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Sample records for febrile neutropenia occurred

  1. Microbial etiology of febrile neutropenia.

    PubMed

    Swati, Mudshingkar; Gita, Nataraj; Sujata, Baveja; Farah, Jijina; Preeti, Mehta

    2010-06-01

    Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case-control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E.coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns. PMID:21629636

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

    PubMed

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

    2014-10-01

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

    PubMed Central

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

    2016-01-01

    Endocan is an endotelial cell specific molecule; previous studies have shown that serum endocan levels increased in cancer and sepsis and are also related to the severity of sepsis. There are no clinical study about serum endocan levels in children with febrile neutropenia. The aim of this study was to evaluate serum endocan levels in pediatric leukemia patients with febrile neutropenia (n=33) and compare them with children with leukemia without fever (n=33) and also with healthy children (n=24). The median serum endocan level in the first group (children with febrile neutropenia) was statistically significantly higher compared to the leukemic children without febrile neutropenia and also control group (P<0.01 for both). No difference was determined between the serum endocan levels of the leukaemia patients without febrile neutropenia and the healthy control group (P>0.05). Serum endocan levels were also similar with febrile neutropenia due to bacterial causes comparing with the idiopathic febril neutropenia. The results of this study showed increased serum endocan in children with leukemia during the febrile neutropenia episode, and no changes of serum endocan levels in children without leukemia without infection/fever. The monitoring of a series of serum endocan levels would be helpful for the course of febrile neutropenia. PMID:27103976

  4. Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia.

    PubMed

    Cortés de Miguel, Sol; Calleja-Hernández, Miguel Ángel; Menjón-Beltrán, Salomón; Vallejo-Rodríguez, Inmaculada

    2015-02-01

    Myelosuppression secondary to chemotherapy remains a serious adverse effect of cancer therapy that causes high morbidity and mortality. Several current European and American guidelines recommend consideration of primary prophylaxis with colony-stimulating factors (CSFs) when the risk of febrile neutropenia is higher than 20 %. The main factors associated with a high risk of febrile neutropenia include the chemotherapy regimen, tumor type, and patient-related factors such as old age and/or comorbidities. The purpose of this paper is to summarize the most relevant clinical trials and updated recommendations of the main guidelines on the role of granulocyte colony-stimulating factors (G-CSFs) in febrile neutropenia, examining whether the combination of G-CSF with chemotherapy improves overall survival. Future directions for G-CSF use are also discussed. PMID:25284722

  5. COST OF FEBRILE NEUTROPENIA TREATMENT IN BOSNIA AND HERZEGOVINA

    PubMed Central

    Catic, Tarik; Mekic-Abazovic, Alma; Sulejmanovic, Samra

    2016-01-01

    Febrile neutropenia is common chemotherapy complication significantly impacting patient’s outcomes, quality of life and costs, too. Febrile neutropenia (FN) often leads to hospitalization, the need for intravenous antibiotics and use of granulocyte colony-stimulating factors (GCSF) in order to avoid its complications. Cost of febrile neutropenia is well described in literature, but no study has been performed in Bosnia and Herzegovina. We have conducted observational cohort study with aim to describe and present costs of FN treatment from payers’ (provider’s) perspective. Only direct medical costs from one middle-sized oncology Clinic in Bosnia and Herzegovina database have been included and presented. We found that overall cost in five months period (January-May 2015) were almost 30.000 euros, or 1.0035 euro per episode/patient in average. The highest cost are allocated to hospitalization (40%), followed by GCSF (36%), while rest of costs are generated by laboratory tests performed and drug application. Proportion of costs is in line with other published studies even with huge differences in absolute values, mainly to low prices of services in Bosnia and Herzegovina. This was the first study on costs of chemotherapy induced FN in Bosnia and Herzegovina suggesting that significant costs are inquired by this conditions and that further research should be performed including larger patient population and other clinical oncology data, including pharmacoeconomic analysis. PMID:27147916

  6. Secondary Infections in Febrile Neutropenia in Hematological Malignancies: More Than Another Febrile Neutropenic Episode

    PubMed Central

    Demirel, Aslıhan; Tabak, Fehmi; Ar, M. Cem; Mete, Bilgül; Öngören, Şeniz; Yemişen, Mücahit; Özaras, Reşat; Eşkazan, Emre; Başlar, Zafer; Mert, Ali; Soysal, Teoman; Ferhanoğlu, Burhan; Aydın, Yıldız; Öztürk, Recep

    2015-01-01

    Objective: Febrile neutropenic episodes (FNEs) are among the major causes of mortality in patients with hematological malignancies. Secondary infections develop either during the empirical antibiotic therapy or 1 week after cessation of therapy for a FNE. The aim of this study was to investigate the risk factors associated with secondary infections in febrile neutropenic patients. Materials and Methods: We retrospectively analyzed 750 FNEs in 473 patients between January 2000 and December 2006. Results: Secondary infections were diagnosed in 152 (20%) of 750 FNEs. The median time to develop secondary infection was 10 days (range: 2-34 days). The duration of neutropenia over 10 days significantly increased the risk of secondary infections (p<0.001). The proportion of patients with microbiologically documented infections was found to be higher in primary infections (271/750, 36%) compared to secondary infections (43/152, 28%) (p=0.038). Age; sex; underlying disease; antibacterial, antifungal, or antiviral prophylaxis; blood transfusion or bone marrow transplantation; central venous catheter; and severity of neutropenia did not differ significantly between primary and secondary infections (p>0.05). While fever of unknown origin (p=0.005) and catheter-related bacteremia (p<0.001) were less frequently observed in secondary infections, the frequency of microbiologically (p=0.003) and clinically (p<0.001) documented infections, fungal pneumonias (p<0.001), infections related to gram-positive bacteria (p=0.04) and fungi (p<0.001), and 30-day mortality rate (p<0.001) were significantly higher in cases of secondary infections (p<0.001). Conclusion: Secondary infections should be regarded as life-threatening complications of febrile neutropenia. Secondary infections represent a more severe and mortal complication and cannot be regarded just as another FNE. PMID:25913035

  7. [Microbiological isolates in patients with febrile neutropenia and hematological neoplasias].

    PubMed

    Figuera Esparza, M; Carballo, M; Silva, M; Figueredo, A; Avilán, J

    2006-09-01

    We studied the frequency of culture isolation, type of microorganism isolated and local pattern of resistance in 309 adult febrile neutropenic inpatients with hematological neoplasm, who were hospitalized between January 1998 and December 2003, in Caracas University Hospital (Hospital Universitario de Caracas), in Venezuela. There were 576 febrile neutropenic episodes. Organisms were isolated in 41% of 940 cultures. The most common organisms involved were gram-negative bacilli (48%), followed by gram-positive cocci (35.1%), fungal (11.5%) and other agents (5.4%). Coagulase-negative staphylococci (22.4%) and Escherichia coli (13.4%) were the most isolated; 58.5% of 479 agents isolated had an antibiogram; 62.2% of coagulase-negative staphylococci and 23.1% coagulase-positive staphylococci were oxacillin-resistant. We did not find any vancomycin-resistant organisms. The gram-negative antimicrobial sensitivity for imipenem was 96.2%, cefepime 81%, and ceftazidime 57.5%. Tazobactam-piperacillin and sulbactam-cefoperazone were tested in 26% of antibiograms and had activity of 57.1% and 77.5%, respectively. Fungi were not characterized. Betalactamases producing gram-negative bacilli were found. In general, micro-biological identification and local vigilance of antibacterial resistance pattern must be done routinely in these patients, in order to improve empiric therapy guidelines. PMID:17099792

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

    PubMed

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

    2013-06-01

    Dengue fever is endemic in many parts of the world but it has not been described as a cause of febrile neutropenia. We describe here clinical features, laboratory values and outcome in 10 children with acute lymphoblastic leukemia (ALL) and with dengue fever as a cause of febrile neutropenia. These data are compared to an age-matched control population of 22 children with proven dengue infection without ALL. Except for fever in all patients and plethoric face in one patient, typical symptoms of dengue such as abdominal pain, myalgias, and headaches, were absent. Mean duration of hospital stay was 6.3±2.0 days in ALL patients vs. 5.0±2.0 in controls (p=0.096). Median platelet count was 13,000/cmm (range 1000-28,000) in cases vs. 31,500 (range 13,000-150,000) in controls (p=0.018). Mean time for recovery for platelet was 6.0±1.3days in ALL patients vs. 2.5±0.9days in controls (p<0.001). All 10 patients survived. In endemic areas, high suspicion of dengue fever should be maintained in children with ALL and febrile neutropenia although typical symptoms may be lacking. Platelet recovery may be significantly delayed. PMID:23756720

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

    PubMed Central

    Yu, Marc Gregory Y.; Villalobos, Ralph Elvi M.; Juan-Bartolome, Ma. Jasmin Marinela C.; Berba, Regina P.

    2015-01-01

    Aim. The study aimed to describe the profile of Filipino febrile neutropenia patients and to determine parameters associated with severe outcomes. Methods. This is a retrospective study of Filipino febrile neutropenia patients admitted to the Philippine General Hospital. Patients were described in terms of clinical presentation and stratified according to the presence or absence of severe outcomes. Prognostic factors were then identified using regression analysis. Results. 115 febrile episodes in 102 patients were identified. Regression analysis yielded prolonged fever >7 days prior to admission (OR 2.43; 95% CI, 0.77–7.74), isolation of a pathogen on cultures (OR 2.69; 95% CI, 1.04–6.98), and nadir absolute neutrophil count (ANC) < 100 during admission (OR 1.96; 95% CI, 0.75–5.12) as significant predictors of poor outcome. Factors that significantly correlated with better outcome were granulocyte colony-stimulating factor (G-CSF) use (OR 0.31; 95% CI, 0.11–0.85) and completeness of antibiotic therapy (OR 0.26; 95% CI, 0.10–0.67). Conclusion. Prolonged fever >7 days prior to admission, positive pathogen on cultures, and nadir ANC < 100 during admission predicted severe outcomes, whereas G-CSF use and complete antibiotic therapy were associated with better outcomes. These prognostic variables might be useful in identifying patients that need more intensive treatment and monitoring. PMID:26421015

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

    PubMed

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

    2016-01-01

    The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers. PMID:26552624

  11. Comparison of the approaches to non-febrile neutropenia developing in children with acute lymphoblastic leukemia.

    PubMed

    Paksu, Muhammet Sukru; Paksu, Sule; Akbalik, Mehtap; Ozyurek, Emel; Duru, Feride; Albayrak, Davut; Fisgin, Tunc

    2012-06-01

    The objectives of this study was to investigate of the influences of high-dose (20 mg/kg/day) methyl prednisolone (HDMP) and granulocyte colony stimulating factor (G-CSF) in shortening the duration of chemotherapy-induced neutropenia encountered in children with ALL receiving maintenance therapy. Sixty-four non-febrile neutropenic attacks developed in 29 patients with ALL receiving St Jude XIII maintenance protocol were evaluated retrospectively. The patients were clinically followed up without drugs for shortening the duration of neutropenia in 21 (32.8%) attacs, while HDMP and G-CSF were administered in 26 (40.6%) and 17 (26.6%) attacks, respectively. After the detection of neutropenia, restoration of neutrophil counts at 2nd or 4th days to the levels that allow resuming the chemotherapy were considered as success. While second day and overall success rates in patients administered HDMP and G-CSF were significantly higher than the patients who were observed clinically. Both second day and overall neutrophil counts were significantly higher in patients administered G-CSF than the other groups. Methyl prednisolone and G-CSF treatments were well-tolerated by the patients. The cost-per neutropenic attack was significantly higher in G-CSF group than of the HDMP group. Especially in patients experiencing frequent neutropenic attacks and hence interruptions of the therapy, one of the myelopoiesis induction therapies can be used to shorten the duration of neutropenia. For this indication short-course HDMP therapy can be considered as an alternative to G-CSF in this patients due to its relatively low cost, amenability to outpatient administration, and well-tolerability by children. PMID:21395681

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

    PubMed

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

    2016-06-01

    An expert group from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, for its acronym in Spanish) and the Spanish Society of Medical Oncology (SEOM, for its acronym in Spanish) have reviewed the main aspects to be considered when evaluating patients with solid cancer and infectious complications contained in this article. Recommendations have, therefore, been put forth regarding the prophylaxis of the most prevalent infections in these patients, the use of vaccines, measures to control infection through vascular catheters, and preventing infection in light of certain surgical maneuvers. The following is a revision of the criteria for febrile neutropenia management and the use of colony-stimulating factors and closes with several guidelines for treating the cancer patient with serious infection. The document concludes with a series of measures to control hospital infection. PMID:26577106

  13. Evaluation of the risk factors for febrile neutropenia associated with hematological malignancy.

    PubMed

    Nakagawa, Yasunori; Suzuki, Kenshi; Masaoka, Toru

    2009-06-01

    Febrile neutropenia (FN) can frequently become a very serious problem. In 2002, Klastersky and colleagues established the Multinational Association for Supportive Care in Cancer (MASCC) score, which consisted of risk factors for conditions that included solid tumors. However, hematopoietic tumors, in comparison to solid tumors, are plagued by such problems as the quantity and quality of abnormalities associated with leukocytes and neutrophils and the requirement for higher dosages of both radio- and chemotherapy. FN is a complication associated with hematological malignancies that can lead to a fatal outcome, but it is avoidable if the appropriate preventive treatment is performed at an early stage. The subjects of the present study consisted of 354 patients with hematopoietic malignancies who were treated at the Japanese Red Cross Medical Center Hospital, Tokyo, between August 2000 and September 2004. They were retrospectively evaluated for the risk factors of FN by applying Wilcoxon's rank sum test. A scoring index was defined and the patients were classified into high- and low-risk groups before evaluation. The following nine risk factors, which may significantly influence the relationship between the time required for defervescence and the duration of neutropenia - age; hematological diseases; the leukocyte count during the febrile period; the reduction in leukocyte count per day before the onset of FN; the prophylactic administration of antimycotic agents; sterilization of the intestinal tract; and urine albumin content, creatine level, and C-reactive protein (CRP) level - were expressed in points and their sum was termed risk points. The range of risk points was classified as 0-3 and 4-9. The time required for defervescence was 5.1 days when the risk points were in the range of 0-3 and 8.1 days when the points were in the range of 4-9. These figures were distributed normally and there was a significant difference between the two groups (P = 0.0016). FN associated with hematological malignancies is somewhat different from that related to other malignancies; it is therefore associated with unique risk factors. Most of the risk factors used in the present study can be evaluated objectively. At the onset of FN, they were expressed in points for evaluation. Further prospective studies are needed to determine whether these risk factors are suitable for use in actual cases. PMID:19554402

  14. Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients

    PubMed Central

    Carmona-Bayonas, A; Gómez, J; González-Billalabeitia, E; Canteras, M; Navarrete, A; Gonzálvez, M L; Vicente, V; Ayala de la Peña, F

    2011-01-01

    Background: Predictive models to identify low-risk febrile neutropenia (FN) have been developed with heterogeneous samples, which included stable and unstable patients, solid tumours, acute leukaemia and bone marrow transplantation. These models fail to recognise 5–15% of cases with unexpected complications, and literature specifically addressing apparently stable patients (ASPs) is scarce. Methods: We reviewed 861 episodes of FN in outpatients with solid tumours, including 692 (80%) episodes with apparent clinical stability. We aimed to investigate the prognosis of this latter group and explore the possibility of stratifying it according to the presenting features. A case–control study was performed and the MASCC index was evaluated. Results: The rates of complications and bacteraemia in ASPs were 7.3% and 6.2%, respectively. The MASCC index yielded a low sensitivity to detect complications (36%). Prognostic factors were identified: ECOG performance status ⩾2, chronic bronchitis, chronic heart failure, stomatitis NCI grade ⩾2, monocytes <200 mm−3 and stress hyperglycaemia. Conclusion: A very simple assessment is useful to classify the patients with FN according to the risk of complications. A few additional variables may predict the clinical course of the patients. We additionally show that the MASCC index applied to this specific group has a low sensitivity to predict complications. PMID:21811253

  15. Risk Factors for Febrile Neutropenia in Children With Solid Tumors Treated With Cisplatin-based Chemotherapy.

    PubMed

    Castelán-Martínez, Osvaldo D; Rodríguez-Islas, Felipe; Vargas-Neri, Jessica L; Palomo-Colli, Miguel A; López-Aguilar, Enrique; Clark, Patricia; Castañeda-Hernández, Gilberto; Rivas-Ruiz, Rodolfo

    2016-04-01

    Febrile neutropenia (FN) is a common and potentially fatal adverse drug reaction of cisplatin-based chemotherapy (CDDPBC) in pediatric patients. Hence, the aim of this study was to determine the incidence and independent risk factors for FN in pediatric patients with solid tumors treated with CDPPBC. Cohort integration was performed in the first cycle of chemotherapy with CDDPBC and patients were followed up to 6 months after the last cycle. FN was defined according to the Common Terminology Criteria for Adverse Events. Relative risks were calculated with confidence intervals at 95% (95% CI) to determine FN risk factors. Multiple logistic regression was performed to identify independent risk factors. One hundred and thirty-nine pediatric patients (median age 7.4 y, range 0.08 to 17 y) were included in the study. FN incidence was 62.5%. Independent risk factors for FN were chemotherapy regimens including anthracyclines (odds ratio [OR]=19.44 [95% CI, 5.40-70.02), hypomagnesaemia (OR=8.20 [95% CI, 1.81-37.14]), and radiotherapy (OR=6.67 [95% CI, 1.24-35.94]). It is therefore concluded that anthracyclines-containing regimens, hypomagnesaemia, and radiotherapy are independent risk factors for FN in patients receiving CDDPBC. PMID:26907640

  16. Lecture: management of chemotherapy-induced febrile neutropenia; guidelines and colony stimulating factors.

    PubMed

    Procopio, Giuseppe; Niger, Monica; Testa, Isabella

    2011-11-01

    Chemotherapy-induced febrile neutropenia (FN) is a major risk factor for severe infections potentially fatal, and also a dose-limiting toxicity, so causing dose reductions and/or delays in scheduled chemotherapy. This lecture provides recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. If expected risk of FN is equal or superior to 20%, a primary prophylaxis of FN with G-CSF is recommended. Primary prophylaxis can be considered in case of intermediate 10-20% risk of FN, in presence of factors that increase the frequency/risk of FN, such as age >65, advanced disease, prior episode of FN, poor performance status, radiotherapy to a wide body area (>20%). In case of low risk of FN (<10%), primary prophylaxis is not recommended. We also described the differences in potency and efficacy between two G-CSF, lenograstim (glycosylated) and filgrastim (non-glycosylated), which should be considered when deciding the G-CSF for each patient, particularly in high risk settings for FN. PMID:22002072

  17. [Febrile neutropenia in onco-hematology patients hospitalized in Intensive Care Unit].

    PubMed

    Saillard, Colombe; Sannini, Antoine; Chow-Chine, Laurent; Blache, Jean-Louis; Brun, Jean-Paul; Mokart, Djamel

    2015-04-01

    Febrile neutropenia in cancer patients is associated with a high mortality. Patients are frequently admitted to Intensive Care Unit (ICU) for severe sepsis or septic shock. Empirical antibiotic treatment, including monotherapy β-lactam covering Pseudomonas aeruginosa, must be prompt. The ICU management is slightly different, due to a particular microbial ecology. A standardized approach to obtain a microbiological documentation is the cornerstone in these patients, leading to an adapted antimicrobial treatment. Systematic reassessment of initial antibiotic regimen should be realised. Neutropenic patients with severe sepsis or septic shock should receive promptly a β-lactam-aminoglycoside combination, as well as glycopeptides in case of severity or absence of documented infection. Early catheter removal should be considered widely. In the actual context of growing resistance, antibiotics saving became a major concern. According to context and microbial documentation, an escalade or de-escalade approach is recommended, to take into account multi-resistant pathogens. The addition of antifugal treatment is also a major issue in these patients and has well-defined indications. In neutropenic patients admitted in the ICU for severe sepsis or septic shock, controlling local microbial epidemiology and the emergence of multi-resistant bacteria are the key issues. PMID:25799163

  18. Chemotherapy continuity and incidence of febrile neutropenia with CHOP therapy in an outpatient setting

    PubMed Central

    USAMI, EISEKI; KIMURA, MICHIO; IWAI, MINA; TAKENAKA, SHOYA; TERAMACHI, HITOMI; YOSHIMURA, TOMOAKI

    2016-01-01

    The cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen is considered to be a standard treatment for non-Hodgkin's lymphoma (NHL). Patients receiving CHOP chemotherapy often experience febrile neutropenia (FN) due to myelotoxicity. The proper management of FN is essential to guarantee a positive outcome of the NHL treatment. Therefore, the present study retrospectively examined chemotherapy continuity and the incidence of FN during CHOP therapy in an outpatient setting. The subjects were 136 patients who received CHOP chemotherapy between January 2012 and December 2014. A total of 31 patients unable to be treated in an outpatient setting were excluded from the study. Of the remaining 105 patients, 73 patients who did not require hospitalization during the chemotherapy treatment were included in the non-hospitalized group, and 32 patients who required hospitalization during chemotherapy treatment were included in the re-hospitalization group. The numbers of patients from these two groups who completed the planned treatment were 71 and 24, respectively (P<0.01). In addition, the duration of granulocyte-colony stimulating factor (G-CSF) treatment was 5.3±1.22 and 6.1±1.46 days, respectively (P<0.01). The numbers of patients experiencing FN in an outpatient setting were 14 and 19, respectively (P<0.01). During administration of primary prophylaxis with G-CSF, the incidence of FN was 21.0% (22/105) in cycle 1. In conclusion, the present study has revealed a requirement to educate patients about infection prevention prior to the first cycle of chemotherapy. Patients who require the administration of long- term G-CSF are at risk of unplanned re-hospitalization, and treating them with polyethylene glycol G-CSF to reduce the number of required injections should be considered as an option. Therefore, proper supportive therapy and management of infection are important to safely treat patients with CHOP in an outpatient setting. PMID:27073670

  19. Epidemiology and characteristics of febrile neutropenia in oncology patients from Spanish tertiary care hospitals: PINNACLE study

    PubMed Central

    DE CASTRO CARPEÑO, JAVIER; GASCÓN-VILAPLANA, PERE; TEJERINA, ANA MARIA CASAS-FERNÁNDEZ-DE; ANTÓN-TORRES, ANTONIO; LÓPEZ-LÓPEZ, RAFAEL; BARNADAS-MOLINS, AGUSTÍ; CRUZ-HERNÁNDEZ, JUAN JESÚS; MASSUTI-SUREDA, BARTOMEU; CAMPS-HERRERO, CARLOS; ARANDA-AGUILAR, ENRIQUE; LASERNA, FRANCISCO JOSÉ REBOLLO

    2015-01-01

    Febrile neutropenia (FN) is one of the most common adverse events associated with myelosuppressive chemotherapy for cancer treatment. The objective of this study was to describe the incidence of hospitalization due to FN in Spanish tertiary care hospitals (PINNACLE study). This epidemiological, retrospective, multicenter, nationwide study involved 119 patients from oncology units of 10 Spanish tertiary care hospitals who were admitted for FN. The primary endpoint was to assess the epidemiology and characteristics of FN. The incidence of admissions due to FN in oncology patients was 2.0% (interquartile range [IQR], 1.6–3.0). In terms of fever and absolute neutrophil count (ANC), 37.0% of the patients had a temperature of ≥38.2°C and an ANC of ≤500/m3. The number of patients who received prophylactic treatment with granulocyte colony-stimulating factor (G-CSF) was significantly higher in the palliative group (32.6%) compared with that in the non-palliative group (13.5%). The hospital length of stay was significantly shorter in patients who received prophylactic G-CSF compared with those who did not (5.0 days; IQR, 4.0–9.0 vs. 7.0 days; IQR, 5.0–11.0, respectively). The hospital length of stay was also significantly shorter in patients receiving palliative treatment (5.0 days; IQR, 3.0–7.0) compared with those receiving non-palliative therapy (7.0 days; IQR, 5.0–12.0). In conclusion, the incidence of admissions due to FN in oncology patients was 2.0% and the duration of hospital stay was 7.0 days. Prophylactic G-CSF treatment was found to be associated with better outcomes and shorter hospital stays. Therefore, the use of this treatment becomes relevant for achieving better clinical outcomes and reducing hospitalization cost in the management of FN. PMID:26137294

  20. A prospective study of chemotherapy-induced febrile neutropenia in the South West London Cancer Network. Interpretation of study results in light of NCAG/NCEPOD findings

    PubMed Central

    Okera, M; Chan, S; Dernede, U; Larkin, J; Popat, S; Gilbert, D; Jones, L; Osuji, N; Sykes, H; Oakley, C; Pickering, L; Lofts, F; Chowdhury, S

    2011-01-01

    Background: Chemotherapy-induced febrile neutropenia is a medical emergency complicating the treatment of many cancer patients. It is associated with considerable morbidity and mortality, as well as impacting on healthcare resources. Methods: A prospective study of all cases of chemotherapy-induced febrile neutropenia in the South West London Cancer Network was conducted over a 4-month period. Factors including demographics, treatment history, management of febrile neutropenia and outcome were recorded. Results and conclusi: Our results reflect those of the recent National Chemotherapy Advisory Group (NCEPOD, 2008)/National Confidential Enquiry into Patient Outcomes and Death reports (NCAG, 2009) and highlight the need for network-wide clinical care pathways to improve outcomes in this area. PMID:21179036

  1. Outpatient antimicrobial protocol for febrile neutropenia: a nonrandomized prospective trial using ceftriaxone, amikacin, and oral adjuvant agents.

    PubMed

    Sahu, S; Bapna, A; Pai, S K; Nair, C N; Kurkure, P A; Advani, S H

    1997-01-01

    Broad-spectrum antimicrobial therapy has revolutionized the management of febrile neutropenia (FN) in cancer patients. In vogue is an effective therapy an an outpatient basis. One thousand three hundred episodes of FN observed in 70 pediatric solid tumors (STs) and 65 cases of hematomalignancy (HM) at a median age of 5.5 years were treated with a protocol using once-a-day injectable ceftriaxone plus amikacin and other oral adjuvant antimicrobial agents. The mean duration of FN in the ST group was 4.0 +/- 1.2 days and in the HM group was 5.0 +/- 2.5 days. The mean duration of antimicrobial cover in the ST group was 5.0 +/- 1.75 days and in the HM group was 6.0 +/- 1.5 days. The overall recrudescence rate was 6% and the mean duration to recrudescence was 4 +/- 1.5 days (range 3-6 days). The objectives of this protocol were cost reduction and utilization of the available inpatient resources optimally by reducing the pressures of hospitalization for febrile neutropenia. We concluded that a selected group of patients with FN can be effectively managed with this regimen on an outpatient basis. PMID:9185205

  2. Could CD64 expression be used as a predictor of positive culture results in children with febrile neutropenia?

    PubMed Central

    Barbosa, Gustavo Göhringer de Almeida; Farias, Mariela Granero; Ludwig, Helena Cocolichio; Stensmann, Isabel; Fernandes, Matheus Vanzin; Michalowski, Mariana Bohns; Daudt, Liane Esteves

    2015-01-01

    Background Early recognition of infectious processes in neutropenic patients is hampered by the fact that these processes may have dissimilar and non-specific clinical presentations. CD64 is a neutrophil surface marker that is not expressed in non-sensitized neutrophils. When the neutrophil is exposed to tumor necrosis factor-alpha it is activated and is measured via the CD64 index. Methods This paper evaluated the relationship between the index value of CD64 on the first day of febrile neutropenia and a positive blood culture. The correlations with white blood count, C-reactive protein and erythrocyte sedimentation rate were also evaluated. This case–control, prospective, diagnostic study included 64 episodes of neutropenia. Case group (n = 14) comprised positive blood cultures, and the control group (n = 50), negative blood cultures. Results The median rates of CD64 were 2.1 (σ ± 3.9) in the case group and 1.76 (σ ± 5.02) in the control group. There was no correlation between the value of the CD64 index and blood cultures. The CD64 index was also not correlated with C-reactive protein positivity. Furthermore, the CD64 index was not able to predict blood culture positivity. The sensitivity was 64.3%, the specificity was 42%, the positive predictive value was 23.7% and the negative predictive value was 80%. For C-reactive protein, the sensitivity, specificity, positive predictive value, and negative predictive value were 71.4%, 32%, 22.7%, and 80%, respectively. Conclusion The CD64 index is not suitable for predicting the positivity of blood cultures in this specific population of patients with febrile neutropenia. PMID:26670402

  3. Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia.

    PubMed

    Hahn-Ast, C; Felder, L; Mayer, K; Mückter, S; Ruhnke, M; Hein, R; Hellmich, M; Schwab, K; Rachow, T; Brossart, P; von Lilienfeld-Toal, M

    2016-05-01

    Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis. PMID:27021301

  4. 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

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

    PubMed Central

    Meidani, Mohsen; Khorvash, Farzin; Abolghasemi, Hojat; Jamali, Bahareh

    2013-01-01

    Background: Neutropenia with fever is a common syndrome in patients with hematologic malignancies who have a high risk of infectious diseases. As early diagnosis of infection in such patients is really important, the aim of this study was to investigate the sensitivity and specificity of procalcitonin (PCT) and C-reactive protein (CRP) in the diagnosis of sepsis in febrile neutropenic patients in a referral malignant care center of Isfahan in 2010-2011. Materials and Methods: In this analytical cross-sectional study, all the febrile neutropenic patients who were admitted in the referral malignant care center in 2010-2011 were evaluated. The data from every individual, including sex, age, admission time, and duration of fever before taking antibiotics were collected. Sixty-four subjects were involved in the study. Blood samples of the subjects were obtained and the levels of PCT, CRP, Absolute neutrophil count (ANC), and white blood cell count were measured, and blood cultures were obtained. According to the test results, the 64 subjects were divided into two groups including patients with sepsis and without sepsis. Results: Mean value of PCT in the sepsis group was 28.65 ± 2.68 and in the non-sepsis group was 2.48 ± 0.66, with a P value of 0.000. In case of CRP, the sepsis group had a mean of 159.48 ± 9.73 and the non-sepsis group had a mean of 126.17 ± 10.63 (P = 0.015). Sensitivity and specificity were analyzed by using receiver operating characteristic (ROC) curve and were found to be 92.5% and 97.3%, respectively, for PCT and 70.5% and 42.1%, respectively, for CRP. Conclusion: PCT can be considered as a predictive factor and a diagnostic marker for the diagnosis of sepsis in febrile neutropenic patients. PMID:24455636

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

    ClinicalTrials.gov

    2013-07-10

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

  7. The efficacy and safety of cefepime or meropenem in the treatment of febrile neutropenia in patients with lung cancer. A randomized phase II study.

    PubMed

    Fujita, Masaki; Matsumoto, Takemasa; Inoue, Yuuichi; Wataya, Hiroshi; Takayama, Koichi; Ishida, Masayuki; Ebi, Noriyuki; Kishimoto, Junji; Ichinose, Yukito

    2016-04-01

    Febrile neutropenia frequently develops after chemotherapy. There is little evidence to indicate the type of antimicrobial agents that should be used in the treatment of febrile neutropenia in patients with solid tumors. The objective is to determine the efficacy and safety of cefepime (CFPM) and meropenem (MEPM) in the treatment of febrile neutropenia in lung cancer patients in a prospective randomized study. FN patients with lung cancer were randomly divided into CFPM or MEPM groups. The primary end-point was the response rate. The secondary end-points were the defervescence rates at 72 h, 7 days, 14 days and the incidence of adverse events. Twenty-one patients were treated with CFPM and 24 patients were treated with MEPM. One patient died of FN. The CFPM treatment completion rate was 17.65% (95% CI; 0.00-35.77%), while the MEPM treatment completion rate was 38.10% (95% CI; 17.33-58.87%). The defervescence rates at 72 h, 7 days, and 14 days were 70.59%, 86.67%, and 100.00%, respectively in the CFPM group; and 65.00%, 84.21%, and 92.31% in the MEPM group. Adverse events were observed in 33.33% of the CFPM group and 45.83% of the MEPM group. The response rate of the CFPM group was 94.12% (95% CI; 73.02-98.95%), while that of the MEPM group was 85.71% (95% CI; 65.36-95.02%). No differences were found in the efficacy or safety of CFPM and MEPM in the treatment of febrile neutropenia in patients with lung cancer. PMID:26867793

  8. Clinical efficacy and safety of biapenem for febrile neutropenia in patients with underlying hematopoietic diseases: a multi-institutional study.

