Results Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O3-8hr) and the number of days (O3-days) with 8-hour ozone averages above 110 μg.m−3 (for a 36-day increase, equivalent to the inter quartile range, in O3-days, odds ratio (95% confidence interval) 2.22 (1.61–3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO2. Both exposure assessment methods and severity scores resulted in very similar findings. SO2 correlated with severity but reached statistical significance only for the model based assignment of exposure. Conclusions The observed associations between asthma severity and air pollution, in particular O3, support the hypothesis that air pollution at levels far below current standards increases asthma severity. PMID:19017701

  6. Impact of pavement conditions on crash severity.

    Science.gov (United States)

    Li, Yingfeng; Liu, Chunxiao; Ding, Liang

    2013-10-01

    Pavement condition has been known as a key factor related to ride quality, but it is less clear how exactly pavement conditions are related to traffic crashes. The researchers used Geographic Information System (GIS) to link Texas Department of Transportation (TxDOT) Crash Record Information System (CRIS) data and Pavement Management Information System (PMIS) data, which provided an opportunity to examine the impact of pavement conditions on traffic crashes in depth. The study analyzed the correlation between several key pavement condition ratings or scores and crash severity based on a large number of crashes in Texas between 2008 and 2009. The results in general suggested that poor pavement condition scores and ratings were associated with proportionally more severe crashes, but very poor pavement conditions were actually associated with less severe crashes. Very good pavement conditions might induce speeding behaviors and therefore could have caused more severe crashes, especially on non-freeway arterials and during favorable driving conditions. In addition, the results showed that the effects of pavement conditions on crash severity were more evident for passenger vehicles than for commercial vehicles. These results provide insights on how pavement conditions may have contributed to crashes, which may be valuable for safety improvement during pavement design and maintenance. Readers should notice that, although the study found statistically significant effects of pavement variables on crash severity, the effects were rather minor in reality as suggested by frequency analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. [Severe hypertension: definition and patients profiles].

    Science.gov (United States)

    Mourad, Jean-Jacques

    2013-05-01

    Severe arterial hypertension gathers relatively different clinical situations explained by the heterogeneity of the definitions of this clinical setting. From a medical point of view, severe hypertension is a short course situation defined by very high values of blood pressure corresponding to grade 3 hypertension. In France, until 2011, the social security also included in the definition of severe HTA chronic situations characterized by moderate blood pressure values requiring at least triple anthihypertensive therapies associated with a clinical or infraclinical target organ damages. These clinical profiles, much more frequent than grade 3 hypertension, allowed the full reimbursement of care costs for these patients. In France, it is estimated that 10% of hypertensive patients present a severe form with an annual incidence of 50,000 patients. The patients with severe hypertension have an increased cardiovascular morbidity justifying a closer clinical monitoring. From an economic point of view, these severe forms of hypertension have a higher cost of care, explained primarily by a more frequent need of specialized referrals, radiological exams and hospitalizations. This excess cost justified the existence of a full coverage of induced costs by the social security, since the incidence of severe hypertension is more frequent in the low social categories, and in patients with economic fragility.

  8. Hospital Management of Severe Hypertriglyceridemia in Children.

    Science.gov (United States)

    Valaiyapathi, Badhma; Ashraf, Ambika P

    2017-01-01

    Severe Hypertriglyceridemia (HTG), i.e., plasma triglyceride levels exceeding 1000 mg/dL, is one of the established causes of acute pancreatitis and severe abdominal pain. There are no established pediatric guidelines regarding treatment of children and adolescents with severe HTG. To review the pathophysiology and etiology of severe HTG in the pediatric age group, and to discuss management options. Severe HTG is usually due to deficient or absent Lipoprotein Lipase (LPL) activity, which can be due to primary genetic etiology or secondary causes triggering HTG in those with underlying genetic susceptibility. Hospitalization is indicated for patients with severe HTG who are symptomatic with abdominal pain or pancreatitis, in those with uncontrolled diabetes requiring insulin, or, in those with substantial elevations of plasma TG. Fasting followed by fat free diet until plasma TG declines to severe pancreatitis, shock or multi-organ failure. Medications such as fibrates and omega-3 fatty acids are not effective if LPL activity is absent or when plasma TG is >1800 mg/dL. Medications only have an adjunct role in the management. Low fat diet, lifestyle changes, weight loss, control of secondary causes, and patient education form the mainstay of management once the patient is discharged. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Monitoring severe accidents using AI techniques

    International Nuclear Information System (INIS)

    No, Young Gyu; Ahn, Kwang Il; Kim, Ju Hyun; Na, Man Gyun; Lim, Dong Hyuk

    2012-01-01

    After the Fukushima nuclear accident in 2011, there has been increasing concern regarding severe accidents in nuclear facilities. Severe accident scenarios are difficult for operators to monitor and identify. Therefore, accurate prediction of a severe accident is important in order to manage it appropriately in the unfavorable conditions. In this study, artificial intelligence (AI) techniques, such as support vector classification (SVC), probabilistic neural network (PNN), group method of data handling (GMDH), and fuzzy neural network (FNN), were used to monitor the major transient scenarios of a severe accident caused by three different initiating events, the hot-leg loss of coolant accident (LOCA), the cold-leg LOCA, and the steam generator tube rupture in pressurized water reactors (PWRs). The SVC and PNN models were used for the event classification. The GMDH and FNN models were employed to accurately predict the important timing representing severe accident scenarios. In addition, in order to verify the proposed algorithm, data from a number of numerical simulations were required in order to train the AI techniques due to the shortage of real LOCA data. The data was acquired by performing simulations using the MAAP4 code. The prediction accuracy of the three types of initiating events was sufficiently high to predict severe accident scenarios. Therefore, the AI techniques can be applied successfully in the identification and monitoring of severe accident scenarios in real PWRs.

  10. Monitoring severe accidents using AI techniques

    Energy Technology Data Exchange (ETDEWEB)

    No, Young Gyu; Ahn, Kwang Il [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Ju Hyun; Na, Man Gyun [Dept. of Nuclear Engineering, Chosun University, Gwangju (Korea, Republic of); Lim, Dong Hyuk [Korea Institute of Nuclear Nonproliferation and Control, Daejon (Korea, Republic of)

    2012-05-15

    After the Fukushima nuclear accident in 2011, there has been increasing concern regarding severe accidents in nuclear facilities. Severe accident scenarios are difficult for operators to monitor and identify. Therefore, accurate prediction of a severe accident is important in order to manage it appropriately in the unfavorable conditions. In this study, artificial intelligence (AI) techniques, such as support vector classification (SVC), probabilistic neural network (PNN), group method of data handling (GMDH), and fuzzy neural network (FNN), were used to monitor the major transient scenarios of a severe accident caused by three different initiating events, the hot-leg loss of coolant accident (LOCA), the cold-leg LOCA, and the steam generator tube rupture in pressurized water reactors (PWRs). The SVC and PNN models were used for the event classification. The GMDH and FNN models were employed to accurately predict the important timing representing severe accident scenarios. In addition, in order to verify the proposed algorithm, data from a number of numerical simulations were required in order to train the AI techniques due to the shortage of real LOCA data. The data was acquired by performing simulations using the MAAP4 code. The prediction accuracy of the three types of initiating events was sufficiently high to predict severe accident scenarios. Therefore, the AI techniques can be applied successfully in the identification and monitoring of severe accident scenarios in real PWRs.

