Sample records for febrile neutropenia occurred

  1. Febrile neutropenia in hematologic malignancies.

    PubMed

    Keng, Michael K; Sekeres, Mikkael A

    2013-12-01

    Febrile neutropenia (FN) can occur at any time during the course of a malignancy, especially hematologic malignancies, from diagnosis to end-stage disease. The majority of FN episodes are typically confined to the period of initial diagnosis and active treatment. Because of suppressed inflammatory responses, fever is often the sole sign of infection. As FN is a true medical emergency, prompt identification of and intervention in FN can prolong survival and improve quality of life. This article reviews FN in the setting of hematologic malignancies, specifically myelodysplastic syndromes and acute leukemias, providing an overview of the definition of fever and neutropenia, diagnostic approach, categories of risk/risk assessment, management in patients at low and high risk, and prophylaxis of infections. PMID:23990311

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

    PubMed

    Solmaz, Soner; Asma, Süheyl; Ozdo?u, Hakan; Yeral, Mahmut; Turunç, Tuba

    2014-10-01

    Febrile neutropenia which is a common complication of cancer treatment, is one of the major causes of morbidity and mortality. Several gram-negative and gram-positive bacteria are responsible for infections in neutropenic patients, however the most common microorganisms are Escherichia coli and coagulase-negative staphylococci, in decreasing order. Although Brucella spp. infections are endemic in Turkey, brucellosis-related febrile neutropenia has only rarely been reported. In this report, a case of brucellosis-related febrile neutropenia in a patient with acute myeloblastic leukemia (AML) was presented. A 56-year-old male patient presenting with fever, petechiae/purpura, leukocytosis, thrombocytopenia, and anemia was admitted to our hospital. Laboratory studies revealed a hemoglobin level of 8.27 g/dl, leukocyte count of 77.100 k/ml, absolute neutrophil count of 200 k/ml, and platelets at 94.200 k/ml. The patient was diagnosed as AML-M1 and piperacillin/tazobactam was started as the first-line antibiotic therapy due to the febrile neutropenia. On admission, blood and urine cultures were negative. Once the fever was controlled, remission/induction chemotherapy was initiated. However, fever developed again on the eight day, and vancomycin was added to the therapy. Since the fever persisted, the antibiotic therapy was gradually replaced with meropenem and linezolid. However, fever continued and the patient's general condition deteriorated. Subsequently performed Brucella tube agglutination test revealed positivity at 1/320 titer and the microorganism grown in blood culture (Bactec 9050; BD, USA) was identified as B.melitensis by conventional methods. Rifampicin and doxycycline therapy was started immediately, however, the patient died due to septic shock. If the tests for brucellosis were performed earlier when response to second step antibiotic therapy lacked in this patient, it was assumed that mortality could be prevented by the prompt initiation of the appropriate treatment. Thus, since brucellosis is endemic in Turkey, it should be considered as a possible agent of febrile neutropenia especially in patients unresponsive to empiric antibiotherapy and appropriate diagnostic tests should be performed. PMID:25492662

  3. Febrile neutropenia in children treated for malignancy.

    PubMed

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

    2015-06-01

    Febrile neutropenia (FN) in children treated for malignancy is a common and direct sequela of chemotherapy. Episodes of FN can be life-threatening, and demand prompt recognition, assessment and treatment with broad spectrum antibiotics. While in the majority of episodes no causal infection is identified, 10-20% are secondary to a bloodstream infection (BSI). A reduction in episodes of BSI could be achieved through robust infection prevention strategies, such as CVL care bundles. Alongside good antimicrobial stewardship, these strategies could reduce the risk of emergent, multi-drug resistant (MDR) infections. Emerging bacterial pathogens in BSI include Viridans Group Streptococci (VGS) and Enterobacteriaceae such as Klebsiella spp. which are known for their ability to carry MDR genes. There is also increased recognition of the role of invasive fungal infection (IFI) in FN, in particular with Aspergillus spp. Novel diagnostics, including multiplex blood and respiratory polymerase chain reaction assays can identify infections early in FN, facilitating targeted therapy, and reducing unnecessary antimicrobial exposure. Given appropriate, and sensitive rapid diagnostics, potential also exists to safely inform the risk assessment of patients with FN, identifying those at low risk of complication, who could be treated in the out-patient setting. Several clinical decision rules (CDR) have now been developed and validated in defined populations, for the risk assessment of children being treated for cancer. Future research is needed to develop a universal CDR to improve the management of children with FN. PMID:25917801

  4. Antimicrobial treatment of febrile neutropenia: pharmacokinetic-pharmacodynamic considerations.

    PubMed

    Goulenok, Tiphaine; Fantin, Bruno

    2013-10-01

    Patients with cancer or hematologic diseases are particularly at risk of infection leading to high morbidity, mortality and costs. Extensive data show that optimization of the administration of antimicrobials according to their pharmacokinetic and pharmacodynamic parameters improves clinical outcome. Evidence is growing that when pharmacokinetic and pharmacodynamic parameters are used to target not only clinical cure but also eradication, the selection resistance is also contained. This is of particular importance in patients with neutropenia in whom increasing rates of drug-resistant Gram-negative bacteria have been reported, particularly Pseudomonas aeruginosa. Based on experimental and clinical studies, pharmacokinetic and pharmacodynamic parameters are discussed in this review for each antibiotic used in febrile neutropenia in order to help physicians improve dosing and optimization of antimicrobial agents. PMID:23807657

  5. Outpatient therapy for febrile neutropenia: clinical and economic implications.

    PubMed

    de Lalla, Fausto

    2003-01-01

    Although febrile episodes in neutropenic patients remain a potentially life-threatening complication of anticancer chemotherapy, considerable progress has been achieved in understanding this issue. Febrile neutropenic patients represent a heterogeneous population that displays a very variable risk for serious medical complications. It has also been ascertained that in low-risk patients, the standard of care can be safely and effectively shifted from traditional hospital-based, parenteral, empiric, broad-spectrum antibacterial therapy to outpatient treatment, even for the entire duration of the febrile episode. Furthermore, in the last years some risk assessment models have been developed to identify, at the onset of febrile episodes, low-risk neutropenic patients who are most likely to have a favourable outcome (and who can effectively and safely be treated on an outpatient basis). With respect to traditional hospital-based therapy, the outpatient treatment of low-risk patients is associated with several advantages, including a conspicuous cost saving. Some strategies for inpatient therapy, such as switching from intravenous to oral antibacterials and early discharge, can allow some cost containment; however, the most substantial decrease in costs can be obtained by using outpatient treatment over the entire febrile episode, especially by using oral antibacterials. In spite of the considerable number of clinical studies published over the past 20 years, only limited pharmacoeconomic data on this issue are available. Future comparative studies between outpatient and inpatient treatment of febrile neutropenia, in addition to clinical outcomes (e.g. survival, time to clinical response), should therefore include the following: (i) a detailed analysis of total costs, specifying the setting of outpatient treatment and the method of administration of antimicrobial agents (home nursing, self administration or treatment at infusion centres or at a low-care unit of the hospital); (ii) cost of inpatient treatment if outpatient therapy fails; and (iii) out-of-pocket expenses incurred by the patients. PMID:12678567

  6. Risk factors associated with complications in patients with chemotherapy-induced febrile neutropenia in emergency department.

    PubMed

    Lynn, Jiun-Jen; Chen, Kuan-Fu; Weng, Yi-Ming; Chiu, Te-Fa

    2013-12-01

    Febrile neutropenia caused by chemotherapy is a frequent medical emergency associated with severe complications in the emergency department (ED). Timely administration of antibiotics is believed to improve patient outcomes for several infectious diseases such as pneumonia and sepsis but has not been thoroughly evaluated for reducing risk of complications in chemotherapy-induced febrile neutropenia. The aim of this study was to evaluate associations between the risk factors and serious complications in patients presenting to the ED with febrile neutropenia. We reviewed the health information system database to identify a retrospective cohort of patients with febrile neutropenia who visited the ED of a tertiary medical hospital from January to December 2008. Only episodes of febrile neutropenia caused by chemotherapy for underlying cancer were included. Serious complications during hospitalization were defined as unstable hemodynamic status, respiratory distress, altered mental status, newly developed arrhythmia that required intervention, and death during hospitalization. Univariate and multivariate logistic regression analysis was performed to determine potential factors associated with serious complications. We further use decision tree approach to help analyze variables. Among a total of 81 febrile neutropenic episodes in 78 patients, 25 (30.8%) episodes of serious complications were identified. Latency of the first dose of antibiotics, pneumonia and platelet counts???50,000/mm(3) were identified as independent factors associated with serious complications of febrile neutropenia. Earlier administration of antibiotics is associated with fewer complications in patients presenting to the ED with febrile neutropenia. PMID:23303687

  7. Clinical practice in febrile neutropenia risk assessment and granulocyte colony-stimulating factor primary prophylaxis of febrile neutropenia in Poland

    PubMed Central

    Chmielowska, Ewa; Filipczyk-Cisar?, Emilia; Krzemieniecki, Krzysztof; Le?niewski-Kmak, Krzysztof; Litwiniuk, Maria M.; Wieruszewska-Kowalczyk, Karolina; Kosno-Kruszewska, El?bieta

    2014-01-01

    Aim of the study The first aim was to investigate the knowledge and awareness of oncologists concerning febrile neutropenia (FN) risk assessment and indications for granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (PP), based on current therapeutic guidelines (PTOK and EORTC). The second aim was to educate the oncologists on best practices for risk assessment and neutropenia management. Material and methods The project participants included 169 oncologists from 7 regions working in large specialist oncological centres, university hospitals, regional and city hospitals, specialist outpatient clinics, and oncological wards in small local hospitals. The participants completed a questionnaire based on seven prepared clinical cases of patients with different tumour types and patient characteristics, receiving chemotherapy (CT), and with different levels of FN risk. Participants answered questions related to FN risk assessment and G-CSF use. After completing the questionnaire, the participants proceeded to an educational module in which they were provided with an analysis of correct diagnostic and therapeutic procedures according to the PTOK and EORTC guidelines. Results and Conclusions Febrile neutropenia risk assessment was found to be a routine procedure performed for over 90% of the clinical cases by the participant oncologists. However, the FN risk assessment of clinical cases was correct and consistent with therapeutic guidelines in only 65% of responses. Indications for G-CSF PP were properly identified in 76% of responses and it appeared that indications for G-CSF PP were more likely to be correctly identified in patients receiving high-risk or low-risk regimens than in those receiving intermediate-risk regimens, where the decision to give G-CSF PP is based on additional assessment of patient risk factors. The vast majority of participants who correctly identified the need for PP administered G-CSF in accordance with the dose and schedule recommended by PTOK and EORTC. PMID:25784841

  8. Management of febrile neutropenia in the era of bacterial resistance

    PubMed Central

    Alp, Sehnaz

    2013-01-01

    Managing cancer patients with fever and neutropenia must be considered as a medical emergency since any delay in initiating appropriate empirical antibacterial therapy may result in high rates of mortality and morbidity. Emerging antibacterial resistance in bacterial pathogens infecting febrile neutropenic patients complicates management, and choosing the type of empirical antimicrobial therapy has become a challenge. To further complicate the decision process, not all neutropenic patients are in same category of susceptibility to develop severe infection. While low-risk patients may be treated with oral antibiotics in the outpatient setting, high-risk patients usually need to be admitted to hospital and receive parenteral broad-spectrum antibiotics until the neutrophil levels recover. These strategies have recently been addressed in two international guidelines from the Infectious Diseases Society of America (IDSA) and the European Conference on Infections in Leukaemia (ECIL). This review gives a brief overview of current antimicrobial resistance problems and their effects in febrile neutropenic cancer patients by summarizing the suggestions from the IDSA and ECIL guidelines. PMID:25165543

  9. Clinical practice in secondary prophylaxis and management of febrile neutropenia in Poland: results of the febrile neutropenia awareness project

    PubMed Central

    Chmielowska, Ewa; Filipczyk-Cisar?, Emilia; Krzemieniecki, Krzysztof; Le?niewski-Kmak, Krzysztof; Litwiniuk, Maria M.; Wieruszewska-Kowalczyk, Karolina; Kosno-Kruszewska, El?bieta

    2014-01-01

    Aim of the study This paper presents the second part of the GoPractice project involving oncologists from seven Polish provinces. The aim of this part of the project was to assess the knowledge of oncologists on indications for granulocyte colony-stimulating factor (G-CSF) secondary prophylaxis (SP) of febrile neutropenia (FN) and FN management based on current therapeutic guidelines (Polish Society of Clinical Oncology [PTOK] and European Organisation for Research and Treatment of Cancer [EORTC]). Material and methods The project involved 169 oncologists from 7 regions working in large specialist oncological centers, university hospitals, regional and city hospitals, specialist outpatient clinics and oncological wards in small, local hospitals. The participants completed a questionnaire based on 7 prepared clinical cases of patients with different tumor types and patient characteristics, receiving chemotherapy (CT) with different levels of FN risk. Participants answered questions related to FN risk assessment and G-CSF use as secondary prophylaxis (SP) and for the management of FN. After completing the questionnaire, the participants proceeded to an educational module in which they were provided with an analysis of correct diagnostic and therapeutic procedures according to the PTOK and EORTC guidelines. Results and Conclusions Indications for G-CSF SP were generally well recognized: in nearly 90% of responses, oncologists assessed correctly indications/lack of indications for secondary prophylaxis, in accordance with guideline recommendations and Experts’ opinion. However, the use of daily G-CSFs was often recommended by the study participants for the management of FN. This clinical practice is contradictory to PTOK and EORTC recommendations and may unnecessarily increase treatment costs. Changing this clinical approach may be achieved through regular training to improve guideline adherence. PMID:25784842

  10. HEDS Discussion Paper: Cost-effectiveness of G-CSFs for febrile neutropenia prophylaxis in breast cancer: Whyte et al

    E-print Network

    Oakley, Jeremy

    prophylaxis in breast cancer: Whyte et al - 2 - #12;HEDS Discussion Paper: Cost-effectiveness of G-CSFs for febrile neutropenia prophylaxis in breast cancer: Whyte et al - 3 - Cost-effectiveness of granulocyte colony- stimulating factor prophylaxis for febrile neutropenia in breast cancer in the United Kingdom

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

    PubMed

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

    2014-04-01

    Aspergillosis usually compromises the respiratory system, but can also affect others. We report a 46 yo female with acute myeloid leukemia, developed febrile neutropenia and dysphagia. Endoscopy revealed esophageal cytomegalovirus-like ulcers, but biopsies showed Aspergillus spp. It's important to consider aspergillosis in the differential diagnosis of esophageal lesions in high-risk patients. PMID:24878914

  12. Pharmacodynamics and pharmacokinetics of antibacterial drugs in the management of febrile neutropenia.

    PubMed

    Lortholary, Olivier; Lefort, Agnès; Tod, Michel; Chomat, Anne-Marie; Darras-Joly, Clémence; Cordonnier, Catherine

    2008-10-01

    We review experimental and clinical data on the pharmacokinetics and pharmacodynamics of antibacterial drugs in febrile neutropenic hosts. Since major pharmacokinetic changes have been reported for various classes of antibiotics in these patients, we advocate the need for adequate initial dosing regimens in all cases. Monitoring drug serum concentrations is mandatory for aminoglycosides and glycopeptides, and special attention should be paid to the dosing frequency of the short half-life beta-lactams to optimise the management of febrile neutropenia, especially in patients with severe sepsis. PMID:18922483

  13. Time to antibiotics and outcomes in cancer patients with febrile neutropenia

    PubMed Central

    2014-01-01

    Background Febrile neutropenia is an oncologic emergency. The timing of antibiotics administration in patients with febrile neutropenia may result in adverse outcomes. Our study aims to determine time-to- antibiotic administration in patients with febrile neutropenia, and its relationship with length of hospital stay, intensive care unit monitoring, and hospital mortality. Methods The study population was comprised of adult cancer patients with febrile neutropenia who were hospitalized, at a tertiary care hospital, between January 2010 and December 2011. Using Multination Association of Supportive Care in Cancer (MASCC) risk score, the study cohort was divided into high and low risk groups. A multivariate regression analysis was performed to assess relationship between time-to- antibiotic administration and various outcome variables. Results One hundred and five eligible patients with median age of 60 years (range: 18–89) and M:F of 43:62 were identified. Thirty-seven (35%) patients were in MASCC high risk group. Median time-to- antibiotic administration was 2.5 hrs (range: 0.03-50) and median length of hospital stay was 6 days (range: 1–57). In the multivariate analysis time-to- antibiotic administration (regression coefficient [RC]: 0.31 days [95% CI: 0.13-0.48]), known source of fever (RC: 4.1 days [95% CI: 0.76-7.5]), and MASCC high risk group (RC: 4 days [95% CI: 1.1-7.0]) were significantly correlated with longer hospital stay. Of 105 patients, 5 (4.7%) died & or required ICU monitoring. In multivariate analysis no variables significantly correlated with mortality or ICU monitoring. Conclusions Our study revealed that delay in antibiotics administration has been associated with a longer hospital stay. PMID:24716604

  14. Independent Factors for Prediction of Poor Outcomes in Patients with Febrile Neutropenia

    PubMed Central

    Günalp, Müge; Koyuno?lu, Merve; Gürler, Serdar; Koca, Ayça; Ye?ilkaya, ?lker; Öner, Emre; Akka?, Meltem; Aksu, Nalan Metin; Demirkan, Arda; Polat, Onur; Elhan, Atilla Halil

    2014-01-01

    Background Febrile neutropenia (FN) is a life-threatening condition that requires urgent management in the emergency department (ED). Recent progress in the treatment of neutropenic fever has underscored the importance of risk stratification. In this study, we aimed to determine independent factors for prediction of poor outcomes in patients with FN. Material/Methods We retrospectively evaluated 200 chemotherapy-induced febrile neutropenic patients who visited the ED. Upon arrival at the ED, clinical data, including sex, age, vital signs, underlying systemic diseases, laboratory test results, estimated GFR, blood cultures, CRP, radiologic examinations, and Multinational Association of Supportive Care in Cancer (MASCC) score of all febrile neutropenic patients were obtained. Outcomes were categorized as “poor” if serious complications during hospitalization, including death, occurred. Results The platelet count <50 000 cells/mm3 (OR 3.90, 95% CI 1.62–9.43), pulmonary infiltration (OR 3.45, 95% CI 1.48–8.07), hypoproteinemia <6 g/dl (OR 3.30, 95% CI 1.27–8.56), respiratory rate >24/min (OR 8.75, 95% CI 2.18–35.13), and MASCC score <21 (OR 9.20, 95% CI 3.98–21.26) were determined as independent risk factors for the prediction of death. The platelet count <50 000 cells/mm3 (OR 3.93, 95% CI 1.42–10.92), serum CRP >50 mg/dl (OR 3.80, 95% CI 1.68–8.61), hypoproteinemia (OR 7.81, 95% CI 3.43–17.78), eGFR ?90 ML/min/1.73 m2 (OR 3.06, 95% CI 1.13–8.26), and MASCC score <21 (OR 3.45, 95% CI 1.53–7.79) were determined as independent risk factors for the prediction of poor clinical outcomes of FN patients. Platelet count, protein level, respiratory rate, pulmonary infiltration, CRP, MASCC score, and eGFR were shown to have a significant association with outcome. Conclusions The results of our study may help emergency medicine physicians to prevent serious complications with proper use of simple independent risk factors besides MASCC score. PMID:25282155

  15. Once daily ceftriaxone and gentamicin for the treatment of febrile neutropenia

    PubMed Central

    Tomlinson, R.; Ronghe, M.; Goodbourne, C.; Price, C.; Lilleyman, J.; Das, S.; Saha, V.

    1999-01-01

    AIMS—To evaluate the pharmacokinetics of once daily (OD) gentamicin and its effectiveness as part of an OD regimen for the empirical treatment of febrile neutropenia in children with cancer.?SUBJECTS—59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) with febrile neutropenia (neutrophil count < 0.5 × 109/l) after chemotherapy.?METHODS—Over one year, 113 febrile neutropenic episodes were treated empirically with an OD antibiotic regimen of ceftriaxone (80 mg/kg; maximum 4 g) and gentamicin (7 mg/kg; infused over 60 minutes, no maximum). The patients were assessed after 48hours.?RESULTS—86 of the 113 episodes settled with the first line antibiotic regimen. In 29 episodes, blood cultures identified a causative bacterial pathogen; for 17 of these, the first line antibiotic regimen was adequate; in four episodes, although the episode settled, ceftriaxone was replaced by a more appropriate antibiotic and OD gentamicin was continued; in the remaining eight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseudomonas aeruginosa. In 27 episodes (24%), resolution was obtained by the empirical introduction of a second line regimen of ceftazidime and a glycopeptide antibiotic, and/or amphotericin. Gentamicin concentrations were measured in 110 episodes and they were all below the 24 hour line indicating that there was no need to change the dosing interval. In two episodes (2%), serum creatinine rose transiently by more than 50% of the baseline concentration. Although there was no vestibular toxicity, three of 30 children who underwent pure tone audiometry reported high frequency hearing loss in one ear.?CONCLUSION—OD gentamicin can be used safely and effectively to treat febrile neutropenia in children with cancer. When used for a short period (< 5 days), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary.?? PMID:10325726

  16. Rates of febrile neutropenia with pegfilgrastim on same day versus next day of CHOP with or without rituximab.

    PubMed

    Cheng, Connie; Gallagher, Erika M; Yeh, Jun-Yen; Earl, Marc A

    2014-09-01

    Febrile neutropenia is a complication of myleotoxic chemotherapy that can markedly decrease quality of life and increase healthcare costs. A granulocyte-colony stimulating factor (G-CSF) is used to increase neutrophil production to reduce the risk of developing febrile neutropenia. However, G-CSF administered on the same day as chemotherapy can worsen and prolong neutropenia. To study and compare the effects of pegfilgrastim on the incidence of febrile neutropenia and grade 4 neutropenia in patients receiving pegfilgrastim on the same day (day 1) versus the next day (day 2 or beyond) of chemotherapy, a retrospective, single-center, nonrandomized, cohort study was carried out of adult non-Hodgkin's lymphoma patients who received pegfilgrastim 6 mg subcutaneously on day 1 or beyond of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with or without rituximab every 3 weeks. Six hundred and fifty-five chemotherapy cycles (320 cycles for the same day and 335 cycles for the next day) were evaluable in 141 patients. Among all cycles, the incidence of febrile neutropenia was 9.4 versus 5.1% in the same-day versus the next-day group (P=0.03). The incidence of febrile neutropenia was the highest after the first cycle in the same-day group, which was 19.4, versus 11.1% for the next-day group (P=0.27). There were three deaths among patients who developed febrile neutropenia, including two in the next-day group versus one in the same-day group. In conclusion, our findings support the need for a randomized phase III study to fully evaluate whether a G-CSF is safer when administered on the next day versus the same day of chemotherapy. PMID:24743519

  17. Febrile neutropenia in adjuvant docetaxel and cyclophosphamide (TC) with prophylactic pegfilgrastim in breast cancer patients: a retrospective analysis

    Microsoft Academic Search

    Nuttapong Ngamphaiboon; Tracey L. O’Connor; Pooja P. Advani; Ellis G. Levine; Ellen B. Kossoff

    US Oncology Research Trial 9735 reported that TC improved overall survival when compared to doxorubicin and cyclophosphamide\\u000a in early-stage breast cancer. Despite 61% grades 3–4 neutropenia in the TC arm, only 5% of patients developed febrile neutropenia\\u000a (FN) without primary prophylactic GCSF (ppGCSF). TC has risen in popularity, particularly in older patients or in those where\\u000a an anthracycline is contraindicated.

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

    PubMed

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

    2015-05-01

    The primary objective of this review was to identify the cost components that were most frequently associated with the economic burden of febrile neutropenia (FN) among patients with lymphoma. The secondary objective was to identify any parameter associated with higher FN cost. Ten cost of illness (COI) studies were identified. General characteristics on study design, country, perspective, and patient population were extracted and systematically reported. It was observed that majority (70%) of the studies employed the perspective of healthcare provider. 20% of the studies considered long-term costs. Estimated costs were adjusted to 2013 US dollars and ranged from US$5819 to US$34,756. The cost components that were most frequently associated with economic burden were ward and medication costs. Inpatient management, male gender, discharged dead, and comorbidity were positively associated with higher FN costs. Future COI studies on FN should focus on the accurate estimation on ward and medication costs. PMID:25600838

  19. [Procalcitonin as a predictor of bacteremia in pediatric patients with malignancies and febrile neutropenia].

    PubMed

    Aliyev, D A; Vezirova, Z Sh; Geyusheva, T F

    2015-02-01

    Dynamics of procalcitonin level was studied in 75 pediatric patients, in whom on back- ground of polychemotherapy conduction for oncological disease bacteremia and neutropenia have occurred. Determination of procalcitonin level as a rapidly reacting biomarker of generalized infectious process permits to establish its progression, to con- duct early diagnosis, to perform timely and adequate treatment measures. PMID:25985703

  20. Persistent Tn polyagglutination syndrome during febrile neutropenia: a case report and review of the literature

    PubMed Central

    2011-01-01

    Introduction Tn polyagglutination syndrome is a rare disorder that has been reported on only a few occasions in the literature, and, to the best of our knowledge, never before in the context of febrile neutropenia. Case presentation We report the case of a 26-year-old Caucasian woman who presented to our emergency department complaining of a persistent fever over the previous three days. She had a history of long-standing refractory pancytopenia with multi-lineage dysplasia and severe neutropenia, but she had rarely experienced infection. The results of a physical examination and multiple laboratory tests were unremarkable. While investigating the possible causes of the refractory, long-standing pancytopenia, the possibility of a polyagglutinable state was suggested. Blood samples were sent to the laboratory for an analysis of mixed-field seed lectin agglutination assay. A serum lectin panel confirmed the final diagnosis of Tn-activation. Conclusions We should include Tn-activation in our differential whenever we encounter cases of refractory long-standing idiopathic cytopenias and inconclusive bone marrow results displaying multi-lineage dysplasia. Novel genetic techniques have recently revealed the interesting pathophysiology of this phenomenon. The recognition and inclusion of Tn polyagglutination syndrome in our differential diagnoses has important clinical implications, given its main associated features, such as severe thrombocytopenia and neutropenia, which are usually linked to a benign clinical course and prognosis. Increased awareness of the polyagglutinable disorders will potentially decrease the need for invasive and costly medical interventions and also raises the need for monitoring of this specific sub-set of patients. In addition, the study of the expression and implications of Tn, and other similar antigens, offers a fascinating perspective for the study of its role in the diagnosis, prognosis and immunotherapy of solid tumors and hematological malignancies. The infrequency with which Tn polyagglutination syndrome is encountered, its clinical features and its pathophysiology make it a formidable diagnostic challenge. PMID:21235740

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

    PubMed Central

    2011-01-01

    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. PMID:21943360

  2. Evaluation of six risk factors for the development of bacteremia in children with cancer and febrile neutropenia

    PubMed Central

    Asturias, E.J.; Corral, J.E.; Quezada, J.

    2010-01-01

    Febrile neutropenia is a well-known entity in children with cancer, being responsible for the high risk for infection that characterizes this population. For this reason, cancer patients are hospitalized so that they can receive prophylactic care. Risk factors have been used to classify patients at a high risk for developing bacteremia. The present study evaluates whether those risk factors (C-reactive protein, hypotension, leukemia as the cancer type, thrombocytopenia, recent chemotherapy, and acute malnutrition) apply to patients at the Unidad Nacional de Oncología Pediátrica. We evaluated 102 episodes in 88 patients, in whom risk factors and blood cultures were tested. We observed no statistical relationship between the six risk factors and bacteremia. There was also no relationship between bacteremia and the simultaneous presence of two, three, or more risk factors. A significant relationship of C-reactive protein and platelet count with other outcome factors was observed. PMID:20404980

  3. Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia

    PubMed Central

    Wong, Michelle; Barqasho, Babilonia; Öhrmalm, Lars; Tolfvenstam, Thomas; Nowak, Piotr

    2013-01-01

    In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p?=?0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p?=?0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p?=?0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p?=?0.0212). PMID:23874493

  4. Colony-stimulating factors for chemotherapy-related febrile neutropenia are associated with improved prognosis in adult acute lymphoblastic leukemia

    PubMed Central

    YE, SHI-GUANG; DING, YI; LI, LIANG; YANG, MENG; ZHANG, WEN-JUN; LIANG, AI-BIN

    2015-01-01

    Colony-stimulating factors (CSF) have been widely used to prevent febrile neutropenia associated with chemotherapy. Due to the high intensity of chemotherapy in acute lymphoblastic leukemia (ALL), CSF as a crucial component of supportive care has played a significant role in the therapy. However, the effectiveness of CSF in treatment has not been identified by large clinical trials until now. The aim of the present study was to evaluate the effect of CSF on the long-term outcome of adult ALL patients. A comprehensive search strategy has been conducted, which covered the Cochrane Central Register of Controlled Trials, PubMed and Web of Science. The result includes seven randomized controlled trials containing a total of 753 patients. The administration of CSF significantly reduced the mortality at the end of the follow-up (RR, 0.85; 95% CI, 0.75–0.95), the mortality at day 30 (RR, 0.41; 95% CI, 0.23–0.74) and the number of patients with infection or severe infections (RR, 0.8; 95% CI, 0.7–0.9 and RR, 0.48; 95% CI, 0.3–0.75). The addition of CSF also marginally increased the number of patients achieving CR (RR, 1.14; 95% CI, 1.05–1.23). The use of CSF also shortened the duration of neutropenia (median days, 8–17 to 12.5–24). In conclusion, CSFs can be administered to ALL patients during myelosuppressive chemotherapy, particularly in the induction phase.

  5. Frequency of Febrile Neutropenia in Breast Cancer Patients Receiving Epirubicin and Docetaxel\\/Paclitaxel with Colony-Stimulating Growth Factors: A Comparison of Filgrastim or Lenograstim with Pegfilgrastim

    Microsoft Academic Search

    Walter Schippinger; Robert Holub; Nadia Dandachi; Thomas Bauernhofer; Hellmut Samonigg

    2006-01-01

    Objective: Recombinant granulocyte colony-stimulating factors (G-CSF) have been shown to be effective in reducing the risk of infections associated with antitumour chemotherapy. This report describes a single-centre experience of the efficacy of pegfilgrastim compared with filgrastim or lenograstim in reducing the incidence of febrile neutropenia in patients receiving combination chemotherapy with taxane and epirubicin in a neoadjuvant and adjuvant setting.

  6. Management of Febrile Neutropenia – a German Prospective Hospital Cost Analysis in Lymphoproliferative Disorders, Non-Small Cell Lung Cancer, and Primary Breast Cancer

    Microsoft Academic Search

    Angela Ihbe-Heffinger; Bernadette J. Paessens; Christoph von Schilling; Margarita Shlaen; Nina Gottschalk; Karin Berger; Rudolf Bernard; Marion Kiechle; Christian Peschel; Volker R. Jacobs

    2011-01-01

    SummaryBackground: Febrile neutropenia\\/leukopenia (FN\\/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. Patients and Methods: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN\\/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast

  7. The economics of febrile neutropenia: implications for the use of colony-stimulating factors 1 Presented in part at the 38th Annual Meeting of the American Society of Hematology, Orlando, Florida, December 1996. 1

    Microsoft Academic Search

    G. H Lyman; N Kuderer; J Greene; L Balducci

    1998-01-01

    The occurrence of fever and neutropenia following cancer chemotherapy generally prompts hospitalisation for evaluation and treatment. Colony-stimulating factors (CSFs) have been shown to reduce the risk of febrile neutropenia (FN) and the need for hospitalisation in such patients. This study was undertaken to obtain estimates of the actual institutional costs associated with FN and the impact of these costs on

  8. The cost of the inpatient management of febrile neutropenia in cancer patients--a micro-costing study in the Irish healthcare setting.

    PubMed

    O'Brien, C; Fogarty, E; Walsh, C; Dempsey, O; Barry, M; Kennedy, M J; McCullagh, L

    2015-01-01

    The objective was to evaluate the resource use and cost of hospitalisation for febrile neutropenia (FN) from the health-payer's perspective. This was a single centre study. Adults undergoing chemotherapy, who were admitted for FN, were identified prospectively. Patient medical records were reviewed retrospectively. Demographics and resource utilisation data were obtained from a cohort of 32 patients (69% female, mean age?=?58.8 years). Twenty-five per cent of patients had more than one FN episode. In total, 42 FN episodes were captured; 60% of episodes had occurred within the first two cycles of chemotherapy. The bootstrap estimation was used to determine mean hospital length of stay (LOS) with standard deviation (±SD) and mean costs ± SD. The mean LOS was 7.3?±?0.5 days. The mean cost per FN episode was €8915?±?718. The major cost driver was hospital bed-stay (mean cost of €6851?±?549). Other cost drivers included antibacterial treatment at €760?±?156, laboratory investigations at €538?±?47 and the requirement for blood bank products at €525?±?189. To our knowledge, this is the first investigation of the cost of chemotherapy induced FN within the context of the Irish healthcare setting. PMID:24472035

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

    PubMed

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

    2015-03-01

    There is paucity of information from eastern India with regard to observed dominant micro-organisms causing febrile neutropenia (FN) in patients with haematological malignancies. To identify the prevalence of pathogenic microorganisms associated with FN. A total number of 268 episodes of FN were analysed from September'2010 to October'2013. The blood samples were inoculated into brain heart infusion broth, glucose broth, Hicombi dual performance media (Himedia, LQ-12) at 37° C for 168 h and Bactec method was also performed for these samples. Blood agar, chocolate agar, MacConkey's agar and cystine lactose electrolyte deficient agar were used for isolation of the microorganisms. A total number of 78 (29.10 %) episodes revealed positive growths. Gram negative bacilli and Gram positive cocci were isolated in 61.53 and 34.61 % cases respectively. The eight commonest isolates were Pseudomonas aeruginosa (14.10 %), methicillin resistant Staphylococcus aureus (MRSA-12.82 %), Acinetobacter sps (11.53 %), coagulase negative Staphylococcus (10.25 %), Klebsiella pneumoniae (8.97 %), Escherichia coli (8.97 %), ESBL E. coli (6.41 %), methicillin sensitive S. aureus (MSSA-6.41 %). Amongst other less common isolates were Citrobacter kosseri (3.84 %), Citrobacter freundii (2.56 %), Ralstonia paucula (2.56 %), Cedecia neteri (1.28 %), methicillin resistant coagulase negative Staphylococcus (2.56 %). Candida spp. including two cases of Candida non-albicans was isolated in 3.84 % of cases. P. aeruginosa was the commonest pathogenic isolates in FN patients associated with haematological malignancies in this study. Gram negative bacteria were the commonest isolates in FN including significant numbers of rare opportunistic micro-organisms. PMID:25548444

  10. Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies

    PubMed Central

    2013-01-01

    Background During febrile neutropenia in only 30 to 60 percent an infectious agent is identified. This diagnostic gap could hypothetically be reduced with the broad implementation of molecular detection techniques like PCR, which has revolutionized the detection of infectious diseases during the last two decades. Findings We performed a longitudinal prospective study (N = 81) of neutropenic patients to assess the role of respiratory viruses in neutropenic fever and to determine the clinical relevance of blind screening for these viruses. Respiratory viruses were recovered in 14% of the patients prior to neutropenia. In 13% of neutropenic patients without fever and in 19% of those with fever, a respiratory virus was detected. Comparing different sample types; nasal swabs performed significantly better (16/117 = 43%), than throat swabs (6/106 = 6%). Throat gurgles did not show significant differences from the latter sample types. Conclusions Blind diagnostic screening for respiratory viruses before or during neutropenia is not useful. Nasal swabs are sensitive and practical option for screening on respiratory viruses. PMID:23805898

  11. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    PubMed Central

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I.; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    Introduction: Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. Materials and Methods: This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Results: Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Conclusion: Our findings have major implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes. PMID:25729741

  12. Monitoring Procalcitonin in Febrile Neutropenia: What Is Its Utility for Initial Diagnosis of Infection and Reassessment in Persistent Fever?

    PubMed Central

    Bally, Frank; Knaup, Marlies; Calandra, Thierry; Marchetti, Oscar

    2011-01-01

    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; p<0.001). PCT >500 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. PMID:21541027

  13. Grade 4 febrile neutropenia and Fournier’s Syndrome associated with triple therapy for hepatitis C virus: A case report

    PubMed Central

    Oliveira, Kelly Cristhian Lima; Cardoso, Emili de Oliveira Bortolon; de Souza, Suzana Carla Pereira; Machado, Flávia Souza; Zangirolami, Carlos Eduardo Alves; Moreira, Alecsandro; Silva, Giovanni Faria; de Oliveira, Cássio Vieira

    2014-01-01

    The use of triple therapy for hepatitis C not only increases the rate of sustained virological responses compared with the use of only interferon and ribavirin (RBV) but also leads to an increased number of side effects. The subject of this study was a 53-year-old male who was cirrhotic with hepatitis C virus genotype 1 A and was a previous null non-responder. We initially attempted retreatment with boceprevir (BOC), Peg-interferon and RBV, and a decrease in viral load was observed in the 8th week. In week 12, he presented with disorientation, flapping, fever, tachypnea, arterial hypotension and tachycardia. He also exhibited leucopenia with neutropenia. Cefepime and filgrastim were initiated, and treatment for hepatitis C was suspended. A myelogram revealed hypoplasia, cytotoxicity and maturational retardation. After 48 h, he developed bilateral inguinal erythema that evolved throughout the perineal area to the root of the thighs, with exulcerations and an outflow of seropurulent secretions. Because we hypothesized that he was suffering from Fournier’s Syndrome, treatment was replaced with the antibiotics imipenem, linezolid and clindamycin. After this new treatment paradigm was initiated, his lesions regressed without requiring surgical debridement. Triple therapy requires knowledge regarding the management of adverse effects and drug interactions; it also requires an understanding of the importance of respecting the guidelines for the withdrawal of treatment. In this case report, we observed an adverse event that had not been previously reported in the literature with the use of BOC. PMID:25018856

  14. Grade 4 febrile neutropenia and Fournier's Syndrome associated with triple therapy for hepatitis C virus: A case report.

    PubMed

    Oliveira, Kelly Cristhian Lima; Cardoso, Emili de Oliveira Bortolon; de Souza, Suzana Carla Pereira; Machado, Flávia Souza; Zangirolami, Carlos Eduardo Alves; Moreira, Alecsandro; Silva, Giovanni Faria; de Oliveira, Cássio Vieira

    2014-06-27

    The use of triple therapy for hepatitis C not only increases the rate of sustained virological responses compared with the use of only interferon and ribavirin (RBV) but also leads to an increased number of side effects. The subject of this study was a 53-year-old male who was cirrhotic with hepatitis C virus genotype 1 A and was a previous null non-responder. We initially attempted retreatment with boceprevir (BOC), Peg-interferon and RBV, and a decrease in viral load was observed in the 8(th) week. In week 12, he presented with disorientation, flapping, fever, tachypnea, arterial hypotension and tachycardia. He also exhibited leucopenia with neutropenia. Cefepime and filgrastim were initiated, and treatment for hepatitis C was suspended. A myelogram revealed hypoplasia, cytotoxicity and maturational retardation. After 48 h, he developed bilateral inguinal erythema that evolved throughout the perineal area to the root of the thighs, with exulcerations and an outflow of seropurulent secretions. Because we hypothesized that he was suffering from Fournier's Syndrome, treatment was replaced with the antibiotics imipenem, linezolid and clindamycin. After this new treatment paradigm was initiated, his lesions regressed without requiring surgical debridement. Triple therapy requires knowledge regarding the management of adverse effects and drug interactions; it also requires an understanding of the importance of respecting the guidelines for the withdrawal of treatment. In this case report, we observed an adverse event that had not been previously reported in the literature with the use of BOC. PMID:25018856

  15. Cost-effectiveness of prophylactic granulocyte colony-stimulating factor for febrile neutropenia in breast cancer patients receiving FEC-D.

    PubMed

    Lee, Esther K; Wong, William W L; Trudeau, Maureen E; Chan, Kelvin K W

    2015-02-01

    5-fluorouracil, epirubicin, cyclophosphamide ? docetaxel (FEC-D) has been associated with higher-than-expected rates of febrile neutropenia (FN) that meet the current guideline threshold of 20 % for primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF). We examined the cost-effectiveness of FEC-D with varying strategies of G-CSF prophylaxis from the perspective of the public payer in Ontario, Canada. A state-transition model was developed to compare three strategies: FEC-D with secondary prophylaxis (SP) only, PP starting with the first cycle of D, and PP starting with the first cycle of FEC. Analysis was conducted for a hypothetical cohort of 50-year-old early-stage breast cancer patients undergoing adjuvant chemotherapy, at a 10-year horizon. Results were expressed in quality-adjusted life-years (QALYs) and 2013 Canadian dollars. Costs and benefits were discounted at 5 %. Event rates, costs, and utilities were derived from the literature. One-way and probabilistic sensitivity analyses were conducted. Using filgrastim, the incremental cost-effectiveness ratios (ICERs) for starting PP with the first cycle of D and starting PP with the first cycle of FEC, compared to using SP only, were $57,886/QALY and $116,186/QALY, respectively. With pegfilgrastim, the ICERs for the same strategies were $90,735/QALY and $149,483/QALY. Compared to using filgrastim SP only, starting PP with D had a 24 % chance of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY, and a 99 % chance at a WTP threshold of $100,000/QALY. Results were sensitive to FN-related parameters, such as the risk of FN per cycle with D and the associated mortality, but were robust to uncertainty in parameters related to breast cancer, such as the utilities and hazard of relapse. FEC-D with PP starting with the first cycle of D is most likely to be cost-effective, especially with increased risk of FN and mortality from FN. PMID:25694355

  16. Pegfilgrastim Administered on the Same Day with Dose-Dense Adjuvant Chemotherapy for Breast Cancer Is Associated with a Higher Incidence of Febrile Neutropenia as Compared to Conventional Growth Factor Support: Matched Case-Control Study of the Hellenic Cooperative Oncology Group

    Microsoft Academic Search

    Dimosthenis V. Skarlos; Eleni Timotheadou; Eleni Galani; Epaminondas Samantas; Irene Grimani; Evangelos Lianos; Gerasimos Aravantinos; Ioannis Xanthakis; George Pentheroudakis; Dimitrios Pectasides; George Fountzilas

    2009-01-01

    Objective: Recombinant human granulocyte-colony-stimulating factors such as filgrastim and pegfilgrastim have been employed as primary and secondary prophylaxis against neutropenia in cancer patients receiving chemotherapy. This study was conducted to evaluate the rate of febrile neutropenia in patients with high-risk early breast cancer receiving dose-dense chemotherapy and, as primary prophylaxis, either pegfilgrastim 6 mg fixed dose on the same day

  17. Review: Drug-Induced Neutropenia - Pathophysiology, Clinical Features, and Management

    Microsoft Academic Search

    Varsha Bhatt; Abdus Saleem

    Drug therapy plays a significant role in causing neutropenia. The neutropenia may be immune mediated or due to direct inhibition of the bone marrow precursors. Recently, due to wide use of chemotherapy, febrile neutropenia has become a common and devastating problem. Neutropenia predisposes to many bacterial and fungal infections with organisms including Gram negative bacilli such as E. coli, Klebsiella,

  18. Febrile neutropenia and related complications in breast cancer patients receiving pegfilgrastim primary prophylaxis versus current practice neutropaenia management: Results from an integrated analysis

    Microsoft Academic Search

    G. von Minckwitz; M. Schwenkglenks; T. Skacel; G. H. Lyman; A. Lopez Pousa; P. Bacon; V. Easton; M. S. Aapro

    2009-01-01

    Granulocyte colony-stimulating factors (G-CSFs) reduce febrile neutropaenia (FN) incidence but may be used inconsistently in current practice (CP). This study compared the efficacy of pegfilgrastim primary prophylaxis (PPP) with CP neutropaenia management in breast cancer. Individual patient data (N=2282) from 11 clinical trials and observational studies using chemotherapy regimens with ?15% FN risk and PPP (6mg, all cycles) or CP

  19. Neulasta (pegfilgrastim): a once-per-cycle option for the management of chemotherapy-induced neutropenia

    Microsoft Academic Search

    Laura Biganzoli; Michael Untch; Tomas Skacel; José-Luis Pico

    2004-01-01

    Neutropenia is a significant hematologic complication induced by cytotoxic chemotherapy. The clinical consequences of chemotherapy-induced neutropenia are often severe and can be potentially life-threatening. Patients who develop febrile neutropenia often need to be hospitalized, reducing their quality of life and increasing costs. Neutropenia can also compromise the ability to deliver chemotherapy at the full dose and on schedule. To help

  20. Molecular nature of antigens implicated in immune neutropenias

    Microsoft Academic Search

    Juergen Bux

    2002-01-01

    Granulocyte (neutrophil) antibodies can cause autoimmune neutropenia, drug-induced neutropenia, immune neutropenia after bone\\u000a marrow transplantation, neonatal immune neutropenia, refractoriness to granulocyte transfusions as well as febrile and pulmonary\\u000a transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens.\\u000a In 1998, the Granulocyte Antigen Working Party of the ISBT introduced a new nomenclature

  1. Clinical characteristics and antimicrobial susceptibilities of viridans streptococcal bacteremia during febrile neutropenia in patients with hematologic malignancies: a comparison between adults and children

    PubMed Central

    2013-01-01

    Background This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies. Methods The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB. Results A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome. Conclusions There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary. PMID:23773209

  2. Febrile seizures

    PubMed Central

    2014-01-01

    Febrile seizure (FS) is the most common seizure disorder of childhood, and occurs in an age-related manner. FS are classified into simple and complex. FS has a multifactorial inheritance, suggesting that both genetic and environmental factors are causative. Various animal models have elucidated the pathophysiological mechanisms of FS. Risk factors for a first FS are a family history of the disorder and a developmental delay. Risk factors for recurrent FS are a family history, age below 18 months at seizure onset, maximum temperature, and duration of fever. Risk factors for subsequent development of epilepsy are neurodevelopmental abnormality and complex FS. Clinicians evaluating children after a simple FS should concentrate on identifying the cause of the child's fever. Meningitis should be considered in the differential diagnosis for any febrile child. A simple FS does not usually require further evaluation such as ordering electroencephalography, neuroimaging, or other studies. Treatment is acute rescue therapy for prolonged FS. Antipyretics are not proven to reduce the recurrence risk for FS. Some evidence shows that both intermittent therapy with oral/rectal diazepam and continuous prophylaxis with oral phenobarbital or valproate are effective in reducing the risk of recurrence, but there is no evidence that these medications reduce the risk of subsequent epilepsy. Vaccine-induced FS is a rare event that does not lead to deleterious outcomes, but could affect patient and physician attitudes toward the safety of vaccination. PMID:25324864

  3. Febrile Seizures

    MedlinePLUS

    ... febrile seizures face an increased risk of developing epilepsy. These children include those who have cerebral palsy, ... intelligence, behavior, school achievement, and the development of epilepsy. Investigators also continue to explore which drugs can ...

  4. Febrile Seizures

    MedlinePLUS

    ... febrile seizures may be treated with the drug diazepam orally or rectally, whenever they have a fever. ... treated with a rectal form of the drug diazepam to stop the seizure and prevent it from ...

  5. Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis

    PubMed Central

    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

  6. Autoimmune neutropenia of infancy with recurrent urinary tract infections: a case report.

    PubMed

    Kanai, Hiroaki; Sato, Hiroki; Takei, Yoshichika

    2015-03-01

    Autoimmune neutropenia of infancy is characterized by minor intercurrent infections despite severe neutropenia; severe bacterial infections are uncommon. An infant developed recurrent urinary tract infections at 9 and 11 months of age. The identified uropathogens were Escherichia coli and Enterococcus faecalis, respectively. Empirical treatment with carbapenems, as broad-spectrum antibiotics, promptly resolved the infection without sequelae. Febrile neutropenic children with cancer and autoimmune neutropenia can develop urinary tract infections; therefore, in such infants, urine culture should be obtained through catheterization. In febrile neutropenic infants with no apparent fever source, cephalosporin monotherapy should not be selected empirically because Enterococci can be the involved pathogens. PMID:24942028

  7. Neutropenia - infants

    MedlinePLUS

    ... white blood cells. These cells, which are called neutrophils, help the body fight infection. This article discusses ... travel wherever they are needed. Low levels of neutrophils occur when the bone marrow cannot replace them ...

  8. Neutropenia and G-CSF in lymphoproliferative diseases

    PubMed Central

    Ria, Roberto; Reale, Antonia; Moschetta, Michele; Dammacco, Franco; Vacca, Angelo

    2013-01-01

    Background Chemotherapy-induced neutropenia is a major cause of morbidity and mortality. It frequently causes dose reductions or treatment delay, which can be prevented or treated by the administration of granulocyte-colony-stimulating factor (G-CSF). However, a better knowledge of the incidence, day of onset after therapy, and duration of neutropenia is essential to optimize the use of G-CSF. Design and methods Six hundred and ninety-four patients from a single institution, affected by lympho-proliferative diseases, were retrospectively reviewed for the occurrence of grade 4 neutropenia and febrile neutropenia (FN). Duration of neutropenia and time of neutrophil nadir were also retrieved. The diagnoses included non-Hodgkin's lymphoma, Hodgkin's lymphoma, and multiple myeloma. Chemotherapy regimens were obviously different according to the diagnosis, disease stage, and first or subsequent lines of therapy. Results No patient received G-CSF as primary prophylaxis. Median nadir did not significantly differ among patients treated with first or successive lines of therapy. The incidence of grade 4 neutropenia and FN ranged from 0 to 94%, depending on the chemotherapy regimen. Patients receiving a first-line chemotherapy regimen had a significantly lower incidence of febrile grade 4 neutropenia compared to patients treated with a second or subsequent line of therapy. The duration of grade 4 neutropenia was significantly longer in patients given second or subsequent lines. Conclusion The results of this study could be useful to define the nadir onset in the hematologic setting in order to correctly tailor timing and duration of G-CSF prophylaxis and to assess the lowest fully effective dose. PMID:23321273

  9. Lipegfilgrastim for the prophylaxis and treatment of chemotherapy-induced neutropenia.

    PubMed

    Ratti, Margherita; Tomasello, Gianluca

    2015-01-01

    Chemotherapy is frequently associated with hematologic toxicity. Neutropenia with or without fever is a relevant cause of morbidity, mortality and costs, compromising treatment administration and clinical outcomes. The development of granulocyte colony-stimulating factors has had a positive impact on the clinician's approach to neutropenia. Such agents, currently used for primary and secondary prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia (FN), are effective in limiting hematologic toxicities and consequently allow the administration of intensive dose-dense regimens. Several biosimilar products of filgrastim have been developed over the years, showing effects similar to the originator drug. Until now, pegfilgrastim has been the only available long-acting factor, requiring just a single administration per chemotherapy cycle. The recent approval of the novel granulocyte colony-stimulating factors, lipegfilgrastim, offers interesting therapeutic alternatives. In fact, similar to pegfilgrastim, it has been demonstrated to reduce the duration of neutropenia and the occurrence of FN during chemotherapy safely. PMID:25409861

  10. Febrile neutropenia and Fusobacterium bacteremia: clinical experience with 13 cases

    Microsoft Academic Search

    P. Fanourgiakis; M. Vekemans; A. Georgala; D. Daneau; A. Vandermies; P. Grenier; M. Aoun

    2003-01-01

    Objectives. To assess the disease spectrum of Fusobacterium bacteremia in our neutropenic patients and review the literature. Methods. This was a 6.5-year retrospective study in which all the records of neutropenic patients with Fusobacterium bacteremia were analyzed. Results. Fusobacterium bacteremia was found in 13 neutropenic patients, 10 with hematological malignancies and 3 with solid tumors. The standard clinical presentation was

  11. Management of Febrile Neutropenia in a Patient With Acute Leukemia

    PubMed Central

    Bryant, Ashley Leak; Walton, AnnMarie; Albrecht, Tara A.

    2013-01-01

    Hematologic cancers comprise an aggregate of several different cancers, such as leukemia, lymphoma, and multiple myeloma. There are more than 100,000 new cases of these hematologic cancers in the United States annually, and more than 50,000 children and adults die from these cancers.1,2 Hematologic cancers affect the body’s blood, bone marrow, and lymphatic system, leaving these patients more susceptible to infections.1 A newly diagnosed patient with acute leukemia receives aggressive chemotherapy treatment and is closely monitored in the hospital for at least 3 to 4 weeks. Treatment-related signs and symptoms including fever, pain, nausea and vomiting, and respiratory distress may bring the patient to the emergency department before his or her next scheduled clinic appointment.3,4 In this article a case study of a patient with acute lymphoblastic leukemia who enters the emergency department will be used to illustrate a common clinical scenario and provide clinical implications for emergency nurses who care for patients with hematologic cancers. PMID:24054730

  12. Systematic reviews and meta-analysis of febrile neutropenia....

    Science.gov Websites

    Manual NCBI News PubMed PubMed Central (PMC) PubMed Clinical Queries PubMed Health All Literature Resources... Proteins BioSystems BLAST (Basic Local Alignment Search Tool)...

  13. Febrile seizures

    MedlinePLUS

    Seizure - fever induced ... an illness, and may not occur when the fever is highest. Ear infections, a cold or viral ... other than symptoms of the illness causing the fever. Often, the child will not need a full ...

  14. Malnutrition and neutropenia in children treated for Burkitt Lymphoma in Malawi

    Microsoft Academic Search

    Trijn Israëls; Wetering van de M. D; Peter Hesseling; Nan van Geloven; Huib N. Caron; Elizabeth M. Molyneux

    2009-01-01

    Background. infection in neutropenic children is a major cause of morbidity and mortality in children treated for cancer. In developing countries, children with cancer are often malnourished at diagnosis. In Blantyre, Malawi, children with Burkitt lymphoma are treated with a local protocol with limited toxicity. The aim of this study was to evaluate the incidence and outcome of febrile neutropenia

  15. Continuous infusion of ceftazidime in febrile neutropenic patients with acute myeloid leukemia

    Microsoft Academic Search

    S. Daenen; Z. Erjavec; D. R. A. Uges; H. G. De Vries-Hospers; P. De Jonge; M. R. Halie

    1995-01-01

    Twelve febrile patients with severe neutropenia, who had undergone aggressive chemotherapy for acute myeloid leukemia, were treated empirically with a continuous infusion of ceftazidime 100 mg\\/kg\\/day after a 500 mg loading dose, in order to study the pharmacokinetics of ceftazidime after continuous infusion and to examine the clinical applicability of continuous infusion in this patient population. Three patients had a

  16. Evaluation and Management of Patients with Isolated Neutropenia

    PubMed Central

    Newburger, Peter E.; Dale, David C.

    2013-01-01

    Neutropenia, defined as an absolute neutrophil count below 1.5 × 109/L, encompasses a wide range of diagnoses, from normal variants to life-threatening acquired and congenital disorders. This review addresses the diagnosis and management of isolated neutropenia, not multiple cytopenias due to splenomegaly, bone marrow replacement, or myelosuppression by chemotherapy or radiation. Laboratory evaluation generally includes repeat complete blood counts with differentials and bone marrow examination with cytogenetics. Neutrophil antibody testing may be useful, but only in the context of clinical and bone marrow findings. The discovery of genes responsible for congenital neutropenias now permits genetic diagnosis in many cases. Management of severe chronic neutropenia includes common-sense precautions to avoid infection; aggressive treatment of bacterial or fungal infections; and administration of granulocyte colony-stimulating factor (G-CSF). Patients with severe congenital neutropenia, particularly those who respond poorly to G-CSF, have a risk of eventually developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and require monitoring for this complication, which can also occur without G-CSF therapy. Patients with cyclic, idiopathic and autoimmune neutropenia have virtually no risk of evolving to MDS or AML. Hematopoietic stem cell transplantation is a curative therapy for congenital neutropenia with MDS/AML or with cytogenetic abnormalities indicating impending conversion. PMID:23953336

  17. Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on gram-positive and resistant bacteria.

    PubMed

    Zinner, S H

    1999-09-01

    Over the past 3 decades, considerable changes have occurred in the types of bacteria causing infection in febrile patients with neutropenia and cancer. Twenty years ago, gram-negative bacteria caused approximately 70% of bloodstream infections. As a probable consequence of long-dwelling intravascular devices, fluoroquinolone prophylaxis, and high-dose chemotherapy-induced mucositis, there has been a shift toward gram-positive coccal bacteremia. In most centers today, approximately 70% of bacteremic isolates are gram-positive cocci. Of potential concern is that antimicrobial-resistant gram-positive organisms are becoming increasingly frequent in patients with neutropenia. Fluoroquinolone-resistant Escherichia coli are being isolated from several cancer centers. Several "new" organisms, such as Stomatococcus mucilaginosus, Bacillus cereus, Leuconostoc species, Corynebacterium jeikeium, Rhodococcus species, Stenotrophomonas maltophilia, Moraxella catarrhalis, Burkholderia cepacia, and Bartonella species, now cause infections in these patients. Careful application of infection-control principles, judicious prophylaxis, appropriate evaluation of new antibiotics, and prompt effective therapy will maximize benefits for these patients. PMID:10530434

  18. Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia

    Microsoft Academic Search

    Jeffrey Crawford

    2003-01-01

    Filgrastim (r-metHuG-CSF) was approved in the United States in 1991 for use in decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy. Colony-stimulating factors such as filgrastim are a significant advance in the supportive care of patients with cancer. However, because of its short half-life, filgrastim requires daily dosing by

  19. Genetics Home Reference: Cyclic neutropenia

    MedlinePLUS

    ... during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that ... during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an ...

  20. Four cases of bacteraemia caused by Fusobacterium nucleatum in febrile, neutropenic patients.

    PubMed

    Terhes, Gabriella; Piukovics, Klára; Urbán, Edit; Nagy, Elisabeth

    2011-07-01

    Although bacteraemia caused by obligate anaerobic bacteria is a rare event, this phenomenon will be an emerging problem among oncohaematological patients. We report four cases of bacteraemia caused by Fusobacterium nucleatum in febrile, neutropenic patients over a 10 month period. All patients had haematological malignancy and severe neutropenia, and three of them suffered from oral mucositis or oedema of the oral mucosal surfaces, which was the probable portal of entry. All isolated strains were susceptible to standard anti-anaerobic antibiotics. PMID:21415204

  1. [Infection control in neutropenia induced by high-dose cytarabine chemotherapy].

    PubMed

    Miyazaki, Masayuki; Senzaki, Kouji; Kiyoi, Hitoshi; Kohno, Shigekatu; Noda, Yukihiro; Nabeshima, Toshitaka

    2004-11-01

    A high-dose cytarabine (Cylocide; Ara-C: HDAC) chemotherapy has been successfully used as a postremission consolidation therapy for acute myeloid leukemia (AML). Although this chemotherapy has been estimated to cause severe myelosuppression, there has been no report about infection risk relating to HDAC chemotherapy. The purpose of this retrospective study is to evaluate the infection risk in AML patients treated with HDAC (n = 18) compared to those treated with standard-dose Ara-C (SDAC, n = 18). The mean duration of severe neutropenia (neutrophils < 500/microl) in HDAC group and SDAC was 14.8 days and 10.4 days, respectively, indicating a significant prolongation in the HDAC group (p < 0.05). The frequency of febrile neutropenia in the HDAC group tended to increase compared to that in the SDAC group (p = 0.093). The average days of usage of quinolone antimicrobial prophylaxis and aminoglycoside antibiotic injection in febrile neutropenia in the HDAC group were significantly longer than those of the SDAC group (quinolone; p < 0.01, aminoglycoside; p < 0.05). The frequency of Streptococcus infection isolated from pharyngeal mucus in the HDAC group was significantly higher than that in the SDAC group (100% versus 75%; p < 0.05). These results suggest that HDAC chemotherapy increased the infection risk compared to SDAC, and especially patients who received HDAC need a further prevention plan against gram-positive bacteria. PMID:15570930

  2. Spotlight on pegfilgrastim in chemotherapy-induced neutropenia.

    PubMed

    Frampton, James E; Keating, Gillian M

    2005-01-01

    Pegfilgrastim (Neulasta), the sustained-duration form of filgrastim (recombinant human granulocyte colony-stimulating factor [G-CSF]), is created by the addition of a polyethylene glycol (PEG) moiety to filgrastim. Its approved indication in the US is to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy.A single subcutaneous injection of pegfilgrastim once per chemotherapy cycle was more effective than placebo as an adjunct to moderately myelosuppressive chemotherapy for breast cancer, no less effective than daily injections of filgrastim as an adjunct to highly myelosuppressive chemotherapy for breast cancer, and as effective as daily filgrastim as an adjunct to chemotherapy for lymphoma (predominantly non-Hodgkin lymphoma [NHL]) and acute myeloid leukemia. Pegfilgrastim has also successfully supported delivery of dose-dense chemotherapy, stem cell mobilization, and stem cell transplantation after high-dose chemotherapy in patients with non-myeloid or myeloid malignancies. By offering a convenient alternative to daily filgrastim, once-per-cycle administration of pegfilgrastim has the potential to simplify the management of chemotherapy-induced neutropenia, further improve patient health-related quality of life, and reduce total treatment costs in breast cancer and NHL, and possibly other cancer settings. Pegfilgrastim should, likewise, permit simplification of G-CSF-based stem cell mobilization and transplantation procedures. PMID:16392893

  3. [Significance of Procalcitonin Measurement in Cases with Febrile Condition during Chemotherapy for Urological Cancer].