    PubMed

    Nakagawa, Yasunori; Suzuki, Kenshi; Hirose, Takayuki; Chou, Takaaki; Fujisawa, Shin; Kida, Michiko; Usuki, Kensuke; Ishida, Yoji; Taniguchi, Shuichi; Kouzai, Yasuji; Tomoyasu, Shigeru; Miyazaki, Koji; Higashihara, Masaaki; Ando, Kiyoshi; Aoki, Sadao; Arai, Ayako; Akiyama, Nobu; Hatake, Kiyohiko; Okamoto, Shinichiro; Dan, Kazuo; Ohyashiki, Kazuma; Urabe, Akio

    2011-02-01

    A multi-institutional study was conducted to assess efficacy and safety of biapenem (BIPM), a carbapenem antibiotic, as an initial-stage therapeutic agent for febrile neutropenia (FN) in patients with hematopoietic diseases. A total of 216 patients from 25 medical institutions were enrolled in this study; of these, 204 were included in the safety analysis and 178 in the efficacy analysis. The combined (excellent and good) response rate was 67.9%, and antipyretic effect (subsidence + tendency to subsidence) was achieved within 3 and 5 days of treatment in 67.3 and 75.9% of patients, respectively. Thus, the clinical responses were gratifying. A response rate of 61.7% (37/60) was observed even in high-risk FN patients in whom neutrophil counts prior to and at 72 h after the start of BIPM were ≤100/μl. BIPM is considered to be a highly promising drug, with prompt onset of clinical benefit, as an initial-stage therapeutic agent for the treatment of FN in patients with hematopoietic diseases. PMID:20602137

  9. Cohort Study of the Impact of Time to Antibiotic Administration on Mortality in Patients with Febrile Neutropenia

    PubMed Central

    Rosa, Regis G.

    2014-01-01

    The time to antibiotic administration (TTA) has been proposed as a quality-of-care measure in febrile neutropenia (FN); however, few data regarding the impact of the TTA on the mortality of adult cancer patients with FN are available. The objective of this study was to determine whether the TTA is a predictor of mortality in adult cancer patients with FN. A prospective cohort study of all consecutive cases of FN, evaluated from October 2009 to August 2011, at a single tertiary referral hospital in southern Brazil was performed. The TTA was assessed as a predictive factor for mortality within 28 days of FN onset using the Cox proportional hazards model. Kaplan-Meier curves were used for an assessment of the mortality rates according to different TTAs; the log-rank test was used for between-group comparisons. In total, 307 cases of FN (169 subjects) were evaluated. During the study period, there were 29 deaths. In a Cox regression analysis, the TTA was independently associated with mortality within 28 days (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.10 to 1.26); each increase of 1 h in the TTA raised the risk of mortality within 28 days by 18%. Patients with FN episodes with a TTA of ≤30 min had lower 28-day mortality rates than those with a TTA of between 31 min and 60 min (3.0% versus 18.1%; log-rank P = 0.0002). Early antibiotic administration was associated with higher survival rates in the context of FN. Efforts should be made to ensure that FN patients receive effective antibiotic therapy as soon as possible. A target of 30 min to the TTA should be adopted for cancer patients with FN. PMID:24752269

  10. 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

  11. Updated Systematic Review and Meta-Analysis of the Performance of Risk Prediction Rules in Children and Young People with Febrile Neutropenia

    PubMed Central

    Phillips, Robert S.; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

    2012-01-01

    Introduction Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. Results We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. Conclusion The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia. PMID:22693615

  12. Evaluation of Bloodstream Infections During Chemotherapy-Induced Febrile Neutropenia in Patients with Malignant Hematological Diseases: Single Center Experience

    PubMed Central

    Piukovics, Klára; Terhes, Gabriella; Lázár, Andrea; Tímár, Flóra; Borbényi, Zita; Urbán, Edit

    2015-01-01

    From year to year, it is important to get an overview of the occurrence of causative agents in febrile neutropenic patients to determine the empiric treatment. Thus our aims were to evaluate a four-year period regarding the prevalence of bloodstream infections and the most important causative agents. During this period, 1,361 patients were treated in our hematology ward because of various hematological disorders. 812 febrile episodes were recorded in 469 patients. At that time, 3,714 blood culture (BC) bottles were sent for microbiological investigations, 759 of them gave positive signal. From the majority of positive blood culture bottles (67.1%), Gram-positive bacteria, mainly coagulase-negative staphylococci (CNS), were grown. Gram-negative bacteria were isolated from 32.9% of the positive blood culture bottles, in these cases the leading pathogen was Escherichia coli. The high prevalence of CNS was attributed to mainly contamination, while lower positivity rate for Gram-negative bacteria was associated with the use of broad-spectrum empiric antibiotic treatment. PMID:26495130

  13. Evaluation of Bloodstream Infections During Chemotherapy-Induced Febrile Neutropenia in Patients with Malignant Hematological Diseases: Single Center Experience.

    PubMed

    Piukovics, Klára; Terhes, Gabriella; Lázár, Andrea; Tímár, Flóra; Borbényi, Zita; Urbán, Edit

    2015-09-01

    From year to year, it is important to get an overview of the occurrence of causative agents in febrile neutropenic patients to determine the empiric treatment. Thus our aims were to evaluate a four-year period regarding the prevalence of bloodstream infections and the most important causative agents. During this period, 1,361 patients were treated in our hematology ward because of various hematological disorders. 812 febrile episodes were recorded in 469 patients. At that time, 3,714 blood culture (BC) bottles were sent for microbiological investigations, 759 of them gave positive signal. From the majority of positive blood culture bottles (67.1%), Gram-positive bacteria, mainly coagulase-negative staphylococci (CNS), were grown. Gram-negative bacteria were isolated from 32.9% of the positive blood culture bottles, in these cases the leading pathogen was Escherichia coli. The high prevalence of CNS was attributed to mainly contamination, while lower positivity rate for Gram-negative bacteria was associated with the use of broad-spectrum empiric antibiotic treatment. PMID:26495130

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

    PubMed

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

    2015-11-01

    Bloodstream infection (BSI) is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the causative bacteria and identify risk factors for BSI associated mortality in febrile neutropenia patients undergoing HSCT, we collected the clinical and microbiological data from patients underwent HSCT between 2008 and 2014 and performed a retrospective analysis. Throughout the study period, among 348 episodes of neutropenic fever in patients underwent HSCT, 89 episodes in 85 patients had microbiological defined BSI with a total of 108 isolates. Gram-negative bacteria (GNB) were the most common isolates (76, 70.3%) followed by gram-positive bacteria (GPB, 29, 26.9%) and fungus (3, 2.8%). As to the drug resistance, 26 multiple drug resistance (MDR) isolates were identified. Resistant isolates (n = 23) were more common documented in GNB, mostly Escherichia coli (9/36, 25%) and Klebsiella pneumonia (6/24, 25%). A total of 12 isolated were resistant to carbapenem including 4 K pneumoniae (4/24, 16.7%), 3 Stenotrophomonas maltophilia, and 1 Pseudomonas aeruginosa and other 4 GNB isolates (Citrobacter freumdii, Pseudomonas stutzeri, Acinetobacter baumanii, and Chryseobacterium indologenes). As to the GPB, only 3 resistant isolates were documented including 2 methicillin-resistant isolates (Staphylococcus hominis and Arcanobacterium hemolysis) and 1 vancomycin-resistant Enterococcus faecium. Among these 85 patients with documented BSI, 11 patients died of BSI as primary or associated cause with a BSI-related mortality of 13.1 ± 3.7% and 90-day overall survival after transplantation at 80.0 ± 4.3%. Patients with high-risk disease undergoing allo-HSCT, prolonged neutropenia (≥15 days) and infection with carbapenem-resistant GNB were associated with BSI associated mortality in univariate and multivariate analyses. Our report revealed a prevalence of GNB in BSI of neutropenic patients undergoing HSCT. Patients with high-risk diseases with prolonged neutropenia and carbapenem-resistant GNB were independent risk factors for BSI-related mortality. PMID:26559260

  15. Value of Serial Quantification of Fungal DNA by a Real-Time PCR-Based Technique for Early Diagnosis of Invasive Aspergillosis in Patients with Febrile Neutropenia

    PubMed Central

    Cuenca-Estrella, Manuel; Meije, Yolanda; Diaz-Pedroche, Carmen; Gomez-Lopez, Alicia; Buitrago, Maria J.; Bernal-Martinez, Leticia; Grande, Carlos; Juan, Rafael San; Lizasoain, Manuel; Rodriguez-Tudela, Juan L.; Aguado, Jose M.

    2009-01-01

    A study was designed to assess the reliability of the serial detection of Aspergillus sp. DNA to diagnose invasive aspergillosis (IA) in patients with febrile neutropenia. Two blood and two serum samples were taken weekly from 83 patients. A total of 2,244 samples were analyzed by real-time quantitative PCR. Twelve (14.4%) patients were diagnosed with IA. Taking two consecutive positive results as the diagnostic criterion, PCR detected 11 cases, with 4 false positives, giving sensitivity, specificity, positive, and negative predictive values of 91.6%, 94.4%, 73.3%, and 98.5%, respectively. On analyzing in conjunction with high-resolution chest tomography (HRCT) and galactomannan (GM) testing, the combination of serial PCR and GM detected 100% of aspergillosis cases, with a positive predictive value of 75.1%. This diagnostic strategy presented, according to CART analysis, a receiver-operator curve with an area under the curve of 0.97 (95% confidence interval, 0.895 to 1.032; P < 0.01), with a relative risk of IA 6.92 times higher than the control population and with predictive success of 95.2%. As regards early diagnosis, the serial detection of Aspergillus DNA took on average 21 days less than HRCT and 68 days less than GM. The serial detection of Aspergillus DNA using real-time quantitative PCR has great diagnostic applicability, which increases when combined with GM quantification. PMID:19109479

  16. Value of serial quantification of fungal DNA by a real-time PCR-based technique for early diagnosis of invasive Aspergillosis in patients with febrile neutropenia.

    PubMed

    Cuenca-Estrella, Manuel; Meije, Yolanda; Diaz-Pedroche, Carmen; Gomez-Lopez, Alicia; Buitrago, Maria J; Bernal-Martinez, Leticia; Grande, Carlos; Juan, Rafael San; Lizasoain, Manuel; Rodriguez-Tudela, Juan L; Aguado, Jose M

    2009-02-01

    A study was designed to assess the reliability of the serial detection of Aspergillus sp. DNA to diagnose invasive aspergillosis (IA) in patients with febrile neutropenia. Two blood and two serum samples were taken weekly from 83 patients. A total of 2,244 samples were analyzed by real-time quantitative PCR. Twelve (14.4%) patients were diagnosed with IA. Taking two consecutive positive results as the diagnostic criterion, PCR detected 11 cases, with 4 false positives, giving sensitivity, specificity, positive, and negative predictive values of 91.6%, 94.4%, 73.3%, and 98.5%, respectively. On analyzing in conjunction with high-resolution chest tomography (HRCT) and galactomannan (GM) testing, the combination of serial PCR and GM detected 100% of aspergillosis cases, with a positive predictive value of 75.1%. This diagnostic strategy presented, according to CART analysis, a receiver-operator curve with an area under the curve of 0.97 (95% confidence interval, 0.895 to 1.032; P < 0.01), with a relative risk of IA 6.92 times higher than the control population and with predictive success of 95.2%. As regards early diagnosis, the serial detection of Aspergillus DNA took on average 21 days less than HRCT and 68 days less than GM. The serial detection of Aspergillus DNA using real-time quantitative PCR has great diagnostic applicability, which increases when combined with GM quantification. PMID:19109479

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Kim, Jane; Marty, Francisco M.; Schwarzinger, Michaël

    2015-01-01

    Background Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. Methods We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran’s Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Results Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27–0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36–1.87) or overall mortality (RR 0.95, 95% CI 0.46–1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Conclusions Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals. PMID:26554923

  19. S1415CD, Prophylactic Colony Stimulating Factor Management in Patients With Breast, Colorectal or Non-Small Cell Lung Cancer Receiving Chemotherapy and With Risk of Developing Febrile Neutropenia

    ClinicalTrials.gov

    2016-04-08

    Febrile Neutropenia; Stage 0 Breast Cancer; Stage 0 Colorectal Cancer; Stage 0 Non-Small Cell Lung Cancer; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Breast Cancer; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

  20. XM02 is superior to placebo and equivalent to Neupogen™ in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy

    PubMed Central

    del Giglio, A; Eniu, A; Ganea-Motan, D; Topuzov, E; Lubenau, H

    2008-01-01

    Background Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen™ after myelotoxic chemotherapy in breast cancer (BC) patients. Methods A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 μg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen™ (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. Results The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen™, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen™ could be demonstrated. Toxicities were similar between XM02 and Neupogen™. Conclusion XM02 was superior to placebo and equivalent to Neupogen™ in reducing DSN after myelotoxic chemotherapy. Trial Registration Current Controlled Trials ISRCTN02270769 PMID:19014494

  1. Severe Neutropenia in Infectious Mononucleosis

    PubMed Central

    Hammond, William P.; Harlan, John M.; Steinberg, Stephen E.

    1979-01-01

    Mild neutropenia is a well-known concomitant of infectious mononucleosis caused by the Epstein-Barr virus (EBV) occurring in the first weeks of illness. However, severe neutropenia (less than 200 polymorphonuclear leukocytes per μl) is not generally regarded as a complication of infectious mononucleosis. Three patients were seen with severe neutropenia and EBV infection, and an additional eight cases were found in the literature. In two of the latter cases the neutropenia was fatal. In the 11 cases the severe neutropenia began 14 to 40 days after illness and usually lasted for three to seven days. At the time of severe neutropenia, studies of marrow specimens showed increased proportions of promyelocytes and myelocytes. Our data suggest that EBV infection is the proximate cause of the severe neutropenia in some patients with infectious mononucleosis and that in such cases close observation and early treatment of suspected superinfections is necessary. PMID:229647

  2. 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

  3. Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim) or Pegfilgrastim Is Cost Effective in Non-Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy

    PubMed Central

    Wang, Xiao Jun; Tang, Tiffany; Farid, Mohamad; Quek, Richard; Tao, Miriam; Lim, Soon Thye; Wee, Hwee Lin; Chan, Alexandre

    2016-01-01

    Objective This study aims to compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP chemotherapy with curative intent. Methods A Markov model was created to compare seven prophylaxis strategies: 1) primary prophylaxis (PP) with nivestim (biosimilar filgrastim) throughout all cycles of chemotherapy; 2) PP with nivestim during the first two cycles of chemotherapy; 3) secondary prophylaxis (SP) with nivestim; 4) PP with pegfilgrastim throughout all cycles of chemotherapy; 5) PP with pegfilgrastim during the first two cycles of chemotherapy; 6) SP with pegfilgrastim; and 7) no prophylaxis (NP). The perspective of a hospital was taken and cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy. A probabilistic sensitivity analysis was conducted. Results Strategies 3, 6, and 7 were dominated in the base case analysis by strategy 5. The costs associated with strategies 2, 5, 1, and 4 were US$3,813, US$4,056, US$4,545, and US$5,331, respectively. The incremental cost-effectiveness ratios for strategy 5 vs. strategy 2, strategy 1 vs. strategy 5, and strategy 4 vs. strategy 1 were US$13,532, US$22,565, and US$30,452, respectively, per episode of FN avoided. Strategy 2 has the highest probability to be cost-effective (ranged from 48% to 60%) when the willingness to pay (WTP) threshold is lower than US$10,000 per FN episode prevented. Conclusion In Singapore, routine PP with granulocyte colony-stimulating factor (nivestim or pegfilgrastim) is cost-effective for reducing the risk of FN in patients receiving R-CHOP. PMID:26871584

  4. Febrile seizures

    MedlinePlus

    American Academy of Pediatrics, Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics . 2008; ...

  5. 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 ...

  6. Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+).

    PubMed

    Camfield, Peter; Camfield, Carol

    2015-06-01

    To review the literature about febrile seizures and GEFS plus with special emphasis on management and outcome. Selected literature review. Febrile seizures are the most common convulsive event in humans, occurring in 2-6% of the population. The aetiology is complex with strong evidence for a heterogeneous genetic predisposition interacting with fever of any cause, with certain viral infections having a greater effect. A large amount of literature has established that febrile seizures have no long-term consequences on cognition or behaviour. Unfortunately, about 40% of children with a first febrile seizure will have a recurrence. The strongest predictor of recurrence is age <14-16 months at the time of the first febrile seizure. Epilepsy follows febrile seizures in ∼3% cases, with the concepts of simple and complex febrile seizures providing relatively weak prediction. Very prolonged febrile seizures may lead to mesial temporal sclerosis and temporal lobe epilepsy although the degree of risk remains uncertain. Investigations beyond establishing the cause of the provoking fever are nearly always unnecessary. Treatment is mainly reassurance and there is some evidence that parents eventually "come to grips" with the fear that their children are dying during a febrile seizure. Antipyretic medications are remarkably ineffective to prevent recurrences. Daily and intermittent prophylactic medications are ineffective or have unacceptable side effects or risks. "Rescue" benzodiazepines may prevent prolonged recurrences for selected patients with a first prolonged febrile seizure although this has not been proven. Genetic epilepsy with febrile seizures plus (GEFS+) is a complex autosomal dominant disorder usually caused by mutations in SCN1A (a voltage-gated sodium channel). One third of patients have febrile seizures only; two thirds have a variety of epilepsy syndromes, both focal and generalized. Febrile seizures may distress parents but rarely have any long-term consequences. Reassurance is the only treatment for the vast majority. Identifying patients with GEFS plus may lead to further investigations and counselling. PMID:25917466

  7. Congenital Neutropenia Syndromes

    MedlinePlus

    ... About NIAID News & Events Volunteer NIAID > Health & Research Topics > Congenital Neutropenia Syndromes Skip Website Tools Website Tools Print this page Order publications Volunteer for Clinical Studies Help people ...

  8. Olanzapine-Induced Neutropenia

    PubMed Central

    Malhotra, Kirti; Vu, Priscilla; Wang, Danielle H.; Lai, Hank; Faziola, Lawrence R.

    2015-01-01

    Olanzapine-induced neutropenia is a rare adverse effect that is currently poorly described in literature. Although neutropenia is a known adverse effect of clozapine, it has been associated with the use of other antipsychotic medications like olanzapine. This case report describes and reviews a case of olanzapine-induced neutropenia in a schizophrenic patient. Although the mechanism of antipsychotic-induced neutropenia is still debated, this report attempts to discuss current theories as well as supply evidence in literature of this rare but potentially dangerous adverse effect. PMID:26266027

  9. Febrile Seizures

    MedlinePlus

    ... Neurological Disorders and Stroke (NINDS). Publicaciones en Español Crisis Epilépticas: Esperanza en la Investigación Convulsiones Febriles Prepared by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  10. Febrile Seizures

    MedlinePlus

    ... list of all NINDS Disorders Publicaciones en Español Crisis Epilépticas: Esperanza en la Investigación Convulsiones Febriles Prepared by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  11. An infant with chronic severe neutropenia

    PubMed Central

    Bhat, Ramesh Y; Varma, Chaitanya P V; Bhatt, Sonia

    2014-01-01

    Neutropenia in infancy and childhood poses a diagnostic challenge as the aetiology ranges from acute life-threatening conditions to chronic benign diseases. Chronic benign neutropenia of infancy is a rare disorder occurring in 1:100 000. The neutrophil count continues to be low for a prolonged period until spontaneous resolution by the age of 3–4 years. Such infants are having higher incidences of minor infections requiring treatment with antibiotics and rare incidences of meningitis and sepsis. The authors describe an infant presenting with fever and cervical lymphadenitis, who was found to have isolated severe neutropenia and its persistence posing a diagnostic challenge. The prolonged course with minor infections and absence of serious underlying conditions finally confirmed chronic benign neutropenia of infancy. PMID:24711472

  12. Pegfilgrastim: a recent advance in the prophylaxis of chemotherapy-induced neutropenia.

    PubMed

    Waladkhani, A-R

    2004-09-01

    Chemotherapy-induced neutropenia is a frequent complication in cancer patients receiving myelosuppressive chemotherapy. Chemotherapy-induced neutropenia can result in febrile neutropenia and potentially life-threatening infections requiring hospitalization and intravenous anti-infectives. Chemotherapy dose may be reduced or delayed as a result of chemotherapy-induced neutropenia, which can negatively impact treatment outcomes. Granulocyte colony-stimulating factors, such as filgrastim, stimulate neutrophil production and can therefore reduce the incidence and severity of chemotherapy-induced neutropenia. Filgrastim undergoes rapid renal clearance and needs to be administered daily. The development of pegfilgrastim represents a significant advance in the management of chemotherapy-induced neutropenia as the longer serum half-life allows once-per-chemotherapy administration, and evidence supports increased prophylactic effectiveness in reducing the incidence of febrile neutropenia. This paper reviews the development of pegfilgrastim and summarizes recent clinical data on the use of this simple, effective and well-tolerated option for the management of chemotherapy-induced neutropenia in patients with cancer. PMID:15305906

  13. Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia.

    PubMed

    Rolston, Kenneth V I

    2005-04-01

    Infection is the most common complication of chemotherapy-induced neutropenia. Bacterial infections predominate during the early stages of a neutropenic episode, whereas invasive fungal infections tend to occur later. The epidemiological pattern of bacterial infection continues to evolve globally and locally at the institutional level, as do patterns of susceptibility and resistance. These trends are often associated with local treatment practices and have a significant effect on the nature of empirical antibiotic therapy. The increasing rates of antimicrobial resistance among both gram-positive and gram-negative pathogens isolated from patients with neutropenia are posing new challenges. These challenges are compounded by the fact that relatively few new drugs are being developed, particularly those that treat resistant gram-negative organisms. They also stress the increasing importance of prevention and control of infection and stewardship of antibiotics as strategies in the overall treatment of patients with febrile neutropenia. The recognition of a subset of low-risk patients with neutropenia has created new opportunities (e.g., outpatient and oral therapy) and new challenges (e.g., infrastructure, safety, and compliance). These challenges may be met, to some extent, by appropriately adapting national guidelines to local and institutional circumstances. PMID:15768330

  14. A Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis

    PubMed Central

    Abers, Michael S.; Ghebremichael, Musie S.; Timmons, Allison K.; Warren, H. Shaw; Poznansky, Mark C.; Vyas, Jatin M.

    2016-01-01

    Prolonged neutropenia is generally thought to be the major factor for invasive pulmonary aspergillosis (IPA). In the present study, we characterize the frequency, severity, and duration of neutropenia that immediately precedes IPA. Prolonged neutropenia was identified in only one third of all IPA cases and occurred exclusively in hematologic patients. PMID:27006961

  15. Colony-Stimulating Factors for Febrile Neutropenia during Cancer Therapy

    PubMed Central

    Bennett, Charles L.; Djulbegovic, Benjamin; Norris, LeAnn B.; Armitage, James O.

    2014-01-01

    A 55-year-old, previously healthy woman received a diagnosis of diffuse large-B-cell lymphoma after the evaluation of an enlarged left axillary lymph node obtained on biopsy. She had been asymptomatic except for the presence of enlarged axillary lymph nodes, which she had found while bathing. She was referred to an oncologist, who performed a staging evaluation. A complete blood count and test results for liver and renal function and serum lactate dehydrogenase were normal. Positron-emission tomography and computed tomography (PET–CT) identified enlarged lymph nodes with abnormal uptake in the left axilla, mediastinum, and retroperitoneum. Results on bone marrow biopsy were normal. The patient’s oncologist recommends treatment with six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (CHOP-R) at 21-day intervals. Is the administration of prophylactic granulocyte colony-stimulating factor (G-CSF) with the first cycle of chemotherapy indicated? PMID:23514290

  16. Severe neutropenia in a renal transplant patient suggesting an interaction between mycophenolate and fenofibrate.

    TOXLINE Toxicology Bibliographic Information

    Alvarez PA; Egozcue J; Sleiman J; Moretti L; Di Girolamo G; Keller GA

    2012-02-01

    OBJECTIVE: To describe a patient in whom initiation of micronized fenofibrate precipitated mycophenolate induced neutropenia.CASE SUMMARY: A 57-year-old man was admitted to the hospital because of febrile neutropenia. He had undergone kidney transplantation seventeen years ago. The patient's immunosuppressive maintenance regimen consisted of mycophenolate mofetil (MMF) 500 mg three times a day, and meprednisone 4 mg daily. His medical history included, hypertension treated with losartan 50mg daily, and dyslipidemia treated with ezetimibe 10mg /simvastatin 20mg for four years (until 2 weeks before admission when micronized fenofibrate 200 mg per day was started because of persistently elevated triglycerides levels. On presentation temperature was 37.8°C and initial laboratory tests showed 3130 White Blood Cell Count(WBC)/μL with neutropenia (absolute neutrophil count (ANC) 313/μL) Fenofibrate and mycophenolate mofetil were discontinued, piperacillin tazobactam 4.5gr three times a day and granulocyte stimulation factor 300 μg/day were started. Three days after admission WBC was 7280/μL, neutrophils: 22%, ANC: 1160/mm(3). Mycophenolate mofetil was restarted and granulocyte stimulation factor was discontinued. One month after discharge his WBC was 4480/μL and ANC 1926/μL.DISCUSSION: The initiation of fenofibrate in a patient on stable and therapeutic doses of mycophenolate may have precipitated mycophenolate induced neutropenia, a well described, dose dependent phenomenon. Mycophenolic acid (MPA) displays a complex pharmacokinetic profile susceptible to potential significant interactions with fenofibrate. Since approximately 99% of MPA and fenofibrate bind to albumin, displacement may occur, leading to increased free MPA. Second competition of fenofibric acid for UGT1A9 an enzyme implicated in conjugation of MPA may have decreased its metabolism. The combination of these two effects may increase the risk of dose dependent neutropenia. Using the Interaction Probability Scale (DIPS), the interaction was designated as probable.CONCLUSIONS: Until further evidence is available, when fenofibrate is started in a renal transplant patient on mycophenolate careful monitoring should be considered to avoid potentially fatal complications.

  17. Effectiveness of a Protective Environment implementation for cancer patients with chemotherapy-induced neutropenia on fever and mortality incidence.

    PubMed

    Stoll, Paula; Silla, Lcia Mariano da Rocha; Cola, Caroline Mioto Menegat; Splitt, Bruno Ismail; Moreira, Leila Beltrami

    2013-04-01

    In a quasiexperimental study conducted to evaluate the impact of a Protective Environment implementation, febrile neutropenia (P = .009), overall mortality (P = .001), and 30-day adjusted mortality (P = .02) were reduced in cancer patients with chemotherapy-induced neutropenia. Our study highlights the potential success of a set of prevention measures mainly designed to reduce invasive environmental fungal infections in allogeneic hematopoietic stem cell transplant patients, in reducing fever and mortality among neutropenic cancer patients. PMID:23102987

  18. Health care-associated infections in hematology-oncology patients with neutropenia: a method of surveillance.

    PubMed

    Ibrahim, Karim Yaqub; Pierrotti, Ligia Camera; Freire, Maristela Pinheiro; Gutierrez, Patricia Pinheiro; Duarte, Laiane do Prado Gil; Bellesso, Marcelo; Pereira, Juliana; de Alencar Fischer Chamone, Dalton; Abdala, Edson

    2013-11-01

    We present a prospective method of surveillance of health care-associated infection in hematology-oncology inpatients with neutropenia. Incidence rates were calculated on the basis of the number of hospitalized patients, the duration of hospital stay (in days), the number of days of neutropenia, and (in cases of central line-associated blood stream infection) the number of central line-days. We detected 11.4 and 66.4 episodes of febrile neutropenia per 1,000 hospital-days and per 1,000 days of neutropenia, respectively. The incidence of central line-associated blood stream infection was 2.6 per 1,000 central line-days. Gram-negative bacteria were the most prevalent pathogens. Efforts should be made to monitor infection rates on hematology-oncology wards. PMID:23769835

  19. Drug-induced immune neutropenia/agranulocytosis.

    PubMed

    Curtis, Brian R

    2014-01-01

    Neutrophils are the most abundant white blood cell in blood and play a critical role in preventing infections as part of the innate immune system. Reduction in neutrophils below an absolute count of 500 cells/pL is termed severe neutropenia or agranulocytosis. Drug-induced immune neutropenia (DIIN) occurs when drug-dependent antibodies form against neutrophil membrane glycoproteins and cause neutrophil destruction. Affected patients have fever, chills, and infections; severe infections left untreated can result in death. Treatment with granulocyte colony-stimulating factor can hasten neutrophil recovery. Cumulative data show that severe neutropenia or agranulocytosis associated with exposure to nonchemotherapy drugs ranges from approximately 1.6 to 15.4 cases per million population per year. Drugs most often associated with neutropenia or agranulocytosis include dipyrone, diclofenac, ticlopidine, calcium dobesilate, spironolactone, antithyroid drugs (e.g., propylthiouracil), carbamazepine, sulfamethoxazole- trimethoprim, [3-lactam antibiotics, clozapine, levamisole, and vancomycin. Assays used for detection of neutrophil drug-dependent antibodies (DDAbs) include flow cytometry, monoclonal antibody immobilization of granulocyte antigens, enzyme-linked immunosorbent assay, immunoblotting, granulocyte agglutination, and granulocytotoxicity. However, testing for neutrophil DDAbs is rarely performed owing to its complexity and lack of availability. Mechanisms proposed for DIIN have not been rigorously studied, but those that have been studied include drug- or hapten-induced antibody formation and autoantibody production against drug metabolite or protein adducts covalently attached to neutrophil membrane proteins. This review will address acute, severe neutropenia caused by neutrophil-reactive antibodies induced by nonchemotherapy drugs-DIIN PMID:25247619

  20. 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 ...

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

    PubMed Central

    Guariglia, Roberto; Martorelli, Maria Carmen; Lerose, Rosa; Telesca, Donatella; Milella, Maria Rita; Musto, Pellegrino

    2016-01-01

    Neutropenia and febrile neutropenia (FN) are frequent and potentially fatal toxicities of myelosuppressive anticancer treatments. The introduction of granulocyte colony-stimulating factors (G-CSFs) in clinical practice has remarkably reduced the duration and severity of neutropenia, as well as the incidence of FN, thus allowing the administration of chemotherapeutic agents at the optimal dose and time with lower risk. The current scenario of G-CSFs in Europe includes filgrastim, lenograstim, some G-CSF biosimilars, and pegfilgrastim. Recently, a novel long-acting G-CSF, lipegfilgrastim, became available. Lipegfilgrastim is a glycopegylated G-CSF, alternative to pegfilgrastim, and has shown in randomized trials, to be equivalent to pegfilgrastim in reducing the incidence of severe neutropenia and FN in patients with breast cancer receiving chemotherapy, with a similar safety profile. Furthermore, lipegfilgrastim was more effective than the placebo in reducing the incidence of severe neutropenia, its duration, and time to absolute neutrophil count recovery, in patients with non-small cell lung cancer receiving myelosuppressive therapy. Although the number of studies currently published is still limited, lipegfilgrastim seems to be a promising drug in the management of chemotherapy-induced neutropenia. PMID:26858523

  2. The genetics of benign neutropenia.

    PubMed

    Paz, Ziv; Nails, Michael; Ziv, Elad

    2011-10-01

    In Israel, Yemenite Jews and other populations including Ethiopian Jews and Bedouins have a low neutrophil count. This phenomenon has been called "benign neutropenia" since it has not been associated with any increased risk of infection and has also been described in other populations around the world including Africans, African Americans and Afro-Carribeans. Here we describe the recent success in mapping the gene that underlies benign neutropenia in African American populations. We discuss the known function of the gene and consider potential mechanisms for the effect on neutropenia. We also consider the possibility that this gene underlies the same effect observed in Yemenite Jews, Ethiopian Jews and Bedouins in Israel. PMID:22097233

  3. TCIRG1-associated congenital neutropenia.

    PubMed

    Makaryan, Vahagn; Rosenthal, Elisabeth A; Bolyard, Audrey Anna; Kelley, Merideth L; Below, Jennifer E; Bamshad, Michael J; Bofferding, Kathryn M; Smith, Joshua D; Buckingham, Kati; Boxer, Laurence A; Skokowa, Julia; Welte, Karl; Nickerson, Deborah A; Jarvik, Gail P; Dale, David C

    2014-07-01

    Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five-generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1. PMID:24753205

  4. Febrile Exanthem with Hyperferritinemia

    PubMed Central

    Caputo, Gina M.; Ryan, Edward F.