  11. Monitoring Severe Accidents Using AI Techniques

    International Nuclear Information System (INIS)

    No, Young Gyu; Kim, Ju Hyun; Na, Man Gyun; Ahn, Kwang Il

    2011-01-01

    It is very difficult for nuclear power plant operators to monitor and identify the major severe accident scenarios following an initiating event by staring at temporal trends of important parameters. The objective of this study is to develop and verify the monitoring for severe accidents using artificial intelligence (AI) techniques such as support vector classification (SVC), probabilistic neural network (PNN), group method of data handling (GMDH) and fuzzy neural network (FNN). The SVC and PNN are used for event classification among the severe accidents. Also, GMDH and FNN are used to monitor for severe accidents. The inputs to AI techniques are initial time-integrated values obtained by integrating measurement signals during a short time interval after reactor scram. In this study, 3 types of initiating events such as the hot-leg LOCA, the cold-leg LOCA and SGTR are considered and it is verified how well the proposed scenario identification algorithm using the GMDH and FNN models identifies the timings when the reactor core will be uncovered, when CET will exceed 1200 .deg. F and when the reactor vessel will fail. In cases that an initiating event develops into a severe accident, the proposed algorithm showed accurate classification of initiating events. Also, it well predicted timings for important occurrences during severe accident progression scenarios, which is very helpful for operators to perform severe accident management

  12. NPP Krsko Severe Accident Management Guidelines Implementation

    International Nuclear Information System (INIS)

    Basic, I.; Krajnc, B.; Bilic-Zabric, T.; Spiler, J.

    2002-01-01

    Severe Accident Management is a framework to identify and implement the Emergency Response Capabilities that can be used to prevent or mitigate severe accidents and their consequences. The USA NRC has indicated that the development of a licensee plant specific accident management program will be required in order to close out the severe accident regulatory issue (Ref. SECY-88-147). Generic Letter 88-20 ties the Accident management Program to IPE for each plant. The SECY-89-012 defines those actions taken during the course of an accident by the plant operating and technical staff to: 1) prevent core damage, 2) terminate the progress of core damage if it begins and retain the core within the reactor vessel, 3) maintain containment integrity as long as possible, and 4) minimize offsite releases. The subject of this paper is to document the severe accident management activities, which resulted in a plant specific Severe Accident Management Guidelines implementation. They have been developed based on the Krsko IPE (Individual Plant Examination) insights, Generic WOG SAMGs (Westinghouse Owners Group Severe Accident Management Guidances) and plant specific documents developed within this effort. Among the required plant specific actions the following are the most important ones: Identification and documentation of those Krsko plant specific severe accident management features (which also resulted from the IPE investigations). The development of the Krsko plant specific background documents (Severe Accident Plant Specific Strategies and SAMG Setpoint Calculation). Also, paper discusses effort done in the areas of NPP Krsko SAMG review (internal and external ), validation on Krsko Full Scope Simulator (Severe Accident sequences are simulated by MAAP4 in real time) and world 1st IAEA Review of Accident Management Programmes (RAMP). (author)

  13. The American 'severe fuel damage program'

    International Nuclear Information System (INIS)

    Sdouz, G.

    1982-03-01

    The TMI-2 accident has initiated a new phase of safety research. It is necessary to consider severe accidents with degraded or molten core. For NRC there was a need for an improved understanding of this reactor behaviour and the 'Severe Fuel Dage Program' was initiated. Planned are in-pile experiments in PBF, NRU and ESSOR and in addition separate effects tests and results from TMI-2. The analytical component of the program is the development of different versions of the code SCDAP for the detailed analysis during severe accident transients. (Author) [de

  14. Function theory of several complex variables

    CERN Document Server

    Krantz, Steven G

    2001-01-01

    The theory of several complex variables can be studied from several different perspectives. In this book, Steven Krantz approaches the subject from the point of view of a classical analyst, emphasizing its function-theoretic aspects. He has taken particular care to write the book with the student in mind, with uniformly extensive and helpful explanations, numerous examples, and plentiful exercises of varying difficulty. In the spirit of a student-oriented text, Krantz begins with an introduction to the subject, including an insightful comparison of analysis of several complex variables with th

  15. Invariant resolutions for several Fueter operators

    Science.gov (United States)

    Colombo, Fabrizio; Souček, Vladimir; Struppa, Daniele C.

    2006-07-01

    A proper generalization of complex function theory to higher dimension is Clifford analysis and an analogue of holomorphic functions of several complex variables were recently described as the space of solutions of several Dirac equations. The four-dimensional case has special features and is closely connected to functions of quaternionic variables. In this paper we present an approach to the Dolbeault sequence for several quaternionic variables based on symmetries and representation theory. In particular we prove that the resolution of the Cauchy-Fueter system obtained algebraically, via Gröbner bases techniques, is equivalent to the one obtained by R.J. Baston (J. Geom. Phys. 1992).

  16. Severe falciparum malaria: A case report

    Science.gov (United States)

    Arcelia, F.; Asymida, F.; Lubis, N. F. M.; Pasaribu, A. P.

    2018-03-01

    Plasmodium parasites caused Malaria. Indonesia is one of the countries in Southeast Asia that endemic to malaria. The burden of malaria is more in the eastern part of Indonesia than the Western part as well as the endemicity. Some cases of malaria will develop to severe form. Usually, the manifestation of children and adult are different. We reported a severe case of malaria in a 14-year-old boy who develops several manifestations such as anemia, hypoglycemia, sepsis and black water fever. We successfully treated the patient with Artesunate intravenous and continued with Dihydroartemisinin-piperaquine.

  17. Severe acute respiratory syndrome: lessons and uncertainties.

    NARCIS (Netherlands)

    Kullberg, B.J.; Voss, A.

    2003-01-01

    The outbreak of severe acute respiratory syndrome (SARS) has produced scientific and epidemiological discoveries with unprecedented speed, and this information has been spread instantaneously to the global health community through the internet. Within a few weeks, the coronavirus associated with

  18. Lightning and severe thunderstorms in event management.

    Science.gov (United States)

    Walsh, Katie M

    2012-01-01

    There are a few national position stands/guidelines that address environmental conditions in athletics, yet they do not govern all outdoor sports. Extreme heat and cold, lightning, and severe wind can all be fatal, yet the majority of outdoor sports have no published guidelines addressing these conditions in relation to activity. Available research on extreme heat and cold conditions in athletics provides prevention strategies, to include acclimatization. Lightning and severe wind are two environmental conditions to which humans cannot accommodate, and they both can be deadly. There are strong positions on extreme heat/cold and lightning safety in athletics, but none affiliated with severe winds. Medical personnel involved in planning large outdoor sporting events must know of the presence of nationally published weather-related documents and apply them to their event. In addition, research needs to be expanded in the realm of establishing guidelines for safety to participants and spectators in severe wind conditions.