    PubMed

    Kurimura, Yuichiro; Takahashi, Satoshi; Hiyama, Yoshiki; Uehara, Teruhisa; Ichihara, Koji; Hashimoto, Jiro; Nishiyama, Naotaka; Kitamura, Hiroshi; Masumori, Naoya

    2015-04-01

    We examined the usefulness of measurement of procalcitonin (PCT) for patients, who developed febrile neutropenia during cancer chemotherapy for urological cancer. Of the Patients who underwent cancer chemotherapy for bladder, renal pelvic or ureteral, and testicular cancer in our department from 2010 to 2013, 51 had febrile events. Their clinical courses and PCT values were retrospectively reviewed and analyzed. PCT was positive in 12 patients and negative in 39. The duration with febrile status was significantly longer in the PCT-positive group than in the PCT-negative group. There was no significant difference between the blood count values in each group, but C-reactive protein (CRP) was significantly higher in the PCT-positive group than in the PCT-negative group. There were no significant differences between the 2 groups in other tests with blood. There were 12 patients with febrile neutropenia (FN) but all were classified into low-risk by the MASCC scoring system. Four of these 12 patients were positive for PCT. Our results suggested that, in patients with a fever of 37.5°C or more during the course of cancer chemotherapy for urologic cancer, bacteremia possibly existed if the patient was positive for PCT. In addition, the duration of fever tended to be longer and the condition was more severe. When the patients with urological cancer undergo cancer chemotherapy manifest high-grade fever, PCT is promising and valuable as an indicator of the severity of infection. PMID:26037672

  4. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities.

    PubMed

    Whiskey, Eromona; Taylor, David

    2007-01-01

    Clozapine remains the antipsychotic of choice for refractory schizophrenia despite its propensity for serious blood disorders. When neutropenia or agranulocytosis occur in people taking clozapine, cessation of treatment is mandated and relapse often results. Because such patients are usually unresponsive to other antipsychotics, many clinicians consider restarting clozapine, despite the risks involved. However, the risks of clozapine rechallenge vary according to the cause and nature of the blood dyscrasia. Neutropenia can arise because of factors unrelated or indirectly related to clozapine treatment. These include benign ethnic neutropenia, concomitant drug therapy, co-existing medical conditions and drug interactions. In such cases, clozapine may be restarted if non-clozapine causes of neutropenia are identified and eliminated, although concurrent treatment with lithium (to induce leukocytosis) is sometimes necessary. Close monitoring of the patient is essential because it is rarely possible to completely rule out the contribution of clozapine to the blood dyscrasia and because lithium does not protect against clozapine-related agranulocytosis. In cases of clozapine-induced neutropenia (as distinct from agranulocytosis, which may have a different pathology) rechallenge may also be considered and, again, lithium co-therapy may be required. Where clozapine is clearly the cause of agranulocytosis, rechallenge should not be considered or undertaken unless there are very exceptional circumstances (severe and prolonged relapse following clozapine discontinuation). In these cases, re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring. Granulocyte colony-stimulating factor is likely to be required as co-therapy, given the very high likelihood of recurrence. Uncertainty over the likely cause of blood dyscrasia in people taking clozapine, coupled with uncertainty over the mechanism by which clozapine causes both neutropenia and agranulocytosis, makes any attempt to restart clozapine a high-risk venture requiring the utmost caution. PMID:17190527

  5. [Consensus on management of children with cancer, neutropenia and fever: Update 2008-2009].

    PubMed

    2010-04-01

    Oncologic patients are more exposed to infecto-contagious diseases (produced by bacteria, virus, fungi, and parasites) related to the own oncologic disease and chemotherapy. Neutropenia is frequent and directly related with infection risk. Approximately, 80% of patients with an absolute neutrophil count < 500 will have a febrile episode, and 20% of those with a count < 100 will have bacteremia and increased risk of infections. Patient categorization, search for organisms through conventional and biomolecular techniques, plus adequate antiinfectious treatment, directly impact on morbidity and mortality. PMID:20467701

  6. Plasma lactoferrin in patients with neutropenia.

    PubMed

    Brown, R D; Yuen, E; Rickard, K A; Vincent, P C; Young, G; Kronenberg, H

    1986-05-01

    This study examines the role of plasma lactoferrin in the assessment of neutropenia. In particular, we have studied lactoferrin as an inhibitor of granulopoiesis and as an indicator of the size of the total blood granulocyte pool (TBGP). Plasma lactoferrin concentration was determined in a heterogeneous group of 30 patients with neutropenia. Serial plasma lactoferrin levels in a patient with cyclic neutropenia correlated with the cycles of the neutrophil count. Patients with splenomegaly had a grossly elevated lactoferrin:neutrophil ratio. Most chronic idiopathic neutropenia patients had no real clinical problems and a normal plasma lactoferrin level. The results provide further evidence to support the concept that plasma lactoferrin indicates the size of the TBGP and the lactoferrin: neutrophil ratio indicates the degree of granulocyte margination. There was no evidence to suggest that lactoferrin acting as a feedback inhibitor of granulopoiesis caused neutropenia in these patients. PMID:3635417

  7. Febrile Illness in the Athlete

    PubMed Central

    Dick, Natalie A.; Diehl, Jason J.

    2014-01-01

    Context: Acute febrile illnesses are common in athletes over the course of training and competition seasons. Complete recovery and rapid yet safe return to participation are critical for competitive athletes. Alterations in thermoregulation, metabolism, fluid homeostasis, muscle strength, and endurance, as well as potential complications for the athlete and others, must be considered. Evidence Acquisition: The PubMed database was searched (1970-2013) for all English-language articles related to febrile illness in sport, using the keywords fever, febrile, body temperature, thermoregulation, infection, illness, disease, exercise, athlete, sport, performance, return to play, metabolism, hydration, and dehydration. Study Design: Clinical review. Level of Evidence: Level 4. Results: Limited data confirm that febrile illness is correlated with alterations in the body’s thermoregulatory system, with increases in metabolic rate, and with effects in fluid homeostasis. Human and animal studies demonstrate a decrease in muscle strength and endurance secondary to muscle catabolism in febrile illness. However, indirect evidence suggests that regular exercise enhances the immune response. No strong clinical research has been published on return to play during or following acute febrile illness, excluding mononucleosis and myocarditis. Conclusion: Fever is correlated with an increase in insensible fluid losses, dehydration, metabolic demands, and dysregulation of body temperature. Fever can have detrimental effects on the musculoskeletal system, including decreasing strength and endurance, generalized muscle catabolism, and increase in perceived fatigue. Participating in strenuous exercise during febrile illness can worsen the illness and has demonstrated increased lethality in animal models. No consensus recommendations support return to activity before resolution of fever, and training should be resumed gradually once fever and dehydration have resolved. PMID:24790692

  8. Genetics Home Reference: Severe congenital neutropenia

    MedlinePLUS

    ... a disease of the blood and bone marrow (myelodysplastic syndrome) during adolescence. Some people with severe congenital neutropenia ... gums ; incidence ; infection ; inflammation ; inheritance ; inherited ; leukemia ; ... neutrophils ; osteopenia ; osteoporosis ; protein ; recessive ; sex chromosomes ; ...

  9. G-CSFs for prevention of febrile neutropenia: systematic review HEDS Discussion Paper 09/07

    E-print Network

    Oakley, Jeremy

    -analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in preventing FN in adults-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 ­ 0.65) for pegfilgrastim, 0

  10. Voriconazole-induced psychosis in a case of acute myeloid leukemia with febrile neutropenia

    PubMed Central

    Singh, Hemendra; Kilara, Nalini; Subramaniyan, Vyjayanthi; Thyloth, Murali

    2015-01-01

    Voriconazole-induced psychosis is a rare side effect. It is important that clinicians are made aware of voriconazole-induced potential psychosis. We report a case of voriconazole-induced psychosis that responded to haloperidol.

  11. Refractory Thrombocytopenia and Neutropenia: a Diagnostic Challenge

    PubMed Central

    Gyan, Emmanuel; Dreyfus, François; Fenaux, Pierre

    2015-01-01

    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. PMID:25745545

  12. Febrile Seizures and Epilepsy: Possible Outcomes

    MedlinePLUS

    ... BETWEEN FE- BRILE SEIZURES AND LATER DEVELOPMENT OF EPILEPSY? Overall, about 6% of children who experienced febrile ... SEIZURES AND LATER DEVELOPMENT OF SPECIFIC TYPES OF EPILEPSY? Epilepsy that does not respond well to standard ...

  13. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia

    PubMed Central

    Averbuch, Diana; Orasch, Christina; Cordonnier, Catherine; Livermore, David M.; Mikulska, Ma?gorzata; Viscoli, Claudio; Gyssens, Inge C.; Kern, Winfried V.; Klyasova, Galina; Marchetti, Oscar; Engelhard, Dan; Akova, Murat

    2013-01-01

    Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4th European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient’s risk factors for resistant bacteria and for a complicated clinical course. An ‘escalation’ approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A ‘de-escalation’ approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72–96 h should be based on the patient’s clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance. PMID:24323983

  14. Cyclic neutropenia in mammals Jorge M. Pacheco,1

    E-print Network

    Traulsen, Arne

    species. The fact that it correctly accounts simultaneously for the cycling periods in dogs and humansCyclic neutropenia in mammals Jorge M. Pacheco,1 Arne Traulsen,2 Tibor Antal,3 and David Dingli4 * Cyclic neutropenia (CN) has been well documented in humans and the gray collie. A recent model

  15. Immune mediated neutropenia in man and animals: a review.

    PubMed

    Chickering, W R; Prasse, K W

    1981-01-01

    Immune mediated neutropenia has been reported in human medical literature with increasing frequency over the past 30 years. A wide variety of causes are known and numerous techniques have been developed to test for the presence of antineutrophil antibody. This paper reviews literature pertaining to the pathogenesis, detection and experimental production of immune mediated neutropenia in man and animals. PMID:15311379

  16. Double-blind comparison of teicoplanin versus vancomycin in febrile neutropenic patients receiving concomitant tobramycin and piperacillin: effect on cyclosporin A-associated nephrotoxicity.

    PubMed Central

    Kureishi, A; Jewesson, P J; Rubinger, M; Cole, C D; Reece, D E; Phillips, G L; Smith, J A; Chow, A W

    1991-01-01

    A prospective, randomized, and double-blind study comparing teicoplanin with vancomycin in the initial management of febrile neutropenic patients was conducted. Teicoplanin was administered at 6 mg per kg of body weight every 24 h (q24h) intravenously (i.v.) after initial loading at 6 mg/kg q12h for three doses. Vancomycin was administered at 15 mg/kg q12h i.v. Patients also received piperacillin (3 g q4h i.v.) and tobramycin (1.5 to 2.0 mg/kg q8h i.v.). Of 53 patients enrolled, 50 were judged to be evaluable. Among these, 25 received teicoplanin and 25 received vancomycin. At enrollment, both groups were comparable in age, sex, renal function, underlying hematologic condition, and concurrent therapy. Both groups had similar sites of infection and microbial pathogens. Empirical antimicrobial therapy resulted in the cure of or improvement in 23 (92%) teicoplanin patients and 21 (84%) vancomycin patients (P = 0.67). Failures occurred with two vancomycin patients but no teicoplanin patients. Clinical response was indeterminate for two patients in each group. Adverse reactions occurred significantly more often in the vancomycin group than in the teicoplanin group (P = 0.01), and these reactions required the termination of the study regimens of 6 vancomycin versus 0 teicoplanin patients (P = 0.02). Nephrotoxicity was observed more frequently in the vancomycin group (10 versus 2 patients; P = 0.02). Subgroup analysis revealed a significant deterioration of renal function when vancomycin and cyclosporin A, but not teicoplanin and cyclosporin A, were used concurrently (P = 0.02). Among patients who received vancomycin and amphotericin B or teicoplanin and amphotericin B concurrently, deterioration in renal function was equivalent in both groups. Teicoplanin in the dosage employed was tolerated better than vancomycin in the empirical treatment of fever and neutropenia in our patient population. PMID:1839490

  17. Immune mediated neutropenia and thrombocytopenia in 3 giant schnauzers

    PubMed Central

    Vargo, Cheryl L.; Taylor, Susan M.; Haines, Deborah M.

    2007-01-01

    Neutropenia, thrombocytopenia, and splenomegaly were recognized in 3 adult female giant schnauzers. Antineutrophil antibodies were demonstrated in 2 dogs. Following splenectomy, administration of prednisone and azathioprine resulted in normalization of neutrophil and platelet numbers in all dogs. PMID:18050797

  18. Predictors of febrile seizure: a matched case-control study.

    PubMed

    Gururaj, A K; Bener, A; Al-Suweidi, E K; Al-Tatari, H M; Khadir, A E

    2001-12-01

    In a prospective matched case-control study carried out to determine risk factors of febrile seizures among children in the United Arab Emirates, 84 patients with febrile seizure were identified and were matched with 84 control febrile patients without seizure in the same age range, who attended the same hospital during the same period of time. Logistic regression analysis showed that the age at first seizure, family history of febrile seizure, duration of fever, and height of temperature were the only significant predictors for febrile seizures. PMID:11827305

  19. The investigation and management of chronic neutropenia in children

    PubMed Central

    James, R M; Kinsey, S E

    2006-01-01

    Unravelling the cause of a neutropenia poses a complex diagnostic challenge. The differential diagnosis ranges from life threatening disease to transient benign causes of little clinical significance. This review offers a practical guide to investigating the neutropenic child, and highlights features that merit specialist referral. Therapeutic options, the role of long term follow up, and the complications of severe chronic neutropenia are considered. PMID:16990357

  20. CLPB variants associated with autosomal-recessive mitochondrial disorder with cataract, neutropenia, epilepsy, and methylglutaconic aciduria.

    PubMed

    Saunders, Carol; Smith, Laurie; Wibrand, Flemming; Ravn, Kirstine; Bross, Peter; Thiffault, Isabelle; Christensen, Mette; Atherton, Andrea; Farrow, Emily; Miller, Neil; Kingsmore, Stephen F; Ostergaard, Elsebet

    2015-02-01

    3-methylglutaconic aciduria (3-MGA-uria) is a nonspecific finding associated with mitochondrial dysfunction, including defects of oxidative phosphorylation. 3-MGA-uria is classified into five groups, of which one, type IV, is genetically heterogeneous. Here we report five children with a form 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. Through a combination of homozygosity mapping in the Greenlandic individuals and exome sequencing in the North American, we identified biallelic variants in the caseinolytic peptidase B homolog (CLPB). The causative variants included one missense variant, c.803C>T (p.Thr268Met), and two nonsense variants, c.961A>T (p.Lys321*) and c.1249C>T (p.Arg417*). The level of CLPB protein was markedly decreased in fibroblasts and liver of affected individuals. CLPB is proposed to function as a mitochondrial chaperone involved in disaggregation of misfolded proteins, resulting from stress such as heat denaturation. PMID:25597511

  1. Risk factors for recurrence of febrile convulsions.

    PubMed

    Thilothammal, N; Devi, V S; Kamala, K G; Banu, K; Ratnam, S R; Ezhilarasi, S

    1992-01-01

    A cohort of hundred children with febrile convulsions, in the age group of 3 months to 5 years were followed up prospectively for one year to study the natural course of the illness, and to determine if specific factors would increase the risk of recurrence of febrile convulsions. The risk factors studied were age of onset under one year, long duration of convulsion (more than 15 minutes), family history of febrile convulsion or epilepsy and combination of two or all of the above factors. Four groups of children with different risk factors were followed up for recurrence of convulsion, after the first attack. A group of children without any risk factor was considered as control and they were also followed up for recurrence of convulsions. Though all the groups with the risk factors, showed a trend towards a higher recurrence rate when compared to controls, the difference observed clinically was not significant statistically. This could be due to the small sample size of each group. A larger study could throw light on the predictive value of these risk factors and narrow down the use of long term anticonvulsant prophylaxis. PMID:1340865

  2. Trends in Neutropenia-Related Inpatient Events

    PubMed Central

    Kozma, Chris M.; Dickson, Michael; Chia, Victoria; Legg, Jason; Barron, Richard

    2012-01-01

    Purpose: Neutropenic complications (NCs) after myelosuppressive chemotherapy are associated with significant morbidity and mortality. We described NC rates by using US hospital discharge data. Materials and Methods: This cross-sectional analysis used data from the US National Inpatient Sample database. Hospital discharges with cancer diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code) from 1989 to 2007 were analyzed for the ICD-9-CM neutropenia code. NC rates per 10,000 discharges were calculated for all adult discharges without radiation therapy (study population, all cancers); lung cancer, breast cancer, and non-Hodgkin's lymphoma (NHL); and all three combined. The use of growth factors and myelosuppressive chemotherapy from 1994 to 2008 was estimated by using the IMS Health Drug Distribution Database. Results: Estimated lung cancer and breast cancer discharges remained relatively steady, whereas NHL discharges increased. NC rates for each study cancer increased two-fold until the late 1990s before stabilizing and/or declining. The average hospital stay for all three cancers decreased from 10.4 days to 7.1 days. The mortality rates for NCs for the three cancers combined decreased at a fairly constant rate from 10% in 1989 to 5.4% in 2007. Estimated discharges for NCs from 1989 to 2007 ranged from 111,000 to 169,000 for the study population, from 57,000 to 103,000 for all cancers, and from 21,000 to 40,000 for the three study cancers. The use of growth factors and myelosuppressive chemotherapy increased from 1994 to 2008. Conclusion: Whereas the number of hospitalizations with cancer diagnoses has remained steady since 1989, hospitalizations for NCs increased approximately two-fold from 1989 to 1997 and then stabilized. PMID:22942808

  3. Risk of epilepsy after febrile convulsions: a national cohort study

    Microsoft Academic Search

    C M Verity; J Golding

    1991-01-01

    OBJECTIVE--To identify children with febrile convulsions, classify their febrile convulsions into simple and complex, and determine the number and type of subsequent afebrile seizures in those children. DESIGN--National population based study. SETTING--United Kingdom. SUBJECTS--16,004 neonatal survivors born during one week in April 1970. MAIN OUTCOME MEASURES--Information about febrile and afebrile seizures obtained from questionnaires at 5 and 10 years of

  4. Supportive care in pediatric oncology: oncologic emergencies and management of fever and neutropenia.

    PubMed

    Henry, Meret; Sung, Lillian

    2015-02-01

    Advancements in the care of children with cancer have, in part, been achieved through improvements in supportive care. Situations that require prompt care can occur at the time of presentation as well as during treatment. This article discusses the approach to children with fever and neutropenia, a complication encountered daily by care providers, as well as oncologic emergencies that can be seen at the time of a child's initial diagnosis: hyperleukocytosis, tumor lysis syndrome, superior vena cava syndrome, and spinal cord compression. PMID:25435110

  5. ORIGINAL CONTRIBUTION A Novel Locus for Generalized Epilepsy With Febrile

    E-print Network

    Boyer, Edmond

    ORIGINAL CONTRIBUTION A Novel Locus for Generalized Epilepsy With Febrile Seizures Plus in French, PhD Background: Generalized epilepsy with febrile sei- zures plus (GEFS ) is a familial autosomal epilepsy. Main Outcome Measures: We analyzed 380 micro- satellite markers and conducted linkage analysis

  6. G-CSF treatment of chemotherapy induced neutropenia -Online supplement

    E-print Network

    G-CSF treatment of chemotherapy induced neutropenia - Online supplement Eliezer Shochat and Vered under chemotherapy We use the following mathematical formulation to describe the G-CSF Neutrophils (GN-marrow to chemotherapy, we assume it is depleted by a certain rate (represented by 1), re- mains low (at Bnadir

  7. Protracted febrile myalgia mimicking polyarteritis nodosa.

    PubMed

    Bircan, Zelal; Usluer, Hale

    2008-08-01

    An insidious onset of unexplained fever, weight loss, skin lesions, abdominal pain, and musculoskeletal pain should suggest the diagnosis of polyarteritis nodosa (PAN). However, familial Mediterranean fever (FMF) with protracted febrile myalgia (PFM) should be kept in mind in the differential diagnosis. In this report, 6 cases of PFM mimicking PAN are described. Patients presented with severe muscle and abdominal pain lasting longer than 4 weeks. Their common medical history included recurrent febrile abdominal pain or arthritis. Physical examination revealed hypertension together with severe muscle tenderness. Laboratory examination revealed high acute phase reactants, negative p-ANCA, normal creatine kinase, and complement levels. Duplex abdominal ultrasonography was normal. Four of 6 patients were hospitalized with initial diagnoses of PAN. Renal and mesenteric angiography performed in 1 patient was normal. Steroid therapy controlled all the severe symptoms including hypertension in all of the cases.FMF with PFM is important in the differential diagnosis of patients with suspected vasculitis especially when myalgia is present. Hypertension may be present as a result of sympathetic discharge because of severe myalgia. Because PFM rapidly responds to a short course of corticosteroids, a rapid diagnosis of PFM in FMF patients can reduce unnecessary workup and decrease the time patients have to suffer. PMID:18636021

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

    PubMed Central

    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

  9. Continuous infusion of ceftazidime in febrile neutropenic patients with acute myeloid leukemia.

    PubMed

    Daenen, S; Erjavec, Z; Uges, D R; De Vries-Hospers, H G; De Jonge, P; Halie, M R

    1995-03-01

    Twelve febrile patients with severe neutropenia, who had undergone aggressive chemotherapy for acute myeloid leukemia, were treated empirically with a continuous infusion of ceftazidime 100 mg/kg/day after a 500 mg loading dose, in order to study the pharmacokinetics of ceftazidime after continuous infusion and to examine the clinical applicability of continuous infusion in this patient population. Three patients had a slight decrease in renal function. All patients attained a steady-state ceftazidime serum level of > 20 micrograms/ml within 180 to 240 min, which was considered effective against most pathogens in neutropenic patients. The median volume of distribution for the patient group was 29.1 l, the elimination half-life was 2.5 h and the clearance of ceftazidime was 7.7 l/h. A subnormal kidney function influenced half-lives and clearance (but not volume of distribution), as expected. When precautions were taken to avoid known interactions between ceftazidime and other compounds to be infused simultaneously, continuous infusion of ceftazidime was applicable for treatment of neutropenic patients without major side effects. PMID:7614958

  10. A revised decision analysis of strategies in the management of febrile children at risk for occult bacteremia

    Microsoft Academic Search

    Loren G Yamamoto; Reginald G Worthley; Marian E Melish; Dexter S. Y Seto

    1998-01-01

    Two decision analysis reports published in 1991 concluded that the strategy of routine blood culture and empiric antibiotics was the superior strategy for febrile children at risk for occult bacteremia. This report describes a decision analysis of treatment strategies for these children considering the following changes that have occurred since then: (1) Hemophilus influenzae B incidence is low because of

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

    PubMed

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

    2011-07-15

    Congenital and acquired neutropenia are rare disorders whose frequency in pediatric age may be underestimated due to remarkable differences in definition or misdiagnosed because of the lack of common practice guidelines. Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document which includes a classification of neutropenia and a comprehensive guideline on diagnosis of neutropenia. PMID:21448998

  12. CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

    PubMed Central

    2013-01-01

    Background 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children. Methods The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. Prospect The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy. Trial registration ClinicalTrials.gov identifier: NCT01370044 PMID:23806032

  13. Molecular epidemiology of catheter-related bloodstream infections caused by coagulase-negative staphylococci in haematological patients with neutropenia.

    PubMed Central

    Müller-Premru, M.; Cernelc, P.

    2004-01-01

    Catheter-related bloodstream infection (CRBSI) caused by coagulase-negative staphylococci (CNS) is common in haematological patients with febrile neutropenia. As the clinical signs of CRBSI are usually scarce and it is difficult to differentiate from blood culture contamination, we tried to confirm CRBSI by molecular typing of CNS isolated from paired blood cultures (one from a peripheral vein and another from the central venous catheter hub). Blood cultures were positive in 59 (36%) out of 163 patients. CNS were isolated in 24 (40%) patients; in 14 from paired blood cultures (28 isolates) and in 10 from a single blood culture. CNS from paired blood cultures were identified as Staphylococcus epidermidis. Antimicrobial susceptibility was determined and bacteria were typed by pulsed-field gel electrophoresis (PFGE) of bacterial genomic DNA. In 13 patients, the antibiotic susceptibility of isolates was identical. The PFGE patterns from paired blood cultures were identical or closely related in 10 patients, thus confirming the presence of CRBSI. In the remaining four patients they were unrelated, and suggested a mixed infection or contamination. Since CNS isolates from three patients had identical PFGE patterns, they were probably nosocomially spread amongst them. PMID:15473156

  14. Influence of febrile disease on the pharmacokinetics of veterinary drugs

    E-print Network

    Paris-Sud XI, Université de

    Influence of febrile disease on the pharmacokinetics of veterinary drugs ASJPAM van Miert Department of Veterinary Basic Sciences, Division of Pharmacology, Pharmacy, Toxicology and Therapy, Faculty of Veterinary Medicine, Utrecht University, PO Box 80176, 3508 TD Utrecht, The Netherlands (Pharmacokinetics

  15. Development of hippocampal sclerosis after a complex febrile seizure

    Microsoft Academic Search

    Andreas Merkenschlager; Horst Todt; Thomas Pfluger; Matthias K. Bernhard

    2009-01-01

    The role of prolonged febrile seizures in the genesis of hippocampal sclerosis is controversial; statistical analysis and\\u000a data from epilepsy surgery suggest a causal relationship. A three-year-old boy had an initial febrile seizure with a transient\\u000a postictal flaccid hemiparesis. Magnetic resonance imaging (MRI) showed no abnormality of the hippocampal areas of both sides.\\u000a At the age of four a prolonged

  16. Management of Febrile Children in the Conjugate Pneumococcal Vaccine Era

    Microsoft Academic Search

    Michael E. Gabriel; Leslie Aiuto; Nina Kohn; Stephen R. Barone

    2004-01-01

    The objective of this study was to evaluate physician attitudes toward the management of young febrile children since the introduction of the conjugate heptavalent pneumococcal vaccine (PCV 7). Seven thousand five hundred pediatricians and 7,500 emergency department (ED) physicians were surveyed with regard to their management of a febrile 7-month-old child and 20-month-old child without an apparent fever focus. Specifically,

  17. [Benign ethnic neutropenia; an unrecognised cause of leukopenia in negroid patients].

    PubMed

    van Rooijen, Cleo R; Slieker, Walentina A T; Simsek, Suat

    2012-01-01

    Leukopenia has a high incidence and is usually a reason for additional testing. Benign ethnic neutropenia is a relatively common cause of neutropenia in the negroid population. It can be the cause of aberrant laboratory results in negroid patients. A 55-year-old woman from Ghana was referred to the outpatient clinic because of malaise, leukopenia and neutropenia. Viral infection, haematological malignancy, auto-immune disease and vitamin deficiency were considered, but could not be confirmed by additional testing. Upon further investigation, the neutropenia in this patient was found to have existed for years. Moreover, our patient's son also had asymptomatic leukopenia. Therefore, benign ethnic neutropenia was considered the most likely diagnosis. Serological analysis of the patient's erythrocytes revealed the absence of Duffy (Fy) blood group antigens Fy(a) and Fy(b), which is associated with benign ethnic neutropenia. PMID:22727232

  18. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    PubMed Central

    Islambulchilar, Mina; Asvadi, Iraj; Sanaat, Zohreh; Esfahani, Ali; Sattari, Mohammadreza

    2015-01-01

    Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally). Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years). The results indicated that the levels of white blood cells are significantly (P<0.05) increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05) lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes. PMID:25789226

  19. Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy

    Microsoft Academic Search

    Melvin H. Freedman; Mary Ann Bonilla; Carol Fier; Audrey Anna Bolyard; Debra Scarlata; Laurence A. Boxer; Sherri Brown; Bonnie Cham; George Kannourakis; Sally E. Kinsey; Pier Georgio; Tammy Cottle; Karl Welte; David C. Dale

    2000-01-01

    Granulocyte colony-stimulating factor (G- CSF) has had a major impact on manage- ment of ''severe chronic neutropenia,'' a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with in- creased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia have devel- oped myelodysplastic syndrome and acute myeloblastic leukemia (MDS\\/AML), which raises the

  20. Undifferentiated febrile illness in Kathmandu, Nepal.

    PubMed

    Thompson, Corinne N; Blacksell, Stuart D; Paris, Daniel H; Arjyal, Amit; Karkey, Abhilasha; Dongol, Sabina; Giri, Abhishek; Dolecek, Christiane; Day, Nick; Baker, Stephen; Thwaites, Guy; Farrar, Jeremy; Basnyat, Buddha

    2015-04-01

    Undifferentiated febrile illnesses (UFIs) are common in low- and middle-income countries. We prospectively investigated the causes of UFIs in 627 patients presenting to a tertiary referral hospital in Kathmandu, Nepal. Patients with microbiologically confirmed enteric fever (218 of 627; 34.8%) randomized to gatifloxacin or ofloxacin treatment were previously reported. We randomly selected 125 of 627 (20%) of these UFI patients, consisting of 96 of 409 (23%) cases with sterile blood cultures and 29 of 218 (13%) cases with enteric fever, for additional diagnostic investigations. We found serological evidence of acute murine typhus in 21 of 125 (17%) patients, with 12 of 21 (57%) patients polymerase chain reaction (PCR)-positive for Rickettsia typhi. Three UFI cases were quantitative PCR-positive for Rickettsia spp., two UFI cases were seropositive for Hantavirus, and one UFI case was seropositive for Q fever. Fever clearance time (FCT) for rickettsial infection was 44.5 hours (interquartile range = 26-66 hours), and there was no difference in FCT between ofloxacin or gatifloxacin. Murine typhus represents an important cause of predominantly urban UFIs in Nepal, and fluoroquinolones seem to be an effective empirical treatment. PMID:25667056

  1. Undifferentiated Febrile Illness in Kathmandu, Nepal

    PubMed Central

    Thompson, Corinne N.; Blacksell, Stuart D.; Paris, Daniel H.; Arjyal, Amit; Karkey, Abhilasha; Dongol, Sabina; Giri, Abhishek; Dolecek, Christiane; Day, Nick; Baker, Stephen; Thwaites, Guy; Farrar, Jeremy; Basnyat, Buddha

    2015-01-01

    Undifferentiated febrile illnesses (UFIs) are common in low- and middle-income countries. We prospectively investigated the causes of UFIs in 627 patients presenting to a tertiary referral hospital in Kathmandu, Nepal. Patients with microbiologically confirmed enteric fever (218 of 627; 34.8%) randomized to gatifloxacin or ofloxacin treatment were previously reported. We randomly selected 125 of 627 (20%) of these UFI patients, consisting of 96 of 409 (23%) cases with sterile blood cultures and 29 of 218 (13%) cases with enteric fever, for additional diagnostic investigations. We found serological evidence of acute murine typhus in 21 of 125 (17%) patients, with 12 of 21 (57%) patients polymerase chain reaction (PCR)-positive for Rickettsia typhi. Three UFI cases were quantitative PCR-positive for Rickettsia spp., two UFI cases were seropositive for Hantavirus, and one UFI case was seropositive for Q fever. Fever clearance time (FCT) for rickettsial infection was 44.5 hours (interquartile range = 26–66 hours), and there was no difference in FCT between ofloxacin or gatifloxacin. Murine typhus represents an important cause of predominantly urban UFIs in Nepal, and fluoroquinolones seem to be an effective empirical treatment. PMID:25667056

  2. Levamisole treatment of a child with severe aphthous stomatitis and neutropenia.

    PubMed

    Verhaegen, H; De Crée, J; De Cock, W; Brugmans, J

    1976-08-01

    The treatment of a 12-year-old girl with a lifelone history of recurrent infections and aphthous stomatitis is reported. A profound neutropenis, first noted at the age of 2 years, occurring at least every month was observed together with multiple mouth ulcers a sore throat and swelling of the jugular glands. Levamisole, originally described as an anthelmintic, has a beneficial effect on the symptoms of recurrent aphthous stomatitis. After levamisole treatment aphthous stomatitis was milder and in the 1-year follow-up period the patient was asymptomatic several times during a phase of obvious neutrophil depression. The child no longer complained of a sore throat with swelling of the jugular glands and the recurrent staphylococcal infections of the skin disappeared. After therapy a marked increase in monocytes at the moment of neutropenia was observed. PMID:981093

  3. Lymphocyte subsets in healthy adult Kuwaiti Arabs with relative benign ethnic neutropenia

    Microsoft Academic Search

    Salim A Kaaba; Suad Al Fadhli; Mona Burhamah; Hassan Al Jafar; Amal Khamis

    2004-01-01

    Relative and absolute neutropenia is frequently seen in the healthy adult Kuwaiti Arab population. Fluorescent monoclonal antibody labelling followed by flow cytometry was used to determine the lymphocyte subsets in 48 normal healthy individuals in the Kuwaiti adult population (24 males and 24 females, age 17–59 years) with relative or absolute neutropenia, and this was compared to age-matched controls (64

  4. Leptospirosis and malaria as causes of febrile illness during a dengue epidemic in Jamaica

    PubMed Central

    Lindo, John; Brown, Paul D; Vickers, Ivan; Brown, Michelle; Jackson, Sandra T; Lewis-Fuller, Eva

    2013-01-01

    Background: Epidemics of febrile illnesses are often associated with rainy seasons in the tropics. During 2007–2008 an epidemic of dengue was identified in Jamaica based on serological testing of sera. Methods: A subset of 3165 of 5400 sera submitted for dengue analysis was tested for Leptospira IgM and malaria IgG using ELISA to determine their role in causing epidemic fever. Findings: Seropositivity for dengue, leptospirosis, and malaria were 38.4 and 6.0 and 6.5%, respectively, indicative of three concurrent epidemics. Mixed exposure to all three diseases was rare (0.1%), as were mixed dengue/malaria (2.4%); dengue/leptospirosis (1.6%), and leptospirosis/malaria (0.03%) exposure. Exposure to dengue and malaria appeared to occur most frequently among children while leptospirosis was more common among adults. Conclusion: While serological diagnosis definitively established that dengue was the main cause of the epidemic febrile illness, the data suggested that there may be other causes of fever, which may occur simultaneously. Consequently, leptospirosis and malaria should be considered as causes of fever during epidemics of dengue in endemic areas. PMID:24188242

  5. Selenium and leptin levels in febrile seizure: a case-control study in children

    PubMed Central

    Khoshdel, Abolfazl; Abbasi, Maedeh

    2013-01-01

    Purpose Febrile seizures (FS) are seizures that occur between the age of 6 and 60 months, but its pathophysiology still is not fully understood. There is limited information about the correlation between levels of selenium and leptin with FS. This study aimed to determine the relationship between serum levels of selenium and leptin in children with FS. Methods This case-control study was conducted in a University Hospital in Shahrekord, Iran, in 2011. The serum levels of selenium and leptin of 25 children with simple febrile seizure (case group) were compared with 25 febrile children without seizure (control group) in acute phase and after three months. The levels of serum selenium and leptin were measured by flame atomic absorption spectrophotometer and enzyme-linked immunosorbent assay method, respectively. Results In acute phase, the mean serum level of selenium in case and control groups were 95.88±42.55 and 113.25±54.43 µg/dL, respectively, and difference was not significant (P=0.415), but after three months, this level had a significant increase in both groups (P<0.001). In acute phase, the mean serum leptin level in case and control groups were 0.94±0.5 and 0.98±0.84 ng/mL, respectively, but difference was not significant (P=0.405). After three months, serum leptin level had no significant change in both groups (P=0.882). Conclusion These observations suggest that serum levels of selenium and leptin have not specific relation with FS but overllay is lower, however, further study is recommended. Also selenium level in stress and acute phase was significantly lower than recovery phase. PMID:23482826

  6. Recurrent febrile syndromes—what a rheumatologist needs to know

    Microsoft Academic Search

    Anna Simon; Hal M. Hoffman

    2009-01-01

    Rheumatologists are likely to be asked to evaluate patients with recurrent febrile syndromes, so it is important that they are familiar with the clinical and diagnostic features, pathophysiology and therapeutic options for these rare autoinflammatory disorders. These syndromes are all characterized by recurrent episodes of fever and systemic inflammation; however, some syndromes have unique historical and physical features that can

  7. [Diagnostic significance of sleep EEG in children with febrile seizures].

    PubMed

    Kovelenova, M V; Rozhkov, V P; Guzeva, V I

    2002-01-01

    To obtain effective criteria for febrile seizures (FS) differential diagnosis and prognosis, clinical examination and EEG recorded during wakefulness and daytime sleep were studied in 75 FS children and 15 controls aged from 6 months to 6 years. According to duration, frequency and complications of FS, all patients were divided into three groups: "simple" FS (n = 35), "complex" FS (n = 25) and "afebrile seizures" (AFS), i.e. those who developed non-febrile seizures after febrile ones (n = 15). In waking state EEG, epileptic activity was found in only 60% of AFS patients. During sleep stages I-III, in 84% of the patients with complex FS as well as in all AFS patients generalized discharges of (poly) spike-waves and (or) focal spikes were detected. Paroxysmal changes, atypical scalp distribution, vertex-potentials and sleep spindles generalization as well as insertion of spikes into arousal-rhythms were determined as additional criteria for unfavorable FS course. In the patients with main features of sympathetic-adrenal reaction during febrile paroxysms, complicated FS course was not found. EEG examination during sleep in children with FS increases an efficacy of differential disease diagnosis. Epileptic discharge detection, along with exposure of paroxysmal transformation of physiological sleep EEG transients, that may be earlier sign of epileptic dysfunction, are recommended for proper prevention and treatment of FS. PMID:11915706

  8. C reactive protein in the evaluation of febrile illness

    Microsoft Academic Search

    A Putto; O Ruuskanen; O Meurman; H Ekblad; H Korvenranta; J Mertsola; H Peltola; H Sarkkinen; M K Viljanen; P Halonen

    1986-01-01

    We studied prospectively 154 febrile children to determine the diagnostic value of the quantitative serum C reactive protein concentrations (CRP). Children with acute otitis media, acute tonsillitis, or treated with antibiotics during the two previous weeks and infants less than 2 months of age were excluded. Ninety seven children were from private paediatric practice and 57 were patients who had

  9. Neutropenia and thrombocytopenia in three dogs treated with anticonvulsants.

    PubMed

    Jacobs, G; Calvert, C; Kaufman, A

    1998-03-01

    Three dogs became lethargic and had poor appetites within 2 months after anticonvulsant treatment was initiated to control seizures. Dogs were neutropenic, thrombocytopenic, and anemic and had splenomegaly. Sensitivity to phenobarbital and related anticonvulsants may induce life-threatening leukopenia, thrombocytopenia, and anemia in dogs. Phenobarbital-induced neutropenia in these 3 dogs may have posed a risk for developing bacteremia. It is important for clinicians to be aware of adverse effects so that adequate precautions can be taken. A baseline hemogram should always be obtained before starting anticonvulsant treatment, and periodic hemograms should be obtained to monitor animals. Furthermore, client education should include instructions on recognizing signs of bacteremia, thrombocytopenia, and anemia. PMID:9524640

  10. Childhood polyclonal T cell lymphocytosis with neutropenia: effects of antilymphocyte globulin and granulocyte colony stimulating factor in vitro and in vivo.

    PubMed

    Laurie, A S; Gibson, F M; Josten, K M; Talbot, P J; Rutherford, T R; Lilleyman, J S; Gordon-Smith, E C

    1992-04-01

    The pathogenesis of the neutropenia that occurs in some patients with chronic T cell lymphocytosis is not well understood. We have investigated a 15-year-old girl with this syndrome. Initial committed bone marrow progenitor numbers (CFUgm) were low but markedly increased in vitro following T cell depletion. Similarly a transient correction of neutropenia was observed following in vivo lymphocyte depletion with antilymphocyte globulin. A sustained neutrophil recovery was achieved with daily therapy using recombinant human granulocyte colony stimulating factor (rhG-CSF) despite persistence of the lymphocytosis; during successful therapy CFUgm numbers remained low, and were not increased by the in vitro addition of rhG-CSF. These observations suggest the possibility of an inhibitory regulatory mechanism specifically acting on neutrophil granulopoiesis. PMID:1374632

  11. ELANE Mutations in Cyclic and Severe Congenital Neutropenia—Genetics and Pathophysiology

    PubMed Central

    Horwitz, Marshall S.; Corey, Seth J.; Grimes, H. Leighton; Tidwell, Timothy

    2012-01-01

    There are two main forms of hereditary neutropenia: cyclic and severe congenital neutropenia (SCN). Cyclic neutropenia is an autosomal dominant disorder in which neutrophil counts fluctuate between nearly normal levels and close to zero with 21-day periodicity. In contrast, SCN, also known as Kostmann syndrome, consists of chronic and profound neutropenia, with a characteristic promyelocytic maturation arrest in the bone marrow. Unlike cyclic neutropenia, SCN displays frequent acquisition of somatic mutations in the gene, CSF3R, encoding the Granulocyte Colony-Stimulating Factor Receptor (G-CSFR), and a strong predisposition to developing myelodysplasia (MDS) and/or acute myeloid leukemia (AML). Cyclic neutropenia is caused by heterozygous mutations in the gene, ELANE (formerly known as ELA2), encoding the neutrophil granule serine protease, neutrophil elastase. SCN is genetically heterogeneous, but it is most frequently associated with ELANE mutations. While some of the different missense mutations in ELANE exhibit phenotype-genotype correlation, the same mutations are sometimes found in patients with either form of inherited neutropenia. The mutations lead to production of a mutant polypeptide, but no common biochemical abnormality, including effects on proteolysis, has been identified. Two non-mutually exclusive theories have been advanced to explain how the mutations might produce neutropenia. The mislocalization hypothesis states that mutations within neutrophil elastase or involving other proteins responsible for its intracellular trafficking cause neutrophil elastase to accumulate in inappropriate subcellular compartments. The misfolding hypothesis proposes that mutations prevent the protein from properly folding, thereby inducing the stress response pathway within the endoplasmic reticulum (ER). We discuss how the mutations themselves provide clues into pathogenesis, describe supporting and contradictory observations for both theories, and highlight outstanding questions relating to pathophysiology of neutropenia. PMID:23351986

  12. Diagnosis and management of primary autoimmune neutropenia in children: insights for clinicians

    PubMed Central

    Dufour, Carlo

    2015-01-01

    Autoimmune neutropenia of infancy (AIN), also called primary autoimmune neutropenia, is a disease in which antibodies recognize membrane antigens of neutrophils, mostly located on immunoglobulin G (IgG) Fc receptor type 3b (Fc?IIIb receptor), causing their peripheral destruction. It is the most frequent type of neutropenia in children under 3–4 years of age and in most cases shows a benign, self-limited course. The diagnosis is based on evidence of indirect antineutrophil antibodies, whose detection frequently remains difficult. In this review we have analyzed the literature regarding AIN and present our personal experience in diagnosis and management. PMID:25642312

  13. Prevalence of Coxiella burnetii Antibodies Among Febrile Patients in Croatia, 2008–2010

    PubMed Central

    Kucinar, Jasmina; Ljubin-Sternak, Suncanica; Kolaric, Branko; Kaic, Bernard; Lazaric-Stefanovic, Lorena; Hunjak, Blazenka; Mlinaric-Galinovic, Gordana

    2012-01-01

    Abstract Despite the widespread distribution of Q fever, the prevalence in humans is not accurately known, because many infected people seroconvert without symptoms or with a mild febrile disease. The aim of this study was to determine the seroprevalence of Q fever in different regions of Croatia. During a 2-year period (2008–2010), serum samples from 552 febrile patients with prolonged cough aged 1–88 were tested for the presence of Coxiella burnetii antibodies by using indirect immunofluorescent assay. Sera from 27.5% patients showed IgG antibodies. Serological evidence of C. burnetii infection was found in patients from all parts of Croatia. Seroprevalence rates significantly differed among regions from 21.5% to 41.2% (p=0.001). Men were more often seropositive (31.6%) than women (22.2%; p=0.016). According to age, a progressive increase in the IgG seropositivity rates was observed as ranging from 6.7% in children less than 10 years of age to 39.2% in patients aged 40–49 (p=0.001). Above the age of 50, the IgG seroprevalence remained stable. Patients from rural areas were more often seropositive than patients from urban areas (40.8% vs. 19%), p<0.001). Acute Q fever was confirmed in 5.8% of patients. Cases occurred throughout the year. A majority of cases were reported during summer months. PMID:22239180

  14. Prevalence of Coxiella burnetii antibodies among febrile patients in Croatia, 2008-2010.

    PubMed

    Vilibic-Cavlek, Tatjana; Kucinar, Jasmina; Ljubin-Sternak, Suncanica; Kolaric, Branko; Kaic, Bernard; Lazaric-Stefanovic, Lorena; Hunjak, Blazenka; Mlinaric-Galinovic, Gordana

    2012-04-01

    Despite the widespread distribution of Q fever, the prevalence in humans is not accurately known, because many infected people seroconvert without symptoms or with a mild febrile disease. The aim of this study was to determine the seroprevalence of Q fever in different regions of Croatia. During a 2-year period (2008-2010), serum samples from 552 febrile patients with prolonged cough aged 1-88 were tested for the presence of Coxiella burnetii antibodies by using indirect immunofluorescent assay. Sera from 27.5% patients showed IgG antibodies. Serological evidence of C. burnetii infection was found in patients from all parts of Croatia. Seroprevalence rates significantly differed among regions from 21.5% to 41.2% (p=0.001). Men were more often seropositive (31.6%) than women (22.2%; p=0.016). According to age, a progressive increase in the IgG seropositivity rates was observed as ranging from 6.7% in children less than 10 years of age to 39.2% in patients aged 40-49 (p=0.001). Above the age of 50, the IgG seroprevalence remained stable. Patients from rural areas were more often seropositive than patients from urban areas (40.8% vs. 19%), p<0.001). Acute Q fever was confirmed in 5.8% of patients. Cases occurred throughout the year. A majority of cases were reported during summer months. PMID:22239180

  15. Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

    PubMed Central

    Ruusuvuori, Eva; Huebner, Antje K; Kirilkin, Ilya; Yukin, Alexey Y; Blaesse, Peter; Helmy, Mohamed; Jung Kang, Hyo; El Muayed, Malek; Christopher Hennings, J; Voipio, Juha; Šestan, Nenad; Hübner, Christian A; Kaila, Kai

    2013-01-01

    Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation during intense GABAA-receptor activation. P13–14 CA VII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13–P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CA VII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS. PMID:23881097

  16. One death and a cluster of febrile complications related to saline abortions.

    PubMed

    Berger, G S; Gibson, J J; Harvey, R P; Tyler, C W; Pakter, J

    1973-07-01

    Case history of a 17-year-old Arkansas girl who died following a saline abortion performed in a New York City hospital in September, 1971, and a report of the subsequent investigation revealing possible contaminating techniques by the attending physician are given. The young woman was single, nulliparous, and at 16 weeks gestation when the abortion was performed by exchange of hypertonic saline and amniotic fluid. The procedure was uneventful, but febrile conditions developed 8 hours after delivery. Despite antibiotic treatment the fever continued and blood cultures later revealed an infection of Staphylococcus aureus. The patient died 12 days after the abortion. An epidemiologic investigation was conducted at the hospital that the girl had attended. Records of 911 patients receiving saline abortions between July 1971 and February 1972 were examined, revealing the development of fever in 44 cases. 57% of these febrile cases occurred in a 3-week period and were associated with 2 physicians whose patients' postinstillation fever rates were 17% compared with 2.5% for all other physicians in the hospital. There was no correlation between the incidence of fever and the patients' age, race, duration of retained placenta or operative removal of the placenta. It is concluded from epidemiologic evidence and direct observation of the physician's procedure that the infection was probably introduced through breaks in sterile technique at the time of fluid exchange. Rigorous aseptic procedures should be followed carefully in all saline abortion procedures. PMID:4720192

  17. Febrile infection-related epilepsy syndrome (FIRES): a nonencephalitic encephalopathy in childhood.

    PubMed

    van Baalen, Andreas; Häusler, Martin; Boor, Rainer; Rohr, Axel; Sperner, Jürgen; Kurlemann, Gerhard; Panzer, Axel; Stephani, Ulrich; Kluger, Gerhard

    2010-07-01

    Encephalitis is generally presumed, even when seizures follow banal febrile infection, and pathogen detection in cerebrospinal fluid fails. This retrospective multicenter case series reports on 22 previously healthy children aged 3-15 years (median 6.5 years) with prolonged or recurrent seizures occurring 2-14 days (median 5 days) after fever onset (19 children with respiratory or nonspecific infections). Cerebrospinal fluid studies revealed 2-42 cells/microl (median 5 cells/microl) and no pathogens. Electroencephalography showed diffuse slowing or multifocal discharges. Neuroimaging demonstrated normal findings in 10 children. Brain biopsies were performed in seven children showing gliosis but no inflammation. Anesthetic barbiturates were used in 14 children with refractory status epilepticus, and immunotherapy in 9. Two children died, eight remained in a state of impaired consciousness, eight developed therapy-refractory epilepsies, two had behavioral disturbances, and two recovered. The lack of evidence for encephalitis suggests another infection-related pathogenesis of this disastrous epileptic encephalopathy. Therefore, we propose the term "febrile infection-related epilepsy syndrome" (FIRES). PMID:20345937

  18. Relapsing-remitting multiple sclerosis and chronic idiopathic neutropenia: a challenging combination

    PubMed Central

    Münzel, Eva Jolanda; Wimperis, Jennie Z; Williams, Anna

    2013-01-01

    We report the challenges of treating relapsing-remitting multiple sclerosis (MS) in a 31-year-old woman with long-standing chronic idiopathic neutropenia. The treatment with the disease-modifying therapy interferon-? was significantly complicated by a further fall in her generally low neutrophil count, to values below 0.5×109/l, although this recovered rapidly when the treatment was stopped. We discuss the difficulties of balancing the risk of neutropenia with a risk of MS relapse. PMID:23417376

  19. HEDS Discussion Paper: Cost-effectiveness of G-CSFs for febrile neutropenia prophylaxis in non-Hodgkin's lymphoma: Whyte et al

    E-print Network

    Oakley, Jeremy

    ; lenograstim and pegfilgrastim. Costs were taken from UK databases and utility values from published sources-effective strategy was primary prophylaxis with pegfilgrastim for a patient with baseline FN risk greater than 22%, secondary prophylaxis with pegfilgrastim for baseline FN risk 8-22%, and no G-CSFs for baseline FN risk less

  20. Observational Study of the Prevalence of Febrile Neutropenia in Patients Who Received Filgrastim or Pegfilgrastim Associated With 3-4 Week Chemotherapy Regimens in Community Oncology Practices

    Microsoft Academic Search

    Vicki A. Morrison; Mitchell Wong; Dawn Hershman; Luis T. Campos; Beiying Ding; Jennifer Malin

    2007-01-01

    FoRMuLAR y MAnA geMenT single injection was required. In these patients treated with a heterogeneous group of chemotherapy regimens with a broad range of risk of FN, overall, an absolute 1.8% increase in the incidence of developing FN was observed in patients who received filgrastim compared with patients who received pegfilgrastim, (absolute rates of 6.5% and 4.7%, respectively).

  1. Intermittent prophylaxis of recurrent febrile seizures with clobazam versus diazepam.

    PubMed

    Sattar, S; Saha, S K; Parveen, F; Banu, L A; Momen, A; Ahmed, A U; Quddush, M R; Karim, M M; Begum, S A; Haque, M A; Hoque, M R

    2014-10-01

    Febrile seizures are the most common type of seizure among children that can be prevented by using prophylactic drugs like Clobazam and Diazepam. The present prospective study was conducted in the Department of Pediatrics, Mymensingh Medical College Hospital and Community Based Medical College Hospital, Bangladesh over a period of 1 year from July 2012 to June 2013 to compare the effectiveness of intermittent Clobazam versus Diazepam therapy in preventing the recurrence of febrile seizures and assessed adverse effects of each drug. A total of 65 patients (32 children administered Clobazam and rest 33 children received Diazepam) of simple and complex febrile seizures aged 6 months to 5 years of both sexes were the study population. Data were collected by interview of the patients, clinical examination and laboratory investigations using the research instrument. Data were analyzed by using Chi-square (?2) Test, Student's 't' Test and Fisher's Exact Test. For all analytical tests, the level of significance was set at 0.05 and p<0.05 was considered significant. The proportion of patients was higher between age 12-36 months and male was predominant in the both Clobazam and Diazepam groups. Over 31% of patients in Clobazam group who experienced episode of fever within 3 months, 40.6% within 6 months and 9.4% within 9 months compared to 36.4% in Diazepam group within 3 months, 45.5% within 6 months & 12.1% within 9 months after discharge from the hospital. Three (9.4%) patients in Clobazam group and 7(21.3%) in Diazepam group who experienced febrile convulsion during the follow up period. From the data adverse effects within 3 and 6 months experienced by the patient's drowsiness, sedation and ataxia were higher in Diazepam group than those in Clobazam group. However, within 9 months lethargy and irritability were somewhat higher in Clobazam group than those in Diazepam group. The mean duration of hospitalization was significantly higher in Diazepam group compared to Clobazam group (6.0±1.0 vs. 4.6±0.08 days, P<0.001). Seven (21.2%) out of 33 children with febrile seizures in Diazepam group had a history of recurrent seizures, whereas 3(9.4%) of 32 children in the Clobazam group. The risks of recurrent febrile seizure in the Diazepam group was 2.6 times greater compared to those in the Clobazam group (P=0.186). The result indicates that Clobazam is safe, efficacious, requires less frequent dosing and has less adverse effects such as drowsiness, sedation, ataxia and irritability as compared to Diazepam. So, Clobazam may be an alternative to Diazepam given intermittently for prevention of recurrent febrile seizures. PMID:25481585

  2. Increasing prevalence of Plasmodium vivax among febrile patients in Nouakchott, Mauritania.

    PubMed

    Ould Ahmedou Salem, Mohamed Salem; Mint Lekweiry, Khadijetou; Mint Deida, Jemila; Ould Emouh, Ahmed; Ould Weddady, Mohamed; Ould Mohamed Salem Boukhary, Ali; Basco, Leonardo K

    2015-03-01

    The occurrence of Plasmodium vivax malaria was reported in Nouakchott, Mauritania in the 1990s. Several studies have suggested the frequent occurrence of P. vivax malaria among Nouakchott residents, including those without recent travel history to the southern part of the country where malaria is known to be endemic. To further consolidate the evidence for P. vivax endemicity and the extent of malaria burden in one district in the city of Nouakchott, febrile illnesses were monitored in 2012-2013 in the Teyarett health center. The number of laboratory-confirmed P. vivax cases has attained more than 2,000 cases in 2013. Malaria transmission occurs locally, and P. vivax is diagnosed throughout the year. Plasmodium vivax malaria is endemic in Nouakchott and largely predominates over Plasmodium falciparum. PMID:25582695

  3. Incidence and potential causative factors associated with chronic benign neutropenia in the Kingdom of Saudi Arabia

    PubMed Central

    2015-01-01

    Background Benign neutropenia often presents in certain populations without any genotype nor phenotype. Middle East countries are among the regions where endemic cases of chronic benign neutropenia are reported in the general population with an incidence of approximately between 10-15%. Not many studies have been performed to ascertain the cause or burden associated with this condition. The objective of the current study was to identify the frequency and characterize the consequences of chronic benign neutropenia in the country of Saudi Arabia. Results Benign neutropenia was found to be high in the Saudi Arabia general population (up to 20%), with an average neutrophil count of 1.48 (range 0.99 – 1.95 × 109cells/L), with Saudis having a higher incidence of chronic benign neutropenia compared to non-Saudis (p = <0.05). Complete blood count analyses showed significant difference in the total white cell count of neutrophils (p < 0.0001), WBC (p < 0.0001), lymphocytes (p < 0.001), monocytes (p < 0.001), eosinophils (p = 0.013) as well as the CD19 B cells (p = 0.008). Conclusions Our study is the first to carefully quantitate benign neutropenia in Saudi Arabia. We identified that this condition is prevalent in the middle aged population (18 years to 55 years). These individuals not only had lower neutrophil counts, but also reduced peripheral blood cells types, especially the B-lymphocyte population (CD19 subset). As B-lymphocytes are involved in antibody production and antigen recognition, a decrease might easily predispose the individuals to infectious agents. As such more mechanistic studies need to be undertaken to understand the cause and potential long-term consequences of benign neutropenia. PMID:25810761

  4. Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry.

    PubMed

    Zeidler, Cornelia; Grote, Ulrike A H; Nickel, Anna; Brand, Beate; Carlsson, Göran; Cortesão, Emília; Dufour, Carlo; Duhem, Caroline; Notheis, Gundula; Papadaki, Helen A; Tamary, Hannah; Tjønnfjord, Geir E; Tucci, Fabio; Van Droogenbroeck, Jan; Vermylen, Christiane; Voglova, Jaroslava; Xicoy, Blanca; Welte, Karl

    2014-08-01

    Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment. PMID:24997149

  5. Dysregulation of myeloid-specific transcription factors in congenital neutropenia.

    PubMed

    Skokowa, Julia; Welte, Karl

    2009-09-01

    Severe congenital neutropenia (CN) is a heterogeneous hematopoietic syndrome with a typical "maturation arrest" of granulocytic precursors at the promyelocytic stage, inherited in an autosomal dominant or recessive manner. Intriguingly, CN patients have the same bone marrow and blood phenotypes irrespective of inheritance. This suggests that mutations in various genes may lead to the dysregulation of the common myeloid transcription factor(s) in CN. To the extensively studied myeloid-specific transcription factors belong CCAAT/enhancer-binding proteins (C/EBPs) (-alpha, -beta, -epsilon) and PU.1. The relative levels of PU.1 and C/EBPalpha in granulocytic-macrophage progenitors have been suggested to regulate monocyte versus neutrophil cell-fate choice. In CN patients, the myelopoietic maturation program is sharply shifted toward monocytopoiesis, with increased levels of monocytes and no granulocytes in the peripheral blood. We found that in myeloid cells from CN patients C/EBPalpha and its target gene inhibitor of DNA binding 1 (Id1) are abrogated due to a lack of lymphoid enhancer-binding factor 1 (LEF-1) expression but PU.1 is slightly upregulated. Based on these findings, we conclude that in LEF-1-deficient myeloid cells from CN patients misbalanced C/EBPalpha/Id1:PU.1 ratio with a strong shift toward PU.1 could play a decisive role in the improper regulation of myelopoiesis with defective granulocytopoiesis and elevated monocytic differentiation. Recently, we identified nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony enhancing factor (PBEF), as an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals and in individuals with CN. Since CN patients respond to G-CSF treatment even in the absence of LEF-1 and C/EBPalpha, we conclude that treatment of CN patients with pharmacological doses of G-CSF activates NAMPT/NAD(+)/SIRT1-dependent "emergency" granulopoiesis via C/EBPbeta. PMID:19796237

  6. Adjunctive Use of Lithium Carbonate for the Management of Neutropenia in Clozapine-Treated Children

    PubMed Central

    Mattai, Anand; Fung, Lawrence; Bakalar, Jennifer; Overman, Gerald; Tossell, Julia; Miller, Rachel; Rapoport, Judith; Gogtay, Nitin

    2009-01-01

    Objective Clozapine, a dibenzodiazepine antipsychotic, is the most effective medication for treatment resistant schizophrenia. However, its use has been limited by the high risk of neutropenia. In children, the rate of neutropenia is higher when compared to adults. We decided to explore the use of lithium to manage neutropenia in childhood-onset schizophrenia (COS) through a systematic audit of COS cases. Methods Medical records were reviewed for patients with childhood-onset schizophrenia (COS) who had been treated with the combination of clozapine and lithium carbonate. Results Seven patients were found to have been treated with both clozapine and lithium. After initiation of lithium, ANC increased significantly in six out of seven subjects by 29% to 106% with a mean of 66%. In addition, six out of seven subjects continued use of both clozapine and lithium for over 2 years (range: 2.0 to 7.2 years) and do not have immediate plans for discontinuation of either medications. Conclusions Our study bolsters support for the use of lithium in the management of neutropenia in children treated with clozapine. Although the coadministration of lithium and clozapine appears effective in the management of neutropenia, it is not without its risks and clinicians must be diligent in their joint use of these medications. PMID:19743394

  7. Infrared thermography detects febrile and behavioural responses to vaccination of weaned piglets.

    PubMed

    Cook, N J; Chabot, B; Lui, T; Bench, C J; Schaefer, A L

    2015-02-01

    An automated, non-invasive system for monitoring of thermoregulation has the potential to mitigate swine diseases through earlier detection. Measurement of radiated temperature of groups of animals by infrared thermography (IRT) is an essential component of such a system. This study reports on the feasibility of monitoring the radiated temperature of groups of animals as a biomarker of immune response using vaccination as a model for febrile disease. In Study A, weaned pigs were either treated with an intramuscular vaccine (FarrowSure Gold), a sham injection of 0.9% saline or left as untreated controls. An infrared thermal camera (FLIR A320) was fixed to the ceiling directly above the pen of animals, and recorded infrared images of the treatment groups at 5 min intervals. The effect on temperature of the spatial distribution of pigs within the pen was significant, with higher temperatures recorded when pigs were grouped together into a single cluster. A higher frequency of clustering behaviour was observed in vaccinated animals compared with controls during a period of the afternoon ~4 to 7 h post-vaccination. The daily mean of the maximum image temperature was significantly higher in vaccinated animals compared with control and sham-treated animals. In the vaccination treated group, the 24 h mean of the maximum temperature was significantly higher during the post-vaccination period compared with the 24 h period before vaccination. Increased temperature in the vaccinated animals occurred from ~3 h, peaked at ~10 h, and remained elevated for up to 20 h post-vaccination. In Study B, the effect of prevalence was tested in terms of the difference in maximum temperature between control and vaccination days. A thermal response to vaccination was detected in a pen of 24 to 26 animals when <10% of the animals were vaccinated. The results support the concept of radiated temperature measurements of groups of animals by IRT as a screening tool for febrile diseases in pig barns. PMID:25274013

  8. Common variants associated with general and MMR vaccine-related febrile seizures

    PubMed Central

    Feenstra, Bjarke; Pasternak, Björn; Geller, Frank; Carstensen, Lisbeth; Wang, Tongfei; Huang, Fen; Eitson, Jennifer L.; Hollegaard, Mads V.; Svanström, Henrik; Vestergaard, Mogens; Hougaard, David M.; Schoggins, John W.; Jan, Lily Yeh; Melbye, Mads; Hviid, Anders

    2014-01-01

    Febrile seizures represent a recognized serious adverse event following measles, mumps, and rubella (MMR) vaccination. We conducted a series of genome-wide association scans comparing children with MMR-related febrile seizures, children with febrile seizures unrelated to vaccination, and controls with no history of febrile seizures. Two loci were distinctly associated with MMR-related febrile seizures, harboring the interferon-stimulated gene IFI44L (rs273259; P = 5.9×10?12 vs. controls; P =1.2×10?9 vs. MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653; P = 9.6×10?11 vs. controls; P = 1.6×10?9 vs. MMR-unrelated febrile seizures). Furthermore, four loci were associated with febrile seizures in general implicating the sodium channel genes SCN1A (rs6432860; P = 2.2×10?16) and SCN2A (rs3769955; P = 3.1×10?10), a TMEM16 family gene (TMEM16C; rs114444506; P = 3.7×10?20), and a region associated with magnesium levels (12q21.33; rs11105468; P = 3.4×10?11). Finally, functional relevance of TMEM16C was demonstrated with electrophysiological experiments in wild-type and knockout rats. PMID:25344690

  9. Recurrence risk after first febrile seizure and effect of short term diazepam prophylaxis

    Microsoft Academic Search

    F U Knudsen

    1985-01-01

    In a prospective randomised study, 289 children admitted consecutively to hospital with their first febrile seizure were allocated, by date of admission, to short term diazepam prophylaxis (n = 152) or to no prophylaxis (n = 137) and followed for 18 months. In untreated children, five major risk factors for recurrent febrile convulsions were identified: age 15 months or less

  10. Assessments of blood lead levels in children with febrile convulsion

    PubMed Central

    Khosravi, Nastaran; Izadi, Anahita; Noorbakhsh, Samileh; Javadinia, Shima; Tabatabaei, Azardokht; Ashouri, Sarvenaz; Asgarian, Ramin

    2014-01-01

    Background: Lead elements have an adverse effect on human health. The most important complications of lead poisoning are disorders of nervous system particularly seizure .This study aimed to evaluate the blood lead levels and its association with convulsion in a group of hospitalized febrile children. Methods: In this analytic cross-sectional study, 60 hospitalized febrile children with 1- 60 month old participated in the study via non-probability convenience sampling method. All of the information included sex, age, weight, blood lead levels and history of convulsion gathered in the questionnaire. Finally all of data were statistically analyzed. Results: 66.7% of samples were male and 33.3% were female. The mean age was 32.57±38.27 months and the mean weight was 13.04±9.61kg. The Mean and Standard deviation of Blood lead level was 4.83±3.50?g/dL. 10% of samples had lead levels greater than 10?g/dL. 53.3% of patients have convulsion and other don’t have it. Blood lead levels was 4.91±3.65?g/dL in children with convulsion and 4.73± 3.38?g/dL in children without it; the difference was not significant (p= 0.8). Conclusion: Overall, no significant association was found between blood lead levels and convulsion. PMID:25664298

  11. Prolonged sleep fragmentation of mice exacerbates febrile responses to lipopolysaccharide

    PubMed Central

    Ringgold, Kristyn M.; Barf, R. Paulien; George, Amrita; Sutton, Blair C.; Opp, Mark R.