    2015-01-01

    Diagnosis of an adult with acute generalized exanthem coupled with spiking fevers, arthralgias, and myalgias requires careful consideration. History and physical examination are basic necessities, while laboratory studies can be valuable adjuncts. The authors present a case of adult onset Stills disease, discuss the differential diagnoses, and highlight the utility of high serum ferritin in identifying this febrile exanthem. PMID:26705442

  5. Novel ELANE Gene Mutation in a Korean Girl with Severe Congenital Neutropenia

    PubMed Central

    Shim, Ye Jee; Kim, Hee-Jin; Suh, Jang Soo

    2011-01-01

    Severe congenital neutropenia is a heterozygous group of bone marrow failure syndromes that cause lifelong infections. Mutation of the ELANE gene encoding human neutrophil elastase is the most common genetic alteration. A Korean female pediatric patient was admitted because of recurrent cervical lymphadenitis without abscess formation. She had a past history of omphalitis and isolated neutropenia at birth. The peripheral blood showed a markedly decreased absolute neutrophil count, and the bone marrow findings revealed maturation arrest of myeloid precursors at the promyelocyte to myelocyte stage. Her direct DNA sequencing analysis demonstrated an ELANE gene mutation (c.607G > C; p.Gly203Arg), but her parents were negative for it. She showed only transient response after subcutaneous 15 µg/kg/day of granulocyte colony stimulating factor administration for six consecutive days. During the follow-up observation period, she suffered from subsequent seven febrile illnesses including urinary tract infection, septicemia, and cellulitis. PMID:22148006

  6. Evaluation of febrile neutropenic episodes in adult patients with solid tumors

    PubMed Central

    YAPICI, OKTAY; GUNSEREN, FILIZ; YAPICI, HAFIZE; MERDIN, ALPARSLAN; YAYLALI, ÜLKÜ ÜSER; MERDIN, FATMA AVCI

    2016-01-01

    The clinical use of cytotoxic chemotherapeutic agents has increased survival in cancer patients. However, treatment-associated bone marrow suppression and neutropenia often render patients prone to life-threatening infections. The aim of this study was to evaluate episodes of febrile neutropenia (FN) in patients with solid tumors, and identify the microorganisms and the factors affecting mortality. A total of 100 primary febrile attacks in cancer patients who were followed up at the Department of Oncology of the Akdeniz University Medical Faculty Hospital between January, 2011 and May, 2012, were retrospectively investigated. FN attacks were classified in three groups as follows: Fever of unknown origin, clinically documented infections and microbiologically documented infections. We found that prolonged neutropenia, Multinational Association for Supportive Care in Cancer (MASCC) score <21 and the presence of metastasis increased mortality. We also compared the three groups of infection categories according to mortality rate, but did not observe any significant differences among these groups. Patients with malignancies should be assessed individually during the FN episodes. It is crucial to keep possible infectious pathogens in mind and evaluate the MASCC score, neutropenia duration and metastatic status of the patients, and start empirical antibiotic therapy immediately. PMID:26998287

  7. Thalidomide-induced severe neutropenia during treatment of multiple myeloma.

    PubMed

    Hattori, Yutaka; Kakimoto, Tsunayuki; Okamoto, Shinichiro; Sato, Norihide; Ikeda, Yasuo

    2004-04-01

    Recent reports have shown that thalidomide has antiangiogenic activity and is effective for the treatment of refractory multiple myeloma. Unlike other antineoplastic drugs, thalidomide is reported to rarely cause severe hematologic toxicity. In Keio University Hospital, 44 patients with refractory multiple myeloma, including 18 who had relapsed after hematopoietic stem cell transplantation, were treated with this drug as a single agent. Severe grade 3 or 4 neutropenia during thalidomide treatment was observed in 10 patients. This phenomenon was not noted in previous reports. Neutropenia usually occurred in the first or second week of treatment. Concomitant progression of thrombocytopenia occurred in 5 cases, and bone marrow hypoplasia without a significant increase in myeloma cell numbers was also observed in 5 cases. Neutropenia was not correlated with anti-tumor response or the plasma concentration of thalidomide but was more frequently observed in patients with a low neutrophil and platelet count, anemia, or a high plasma cell percentage in the bone marrow before thalidomide treatment. Thus, this drug should be used carefully for patients with pretreatment cytopenia or a high tumor burden in the bone marrow. PMID:15168599

  8. Early-Onset Neutropenia Induced by Rituximab in a Patient with Lupus Nephritis and Hemolytic Anemia

    PubMed Central

    Arroyo-Ávila, Mariangelí; Fred-Jiménez, Ruth M.; Vilá, Luis M.

    2015-01-01

    Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 109/L) after the second weekly rituximab infusion (375 mg/m2 weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections. PMID:25767732

  9. Genetic background of febrile seizures.

    PubMed

    Saghazadeh, Amene; Mastrangelo, Mario; Rezaei, Nima

    2014-01-01

    Febrile seizures (FSs) occur in children older than 1 month and without prior afebrile seizures in the absence of a central nervous system infection or acute electrolyte imbalance. Their pathogenesis is multifactorial. The most relevant familial studies evidence an occurrence rate ranging from 10% to 46% and median recurrence rate of 36% in children with positive familial history for FS. The main twin studies demonstrated a higher concordance rate in monozygotic twins with FS than in dizygotic ones. Linkage studies have proposed 11 chromosomal locations responsible to FS attributed to FEB1 to FEB11. Population-based association studies have shown at least one positive association for 14 of 41 investigated genes with FS. The proinflammatory cytokine interleukin 1β (IL-1β) was the most investigated and also gene associated with susceptibility to FS. A possible role in the overlapping of epilepsy and FS was found for 16 of 36 investigated genes. SCN1A, IL-1β, CHRNA4, and GABRG2 were the most commonly involved genes in this context. The genetic background of FS involves the regulation of different processes, including individual and familial susceptibility, modulation of immune response, and neuronal excitability and interactions with exogenous agents such as viruses. PMID:24399675

  10. Food-borne bacteremic illnesses in febrile neutropenic children

    PubMed Central

    Lee, Anselm Chi-wai; Siao-ping Ong, Nellie Dawn

    2011-01-01

    Bacteremia following febrile neutropenia is a serious complication in children with malignancies. Preventive measures are currently targeted at antimicrobial prophylaxis, amelioration of drug-induced neutropenia, and nosocomial spread of pathogens, with little attention to community-acquired infections. A retrospective study was conducted at a pediatric oncology center during a 3-year period to identify probable cases of food-borne infections with bacteremia. Twenty-one bacteremic illnesses affecting 15 children receiving chemotherapy or hematopoietic stem cell transplantation were reviewed. Three (14%) episodes were highly suspected of a food-borne origin: a 17-year-old boy with osteosarcoma contracted Sphingomonas paucimobilis septicemia after consuming nasi lemak bought from a street hawker; a 2-year-old boy with acute lymphoblastic leukemia developed Chryseobacterium meningosepticum septicemia after a sushi dinner; a 2-year-old girl was diagnosed with acute lymphoblastic leukemia and Lactobacillus bacteremia suspected to be of probiotic origin. All of them were neutropenic at the time of the infections and the bacteremias were cleared with antibiotic treatment. Food-borne sepsis may be an important, but readily preventable, cause of bloodstream infections in pediatric oncology patients, especially in tropical countries with an abundance of culinary outlets. PMID:22184532

  11. Genetics Home Reference: severe congenital neutropenia

    MedlinePlus

    ... Alter BP, Link DC, Stein S, Rodger E, Bolyard AA, Aprikyan AA, Bonilla MA, Dror Y, Kannourakis G, Newburger PE, ... 2):210-3. Epub 2007 Nov 20. Schäffer AA, Klein C. Genetic heterogeneity in severe congenital neutropenia: ...

  12. Granulocyte Antibodies in Korean Neonates with Neutropenia

    PubMed Central

    Chey, Myoung-Jae; Han, Kyou Sup

    2006-01-01

    Neonatal alloimmune neutropenia (NAN) is a disease that can cause severe and prolonged neutropenia in neonates. However, no report is available on the incidence of granulocyte antibody in neonates, the target antigen of this antibody, and the estimated incidence of NAN in Korea. Among a total of 856 neonates admitted to a neonatal intensive care unit (NICU) over a five year period, a total of 105 neonates with neutropenia were enrolled in this study. Positive reactions were observed in the sera of six neonates (5.7%, 6/105) by mixed passive hemagglutination assay (MPHA). To confirm the presence of NAN, MPHA and granulocyte antigen typing (HNA-1a, -1b, -2a, -4a, and -5a) were performed on neonatal and maternal blood. To differentiate granulocyte antibody and HLA antibody, MPHA was also performed using HLA antibody adsorbed serum. We confirmed three cases (2.9%, 3/105) of NAN among neonates with neutropenia in which granulocyte antibody specificities (two anti-HNA-1b and one anti-HNA-1a) and fetomaternal granulocyte antigen mismatches were identified. In this study, the estimated incidence of NAN was 0.35% (3/856) among neonates admitted to NICUs in Korea. PMID:16891804

  13. 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

  14. Neutrophil kinetics of recombinant human granulocyte colony-stimulating factor-induced neutropenia in rats

    SciTech Connect

    Okada, Yuji; Kawagishi, Mayumi; Kusaka, Masaru )

    1990-01-01

    Single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) immediately induced a decrease in the number of circulating neutrophils in rats. This neutropenia occurred 10 minutes after the injection but disappeared 40 minutes after injection. This transient neutropenia was dose-dependently induced by rhG-CSF and also induced by repeated injections. We studied the kinetics of circulating neutrophils in transient neutropenia. rhG-CSF markedly decreased the number of {sup 3}H-diisopropylfluorophosphate ({sup 3}H-DFP) labeled neutrophils in the circulation 10 minutes after injection but the labeled neutrophils recovered to near the control level 40 minutes after the injection. These results indicate that the neutrophil margination accounts for the neutrophenia and the marginated neutrophils return to the circulation.

  15. Febrile convulsions: acute seizure characteristics and anti-convulsant therapy.

    PubMed

    Ling, S G

    2000-09-01

    A descriptive study using data from the medical records of 448 children with febrile convulsion was carried out to determine the seizure characteristics and use of anti-convulsant therapy for febrile convulsions in a Malaysian hospital. There was a higher incidence of multiple seizures and a lower incidence of focal seizures in the local population than in studies done among Western populations. The majority of initial seizures occurred within 24 h of fever onset. Transient neurological abnormalities following an acute seizure were common. A quarter of children referred by general practitioners had been given anti-convulsants prior to referral but up to 20% of general practitioners had used ineffective routes for administering diazepam. However, diazepam used in the hospital was found to be effective in controlling acute febrile seizures. PMID:11064777

  16. Febrile/cold agglutinins

    MedlinePlus

    ... result means there were agglutinins in your blood sample. Warm agglutinins may occur with: Infections, including brucellosis , rickettsial disease , salmonella infection , and tularemia Inflammatory bowel disease Lymphoma Systemic ...

  17. Recent Research on Febrile Seizures: A Review

    PubMed Central

    Syndi Seinfeld, DO; Pellock, John M.

    2014-01-01

    Febrile seizures are common and mostly benign. They are the most common cause of seizures in children less than five years of age. There are two categories of febrile seizures, simple and complex. Both the International League against Epilepsy and the National Institute of Health has published definitions on the classification of febrile seizures. Simple febrile seizures are mostly benign, but a prolonged (complex) febrile seizure can have long term consequences. Most children who have a febrile seizure have normal health and development after the event, but there is recent evidence that suggests a small subset of children that present with seizures and fever may have recurrent seizure or develop epilepsy. This review will give an overview of the definition of febrile seizures, epidemiology, evaluation, treatment, outcomes and recent research. PMID:25383238

  18. Chemotherapy-induced neutropenia during adjuvant treatment for cervical cancer patients: development and validation of a prediction model

    PubMed Central

    Huang, Kecheng; Luo, Aiyue; Li, Xiong; Li, Shuang; Wang, Shixuan

    2015-01-01

    An artificial neuron network (ANN) model combining both the genetic risk factors and clinical factorsmay be effective in prediction of chemotherapy-induced adverse events. Purpose: To identify genetic factors and clinical factors associated with bone marrow suppression in cervical cancer patient, and to build a model for chemotherapy-induced neutropenia prediction. Methods: We performed a genome wide association study on a cohort to identify genetic determinants. Samples were genotyped using the Axiom CHB 1.0. The primary analyses focused on the scan of 657178 single-nucleotide polymorphisms (SNPs). Artificial neural network were used to integrating clinical factors and genetic factors to predict the occurrence of neutropenia. Results: 32 variants associated with neutropenia in the patients after chemotherapy were found (P<1 10-4). During internal validation and external validation, artificial neural network performed well in predicting neutropenia with considerable accuracy, which is 88.9% and 81.7% respectively. ROC analysis had acceptable areas under the curve of 0.897 for the internal validation sample and 0.782 for the external validation sample. Conclusion: Neutropenia may be associated with both genetic factors and clinical factors. Our study found that the artificial neural networks model based on the multiple risk factors jointly, can effectively predict the occurring of neutropenia, which provides some guidance before the starting of chemotherapy. PMID:26379877

  19. Cardiomyopathy in a male patient with neutropenia and growth delay

    PubMed Central

    2014-01-01

    Neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, ranging from severe (<500 neutrophils/mm3) to mild (500–1500 neutrophils/mm3), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections whose severity is roughly inversely proportional to the circulating neutrophil counts. When neutropenia is detected, an attempt should be made to establish the etiology, and to distinguish acquired forms (the most frequent, including post viral neutropenia and autoimmune neutropenia) and congenital forms (rare disorders) that may be either isolated or part of a complex rare genetic disease. We report on a male patient initially diagnosed with isolated neutropenia who later turned out to be affected with Barth syndrome, a rare complex inherited disorder. PMID:24887148

  20. Cardiomyopathy in a male patient with neutropenia and growth delay.

    PubMed

    Folsi, Veronica; Miglietti, Nunzia; Lombardi, Annamaria; Boccacci, Sara; Utyatnikova, Tatiana; Donati, Chiara; Squassabia, Livia; Gazzola, Laura; Bosio, Ilaria; Borghi, Adele; Grassi, Veronica; Notarangelo, Lucia D; Plebani, Alessandro

    2014-01-01

    Neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, ranging from severe (<500 neutrophils/mm(3)) to mild (500-1500 neutrophils/mm(3)), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections whose severity is roughly inversely proportional to the circulating neutrophil counts.When neutropenia is detected, an attempt should be made to establish the etiology, and to distinguish acquired forms (the most frequent, including post viral neutropenia and autoimmune neutropenia) and congenital forms (rare disorders) that may be either isolated or part of a complex rare genetic disease. We report on a male patient initially diagnosed with isolated neutropenia who later turned out to be affected with Barth syndrome, a rare complex inherited disorder. PMID:24887148

  1. Adequacy of High-Dose Cefepime Regimen in Febrile Neutropenic Patients with Hematological Malignancies

    PubMed Central

    Roberts, Michael S.; Tiong, Ing Soo; Gardner, Julia H.; Lehman, Sheila; Peake, Sandra L.; Hahn, Uwe; Warner, Morgyn S.; Roberts, Jason A.

    2015-01-01

    While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic/pharmacodynamic target attainment from a 2-g intravenous (i.v.) every 8 h (q8h) cefepime regimen in febrile neutropenic patients with hematological malignancies. Cefepime plasma concentrations were measured in the 3rd, 6th, and 9th dosing intervals at 60% of the interval and/or trough point. The selected pharmacokinetic/pharmacodynamic targets were the proportion of the dosing interval (60% and 100%) for which the free drug concentration remains above the MIC (fT>MIC). Target attainment was assessed in reference to the MIC of isolated organisms if available or empirical breakpoints if not. The percentage of fT>MIC was also estimated by log-linear regression analysis. All patients achieved >60% fT>MIC in the 3rd and 6th dosing intervals. A 100% fT>MIC was not attained in 6/12, 4/10, and 4/9 patients in the 3rd, 6th, and 9th dose intervals, respectively, or in 14/31 (45%) of the dosing intervals investigated. On the other hand, 29/31 (94%) of trough concentrations were at or above 4 mg/liter. In conclusion, for patients with normal renal function, a high-dose 2-g i.v. q8h cefepime regimen appears to provide appropriate exposure if the MIC of the organism is ≤4 mg/liter but may fail to cover less susceptible organisms. PMID:26124158

  2. Evidence on the use of paracetamol in febrile children.

    PubMed Central

    Russell, Fiona M.; Shann, Frank; Curtis, Nigel; Mulholland, Kim

    2003-01-01

    Antipyretics, including acetaminophen (paracetamol), are prescribed commonly in children with pyrexia, despite minimal evidence of a clinical benefit. A literature review was performed by searching Medline and the Cochrane databases for research papers on the efficacy of paracetamol in febrile illnesses in children and adverse outcomes related to the use of paracetamol. No studies showed any clear benefit for the use of paracetamol in therapeutic doses in febrile children with viral or bacterial infections or with malaria. Some studies suggested that fever may have a beneficial role in infection, although no definitive prospective studies in children have been done to prove this. The use of paracetamol in therapeutic doses generally is safe, although hepatotoxicity has occurred with recommended dosages in children. In developing countries where malnutrition is common, data on the safety of paracetamol are lacking. The cost of paracetamol for poor families is substantial. No evidence shows that it is beneficial to treat febrile children with paracetamol. Treatment should be given only to children who are in obvious discomfort and those with conditions known to be painful. The role of paracetamol in children with severe malaria or sepsis and in malnourished, febrile children needs to be clarified. PMID:12856055

  3. Approach to the patient with neutropenia in childhood

    PubMed Central

    Celkan, Tiraje; Koç, Begüm Şirin

    2015-01-01

    Neutrophils have an important role in host defense and acute inflammation. It is well known that susceptibility to infection increases when the neutrophil count is low. Neutropenia were classified as mild, moderate and severe according to the neutrophil counts, or acute and chronic depending on the duration of neutropenia, or congenital and acquired according to the mechanism. The patients with neutropenia are clinically different due to underlying mechanism, they have life- threatening infections or no infection may be observed. The most common cause of acquired neutropenia is viral infection, followed by drugs and autoimmune neutropenia. Congenital neutropenia are usually diagnosed by acute and life- threatening invasive bacterial and fungal infections. Immune system disorders and other systemic abnormalities may be accompanied or not. Recent years, novel single gen defects causing congenital neutropenia were defined through advanced genetic techniques. Molecular diagnosis is useful for risk stratification, choice of therapy and prognosis on follow- up. This review was prepared for pediatricians as a guide focused on approach neutropenia, which tests should be performed and when should be referred to a specialist. PMID:26568688

  4. Dose Schedule Optimization and the Pharmacokinetic Driver of Neutropenia

    PubMed Central

    Patel, Mayankbhai; Palani, Santhosh; Chakravarty, Arijit; Yang, Johnny; Shyu, Wen Chyi; Mettetal, Jerome T.

    2014-01-01

    Toxicity often limits the utility of oncology drugs, and optimization of dose schedule represents one option for mitigation of this toxicity. Here we explore the schedule-dependency of neutropenia, a common dose-limiting toxicity. To this end, we analyze previously published mathematical models of neutropenia to identify a pharmacokinetic (PK) predictor of the neutrophil nadir, and confirm this PK predictor in an in vivo experimental system. Specifically, we find total AUC and Cmax are poor predictors of the neutrophil nadir, while a PK measure based on the moving average of the drug concentration correlates highly with neutropenia. Further, we confirm this PK parameter for its ability to predict neutropenia in vivo following treatment with different doses and schedules. This work represents an attempt at mechanistically deriving a fundamental understanding of the underlying pharmacokinetic drivers of neutropenia, and provides insights that can be leveraged in a translational setting during schedule selection. PMID:25360756

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

    PubMed Central

    2011-01-01

    The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l. When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia. PMID:21595885

  6. Febrile response after knee and hip arthroplasty.

    PubMed

    Shaw, J A; Chung, R

    1999-10-01

    Documentation of the normal fever response after total knee and hip replacement is important to avoid an unnecessary workup for sepsis, and to provide justification for early discharge (dictated by the current medical reimbursement climate) despite persistent postoperative fever. One hundred patients who underwent total knee arthroplasty and 100 patients who underwent total hip arthroplasty were reviewed, several of whom had extensive sepsis workups for evaluation of postoperative fever. No patient in this series had a documented joint infection. All patients were treated with warfarin for deep vein thombrosis prophylaxis. All patients used incentive spirometry and were started on ambulation training on postoperative Day 1. All were given antibiotic prophylaxis for 48 hours. The maximum daily postoperative temperature occurred in most patients on postoperative Day 1 and gradually leveled off toward normal by postoperative Day 5. Only one patient had a maximum temperature on postoperative Day 4 that was greater than that on postoperative Day 3. Patients undergoing revision procedures tended to have a more pronounced febrile response, but the differences were not statistically significant. No significant differences were seen between patients who had epidural anesthesia and patients who had general anesthesia. Seventeen patients had postoperative chest radiographs for evaluation of fever. None had significant atelectasis. The presence of a positive urine culture had no effect on the fever response, with most positive results being identified after the fever had returned toward normal. Postoperative fever after total joint arthroplasty is a normal inflammatory response. A workup for sepsis is not indicated in the perioperative period unless corroborating signs or symptoms are present. Early discharge is appropriate if the febrile response is decreasing progressively. PMID:10546613

  7. Neutropenia in rheumatoid arthritis: studies on possible contributing factors.

    PubMed Central

    Bucknall, R C; Davis, P; Bacon, P A; Jones, J V

    1982-01-01

    Twenty-five patients with rheumatoid arthritis (RA) and neutropenia, of whom 19 had a palpable spleen, were compared with 24 patients with uncomplicated RA, and 16 patients with RA and associated splenomegaly without neutropenia. Clinically patients with neutropenia had evidence of a more systemic disease as assessed by prevalence of rheumatoid nodules, weight loss, and recurrent infections. However, there was less evidence of active synovitis than in the other 2 groups. Marrow neutrophil reserve was studied by means of a hydrocortisone stimulation test and was found to be lower in all 3 groups than in normal persons but with most marked depletion in the neutropenic group. Removal of the spleen in some patients with neutropenia resulted in a significant increase in marrow neutrophil reserve. Circulating immune complexes as detected by anticomplementary activity and platelet aggregation tests were detected in 68% of the RA neutropenia group, 31% of the RA splenomegaly group, and 8% of the uncomplicated RA group. Our results show that, assessed both clinically and by the above tests, patients with neutropenia have a greater prevalence of abnormalities which may be directly related to their neutropenia. Patients with splenomegaly alone closely resemble patients with uncomplicated RA. PMID:6979979

  8. Febrile Illness with Skin Rashes

    PubMed Central

    2015-01-01

    Skin rashes that appear during febrile illnesses are in fact caused by various infectious diseases. Since infectious exanthematous diseases range from mild infections that disappear naturally to severe infectious diseases, focus on and basic knowledge of these diseases is very important. But, these include non-infectious diseases, so that comprehensive knowledge of these other diseases is required. Usually, early diagnostic testing for a febrile illness with a rash is inefficient. For clinical diagnosis of diseases accompanied by skin rash and fever, a complete history must be taken, including recent travel, contact with animals, medications, and exposure to forests and other natural environments. In addition, time of onset of symptoms and the characteristics of the rash itself (morphology, location, distribution) could be helpful in the clinical diagnosis. It is also critical to understand the patient's history of specific underlying diseases. However, diagnostic basic tests could be helpful in diagnosis if they are repeated and the clinical course is monitored. Generally, skin rashes are nonspecific and self-limited. Therefore, it could be clinically meaningful as a characteristic diagnostic finding in a very small subset of specific diseases. PMID:26483989

  9. Characteristics and outcomes of neutropenia after orthotopic liver transplantation.

    PubMed

    Alraddadi, Basem; Nierenberg, Natalie E; Price, Lori Lyn; Chow, Jennifer K L; Poutsiaka, Debra D; Rohrer, Richard J; Cooper, Jeffrey T; Freeman, Richard B; Snydman, David R

    2016-02-01

    Neutropenia after orthotopic liver transplantation (LT) is relatively common, but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] ≤ 1000/mm(3) ) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, bloodstream infection (BSI), invasive fungal infection, cytomegalovirus (CMV) disease, and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC < 500/mm(3) ). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (hazard ratio [HR] 1.15; 95% confidence interval [CI], 1.03-1.30; P = 0.02), BSI (HR, 2.89; 95% CI, 1.63-5.11; P < 0.001), CMV disease (HR, 4.28; 95% CI, 1.55-11.81; P = 0.005), baseline tacrolimus trough level (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and later era LT (2004-2009 versus 1999-2003; HR, 2.28; 95% CI, 1.43-3.65; P < 0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR, 3.76; 95% CI, 1.84-7.68; P < 0.001). In conclusion, our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality. Liver Transpl 22:217-225, 2016. © 2015 AASLD. PMID:26336061

  10. Treatment of periodontitis as a manifestation of neutropenia with or without systemic antibiotics: a systematic review.

    PubMed

    Schmidt, Julia C; Walter, Clemens; Rischewski, Johannes R; Weiger, Roland

    2013-01-01

    The purposes of this paper were to systematically review the clinical presentations and management of periodontitis patients with neutropenia and present a patient with severe autoimmune neutropenia. Twenty-four case reports describing a total of 33 patients were identified. The reported signs and symptoms occurred in either a generalized or localized pattern. Improvements in periodontal condition were observed in 86% of patients who were administered adjuvant systemic antibiotics compared to 47% of patients who were not given supplemental therapy. Granulocyte-colony stimulating factor was administered to 67% of the neutropenic patients, and both improvement and progression of the hematological condition were monitored. Scaling and root planing, in combination with systemic antibiotics to supplement therapy for the underlying disease, have been successful in most cases. PMID:23635971

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

    PubMed

    Sharma, Pravesh; Davis, Jeffrey; Rachamallu, Vivekananda; Aligeti, Manish

    2016-01-01

    This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient's psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient's laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner. PMID:26904343

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

    PubMed Central

    Sharma, Pravesh; Davis, Jeffrey; Rachamallu, Vivekananda; Aligeti, Manish

    2016-01-01

    This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient's psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient's laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner. PMID:26904343

  13. Neutropenia is not required for clinical remission during azathioprine therapy in inflammatory bowel disease.

    PubMed

    Persley, K M; Present, D H

    2001-09-01

    Inflammatory bowel disease is an idiopathic chronic inflammatory process of the gastrointestinal tract. The aetiology remains unknown but probably involves a combination of genetic susceptibility, environmental triggers and abnormal immune regulation. Immunomodulators are effective in treating inflammatory bowel disease. Azathioprine and 6-mercaptopurine (6MP) are the most frequently used immunomodulator agents. These agents are probably underused by many clinicians because of concerns about myelosuppression, pancreatitis, allergic reactions and hepatotoxicity, which can occur in a fraction of patients taking these drugs. Therefore, clinicians have sought ways to optimize therapeutic response and limit toxic side effects. Neutropenia, although uncommon, can occur in patients taking azathioprine or 6MP. The question of neutropenia effecting clinical response has been raised as a possible indicator of therapeutic response. In the study from Campbell and Ghosh [7] in this issue of the European Journal of Gastroenterology and Hepatology, no difference in relapse rates was noted between neutropenic and non-neutropenic patients. In fact, severe life-threatening neutropenia was seen in four patients. PMID:11564954

  14. Immune mediated neutropenia and thrombocytopenia in 3 giant schnauzers.

    PubMed

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

    2007-11-01

    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

  15. Effect of therapy on the neutropenia of hyperthyroidism

    SciTech Connect

    Eakin, D.L.; Peake, R.L.; Weiss, G.B.

    1983-03-01

    Observations in a patient with recurrent hyperthyroidism, each time associated with neutropenia which resolved after therapy, prompted a chart review of other patients referred for radioactive iodine therapy. Of 99 untreated patients, 18 had neutrophil counts of less than 2,000/cu mm. After therapy with either thionamides or /sup 131/I, 41 of 53 (77%) evaluable patients had an increase in neutrophil count. Eleven of these evaluable patients had neutropenia before therapy; after therapy, all 11 had an increase in their neutrophil counts into the normal range, with a mean increase of 170%. In one patient, studies on the mechanism of neutropenia indicate that bone marrow production and reserve remain normal and that circulating neutrophils are normally marginated. A decreased neutrophil circulation time may be the cause of neutropenia associated with hyperthyroidism.

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

    PubMed

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

    2015-01-01

    Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An online survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for "Decreased" and "Increased" risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%); the majority defined a febrile event as temperature >38.3°C and/or 2 events >38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) <500/μL. Majority of respondents recommended "Decreased" and "Increased" patients present to a local emergency department (ED) if they live >2 hours away. Respondents were significantly more likely to have a "Decreased Risk" patient travel over 2 hours if they rated the local ED as "Poor to Fair" on ability to access Port-a-caths (P = .048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL; 40% preferred discharge on oral antibiotics when the ANC <500/μL. Triaging for febrile pediatric patients with cancer is significantly influenced by the providers' perceptions of local EDs. Future investigation of local hospitals' ability to provide urgent evaluation, combined with parental perspectives, could lead to improvements in timely and effective management. PMID:26086779

  17. Primary immune-mediated neutropenia in a cat

    PubMed Central

    Waugh, Carly E.; Scott, Katherine D.; Bryan, Laura K.

    2014-01-01

    An 18-month-old male castrated indoor Himalayan cat was presented for recurrent fever, lethargy, and uveitis. Persistent neutropenia was identified and tests for infectious disease and bone marrow cytology were performed. Primary immune-mediated neutropenia was diagnosed and successfully treated. At the time of writing this report, 24 mo after the initial diagnosis. the patient was clinically normal and not receiving therapy. PMID:25392551

  18. Primary immune-mediated neutropenia in a cat.

    PubMed

    Waugh, Carly E; Scott, Katherine D; Bryan, Laura K

    2014-11-01

    An 18-month-old male castrated indoor Himalayan cat was presented for recurrent fever, lethargy, and uveitis. Persistent neutropenia was identified and tests for infectious disease and bone marrow cytology were performed. Primary immune-mediated neutropenia was diagnosed and successfully treated. At the time of writing this report, 24 mo after the initial diagnosis. the patient was clinically normal and not receiving therapy. PMID:25392551

  19. Neutrophil elastase in cyclic and severe congenital neutropenia

    PubMed Central

    Duan, Zhijun; Korkmaz, Brice; Lee, Hu-Hui; Mealiffe, Matthew E.; Salipante, Stephen J.

    2007-01-01

    Mutations in ELA2 encoding the neutrophil granule protease, neutrophil elastase (NE), are the major cause of the 2 main forms of hereditary neutropenia, cyclic neutropenia and severe congenital neutropenia (SCN). Genetic evaluation of other forms of neutropenia in humans and model organisms has helped to illuminate the role of NE. A canine form of cyclic neutropenia corresponds to human Hermansky-Pudlak syndrome type 2 (HPS2) and results from mutations in AP3B1 encoding a subunit of a complex involved in the subcellular trafficking of vesicular cargo proteins (among which NE appears to be one). Rare cases of SCN are attributable to mutations in the transcriptional repressor Gfi1 (among whose regulatory targets also include ELA2). The ultimate biochemical consequences of the mutations are not yet known, however. Gene targeting of ELA2 has thus far failed to recapitulate neutropenia in mice. The cycling phenomenon and origins of leukemic transformation in SCN remain puzzling. Nevertheless, mutations in all 3 genes are capable of causing the mislocalization of NE and may also induce the unfolded protein response, suggesting that there might a convergent pathogenic mechanism focusing on NE. PMID:17053055

  20. Febrile Seizures and Epilepsy: Possible Outcomes

    MedlinePlus

    ... status epilepticus in children: The FEB- STAT Study. Neurology 2012;79:871– 877. 2. Graves RC, Oehler ... Am J Epidemiol 2007;165:911–918. e82 Neurology 79 August 28, 2012 Febrile seizures: Possible outcomes ...