  19. Plasmapheresis in the management of severe hypertriglyceridemia.

    Science.gov (United States)

    Seda, Gilbert; Meyer, Jill M; Amundson, Dennis E; Daheshia, Massoud

    2013-08-01

    Plasmapheresis can benefit a variety of critically ill patients. A woman with diabetic ketoacidosis and severe hypertriglyceridemia was treated with plasmapheresis when conventional treatments did not markedly reduce her triglyceridemia. The patient was admitted to a medical intensive care unit because of diabetic ketoacidosis with severe lipemia. The lipemia-associated interference in laboratory studies made treatment of electrolyte abnormalities extremely difficult. The hypertriglyceridemia was initially treated with insulin, antilipidemic medications, and heparin, but the levels of triglycerides remained elevated, delaying results of needed laboratory studies for hours. After plasmapheresis, the serum level of triglycerides decreased by 77% in less than 24 hours. Severe lipemia interferes with photometric laboratory studies, yielding an underestimation of serum levels of electrolytes. Plasmapheresis is safe, rapid, and effective for emergent management of severe hypertriglyceridemia in critically ill patients. The impact of the procedure on critical care nursing is growing as nurses become involved in the treatment and follow-up care of patients who have plasmapheresis.

  20. Severe accidents in Nuclear Power Plants

    International Nuclear Information System (INIS)

    Valle Cepero, R.; Castillo Alvarez, J.; Ramon Fuente, J.

    1996-01-01

    For the assessment of the safety of nuclear power plants it is of great importance the analyses of severe accidents since they allow to estimate the possible failure models of the containment, and also permit knowing the magnitude and composition of the radioactive material that would be released to the environment in case of an accident upon population and the environment. This paper presents in general terms the basic principles for conducting the analysis of severe accidents, the fundamental sources in the generation of radionuclides and aerosols, the transportation and deposition processes, and also makes reference to de main codes used in the modulation of severe accidents. The final part of the paper contents information on how severe accidents are dialed with the regulatory point view in different countries

  1. Postpartum Depression After Mild and Severe Preeclampsia

    NARCIS (Netherlands)

    Hoedjes, Meeke; Berks, Durk; Vogel, Ineke; Franx, Arie; Bangma, Meike; Darlington, Anne-Sophie E.; Visser, Willy; Duvekot, Johannes J.; Habbema, J. Dik F.; Steegers, Eric A. P.; Raat, Hein

    2011-01-01

    Objective: To describe the prevalence of postpartum depressive symptoms after preeclampsia, to assess the extent to which the prevalence of postpartum depressive symptoms differs after mild and severe preeclampsia, and to investigate which factors contribute to such differences. Methods: Women

  2. Learning about Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    ... immunodeficiency From The Journal of Allergy and Clinical Immunology Learning About Severe Combined Immunodeficiency (SCID) What is ... immunodeficiency From The Journal of Allergy and Clinical Immunology Get Email Updates Privacy Copyright Contact Accessibility Plug- ...

  3. Correlates of Illness Severity in Infectious Mononucleosis

    Directory of Open Access Journals (Sweden)

    John Odame

    2014-01-01

    Full Text Available INTRODUCTION: Understanding the spectrum and frequencies of Epstein-Barr virus (EBV complications and markers of illness severity in immunocompetent patients with primary EBV infection will inform management of patients with EBV-related illnesses.

  4. Selected Geomagnetic Measurements From Several Satellites

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — More than 17 million selected magnetic observations from several orbiting low-altitude satellites are contained in this digital collection. Except for MAGSAT, all...

  5. Chemical phenomena under severe accident conditions

    International Nuclear Information System (INIS)

    Powers, D.A.

    1988-01-01

    A severe nuclear reactor accident is expected to involve a vast number of chemical processes. The chemical processes of major safety significance begin with the production of hydrogen during steam oxidation of fuel cladding. Physico-chemical changes in the fuel and the vaporization of radionuclides during reactor accidents have captured much of the attention of the safety community in recent years. Protracted chemical interactions of core debris with structural concrete mark the conclusion of dynamic events in a severe accident. An overview of the current understanding of chemical processes in severe reactor accident is provided in this paper. It is shown that most of this understanding has come from application of findings from other fields though a few areas have in the past been subject to in-depth study of a fundamental nature. Challenges in the study of severe accident chemistry are delineated

  6. Optimal severance payment: theory and practice

    Czech Academy of Sciences Publication Activity Database

    Jeong, Byeongju

    -, č. 255 (2005), s. 1-22 ISSN 1211-3298 Institutional research plan: CEZ:AV0Z70850503 Keywords : severance payment * optimal separation Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp255.pdf

  7. Bariatric surgery for severely obese adolescents.

    Science.gov (United States)

    Fitzgerald, Dominic A; Baur, Louise

    2014-09-01

    Severe obesity is increasing in adolescents and is associated with cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnoea, polycystic ovarian syndrome and a range of musculoskeletal problems. Premature death is the inevitable outcome of persistent severe obesity in adolescents. In adults with severe obesity, medical and lifestyle interventions have been shown to be expensive and less effective in terms of weight loss than has bariatric surgery. The single completed randomised controlled trial in adolescents shows the same outcome. This is supported by meta analyses of bariatric surgery in adolescent subjects. A more aggressive approach to severe obesity, utilising bariatric surgery in selected cases, within the context of a multi-disciplinary team, is required. Copyright © 2014. Published by Elsevier Ltd.

  8. Co-morbidities in severe asthma

    DEFF Research Database (Denmark)

    Porsbjerg, Celeste; Menzies-Gow, Andrew

    2017-01-01

    Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma...... to identify treatment barriers and triggers of asthma symptoms, including co-morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma. This review provides the clinician with an overview of the prevalence and clinical...... impact of the most common co-morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD...

  9. Thromboelastography in patients with severe sepsis

    DEFF Research Database (Denmark)

    Haase, Nicolai; Ostrowski, Sisse Rye; Wetterslev, Jørn

    2015-01-01

    PURPOSE: To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis. METHODS: Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156......) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox...... bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial. CONCLUSIONS: In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding....

  10. Deterministic analyses of severe accident issues

    International Nuclear Information System (INIS)

    Dua, S.S.; Moody, F.J.; Muralidharan, R.; Claassen, L.B.