    2013-01-01

    Background Sleep disruption is a frequent occurrence in modern society. Whereas many studies have focused on the consequences of total sleep deprivation, few have investigated the condition of sleep disruption. New Method We disrupted sleep of mice during the light period for 9 consecutive days using an intermittently-rotating disc. Results Electroencephalogram (EEG) data demonstrated that non-rapid eye movement (NREM) sleep was severely fragmented and REM sleep was essentially abolished during the 12 h light period. During the dark period, when sleep was not disrupted, neither NREM sleep nor REM sleep times differed from control values. Analysis of the EEG revealed a trend for increased power in the peak frequency of the NREM EEG spectra during the dark period. The fragmentation protocol was not overly stressful as body weights and water consumption remained unchanged, and plasma corticosterone did not differ between mice subjected to 3 or 9 days of sleep disruption and home cage controls. However, mice subjected to 9 days of sleep disruption by this method responded to lipopolysaccharide with an exacerbated febrile response. Comparison with existing methods Existing methods to disrupt sleep of laboratory rodents often subject the animal to excessive locomotion, vibration, or sudden movements. This method does not suffer from any of these confounds. Conclusions This study demonstrates that prolonged sleep disruption of mice exacerbates febrile responses to lipopolysaccharide. This device provides a method to determine mechanisms by which chronic insufficient sleep contributes to the etiology of many pathologies, particularly those with an inflammatory component. PMID:23872243

  12. Febrile response induced by cecal ligation and puncture (CLP) in rats: involvement of prostaglandin E2 and cytokines.

    PubMed

    Figueiredo, Maria José; Soares, Denis Melo; Soares, Denis de Melo; Martins, Juliano Manvailer; Machado, Renes de Resende; Sorgi, Carlos Arterio; Faccioli, Lucia Helena; Melo, Miriam Cristina Contin de; de Melo, Miriam Cristina Contin; Malvar, David do Carmo; Souza, Glória E P

    2012-05-01

    The purpose of the present study was to better understand the events involved in the febrile response induced by cecal ligation and puncture (CLP), a complex infectious process. To this end, we conducted in vivo experiments in rats examining (1) fever development, (2) bacterial number in the infection focus and in blood, (3) peripheral and hypothalamic synthesis of cytokines, (4) hypothalamic and cerebrospinal fluid (CSF) synthesis of prostaglandin E(2) (PGE(2)), (5) the effect of anti-IL-6 antibody on fever, and (6) the effect of celecoxib on fever and hypothalamic synthesis of PGE(2) after CLP induction. We found that CLP promotes fever and animal death depending on the number of punctures. The peak of CLP-induced fever overlapped with the maximal increase in the number of bacteria in the infectious focus and blood, which occurred at 6 and 12 h. The peak of the febrile response also coincided with increased amounts of interleukin (IL)-1?, IL-6 and IL-10 in the peritoneal exudate and serum; IL-6 in the hypothalamus and PGE(2) in the CSF and predominantly in the hypothalamus. Moreover, intracerebroventricularly injected anti-IL-6 antibody reduced the febrile response while celecoxib reduced the fever and PGE(2) amount in the hypothalamus induced by CLP. Tumor necrosis factor (TNF)-? peaked at 3 h at all sites studied. Conversely, IL-10 concentration decreased in the hypothalamus. These findings show that the peak of CLP-induced fever is accompanied by an increase of bacteria in peritoneal fluid (local infection) and blood; local synthesis of pyrogenic (IL-1?, IL-6) and antipyretic (IL-10) cytokines and central production of IL-6 and PGE(2), suggesting that these last are the central mediators of this response. PMID:22203392

  13. Yeast Colonization and Drug Susceptibility Pattern in the Pediatric Patients With Neutropenia

    PubMed Central

    Haddadi, Pedram; Zareifar, Soheila; Badiee, Parisa; Alborzi, Abdolvahab; Mokhtari, Maral; Zomorodian, Kamiar; Pakshir, Keyvan; Jafarian, Hadis

    2014-01-01

    Background: Pediatric patients with neutropenia are vulnerable to invasive Candida infections. Candida is the primary cause of fungal infections, particularly in immunosuppressed patients. Candida albicans has been the most common etiologic agent of these infections, affecting 48% of patients Objectives: The aim of this study was to identify Candida spp. isolated from children with neutropenia and determine the antifungal susceptibility pattern of the isolated yeasts. Patients and Methods: In this study 188 children with neutropenia were recruited, fungal surveillance cultures were carried out on nose, oropharynx, stool, and urine samples. Identification of Candida strains was performed using germ tube and chlamydospore production tests on an API 20 C AUX system. Susceptibility testing on seven antifungal agents was performed using the agar-based E-test method. Results: A total of 229 yeasts were isolated. Among those, C. albicans was the most common species followed by C. krusei, C. parapsilosis, C. glabrata, C. tropicalis, C. famata, C. dubliniensis, C. kefyr, and other Candida species. C. glabrata was the most resistant isolated yeasts, which was 70% resistant to fluconazole and 50% to itraconazole, 7.5% to amphotericin B and 14% to ketoconazole. All the tested species were mostly sensitive to caspofungin. Conclusions: Knowledge about the susceptibility patterns of colonized Candida spp. can be helpful for clinicians to manage pediatric patients with neutropenia. In this study, caspofungin was the most effective antifungal agent against the colonized Candida spp. followed by conventional amphotericin B. PMID:25485060

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

    PubMed Central

    do Nascimento, Talita Garcia; de Andrade, Marceila; de Oliveira, Rosemeire Aparecida; de Almeida, Ana Maria; Gozzo, Thais de Oliveira

    2014-01-01

    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.

  15. IFN/RBV treatment induced neutropenia and its correction with neupogen in patients with hepatitis C.

    PubMed

    Sharvadze, L; Gochitashvili, N; Tophuria, A; Bolokadze, N; Tsertsvadze, T

    2007-06-01

    The aim of the study was to observe the frequency of neutropenia during Pegylated Interferon/Ribavirin therapy in patient with chronic hepatitis C; to compare the efficacy of two strategies of management of neutropenia--with Interferon dose modification and with Neupogen administration; to compare the effectiveness rate of sustained viral response (SVR) in patients with Pegylated Interferon dose modification and in patients treated by using granulocyte colony-stimulating factor G-CSF-filgrastim. (Neupogen). Study enrolled 47 patients with chronic active hepatitis C, aged 23-64. (38 male and 9 female). All patients had HCV genotype 1b. Significant neurtopenia (ANC<750 mm3) and severe neurtopenia (ANC<500 mm3) developed in 41 of 47 patients (87%). 41 patients with neurtopenia were randomized into two groups. The first group--22 patients who received granulocyte colony-stimulating factor (G-CSF, or filgrastim) 300 mcg s/c weekly for correction of neutropenia and the second group--19 patients treated either with Interferon dose reduction or temporarily inhibit of Interferon treatment. In all 22 patients of the first group neutropenia was normalized without reduction and/or inhibit of Pegylated interferon. Neupogen was well tolerated and in all 22 patients the improvement of quality of life (QOL) was observed. It was concluded that dose reduction or temporary inhibit of Pegylated Interferon in the second group negatively acts on antiviral treatment response in patients with HCV genotype 1. In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose (without reduction). Neupogen has the potential to improve adherence rates, which may in turn improve SVR. PMID:17660602

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

    PubMed

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

    2012-02-01

    The management of congenital and acquired neutropenias presents some differences according to the type of the disease. Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is not standardized and scanty data are available on the best schedule to apply. The frequency and the type of longitudinal controls in patients affected with neutropenias are not usually discussed in the literature. The Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document that includes recommendations on neutropenia treatment and timing of follow-up. PMID:22213173

  17. Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia.

    PubMed

    White, M H; Bowden, R A; Sandler, E S; Graham, M L; Noskin, G A; Wingard, J R; Goldman, M; van Burik, J A; McCabe, A; Lin, J S; Gurwith, M; Miller, C B

    1998-08-01

    We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment. PMID:9709879

  18. Cerebral hemiatrophy associated with hippocampal sclerosis following a single prolonged febrile seizure

    Microsoft Academic Search

    Iren Orosz; Christoph Härtel; Stefan Gottschalk; Katharina von Hof; Christian G. Bien; Jürgen Sperner

    2011-01-01

    The etiological relation of prolonged febrile seizures with hippocampal sclerosis and cerebral hemiatrophy is controversial.\\u000a Causal relationship is mainly adopted from retrospective statistical analysis and data from epilepsy surgery. We report a\\u000a 17-month-old boy who had a prolonged febrile seizure with a transient postictal flaccid hemiparesis and anisocoria. Family\\u000a history was unremarkable. Magnetic resonance imaging (MRI) revealed abnormal results in

  19. Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study

    Microsoft Academic Search

    C M Verity; E M Ross; J Golding

    1993-01-01

    OBJECTIVE--To study outcome after lengthy febrile convulsions and status epilepticus in children. DESIGN--Population based birth cohort study. SETTING--The child health and education study (16,004 neonatal survivors born in one week in April 1970). SUBJECTS--Information available for 14,676 children. OUTCOME MEASURES--Clinical information and tests of intellectual performance at five and 10 years after birth. RESULTS--19 children had lengthy febrile convulsions and

  20. JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family.

    PubMed

    Baris, S; Karakoc-Aydiner, E; Ozen, A; Delil, K; Kiykim, A; Ogulur, I; Baris, I; Barlan, I B

    2015-05-01

    Recently autosomal recessively inherited mutations in the gene encoding Jagunal homolog 1 (JAGN1) was described as a novel disease-causing gene of severe congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by abnormality in endoplasmic reticulum structure, absence of granules, abnormal N-glycosylation of proteins and susceptibility to apoptosis. These findings imply the role of JAGN1 in neutrophil survival. Here, we report two siblings with a homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement. PMID:25851723

  1. Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog

    PubMed Central

    Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry

    2011-01-01

    Glucocorticoid-deficient hypoadrenocorticism (GDH) with immune-mediated-neutropenia (IMN) and -thrombocytopenia (IMT) were diagnosed in a 3-year-old Labrador retriever dog. Glucocorticoid-deficient hypoadrenocorticism is rare and diagnostically challenging as clinical signs and laboratory abnormalities are often nonspecific. Immune-mediated cytopenias and other autoimmune disorders, as part of an autoimmune polyglandular syndrome have been reported with hypoadrenocorticism in humans. This is the first reported case of hypoadrenocorticism and bicytopenia in a dog. PMID:22467971

  2. Evaluation of infection control advice for patients at risk of chemotherapy-induced neutropenia in 2 pediatric oncology centers: Cape Town, South Africa, and Newcastle-Upon-Tyne, UK.

    PubMed

    Woolner, Andrea Forman; Davidson, Alan; Skinner, Rod; King, Derek

    2012-02-01

    Childhood cancers are treated with myelotoxic chemotherapy. Resultant neutropenia can lead to life-threatening infections. There is no consistent guidance on infection control precautions for neutropenic patients who are not yet febrile or infected. Although it is not possible to eradicate infection risk, it is conceivable that the risk could be reduced by effective infection prevention. This study compared infection control measures advised to pediatric and adolescent oncology patients receiving chemotherapy in 2 centers (Cape Town, South Africa, and Newcastle, UK). Prospective, observational, cross-sectional surveys of staff and patients/parents were undertaken using standardized, study-specific questionnaires. Seventy-eight staff and 56 patients/parents participated. Precautions advised in Newcastle were significantly different to Cape Town (all P < .05), except both agreed inpatient isolation was unnecessary. Over 40% of patients/parents felt isolation was important (P < .01). In Cape Town, staff and patients had similar views. In Newcastle, patients/parents had stricter opinions on particular precautions than staff, for example, attending school, playing outside and avoiding busy places (P < .01). Patient/parent responses were similar between centers. Over 90% of staff felt advising patients/parents about hand washing was important. Currently infection prevention advice is inconsistent. Further research is needed to elucidate effective guidance for infection prevention in pediatric neutropenic patients. PMID:22304013

  3. Single intramuscular injection of diclofenac sodium in febrile pediatric patients

    PubMed Central

    Lee, Jun Yeol; Cho, Jun Hwi; Shin, Myoung Cheol; Ohk, Taek Geun; Lee, Hui Young; Park, Chan Woo

    2015-01-01

    Objectives: There are few reports on the effectiveness and safety of intramuscular (IM) antipyretic injections in pediatric patients. This study reports the efficacy and adverse effects of a single IM injection of diclofenac sodium in pediatric patients. Materials and Methods: This was an observational study in which records of febrile pediatric patients presenting to the emergency department were analyzed. Subjects included pediatric patients presenting to the emergency department with a temperature of 38°C or higher. Infants under 12 months of age were excluded. Patients were excluded if they received antipyretics within 4 h prior to presenting to the emergency department. Body temperature was measured at 30–60 min intervals following diclofenac sodium injections. Fever alleviation was defined as the temperature decline to 1°C below the temperature at presentation. Patients who received diclofenac sodium twice or more on different days were observed for side effects such as allergic reaction. Records from the emergency department and outpatient clinics were analyzed. Results: The dose of diclofenac sodium injected was approximately 2 mg/kg. The average time elapsed until antipyresis was 69.1 ± 23.8 min. The average temperature reduction after 1 h was 1.1 ± 0.6°C. The average proportion of temperature change after 1 h was 40.6 ± 22.2%. During the period at the emergency department, there were no reported serious side effects. Conclusions: A single dose of diclofenac sodium provided effective antipyresis in pediatric patients. Serious side effects were not observed.

  4. Diagnostic significance of indium-111 granulocyte scintigraphy in febrile patients

    SciTech Connect

    Syrjaelae, M.T.Va.; Valtonen, V.; Liewendahl, K.; Myllylae, G.

    1987-02-01

    Sixty-eight patients with fever of unknown origin, 32 patients with postoperative fever, and 26 patients with therapy-resistant fever after bacteremia were investigated with (/sup 111/In) granulocyte scintigraphy for the detection of abscesses. The results showed that the value of (/sup 111/In)granulocyte scintigraphy in the detection of infectious foci vary in these three types of febrile conditions. The overall sensitivity and specificity were 86.5% and 87.8%, respectively. We observed, however, a relatively low predictive value of a positive result in the fever of unknown origin group (73.1%), and also a low predictive value of a negative result in the bacteremia group (66.7%). The C-reactive protein (CRP) levels in patients with a true-positive scintigram were significantly (p less than 0.001) higher than in patients with a true-negative scintigram. There was also a significant positive correlation (p less than 0.01) between the serum CRP concentration and the intensity of the granulocyte accumulations. There was no correlation between the peripheral leukocyte count or the erythrocyte sedimentation rate (ESR) and the intensity of the granulocyte uptake. Therefore CRP, but not the leukocyte count or ESR, appears useful for selecting the patients who benefit most from granulocyte scintigraphy.

  5. Acute Febrile Illness Surveillance in a Tertiary Hospital Emergency Department: Comparison of Influenza and Dengue Virus Infections

    PubMed Central

    Lorenzi, Olga D.; Gregory, Christopher J.; Santiago, Luis Manuel; Acosta, Héctor; Galarza, Ivonne E.; Hunsperger, Elizabeth; Muñoz, Jorge; Bui, Duy M.; Oberste, M. Steven; Peñaranda, Silvia; García-Gubern, Carlos; Tomashek, Kay M.

    2013-01-01

    In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2–7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs. PMID:23382160

  6. Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures

    Microsoft Academic Search

    M. Uhari; H. Rantala; L. Vainionpää; R. Kurttila

    1995-01-01

    See commentary, “Prevention of recurrent febrile seizures”Acetaminophen and low doses of diazepam were evaluated for the prevention of recurrences of febrile seizures in a placebo-controlled, double-blind trial. Children after their first febrile seizure were assigned to receive either one dose of rectally administered diazepam, and then, after 6 hours, oral doses of 0.2 mg\\/kg three times a day for the

  7. LH750 hematology analyzers to identify malaria and dengue and distinguish them from other febrile illnesses.

    PubMed

    Sharma, P; Bhargava, M; Sukhachev, D; Datta, S; Wattal, C

    2013-06-15

    INTRODUCTION: Tropical febrile illnesses such as malaria and dengue are challenging to differentiate clinically. Automated cellular indices from hematology analyzers may afford a preliminary rapid distinction. METHODS: Blood count and VCS parameters from 114 malaria patients, 105 dengue patients, and 105 febrile controls without dengue or malaria were analyzed. Statistical discriminant functions were generated, and their diagnostic performances were assessed by ROC curve analysis. RESULTS: Three statistical functions were generated: (i) malaria-vs.-controls factor incorporating platelet count and standard deviations of lymphocyte volume and conductivity that identified malaria with 90.4% sensitivity, 88.6% specificity; (ii) dengue-vs.-controls factor incorporating platelet count, lymphocyte percentage and standard deviation of lymphocyte conductivity that identified dengue with 81.0% sensitivity and 77.1% specificity; and (iii) febrile-controls-vs.-malaria/dengue factor incorporating mean corpuscular hemoglobin concentration, neutrophil percentage, mean lymphocyte and monocyte volumes, and standard deviation of monocyte volume that distinguished malaria and dengue from other febrile illnesses with 85.1% sensitivity and 91.4% specificity. CONCLUSIONS: Leukocyte abnormalities quantitated by automated analyzers successfully identified malaria and dengue and distinguished them from other fevers. These economic discriminant functions can be rapidly calculated by analyzer software programs to generate electronic flags to trigger-specific testing. They could potentially transform diagnostic approaches to tropical febrile illnesses in cost-constrained settings. PMID:23773224

  8. A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots

    PubMed Central

    Bejon, Philip; Williams, Thomas N; Nyundo, Christopher; Hay, Simon I; Benz, David; Gething, Peter W; Otiende, Mark; Peshu, Judy; Bashraheil, Mahfudh; Greenhouse, Bryan; Bousema, Teun; Bauni, Evasius; Marsh, Kevin; Smith, David L; Borrmann, Steffen

    2014-01-01

    Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or ‘hotspots’ of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive malaria smears per homestead, and (b) the mean age of children with malaria per homestead. These two measures were inversely correlated, indicating that children in homesteads at higher transmission acquire immunity more rapidly. This inverse correlation increased gradually with increasing spatial scale of analysis, and hotspots of febrile malaria were identified at every scale. We found hotspots within hotspots, down to the level of an individual homestead. Febrile malaria hotspots were temporally unstable, but 4 km radius hotspots could be targeted for 1 month following 1 month periods of surveillance. DOI: http://dx.doi.org/10.7554/eLife.02130.001 PMID:24843017

  9. Febrile temperatures unmask biophysical defects in Nav1.1 epilepsy mutations supportive of seizure initiation

    PubMed Central

    Kahlig, Kristopher M.; Das, Joost H.G.; van Kempen, Marjan J.A.; Lindhout, Dick; Koeleman, Bobby P.C.; Rook, Martin B.

    2013-01-01

    Generalized epilepsy with febrile seizures plus (GEFS+) is an early onset febrile epileptic syndrome with therapeutic responsive (a)febrile seizures continuing later in life. Dravet syndrome (DS) or severe myoclonic epilepsy of infancy has a complex phenotype including febrile generalized or hemiclonic convulsions before the age of 1, followed by intractable myoclonic, complex partial, or absence seizures. Both diseases can result from mutations in the Nav1.1 sodium channel, and initially, seizures are typically triggered by fever. We previously characterized two Nav1.1 mutants—R859H (GEFS+) and R865G (DS)—at room temperature and reported a mixture of biophysical gating defects that could not easily predict the phenotype presentation as either GEFS+ or DS. In this study, we extend the characterization of Nav1.1 wild-type, R859H, and R865G channels to physiological (37°C) and febrile (40°C) temperatures. At physiological temperature, a variety of biophysical defects were detected in both mutants, including a hyperpolarized shift in the voltage dependence of activation and a delayed recovery from fast and slow inactivation. Interestingly, at 40°C we also detected additional gating defects for both R859H and R865G mutants. The GEFS+ mutant R859H showed a loss of function in the voltage dependence of inactivation and an increased channel use-dependency at 40°C with no reduction in peak current density. The DS mutant R865G exhibited reduced peak sodium currents, enhanced entry into slow inactivation, and increased use-dependency at 40°C. Our results suggest that fever-induced temperatures exacerbate the gating defects of R859H or R865G mutants and may predispose mutation carriers to febrile seizures. PMID:24277604

  10. Shwachman-Bodian-Diamond syndrome: metaphyseal chondrodysplasia in children with pancreatic insufficiency and neutropenia.

    PubMed

    Levin, Terry L; Mäkitie, Outi; Berdon, Walter E; Lachman, Ralph S

    2015-07-01

    Shwachman-Bodian-Diamond syndrome (OMIM 260400) was identified in 1964 by pediatricians Harry Shwachman, a leader in cystic fibrosis, and Louis K. Diamond, a hematologist, along with pediatrician and morbid anatomist Martin Bodian. Initially the syndrome's clinical presentation included exocrine pancreatic insufficiency (lipomatous replacement of the pancreas) and neutropenia. In 1967 skeletal changes of metaphyseal chondrodysplasia were also described, completing the triad of findings; these abnormalities are present in all affected children and should be viewed as an integral feature of the syndrome, also called Shwachman-Diamond syndrome. PMID:25416932

  11. Prevalence of Bacterial Febrile Illnesses in Children in Kilosa District, Tanzania

    PubMed Central

    Chipwaza, Beatrice; Mhamphi, Ginethon G.; Ngatunga, Steve D.; Selemani, Majige; Amuri, Mbaraka; Mugasa, Joseph P.; Gwakisa, Paul S.

    2015-01-01

    Introduction Bacterial etiologies of non-malaria febrile illnesses have significantly become important due to high mortality and morbidity, particularly in children. Despite their importance, there are few reports on the epidemiology of these diseases in Tanzania, and the true burden of such illnesses remains unknown. This study aimed to identify the prevalence of leptospirosis, brucellosis, typhoid fever and urinary tract infections and their rate of co-infections with malaria. Methods A cross-sectional study was conducted at Kilosa district hospital in Tanzania for 6 months. Febrile children aged from 2–13 years were recruited from the outpatient department. Patients were screened by serological tests such as IgM and IgG ELISA, and microscopic agglutination test. Results A total of 370 patients were enrolled; of these 85 (23.0%) had malaria parasites, 43 (11.6%) had presumptive acute leptospirosis and 26/200 (13%) had confirmed leptospirosis. Presumptive acute brucellosis due to B. abortus was identified among 26 (7.0%) of patients while B. melitensis was detected in 57 (15.4%) of the enrolled patients. Presumptive typhoid fever due to S. Typhi was identified in thirty eight (10.3%) of the participants and 69 (18.6%) had urinary tract infections. Patients presented with similar symptoms; therefore, the identification of these diseases could not be done based on clinical ground alone. Co-infections between malaria and bacterial febrile illnesses were observed in 146 patients (39.5%). Although antibacterials and/or anti-malarials were prescribed in most patients, some patients did not receive the appropriate treatment. Conclusion The study has underscored the importance of febrile bacterial diseases including zoonoses such as leptospirosis and brucellosis in febrile children, and thus such illnesses should be considered by clinicians in the differential diagnoses of febrile diseases. However, access to diagnostic tests for discrimination of febrile illnesses is needed. This would allow febrile patients to receive the correct diagnoses and facilitation of accurate and prompt treatment. PMID:25955522

  12. Cardiac arrest associated with febrile illness due to U.K. acquired Cyclospora cayetanensis.

    PubMed

    Burrell, Christopher; Reddy, Srinivasulu; Haywood, Guy; Cunningham, Richard

    2007-01-01

    This report describes a 43 yr old man diagnosed with U.K. acquired cyclospora cayetanensis infection resulting in fever and diarrhoea. In course of the febrile illness, he suffered an out of hospital cardiac arrest. Extensive cardiac investigation including a transthoracic echocardiogram, coronary angiogram, and cardiac electrophysiological studies failed to identify the cause. The possible links between cyclospora infection and cardiac arrest are explored. Fever has been reported as a precipitant for idiopathic ventricular fibrillation in patients with the Brugada syndrome but also rarely in individuals with normal hearts. Clinicians should be aware of a possible link between any febrile illness and potentially fatal ventricular dysrhythmia. PMID:16684571

  13. Febrile convulsions in a national cohort followed up from birth. I--Prevalence and recurrence in the first five years of life

    Microsoft Academic Search

    C M Verity; N R Butler; J Golding

    1985-01-01

    Of 13 135 children followed up from birth to the age of 5 years, 303 (2.3%) had febrile convulsions. Prior neurological abnormality had been noted in 13. Of the 290 remaining children, 57 (20%) presented with a complex convulsion, and 103 children (35%) went on to have further febrile convulsions. The risk of further febrile convulsions varied with the age

  14. Peg-filgrastim and cabazitaxel in prostate cancer patients.

    PubMed

    Di Lorenzo, Giuseppe; D?Aniello, Carmine; Buonerba, Carlo; Federico, Piera; Rescigno, Pasquale; Puglia, Livio; Ferro, Matteo; Bosso, Davide; Cavaliere, Carla; Palmieri, Giovannella; Sonpavde, Guru; De Placido, Sabino

    2013-01-01

    To determine the impact of prophylaxis with granulocyte-colony stimulating growth factor (G-CSF) on the risk of febrile neutropenia in a cohort of patients enrolled at the University Federico II of Naples and treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC). We carried out a retrospective review of prospectively collected data of patients enrolled at our institution in a compassionate-use programme with cabazitaxel, aimed at providing early access to the drug before its commercial availability in mCRPC patients. Besides baseline clinical and demographic characteristics, data on treatment efficacy and toxicity, as well as those on the use of G-CSF per patient per cycle were extracted. Progression-free survival and overall survival were calculated using the Kaplan-Meier method. Fisher's exact test was used to explore a relationship between a single event of grade 3 or more neutropenia or febrile neutropenia and previous use of G-CSF. Univariate analysis was carried out to evaluate predictors of grade 3 or more neutropenia and/or febrile neutropenia. Of 34 patients enrolled at our institution from December 2010 to December 2011, 32 had received at least one dose of cabazitaxel and were included in the analysis. Patients received a median of 10 cabazitaxel cycles. Grade 3 or more neutropenia was common, occurring in 64.5% of patients. Three patients (9.3%) developed febrile neutropenia. Twenty-seven patients received prophylaxis with G-CSF during at least one cycle using peg-filgrastim. The risk of grade 3 or more neutropenia and/or febrile neutropenia per patient and per cycle was seven times lower when G-CSF was used. Baseline neutrophil count of less than 4570/mm was the strongest predictor of grade 3 or more neutropenia and/or febrile neutropenia. No toxic death was reported. Only one patient discontinued cabazitaxel because of an adverse event. Our analysis suggests that prophylaxis with peg-filgrastim may considerably reduce the incidence of grade 3 or more neutropenia and, possibly, of febrile neutropenia in mCRPC patients treated with cabazitaxel. Further analyses involving a larger population are warranted to confirm our results. PMID:23044721

  15. Meta-analysis of neutropenia or leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy

    Microsoft Academic Search

    Kohei Shitara; Keitaro Matsuo; Isao Oze; Ayako Mizota; Chihiro Kondo; Motoo Nomura; Tomoya Yokota; Daisuke Takahari; Takashi Ura; Kei Muro

    Purpose  We performed a systematic review and meta-analysis to determine the impact of neutropenia or leukopenia experienced during\\u000a chemotherapy on survival.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Eligible studies included prospective or retrospective analyses that evaluated neutropenia or leukopenia as a prognostic factor\\u000a for overall survival or disease-free survival. Statistical analyses were conducted to calculate a summary hazard ratio and\\u000a 95% confidence interval (CI) using random-effects or

  16. Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia.

    PubMed

    Hoggatt, Jonathan; Tate, Tiffany A; Pelus, Louis M

    2015-01-01

    Chemotherapy, irradiation, and other agents are widely used to target the process of cell division in neoplastic cells. However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening. Neutropenia is the most serious hematologic toxicity of chemotherapy, which can result in patient morbidity and mortality due to opportunistic infection and often is the limiting factor in dose escalation or duration of chemotherapeutic administration. Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy. Treatment of iatrogenic and congenic neutropenia was changed in the early 1990s with the introduction of filgrastim (Neupogen(®)) and pegfilgrastim (Neulasta(®)). With the expiration of patent lives of both of these drugs, biosimilars have begun to emerge. In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex(®)), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace. PMID:25878498

  17. Building-associated risk of febrile acute respiratory diseases in Army trainees

    Microsoft Academic Search

    J. F. Brundage; R. M. Scott; W. M. Lednar; D. W. Smith; R. N. Miller

    1988-01-01

    Airborne transmission of infectious agents and associations of indoor air pollutants with respiratory illnesses are well documented. We hypothesized that energy conservation measures that tighten buildings also increase risks of respiratory infection among building occupants. At four Army training centers during a 47-month period, incidence rates of febrile acute respiratory disease were compared between basic trainees in modern (energy-efficient design

  18. Effects of an educational program on parents with febrile convulsive children

    Microsoft Academic Search

    Mei-Chin Huang; Ching-Chuan Liu; Chao-Ching Huang

    1998-01-01

    The purpose of this study was to characterize the effects of an educational program on knowledge, attitude, concern, and first-aid measures among parents with febrile convulsive children. All parents completed a pretest questionnaire 3 weeks before the meeting. The parents were assigned randomly into experimental (n = 65) and control (n = 64) groups on the day they attended the

  19. CSF Glucose Concentrations in Infants with Febrile Convulsions and the Possible Effect of Acetaminophen

    Microsoft Academic Search

    Mahmoud Mohammadi; Mohammad R. Mohebbi; Fariba Naderi

    The present study was done to explore the relationship between the cerebrospinal fluid (CSF) glucose concentration, body temperature, seizure duration, and acetaminophen administration. Retrospective record review of 117 consecutive febrile convulsive infants aging 3 to 18 months admitted to Bahrami Children Hospital were studied. There was a positive correlation between CSF glucose level and body temperature in those who had

  20. Cultural categorization of febrile illnesses in correlation with herbal remedies used for treatment in Southwestern Nigeria

    Microsoft Academic Search

    E. O Ajaiyeoba; O Oladepo; O. I Fawole; O. M Bolaji; D. O Akinboye; O. A. T Ogundahunsi; C. O Falade; G. O Gbotosho; O. A Itiola; T. C Happi; O. O Ebong; I. M Ononiwu; O. S Osowole; O. O Oduola; J. S Ashidi; A. M. J Oduola

    2003-01-01

    The ethnographic study was conducted in two communities in Oyo State in Southwestern Nigeria. The study sites consisted of a rural and an urban local government area located in the tropical rain forest zone of Nigeria. The study was designed to obtain information on febrile illnesses and herbal remedies for treatment with the aim of identifying potential antimalarial drugs. The

  1. Immune Determinants of Organism and Outcome in Febrile Hospitalized Thai Patients with Bloodstream Infections

    Microsoft Academic Search

    JANINE JASON; LENNOX ARCHIBALD; L. CLIFFORD MCDONALD; W. MICHAEL HART; SUNTHORN RHEANPPUMIKANKIT; SOMSIT TANSUPHWASWADIKUL; MARTHA G. BYRD; JOSHUA LARNED; ALISON HAN; TIMOTHY A. GREEN; WILLIAM R. JARVIS

    1999-01-01

    Opportunistic infections (OI) and the human immunodeficiency virus (HIV) cause significant morbidity and mortality in developing countries. Immune cell and cytokine profiles may be related to the type and course of OI and to the OI-HIV interaction. Examining cell-specific cytokine production ex vivo has only recently become feasible. In Thailand, 53 febrile, hospitalized adults were enrolled in a study of

  2. Arboviral Etiologies of Acute Febrile Illnesses in Western South America, 2000–2007

    Microsoft Academic Search

    Brett M. Forshey; Carolina Guevara; V. Alberto Laguna-Torres; Manuel Cespedes; Jorge Vargas; Alberto Gianella; Efrain Vallejo; César Madrid; Nicolas Aguayo; Eduardo Gotuzzo; Victor Suarez; Ana Maria Morales; Luis Beingolea; Nora Reyes; Juan Perez; Monica Negrete; Claudio Rocha; Amy C. Morrison; Kevin L. Russell; Patrick J. Blair; James G. Olson; Tadeusz J. Kochel

    2010-01-01

    BackgroundArthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to

  3. Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study

    PubMed Central

    Atladóttir, Hjördis Ósk; Henriksen, Tine Brink; Schendel, Diana E.; Parner, Erik T.

    2015-01-01

    OBJECTIVES Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelopment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of antibiotics reported by the mother during pregnancy and the risk for autism spectrum disorder (ASD) and infantile autism in the offspring. METHODS We used a population-based cohort consisting of 96 736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD. RESULTS Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism. CONCLUSIONS Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism. The results may be due to multiple testing; the few positive findings are potential chance findings. PMID:23147969

  4. Chikungunya as a Cause of Acute Febrile Illness in Southern Sri Lanka

    PubMed Central

    Reller, Megan E.; Akoroda, Ufuoma; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikaarachchi, Wasantha; Strouse, John J.; Chua, Robert; Hou, Yan'an; Chow, Angelia; Sessions, October M.; Østbye, Truls; Gubler, Duane J.; Woods, Christopher W.; Bodinayake, Champica

    2013-01-01

    Background Chikungunya virus (CHIKV) re-emerged in Sri Lanka in late 2006 after a 40-year hiatus. We sought to identify and characterize acute chikungunya infection (CHIK) in patients presenting with acute undifferentiated febrile illness in unstudied rural and semi-urban southern Sri Lanka in 2007. Methodology/Principal Findings We enrolled febrile patients ? 2 years of age, collected uniform epidemiologic and clinical data, and obtained serum samples for serology, virus isolation, and real-time reverse-transcriptase PCR (RT-PCR). Serology on paired acute and convalescent samples identified acute chikungunya infection in 3.5% (28/797) patients without acute dengue virus (DENV) infection, 64.3% (18/28) of which were confirmed by viral isolation and/or real-time RT-PCR. No CHIKV/DENV co-infections were detected among 54 patients with confirmed acute DENV. Sequencing of the E1 coding region of six temporally distinct CHIKV isolates (April through October 2007) showed that all isolates posessed the E1-226A residue and were most closely related to Sri Lankan and Indian isolates from the same time period. Except for more frequent and persistent musculoskeletal symptoms, acute chikungunya infections mimicked DENV and other acute febrile illnesses. Only 12/797 (1.5%) patients had serological evidence of past chikungunya infection. Conclusions/Significance Our findings suggest CHIKV is a prominent cause of non-specific acute febrile illness in southern Sri Lanka. PMID:24312651

  5. Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review

    PubMed Central

    Prasad, Namrata; Murdoch, David R.; Reyburn, Hugh; Crump, John A.

    2015-01-01

    Background With apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries. Methods and Findings We conducted a systematic review of studies conducted in low-and-middle income countries 1980–2013 that prospectively assessed consecutive febrile patients admitted to hospital using rigorous laboratory-based case definitions. We found 45 eligible studies describing 54,578 patients; 9,771 (17.9%) had a positive result for ?1 pathogen meeting diagnostic criteria. There were no eligible studies identified from Southern and Middle Africa, Eastern Asia, Oceania, Latin American and Caribbean regions, and the European region. The median (range) number of diagnostic tests meeting our confirmed laboratory case definitions was 2 (1 to 11) per study. Of diagnostic tests, 5,052 (10.3%) of 49,143 had confirmed bacterial or fungal bloodstream infection; 709 (3.8%) of 18,142 had bacterial zoonosis; 3,488 (28.5%) of 12,245 had malaria; and 1,804 (17.4%) of 10,389 had a viral infection. Conclusions We demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens. High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed. PMID:26126200

  6. Sweet's syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis

    PubMed Central

    Cohen, Philip R

    2007-01-01

    Sweet's syndrome (the eponym for acute febrile neutrophilic dermatosis) is characterized by a constellation of clinical symptoms, physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions (papules, nodules, and plaques), and a diffuse infiltrate consisting predominantly of mature neutrophils that are typically located in the upper dermis. Several hundreds cases of Sweet's syndrome have been published. Sweet's syndrome presents in three clinical settings: classical (or idiopathic), malignancy-associated, and drug-induced. Classical Sweet's syndrome (CSS) usually presents in women between the age of 30 to 50 years, it is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately one-third of patients with CSS experience recurrence of the dermatosis. The malignancy-associated Sweet's syndrome (MASS) can occur as a paraneoplastic syndrome in patients with an established cancer or individuals whose Sweet's syndrome-related hematologic dyscrasia or solid tumor was previously undiscovered; MASS is most commonly related to acute myelogenous leukemia. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer. Hence, MASS can be the cutaneous harbinger of either an undiagnosed visceral malignancy in a previously cancer-free individual or an unsuspected cancer recurrence in an oncology patient. Drug-induced Sweet's syndrome (DISS) most commonly occurs in patients who have been treated with granulocyte-colony stimulating factor, however, other medications may also be associated with DISS. The pathogenesis of Sweet's syndrome may be multifactorial and still remains to be definitively established. Clinical and laboratory evidence suggests that cytokines have an etiologic role. Systemic corticosteroids are the therapeutic gold standard for Sweet's syndrome. After initiation of treatment with systemic corticosteroids, there is a prompt response consisting of dramatic improvement of both the dermatosis-related symptoms and skin lesions. Topical application of high potency corticosteroids or intralesional corticosteroids may be efficacious for treating localized lesions. Other first-line oral systemic agents are potassium iodide and colchicine. Second-line oral systemic agents include indomethacin, clofazimine, cyclosporine, and dapsone. The symptoms and lesions of Sweet's syndrome may resolved spontaneously, without any therapeutic intervention; however, recurrence may follow either spontaneous remission or therapy-induced clinical resolution. PMID:17655751

  7. Micafungin versus Fluconazole for Prophylaxis against Invasive Fungal Infections during Neutropenia in Patients Undergoing Hematopoietic Stem Cell Transplantation

    Microsoft Academic Search

    Voravit Ratanatharathorn; Daniel E. Stepan; Carole B. Miller; Jeffrey H. Lipton; David H. Vesole; Nancy Bunin; Donna A. Wall; John W. Hiemenz; Yoichi Satoi; Jeanette M. Lee; Thomas J. Walsh

    2004-01-01

    5 for the National Institute of Allergy and Infectious Diseases Mycoses Study Group a We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg

  8. The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study

    PubMed Central

    Ye, Ying; Carlsson, Göran; Karlsson-Sjöberg, Jenny M. T.; Borregaard, Niels; Modéer, Thomas U.; Andersson, Mats L.; Pütsep, Katrin L-A.

    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 accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R?=?0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R?=?0.405) (P?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 in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency, and in conditions in which bone marrow myelopoiesis is negatively affected. PMID:26119962

  9. The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study.

    PubMed

    Ye, Ying; Carlsson, Göran; Karlsson-Sjöberg, Jenny M T; Borregaard, Niels; Modéer, Thomas U; Andersson, Mats L; Pütsep, Katrin L-A

    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 accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R?=?0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R?=?0.405) (P?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 in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency, and in conditions in which bone marrow myelopoiesis is negatively affected. PMID:26119962

  10. Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relations with disease activity, antibodies to double stranded DNA, and neutropenia

    Microsoft Academic Search

    P A Courtney; A D Crockard; K Williamson; A E Irvine; R J Kennedy; A L Bell

    1999-01-01

    OBJECTIVETo quantify the percentage of apoptotic peripheral blood neutrophils in systemic lupus erythematosus (SLE) and to determine the relations with disease activity and neutropenia.METHODSNeutrophil apoptosis in SLE patients (n =50) was assessed by flow cytometry using annexin V binding and fluorescent labelled anti-fas. Rheumatoid arthritis (RA, n =20) and inflammatory bowel disease patients (IBD, n =20) were studied as disease

  11. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

    PubMed Central

    Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.

    2010-01-01

    Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ? 1.3 × 109/l), anemia (hemoglobin ? 10 g/dl), and thrombocytopenia (platelets ? 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784

  12. Microbes of the tonsils in PFAPA (Periodic Fever, Aphtous stomatitis, Pharyngitis and Adenitis) syndrome - a possible trigger of febrile episodes.

    PubMed

    Lantto, Ulla; Koivunen, Petri; Tapiainen, Terhi; Glumoff, Virpi; Hirvikoski, Pasi; Uhari, Matti; Renko, Marjo

    2015-06-01

    Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis (PFAPA) is a childhood febrile syndrome that is often cured by tonsillectomy (TE). We hypothesized that microbes present in the tonsils may act as a trigger for the activation of inflammasomes and investigated the microbiology of the tonsils in PFAPA patients and controls. We recruited 31 consecutive children who underwent TE due to PFAPA; 24 children who underwent TE due to other reasons served as controls. We cultured all the samples for bacteria, mycobacteria, yeasts, and viruses and used PCR for 15 viruses. Also biofilm formation and histologic findings were identified. The samples of the patients yielded Candida albicans more often than did the controls (16 vs 0%, p = 0.003). Staphylococcus aureus occurred in only 10% of the patients, but in 38% of the controls (p = 0.01). Varicella zoster and Herpes simplex viruses occurred less often in patients than in controls. Biofilm was present in 55% of PFAPA tonsils, but in only 24% of the controls (p = 0.03). The microbes found in the tonsils of PFAPA patients showed significant differences from those of controls. This may in part explain the efficacy of TE in PFAPA. PMID:25907769

  13. Relationship between the population incidence of febrile convulsions in young children in Sydney, Australia and seasonal epidemics of influenza and respiratory syncytial virus, 2003-2010: a time series analysis

    PubMed Central

    2011-01-01

    Background In 2010, intense focus was brought to bear on febrile convulsions in Australian children particularly in relation to influenza vaccination. Febrile convulsions are relatively common in infants and can lead to hospital admission and severe outcomes. We aimed to examine the relationships between the population incidence of febrile convulsions and influenza and respiratory syncytial virus (RSV) seasonal epidemics in children less than six years of age in Sydney Australia using routinely collected syndromic surveillance data and to assess the feasibility of using this data to predict increases in population rates of febrile convulsions. Methods Using two readily available sources of routinely collected administrative data; the NSW Emergency Department (ED) patient management database (1 January 2003 - 30 April 2010) and the Ambulance NSW dispatch database (1 July 2006 - 30 April 2010), we used semi-parametric generalized additive models (GAM) to determine the association between the population incidence rate of ED presentations and urgent ambulance dispatches for 'convulsions', and the population incidence rate of ED presentations for 'influenza-like illness' (ILI) and 'bronchiolitis' - proxy measures of influenza and RSV circulation, respectively. Results During the study period, when the weekly all-age population incidence of ED presentations for ILI increased by 1/100,000, the 0 to 6 year-old population incidence of ED presentations for convulsions increased by 6.7/100,000 (P < 0.0001) and that of ambulance calls for convulsions increased by 3.2/100,000 (P < 0.0001). The increase in convulsions occurred one week earlier relative to the ED increase in ILI. The relationship was weaker during the epidemic of pandemic (H1N1) 2009 influenza virus. When the 0 to 3 year-old population incidence of ED presentations for bronchiolitis increased by 1/100,000, the 0 to 6 year-old population incidence of ED presentations for convulsions increased by 0.01/100,000 (P < 0.01). We did not find a meaningful and statistically significant association between bronchiolitis and ambulance calls for convulsions. Conclusions Influenza seasonal epidemics are associated with a substantial and statistically significant increase in the population incidence of hospital attendances and ambulance dispatches for reported febrile convulsions in young children. Monitoring syndromic ED and ambulance data facilitates rapid surveillance of reported febrile convulsions at a population level. PMID:22029484

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

    PubMed Central

    Chen, Li-Li; Toyoguchi, Mitsuko; Shimakawa, Machiko; Hori, Sadao

    2011-01-01

    We report a rare case of chronic refractory uveitis in a patient with childhood-onset cyclic neutropenia (CN). A 19-year-old woman, who had a history of CN beginning at age 2, presented with bilateral chronic nongranulomatous uveitis, complicated cataract, retinal vasculitis, cystoids macular edema, and vitreous hemorrhage. She had recurrent episodes of oral ulcers, tonsillitis, genital ulcers, and folliculitis during neutropenic nadir. After the resumption of granulocyte colony-stimulating factor therapy for her CN, vitreous hemorrhage in both eyes followed. Her eyes were treated with topical corticosteroids, retinal photocoagulation, and cataract surgery. Blood and bone marrow test results confirmed the diagnosis of CN. She also fulfilled the diagnostic criteria of Behçet's disease, though clinical features of her uveitis were dissimilar to those found in that disease. PMID:21677883

  15. Rituximab associated neutropenia: Description of three cases and an insight into the underlying pathogenesis

    PubMed Central

    Weissmann-Brenner, Alina; Brenner, Baruch; Belyaeva, Inessa; Lahav, Meir; Rabizadeh, Esther

    2011-01-01

    Summary Background To describe Rituximab associated neutropenia (RAN), and to explore its underlying mechanism. Case Report We describe three patients with RAN. The effect of patient’s plasma on colony forming unit, Granulocyte-Monocyte (CFU-GM) was measured by the addition of plasma to the culture of a healthy bone-marrow. Repeated tests were performed after recovery of white count. In the leukopenic period the patient’s plasma inhibited CFU growth completely. Control plasma did not have such an effect. Addition of patient’s cell supernatant to bone marrow cells did not change the number of CFU. The same effect was demonstrated in normal control. After recovery the patient’s plasma did not inhibit colony formation, similar to control. Conclusions RAN is a clinically significant side effect. It may take place during treatment or several months afterwards. Circulating antibodies in the plasma may be responsible for this unique BM toxicity. PMID:22037749

  16. The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15?781 febrile illnesses

    PubMed Central

    2010-01-01

    Objectives To evaluate current processes by which young children presenting with a febrile illness but suspected of having serious bacterial infection are diagnosed and treated, and to develop and test a multivariable model to distinguish serious bacterial infections from self limiting non-bacterial illnesses. Design Two year prospective cohort study. Setting The emergency department of The Children’s Hospital at Westmead, Westmead, Australia. Participants Children aged less than 5 years presenting with a febrile illness between 1 July 2004 and 30 June 2006. Intervention A standardised clinical evaluation that included mandatory entry of 40 clinical features into the hospital’s electronic record keeping system was performed by physicians. Serious bacterial infections were confirmed or excluded using standard radiological and microbiological tests and follow-up. Main outcome measures Diagnosis of one of three key types of serious bacterial infection (urinary tract infection, pneumonia, and bacteraemia), and the accuracy of both our clinical decision making model and clinician judgment in making these diagnoses. Results We had follow-up data for 93% of the 15?781 instances of febrile illnesses recorded during the study period. The combined prevalence of any of the three infections of interest (urinary tract infection, pneumonia, or bacteraemia) was 7.2% (1120/15?781, 95% confidence interval (CI) 6.7% to 7.5%), with urinary tract infection the diagnosis in 543 (3.4%) cases of febrile illness (95% CI 3.2% to 3.7%), pneumonia in 533 (3.4%) cases (95% CI 3.1% to 3.7%), and bacteraemia in 64 (0.4%) cases (95% CI 0.3% to 0.5%). Almost all (>94%) of the children with serious bacterial infections had the appropriate test (urine culture, chest radiograph, or blood culture). Antibiotics were prescribed acutely in 66% (359/543) of children with urinary tract infection, 69% (366/533) with pneumonia, and 81% (52/64) with bacteraemia. However, 20% (2686/13?557) of children without bacterial infection were also prescribed antibiotics. On the basis of the data from the clinical evaluations and the confirmed diagnosis, a diagnostic model was developed using multinomial logistic regression methods. Physicians’ diagnoses of bacterial infection had low sensitivity (10-50%) and high specificity (90-100%), whereas the clinical diagnostic model provided a broad range of values for sensitivity and specificity. Conclusions Emergency department physicians tend to underestimate the likelihood of serious bacterial infection in young children with fever, leading to undertreatment with antibiotics. A clinical diagnostic model could improve decision making by increasing sensitivity for detecting serious bacterial infection, thereby improving early treatment. PMID:20406860

  17. Community Knowledge and Attitudes and Health Workers' Practices regarding Non-malaria Febrile Illnesses in Eastern Tanzania

    PubMed Central

    Chipwaza, Beatrice; Mugasa, Joseph P.; Mayumana, Iddy; Amuri, Mbaraka; Makungu, Christina; Gwakisa, Paul S.

    2014-01-01

    Introduction Although malaria has been the leading cause of fever for many years, with improved control regimes malaria transmission, morbidity and mortality have decreased. Recent studies have increasingly demonstrated the importance of non-malaria fevers, which have significantly improved our understanding of etiologies of febrile illnesses. A number of non-malaria febrile illnesses including Rift Valley Fever, dengue fever, Chikungunya virus infection, leptospirosis, tick-borne relapsing fever and Q-fever have been reported in Tanzania. This study aimed at assessing the awareness of communities and practices of health workers on non-malaria febrile illnesses. Methods Twelve focus group discussions with members of communities and 14 in-depth interviews with health workers were conducted in Kilosa district, Tanzania. Transcripts were coded into different groups using MaxQDA software and analyzed through thematic content analysis. Results The study revealed that the awareness of the study participants on non-malaria febrile illnesses was low and many community members believed that most instances of fever are due to malaria. In addition, the majority had inappropriate beliefs about the possible causes of fever. In most cases, non-malaria febrile illnesses were considered following a negative Malaria Rapid Diagnostic Test (mRDT) result or persistent fevers after completion of anti-malaria dosage. Therefore, in the absence of mRDTs, there is over diagnosis of malaria and under diagnosis of non-malaria illnesses. Shortages of diagnostic facilities for febrile illnesses including mRDTs were repeatedly reported as a major barrier to proper diagnosis and treatment of febrile patients. Conclusion Our results emphasize the need for creating community awareness on other causes of fever apart from malaria. Based on our study, appropriate treatment of febrile patients will require inputs geared towards strengthening of diagnostic facilities, drugs availability and optimal staffing of health facilities. PMID:24852787

  18. Itaya virus, a Novel Orthobunyavirus Associated with Human Febrile Illness, Peru

    PubMed Central

    Hontz, Robert D.; Guevara, Carolina; Halsey, Eric S.; Silvas, Jesus; Santiago, Felix W.; Widen, Steven G.; Wood, Thomas G.; Casanova, Wilma; Vasilakis, Nikos; Watts, Douglas M.; Kochel, Tadeusz J.; Ebihara, Hideki

    2015-01-01

    Our genetic analyses of uncharacterized bunyaviruses isolated in Peru identified a possible reassortant virus containing small and large gene segment sequences closely related to the Caraparu virus and a medium gene segment sequence potentially derived from an unidentified group C orthobunyavirus. Neutralization tests confirmed serologic distinction among the newly identified virus and the prototype and Caraparu strains. This virus, named Itaya, was isolated in 1999 and 2006 from febrile patients in the cities of Iquitos and Yurimaguas in Peru. The geographic distance between the 2 cases suggests that the Itaya virus could be widely distributed throughout the Amazon basin in northeastern Peru. Identification of a new Orthobunyavirus species that causes febrile disease in humans reinforces the need to expand viral disease surveillance in tropical regions of South America. PMID:25898901

  19. Building-associated risk of febrile acute respiratory diseases in Army trainees.

    PubMed

    Brundage, J F; Scott, R M; Lednar, W M; Smith, D W; Miller, R N

    1988-04-01

    Airborne transmission of infectious agents and associations of indoor air pollutants with respiratory illnesses are well documented. We hypothesized that energy conservation measures that tighten buildings also increase risks of respiratory infection among building occupants. At four Army training centers during a 47-month period, incidence rates of febrile acute respiratory disease were compared between basic trainees in modern (energy-efficient design and construction) and old barracks. Rates of febrile acute respiratory disease were significantly higher among trainees in modern barracks (adjusted relative risk estimate, 1.51; 95% confidence interval, 1.46 to 1.56), and relative risks were consistent at the four centers. These results support the hypothesis that tight buildings with closed ventilation systems significantly increase risks of respiratory-transmitted infection among congregated, immunologically susceptible occupants. PMID:3346987

  20. Itaya virus, a Novel Orthobunyavirus Associated with Human Febrile Illness, Peru.

    PubMed

    Hontz, Robert D; Guevara, Carolina; Halsey, Eric S; Silvas, Jesus; Santiago, Felix W; Widen, Steven G; Wood, Thomas G; Casanova, Wilma; Vasilakis, Nikos; Watts, Douglas M; Kochel, Tadeusz J; Ebihara, Hideki; Aguilar, Patricia V

    2015-05-01

    Our genetic analyses of uncharacterized bunyaviruses isolated in Peru identified a possible reassortant virus containing small and large gene segment sequences closely related to the Caraparu virus and a medium gene segment sequence potentially derived from an unidentified group C orthobunyavirus. Neutralization tests confirmed serologic distinction among the newly identified virus and the prototype and Caraparu strains. This virus, named Itaya, was isolated in 1999 and 2006 from febrile patients in the cities of Iquitos and Yurimaguas in Peru. The geographic distance between the 2 cases suggests that the Itaya virus could be widely distributed throughout the Amazon basin in northeastern Peru. Identification of a new Orthobunyavirus species that causes febrile disease in humans reinforces the need to expand viral disease surveillance in tropical regions of South America. PMID:25898901

  1. [Evaluation of the protocol for management of the first uncomplicated febrile convulsion].

    PubMed

    Collet, J P; Gallet, S; Etokabeka, F; Hermier, M; Danzon, A; Descos, B; David, L; François, R; Floret, D

    1986-01-01

    A protocol of rationalized management of the first non complicated febrile seizure was used in 42 children and the results were compared with those observed in the past without the new protocol. The quality of medical data collected from the parents and those given to the family and their practitioner have been improved; the duration of the hospitalization was shorter, the examinations were fewer and the savings realised per child were 3,175 francs. PMID:3808844

  2. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2 ?\\/?, but not in cyclooxygenase-1 ?\\/? mice

    Microsoft Academic Search

    S Li; Y Wang; K Matsumura; L. R Ballou; S. G Morham; C. M Blatteis

    1999-01-01

    Various lines of evidence have implicated inducible cyclooxygenase-2 (COX-2) in fever production. Thus, its expression is selectively enhanced in brain after peripheral exogenous (e.g., lipopolysaccharide [LPS]) or endogenous (e.g., interleukin-1) pyrogen administration, while selective COX-2 inhibitors suppress the fever induced by these pyrogens. In this study, we assessed the febrile response to LPS of congenitally constitutive COX-1 (COX-1?\\/?) and COX-2

  3. Tepid Sponging to Reduce Temperature in Febrile Children in a Tropical Climate

    Microsoft Academic Search

    A. F. Mahar; S. J. Allen; P. Milligan; S. Suthumnirund; T. Chotpitayasunondh; A. Sabchareon; J. B. S. Coulter

    1994-01-01

    The effectiveness of tepid sponging, in addition to antipyretic medication, in the reduction of temperature in febrile children living in a tropical environment, was assessed in a prospective, randomized, open trial. Seventy-five children aged between 6 and 53 months who attended the casualty department of the Children's Hospital, Bangkok, Thailand, with fever (rectal temperature ?38.5°C) of presumed viral origin were

  4. Hyperthermia-Induced Febrile Seizures Have Moderate and Transient Effects on Spatial Learning in Immature Rats

    PubMed Central

    Yagoubi, Nawel; Jomni, Yosra; Sakly, Mohsen

    2015-01-01

    The aim of this study was to characterize a novel animal model hyperthermia-induced febrile seizure and to investigate the impacts of repetitive febrile seizures on spatial learning and memory performances in immature rats. Methods. Rats were subjected to hyperthermia exposure one, two, or three times in 10-day intervals during 30?min in a water bath warmed at 45–50°C and their behaviour was monitored. Morris water maze spatial learning and memory were examined for control and treated groups. Results showed that rats subjected to 30-minute hyperthermia hot water developed rapidly myoclonic jerks and then generalized seizures. After a single hyperthermia exposure, the time for generalised tonic-clonic seizures appearance was 16.08 ± 0.60?min and it decreased gradually with repetitive exposure to reach 12.46 ± 0.39?min by the third exposure. Febrile seizures altered the spatial learning and memory abilities in Morris water maze and increased the time spent to attain the platform after one or two exposures, while after a third exposure rats exhibited the same latency compared to controls. Similar results were obtained in probe test where rats, subjected to hyperthermia for one or two episodes, spent less time in the target quadrant compared to corresponding controls. Further, when platform was moved from northwest to southwest quadrant, memory transfer test indicated that after one or two hyperthermia exposures cognitive performances were slightly altered, while after a third exposure the latency to escape increased significantly compared to untreated group. It was concluded that 30?min of hyperthermia hot water was sufficient to induce febrile seizures in immature rats and an increase of susceptibility was observed with repetitive hyperthermia exposure. Hyperthermia treatment impaired cognitive performances but the effects were mostly transient and moderate.

  5. Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas.

    PubMed

    Camps, M; Vilella, A; Marcos, M A; Letang, E; Muñoz, J; Salvadó, E; González, A; Gascón, J; Jiménez de Anta, M T; Pumarola, T

    2008-04-01

    Fifty million people are estimated to travel from industrial countries to the tropics annually. In spite of exhaustive studies and widely different diagnosis among returned patients, some cases of febrile illnesses remain without an etiological diagnosis, suggesting that these cases could be due to viral respiratory tract infections. From August 2005 to October 2006, 118 febrile patients without a specific diagnosis in their first visit at the Center for International Health of the Hospital Clínic of Barcelona were included. In all of them, in order to study respiratory viruses, a nasopharyngeal swab was collected. Clinical and radiological features and epidemiological data, as well as other samples for microbiologic studies, were also collected during consultation. Based on the physician's judgment at the time of consultation, patients were classified into four groups: respiratory symptoms (62%), febrile syndrome with nonspecific symptoms (24%), digestive symptoms (10%), and patients presenting both respiratory and digestive symptoms (4%). A pathogen microorganism was detected in 61 patients (52%). Respiratory viruses were detected in 44 out of 118 (37%) travelers included in the study, representing 56% of the patients with respiratory symptoms. The most frequently viruses detected were influenza virus (38%), rhinovirus (23%), adenovirus (9%), and respiratory syncytial virus (9%). Respiratory viruses have been shown to play an important role in imported fever. In light of the fact that international tourism is an increasing phenomenon, new strategies to prevent the spread of respiratory viruses should be considered, specially for influenza when a vaccine is available. PMID:18297697

  6. "Naturally occurring asbestos

    NASA Astrophysics Data System (ADS)

    Cagnard, F.; Lahondère, D.; Blein, O.; Lahfid, A.; Wille, G.