  1. 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 patients 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 7296 h should be based on the patients 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

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

    PubMed Central

    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

    2015-01-01

    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

  3. Immune-mediated neutropenia suspected in five dogs.

    PubMed

    Perkins, M C; Canfield, P; Churcher, R K; Malik, R

    2004-01-01

    Five cases of suspected immune-mediated neutropenia in dogs are described. Clinical signs varied depending on whether the animals had a systemic infection or concurrent immune-mediated disease. Patients were diagnosed by excluding other causes of neutropenia, supportive bone marrow aspirate findings, an initial favourable response to corticosteroid administration in four of the cases, and concurrent immune-mediated disease. Four of the dogs were receiving medications at the time of diagnosis, and immune-mediated neutropenia secondary to drug therapy cannot be excluded. This study shows that appropriate immunosuppressive treatment can lead to a favourable outcome, however, care is required to avoid adverse effects associated with corticosteroid use. It is also imperative that medications are not withdrawn abruptly as a second remission may not always be achievable. PMID:15088959

  4. The changing face of febrile neutropenia-from monotherapy to moulds to mucositis. Prevention of mould infections.

    PubMed

    Maschmeyer, Georg

    2009-05-01

    Isolation of patients at risk of invasive mould infection might be suitable for the reduction of invasive aspergillosis or zygomycosis, if combined with high-efficiency particulate air filtration. Prophylactic wearing of filtering masks of N95 or FFP2 standards has not yet been demonstrated to be efficacious in reducing invasive mould infections outside of scenarios with excessive contamination of room air by fungal spore-loaded dust. The oral broad-spectrum antifungal azoles posaconazole and voriconazole offer protection against invasive Aspergillus infections in severely neutropenic leukaemia patients and allogeneic haematopoietic stem cell transplant recipients; however, their routine use might result not only in considerable side effects, but also in the spread of multi-azole-resistant Aspergillus species, so that careful selection of suitable high-risk patient populations is mandatory. PMID:19372178

  5. Tackling antibiotic resistance in febrile neutropenia: current challenges with and recommendations for managing infections with resistant Gram-negative organisms.

    PubMed

    Nouér, Simone A; Nucci, Marcio; Anaissie, Elias

    2015-10-01

    Multidrug resistant (MDR) Gram-negative bacteria (GNB) have emerged as important pathogens and a serious challenge in the management of neutropenic patients worldwide. The great majority of infections are caused by the Enterobacteriaceae (especially Escherichia coli and Klebsiella spp.) and Pseudomonas aeruginosa, and less frequently Acinetobacter spp. and Stenotrophomonas maltophilia. A broader-spectrum empiric antibiotic regimen is usually recommended in patients with a history of prior bloodstream infection caused by a MDR GNB, in those colonized by a MDR GNB, and if MDR GNBs are frequently isolated in the initial blood cultures. In any situation, de-escalation to standard empiric regimen is advised if infection with MDR GNB is not documented. PMID:26115679

  6. Febrile Seizures and Febrile Seizure Syndromes: An Updated Overview of Old and Current Knowledge

    PubMed Central

    Khair, Abdulhafeez M.; Elmagrabi, Dalal

    2015-01-01

    Febrile seizures are the most common paroxysmal episode during childhood, affecting up to one in 10 children. They are a major cause of emergency facility visits and a source of family distress and anxiety. Their etiology and pathophysiological pathways are being understood better over time; however, there is still more to learn. Genetic predisposition is thought to be a major contributor. Febrile seizures have been historically classified as benign; however, many emerging febrile seizure syndromes behave differently. The way in which human knowledge has evolved over the years in regard to febrile seizures has not been dealt with in depth in the current literature, up to our current knowledge. This review serves as a documentary of how scientists have explored febrile seizures, elaborating on the journey of knowledge as far as etiology, clinical features, approach, and treatment strategies are concerned. Although this review cannot cover all clinical aspects related to febrile seizures at the textbook level, we believe it can function as a quick summary of the past and current sources of knowledge for all varieties of febrile seizure types and syndromes. PMID:26697219

  7. Febrile seizures in Kaduna, north western Nigeria

    PubMed Central

    Eseigbe, E. E.; Adama, S. J.; Eseigbe, P.

    2012-01-01

    Background: Febrile seizure is the most common seizure of childhood and has a good prognosis. However its presentation is fraught with poor management, with grave consequences, in our environment. Thus a review of its current status is important. Objective: To review the status of febrile seizures in Kaduna metropolis. Materials and Methods: A review of cases seen in the Department of Paediatrics, 44 Nigeria Army Reference Hospital, Kaduna between June 2008 and June 2010. Results: Out of the 635 cases admitted in the department 17 (2.7%) fulfilled the criteria for febrile seizures. There were 11 Males and 6 Females (M: F, 1.8:1). Age range was from 9 months to 5 years with a mean of 2.2 years ± 1.1 and peak age of 3 years. Twelve (70.6%) were in the upper social classes (I-III). Fever, convulsion, catarrh and cough were major presenting symptoms. Incidence of convulsion was least on the 1st day of complaint. Fourteen (82.4%) of the cases were simple febrile seizures while 3 were complex. There was a positive family history in 5 (29.4%) of the cases. Eleven (64.7%) had orthodox medication at home, before presentation, 5 (29.4%) consulted patient medicine sellers and 7 (41.7%) received traditional medication as part of home management. Malaria and acute respiratory infections were the identifiable causes. Standard anti-malaria and anti-biotic therapy were instituted, where indicated. All recovered and were discharged. Conclusion: There was a low prevalence of febrile seizures among the hospitalized children and a poor pre-hospitalization management of cases. It highlighted the need for improved community awareness on the prevention and management of febrile seizures. PMID:23293414

  8. Fatal bacteremic melioidosis in patients with prolonged neutropenia.

    PubMed

    Sridhar, Siddharth; Teng, Jade L L; Lau, Susanna K P; Woo, Patrick C Y

    2016-03-01

    Melioidosis, an infection with an expanding geographic range, is extremely rare in neutropenic patients. We report bacteremic melioidosis (ST-70 and ST-660) in 2 patients with prolonged neutropenia, who succumbed despite appropriate antibiotics. Clinicians should be aware of this emerging infection in neutropenic patients residing in or returning from endemic areas. PMID:26712267

  9. Borrelia crocidurae Infection in Acutely Febrile Patients, Senegal

    PubMed Central

    Mediannikov, Oleg; Socolovschi, Cristina; Bassene, Hubert; Diatta, Georges; Ratmanov, Pavel; Fenollar, Florence; Sokhna, Cheikh

    2014-01-01

    As malaria cases in Africa decline, other causes of acute febrile illness are being explored. To determine incidence of Borrelia crocidurae infection during June 2010–October 2011, we collected 1,566 blood specimens from febrile patients in Senegal. Incidence was high (7.3%). New treatment strategies, possibly doxycycline, might be indicated for febrile patients. PMID:25062495

  10. Febrile Convulsions: Their Significance for Later Intellectual Development and Behaviour.

    ERIC Educational Resources Information Center

    Wallace, S.J.

    1984-01-01

    Concludes that intellectual and behavioral outcomes in children who have had febrile convulsions are dependent on preseizure status, unilaterality of the initial fit, recurrent febrile seizures, continued neurological abnormalities, the advent of fits when afebrile, and socioeconomic status. Suggests that a febrile convulsion should be followed up…

  11. Febrile Convulsions: Their Significance for Later Intellectual Development and Behaviour.

    ERIC Educational Resources Information Center

    Wallace, S.J.

    1984-01-01

    Concludes that intellectual and behavioral outcomes in children who have had febrile convulsions are dependent on preseizure status, unilaterality of the initial fit, recurrent febrile seizures, continued neurological abnormalities, the advent of fits when afebrile, and socioeconomic status. Suggests that a febrile convulsion should be followed up

  12. Hippocampal Sclerosis After Febrile Status Epilepticus: The FEBSTAT Study

    PubMed Central

    Lewis, Darrell V.; Shinnar, Shlomo; Hesdorffer, Dale C.; Bagiella, Emilia; Bello, Jacqueline A.; Chan, Stephen; Xu, Yuan; MacFall, James; Gomes, William A.; Moshé, Solomon L.; Mathern, Gary W.; Pellock, John M.; Nordli, Douglas R.; Frank, L. Matthew; Provenzale, James; Shinnar, Ruth C.; Epstein, Leon G.; Masur, David; Litherland, Claire; Sun, Shumei

    2014-01-01

    Objective Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine if FSE produces acute hippocampal injury that evolves to HS. Methods FEBSTAT and two affiliated studies prospectively recruited 226 children aged 1 month to 6 years with FSE and controls with simple febrile seizures. All had acute MRIs and follow-up MRIs were obtained at approximately 1 year later in the majority. Visual interpretation by two neuroradiologists informed only of subject age was augmented by hippocampal volumetrics, analysis of the intra-hippocampal distribution of T2 signal, and apparent diffusion coefficients. Results Hippocampal T2 hyperintensity, maximum in Sommer's sector, occurred acutely after FSE in 22 of 226 children in association with increased volume. Follow-up MRIs obtained on 14 of the 22 with acute T2 hyperintensity showed HS in 10 and reduced hippocampal volume in 12. In contrast, follow-up of 116 children without acute hyperintensity showed abnormal T2 signal in only 1 (following another episode of FSE). Furthermore, compared to controls with simple febrile seizures, FSE subjects with normal acute MRIs had abnormally low right to left hippocampal volume ratios, smaller hippocampi initially and reduced hippocampal growth. Interpretation Hippocampal T2 hyperintensity after FSE represents acute injury often evolving to a radiological appearance of HS after one year. Furthermore, impaired growth of normal appearing hippocampi after FSE suggests subtle injury even in the absence of T2 hyperintensity. Longer follow-up is needed to determine the relationship of these findings to TLE. PMID:24318290

  13. Chemotherapy-induced neutropenia is associated with prolonged remission duration and survival time in canine lymphoma.

    PubMed

    Wang, S L; Lee, J J; Liao, A T

    2015-07-01

    Myelosuppression is one of the most common side effects of chemotherapy. The aim of this study was to determine whether chemotherapy-induced neutropenia is a positive prognostic indicator for remission and survival time in dogs with lymphoma. Fifty dogs with multicentric lymphoma received CHOP-based (C-cyclophosphamide; H-hydroxydaunorubicin; O-vincristine; P-prednisolone) chemotherapy using conventional dosages. Complete blood counts were recorded to determine the presence or absence of neutropenia after treatment. Toxicity, remission, and survival times were recorded and analysed. Thirteen dogs had chemotherapy-induced neutropenia and 37 had no neutropenia during the study period. No statistical difference was found between the groups for signalment or the presence of historical negative prognostic factors, except for bodyweight (P = 0.02). The median first remission times in the neutropenia and no neutropenia groups were 812 and 219 days, respectively (P <0.01). The median survival times of dogs in the neutropenia and no neutropenia groups were 952 and 282 days, respectively (P <0.01). Dogs with lymphoma that had chemotherapy-induced neutropenia exhibited significantly increased remission and survival times compared with dogs without neutropenia. Chemotherapeutic dosages may be adjusted individually to induce neutropenia without severe adverse effects in order to achieve longer remission and survival times. PMID:26004824

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

    PubMed Central

    Angelis, Dimitrios; Kubicky, Rita Ann; Zubrow, Alan B.

    2015-01-01

    Maternal Graves' disease is relatively uncommon with an estimated incidence of 0.4%–1% of all pregnancies, but only 1–5% of newborns delivered to mothers with Graves' disease develop overt clinical signs and symptoms of hyperthyroidism. Here, we describe a case of a 1380-gram female neonate who was born at 30-week gestation to a mother with Graves' disease. Our patient presented with hyperthyroidism followed by transient hypothyroidism requiring treatment with levothyroxine. While hyperthyroid, she was treated with methimazole, iodine, and a beta-blocker. 20 days after the initiation of methimazole, she developed neutropenia. The neutrophil counts started to improve immediately after the initiation of the weaning of methimazole. To the best of our knowledge, this is the first case reported in the literature of methimazole induced neutropenia in a preterm infant being treated for neonatal Graves' disease. PMID:25810932

  15. Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register.

    PubMed

    Ferry, C; Ouachée, M; Leblanc, T; Michel, G; Notz-Carrére, A; Tabrizi, R; Flood, T; Lutz, P; Fischer, A; Gluckman, E; Donadieu, J

    2005-01-01

    Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe congenital neutropenia (SCN). Among 101 cases of SCN included in the French Severe Chronic Neutropenia Registry, nine patients received HSCT between 1993 and 2003, in seven institutions. The indications were nonresponse to G-CSF therapy in four cases, bone marrow failure in one case, and myelodysplastic syndrome or leukemia in four cases. The conditioning regimen consisted of total body irradiation in two cases and chemotherapy alone in the other seven cases. Seven patients received stem cells from unrelated donors and two from identical siblings. Engraftment occurred in all but one of the patients. Three patients died. The respective causes of death were graft-versus-host disease, infection, and EBV post-transplant lymphoproliferative disease. Six patients are alive and in complete remission, with a median follow-up of 3.1 years. These results indicate that HSCT is feasible for patients with SCN who do not respond to G-CSF, who have malignant transformation, or who are at a high risk of malignant transformation, even if an HLA-identical sibling donor is not available. PMID:15489867

  16. Inheritance of febrile seizures in sudden unexplained death in toddlers.

    PubMed

    Holm, Ingrid A; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R; Kinney, Hannah C; Krous, Henry F

    2012-04-01

    Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

  17. Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

    PubMed Central

    Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.

    2014-01-01

    Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

  18. Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry

    PubMed Central

    Salmon, J H; Cacoub, P; Combe, B; Sibilia, J; Pallot-Prades, B; Fain, O; Cantagrel, A; Dougados, M; Andres, E; Meyer, O; Carli, P; Pertuiset, E; Pane, I; Maurier, F; Ravaud, P; Mariette, X; Gottenberg, J E

    2015-01-01

    Objectives To evaluate the prevalence of late-onset neutropenia and its complications in patients treated with rituximab (RTX) for rheumatoid arthritis (RA) and other autoimmune diseases (AIDs) in a prospective registry. Methods The AutoImmunity and Rituximab registry is an independent 7-year prospective registry promoted by the French Society of Rheumatology. For each episode of neutropenia, data were validated by the clinician in charge of the patient. Results Among 2624 patients treated with RTX for refractory AIDs, and at least 1 follow-up visit (a total follow-up of 4179 patient-years in RA and 987 patient-years in AIDs), late-onset neutropenia was observed in 40 patients (25 RA (1.3% of patients with RA, 0.6/100 patient-years), and AIDs in 15 (2.3% of patients with AIDs, 1.5/100 patient-years)). 6 patients (15%) had neutrophils <500/mm3, 8 (20%) had neutrophils between 500 and 1000/mm3, and 26 (65%) had neutrophils between 1000 and 1500/mm3. Neutropenia occurred after a median period of 4.5 (3–6.5) months after the last RTX infusion in patients with RA, and 5 (3–6.5) months in patients with AIDs. 5 patients (12.5%), 4 of them with neutrophils lower than 500/mm3, developed a non-opportunistic serious infection and required antibiotics and granulocyte colony-stimulating factor injections, with a favourable outcome. After resolution of their RTX-related neutropenia, 19 patients (47.5%) were re-treated, and neutropenia reoccurred in 3 of them. Conclusions Late-onset neutropenia might occur after RTX and may result in serious infections. Thus, monitoring of white cell count should be performed after RTX. However, in this large registry of patients with AIDs, the frequency of RTX-induced neutropenia was much lower than that previously reported in patients treated for blood malignancies or AIDs. PMID:26509060

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

    PubMed

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

    2015-09-01

    The purpose of this report is to discuss the treatment of a patient with cyclic neutropenia. This patient presented with flared teeth, thin alveolar bone, and mobile teeth. A staged approach was used to remove her teeth, augment the bone, use immediate fixed provisional to determine the type of final prostheses, and ultimately to use cone-shaped overdenture attachments to retain her final prostheses. The result was rehabilitation of the patient with esthetic full-arch fixed-removable dentures with no adverse sequelae in this patient with this systemic disease. PMID:25913513

  20. Techniques for induction of neutropenia and granulocytosis in rats.

    PubMed

    Popovic, V; Schaffer, R; Popovic, P

    1976-09-01

    After a single administration of vinblastine, rats develop profound neutropenia. The agranulocytosis lasts 3 days, and it is observed on the third, fourth and fifth day after vinblastine administration. The granulocytosis that develops on days 7-14 after vinblastine administration was significantly increased when androgenic steroids were administered. Deca-Durabolin induced greater granulocytosis than testosterone. The peak values were observed 10 and 12 days, respectively, after drug administration. All values of WBC's, granulocytes and hematocrit ratios were obtained in unanesthetized, unrestrained rats from an aortic cannula implanted at least 10 days prior to the experiment. PMID:976388

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

    PubMed

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

    2016-04-01

    Benign ethnic neutropenia (BEN) is an asymptomatic condition reported in adults of African and Middle Eastern descent. The clinical description in children is currently lacking. In our urban outpatient pediatric hematology clinic, the median neutrophil count of children with BEN was lower than previous reports in adults at 893×10 cells/L, but increased with older age. There was an equal male to female ratio and 24% of our BEN children reported ethnicities other than African or Middle Eastern. Children with BEN had a clinical course comparable with other healthy children including otherwise normal blood counts, except for mild anemia. PMID:26925714

  2. Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination

    PubMed Central

    Harada, Saori; Yamazaki, Sho; Nakamura, Fumihiko; Morita, Ken; Yoshimi, Akihide; Shinozaki-Ushiku, Aya; Fukayama, Masashi; Kurokawa, Mineo

    2014-01-01

    Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma. PMID:25337296

  3. [Febrile ulceronecrotic Mucha-Habermann disease].

    PubMed

    Dupin, A; Bosset, D; Atger, L; Chevallier, B; Saiag, P; Benoist, G

    2016-01-01

    Pityriasis lichenoides et varioliformis acuta (PLEVA) is an inflammatory skin disease that is unknown to pediatricians. The ulceronecrotic febrile form is a rare and potentially lethal variant. We report the case of a 7-year-old boy with a papulovesicular eruption lasting for 4weeks, secondarily associated with ulcers and necrotic crusts, fever, and systemic signs. After exploring infectious causes such as chickenpox, we discussed and confirmed PLEVA with histological analysis. Systemic steroids and methotrexate improved the symptoms. It is necessary to mention PLEVA in case of prolonged papulovesicular eruption. Prompt diagnosis allows appropriate treatment, although there is no consensus on therapeutic guidelines. PMID:26552626

  4. Iron Deficiency and Iron Deficiency Anemia in Children with Febrile Seizure

    PubMed Central

    Fallah, R; Tirandazi, B; Akhavan Karbasi, S; Golestan, M

    2013-01-01

    Background Febrile seizure (FS) is the most common childhood seizures which occur in 2-5% of children. Studies about association between iron deficiency and febrile seizure have shown contradictory results. The purpose of this study was to compare the iron status of children with first febrile seizure and healthy control group. Materials and Methods In an analytic case-control study , iron status of 6 to 60 months old admitted children with first FS to Shahid Sadoughi Hospital from December 2011 to August 2012 was evaluated and compared with healthy age and sex matched control children whom were referred for routine health care to primary health care center of Azadshar Yazd, Iran. Results Forty five (44%) girls and 55 boys with a mean age of 23.7 ± 14.3 months were evaluated. In children with FS , hemoglobin level (11.46 ± 1.18 g/dl vs. 11.9 ± 0.89 g/dl, p= 0.042) , serum iron levels (48.91 ± 22.96 μg/dl vs. 75.13 ± 35.57 μg/dl , p= 0.001) and serum ferritin level (38.52 ± 11.38 ng/ml vs. 54.32 ± 13.46 ng/ml, p= 0.001) were lower than in healthy children group . Iron deficiency (48% vs. 28% , odds ratio 4.3, p=0.03) and iron deficiency anemia (22% vs. 10% , odds ratio = 3.16, p= 0.04) were more frequent in children with FS. Conclusion Based on the result of this study, iron deficiency could be an important risk factor for development of febrile convulsion. Evaluation of iron status is encouraged to be performed in children with febrile seizure. PMID:24575264

  5. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    ERIC Educational Resources Information Center

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal

  6. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    ERIC Educational Resources Information Center

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

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

    PubMed Central

    Caselli, Désirée; Cesaro, Simone; Aricò, Maurizio

    2016-01-01

    Advances in chemotherapy and surgery allows the majority of patients to survive cancer diseases. Yet, the price may be a proportion of patients dying of complications due to treatment-induced infectious complications, such as neutropenia. With the aim of decreasing morbidity and mortality related to infectious complications, recombinant human granulocyte colony-stimulating factor (G-CSF), filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia. A biosimilar is a copy of an approved original biologic medicine whose data protection has expired. The patent for filgrastim expired in Europe in 2006 and in the US in 2013. This review analyses the available evidence to be considered in order to design a strategy of use of G-CSF and its biosimilars. The clinical and safety outcomes of biosimilars are well within the range of historically reported data for originator filgrastim. This underscores the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice. Biosimilars can play an important role by offering the opportunity to reduce costs, thus contributing to the financial sustainability of treatment programs. PMID:26937170

  8. A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

    PubMed Central

    Colombo, Elisa A.; Carra, Silvia; Fontana, Laura; Bresciani, Erica; Cotelli, Franco; Larizza, Lidia

    2015-01-01

    Poikiloderma with Neutropenia (PN) is an autosomal recessive genodermatosis characterized by early-onset poikiloderma, pachyonychia, hyperkeratosis, bone anomalies and neutropenia, predisposing to myelodysplasia. The causative C16orf57/USB1 gene encodes a conserved phosphodiesterase that regulates the stability of spliceosomal U6-RNA. The involvement of USB1 in splicing has not yet allowed to unveil the pathogenesis of PN and how the gene defects impact on skin and bone tissues besides than on the haematological compartment. We established a zebrafish model of PN using a morpholino-knockdown approach with two different splicing morpholinos. Both usb1-depleted embryos displayed developmental abnormalities recapitulating the signs of the human syndrome. Besides the pigmentation and osteochondral defects, usb1-knockdown caused defects in circulation, manifested by a reduced number of circulating cells. The overall morphant phenotype was also obtained by co-injecting sub-phenotypic dosages of the two morpholinos and could be rescued by human USB1 RNA. Integrated in situ and real-time expression analyses of stage-specific markers highlighted defects of primitive haematopoiesis and traced back the dramatic reduction in neutrophil myeloperoxidase to the myeloid progenitors showing down-regulated pu.1 expression. Our vertebrate model of PN demonstrates the intrinsic requirement of usb1 in haematopoiesis and highlights PN as a disorder of myeloid progenitors associated with bone marrow dysfunction. PMID:26522474

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

    PubMed Central

    Tröger, Wilfried; Jezdić, Svetlana; Ždrale, Zdravko; Tišma, Nevena; Hamre, Harald J.; Matijašević, Miodrag

    2009-01-01

    Background: Chemotherapy for breast cancer often deteriorates quality of life, augments fatigue, and induces neutropenia. Mistletoe preparations are frequently used by cancer patients in Central Europe. Physicians have reported better quality of life in breast cancer patients additionally treated with mistletoe preparations during chemotherapy. Mistletoe preparations also have immunostimulant properties and might therefore have protective effects against chemotherapy-induced neutropenia. Patients and Methods: We conducted a prospective randomized open label pilot study with 95 patients randomized into three groups. Two groups received Iscador® M special (IMS) or a different mistletoe preparation, respectively, additionally to chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluoro-uracil (CAF). A control group received CAF with no additional therapy. Here we report the comparison IMS (n = 30) vs. control (n = 31). Quality of life including fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Neutropenia was defined as neutrophil counts <1,000/μl and assessed at baseline and one day before each CAF cycle. Results: In the descriptive analysis all 15 scores of the EORTC-QLQ-C30 showed better quality of life in the IMS group compared to the control group. In 12 scores the differences were significant (p < 0.02) and nine scores showed a clinically relevant and significant difference of at least 5 points. Neutropenia occurred in 3/30 IMS patients and in 8/31 control patients (p = 0.182). Conclusions: This pilot study showed an improvement of quality of life by treating breast cancer patients with IMS additionally to CAF. CAF-induced neutropenia showed a trend to lower frequency in the IMS group. PMID:21556248

  10. Undifferentiated febrile illnesses in military personnel.

    PubMed

    Burns, Daniel S; Bailey, Mark S

    2013-09-01

    Undifferentiated febrile illnesses (UFIs) present with acute symptoms, objective fever and no specific organ focus on clinical assessment. The term is mostly used in developing and tropical countries where a wide range of infections may be responsible. Laboratory diagnosis often requires specialist microbiology investigations that are not widely available, and serology tests that only become positive during convalescence. Optimal clinical management requires a good travel history, awareness of local endemic diseases, an understanding of the features that may help distinguish different causes and appropriate use of empirical antibiotics. This review describes the most common examples of UFI in military personnel on overseas deployments, and provides a practical approach to their initial management. PMID:24109142

  11. Molecular Factors and Biochemical Pathways Induced by Febrile Temperature in Intraerythrocytic Plasmodium falciparum Parasites▿ †

    PubMed Central

    Oakley, Miranda S. M.; Kumar, Sanjai; Anantharaman, Vivek; Zheng, Hong; Mahajan, Babita; Haynes, J. David; Moch, J. Kathleen; Fairhurst, Rick; McCutchan, Thomas F.; Aravind, L.

    2007-01-01

    Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodium falciparum parasite cultures incubated at 37°C and 41°C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. Of these, 163 genes (49%) were upregulated by twofold or greater, and 173 genes (51%) were downregulated by twofold or greater. In-depth sensitive sequence profile analysis revealed that febrile temperature-induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biologic functional predictions for at least 100 distinct genes previously annotated as “hypothetical.” We find that cultivation of P. falciparum parasites at 41°C leads to parasite death in a time-dependent manner. The presence of the “crisis forms” and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling-positive parasites following heat treatment strongly support the notion that an apoptosis-like cell death mechanism might be induced in response to febrile temperatures. These studies enhance the possibility of designing vaccines and drugs on the basis of disruption in molecules and pathways of parasite survival and virulence activated in response to febrile temperatures. PMID:17283083

  12. Autoimmune Neutropenia as a Cause of Periodontal Disease in Preschool Children.

    PubMed

    Hajishengallis, Evlambia; Rashewsky, Stephanie; Kulkarni, Cyelee; Stathopoulou, Panagiota

    2016-01-01

    In autoimmune neutropenia, autoantibodies attack neutrophils resulting in their destruction or alteration of their function. Since neutrophils have important immunologic functions, aberrations in their homeostasis lead to increased susceptibility to diseases, such as periodontitis. Periodontitis as a manifestation of neutropenia can affect adults and children. In this paper, we describe the treatment of periodontal disease in a 2-year-old female with autoimmune neutropenia. The importance of an interdisciplinary approach, frequent recalls, and meticulous mechanical therapy in stabilizing her periodontal condition, despite ongoing systemic infections is emphasized. PMID:26696110

  13. Epilepsy in children with a history of febrile seizures

    PubMed Central

    Lee, Sang Hyun; Byeon, Jung Hye; Kim, Gun Ha; Eun, Baik-Lin

    2016-01-01

    Purpose Febrile seizure, the most common type of pediatric convulsive disorder, is a benign seizure syndrome distinct from epilepsy. However, as epilepsy is also common during childhood, we aimed to identify the prognostic factors that can predict epilepsy in children with febrile seizures Methods The study comprised 249 children at the Korea University Ansan Hospital who presented with febrile seizures. The relationship between the subsequent occurrence of epilepsy and clinical factors including seizure and fever-related variables were analyzed by multivariate analysis. Results Twenty-five patients (10.0%) had additional afebrile seizures later and were diagnosed with epilepsy. The subsequent occurrence of epilepsy in patients with a history of febrile seizures was associated with a seizure frequency of more than 10 times during the first 2 years after seizure onset (P<0.001). Factors that were associated with subsequent occurrence of epilepsy were developmental delay (P<0.001), preterm birth (P=0.001), multiple seizures during a febrile seizure attack (P=0.005), and epileptiform discharges on electroencephalography (EEG) (P=0.008). Other factors such as the age at onset of first seizure, seizure duration, and family history of epilepsy were not associated with subsequent occurrence of epilepsy in this study. Conclusion Febrile seizures are common and mostly benign. However, careful observation is needed, particularly for prediction of subsequent epileptic episodes in patients with frequent febrile seizures with known risk factors, such as developmental delay, history of preterm birth, several attacks during a febrile episode, and epileptiform discharges on EEG. PMID:26958066

  14. 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

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

    ClinicalTrials.gov

    2012-09-20

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

  16. 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

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

    PubMed

    Koh, Andrew Y; Köhler, Julia R; Coggshall, Kathleen T; Van Rooijen, Nico; Pier, Gerald B

    2008-02-01

    Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections. PMID:18282097

  18. Optimum management of pediatric patients with fever and neutropenia.

    PubMed

    Gaur, Aditya H; Flynn, Patricia M; Shenep, Jerry L

    2004-09-01

    Fever with neutropenia is a common clinical problem in patients receiving cancer treatment. Prevention and optimum management of infectious complications is critical to the overall success of cancer therapy. This article provides an overview of the current status of this evolving subject. While the basic principles of rapid institution of broad spectrum antibiotics, early intervention with empiric antifungal therapy and continuation of antimicrobials during period of risk are unlikely to change, there is increasing interest in titrating this aggressive approach based on the projected risk of the development of a serious invasive infection. Oral antibiotic therapy and outpatient management are currently being studied in pediatric oncology patients, but even when successful these alternatives to the traditional "in hospital, parenteral antibiotic therapy" approach are unlikely to be applicable in all patient populations and clinical settings. While there is no replacement for clinical acumen and careful monitoring, judicious use of diagnostic resources such as blood cultures and imaging studies is a key component of optimum care. Selection of empiric antibiotics based on ongoing monitoring of antimicrobial susceptibility patterns is emphasized. PMID:15448391

  19. Inherited biallelic CSF3R mutations in severe congenital neutropenia

    PubMed Central

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

    2014-01-01

    Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frameshifts and premature stop codons (NM_000760.3:c.948_963del, NP_000751.1:p.Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis. PMID:24753537

  20. Copeptin as a Serum Biomarker of Febrile Seizures

    PubMed Central

    Schillinger, Paula; Cayir, Sevgi; Skendaj, Roswitha; Ramser, Michel; Weber, Peter; Wellmann, Sven

    2015-01-01

    Background and Objectives Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion. Methods This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment. Clinical Trial Registration: NCT01884766. Results Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6]) compared to febrile controls (5.6 pmol/L [4.1-9.4]; p <0.001), with no differences between febrile and epileptic seizures (21.4 pmol/L [16.1-46.6]; p = 0.728). In a multivariable regression model, seizures were the major determinant of serum copeptin (beta 0.509; p <0.001), independently of clinical and baseline laboratory indices. The area under the receiver operating curve for copeptin was 0.824 (95% CI 0.753-0.881), significantly higher compared to prolactin (0.667 [0.585-0.742]; p <0.001). The diagnostic accuracy of copeptin increased with decreasing time elapsed since the convulsive event (at 120 min: 0.879 [0.806-0.932] and at <60 min: 0.975 [0.913-0.997]). Conclusions Circulating copeptin has high diagnostic accuracy in febrile seizures and may be a useful adjunct for accurately diagnosing postictal states in the emergency setting. PMID:25894585

  1. Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy

    PubMed Central

    Blackwell, K.; Semiglazov, V.; Krasnozhon, D.; Davidenko, I.; Nelyubina, L.; Nakov, R.; Stiegler, G.; Singh, P.; Schwebig, A.; Kramer, S.; Harbeck, N.