    2004-01-01

    Severe accidents in light water reactors involve complex physical phenomena. In the past there has been a heavy reliance on simple assumptions regarding physical phenomena alongside of probability methods to evaluate risks associated with severe accidents. Recently GE has developed realistic methodologies that permit deterministic evaluations of severe accident progression and of some of the associated phenomena in the case of Boiling Water Reactors (BWRs). These deterministic analyses indicate that with appropriate system modifications, and operator actions, core damage can be prevented in most cases. Furthermore, in cases where core-melt is postulated, containment failure can either be prevented or significantly delayed to allow sufficient time for recovery actions to mitigate severe accidents

  11. Recurrent severe vomiting due to hyperthyroidism

    OpenAIRE

    Chen, Li-ying; Zhou, Bo; Chen, Zhou-wen; Fang, Li-zheng

    2010-01-01

    Thyrotoxicosis may present in many ways; severe vomiting as a prominent symptom of thyrotoxicosis is uncommon. In this paper, we report a 24-year-old Chinese male with hyperthyroidism who presented with recurrent severe vomiting. The patient had had intermittent vomiting for seven years and had lost approximately 15 kg of weight. Gastroscopic examinations revealed chronic gastritis and one occasion peptic ulcer. He was treated with antacid and proton pump inhibitors, but his symptoms had no r...

  12. Pulse Clarithromycin Therapy In Severe ACNE Vulgaris

    Directory of Open Access Journals (Sweden)

    Rathi Sanjay K

    2002-01-01

    Full Text Available Three patients with severe acne vulgaris, not responding with long courses of doxycycline, minocycline and erythromycin were given oral clarithromycin in pulsed regimen. The patients were given 7 days course of clarithromycin 250mg twice daily, which was repeated after a gap of 10 days. Such 3 courses were given. The lesions responded significantly. No significant side effect was noted. Pulse clarithromycin therapy seems to be a good alternative and effective tool in the management of severe acne vulgaris.

  13. Seckel syndrome with severe sinus bradycardia.

    Science.gov (United States)

    Ramasamy, Chandramohan; Satheesh, Santhosh; Selvaraj, Raja

    2015-03-01

    Seckel syndrome is an uncommon form of microcephalic dwarfism. The authors report a young boy with Seckel syndrome who presented with severe sinus bradycardia with symptoms of syncope and presyncope. Implantation of a permanent pacemaker was necessary in view of the severe symptoms. Although uncommon, cardiac abnormalities have been rarely reported in Seckel syndrome. This is the one of the few reports of rhythm abnormalities in this condition.

  14. Severe Neurotoxicity Following Ingestion of Tetraethyl Lead

    OpenAIRE

    Wills, Brandon K.; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

    2010-01-01

    Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80–90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symp...

  15. National practices in relation to severe accidents

    International Nuclear Information System (INIS)

    Soda, Kunihisa

    1989-01-01

    After the accidents at Three Mile Island and Chernobyl, many studies have been carried out on severe accidents by various organizations including IAEA and OECD/CSNI. In the present article, measures taken in different countries against severe accidents are outlined based on the results of these studies. In Sweden, policies for the management of a severe accident and reduction in the release of radioactive materials were established based on reports issued by the Atomic Energy Committee, which was set up after the Three Mile Island accident. The current policies require that filter vents be provided where necessary. France, following Sweden, adopted the use of filter vents. Operation procedures to be followed in the event of a severe accident have been established in the nation. The measures against severe accidents adopted in West Germany mainly focus on the weakening of the effects of accidents, and are not covered by the design standards. The use of filter vents are also required in Finland and Switzerland. In the U.S., a program for individual plant examination will be implemented over the three-year period beginning in 1989. Studies on measures against severe accidents seem to be performed also in the Soviet Union. (N.K.)

  16. Jose Cabrera NPP severe accident management activities

    International Nuclear Information System (INIS)

    Blanco, J.; Almeida, P.; Saiz, J.; Sastre, J.L.; Delgado, R.

    1998-01-01

    To prepare a common acting plan with respect to Severe Accident Management, in 1994 was founded the severe accident management ''ad-hoc'' working group from the Spanish Westinghouse PWR Nuclear Power Plant Owners Group. In this group actively collaborated the Jose Cabrera NPP Training Centre and the Department of Nuclear Engineering of UNION FENOSA. From this moment, Jose Cabrera NPP began the planning of its specific Severe Accident Management Program, which main point are Severe Accident Management Guidelines (SAMG). To elaborate this guidelines, the Spanish translation of Westinghouse Owners Group (WOG) Severe Accident Management Guidelines were considered the reference documents. The implementation of this Guidelines to Jose Cabrera NPP started on January 1997. Once the specific guidelines have been implemented to the plant, training activities for the personnel involved in severe accident issues will be developed. To prepare the training exercises MAAP4 code will be used, and with this intention, a specific Jose Cabrera NPP MAAP-GRAAPH screen has been developed. Furthermore, a wide selection of MAAP input files for the simulation of different scenarios and accidental events is available. (Author)

  17. Model for predicting the injury severity score.

    Science.gov (United States)

    Hagiwara, Shuichi; Oshima, Kiyohiro; Murata, Masato; Kaneko, Minoru; Aoki, Makoto; Kanbe, Masahiko; Nakamura, Takuro; Ohyama, Yoshio; Tamura, Jun'ichi

    2015-07-01

    To determine the formula that predicts the injury severity score from parameters that are obtained in the emergency department at arrival. We reviewed the medical records of trauma patients who were transferred to the emergency department of Gunma University Hospital between January 2010 and December 2010. The injury severity score, age, mean blood pressure, heart rate, Glasgow coma scale, hemoglobin, hematocrit, red blood cell count, platelet count, fibrinogen, international normalized ratio of prothrombin time, activated partial thromboplastin time, and fibrin degradation products, were examined in those patients on arrival. To determine the formula that predicts the injury severity score, multiple linear regression analysis was carried out. The injury severity score was set as the dependent variable, and the other parameters were set as candidate objective variables. IBM spss Statistics 20 was used for the statistical analysis. Statistical significance was set at P  Watson ratio was 2.200. A formula for predicting the injury severity score in trauma patients was developed with ordinary parameters such as fibrin degradation products and mean blood pressure. This formula is useful because we can predict the injury severity score easily in the emergency department.