    2012-04-01

    The term asbestos refers to six silicate minerals from amphibole and serpentine groups. By definition, it consists in bundles of thin and flexible long fibers, with high-tensile strength, and chemical and heat resistance. In contrast to asbestos found within commercial products and mining, the specific term ''naturally occurring asbestos'' (NOA) refers to asbestiform minerals occurring within rocks or soils that can be released by human activities or weathering processes. The fact that the exposure to asbestos is related to lung pathologies is now widely demonstrated (e.g. asbestosis, mesothelioma and lung cancer). However, if health risks associated with exposure to NOA exist, they are not yet well documented. The crystallization of natural asbestos occurs in specific Mg-rich lithologies associated with peculiar structural and metamorphic conditions. By recognizing and combining such specific geologic criteria, the presence or the absence of asbestos in bedrock terrains can be reasonably predicted and maps of NOA hazard can be drawn. We present here new results of geological mapping and petrological study concerning the evaluation of the NOA hazard in the Alps and Corsica, in France. The three folds approach consists in (1) a determination of lithologies with potential NOA from a bibliographic compilation and extraction of target zones from a geological geodatabase (2) a geological mapping of the target zones followed by a petrological characterization of sampled asbestiform minerals in the laboratory (optical microscopy, TEM, SEM, and Raman spectroscopy technics), and (3) the drawing of the final map of NOA hazard, at regional-scale. Occurrence criteria can be retained as follows: 1. NOA are abundant in the internal zones of the Alps and Corsica, especially within ophiolitic complexes. Natural asbestos are mostly concentrated within ultramafic rocks but can also occur within basic lithologies such as Mg-metagabbros, metabasalts and meta-pillow-lavas, 2. Asbestos is commonly located within fractures, shear-bands or shear-planes, developed during late retrograde metamorphic history, 3. Tremolite-actinolite-type asbestos is abundant both in ultramafic and mafic rocks, 4. Natural asbestos occur in few places within the external zones of the Alps, especially within hercynian ophiolitic massifs or concentrated in late Alpine fractures affecting leptyno-amphibolic lithologies.

  7. Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study

    Microsoft Academic Search

    H E Innes; D B Smith; S M O'Reilly; P I Clark; V Kelly; E Marshall

    2003-01-01

    Neutropenic sepsis remains a potentially life-threatening complication of anticancer chemotherapy. However, it is possible to identify patients who are at low risk for serious complications and for whom less-intensive, more-convenient treatment may be appropriate. The aim of this study was to assess the efficacy and safety of oral antibiotics in conjunction with early hospital discharge in comparison with standard in-patient

  8. Treatment of neutropenia-related fungal infections with granulocyte colony-stimulating factor-elicited white blood cell transfusions: a pilot study

    Microsoft Academic Search

    MC Dignani; EJ Anaissie; JP Hester; S O’Brien; SE Vartivarian; JH Rex; H Kantarjian; DB Jendiroba; B Lichtiger; BS Andersson; EJ Freireich

    1997-01-01

    Neutropenia-related fungal infections can be life-threatening despite antifungal therapy. We evaluated the role of recombinant granulocyte colony-stimulating factor (rG-CSF)-elicited white blood cell (WBC) transfusions in patients with neutropenia-related fungal infections. Adult patients with hematologic malignancies, absolute neutrophil counts (ANC) <500\\/?l and fungal infections refractory to amphotericin b, received daily transfusions of rg-csf-elicited and irradiated wbc transfusions from related donors. donors

  9. Management of febrile children under five years in hospitals and health centres of rural Ghana

    PubMed Central

    2014-01-01

    Background The case management of febrile children in hospitals’ and health centres’ pre-roll out of the new WHO policy on parasitological diagnosis was assessed. The delivery of artemisinin combination therapy (ACT) at these two levels of the health system was compared. Methods Structured observations and exit interviews of 1,222 febrile children attending five hospitals and 861 attending ten health centres were conducted in six districts of the Brong Ahafo Region of Ghana. Effectiveness of delivery of case management of malaria was assessed. Proportions of children receiving ACT, anti-malarial monotherapy and antibiotics were described. Predictors of: a febrile child being given an ACT, a febrile child being given an antibiotic and of carers knowing how to correctly administer the ACT were assessed using logistic regression models stratified by hospitals and health centres. Results The system’s effectiveness of delivering an ACT to febrile children diagnosed with malaria (parasitologically or clinically) was 31.4 and 42.4% in hospitals and health centres, respectively. The most ineffective process was that of ensuring that carers knew how to correctly administer the ACT. Overall 278 children who were not given an ACT were treated with anti-malarial monotherapy other than quinine. The majority of these children, 232/278 were given amodiaquine, 139 of these were children attending hospitals and 93 attending health centres. The cadre of health staff conducting consultation was a common predictor of the outcomes of interest. Presenting symptoms and examinations conducted were predictive of being given an ACT in hospitals and antibiotic in hospitals and health centres but not of being given an ACT in health centres. Treatment-seeking factors were predictive of being given an ACT if it was more than seven days since the fever began and an antibiotic in hospitals but not in health centres. Conclusion Interventions to improve adherence to negative parasitological tests are needed, together with guidance on dispensing of antibiotics, but improving the education of carers on how to administer ACT will lead to the greatest immediate increase in the effectiveness of case management. Guidance is needed on implementation of the new test-based treatment for malaria policy in health facilities. PMID:25008574

  10. Arboviral Etiologies of Acute Febrile Illnesses in Western South America, 2000–2007

    PubMed Central

    Forshey, Brett M.; Guevara, Carolina; Laguna-Torres, V. Alberto; Cespedes, Manuel; Vargas, Jorge; Gianella, Alberto; Vallejo, Efrain; Madrid, César; Aguayo, Nicolas; Gotuzzo, Eduardo; Suarez, Victor; Morales, Ana Maria; Beingolea, Luis; Reyes, Nora; Perez, Juan; Negrete, Monica; Rocha, Claudio; Morrison, Amy C.; Russell, Kevin L.; J. Blair, Patrick; Olson, James G.; Kochel, Tadeusz J.

    2010-01-01

    Background Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to describe the arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and to provide detailed epidemiological analysis of arbovirus infection in Iquitos, Peru, where more extensive monitoring was conducted. Methodology/Findings A clinic-based syndromic surveillance system was implemented in 13 locations in Ecuador, Peru, Bolivia, and Paraguay. Serum samples and demographic information were collected from febrile participants reporting to local health clinics or hospitals. Acute-phase sera were tested for viral infection by immunofluorescence assay or RT-PCR, while acute- and convalescent-phase sera were tested for pathogen-specific IgM by ELISA. Between May 2000 and December 2007, 20,880 participants were included in the study, with evidence for recent arbovirus infection detected for 6,793 (32.5%). Dengue viruses (Flavivirus) were the most common arbovirus infections, totaling 26.0% of febrile episodes, with DENV-3 as the most common serotype. Alphavirus (Venezuelan equine encephalitis virus [VEEV] and Mayaro virus [MAYV]) and Orthobunyavirus (Oropouche virus [OROV], Group C viruses, and Guaroa virus) infections were both observed in approximately 3% of febrile episodes. In Iquitos, risk factors for VEEV and MAYV infection included being male and reporting to a rural (vs urban) clinic. In contrast, OROV infection was similar between sexes and type of clinic. Conclusions/Significance Our data provide a better understanding of the geographic range of arboviruses in South America and highlight the diversity of pathogens in circulation. These arboviruses are currently significant causes of human illness in endemic regions but also have potential for further expansion. Our data provide a basis for analyzing changes in their ecology and epidemiology. PMID:20706628

  11. Cultural categorization of febrile illnesses in correlation with herbal remedies used for treatment in Southwestern Nigeria.

    PubMed

    Ajaiyeoba, E O; Oladepo, O; Fawole, O I; Bolaji, O M; Akinboye, D O; Ogundahunsi, O A T; Falade, C O; Gbotosho, G O; Itiola, O A; Happi, T C; Ebong, O O; Ononiwu, I M; Osowole, O S; Oduola, O O; Ashidi, J S; Oduola, A M J

    2003-04-01

    The ethnographic study was conducted in two communities in Oyo State in Southwestern Nigeria. The study sites consisted of a rural and an urban local government area located in the tropical rain forest zone of Nigeria. The study was designed to obtain information on febrile illnesses and herbal remedies for treatment with the aim of identifying potential antimalarial drugs. The study revealed that fever is a general term for describing illnesses associated with elevated body temperature. The indigenous Yoruba ethnic population has categorized fever based on symptoms and causes. The present communication is the result of focus group discussion and semi-structured questionnaire administered to traditional healers, herb sellers, elders and mothers. This was on types of fevers, symptoms and causes of febrile illnesses. The investigation also included use of traditional herbs in the prevention and treatment of the illnesses in the two communities.A total of 514 respondents were interviewed. This was made up of 266 (51.8%) from Atiba local government area (LGA), an urban centre while 248 (48.2%) respondents were interviewed from Itesiwaju LGA, a rural community. The LGAs are located in Oyo State of Nigeria. The respondents proffered 12 types of febrile illnesses in a multiple response answering system in Yoruba language. The most common ones (direct translation into English) were: yellow fever (39.1%), typhoid (34.8%), ordinary (28.8%), rainy season (20.8%) and headache (10.5%) fevers, respectively. Perceived causes of each of the febrile illnesses included stress, mosquito bites, unclean water, rains and over exposure to the sun. Methods of fever prevention were mainly with the use of herbal decoctions, powdered herbs, orthodox medications and maintenance of proper hygiene. Of a total of 112 different herbal remedies used in the treatment of the febrile illnesses compiled from the study, 25 recipes are presented. Recipes consisted of 2-7 ingredients. Oral decoctions (84%), oral powders (63%), use as soaps and creams (40%) in a multiple response system, were the most prevalent routes of administration of prepared herbs used in the treatment of the fevers. Boiling in water or alcohol was the most common method used in the preparation of the remedies. The four most frequently mentioned (multiple response system) plants in the Southwest ethnobotany for fevers were Azadirachta indica (87.5%), Mangifera indica (75.0%), Morinda lucida (68.8%) and Citrus medica (68.8%). PMID:12639738

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

    PubMed Central

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

    2013-01-01

    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-? (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 and survival thus underlies neutropenia in G6PC3?/? deficiency, both originating from a reduced ability to utilize glucose. Hoxb8-dependent cells are a model to study differentiation and survival of the neutrophil lineage. PMID:23686134

  13. C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3? end modification

    PubMed Central

    Mroczek, Seweryn; Krwawicz, Joanna; Kutner, Jan; Lazniewski, Michal; Kuci?ski, Iwo; Ginalski, Krzysztof; Dziembowski, Andrzej

    2012-01-01

    C16orf57 encodes a human protein of unknown function, and mutations in the gene occur in poikiloderma with neutropenia (PN), which is a rare, autosomal recessive disease. Interestingly, mutations in C16orf57 were also observed among patients diagnosed with Rothmund-Thomson syndrome (RTS) and dyskeratosis congenita (DC), which are caused by mutations in genes involved in DNA repair and telomere maintenance. A genetic screen in Saccharomyces cerevisiae revealed that the yeast ortholog of C16orf57, USB1 (YLR132C), is essential for U6 small nuclear RNA (snRNA) biogenesis and cell viability. Usb1 depletion destabilized U6 snRNA, leading to splicing defects and cell growth defects, which was suppressed by the presence of multiple copies of the U6 snRNA gene SNR6. Moreover, Usb1 is essential for the generation of a unique feature of U6 snRNA; namely, the 3?-terminal phosphate. RNAi experiments in human cells followed by biochemical and functional analyses confirmed that, similar to yeast, C16orf57 encodes a protein involved in the 2?,3?-cyclic phosphate formation at the 3? end of U6 snRNA. Advanced bioinformatics predicted that C16orf57 encodes a phosphodiesterase whose putative catalytic activity is essential for its function in vivo. Our results predict an unexpected molecular basis for PN, DC, and RTS and provide insight into U6 snRNA 3? end formation. PMID:22899009

  14. Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper deficiency after gastric bypass surgery.

    PubMed

    Yarandi, Shadi S; Griffith, Daniel P; Sharma, Rahul; Mohan, Arun; Zhao, Vivian M; Ziegler, Thomas R

    2014-01-01

    Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations. Here we present a case of an undiagnosed copper deficiency several years after bariatric gastric bypass surgery, in a patient who concomitantly used zinc-containing denture cream for several years, associated with anemia, neutropenia, myelopathy, respiratory failure, and bilateral optic neuropathy, which caused major vision loss. This patient was also a heterozygote carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism, which may affect copper metabolism. Intravenous copper repletion resulted in rapid correction of hematologic indices. However, neurological manifestations, including vision loss responded only modestly to copper supplementation, despite achieving normal blood copper concentrations. Clinicians should consider copper deficiency in patients at risk, as in this case, as a delayed diagnosis can lead to irreversible disability due to neurological manifestations. PMID:24583748

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

    PubMed

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

    2015-03-01

    The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12?305 individuals/year treated with clozapine (308±133?mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100?000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age. PMID:25486383

  16. Anti-D immunoglobulin-induced prolonged intravascular hemolysis and neutropenia.

    PubMed

    Alioglu, Bulent; Avci, Zekai; Ozyurek, Emel; Ozbek, Namik

    2007-09-01

    Intravenous anti-D immunoglobulin (anti-D IVIG) is indicated for the treatment of immune thrombocytopenic purpura (ITP) in nonsplenectomized patients who are Rh(D)-positive. Recent reports have described episodes of intravascular hemolysis after anti-D IVIG. We report an adolescent boy with chronic ITP who required multiple transfusions of erythrocyte suspensions when intravascular hemolysis persisted for 6 months after anti-D IVIG treatment. He did not have hemolytic anemia before treatment. The features of our case suggest that pediatric patients treated with anti-D IVIG for ITP should be closely monitored for signs and symptoms of hemoglobinemia and/or hemoglobinuria, and clinically significant anemia. Our case proposes that persistence of immune hemolysis after this treatment may be related to presence of previously defined predisposing agents like tuberculosis and antituberculous therapy. Our observations suggest that steroid therapy can be effective in patients who developed prolonged hemolytic anemia and neutropenia after anti-D IVIG therapy. PMID:17805040

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

    PubMed

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

    2015-08-01

    The role of vascular endothelial growth factor A (VEGFA) in tumor angiogenesis is well established and accordingly, molecules targeting VEGFA or its receptors are being presently used in the clinics for treatment of several types of cancer. However, these antiangiogenic agents are expensive and have serious side effects. Thus identification of newer drugs with manageable systemic side effects or toxicities is of immense clinical importance. Since we have reported earlier that dopamine (DA) inhibits VEGFA induced angiogenesis in experimental tumor models, we therefore sought to investigate whether DA treatment results in similar toxicities like other antiangiogenic agents. Our results indicated that unlike sunitinib, another commonly used antiangiogenic agent in the clinics which targets VEGF receptors, DA [50 mg/kg/days × 7days intraperitoneally (i.p.)] not only could inhibit tumor angiogenesis and growth of HT29 human colon cancer and LLC (Lewis lung carcinoma) in mice, it also did not cause hypertension, hematological, renal and hepatic toxicities in normal, HT29 and LLC tumor bearing animals. Furthermore and interestingly, in contrast to the currently used antiangiogenic agents, DA also prevented 5-fluorouracil (5FU) induced neutropenia in HT29 colon cancer bearing mice. This action of DA was through inhibition of 5FU mediated suppression of colony forming unit-granulocyte macrophage colony forming units in the bone marrow. Thus our results indicate that DA may be safely used as an antiangiogenic drug for the treatment of malignant tumors. PMID:25556636

  18. Naturally Occurring Food Toxins

    PubMed Central

    Dolan, Laurie C.; Matulka, Ray A.; Burdock, George A.

    2010-01-01

    Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States. PMID:22069686

  19. Naturally occurring food toxins.

    PubMed

    Dolan, Laurie C; Matulka, Ray A; Burdock, George A

    2010-09-01

    Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States. PMID:22069686

  20. Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study

    PubMed Central

    Crump, John A.; Morrissey, Anne B.; Nicholson, William L.; Massung, Robert F.; Stoddard, Robyn A.; Galloway, Renee L.; Ooi, Eng Eong; Maro, Venance P.; Saganda, Wilbrod; Kinabo, Grace D.; Muiruri, Charles; Bartlett, John A.

    2013-01-01

    Introduction The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. Methods and Findings We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Conclusions Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts. PMID:23875053

  1. A Prospective Study of the Causes of Febrile Illness Requiring Hospitalization in Children in Cambodia

    PubMed Central

    Chheng, Kheng; Carter, Michael J.; Emary, Kate; Chanpheaktra, Ngoun; Moore, Catrin E.; Stoesser, Nicole; Putchhat, Hor; Sona, Soeng; Reaksmey, Sin; Kitsutani, Paul; Sar, Borann; van Doorn, H. Rogier; Uyen, Nguyen Hanh; Van Tan, Le; Paris, Daniel; Blacksell, Stuart D.; Amornchai, Premjit; Wuthiekanun, Vanaporn; Parry, Christopher M.; Day, Nicholas P. J.; Kumar, Varun

    2013-01-01

    Background Febrile illnesses are pre-eminent contributors to morbidity and mortality among children in South-East Asia but the causes are poorly understood. We determined the causes of fever in children hospitalised in Siem Reap province, Cambodia. Methods and Findings A one-year prospective study of febrile children admitted to Angkor Hospital for Children, Siem Reap. Demographic, clinical, laboratory and outcome data were comprehensively analysed. Between October 12th 2009 and October 12th 2010 there were 1225 episodes of febrile illness in 1180 children. Median (IQR) age was 2.0 (0.8–6.4) years, with 850 (69%) episodes in children <5 years. Common microbiological diagnoses were dengue virus (16.2%), scrub typhus (7.8%), and Japanese encephalitis virus (5.8%). 76 (6.3%) episodes had culture-proven bloodstream infection, including Salmonella enterica serovar Typhi (22 isolates, 1.8%), Streptococcus pneumoniae (13, 1.1%), Escherichia coli (8, 0.7%), Haemophilus influenzae (7, 0.6%), Staphylococcus aureus (6, 0.5%) and Burkholderia pseudomallei (6, 0.5%). There were 69 deaths (5.6%), including those due to clinically diagnosed pneumonia (19), dengue virus (5), and melioidosis (4). 10 of 69 (14.5%) deaths were associated with culture-proven bloodstream infection in logistic regression analyses (odds ratio for mortality 3.4, 95% CI 1.6–6.9). Antimicrobial resistance was prevalent, particularly in S. enterica Typhi, (where 90% of isolates were resistant to ciprofloxacin, and 86% were multi-drug resistant). Comorbid undernutrition was present in 44% of episodes and a major risk factor for acute mortality (OR 2.1, 95% CI 1.1–4.2), as were HIV infection and cardiac disease. Conclusion We identified a microbiological cause of fever in almost 50% of episodes in this large study of community-acquired febrile illness in hospitalized children in Cambodia. The range of pathogens, antimicrobial susceptibility, and co-morbidities associated with mortality described will be of use in the development of rational guidelines for infectious disease treatment and control in Cambodia and South-East Asia. PMID:23593267

  2. Altered Pharmacokinetics of Piperacillin in Febrile Neutropenic Patients with Hematological Malignancy

    PubMed Central

    Roberts, Michael S.; Warner, Morgyn S.; Hahn, Uwe; Robertson, Thomas A.; Yeend, Sue; Phay, Andy; Lehman, Sheila; Lipman, Jeffrey; Peake, Sandra L.; Roberts, Jason A.

    2014-01-01

    This study assessed the pharmacokinetics and dosing adequacy of piperacillin in febrile neutropenic patients after the first dose. Pharmacokinetic analysis was performed using noncompartmental methods. We observed an elevated volume of distribution (29.7 ± 8.0 liters [mean ± standard deviation]) and clearance (20.2 ± 7.5 liters/h) compared to data from other patient populations. Antibiotic exposure did not consistently result in therapeutic targets. We conclude that alternative dosing strategies guided by therapeutic drug monitoring may be required to optimize exposure. PMID:24687508

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

    PubMed

    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 12 months after treatment and could be maintained at low level by supportive periodontal care at 3-month intervals. PMID:9763332

  4. Acute HIV-1 infection is as common as malaria in young febrile adults seeking care in coastal Kenya

    PubMed Central

    Sanders, Eduard J.; Mugo, Peter; Prins, Henrieke A.B.; Wahome, Elizabeth; Thiong’o, Alexander N.; Mwashigadi, Grace; van der Elst, Elisabeth M.; Omar, Anisa; Smith, Adrian D.; Graham, Susan M.

    2014-01-01

    Background: Febrile adults are usually not tested for acute HIV-1 infection (AHI) in Africa. We assessed a strategy to diagnose AHI among young adult patients seeking care. Methods: Young adults (<30 years) who met predefined AHI criteria at care seeking, including fever, sexually transmitted disease symptoms, diarrhoea, body pains or multiple partners were referred from five pharmacies and screened at five health facilities. Prevalent HIV-1 was diagnosed by nationally recommended serial rapid HIV-1 testing. Willing HIV-1-negative patients were evaluated for AHI, defined as a positive p24 antigen test, and subsequent seroconversion or RNA detection. Febrile patients evaluated for AHI were also screened for malaria using a rapid test, with PCR confirmation of positives. Results: In 3602 adults seeking care, overall HIV-1 prevalence was 3.9%: 7.6% (68/897) among patients meeting AHI criteria vs. 2.6% (71/2705) among those who did not (P?febrile patients (prevalence 0.4%, 95% CI 0.0–2.0%, P?=?0.1). Malaria was confirmed by PCR in four (1.7%) of the 241 febrile patients. Conclusion: AHI was as common as confirmed malaria in young febrile adults seeking care. An AHI detection strategy targeting young febrile adults seeking care at pharmacies and health facilities is feasible and should be considered as an HIV-prevention strategy in high-transmission settings. PMID:24556872

  5. Utility of the Tourniquet Test and the White Blood Cell Count to Differentiate Dengue among Acute Febrile Illnesses in the Emergency Room

    Microsoft Academic Search

    Christopher J. Gregory; Olga D. Lorenzi; Lisandra Colón; Arleene Sepúlveda García; Luis M. Santiago; Ramón Cruz Rivera; Liv Jossette Cuyar Bermúdez; Fernando Ortiz Báez; Delanor Vázquez Aponte; Kay M. Tomashek; Jorge Gutierrez; Luisa Alvarado

    2011-01-01

    Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the

  6. Changes in Cerebrospinal Fluid Biomarkers in Human Herpesvirus-6-Associated Acute Encephalopathy/Febrile Seizures

    PubMed Central

    Tanuma, Naoyuki; Miyata, Rie; Nakajima, Keisuke; Okumura, Akihisa; Kubota, Masaya; Hamano, Shin-ichiro; Hayashi, Masaharu

    2014-01-01

    To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6) infection, we measured the levels of oxidative stress markers 8-hydroxy-2?-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL), tau protein, and cytokines in cerebrospinal fluid (CSF) obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy) (n = 16) and complex febrile seizures associated with HHV-6 (HHV-6 complex FS) (n = 10). We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure), the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection. PMID:25294958

  7. Leukocyte Populations and C-Reactive Protein as Predictors of Bacterial Infections in Febrile Outpatient Children

    PubMed Central

    Kaya, Zühre; Küçükcongar, Aynur; Vurall?, Do?u?; Emeksiz, Hamdi Cihan; Gürsel, Türkiz

    2014-01-01

    Objective: Infections remain the major cause of unnecessary antibiotic use in pediatric outpatient settings. Complete blood count (CBC) is the essential test in the diagnosis of infections. C-reactive protein (CRP) is also useful for assessment of young children with serious bacterial infections. The purpose of the study was to evaluate leukocyte populations and CRP level to predict bacterial infections in febrile outpatient children. Materials and Methods: The values of CBC by Cell-DYN 4000 autoanalyzer and serum CRP levels were evaluated in 120 febrile patients with documented infections (n:74 bacterial, n:46 viral) and 22 healthy controls. Results: The mean CRP, neutrophil and immature granulocyte (IG) values were significantly higher in bacterial infections than in viral infections and controls (p<0.05). C-reactive protein was significantly correlated with neutrophil level in bacterial infections (r: 0.76, p<0.05). Specificity of IG was greatest at 93%, only a modest 56% for neutrophil and mild 18% for CRP, whereas 100% for combination of IG, neutrophil and CRP. Conclusion: Acute bacterial infection seems to be very unlikely in children with normal leukocyte populations and CRP values, even if clinically signs and symptoms indicate acute bacterial infections. PMID:24764729

  8. ? lactam monotherapy versus ? lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis

    PubMed Central

    Paul, Mical; Soares-Weiser, Karla; Leibovici, Leonard

    2003-01-01

    Objective To compare the effectiveness of ? lactam monotherapy versus ? lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia. Data sources Medline, Embase, Lilacs, the Cochrane Library, and conference proceedings to 2002. References of included studies and contact with authors. No restrictions on language, year of publication, or publication status. Study selection All randomised trials of ? lactam monotherapy compared with ? lactam-minoglycoside combination therapy as empirical treatment for patients with fever and neutropenia. Data selection Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. An intention to treat approach was used. Relative risks were pooled with the random effect model. Main outcome measure All cause fatality. Results Forty seven trials with 7807 patients met inclusion criteria. Nine trials compared the same ? lactam. There was no significant difference in all cause fatality (relative risk 0.85, 95% confidence interval 0.72 to 1.02). For success of treatment there was a significant advantage with monotherapy (0.92, 0.85 to 0.99), though there was considerable heterogeneity among trials. There was no significant difference between monotherapy and combination treatment in trials that compared the same ? lactam, whereas there was major advantage with monotherapy in trials that compared different ? lactams (0.87, 0.80 to 0.93). Rates of superinfection were similar. Adverse events, including those associated with severe morbidity, were significantly more common in the combination treatment group. Detected flaws in methods did not affect results. Conclusions For patients with fever and neutropenia there is no clinical advantage in treatment with ? lactam-aminoglycoside combination therapy. Broad spectrum ? lactams as monotherapy should be regarded as the standard of care for such patients. PMID:12763980

  9. Safety and efficacy of systematic administration of Filgrastim to prevent neutropenia and infections in patient with hepatitis C.

    PubMed

    Sharvadze, L; Karchava, M; Bolokadze, N; Gatserelia, L; Tsertsvadze, T

    2009-10-01

    The aim of 36 months follow up study was to assess the safety and efficacy of Filgrastim (Neupogen) for preventing neutropenia and bacterial infection during combination therapy of chronic HCV infection with pegilated interferon alfa and ribavirin. Study enrolled 64 patients with chronic active hepatitis C, aged 20-65. Among them 49 were male and 15 female). Among 64 patients: 5 patients had HCV genotype 1a, 24 patients HCV genotype 1b, 17 patients HCV genotype 2a/2c and 18 patients HCV genotype 3a. Treatment regimen for chronic hepatitis C patients was as follows: Pegylated interferon alfa 2a (Pegasys) 180 micro kg or alfa 2b (PegIntron) 1,5 micro g/kg. and ribavirin (RBV). RBV daily dose was adjusted by body weight- 1000/1200 mg. Treatment duration was 48 weeks for HCV genotype 1 patient and 24 weeks for HCV non 1 genotype accordingly. The patients were divided into two groups: 29 patients (1st group) besides combination antiviral therapy (pegilated interferon alfa plus ribavirin) systematically received Filgrastim and other 35 patients (2nd group) - same antiviral therapy without administration of Filgrastim. Selection of patients was performed by computerized randomization method. HCV antibodies were detected by ELISA and RIBA. HCV RNA by Real time PCR. HCV genotype- by Inno-Lipa. Among 2nd group 35 patients (without Filgrastim administration) during antiviral therapy 8 patients (22.8%) developed different bacterial infections.(3 patients- urinary tract infection, 2 patients- pneumonia, 1 patient- bronchitis, 1 patients - sinusitis and 1 patient-gingivitis/stomatitis). 7 patients required interferon dose modification (dose reduction) and in 5 patients treatment stopped due to severe neutropenia. Among 1st group patients (with filgrastim administration) only one patient developed bacterial infection (urinary tract infection). None of patients, due to neutropenia, required neither stoppage of therapy, nor interferon dose reduction. The quality of life of 1st group patients was better in comparison of 2nd group patients. Filgrastim was safe and effective for prevention neutropenia and bacterial infections in Hepatitis C patients with Peg-INF/RBV combination antiviral therapy. Filgrastim was well tolerated by patients. It gives possibility to maintain interferon dose during treatment period and significantly improves the patient's quality of live. PMID:19893121

  10. Functional Effects of Two Voltage-Gated Sodium Channel Mutations That Cause Generalized Epilepsy with Febrile Seizures Plus Type 2

    E-print Network

    Goldin, Alan L.

    Functional Effects of Two Voltage-Gated Sodium Channel Mutations That Cause Generalized Epilepsy that cause generalized epilepsy with febrile seizures plus (GEFS ) have been identified previously in the SCN that either an increase or decrease in sodium channel activity can result in seizures. Key words: epilepsy

  11. High Seroprevalence of Antibodies against Spotted Fever and Scrub Typhus Bacteria in Patients with Febrile Illness, Kenya

    PubMed Central

    Thiga, Jacqueline W.; Mutai, Beth K.; Eyako, Wurapa K.; Ng’ang’a, Zipporah; Jiang, Ju; Richards, Allen L.

    2015-01-01

    Serum samples from patients in Kenya with febrile illnesses were screened for antibodies against bacteria that cause spotted fever, typhus, and scrub typhus. Seroprevalence was 10% for spotted fever group, <1% for typhus group, and 5% for scrub typhus group. Results should help clinicians expand their list of differential diagnoses for undifferentiated fevers. PMID:25811219

  12. Serious Bacterial Infections in Febrile Infants Younger Than 90 Days of Age: The Importance of Ampicillin-Resistant Pathogens

    Microsoft Academic Search

    Carrie L. Byington; Kristine K. Rittichier; Kathlene E. Bassett; Heidi Castillo; Tiffany S. Glasgow; Judy Daly; Andrew T. Pavia

    2010-01-01

    Background. Intrapartum antibiotic pro- phylaxis against group B Streptococcus (GBS) has re- duced the occurrence of serious bacterial infections (SBI) in young infants caused by GBS. Recommendations for initial antibiotic therapy for the febrile infant 1 to 90 days old were developed when infections with GBS were common and antibiotic resistance was rare. Objective. To document the pathogens responsible for

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

    Microsoft Academic Search

    Fan Dong; Russell K. Brynes; Nicola Tidow; Karl Welte; Bob Löwenberg; Ivo P. Touw

    1995-01-01

    BACKGROUND. In severe congenital neutropenia the maturation of myeloid\\u000a progenitor cells is arrested. The myelodysplastic syndrome and acute\\u000a myeloid leukemia develop in some patients with severe congenital\\u000a neutropenia. Abnormalities in the signal-transduction pathways for\\u000a granulocyte colony-stimulating factor (G-CSF) may play a part in the\\u000a progression to acute myeloid leukemia. METHODS. We isolated genomic DNA\\u000a and RNA from hematopoietic cells obtained

  14. Alarm signs and antibiotic prescription in febrile children in primary care: an observational cohort study

    PubMed Central

    Elshout, Gijs; van Ierland, Yvette; Bohnen, Arthur M; de Wilde, Marcel; Oostenbrink, Rianne; Moll, Henriëtte A; Berger, Marjolein Y

    2013-01-01

    Background Although fever in children is often self-limiting, antibiotics are frequently prescribed for febrile illnesses. GPs may consider treating serious infections by prescribing antibiotics. Aim To examine whether alarm signs and/or symptoms for serious infections are related to antibiotic prescription in febrile children in primary care. Design and setting Observational cohort study involving five GP out-of-hours services. Method Clinical information was registered and manually recoded. Children (<16 years) with fever having a face-to-face contact with a GP were included. Children who were already using antibiotics or referred to secondary care were excluded. The relation between alarm signs and/or symptoms for serious infections and antibiotic prescription was tested using multivariate logistic regression. Results Of the 8676 included patients (median age 2.4 years), antibiotics were prescribed in 3167 contacts (36.5%). Patient characteristics and alarm signs and/or symptoms positively related to antibiotic prescription were: increasing age (odds ratio [OR] = 1.03; 95% confidence interval [95% CI] = 1.02 to 1.05), temperature measured by GP (OR = 1.72; 95% CI = 1.59 to 1.86), ill appearance (OR = 3.93; 95% CI = 2.85 to 5.42), being inconsolable (OR = 2.27; 95% CI = 1.58 to 3.22), shortness of breath (OR = 2.58; 95% CI = 1.88 to 3.56), duration of fever (OR = 1.31; 95% CI = 1.26 to 1.35). Negative associations were found for neurological signs (OR = 0.45; 95% CI = 0.27 to 0.76), signs of urinary tract infection (OR = 0.63; 95% CI = 0.49 to 0.82), and vomiting and diarrhoea (OR = 0.65; 95% CI = 0.57 to 0.74). These variables explained 19% of the antibiotic prescriptions. Conclusion Antibiotics are often prescribed for febrile children. These data suggest that treatment of a supposed serious bacterial infection is a consideration of GPs. However, the relatively low explained variation indicates that other considerations are also involved. PMID:23834880

  15. Genetic correction of HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis

    PubMed Central

    Morishima, Tatsuya; Watanabe, Ken-ichiro; Niwa, Akira; Hirai, Hideyo; Saida, Satoshi; Tanaka, Takayuki; Kato, Itaru; Umeda, Katsutsugu; Hiramatsu, Hidefumi; Saito, Megumu K.; Matsubara, Kousaku; Adachi, Souichi; Kobayashi, Masao; Nakahata, Tatsutoshi; Heike, Toshio

    2014-01-01

    HAX1 was identified as the gene responsible for the autosomal recessive type of severe congenital neutropenia. However, the connection between mutations in the HAX1 gene and defective granulopoiesis in this disease has remained unclear, mainly due to the lack of a useful experimental model for this disease. In this study, we generated induced pluripotent stem cell lines from a patient presenting for severe congenital neutropenia with HAX1 gene deficiency, and analyzed their in vitro neutrophil differentiation potential by using a novel serum- and feeder-free directed differentiation culture system. Cytostaining and flow cytometric analyses of myeloid cells differentiated from patient-derived induced pluripotent stem cells showed arrest at the myeloid progenitor stage and apoptotic predisposition, both of which replicated abnormal granulopoiesis. Moreover, lentiviral transduction of the HAX1 cDNA into patient-derived induced pluripotent stem cells reversed disease-related abnormal granulopoiesis. This in vitro neutrophil differentiation system, which uses patient-derived induced pluripotent stem cells for disease investigation, may serve as a novel experimental model and a platform for high-throughput screening of drugs for various congenital neutrophil disorders in the future. PMID:23975175

  16. Dengue and Other Common Causes of Acute Febrile Illness in Asia: An Active Surveillance Study in Children

    PubMed Central

    Capeding, Maria Rosario; Chua, Mary Noreen; Hadinegoro, Sri Rezeki; Hussain, Ismail I. H. M.; Nallusamy, Revathy; Pitisuttithum, Punnee; Rusmil, Kusnandi; Thisyakorn, Usa; Thomas, Stephen J.; Huu Tran, Ngoc; Wirawan, Dewa Nyoman; Yoon, In-Kyu; Bouckenooghe, Alain; Hutagalung, Yanee; Laot, Thelma; Wartel, Tram Anh

    2013-01-01

    Background Common causes of acute febrile illness in tropical countries have similar symptoms, which often mimic those of dengue. Accurate clinical diagnosis can be difficult without laboratory confirmation and disease burden is generally under-reported. Accurate, population-based, laboratory-confirmed incidence data on dengue and other causes of acute fever in dengue-endemic Asian countries are needed. Methods and principal findings This prospective, multicenter, active fever surveillance, cohort study was conducted in selected centers in Indonesia, Malaysia, Philippines, Thailand and Vietnam to determine the incidence density of acute febrile episodes (?38°C for ?2 days) in 1,500 healthy children aged 2–14 years, followed for a mean 237 days. Causes of fever were assessed by testing acute and convalescent sera from febrile participants for dengue, chikungunya, hepatitis A, influenza A, leptospirosis, rickettsia, and Salmonella Typhi. Overall, 289 participants had acute fever, an incidence density of 33.6 per 100 person-years (95% CI: 30.0; 37.8); 57% were IgM-positive for at least one of these diseases. The most common causes of fever by IgM ELISA were chikungunya (in 35.0% of in febrile participants) and S. Typhi (in 29.4%). The overall incidence density of dengue per 100 person-years was 3.4 by nonstructural protein 1 (NS1) antigen positivity (95% CI: 2.4; 4.8) and 7.3 (95% CI: 5.7; 9.2) by serology. Dengue was diagnosed in 11.4% (95% CI: 8.0; 15.7) and 23.9% (95% CI: 19.1; 29.2) of febrile participants by NS1 positivity and serology, respectively. Of the febrile episodes not clinically diagnosed as dengue, 5.3% were dengue-positive by NS1 antigen testing and 16.0% were dengue-positive by serology. Conclusions During the study period, the most common identified causes of pediatric acute febrile illness among the seven tested for were chikungunya, S. Typhi and dengue. Not all dengue cases were clinically diagnosed; laboratory confirmation is essential to refine disease burden estimates. PMID:23936565

  17. High Frequency of Thyroid Disorders in Patients Presenting With Neutropenia to an Outpatient Hematology Clinic STROBE-Compliant Article.

    PubMed

    Kyritsi, Eleni Magdalini A; Yiakoumis, Xanthi; Pangalis, Gerasimos A; Pontikoglou, Charalampos; Pyrovolaki, Katerina; Kalpadakis, Christina; Mavroudi, Irini; Koutala, Helen; Mastrodemou, Semeli; Vassilakopoulos, Theodoros P; Vaiopoulos, George; Diamanti-Kandarakis, Evanthia; Papadaki, Helen A; Angelopoulou, Maria K

    2015-06-01

    Granulopoiesis abnormalities have been described in association with thyroid disorders (TD). However, data regarding systematic evaluation of adult neutropenia and concurrent or prior TD are scarce.To investigate the frequency of TD among patients presenting with neutropenia, and the immunophenotypic and immunologic profile of neutropenic patients with concomitant thyroidopathy.Two hundred eighteen consecutive neutropenic patients were prospectively evaluated in our outpatient Hematology Clinic, with a detailed laboratory screen, including thyroid function tests, antineutrophil antibodies, blood lymphocytes immunophenotyping, and detection of T-cell clonality by PCR.Among 218 patients with neutropenia, 95 (43.6%) had TD, 65 chronic immunologic neutropenia, 20 clonal proliferation of T-large granular lymphocytes (T-LGL), 5 autoimmune disorders, and 33 other diagnoses. TD-patients had an increased frequency of recurrent infections compared with other patients (P?=?0.045). The following correlations were found: negative correlation between FT3 and absolute neutrophil count (ANC) (r?=?-0.274, P?=?0.007), negative correlation between TPO-Abs/TG-Abs and C4 (r?=?-0.16, P?=?0.045; r?=?-0.266, P?=?0.001), and CD4 counts were inversely correlated to T4 and positively to TSH (r?=?-0.274, P?=?0.024; r?=?0.16, P?=?0.045). In addition, TD-patients had significantly higher percentages of CD4 lymphocytes (P?=?0.003). Among TD-patients, 23.4% had Hashimoto thyroiditis (HT), 4.1%, Graves disease (GD), 8.2% nontoxic multinodular goiter (NTMG), 5% subclinical hypothyroidism, and 2.8% had undergone total thyroidectomy associated with nodules (TTM). Thirteen TD-patients displayed T-LGL. Patients with autoimmune thyroidopathy had an increased frequency of concomitant autoimmune manifestations (P?=?0.03). Significant differences between the different thyroidopathies included: HT-patients had higher percentages of B-lymphocytes, while the opposite was evident for the TTM-subgroup (P?=?0.009, 0.02); GD-patients showed an increase of the proportion of NK cells and a decrease in the percentage of TCR??+ lymphocytes (P?=?0.001, 0.045); and NTMG-patients had significantly higher ANC (P?=?0.004) compared to other thyroidopathies. Antineutrophil antibodies were found in 37.2% of TD-patients tested. Anti-TPO titers were significantly higher in patients with positive antineutrophil antibodies (P?=?0.04).The frequency of TD among neutropenic patients may be higher than previously reported. The existence of antineutrophil antibodies, as well as the different distribution of lymphocyte subsets among patients with different TD, suggests both humoral and cellular mechanisms in the pathophysiology of thyroid disease-associated neutropenia. PMID:26061308

  18. Early hypoactivity of hippocampal rhythms during epileptogenesis after prolonged febrile seizures in freely-moving rats.

    PubMed

    Feng, Bo; Tang, Yang-Shun; Chen, Bin; Xu, Zheng-Hao; Wang, Yi; Wu, Deng-Chang; Zhao, Hua-Wei; Zhang, Shi-Hong; Chen, Zhong

    2015-06-01

    Prospective and experimental studies have shown that individuals with early-life complex/prolonged febrile seizures (FSs) have a high incidence of temporal lobe epilepsy during adulthood, revealing a close relationship between FSs and epilepsy. However, little is known about how epileptogenesis develops after FSs. The present study was designed to investigate acquired seizure susceptibility and analyze local field potentials during the latent period after FSs. We found that the seizure susceptibility decreased in 35-day-old (P35) FS rats but increased in P60 FS rats. Consistently, hippocampal electroencephalogram (EEG) power in every band was decreased at P35 but increased at P60 in FS rats. Our results provide direct evidence for hypoactivity but not hyperactivity during the early phase of the latent period, displaying a broad decrease in hippocampal rhythms. These characteristic EEG changes can be a useful biomarker for the early diagnosis of epileptogenesis induced by FSs. PMID:25913039

  19. Limitations of indium-111 leukocyte scanning in febrile renal transplant patients

    SciTech Connect

    Sebrechts, C.; Biberstein, M.; Klein, J.L.; Witztum, K.F.

    1986-04-01

    Indium-111-labeled leukocyte scanning was evaluated as a technique for investigating possible abscess as the cause of fever in 10 renal allograft recipients under therapy for rejection, acute tubular necrosis, or urinary infection. The usefulness of the method in this setting was found to be limited by marked nonspecificity of renal, pulmonary, and other focal leukocyte accumulation. Although wound infections were correctly identified, false-positive scans resulted in multiple nonproductive consultations and radiologic procedures (some invasive) and contributed to the decision to perform one negative exploratory laparotomy. Such generalized nonspecificity in this patient population is in distinct contrast to the experience with this diagnostic test in nontransplant patients, and has not previously been reported. Possible explanations and implications of these findings are discussed. Consequently, great caution is recommended in the use of indium-111 leukocyte scans to diagnose infection in febrile renal transplant patients who present in a similar clinical setting.

  20. Viral hemorrhagic fever cases in the country of Georgia: Acute Febrile Illness Surveillance Study results.

    PubMed

    Kuchuloria, Tinatin; Imnadze, Paata; Chokheli, Maiko; Tsertsvadze, Tengiz; Endeladze, Marina; Mshvidobadze, Ketevan; Clark, Danielle V; Bautista, Christian T; Abdel Fadeel, Moustafa; Pimentel, Guillermo; House, Brent; Hepburn, Matthew J; Wölfel, Silke; Wölfel, Roman; Rivard, Robert G

    2014-08-01

    Minimal information is available on the incidence of Crimean-Congo hemorrhagic fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537 patients with fever ? 38°C for ? 48 hours without a diagnosis were enrolled into a sentinel surveillance study to investigate the incidence of nine pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM) antibodies. Two of the patients enrolled in the study had acute renal failure. These 2 of 537 enrolled patients were the only patients in the study positive for hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus are contributing causes of acute febrile syndromes of infectious origin in Georgia. These findings support introduction of critical diagnostic approaches and confirm the need for additional surveillance in Georgia. PMID:24891463

  1. Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats.

    PubMed

    Kanashiro, Alexandre; Pessini, Andréa C; Machado, Renes R; Malvar, David do C; Aguiar, Fernando A; Soares, Denis Melo; do Vale, Mariana L; de Souza, Glória E Petto

    2009-05-01

    The present study investigated the febrile response in zymosan-induced arthritis, as well as the increase in PGE(2) concentration in the cerebrospinal fluid (CSF), along with the effects of antipyretic drugs on these responses in rats. Zymosan intra-articularly injected at the dose of 0.5 mg did not affect the body core temperature (Tc) compared with saline (control), whereas at doses of 1 and 2 mg, zymosan promoted a flattened increase in Tc and declined thereafter. The dose of 4 mg of zymosan was selected for further experiments because it elicited a marked and long-lasting Tc elevation starting at 3 1/2 h, peaking at 5 1/2 h, and remaining until 10 h. This temperature increase was preceded by a decrease in the tail skin temperature, as well as hyperalgesia and edema in the knee joint. No febrile response was observed in the following days. In addition, zymosan-induced fever was not modified by the sciatic nerve excision. Zymosan increased PGE(2) concentration in the CSF but not in the plasma. Oral pretreatment with ibuprofen (5-20 mg/kg), celecoxib (1-10 mg/kg), dipyrone (60-240 mg/kg), and paracetamol (100-200 mg/kg) or subcutaneous injection of dexamethasone (0.25-1.0 mg/kg) dose-dependently reduced or prevented the fever during the zymosan-induced arthritis. Celecoxib (5 mg/kg), paracetamol (150 mg/kg), and dipyrone (120 mg/kg) decreased CSF PGE(2) concentration and fever during zymosan-induced arthritis, suggesting the involvement of PGE(2) in this response. PMID:19244587

  2. Proton pump inhibitor-induced Sweet’s syndrome: report of acute febrile neutrophilic dermatosis in a woman with recurrent breast cancer

    PubMed Central

    Cohen, Philip R.

    2015-01-01

    Background: Sweet’s syndrome, also referred to as acute febrile neutrophilic dermatosis, can either occur as an idiopathic disorder or associated with another condition, including cancer, or induced by exposure to a drug. Proton pump inhibitors selectively inhibit gastric parietal cell H+-K+-adenosine triphosphatase and are most commonly used for the treatment of gastroesophageal reflux disease. Purpose: Proton pump inhibitor-associated Sweet’s syndrome is described in a woman with recurrent breast cancer. Methods: PubMed was used to search the following terms, separately and in combination: acute febrile neutrophilic dermatosis, breast cancer, malignancy, paraneoplastic, proton pump inhibitor, and Sweet’s syndrome. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Results: Proton pump inhibitors have previously been associated with cutaneous adverse reactions including maculopapular rash, subacute cutaneous lupus erythematosus and toxic epidermal necrolysis. However, drug-induced Sweet’s syndrome has not been observed in patients receiving proton pump inhibitors. The reported woman developed Sweet’s syndrome after initial exposure and subsequent repeat challenge to proton pump inhibitors; subsequent studies also observed recurrence of her breast cancer presenting as metastases to her stomach and bone. Conclusions: Drug-induced Sweet’s syndrome has most commonly been associated with granulocyte colony stimulating factor in oncology patients. Malignancy-associated Sweet’s syndrome has been observed in patients with solid tumors, including breast cancer. Confirmation of proton pump inhibitor-induced Sweet’s syndrome, by repeat challenge with another medication in the same class of drug, was observed in a woman with breast cancer; although the subsequent discovery of recurrent breast cancer presenting as gastric mucosa and vertebral metastases also raises the possibility of concurrent paraneoplastic Sweet’s syndrome, her Sweet’s syndrome symptoms and lesions resolved without recurrence while her recurrent metastatic visceral malignancy persisted. In summary, medication-associated Sweet’s syndrome can occur in oncology patients and proton pump inhibitors should be added to the list of medications associated with the potential to cause drug-induced Sweet’s syndrome.

  3. Severe congenital neutropenia due to G6PC3 deficiency: early and delayed phenotype in two patients with two novel mutations.

    PubMed

    Notarangelo, Lucia Dora; Savoldi, Gianfranco; Cavagnini, Sara; Bennato, Veronica; Vasile, Sabrina; Pilotta, Alba; Plebani, Alessandro; Porta, Fulvio

    2014-01-01

    Severe Congenital Neutropenia type 4 (SCN4, OMIM 612541) is a rare autosomal recessive disease due to mutations in the G6PC3 gene. The phenotype comprises neutropenia of variable severity and other anomalies including congenital heart defects, prominent superficial veins, uro-genital anomalies, facial dysmorphism, growth and developmental delay and intermittent thrombocytopenia. In some patients, SCN represents the only manifestation of the disease. Variable findings have been reported at bone marrow examination ranging from a maturation arrest at the myelocyte/promyelocyte stage (either in a hypocellular or hypercellular context) to myelokathexis. Here we report two patients harbouring two novel mutations in the G6PC3 gene, including the first Italian patient even described. Both the patients share profound neutropenia with severe infections early in life; in one case non-hematopoietic stigmata of the syndrome, including evident facial dysmorphism and vascular anomalies, appeared gradually over time, prominently in the second decade. Therefore, G6PC3 defects should be considered in any case of congenital, unexplained neutropenia regardless of the clinical phenotype. Both patients are on G-CSF treatment with no evidence of malignant evolution. Even if G6PC3 deficiency seems not to have a propensity towards malignancy, a careful evaluation is warranted. PMID:25391451

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

    PubMed Central

    2012-01-01

    Background WHIM syndrome (WS), a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the light of the recent development of new CXCR4 inhibitors. Objective This study aims to describe the natural history of WS based on a French cohort of 8 patients. Methods We have reviewed the clinical, biological and immunological features of patients with WS enrolled into the French Severe Chronic Neutropenia Registry. Results We identified four pedigrees with WS comprised of eight patients and one foetus. Estimated incidence for WS was of 0.23 per million births. Median age at the last visit was 29 years. Three pedigrees encompassing seven patients and the fetus displayed autosomal dominant heterozygous mutations of the CXCR4 gene, while one patient presented a wild-type CXCR4 gene. Two subjects exhibited congenital conotruncal heart malformations. In addition to neutropenia and myelokathexis, all patients presented deep monocytopenia and lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well as severe bacterial infections that were curable with antibiotics. Four patients with late onset prophylaxis developed chronic obstructive pulmonary disease (COPD). Two patients reported atypical mycobacteria infections which in one case may have been responsible for one patient’s death due to liver failure at the age of 40.6 years. HPV-related disease manifested in five subjects and progressed as invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5 years. In addition, two patients developed T cell lymphoma skin cancer and basal cell carcinoma at the age of 38 and 65 years. Conclusions Continuous prophylactic anti-infective measures, when started in early childhood, seem to effectively prevent further bacterial infections and the consequent development of COPD. Long-term follow up is needed to evaluate the effect of early anti-HPV targeted prophylaxis on the development of skin and genital warts. PMID:23009155

  5. Emergence of Carbapenem resistant Gram negative and vancomycin resistant Gram positive organisms in bacteremic isolates of febrile neutropenic patients: A descriptive study

    Microsoft Academic Search

    Seema Irfan; Faiza Idrees; Vikram Mehraj; Faizah Habib; Salman Adil; Rumina Hasan

    2008-01-01

    BACKGROUND: This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant Enterococcus species. METHODS: A descriptive study was performed by reviewing the blood culture reports from febrile neutropenic patients during the two study periods i.e., 1999–00 and 2001–06. Blood cultures were

  6. Risk factors for bacteremia with uropathogen not cultured from urine in adults with febrile urinary tract infection.

    PubMed

    van Nieuwkoop, Cees; Bonten, Tobias N; Wout, Jan W Van't; Becker, Martin J; Groeneveld, Geert H; Jansen, Casper L; van der Vorm, Eric R; Ijzerman, Ed P; Rothbarth, Philip H; Termeer-Veringa, Etel M; Kuijper, Ed J; van Dissel, Jaap T

    2010-06-01

    In a prospective study involving 642 patients with febrile urinary tract infection (UTI), we found antimicrobial pretreatment (odds ratio [OR], 3.3), an indwelling urinary catheter (OR, 2.8), and malignancy (OR, 2.7) to be independent risk factors for bacteremia with a uropathogen that was not cultured or recognized in the urine. Although the diagnostic value of blood cultures has been questioned in UTI, we advocate performing blood cultures for patients with these risk factors. PMID:20420504

  7. Molecular Epidemiology of an Outbreak of Febrile Gastroenteritis Caused by Listeria monocytogenes in Cold-Smoked Rainbow Trout

    Microsoft Academic Search

    M. K. MIETTINEN; A. SIITONEN; P. HEISKANEN; H. HAAJANEN; K. J. BJORKROTH; H. J. KORKEALA

    1999-01-01

    Febrile gastroenteritis in five healthy persons was associated with the consumption of vacuum-packed cold-smoked rainbow trout containing Listeria monocytogenes. L. monocytogenes isolates from the incriminated fish product lot and the stool samples were all of serotype 1\\/2a and were indistinguishable by pulsed-field gel electrophoresis employing AscI and SmaI. Listeria monocytogenes is a food-borne pathogen causing lis- teriosis mainly in immunocompromised

  8. An increase of hippocampal calretinin-immunoreactive neurons correlates with early febrile seizures in temporal lobe epilepsy

    Microsoft Academic Search

    Ingmar Blümcke; Heinz Beck; Bernhard Suter; Dietmar Hoffmann; Hans J. Födisch; Helmut K. Wolf; Johannes Schramm; Christian E. Elger; Otmar D. Wiestler

    1999-01-01

    Numerous studies indicate that initial precipitating injuries (IPI) such as febrile seizures during early childhood may play\\u000a a pivotal role in the pathogenesis of temporal lobe epilepsy (TLE) and Ammon’s horn sclerosis (AHS). Previous data demonstrate\\u000a an increase of horizontally oriented neurons in molecular layers of hippocampal subfields, which are immunoreactive for calretinin\\u000a (CR-ir) and resemble Cajal-Retzius-like cells. Cajal-Retzius cells

  9. Non-typhoidal Salmonella rates in febrile children at sites in five Asian countries.

    PubMed

    Khan, M Imran; Ochiai, R L; von Seidlein, L; Dong, B; Bhattacharya, S K; Agtini, M D; Bhutta, Z A; Do, G C; Ali, M; Kim, D R; Favorov, M; Clemens, J D

    2010-08-01

    There is increased recognition of non-typhoidal Salmonella (NTS) as a major cause of severe febrile illness in sub-Saharan Africa. However, little is known about community-based incidence of NTS in Asia. In a multicentre, community-based prospective Salmonella surveillance study, we identified a total of six NTS cases: three in Karachi, Pakistan, one in Kolkata, India, and two in North Jakarta, Indonesia. No NTS cases were identified in Hechi, People's Republic of China, and Hue, Viet Nam. Three cases were in children under 3 years, and one case was in a child aged 10 years and one in a child aged 15 years. Only one case was an adult (29 years). The highest incidence of NTS infection was in Karachi (7.2 culture-proven NTS cases per 100,000 person years in age group of 2-15 years). However, in comparison with sub-Saharan Africa, the NTS burden in Asia appears rather limited. PMID:20545918

  10. Sleep, but not febrile responses of Fisher 344 rats to immune challenge are affected by aging.

    PubMed

    Imeri, Luca; Ceccarelli, Piera; Mariotti, Maurizio; Manfridi, Alfredo; Opp, Mark R; Mancia, Mauro

    2004-07-01

    Sleep is altered in response to infection and immune challenge in humans and non-human animals. Although there are changes in sleep and facets of immune function with aging, sleep responses of aged subjects to immune challenge have received little, if any attention. To test the hypothesis that aging affects sleep responses to immune challenge, intracerebroventricular injections of interleukin 1 (IL-1) were given to young and aged rats and subsequent sleep-wake behavior was determined. Under basal conditions and in the absence of an immune challenge, sleep patterns of young (3 months) and aged (25-27 months) Fisher 344 rats did not differ. In young animals, IL-1 (2.5 ng) enhanced non-rapid eye movement (NREM) sleep, inhibited rapid eye movement (REM) sleep, and induced fever. In aged animals, IL-1 administration did not alter NREM sleep, but REM sleep was inhibited and brain temperature increased to the same extent observed in young animals. These results show that alterations in sleep following immune challenge are impacted by aging, whereas febrile responses are not. Since it has been postulated that enhanced NREM sleep may facilitate recovery from microbial infection, the present results also suggest that the lack of NREM sleep responses of aged rats to immune challenge may contribute to the increased infection-induced morbidity and mortality of aged organisms. PMID:15157957

  11. T2 relaxation time post febrile status epilepticus predicts cognitive outcome.

    PubMed

    Barry, Jeremy M; Choy, ManKin; Dube, Celine; Robbins, Ashlee; Obenaus, Andre; Lenck-Santini, Pierre Pascal; Scott, Rod C; Baram, Tallie Z; Holmes, Gregory L

    2015-07-01

    Evidence from animal models and patient data indicates that febrile status epilepticus (FSE) in early development can result in permanently diminished cognitive abilities. To understand the variability in cognitive outcome following FSE, we used MRI to measure dynamic brain metabolic responses to the induction of FSE in juvenile rats. We then compared these measurements to the ability to learn an active avoidance spatial task weeks later. T2 relaxation times were significantly lower in FSE rats that were task learners in comparison to FSE non-learners. While T2 time in whole brain held the greatest predictive power, T2 in hippocampus and basolateral amygdala were also excellent predictors. These signal differences in response to FSE indicate that rats that fail to meet metabolic and oxygen demand are more likely to develop spatial cognition deficits. Place cells from FSE non-learners had significantly larger firing fields and higher in-field firing rate than FSE learners and control animals and imply increased excitability in the pyramidal cells of FSE non-learners. These findings suggest a mechanistic cause for the spatial memory deficits in active avoidance and are relevant to other acute neurological insults in early development where cognitive outcome is a concern. PMID:25939697

  12. Levamisole treatment of a child with severe aphthous stomatitis and neutropenia

    Microsoft Academic Search

    H. Verhaegen; J. De Crée; W. De Cock; J. Brugmans

    1976-01-01

    The treatment of a 12-year-old girl with a lifelone history of recurrent infections and aphthous stomatitis is reported. A profound neutropenis, first noted at the age of 2 years, occurring at least every month was observed together with multiple mouth ulcers a sore throat and swelling of the jugular glands. Levamisole, originally described as an anthelmintic, has a beneficial effect

  13. Resolution of inflammatory colitis with pegfilgrastim treatment in a case of severe congenital neutropenia due to glucose 6 phosphatase catalytic subunit-3 deficiency.

    PubMed

    Kaya, Zühre; E?rita?, Odül; Albayrak, Meryem; Göçün, Pinar Uyar; Koçak, Ulker; Dalgiç, Buket; Gürsel, Türkiz

    2014-07-01

    Glucose 6 phosphatase catalytic subunit-3 (G6PC3) deficiency is a heterogenous disorder characterized by severe congenital neutropenia and a variety of extrahematopoietic manifestations. Inflammatory bowel disease like colitis is an uncommon complication of G6PC3 deficiency, described only in adolescent and adults. Herein, we describe inflammatory colitis in a 10-year-old girl with severe congenital neutropenia due to G6PC3 deficiency while she was on a high-dose filgrastim. Switching from filgrastim to (pegylated filgrastim) Pegfilgrastim led to rapid resolution of colitis, weight gain, and decreased infections. Pegfilgrastim seems to be a better remedy for treatment of G6PC3 deficiency complicated with inflammatory bowel disease. PMID:24322501

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

    SciTech Connect

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

    1987-05-01

    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 (/sup 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.

  15. Anti-CD18 antibody attenuates neutropenia and alveolar capillary-membrane injury during gram-negative sepsis.

    PubMed

    Walsh, C J; Carey, P D; Cook, D J; Bechard, D E; Fowler, A A; Sugerman, H J

    1991-08-01

    Activated polymorphonuclear leukocytes (PMNs) are implicated in the pathogenesis of acute lung injury (ALI) associated with sepsis. Adhesion of activated PMNs to endothelial monolayers is mediated by the CD18 adhesion-receptor complex on the PMN cell surface. Monoclonal antibody 60.3 (MoAb 60.3) blocks CD18-dependent PMN-endothelial adhesion in vitro and in vivo. This study was designed to determine the role of CD18-dependent PMN adhesion in ALI associated with gram-negative sepsis. Anesthetized, ventilated (FiO2 0.5, positive end-expiratory pressure 5 cm H2O) pigs received sterile saline (control, n = 8) or live Pseudomonas aeruginosa, 5 x 10(8) colony-forming units/ml at 0.3 ml/20 kg/min (septic, n = 9) for 1 hour. A third group (n = 7) received MoAb 60.3, 2 mg/kg intravenously, 15 minutes before Pseudomonas infusion. Animals were studied for 300 minutes. MoAb 60.3 significantly (p less than 0.05) attenuated the neutropenia seen in sepsis (15 +/- 1 vs 6 +/- 1 x 10(3) PMNs/mm3 at 300 min). Alveolar-capillary membrane injury was assessed by bronchoalveolar-lavage protein content and extravascular lung water determination. MoAb 60.3 significantly (p less than 0.05) reduced BAL protein at 300 minutes (388 +/- 75 vs 1059 +/- 216 micrograms/ml in septic animals) and attenuated the increase in extravascular lung water to 240 minutes (7.1 +/- 2 vs 14.2 +/- 1.2 ml/kg in septic animals). Systemic hypotension, decreased cardiac index, pulmonary hypertension, and relative hypoxemia, all characteristic of this model, were not altered by MoAb 60.3. These data suggest that, in this model of septic ALI, neutropenia is, in part, CD18 dependent and that blocking CD18-dependent PMN adhesion protects the alveolar-capillary membrane independently of altered hemodynamic status. PMID:1677491

  16. The Incidence of Leukemia and Mortality from Sepsis in Patients with Severe Congenital Neutropenia Receiving Long Term G-CSF Therapy

    Microsoft Academic Search

    Philip S. Rosenberg; Blanche P. Alter; Audrey A. Bolyard; Mary Ann Bonilla; Laurence A. Boxer; Bonnie Cham; Carol Fier; Melvin Freedman; George Kannourakis; Sally Kinsey; Beate Schwinzer; Connie Zeidler; Karl Welte; David C. Dale

    2006-01-01

    In patients with severe congenital neutro- penia (SCN), sepsis mortality is reduced by treatment with granulocyte colony- stimulating factor (G-CSF), but my- elodsyplastic syndrome and acute my- eloid leukemia (MDS\\/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman- Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN,

  17. Nav1.1 Dysfunction in Genetic Epilepsy with Febrile Seizures Plus or Dravet Syndrome

    PubMed Central

    Volkers, Linda; Kahlig, Kristopher M.; Verbeek, Nienke E.; Das, Joost H.G.; van Kempen, Marjan J.A.; Stroink, Hans; Augustijn, Paul; van Nieuwenhuizen, Onno; Lindhout, Dick; George, Alfred L.; Koeleman, Bobby P.C.; Rook, Martin B.