    2015-01-01

    Background Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen®, in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC). Patients and methods A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomized 1:1:1:1 into four arms. Two arms received only one product (nonalternating), biosimilar or reference, and two arms (alternating) received alternating treatments during each cycle (biosimilar then reference or vice versa). The primary end point was duration of severe neutropenia (DSN) during cycle 1. Results The baseline characteristics were balanced between the four treatment arms. Noninferiority of biosimilar versus the reference was demonstrated: DSN (days) in cycle 1 was 1.17 ± 1.11 (biosimilar, N = 101) and 1.20 ± 1.02 (reference, N = 103), 97.5% confidence interval lower boundary for the difference was −0.26 days (above the predefined limit of −1 day). No clinically meaningful differences were observed regarding any other efficacy parameter: incidence of febrile neutropenia (FN); hospitalization due to FN; incidence of infections; depth and time of absolute neutrophil count (ANC) nadir and time to ANC recovery during cycle 1 and across all cycles. The pattern and frequency of adverse events were similar across all treatments. Conclusion This study demonstrates that biosimilar and the reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially benefiting public health by increasing access to filgrastim treatment. Study number NCT01519700. PMID:26122726

  2. Febrile illness experience among Nigerian nomads

    PubMed Central

    2012-01-01

    Background An understanding of the febrile illness experience of Nigerian nomadic Fulani is necessary for developing an appropriate strategy for extending malaria intervention services to them. An exploratory study of their malaria illness experience was carried out in Northern Nigeria preparatory to promoting malaria intervention among them. Methods Ethnographic tools including interviews, group discussions, informal conversations and living-in-camp observations were used for collecting information on local knowledge, perceived cause, severity and health seeking behaviour of nomadic Fulani in their dry season camps at the Gongola-Benue valley in Northeastern Nigeria. Results Nomadic Fulani regarded pabboje (a type of "fever" that is distinct from other fevers because it "comes today, goes tomorrow, returns the next") as their commonest health problem. Pabboje is associated with early rains, ripening corn and brightly coloured flora. Pabboje is inherent in all nomadic Fulani for which treatment is therefore unnecessary despite its interference with performance of duty such as herding. Traditional medicines are used to reduce the severity, and rituals carried out to make it permanently inactive or to divert its recurrence. Although modern antimalaria may make the severity of subsequent pabboje episodes worse, nomads seek treatment in private health facilities against fevers that are persistent using antimalarial medicines. The consent of the household head was essential for a sick child to be treated outside the camp. The most important issues in health service utilization among nomads are the belief that fever is a Fulani illness that needs no cure until a particular period, preference for private medicine vendors and the avoidance of health facilities. Conclusions Understanding nomadic Fulani beliefs about pabboje is useful for planning an acceptable community participatory fever management among them. PMID:22292982

  3. [Intense neutropenia of 14 years duration as the only manifestation of a myelodysplastic syndrome].

    PubMed

    Las Heras, G; Marti, J M; Villamor, N; Ribera, J M; Feliu, E; Rozman, C

    1995-11-11

    Myelodysplastic syndromes (MDS) are a group of acquired hemopathies characterized by peripheral cytopenias due to ineffective hematopoiesis and a high risk of transformation into acute non lymphoblastic leukemia (ANLL) which, in most cases, usually occurs from 6 months to 4 years after diagnosis. A patient with extreme neutropenia with intense dysgranulopoiesis as the only manifestations of MDS is described. The patient was controlled over 14 years and presented multiple infectious episodes, in various locations, throughout the evolution, some being very severe and generally caused by gram-negative germs. Likewise, during this time the patient received different treatments (oxymetholone, prednisone and lithium carbonate) with no hematologic response being observed. The leukocyte count remained around 3 x 10(9)/L with a mean proportion of neutrophils of 12% with no variations being found in the bone marrow aspirates carried out throughout the evolution (total of 9). At 14 years the diagnosis of MDS evolved to ANLL. The patient died shortly after the acute transformation due to respiratory failure secondary to bilateral pneumonia. In this case three peculiar features are of note: the almost exclusive involvement of the granulopoietic series without either anemia or thrombocytopenia, the long evolution of AREB, with acute transformation 14 years after diagnosis and the severity of the infections, among which recurrent lingual granulopenic ulcers were of note. PMID:8523943

  4. 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

  5. Recognition memory is impaired in children after prolonged febrile seizures.

    PubMed

    Martinos, Marina M; Yoong, Michael; Patil, Shekhar; Chin, Richard F M; Neville, Brian G; Scott, Rod C; de Haan, Michelle

    2012-10-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal injury may be evident in human children after prolonged febrile seizures. The current study addressed this question by investigating memory abilities in 26 children soon after a prolonged febrile seizure (median: 37.5 days) and compared their results to those of 37 normally developing children. Fifteen patients were reassessed at a mean of 12.5 months after their first assessment to determine the transiency of any observed effects. We used the visual paired comparison task to test memory abilities in our group, as this task does not depend on verbal abilities and also because successful performance on the task has been proven to depend on the presence of functional hippocampi. Our findings show that patients perform as well as controls in the absence of a delay between the learning phase and the memory test, suggesting that both groups are able to form representations of the presented stimulus. However, after a 5-min delay, patients' recognition memory is not different from chance, and comparison of patients and controls points to an accelerated forgetting rate in the prolonged febrile seizure group. The patients' performance was not related to the time elapsed from the acute event or the duration of the prolonged febrile seizure, suggesting that the observed effect is not a by-product of the seizure itself or a delayed effect of medication administered to terminate the seizure. By contrast, performance was related to hippocampal size; participants with the smallest mean hippocampal volumes revealed the biggest drop in performance from the immediate to the delayed paradigm. At follow-up, children were still showing deficiencies in recognizing a face after a 5-min delay. Similarly, this suggests that the observed memory impairments are not a transient effect of the prolonged febrile seizures. This is the first report of such impairments in humans, and it is clinically significant given the links between mesial temporal sclerosis and prolonged febrile seizures. The persistence of these impairments a year onwards signals the potential benefits of intervention in these children who run the risk of developing episodic memory deficits in later childhood. PMID:22945967

  6. Serious neutropenia following neoadjuvant chemotherapy for locally advanced breast cancer: A case report

    PubMed Central

    WANG, ZHEN; CHEN, JUN-QIANG; LIU, JIN-LU; QIN, XIN-GAN

    2016-01-01

    Neoadjuvant chemotherapy has been widely used in patients with locally advanced breast cancer (LABC) to increase the chance of breast conservation. Among the most active adjuvant chemotherapy regimens, doxorubicin and cyclophosphamide are the most common drugs used for breast cancer in adjuvant and advanced settings, and taxanes are added to neoadjuvant regimens to improve the pathological complete response rates. However, chemotherapy is often associated with a variety of acute and long-term side effects, and neutropenia is one of the most common chemotherapy-associated toxicities. Lethal neutropenia is rarely reported in clinics. The present study reports the case of a patient with LABC that received 1 cycle of neoadjuvant chemotherapy [intravenous docetaxel (75 mg/m2), pirarubicin (45 mg/m2) and cyclophosphamide (500 mg/m2) on day 2 in 3-weekly intervals] and succumbed to neutropenia and subsequent multiple organ dysfunction syndrome. The present study suggests that neutropenia may be associated with significant mortality if not managed appropriately. Based on the findings of the present study, individual chemotherapy regimens, dosing schedules, effective methods of the prevention and management of neutropenia, and the management of the discharged patient require additional consideration. PMID:26893787

  7. Continuing clozapine with granulocyte colony-stimulating factor in patients with neutropenia

    PubMed Central

    Harvey, Jake; Sengupta, Samrat

    2013-01-01

    Background: The current guidelines dictate that clozapine should be stopped following the emergence of neutropenia. Various alternative approaches have been tried in the past, among them one rarely used alternative being to continue treatment with clozapine with coprescription of granulocyte colony-stimulating factor (G-CSF). Aim and method: In this case series we aim to describe the treatment and progress of a number of patients in a secure psychiatric hospital in the UK. These patients were restarted on clozapine in combination with G-CSF, in spite of previous neutropenia associated with clozapine treatment. Discussion and conclusion: We hope that this case series will raise the profile of a potentially effective alternative to discontinuing clozapine after neutropenia. PMID:24167701

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

    PubMed Central

    Donskov, Frede; Michaelson, M Dror; Puzanov, Igor; Davis, Mellar P; Bjarnason, Georg A; Motzer, Robert J; Goldstein, David; Lin, Xun; Cohen, Darrel P; Wiltshire, Robin; Rini, Brian I

    2015-01-01

    Background: Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities. Methods: In sunitinib-treated mRCC patients (N=770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure ⩾140 mm Hg), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand–foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. Results: On-treatment neutropenia and hypertension were associated with longer PFS (P=0.0276 and P<0.0001, respectively) and OS (P=0.0014 and P<0.0001, respectively), independent of baseline prognostic factors, including International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. By 12-week landmark analysis, neutropenia was significantly associated with longer PFS and OS (P=0.013 and P=0.0122, respectively) and hypertension or hand–foot syndrome with longer OS (P=0.0036 and P=0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63−0.67) for IMDC classification alone and 0.72 (95% CI: 0.70−0.74) when combined with hypertension and neutropenia. Considering hypertension and neutropenia (developing both vs neither) changed IMDC-predicted median OS in each IMDC risk group (favourable: 45.3 vs 19.5 months; intermediate: 32.5 vs 8.0 months; poor: 21.1 vs 4.8 months). Conclusions: On-treatment neutropenia and hypertension are independent biomarkers of sunitinib efficacy and may add prognostic accuracy to the IMDC model. PMID:26492223

  9. Concurrent bacteraemia and malaria in febrile Nigerian infants.

    PubMed

    Ayoola, Omolola O; Adeyemo, Adebowale A; Osinusi, Kikelomo

    2005-01-01

    In the tropics, febrile illnesses are often presumed to be due to malaria, because of its endemicity, and treatment can lead to delay in diagnosis or failure to detect severe infections such as bacteraemia. This study sought to determine the prevalence of bacteraemia and malaria parasitaemia in febrile post-neonatal infants (age 1-12 months) at the University College Hospital, Ibadan, Nigeria, and the bacterial aetiological agents of bacteraemia in the infants. Therefore, 102 infants aged 1-12 months who presented with fever with a negative history of antimicrobial use in the week prior to presentation were evaluated and had blood cultures done for the detection of aerobic organisms by standard methods and blood films for malaria parasites. Bacteraemia was found in 38.2% of the infants, malaria parasitaemia was found in 46.1%. The most common organisms isolated were Escherichia coli (35.9%), Staphylococcus aureus (33.3%) and Klebsiella spp. (10.3%). Febrile children should be investigated for the presence of bacterial infection even if the blood film for malaria parasites is positive. Where laboratory facilities are not available, consideration should be given to the use of both anti-malarial therapy and empiric antibiotic therapy in the management of febrile infants, depending on the clinician's judgement. PMID:15712544

  10. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers.

    PubMed

    Dubé, Céline M; Ravizza, Teresa; Hamamura, Mark; Zha, Qinqin; Keebaugh, Andrew; Fok, Kimberly; Andres, Adrienne L; Nalcioglu, Orhan; Obenaus, Andre; Vezzani, Annamaria; Baram, Tallie Z

    2010-06-01

    Whether long febrile seizures (FSs) can cause epilepsy in the absence of genetic or acquired predisposing factors is unclear. Having established causality between long FSs and limbic epilepsy in an animal model, we studied here if the duration of the inciting FSs influenced the probability of developing subsequent epilepsy and the severity of the spontaneous seizures. We evaluated if interictal epileptifom activity and/or elevation of hippocampal T2 signal on magnetic resonance image (MRI) provided predictive biomarkers for epileptogenesis, and if the inflammatory mediator interleukin-1beta (IL-1beta), an intrinsic element of FS generation, contributed also to subsequent epileptogenesis. We found that febrile status epilepticus, lasting an average of 64 min, increased the severity and duration of subsequent spontaneous seizures compared with FSs averaging 24 min. Interictal activity in rats sustaining febrile status epilepticus was also significantly longer and more robust, and correlated with the presence of hippocampal T2 changes in individual rats. Neither T2 changes nor interictal activity predicted epileptogenesis. Hippocampal levels of IL-1beta were significantly higher for >24 h after prolonged FSs. Chronically, IL-1beta levels were elevated only in rats developing spontaneous limbic seizures after febrile status epilepticus, consistent with a role for this inflammatory mediator in epileptogenesis. Establishing seizure duration as an important determinant in epileptogenesis and defining the predictive roles of interictal activity, MRI, and inflammatory processes are of paramount importance to the clinical understanding of the outcome of FSs, the most common neurological insult in infants and children. PMID:20519523

  11. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers

    PubMed Central

    Dubé, Celiné M.; Ravizza, Teresa; Hamamura, Mark; Zha, Qinqin; Keebaugh, Andrew; Fok, Kimberly; Andres, Adrienne M.; Nalcioglu, Orhan; Obenaus, Andre; Vezzani, Annamaria; Baram, Tallie Z.

    2010-01-01

    Whether long febrile seizures (FS) can cause epilepsy in the absence of genetic or acquired predisposing factors is unclear. Having established causality between long FS and limbic epilepsy in an animal model, we studied here if the duration of the inciting FS influenced the probability of developing subsequent epilepsy and the severity of the spontaneous seizures. We evaluated if interictal epileptifom activity and/or elevation of hippocampal T2 signal on MRI provided predictive biomarkers for epileptogenesis, and if the inflammatory mediator interleukin-1β (IL-1β), an intrinsic element of FS generation, contributed also to subsequent epileptogenesis. We found that febrile status epilepticus, lasting an average of 64 minutes, increased the severity and duration of subsequent spontaneous seizures compared with FS averaging 24 minutes. Interictal activity in rats sustaining febrile status epilepticus was also significantly longer and more robust, and correlated with the presence of hippocampal T2 changes in individual rats. Neither T2 changes nor interictal activity predicted epileptogenesis. Hippocampal levels of IL-1β were significantly higher for over 24 hours after prolonged FS. Chronically, IL-1β levels were elevated only in rats developing spontaneous limbic seizures after febrile status epilepticus, consistent with a role for this inflammatory mediator in epileptogenesis. Establishing seizure duration as an important determinant in epileptogenesis, and defining the predictive roles of interictal activity, MRI, and inflammatory processes are of paramount importance to the clinical understanding of the outcome of FS, the most common neurological insult in infants and children. PMID:20519523

  12. 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

  13. Identification of a New Locus for Generalized Epilepsy with Febrile Seizures Plus (GEFS+) on Chromosome 2q24-q33

    PubMed Central

    Moulard, Bruno; Guipponi, Michel; Chaigne, Denys; Mouthon, Dominique; Buresi, Catherine; Malafosse, Alain

    1999-01-01

    Summary We report the identification of a new locus for generalized epilepsy with febrile seizures plus (GEFS+). Six family members manifested isolated typical febrile seizures (FS), and five had typical FS associated with generalized epilepsy (FS+, generalized tonic/clonic seizures). Afebrile seizures occurred from childhood until the teenage years. The maximum two-point LOD score was 3.99 for markers D2S294 and D2S2314. Flanking markers place the GEFS+ locus between D2S141 and D2S116, with multipoint analysis favoring the 13-cM interval spanned by D2S294 and D2S364. This locus is the second GEFS+ locus to be reported, which suggests that this syndrome is genetically heterogeneous. PMID:10521305

  14. Dengue and Chikungunya Fever among Viral Diseases in Outpatient Febrile Children in Kilosa District Hospital, Tanzania

    PubMed Central

    Chipwaza, Beatrice; Mugasa, Joseph P.; Selemani, Majige; Amuri, Mbaraka; Mosha, Fausta; Ngatunga, Steve D.; Gwakisa, Paul S.

    2014-01-01

    Introduction Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria. Methods A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2–13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used. Results A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35–3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus. Conclusion Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended. PMID:25412076

  15. Neutropenia in three patients with rheumatic disorders. Suppression of granulopoiesis by control-sensitive thymus-dependent lymphocytes.

    PubMed Central

    Bagby, G C; Gabourel, J D

    1979-01-01

    A man with polymyalgia rheumatica (patient 1) and two patients (2 and 3) with Felty's syndrome had neutropenia at the time of diagnosis. Bone marrow samples in each patient were cellular but showed an "arrest" of granulocyte maturation at the myelocyte stage. Agar colony growth of marrow cells from each patient was subnormal but increased after removal of sheep erythrocytes rosette-forming cells (thymus-dependent [T] cells) from marrow cell suspensions before culture. Preincubation of marrow cells with cortisol also enhanced colony growth. Maximum enhancement with cortisol occurred at 1 mM (patient 1), 1 microM (patient 2), and 10 nM (patient 3). Cortisol failed to enhance colony growth after removal of T cells from marrow cell suspensions. Peripheral blood lymphocytes (PBL) and PBL-conditioned medium from all three patients inhibited colony growth of normal human marrow cells. Cortisol treatment of PBL or T depletion from PBL abrogated the inhibition in coculture and with conditioned medium. Prednisone therapy resulted in the disappearance of suppressor T-cell function concomitant with hematologic improvement in patients 2 and 3, but suppressor T cells persisted in patient 1, who did not respond to prednisone. We conclude that cortisol-sensitive T lymphocytes inhibited granulopoiesis in vitro probably by elaboration of a soluble factor or factors. Our results suggest (a) that neutropenia in these patients resulted, at least in part, from T-cell suppression of granulopoiesis, (b) that the effectiveness of prednisone therapy was a result of its inhibition of suppressor T cells, and (c) that responses to glucocorticoid therapy may be predicted in such patients with the agar culture technique and cortisol dose response in vitro. PMID:312812

  16. 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

  17. 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

  18. 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. PMID:26107839

  19. Recovery of hair coat color in Gray Collie (cyclic neutropenia)-normal bone marrow transplant chimeras.

    PubMed Central

    Yang, T. J.

    1978-01-01

    Gray Collie-normal bone marrow transplantation chimeras showed normal coloration of the hair coat on tails and several other areas 2 years after successful transplantation of bone marrow to correct cyclic neutropenia of the Gray Collie syndrome. Images Figures 1-2 PMID:347941

  20. 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

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

    PubMed Central

    2009-01-01

    Background Five cases of severe neutropenia (neutrophil counts < 0.5 per 109 cells/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. Methods Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. Results We compare cases of severe neutropenia associated with tainted cocaine (NATC) identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55%) were from Alberta; 19(45%) were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used); 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%). Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA). Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in Alberta Interpretation Our findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness of the differential diagnosis will assist clinicians with case timely detection and appropriate management. PMID:19919709

  2. Use of Granulocyte ColonyStimulating Factor During Pregnancy in Women With Chronic Neutropenia

    PubMed Central

    Boxer, Laurence A.; Bolyard, Audrey Anna; Kelley, Merideth L.; Marrero, Tracy M.; Phan, Lan; Bond, Jordan M.; Newburger, Peter E.; Dale, David C.

    2014-01-01

    Objective To report outcomes associated with the administration of granulocyte colonystimulating factor (G-CSF) to women with chronic neutropenia during pregnancy. Methods We conducted an observational study of women of child-bearing potential with congenital, cyclic, idiopathic, or autoimmune neutropenia enrolled in the Severe Chronic Neutropenia International Registry to determine outcomes of pregnancies, without and with chronic G-CSF therapy, 19992014. Treatment decisions were made by the patients personal physicians. A research nurse conducted telephone interviews of all enrolled U.S. women of child-bearing potential using a standard questionnaire. Comparisons utilized Fishers exact test analysis and Students t-test. Results One-hundred seven women reported 224 pregnancies, 124 without G-CSF therapy and 100 on chronic G-CSF therapy (median dose: 1.0 mcg/kg/day, range 0.028.6 mcg/kg/day). There were no significant differences in adverse events between the groups considering all pregnancies or individual mothers, e.g., spontaneous terminations (all pregnancies: no G-CSF 27/124, G-CSF 13/100; P=0.11, Fishers exact test,), preterm labors (all pregnancies, no G-CSF 9/124, G-CSF 2/100, P=0.12,). A study with at least 300 per group would be needed to detect a difference in these events with 80% statistical power (alpha=0.05). Four newborns of mothers with idiopathic or autoimmune neutropenia not on G-CSF (4/101) had life-threatening infections, whereas there were no similar events (0/90) in the treated group, but this difference was also not statistically significant. (p=0.124). Adverse events in the neonates were similar for the two groups. Conclusions This observational study showed no significant adverse effects of administration of G-CSF to women with severe chronic neutropenia during pregnancy. PMID:25560125

  3. The effect of clinical characteristics on the performance of galactomannan and PCR for the diagnosis of invasive aspergillosis in febrile neutropenic patients.

    PubMed

    Oz, Yasemin; Aslan, Muge; Aksit, Filiz; Metintas, Selma; Gunduz, Eren

    2016-02-01

    Rapid diagnosis and early treatment of invasive aspergillosis is crucial for the management of the patients with haematological malignancy. We evaluated 358 sera from 78 febrile neutropenic episodes in patient with invasive aspergillosis (IA) (one proven, 17 probable, and 60 possible) and 83 episodes in patients with no IA according to the EORTC/MSG criteria. Patient's specimens were tested by Mycassay Aspergillus PCR (first commercial real-time PCR test) and in house real-time PCR to investigate the presence of Aspergillus DNA, and by ELISA for detect the galactomannan (GM) antigen. We systematically investigated the medical background that can be effective on the test results. The hospitalisation period was longer in proven/probable episodes when compared with no IA (P = 0.001) and possible episodes. With regard to duration of neutropenia, the differences between both proven/probable with no IA (P = 0.023) and possible with no IA (P = 0.002) were highly significant. Similarly, the rates of T cell suppressant therapy in group proven/probable and possible episodes were significantly higher than in no IA (P = 0.005). There are significant differences in the performance of GM and PCR-based tests among studies, and standardisation is required. Therefore, it can be useful to determine the effective factors on these tests. The use of larger volume of sera improved the performance of real-time PCR for detection of Aspergillus DNA in high-risk adult patients in the present study. Some host factors such as duration of neutropenia and administration of T cell suppressants related to the development of IA. PMID:26627843

  4. [Febrile torticollis: an atypical presentation of Kawasaki disease].

    PubMed

    Runel-Belliard, C; Lasserre, S; Quinet, B; Grimprel, E

    2009-02-01

    Kawasaki disease is a form of idiopathic systemic vasculitis. Diagnosis is based upon specific clinical parameters. Cardiac manifestations explain the mortality rate. They can be reduced by early treatment using intravenous immunoglobulin. Atypical Kawasaki disease is difficult to diagnose and can delay diagnosis. We report a case of Kawasaki disease with arthritis in a 4-year-old girl whose initial presentation was a febrile torticollis. A literature review details the atypical early signs of Kawasaki disease revealed by torticollis. PMID:19112010

  5. Acute febrile torticollis in youth: clinical investigation and current management

    PubMed Central

    Ouattassi, Naouar; Chmiel, Mohammed; Kerouiti, Zakaria El; Ridal, Mohammed; Alami, Mohammed Nouredine

    2015-01-01

    Acute febrile torticollis in children is a rare and a special clinical picture of variable causes. It may indicate an inflammatory or an infectious pathology affecting any of the anatomical structures of the neck. Treatment is quite clearly defined, and it may be a therapeutic emergency. It is a condition that all ENT specialists must be familiar with since they are most likely to be the first physician to whom such a child is brought PMID:26328000

  6. Febrile response to infection in the American alligator (Alligator mississippiensis).

    PubMed

    Merchant, Mark; Williams, Stephanie; Trosclair, Phillip L; Elsey, Ruth M; Mills, Kaili

    2007-12-01

    Temperature probes were inserted into the stomachs of juvenile American alligators (Alligator mississippiensis) maintained outdoors at ambient fluctuating temperatures. Internal body temperatures (T(b)) were measured every 15 min for two days, and then the alligators were injected with bacterial lipopolysaccharide (LPS), pyrogen-free saline, or left untreated. Alligators injected intraperitoneally with LPS exhibited maximum T(b)s 2.6+/-1.1 degrees C and 3.5+/-1.2 degrees C higher than untreated control animals on days one and two after treatment, respectively. T(b)s for these animals fell to within control ranges by day three postinjection. Similarly, mean preferred body temperatures (MPBTs) were significantly higher for LPS-injected alligators on days one (4.2+/-1.8 degrees C) and two (3.5+/-1.6 degrees C) after treatment. Intraperitoneal injection of heat-killed Aeromonas hydrophila, a gram-negative bacterium known to infect crocodilians, resulted in a fever while injection of Staphylococcus aureus (gram positive) did not elicit a febrile response. Injection of LPS in alligators maintained indoors in a constant temperature environment resulted in no increase in internal T(b). These results indicate that alligators did not exhibit a febrile response in the absence of a thermal gradient, and suggest that febrile responses observed are probably behavioral in nature. PMID:17977038

  7. Long term outcome of prophylaxis for febrile convulsions.

    PubMed Central

    Knudsen, F U; Paerregaard, A; Andersen, R; Andresen, J

    1996-01-01

    A cohort of 289 children with febrile convulsions who had been randomised in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures) was followed up 12 years later. The study focused on the occurrence of epilepsy and on neurological, motor, intellectual, cognitive, and scholastic achievements in the cohort. At follow up the two groups were of almost identical age (14.0 v 14.1 years), body weight (58.2 v 57.2 kg), height (168.2 v 167.7 cm), and head circumference (55.9 v 56.2 cm). The occurrence of epilepsy (0.7% v 0.8%), neurological examination, fine and gross motor development on the Stott motor test, intellectual performance on the Wechsler intelligence scale for children verbal IQ (105 v 105), performance IQ (114 v 111), and full scale IQ (110 v 108), cognitive abilities on a neuropsychological test battery, including short and long term, auditory and visual memory, visuomotor tempo, computer reaction time, reading test, and scholastic achievement were also very similar. Children with simple and complex febrile convulsions had the same benign outcome. The long term prognosis in terms of subsequent epilepsy, neurological, motor, intellectual, cognitive, and scholastic ability was not influenced by the type of treatment applied in early childhood. Preventing new febrile convulsions appears no better in the long run than abbreviating them. PMID:8660037

  8. A Severe Congenital Neutropenia Type 4 Case (G6PC3 Mutation) Presented With Large Platelets in the Peripheral Smear.

    PubMed

    Kaymak Cihan, Meriç; Bolat, Fatih; Onay, Hüseyin; Sari, Ahmet; Ünver Korğali, Elif; Aslan, Şükran; Cura, Ceylan; İçağasioğlu, Dilara

    2016-05-01

    Severe congenital neutropenia type 4 is a disorder of the hematopoietic system associated with mutations in the glucose-6-phosphatase catabolic 3 (G6PC3) gene. This disorder is characterized by neutropenia, congenital heart defects, urogenital malformations, and prominent superficial veins. To our knowledge, although intermittent thrombocytopenia is observed in this mutation, the coexistence of large thrombocytes is rarely seen. Here we present a case of severe congenital neutropenia type 4 with G6PC3 mutation and large platelets in the peripheral smear. PMID:26808373

  9. Trace Elements in Febrile Seizure Compared to Febrile Children Admitted to an Academic Hospital in Iran, 2011

    PubMed Central

    Amouian, Sepideh; Mohammadian, Sakineh; Behnampour, Naser; Tizrou, Mohsen

    2013-01-01

    Background and Aim: Pathogenesis of Febrile Convulsion (FC) is unknown but some elements and genetic predispositions have been considered in the top list. This case-control study was designed to compare some trace elements in paediatrics who were admitted with FC and those in febrile ones without seizure attacks at an academic hospital in northeast of Iran. Material and Methods: This case-control study was done from June 2010 to July 2011 on 160 paediatrics (6-months to 5-years old) who were diagnosed with FC and on 160 age-matched febrile children as control group. Data on the age, gender, past history of fever and convulsion, age at the first episode of seizure and family history of FC were gathered by using a designed checklist. Complete Blood Count (CBC), serum iron, Total Iron Binding Capacity (TIBC), zinc, magnesium and calcium were tested after taking informed consents from the parents. Serum levels of trace elements were measured by a photometric method. Independent t-test or non-parametric Mann-Whitney test were used to compare means between two groups. Results: There were no significant differences between the cases and controls with regards to the gender or age. TIBC and magnesium were lower in FC, but calcium, iron and zinc were higher in FC as compared to those in the other group (not significant). Conclusions: So, it could be said that deficiency of trace elements was not significantly related to febrile convulsion in our study and it seemed that these tests were not necessary in FC cases. But further investigations on other trace elements are needed. PMID:24298483

  10. Increasing Prevalence of Plasmodium vivax among Febrile Patients in Nouakchott, Mauritania

    PubMed Central

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

    2015-01-01

    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

  11. 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

  12. Sporadic Centronuclear Myopathy with Muscle Pseudohypertrophy, Neutropenia, and Necklace Fibers due to a DNM2 mutation

    PubMed Central

    Liewluck, Teerin; Lovell, Tracy L.; Bite, Anna V.; Engel, Andrew G.

    2010-01-01

    Dynamin 2 gene (DNM2) mutations result in an autosomal dominant centronuclear myopathy (CNM) and a Charcot-Marie-Tooth (CMT) neuropathy. DNM2-CMT but not DNM2-CNM patients were noted to have neutropenia. We here report a man with paravertebral muscles hypertrophy and mild neutropenia. His muscle biopsy was typical for CNM with additional “necklace” fibers. Sequencing of DNM2 revealed a known heterozygous c.1269C>T (p.Arg369Trp) mutation. Necklace fibers were considered as a pathological hallmark of late onset X-linked CNM due to mutations in MTM1 but have not been observed in DNM2-CNM. The findings broaden the features of DNM2-myopathy. PMID:20817456

  13. CLPB Mutations Cause 3-Methylglutaconic Aciduria, Progressive Brain Atrophy, Intellectual Disability, Congenital Neutropenia, Cataracts, Movement Disorder

    PubMed Central

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

    2015-01-01

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria. PMID:25597510

  14. Acute febrile encephalopathy in adults from Northwest India

    PubMed Central

    Bhalla, Ashish; Suri, Vika; Varma, Subhash; Sharma, Navneet; Mahi, Sushil; Singh, Paramjeet; Khandelwal, Niranjan K

    2010-01-01

    Background: Acute onset fever with altered mentation is a common problem encountered by the physician practicing in tropical countries. Central nervous system (CNS) infections are the most common cause resulting in fever with altered mentation in children. Aim: In this study, we have tried to analyze the cause of encephalopathy following short febrile illness in adults presenting to a tertiary care center in Northwestern part of India. Setting and Design: A prospective observational study carried out in a tertiary care center in the Northwestern India over a period of 1 year. Material and Methods A total of 127 patients with fever of less than 2 weeks duration along with alteration in mentation were studied prospectively over a period of 12 months. The demographic variables were recorded in detail. In addition to routine investigations, cerebrospinal fluid analysis, noncontrast- and contrast-enhanced computed tomography, along with magnetic resonance imaging were performed in all the subjects. Statistical Analysis The results were analyzed using SPSS statistical software. The values were expressed as mean with standard deviation for contiguous variable as percentage for the others. Results and Conclusion Out of these, 70% had primary CNS infection as the etiology. A total of 33% patients had meningitis, 29.9% had evidence of meningoencephalitis, and 12.7% were diagnosed as sepsis-associated encephalopathy. These were followed by cerebral malaria, leptospirosis, and brain abscess as the cause of febrile encephalopathy in adults. Among the noninfectious causes, acute disseminated encephalomyelitis, cortical venous thrombosis, and neuroleptic malignant syndrome were documented in 2.36% each. In 11% of the patients, the final diagnosis could not be made in spite of the extensive investigations. Our study demonstrates that acute febrile encephalopathy in adults is a heterogeneous syndrome with primary CNS infections being the commonest etiology. PMID:20930964

  15. Predictors of bacteraemia among febrile infants in Ibadan, Nigeria.

    PubMed

    Ayoola, Omolola O; Adeyemo, Adebowale A; Osinusi, Kikelomo

    2002-09-01

    Fever is a common complaint in infancy, and bacteraemia is one of the more serious causes of such fever. However, there exists scanty data on risk of bacteraemia among febrile infants of developing countries and what clinical predictors, if any, could identify those febrile infants with bacteraemia. To address this issue, 102 infants aged 1-12 month(s) attending the Children's Emergency Ward of University College Hospital, Ibadan, Nigeria, with rectal temperatures of > or = 38 degrees C and with a negative history of antimicrobial use for at least one week prior to presentation, were studied to identify clinical predictors of bacteraemia. Infants, meeting the eligibility criteria of the study, underwent a full clinical evaluation and had blood cultures done for aerobic organisms by standard methods. Over 38% of the infants had bacteraemia. Escherichia coli (35.9%), Staphylococcus aureus (33.3%), and Klebsiella spp. (10.3%) of positive cultures were commonly isolated. Three variables, age of < or = 6 months, restlessness, and a white cell count of >15,000/mm3, were significant independent predictors of bacteraemia. Each of these variables was associated with a 3-6-fold increase in risk of bacteraemia (age of < or = 6 months: odds ratio 3.2, p = 0.017; restlessness: odds ratio 6.3, p = 0.019; and white cell count of >15,000/mm3: odds ratio 5.4, p = 0.024). The variables, in combination, correctly classified 70% of the infants into 'bacteraemia' or 'no bacteraemia'. It is concluded that; in the setting of the study, about 4 in 10 febrile infants would have a positive blood culture for aerobic organisms and that age of < or = 6 months, restlessness, and a white cell count of > or = 15,000/mm3 are associated with a significantly increased risk of bacteraemia. Clinicians practising in such a setting need to be aware of the increased risk of bacteraemia in infants with these clinical features. PMID:12430758

  16. Evaluation of factors associated with prolonged hospital stay and outcome of febrile neutropenic patients receiving chemotherapy: 70 cases (1997-2010).