  18. Application Study of Fire Severity Classification

    International Nuclear Information System (INIS)

    Kim, In Hwan; Kim, Hyeong Taek; Jee, Moon Hak; Kim, Yun Jung

    2013-01-01

    This paper introduces the Fire Incidents Severity Classification Method for Korean NPPs that may be derived directly from the data fields and feasibility study for domestic uses. FEDB was characterized in more detail and assessed based on the significance of fire incidents in the updated database and five fire severity categories were defined. The logical approach to determine the fire severity starts from the most severe characteristics, namely challenging fires, and continues to define the less challenging and undetermined categories in progress. If the FEDB is utilized for Korean NPPs, the ways of Fire Severity Classification suggested in 2.4 above can be utilized for the quantitative fire risk analysis in future. The Fire Events Database (FEDB) is the primary source of fire data which are used for fire frequency in Fire PSA (Probabilistic Safety Assessment). The purpose of its development is to calculate the quantitative fire frequency at the comprehensive and consolidated source derived from the fire incident information available for Nuclear Power Plants (NPPs). Recently, the Fire Events Database (FEDB) was updated by Electric Power Research Institute (EPRI) and Nuclear Regulatory Commission (NRC) in U. S. The FEDB is intended to update the fire event history up to 2009. A significant enhancement to it is the reorganization and refinement of the database structure and data fields. It has been expanded and improved data fields, coding consistency, incident detail, data review fields, and reference data source traceability. It has been designed to better support several Fire PRA uses as well

  19. Use of biologics in severe food allergies.

    Science.gov (United States)

    Fiocchi, Alessandro; Pecora, Valentina; Valluzzi, Rocco L; Fierro, Vincenzo; Mennini, Maurizio

    2017-06-01

    Severe cases of food allergy account for the majority of the burden in terms of risks, quality of life, and resource expenditure. The traditional approach to these forms has been strict avoidance. More recently, Oral ImmunoTherapy (OIT) has gained a role in their management. However, in severe food allergies OIT is often infeasible. Case reports, observational, and prospective studies have recently proposed different approaches to severe food allergy. The majority of them include the use of biologics. Omalizumab has been the most studied drug for severe food allergies, and its role as adjuvant treatment to OIT is well established. Interest has been raised on other biologics, as dupilumab, reslizumab, and mepolizumab. Toll-like receptor agonists, and gene therapy using adeno-associated virus coding for Omalizumab are promising alternatives. The recent studies are deeply influencing the clinical practice. We review the modifications of the clinical approach to severe food allergies so far available. We indicate the possible evolutions of treatment with biologics in severe food allergies.

  20. Conclusions on severe accident research priorities

    International Nuclear Information System (INIS)

    Klein-Heßling, W.; Sonnenkalb, M.; Jacquemain, D.; Clément, B.; Raimond, E.; Dimmelmeier, H.; Azarian, G.; Ducros, G.; Journeau, C.; Herranz Puebla, L.E.; Schumm, A.; Miassoedov, A.; Kljenak, I.; Pascal, G.; Bechta, S.; Güntay, S.; Koch, M.K.; Ivanov, I.; Auvinen, A.; Lindholm, I.

    2014-01-01

    Highlights: • Estimation of research priorities related to severe accident phenomena. • Consideration of new topics, partly linked to the severe accidents at Fukushima. • Consideration of results of recent projects, e.g. SARNET, ASAMPSA2, OECD projects. - Abstract: The objectives of the SARNET network of excellence are to define and work on common research programs in the field of severe accidents in Gen. II–III nuclear power plants and to further develop common tools and methodologies for safety assessment in this area. In order to ensure that the research conducted on severe accidents is efficient and well-focused, it is necessary to periodically evaluate and rank the priorities of research. This was done at the end of 2008 by the Severe Accident Research Priority (SARP) group at the end of the SARNET project of the 6th Framework Programme of European Commission (FP6). This group has updated this work in the FP7 SARNET2 project by accounting for the recent experimental results, the remaining safety issues as e.g. highlighted by Level 2 PSA national studies and the results of the recent ASAMPSA2 FP7 project. These evaluation activities were conducted in close relation with the work performed under the auspices of international organizations like OECD or IAEA. The Fukushima-Daiichi severe accidents, which occurred while SARNET2 was running, had some effects on the prioritization and definition of new research topics. Although significant progress has been gained and simulation models (e.g. the ASTEC integral code, jointly developed by IRSN and GRS) were improved, leading to an increased confidence in the predictive capabilities for assessing the success potential of countermeasures and/or mitigation measures, most of the selected research topics in 2008 are still of high priority. But the Fukushima-Daiichi accidents underlined that research efforts had to focus still more to improve severe accident management efficiency

  1. Correlates of illness severity in infectious mononucleosis

    Science.gov (United States)

    Odame, John; Robinson, Joan; Khodai-Booran, Nasser; Yeung, Simon; Mazzulli, Tony; Stephens, Derek; Allen, Upton D

    2014-01-01

    INTRODUCTION: Understanding the spectrum and frequencies of Epstein-Barr virus (EBV) complications and markers of illness severity in immunocompetent patients with primary EBV infection will inform management of patients with EBV-related illnesses. OBJECTIVES: To determine the clinical and laboratory correlates of illness severity among infants, children and youth with infectious mononucleosis (IM). METHODS: Study subjects with confirmed IM were prospectively enrolled. Illness severity was assessed at baseline and at six weeks using a scoring tool. Peripheral blood viral loads served as a measure of viral burden. RESULTS: Among 32 children and young adults with IM, the median age was 16 years (range two to 24 years). The predominant clinical findings were lymphadenopathy (23 of 32 [72%]), pharyngitis (16 of 32 [50%]), fever (nine of 32 [28%]) and splenomegaly (six of 32 [19%]). With respect to symptoms or signs that persisted to at least six weeks after illness onset, the predominant complaint was lymphadenopathy in 35% of subjects available for reassessment. Deranged liver function tests were present at presentation in up to 44% of subjects. Patients with the highest viral loads at presentation had significantly higher illness severity scores associated with fatigue (P=0.02). Other than the scores associated with fatigue, viral load values were not significantly correlated with the illness severity scores at baseline and at six weeks. CONCLUSION: In IM, viral loads are not necessarily correlated with illness severity, with the exception of fatigue. EBV-related hepatitis is common in IM, confirming the status of this virus as a relatively common cause of transient hepatitis in children and youth. This entity is not necessarily a marker of disease severity. PMID:25371691

  2. Severe accident testing of electrical penetration assemblies

    International Nuclear Information System (INIS)

    Clauss, D.B.

    1989-11-01

    This report describes the results of tests conducted on three different designs of full-size electrical penetration assemblies (EPAs) that are used in the containment buildings of nuclear power plants. The objective of the tests was to evaluate the behavior of the EPAs under simulated severe accident conditions using steam at elevated temperature and pressure. Leakage, temperature, and cable insulation resistance were monitored throughout the tests. Nuclear-qualified EPAs were produced from D. G. O'Brien, Westinghouse, and Conax. Severe-accident-sequence analysis was used to generate the severe accident conditions (SAC) for a large dry pressurized-water reactor (PWR), a boiling-water reactor (BWR) Mark I drywell, and a BWR Mark III wetwell. Based on a survey conducted by Sandia, each EPA was matched with the severe accident conditions for a specific reactor type. This included the type of containment that a particular EPA design was used in most frequently. Thus, the D. G. O'Brien EPA was chosen for the PWR SAC test, the Westinghouse was chosen for the Mark III test, and the Conax was chosen for the Mark I test. The EPAs were radiation and thermal aged to simulate the effects of a 40-year service life and loss-of-coolant accident (LOCA) before the SAC tests were conducted. The design, test preparations, conduct of the severe accident test, experimental results, posttest observations, and conclusions about the integrity and electrical performance of each EPA tested in this program are described in this report. In general, the leak integrity of the EPAs tested in this program was not compromised by severe accident loads. However, there was significant degradation in the insulation resistance of the cables, which could affect the electrical performance of equipment and devices inside containment at some point during the progression of a severe accident. 10 refs., 165 figs., 16 tabs