    2011-01-01

    Relatively few SCN1A mutations associated with genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS) have been functionally characterized. In contrast to GEFS+, many mutations detected in DS patients are predicted to have complete loss-of-function. However, functional consequences are not immediately apparent for DS missense mutations. Therefore, we performed biophysical analysis of three SCN1A missense mutations (R865G, R946C, and R946H) we detected in six patients with DS. Furthermore, we compared the functionality of the R865G DS mutation with that of a R859H mutation detected in a GEFS+ patient; both mutations reside in the same voltage sensor domain of Nav1.1. The four mutations were co-expressed with ?1 and ?2-subunits in tsA201 cells and characterized using the whole-cell patch clamp technique. The two DS mutations, R946C and R946H, were non-functional. However, the novel voltage sensor mutants R859H (GEFS+) and R865G (DS) produced sodium current densities comparable to wild-type channels. Both mutants had negative shifts in the voltage dependence of activation, slower recovery from inactivation, and increased persistent current. Only the GEFS+ mutant exhibited a loss-of-function in voltage dependent channel availability. Our results suggest that the R859H mutation causes GEFS+ by a mixture of biophysical defects in Nav1.1 gating. Interestingly, while loss of Nav1.1 function is common in DS, the R865G mutation may cause DS by overall gain-of-function defects. PMID:21864321

  18. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations

    PubMed Central

    Potts, James A.; Rothman, Alan L.

    2009-01-01

    Summary OBJECTIVE Clinicians in resource-poor countries need to identify patients with dengue using readily-available data. The objective of this systematic review was to identify clinical and laboratory features that differentiate dengue fever (DF) and/or dengue hemorrhagic fever (DHF) from other febrile illnesses (OFI) in dengue-endemic populations. METHODS Systematic review of the literature from 1990-Oct. 30, 2007 including English publications comparing dengue and OFI. RESULTS Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children only, and four assessed adults only. Patients with dengue had significantly lower platelet, white blood cell (WBC) and neutrophil counts, and a higher frequency of petechiae than OFI patients. Higher frequencies of myalgia, rash, hemorrhagic signs, lethargy/prostration, and arthralgia/joint pain and higher hematocrits were reported in adult patients with dengue but not in children. Most multivariable models included platelet count, WBC, rash, and signs of liver damage; however, none had high statistical validity and none considered changes in clinical features over the course of illness. CONCLUSIONS Several individual clinical and laboratory variables distinguish dengue from OFI; however, some variables may be dependent on age. No published multivariable model has been validated. Study design, populations, diagnostic criteria, and data collection methods differed widely across studies, and the majority of studies did not identify specific etiologies of OFIs. More prospective studies are needed to construct a valid and generalizable algorithm to guide the differential diagnosis of dengue in endemic countries. PMID:18803612

  19. Pediatric patients who receive antibiotics for fever and neutropenia in less than 60 min have decreased intensive care needs

    PubMed Central

    Salstrom, Jennifer L; Coughlin, Rebecca L; Pool, Kathleen; Bojan, Melissa; Mediavilla, Camille; Schwent, William; Rannie, Michael; Law, Dawn; Finnerty, Michelle; Hilden, Joanne

    2015-01-01

    Background Antibiotic delivery to patients with fever and neutropenia (F&N) in <60 min is an increasingly important quality measure for oncology centers, but several published reports indicate that a time to antibiotic delivery (TTA) of <60 min is quite difficult to achieve. Here we report a quality improvement (QI) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N. Procedure We used Lean-Methodology and a Plan-Do-Study-Act approach to direct QI efforts and prospectively tracked TTA measures and associated clinical outcomes (length of stay, duration of fever, use of imaging studies to search for occult infection, bacteremia, intensive care unit (ICU) consultation or admission, and mortality). We then performed statistical analysis to determine the impact of our QI interventions on total TTA, sub-process times, and clinical outcomes. Results Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in <60 min nearly 100% of the time. All TTA sub-process times also improved. Moreover, achieving TTA <60 min significantly reduced the need for ICU consultation or admission (P = 0.003) in this population. Conclusion Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes. These data indicate that decreasing TTA to <60 min is achievable and associated with improved outcomes in pediatric patients with cancer and F&N. PMID:25663663

  20. Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3

    PubMed Central

    Banka, Siddharth; Chervinsky, Elena; Newman, William G; Crow, Yanick J; Yeganeh, Shay; Yacobovich, Joanne; Donnai, Dian; Shalev, Stavit

    2011-01-01

    Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive condition, which was defined recently with identification of the causative mutations in G6PC3. To date there are only three reports in the literature describing patients with SCN4 with mutations in the G6PC3 gene. We report four individuals with SCN4 who belong to a single large consanguineous kindred. We provide an overview of the non-haematological features of the condition with a focus on the adult phenotype, which has not been previously described in detail. We show that the superficial venous changes seen in SCN4 patients can develop into varicose veins and venous ulcers in adulthood. We review the range of congenital anomalies associated with SCN4. We demonstrate that secundum atrial septal defect, patent ductus arteriosus and valvular defects are the most frequent cardiac anomalies in SCN4. Drawing parallels with type 1 glycogen storage disease, we propose that poor growth of prenatal onset, mild-to-moderate learning disability, primary pulmonary hypertension, delayed or incomplete puberty, hypothyroidism and dysmorphism likely represent features of this syndrome. We also suggest monitoring for lipid anomalies, and kidney and liver function in affected patients. Delineation of the SCN4 phenotype may help in appropriate treatment and management and provide further insights into the pathogenesis of this multisystem disease. PMID:20717171

  1. Naturally occurring methyl salicylate glycosides.

    PubMed

    Mao, Ping; Liu, Zizhen; Xie, Meng; Jiang, Rui; Liu, Weirui; Wang, Xiaohong; Meng, Shen; She, Gaimei

    2014-01-01

    As an important part of non steroids anti-inflammation drug (NSAIDs), salicylate has developed from natural substance salicylic acid to natrium salicylicum, to aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic acid, is modified with a -COOH group integrated one methyl radical into formic ether, and a -OH linked with a monosaccharide, a disaccharide or a trisaccharide unit by glycosidic linkage. It has the similar pharmacological activities, anti-inflammatory, analgesic, antipyretic and antithrombotic as the previous salicylates' without resulting in serious side effects, particularly the gastrointestinal toxicity. Owing to the superiority of those significant bioactivities, methyl salicylate glycosides have became a hot research area in NSAIDs for several years. This paper compiles all 9 naturally occurring methyl salicylate glycosides, their distribution of the resource and pharmacological mechanism, which could contribute to the new drug discovery. PMID:24329991

  2. Syndromic surveillance: etiologic study of acute febrile illness in dengue suspicious cases with negative serology. Brazil, Federal District, 2008.

    PubMed

    Silva, Ailton Domicio da; Evangelista, Maria do Socorro Nantua

    2010-01-01

    With the aim of identifying the etiology of acute febrile illness in patients suspected of having dengue, yet with non reagent serum, a descriptive study was conducted with 144 people using secondary serum samples collected during convalescence. The study was conducted between January and May of 2008. All the exams were re-tested for dengue, which was confirmed in 11.8% (n = 17); the samples that remained negative for dengue (n = 127) were tested for rubella, with 3.9% (n = 5) positive results. Among those non reactive for rubella (n = 122), tests were made for leptospirosis and hantavirus. Positive tests for leptospirosis were 13.9% (n = 17) and none for hantavirus. Non reactive results (70.8%) were considered as Indefinite Febrile Illness (IFI). Low schooling was statistically associated with dengue, rubella and leptospirosis (p = 0.009), dyspnea was statistically associated with dengue and leptospirosis (p = 0.012), and exanthem/petechia with dengue and rubella (p = 0.001). Among those with leptospirosis, activities in empty or vacant lots showed statistical association with the disease (p = 0.013). Syndromic surveillance was shown to be an important tool in the etiologic identification of IFI in the Federal District of Brazil. PMID:21049226

  3. The Influence of Different Fever Definitions on the Rate of Fever in Neutropenia Diagnosed in Children with Cancer

    PubMed Central

    Ammann, Roland A.; Teuffel, Oliver; Agyeman, Philipp; Amport, Nadine; Leibundgut, Kurt

    2015-01-01

    Background The temperature limit defining fever (TLDF) is based on scarce evidence. This study aimed to determine the rate of fever in neutropenia (FN) episodes additionally diagnosed by lower versus standard TLDF. Methods In a single center using a high TLDF (39.0°C tympanic temperature, LimitStandard), pediatric patients treated with chemotherapy for cancer were observed prospectively. Results of all temperature measurements and CBCs were recorded. The application of lower TLDFs (LimitLow; range, 37.5°C to 38.9°C) versus LimitStandard was simulated in silicon, resulting in three types of FN: simultaneous FN, diagnosed at both limits within 1 hour; earlier FN, diagnosed >1hour earlier at LimitLow; and additional FN, not diagnosed at LimitStandard. Results In 39 patients, 8896 temperature measurements and 1873 CBCs were recorded during 289 months of chemotherapy. Virtually applying LimitStandard resulted in 34 FN diagnoses. The predefined relevantly (?15%) increased FN rate was reached at LimitLow 38.4°C, with total 44 FN, 23 simultaneous, 11 earlier, and 10 additional (Poisson rate ratioAdditional/Standard, 0.29; 95% lower confidence bound, 0.16). Virtually applying 37.5°C as LimitLow led to earlier FN diagnosis (median, 4.5 hours; 95% CI, 1.0 to 20.8), and to 53 additional FN diagnosed. In 51 (96%) of them, spontaneous defervescence without specific therapy was observed in reality. Conclusion Lower TLDFs led to many additional FN diagnoses, implying overtreatment because spontaneous defervescence was observed in the vast majority. Lower TLDFs led as well to relevantly earlier diagnosis in a minority of FN episodes. The question if the high TLDF is not only efficacious but as well safe remains open. PMID:25671574

  4. Exploring the Association of Hemoglobin Level and Adverse Events in Children with Cancer Presenting with Fever in Neutropenia

    PubMed Central

    Ammann, Roland A.; Niggli, Felix K.; Leibundgut, Kurt; Teuffel, Oliver; Bodmer, Nicole

    2014-01-01

    Background In children and adolescents with fever in neutropenia (FN) during chemotherapy for cancer, hemoglobin ?90 g/L at presentation with FN had been associated with adverse events (AE). This analysis explored three hypothetical pathophysiological mechanisms potentially explaining this counterintuitive finding, and further analyzed the statistical association between hemoglobin and AE. Methods Two of 8 centers, reporting on 311 of 421 FN episodes in 138 of 215 patients participated in this retrospective analysis based on prospectively collected data from three databases (SPOG 2003 FN, transfusion and hematology laboratories). Associations with AE were analyzed using mixed logistic regression. Results Hemoglobin was ?90 g/L in 141 (45%) of 311 FN episodes, specifically in 59/103 (57%) episodes with AE, and in 82/208 (39%) without (OR, 2.3; 99%CI, 1.1–4.9; P?=?0.004). In FN with AE, hemoglobin was bimodally distributed with a dip around 85 g/L. There were no significant interactions for center, age and sex. In multivariate mixed logistic regression, AE was significantly and independently associated with leukopenia (leukocytes <0.3 G/L; OR, 3.3; 99%CI, 1.1–99; P?=?0.004), dehydration (hemoglobinPresentation/hemoglobin8–72 hours ?1.10 in untransfused patients; OR, 3.5; 99%CI, 1.1–11.4; P?=?0.006) and non-moderate anemia (difference from 85 g/L; 1.6 per 10 g/L; 1.0–2.6; P?=?0.005), but not with recent transfusion of packed red blood cells (pRBC), very recent transfusion of pRBC or platelets, or with hemoglobin ?90 g/L as such. Conclusions Non-moderate anemia and dehydration were significantly and relevantly associated with the risk of AE in children with cancer and FN. These results need validation in prospective cohorts before clinical implementation. PMID:25020130

  5. Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia.

    PubMed Central

    Gøtzsche, P. C.; Johansen, H. K.

    1997-01-01

    OBJECTIVE: To determine whether antifungal agents given prophylactically or empirically decrease morbidity and mortality in patients with cancer complicated by neutropenia. DESIGN: Meta-analysis of randomised trials of amphotericin B, various lipid soluble formulations of amphotericin B (for example, AmBisome), fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment. SETTING: Trials conducted anywhere in the world. SUBJECTS: Patients with cancer complicated by neutropenia. MAIN OUTCOME MEASURES: Mortality, invasive fungal infection (defined as positive blood culture, oesophageal candidiasis, or lung or deep tissue infection), and colonisation. RESULTS: 24 trials with 2758 randomised patients were reviewed; the total number of deaths was 434. Prophylactic or empirical treatment with antifungals as a group bad no effect on mortality (odds ratio 0.92; 95% confidence interval 0.74 to 1.14). Amphotericin B decreased mortality significantly (0.58; 0.37 to 0.93) but the studies were small and the difference in number of deaths was only 15. Antifungal treatment decreased the incidence of invasive fungal infection (0.47; 0.35 to 0.64) and fungal colonisation (0.45; 0.30 to 0.69). For every 73 patients treated (95% confidence interval to 48 to 158) one case of fungal invasion was prevented in surviving patients. CONCLUSIONS: There seems to be no survival benefit of antifungal agents given prophylactically or empirically to patients with cancer complicated by neutropenia. These agents should be restricted to patients with proved infection and those in randomised trials. A large, definitive placebo controlled trial of amphotericin B is needed. PMID:9154027

  6. Real-time broad-range PCR versus blood culture. A prospective pilot study in pediatric cancer patients with fever and neutropenia

    Microsoft Academic Search

    Roland A. Ammann; Franziska Zucol; Christoph Aebi; Felix K. Niggli; Thomas Kühne; David Nadal

    2007-01-01

    Materials and methods  In a pilot study, results of real-time broad-range (16S rRNA) polymerase chain reaction (PCR) performed on 45 blood samples\\u000a of pediatric cancer patients with fever and neutropenia were compared with blood culture results.\\u000a \\u000a \\u000a \\u000a Results  The PCR assay used, having proven a high sensitivity in artificially spiked blood samples, was positive in only three of ten\\u000a blood culture-positive samples, and

  7. Cytokines, but not corticotropin-releasing factor and endothelin-1, participate centrally in the febrile response in zymosan-induced arthritis in rats.

    PubMed

    Kanashiro, Alexandre; Figueiredo, Maria J; Malvar, David do C; Souza, Glória E P

    2015-06-12

    Recent literature has revealed that centrally generated prostaglandins participate in the febrile response in zymosan-induced arthritis in rats. However, it is not clear whether other centrally acting pyrogenic mediators such as cytokines, endothelins (ETs), and the corticotropin-releasing factor (CRF) contribute to the febrile response in this model. In the present study, rats were pretreated with intracerebroventricular (i.c.v.) injections of soluble TNF receptor I (sTNFRI), recombinant IL-1 receptor antagonist (IL-1ra), anti-rat IL-6 monoclonal antibody (AbIL-6), ?-helical CRF9-41 (a nonselective CRF1/CRF2 receptor antagonist), BQ-123 (an ETA receptor antagonist), BQ-788 (an ETB receptor antagonist), and artificial cerebrospinal fluid (aCSF, control) prior to an intra-articular zymosan (4mg) injection. Rectal temperatures were measured with a telethermometer. The administration of IL-1ra (200µg), sTNFRI (500ng), and AbIL-6 (5µg) attenuated body temperature elevations after a zymosan injection. The administration of BQ-788 (3pmol), BQ-123 (3pmol), and ?-helical CRF9-41 (25µg) did not affect the zymosan-induced febrile response. All the compounds used to pretreat the animals did not significantly alter their basal body temperatures. Together, the results here demonstrate that the febrile response in zymosan-induced arthritis in rats depends on the centrally acting pyrogenic cytokines TNF-?, IL-1?, and IL-6, but does not depend on either CRF or ET-1. PMID:25819555

  8. A comparison of LPS-induced febrile responses across heat-tolerant and heat–sensitive Bos Taurus cattle in different thermal environments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accurate detection of fever in cattle is an important step in maintaining health of a herd. There is little information on several fronts regarding the differences in febrile response to a lipopolysaccharide (LPS) challenge. These include differences in hot (HS) and thermoneutral (TN) environments a...

  9. Febrile convulsions in a national cohort followed up from birth. II--Medical history and intellectual ability at 5 years of age

    Microsoft Academic Search

    C M Verity; N R Butler; J Golding

    1985-01-01

    Three hundred and three children with febrile convulsions were identified in a national birth cohort of 13 135 children followed up from birth to the age of 5 years. Breech delivery (p less than 0.05) was the only significantly associated prenatal or perinatal factor. There were no associations with socioeconomic factors. Excluding the 13 known to be neurologically abnormal before

  10. Steroid Unresponsive Case of Ulcerative Mucha-Habermann Disease (Febrile Ulcernecrotic Mucha-Habermann Disease) Treated with Methotrexate

    PubMed Central

    Shah, Deepam J; Dhir, Rajeev; Shah, Harsh; Chawla, Naveen

    2014-01-01

    A 20 year old male presented with fever associated with eruption of papules, plaques and vesiculobullous lesions on the chest, back, extremities, palms, soles, and genital mucosa of 20 days duration. Histopathological examination revealed epidermal clefts, edema and vacuolar degeneration of keratinocytes, basal cell degeneration, and dermal perivascular lymphocytic infiltrate. On the basis of clinical features and histology, a diagnosis of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) was made. Treatment with doxycycline (100 mg BD for 4 weeks) and oral prednisolone 60 mg/day tapered to 25 mg in 4 weeks led to initial response that was followed by a relapse on tapering steroid. Addition of methotrexate (7.5 mg increased to 15 mg in 2 weeks) led to a dramatic response. PMID:25484416

  11. Restless leg syndrome, periodic limb movements, febrile seizures and Attention deficit hyperactivity disorder in an Indian family.

    PubMed

    Gupta, Meena; Batra, Amit; Trivedi, Anurag; Chowdhury, Debashish; Khwaja, Geeta A

    2012-01-01

    Restless leg syndrome (RLS) is a common neurological disorder which can affect individuals of all age groups and incidence increasing with age. It can cause severe sleep disruption and negatively impact quality of life of an individual. Its diagnosis is clinical, based on essential criteria of International RLS Study Group. It can be idiopathic or associated with various medical and other neurological disorders. Idiopathic RLS can be sporadic or may have a familial inheritance, with several genetic loci been reported till date. RLS has a strong association with periodic limb movements, both sleep and awake. Very few studies of familial RLS/Periodic limb movements in sleep and their associations have been reported. We report an Indian family with autosomal dominant RLS/PLMS, with RLS and PLMS as well as psychiatric disorders, febrile seizures and Attention Deficit Hyperactivity Disorder in different family members, over three generations. PMID:22412272

  12. An Evaluation of the Clinical Assessments of Under-Five Febrile Children Presenting to Primary Health Facilities in Rural Ghana

    PubMed Central

    Baiden, Frank; Owusu-Agyei, Seth; Bawah, Justina; Bruce, Jane; Tivura, Mathilda; Delmini, Rupert; Gyaase, Stephaney; Amenga-Etego, Seeba; Chandramohan, Daniel; Webster, Jayne

    2011-01-01

    Background The shift to test-based management of malaria represents an important departure from established practice under the Integrated Management of Childhood Illnesses (IMCI). The possibility of false results of tests for malaria and co-morbidity, however, make it important that guidelines in IMCI case assessment are still followed. Methods and Findings We conducted a cross-sectional observational study to evaluate current practices in IMCI-based assessment of febrile children in 10 health centres and 5 district hospitals, with follow up of a subset of children to determine day 7–10 post-treatment clinical outcome. Clinical consultation, examination and prescribing practices were recorded using a checklist by trained non-medical observers. The facility case management of 1,983 under-five years old febrile children was observed and 593 followed up at home on days 5–10. The mean number of tasks performed from the 11 tasks expected to be done by the IMCI guidelines was 6 (SD 1.6). More than 6 tasks were performed in only 35% of children and this varied substantially between health facilities (range 3–85%). All 11 tasks were performed in only 1% of children. The most commonly performed tasks were temperature measurement (91%) and weighing (88%). Respiratory rate was checked in only 4% of children presenting with cough or difficulty in breathing. The likelihood of performing “better than average number of tasks” (>6) was higher when the consultation was done by medical assistants than doctors (O.R.?=?3.16, 1.02–9.20). The number of tasks performed during assessment did not, however, influence clinical outcome (O.R.?=?1.02, 0.83–1.24). Conclusion Facility-tailored interventions are needed to improve adherence to IMCI guidelines incorporating test-based management of malaria. Studies are needed to re-evaluate the continued validity of tasks defined in IMCI case assessment guidelines. PMID:22174932

  13. Clinical and laboratory features that discriminate dengue from other febrile illnesses: a diagnostic accuracy study in Rio de Janeiro, Brazil

    PubMed Central

    2013-01-01

    Background Dengue is an acute febrile illness caused by an arbovirus that is endemic in more than 100 countries. Early diagnosis and adequate management are critical to reduce mortality. This study aims to identify clinical and hematological features that could be useful to discriminate dengue from other febrile illnesses (OFI) up to the third day of disease. Methods We conducted a sectional diagnostic study with patients aged 12 years or older who reported fever lasting up to three days, without any evident focus of infection, attending an outpatient clinic in the city of Rio de Janeiro, Brazil, between the years 2005 and 2008. Logistic regression analysis was used to identify symptoms, physical signs, and hematological features valid for dengue diagnosis. Receiver-operating characteristic (ROC) curve analyses were used to define the best cut-off and to compare the accuracy of generated models with the World Health Organization (WHO) criteria for probable dengue. Results Based on serological tests and virus genome detection by polymerase chain reaction (PCR), 69 patients were classified as dengue and 73 as non-dengue. Among clinical features, conjunctival redness and history of rash were independent predictors of dengue infection. A model including clinical and laboratory features (conjunctival redness and leukocyte counts) achieved a sensitivity of 81% and specificity of 71% and showed greater accuracy than the WHO criteria for probable dengue. Conclusions We constructed a predictive model for early dengue diagnosis that was moderately accurate and performed better than the current WHO criteria for suspected dengue. Validation of this model in larger samples and in other sites should be attempted before it can be applied in endemic areas. PMID:23394216

  14. Homozygosity mapping and whole-exome sequencing to detect SLC45A2 and G6PC3 mutations in a single patient with oculocutaneous albinism and neutropenia.

    PubMed

    Cullinane, Andrew R; Vilboux, Thierry; O'Brien, Kevin; Curry, James A; Maynard, Dawn M; Carlson-Donohoe, Hannah; Ciccone, Carla; Markello, Thomas C; Gunay-Aygun, Meral; Huizing, Marjan; Gahl, William A

    2011-10-01

    We evaluated a 32-year-old woman whose oculocutaneous albinism (OCA), bleeding diathesis, neutropenia, and history of recurrent infections prompted consideration of the diagnosis of Hermansky-Pudlak syndrome type 2. This was ruled out because of the presence of platelet ?-granules and absence of AP3B1 mutations. As parental consanguinity suggested an autosomal recessive mode of inheritance, we employed homozygosity mapping, followed by whole-exome sequencing, to identify two candidate disease-causing genes, SLC45A2 and G6PC3. Conventional dideoxy sequencing confirmed pathogenic mutations in SLC45A2, associated with OCA type 4 (OCA-4), and G6PC3, associated with neutropenia. The substantial reduction of SLC45A2 protein in the patient's melanocytes caused the mislocalization of tyrosinase from melanosomes to the plasma membrane and also led to the incorporation of tyrosinase into exosomes and secretion into the culture medium, explaining the hypopigmentation in OCA-4. Our patient's G6PC3 mRNA expression level was also reduced, leading to increased apoptosis of her fibroblasts under endoplasmic reticulum stress. To our knowledge, this report describes the first North American patient with OCA-4, the first culture of human OCA-4 melanocytes, and the use of homozygosity mapping, followed by whole-exome sequencing, to identify disease-causing mutations in multiple genes in a single affected individual. PMID:21677667

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

    PubMed Central

    Voulgari, Christina; Giannas, Raphael; Paterakis, Georgios; Kanellou, Anna; Anagnostopoulos, Nikolaos; Pagoni, Stamata

    2015-01-01

    Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated by Streptococcus pneumonia and sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy. PMID:25755670

  16. IBMFS - Severe Congenital Neutropenia

    Cancer.gov

    SCN patients have very low white blood counts. Since white cells help the body to fight off infection, children with this disorder develop serious infections during infancy. The physical appearance is normal. Males and females are affected equally.

  17. Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers’ practices in Zanzibar

    PubMed Central

    2013-01-01

    Background In Zanzibar, malaria prevalence dropped substantially in the last decade and presently most febrile patients seen in primary health care facilities (PHCF) test negative for malaria. The availability of rapid diagnostic tests (RDTs) allows rural health workers to reliably rule out malaria in fever patients. However, additional diagnostic tools to identify alternative fever causes are scarce, often leaving RDT-negative patients without a clear diagnosis and management plan. This pilot study aimed to explore health workers’ practices with febrile children and identify factors influencing their diagnostic and management decisions in non-malarial fever patients. Methods Semi-structured key informant interviews were conducted with 12 health workers in six PHCFs in North A district, Zanzibar, April to June 2011. Interviews were coded using Atlas.ti to identify emerging themes that play a role in the diagnosis and management of febrile children. Results The following themes were identified: 1) health workers use caregivers’ history of illness and RDT results for initial diagnostic and management decisions, but suggest caregivers need more education to prevent late presentation and poor health outcomes; 2) there is uncertainty regarding viral versus bacterial illness and health workers feel additional point-of-care diagnostic tests would help with differential diagnoses; 3) stock-outs of medications and limited caregivers’ resources are barriers to delivering good care; 4) training, short courses and participation in research as well as; 5) weather also influences diagnostic decision-making. Conclusions This pilot study found that health workers in Zanzibar use caregiver history of fever and results of malaria RDTs to guide management of febrile children. However, since most febrile children test negative for malaria, health workers believe additional training and point-of-care tests would improve their ability to diagnose and manage non-malarial fevers. Educating caregivers on signs and symptoms of febrile illness, as well as the introduction of additional tests to differentiate between viral and bacterial illness, would be important steps to get children to PHCFs earlier and decrease unnecessary antibiotic prescribing without compromising patient safety. More research is needed to expand an understanding of what would improve fever management in other resource-limited settings with decreasing malaria. PMID:23356837

  18. A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment.

    PubMed

    Younossi, Z M; Nader, F H; Bai, C; Sjogren, R; Ong, J P; Collantes, R; Sjogren, M; Farmer, D; Ramsey, L; Terra, K; Gujral, H; Gurung, C; Srishord, M; Fang, Y

    2008-05-01

    Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors. This phase II clinical trial assesses the dose, efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus (HCV). Chronic hepatitis C patients (n = 101) received pegylated interferon alpha-2b (1.5 mug/kg once weekly) and ribavirin (800-1400 mg once daily). Patients with anaemia [haemoglobin (Hb) neutropenia [absolute neutrophil count (ANC) /= 0.75 x 10(9)/L and <10 x 10(9)/L. During antiviral therapy, 52% of patients required darbepoetin alpha, filgrastim or both. Hb at the time of darbepoetin alpha initiation was 10.2 +/- 0.4 g/dL. After 81 days of darbepoetin alpha, Hb increased by 1.9 +/- 1.0 g/dL to 12.1 +/- 1.1 g/dL (P < 0.0001). Filgrastim resulted in a significant increase in ANC [0.75 +/- 0.16 x 109/L to 8.28 +/- 5.67 x 10(9)/L (P < 0.0001)]. In treatment-naïve patients, 48% achieved sustained virological response (SVR), whereas 27% of patients previously treated with a course of pegylated interferon alpha achieved SVR. Low viral load, nongenotype 1 and treatment with growth factors were independently associated with SVR. Mild and severe anaemia were associated with quality of life impairments. Darbepoetin alpha resulted in an improvement in the Vitality domain of Short Form-36. No significant adverse events were related to growth factors. During anti-HCV therapy, filgrastim improved neutropenia and darbepoetin alpha improved both anaemia and quality of life. Future randomized clinical trials are needed to establish the impact of growth factors in improving sustained virological response. PMID:18194172

  19. Effects of Febrile Temperature on Adenoviral Infection and Replication: Implications for Viral Therapy of Cancer

    Microsoft Academic Search

    Stephen H. Thorne; Gabriel Brooks; Yeun-Ling Lee; Tina Au; Lawrence F. Eng; Tony Reid

    2005-01-01

    We previously conducted a phase I\\/II study using arterial infusions of ONYX-015 (dl1520), a replication- selective adenoviral vector, with E1b deleted, for patients with metastatic colorectal cancer. No dose-limiting toxicities occurred, but >90% of the patients experienced fever. The effects of temperature on the replication of dl1520 in normal and transformed cells had not been studied. Therefore, replication and cell

  20. A novel SCN5A mutation V1340I in Brugada syndrome augmenting arrhythmias during febrile illness

    PubMed Central

    Samani, Kaveh; Wu, Geru; Ai, Tomohiko; Shuraih, Mossaab; Mathuria, Nilesh S.; Li, Zhaohui; Sohma, Yoshiro; Purevjav, Enkhsaikhan; Xi, Yutao; Towbin, Jeffrey A.; Cheng, Jie; Vatta, Matteo

    2009-01-01

    BACKGROUND Mutations in the SCN5A gene, which encodes the cardiac sodium channel, have been implicated in the pathogenesis of Brugada syndrome (BrS). Febrile illnesses have been recognized to unmask and/or trigger the BrS phenotype. However, the patho-physiological mechanism has not been fully elucidated. OBJECTIVE A novel SCN5A missense mutation, V1340I, was identified in a patient with BrS suffering from frequent episodes of polymorphic ventricular tachycardia (VT) and syncope associated with fever. The biophysical modifications of hNav1.5 by V1340I were studied. METHODS The effects of the V1340I mutation were studied in the 2 splice variants, SCN5A and SCN5A-Q1077del (delQ), using patch-clamp techniques at various temperatures between 22°C and 40°C. RESULTS At 22°C, V1340I-SCN5A generated markedly diminished sodium currents compared to the wild-type (WT) SCN5A. On the contrary, V1340I-delQ generated almost identical current density compared to the WT-delQ. However, V1340I-delQ significantly attenuated the peak current density compared to the WT-delQ at 32°C, 37°C and 40°C. The voltage dependency of steady-state activation was leftward shifted both in WT-delQ and V1340I-delQ at 40°C. In addition, the V1340I-delQ accelerated the recovery time course from fast inactivation compared to the WT-delQ at 40°C. Immunohistochemical staining showed that both V1340I-SCN5A and V1340I-dQ were expressed in the plasma membrane. CONCLUSION Our study supports the concept that febrile illness predisposes individuals who carry a loss of function SCN5A mutation, such as V1340I, to fever-induced ventricular arrhythmias in BrS by significantly reducing the sodium currents in the hyperthermic state. PMID:19648062

  1. Treatment actions and treatment failure: case studies in the response to severe childhood febrile illness in Mali

    PubMed Central

    2012-01-01

    Background Appropriate home management of illness is vital to efforts to control malaria. The strategy of home management relies on caregivers to recognize malaria symptoms, assess severity and promptly seek appropriate care at a health facility if necessary. This paper examines the management of severe febrile illness (presumed malaria) among children under the age of five in rural Koulikoro Region, Mali. Methods This research examines in-depth case studies of twenty-five households in which a child recently experienced a severe febrile illness, as well as key informant interviews and focus group discussions with community members. These techniques were used to explore the sequence of treatment steps taken during a severe illness episode and the context in which decisions were made pertaining to pursing treatments and sources of care, while incorporating the perspective and input of the mother as well as the larger household. Results Eighty-one participants were recruited in 25 households meeting inclusion criteria. Children's illness episodes involved multiple treatment steps, with an average of 4.4 treatment steps per episode (range: 2–10). For 76% of children, treatment began in the home, but 80% were treated outside the home as a second recourse. Most families used both traditional and modern treatments, administered either inside the home by family members, or by traditional or modern healers. Participants’ stated preference was for modern care, despite high rates of reported treatment failure (52%, n=12), however, traditional treatments were also often deemed appropriate and effective. The most commonly cited barrier to seeking care at health facilities was cost, especially during the rainy season. Financial constraints often led families to use traditional treatments. Conclusions Households have few options available to them in moments of overlapping health and economic crises. Public health research and policy should focus on the reducing barriers that inhibit poor households from promptly seeking appropriate health care. Enhancing the quality of care provided at community health facilities and supporting mechanisms by which treatment failures are quickly identified and addressed can contribute to reducing subsequent treatment delays and avoid inappropriate recourse to traditional treatments. PMID:23127128

  2. A Comparative Study of Ceftriaxone plus Amikacin, Ceftazidime plus Amikacin and Imipenem\\/Cilastatin in the Empiric Therapy of Febrile Granulocytopenic Cancer Patients

    Microsoft Academic Search

    Cheng-Yi Liu; Fu-Der Wang

    1989-01-01

    In a prospective, randomized study we compared ceftriaxone (active ingredient of RocephinTM) plus amikacin, ceftazidime plus amikacin and imipenem\\/cilastatin in the empiric therapy of febrile granulocytopenic ( < 500\\/mm3) patients with cancer or aplastic anemia. Of 27 evaluable episodes, 12 were treated with ceftriaxone plus amikacin, 5 with ceftazidime plus amikacin and 10 with imipenem\\/cilastatin. 56% were culture-positive. Septicemia was

  3. A Role of SCN9A in Human Epilepsies, As a Cause of Febrile Seizures and As a Potential Modifier of Dravet Syndrome

    Microsoft Academic Search

    Nanda A. Singh; Chris Pappas; E. Jill Dahle; Lieve R. F. Claes; Timothy H. Pruess; Peter De Jonghe; Joel Thompson; Missy Dixon; Christina Gurnett; Andy Peiffer; H. Steve White; Francis Filloux; Mark F. Leppert

    2009-01-01

    A follow-up study of a large Utah family with significant linkage to chromosome 2q24 led us to identify a new febrile seizure (FS) gene, SCN9A encoding Nav1.7. In 21 affected members, we uncovered a potential mutation in a highly conserved amino acid, p.N641Y, in the large cytoplasmic loop between transmembrane domains I and II that was absent from 586 ethnically

  4. The Impact of a Community Awareness Strategy on Caregiver Treatment Seeking Behaviour and Use of Artemether-Lumefantrine for Febrile Children in Rural Kenya

    PubMed Central

    Wasunna, Beatrice; Okiro, Emelda A.; Webster, Jayne; Todd, Jim; Snow, Robert W.; Jones, Caroline

    2015-01-01

    Background Access to prompt and effective treatment is the cornerstone for malaria control. Population Services International in collaboration with the Ministry of Health launched a malaria behaviour change communication intervention in Nyanza province, Kenya. The initiative aimed to improve: symptom recognition and prompt access to government health facilities for febrile children; effective treatment with the recommended first-line drug artemether-lumefantrine (AL) in public health facilities and adherence to the AL regimen. Methods Pre- and post-intervention cross-sectional household surveys were used to evaluate the impact of the intervention on prompt and correct use of AL for febrile children below five years of age. The primary outcome was the proportion of children below five years of age with fever in the last 14 days accessing AL within 48 hours of fever onset. Results There was an increase from 62.8% pre-intervention to 79.4% post-intervention (95% CI: 11.1, 22.1) in caregivers who reported seeking formal treatment promptly (on the same day, or next day) for their febrile children. However, there was a decrease in the use of government health facilities in the post-intervention period. There was a small increase in the proportion of children accessing AL within 48 hours of fever onset [18.4% vs 23.5% (0.1–10.0)]. Conclusion The findings of this evaluation demonstrate that interventions that target only one sector may have a limited impact on improvements in prompt and effective treatment where multiple sources of treatments are sought for febrile illness. Additionally, the context in which an intervention is implemented is likely to influence the process and outcomes. PMID:26135143

  5. Value of Imaging Studies After a First Febrile Urinary Tract Infection in Young Children: Data From Italian Renal Infection Study 1

    Microsoft Academic Search

    Giovanni Montini; Pietro Zucchetta; Lisanna Tomasi; Enrico Talenti; Waifro Rigamonti; Giorgio Picco; Alberto Ballan; Andrea Zucchini; Laura Serra; Vanna Canella; Marta Gheno; Andrea Venturoli; Marco Ranieri; Valeria Caddia; Carla Carasi; Roberto Dall' Amico; Ian Hewitt; Donadi Piave

    2010-01-01

    OBJECTIVE.We examined the diagnostic accuracy of routine imaging studies (ultra- sonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection. METHODS.This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children 2 years of age, with normal prenatal ultrasound results,

  6. Impact of a Clinical Decision Model for Febrile Children at Risk for Serious Bacterial Infections at the Emergency Department: A Randomized Controlled Trial

    PubMed Central

    de Vos-Kerkhof, Evelien; Nijman, Ruud G.; Vergouwe, Yvonne; Polinder, Suzanne; Steyerberg, Ewout W.; van der Lei, Johan; Moll, Henriëtte A.; Oostenbrink, Rianne

    2015-01-01

    Objectives To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED). Methods Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n=219) or the control group (usual care; n=220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for “pneumonia” and “other SBI”. Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses’ compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs. Results The decision model had good discriminative ability for both pneumonia (n=33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n=22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value<0.05) and more urine-dipstick testing (71% vs. 61%, p-value<0.05). Conclusions In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing. Trial Registration Nederlands Trial Register NTR2381 PMID:26024532

  7. Identification of a Novel Human Papillomavirus by Metagenomic Analysis of Samples from Patients with Febrile Respiratory Illness

    PubMed Central

    Mokili, John L.; Dutilh, Bas E.; Lim, Yan Wei; Schneider, Bradley S.; Taylor, Travis; Haynes, Matthew R.; Metzgar, David; Myers, Christopher A.; Blair, Patrick J.; Nosrat, Bahador; Wolfe, Nathan D.; Rohwer, Forest

    2013-01-01

    As part of a virus discovery investigation using a metagenomic approach, a highly divergent novel Human papillomavirus type was identified in pooled convenience nasal/oropharyngeal swab samples collected from patients with febrile respiratory illness. Phylogenetic analysis of the whole genome and the L1 gene reveals that the new HPV identified in this study clusters with previously described gamma papillomaviruses, sharing only 61.1% (whole genome) and 63.1% (L1) sequence identity with its closest relative in the Papillomavirus episteme (PAVE) database. This new virus was named HPV_SD2 pending official classification. The complete genome of HPV-SD2 is 7,299 bp long (36.3% G/C) and contains 7 open reading frames (L2, L1, E6, E7, E1, E2 and E4) and a non-coding long control region (LCR) between L1 and E6. The metagenomic procedures, coupled with the bioinformatic methods described herein are well suited to detect small circular genomes such as those of human papillomaviruses. PMID:23554892

  8. High-dose immunoglobulines and extracorporeal photochemotherapy in the treatment of febrile ulceronecrotic Mucha-Habermann disease.

    PubMed

    Marenco, Federica; Fava, Paolo; Fierro, Maria Teresa; Quaglino, Pietro; Bernengo, Maria Grazia

    2010-01-01

    Febrile ulcero-necrotic Mucha-Habermann disease (FUMHD) is a rare subtype of pityriasis lichenoides et varioliformis acuta (only 41 cases described to date), characterized by an acute onset of ulcero-necrotic papules accompanied by high fever and severe constitutional symptoms. We report a case of a 23-year-old man with a steroid-resistant FUMHD treated by intravenous immunoglobulins (IVIG) combined with methotrexate. Only one case of FUMHD treated by IVIG has been reported to date in literature. Also in our case, IVIG proved to be effective in inducing a dramatic improvement of ulceration and in arresting the appearance of new lesions. Moreover, in our experience we decided to perform a maintenance treatment with extracorporeal photochemotherapy (ECP), to the best of our knowledge not previously used in the treatment of pityriasis lichenoides et varioliformis acuta. ECP, which involves extracorporeal exposure of peripheral blood mononuclear cells to photo-activated 8-methoxypsoralen, induces an immunological reaction against auto-reactive T cell clones, without immune-depression and thus could potentially be useful particularly in FUMHD avoiding the risk of an infective reactivation. PMID:20666830

  9. Single Nucleotide Variations in CLCN6 Identified in Patients with Benign Partial Epilepsies in Infancy and/or Febrile Seizures

    PubMed Central

    Yamamoto, Toshiyuki; Shimojima, Keiko; Sangu, Noriko; Komoike, Yuta; Ishii, Atsushi; Abe, Shinpei; Yamashita, Shintaro; Imai, Katsumi; Kubota, Tetsuo; Fukasawa, Tatsuya; Okanishi, Tohru; Enoki, Hideo; Tanabe, Takuya; Saito, Akira; Furukawa, Toru; Shimizu, Toshiaki; Milligan, Carol J.; Petrou, Steven; Heron, Sarah E.; Dibbens, Leanne M.; Hirose, Shinichi; Okumura, Akihisa

    2015-01-01

    Nucleotide alterations in the gene encoding proline-rich transmembrane protein 2 (PRRT2) have been identified in most patients with benign partial epilepsies in infancy (BPEI)/benign familial infantile epilepsy (BFIE). However, not all patients harbor these PRRT2 mutations, indicating the involvement of genes other than PRRT2. In this study, we performed whole exome sequencing analysis for a large family affected with PRRT2-unrelated BPEI. We identified a non-synonymous single nucleotide variation (SNV) in the voltage-sensitive chloride channel 6 gene (CLCN6). A cohort study of 48 BPEI patients without PRRT2 mutations revealed a different CLCN6 SNV in a patient, his sibling and his father who had a history of febrile seizures (FS) but not BPEI. Another study of 48 patients with FS identified an additional SNV in CLCN6. Chloride channels (CLCs) are involved in a multitude of physiologic processes and some members of the CLC family have been linked to inherited diseases. However, a phenotypic correlation has not been confirmed for CLCN6. Although we could not detect significant biological effects linked to the identified CLCN6 SNVs, further studies should investigate potential CLCN6 variants that may underlie the genetic susceptibility to convulsive disorders. PMID:25794116

  10. Disruption of Fgf13 Causes Synaptic Excitatory-Inhibitory Imbalance and Genetic Epilepsy and Febrile Seizures Plus.

    PubMed

    Puranam, Ram S; He, Xiao Ping; Yao, Lijun; Le, Tri; Jang, Wonjo; Rehder, Catherine W; Lewis, Darrell V; McNamara, James O

    2015-06-10

    We identified a family in which a translocation between chromosomes X and 14 was associated with cognitive impairment and a complex genetic disorder termed "Genetic Epilepsy and Febrile Seizures Plus" (GEFS(+)). We demonstrate that the breakpoint on the X chromosome disrupted a gene that encodes an auxiliary protein of voltage-gated Na(+) channels, fibroblast growth factor 13 (Fgf13). Female mice in which one Fgf13 allele was deleted exhibited hyperthermia-induced seizures and epilepsy. Anatomic studies revealed expression of Fgf13 mRNA in both excitatory and inhibitory neurons of hippocampus. Electrophysiological recordings revealed decreased inhibitory and increased excitatory synaptic inputs in hippocampal neurons of Fgf13 mutants. We speculate that reduced expression of Fgf13 impairs excitability of inhibitory interneurons, resulting in enhanced excitability within local circuits of hippocampus and the clinical phenotype of epilepsy. These findings reveal a novel cause of this syndrome and underscore the powerful role of FGF13 in control of neuronal excitability. PMID:26063919

  11. Novel HCN2 mutation contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner.

    PubMed

    Nakamura, Yuki; Shi, Xiuyu; Numata, Tomohiro; Mori, Yasuo; Inoue, Ryuji; Lossin, Christoph; Baram, Tallie Z; Hirose, Shinichi

    2013-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated currents, known as I h, are involved in the control of rhythmic activity in neuronal circuits and in determining neuronal properties including the resting membrane potential. Recent studies have shown that HCN channels play a role in seizure susceptibility and in absence and limbic epilepsy including temporal lobe epilepsy following long febrile seizures (FS). This study focused on the potential contributions of abnormalities in the HCN2 isoform and their role in FS. A novel heterozygous missense mutation in HCN2 exon 1 leading to p.S126L was identified in two unrelated patients with FS. The mutation was inherited from the mother who had suffered from FS in a pedigree. To determine the effect of this substitution we conducted whole-cell patch clamp electrophysiology. We found that mutant channels had elevated sensitivity to temperature. More specifically, they displayed faster kinetics at higher temperature. Kinetic shift by change of temperature sensitivity rather than the shift of voltage dependence led to increased availability of I h in conditions promoting FS. Responses to cyclic AMP did not differ between wildtype and mutant channels. Thus, mutant HCN2 channels cause significant cAMP-independent enhanced availability of I h during high temperatures, which may contribute to hyperthermia-induced neuronal hyperexcitability in some individuals with FS. PMID:24324597

  12. Weekly Carboplatin Reduces Toxicity During Synchronous Chemoradiotherapy for Merkel Cell Carcinoma of Skin

    SciTech Connect

    Poulsen, Michael [Division of Cancer Services, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD (Australia)], E-mail: michael_poulsen@health.qld.gov.au; Walpole, Euan; Harvey, Jennifer [Division of Cancer Services, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD (Australia); Dickie, Graeme [Division of Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD (Australia); O'Brien, Peter [Department of Radiation Oncology, Newcastle Mater Misericordia Hospital, Newcastle, NSW (Australia); Keller, Jacqui; Tpcony, Lee [Division of Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD (Australia); Rischin, Danny [Department of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC (Australia)

    2008-11-15

    Purpose: The toxicity of radiotherapy (RT) combined with weekly carboplatin and adjuvant carboplatin and etoposide was prospectively assessed in a group of patients with high-risk Stage I and II Merkel cell carcinoma of the skin. This regimen was compared with the Trans-Tasman Radiation Oncology Group 96:07 study, which used identical eligibility criteria but carboplatin and etoposide every 3 weeks during RT. Patients and Methods: Patients were eligible if they had disease localized to the primary site and lymph nodes, with high-risk features. RT was delivered to the primary site and lymph nodes to a dose of 50 Gy and weekly carboplatin (area under the curve of 2) was given during RT. This was followed by three cycles of carboplatin and etoposide. A total of 18 patients were entered into the study, and their data were compared with the data from 53 patients entered into the Trans-Tasman Radiation Oncology Group 96:07 study. Results: Involved lymph nodes (Stage II) were present in 14 patients (77%). Treatment was completed as planned in 16 patients. The weekly carboplatin dose was delivered in 17 patients, and 15 were able to complete all three cycles of adjuvant carboplatin and etoposide. Grade 3 and 4 neutrophil toxicity occurred in 7 patients, but no cases of febrile neutropenia developed. Compared with the Trans-Tasman Radiation Oncology Group 96:07 protocol (19 of 53 cases of febrile neutropenia), the reduction in the febrile neutropenia rate (p = 0.003) and decrease in Grade 3 skin toxicity (p = 0.006) were highly statistically significant. Conclusion: The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen.

  13. Validation of reference genes for quantitative real-time PCR studies in the dentate gyrus after experimental febrile seizures

    PubMed Central

    2012-01-01

    Background Quantitative real-time PCR (qPCR) is a commonly used technique to quantify gene expression levels. Validated normalization is essential to obtain reliable qPCR data. In that context, normalizing to multiple reference genes has become the most popular method. However, expression of reference genes may vary per tissue type, developmental stage and in response to experimental treatment. It is therefore imperative to determine stable reference genes for a specific sample set and experimental model. The present study was designed to validate potential reference genes in hippocampal tissue from rats that had experienced early-life febrile seizures (FS). To this end, we applied an established model in which FS were evoked by exposing 10-day old rat pups to heated air. One week later, we determined the expression stability of seven frequently used reference genes in the hippocampal dentate gyrus. Results Gene expression stability of 18S rRNA, ActB, GusB, Arbp, Tbp, CycA and Rpl13A was tested using geNorm and Normfinder software. The ranking order of reference genes proposed by geNorm was not identical to that suggested by Normfinder. However, both algorithms indicated CycA, Rpl13A and Tbp as the most stable genes, whereas 18S rRNA and ActB were found to be the least stably expressed genes. Conclusions Our data demonstrate that the geometric averaging of at least CycA, Rpl13A and Tbp allows reliable interpretation of gene expression data in this experimental set-up. The results also show that ActB and 18S rRNA are not suited as reference genes in this model. PMID:23237195

  14. Clinical differences between respiratory viral and bacterial mono- and dual pathogen detected among Singapore military servicemen with febrile respiratory illness

    PubMed Central

    Ho, Zheng Jie Marc; Zhao, Xiahong; Cook, Alex R; Loh, Jin Phang; Ng, Sock Hoon; Tan, Boon Huan; Lee, Vernon J

    2015-01-01

    Background Although it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population-level studies describing its impact on clinical disease. Methods Between May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono-pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation. Results In total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non-smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono-infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono-pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono-pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono-pathogens, there were few differences between distinct dual-pathogen pairs and their respective mono-pathogen counterparts. Conclusion A substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono-pathogen indicate the likely presence of complex microbial interactions between the various pathogens. PMID:25827870

  15. A Clinical Diagnostic Model for Predicting Influenza among Young Adult Military Personnel with Febrile Respiratory Illness in Singapore

    PubMed Central

    Lee, Vernon J.; Yap, Jonathan; Cook, Alex R.; Tan, Chi Hsien; Loh, Jin-Phang; Koh, Wee-Hong; Lim, Elizabeth A. S.; Liaw, Jasper C. W.; Chew, Janet S. W.; Hossain, Iqbal; Chan, Ka Wei; Ting, Pei-Jun; Ng, Sock-Hoon; Gao, Qiuhan; Kelly, Paul M.; Chen, Mark I.; Tambyah, Paul A.; Tan, Boon Huan

    2011-01-01

    Introduction Influenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratory illness (FRI) to determine predictors of influenza infection. Methods Personnel with FRI (defined as fever?37.5°C, with cough or sore throat) were recruited from the sentinel surveillance system in the Singapore military. Nasal washes were collected, and tested using the Resplex II and additional PCR assays for etiological determination. Interviewer-administered questionnaires collected information on patient demographics and clinical features. Univariate comparison of the various parameters was conducted, with statistically significant parameters entered into a multivariate logistic regression model. The final multivariate model for influenza versus non-influenza cases was used to build a predictive probability clinical diagnostic model. Results 821 out of 2858 subjects recruited from 11 May 2009 to 25 Jun 2010 had influenza, of which 434 (52.9%) had 2009 influenza A (H1N1), 58 (7.1%) seasonal influenza A (H3N2) and 269 (32.8%) influenza B. Influenza-positive cases were significantly more likely to present with running nose, chills and rigors, ocular symptoms and higher temperature, and less likely with sore throat, photophobia, injected pharynx, and nausea/vomiting. Our clinical diagnostic model had a sensitivity of 65% (95% CI: 58%, 72%), specificity of 69% (95% CI: 62%, 75%), and overall accuracy of 68% (95% CI: 64%, 71%), performing significantly better than conventional influenza-like illness (ILI) criteria. Conclusions Use of a clinical diagnostic model may help predict influenza better than the conventional ILI definition among young adults with FRI. PMID:21399686

  16. Two patients with nonimmune chronic idiopathic neutropenia of adults developing acute myeloid leukemia with aberrant phenotype and complex karyotype but no mutations in granulocyte colony-stimulating factor receptor

    Microsoft Academic Search

    H. A. Papadaki; T. Kosteas; C. Gemetzi; M. Alexandrakis; M. Psyllaki; G. D. Eliopoulos

    2002-01-01

    It has been suggested that some cases of nonimmune chronic idiopathic neutropenia of adults (NI-CINA) may be considered preleukemic disorders. This paper describes two patients with NI-CINA who developed acute myeloid leukemia (AML) 34 and 64 months, respectively, following NI-CINA diagnosis. Patient 1 presented erythema nodosum and patient 2 polyarthritis of the large joints 9 and 2 months, respectively, before

  17. Utility of the Tourniquet Test and the White Blood Cell Count to Differentiate Dengue among Acute Febrile Illnesses in the Emergency Room

    PubMed Central

    Gregory, Christopher J.; Lorenzi, Olga D.; Colón, Lisandra; Sepúlveda García, Arleene; Santiago, Luis M.; Cruz Rivera, Ramón; Cuyar Bermúdez, Liv Jossette; Ortiz Báez, Fernando; Vázquez Aponte, Delanor; Tomashek, Kay M.; Gutierrez, Jorge; Alvarado, Luisa

    2011-01-01

    Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm3) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2–7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue. PMID:22163057

  18. Utility of the tourniquet test and the white blood cell count to differentiate dengue among acute febrile illnesses in the emergency room.

    PubMed

    Gregory, Christopher J; Lorenzi, Olga D; Colón, Lisandra; García, Arleene Sepúlveda; Santiago, Luis M; Rivera, Ramón Cruz; Bermúdez, Liv Jossette Cuyar; Báez, Fernando Ortiz; Aponte, Delanor Vázquez; Tomashek, Kay M; Gutierrez, Jorge; Alvarado, Luisa

    2011-12-01

    Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm(3)) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2-7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue. PMID:22163057

  19. Adverse events occurring after smallpox vaccination.

    PubMed

    Lane, J Michael; Goldstein, Joel

    2003-07-01

    We reviewed the literature on adverse events reported to occur after smallpox vaccination. Nearly one-half of the United States population is vaccinia-naïve and may be at risk for development of serious adverse events. We describe the clinical features of postvaccinial central nervous system disease, progressive vaccinia, eczema vaccinatum, accidental implantations, "generalized vaccinia," and the common erythematous and/or urticarial rashes. In the 1960s, death occurred approximately once in every million primary vaccinations, with fatalities resulting from progressive vaccinia, postvaccinial encephalitis, and eczema vaccinatum. Death in revaccinees occurred less commonly and almost entirely from progressive vaccinia. In today's population, death rates might be higher because of the increased prevalence of immune deficiency and atopic dermatitis. PMID:12913830

  20. Oral ezatiostat HCl (Telintra®, TLK199) and Idiopathic Chronic Neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor

    PubMed Central

    2011-01-01

    Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent fevers, chronic mucosal inflammation, and severe systemic infections. The severity and risk of complications, including serious infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 × 109/L. This case report describes a 64-year-old female with longstanding rheumatoid arthritis who subsequently developed ICN with frequent episodes of sepsis requiring hospitalization and prolonged courses of antibiotics over a 4-year period. She was treated with granulocyte colony stimulating factors (G-CSF) but had a delayed, highly variable, and volatile response. She was enrolled in a clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat, a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. She responded by the end of the first month of treatment with stabilization of her ANC (despite tapering and then stopping G-CSF), clearing of fever, and healing of areas of infection. This ANC response to ezatiostat treatment has now been sustained for over 8 months and continues. These results suggest potential roles for ezatiostat in the treatment of patients with ICN who are not responsive to G-CSF, as an oral therapy alternative, or as an adjunct to G-CSF, and further studies are warranted. PMID:22047626

  1. Association of neutropenia in systemic lupus erythematosus (SLE) with anti-Ro and binding of an immunologically cross-reactive neutrophil membrane antigen.

    PubMed

    Kurien, B T; Newland, J; Paczkowski, C; Moore, K L; Scofield, R H

    2000-04-01

    SLE is associated with the production of autoantibodies to self-constituents. In particular, certain ribonucleoprotein particles are targeted. Despite the multitude of autoantibodies produced and the remarkable concentrations of these antibodies in the sera of SLE patients, there have been little data that the autoantibodies found in SLE are involved in the pathogenesis of disease or its manifestations. The present work demonstrates that anti-Ro (or SSA) is associated with granulocytopenia, binds the surface of granulocytes and fixes complement to this membrane surface. Binding is a property of anti-Ro Fab fragments and can be inhibited by 60-kD Ro. However, the antigen bound on the surface of granulocytes is a 64 000 mol. wt protein that is a novel autoantigen in SLE. As suggested by inhibition studies, sequence identity between 60-kD Ro and eight tandem repeats in the 64-kD antigen may be responsible for the observed serologic cross-reactivity. These data imply that anti-Ro antibodies that also bind the 64-kD protein mediate neutropenia in patients with SLE. PMID:10759785

  2. Granulocyte-colony stimulating factor response is superior to neutropenia duration in predicting the risk of infection after high-dose chemotherapy for myeloma and lymphoma.

    PubMed

    Straka, Christian; Salwender, Hans; Schnabel, Brigitte; Sandherr, Michael; Wandt, Hannes; Hübel, Kai; Scheid, Christof; Metzner, Bernd; Hentrich, Marcus; Franke, Daniel; Weidenegger, Gloria; Freund, Mathias; Sezer, Orhan; Einsele, Hermann; Hinke, Axel; Emmerich, Bertold

    2015-02-01

    The patient granulocyte-colony stimulating factor (G-CSF) response is represented by the leukocyte peak in the blood induced by a single dose of G-CSF after chemotherapy, and is correlated with subsequent neutropenic infection risk. General patterns for a meaningful risk group stratification, have not yet been determined. Two independent data sets including a total of 306 cases with myeloma or lymphoma and autologous blood stem cell transplant were available. An infection susceptibility curve plotted according to ranked G-CSF responses from a multicenter study reproduced and validated a curve from the previous single center. Two trend changes were seen within these curves at around 11,000 and 22,000 leukocytes/?L, which separated three groups with a high, medium and low risk of infection. While G-CSF response is related to the consecutive duration of neutropenia, it retains additional independent predictive information for infection risk (p<0.0001) and, more important, is a tool available before the onset of the critical period. PMID:24794810

  3. [Exacerbation of autoimmune neutropenia to agranulocytosis in association with severe autoimmune thrombocytopenia and hemolytic anemia in a patient with Sjögren's syndrome].

    PubMed

    Shimoji, Sonoko; Takiuchi, Yohko; Maruoka, Hayato; Inoue, Daichi; Kimura, Takaharu; Mori, Minako; Nagai, Yuya; Togami, Katuhiro; Tabata, Sumie; Kurata, Masayuki; Matsushita, Akiko; Nagai, Kenichi; Takahashi, Takayuki

    2011-07-01

    A 73-year-old woman with Sjögren's syndrome and autoimmune neutropenia (AIN) associated with large granular lymphocytosis of the polyclonal T cell type, demonstrated autoimmune thrombocytopenia (AIT) at diagnosis of sigmoid colon cancer. Ten months later, both AIN and AIT had exacerbated to agranulocytosis and severe thrombocytopenia below 10×10(9)/L, respectively. There were no dysplastic features of bone marrow hematopoietic cells. Furthermore, an in vitro assay of hematopoietic progenitors showed normal granuloid and erythroid colony formation. Although we serially treated her with prednisolone (oral), filgrastim, intravenous high-dose immunoglobulin infusion, cyclophosphamide (oral), danazol, cyclosporine A (oral), and rituximab, number of neutrophils and platelets elevated only temporarily. During the course of agranulocytosis and severe thrombocytopenia, the patient also developed autoimmune hemolytic anemia (AIHA). She died of pneumonia 5 months after the onset of agranulocytosis. This case is very unique and novel in terms of autoimmune phenomena simultaneously directed to granulocytes, platelets, and red blood cells under the background of Sjögren's syndrome. PMID:21821986

  4. Anti-SSB/La is one of the antineutrophil autoantibodies responsible for neutropenia and functional impairment of polymorphonuclear neutrophils in patients with systemic lupus erythematosus

    PubMed Central

    Hsieh, S-C; Yu, H-S; Lin, W-W; Sun, K-H; Tsai, C-Y; Huang, D-F; Tsai, Y-Y; Yu, C-L

    2003-01-01

    Decreased number and impaired functions of polymorphonuclear neutrophils (PMN) due to the presence of anti-PMN autoantibodies in the serum render patients with systemic lupus erythematosus (SLE) susceptible to bacterial infections. However, the cognate antigens and pathological mechanisms of anti-PMN autoantibodies in SLE are rarely reported in the literature. In this study, we found approximately 20% of SLE sera contained anti-PMN autoantibodies detected by human PMN-coated cellular ELISA. A membrane protein with molecular weight of 50 kDa was identified as the cognate antigen of anti-PMN in Western blot after membrane-biotinylation and streptavidin column elution. The 50 kDa molecule was proved to be SSB/La after immunoscreening, molecular cloning and nucleotide sequencing of the gene from the human leucocyte cDNA library. Human anti-SSB/La autoantibodies purified from active SLE sera passing through the recombinant SSB/La conjugated Sepharose 4B affinity column could bind and penetrate into normal human PMN. Functional analysis revealed that the anti-SSB/La autoantibodies exerted a number of potent effects on human PMN, including suppressed phagocytosis, accelerated apoptosis and enhanced IL-8 production. These in vitro results suggest that anti-SSB/La is one of the anti-PMN autoantibodies capable of penetrating into PMN and responsible for neutropenia and functional impairment of PMN in patients with SLE. PMID:12605705

  5. Introduction Diel vertical migration occurs when plankton

    E-print Network

    New Hampshire, University of

    over a 24 h cycle. Zooplankton typically migrate nocturnally, occupying depths near the hypolimnion and can occur among both marine and freshwater plankton (Lampert & Sommer 1997). Although there have been many studies on zooplankton DVM, little is known about the daily vertical movements of phytoplank- ton

  6. Phonetic Recalibration Only Occurs in Speech Mode

    ERIC Educational Resources Information Center

    Vroomen, Jean; Baart, Martijn

    2009-01-01

    Upon hearing an ambiguous speech sound dubbed onto lipread speech, listeners adjust their phonetic categories in accordance with the lipread information (recalibration) that tells what the phoneme should be. Here we used sine wave speech (SWS) to show that this tuning effect occurs if the SWS sounds are perceived as speech, but not if the sounds…

  7. PATTERNS & PHENOTYPES Osteoblast Maturation Occurs in Overlapping

    E-print Network

    Behe, Michael J.

    of osteo- blast maturity. We suggest a model for growth where new cells are continually added to the distalPATTERNS & PHENOTYPES Osteoblast Maturation Occurs in Overlapping Proximal-Distal Compartments maturity increases in a distal-proximal manner, and osteoblast maturation can be detected similarly when

  8. Preferential flow occurs in unsaturated conditions

    USGS Publications Warehouse

    Nimmo, John R.