    PubMed

    Britton, B M; Kelleher, M E; Gregor, T P; Sorenmo, K U

    2014-12-01

    Febrile neutropenia (FN) is an important sequela in veterinary patients receiving chemotherapy. The purpose of this study was to identify factors associated with prolonged hospital stay and outcome in canine patients developing FN secondary to chemotherapy administration. Medical records of 70 dogs treated for FN at the University of Pennsylvania from 1997 to 2010 were retrospectively evaluated. The mean interval between chemotherapy and hospitalization was 7 days. Two-thirds of treated patients had lymphoma. The majority of patients (70%) received vincristine or doxorubicin prior to the development of FN. Tachycardia at admission, complicating medical issues, G-CSF use and decreasing neutrophil count after admission were associated with prolonged hospital stay. Hypotension and G-CSF use were significantly associated with death in-hospital. Mortality was 8.5%. Identification of factors associated with prolonged hospital stay and mortality in patients with FN may enable the development of risk-adapted treatment guidelines to minimize chemotherapy-associated morbidity and mortality. PMID:22998454

  17. In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.

    PubMed Central

    Zheng, Y H; Sentsui, H; Nakaya, T; Kono, Y; Ikuta, K

    1997-01-01

    Equine infectious anemia virus (EIAV) is a good model for studying mechanisms generating escaped retrovirus variants. We previously sequenced the entire gp90-encoding region of 22 cDNA clones obtained from five antigenically distinct isolates (F1V to F5V) recovered during febrile episodes in horse 493 experimentally infected with the Japanese virulent EIAV strain V70. The results showed that the mutations occurred in the principal neutralizing domain (PND) by insertions/duplications. In this study, we further characterized the PND of virus isolates sequentially recovered during 22 febrile episodes in seven horses newly infected with V70 or one of the V70-derived variants. Sequencing of 70 cDNA clones derived from the 22 episodes confirmed the generation of various new viral quasispecies with insertions/duplications in the PND. Although the insertion/duplication sequences in a total of 92 cDNA clones were extensively heterogeneous, we hypothesized that all the insertions/duplications occurred during reverse transcription from viral genomic RNA to minus strand DNA. The insertion/duplication regions were derived from a part of the PND sequence, which consisted of five small units. These small units, some with various substitutions and/or deletions, were also generated, especially in regions with insertions/duplications. Of particular note was that all these virus variants, except for two cDNA variants, were generated by essentially four different duplication pathways. Thus, these results extend the significance of insertions/duplications in the PND to the novel generation of EIAV in vivo during febrile episodes. PMID:9188568

  18. 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

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

    PubMed

    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

    2014-12-01

    Febrile seizures represent a 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) versus controls, P = 1.2 × 10(-9) versus MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653: P = 9.6 × 10(-11) versus controls, P = 1.6 × 10(-9) versus 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 (ANO3; rs114444506: P = 3.7 × 10(-20)) and a region associated with magnesium levels (12q21.33; rs11105468: P = 3.4 × 10(-11)). Finally, we show the functional relevance of ANO3 (TMEM16C) with electrophysiological experiments in wild-type and knockout rats. PMID:25344690

  20. Febrile Seizures and Behavioural and Cognitive Outcomes in Preschool Children: The Generation R Study

    ERIC Educational Resources Information Center

    Visser, Annemarie M.; Jaddoe, Vincent W. V.; Ghassabian, Akhgar; Schenk, Jacqueline J.; Verhulst, Frank C.; Hofman, Albert; Tiemeier, Henning; Moll, Henriette A.; Arts, Willem Frans M.

    2012-01-01

    Aim: General developmental outcome is known to be good in school-aged children who experienced febrile seizures. We examined cognitive and behavioural outcomes in preschool children with febrile seizures, including language and executive functioning outcomes. Method: This work was performed in the Generation R Study, a population-based cohort

  1. Febrile Seizures and Behavioural and Cognitive Outcomes in Preschool Children: The Generation R Study

    ERIC Educational Resources Information Center

    Visser, Annemarie M.; Jaddoe, Vincent W. V.; Ghassabian, Akhgar; Schenk, Jacqueline J.; Verhulst, Frank C.; Hofman, Albert; Tiemeier, Henning; Moll, Henriette A.; Arts, Willem Frans M.

    2012-01-01

    Aim: General developmental outcome is known to be good in school-aged children who experienced febrile seizures. We examined cognitive and behavioural outcomes in preschool children with febrile seizures, including language and executive functioning outcomes. Method: This work was performed in the Generation R Study, a population-based cohort…

  2. Febrile Seizures and Behavioural and Cognitive Outcomes in Preschool Children: An Old Issue Revisited

    ERIC Educational Resources Information Center

    Deonna, Thierry

    2012-01-01

    The possible deleterious role of febrile seizures on development is an old issue. It took a long time to realize that impaired development or occurrence of chronic epilepsy affected a very small minority of children with febrile seizures. These children either had pre-existing brain damage, specific genetic epileptic conditions, or seizure-induced

  3. Febrile Seizures and Behavioural and Cognitive Outcomes in Preschool Children: An Old Issue Revisited

    ERIC Educational Resources Information Center

    Deonna, Thierry

    2012-01-01

    The possible deleterious role of febrile seizures on development is an old issue. It took a long time to realize that impaired development or occurrence of chronic epilepsy affected a very small minority of children with febrile seizures. These children either had pre-existing brain damage, specific genetic epileptic conditions, or seizure-induced…

  4. 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

  5. The relationship between iron deficiency anemia and simple febrile convulsion in children

    PubMed Central

    Yousefichaijan, Parsa; Eghbali, Aziz; Rafeie, Mohammad; Sharafkhah, Mojtaba; Zolfi, Mohaddeseh; Firouzifar, Mohammadreza

    2014-01-01

    Background: Simple febrile convulsion is the most common disease of the nervous system in children. There are hypotheses that iron deficiency may affect febrile convulsion and the threshold of neuron excitation. Aims: This study was conducted with the objective of finding the effects of iron deficiency anemia on simple febrile convulsion episodes. Settings and Design: The study was conducted at AmirKabir Hospital of Arak Medical Sciences University, Arak, Iran. This is a case-control study. Materials and Methods: In this study, 382 children who were selected according to our inclusion and exclusion factors, were divided into two groups of case (febrile convulsion) and control (other factors causing fever) by their cause of hospitalization. After fever subsided, 5 ml blood sample was taken from each child and complete blood count and iron profile tests were performed. Statistical Analysis: The results were interpreted using descriptive statistics and independent t-test. Results: The prevalence of anemia in the group with febrile convulsion was significantly less than that in the control group: 22.5% of the children in the group with febrile convulsion and 34% in the control group exhibited anemia (P < 0.001). Moreover, the group with febrile convulsion had significantly higher blood indices, such as Hb, Hct, MCV, MCH, and MCHC, compared to the control group (P < 0.001). Conclusions: Iron deficiency can prevent febrile convulsion in children and probably increases the threshold of neuron excitation in fever. PMID:25250062

  6. Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation.

    PubMed

    Fioredda, Francesca; Iacobelli, Simona; van Biezen, Anja; Gaspar, Bobby; Ancliff, Phil; Donadieu, Jean; Aljurf, Mahmoud; Peters, Christina; Calvillo, Michaela; Matthes-Martin, Susanne; Morreale, Giuseppe; van 't Veer-Tazelaar, Nelleke; de Wreede, Liesbeth; Al Seraihy, Amal; Yesilipek, Akif; Fischer, Alain; Bierings, Marc; Ozturk, Gulyuz; Smith, Owen; Veys, Paul; Ljungman, Per; Peffault de Latour, Régis; Sánchez de Toledo Codina, José; Or, Reuven; Ganser, Arnold; Afanasyev, Boris; Wynn, Robert; Kalwak, Krzysztof; Marsh, Judith; Dufour, Carlo

    2015-10-15

    Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken. PMID:26185129

  7. 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

  8. Towards individually tailored empiric antibiotic therapy in febrile granulocytopenic patients.

    PubMed

    de Pauw, B E; Donnelly, J P; Elves, A; Verhagen, C; Nováková, I R; Van der Meer, J W

    1990-10-01

    The objective of this retrospective analysis was to study the possibility of a treatment strategy for febrile, granulocytopenic patients based on relative infective risks. Data from 441 adult febrile, granulocytopenic patients treated initially with antibacterial monotherapy were reassessed in terms of infection risk and outcome. Two different risk-groups were identified, namely those without and those with a clinical focus of infection (e.g. the respiratory tract and skin and soft tissue). Patients with a focus took longer to respond (4-8 days to defervesce) than those with unexplained fever, urinary tract infection or bacteraemia (2-3 days to defervesce). Patients with respiratory tract and skin and soft tissue infections received additional antibiotics more frequently (greater than 15% versus less than 10%) and were treated for a longer period (50% greater than or equal to 9 versus less than or equal to 8 days). More often the bone marrow had recovered at the time of response (48% versus 65%). These data suggest that a differentiated approach in the selection of initial antibiotics may be feasible, based upon continuous assessment of the patient's clinical condition. Antibiotic therapy may be postponed in patients without a focus of infection who show slowly increasing temperature. Patients with upper respiratory tract and skin and soft tissue infections may benefit from initial addition of penicillin and a glycopeptide, respectively. In cases of lower respiratory infections, antifungal therapy should be considered at an early stage. PMID:2250752

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

    PubMed

    Osugi, Jun; Owada, Yuki; Yamaura, Takumi; Muto, Satoshi; Okabe, Naoyuki; Matsumura, Yuki; Higuchi, Mitsunori; Suzuki, Hiroyuki; Gotoh, Mitsukazu

    2016-01-01

    Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK) gene rearrangement, is generally well tolerated. In contrast, neutropenia induced by crizotinib is a commonly reported grade 3 or 4 adverse event. In such cases, interruption and dose reduction of crizotinib might be necessary for some patients with severe neutropenia. However, information concerning clinical experience and management of severe neutropenia is currently limited. In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described. PMID:26933419

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

    PubMed Central

    Osugi, Jun; Owada, Yuki; Yamaura, Takumi; Muto, Satoshi; Okabe, Naoyuki; Matsumura, Yuki; Higuchi, Mitsunori; Suzuki, Hiroyuki; Gotoh, Mitsukazu

    2016-01-01

    Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK) gene rearrangement, is generally well tolerated. In contrast, neutropenia induced by crizotinib is a commonly reported grade 3 or 4 adverse event. In such cases, interruption and dose reduction of crizotinib might be necessary for some patients with severe neutropenia. However, information concerning clinical experience and management of severe neutropenia is currently limited. In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described. PMID:26933419

  11. Presepsin (Scd14) as a Marker of Serious Bacterial Infections in Chemotherapy Induced Severe Neutropenia

    PubMed Central

    Olad, Elham; Sedighi, Iraj; Mehrvar, Azim; Tashvighi, Maryam; Fallahazad, Vahid; Hedayatiasl, Amirabbas; Esfahani, Hossein

    2014-01-01

    Objective: Timely detection of serious bacterial infections or prediction of sepsis and death is of paramount importance in neutropenic patients especially in oncology settings. The aim of this study was to determine a rapid and secure predictor of sepsis in severe neutropenic cancer children. Methods: In addition to blood culture, we have evaluated serum soluble CD14 on this role and measured it in 39 neutropenic episodes in Mahak pediatric oncology center from September 2012 to January 2013. Fifteen episodes had positive bacterial cultures and 18 had fever. The mean sCD14 values were compared in the presence or absence of fever, positive blood culture and other clinical conditions. Also, mean levels compared in different white cell counts and different four combination settings of fever and blood culture. Findings: It was statistically higher in febrile episodes, in the presence of oral mucositis, indwelling catheter infection, otitis media, and post toxic epidermal necrolysis sepsis and in instances of death within 15 days. Leukocyte count did not affect sCD14 level and in combinations of fever and blood culture, mean sCD14 values were ranked as follow: febrile culture negatives, febrile culture positives, afebrile culture positives and afebrile culture negatives. Conclusion: Although sCD14 was not sensitive in detection of bacteremia, in the absence of clinically detectable source of infection, it was significantly higher in culture positives. PMID:26019777

  12. Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae bacteremia in febrile neutropenic children.

    PubMed

    Han, Seung Beom; Jung, Seung Won; Bae, E Young; Lee, Jae Wook; Lee, Dong-Gun; Chung, Nack-Gyun; Jeong, Dae Chul; Cho, Bin; Kang, Jin Han; Kim, Hack-Ki; Park, Yeon-Joon

    2015-04-01

    This retrospective study was conducted to evaluate clinical outcomes of bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their antibiotic susceptibilities in febrile neutropenic children. Clinical characteristics, prognosis, and antibiotic susceptibilities were reviewed and compared between febrile neutropenic children with bacteremia caused by ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae. A total of 61 episodes of E. coli and K. pneumoniae bacteremia, including 21 episodes (34.4%) due to ESBL-producing strains, were diagnosed. There was no significant factor associated with bacteremia by ESBL-producing strains. Empirical antibiotics were appropriate in 85.7% of the ESBL group and 95.0% of the non-ESBL group. In the entire study population, seven deaths (11.5%), including three deaths (4.9%) due to E. coli and K. pneumoniae bacteremia, occurred. The complication and mortality rates were not significantly different between the two groups. Antibiotic susceptibility rates were significantly lower in the ESBL group than in the non-ESBL group in most antibiotics. Although 52.4% and 66.7% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam and cefepime, respectively, 96.7% of all the isolates and 90.5% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam or cefepime in combination with aminoglycoside. In conclusion, the ESBL group did not show a significantly unfavorable outcome, and empirical therapy with piperacillin/tazobactam or cefepime in combination with aminoglycoside might be more useful for febrile neutropenic children, instead of β-lactam monotherapy in institutions with high prevalence of ESBL-producing E. coli and K. pneumoniae. PMID:25398058

  13. Bacterial translocation is reduced by a specific nutritional combination in mice with chemotherapy-induced neutropenia.

    PubMed

    Faber, Joyce; van Limpt, Kees; Kegler, Diane; Luiking, Yvette; Garssen, Johan; van Helvoort, Ardy; Vos, Arjan Paul; Knol, Jan

    2011-07-01

    Immune function is compromised in many cancer patients, leading to an increased risk of (infectious) complications. Chemotherapy-induced neutropenia is a common cause of treatment-induced immune suppression. In the present study, the effect of a specific nutritional combination (SNC) on bacterial translocation was studied in a model of chemotherapy-induced neutropenia in C3H/HeN mice colonized with Pseudomonas aeruginosa PAO-1. Dietary intervention started after stable colonization with P. aeruginosa to compare the SNC containing high protein, l-leucine, fish oil, and specific oligosaccharides to an isoenergetic control diet. After 3 wk, the mice were treated with cyclophosphamide to induce neutropenia. This rendered the mice susceptible to Pseudomonas translocation, which was quantified 5 d later. Intervention with the SNC resulted in a reduced incidence and intensity of bacterial translocation to the liver (P < 0.05) and a similar trend in the lungs (P ≤ 0.057). In addition, the SNC reduced the fecal pH (P < 0.05) and decreased P. aeruginosa counts in fecal samples (P < 0.05). Moreover, plasma concentrations of proinflammatory cytokines were correlated with the reduced bacterial translocation to the liver (ρ > 0.78; P < 0.001). In conclusion, dietary intervention with the SNC significantly reduced the incidence and severity of P. aeruginosa translocation in a mouse model of chemotherapy-induced immune suppression. Several mechanisms might have played a role, including the modulation of the intestinal microbiota, an improved gut barrier function, immune function, and a reduced inflammatory state. These results suggest an opportunity to develop new applications in cancer patients, with the aim to reduce infectious and other complications. PMID:21562235

  14. JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia

    PubMed Central

    Boztug, Kaan; Järvinen, Päivi M.; Salzer, Elisabeth; Racek, Tomas; Mönch, Sebastian; Garncarz, Wojciech; Gertz, E. Michael; Schäffer, Alejandro A.; Antonopoulos, Aristotelis; Haslam, Stuart M.; Schieck, Lena; Puchałka, Jacek; Diestelhorst, Jana; Appaswamy, Giridharan; Lescoeur, Brigitte; Giambruno, Roberto; Bigenzahn, Johannes W.; Elling, Ulrich; Pfeifer, Dietmar; Conde, Cecilia Domínguez; Albert, Michael H.; Welte, Karl; Brandes, Gudrun; Sherkat, Roya; van der Werff ten Bosch, Jutte; Rezaei, Nima; Etzioni, Amos; Bellanné-Chantelot, Christine; Superti-Furga, Giulio; Penninger, Josef M.; Bennett, Keiryn L.; von Blume, Julia; Dell, Anne; Donadieu, Jean; Klein, Christoph

    2016-01-01

    Analysis of patients with severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling differentiation, maintenance, and decay of neutrophils. We identify 9 distinct homozygous mutations in the gene encoding Jagunal homolog 1 (JAGN1) in 14 SCN patients. JAGN1-mutant granulocytes are characterized by ultrastructural defects, paucity of granules, aberrant N-glycosylation of multiple proteins, and increased apoptosis. JAGN1 participates in the secretory pathway and is required for granulocyte-colony stimulating factor receptor-mediated signaling. JAGN1 emerges as a factor necessary in differentiation and survival of neutrophils. PMID:25129144

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

    PubMed

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

    2006-04-01

    We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) x 10(9)/L with a median value of 1.02 x 10(9)/L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others. PMID:16550514

  16. Evaluation of Selenium Levels and Mean Platelet Volume in Patients with Simple Febrile Convulsion

    PubMed Central

    Abuhandan, Mahmut; Solmaz, Abdullah; Geter, Suleyman; Kaya, Cemil; Guzel, Bulent; Yetkin, Ilhan; Koca, Bulent

    2014-01-01

    Objective: This study aimed to evaluate serum selenium levels and mean platelet volume in children who experience simple febrile convulsion. Methods: The study comprised 42 patients diagnosed with simple febrile convulsions and a control group of 30 healthy children. Blood samples were taken following a febrile convulsion. Selenium levels in the serum of both the patients and control subjects were measured with the hydride formation method on an atomic absorption spectrometry device and mean platelet volume was evaluated. Findings: When the mean values of the febrile convulsion patients were compared with those of the control group, the mean selenium levels and thrombocyte count were found to be statistically significantly low (P=0.002, P=0.01 respectively) and the mean platelet volume values were statistically significantly high (P=0.002). Conclusion: While low serum selenium levels cause the onset of a febrile seizure in patients with simple febrile convulsion, it is thought that the increased mean platelet volume shows infection activity causing febrile convulsion. PMID:25755861

  17. PRRT2 mutations are related to febrile seizures in epileptic patients.

    PubMed

    He, Zheng-Wen; Qu, Jian; Zhang, Ying; Mao, Chen-Xue; Wang, Zhi-Bin; Mao, Xiao-Yuan; Deng, Zhi-Yong; Zhou, Bo-Ting; Yin, Ji-Ye; Long, Hong-Yu; Xiao, Bo; Zhang, Yu; Zhou, Hong-Hao; Liu, Zhao-Qian

    2014-01-01

    Previous studies reported that the proline-rich transmembrane protein 2 (PRRT2) gene was identified to be related to paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions with PKD, PKD with migraine and benign familial infantile epilepsy (BFIE). The present study explores whether the PRRT2 mutation is a potential cause of febrile seizures, including febrile seizures plus (FS+), generalized epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS); thus, it may provide a new drug target for personalized medicine for febrile seizure patients. We screened PRRT2 exons in a cohort of 136 epileptic patients with febrile seizures, including FS+, GEFS+ and DS. PRRT2 genetic mutations were identified in 25 out of 136 (18.4%) febrile seizures in epileptic patients. Five loss-of-function and coding missense mutations were identified: c.649delC (p.R217Efs*12), c.649_650insC (p.R217Pfs*8), c.412C>G (p.Pro138Ala), c.439G>C (p.Asp147His) and c.623C>A (p.Ser208Tyr). PRRT2 variants were probably involved in the etiology of febrile seizures in epileptic patients. PMID:25522171

  18. Naturally occurring chemical carcinogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products are chemicals found in nature which have unique pharmacological effects. Humans are exposed to many of these bioactive naturally occurring chemicals via the air breathed, the water drunk and the food eaten. Exposure also occurs in clinical settings. Naturally occurring chemicals ...

  19. Pharmacological neutropenia prevents endothelial dysfunction but not smooth muscle functions impairment induced by middle cerebral artery occlusion

    PubMed Central

    Pétrault, Olivier; Ouk, Thavarak; Gautier, Sophie; Laprais, Maud; Gelé, Patrick; Bastide, Michèle; Bordet, Régis

    2005-01-01

    The polymorphonuclear neutrophils (PMN) activation and mobilization observed in acute cerebral infarction contribute to the brain tissue damage, but PMN could also be involved in postischemic functional injury of ischemied blood vessel. This study was undertaken to investigate whether pharmacological neutropenia could modify the postischemic endothelial dysfunction in comparison to smooth muscle whose impairment is likely more related to reperfusion and oxidative stress. A cerebral ischemia–reperfusion by endoluminal occlusion of right middle cerebral artery (MCA) was performed 4 days after intravenous administration of vinblastine or 12 h after RP-3 anti-rat neutrophils monoclonal antibody (mAb RP-3) injection into the peritoneal cavity, on male Wistar rats with 1-h ischemia then followed by 24-h reperfusion period. Brain infarct volume was measured by histomorphometric analysis and vascular endothelial and smooth muscle reactivity of MCA was analysed using Halpern myograph. Neutropenia induced a neuroprotective effect as demonstrated by a significant decrease of brain infarct size. In parallel to neuroprotection, neutropenia prevented postischemic impairment of endothelium-dependent relaxing response to acetylcholine. In contrast, smooth muscle functional alterations were not prevented by neutropenia. Ischemia–reperfusion-induced myogenic tone impairment remained unchanged in vinblastine and mAb RP-3-treated rats. Postischemic Kir2.x-dependent relaxation impairment was not prevented in neutropenic conditions. The fully relaxation of smooth muscle response to sodium nitroprusside was similar in all groups. Our results evidenced the dissociate prevention of pharmacologically induced neutropenia on postischemic vascular endothelial and smooth muscle impairment. The selective endothelial protection by neutropenia is parallel to a neuroprotective effect suggesting a possible relationship between the two phenomena. PMID:15700030

  20. Effect of granulocyte colony-stimulating factor on chemotherapy-induced neutropenia in children with cancer.

    PubMed

    Kalmanti, M; Lydaki, E; Dimitriou, H; Kalmantis, T; Vlachonicolis, I; Kambourakis, A; Zioga, I; Bolonaki, I

    1994-01-01

    We investigated the effects of recombinant granulocyte colony-stimulating factor (G-CSF) administration on duration of neutropenia, antibiotic therapy, and hospitalization days in 25 children with malignancies (Group A: 12 leukemia and lymphoma; Group B: 13 tumors) who were undergoing chemotherapy. We compared the effect of G-CSF with a control group of 21 children with equivalent diseases and chemotherapy that did not receive G-CSF treatment. All 25 children received 5 micrograms/kg/day of G-CSF at the end of chemotherapy courses when absolute neutrophil counts were < or = 1000/mm3. The effect of G-CSF on median neutrophil profiles, antibiotic therapy, and hospitalization days was studied for both groups at the 1st and 4th cycle of chemotherapy. During both cycles, children who received G-CSF showed a faster rise of absolute neutrophil count (P < 0.001) and fewer hospitalization days (P < 0.05), and not as many received systemic antibiotic therapy (P < 0.0001). We conclude that G-CSF accelerates neutrophil recovery in chemotherapy-induced neutropenia in childhood malignancies. PMID:7515635

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

    PubMed

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

    2012-01-01

    Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF) that stimulates the proliferation, differentiation and function of neutrophils, is approved for the prevention of CIN. To eliminate the burden of daily filgrastim injection, pegfilgrastim, a long-acting form of filgrastim, was developed by covalently attaching a 20-kDa polyethylene glycol molecule to filgrastim to increase molecular size and thus reduce renal elimination. Consequently, neutrophil-mediated clearance is the primary mechanism for pegfilgrastim elimination. Therefore, after a single pegfilgrastim injection following chemotherapy treatment, pegfilgrastim concentration is sustained during neutropenia and decreases with neutrophil recovery. Pegfilgrastim has received marketing authorization approval from many regions to reduce the incidence of CIN based on the similar efficacy and safety of a single injection of 6 mg of pegfilgrastim administered once per chemotherapy cycle and 10 to 11 daily injections of filgrastim at 5 µg/kg. The efficient self-regulating clearance of pegfilgrastim allows administration once per chemotherapy cycle, thereby providing a more convenient treatment regimen than filgrastim. PMID:23296266

  2. Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms

    PubMed Central

    Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C.; Trump, Lisa; Salipante, Stephen J.; Cheng, Jerry C.; Donadieu, Jean; Glaubach, Taly; Corey, Seth J.; Grimes, H. Leighton; Lutzko, Carolyn; Cancelas, Jose A.

    2014-01-01

    Hereditary neutropenia is usually caused by heterozygous germline mutations in the ELANE gene encoding neutrophil elastase (NE). How mutations cause disease remains uncertain, but two hypotheses have been proposed. In one, ELANE mutations lead to mislocalization of NE. In the other, ELANE mutations disturb protein folding, inducing an unfolded protein response in the endoplasmic reticulum (ER). In this study, we describe new types of mutations that disrupt the translational start site. At first glance, they should block translation and are incompatible with either the mislocalization or misfolding hypotheses, which require mutant protein for pathogenicity. We find that start-site mutations, instead, force translation from downstream in-frame initiation codons, yielding amino-terminally truncated isoforms lacking ER-localizing (pre) and zymogen-maintaining (pro) sequences, yet retain essential catalytic residues. Patient-derived induced pluripotent stem cells recapitulate hematopoietic and molecular phenotypes. Expression of the amino-terminally deleted isoforms in vitro reduces myeloid cell clonogenic capacity. We define an internal ribosome entry site (IRES) within ELANE and demonstrate that adjacent mutations modulate IRES activity, independently of protein-coding sequence alterations. Some ELANE mutations, therefore, appear to cause neutropenia via the production of amino-terminally deleted NE isoforms rather than by altering the coding sequence of the full-length protein. PMID:24184683

  3. Clinical validity of new genetic biomarkers of irinotecan neutropenia: an independent replication study.

    PubMed

    Crona, D J; Ramirez, J; Qiao, W; de Graan, A-J; Ratain, M J; van Schaik, R H N; Mathijssen, R H J; Rosner, G L; Innocenti, F

    2016-02-01

    The overall goal of this study was to provide evidence for the clinical validity of nine genetic variants in five genes previously associated with irinotecan neutropenia and pharmacokinetics. Variants associated with absolute neutrophil count (ANC) nadir and/or irinotecan pharmacokinetics in a discovery cohort of cancer patients were genotyped in an independent replication cohort of 108 cancer patients. Patients received single-agent irinotecan every 3 weeks. For ANC nadir, we replicated UGT1A1*28, UGT1A1*93 and SLCO1B1*1b in univariate analyses. For irinotecan area under the concentration-time curve (AUC0-24), we replicated ABCC2 -24C>T; however, ABCC2 -24C>T only predicted a small fraction of the variance. For SN-38 AUC0-24 and the glucuronidation ratio, we replicated UGT1A1*28 and UGT1A1*93. In addition to UGT1A1*28, this study independently validated UGT1A1*93 and SLCO1B1*1b as new predictors of irinotecan neutropenia. Further demonstration of their clinical utility will optimize irinotecan therapy in cancer patients. PMID:25869015

  4. Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms.