  3. Cost per severe accident as an index for severe accident consequence assessment and its applications

    International Nuclear Information System (INIS)

    Silva, Kampanart; Ishiwatari, Yuki; Takahara, Shogo

    2014-01-01

    The Fukushima Accident emphasizes the need to integrate the assessments of health effects, economic impacts, social impacts and environmental impacts, in order to perform a comprehensive consequence assessment of severe accidents in nuclear power plants. “Cost per severe accident” is introduced as an index for that purpose. The calculation methodology, including the consequence analysis using level 3 probabilistic risk assessment code OSCAAR and the calculation method of the cost per severe accident, is proposed. This methodology was applied to a virtual 1,100 MWe boiling water reactor. The breakdown of the cost per severe accident was provided. The radiation effect cost, the relocation cost and the decontamination cost were the three largest components. Sensitivity analyses were carried out, and parameters sensitive to cost per severe accident were specified. The cost per severe accident was compared with the amount of source terms, to demonstrate the performance of the cost per severe accident as an index to evaluate severe accident consequences. The ways to use the cost per severe accident for optimization of radiation protection countermeasures and for estimation of the effects of accident management strategies are discussed as its applications. - Highlights: • Cost per severe accident is used for severe accident consequence assessment. • Assessments of health, economic, social and environmental impacts are included. • Radiation effect, relocation and decontamination costs are important cost components. • Cost per severe accident can be used to optimize radiation protection measures. • Effects of accident management can be estimated using the cost per severe accident

  4. Severe accident management. Optimized guidelines and strategies

    International Nuclear Information System (INIS)

    Braun, Matthias; Löffler, Micha; Plank, Hermann; Asse, Dietmar; Dimmelmeier, Harald

    2014-01-01

    The highest priority for mitigating the consequences of a severe accident with core melt lies in securing containment integrity, as this represents the last barrier against fission product release to the environment. Containment integrity is endangered by several physical phenomena, especially highly transient phenomena following high-pressure reactor pressure vessel failure (like direct containment heating or steam explosions which can lead to early containment failure), hydrogen combustion, quasi-static over-pressure, temperature failure of penetrations, and basemat penetration by core melt. Each of these challenges can be counteracted by dedicated severe accident mitigation hardware, like dedicated primary circuit depressurization valves, hydrogen recombiners or igniters, filtered containment venting, containment cooling systems, and core melt stabilization systems (if available). However, besides their main safety function these systems often have also secondary effects that need to be considered. Filtered containment venting causes (though limited) fission product release into the environment, primary circuit depressurization leads to loss of coolant, and an ex-vessel core melt stabilization system as well as hydrogen igniters can generate high pressure and temperature loads on the containment. To ensure that during a severe accident any available systems are used to their full beneficial extent while minimizing their potential negative impact, AREVA has implemented a severe accident management for German nuclear power plants. This concept makes use of extensive numerical simulations of the entire plant, quantifying the impact of system activations (operational systems, safety systems, as well as dedicated severe accident systems) on the accident progression for various scenarios. Based on the knowledge gained, a handbook has been developed, allowing the plant operators to understand the current state of the plant (supported by computational aids), to predict

  5. Predictors of Severity in Pediatric Scrub Typhus.

    Science.gov (United States)

    Narayanasamy, Dinesh Kumar; Arun Babu, Thirunavukkarasu; Vijayadevagaran, Vijayasankar; Kittu, Devi; Ananthakrishnan, Shanthi

    2018-01-24

    To identify the factors that can predict the severity of scrub typhus in children. This prospective study was conducted at a tertiary care teaching hospital between November 2014 to October 2016. All children scrub typhus were included in the study. These children were followed during the hospital course and their laboratory results, response to treatment and complications were documented. Cases of 'severe scrub typhus' were identified based on criteria from published adult and pediatric studies. Out of 930 children with fever for more than 7d, IgM ELISA for scrub typhus was positive in 230 children. Ninety one (40.6%) cases fulfilled the criteria of 'severe scrub typhus' in children. Out of 45 factors, 27 potential factors were studied. The multivariate analysis identified 5 factors, breathlessness (OR: 6.85, 95%CI: 2.69 to 9.87), altered sensorium (OR: 11.48, 95% CI 3.43 to 10.19), leucocytosis (OR: 3.38, 95% CI 1.12 to 10.16), hypoalbuminemia (OR: 10.78, 95% CI 2.66 to 48.76), and hyponatremia (OR: 10.08, 95% CI 2.11 to 23.42) to be significantly associated with the 'severe scrub typhus' cases. Breathlessness, altered sensorium, leucocytosis, hypoalbuminemia, and hyponatremia predict severity in childhood scrub typhus. Presence of these factors should alert the treating physician regarding the need for intensive monitoring, treatment or referral.

  6. Severe accident issue resolution -- definition and perspective

    International Nuclear Information System (INIS)

    Harper, F.T.

    1995-01-01

    The purpose of this discussion is to introduce the session on the Progress on the Resolution of Severe Accident Issues. There has been much work in the area of resolution of severe accident issues over the past few years. This work has been focused on those issues most important to risk as assessed by comprehensive studies such as NUREG-1150. In particular, issues associated with early containment failure have been analyzed. These efforts to resolve issues have been hampered by the fact that open-quotes issue resolutionclose quotes has not always been well defined. The term open-quotes issue resolutionclose quotes conjures tip different images for the regulator, the accident analyst, the physicist, and the probabalist. In fact it is common to have as many different images of issue resolution as there are people in the room. This issue is complicated by the fact that the uncertainty in severe accident issues is enormous. (When convolved, the quantitative uncertainty in an integrated analysis due to severe accident issues can span several orders of magnitude.) In this summary, hierarchy is presented in an attempt to add some perspective to the resolution of issues in the face of large uncertainties. Recommendations are also made for analysts communicating in the area of issue resolution

  7. Severe hypertriglyceridemia-related acute pancreatitis.

    Science.gov (United States)

    Stefanutti, Claudia; Labbadia, Giancarlo; Morozzi, Claudia

    2013-04-01

    Acute pancreatitis is a potentially life-threatening complication of severe hypertriglyceridemia. In some cases, inborn errors of metabolism such as lipoprotein lipase deficiency, apoprotein C-II deficiency, and familial hypertriglyceridemia have been reported as causes of severe hypertriglyceridemia. More often, severe hypertriglyceridemia describes various clinical conditions characterized by high plasma levels of triglycerides (>1000 mg/dL), chylomicron remnants, or intermediate density lipoprotein like particles, and/or chylomicrons. International guidelines on the management of acute pancreatitis are currently available. Standard therapeutic measures are based on the use of lipid-lowering agents (fenofibrate, gemfibrozil, niacin, Ω-3 fatty acids), low molecular weight heparin, and insulin in diabetic patients. However, when standard medical therapies have failed, non-pharmacological approaches based upon the removal of triglycerides with therapeutic plasma exchange can also provide benefit to patients with severe hypertriglyceridemia and acute pancreatitis. Plasma exchange could be very helpful in reducing triglycerides levels during the acute phase of hyperlipidemic pancreatitis, and in the prevention of recurrence. The current evidence on management of acute pancreatitis and severe hypertriglyceridemia, focusing on symptoms, treatment and potential complications is reviewed herein. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  8. Use of simulators in severe accident management

    International Nuclear Information System (INIS)

    Evans, R.C.