    2012-01-01

    Because it commonly generates high-speed, high-volume flow with minimal exposure to solid earth materials, preferential flow in the unsaturated zone is a dominant influence in many problems of infiltration, recharge, contaminant transport, and ecohydrology. By definition, preferential flow occurs in a portion of a medium – that is, a preferred part, whether a pathway, pore, or macroscopic subvolume. There are many possible classification schemes, but usual consideration of preferential flow includes macropore or fracture flow, funneled flow determined by macroscale heterogeneities, and fingered flow determined by hydraulic instability rather than intrinsic heterogeneity. That preferential flow is spatially concentrated associates it with other characteristics that are typical, although not defining: it tends to be unusually fast, to transport high fluxes, and to occur with hydraulic disequilibrium within the medium. It also has a tendency to occur in association with large conduits and high water content, although these are less universal than is commonly assumed. Predictive unsaturated-zone flow models in common use employ several different criteria for when and where preferential flow occurs, almost always requiring a nearly saturated medium. A threshold to be exceeded may be specified in terms of the following (i) water content; (ii) matric potential, typically a value high enough to cause capillary filling in a macropore of minimum size; (iii) infiltration capacity or other indication of incipient surface ponding; or (iv) other conditions related to total filling of certain pores. Yet preferential flow does occur without meeting these criteria. My purpose in this commentary is to point out important exceptions and implications of ignoring them. Some of these pertain mainly to macropore flow, others to fingered or funneled flow, and others to combined or undifferentiated flow modes.

  9. Similar Occurrence of Febrile Episodes Reported in Non-Atopic Children at Three to Five Years of Age after Prebiotics Supplemented Infant Formula

    PubMed Central

    van Stuijvenberg, Margriet; Stam, José; Grüber, Christoph; Mosca, Fabio; Arslanoglu, Sertac; Chirico, Gaetano; Braegger, Christian P.; Riedler, Josef; Boehm, Günther; Sauer, Pieter J. J.

    2015-01-01

    This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday. PMID:26076141

  10. Naturally occurring products in cancer therapy

    PubMed Central

    Rajesh, E.; Sankari, Leena S.; Malathi, L.; Krupaa, Jayasri R.

    2015-01-01

    Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery. These products, especially phytochemicals have been extensively studies and have exhibited anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. This concept is gaining attention because it is a cost-effective alternative to cancer treatment. In this article, we have discussed some of the naturally occurring products used in cancer treatment. PMID:26015704

  11. Naturally occurring products in cancer therapy.

    PubMed

    Rajesh, E; Sankari, Leena S; Malathi, L; Krupaa, Jayasri R

    2015-04-01

    Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery. These products, especially phytochemicals have been extensively studies and have exhibited anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. This concept is gaining attention because it is a cost-effective alternative to cancer treatment. In this article, we have discussed some of the naturally occurring products used in cancer treatment. PMID:26015704

  12. A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia

    PubMed Central

    Russell, A; Emmerson, A; Wilkinson, N; Chant, T; Sweet, D; Halliday, H; Holland, B; Davies, E

    2001-01-01

    OBJECTIVES—The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy.?DESIGN—Neonates (? 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of ? 5 × 109/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 µg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups.?RESULTS—Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p ? 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001).?CONCLUSIONS—In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.? PMID:11320043

  13. Persulfate activation by naturally occurring trace minerals.

    PubMed

    Teel, Amy L; Ahmad, Mushtaque; Watts, Richard J

    2011-11-30

    The potential for 13 naturally occurring minerals to mediate the decomposition of persulfate and generate a range of reactive oxygen species was investigated to provide fundamental information on activation mechanisms when persulfate is used for in situ chemical oxidation (ISCO). Only four of the minerals (cobaltite, ilmenite, pyrite, and siderite) promoted the decomposition of persulfate more rapidly than persulfate-deionized water control systems. The other nine minerals decomposed persulfate at the same rate or more slowly than the control systems. Mineral-mediated persulfate activation was conducted with the addition of one of three probe compounds to detect the generation of reactive oxygen species: anisole (sulfate+hydroxyl radical), nitrobenzene (hydroxyl radical), and hexachloroethane (reductants and nucleophiles). The reduced mineral pyrite promoted rapid generation of sulfate+hydroxyl radical. However, the remainder of the minerals provided minimal potential for the generation of reactive oxygen species. The results of this research demonstrate that the majority of naturally occurring trace minerals do not activate persulfate to generate reactive oxygen species, and other mechanisms of activation are necessary to promote contaminant destruction in the subsurface during persulfate ISCO. PMID:21968122

  14. Nipah virus entry can occur by macropinocytosis

    SciTech Connect

    Pernet, Olivier; Pohl, Christine; Ainouze, Michelle; Kweder, Hasan [Molecular Basis of Paramyxovirus Entry, INSERM U758 Virologie Humaine IFR 128 BioSciences Gerland-Lyon Sud, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07 (France); Buckland, Robin, E-mail: robin.buckland@inserm.f [Molecular Basis of Paramyxovirus Entry, INSERM U758 Virologie Humaine IFR 128 BioSciences Gerland-Lyon Sud, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07 (France)

    2009-12-20

    Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in Asia with high mortality in man. NiV is a member, with Hendra virus (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV entry, like that of other paramyxoviruses, is believed to occur via pH-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor kinase activity and we find that ephrinB2's cytoplasmic domain is required for entry but is dispensable for post-entry viral spread. The mutation of a single tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry. Moreover, our results show that NiV entry is inhibited by constructions and drugs specific for the endocytic pathway of macropinocytosis. Our findings could potentially permit the rapid development of novel low-cost antiviral treatments not only for NiV but also HeV.

  15. Out-of-Pocket Costs and Other Determinants of Access to Healthcare for Children with Febrile Illnesses: A Case-Control Study in Rural Tanzania

    PubMed Central

    Castellani, Joëlle; Mihaylova, Borislava; Evers, Silvia M. A. A.; Paulus, Aggie T. G.; Mrango, Zakayo E.; Kimbute, Omari; Shishira, Joseph P.; Mulokozi, Francis; Petzold, Max; Singlovic, Jan; Gomes, Melba

    2015-01-01

    Objectives To study private costs and other determinants of access to healthcare for childhood fevers in rural Tanzania. Methods A case-control study was conducted in Tanzania to establish factors that determine access to a health facility in acute febrile illnesses in children less than 5 years of age. Carers of eligible children were interviewed in the community; cases were represented by patients who went to a facility and controls by those who did not. A Household Wealth Index was estimated using principal components analysis. A multivariable logistic regression analysis was performed to understand the factors which influenced attendance of healthcare facility including severity of the illness and household wealth/socio-demographic indicators. To complement the data on costs from community interviews, a hospital-based study obtained details of private expenditures for hospitalised children under the age of 5. Results Severe febrile illness is strongly associated with health facility attendance (OR: 35.76, 95%CI: 3.68-347.43, p = 0.002 compared with less severe febrile illness). Overall, the private costs of an illness for patients who went to a hospital were six times larger than private costs of controls ($5.68 vs. $0.90, p<0.0001). Household wealth was not significantly correlated with total costs incurred. The separate hospital based cost study indicated that private costs were three times greater for admissions at the mission versus public hospital: $13.68 mission vs. $4.47 public hospital (difference $ 9.21 (95% CI: 7.89 -10.52), p<0.0001). In both locations, approximately 50% of the cost was determined by the duration of admission, with each day in hospital increasing private costs by about 12% (95% CI: 5% - 21%). Conclusion The more severely ill a child, the higher the probability of attending hospital. We did not find association between household wealth and attending a health facility; nor was there an association between household wealth and private cost. PMID:25861012

  16. The role of local induction of tumor necrosis factor by LPS within a subcutaneous air pouch in the development of a febrile response in guinea pigs.

    PubMed

    Roth, J; Störr, B; Martin, D; Voigt, K; Zeisberger, E

    2000-01-01

    In rats, fever can be induced by injection of bacterial lipopolysaccharide (LPS) into a subcutaneous air pouch. This febrile response is in part dependent on the local action of interleukin-1beta within the pouch. In the present study, we tried to find out if this model of fever induction can be applied in guinea pigs and if the local LPS-induced formation of tumor necrosis factor-alpha (TNF-alpha) participates in the development of the febrile response. A dose of 100 microg/kg LPS was injected into a subcutaneous air pouch along with solvent (0.9% saline), or 100 mg/kg pentoxifylline, or 1 mg/animal soluble 55-kD TNF receptor (referred to as TNF-binding protein, TNF bp). The mean LPS-induced concentration of TNF in the lavage of the air pouch (measured 60 min after injection) was 17,765 pg/ml in animals injected with LPS and solvent. This value was reduced to 7,631 pg/ml if pentoxifylline was injected along with LPS into the pouch. If LPS was injected along with TNF bp, no bioactive TNF was detected in the lavage of the air pouch. Simultaneously, TNF was measured in blood plasma. Circulating concentrations of TNF were about 5-8% of the values detected in the lavage of the air pouch (mean values: 1,366 pg/ml in response to LPS plus solvent; 377 pg/ml in response to LPS plus pentoxifylline; no circulating TNF at all in response to LPS plus TNF bp). These data indicated a small spill-over of TNF from the air pouch into the circulation. Neither the reduction of local TNF formation in the air pouch by pentoxifylline nor the complete neutralization of TNF within the pouch by TNF bp resulted in a significant attenuation of the febrile response induced by injection of LPS into the subcutaneous air pouch. If there were an activation of cutaneous nerves to induce fever by a local formation of cytokines within the air pouch, TNF would not represent a likely candidate to be responsible for such a neural stimulation. PMID:10810248

  17. The Potential Impact of Improving Appropriate Treatment for Fever on Malaria and Non-Malarial Febrile Illness Management in Under-5s: A Decision-Tree Modelling Approach

    PubMed Central

    Rao, V. Bhargavi; Schellenberg, David; Ghani, Azra C.

    2013-01-01

    Background As international funding for malaria programmes plateaus, limited resources must be rationally managed for malaria and non-malarial febrile illnesses (NMFI). Given widespread unnecessary treatment of NMFI with first-line antimalarial Artemisinin Combination Therapies (ACTs), our aim was to estimate the effect of health-systems factors on rates of appropriate treatment for fever and on use of ACTs. Methods A decision-tree tool was developed to investigate the impact of improving aspects of the fever care-pathway and also evaluate the impact in Tanzania of the revised WHO malaria guidelines advocating diagnostic-led management Results Model outputs using baseline parameters suggest 49% malaria cases attending a clinic would receive ACTs (95% Uncertainty Interval:40.6–59.2%) but that 44% (95% UI:35–54.8%) NMFI cases would also receive ACTs. Provision of 100% ACT stock predicted a 28.9% increase in malaria cases treated with ACT, but also an increase in overtreatment of NMFI, with 70% NMFI cases (95% UI:56.4–79.2%) projected to receive ACTs, and thus an overall 13% reduction (95% UI:5–21.6%) in correct management of febrile cases. Modelling increased availability or use of diagnostics had little effect on malaria management outputs, but may significantly reduce NMFI overtreatment. The model predicts the early rollout of revised WHO guidelines in Tanzania may have led to a 35% decrease (95% UI:31.2–39.8%) in NMFI overtreatment, but also a 19.5% reduction (95% UI:11–27.2%), in malaria cases receiving ACTs, due to a potential fourfold decrease in cases that were untested or tested false-negative (42.5% vs.8.9%) and so untreated. Discussion Modelling multi-pronged intervention strategies proved most effective to improve malaria treatment without increasing NMFI overtreatment. As malaria transmission declines, health system interventions must be guided by whether the management priority is an increase in malaria cases receiving ACTs (reducing the treatment gap), reducing ACT waste through unnecessary treatment of NMFI or expanding appropriate treatment of all febrile illness. PMID:23922770

  18. Juvenile polyposis occurring in hereditary hemorrhagic telangiectasia.

    PubMed

    Inoue, S; Matsumoto, T; Iida, M; Hoshika, K; Shimizu, M; Hisamoto, N; Kihara, T

    1999-01-01

    Various extraintestinal manifestations may occur in juvenile polyposis, but hereditary hemorrhagic telangiectasia has rarely been reported in this type of polyposis. The authors treated a 14-year-old girl with rectal bleeding and anemia who had multiple polyps of the colorectum. Large polyps were removed and histologically diagnosed as juvenile polyps. She was later diagnosed as having telangiectasia of the skin, and arteriovenous malformations in the lung and in the liver, all of which were compatible with the diagnosis of hereditary hemorrhagic telangiectasia. At age 32, she had multiple ulcers in the ileum and in the colon. The coexistence of juvenile polyposis and hereditary hemorrhagic telangiectasia may be a clue for the understanding of the histopathogenesis of juvenile polyposis. PMID:9892274

  19. Tetrahydroberberine, a pharmacologically active naturally occurring alkaloid.

    PubMed

    Pingali, Subramanya; Donahue, James P; Payton-Stewart, Florastina

    2015-04-01

    Tetrahydroberberine (systematic name: 9,10-dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the molecule is observed, with an angle of 24.72?(5)° between the arene rings at the two ends of the reduced quinolizinium core. The intermolecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole -CH2···OCH3 and -OCH3···OCH3 interactions between neighboring molecules. PMID:25836282

  20. Naturally occurring antinociceptive substances from plants.

    PubMed

    Calixto, J B; Beirith, A; Ferreira, J; Santos, A R; Filho, V C; Yunes, R A

    2000-09-01

    Despite the progress that has occurred in recent years in the development of therapy, there is still a need for effective and potent analgesics, especially for the treatment of chronic pain. One of the most important analgesic drugs employed in clinical practice today continues to be the alkaloid morphine. In this review, emphasis will be given to the important contribution and the history of Papaver somniferum, Salix species, Capsicum species and Cannabis sativa in the development of new analgesics and their importance in the understanding of the complex pathways related to electrophysiological and molecular mechanisms associated with pain transmission. Recently discovered antinociceptive substances include alkaloids, terpenoids and flavonoid. Plant-derived substances have, and will certainly continue to have, a relevant place in the process of drug discovery, particularly in the development of new analgesic drugs. PMID:10960893

  1. Thermodynamic characterization of naturally occurring RNA tetraloops.

    PubMed

    Sheehy, Justin P; Davis, Amber R; Znosko, Brent M

    2010-02-01

    Although tetraloops are one of the most frequently occurring secondary structure motifs in RNA, less than one-third of the 30 most frequently occurring RNA tetraloops have been thermodynamically characterized. Therefore, 24 stem-loop sequences containing common tetraloops were optically melted, and the thermodynamic parameters DeltaH degrees , DeltaS degrees , DeltaG degrees (37,) and T(M) for each stem-loop were determined. These new experimental values, on average, are 0.7 kcal/mol different from the values predicted for these tetraloops using the model proposed by Vecenie CJ, Morrow CV, Zyra A, Serra MJ. 2006. Biochemistry 45: 1400-1407. The data for the 24 tetraloops reported here were then combined with the data for 28 tetraloops that were published previously. A new model, independent of terminal mismatch data, was derived to predict the free energy contribution of previously unmeasured tetraloops. The average absolute difference between the measured values and the values predicted using this proposed model is 0.4 kcal/mol. This new experimental data and updated predictive model allow for more accurate calculations of the free energy of RNA stem-loops containing tetraloops and, furthermore, should allow for improved prediction of secondary structure from sequence. It was also shown that tetraloops within the sequence 5'-GCCNNNNGGC-3' are, on average, 0.6 kcal/mol more stable than the same tetraloop within the sequence 5'-GGCNNNNGCC-3'. More systemic studies are required to determine the full extent of non-nearest-neighbor effects on tetraloop stability. PMID:20047989

  2. A large outbreak of Opisthorchis felineus in Italy suggests that opisthorchiasis develops as a febrile eosinophilic syndrome with cholestasis rather than a hepatitis-like syndrome.

    PubMed

    Traverso, A; Repetto, E; Magnani, S; Meloni, T; Natrella, M; Marchisio, P; Giacomazzi, C; Bernardi, P; Gatti, S; Gomez Morales, M A; Pozio, E

    2012-06-01

    We describe the greatest Italian human acute opisthorchiasis outbreak acquired from eating raw tenches. Out of 52 people with suspected opisthorchiasis, 45 resulted in being infected. The most frequent symptoms and laboratory findings were fever, abdominal pain and eosinophilia. Seven tri-phasic computed tomography (CT) scans were done, showing multiple hypodense nodules with hyper-enhancement in the arterial phase. All patients took one day of praziquantel 25 mg/kg TID without failures. Reported symptoms suggested a febrile eosinophilic syndrome with cholestasis rather than a hepatitis-like syndrome. It seems common to find hepatic imaging alterations during acute opisthorchiasis: CT scan could be the most suitable imaging examination. Even if stool test remains the diagnostic gold standard, we found earlier positivity with the serum antibody test. Without previous freezing, the consumption of raw freshwater fish should be avoided. PMID:21938537

  3. Clinical and Laboratory Features That Differentiate Dengue from Other Febrile Illnesses in an Endemic Area—Puerto Rico, 2007–2008

    PubMed Central

    Gregory, Christopher J.; Santiago, Luis Manuel; Argüello, D. Fermin; Hunsperger, Elizabeth; Tomashek, Kay M.

    2010-01-01

    Dengue infection can be challenging to diagnose early in the course of infection before severe manifestations develop, but early diagnosis can improve patient outcomes and promote timely public health interventions. We developed age-based predictive models generated from 2 years of data from an enhanced dengue surveillance system in Puerto Rico. These models were internally validated and were able to differentiate dengue infection from other acute febrile illnesses with moderate accuracy. The accuracy of the models was greater than either the current World Health Organization case definition for dengue fever or a proposed modification to this definition, while requiring the collection of fewer data. In young children, thrombocytopenia and the absence of cough were associated with dengue infection; for adults, rash, leucopenia, and the absence of sore throat were associated with dengue infection; in all age groups, retro-orbital pain was associated with dengue infection. PMID:20439977

  4. Febrile pleuropericarditis, a potentially life-threatening adverse event of balsalazide--case report and literature review of the side effects of 5-aminosalicylates.

    PubMed

    Coman, Roxana M; Glover, Sarah C; Gjymishka, Altin

    2014-05-01

    Ulcerative colitis (UC) is an idiopathic chronic inflammatory disorder that affects the colonic mucosa. One class among the drugs used for its treatment is the 5-aminosalicylates (5-ASAs). While highly efficacious in treating mild-to-moderate UC, 5-ASAs are associated with rare but potentially life-threatening side effects such as pericarditis, myocarditis and pneumonitis. These adverse events appear to be caused by a hypersensitivity reaction and resolve after cessation of 5-ASA drugs. This article presents a case report of febrile pleuropericarditis in a UC patient treated with balsalazide, and provides a thorough literature review of the rare side effects of 5-ASAs, their incidence, clinical presentation, differential diagnosis and treatment. In conclusion, the clinicians should be aware that this type of adverse events to 5-ASA compounds can be easily overlooked but it has significant morbidity if not promptly diagnosed. PMID:24689504

  5. Study of acute febrile illness: a 10-year descriptive study and a proposed algorithm from a tertiary care referral hospital in rural Kerala in Southern India.

    PubMed

    Ittyachen, Abraham M; Ramachandran, Reshmi

    2015-04-01

    Acute febrile illness (AFI), the initial diagnosis of whose cause is often presumptive, can sometimes be a challenge for the treating physician. To address this issue we carried out a hospital- based descriptive study. More than half (51.5%) of the patients were presumed to have viral fever. Most of the patients (60%) were in the productive phase of life (age range, 18-45 years). The outcome was worst among those aged over 65 years. A definite seasonal trend was observed with a peak in incidence with the arrival of the monsoon in Kerala. Public awareness regarding fevers in the pre-monsoon season should be heightened. Special care should be given to the elderly as they are often the most vulnerable. The use of the proposed locally based algorithm may avoid unnecessary investigations and treatment. PMID:25540169

  6. Introduction to naturally occurring radioactive material

    SciTech Connect

    Egidi, P.

    1997-08-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose-based standards. So when is TENORM a problem? Where is it a problem? That depends on when, where, and whom you talk to! We will start by reviewing background radioactivity, then we will proceed to the geology, mobility, and variability of these radionuclides. We will then review some of the industrial sectors affected by TENORM, followed by a brief discussion on regulatory aspects of the issue.

  7. Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

    PubMed Central

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to generate adaptive mechanisms, what has implications for epilepsy management and drug discovery. PMID:26011637

  8. Mapping the Aetiology of Non-Malarial Febrile Illness in Southeast Asia through a Systematic Review—Terra Incognita Impairing Treatment Policies

    PubMed Central

    Acestor, Nathalie; Cooksey, Richard; Newton, Paul N.; Ménard, Didier; Guerin, Philippe J.; Nakagawa, Jun; Christophel, Eva; González, Iveth J.; Bell, David

    2012-01-01

    Background An increasing use of point of care diagnostic tests that exclude malaria, coupled with a declining malaria burden in many endemic countries, is highlighting the lack of ability of many health systems to manage other causes of febrile disease. A lack of knowledge of distribution of these pathogens, and a lack of screening and point-of-care diagnostics to identify them, prevents effective management of these generally treatable contributors to disease burden. While prospective data collection is vital, an untapped body of knowledge already exists in the published health literature. Methods Focusing on the Mekong region of Southeast Asia, published data from 1986 to 2011 was screened to for frequency of isolation of pathogens implicated in aetiology of non-malarial febrile illness. Eligibility criteria included English-language peer-reviewed studies recording major pathogens for which specific management is likely to be warranted. Of 1,252 identified papers, 146 met inclusion criteria and were analyzed and data mapped. Results Data tended to be clustered around specific areas where research institutions operate, and where resources to conduct studies are greater. The most frequently reported pathogen was dengue virus (n?=?70), followed by Orientia tsutsugamushi and Rickettsia species (scrub typhus/murine typhus/spotted fever group n?=?58), Leptospira spp. (n?=?35), Salmonella enterica serovar Typhi and Paratyphi (enteric fever n?=?24), Burkholderia pseudomallei (melioidosis n?=?14), and Japanese encephalitis virus (n?=?18). Wide tracts with very little published data on aetiology of fever are apparent. Discussion and Conclusions This mapping demonstrates a very heterogeneous distribution of information on the causes of fever in the Mekong countries. Further directed data collection to address gaps in the evidence-base, and expansion to a global database of pathogen distribution, is readily achievable, and would help define wider priorities for research and development to improve syndromic management of fever, prioritize diagnostic development, and guide empirical therapy. PMID:22970193

  9. Naturally occurring hydroxytyrosol: synthesis and anticancer potential.

    PubMed

    Bernini, R; Merendino, N; Romani, A; Velotti, F

    2013-01-01

    Several epidemiological and animal studies have suggested that polyphenols, a group of secondary plant metabolites occurring mainly in the plant kingdom, may have a protective effect against some chronic degenerative diseases such as cancer. Polyphenols are part of the human diet, being present in vegetal food and beverages. Among them, an olive biophenol named hydroxytyrosol [2-(3,4- dihydroxyphenyl)ethanol, HTyr] has recently received particular attention because of its antioxidant, antiproliferative, pro-apoptotic, and anti-inflammatory activities, which have the potential to specifically counteract all cancer hallmarks, thus representing the expectant biological activities underlying the anti-tumor properties of this polyphenol. After a description of the synthetic procedures to prepare pure HTyr, this review takes into consideration the chemopreventive and chemotherapeutic potential of HTyr as the result of its antioxidant, antiproliferative and anti-inflammatory activities. In particular, the review is focused on the current knowledge of the main cellular and molecular mechanisms used by HTyr to affect carcinogenesis, highlighting the specific oncogenic and inflammatory signaling pathways potentially targeted by HTyr. PMID:23244583

  10. Clinical Laboratory Quality Practices When Hemolysis Occurs.

    PubMed

    Howanitz, Peter J; Lehman, Christopher M; Jones, Bruce A; Meier, Frederick A; Horowitz, Gary L

    2015-07-01

    Context .- Hemolyzed specimens delay clinical laboratory results, proliferate unnecessary testing, complicate physician decisions, injure patients indirectly, and increase health care costs. Objective .- To determine quality improvement practices when hemolysis occurs. Design .- We used the College of American Pathologists (CAP) Survey Program to distribute a Q-Probes-type questionnaire about hemolysis practices to CAP Chemistry Survey participants. Results .- Of 3495 participants sent the questionnaire, 846 (24%) responded. Although 85%, 69%, and 55% of participants had written hemolysis policies for potassium, lactate dehydrogenase, and glucose, respectively, only a few (46%, 40%, and 40%) had standardized hemolysis reports between their primary and secondary chemistry analyzers for these 3 analytes. Most participants (70%) had not attempted to validate the manufacturers' hemolysis data for these 3 analytes; however, essentially all who tried, succeeded. Forty-nine percent of participants had taken corrective action to reduce hemolysis during the past year and used, on average, 2.4 different actions, with collection and distribution of hemolysis data to administrative leadership (57%), troubleshooting outliers (55%), retraining phlebotomist (53%), and establishment of quality improvement teams among the laboratory and at problem locations (37%) being the most common actions. When asked to assess their progress in reducing hemolysis, 70% noted slow to no progress, and 2% gave up on improvement. Upon measuring potassium, lactate dehydrogenase, and glucose, approximately 60% of participants used the same specimen flag for hemolysis as for lipemia and icterus. Conclusions .- Hemolysis decreases the quality and increases the cost of health care. Practices for measuring, reporting, and decreasing hemolysis rates need improvement. PMID:26125430

  11. Differential dormancy of co-occurring copepods

    NASA Astrophysics Data System (ADS)

    Ohman, Mark D.; Drits, Aleksandr V.; Elizabeth Clarke, M.; Plourde, Stéphane

    1998-08-01

    Four species of planktonic calanoid copepods that co-occur in the California Current System ( Eucalanus californicus Johnson, Rhincalanus nasutus Giesbrecht, Calanus pacificus californicus Brodsky, and Metridia pacifica Brodsky) were investigated for evidence of seasonal dormancy in the San Diego Trough. Indices used to differentiate actively growing from dormant animals included developmental stage structure and vertical distribution; activity of aerobic metabolic enzymes (Citrate Synthase and the Electron Transfer System complex); investment in depot lipids (wax esters and triacylglycerols); in situ grazing activity from gut fluorescence; and egg production rates in simulated in situ conditions. None of the 4 species exhibited a canonical calanoid pattern of winter dormancy - i.e., synchronous developmental arrest as copepodid stage V, descent into deep waters, reduced metabolism, and lack of winter reproduction. Instead, Calanus pacificus californicus has a biphasic life history in this region, with an actively reproducing segment of the population in surface waters overlying a deep dormant segment in winter. Eucalanus californicus is dormant as both adult females and copepodid V's, although winter females respond relatively rapidly to elevated food and temperature conditions; they begin feeding and producing eggs within 2-3 days. Rhincalanus nasutus appears to enter dormancy as adult females, although the evidence is equivocal. Metridia pacifica shows no evidence of dormancy, with sustained active feeding, diel vertical migration behavior, and elevated activity of metabolic enzymes in December as well as in June. The four species also differ markedly in water content, classes of storage lipids, and specific activity of Citrate Synthase. These results suggest that copepod dormancy traits and structural composition reflect diverse adaptations to regional environmental conditions rather than a uniform, canonical series of traits that remain invariant among taxa and fixed across a species' range. Such interspecific and regional differences in life history traits need to be incorporated in models simulating Eastern Boundary Current pelagic ecosystem dynamics.

  12. Sundew adhesive: a naturally occurring hydrogel.

    PubMed

    Huang, Yujian; Wang, Yongzhong; Sun, Leming; Agrawal, Richa; Zhang, Mingjun

    2015-06-01

    Bioadhesives have drawn increasing interest in recent years, owing to their eco-friendly, biocompatible and biodegradable nature. As a typical bioadhesive, sticky exudate observed on the stalked glands of sundew plants aids in the capture of insects and this viscoelastic adhesive has triggered extensive interests in revealing the implied adhesion mechanisms. Despite the significant progress that has been made, the structural traits of the sundew adhesive, especially the morphological characteristics in nanoscale, which may give rise to the viscous and elastic properties of this mucilage, remain unclear. Here, we show that the sundew adhesive is a naturally occurring hydrogel, consisting of nano-network architectures assembled with polysaccharides. The assembly process of the polysaccharides in this hydrogel is proposed to be driven by electrostatic interactions mediated with divalent cations. Negatively charged nanoparticles, with an average diameter of 231.9 ± 14.8 nm, are also obtained from this hydrogel and these nanoparticles are presumed to exert vital roles in the assembly of the nano-networks. Further characterization via atomic force microscopy indicates that the stretching deformation of the sundew adhesive is associated with the flexibility of its fibrous architectures. It is also observed that the adhesion strength of the sundew adhesive is susceptible to low temperatures. Both elasticity and adhesion strength of the sundew adhesive reduce in response to lowering the ambient temperature. The feasibility of applying sundew adhesive for tissue engineering is subsequently explored in this study. Results show that the fibrous scaffolds obtained from sundew adhesive are capable of increasing the adhesion of multiple types of cells, including fibroblast cells and smooth muscle cells, a property that results from the enhanced adsorption of serum proteins. In addition, in light of the weak cytotoxic activity exhibited by these scaffolds towards a variety of mammal cells, evidence is sufficient to propose that sundew adhesive is a promising nanomaterial worth further exploitation in the field of tissue engineering. PMID:25948615

  13. Commonly occurring plant flavonoids have estrogenic activity.

    PubMed

    Miksicek, R J

    1993-07-01

    A remarkable diversity of naturally occurring and synthetic compounds have been shown to mimic the biological effects of 17 beta-estradiol by virtue of their ability to bind to and activate the nuclear estrogen receptor. This report extends the family of nonsteroidal estrogens to include several multiply hydroxylated chalcones, flavanones, and flavones. The hormone-like activity of these natural plant products is indicated by their ability to stimulate an estrogen receptor-dependent transcriptional response and to promote growth of estrogen-dependent MCF7 cells in culture. The transcriptional response can be inhibited by the steroidal estrogen antagonist ICI-164,384 and is specific for the estrogen receptor. Evidence is presented to show that selected hydroxylated flavonoids interact directly with the estrogen receptor, based on their ability to compete for the binding of 17 beta-[3H]estradiol to the receptor in cell-free extracts. These compounds are less active, on a molar basis, than 17 beta-estradiol or the synthetic dihydroxystilbene estrogens, but they have potencies comparable to those of other known phytoestrogens. Together, these findings broaden our understanding of the structure-activity relationships for nonsteroidal estrogens and present a series of new chemical prototypes for the future development of potentially useful agonists and antagonists for this nuclear receptor. The wide distribution of weakly estrogenic flavonoid pigments in food crops and medicinal plants raises additional questions about the possible health risks and benefits of these compounds, meriting closer examination of their presence in the human diet. PMID:8341277

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

    PubMed Central

    2012-01-01

    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 main cutaneous and haematological clinical signs of PN patients. PMID:22269211

  15. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients: Guidelines of the infectious diseases working party of the German Society of Haematology and Oncology.

    PubMed

    Maschmeyer, Georg; Beinert, Thomas; Buchheidt, Dieter; Cornely, Oliver A; Einsele, Hermann; Heinz, Werner; Heussel, Claus Peter; Kahl, Christoph; Kiehl, Michael; Lorenz, Joachim; Hof, Herbert; Mattiuzzi, Gloria

    2009-09-01

    Patients with neutropenia lasting for more than 10d, who develop fever and pulmonary infiltrates, are at risk of treatment failure under conventional broad-spectrum antibacterial therapy. Filamentous fungi are predominant causes of failure, however, multi-resistant gram-negative rods such as Pseudomonas aeruginosa or Stenotrophomonas maltophilia may be involved. Prompt addition of mould-active systemic antifungal therapy, facilitated by early thoracic computed tomography, improves clinical outcome. Non-culture-based diagnostic procedures to detect circulating antigens such as galactomannan or 1,3-beta-d-glucan, or PCR techniques to amplify circulating fungal DNA from blood, bronchoalveolar lavage or tissue specimens, may facilitate the diagnosis of invasive pulmonary aspergillosis. CT-guided bronchoalveolar lavage is useful in order to identify causative microorganisms such as multidrug-resistant bacteria, filamentous fungi or Pneumocystis jiroveci. For pre-emptive antifungal treatment, voriconazole or liposomal amphotericin B is preferred. In patients given broad-spectrum azoles for antifungal prophylaxis, non-azole antifungals or antifungal combinations might become first choice in this setting. Antifungal treatment should be continued for at least 14 d before non-response and treatment modification are considered. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their aetiological relevance for pulmonary infiltrates. PMID:19467584

  16. A molecular survey of febrile cases in malaria-endemic areas along China-Myanmar border in Yunnan province, People’s Republic of China

    PubMed Central

    Zhou, Xia; Huang, Ji-Lei; Njuabe, Metoh Theresia; Li, Sheng-Guo; Chen, Jun-Hu; Zhou, Xiao-Nong

    2014-01-01

    Background: Imported malaria is a major threat to neighboring malaria-eliminating countries such as P.R. China and is difficult to monitor. A molecular survey of febrile patients with a history of traveling abroad along the Myanmar-China endemic border areas from January 2008 to August 2012 was carried out. The rates of infection with species of Plasmodium and compliance of microscopy diagnosis with nested PCR (Polymerase Chain Reaction) results were calculated. Results: Plasmodium genus-specific nested PCR confirmed that 384 cases were positive. Further species-specific nested PCR showed that the rate of Plasmodium vivax infection was 55% (213/384); that of Plasmodium falciparum was 21% (81/384) and 17% (67/384) of cases were co-infection cases of P. vivax and P. falciparum; the remaining 6% (23/384) of cases were caused by other species, such as Plasmodium ovale, P. malaria, P. knowlesi or mixed infections of Plasmodium. In total there was 13% (50/384) false microscopy diagnosis including 6% (22/384) error in species diagnosis and 7% (28/384) undiagnosed cases in co-infection or low parasitemia malaria cases. Conclusions: This study indicates that there are considerable numbers of malaria cases in the China-Myanmar endemic border areas that remain undiagnosed or misdiagnosed by microscopy, especially in low-level and/or complex co-infection cases. It is urgent to develop accurate rapid diagnostic tests and apply PCR confirmation for efficient surveillance. PMID:24954235

  17. Central mediators involved in the febrile response induced by polyinosinic-polycytidylic acid: lack of involvement of endothelins and substance P.

    PubMed

    Bastos-Pereira, A L; Leite, M C G; Fraga, D; Zampronio, A R

    2015-01-15

    The present study evaluated the involvement of interleukin(IL)-1?, tumor necrosis factor-? (TNF-?), IL-6, interferon(IFN)-?, prostaglandins of the E2 series, endothelins, substance P and opioids within the central nervous system in polyinosinic:polycytidylic acid (Poly I:C)-induced fever in rats. Poly I:C injection induced a febrile response which was reduced by intracerebroventricular administration of the antibodies against TNF-?, IL-6, or IFN-?, or by IL-1 or ? receptor antagonists. Intraperitoneal injection of indomethacin or oral administration of celecoxib also reduced Poly I:C-induced fever. Poly I:C increased prostaglandin E2 levels in the cerebrospinal fluid of the animals which was also reduced by indomethacin. The intracerebroventricular injection of ETB or NK1 receptor antagonists did not alter Poly I:C-induced fever. These data suggest the involvement of IL-1?, TNF-?, IL-6, IFN-?, prostaglandin E2, and opioids but not endothelins and substance P on Poly I:C-induced fever. PMID:25595258

  18. Application of Polymerase Chain Reaction to Detect Burkholderia Pseudomallei and Brucella Species in Buffy Coat from Patients with Febrile Illness Among Rural and Peri-Urban Population

    PubMed Central

    Nandagopal, Balaji; Sankar, Sathish; Lingesan, Karthikeyan; Appu, KC; Sridharan, Gopalan; Gopinathan, Anilkumar

    2012-01-01

    Context: Melioidosis and Brucellosis are important endemic infections among people in India, especially in rural settings. Conventional detection techniques have several limitations. Only a few studies exist on the prevalence of Melioidosis and Brucellosis in rural area especially in India. Aim: We sought to evaluate detection of Burkholderia pseudomallei and Brucella spp. among patients presenting febrile illness. Material and Methods: Previously described polymerase chain reaction (PCR) assays for both pathogens were evaluated with Deoxyribonucleic acid extracts of buffy coat samples collected from 301 patients recruited prospectively. Data was not amenable to statistical analysis. Results: The PCR showed specific amplification and no non-specific amplification with heterologous Gram-negative bacilli. The lower limit of detection of the assay for B. pseudomallei was determined to be 1 colony-forming unit /mL and for Brucella it was 1.95 × 103 plasmids per microliter. Blood culture in automated blood culture system was negative for all the samples. This prospective study carried out in southern India for the first time. PCR for Brucella was positive in 1% of the patient samples whereas 0.3% was positive for B. pseudomallei. Conclusion: The finding of Brucella and Burkholderia infections in our populations leads us to suggest that tests for Brucella and B. pseudomallei should also form part of a diagnostic platform for patients with Pyrexia of unknown origin in tropical developing countries. PMID:22529625

  19. Lipopolysaccharide-binding protein: a possible diagnostic marker for Gram-negative bacteremia in neutropenic cancer patients

    Microsoft Academic Search

    Claudi S. M. Oude Nijhuis; Edo Vellenga; Simon M. G. J. Daenen; Jourik A. Gietema; Harry J. M. Groen; Willem A. Kamps

    2003-01-01

    Objective Cancer patients with febrile neutropenia after chemotherapy have a variable risk of bacterial infection. Especially Gram-negative bacteremia is associated with high mortality and\\/or morbidity. Early diagnosis of patients with Gram-negative bacteremia at the onset of febrile neutropenia is potentially useful in tailoring therapy. Design and setting Prospective study at the Department of Pediatric Oncology and Internal Medicine of a

  20. Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C

    PubMed Central

    Applegate, Tanya L; Gaudieri, Silvana; Plauzolles, Anne; Chopra, Abha; Grebely, Jason; Lucas, Michaela; Hellard, Margaret; Luciani, Fabio; Dore, Gregory J; Matthews, Gail V

    2014-01-01

    Background Directly Acting Antivirals (DAAs) are predicted to transform hepatitis C (HCV) therapy, yet little is known about the prevalence of naturally occurring resistance mutations in recently acquired HCV. This study aimed to determine the prevalence and frequency of drug resistance mutations in the viral quasispecies among HIV positive and negative individuals with recent HCV. Methods The NS3 protease, NS5A and NS5B polymerase genes were amplified from fifty genotype 1a participants of the Australian Trial in Acute Hepatitis C. Amino acid variations at sites known to be associated with possible drug resistance were analysed by ultra-deep pyrosequencing. Results Twelve percent of individuals harboured dominant resistance mutations, while 36% demonstrated non dominant resistant variants below that detectable by bulk sequencing (ie < 20%) but above a threshold of 1%. Resistance variants (< 1%) were observed at most sites associated with DAA resistance from all classes, with the exception of sofosbuvir. Conclusions Dominant resistant mutations were uncommonly observed in the setting of recent HCV. However, low level mutations to all DAA classes were observed by deep sequencing at the majority of sites, and in most individuals. The significance of these variants and impact on future treatment options remains to be determined. PMID:25105742

  1. Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy

    PubMed Central

    2013-01-01

    Background Lipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy. This phase III, double-blind, randomized, active-controlled, noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy. Methods Patients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ?1.5?×?109 cells/L were randomized to a single 6-mg subcutaneous injection of lipegfilgrastim (n?=?101) or pegfilgrastim (n?=?101) on day 2 of each 21-day chemotherapy cycle (4 cycles maximum). The primary efficacy endpoint was the duration of severe neutropenia during cycle 1. Results Cycle 1: The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days, respectively (??=??0.218 [95% confidence interval: –0.498%, 0.062%], p?=?0.126), and no severe neutropenia was observed in 56% and 49% of patients in the lipegfilgrastim and pegfilgrastim groups, respectively. All cycles: In the efficacy population, febrile neutropenia occurred in three pegfilgrastim-treated patients (all in cycle 1) and zero lipegfilgrastim-treated patients. Drug-related adverse events in the safety population were reported in 28% and 26% of patients i006E the lipegfilgrastim and pegfilgrastim groups, respectively. Conclusion This study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Trial Registration Eudra EEACTA200901599910 The study protocol, two global amendments (Nos. 1 and 2), informed consent documents, and other appropriate study-related documents were reviewed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees (IECs). PMID:23945072

  2. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

  3. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

  4. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

  5. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

  6. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

  7. Mechanism of Prion Propagation: Amyloid Growth Occurs by Monomer Addition

    E-print Network

    Vale, Ronald D.

    Mechanism of Prion Propagation: Amyloid Growth Occurs by Monomer Addition Sean R. Collins, Adam yeast prion protein Sup35. Rapid polymerization occurs in the absence of observable intermediates of prion propagation: Amyloid growth occurs by monomer addition. PLoS Biol 2(10): e321. Introduction Many

  8. Causes and Outcomes of Pediatric Injuries Occurring at School.

    ERIC Educational Resources Information Center

    Di Scala, Carla; Gallagher, Susan Scavo; Schneps, Sue E.

    1997-01-01

    Used the National Pediatric Trauma Registry, which collects data on child injuries requiring hospitalization, to examine causes and outcomes of injuries occurring at school. Analysis of 1,558 cases indicated that most injuries were unintentional and occurred among students age 10-14 years. Nearly half occurred in recreational areas. Falls and…

  9. Functional and biochemical analysis of a sodium channel beta1 subunit mutation responsible for generalized epilepsy with febrile seizures plus type 1.

    PubMed

    Meadows, Laurence S; Malhotra, Jyoti; Loukas, Andrew; Thyagarajan, Veena; Kazen-Gillespie, Kristin A; Koopman, Matthew C; Kriegler, Steven; Isom, Lori L; Ragsdale, David S

    2002-12-15

    Generalized epilepsy with febrile seizures plus type 1 is an inherited human epileptic syndrome, associated with a cysteine-to-tryptophan (C121W) mutation in the extracellular immunoglobin domain of the auxiliary beta1 subunit of the voltage-gated sodium channel. The mutation disrupts beta1 function, but how this leads to epilepsy is not understood. In this study, we make several observations that may be relevant for understanding why this beta1 mutation results in seizures. First, using electrophysiological recordings from mammalian cell lines, coexpressing sodium channel alpha subunits and either wild-type beta1 or C121Wbeta1, we show that loss of beta1 functional modulation, caused by the C121W mutation, leads to increased sodium channel availability at hyperpolarized membrane potentials and reduced sodium channel rundown during high-frequency channel activity, compared with channels coexpressed with wild-type beta1. In contrast, neither wild-type beta1 nor C121Wbeta1 significantly affected sodium current time course or the voltage dependence of channel activation. We also show, using a Drosophila S2 cell adhesion assay, that the C121W mutation disrupts beta1-beta1 homophilic cell adhesion, suggesting that the mutation may alter the ability of beta1 to mediate protein-protein interactions critical for sodium channel localization. Finally, we demonstrate that neither functional modulation nor cell adhesion mediated by wild-type beta1 is occluded by coexpression of C121Wbeta1, arguing against the idea that the mutant beta1 acts as a dominant-negative subunit. Together, these data suggest that C121Wbeta1 causes subtle effects on channel function and subcellular distribution that bias neurons toward hyperexcitabity and epileptogenesis. PMID:12486163

  10. Evaluation of the Nitrite Test in Screening for Urinary Tract Infection in Febrile Children with Sickle Cell Anaemia in Maiduguri- Nigeria.

    PubMed

    Mava, Y; Ambe, J P; Bello, M; Watila, I; Pius, S

    2011-01-01

    BACKGROUND: Urinary tract infection is a significant cause of morbidity in children with sickle cell anaemia (SCA). Individuals with SCA have increased risk of urinary tract infection (UTI). Facilities for urine culture may not be available in most rural and even some urban areas in most developing countries like Nigeria. It will therefore be useful to have a simple means of screening such children for UTI with the intent of prompt treatment. MATERIALS AND METHODS: The study will evaluate the usefulness of the nitrite test in detecting UTI in febrile SCA children. This study was carried out in the Department of Paediatrics University of Maiduguri Teaching Hospital and State Specialist Hospital Maiduguri. RESULTS: The study consisted of 250 children aged 6 months to 15 years with SCA presenting with fever (temperature ? 37. 5°C). Midstream urine specimen was collected from older children and suprapubic bladder aspiration of urine specimen was collected from infants. Samples were subjected to nitrite test, culture and sensitivity. There was significant bacteriuria in 65 (26+) children with SCA. A positive test for nitrite was obtained in 43 of the 65 (66.2+) children. The nitrite test has a specificity of 93.5+ in detecting bacteriuria, a sensitivity of 66.2+, a positive predictive value of 78.2+ and a negative predictive value of 93.5+. A positive nitrite test was significantly associated with bacteriuria, while a negative test was also significantly associated with an absence of bacteriuria. CONCLUSIONS: From this study, the nitrite test is useful as a screening test for UTI in SCA children. However in sick children with SCA, microscopy, culture and sensitivity should still be done in spite of a negative nitrite test. PMID:21968796

  11. Association between Iron Deficiency Anemia and Febrile Convulsion in 3- to 60-Month-Old Children: A Systematic Review and Meta-Analysis

    PubMed Central

    Habibian, Narges; Alipour, Abbas; Rezaianzadeh, Abbas

    2014-01-01

    Controversy exists regarding the association between Iron Deficiency Anemia (IDA), iron status, and Febrile Convulsion (FC) during childhood. In this article, a systematic review and meta-analysis is conducted in order to determine possible association and the degree of association between these statuses and FC. To identify all studies related to IDA and FC, various references such as MEDLINE (PubMed), Embase (OVID), Web of sciences (Thomson Reuters) and Google scholar were searched (up until 15 January 2013). Heterogeneity was assessed using the Q statistic, Tau2, and I2. Additionally, subgroup analyses were performed. The outcome of primary interest was the overall Odds Ratio (OR) of FC for IDA and standard mean differences (SMD) of ferritin level. In total, 21 articles were considered to assess the association between IDA and FC. Anemia was more prevalent among the FC patients compared with the controls and the overall OR was 1.52 (95% CI=1.03 to 2.25). In addition, the pooled OR for 17 studies performed in the populations with low and moderate prevalence of anemia was 2.04 (95% CI=1.46 to 2.85). Furthermore, 12 studies assessed the association between the ferritin level and FC. The overall SMD was -0.02 with a 95% CI of -0.09 to 0.06. Besides, the pooled SMD of ferritin was -0.57 (95% CI=-0.7 to -0.46) in 6 studies reporting no difference between the FC and the control group with respect to temperature. IDA was associated with a moderate increased risk of FC in children, particularly in the areas with low and moderate prevalence of anemia. PMID:25429171

  12. Introducing the concept of a new pre-referral treatment for severely ill febrile children at community level: a sociological approach in Guinea-Bissau

    PubMed Central

    2014-01-01

    Background Innovative strategies are needed to tackle childhood mortality in the rural tropics. Artesunate suppositories were developed to bring emergency treatment closer to severely ill children with malaria in rural areas where injectable treatment is not possible for several hours. Adding an antibacterial rectal drug would extend this strategy to treat non-malarial febrile illness as well. The objective of these studies was to assess acceptability of such a new pre-referral strategy by healthcare providers and likely uptake by the population. Methods Two qualitative studies were conducted between May and July 2009. Study 1 investigated the acceptability of introducing a combined antimalarial-antibacterial suppository by interviewing 27 representatives of the three administrative levels (central government, regional, local) of the health sector; Study 2 investigated treatment-seeking behaviour and acceptability of this intervention at community level by interviewing 74 mothers in 2 villages. Results and Conclusions Up to 92% of health representatives were in favour of introducing a new pre-referral strategy to tackle both malaria and non-malaria related severe illnesses in Guinea-Bissau, provided it was endorsed by international health authorities. The main obstacles to implementation were the very limited human and financial resources. In the two villages surveyed, 44% of the mothers associated severe illness with fever only, or fever plus one additional symptom. Mothers’ judgement of severity and ensuing decisions were not specific for serious illness, indicating that initial training to recognize signs of severe disease and treatment availability for non-severe, fever-associated symptoms will be required to prevent overuse of a new intervention designed as a pre-referral treatment for severely ill children. Level C health centres were the first resort in both villages (50% and 87% of respondents respectively). This information is encouraging for the implementation of a pre-referral treatment. PMID:24502695

  13. Clozapine treatment of patients with refractory schizophrenia, concurrent dengue infection and hematological abnormalities: three case reports

    PubMed Central

    Rezende, Tatiana M.N.; Morais, Silvio L.; Crippa, José A.S.; Dursun, Serdar M.; Baker, Glen B.; Hallak, Jaime E.C.

    2013-01-01

    Background: Dengue is a febrile illness that is most common in tropical areas but is recognized worldwide as one of the most important arbovirus diseases of humans. This febrile illness generally has a course with mild alterations in white blood cell count, but there are also rare cases of severe neutropenia or agranulocytosis during dengue infection. Clozapine (CLZ) remains the most effective treatment for schizophrenia, but because of its poor side effect profile, in particular due to the increased risk of neutropenia and agranulocytosis, it is generally used for patients whose condition responds poorly to other antipsychotics. Methods: We report three cases of dengue infection in patients with refractory schizophrenia who were using CLZ, and we discuss the implications of this infection on the continuation of CLZ treatment in these patients. Results: Of these three cases with dengue infection and co-occurence of CLZ use, the first would be classified as severe neutropenia and the second as moderate leucopenia; the last case had a white blood cell (WBC) count inside the normal range, and had no need to change his antipsychotic. The first and the second patient presented a worsening in their schizophrenic psychopathologies, after CLZ withdrawal, evolving into catatonic states, that were reverted after the careful reintroduction of CLZ. Discussion: It is very likely that during dengue epidemics many patients with schizophrenia and using CLZ have their treatment permanently discontinued given WBC count concerns, causing relapse of symptoms of schizophrenia and impairment of quality of life of these patients.This is the first report of neutropenia cases among CLZ-treated patients during dengue infection that describes the withdrawal of CLZ and its successful readministration. PMID:24167679

  14. Diagnostic Testing of Pediatric Fevers: Meta-Analysis of 13 National Surveys Assessing Influences of Malaria Endemicity and Source of Care on Test Uptake for Febrile Children under Five Years

    PubMed Central

    Johansson, Emily White; Gething, Peter W.; Hildenwall, Helena; Mappin, Bonnie; Petzold, Max; Peterson, Stefan Swartling; Selling, Katarina Ekholm

    2014-01-01

    Background In 2010, the World Health Organization revised guidelines to recommend diagnosis of all suspected malaria cases prior to treatment. There has been no systematic assessment of malaria test uptake for pediatric fevers at the population level as countries start implementing guidelines. We examined test use for pediatric fevers in relation to malaria endemicity and treatment-seeking behavior in multiple sub-Saharan African countries in initial years of implementation. Methods and Findings We compiled data from national population-based surveys reporting fever prevalence, care-seeking and diagnostic use for children under five years in 13 sub-Saharan African countries in 2009–2011/12 (n?=?105,791). Mixed-effects logistic regression models quantified the influence of source of care and malaria endemicity on test use after adjusting for socioeconomic covariates. Results were stratified by malaria endemicity categories: low (PfPR2–10<5%), moderate (PfPR2–10 5–40%), high (PfPR2–10>40%). Among febrile under-fives surveyed, 16.9% (95% CI: 11.8%–21.9%) were tested. Compared to hospitals, febrile children attending non-hospital sources (OR: 0.62, 95% CI: 0.56–0.69) and community health workers (OR: 0.31, 95% CI: 0.23–0.43) were less often tested. Febrile children in high-risk areas had reduced odds of testing compared to low-risk settings (OR: 0.51, 95% CI: 0.42–0.62). Febrile children in least poor households were more often tested than in poorest (OR: 1.63, 95% CI: 1.39–1.91), as were children with better-educated mothers compared to least educated (OR: 1.33, 95% CI: 1.16–1.54). Conclusions Diagnostic testing of pediatric fevers was low and inequitable at the outset of new guidelines. Greater testing is needed at lower or less formal sources where pediatric fevers are commonly managed, particularly to reach the poorest. Lower test uptake in high-risk settings merits further investigation given potential implications for diagnostic scale-up in these areas. Findings could inform continued implementation of new guidelines to improve access to and equity in point-of-care diagnostics use for pediatric fevers. PMID:24748201

  15. A Fatal Spontaneous Gas Gangrene due to Clostridium perfringens during Neutropenia of Allogeneic Stem Cell Transplantation: Case Report and Literature Review

    PubMed Central

    Lee, Hae-Lim; Cho, Sung-Yeon; Ko, Yumi; Hyun, Ji In; Kim, Bo Kyoung; Seo, Jae Hyun; Lee, Jung Woo; Lee, Seok

    2014-01-01

    Most cases of gas gangrene caused by Clostridium species begin with trauma-related injuries but in rare cases, spontaneous gas gangrene (SGG) can occur when patients have conditions such as advanced malignancy, diabetes, or immunosuppression. Clostridium perfringens, a rare cause of SGG, exists as normal flora of skin and intestines of human. Adequate antibiotics with surgical debridement of infected tissue is the only curative therapeutic management. Mortality rate among adults is reported range of 67-100% and majority of deaths are occurred within 24 hours of onset. We experienced a case of SGG on the trunk, buttock and thigh in a neutropenic patient with acute lymphoblastic leukemia. His clinical course was rapid and fatal during pre-engraftment neutropenic period of allogeneic stem cell transplantation. PMID:25298910

  16. Rapid diagnostic tests to improve treatment of malaria and other febrile illnesses: patient randomised effectiveness trial in primary care clinics in Afghanistan

    PubMed Central

    Mikhail, Amy; Mayan, Ismail; Cundill, Bonnie; Anwar, Mohammed; Bakhtash, Sayed Habib; Mohammed, Nader; Rahman, Habib; Zekria, Rohullah; Whitty, Christopher J M; Rowland, Mark

    2014-01-01

    Objective To assess the impact of rapid diagnostic tests on the diagnostic accuracy and treatment of malaria and non-severe fever in an Asian setting. Design Patient randomised trial in primary level clinics. Setting Two areas of Afghanistan where Plasmodium vivax and Plasmodium falciparum are endemic; one area with moderate transmission (eastern region) and one with low transmission (northern region). Participants 5794 patients of all ages with suspected malaria enrolled by 80 clinicians in 22 clinics. Interventions Malaria rapid diagnostic tests were compared with clinical diagnosis where no parasite diagnostic test was available, longer established field microscopy, and recently introduced microscopy. Main outcome measures Proportion of patients appropriately treated with an antimalarial, defined as patients with P vivax who received chloroquine, patients with P falciparum who received artemisinin based combination therapy, and patients with no malaria parasites who did not receive an antimalarial. Secondary outcomes included diagnostic test accuracy and the proportion of patients negative for malaria who received antibiotics and antimalarials. Results In the low transmission area, comparing rapid diagnostic tests with clinical diagnosis, 65% (212/325) versus 12% (40/321) of febrile patients were appropriately treated for malaria (adjusted odds ratio 92.7, 95% confidence interval 12.4 to 694.1, P<0.001). The proportion of patients who were negative for malaria and received an antibiotic was 57% (185/325) in the rapid diagnostic test arm compared with 14% (46/321) in the clinical diagnosis arm (16.9, 3.8 to 75.4, P<0.001). In the comparison of rapid diagnostic test with microscopy in the moderate transmission area, 83.6% (1696/2028) versus 76.3% (1512/1983) of patients were appropriately treated for malaria (1.70, 1.30 to 2.23, P<0.001). A higher proportion of P falciparum cases received appropriate treatment with artemisinin based combination therapy when malaria was diagnosed by rapid diagnostic test (82%, 58/71 v 32%, 24/76; 9.2, 3.88 to 21.66, P<0.001). Conclusions In South and central Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance. PMID:24948695

  17. Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts.

    PubMed

    Segal, Brahm H; Almyroudis, Nikolaos G; Battiwalla, Minoo; Herbrecht, Raoul; Perfect, John R; Walsh, Thomas J; Wingard, John R

    2007-02-01

    Invasive fungal infection (IFI) is a leading cause of infection-related mortality among patients with cancer and prolonged neutropenia and among allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Invasive candidiasis was the principal IFI in the period predating fluconazole prophylaxis, whereas today, invasive aspergillosis and other mold infections cause the majority of deaths from fungal infection in this patient population. The changing epidemiology of IFI, in addition to advances made in antifungal therapeutics and early diagnosis of IFI, warrant a reevaluation of earlier strategies aimed at prevention and early treatment of IFI that were developed several years ago. Here, we propose that persistent neutropenic fever is nonspecific for an IFI and should not be used as the sole criterion for empirical modification in the antifungal regimen in a patient receiving mold-active prophylaxis. We explore the potential benefits and gaps in knowledge associated with employing chest CT scans and laboratory markers as diagnostic adjuncts for IFI. Finally, we discuss the implications of newer antifungal agents and diagnostic adjuncts in the design of future clinical trials to evaluate prophylaxis and early prevention strategies. PMID:17205448

  18. Verrucous carcinoma occurring in a lesion of oral lichen planus.

    PubMed

    Warshaw, E M; Templeton, S F; Washington, C V

    2000-04-01

    Verrucous carcinoma of the oral cavity is relatively rare. Well-documented associations include human papillomavirus and carcinogens such as tobacco. Less well understood is the association with chronic inflammation, such as seen in lichen planus. Verrucous carcinoma has previously been described occurring in lesions of lichen planus of the foot and penis. We report the first case, to our knowledge, of verrucous carcinoma occurring in a lesion of oral lichen planus. PMID:10795082

  19. Adverse events occurring during interhospital transfer of the critically ill

    Microsoft Academic Search

    P W Barry; C Ralston

    1994-01-01

    OBJECTIVE--To determine what complications children have during interhospital transfer for intensive care, and how often these complications occur. DESIGN--Observational study of all children transferred over a six month period, including interviews with patient escort, patient review, and severity of illness scoring. MAIN OUTCOME MEASURES--Timing and method of transport; complications occurring during transport; the equipment and experience of the escort; patient

  20. Enhancing Validity in Co-occurring Disorders Treatment Research

    PubMed Central

    McHugo, Gregory J.; Drake, Robert E.; Brunette, Mary F.; Xie, Haiyi; Essock, Susan M.; Green, Alan I.

    2006-01-01

    Despite the high prevalence of co-occurring mental health and substance-use disorders, there has been a relative lack of treatment research with this population, and the existing research often has limited validity. This article explores some of the barriers to the conduct of research on promising interventions for substance-abuse treatment for people with co-occurring disorders, using the concepts of external and ecological validity to make recommendations for future investigation. The central recommendation is to move rapidly from efficacy studies to more credible and valid effectiveness studies, in order to facilitate the adoption of evidence-based interventions in routine practice settings. PMID:16849398

  1. Granulocyte antigen systems and antibodies and their clinical significance

    SciTech Connect

    McCullough, J.

    1983-03-01

    Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems. These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases. Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established. Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies. Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy.

  2. Predictive model of squeal noise occurring on a laboratory brake

    Microsoft Academic Search

    Oliviero Giannini; Aldo Sestieri

    2006-01-01

    This paper on brake squeal instability presents a reduced order model of a laboratory brake considered in a previous paper, and presents a description of the squeal mechanism occurring during experiments.The model uses the modal parameters of the laboratory brake components, the disc and the caliper, when they are not in contact between them. Successively, the caliper and the disc

  3. Crustacea: A Primitive Mediterranean Group also Occurs in North America

    Microsoft Academic Search

    Bassett Maguire Jr.

    1964-01-01

    A new species of the genus Monodella (class Crustacea, order Thermosbaenacea) has been found in a cave pool in Texas. Previously the order was believed to be restricted to the Mediterranean area. The new evidence indicates that the order is older than was believed, or that invasion of fresh or brackish water has occurred more than once within the order.

  4. Crustacea: A Primitive Mediterranean Group also Occurs in North America.

    PubMed

    Maguire, B

    1964-11-13

    A new species of the genus Monodella (class Crustacea, order Thermosbaenacea) has been found in a cave pool in Texas. Previously the order was believed to be restricted to the Mediterranean area. The new evidence indicates that the order is older than was believed, or that invasion of fresh or brackish water has occurred more than once within the order. PMID:17777061

  5. Changes occurring to minimally disturbed soil and to plant covers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the transition to organic production certain materials and practices, as described under US law, can not be used. During the transition period growers may, or may not, disturb the soil. There is little known about changes that occur if the soil is minimally disturbed during the transition t...

  6. Improving Home Automation by Discovering Regularly Occurring Device Usage Patterns

    E-print Network

    Cook, Diane J.

    Improving Home Automation by Discovering Regularly Occurring Device Usage Patterns Edwin O in an environment can be mined to discover significant patterns, which an intelligent agent could use to automate of two prediction algorithms, thus demonstrating multiple uses for a home automation system. Finally, we

  7. MAGNETIC TOPOLOGIES: WHERE WILL RECONNECTION OCCUR ? Pascal Demoulin

    E-print Network

    Demoulin, Pascal

    1 MAGNETIC TOPOLOGIES: WHERE WILL RECONNECTION OCCUR ? Pascal D´emoulin Observatoire de Paris to power flares is thought to come from the coronal magnetic field. However, such energy release is efficient only at very small scales. Magnetic configurations with a complex topology, i.e. with sepa

  8. Signs of Learning: Understanding Naturally Occurring Internet Learning Communities

    Microsoft Academic Search

    Gary Shank

    The purpose of this study is to explore principles and dynamics of naturally- occurring learning communities on the Internet. Specifically, three long-standing and stable USENET groups will be targeted. This cyber-ethnography will be guided by the fundamental principles of activity theory, which insist that cognition and learning is best understood within social and cultural frames. The social and cultural frames,

  9. Retroperitoneal uterine leiomyoma occurring 5 years after hysterectomy for fibroids.

    PubMed

    Fukamachi, Nobuyuki; Togami, Shinichi; Iwamoto, Ichiro; Tsuji, Takahiro; Nomoto, Mitsuharu; Goto, Masamichi; Kamiyama, Takuro; Fukukura, Yoshihiko; Douchi, Tsutomu

    2007-12-01

    We encountered a 49-year-old, multiparous female with a very rare isolated retroperitoneal uterine leiomyoma measuring 72 x 43 mm in diameter occurring 5 years after hysterectomy for fibroids. The case was preliminarily diagnosed as right ovarian cancer or fibroma. An edematous, isolated solid tumor in the right retroperitoneal cavity was surgically resected. Pathological findings demonstrated uterine leiomyoma. PMID:18001458

  10. Phototendering of wool sensitized by naturally occurring polyphenolic dyes

    Microsoft Academic Search

    Gerald J Smith; Ian J Miller; Vincent Daniels

    2005-01-01

    A number of naturally occurring polyphenolics have been used since antiquity to dye wool. These colourants, originally extracted from plants and insects, can be fixed to wool fibres by a metal ion mordant with the free carboxylic acid and sulphydryl groups present in wool protein providing the necessary metal ion binding sites.Wool undergoes a variety of chemical reactions induced by

  11. PURDUE EXTENSION Stormwater is the runoff that occurs during

    E-print Network

    PURDUE EXTENSION FNR-256 Stormwater is the runoff that occurs during rainstorms. In natural systems the slope or gradient. Most neighborhoods have storm sewer systems that take this accumulated stormwater to the nearest storm drain. Stormwater can cause problems because it picks up pollutants on the ground

  12. If a fire should occur... CLOSE the doors to

    E-print Network

    Rose, Michael R.