    PubMed

    Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C; Trump, Lisa; Salipante, Stephen J; Cheng, Jerry C; Donadieu, Jean; Glaubach, Taly; Corey, Seth J; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A; Horwitz, Marshall S

    2014-01-23

    Hereditary neutropenia is usually caused by heterozygous germline mutations in the ELANE gene encoding neutrophil elastase (NE). How mutations cause disease remains uncertain, but two hypotheses have been proposed. In one, ELANE mutations lead to mislocalization of NE. In the other, ELANE mutations disturb protein folding, inducing an unfolded protein response in the endoplasmic reticulum (ER). In this study, we describe new types of mutations that disrupt the translational start site. At first glance, they should block translation and are incompatible with either the mislocalization or misfolding hypotheses, which require mutant protein for pathogenicity. We find that start-site mutations, instead, force translation from downstream in-frame initiation codons, yielding amino-terminally truncated isoforms lacking ER-localizing (pre) and zymogen-maintaining (pro) sequences, yet retain essential catalytic residues. Patient-derived induced pluripotent stem cells recapitulate hematopoietic and molecular phenotypes. Expression of the amino-terminally deleted isoforms in vitro reduces myeloid cell clonogenic capacity. We define an internal ribosome entry site (IRES) within ELANE and demonstrate that adjacent mutations modulate IRES activity, independently of protein-coding sequence alterations. Some ELANE mutations, therefore, appear to cause neutropenia via the production of amino-terminally deleted NE isoforms rather than by altering the coding sequence of the full-length protein. PMID:24184683

  5. Autopsy study of febrile deaths during monsoon at a tertiary care institute in India: Is malaria still a challenge?

    PubMed Central

    Gupta, Anurag; Dhume, Varsha; Puranik, Gururaj Venkatesh; Kavishwar, Vikas

    2015-01-01

    Background: To utilise an autopsy-based approach to study the febrile deaths and deaths due to malaria during monsoon period of three years at a tertiary care teaching hospital in Mumbai, India. Materials and Methods: All autopsies done at the hospital during monsoon period from 2005 to 2007 when fever was the main presenting symptom were included in the study. Monsoon period was defined from June to September. A study on the duration of hospital stay of malaria deaths was also attempted. Results: There were 202 autopsies of febrile illness during the study period. Malaria resulted in 20.8% of the deaths besides other causes. A majority of deaths had intrapulmonary haemorrhages as the only pathological finding. Incidence of malaria deaths was more during monsoon period than the non-monsoon period. Plasmodium falciparum was the most common species responsible for malaria deaths while cerebral malaria was the most common mode of death. In 27% of the cases, post-mortem examination helped to arrive at the correct final diagnosis. In 88.1% of the cases, malaria deaths occurred within the first 24 hours of admission to the hospital. Conclusion: The study reiterates the fact that malaria remains a preventable but major cause of death in India, predominantly during the monsoon period. The study also emphasises the importance of developing treatment protocols for malaria during such crucial times besides reinforcing the existing preventive measures. PMID:25657486

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

    PubMed

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

    2016-04-01

    This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site. PMID:26711434

  7. Breastfeeding During Early Infancy is Associated with a Lower Incidence of Febrile Illnesses.

    PubMed

    Libraty, Daniel H; Capeding, Rosario Z; Obcena, Anamae; Brion, Job D; Tallo, Veronica

    2013-06-24

    Human breast milk is known to contain immunoprotective, antimicrobial, and anti-inflammatory agents. In a prospective clinical study of dengue virus infections during infancy, we examined the correlation between breastfeeding and the development of febrile illnesses in an infant population. We found that breastfeeding status and the frequency of breastfeeding during early infancy was associated with a lower incidence of febrile illnesses. PMID:24465289

  8. Febrile infection-related epilepsy syndrome is not caused by SCN1A mutations.

    PubMed

    Carranza Rojo, Daniel; Harvey, A Simon; Iona, Xenia; Dibbens, Leanne M; Damiano, John A; Arsov, Todor; Gill, Deepak; Freeman, Jeremy L; Leventer, Richard J; Vincent, Angela; Berkovic, Samuel F; McMahon, Jacinta M; Scheffer, Ingrid E

    2012-06-01

    Two distinctive epileptic encephalopathies, febrile infection-related epilepsy syndrome (FIRES) and Dravet syndrome (DS), present with febrile status epilepticus in a normal child followed by refractory focal seizures and cognitive decline although there are differentiating features. Abnormalities of the sodium channel gene SCN1A are found in 75% of DS patients. We found no SCN1A mutations or copy number variants in 10 patients with FIRES. Other genetic etiologies deserve consideration. PMID:22386634

  9. TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain.

    PubMed

    Huang, Wen-Xian; Yu, Fang; Sanchez, Russell M; Liu, Yu-Qiang; Min, Jia-Wei; Hu, Jiang-Jian; Bsoul, Najeeb Bassam; Han, Song; Yin, Jun; Liu, Wan-Hong; He, Xiao-Hua; Peng, Bi-Wen

    2015-08-01

    Febrile seizure (FS) is the most common seizure disorder in children, and children with FS are regarded as a high risk for the eventual development of epilepsy. Brain inflammation may be implicated in the mechanism of FS. Transient receptor potential vanilloid 1 (TRPV1) is believed to act as a monitor and regulator of body temperature. The role of inflammation in synaptic plasticity mediation indicates that TRPV1 is relevant to several nervous system diseases, such as epilepsy. Here, we report a critical role for TRPV1 in a febrile seizure mouse model and reveal increased levels of pro-inflammatory factors in the immature brain. Animals were subjected to hyperthermia for 30 min, which generates seizures lasting approximately 20 min, and then were used for experiments. To invoke frequently repetitive febrile seizures, mice are exposed to hyperthermia for three times daily at an interval of 4h between every time induced seizure, and a total of 4 days to induce. Behavioral testing for febrile seizures revealed that a TRPV1 knock-out mouse model demonstrated a prolonged onset latency and a shortened duration and seizure grade of febrile seizure when compared with wild type (WT) mice. The expression levels of both TRPV1 mRNA and protein increased after a hyperthermia-induced febrile seizure in WT mice. Notably, TRPV1 activation resulted in a significant elevation in the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and HMGB1) in the hippocampus and cortex. These data indicate that the reduction of TRPV1 expression parallels a decreased susceptibility to febrile seizures. Thus, preventative strategies might be developed for use during febrile seizures. PMID:25801060

  10. Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach

    PubMed Central

    Decuypere, Saskia; Maltha, Jessica; Deborggraeve, Stijn; Rattray, Nicholas J. W.; Issa, Guiraud; Bérenger, Kaboré; Lompo, Palpouguini; Tahita, Marc C.; Ruspasinghe, Thusitha; McConville, Malcolm; Goodacre, Royston; Tinto, Halidou; Jacobs, Jan; Carapetis, Jonathan R.

    2016-01-01

    Introduction Non-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabololome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness. Methodology We conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis. Principal Findings The plasma metabolome profile of malaria and non-malaria patients revealed fundamental differences in host response, including a differential activation of the hypothalamic-pituitary-adrenal axis. A simple corticosteroid signature was a good classifier of severe malaria and non-malaria febrile patients (AUC 0.82, 95% CI: 0.70–0.93). Patients with BSI were characterized by upregulated plasma bile metabolites; a signature of two bile metabolites was estimated to have a sensitivity of 98.1% (95% CI: 80.2–100) and a specificity of 82.9% (95% CI: 54.7–99.9) to detect BSI in children younger than 5 years. This BSI signature demonstrates that host metabolites can have a superior diagnostic sensitivity compared to pathogen-detecting tests to identify infections characterized by low pathogen load such as BSI. Conclusions This study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings. PMID:26943791

  11. A semimechanistic-physiologic population pharmacokinetic/pharmacodynamic model for neutropenia following pemetrexed therapy.

    TOXLINE Toxicology Bibliographic Information

    Latz JE; Karlsson MO; Rusthoven JJ; Ghosh A; Johnson RD

    2006-04-01

    PURPOSE: The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response.PATIENTS AND METHODS: Data from 279 patients who received 1,136 treatment cycles without folic acid or vitamin B12 supplementation during participation in one of eight phase II cancer trials were available for analysis. Starting doses were 500 or 600 mg pemetrexed per m2 body surface area (BSA), administered as 10-min intravenous infusions every 21 days (1 cycle). The primary analyses included 105 patients (279 cycles) for which selected covariates-including vitamin deficiency marker data (i.e., homocysteine, cystathionine, methylmalonic acid, and methylcitrate [I, II, and total] plasma concentrations)-were available. Classical statistical multivariate regression analyses and a semimechanistic-physiologic population PK/PD model were used to evaluate neutropenic response to single-agent pemetrexed administration.RESULTS: The timecourse of neutropenia following single-agent pemetrexed administration was adequately described by a semimechanistic-physiologic model. Population estimates for system-based model parameters (i.e., baseline neutrophil count, mean transit time, and the feedback parameter), which mathematically represent current understanding of the process and physiology of hematopoiesis, were consistent with previously reported values. The population PK/PD model included homocysteine, cystathionine, albumin, total protein, and BSA as covariates relative to neutropenic response.CONCLUSION: These results support the programmatic decision to introduce folic acid and vitamin B12 supplementation during pemetrexed clinical development as a means of normalizing patient homocysteine levels, thereby managing the risk of severe neutropenia secondary to pemetrexed administration. The current results also suggest that the addition of vitamin B6 supplementation to normalize patient cystathionine levels may further decrease the incidence of grade 4 neutropenia following pemetrexed administration. The results also suggest the use of folic acid as a means of lessening hematologic toxicity following administration of cytotoxic agents other than antifolates.

  12. An outbreak of febrile gastroenteritis associated with jellied pork contaminated with Listeria monocytogenes.

    PubMed

    Pichler, Juliane; Much, Peter; Kasper, Sabine; Fretz, Rainer; Auer, Bettina; Kathan, Julia; Mann, Michaela; Huhulescu, Steliana; Ruppitsch, Werner; Pietzka, Ariane; Silberbauer, Karl; Neumann, Christian; Gschiel, Ernst; de Martin, Alfred; Schuetz, Angelika; Gindl, Josef; Neugschwandtner, Ernst; Allerberger, Franz

    2009-01-01

    In September 2008, the Austrian Agency for Health and Food Safety (AGES) learned of an outbreak of diarrheal illness that included a 71-year-old patient hospitalized for gastroenteritis with a blood culture positive for Listeria monocytogenes. Three stool specimens provided by seven of 19 persons attending a day trip to a foreign city, including a final break at an Austrian tavern, yielded L. monocytogenes. All isolates were of serovar 4b and had fingerprints indistinguishable from each other. A cohort study revealed that the outbreak of gastroenteritis occurred among 16 persons who had eaten dinner at the wine tavern on September 6. Of the 15 persons who ate from platters of mixed cold-cuts, 12 (80%) developed symptoms of febrile gastroenteritis within 24-48 h. The median age of those who became ill was 62 years. A 72-year-old patient recovered from gastroenteritis but was hospitalized with bacterial meningitis on day 19 after the dinner. The epidemiological investigation identified the consumption of mixed cold-cuts (including jellied pork) at the wine tavern as the most likely vehicle of the foodborne outbreak (P = 0.0015). This hypothesis was confirmed by microbiological investigation of jellied pork produced by the tavern owner on September 3. L. monocytogenes was isolated from leftover food in numbers of 3 x 10(3)-3 x 10(4) colony forming units/g and was indistinguishable from the clinical outbreak isolates. Symptoms reported by the 12 patients included unspecified fever (12x), diarrhea (9x), headache (5x), vomiting (4x), body aches (2x) and sore throat (1x). Active case finding identified one case of rhombencephalitis (female, age 48) among another group of four guests, among whom only the patient and her asymptomatic husband had eaten jellied pork on September 6. This is the first outbreak of L. monocytogenes-associated gastroenteritis reported in Austria. The occurrence of a secondary case of meningitis (diagnosed on day 19 after consumption of jellied pork) indicates a significant risk of systemic listeriosis among elderly patients with febrile gastroenteritis caused by L. monocytogenes; antibiotic therapy should therefore be considered in such cases of documented listerial gastroenteritis. PMID:19280142

  13. 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

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

    PubMed Central

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

    2016-01-01

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

  15. 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 < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low 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

  16. Pre-Hospital Risk Factors for Inpatient Death from Severe Febrile Illness in Malian Children

    PubMed Central

    Willcox, Merlin L.; Dicko, Moussa I.; Graz, Bertrand; Forster, Mathieu; Shinkins, Bethany; Diakite, Chiaka; Giani, Sergio; Falquet, Jacques; Diallo, Drissa; Dembélé, Eugène

    2014-01-01

    Background Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality. Methods Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period. Findings The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08–3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome. Interpretation Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality. PMID:25075623

  17. Outpatient Management of Febrile Children With Sickle Cell Disease.

    PubMed

    Sokol, Elizabeth; Obringer, Emily; Palama, Brett; Hageman, Joseph; Peddinti, Radhika

    2016-03-01

    The electronic medical records at 2 children's hospitals were reviewed from June 1, 2011 to May 31, 2013 for all patients with sickle cell disease who presented with fever. Of a total of 390 blood cultures drawn, 11 cultures (2.8%) turned positive with only 1 (0.3%) growing a true pathogen. This culture turned positive in 13 hours. There were 154 patients who received exclusive outpatient management of fever. Fourteen patients (9.1%) completed 1 acute care visit, 16 patients (10.4%) completed 2 acute care visits, and 124 patients (80.5%) completed 3 acute care visits. Of those treated exclusively as outpatients, there was 1 positive culture that was considered a contaminant. Although the overall rate of positivity was low, this study confirms previous findings that pediatric blood cultures become positive with pathogens within 48 hours. Given the high rate of compliance and early time to positivity of true pathogens, we suggest that follow-up for the febrile sickle cell disease patients can be treated on an outpatient basis. PMID:26149843

  18. Protective effect of carnosine on febrile seizures in immature mice.

    PubMed

    Dai, Yun-Jian; Wu, Deng-Chang; Feng, Bo; Hou, Wei-wei; Xu, Ceng-Lin; Ohtsu, Hiroshi; Chen, Zhong; Hu, Wei-Wei

    2015-02-19

    Febrile seizures (FSs) are the most common type of convulsions in childhood and complex FSs represent an increased risk for development of temporal lobe epilepsy. The aim of this study was to analyze the anticonvulsant effects of carnosine, an endogenous dipeptide composed of alanine and histidine, on hyperthermia induced seizure in immature mice. Injection of carnosine significantly increased the latency and decreased the duration of FSs in a dose-dependent manner. In addition, histidine had similar effects on FSs as carnosine. The protective effect of carnosine or histidine was completely abolished by α-fluoromethylhistidine (α-FMH), a selective and irreversible histidine decarboxylase inhibitor, or in histidine decarboxylase deficient (HDC-KO) mice. Peripheral carnosine administration increased the level of carnosine, histidine and histamine in the cortex and hippocampus of mice pups, but decreased glutamate contents in the cortex and hippocampus. These results indicate that carnosine can protect against FSs in mice pups through its conversion to histamine, suggesting that it may serve as an efficient anti-FSs drug in the future. PMID:25562630

  19. Acute febrile respiratory illness in the ICU: reducing disease transmission.

    PubMed

    Sandrock, Christian; Stollenwerk, Nicholas

    2008-05-01

    Acute febrile respiratory illness (FRI) leading to respiratory failure is a common reason for admission to the ICU. Viral pneumonia constitutes a portion of these cases, and often the viral etiology goes undiagnosed. Emerging viral infectious diseases such as severe acute respiratory syndrome and avian influenza present with acute FRIs progressing to respiratory failure and ARDS. Therefore, early recognition of a viral cause of acute FRI leading to ARDS becomes important for protection of health-care workers (HCWs), lessening spread to other patients, and notification of public health officials. These patients often have longer courses of viral shedding and undergo higher-risk procedures that may potentially generate aerosols, such as intubation, bronchoscopy, bag-valve mask ventilation, noninvasive positive pressure ventilation, and medication nebulization, further illustrating the importance of early detection and isolation. A small number of viral agents lead to acute FRI, respiratory failure, and ARDS: seasonal influenza, avian influenza, coronavirus associated with severe ARDS, respiratory syncytial virus, adenovirus, varicella, human metapneumovirus, and hantavirus. A systematic approach to early isolation, testing for these agents, and public health involvement becomes important in dealing with acute FRI. Ultimately, this approach will lead to improved HCW protection, reduction of transmission to other patients, and prevention of transmission in the community. PMID:18460521

  20. Novel GABRG2 mutations cause familial febrile seizures

    PubMed Central

    Boillot, Morgane; Morin-Brureau, Mélanie; Picard, Fabienne; Weckhuysen, Sarah; Lambrecq, Virginie; Minetti, Carlo; Striano, Pasquale; Zara, Federico; Iacomino, Michele; Ishida, Saeko; An-Gourfinkel, Isabelle; Daniau, Mailys; Hardies, Katia; Baulac, Michel; Dulac, Olivier; Leguern, Eric; Nabbout, Rima

    2015-01-01

    Objective: To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) and subsequently search for additional mutations in a cohort of 107 families with FS, with or without epilepsy. Methods: The cohort consisted of 1 large family with FS and TLE, 64 smaller French families recruited through a national French campaign, and 43 Italian families. Molecular analyses consisted of whole-exome sequencing and mutational screening. Results: Exome sequencing revealed a p.Glu402fs*3 mutation in the γ2 subunit of the GABAA receptor gene (GABRG2) in the large family with FS and TLE. Three additional nonsense and frameshift GABRG2 mutations (p.Arg136*, p.Val462fs*33, and p.Pro59fs*12), 1 missense mutation (p.Met199Val), and 1 exonic deletion were subsequently identified in 5 families of the follow-up cohort. Conclusions: We report GABRG2 mutations in 5.6% (6/108) of families with FS, with or without associated epilepsy. This study provides evidence that GABRG2 mutations are linked to the FS phenotype, rather than epilepsy, and that loss-of-function of GABAA receptor γ2 subunit is the probable underlying pathogenic mechanism. PMID:27066572

  1. Current spectrum of bacterial infections in patients with nosocomial fever and neutropenia

    PubMed Central

    Yadegarynia, Davood; Fatemi, Alireza; Mahdizadeh, Masih; Kabiri Movahhed, Reihaneh; Alizadeh, Mohammad Afshin

    2013-01-01

    Background: Neutropenic patients are vulnerable to a wide spectrum of infectious agents. The aim of this study was to determine the current frequency of bacterial infections in patients with nosocomial fever and neutropenia. Methods: In a retrospective study, the neutropenic patients’ specimens with nosocomial fever were cultured on blood and MacConkey agar plates and evaluated at microbiology laboratory. Ninety-five significant isolates as species level were recognized by bacteriological techniques. Results: The most observed microorganism was Escherichia coli, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Coagulase positive staphylococci and Coagulase negative staphylococci. One fungal infection was also observed. Overall, 67% of the organisms were gram negative, 29.8% gram positive, and 3.2% polymicrobial. Conclusion: The changing pattern of infectious agents in neutropenic patients overtime postulates the necessity of other studies to give the most up-to-date insight of the organisms to physicians. PMID:24009963

  2. Assessing the prevalence distribution of abnormal laboratory tests in patients with simple febrile seizure

    PubMed Central

    Yousefichaijan, Parsa; Dorreh, Fatemeh; Abbasian, Ladan; Pakniyat, Abdol Ghader

    2015-01-01

    Introduction: Febrile seizure is an important issue in pediatric practice. Even some pediatricians do not have a proper approach to febrile seizure, making the sick child undergo complex laboratory tests or invasive procedures or even long-term treatment with anticonvulsant drugs. In spite of multiple studies, many controversies have still remained about the significance of febrile seizure. The goal of this study is to assess the prevalence distribution of routinely requested laboratory tests results in simple febrile seizure. Materials and Methods: In a descriptive study, 549 patients with simple febrile seizure were studied. The routine lab tests including complete blood count, electrolyte, urine analysis, and cerebrospinal fluid (CSF) analysis had already been performed for all patients and the results had been recorded in their medical data. These results were collected and statistically analyzed through SPSS software. Results: About 58.7% of our cases were male. Most of the cases were 12–24 months old and the mean body temperature of them was 38.2°C. 99.3% of blood sugar tests, 98% of blood calcium tests, 100% and 99.5% of sodium, and potassium tests, respectively, 100% of blood creatinine, 96.9% of blood urea nitrogen, and 99.1% of urine analysis tests were normal. CSF analysis was done in only 49 cases and the results were normal in all of them. Conclusion: The percentage of abnormal laboratory test results was not statistically significant in febrile seizure and shows that performing all these tests in all patients with simple febrile seizure as routine is not necessary. PMID:26167207

  3. Iron-deficiency Anemia in Children with Febrile Seizure: A Case-Control Study

    PubMed Central

    GHASEMI, Fateme; VALIZADEH, Fateme; TAEE, Nadere

    2014-01-01

    Objective Considering the recurrence of febrile seizure and costs for families, many studies have attempted to identify its risk factors. Some recent studies have reported that anemia is more common in children with febrile convulsion, whereas others have reported that iron deficiency raises the seizure threshold. This study was done to compare iron-deficiency anemia in children with first FS with children having febrile illness alone and with healthy children. Materials & Methods This case-control study evaluated 300 children in three groups (first FS, febrile without convulsion, and healthy) in Khoramabad Madani Hospital from September 2009 to September 2010. Body temperature on admission was measured using the tympanic method. CBC diff, MCV, MCH, MCHC, serum iron, plasma ferritin and TIBC tests were performed for all participants. Data were analyzed by frequency, mean, standard deviation, ANOVA, and chi-square statistical tests. Odds ratios were estimated by logistic regression at a confidence level of 95%. Results Forty percent of the cases with FS had iron-deficiency anemia, compared to 26% of children with febrile illness without seizure and 12% of healthy children. The Odds ratio for iron-deficiency anemia in the patients with FS was 1.89 (95% CI, 1.04-5.17) compared to the febrile children without convulsion and 2.21 (95% CI, 1.54-3.46) compared to the healthy group. Conclusion Children with FS are more likely to be iron-deficient than those with febrile illness alone and healthy children. Thus, iron-deficiency anemia could be a risk factor for FS. PMID:24949050

  4. Identification of factors associated with postoperative febrile urinary tract infection after ureteroscopy for urinary stones.

    PubMed

    Mitsuzuka, Koji; Nakano, Osamu; Takahashi, Norio; Satoh, Makoto

    2016-06-01

    The aim of this study was to elucidate risk factors associated with postoperative febrile UTI after URS for urinary stones. Data from 153 patients undergoing URS for renal and/or ureteral stones between 2011 and 2013 at a single center were reviewed to detect factors predicting postoperative febrile UTI. URS for residual stones was excluded. Postoperative febrile UTI was defined as body temperature >38 °C and was graded according to the Clavien grading system. The definition of pyuria was 10 or more white blood cells per high power field. Median age of the patients was 57 (range 17-89) years. Of the 153 patients, 98 (64.1 %) were male, 10 (6.5 %) had Eastern Cooperative Oncology Group performance status 2 or greater, 14 (9.2 %) had Charlson comorbidity index 3 or greater. Before URS, 69 (45.1 %) had pyuria, 27 (17.6 %) had acute pyelonephritis, 42 (27.5 %) had ureteral stent, and 50 (32.7 %) were treated with antibiotics. After URS, 28 (18.3 %) developed febrile UTI (Clavien grade I, n = 16; grade II, n = 10; grade III, n = 1; grade IV, n = 1). Preoperative pyuria and acute pyelonephritis were significant factors for postoperative febrile UTI (pyuria: odds ratio 3.62, 95 % CI 1.26-8.11, P value 0.017; pyelonephritis: odds ratio 4.43, 95 % CI 1.06-11.16, P value 0.044). Degree of pyuria was likely to be associated with severity of postoperative febrile UTI, and two cases (1.3 %) with severe pyuria developed sepsis. Careful management is needed for patients with preoperative pyelonephritis or pyuria; risk factors for postoperative febrile UTI to avoid sepsis. PMID:26321205

  5. Distribution Of Febrile Seizure Duration And Associations With Development

    PubMed Central

    Hesdorffer, Dale C.; Benn, Emma K.T.; Bagiella, Emilia; Nordli, Douglas; Pellock, John; Hinton, Veronica; Shinnar, Shlomo

    2011-01-01

    Objectives In prior studies of febrile seizures (FS), prolonged FS are defined, absent empirical evidence, as lasting 10 or 15 minutes or more. We assessed the distribution of FS duration in a cohort with first FS, and the association between FS duration and baseline characteristics of the children. Methods We calculated the observed cumulative probability, S(t), that a FS would last at least t minutes, S(t) = exp(−t/ τ) . Data were also fit using a model obtained as the sum of two exponential distributions [S(t) = αexp(−t/τ1)+(1-α)exp(−t/τ2)]. After assessing the best fit, the cut off defining long FS was determined. Logisitic regression was used to examine associations between long FS and baseline characteristics, behavior and development. Results In 158 children with a first FS, median duration was 4.0 minutes. Duration of FS was best fit by a two-component mixture exponential model. Using this model we identified one population that accounts for 82.3% of FS and has a mean duration of 3.8 minutes (short FS) and a second population that accounts for 17.7% of FS and has a mean duration of 39.8 minutes (long FS). Long FS were significantly associated with developmental delay (p=0.010) and delays and younger age at first FS (p=0.048). Interpretation Like the distribution of afebrile seizure duration in children, the distribution of first FS duration is best modeled by assuming two populations. Developmental delay and younger age are associated with prolonged FS. Our data lend further support to defining 10 minutes as the upper limit for a simple FS. PMID:21437934

  6. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

    PubMed Central

    Kasperavičiūtė, Dalia; Catarino, Claudia B.; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Bárbara; Hessel, Ellen V. S.; Hallmann, Kerstin; Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P.; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J.; Zumsteg, Dominik; Duncan, Susan; Kälviäinen, Reetta K.; Eriksson, Kai J.; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M.; Stogmann, Elisabeth; Zimprich, Fritz; Théâtre, Emilie; Smith, Colin; O’Brien, Terence J.; Meng Tan, K.; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R.; Buono, Russell J.; Hakonarson, Hakon; Chaves, João; Costa, Paulo P.; Silva, Berta M.; da Silva, António M.; de Graan, Pierre N. E.; Koeleman, Bobby P. C.; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S.; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo M.; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E.; Berkovic, Samuel F.; Weale, Michael E.; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L.; Kunz, Wolfram S.

    2013-01-01

    Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26–1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures. PMID:24014518

  7. "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.

  8. Estimating the Incidence of Typhoid Fever and Other Febrile Illnesses in Developing Countries

    PubMed Central

    Youssef, Fouad G.; Luby, Stephen P.; Wasfy, Momtaz O.; Rangel, Josefa M.; Taalat, Maha; Oun, Said A.; Mahoney, Frank J.

    2003-01-01

    To measure the incidence of typhoid fever and other febrile illnesses in Bilbeis District, Egypt, we conducted a household survey to determine patterns of health seeking among persons with fever. Then we established surveillance for 4 months among a representative sample of health providers who saw febrile patients. Health providers collected epidemiologic information and blood (for culture and serologic testing) from eligible patients. After adjusting for the provider sampling scheme, test sensitivity, and seasonality, we estimated that the incidence of typhoid fever was 13/100,000 persons per year and the incidence of brucellosis was 18/100,000 persons per year in the district. This surveillance tool could have wide applications for surveillance for febrile illness in developing countries. PMID:12737736

  9. Infectious Etiologies of Acute Febrile Illness among Patients Seeking Health Care in South-Central Cambodia

    PubMed Central

    Kasper, Matthew R.; Blair, Patrick J.; Touch, Sok; Sokhal, Buth; Yasuda, Chadwick Y.; Williams, Maya; Richards, Allen L.; Burgess, Timothy H.; Wierzba, Thomas F.; Putnam, Shannon D.

    2012-01-01

    The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations. PMID:22302857

  10. The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib

    PubMed Central

    Zhou, Jian-Guo; Tian, Xu; Cheng, Long; Zhou, Quan; Liu, Yuan; Zhang, Yu; Bai, Yu-ju; Ma, Hu

    2015-01-01

    Abstract Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21–0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11–0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinb with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78–1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34–1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07–0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01–0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined to detect an RR of 0.38 for neutropenia, and 78.03% for an RR of 0.32 for leukopenia. The present meta-analysis suggested that erlotinib could decrease the incidence of neutropenia and leukopenia in patients with advanced NSCLC undergoing erlotinib regardless of whether combined with CT or not. The subgroup analysis revealed that erlotinib combine with CT did not affect the incidence; however, erlotinib alone could significantly decrease the incidence of neutropenia and leukopenia compared with CT alone. PMID:26448029

  11. Acute Undifferentiated Febrile Illness in Rural Cambodia: A 3-Year Prospective Observational Study

    PubMed Central

    Mueller, Tara C.; Siv, Sovannaroth; Khim, Nimol; Kim, Saorin; Fleischmann, Erna; Ariey, Frédéric; Buchy, Philippe; Guillard, Bertrand; González, Iveth J.; Christophel, Eva-Maria; Abdur, Rashid; von Sonnenburg, Frank; Bell, David; Menard, Didier

    2014-01-01

    In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects. PMID:24755844

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

    PubMed

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

    2013-12-01

    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

  13. Acute undifferentiated febrile illness in rural Cambodia: a 3-year prospective observational study.

    PubMed

    Mueller, Tara C; Siv, Sovannaroth; Khim, Nimol; Kim, Saorin; Fleischmann, Erna; Ariey, Frédéric; Buchy, Philippe; Guillard, Bertrand; González, Iveth J; Christophel, Eva-Maria; Abdur, Rashid; von Sonnenburg, Frank; Bell, David; Menard, Didier

    2014-01-01

    In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects. PMID:24755844

  14. Naturally occuring mutagens.

    PubMed

    Clark, A M

    1976-01-01

    Naturally occurring mutagens have usually been discovered as a result of outbreaks of disease in agricultural livestock, or as a result of epidemiological studies of cancer of the liver in man. Subsequent work has then shown that the toxic agents responsible often have mutagenic properties. Examples are the pyrrolizidine alkaloids, cyasin, a range of mycotoxins produced by various fungi, and at least two unidentified toxic agents in bracken. Commonly the toxic agent itself does not show high biological activity, but after ingestion it is converted by metabolic processes into the active mutagen or carcinogen. Some of these toxic substances have been responsible for considerable losses of agricultural livestock and therefore are of economic significance. From the view-point of genetic hazards to man, the most significant compounds are probably the mycotoxins, e.g. aflatoxin, because of the common risk of fungal contamination of food, especially in tropical regions. No information is yet available on the effects of these mutagens on natural populations of animals. Plants containing the pyrrolizidine alkaloids are found in areas of Africa and the Middle East where plagues of the migratory locust occur. Although it is known that some of the alkaloids can induce chromosomal damage in grasshoppers, whether such damage ever becomes a significant factor under ecological conditions is not known. In some cases, insects have not only evolved resistance towards mutagenic alkaloids but have become dependent on them for certain purposes. The males of certain Danaid butterflies feed on plants containing pyrrolizidine alkaloids. After ingestion, the alkaloids are metabolised to dihydropyrrolizine derivatives, which are then secreted on special organs (hair pencils) and, following dissemination into the atmosphere, act as pheromones for the stimulation of mating behaviour. PMID:958226

  15. Clinical and Economic Burden of Emergency Department Presentations for Neutropenia Following Outpatient Chemotherapy for Cancer in Victoria, Australia

    PubMed Central

    Craike, Melinda; Slavin, Monica

    2012-01-01

    Objective. To examine the clinical characteristics and financial charges associated with treating adult cancer patients receiving chemotherapy in outpatient clinics who presented to the emergency department (ED) with neutropenia. Design and Setting. A retrospective audit was conducted across two health services involving ED episodes and subsequent hospital admissions of patients who received chemotherapy through day oncology from January 1 to December 31, 2007 and presented to the ED with neutropenia. ED data were collected from the Victorian Emergency Minimum Dataset and charges were collected from Health Information Services. Descriptive and bivariate statistics were used to describe the patient and clinical characteristics and financial outcomes, and to explore associations between these factors. Results. In total, 200 neutropenic episodes in 159 outpatients were seen in the ED over the survey period. The mean patient age was 56.6 years (standard deviation, 13.2 years) and 47.2% were male. Overall, 70.0% of ED episodes were triaged as Australasian Triage Scale 2 (emergency). The median ED wait time was 10 minutes and the median ED length of stay was 6.8 hours. The median charge for each ED episode was $764.08 Australian dollars. The total combined ED and inpatient charge per episode was in the range of $144.27–$174,732.68, with a median charge of $5,640.87. Conclusions. This study provides important insights into the clinical and economic burden of neutropenia from both the ED and inpatient perspectives. Alternative treatment models, such as outpatient treatment, early discharge programs or prophylactic interventions to reduce the clinical and economic burden of neutropenia on our health system, must be explored. PMID:22707511

  16. 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 < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low 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

  17. 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

  18. Role of routine investigations in children presenting with their first febrile convulsion.

    PubMed Central

    Rutter, N; Smales, O R

    1977-01-01

    To assess the role of routine investigations in children presenting with their first febrile convulsion, the results of investigations carried out in 328 children over a 2-year period were reviewed. Lumber puncture was performed in 96% of cases and resulted in the detection of 4 cases of unsuspected meningitis, one of which was bacterial. 2 children had normal lumbar punctures on admission but developed meningococcal meningitis within 48 hours. Sugar, calcium, urea, and electrolyte estimations, and blood counts were commonly performed but were unhelpful. We suggest that lumbar puncture in those children presenting with their first febrile convulsion under the age of 18 months is the only useful routine investigation. PMID:848997

  19. Glucose-6-phosphatase-β, implicated in a congenital neutropenia syndrome, is essential for macrophage energy homeostasis and functionality

    PubMed Central

    Jun, Hyun Sik; Cheung, Yuk Yin; Lee, Young Mok; Mansfield, Brian C.