    1994-01-01

    The U.S. nuclear utility industry is moving in a deliberate fashion through a coordinated industry severe accident working group to study and augment, where appropriate, the existing utility organizational and emergency planning structure to address accident and severe accident management. Full-scope simulators are used extensively to train licensed operators for their initial license examinations and continually thereafter in licensed operator requalification training and yearly examinations. The goal of the training (both initial and requalification) is to ensure that operators possess adequate knowledge, skills and abilities to prevent an event from progressing to core damage. The use of full-scope simulators in severe accident management training is in large part viewed by the industry as being premature. The working group study has not progressed to the point where the decision to employ full-scope simulators can be logically considered. It is not however premature to consider part-task or work station simulators as invaluable research tools to support the industry's study. These simulators could be employed, subject to limitations in the current state of knowledge regarding severe accident progression and phenomenological responses, in the validation and verification (V and V) of severe accident models or codes as they are developed. The U.S. nuclear utility industry has made substantial strides in the past 12 years in the accident prevention, mitigation and management arena. These strides are a product of the industry's preference for a logical and systematic approach to change. (orig.)

  9. Anaesthetic management of patients with severe sepsis.

    Science.gov (United States)

    Eissa, D; Carton, E G; Buggy, D J

    2010-12-01

    Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

  10. Coolability of severely degraded CANDU cores

    International Nuclear Information System (INIS)

    Meneley, D.A.; Blahnik, C.; Rogers, J.T.; Snell, V.G.; Mijhawan, S.

    1995-07-01

    Analytical and experimental studies have shown that the separately cooled moderator in a CANDU reactor provides an effective heat sink in the event of a loss-of-coolant accident (LOCA) accompanied by total failure of the emergency core cooling system (ECCS). The moderator heat sink prevents fuel melting and maintains the integrity of the fuel channels, therefore terminating this severe accident short of severe core damage. Nevertheless, there is a probability, however low, that the moderator heat sink could fail in such an accident. The pioneering work of Rogers (1984) for such a severe accident using simplified models showed that the fuel channels would fail and a bed of dry, solid debris would be formed at the bottom of the calandria which would heat up and eventually melt. However, the molten pool of core material would be retained in the calandria vessel, cooled by the independently cooled shield-tank water, and would eventually re solidify. Thus, the calandria vessel would act inherently as a core-catcher as long as the shield tank integrity is maintained. The present paper reviews subsequent work on the damage to a CANDU core under severe accident conditions and describes an empirically based mechanistic model of this process. It is shown that, for such severe accident sequences in a CANDU reactor, the end state following core disassembly consists of a porous bed of dry solid, coarse debris, irrespective of the initiating event and the core disassembly process. (author). 48 refs., 3 tabs., 18 figs

  11. Coolability of severely degraded CANDU cores. Revised

    International Nuclear Information System (INIS)

    Meneley, D.A.; Blahnik, C.; Rogers, J.T.; Snell, V.G.; Nijhawan, S.

    1996-01-01

    Analytical and experimental studies have shown that the separately cooled moderator in a CANDU reactor provides an effective heat sink in the event of a loss-of-coolant accident (LOCA) accompanied by total failure of the emergency core cooling system (ECCS). The moderator heat sink prevents fuel melting and maintains the integrity of the fuel channels, therefore terminating this severe accident short of severe core damage. Nevertheless, there is a probability, however low, that the moderator heat sink could fail in such an accident. The pioneering work of Rogers (1984) for such a severe accident using simplified models showed that the fuel channels would fail and a bed of dry, solid debris would be formed at the bottom of the calandria which would heat up and eventually melt. However, the molten pool of core material would be retained in the calandria vessel, cooled by the independently cooled shield-tank water, and would eventually resolidify. Thus, the calandria vessel would act inherently as a 'core-catcher' as long as the shield tank integrity is maintained. The present paper reviews subsequent work on the damage to a CANDU core under severe accident conditions and describes an empirically based mechanistic model of this process. It is shown that, for such severe accident sequences in a CANDU reactor, the end state following core disassembly consists of a porous bed of dry solid, coarse debris, irrespective of the initiating event and the core disassembly process. (author)

  12. Interaction of radionuclides in severe accident conditions

    International Nuclear Information System (INIS)

    Nagrale, Dhanesh B.; Bera, Subrata; Deo, Anuj Kumar; Paul, U.K.; Prasad, M.; Gaikwad, A.J.

    2015-01-01

    Nuclear power plants are designed with inherent engineering safety systems and associated operational procedures that provide an in-depth defence against accidents. Radionuclides such as Iodine, Cesium, Tellurium, Barium, Strontium, Rubidium, Molybdenum and many others may get released during a severe accident. Among these, Iodine, one of the fission products, behaviour is significant for the analysis of severe accident consequences because iodine is a chemically more active to the potential components released to the environment. During severe accident, Iodine is released and transported in aqueous, organic and inorganic forms. Iodine release from fuel, iodine transport in primary coolant system, containment, and reaction with control rods are some of the important phases in a severe accident scenario. The behaviour of iodine is governed by aerosol physics, depletion mechanisms gravitational settling, diffusiophoresis and thermophoresis. The presence of gaseous organic compounds and oxidizing compounds on iodine, reactions of aerosol iodine with boron and formation of cesium iodide which results in more volatile iodine release in containment play significant roles. Water radiolysis products due to presence of dissolved impurities, chloride ions, organic impurities should be considered while calculating iodine release. Containment filtered venting system (CFVS) consists of venturi scrubber and a scrubber tank which is dosed with NaOH and NaS_2O_3 in water where iodine will react with the chemicals and convert into NaI and Na_2SO_4. This paper elaborates the issues with respect to interaction of radionuclides and its consideration in modeling of severe accident. (author)

  13. Kiss-induced severe anaphylactic reactions

    Directory of Open Access Journals (Sweden)

    Atanasković-Marković Marina

    2010-01-01

    Full Text Available Introduction. Ingestion is the principal route for food allergens to trigger allergic reaction in atopic persons. However, in some highly sensitive patients severe symptoms may develop upon skin contact and by inhalation. The clinical spectrum ranges from mild facial urticaria and angioedema to life-threatening anaphylactic reactions. Outline of Cases. We describe cases of severe anaphylactic reactions by skin contact, induced by kissing in five children with prior history of severe anaphylaxis caused by food ingestion. These cases were found to have the medical history of IgE mediated food allergy, a very high total and specific serum IgE level and very strong family history of allergy. Conclusion. The presence of tiny particles of food on the kisser's lips was sufficient to trigger an anaphylactic reaction in sensitized children with prior history of severe allergic reaction caused by ingestion of food. Allergic reaction provoked with food allergens by skin contact can be a risk factor for generalized reactions. Therefore, extreme care has to be taken in avoiding kissing allergic children after eating foods to which they are highly allergic. Considering that kissing can be a cause of severe danger for the food allergic patient, such persons should inform their partners about the risk factor for causing their food hypersensitivity.