    If a fire should occur... · CLOSE the doors to stop the spread of the fire · SOUND the alarm, alert · SimplexGrinnell · United States Fire Administration · University of Texas System Living With Fire others to the danger · GET OUT of the building · NOTIFY the fire department DO NOT go back

  13. "Understanding occurs when there is quality dialogue between

    E-print Network

    Auckland, University of

    Sakamoto Current student PhD (Dance Studies) National Institute of Creative Arts and Industries"Understanding occurs when there is quality dialogue between different cultural identities" Hiromi there is a depth of quality inter-cultural dialogue. The University can give you a strong theoretical base

  14. Naturally occurring arsenic in groundwaters of the midwestern United States

    Microsoft Academic Search

    Nic Korte

    1991-01-01

    High concentrations of naturally occurring arsenic are present in alluvial groundwater systems in the midwestern United States. These occurrences tend to be sporadic because the arsenic is mobilized only under a narrow range of redox conditions. The reducing conditions must be sufficient to reduce and dissolve iron and manganese but not to produce sulfide. Typically, the affected aquifers are relatively

  15. A singular perturbation approach to integral equations occurring in poroelasticity

    Microsoft Academic Search

    C. Atkinson; R. V. Craster

    1994-01-01

    Singular perturbation theory is used to solve the integral equations which occur when treating finite-length crack problems in porous elastic materials. The method provides the stress intensity factors which characterize the near crack tip stress and displacement fields for small times. The method also gives the stress and pore pressure fields on the fracture plane for small times relative to

  16. Integrative Priming Occurs Rapidly and Uncontrollably during Lexical Processing

    ERIC Educational Resources Information Center

    Estes, Zachary; Jones, Lara L.

    2009-01-01

    Lexical priming, whereby a prime word facilitates recognition of a related target word (e.g., "nurse" [right arrrow] "doctor"), is typically attributed to association strength, semantic similarity, or compound familiarity. Here, the authors demonstrate a novel type of lexical priming that occurs among unassociated, dissimilar, and unfamiliar…

  17. Plenary paper Functional consequences of naturally occurring mutations in human

    E-print Network

    Hill, Chris

    pedi- grees with familial porphyria cutanea tarda (F-PCT). All but one mutation al- tered a restriction of uroporphyrinogen decarboxylase (URO-D) in hepatocytes is responsible for the most common form of porphyria in humans, porphyria cutanea tarda (PCT).1,2 PCT occurs with a prevalence of 1 to 5 per 25 0001

  18. Does the Branly effect occur in spark plasma sintering?

    NASA Astrophysics Data System (ADS)

    Guyot, P.; Rat, V.; Coudert, J. F.; Jay, F.; Maître, A.; Pradeilles, N.

    2012-03-01

    Spark plasma sintering (SPS) is a non-conventional method of powder consolidation. We show that the Branly effect can occur in SPS of copper powder in the early stages of the process due to inductive effects generated by the applied pulsed current. It leads to the formation of melting zones between contact areas of copper grains which can enhance material densification.

  19. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

    Microsoft Academic Search

    Xuyang Li; Eric M. Eastman; Ruxandra Draghia-Akli; Robert J. Schwartz

    1999-01-01

    Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity

  20. Mineralogical Characteristics of Carbonate Rock-Hosted Naturally Occurring Asbestos

    NASA Astrophysics Data System (ADS)

    Shin, E.; Roh, Y.

    2012-12-01

    Naturally Occurring Asbestos (NOA) occurs in rocks and soils as a result of natural weathering and human activities. The parent rocks of asbestos have been associated with ultramafic and mafic rocks, and carbonate rock. The previous studies on naturally occurring asbestos were mainly limited to ultramafic and mafic rock-hosted asbestos and studies on carbonate rock-hosted asbestos are relatively rare in South Korea. Therefore, this study was aimed to characterize mineralogy of carbonate rock-hosted NOA at Muju and Jangsu, Jeonbuk province and Seosan and Asan, Chungnam province. The rock types at the four sites are consisting mainly of Precambrian metasedimentary rock. XRD and PLM analyses showed fibrous minerals in the sites were tremolite and actinolite of acicular and columnar forms. SEM-EDS analyses showed that asbestiform tremolite and actinolite had various ratios of length and diameters over 12:1, and needle and columnar forms. A columnar forms of tremolite and actinolite were showed small acicular at the edge of the particle. Its main chemical compositions are mainly Si, O, Mg, Ca, which were identical to tremolite. Actinolite contains Fe in addition to Si, O, Mg, Ca. EPMA analyses of asbestos occurred at Muju indicated that chemical composition are 55% SiO2, 23.2% MgO, 13.1 % CaO, and 0.61 % FeO and the chemical formula calculated as (K0.01Na0.01)Ca2.01(Mg4.94Fe0.05) (Al0.004Si7.98)O22(OH)2, which is close to ideal tremolite. In addition to tremolite, actinolite was also occurred at Seosan, Chungnam. XRD analyses showed that antigorite was existed at Muju, but PLM and SEM analyses showed the antigorite was platy structure, not asbestiform. These results indicate that asbestiform tremolite and actinolite with acicular forms contains in carbonate rocks at Muju and Jangsu, Jeonbuk and Seosan and Asan, Chungnam province South Korea.

  1. The characteristics of gas hydrates occurring in natural environment

    NASA Astrophysics Data System (ADS)

    Lu, H.; Moudrakovski, I.; Udachin, K.; Enright, G.; Ratcliffe, C.; Ripmeester, J.

    2009-12-01

    In the past few years, extensive analyses have been carried out for characterizing the natural gas hydrate samples from Cascadia, offshore Vancouver Island; Mallik, Mackenzie Delta; Mount Elbert, Alaska North Slope; Nankai Trough, offshore Japan; Japan Sea and offshore India. With the results obtained, it is possible to give a general picture of the characteristics of gas hydrates occurring in natural environment. Gas hydrate can occur in sediments of various types, from sands to clay, although it is preferentially enriched in sediments of certain types, for example coarse sands and fine volcanic ash. Most of the gas hydrates in sediments are invisible, occurring in the pores of the sediments, while some hydrates are visible, appearing as massive, nodular, planar, vein-like forms and occurring around the seafloor, in the fractures related to fault systems, or any other large spaces available in sediments. Although methane is the main component of most of the natural gas hydrates, C2 to C7 hydrocarbons have been recognized in hydrates, sometimes even in significant amounts. Shallow marine gas hydrates have been found generally to contain minor amounts of hydrogen sulfide. Gas hydrate samples with complex gas compositions have been found to have heterogeneous distributions in composition, which might reflect changes in the composition of the available gas in the surrounding environment. Depending on the gas compositions, the structure type of a natural gas hydrate can be structure I, II or H. For structure I methane hydrate, the large cages are almost fully occupied by methane molecules, while the small cages are only partly occupied. Methane hydrates occurring in different environments have been identified with almost the same crystallographic parameters.

  2. Phase I Results of Vinorelbine With Concurrent Radiotherapy in Elderly Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer: West Japan Thoracic Oncology Group (WJTOG3005-DI)

    SciTech Connect

    Harada, Hideyuki, E-mail: h.harada@scchr.jp [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Seto, Takashi [Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka (Japan); Igawa, Satoshi [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Tsuya, Asuka [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Wada, Mayuko [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Kaira, Kyoichi; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Hayakawa, Kazushige [Department of Radiology, Kitasato University School of Medicine, Kanagawa (Japan); Nishimura, Tetsuo [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Masuda, Noriyuki [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan)

    2012-04-01

    Purpose: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m{sup 2} in Level 1 and 25 mg/m{sup 2} in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m{sup 2}) on Days 1 and 8 every 3 weeks for two cycles. Results: Four patients were enrolled at Level 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively. Conclusions: Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.

  3. Documentation of Associated Injuries Occurring With Radial Head Fracture

    Microsoft Academic Search

    Roger P. van Riet; Bernard F. Morrey

    2008-01-01

    We believe a better way is needed to accurately describe the spectrum of associated injuries that commonly occur in conjunction\\u000a with a radial head fracture. A review of our institution’s experience with 333 radial head fractures from 1997 to 2002 documented\\u000a 88 (26%) associated injuries. Based on this clinical experience, our goal was to develop an accurate and comprehensive description

  4. Ecology and Geography of Human Monkeypox Case Occurences Across Africa

    E-print Network

    Ellis, Christine K.; Carroll, Darin S.; Lash, R. Ryan; Peterson, A. Townsend; Damon, Inger K.; Malekani, Jean M.; Formenty, Pierre

    2012-04-01

    from West and Central Africa do not appear to occur under different environmental circumstances (Levine et al., 2007). We analyze a more-refined occurrence data set, utilizing more-diverse environmental parameters, in an attempt to shed addi- tional... (EM), virus culture, and serology; whereas PCR, EM, and tissue culture were used for case definition by the CDC (Learned et al., 2005; Levine et al., 2007). Overall, 404 human monkeypox cases were available and were referenced geographically...

  5. Scrap metal management issues associated with naturally occurring radioactive material

    Microsoft Academic Search

    K. P. Smith; D. L. Blunt

    1995-01-01

    Certain industrial processes sometimes generate waste by-products that contain naturally occurring radioactive material (NORM) at elevated concentrations. Some industries, including the water treatment, geothermal energy, and petroleum industries, generate scrap metal that may be contaminated with NORM wastes. Of these three industries, the petroleum industry probably generates the largest quantity of NORM-contaminated equipment, conservatively estimated at 170,000 tons per year.

  6. Treatment of spontaneously occurring veterinary tumors with photodynamic therapy

    Microsoft Academic Search

    Masoud Panjehpour; Alfred Legendre; Rick E. Sneed; Bergein F. Overholt

    1992-01-01

    Chloroaluminum phthalocyanine tetrasulfonate was administered intravenously (1.0 mg\\/kg) to client owned cats and a dog with spontaneously occurring squamous cell carcinoma of head and neck. Light was delivered 48 hours post injection of the photosensitizer. An argon- pumped dye-laser was used to illuminate the lesions with 675 nm light delivered through a microlens fiber and\\/or a cylindrical diffuser. The light

  7. Tribology of naturally occurring boric acid films on boron carbide

    Microsoft Academic Search

    A. Erdemir; C. Bindal; C. Zuiker; E. Savrun

    1996-01-01

    In this paper, we describe the formation and self-lubricating mechanisms of naturally occurring boric acid films on boron carbide (B4C) substrates. The sliding friction coefficients of yttria\\/partially stabilized zirconia pins against plain B4C substrates are quite high at 0.3–0.4, but are 6–10 times lower against the B4C substrates subjected to annealing at 800°C. We determined that this low friction was

  8. Can the Simultaneous Experience of Opposing Emotions Really Occur?

    Microsoft Academic Search

    Jack W. Brehm; Anca M. Miron

    2006-01-01

    Various investigators have proposed that people may feel simultaneous positive and negative affect. However, experimental\\u000a evidence from tests of a recent theory about the intensity of emotion (J. W. Brehm, 1999) suggests that even when they are\\u000a invited by the experimental design, positive and negative emotions do not occur at the same time. When people have been instigated\\u000a to feel

  9. A study of reactions occurring during the carbonitriding process

    Microsoft Academic Search

    J. Slycke; T. Ericsson

    1981-01-01

    The reactions occurring during the carbonitriding process have been studied theoretically and experimentally. A model for\\u000a the prediction of the amount of residual ammonia in the furnace from the process parameters, temperature, inlet gas composition\\u000a and flow-rate is presented. It takes account of ammonia decomposition and formation of the hydrogen cyanide. The ammonia addition\\u000a and decomposition also cause a dilution

  10. Potentiating the naturally occurring process for repair of damaged heart.

    PubMed

    Li, Ming; Ng, Shi Chung

    2014-01-01

    This article reviews the current progresses in application of both exogenous and endogenous progenitor cells/stem cells for cardiac repair, and the current understanding of the naturally-occurring process for physiological myocyte turnover and possibly cardiac repair. In particular the development of methods for potentiating the naturally-occurring mechanism for substantial repair of pathologically damaged cardiac tissues is discussed. In the last decade, tremendous efforts to identify both exogenous and endogenous progenitor cells/stem cells possessing capacities of differentiating into cardiac lineages have been made for potential cardiac repair. Although many impressive progresses have been made in the application of differently sourced progenitor cells/stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cell (iPS), bone marrow-derived mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), umbilical cord blood cells (UCBs), residential cardiac stem cells (CSCs), cardiac resident fibroblasts (CRFs), or adipose tissue-derived stem cells (ASCs) for repair of damaged heart, however, inevitable controversies exist concerning: (i) the immune compatibility of the exogenous donor progenitors/stem cells, (ii) the tumorigenicity with ESCs and iPS, and (iii) the efficiency of these exogenous or endogenous progenitors/ stem cells to acquire cardiac lineages to reconstitute the lost cardiac tissues. The recent recognition of some active small molecules that can induce myocardial regeneration to repair damaged heart tissues through enhancing the naturally-occurring cardiac-repair mechanism has offered the hope for clinical translation of the technology. Potentiating the naturally-occurring process for cardiac repair by administration of such small molecules has provided a promising strategy for reconstruction of damaged cardiac tissues after heart infarction. Therefore, this article is in favor of the notion that such small molecules with the activity of manipulating gene expressions in such a way of inducing endogenous stem cells to commit cardiac lineage differentiation and consequently myocardial regeneration may fulfill the dream of substantial repair of damaged heart. PMID:23844738

  11. Breast carcinomas occurring in young women (< 35 years) are different.

    PubMed Central

    Walker, R. A.; Lees, E.; Webb, M. B.; Dearing, S. J.

    1996-01-01

    One hundred and sixty-three breast carcinomas occurring in women aged between 26 and 44 years were examined for pathological features, oestrogen and progesterone receptor status, proliferation as determined by Ki-67 labelling and the presence of c-erbB-2 and p53 protein, and were compared with a control group of carcinomas from women in the 50-67 years age group. Carcinomas occurring in women aged under 35 years had a significantly high incidence of being poorly differentiated and of having high proliferation rates. This group also had a significantly high incidence of p53 protein staining. Carcinomas in the under 30 years age group had a lower incidence of oestrogen and progesterone receptor positivity. No differences were found in c-erbB-2-positive staining between the groups. Infiltrating lobular carcinomas were only identified in women aged 40 years and over. There was a higher incidence of a family history in the 35-44 years age group (18%) than in the under 35 years age group (11%). Breast carcinomas occurring in women aged under 35 years are more aggressive. An important finding is the high incidence of p53 positivity, which may indicate genetic instability. Images Figure 1 PMID:8956795

  12. Natural transformation of Campylobacter jejuni occurs beyond limits of growth.

    PubMed

    Vegge, Christina S; Brøndsted, Lone; Ligowska-Marz?ta, Ma?gorzata; Ingmer, Hanne

    2012-01-01

    Campylobacter jejuni is a human bacterial pathogen. While poultry is considered to be a major source of food borne campylobacteriosis, C. jejuni is frequently found in the external environment, and water is another well-known source of human infections. Natural transformation is considered to be one of the main mechanisms for mediating transfer of genetic material and evolution of the organism. Given the diverse habitats of C. jejuni we set out to examine how environmental conditions and physiological processes affect natural transformation of C. jejuni. We show that the efficiency of transformation is correlated to the growth conditions, but more importantly that transformation occurs at growth-restrictive conditions as well as in the late stationary phase; hence revealing that growth per se is not required for C. jejuni to be competent. Yet, natural transformation of C. jejuni is an energy dependent process, that occurs in the absence of transcription but requires an active translational machinery. Moreover, we show the ATP dependent ClpP protease to be important for transformation, which possibly could be associated with reduced protein glycosylation in the ClpP mutant. In contrast, competence of C. jejuni was neither found to be involved in DNA repair following DNA damage nor to provide a growth benefit. Kinetic studies revealed that several transformation events occur per cell cycle indicating that natural transformation of C. jejuni is a highly efficient process. Thus, our findings suggest that horizontal gene transfer by natural transformation takes place in various habitats occupied by C. jejuni. PMID:23049803

  13. Leaching Properties of Naturally Occurring Heavy Metals from Soils

    NASA Astrophysics Data System (ADS)

    Zhang, M.; Hoshino, M.; Yoshikawa, M.; Hara, J.; Sugita, H.

    2014-12-01

    The major threats to human health from heavy metals are associated with exposure to arsenic, lead, cadmium, chromium, mercury, as well as some other elements. The effects of such heavy metals on human health have been extensively studied and reviewed by international organizations such as WHO. Due to their toxicity, heavy metal contaminations have been regulated by national environmental standards in many countries, and/or laws such as the Soil Contamination Countermeasures Act in Japan. Leaching of naturally occurring heavy metals from the soils, especially those around abandoned metal mines into surrounding water systems, either groundwater or surface water systems, is one of the major pathways of exposure. Therefore, understanding the leaching properties of toxic heavy metals from naturally polluted soils is of fundamentally importance for effectively managing abandoned metal mines, excavated rocks discharged from infrastructure constructions such as tunneling, and/or selecting a pertinent countermeasure against pollution when it is necessary. In this study, soil samples taken from the surroundings of abandoned metal mines in different regions in Japan were collected and analyzed. The samples contained multiple heavy metals such as lead, arsenic and chromium. Standard leaching test and sequential leaching test considering different forms of contaminants, such as trivalent and pentavalent arsenics, and trivalent and hexavalent chromiums, together with standard test for evaluating total concentration, X-ray Fluorescence Analysis (XRF), X-ray diffraction analysis (XRD) and Cation Exchange Capacity (CEC) tests were performed. In addition, sequential leaching tests were performed to evaluate long-term leaching properties of lead from representative samples. This presentation introduces the details of the above experimental study, discusses the relationships among leaching properties and chemical and mineral compositions, indicates the difficulties associated with remediation of naturally polluted sites, and emphasizes the importance of risk-based countermeasures against naturally occurring heavy metals. Keywords: Leaching properties, Control Factor, Naturally Occurring Heavy Metals, Lead, Arsenic, Chromium

  14. An update on antitumor activity of naturally occurring chalcones.

    PubMed

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. PMID:23690855

  15. Expansion series of integral functions occurring in unsteady aerodynamics

    NASA Technical Reports Server (NTRS)

    Ueda, T.

    1982-01-01

    Attention is given to two real integral functions which occur in the kernel of singular integral equations for subsonic unsteady lifting surfaces. The arguments k, r, and X of the functions correspond to the reduced frequency, spanwise distance, and modified coordinate in the flow direction, respectively. The value of the parameter nu in the functions depends on geometrical conditions. The considered investigation has the objective to present a series for general values of the nonnegative integer nu in order to compute efficiently the integral functions. The approach makes it possible to avoid any approximation or numerical quadrature.

  16. Emissions of naturally occuring radioactivity: Stauffer elemental phosphorus plant

    SciTech Connect

    Andrews, V.E.

    1982-11-01

    Naturally occurring radioactivity was measured in the atmospheric emissions and process materials of a thermal phosphate (elemental phosphorus) plant. Representative exhaust stack samples were collected from each process in the plant. The phosphate ore contained about 120 parts per million uranium. The radioactivity emitted in greatest quantity was radon-222 with an annual release from the plant of 8.3 curies. Emissions of lead-210 and polonium-210 were measured at 280 and 200 millicuries per year. Annual emissions of each of the other radionuclides of the uranium decay chain were estimated to be 4.2 millicuries. The slag pile was determined not to be a source of radon.

  17. Acute ocular myositis occurring under etanercept for rheumatoid arthritis.

    PubMed

    Couderc, Marion; Mathieu, Sylvain; Tournadre, Anne; Dubost, Jean-Jacques; Soubrier, Martin

    2014-10-01

    Ocular myositis is a rare disorder characterized by inflammation of single or multiple extra-ocular eye muscles presenting with painful diplopia and/or ophthalmoplegia. The etiology remains obscure and it is rarely associated with rheumatoid arthritis. We here reported the case of a 61-year-old woman treated by TNF-? blockade, namely etanercept, for rheumatoid arthritis for ten years who developed an acute ocular myositis. The patient improved after etanercept was stopped and initiation of high doses of corticosteroids. To our knowledge, this is the second report of ocular myositis occurring under TNF-? blockade treatment for rheumatoid arthritis. PMID:24746476

  18. Amino acid preferences of small, naturally occurring polypeptides.

    PubMed

    Villar, H O; Koehler, R T

    2000-03-01

    An analysis of amino acid composition of small, naturally occurring peptides ranging in size from 3 to 50 residues has been carried out. The purpose of the study is to determine whether differential trends in amino acid usage exist for small peptides compared to larger polypeptides and proteins. Results indicate that Cys, Trp, and Phe are substantially more frequent in peptides compared to their abundance in proteins at large. Aliphatic hydrophobic residues, particularly Leu and Ile, are somewhat underrepresented, while the frequency of Glu is significantly reduced. The shorter peptides are also more frequently neutral and become increasingly charged as their size increases. PMID:10679627

  19. MMP-Dependent Shedding of ICAM-5 Occurs With LTP

    PubMed Central

    Conant, Katherine; Wang, Yue; Szklarczyk, Arek; Dudak, Amanda; Mattson, Mark P.; Lim, Seung T.

    2010-01-01

    Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that can be released or activated in a neuronal activity dependent manner. Although pathologically elevated levels of MMPs may be synaptotoxic, physiologically appropriate levels of MMPs may instead enhance synaptic transmission. MMP inhibitors can block long term potentiation (LTP), and at least one family member can affect an increase in the volume of dendritic spines. While the mechanism by which MMPs affect these changes is not completely understood, one possibility is that the cleavage of specific synaptic cell adhesion molecules plays a role. In the present study, we have examined the ability of neuronal activity to stimulate rapid MMP dependent shedding of the intercellular adhesion molecule-5 (ICAM-5), a synaptic adhesion molecule that is thought to inhibit the maturation and enlargement of dendritic spines. Since such cleavage would likely occur within minutes if it were relevant to a process such as LTP, we focused on post stimulus time points of thirty minutes or less. We show that NMDA can stimulate rapid shedding of ICAM-5 from cortical neurons in dissociated cell cultures and that such shedding is diminished by pretreatment of cultures with inhibitors that target MMP-3 and -9, proteases thought to influence synaptic plasticity. Additional studies suggest that MMP mediated cleavage of ICAM-5 occurs at amino acid 780, so that the major portion of the ectodomain is released. Since reductions in ICAM-5 have been linked to changes in dendritic spine morphology that are associated with LTP, we also examined the possibility that MMP dependent ICAM-5 shedding occurs following high frequency tetanic stimulation of hippocampal slices. Results show that the shedding of ICAM-5 occurs in association with LTP, and that both LTP and the associated ICAM-5 shedding are reduced when slices are pretreated with an MMP inhibitor. Together, these findings suggest that neuronal activity is linked to the shedding of a molecule that may inhibit dendritic spine enlargement and that MMPs can affect this change. While further studies will be necessary to determine the extent to which cleavage of ICAM-5 in particular contributes to MMP dependent LTP, our data support an emerging body of literature suggesting that MMPs are critical mediators of synaptic plasticity. PMID:20045450

  20. Emissions of naturally occurring radioactivity: fireclay mine and refractory plant

    SciTech Connect

    Andrews, V.E.

    1981-02-01

    Atmospheric emissions of naturally occurring radioactivity were measured at a fireclay mine and the associated plant that produces refractory brick products. The only significant radioactive emission from the mine was radon-222. An analysis of the ore radioactivity and surface area of the mine indicated that the radon released is comparable to that from any similar surface area of similar radioactivity. The major particulate radioactivity from the refractory operation was polonium-210, released as the brick was fired. Approximately 26 percent of the polonium-210 in green brick was driven off in the kilns.

  1. The sensitizing capacity of chimaphilin, a naturally-occurring quinone.

    PubMed

    Hausen, B M; Schiedermair, I

    1988-09-01

    Chimaphilin is a yellow naphthoquinone which occurs naturally in various chimaphila and Pyrola species. In Chimaphila umbellata (winter green) and C. maculata, it is a major constituent. Folk medicine recommends the leaves of Chimaphila species as a topical application to treat skin diseases. Since 1887, winter green is claimed to have caused dermatitis and to have been responsible for "idiosyncrasy". Experimental sensitization using the open epicutaneous as well as Freund's complete adjuvant technique has now revealed that chimaphilin is a moderate contact sensitizer. PMID:3191678

  2. Naturally occurring crystalline phases: analogues for radioactive waste forms

    SciTech Connect

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  3. On the mechanical friction losses occurring in automotive differential gearboxes.

    PubMed

    Antoni, Grégory

    2014-01-01

    In the automobile industry, the mechanical losses resulting from friction are largely responsible for various kinds of surface damage, such as the scuffing occurring in some mechanical assemblies. These scuffing processes seem to be due to a local loss of lubrication between certain mechanical elements of the same assembly, leading to a sharp increase in the friction, which can lead to a surface and volume damage in some of them, and even can cause, in the worst case, the whole destruction of the mechanical system if it has continued to operate. Predicting and checking the occurrence of this kind of undesirable phenomena, especially in some principal systems of the vehicle, represents nowadays, a crucial challenge in terms of automobile reliability and safety. This study focuses on the mechanical friction losses liable to occur in differential automobile gearboxes, which can lead in the long term to the scuffing of these mechanical systems. The friction losses involved were modeled, using a simple analytical approach, which is presented and discussed. PMID:24719579

  4. Naturally Occurring Radioactive Materials in Cargo at US Borders

    SciTech Connect

    Kouzes, Richard T.; Ely, James H.; Evans, John C.; Hensley, Walter K.; Lepel, Elwood A.; McDonald, Joseph C.; Schweppe, John E.; Siciliano, Edward R.; Strom, Daniel J.; Woodring, Mitchell L.

    2006-01-01

    In the U.S. and other countries, large numbers of vehicles pass through border crossings each day. The illicit movement of radioactive sources is a concern that has resulted in the installation of radiation detection and identification instruments at border crossing points. This activity is judged to be necessary because of the possibility of an act of terrorism involving a radioactive source that may include any number of dangerous radionuclides. The problem of detecting, identifying, and interdicting illicit radioactive sources is complicated by the fact that many materials present in cargo are somewhat radioactive. Some cargo contains naturally occurring radioactive material or technologically-enhanced naturally occurring radioactive material that may trigger radiation portal monitor alarms. Man-made radioactive sources, especially medical isotopes, are also frequently observed and produce alarms. Such nuisance alarms can be an operational limiting factor for screening of cargo at border crossings. Information about the nature of the radioactive materials in cargo that can interfere with the detection of radionuclides of concern is necessary. This paper provides such information for North American cargo, but the information may also be of use to border control officials in other countries. (PIET-43741-TM-361)

  5. Thermal resistance of naturally occurring airborne bacterial spores.

    PubMed Central

    Puleo, J R; Bergstrom, S L; Peeler, J T; Oxborrow, G S

    1978-01-01

    Simulation of a heat process used in the terminal dry-heat decontamination of the Viking spacecraft is reported. Naturally occurring airborne bacterial spores were collected on Teflon ribbons in selected spacecraft assembly areas and subsequently subjected to dry heat. Thermal inactivation experiments were conducted at 105, 111.7, 120, 125, 130, and 135 degrees C with a moisture level of 1.2 mg of water per liter. Heat survivors were recovered at temperatures of 135 degrees C when a 30-h heating cycle was employed. Survivors were recovered from all cycles studied and randomly selected for identification. The naturally occurring spore population was reduced an average of 2.2 to 4.4 log cycles from 105 to 135 degrees C. Heating cycles of 5 and 15 h at temperature were compared with the standard 30-h cycle at 111.7, 120, and 125 degrees C. No significant differences in inactivation (alpha = 0.05) were observed between 111.7 and 120 degrees C. The 30-h cycle differs from the 5-and 15-h cycles at 125 degrees C. Thus, the heating cycle can be reduced if a small fraction (about 10-3 to 10-4) of very resistant spores can be tolerated. PMID:727780

  6. Implementing Residential Integrated Treatment for Co-occurring Disorders.

    PubMed

    McKee, Shari A; Harris, Grant T; Cormier, Catherine A

    2013-07-01

    Objective: Much is now known about effective treatment for co-occurring substance abuse and psychiatric difficulties and many evidence-based practice recommendations have been disseminated. Implementation of these recommended interventions in daily clinical practice has been more of a struggle. This article describes successful implementation of integrated treatment for co-occurring disorders in a small residential program. Methods: A traditional 28-day addiction service was transformed into a 3-month integrated treatment program and 155 individuals with co-occurring disorders agreed to participate in its evaluation. The transformation entailed a completely new manualized service, training in a number of clinical interventions for all program clinicians, ongoing clinical supervision, and formal measurement of clients' backgrounds, substance abuse, quality of life, mental health symptoms, self-esteem, and satisfaction with the program. We also obtained collateral informants' reports on participants' symptoms, substance use, and quality of life. Fidelity to the treatment model was continuously assessed, as were participants' knowledge and skill acquisition. In addition, impact of the implementation on the program clinicians' morale and attitudes toward evidence-based practices was assessed, as was staff turnover and per diem costs. Results: Despite very problematic clinical and sociodemographic histories, the 86 participants who completed the program showed clinically significant mental health symptom improvement, acquisition of knowledge and skill, and high self-esteem and satisfaction with the program. Program fidelity, clinician morale, commitment to the program, and attitudes toward evidence-based practice were uniformly high. These successes were achieved while maintaining the lowest per-inpatient day cost of all hospital inpatient units. Conclusions: The findings support the contention that evidence-based integrated treatment can be implemented with fidelity in regular clinical practice to the benefit of participants, staff, and the hospital. Our experience was that having a scientist-practitioner working as a staff member on the program to lead the implementation was a key element. Future reports will focus on longer-term follow-up of substance use and quality of life outcomes. PMID:23976887

  7. Thermoradiation Inactivation of Naturally Occurring Bacterial Spores in Soil

    PubMed Central

    Reynolds, Marcel C.; Lindell, Kermit F.; David, Thomas J.; Favero, Martin S.; Bond, Walter W.

    1974-01-01

    Samples of soil collected from the Kennedy Space Center near the spacecraft assembly facilities were found to contain microorganisms very resistant to conventional sterilzation techniques. The inactivation kinetics of the naturally occurring spores in soil were investigated by using dry heat and ionizing radiation, first separately and then simultaneously. Dry-heat inactivation kinetics of spores was determined at 105 and 125 C; radiation inactivation kinetics was determined for dose rates of 660 and 76 krads/h at 25 C. Simultaneous combinations of heat and radiation were then investigated at 105, 110, 115, 120, and 125 C, with a dose rate of 76 krads/h. Combined treatment was found to be highly synergistic, requiring greatly reduced radiation doses to accomplish sterilization of the population. PMID:4422167

  8. Geomagnetic field excursions occurred often during the last million years

    NASA Astrophysics Data System (ADS)

    ODP Leg 172 Scientific Party; Lund, Steve P.; Acton, Gary; Clement, Brad; Hastedt, Margaret; Okada, Mokoto; Williams, Trevor

    Scientists studying western North Atlantic Ocean deep-sea sediments have discovered that the Earth's magnetic field underwent 14 local excursions since the last global magnetic-field polarity reversal 780,000 years ago. These excursions coincide with similar excursions identified elsewhere on the planet—leading to the conclusion that excursions are global in nature, occur a significant portion of the time, and are an integral part of geomagnetic field secular variation between reversals. Excursions are defined [Verosub and Banerjee, 1977] as anomalous magnetic field directions whose equivalent virtual geomagnetic poles (VGPs) are more than 45° away from the North Geographic Pole, while VGPs within 45° of the North Geographic Pole are considered to be typical secular variation. (VGPs are calculated from local magnetic field directions which locate the magneticfield North Pole by assuming that the directions are caused by a simple dipole or bar magnet situated at the center of the Earth.)

  9. Terrestrial structured radio emissions occurring close to the equatorial regions

    NASA Astrophysics Data System (ADS)

    Boudjada, Mohammed Y.; Galopeau, Patrick H. M.; Sawas, Sami; Berthelier, Jean-Jacques

    2015-04-01

    We study the occurrence of terrestrial radio emissions observed by the electric field experiment (ICE) onboard DEMETER micro-satellite. We principally consider the ICE observations recorded in the HF frequency range between 10 kHz and 3.175 MHz. A dynamic spectrum is recorded each half-orbit with a time and frequency resolutions, respectively, in the order of 3.25 kHz and 2.048 sec. The terrestrial structured radio emission is found to occur when the satellite is approaching the equatorial region of the Earth. It appears as a structured narrow band 'continuum' with a positive or negative low frequency drift rate, less than 1 kHz/s. The bandwidth is, on average, of about 30 kHz. We derive from our investigation the beam and the probable location of the emission source. We discuss the origin of this terrestrial radio emission and its dependence, or not, on the solar and geomagnetic activities.

  10. A Novel Syndrome Definition Validation Approach for Rarely Occurring Diseases

    PubMed Central

    Silva, Julio C.; Shah, Shital C.; Rumoro, Dino P.; Hallock, Marilyn M.; Gibbs, Gillian S.; Waddell, Michael J.

    2013-01-01

    Objective To develop and test a novel syndrome definition validation approach for rarely occurring diseases. Introduction Early detection of rarely occurring but potentially harmful diseases such as bio-threat agents (e.g., anthrax), chemical agents (e.g., sarin), and naturally occurring diseases (e.g., meningitis) is critical for rapid initiation of treatment, infection control measures, and emergency response plans. To facilitate clinicians’ ability to detect these diseases, various syndrome definitions have been developed. Due to the rarity of these diseases, standard statistical methodologies for validating syndrome definitions are not applicable. Methods Syndrome definitions were developed by researchers for the Geographic Utilization of Artificial Intelligence in Real-Time for Disease Identification and Alert Notification (GUARDIAN) surveillance system (1). The main steps for validation of the syndrome definitions were: Partition of literature articles: Literature articles that described positive cases were randomly divided to generate detection (75% of articles) and testing (25% of articles) syndrome definitions.Synthetic case generation: Syndrome definitions and associated statistical measures were reverse engineered using probability of occurrence and inverse Gaussian function to generate potentially infinite positive artificial cases.Clinical filter application: To avoid clinically incompatible combinations of newly generated symptoms, rules based on clinically guided knowledge from emergency department (ED) physicians were applied. Steps 2 and 3 were repeated for both detection and testing syndrome definitions.Detection phase validation: ED negative case sample: Detection syndrome definitions were tested using a random sample of negative ED cases. Knowledge gained through false positive cases was utilized to modify the surveillance algorithms and system thresholds.10-fold cross-validation: Standard 10-fold cross-validation on detection articles of positive cases and ED negative cases was utilized to generate performance metrics. Suspected cases were reviewed by ED clinicians for threshold enhancement.Literature articles (n=1): The ability of syndrome definitions to correctly flag literature articles with n=1 case was documented.Testing phase validation: Testing sample: Synthetic positive cases generated from the testing articles along with another set of ED negative cases were evaluated by the respective syndrome definition. Suspected cases were clinically evaluated.Literature articles (n=1): Similar to detection step 4c, articles with n=1 were tested using syndrome definitions.True positive samples: When available, true positive cases from an ED were identified and sent through the GUARDIAN system.Multi-syndrome validation: A combined sample of positive cases of multiple syndromes and ED negative cases were evaluated for detection of individual syndromes among other similar syndromes. Results To demonstrate the validation approach, the anthrax syndrome definition was utilized. This syndrome definition was developed with 25 articles containing positive anthrax cases used for detection, and the remaining 11 articles used for testing. With a 10-fold cross validation of the detection phase, the initial results showed accuracy was 99.4% (false positive rate of 0.65% and false negative rate of 0.00%). The testing phase initial validation revealed 99.2% accuracy for the anthrax syndrome definition. Conclusions Syndrome specific synthetic samples that are validated through clinical filters allowed the generation of an unlimited number of positive cases. Correct identification by GUARDIAN of these cases indicates robust and reliable syndrome definitions. Utilization of these cases, in conjunction with adherence to a methodological process, was the cornerstone of the GUARDIAN syndrome definition validation approach. The validation approach was successfully demonstrated on anthrax and can be applied to other bio-threat agents, chemical agents, and naturally occurring diseases.

  11. Observe animations of processes that occur along plate boundaries

    NSDL National Science Digital Library

    TERC. Center for Earth and Space Science Education

    2003-01-01

    Here are three animations that reveal how tectonic plates move relative to each other at three types of plate boundaries--transform, convergent, and divergent boundaries. Key features such as the asthenosphere are labeled in the animations. In addition, each animation is equipped with movie control buttons that allow students to play, pause, and move forward and backward through each clip. The animation of a transform boundary shows the North American and Pacific plates sliding past one another, while an oceanic plate subducts under a continental plate producing volcanic activity in the convergent boundary animation. Two coordinated movie clips are used to demonstrate what occurs at a divergent boundary from different viewpoints. Copyright 2005 Eisenhower National Clearinghouse

  12. Duodenal diverticula occurring in a family--chance or inheritance?

    PubMed Central

    Sternberg, A.; Deutsch, A. A.; Kott, I.; Reiss, R.

    1984-01-01

    The incidence, aetiology and possible inheritance of duodenal diverticula remain controversial. These aspects are discussed through the presentation of a family, in which duodenal diverticula occurred in a man and his two sons. To the best of our knowledge, this is the first such family documented in the medical literature. This familial occurrence may be attributed solely to the high incidence of duodenal diverticula in the general population (set by various authors at up to 14.2%), and, therefore, of no hereditary significance at all. We believe a screening study of the families of individuals with proven duodenal diverticula is most desirable, for it could shed light upon the controversial questions of incidence, aetiology, and inheritance patterns of duodenal diverticula. PMID:6431400

  13. Is anyone regulating naturally occurring radioactive material? A state survey

    SciTech Connect

    Gross, E.M.; Barisas, S.G.

    1993-08-01

    As far as we know, naturally occurring radioactive material (NORM) has surrounded humankind since the beginning of time. However, recent data demonstrating that certain activities concentrate NORM have increased concern regarding its proper handling and disposal and precipitated the development of new NORM-related regulations. The regulation of NORM affects the management of government facilities as well as a broad range of industrial processes. Recognizing that NORM regulation at the federal level is extremely limited, Argonne National Laboratory (ANL) conducted a 50-state survey to determine the extent to which states have assumed the responsibility for regulating NORM as well as the NORM standards that are currently being applied at the state level. Though the survey indicates that NORM regulation comprises a broad spectrum of controls from full licensing requirements to virtually no regulation at afl, a trend is emerging toward recognition of the need for increased regulation of potential NORM hazards, particularly in the absence of federal standards.

  14. Metabolic mechanism of phenyllactic acid naturally occurring in Chinese pickles.

    PubMed

    Li, Xingfeng; Ning, Yawei; Liu, Dou; Yan, Aihong; Wang, Zhixin; Wang, Shijie; Miao, Ming; Zhu, Hong; Jia, Yingmin

    2015-11-01

    Phenyllactic acid, a phenolic acid phytochemical with the antimicrobial activity, was rarely reported in food besides honey and sourdough. This study evidenced a new food source of phenyllactic acid and elucidated its metabolic mechanism. Phenyllactic acid naturally occurred in Chinese pickles with concentrations ranged from 0.02 to 0.30mM in 23 pickle samples including homemade and commercial ones. Then, lactic acid bacteria capable of metabolizing phenyllactic acid were screened from each homemade pickle and a promising strain was characterized as Lactobacillus plantarum. Moreover, the investigation of the metabolic mechanism of phenyllactic acid in pickles suggested that the yield of phenyllactic acid was positively related to the content of phenylalanine in food, and the addition of phenylalanine as precursor substance could significantly promote the production of phenyllactic acid. This investigation could provide some insights into the accumulation of phenyllactic acid in pickle for long storage life. PMID:25976820

  15. Using Administrative Data to Identify Naturally Occurring Networks of Physicians

    PubMed Central

    Landon, Bruce E.; Onnela, Jukka-Pekka; Keating, Nancy L.; Barnett, Michael L.; Paul, Sudeshna; O’Malley, A. James; Keegan, Thomas; Christakis, Nicholas A.

    2013-01-01

    Background Physicians naturally form networks. Networks could form a rational basis for Accountable Care Organizations (ACOs) for defined populations of Medicare beneficiaries. Objectives To use methods from network science to identify naturally occurring networks of physicians that might be best suited to becoming ACOs. Research Design, Subjects, and Measures Using nationally representative claims data from the Medicare program for CY 2006 on 51 hospital referral regions (HRRs), we used a network-science based community-detection algorithm to identify groups of physicians likely to have pre-established relationships. We examined the proportion of care delivered within communities and compared our results to potential ACOs organized around single hospitals. Results We studied 4,586,044 Medicare beneficiaries from 51 HRRs who were seen by 68,288 active physicians practicing in those HRRs. The median community-based network ACO had 150 physicians with 5,928 ties whereas the median hospital-based network ACO had 96 physicians with 3,276 ties. Seventy-seven percent of physician visits occurred with physicians in the community-based networks as compared with 56% with physicians in the hospital-based networks; however, just 8% of specialist visits were to specialists within the hospital-based networks as compared with 60% of specialist visits within the community-based networks. Some markets seemed better suited to developing ACOs based on network communities than others. Conclusions We present a novel approach to identifying groups of physicians that might readily function as ACOs. Organic networks identified and defined in this natural and systematic manner already have physicians who exhibit close working relationships, and who, importantly, keep the vast majority of care within the networks. PMID:23807593

  16. Naturally Occurring Animal Models of Human Hepatitis E Virus Infection

    PubMed Central

    Yugo, Danielle M.; Cossaboom, Caitlin M.; Meng, Xiang-Jin

    2014-01-01

    Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations. PMID:24936039

  17. Kinetic plasma processes occurring in the outer plasmasphere

    NASA Technical Reports Server (NTRS)

    Wilson, Gordon R.

    1992-01-01

    One area of data analysis work that was begun under this contract is the fitting of the perpendicular velocity distributions of equatorially trapped ions with a Kappa function. This type of characterization of the trapped ions will be very useful for comparison with velocity distributions produced by the model. A second area of data analysis is to study data from consecutive passes when DE 1's apogee was near the magnetic equator and the spacecraft was often skimming along nearly the same L shell. In 1982 three such periods occurred in May, June, and July. For these consecutive events we have Kp histories, density measurements from a number of sources (Whistler data, DE SFR, ISEE SFR) and consecutive samples of ion pitch angle distributions along field lines. It is clear from this data how the pitch angle distributions evolve during a flux tube refilling event. Our modeling of the flow of plasma along closed field lines is following two basic tracks. The first is a study of the basic refilling process without the effect of wave-particle heating near the equator or the effect of large or abrupt field-aligned electric potential drops. This model includes the effects of Coulomb self-collisions and collisions with the O+ ions in the topside ionosphere. The second track is a study of the effects of wave produced pitch-angle scattering and perpendicular heating occurring near the magnetic equator, in connection with the development of large potential drops that result from electron heating and the development of density gradients.

  18. Forecasting Seizures in Dogs with Naturally Occurring Epilepsy

    PubMed Central

    Stead, S. Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H.; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W. Douglas; Litt, Brian; Worrell, Gregory A.

    2014-01-01

    Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), low-gamma (30–70 Hz), and high-gamma (70–180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring. PMID:24416133

  19. Toxoplasma antigens recognized by naturally occurring human antibodies.

    PubMed Central

    Potasman, I; Araujo, F G; Remington, J S

    1986-01-01

    Sera of most adults have high agglutination test titers to Toxoplasma gondii whether or not the adults have other serological evidence of the infection. This finding has been attributed to the presence of naturally occurring antibodies to T. gondii. Consistent with this observation, we have recently noted that protein blots (PB) of sera of individuals not previously infected with T. gondii had immunoglobulin G (IgG) and IgM antibodies to antigens of the parasite. To further define the antigens recognized by these naturally occurring antibodies, we studied PB of sera of 44 adults and 9 children who had no serological evidence of the infection. Multiple antigens of T. gondii with molecular weights of 15,000 to greater than 205,000 were recognized by IgG and IgM natural antibodies of each of the sera. Although a relatively consistent pattern was noted on the IgM PB of the sera of the adults in the molecular weight range of 48,000 to 85,000, greater heterogeneity was noted on the IgG PB. The most common bands noted on the latter were of approximately 30,000 and 92,000 molecular weight. All of the PB obtained with the serial sera collected at yearly intervals from the children revealed bands; in some cases, new bands had appeared with time, and in others the pattern was constant. In children older than 8 years, the patterns of the PB were similar to those noted in PB of sera of the adults. Images PMID:3536997

  20. Naturally occurring mastitis disrupts developmental competence of bovine oocytes.

    PubMed

    Roth, Z; Dvir, A; Kalo, D; Lavon, Y; Krifucks, O; Wolfenson, D; Leitner, G

    2013-10-01

    We examined the effects of naturally occurring mastitis on bovine oocyte developmental competence in vitro. Specifically, we investigated the effects of intramammary infection on the ovarian pool of oocytes (i.e., follicle-enclosed oocytes) and their ability to undergo in vitro maturation, fertilization, and further development to the blastocyst stage. Culled Holstein cows (n=50) from 9 commercial dairy farms in Israel were allotted to 3 groups according to somatic cell count (SCC) records of the last 3 monthly milk tests as well as of quarter samples collected before slaughter: (1) low SCC (n=7), (2) medium SCC (n=16), or (3) high SCC (n=27). Means of SCC values differed among low-, medium-, and high-SCC groups: 148,000, 311,000 and 1,813,000 cell/mL milk, respectively. Milk yield and days in milk did not differ among the 3 groups. Bacterial isolates included coagulase-negative staphylococci, Escherichia coli, Streptococcus dysgalactiae, or no bacteria found. Ovaries were collected at the abattoir and brought to the laboratory. Cumulus oocyte complexes were recovered separately from each cow and subjected individually to in vitro maturation and fertilization, followed by 8d in culture. The number of aspirated oocytes did not differ among groups, with a range of 17 to 21 oocytes per cow. The proportion of oocytes that cleaved into 2- to 4-cell-stage embryos (86.1 ± 3.4%) did not differ among groups. In contrast, mean percentages of embryos developed to the blastocyst stage on d 7 and 8 after fertilization were less in both medium- and-high SCC groups than in the low-SCC group (5.6 ± 2.3 and 4.1 ± 1.8 vs. 18.1 ± 4.6%, respectively). Additional analysis indicated that cleavage and blastocyst-formation rates did not differ among the bacterial types in the low-, medium-, and high-SCC groups. These are the first results to demonstrate that naturally occurring mastitis disrupts the developmental competence of the ovarian pool of oocytes, (i.e., oocytes at the germinal vesicle stage). The disruption was associated with elevation of SCC rather than bacterial type. The results may provide a partial explanation for the low fertility of cows that have contracted mastitic pathogens before insemination. PMID:23957998

  1. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  2. Volatile analysis of ground almonds contaminated with naturally occurring fungi.

    PubMed

    Beck, John J; Mahoney, Noreen E; Cook, Daniel; Gee, Wai S

    2011-06-01

    Aflatoxigenic aspergilli inflict major economic damage to the tree nut industry of California, with the highest negative impact to almonds. Aspergilli and fungi in general are known to emit volatiles in varying quantity and composition dependent upon their growth media. The goal of the study was to determine the volatile emission of whole and blanched almonds that had been picked out and labeled as inedible by processors. The aflatoxin content and number of colony forming units of each sample were also determined. A total of 23 compounds were consistently detected and identified. Several volatiles from the blanched almonds demonstrated significant increases when compared to the emissions of whole almonds. Several of these volatiles are considered fatty acid decomposition products and included hexanal, heptanal, octanal, nonanal, 3-octen-2-one, tetramethylpyrazine, and decanal. The almond samples investigated were characteristic of a typical postharvest environment and illustrative of potential contamination within a stockpile or transport container. Volatiles indicative of fatty acid decomposition were predominant in the samples that underwent some form of blanching. The emission amounts of hexanal, heptanal, octanal, and hexanoic acid increased 3-fold in samples contaminated with aflatoxin; however, due to variability between samples they could not be considered as indicator volatiles for aflatoxin content. The emission profile of volatiles from almond kernels contaminated with naturally occurring aspergilli and associated fungi is heretofore unreported. PMID:21528918

  3. Documentation of Associated Injuries Occurring With Radial Head Fracture

    PubMed Central

    van Riet, Roger P.

    2008-01-01

    We believe a better way is needed to accurately describe the spectrum of associated injuries that commonly occur in conjunction with a radial head fracture. A review of our institution’s experience with 333 radial head fractures from 1997 to 2002 documented 88 (26%) associated injuries. Based on this clinical experience, our goal was to develop an accurate and comprehensive description of associated injuries. A shorthand suffix method first recognizes the type of radial head fracture with the traditional Mason classification, followed by abbreviations designating the articular injuries, coronoid (c) and olecranon (o), and the ligamentous injuries, lateral collateral ligament (l), medial collateral ligament (m), and distal radioulnar joint (d). The proposed system offers a logical and reproducible (98%) extension of the current Mason fracture classification to document the presence of additional articular and ligamentous injuries. This provides an opportunity to standardize the communication of fracture type with further details of other injuries that ultimately can help with better understanding of treatment outcome based on the precise injury complex. PMID:18196384

  4. Naturally occurring mutants inform SHBG structure and function.

    PubMed

    Wu, Tsung-Sheng; Hammond, Geoffrey L

    2014-07-01

    SHBG transports and regulates the activities of androgens and estrogens. Several single nucleotide polymorphisms in the human SHBG gene have been linked to sex steroid-dependent diseases, including those associated with the metabolic syndrome. The N-terminal laminin G-like domain of SHBG includes binding sites for calcium, sex steroids, and fibulin family members, as well as a dimerization domain. We have found that 8 of 18 uncharacterized nonsynonymous single nucleotide polymorphisms within this domain alter the production or biochemical properties of SHBG in ways not previously recognized. O-Linked glycosylation at Thr7 is disrupted in SHBG T7N, whereas abnormal glycosylation of SHBG G195E limits its secretion. Three SHBG mutants (R135C, L165M, and E176K) bind estradiol with abnormally high affinity. SHBG R135C also has an increased interaction with fibulin-2. Two different substitutions within the dimer interface at R123 (R123H and R123C) reduce the affinity for 5?-dihydrotestosterone, while increasing the relative binding affinity for estradiol. SHBG T48I is defective in calcium binding, which leads to a defect in dimerization, reduced affinity for sex steroids, and an enhanced interaction with fibulin-2, which can all be restored by calcium supplementation. These naturally occurring mutants provide insight into SHBG structure and function, and defects in SHBG production or function need to be considered in the context of its utility as a biomarker of diseases. PMID:24892637

  5. Application of the Commission's recommendations to naturally occurring radioactive material.

    PubMed

    Lecomte, J-F

    2015-06-01

    Since publication of the 2007 Recommendations (ICRP Publication 103), the International Commission on Radiological Protection has focused on preparing a series of publications dedicated to different types of existing exposure situations, such as radon exposure, cosmic exposure in aviation, and exposure to naturally occurring radioactive material (NORM). The publication related to NORM will present the main types of corresponding activities, and describe the characteristics of NORM exposure. It will also develop a conceptual framework for the practical application of the Commission's system to NORM exposure. In particular, the publication will explain why NORM activities are generally considered to be existing exposure situations, and when some of them should be managed as planned exposure situations. It will indicate when the workers should be considered as occupationally exposed. It will also provide recommendations regarding application of the three principles of radiological protection. The need to consider the justification of the re-use or recycling of residues carefully will be highlighted. Guidance will be provided for selection of the reference level, and for implementation of the optimisation process through a graded approach including both prevention and mitigation of exposures. Flexibility will be recommended for the application of dose limits, notably when the situation is managed as a planned exposure situation. PMID:25816272

  6. Design of Bioactive Peptides from Naturally Occurring ?-Conotoxin Structures*

    PubMed Central

    Stevens, Marijke; Peigneur, Steve; Dyubankova, Natalia; Lescrinier, Eveline; Herdewijn, Piet; Tytgat, Jan

    2012-01-01

    To date, cone snail toxins (“conotoxins”) are of great interest in the pursuit of novel subtype-selective modulators of voltage-gated sodium channels (Navs). Navs participate in a wide range of electrophysiological processes. Consequently, their malfunctioning has been associated with numerous diseases. The development of subtype-selective modulators of Navs remains highly important in the treatment of such disorders. In current research, a series of novel, synthetic, and bioactive compounds were designed based on two naturally occurring ?-conotoxins that target Navs. The initial designed peptide contains solely 13 amino acids and was therefore named “Mini peptide.” It was derived from the ?-conotoxins KIIIA and BuIIIC. Based on this Mini peptide, 10 analogues were subsequently developed, comprising 12–16 amino acids with two disulfide bridges. Following appropriate folding and mass verification, blocking effects on Navs were investigated. The most promising compound established an IC50 of 34.1 ± 0.01 nm (R2-Midi on Nav1.2). An NMR structure of one of our most promising compounds was determined. Surprisingly, this structure does not reveal an ?-helix. We prove that it is possible to design small peptides based on known pharmacophores of ?-conotoxins without losing their potency and selectivity. These data can provide crucial material for further development of conotoxin-based therapeutics. PMID:22773842

  7. Sequestering Naturally Occurring Liquid Carbon Dioxide in the Deep Ocean

    NASA Astrophysics Data System (ADS)

    Capron, M. E.

    2008-12-01

    Liquid carbon dioxide has been found as shallow as 1,500 meters in seafloor ooze. Did the liquid carbon dioxide originate from volcanic activity? Or did bacteria convert organic matter, which started as atmospheric carbon dioxide, into methane and liquid carbon dioxide? At typical ocean temperatures carbon dioxide coming out of solution below 600 meters will be liquid. Therefore, one likely mechanism for generating liquid carbon dioxide in seafloor ooze is the bacterial decomposition of organic matter. This paper examines quantitative and qualitative bacterial decomposition of aquatic biomass, with an emphasis on assessing and demonstrating feasibility. Calculations suggest natural processes sequestering liquid carbon dioxide in the seafloor can be sustainably increased to decrease atmospheric carbon dioxide concentrations. First, algae growing on the ocean surface absorb carbon dioxide. The algae are then gathered into a submerged container. Naturally occurring bacteria will digest the algae producing methane, liquid carbon dioxide, and ammonium. The ammonium can be recycled as a nutrient for growing more algae. Bacterial decomposition continues in dilute solutions with any biomass. The process does not require any particular biomass. Also, concentrating the biomass by removing water is not essential. The buoyancy provided by water allows relatively inexpensive tension fabric structures to contain the dilute algae and decomposition products. Calculations based on algae growth in open ponds and experience with bacterial decomposition at 1 to 5 bar pressures suggest the economics of the associated macro-algae growing and harvesting can favor increasing ocean species diversity.

  8. Predictive model of squeal noise occurring on a laboratory brake

    NASA Astrophysics Data System (ADS)

    Giannini, Oliviero; Sestieri, Aldo

    2006-09-01

    This paper on brake squeal instability presents a reduced order model of a laboratory brake considered in a previous paper, and presents a description of the squeal mechanism occurring during experiments. The model uses the modal parameters of the laboratory brake components, the disc and the caliper, when they are not in contact between them. Successively, the caliper and the disc are put in contact through the pad that is modeled as a one degree of freedom system while the Coulomb law models the friction interaction between them. No stick slip motion of the pad is considered, because it was not observed in the experimental tests. As a result the model is linear and particularly suited for a parametric analysis. The stability of the model is studied by a complex eigenvalue analysis and the obtained results show a good agreement with the experimental data, provided that the key parameters of the model are consistent with the experimental set-up. The key role of the disc and the pad dynamics are discussed.

  9. Scrap metal management issues associated with naturally occurring radioactive material

    SciTech Connect

    Smith, K.P.; Blunt, D.L.

    1995-08-01

    Certain industrial processes sometimes generate waste by-products that contain naturally occurring radioactive material (NORM) at elevated concentrations. Some industries, including the water treatment, geothermal energy, and petroleum industries, generate scrap metal that may be contaminated with NORM wastes. Of these three industries, the petroleum industry probably generates the largest quantity of NORM-contaminated equipment, conservatively estimated at 170,000 tons per year. Equipment may become contaminated when NORM-containing scale or sludge accumulates inside water-handling equipment. The primary radionuclides of concern in these NORM wastes are radium-226 and radium-228. NORM-contaminated equipment generated by the petroleum industry currently is managed several ways. Some equipment is routinely decontaminated for reuse; other equipment becomes scrap metal and may be disposed of by burial at a licensed landfill, encapsulation inside the wellbore of an abandoned well, or shipment overseas for smelting. In view of the increased regulatory activities addressing NORM, the economic burden of managing NORM-contaminated wastes, including radioactive scrap metal, is likely to continue to grow. Efforts to develop a cost-effective strategy for managing radioactive scrap metal should focus on identifying the least expensive disposition options that provide adequate protection of human health and the environment. Specifically, efforts should focus on better characterizing the quantity of radioactive scrap available for recycle or reuse, the radioactivity concentration levels, and the potential risks associated with different disposal options.

  10. Oligodontia and curly hair occur with ectodysplasin-a mutations.

    PubMed

    Lee, K E; Ko, J; Shin, T J; Hyun, H K; Lee, S H; Kim, J W

    2014-04-01

    Oligodontia is the developmental absence of more than 5 permanent teeth except for the third molar. Familial oligodontia can occur as an isolated form or as part of a genetic syndrome. Mutations in the MSX1, PAX9, AXIN2, EDA, and WNT10A genes have been identified in familial non-syndromic oligodontia. Ectodermal dysplasia is a group of syndromes involving abnormalities of the ectodermal structures and is comprised of more than 150 different forms. Mutations in the ectodysplasin-A (EDA) gene have been associated with X-linked hypohidrotic ectodermal dysplasia, and partial disruption of the EDA signaling pathway has been shown to cause an isolated form of oligodontia. We identified 2 X-linked oligodontia families and performed mutational analysis of the EDA gene. The mutational analysis revealed 2 novel EDA mutations: c.866G>T, p.Arg289Leu and c.1135T>G, p.Phe379Val (reference sequence NM_001399.4). These mutations were perfectly segregated with oligodontia and curly hair within each family and were not found in the 150 control X-chromosomes with the same ethnic background and in the exome variant server. This study broadens the mutational spectrum of the EDA gene and the understanding of X-linked oligodontia with curly hair. PMID:24487376

  11. Solution of naturally-occurring glasses in the geological environment

    SciTech Connect

    Glass, B.P.

    1982-12-01

    As part of a study to investigate the feasibility of putting nuclear wastes in glass containers and burying them on land or dumping them in the ocean, we have made a study of the amount of solution experienced by naturally occurring glasses from two land sites and thirty-four deep-sea sites. The glasses used in this study are microtektites from three strewn fields (Australasian, Ivory Coast, and North American) and from the Zhamanshin impact crater in southern Siberia. The microtektites range in age from 0.7 to 35 m.y. and they have a wide range in composition. Although several criteria for determining the amount of solution were considered, most of the conclusions are based on two criteria: (1) width of cracks, and (2) elevation of silica-rich inclusions above the adjacent microtektite surface. The amount of solution was determined for about 170 microtektites; and measured amounts of solution range from 0.2 to at least 28 {mu}m, but most are less than 5 {mu}m. There appears to be no systematic relationship between age and amount of solution. 21 refs., 7 tabs.

  12. Retinoic acid receptor agonist activity of naturally occurring diterpenes.

    PubMed

    Tanabe, Hiroki; Yasui, Tomohiro; Kotani, Hitoshi; Nagatsu, Akito; Makishima, Makoto; Amagaya, Sakae; Inoue, Makoto

    2014-06-15

    Recent accumulating evidence indicates that all-trans retinoic acid (ATRA) may be useful for preventing or treating inflammation, allergy, and autoimmune diseases, despite its severe side effects. In this study, screening of 99 crude drugs for retinoic acid receptor (RAR) ligands by luciferase reporter assay demonstrated that the methanol extract of Aralia cordata Rhizoma most effectively activates the transcriptional activity of RAR?. Pimaradienoic acid (ent-pimara-8(14),15-dien-19-oic acid) was subsequently isolated as the constituent capable of activating RAR. Pimaric acid and abietic acid, which have similar structures to pimaradienoic acid, were also found to be novel RAR agonists, although abietic acid only slightly activated peroxisome proliferator-activated receptor gamma. These three natural RAR agonists with diterpene structures, while structurally different from ATRA, were able to increase the mRNA levels of the constitutive androstane receptor in HepG2 cells, induce F9 cell differentiation followed by Cyp26a1 mRNA expression, and differentiate HL-60 cells via RAR activation in a different manner from ATRA. These results demonstrate that some diterpenes exist as naturally occurring RAR agonists and that the differences in chemical structure between ATRA and these diterpenes may induce distinct gene activation and a specific cellular response. PMID:24799257

  13. Laboratory observation of naturally occurring dust-density waves

    NASA Astrophysics Data System (ADS)

    Flanagan, Tim; Goree, John

    2010-11-01

    Dust-density waves are electrostatic compressional waves that propagate in dusty plasma. Compared to the more familiar ion-acoustic waves, in dust-density waves, inertia is provided by dust particles (instead of ions) while pressure is provided by the ions as well as electrons (not just electrons). In a laboratory experiment, we observed dust density waves in a 3D void-free dusty plasma. The waves occur naturally due to an ion-flow instability. Dust particles (4.8 microns) are levitated within the volume of a glass box that rests atop an electrode in a radio-frequency glow discharge plasma. Horizontal confinement of dust particles is provided by the plasma's natural electric field that is enhanced by the walls of the glass box, while vertical confinement is due to the electrode's sheath. We observed dust-density waves with planar wave fronts propagating in alignment with flowing ions. By directly imaging the dust particles with a 500 frame-per-second camera, we monitor the dust density modulations in both space and time. A typical wave propagates at 40 mm/s with a frequency of 24 Hz. In this work, we characterize these waves and their growth as they propagate.