  14. United States position on severe accidents

    International Nuclear Information System (INIS)

    Ross, D.F.

    1988-01-01

    The United States policy on severe accidents was published in 1985 for both new plant applications and for existing plants. Implementation of this policy is in progress. This policy, aided by a related safety goal policy and by analysis capabilities emerging from improved understanding of accident phenomenology, is viewed as a logical development from the pioneering work in the WASH-1400 Reactor Safety Study published by the United States Nuclear Regulatory Commission (NRC) in 1975. This work provided an estimate of the probability and consequences of severe accidents which, prior to that time, had been mostly evaluated by somewhat arbitrary assumptions dating back 30 years. The early history of severe accident evaluation is briefly summarized for the period 1957-1979. Then, the galvanizing action of Three Mile Island Unit 2 (TMI-2) on severe accident analysis, experimentation and regulation is reviewed. Expressions of US policy in the form of rulemaking, severe accident policy, safety research, safety goal policy and court decisions (on adequacy of safety) are discussed. Finally, the NRC policy as of March 1988 is stated, along with a prospective look at the next few years. (author). 19 refs

  15. Uncertainties and severe-accident management

    International Nuclear Information System (INIS)

    Kastenberg, W.E.

    1991-01-01

    Severe-accident management can be defined as the use of existing and or alternative resources, systems, and actions to prevent or mitigate a core-melt accident. Together with risk management (e.g., changes in plant operation and/or addition of equipment) and emergency planning (off-site actions), accident management provides an extension of the defense-indepth safety philosophy for severe accidents. A significant number of probabilistic safety assessments have been completed, which yield the principal plant vulnerabilities, and can be categorized as (a) dominant sequences with respect to core-melt frequency, (b) dominant sequences with respect to various risk measures, (c) dominant threats that challenge safety functions, and (d) dominant threats with respect to failure of safety systems. Severe-accident management strategies can be generically classified as (a) use of alternative resources, (b) use of alternative equipment, and (c) use of alternative actions. For each sequence/threat and each combination of strategy, there may be several options available to the operator. Each strategy/option involves phenomenological and operational considerations regarding uncertainty. These include (a) uncertainty in key phenomena, (b) uncertainty in operator behavior, (c) uncertainty in system availability and behavior, and (d) uncertainty in information availability (i.e., instrumentation). This paper focuses on phenomenological uncertainties associated with severe-accident management strategies

  16. The development of severe accident analysis technology

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heuy Dong; Cho, Sung Won; Kim, Sang Baek; Park, Jong Hwa; Lee, Kyu Jung; Park, Lae Joon; Hu, Hoh; Hong, Sung Wan [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1993-07-01

    The objective of the development of severe accident analysis technology is to understand the severe accident phenomena such as core melt progression and to provide a reliable analytical tool to assess severe accidents in a nuclear power plant. Furthermore, establishment of the accident management strategies for the prevention/mitigation of severe accidents is also the purpose of this research. The study may be categorized into three areas. For the first area, two specific issues were reviewed to identify the further research direction, that is the natural circulation in the reactor coolant system and the fuel-coolant interaction as an in-vessel and an ex-vessel phenomenological study. For the second area, the MELCOR and the CONTAIN codes have been upgraded, and a validation calculation of the MELCOR has been performed for the PHEBUS-B9+ experiment. Finally, the experimental program has been established for the in-vessel and the ex-vessel severe accident phenomena with the in-pile test loop in KMRR and the integral containment test facilities, respectively. (Author).

  17. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

    Science.gov (United States)

    Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

    2014-01-01

    Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

  18. Real-time investigation of antibiotics-induced oxidative stress and superoxide release in bacteria using an electrochemical biosensor.

    Science.gov (United States)

    Liu, Xiaobo; Marrakchi, Mouna; Jahne, Michael; Rogers, Shane; Andreescu, Silvana

    2016-02-01

    The involvement of oxidative stress in the mechanism of antibiotics-meditated cell death is unclear and subject to debate. The kinetic profile and a quantitative relationship between the release of reactive oxygen species (ROS), bacteria and antibiotic type remain elusive. Here we report direct measurements and analytical quantification of the release of superoxide radicals (O2(·-)), a major contributor to ROS, in antibiotics-treated bacterial cultures using a cytochrome c electrochemical biosensor. The specificity of electrochemical measurements was established by the addition of superoxide dismutase (SOD) which decreased the O2(·-) signal. Measurements using a general ROS-specific fluorescence dye and colony forming units (CFU) assays were performed side-by-side to determine the total ROS and establish the relationship between ROS and the degree of lethality. Exposure of Escherichia coli and Listeria monocytogenes cultures to antibiotics increased the release of O2(·-) radicals in a dose-dependent manner, suggesting that the transmembrane generation of ROS may occur as part of the antibiotic action. The study provides a quantitative methodology and fundamental knowledge to further explore the role of oxidative stress in antibiotics-meditated bacterial death and to assess physiological changes associated with the complex metabolic events related to oxidative stress and bacterial resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Subinhibitory Concentrations of Bacteriostatic Antibiotics Induce relA-Dependent and relA-Independent Tolerance to beta-Lactams

    Czech Academy of Sciences Publication Activity Database

    Kudrin, P.; Varik, V.; Oliveira, S. R. A.; Beljantseva, J.; Del Peso Santos, T.; Dzhygyr, I.; Rejman, Dominik; Cava, F.; Tenson, T.; Hauryliuk, V.

    2017-01-01

    Roč. 61, č. 4 (2017), č. článku e02173-16. ISSN 0066-4804 R&D Projects: GA ČR GA15-11711S Institutional support: RVO:61388963 Keywords : beta-lactam * RelA * antibiotics * mupirocin * persistence * ppGpp Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.302, year: 2016 http://aac.asm.org/content/61/4/e02173-16.full

  20. Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-alpha Release by Mononuclear Cells in Healthy Adults

    NARCIS (Netherlands)

    Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost

    2016-01-01

    OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,