  14. Explanation for naturally occurring supernumerary limbs in amphibians.

    PubMed

    Sessions, S K; Ruth, S B

    1990-04-01

    The occasional occurrence of high frequencies of limb abnormalities, including extra limbs, in natural populations of amphibians has long been a puzzle. In this paper we report the discovery of a population in which such limb abnormalities appear to be caused by a parasitic flatworm (trematode) that uses amphibians as intermediate hosts. The cercarial larval stage of the trematode attacks amphibians, penetrating the skin to form cysts (metacercariae). The cysts are preferentially localized in the cloacal region, including the developing hind limb regions in larvae of both frogs (Hyla regilla) and salamanders (Ambystoma macrodactylum). A wide range of limb abnormalities are seen, including duplicated limb structures ranging from extra digits to several extra whole limbs. We hypothesize that these limb abnormalities result from localized regulatory responses of developing and regenerating limb tissues to mechanical disruption caused by the trematode cysts. We have tested this idea by implanting inert resin beads into developing limb buds of frogs and salamanders. Since this treatment can cause supernumerary limb structures, our hypothesis is sufficient to explain the naturally occurring extra limbs. PMID:2348164

  15. Multisensor analysis of recent heavy precipitation events occurred over Italy

    NASA Astrophysics Data System (ADS)

    Dietrich, Stefano; Panegrossi, Giulia; Di Paola, Francesco; Sanò, Paolo; Casella, Daniele; Petracca, Marco; Baldini, Luca; Roberto, Nicoletta; Mugnai, Alberto

    2013-04-01

    Satellite-based microwave and infrared measurements, together with 3-D lightning data provided by LINET network, will be jointly used to describe and analyze the microphysical characteristics and the evolution of recent severe storms occurred over Italy. In addition, passive microwave precipitation retrieval algorithms (Sanò et al., 2013, Casella et al., 2013, Mugnai et al., 2013, Smith et al., 2013) will be applied to obtain instantaneous rain fields corresponding to LEO overpasses, while IR and lightning data will be also used to reproduce the time continuous evolution of precipitation (Dietrich et al., 2011, Di Paola et al., 2012). For two heavy precvipitation events observed during the HyMeX (Hydrological cycle in the Mediterranean eXperiment) SOP1.1 in the Central Italy target area in October 2012, the Polarimetric C-band radar (ISAC/CNR Polar 55C) located in Rome will provide also the ground reference for precipitation, microphysics structure, and volumetric distribution of precipitating clouds. Future perspectives of the utilization of the above techniques in supporting the operational activity of the Italian Civil Protection department will be discussed with the help of advanced graphical multisensor representation of real time remotely sensed quantities.

  16. Visualizing Global Earthquakes â Where and Why do Earthquakes Occur?

    NSDL National Science Digital Library

    Cara Harwood

    This screenshot from this visualization shows a map of tectonic plate boundaries. The visualization transitions between global earthquake distribution to a map of plate boundaries, to clearly illustrate how they are related. This visualization also includes an overview of the distribution and magnitude of earthquakes at different types of plate boundaries. Click the image to enlarge or view the MP4 movie ( 31.1MB Jul27 11). The purpose of this activity is to introduce students to the distribution of earthquakes at and below the surface of earth and how their distribution is related to the geometry and type of plate boundaries. Because the depth of earthquakes can be difficult for students to visualize in 2D representations, this activity allows students to visualize the 3D distribution of earthquakes within Earth's surface, which is essential for understanding how different types of earthquakes occur in different tectonic settings. Talking points and questions are included to use this visualization as part of an interactive lecture. In addition to playing back the visualization, instructors can also download the visualization software and data set and explore it themselves.

  17. Biophysical characterization of naturally occurring titin M10 mutations.

    PubMed

    Rudloff, Michael W; Woosley, Alec N; Wright, Nathan T

    2015-06-01

    The giant proteins titin and obscurin are important for sarcomeric organization, stretch response, and sarcomerogenesis in myofibrils. The extreme C-terminus of titin (the M10 domain) binds to the N-terminus of obscurin (the Ig1 domain) in the M-band. The high-resolution structure of human M10 has been solved, along with M10 bound to one of its two known molecular targets, the Ig1 domain of obscurin-like. Multiple M10 mutations are linked to limb-girdle muscular dystrophy type 2J (LGMD2J) and tibial muscular dystrophy (TMD). The effect of the M10 mutations on protein structure and function has not been thoroughly characterized. We have engineered all four of the naturally occurring human M10 missense mutants and biophysically characterized them in vitro. Two of the four mutated constructs are severely misfolded, and cannot bind to the obscurin Ig1 domain. One mutation, H66P, is folded at room temperature but unfolds at 37°C, rendering it binding incompetent. The I57N mutation shows no significant structural, dynamic, or binding differences from the wild-type domain. We suggest that this mutation is not directly responsible for muscle wasting disease, but is instead merely a silent mutation found in symptomatic patients. Understanding the biophysical basis of muscle wasting disease can help streamline potential future treatments. PMID:25739468

  18. [Occurence of diarylheptanoids in Corylus species native to Hungary].

    PubMed

    Riethmüller, Eszter; Tóth, Gerg?; Alberti, Agnes; Végh, Krisztina; Béni, Szabolcs; Balogh, György Tibor; Kéry, Agnes

    2015-01-01

    Since the last decade naturally occurring diarylheptanoids have been in the focus of scientific interest due to their various. beneficial biological effects. Besides the outstanding importance of the curcuminoids isolated from members of the Curcuma genus (Zingiberaceae), several different diarylheptanoids identified in Alnus species (Betulaceae) have been proved to possess notable pharmacological effects. Chemoprotective, neuroprotective, hepatoprotective, antiviral, antibacterial, antiinflammatory and antioxidant activities suggest their potential role in clinical practice. The aim of our study was the phytochemical investigation of the Corylus (Betulaceae) species native to Hungary: the Common hazel (Corylus avellana L.), the Turkish hazel (Corylus colurna L.) and the Filbert (Corylus maxima Mill.) in order to characterise their phenolic-profile. Although these plants have been used in the traditional medicine for long time, literature data considering their phytochemical composition is limited to the flavonoid and hydroxycinnamic-acid derivatives of C. avellana leaves. No previous studies have been published reporting the presence of diarylheptanoid compounds in any of the Corylus species. Soxhlet extraction with solvents of increasing polarity was performed on the bark and leaves of the mentioned three Corylus species. The phenolic-profile of the methanolic and ethyl acetate extracts was investigated by HPLC-DAD-ESI-TOF-MS and HPLC-DAD-ESI-MS/MS methods. Altogether 37 different phenolic compounds were detected in the extracts: twenty diarylheptanoids (1-20), nine flavonols (21-29) and eight other phenolics: caffeic and quinic acid derivatives and flavanones (30-37). The main compounds of the extracts were identified as myricetin- quercetin- and kaempferol-3-O-rhanmosides. PMID:26137784

  19. Committed effective dose from naturally occuring radionuclides in shellfish

    NASA Astrophysics Data System (ADS)

    Khandaker, Mayeen Uddin; Wahib, Norfadira Binti; Amin, Yusoff Mohd.; Bradley, D. A.

    2013-07-01

    Recognizing their importance in the average Malaysian daily diet, the radioactivity concentrations in mollusc- and crustacean-based food have been determined for key naturally occuring radionuclides. Fresh samples collected from various maritime locations around peninsular Malaysia have been processed using standard procedures; the radionuclide concentrations being determined using an HPGe ?-ray spectrometer. For molluscs, assuming secular equilibrium, the range of activities of 238U (226Ra), 232Th (228Ra) and 40K were found to be 3.28±0.35 to 5.34±0.52, 1.20±0.21 to 2.44±0.21 and 118±6 to 281±14 Bq kg-1 dry weight, respectively. The respective values for crustaceans were 3.02±0.57 to 4.70±0.52, 1.38±0.21 to 2.40±0.35 and 216±11 to 316±15 Bq kg-1. The estimated average daily intake of radioactivity from consumption of molluscs are 0.37 Bq kg-1 for 238U (226Ra), 0.16 Bq kg-1 for 232Th (228Ra) and 18 Bq kg-1 for 40K; the respective daily intake values from crustaceans are 0.36 Bq kg-1, 0.16 Bq kg-1 and 23 Bq kg-1. Associated annual committed effective doses from molluscs are estimated to be in the range 21.3 to 34.7 ?Sv for 226Ra, 19.3 to 39.1 ?Sv for 228Ra and 17.0 to 40.4 ?Sv for 40K. For crustaceans, the respective dose ranges are 19.6 to 30.5 ?Sv, 22.0 to 38.4 ?Sv and 31.1 to 45.5 ?Sv, being some several times world average values.

  20. Does thermal convection occur in mammalian burrows during the night?

    NASA Astrophysics Data System (ADS)

    Ganot, Y.; Weisbrod, N.; Dragila, M. I.; Nachshon, U.

    2010-12-01

    Burrowing is a common habit of mammals in arid zones, yet knowledge of environmental conditions within animal burrows, and especially of the way burrows are ventilated, is scarce. The ventilation rate of a burrow controls air composition within the burrow by driving gas exchange between the lower part of the burrow where the animal typically lives, and the atmosphere. Ventilation can be achieved by the following mechanisms: (1) diffusion; (2) external winds; (3) movement of the inhabitant within the burrow (the 'piston-effect'); and (4) natural thermal convection, a process by which a natural thermal gradient between burrow and atmosphere creates a density gradient which induces air flow. Here we investigate the role of thermal convection in burrow ventilation. For this purpose, artificial burrows (65 cm in depth and 7 cm in diameter) were drilled in loess soil in the Negev Desert of Israel and a network of thermocouples was installed to continuously monitor and record temperature distribution within these burrows. The results show that free convection occurs on a daily basis during the night and early morning. During these times, burrow air temperature was warmer than atmospheric air, and temperature readings pointed to the regular occurrence of convection flow in a thermosyphon pattern. Volume fluxes were calculated based on analytical solution and empirical correlations. For the artificial burrows investigated, an average CO2 volume flux of about 15 liter/hour was calculated during the night when convective conditions prevailed. For comparison, CO2 volume flux by steady-state diffusion alone is 3 orders of magnitude lower.

  1. Why does rem sleep occur? A wake-up hypothesis.

    PubMed

    Klemm, W R

    2011-01-01

    Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses rapid eye movement (REM) to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, (1) when first going to sleep, the brain plunges into Stage N3 (formerly called Stage IV), a deep abyss of sleep, and, as the night progresses, the sleep is punctuated by episodes of REM that become longer and more frequent toward morning, (2) conscious-like dreams are a reliable component of the REM state in which the dreamer is an active mental observer or agent in the dream, (3) the last awakening during a night's sleep usually occurs in a REM episode during or at the end of a dream, (4) both REM and awake consciousness seem to arise out of a similar brainstem ascending arousal system (5) N3 is a functionally perturbed state that eventually must be corrected so that embodied brain can direct adaptive behavior, and (6) cortico-fugal projections to brainstem arousal areas provide a way to trigger increased cortical activity in REM to progressively raise the sleeping brain to the threshold required for wakefulness. This paper shows how the hypothesis conforms to common experience and has substantial predictive and explanatory power regarding the phenomenology of sleep in terms of ontogeny, aging, phylogeny, abnormal/disease states, cognition, and behavioral physiology. That broad range of consistency is not matched by competing theories, which are summarized herein. Specific ways to test this wake-up hypothesis are suggested. Such research could lead to a better understanding of awake consciousness. PMID:21922003

  2. Comparison of Antimicrobial Sensitivity to Older and Newer Quinolones versus Piperacillin-Tazobactam, Cefepime and Meropenem in Febrile Patients with Cancer in two Referral Pediatric Centers in Tehran, Iran

    PubMed Central

    Nateghian, AR.; Robinson, JL.; Vosough, P.; Navidinia, M.; Malekan, M.; Mehrvar, A.; Sobouti, B.; Bahadoran, P.; Gholinejad, Z.

    2014-01-01

    Background Infection in pediatric cancer patients has become a concerning problem due to increasing antimicrobial resistance. The goal of this study was to determine the antimicrobial resistance patterns of blood isolates from pediatric oncology patients in Iran to determine if there was significant resistance to quinolones Methods Children with cancer who were admitted with or developed fever during admission to Aliasghar Children’s Hospital or Mahak Hospitals July 2009 through June 2011 were eligible for enrollment. Two blood cultures were obtained. Antimicrobial sensitivity test was performed for ciprofloxacin, moxifloxacin, gatifloxacin, meropenem, cefepime, and piperacillin-tazobactam on isolates from children who were bacteremic. Results Blood cultures were positive for 38 episodes in 169 enrolled children but 9 episodes were excluded as blood cultures were thought to be contaminated, yielding a bacteremia rate of 29/160 (18%). The mean age of children and the stage of malignancy did not differ between those with and without bacteremia. Meropenem was the most likely antibiotic to cover isolates (97%) with cefepime having the lowest coverage rate (21%). Quinolone coverage ranged from 63% to 76%. Conclusion Quinolones may not be suitable for use as empiric therapy in febrile pediatric oncology patients in Iran. PMID:25045453

  3. Economic Analysis of Prophylactic Pegfilgrastim in Adult Cancer Patients Receiving Chemotherapy

    Microsoft Academic Search

    Adi Eldar-Lissai; Leon E. Cosler; Eva Culakova; Gary H. Lyman

    2008-01-01

    ObjectivesNeutropenia and its complications, including febrile neutropenia (FN), are a common side effect of cancer chemotherapy. Results of clinical trials showed that prophylactic use of granulocyte colony-stimulating factors (G-CSF) is effective in preventing FN. In this study, the cost effectiveness (measured as cost per quality-adjusted time [days]) of three treatment alternatives were evaluated: no G-CSF, filgrastim administered daily for 7–12

  4. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

    PubMed

    Maschmeyer, G; Carratalà, J; Buchheidt, D; Hamprecht, A; Heussel, C P; Kahl, C; Lorenz, J; Neumann, S; Rieger, C; Ruhnke, M; Salwender, H; Schmidt-Hieber, M; Azoulay, E

    2015-01-01

    Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, ?-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons. PMID:24833776

  5. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)†

    PubMed Central

    Maschmeyer, G.; Carratalà, J.; Buchheidt, D.; Hamprecht, A.; Heussel, C. P.; Kahl, C.; Lorenz, J.; Neumann, S.; Rieger, C.; Ruhnke, M.; Salwender, H.; Schmidt-Hieber, M.; Azoulay, E.

    2015-01-01

    Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, ?-d-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons. PMID:24833776

  6. Sarcocystis nesbitti Causes Acute, Relapsing Febrile Myositis with a High Attack Rate: Description of a Large Outbreak of Muscular Sarcocystosis in Pangkor Island, Malaysia, 2012

    PubMed Central

    Italiano, Claire M.; Wong, Kum Thong; AbuBakar, Sazaly; Lau, Yee Ling; Ramli, Norlisah; Syed Omar, Sharifah Faridah; Kahar Bador, Maria; Tan, Chong Tin

    2014-01-01

    Background From the 17th to 19th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak. Methodology/Principal Findings All retreat participants were identified, and clinical and epidemiological information was obtained via clinical review and self-reported answers to a structured questionnaire. Laboratory, imaging and muscle biopsy results were evaluated and possible sources of exposure, in particular water supply, were investigated. At an average of 9–11 days upon return from the retreat, 89 (97%) of the participants became ill. A vast majority of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia was present in 91% of patients. Facial swelling from myositis of jaw muscles occurred in 9 (10%) patients. The median duration of symptoms was 17 days (IQR 7 to 30 days; range 3 to 112). Out of 4 muscle biopsies, sarcocysts were identified in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one biopsy without observed sarcocyst. Non-Malaysians had a median duration of symptoms longer than that of Malaysians (27.5 days vs. 14 days, p?=?0.001) and were more likely to experience moderate or severe myalgia compared to mild myalgia (83.3% vs. 40.0%, p?=?0.002). Conclusions/Significance The similarity of the symptoms and clustered time of onset suggests that all affected persons had muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever reported, with the specific Sarcocystis species identified. The largely non-specific clinical features of this illness suggest that S. nesbitti may be an under diagnosed infection in the tropics. PMID:24854350

  7. electromagnetic wave does occur in the OLED sample. Hence, the superluminal effect may occur in the OLED sample as well. Next

    E-print Network

    Gürel, Levent

    electromagnetic wave does occur in the OLED sample. Hence, the superluminal effect may occur) that the index is effectively extremely large. The existence of ultra-high indices of refraction may sound in. CONCLUSION In conclusion, a novel high-speed-frequency electromagnetic char- acteristic of a power-OFF blue

  8. Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia

    PubMed Central

    Sadashiv, Santhosh K; Hilton, Christie; Khan, Cyrus; Rossetti, James M; Benjamin, Heather L; Fazal, Salman; Sahovic, Entezam; Shadduck, Richard K; Lister, John

    2014-01-01

    Acute myeloid leukemia (AML) patients aged ?60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m2/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20–30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m2/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13–724 days). Grade 3–4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1–2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m2/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML. PMID:25132519

  9. Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004.

    PubMed

    Hasle, Henrik; Abrahamsson, Jonas; Forestier, Erik; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur Gísli; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward

    2012-08-01

    There are no data on the role of postconsolidation therapy with gemtuzumab ozogamicin (GO; Mylotarg) in children with acute myeloid leukemia (AML). The NOPHO-AML 2004 protocol studied postconsolidation randomization to GO or no further therapy. GO was administered at 5 mg/m(2) and repeated after 3 weeks. We randomized 120 patients; 59 to receive GO. Survival was analyzed on an intention-to-treat basis. The median follow-up for patients who were alive was 4.2 years. Children who received GO showed modest elevation of transaminase and bilirubin without signs of veno-occlusive disease. Severe neutropenia followed 95% and febrile neutropenia 40% of the GO courses. Only a moderate decline in platelet count and a minor decrease in hemoglobin occurred. Relapse occurred in 24 and 25 of those randomized to GO or no further therapy. The median time to relapse was 16 months versus 10 months (nonsignificant). The 5-year event-free survival and overall survival was 55% versus 51% and 74% versus 80% in those randomized to receive GO or no further therapy, respectively. Results were similar in all subgroups. In conclusion, GO therapy postconsolidation as given in this trial was well tolerated, showed a nonsignificant delay in time to relapse, but did not change the rate of relapse or survival (clinicaltrials.gov identifier NCT00476541). PMID:22730539

  10. 15 CFR 270.320 - Entry and inspection of site where a building failure has occurred.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...inspection of site where a building failure has occurred. 270.320 Section 270.320...inspection of site where a building failure has occurred. When the Director establishes...inspect the site where the building failure has...

  11. 33 CFR 150.512 - What occurs during the weekly tests and inspections?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...What occurs during the weekly tests and inspections? 150.512...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.512 What occurs during the weekly tests and inspections? The...

  12. 33 CFR 150.512 - What occurs during the weekly tests and inspections?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...What occurs during the weekly tests and inspections? 150.512...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.512 What occurs during the weekly tests and inspections? The...

  13. 33 CFR 150.512 - What occurs during the weekly tests and inspections?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...What occurs during the weekly tests and inspections? 150.512...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.512 What occurs during the weekly tests and inspections? The...

  14. 33 CFR 150.513 - What occurs during the monthly tests and inspections?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...What occurs during the monthly tests and inspections? 150.513...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.513 What occurs during the monthly tests and inspections?...

  15. 33 CFR 150.512 - What occurs during the weekly tests and inspections?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...What occurs during the weekly tests and inspections? 150.512...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.512 What occurs during the weekly tests and inspections? The...

  16. 33 CFR 150.513 - What occurs during the monthly tests and inspections?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...What occurs during the monthly tests and inspections? 150.513...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.513 What occurs during the monthly tests and inspections?...

  17. 33 CFR 150.513 - What occurs during the monthly tests and inspections?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...What occurs during the monthly tests and inspections? 150.513...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.513 What occurs during the monthly tests and inspections?...

  18. 33 CFR 150.513 - What occurs during the monthly tests and inspections?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...What occurs during the monthly tests and inspections? 150.513...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.513 What occurs during the monthly tests and inspections?...

  19. 33 CFR 150.513 - What occurs during the monthly tests and inspections?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...What occurs during the monthly tests and inspections? 150.513...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.513 What occurs during the monthly tests and inspections?...

  20. 33 CFR 150.512 - What occurs during the weekly tests and inspections?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...What occurs during the weekly tests and inspections? 150.512...GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS...Specialty Equipment Frequency of Tests and Inspections § 150.512 What occurs during the weekly tests and inspections? The...

  1. Bloodstream infections in patients with hematological malignancies: which is more fatal – cancer or resistant pathogens?

    PubMed Central

    Gedik, Habip; ?im?ek, Funda; Kantürk, Arzu; Yildirmak, Taner; Arica, Deniz; Aydin, Demet; Demirel, Naciye; Yoku?, Osman

    2014-01-01

    Background The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. Methods In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. Results During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole. Conclusion BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible or probable invasive fungal infections with an absence of pulmonary findings due to increase azole resistance. PMID:25258539

  2. Risk of hospitalization for neutropenic complications of chemotherapy in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis: A retrospective cohort study

    Microsoft Academic Search

    Derek Weycker; Jennifer Malin; John Kim; Rich Barron; John Edelsberg; Alex Kartashov; Gerry Oster

    2009-01-01

    Background: In a meta-analysis of data from randomized trials, the risk of febrile neutropenia during myelosuppressive chemotherapy was reported to be lower with pegfilgrastim prophylaxis than filgrastim prophylaxis. However, there is limited information on the comparative effectiveness of these agents in clinical practice.Objective: This study was undertaken to compare the risks of hospitalization for neutropenic complications of chemotherapy in US

  3. TOXICITY OF A TRADITIONAL CHINESE MEDICINE, GANODERMA LUCIDUM, IN CHILDREN WITH CANCER

    Microsoft Academic Search

    Simerpal K Gill; Michael J Rieder

    Background Cancer is one of the most common severe diseases in Canadian children, and chemotherapy treatment leads to numerous, potentially fatal, adverse side effects including febrile neutropenia and leukopenia. In an attempt to prevent opportunistic infections, Ganoderma lucidum, a mushroom that has been used in Traditional Chinese Medicine for thousands of years, is being used by some people as an

  4. Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies?

    Microsoft Academic Search

    M Karthaus; C Rosenthal; A Ganser

    1999-01-01

    Oral mucositis is a major dose-limiting toxic effect of intensive cancer chemotherapy. Oral complications may lead to dose reduction or delay in further cancer treatment. Mucositis can be caused directly by cytotoxic effects and indirectly by sustained neutropenia after cytostatic therapy. An impaired mucosal barrier predisposes to life-threatening septic complications during aplasia. The prevalence of an oral focus in febrile

  5. An unusual cause of febrile hepatitis.

    PubMed

    Stelzer, Teresa; Kohler, Sibylle; Marques Maggio, Ewerton; Heuss, Ludwig Theodor

    2015-01-01

    We describe the case of a 51-year-old man with recently diagnosed ulcerative colitis who developed fever and elevated liver enzymes as well as cholestasis a few weeks after starting treatment with mesalazine. As no obvious cause was found and fever persisted, liver biopsy was performed and revealed granulomatous hepatitis. The patient recovered completely after cessation of mesalazine, so that a drug-induced granulomatous hepatitis after exclusion of other differential diagnoses in an extensive work up was assumed. The present case demonstrates that even though drug-induced liver injury due to mesalazine is rare, it should be considered in unclear cases and lead to prompt discontinuation of mesalazine. PMID:26113581

  6. Astrovirus MLB2 Viremia in Febrile

    E-print Network

    Wang, David

    Jiang, Carl J. Franz, George M. Weinstock, Gregory A. Storch, and David Wang Astroviruses cause diarrhea. The evaluation included a leukocyte count, with results (7.8 × 103 cells/mm3 ) within the reference values

  7. Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group

    PubMed Central

    Kim, J G; Sohn, S K; Chae, Y S; Song, H S; Kwon, K-Y; Do, Y R; Kim, M K; Lee, K H; Hyun, M S; Ryoo, H M; Bae, S H; Park, K U; Lee, W S; Baek, J H; Chung, H Y; Yu, W

    2008-01-01

    The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65?mg?m?2 plus oxaliplatin 120?mg?m?2 on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7–59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3–7.2) months and 9.9 (95% CI; 7.8–12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer. PMID:18212754

  8. A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL

    PubMed Central

    Awan, Farrukh; Flinn, Ian W.; Berdeja, Jesus G.; Wiley, Elizabeth; Mansoor, Sharmeen; Huang, Ying; Lozanski, Gerard; Foster, Paul A.; Byrd, John C.

    2014-01-01

    CD19 is ubiquitously expressed on chronic lymphocytic leukemia (CLL) cells and is therefore an attractive candidate for antibody targeting. XmAb5574 (aka MOR00208) is a novel humanized CD19 monoclonal antibody with an engineered Fc region to enhance Fc? receptor binding affinity. Here we report results of a first in human phase 1 trial of XmAb5574 in patients with relapsed or refractory CLL. Twenty-seven patients were enrolled to 6 escalating dose levels, with expansion at the highest dose level of 12 mg/kg. Nine doses of XmAb5574 were infused over 8 weeks. No maximal tolerated dose was reached, and the drug was generally well tolerated, with infusion reactions of grades 1 and 2 being the most common toxicities. Grade 3 and 4 toxicities occurred in 5 patients and included neutropenia, thrombocytopenia, increased aspartate aminotransferase, febrile neutropenia, and tumor lysis syndrome. XmAb5574 showed preliminary efficacy, with 18 patients (66.7%) responding by physical examination criteria and laboratory studies, and 8 patients (29.6%) responding by computed tomography criteria. Pharmacokinetics showed a half-life of 14 days with clearance that was not dose-dependent. In conclusion, this phase 1 trial demonstrates safety and preliminary efficacy of a novel Fc-engineered CD19 monoclonal antibody XmAb5574 and justifies movement into the phase 2 setting. This trial was registered at www.clinicaltrials.gov as #NCT01161511. PMID:25301708

  9. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313.

    PubMed

    Persky, Daniel O; Miller, Thomas P; Unger, Joseph M; Spier, Catherine M; Puvvada, Soham; Stea, B Dino; Press, Oliver W; Constine, Louis S; Barton, Kevin P; Friedberg, Jonathan W; LeBlanc, Michael; Fisher, Richard I

    2015-01-01

    In the S0313 trial, we evaluated the impact of adding ibritumomab tiuxetan consolidation to 3 cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy plus involved field radiotherapy (IFRT) in patients with limited-stage aggressive B-cell non-Hodgkin lymphoma (LD-NHL). Patients with at least 1 stage-modified adverse risk factor (nonbulky stage II, age >60 years, elevated lactate dehydrogenase, or World Health Organization performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40 to 50 Gy of IFRT. An ibritumomab tiuxetan regimen was initiated 3 to 6 weeks following IFRT. Forty-six patients were registered and eligible, with median follow-up of 7.3 years. The progression-free survival estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. The overall survival estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. Grade 4 adverse events occurring more than once included neutropenia (8), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. In conclusion, patients with high-risk LD-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. The clinical trial was registered at www.clinicaltrials.gov as #NCT00070018. PMID:25395425

  10. Pegfilgrastim use during chemotherapy: current and future applications.

    PubMed

    Wolf, Todd; Densmore, John J

    2004-11-01

    Chemotherapy-induced myelosuppression is the most common dose-limiting side effect of cancer chemotherapy. Neutropenia is a serious risk with chemotherapy, associated with infectious complications, use of intravenous antibiotics, hospitalization, and even death. The occurrence of febrile neutropenia can lead to dose reductions and delay in subsequent cycles of chemotherapy that may have a detrimental affect on overall survival and disease-free survival. Granulocyte colony-stimulating factors (G-CSF) can reduce the duration of severe neutropenia, the incidence of febrile neutropenia, and allow planned dosing and timing of chemotherapy. Filgrastim is a G-CSF that has demonstrated benefit for the treatment and prophylaxis of chemotherapy-induced neutropenia (CIN), but its short half-life requires repeated daily subcutaneous injection. Pegfilgrastim is a recombinant G-CSF created by attaching a polyethylene glycol (PEG) molecule to the filgrastim protein. Once-per-cycle dosing of pegfilgrastim has been evaluated in clinical trials using myelosuppressive chemotherapy in breast cancer, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Trials have demonstrated that pegfilgrastim is comparable in safety and efficacy to filgrastim for decreasing the duration of severe neutropenia after chemotherapy in patients with nonmyeloid malignancy. This review will summarize recent clinical trial results and novel uses of pegfilgrastim. PMID:15496275

  11. Phenology and resource use in three co-occurring grassland annuals

    Microsoft Academic Search

    S. L. Gulmon; N. R. Chiariello; H. A. Mooney; C. C. Chu

    1983-01-01

    Water resource partitioning among three co-occurring species of the California annual grassland was investigated. Plantago erecta, Clarkia rubicunda and Hemizonia luzulifolia differ in lifespan. The lifespan of Plantago is coincident with the October–May rainy season, but the other two species reproduce during summer when no precipitation occurs, and thus depend on stored water.

  12. The potential for ill-posedness of multiplication operators occurring in inverse problems

    E-print Network

    The potential for ill-posedness of multiplication operators occurring in inverse problems Bernd mapping in L2(0, 1) occurring in linear ill-posed operator equations and in the linearization of nonlinear ill-posed operator equations with compact forward operators. We give examples of nonlinear inverse

  13. Conditioning-specific reflex modification occurs when an unconditionedresponse(UR)ismodifiedinthe absence

    E-print Network

    not generalize from air puff to electro- dermal stimulation even though conditioning occurs to comparable levels can be obtained only at high air puff intensi- ties even though conditioning is supported by lower airConditioning-specific reflex modification occurs when an unconditionedresponse

  14. Investigation into defects occurring on the polymer surface during the photolithography process

    Microsoft Academic Search

    D. Bosc; A. Maalouf; S. Haesaert; F. Henrio

    2007-01-01

    With a view to improving the realisation of polymer optical waveguide some features relevant to the photolithography process are analysed. This paper focuses on defects that occur on the surface of polymer layers involved in the process. For example, depending on the heat treatment or the deposited material, some worm-like defects appear on the polymer surface. When they occur, the

  15. Importance of the Equlibrium Node in Preventing the Voltage Collapse Occurs in the Wind Power System

    E-print Network

    Lavaei, Javad

    Importance of the Equlibrium Node in Preventing the Voltage Collapse Occurs in the Wind Power collapse will occurs in a wind power system is discussed next. The method of power flow calculation is the specific analysis of a given simplified wind power system. Keywords--voltage collapse; Newton

  16. Consequences of Co-Occurring Attention-Deficit/Hyperactivity Disorder on Children's Language Impairments

    ERIC Educational Resources Information Center

    Redmond, Sean M.; Ash, Andrea C.; Hogan, Tiffany P.

    2015-01-01

    Purpose: Co-occurring attention-deficit/hyperactivity disorder (ADHD) and communication disorders represent a frequently encountered challenge for school-based practitioners. The purpose of the present study was to examine in more detail the clinical phenomenology of co-occurring ADHD and language impairments (LIs). Method: Measures of nonword…

  17. 30 CFR 254.46 - Whom do I notify if an oil spill occurs?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... false Whom do I notify if an oil spill occurs? 254.46 Section 254...DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES...254.46 Whom do I notify if an oil spill occurs? (a) You must...

  18. 30 CFR 254.46 - Whom do I notify if an oil spill occurs?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... false Whom do I notify if an oil spill occurs? 254.46 Section 254...DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES...254.46 Whom do I notify if an oil spill occurs? (a) You must...

  19. 30 CFR 254.46 - Whom do I notify if an oil spill occurs?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... false Whom do I notify if an oil spill occurs? 254.46 Section 254...DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES...254.46 Whom do I notify if an oil spill occurs? (a) You must...

  20. 30 CFR 254.46 - Whom do I notify if an oil spill occurs?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... false Whom do I notify if an oil spill occurs? 254.46 Section 254...DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES...254.46 Whom do I notify if an oil spill occurs? (a) You must...

  1. 30 CFR 254.46 - Whom do I notify if an oil spill occurs?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... false Whom do I notify if an oil spill occurs? 254.46 Section 254...DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES...254.46 Whom do I notify if an oil spill occurs? (a) You must...

  2. A M=9 earthquake occurred beneath Seattle in January 1700. Earthquakes release strain energy

    E-print Network

    Colorado at Boulder, University of

    A M=9 earthquake occurred beneath Seattle in January 1700. Earthquakes release strain energy, sufficient to drive another 8earthquake. A curious phenomenon observed every 14 months to occur near obtained from the biaxial tiltmeter at Shelton during the Sumatra Mw=9.3 earthquake region of slow

  3. Students will understand that chemical and physical changes occur in matter.

    NSDL National Science Digital Library

    Mrs. Schmidt

    2007-10-08

    Evaluate evidence that indicates a physical change has occured. IPPEX: Interactive: Matter This will help you identify the physical properties of matter! Chem4Kids: Matter Compare changes in substances that indicate a physical change has occured Physical Changes Chemical Changes Thiese sites will help you identify the physical and chemical changes. ...

  4. 15 CFR 70.3 - Effect of boundary changes occurring or reported after the cutoff dates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...changes occurring or reported after the cutoff dates. 70.3 Section 70.3 Commerce...CENSUS, DEPARTMENT OF COMMERCE CUTOFF DATES FOR RECOGNITION OF BOUNDARY CHANGES FOR...changes occurring or reported after the cutoff dates. The Bureau of the Census...

  5. [Chemical investigation of naturally occurring drug materials. Elucidation of scientific basis for traditional medicines and exploitation of new naturally occurring drugs].

    PubMed

    Kitagawa, I

    1992-01-01

    In search of new biologically active compounds in nature, we have been investigating naturally occurring substances on the following subjects: I. chemical studies on naturally occurring drug materials [a) elucidation of bioactive constituents in natural drugs, b) elucidation of scientific basis for crude drug processing, and c) investigation of bioactive constituents in food materials], II. exploitation of new pharmaceuticals in nature [a) investigation of marine natural products and b) exploitation of Indonesian medicinal plants], and III. synthetic studies on bioactive natural products [a) chemical modification of naturally abundant carbohydrates and terpenoids and b) synthetic studies of complex lipids]. This article reviews the results obtained in our laboratory since 1978 on the subjects of I-a, b, c, II-a, and III-a. PMID:1578342

  6. DECIPHERING NATURALLY-OCCURRING PB CONTAMINATION IMPACTING DRINKING WATER WELLS: SHAKER VILLAGE CATCHMENT, MAINE.

    EPA Science Inventory

    Trace Pb concentrations in groundwater within glacial deposits across Maine fluctuate considerably. Deciphering the distribution and sources of naturally occurring Pb in groundwater with only the use of conventional anomaly identification techniques presents a challenge. In a rep...

  7. Naturally Occurring Attitude and Behavior Changes: Content and Duration of the Change Process.

    ERIC Educational Resources Information Center

    Horst, Leslie; Des Jarlais, Don C.

    1984-01-01

    Investigated college students' (N=160) reports of naturally-occurring recent attitude or behavior changes in two studies. Results indicated that students reported changes which reflected their everyday concerns and were derived from their direct experience. (LLL)

  8. Dual Diagnosis: Adolescents with Co-Occurring Brain Disorders and Substance Abuse Disorders

    MedlinePLUS

    ... Dual Diagnosis: Adolescents with Co-occurring Brain Disorders & Substance Abuse Disorders Adolescents are often referred to treatment for ... do model programs for treating mental illness and substance abuse look like? There is a growing number of ...

  9. Struggles in Occupancy Management Perform data analysis to characterize the issues occurring

    E-print Network

    Management Characteristics of Patient Population Occupancy Visualization Tool Conclusions Future Work Management of Admissions and Discharge Process at Bridgepoint Health Neuro-Rehabilitation Amanda Bell, JustinStruggles in Occupancy Management · Perform data analysis to characterize the issues occurring

  10. Structure and forcing of teleconnection patterns occurring in general circulation model simulations

    SciTech Connect

    Malone, R.C.; Pitcher, E.J.; Blackmon, M.L.; Geisler, J.E.

    1984-01-01

    Several characteristics of teleconnection-pattern fluctuations occurring in general circulation model (GCM) simulations were examined. The model used is the NCAR Community Climate Model. 7 references, 3 figures. (ACR)

  11. REMOVAL OF ARSENIC FROM GROUNDWATER USING NATURALLY OCCURRING IRON OXIDES IN RURAL REGIONS OF MONGOLIA

    EPA Science Inventory

    We have found that the iron oxide particles produced by grinding naturally occurring iron ores are very effective in removing arsenic from water. The arsenic adsorption isothermal of the particles h...

  12. CHARACTERIZATION OF CASEINS CROSSLINKED BY A NATURALLY OCCURRING CROSSLINKING AGENT-GENIPIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing economic and environmental pressures demand more effective utilization of natural resources. Genipin, a naturally occurring crosslinking agent obtained from the fruit of Gardenia jasminoides, has recently attracted much attention due to its low cytotoxicity compared to traditional crossli...

  13. The role of naturally occurring waterholes in determining the distribution of Florida Key Deer

    E-print Network

    Kim, Ji Yeon

    2009-05-15

    The purpose of my research was to test the hypothesis that the availability of fresh, naturally occurring water may limit the distribution of Florida Key Deer (Odocoileus virginianus clavium). More specifically, I was trying to determine...

  14. Language Shift Co-occurs with Positive Attitudes toward the Heritage Language.

    ERIC Educational Resources Information Center

    Shin, Fay; Lee, Bo

    2003-01-01

    Suggests that language shift among nonnative English speakers can co-occur with positive attitudes toward the heritage language. Discusses results of a study of Hmong-speaking children in California. (Author/VWL)

  15. Canine viral enteritis. II. Morphologic lesions in naturally occurring parvovirus infection.

    PubMed

    Cooper, B J; Carmichael, L E; Appel, M J; Greisen, H

    1979-04-01

    The morphologic lesions associated with naturally occurring canine parvovirus infection are described. The disease is characterized by necrosis of crypt epithelium in the small intestine and of lymphoid tissue in Peyers patches, lymph nodes, spleen and thymus. PMID:467076

  16. Childhood vision impairment, hearing loss and co-occurring autism spectrum disorder

    PubMed Central

    Kancherla, Vijaya; Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn

    2015-01-01

    Background Limited population-based data on prevalence of childhood vision impairment (VI) and hearing loss (HL), and their co-occurrence with autism spectrum disorder (ASD) exists. Objective To examine prevalence and characteristics of VI, HL and co-occurring ASD among 8-year-olds in metropolitan Atlanta 2000–2008. Methods We used data from the population-based Metropolitan Atlanta Developmental Disabilities Surveillance Program. Prevalence, birth and parental characteristics, presence and severity of other co-occurring developmental disabilities, and age of earliest identification of ASD, were examined for children with VI and HL, by co-occurring ASD. Results VI and HL prevalences were 1.2 and 1.3 per 1000 8-year-olds, respectively. Approximately 6–7% of children with VI or HL had co-occurring ASD. Children with VI or HL with co-occurring ASD differed from those without co-occurring ASD by select birth characteristics and the presence of other co-occurring DDs. The median age of earliest known ASD diagnosis was significantly later among children with VI and ASD compared to children with ASD without VI (79 vs. 56 months). Children with HL and ASD were first evaluated by a community provider significantly earlier than those with ASD without HL (40 vs. 50 months). Conclusions The frequency of co-occurring ASD with VI and HL is higher than the population prevalence of ASD. The significant delays in diagnosis of ASD in children with VI and lack of earlier diagnosis of ASD among children with HL despite earlier evaluation highlight the importance of developing screening tools for early identification of ASD among children with VI and HL. PMID:24060256

  17. Proton magnetic resonance studies of the chemical shifts occurring in propionic acid-dioxane solutions 

    E-print Network

    Oldham, William J. Bryan

    1958-01-01

    LIB' OF FIQUHRB PIGUBRB 1, Observers ohemi, cal shiftsoccurring in aqueous solutions of propiolLic acid o ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 23 2 ~ Chemical shifts occurring in propionic acyl-diarane solull iona...~ted values of the equilibr1um constant for the dimermonomer dissociation in propionic acid&ioxsne solut ious o ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 32 4, Calculated values of the shifx occurring 'u propionic acid&hexane solutions at 73 C...

  18. Evidence for remembering when events occurred in a rodent model of episodic memory

    PubMed Central

    Zhou, Wenyi; Crystal, Jonathon D.

    2009-01-01

    The content of episodic memory consists of representations of unique past events. Episodic memories are grounded in a temporal framework (i.e., we remember when an event occurred). It has recently been argued that episodic-like memory in rats is qualitatively different from human episodic memory because, rather than remembering when an earlier past event occurred, rats used the cue of how long ago it occurred. We asked, therefore, whether rats remember the time of day at which they encountered a distinctive event, in addition to what occurred and where it happened. Rats were tested in the morning and afternoon, on separate days. A distinctive flavor (chocolate) was replenished at a daily-unique location at only one of these times. The interval between first and second daily opportunities to eat (study and test, respectively) was constant. Rats adjusted their revisits to the chocolate location at different times of day by using time of day rather than the cue of how long ago an event occurred. Two lines of evidence suggest that rats remembered the time at which the distinctive event occurred. First, under conditions in which the time of test (but not time of study) was novel, rats immediately transferred their knowledge of the chocolate contingency to the new test time. Second, under conditions in which predictions for study and test times were put in conflict, rats again used study time. Our results suggest that, at the time of memory assessment, rats remember when a recent episode occurred, similar to human episodic memory. PMID:19458264

  19. Results of a Randomized Phase II Study of Oral Sapacitabine in Elderly Patients with Previously Untreated or First Relapsed Acute Myeloid Leukemia

    PubMed Central

    Kantarjian, Hagop; Faderl, Stefan; Garcia-Manero, Guillermo; Luger, Selina; Venugopal, Parameswaran; Maness, Lori; Wetzler, Meir; Coutre, Steven; Stock, Wendy; Claxton, David; Goldberg, Stuart L.; Arellano, Martha; Strickland, Stephen A.; Seiter, Karen; Schiller, Gary; Jabbour, Elias; Chiao, Judy; Plunkett, William

    2014-01-01

    Purpose Current treatment of acute myeloid leukemia (AML) is not adequate for most elderly patients. This is the first part of an ongoing study of AML and myelodysplastic syndromes (MDS) and evaluated the efficacy and toxicity of sapacitabine, a novel oral cytosine nucleoside analog, in previously untreated or first relapsed elderly patients with AML. Patients and Methods Patients aged 70 years or older with adequate performance status were randomized to receive one of the three schedules of oral sapacitabine: A) 200 mg twice daily x 7 days; B) 300 mg twice daily x 7 days; C) 400 mg twice daily x 3 days, then weekly x 2 weeks. Randomization is stratified by previously untreated vs. previously treated for AML. The intent-to treatment population includes all patients who have received at least one dose of sapacitabine. The primary endpoint was 1-year survival. The trial is registered at clinicaltrials.gov (NCT00590187). Results A total of 105 patients were treated including 86 patients with previously untreated and 19 patients with first relapsed AML. The median age was 77 years (range 70-91). Among the 60 randomized patients, the 1-year survival rates were 35% in arm A (95% CI, 16 to 59%), 10% in arm B (95% CI, 2 to 33%), and 30% in arm C (95% CI, 13 to 54%). The overall response rates were 45% on arm A (2 CRs, 1 CRi, and 6 HIs), 30% on arm B (1 CR, 1 CRp, 1 PR and 3 HIs), and 45% on arm C (5 CRs, 1 CRi and 3 HIs) with more complete remissions (CR) occurring on arm C (25%) as compared to arm A (10%) and arm B (5%). The 30-day mortality was 13% and 60-day mortality was 26%. The most common grade 3-4 adverse events were anemia, neutropenia, thrombocytopenia, febrile neutropenia and pneumonia. The most common serious adverse events were myelosuppression-related complications with febrile neutropenia and pneumonia being the most common ones. Conclusion Sapacitabine is active in elderly patients with AML and is well-tolerated. The 400 mg dose schedule has better efficacy profile. Future investigations aim to combine sapacitabine with other low-intensity therapies in elderly patients with AML. PMID:23075701

  20. Current status of co-occurring mood and substance use disorders: a new therapeutic target.

    PubMed

    Pettinati, Helen M; O'Brien, Charles P; Dundon, William D

    2013-01-01

    Mood and substance use disorders commonly co-occur, yet there is little evidence-based research to guide the pharmacologic management of these comorbid disorders. The authors review the existing empirical findings, some of which may call into question current clinical pharmacotherapy practices for treating co-occurring mood and substance use disorders. The authors also highlight knowledge gaps that can serve as a basis for future research. The specific mood disorders reviewed are bipolar and major depressive disorders (either one co-occurring with a substance use disorder). Overall, findings from the relatively small amount of available data indicate that pharmacotherapy for managing mood symptoms can be effective in patients with substance dependence, although results have not been consistent across all studies. Also, in most studies, medications for managing mood symptoms did not appear to have an impact on the substance use disorder. In a recent trial for comorbid major depression and alcohol dependence, combination treatment with a medication for depression and another for alcohol dependence was found to reduce depressive symptoms and excessive drinking simultaneously. However, research has only begun to address optimal pharmacologic management of co-occurring disorders. In addition, current clinical treatment for alcohol and drug dependence often excludes new pharmacotherapies approved by the U.S. Food and Drug Administration for treating certain types of addiction. With new data becoming available, it appears that we need to revisit current practice in the pharmacological management of co-occurring mood and substance use disorders. PMID:23223834

  1. A naturally occurring, noncanonical GTP aptamer made of simple tandem repeats

    PubMed Central

    Curtis, Edward A; Liu, David R

    2014-01-01

    Recently, we used in vitro selection to identify a new class of naturally occurring GTP aptamer called the G motif. Here we report the discovery and characterization of a second class of naturally occurring GTP aptamer, the “CA motif.” The primary sequence of this aptamer is unusual in that it consists entirely of tandem repeats of CA-rich motifs as short as three nucleotides. Several active variants of the CA motif aptamer lack the ability to form consecutive Watson-Crick base pairs in any register, while others consist of repeats containing only cytidine and adenosine residues, indicating that noncanonical interactions play important roles in its structure. The circular dichroism spectrum of the CA motif aptamer is distinct from that of A-form RNA and other major classes of nucleic acid structures. Bioinformatic searches indicate that the CA motif is absent from most archaeal and bacterial genomes, but occurs in at least 70 percent of approximately 400 eukaryotic genomes examined. These searches also uncovered several phylogenetically conserved examples of the CA motif in rodent (mouse and rat) genomes. Together, these results reveal the existence of a second class of naturally occurring GTP aptamer whose sequence requirements, like that of the G motif, are not consistent with those of a canonical secondary structure. They also indicate a new and unexpected potential biochemical activity of certain naturally occurring tandem repeats. PMID:24824832

  2. Radon anomalies preceding earthquakes which occurred in the UK, in summer and autumn 2002.

    PubMed

    Crockett, R G M; Gillmore, G K; Phillips, P S; Denman, A R; Groves-Kirkby, C J

    2006-07-01

    During the course of an investigation into domestic radon levels in Northamptonshire, two hourly sampling real-time radon detectors were operated simultaneously in separate locations 2.25 km apart in Northampton, in the English East Midlands, for a 25-week period. This period of operation encompassed the period in September 2002 during which the Dudley earthquake (magnitude - 5.0) and smaller aftershocks occurred in the English West Midlands, UK. We report herein our observations regarding the occurrence of simultaneous short-period radon anomalies and their timing in relation to the Dudley, and other, earthquakes which occurred during the monitoring period. Analysis of the radon time-series reveals a short period when the two time-series displayed simultaneous in-phase short-term (6-9 h) radon anomalies prior to the main Dudley earthquake. Subsequent investigation revealed that a similar period occurred prior to another smaller but recorded earthquake in the English Channel. PMID:16165194

  3. Affective Awareness in Parenting of Fathers with Co-Occurring Substance Abuse and Intimate Partner Violence

    PubMed Central

    Stover, Carla Smith; Spink, Andrea

    2013-01-01

    Purpose Few studies have examined the parenting of fathers with co-occurring Substance Abuse (SA) and Intimate Partner Violence (IPV) problems. None have specifically interviewed men with these co-occurring issues using qualitative methods about their reflective functioning in relation to their children. This qualitative study was designed to provide evidence of the reflective capacity of fathers with co-occurring SA and IPV. Approach To assess this, men were asked to describe examples of negative emotions they experienced as parents and how they perceived their children responded to those emotions. Forty fathers with co-occurring SA and IPV were interviewed using the Revised Parent Development Interview. Interviews were coded for reflective functioning and for themes that emerged related to angry and guilty feelings these fathers experienced as parents. Findings Overall, fathers in the sample had a very limited capacity to think about the thoughts and feelings of their children. The desire to spend more time with their child and an inability to provide financially were two common themes. Anger toward the child’s mother for not providing adequate care and a focus on shielding the child from his anger were also reported frequently. Fathers did not report feelings of guilt related to their substance use or aggression in their relationships. Originality This paper is one of the first to explore reflective functioning of fathers with co-occurring IPV and SA. These findings are discussed in relation to their implications for intervention with fathers with co-occurring SA and IPV issues. PMID:23710257

  4. Compensatory mutations occur within the electrostatic interaction range of deleterious mutations in protein structure.

    PubMed

    Bhattacherjee, Amrita; Mallik, Saurav; Kundu, Sudip

    2015-01-01

    A compensatory mutation (CM) counter balances lethal effects of a deleterious mutation (DM), ensuring the persistence of both through natural selection. However, little is known about the biological aspects of CMs those restore the structural alterations of proteins caused by slightly DMs. Here, by analyzing the evolution of the UDP-glycosyltransferase 73B4 protein among monocot-dicot plants, we investigate the occurrence of CMs around slightly DMs in 3D space. Our results illustrate that CMs exhibit significantly higher tendency to occur within the range of electrostatic interaction around the slightly DMs, compared to occurring randomly in the protein. PMID:25399321

  5. Chemical constituents of peppers (Piper spp.) and application to food preservation: naturally occurring antioxidative compounds.

    PubMed Central

    Nakatani, N; Inatani, R; Ohta, H; Nishioka, A

    1986-01-01

    In a structure analysis of the compounds of the genus Piper (Family Piperaceae), we identified five phenolic amides from Piper nigrum, seven compounds from P. retrofractum, and two compounds from P. baccatum. All the phenolic amides possess significant antioxidant activities that are more effective than the naturally occurring antioxidant, alpha-tocopherol. One amide, feruperine, has antioxidant activity as high as the synthetic antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Naturally occurring antioxidants, therefore, may surpass BHA and BHT in their ability to inactivate mutagens in food. PMID:3757949

  6. Size dependent fluorescence tuning of naturally occurring betacyanin with silver nano particles

    NASA Astrophysics Data System (ADS)

    Sarkar, Arindam; Thankappan, Aparna; Nampoori, V. P. N.

    2014-10-01

    Light absorption and scattering of metal nano partilces occur in very narrow range of wavelengths. This is also dependent on the geometry and shape of metal nano particles. It is also known that scattering is related to (volume)2 and absorption is related to the volume of the spherical metal nano particles. In our work we show that using this principle metal nano particles enable fluorescence tuning of dyes. In our experiment we show such tuning in naturally occurring betacyanin extracted from red beetroot. We also show that such tuning is dependent on the size variation of the silver nano particles.

  7. Treatment Strategies for Co-Occurring ADHD and Substance Use Disorders

    PubMed Central

    Mariani, John J.; Levin, Frances R.

    2009-01-01

    Attention-deficit hyperactivity disorder (ADHD) is a common co-occurring mental disorder among patients with substance use disorders (SUD). Clinicians must be cognizant of the complicated nature of diagnosis and treatment of ADHD when comorbid with SUD. Pharmacotherapy remains the mainstay of treatment for ADHD, although complementary psychotherapeutic approaches have been developed. Psychostimulant medications are the most commonly used medications to treat ADHD, but many clinicians are reluctant to prescribe stimulants to patients with SUD. Recommendations for treatment planning and clinical management for patients with co-occurring ADHD and SUD are discussed. PMID:17453606

  8. In Vivo Reactivation of Latent Herpes Simplex Virus 1 in Mice Can Occur in the Brain before Occurring in the Trigeminal Ganglion

    PubMed Central

    Yao, Hui-Wen; Ling, Pin; Tung, Yuk-Ying; Hsu, Sheng-Min

    2014-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) establishes latency in neurons of the brains and sensory ganglia of humans and experimentally infected mice. The latent virus can reactivate to cause recurrent infection. Both primary and recurrent infections can induce diseases, such as encephalitis. In humans, the majority of encephalitis cases occur as a recurrent infection. However, in the past, numerous mouse studies documented that viral reactivation occurs efficiently in the ganglion, but extremely rarely in the brain, when assessed ex vivo by cultivating minced tissue explants. Here, we compare the brains and the trigeminal ganglia of mice latently infected with HSV-1 (strain 294.1 or McKrae) for levels of viral genomes and in vivo reactivation. The numbers of copies of 294.1 and McKrae genomes in the brain stem were significantly greater than those in the trigeminal ganglion. Most importantly, 294.1 and McKrae reactivation was detected in the brain stems earlier than in the trigeminal ganglia of mice treated with hyperthermia to reactivate latent virus in vivo. In addition, the brain stem yielded reactivated virus at a high frequency compared with the trigeminal ganglion, especially in mice latently infected with 294.1 after hyperthermia treatment. These results provide evidence that recurrent brain infection can be induced by the reactivation of latent virus in the brain in situ. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes latency in neurons of the brains and sensory ganglia of humans and experimentally infected mice. The latent virus can reactivate to cause recurrent infection. In the past, studies of viral reactivation focused on the ganglion, because efficient viral reactivation was detected in the ganglion but not in the brain when assessed ex vivo by cultivating mouse tissue explants. In this study, we report that the brain contains more viral genomes than the trigeminal ganglion in latently infected mice. Notably, the brain yields reactivated virus early and efficiently compared with the trigeminal ganglion after mice are stimulated to reactivate latent virus. Our findings raise the potential importance of HSV-1 latent infection and reactivation in the brain. PMID:25031345

  9. Factors affecting the photoyellowing which occurs during the photoinitiated polymerization of acrylates

    Microsoft Academic Search

    Nergis Arsu; R. Stephen Davidson; Richard Holman

    1995-01-01

    The influence of the type of photoinitiator, type of polymerizable reactive diluent and added amine synergist on the yellowing which occurs during the curing of clear films is examined. Type I photoinitiators based on acetophenone give rise to the least yellowing. The presence of amines, such as N-methyldiethanolamine, increases yellowing to a noticeable extent. Amino groups present in the initiator

  10. LETTERS TO THE EDITOR RE: ``HOW MANY FOODBORNE OUTBREAKS OF SALMONELLA INFECTION OCCURRED IN

    E-print Network

    Boehning, Dankmar

    LETTERS TO THE EDITOR RE: ``HOW MANY FOODBORNE OUTBREAKS OF SALMONELLA INFECTION OCCURRED IN FRANCE outbreaks of Salmonella infection that had oc- curred in France during the year 1995. The data provided), the Ministry of Agriculture (MA), and the National Salmonella and Shigella Reference Center (NRC). A complete

  11. Naturally-Occurring Comprehension Strategies Instruction in 9th-Grade Language Arts Classrooms

    Microsoft Academic Search

    Øistein Anmarkrud; Ivar Bråten

    2011-01-01

    In this descriptive classroom study, we used video-based observations supplemented with teacher interviews to provide precise information about the instruction of comprehension strategies that naturally occurred in 4 Norwegian lower-secondary language arts classrooms while students worked with expository texts. The results showed that the teachers varied vastly with respect to the amount of comprehension strategies instruction, that the repertoire of

  12. Drugs, Guns, and Disadvantaged Youths: Co-Occurring Behavior and the Code of the Street

    ERIC Educational Resources Information Center

    Allen, Andrea N.; Lo, Celia C.

    2012-01-01

    Guided by Anderson's theory of the code of the street, this study explored social mechanisms linking individual-level disadvantage factors with the adoption of beliefs grounded in the code of the street and with drug trafficking and gun carrying--the co-occurring behavior shaping violence among young men in urban areas. Secondary data were…

  13. Vitamin B12 Production and Depletion in a Naturally Occurring Eutrophic Lake1

    PubMed Central

    Gillespie, Paul A.; Morita, Richard Y.

    1972-01-01

    The distribution of vitamin B12 within Upper Klamath Lake was surveyed at approximately monthly intervals during a period from September 1968 to November 1969. High concentrations (up to 1.8 ?g/g of dry sediment) characteristically occurred at the water-sediment interface, with a sharp decline below this area. A heavy bloom of Aphanizomenon flos-aquae occurred from the latter part of May through October 1969. B12 concentrations of the uppermost sediments, from all but one sampling site, increased gradually through the bloom, followed by a drastic increase during the die-off period. B12 is probably not a limiting factor for primary productivity, since sufficient levels of this vitamin were found to occur throughout the year. Of 42 cultures isolated from Upper Klamath Lake water and sediments, 20 were found capable of producing 50 pg or more of B12/ml of medium. Phytoplankton samples were found to contain up to 5 ?g of B12/g of dry material. Degradation of B12 occurred in sterilized as well as fresh sediment samples. PMID:4622828

  14. Recalibration of Visual Stability Mechanism Occurs in a Higher-Order Visual System

    NASA Astrophysics Data System (ADS)

    Takahara, Kunimitsu; Okajima, Katsunori; Takase, Masanori

    We investigated whether an adaptation effect occurs in a virtual environment where an extent of retinal image motion caused by head rotation is modulated depending on the extent of the rotation. We defined the value #x201C;Gain#x201D;, as the ratio of #x201C;the angular velocity of retinal motion in the virtual environment#x201D; to #x201C;the angular velocity of head motion in the real environment#x201D;. Subjects rotated their heads in the adaptation phase in which one of three Gains (0.5, 1.0, and 1.5) was adapted; the phase lasted one period (3 min). Immediately afterwards, they adjusted the Gain to enable them to perceive a #x201C;stable environment#x201D; in the test phase. The results showed that adjusted Gains in the test phase tended to shift to the adaptation Gains. In addition, we tested whether the adaptation effect occurs in the somatic system and whether interocular transfer occurs, and found that the somatic system was not modulated by immersion in the conflicting environment but interocular transfer was observed. These results indicate that our visual stability system can adapt to such virtual environments within short minutes and that the adaptation effect occurs in our binocular visual system.

  15. MALDI-TOF Mass Spectrometry of Naturally-Occurring Mixtures of Mono- and Di-rhamnolipids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been developed for high-throughput screening of naturally-occurring mixtures of rhamnolipids from Pseudomonas spp. Mono- and di-rhamnolipids are readily distinguished by characteristic molecular adduct i...

  16. INVESTIGATION OF THE PHYSICAL CONDITIONS CON-TROLLING SPAWNING OF OYSTERS AND THE OCCUR-

    E-print Network

    was to study the effect of the physical conditions on the oyster and oyster larvre in this typical location. These studies were conducted under the direction of Dr. Paul S. Galtsoff, in charge of oyster investigationsINVESTIGATION OF THE PHYSICAL CONDITIONS CON- TROLLING SPAWNING OF OYSTERS AND THE OCCUR- RENCE

  17. --Tinnitus is a consciously experienced `ringing' sensation in the auditory system, which occurs without the

    E-print Network

    Barreto, Armando

    Abstract. -- Tinnitus is a consciously experienced `ringing' sensation in the auditory system, which occurs without the presence of an actual auditory stimulation. The study of tinnitus has resulted for this phenomenon has not been confirmed. In the majority of cases, external acoustic stimulation masks the tinnitus

  18. Does Naturally Occurring Comprehension Strategies Instruction Make a Difference when Students Read Expository Text?

    ERIC Educational Resources Information Center

    Braten, Ivar; Anmarkrud, Oistein

    2013-01-01

    The present study examined whether observed differences in naturally occurring classroom instruction of reading comprehension strategies were reflected in students' independent use of strategies to comprehend expository text. Based on a descriptive classroom study in 4 ninth-grade language arts classrooms, participants were divided into two groups…

  19. Joining of Advanced Materials: An The revolution which has occurred in materials science

    E-print Network

    Eagar, Thomas W.

    I ) J Joining of Advanced Materials: An Overview The revolution which has occurred in materials science and engineering has not been matched by improve- ments in joining science and technology. 1t is becoming increasingly apparent that the usefulness of many new materials is limited by our ability

  20. Treatment of Co-Occurring Substance Abuse and Suicidality among Adolescents: A Randomized Trial

    ERIC Educational Resources Information Center

    Esposito-Smythers, Christianne; Spirito, Anthony; Kahler, Christopher W.; Hunt, Jeffrey; Monti, Peter

    2011-01-01

    Objective: This study tested a cognitive-behavioral treatment protocol for adolescents with a co-occurring alcohol or other drug use disorder (AOD) and suicidality in a randomized clinical trial. Method: Forty adolescents (M[subscript age] = 15 years; 68% female, 89% White) and their families recruited from an inpatient psychiatric hospital were…