    2012-01-01

    Glucose-6-phosphatase-β (G6Pase-β or G6PC3) deficiency, also known as severe congenital neutropenia syndrome 4, is characterized not only by neutropenia but also by impaired neutrophil energy homeostasis and functionality. We now show the syndrome is also associated with macrophage dysfunction, with murine G6pc3−/− macrophages having impairments in their respiratory burst, chemotaxis, calcium flux, and phagocytic activities. Consistent with a glucose-6-phosphate (G6P) metabolism deficiency, G6pc3−/− macrophages also have a lower glucose uptake and lower levels of G6P, lactate, and ATP than wild-type macrophages. Furthermore, the expression of NADPH oxidase subunits and membrane translocation of p47phox are down-regulated, and G6pc3−/− macrophages exhibit repressed trafficking in vivo both during an inflammatory response and in pregnancy. During pregnancy, the absence of G6Pase-β activity also leads to impaired energy homeostasis in the uterus and reduced fertility of G6pc3−/− mothers. Together these results show that immune deficiencies in this congenital neutropenia syndrome extend beyond neutrophil dysfunction. PMID:22246029

  20. Long-term neuroplasticity effects of febrile seizures in the developing brain.

    PubMed

    Chang, Ying-Chao; Huang, Chao-Ching; Huang, Song-Chei

    2008-01-01

    Febrile seizures (FS) are the most common seizure disorder in childhood, occurring in 2%-5% of children. Regarding the large number of children with FS, it is important to delineate whether early-life FS alters long-term neuroplasticity, especially the neurocognitive function and subsequent temporal lobe epilepsy (TLE). Recent epidemiological studies reassure that most FS do not adversely affect global intelligence and hippocampal function, such as memory. However, there are concerns regarding those children who experience FS during the first postnatal year, having prior developmental delay and pre- or peri-natal events. The epidemiological data do not support a causal relationship between FS and TLE. However, magnetic resonance imaging studies confirmed that prolonged and focal FS can occasionally produce acute hippocampal injury that evolves into atrophy. Moreover, the common coexistence of hippocampal sclerosis and asymmetric cortical dysgenesis in TLE patients argues for a 'double-hit' theory for TLE. Animal studies have revealed that the exposure of hippocampal neurons to FS early in life, particularly prolonged or frequently repetitive FS, or together with brain malformation, may lead to sustained dysfunction of these cells including long-term memory impairment or epileptogenesis, in spite of the absence of neuronal damage. Recent clinical and molecular genetic studies suggest that the relationship between FS and later epilepsy is frequently genetic, and there are a number of syndrome-specific genes for FS. However, these channelopathies account for a small proportion of FS cases. The clinical management, therefore, is based mainly on the phenotypic features of FS and the subsequent seizures. PMID:18567412

  1. Neural Correlates of Recognition Memory in Children with Febrile Seizures: Evidence from Functional Magnetic Resonance Imaging

    PubMed Central

    Kipp, Kerstin H.; Opitz, Bertram; Becker, Martina; Hofmann, Juliane; Krick, Christoph; Gortner, Ludwig; Mecklinger, Axel

    2012-01-01

    Febrile seizures (FS) are assumed to not have adverse long-term effects on cognitive development. Nevertheless, FS are often associated with hippocampal sclerosis which can imply episodic memory deficits. This interrelation has hardly been studied so far. In the current study 13 children who had suffered from FS during infancy and 14 control children (7 to 9-years-old) were examined for episodic and semantic memory with standardized neuropsychological tests. Furthermore, using functional magnetic resonance imaging (fMRI) we studied neuronal activation while the children performed a continuous recognition memory task. The analysis of the behavioral data of the neuropsychological tests and the recognition memory experiment did not reveal any between-group differences in memory performance. Consistent with other studies fMRI revealed repetition enhancement effects for both groups in a variety of brain regions (e.g., right middle frontal gyrus, left parahippocampal gyrus) and a repetition suppression effect in the right superior temporal gyrus. Different neural activation patterns between both groups were obtained selectively within the right supramarginal gyrus (BA 40). In the control group correct rejections of new items were associated with stronger activation than correctly identified old items (HITs) whereas in the FS group no difference occurred. On the background that the right supramarginal gyrus is assumed to mediate a top-down process to internally direct attention toward recollected information, the results could indicate that control children used strategic recollection in order to reject new items (recall-to-reject). In contrast, the missing effect in the FS group could reflect a lack of strategy use, possibly due to impaired recollective processing. This study demonstrates that FS, even with mainly benign courses, can be accompanied by selective modifications in the neural structures underlying recognition memory. PMID:22347857

  2. 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

  3. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells

    PubMed Central

    Nayak, Ramesh C.; Trump, Lisa R.; Aronow, Bruce J.; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M.; Valencia, C. Alexander; Paddison, Patrick J.; Horwitz, Marshall S.; Grimes, H. Leighton; Lutzko, Carolyn; Cancelas, Jose A.

    2015-01-01

    Severe congenital neutropenia (SCN) is often associated with inherited heterozygous point mutations in ELANE, which encodes neutrophil elastase (NE). However, a lack of appropriate models to recapitulate SCN has substantially hampered the understanding of the genetic etiology and pathobiology of this disease. To this end, we generated both normal and SCN patient–derived induced pluripotent stem cells (iPSCs), and performed genome editing and differentiation protocols that recapitulate the major features of granulopoiesis. Pathogenesis of ELANE point mutations was the result of promyelocyte death and differentiation arrest, and was associated with NE mislocalization and activation of the unfolded protein response/ER stress (UPR/ER stress). Similarly, high-dose G-CSF (or downstream signaling through AKT/BCL2) rescues the dysgranulopoietic defect in SCN patient–derived iPSCs through C/EBPβ-dependent emergency granulopoiesis. In contrast, sivelestat, an NE-specific small-molecule inhibitor, corrected dysgranulopoiesis by restoring normal intracellular NE localization in primary granules; ameliorating UPR/ER stress; increasing expression of CEBPA, but not CEBPB; and promoting promyelocyte survival and differentiation. Together, these data suggest that SCN disease pathogenesis includes NE mislocalization, which in turn triggers dysfunctional survival signaling and UPR/ER stress. This paradigm has the potential to be clinically exploited to achieve therapeutic responses using lower doses of G-CSF combined with targeting to correct NE mislocalization. PMID:26193632

  4. Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model

    PubMed Central

    Grguric-Smith, Laryssa M.; Lee, Hiu H.; Gandhi, Jay A.; Brennan, Melissa B.; DeLeon-Rodriguez, Carlos M.; Coelho, Carolina; Han, George; Martinez, Luis R.

    2015-01-01

    The Gram negative coccobacillus Acinetobacter baumannii has become an increasingly prevalent cause of hospital-acquired infections in recent years. The majority of clinical A. baumannii isolates display high-level resistance to antimicrobials, which severely compromises our capacity to care for patients with A. baumannii disease. Neutrophils are of major importance in the host defense against microbial infections. However, the contribution of these cells of innate immunity in host resistance to cutaneous A. baumannii infection has not been directly investigated. Hence, we hypothesized that depletion of neutrophils increases severity of bacterial disease in an experimental A. baumannii murine wound model. In this study, the Ly-6G-specific monoclonal antibody (mAb), 1A8, was used to generate neutropenic mice and the pathogenesis of several A. baumannii clinical isolates on wounded cutaneous tissue was investigated. We demonstrated that neutrophil depletion enhances bacterial burden using colony forming unit determinations. Also, mAb 1A8 reduces global measurements of wound healing in A. baumannii-infected animals. Interestingly, histological analysis of cutaneous tissue excised from A. baumannii-infected animals treated with mAb 1A8 displays enhanced collagen deposition. Furthermore, neutropenia and A. baumannii infection alter pro-inflammatory cytokine release leading to severe microbial disease. Our findings provide a better understanding of the impact of these innate immune cells in controlling A. baumannii skin infections. PMID:26528277

  5. 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

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

    PubMed Central

    Shirdel, Elize A.; Korenberg, Michael J.; Madarnas, Yolanda

    2011-01-01

    Background. Delivery of full doses of adjuvant chemotherapy on schedule is key to optimal breast cancer outcomes. Neutropenia is a serious complication of chemotherapy and a common barrier to this goal, leading to dose reductions or delays in treatment. While past research has observed correlations between complete blood count data and neutropenic events, a reliable method of classifying breast cancer patients into low- and high-risk groups remains elusive. Patients and Methods. Thirty-five patients receiving adjuvant chemotherapy for early-stage breast cancer under the care of a single oncologist are examined in this study. FOS-3NN stratifies patient risk based on complete blood count data after the first cycle of treatment. All classifications are independent of breast cancer subtype and clinical markers, with risk level determined by the kinetics of patient blood count response to the first cycle of treatment. Results. In an independent test set of patients unseen by FOS-3NN, 19 out of 21 patients were correctly classified (Fisher's exact test probability P < 0.00023 [2 tailed], Matthews' correlation coefficient +0.83). Conclusions. We have developed a model that accurately predicts neutropenic events in a population treated with adjuvant chemotherapy in the first cycle of a 6-cycle treatment. PMID:22454638

  7. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells.

    PubMed

    Nayak, Ramesh C; Trump, Lisa R; Aronow, Bruce J; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M; Valencia, C Alexander; Paddison, Patrick J; Horwitz, Marshall S; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A

    2015-08-01

    Severe congenital neutropenia (SCN) is often associated with inherited heterozygous point mutations in ELANE, which encodes neutrophil elastase (NE). However, a lack of appropriate models to recapitulate SCN has substantially hampered the understanding of the genetic etiology and pathobiology of this disease. To this end, we generated both normal and SCN patient-derived induced pluripotent stem cells (iPSCs), and performed genome editing and differentiation protocols that recapitulate the major features of granulopoiesis. Pathogenesis of ELANE point mutations was the result of promyelocyte death and differentiation arrest, and was associated with NE mislocalization and activation of the unfolded protein response/ER stress (UPR/ER stress). Similarly, high-dose G-CSF (or downstream signaling through AKT/BCL2) rescues the dysgranulopoietic defect in SCN patient-derived iPSCs through C/EBPβ-dependent emergency granulopoiesis. In contrast, sivelestat, an NE-specific small-molecule inhibitor, corrected dysgranulopoiesis by restoring normal intracellular NE localization in primary granules; ameliorating UPR/ER stress; increasing expression of CEBPA, but not CEBPB; and promoting promyelocyte survival and differentiation. Together, these data suggest that SCN disease pathogenesis includes NE mislocalization, which in turn triggers dysfunctional survival signaling and UPR/ER stress. This paradigm has the potential to be clinically exploited to achieve therapeutic responses using lower doses of G-CSF combined with targeting to correct NE mislocalization. PMID:26193632

  8. Osteoporosis in children with severe congenital neutropenia: bone mineral density and treatment with bisphosphonates.

    PubMed

    Borzutzky, Arturo; Reyes, María Loreto; Figueroa, Valeria; García, Cristián; Cavieres, Mirta

    2006-04-01

    A high incidence of decreased bone mineral density (BMD) has been described in patients with severe congenital neutropenia (SCN). The objectives of the study are to describe changes in BMD in children with SCN treated with granulocyte colony-stimulating factor and evaluate the response to treatment with bisphosphonates in those who had osteoporosis. A prospective open-label study was performed evaluating BMD and metabolism in 9 Chilean patients with SCN, administrating bisphosphonates in those with osteoporosis. Follow-up ranged between 7 months and 3.5 years. Six out of 9 patients had reduced BMD on initial assessment: 3 had osteoporosis (z score <-2) and 3 had osteopenia (z score <-1). Four children presented vertebral fractures. Two presented osteopenia on follow-up without clinical symptoms. Five patients were treated with bisphosphonates, increasing their BMD z score (mean increase 1.2, range 0.27 to 2.62). z Score of hydroxyproline/creatinine ratios, which was elevated in 4 patients with osteoporosis, decreased during treatment (mean decrease 2.18, range 1.56 to 2.53). Four patients remodeled and reexpanded fractured vertebrae during treatment. No side effects of bisphosphonates were seen on follow-up. Osteoporosis is an important comorbidity in SCN patients probably due to increased bone resorption. Bisphosphonates seem to be an effective treatment for osteoporosis in these patients. PMID:16679916

  9. 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

  10. Naturally occurring cardiac glycosides.

    PubMed

    Radford, D J; Gillies, A D; Hinds, J A; Duffy, P

    1986-05-12

    Cardiac glycoside poisoning from the ingestion of plants, particularly of oleanders, occurs with reasonable frequency in tropical and subtropical areas. We have assessed a variety of plant specimens for their cardiac glycoside content by means of radioimmunoassays with antibodies that differ in their specificity for cardiac glycosides. Significant amounts of immunoreactive cardiac glycoside were found to be present in the ornamental shrubs: yellow oleander (Thevetia peruviana); oleander (Nerium oleander); wintersweet (Carissa spectabilis); bushman's poison (Carissa acokanthera); sea-mango (Cerbera manghas); and frangipani (Plumeria rubra); and in the milkweeds: redheaded cotton-bush (Asclepias curassavica); balloon cotton (Asclepias fruiticosa); king's crown (Calotropis procera); and rubber vine (Cryptostegia grandifolia). The venom gland of the cane toad (Bufo marinus) also contained large quantities of cardiac glycosides. The competitive immunoassay method permits the rapid screening of specimens that are suspected to contain cardiac glycosides. Awareness of the existence of these plant and animal toxins and their dangers allows them to be avoided and poisoning prevented. The method is also useful for the confirmation of the presence of cardiac glycosides in serum in cases of poisoning. PMID:3086679

  11. Diagnosis and management of febrile infants (0-3 months).

    PubMed Central

    Hui, Charles; Neto, Gina; Tsertsvadze, Alexander; Yazdi, Fatemeh; Tricco, Andrea C; Tsouros, Sophia; Skidmore, Becky; Daniel, Raymond

    2012-01-01

    OBJECTIVES To review the evidence for diagnostic accuracy of screening for serious bacterial illness (SBI) and invasive herpes simplex virus (HSV) infection in febrile infants 3 months or younger; ascertain harms and benefits of various management strategies; compare prevalence of SBI and HSV between different clinical settings; determine how well the presence of viral infection predicts against SBI; and review evidence on parental compliance to return for followup assessments (infants less than 6 months). DATA SOURCES MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, abstracts, and unpublished materials. REVIEW METHODS Two independent reviewers screened the literature and extracted data on population characteristics, index/diagnostic test characteristics. Diagnostic test accuracy studies were assessed using Quality Assessment of Diagnostic Accuracy Studies. RESULTS Eighty-four original studies were included. The combined clinical and laboratory criteria (Rochester, Philadelphia, Boston, and Milwaukee) demonstrated similar overall accuracy (sensitivity: 84.4 percent to 100.0 percent; specificity: 26.6 percent to 69.0 percent; negative predictive value: 93.7 percent to 100.0 percent; and positive predictive value: 3.3 percent to 48.6 percent) for identifying infants with SBI. The criteria based on history of recent immunization or rapid influenza test demonstrated higher sensitivity but lower specificity compared with criteria based on age, gender, and the degree of fever. The overall accuracy of C-reactive protein was greater than that for absolute neutrophil count and absolute band counts , white blood cell, and procalcitonin. For correctly identifying infants with and without SBI (or bacteremia), the Boston, Philadelphia, and Milwaukee criteria/protocol showed better overall accuracy when applied to older infants versus neonates. The Rochester criteria were more accurate in neonates than in older infants. Evidence on HSV was scarce. Most of the criteria/protocols demonstrated high negative predictive values and low positive predictive values for correctly predicting the absence or presence of SBI. In studies reporting outcomes of delayed treatment for infants with SBI initially classified as low risk, all infants recovered uneventfully. The reported adverse events following immediate antibiotic therapy were limited to drug related rash and infiltration of intravenous line. There was a higher prevalence of SBI in infants without viral infection or clinical bronchiolitis compared to infants with viral infection or bronchiolitis. The prevalence of SBI tended to be higher in the emergency departments versus primary care setting offices. The parental compliance to followup for return visits/reassessment of infants after initial examination across four studies ranged from 77.4 percent to 99.8 percent. There was no evidence to determine the influence of parental factors and clinical settings on the degree of parental compliance. CONCLUSIONS Overall, the focus of the literature has been on ruling out SBI. Harms associated with testing or management strategies have been less well studied. Combined criteria showed fairly high sensitivity and (therefore) reliability in not missing possible cases of SBI. Attempts to identify high-risk groups specifically, described in a minority of reports, were not as successful. There is very little literature on factors associated with compliance to followup care, although that information could be crucial to improving management strategies in the low-risk group. Future studies should focus on identifying the risks associated with testing and management strategies and factors that predict compliance. PMID:24422856

  12. Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients.

    PubMed

    Nováková, I; Donnelly, J P; De Pauw, B

    1991-04-01

    In a prospective randomized study, 120 febrile, granulocytopenic patients received as initial therapy ceftazidime with or without teicoplanin. At the onset of fever, patients had no obvious infectious focus. For 103 assessable episodes, initial bacteremias were detected in 18 of 51 patients (35%) given ceftazidime and 20 of 52 patients (38%) given the combination; 13 and 17 bacteremias caused by gram-positive bacteria occurred in these groups, respectively. There was no difference in terms of the final response (25 of 51 patients [49%] treated with ceftazidime alone versus 33 of 52 patients [63%] given the combination), and the morbidity was comparable for both treatment groups. The duration of fever and of total antibiotic therapy were similar in both groups. Initial therapy was modified in 26 patients (51%) treated with ceftazidime, with 20 surviving the infection, and in 19 patients (37%) treated with the combination, with 15 surviving. Persistent fever was the main reason for changing treatment, and no patient died of a gram-positive infection. Subsequent infective events occurred in 16 patients (31%) given ceftazidime and in 25 patients (48%) given the combination. Lung infiltrates developed in 12 and 13 patients, respectively, but more new infections occurred in the combination group. Allergic skin reactions were also more frequent in this group. Thus, while teicoplanin provides simple, reliable, and safe treatment of patients with presumed gram-positive infections, it is not useful when given empirically to this patient population, and treatment may result in more infective complications and adverse events. PMID:1829879

  13. Expression Profiling after Prolonged Experimental Febrile Seizures in Mice Suggests Structural Remodeling in the Hippocampus.

    PubMed

    Jongbloets, Bart C; van Gassen, Koen L I; Kan, Anne A; Olde Engberink, Anneke H O; de Wit, Marina; Wolterink-Donselaar, Inge G; Groot Koerkamp, Marian J A; van Nieuwenhuizen, Onno; Holstege, Frank C P; de Graan, Pierre N E

    2015-01-01

    Febrile seizures are the most prevalent type of seizures among children up to 5 years of age (2-4% of Western-European children). Complex febrile seizures are associated with an increased risk to develop temporal lobe epilepsy. To investigate short- and long-term effects of experimental febrile seizures (eFS), we induced eFS in highly febrile convulsion-susceptible C57BL/6J mice at post-natal day 10 by exposure to hyperthermia (HT) and compared them to normotherm-exposed (NT) mice. We detected structural re-organization in the hippocampus 14 days after eFS. To identify molecular candidates, which entrain this structural re-organization, we investigated temporal changes in mRNA expression profiles eFS 1 hour to 56 days after eFS. We identified 931 regulated genes and profiled several candidates using in situ hybridization and histology at 3 and 14 days after eFS. This is the first study to report genome-wide transcriptome analysis after eFS in mice. We identify temporal regulation of multiple processes, such as stress-, immune- and inflammatory responses, glia activation, glutamate-glutamine cycle and myelination. Identification of the short- and long-term changes after eFS is important to elucidate the mechanisms contributing to epileptogenesis. PMID:26684451

  14. Expression Profiling after Prolonged Experimental Febrile Seizures in Mice Suggests Structural Remodeling in the Hippocampus

    PubMed Central

    Jongbloets, Bart C.; van Gassen, Koen L. I.; Kan, Anne A.; Olde Engberink, Anneke H. O.; de Wit, Marina; Wolterink-Donselaar, Inge G.; Groot Koerkamp, Marian J. A.; van Nieuwenhuizen, Onno; Holstege, Frank C. P.; de Graan, Pierre N. E.

    2015-01-01

    Febrile seizures are the most prevalent type of seizures among children up to 5 years of age (2–4% of Western-European children). Complex febrile seizures are associated with an increased risk to develop temporal lobe epilepsy. To investigate short- and long-term effects of experimental febrile seizures (eFS), we induced eFS in highly febrile convulsion-susceptible C57BL/6J mice at post-natal day 10 by exposure to hyperthermia (HT) and compared them to normotherm-exposed (NT) mice. We detected structural re-organization in the hippocampus 14 days after eFS. To identify molecular candidates, which entrain this structural re-organization, we investigated temporal changes in mRNA expression profiles eFS 1 hour to 56 days after eFS. We identified 931 regulated genes and profiled several candidates using in situ hybridization and histology at 3 and 14 days after eFS. This is the first study to report genome-wide transcriptome analysis after eFS in mice. We identify temporal regulation of multiple processes, such as stress-, immune- and inflammatory responses, glia activation, glutamate-glutamine cycle and myelination. Identification of the short- and long-term changes after eFS is important to elucidate the mechanisms contributing to epileptogenesis. PMID:26684451

  15. Possible Role of Rickettsia felis in Acute Febrile Illness among Children in Gabon

    PubMed Central

    Mourembou, Gaël; Lekana-Douki, Jean Bernard; Mediannikov, Oleg; Nzondo, Sydney Maghendji; Kouna, Lady Charlene; Essone, Jean Claude Biteghe Bi; Fenollar, Florence

    2015-01-01

    Rickettsia felis has been reported to be a cause of fever in sub-Saharan Africa, but this association has been poorly evaluated in Gabon. We assessed the prevalence of this bacterium among children <15 years of age in 4 areas of Gabon; the locations were in urban, semiurban, and rural areas. DNA samples from 410 febrile children and 60 afebrile children were analyzed by quantitative PCR. Overall, the prevalence of R. felis among febrile and afebrile children was 10.2% (42/410 children) and 3.3% (2/60 children), respectively. Prevalence differed among febrile children living in areas that are urban (Franceville, 1.3% [1/77]), semiurban (Koulamoutou, 2.1% [3/141]), and rural (Lastourville, 11.2% [15/134]; Fougamou, 39.7% [23/58]). Furthermore, in a rural area (Fougamou), R. felis was significantly more prevalent in febrile (39.7% [23/58]) than afebrile children (5.0% [1/20]). Additional studies are needed to better understand the pathogenic role of R. felis in this part of the world. PMID:26402580

  16. Iron Status and Febrile Seizure- A Case Control Study in Children Less Than 3 Years

    PubMed Central

    SADEGHZADEH, Mansour; KHOSHNEVIS ASL, Parisa; MAHBOUBI, Esrafil

    2012-01-01

    Objective Febrile seizure is one of the most common neurological conditions of childhood. Several theories, such as iron deficiency anemia have been proposed as the pathogenesis of this condition. The aim of this study was to find the association between iron deficiency anemia and febrile seizures in children aged 6 months to 3 years admitted in Valie Asr hospital in Zanjan. Materials &Methods Hemoglobin (Hb), mean corpuscular volume (MCV), serum iron (SI), total iron binding capacity (TIBC) and SI/TIBC ratio were assessed in one hundred children with febrile seizures and compared to the values of one hundred healthy children presenting in a heath care center in the same period as the control group. Results A total of 6% of cases had iron deficiency anemia which was similar to the control group. In the case group SI/TIBC ratio below 12% was seen in 58% of children which was significantly higher than that of the control group (29%). Conclusion The results of this study suggest that although anemia was not common among febrile seizure patients, iron deficiency was more frequent in these patients. PMID:24665277

  17. Prenatal Stress and Risk of Febrile Seizures in Children: A Nationwide Longitudinal Study in Denmark

    ERIC Educational Resources Information Center

    Li, Jiong; Olsen, Jorn; Obel, Carsten; Christensen, Jakob; Precht, Dorthe Hansen; Vestergaard, Mogens

    2009-01-01

    We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost a close relative during pregnancy or within 1 year

  18. Value of Provoked or Spontaneous Flank Pain in Men with Febrile Urinary Tract Infections

    PubMed Central

    Bruyère, Franck; Ruimy, Joseph-Alain; Bernard, Louis; Elfassi, Raphael; Boyer, Olivier; Amann, Fabrice; Meria, Paul

    2014-01-01

    Background: Our objective was to identify the clinical, laboratory and radiological characteristics of febrile urinary tract infections (UTI) in men and to focus on the value of flank pain in these men managed in an ambulatory care system. Methods: A network was designed to manage men with febrile UTI without hospitalization according to an algorithm designed with different specialists. The patients’ characteristics were prospectively recorded and each patient was followed up until completely cured. We artificially divided patients into two groups. Group 1: men without flank pain diagnosed as prostatitis and a second group (Group 2) of men with flank pain or provoked flank pain more likely to have a pyelonephritis. Groups were compared to find arguments to differentiate prostatitis to pyelonephritis. Results: 350 men were included in the study, half of these men reported urinary symptoms (dysuria, urgency and burning urination). The negative predictive values of the nitrite and leukocytes test were poor alone or in combination. The renal ultrasound was never informative. None of the patients failed to respond to the treatment. No difference was found between groups. Conclusions: Laboratory test results and radiological features had a poor predictive value. Men with suspected pyelonephritis did not evolve differently from those with suspected prostatitis. Monitoring and treatment of men with febrile UTI does not seem to depend on the existence of a pyelonephritis suspected after the presence of a lumbar pain. Ambulatory management of febrile UTI is feasible and safe, requiring an efficient network for patient’s surveillance.

  19. Prenatal Stress and Risk of Febrile Seizures in Children: A Nationwide Longitudinal Study in Denmark

    ERIC Educational Resources Information Center

    Li, Jiong; Olsen, Jorn; Obel, Carsten; Christensen, Jakob; Precht, Dorthe Hansen; Vestergaard, Mogens

    2009-01-01

    We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost a close relative during pregnancy or within 1 year…

  20. 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

  1. Chikungunya Virus as Cause of Febrile Illness Outbreak, Chiapas, Mexico, 2014

    PubMed Central

    Kautz, Tiffany F.; Díaz-González, Esteban E.; Erasmus, Jesse H.; Malo-García, Iliana R.; Langsjoen, Rose M.; Patterson, Edward I.; Auguste, Dawn I.; Forrester, Naomi L.; Sanchez-Casas, Rosa Maria; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M.; Fernández-Salas, Ildefonso

    2015-01-01

    Since chikungunya virus (CHIKV) was introduced into the Americas in 2013, its geographic distribution has rapidly expanded. Of 119 serum samples collected in 2014 from febrile patients in southern Mexico, 79% were positive for CHIKV or IgM against CHIKV. Sequencing results confirmed CHIKV strains closely related to Caribbean isolates. PMID:26488312

  2. Seroepidemiology of Selected Arboviruses in Febrile Patients Visiting Selected Health Facilities in the Lake/River Basin Areas of Lake Baringo, Lake Naivasha, and Tana River, Kenya

    PubMed Central

    Lwande, Olivia; Orindi, Benedict; Irura, Zephania; Ongus, Juliette; Sang, Rosemary

    2015-01-01

    Abstract Introduction: Arboviruses cause emerging and re-emerging infections affecting humans and animals. They are spread primarily by blood-sucking insects such as mosquitoes, ticks, midges, and sandflies. Changes in climate, ecology, demographic, land-use patterns, and increasing global travel have been linked to an upsurge in arboviral disease. Outbreaks occur periodically followed by persistent low-level circulation. Aim: This study was undertaken to determine the seroepidemiology of selected arboviruses among febrile patients in selected lake/river basins of Kenya. Methods: Using a hospital-based cross-sectional descriptive survey, febrile patients were recruited and their serum samples tested for exposure to immunoglobulin M (IgM) and IgG antibodies against Crimean–Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), West Nile virus (WNV), and chikungunya virus (CHIKV). Samples positive for CHIKV and WNV were further confirmed by the plaque reduction neutralization test (PRNT). Results: Of the 379 samples examined, 176 were IgG positive for at least one of these arboviruses (46.4%, 95% confidence interval [CI] 41.4–51.5%). Virus-specific prevalence for CCHF, RVF, WN, and CHIK was 25.6%, 19.5%, 12.4%, and 2.6%, respectively. These prevalences varied significantly with geographical site (p<0.001), with Tana recording the highest overall arboviral seropositivity. PRNT results for Alphaviruses confirmed that the actual viruses circulating in Baringo were Semliki Forest virus (SFV) and CHIKV, o'nyong nyong virus (ONNV) in Naivasha, and SFV and Sindbis virus (SINDV) in Tana delta. Among the flaviviruses tested, WNV was circulating in all the three sites. Conclusion: There is a high burden of febrile illness in humans due to CCHFV, RVFV, WNV, and CHIKV infection in the river/lake basin regions of Kenya. PMID:25700043

  3. Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

    PubMed

    Awad, Patricia N; Sanon, Nathalie T; Chattopadhyaya, Bidisha; Carriço, Josianne Nunes; Ouardouz, Mohamed; Gagné, Jonathan; Duss, Sandra; Wolf, Daniele; Desgent, Sébastien; Cancedda, Laura; Carmant, Lionel; Di Cristo, Graziella

    2016-07-01

    Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. PMID:26875662

  4. Possible role of trace elements in epilepsy and febrile seizures: a meta-analysis.

    PubMed

    Saghazadeh, Amene; Mahmoudi, Maryam; Meysamie, Alipasha; Gharedaghi, Maryam; Zamponi, Gerald W; Rezaei, Nima

    2015-11-01

    Seizures are among the most common causes of apparent life-threatening events. There are discrepancies among the published reports on the correlation between epilepsy/febrile seizures and deficiency or overload of trace elements. The objective of this review and meta-analysis was to examine the present knowledge on the concentrations of the most investigated trace metals, including zinc, copper, selenium, and magnesium, in patients with epilepsy and febrile seizures. The PubMed and Scopus databases were searched to identify case-control studies that compared the concentration of zinc, copper, magnesium, and selenium in serum, hair, or cerebrospinal fluid between patients with epilepsy/febrile seizures and controls. A total of 60 articles were included in the present study (40 pertaining to epilepsy and 25 pertaining to febrile seizures). The serum concentration of zinc in nontreated patients with epilepsy was significantly higher than in controls (P = 0.034). There were significantly reduced serum concentrations of zinc (P = 0.018) and selenium (P = 0.012) in patients with febrile seizures compared with controls. The concentrations of copper, magnesium, and zinc were all significantly altered in patients with epilepsy who received antiepileptic drugs compared with untreated patients with epilepsy. Designing treatments to selectively restore zinc levels may be a strategy for treating patients with epilepsy. It is still unclear whether these ions are causal to, or a cofactor in, the development of epilepsy. Knowledge of the effects of various antiepileptic drugs on trace element homeostasis could potentially be used to effectively guide appropriate therapeutic strategies in the future. PMID:26433016

  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. Intermittent Diazepam versus Continuous Phenobarbital to Prevent Recurrence of Febrile Seizures: A Randomized Controlled Trial

    PubMed Central

    SALEHIOMRAN, Mohammadreza; HOSEINI, Seyed Mohammad; GHABELI JUIBARY, Ali

    2016-01-01

    Objective Febrile seizure is the most common neurologic problem in children between 3 months to 5 years old. Two to five percent of children aged less than five yr old will experience it at least one time. This type of seizure is age dependent and its recurrence rate is about 33% overalls and 50% in children less than one yr old. The prophylactic treatment is still controversial, so we conducted a randomized controlled clinical trial to find out the effectiveness of continuous phenobarbital versus intermittent diazepam for febrile seizure. Materials & Methods This clinical trial was conducted in the Department of Pediatric Neurology, Babol University of Medical Sciences, Babol, Iran between March 2008 and October 2010. All children from 6 month to 5 yr old referred to Amirkola Children’s Hospital, Babol, Iran were enrolled in the study. Children with febrile seizure that had indication for prophylaxis but did not receive any prophylaxis previously were enrolled in the study. For prophylactic anti convulsion therapy, patients were divided randomly in two groups. One group received continuous phenobarbital and another treated with intermittent diazepam whenever the children experienced an episode of febrile illness for up to one year after their last convulsion. Results Of all 145 studied cases, the recurrent rate in children under prophylaxis with diazepam was 11/71 and in phenobarbital group was 17/74. There was no significant difference in the recurrence rate in both groups. Conclusion There was no significant difference in the effectiveness of phenobarbital and diazepam in prevention of recurrent in febrile seizure and we think that in respect of lower complication rate in diazepam administration, it cloud be better choice than phenobarbital. PMID:27057183

  7. 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

  8. 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

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

    PubMed

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

    2015-11-21

    The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy. PMID:26343861

  10. 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

  11. Granulocyte transfusions for preventing infections in people with neutropenia or neutrophil dysfunction

    PubMed Central

    Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Blanco, Patricia; Hopewell, Sally; Trivella, Marialena; Massey, Edwin

    2015-01-01

    Background Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in people with prolonged disease-related or therapy-related neutropenia. Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in people who lack their own functional granulocytes. This is an update of a Cochrane review first published in 2009. Objectives To determine the effectiveness and safety of prophylactic granulocyte transfusions compared with a control population not receiving this intervention for preventing all-cause mortality, mortality due to infection, and evidence of infection due to infection or due to any other cause in people with neutropenia or disorders of neutrophil function. Search methods We searched for randomised controlled trials (RCTs) and quasi-RCTs in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to April 20 2015. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs comparing people receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results Twelve trials met the inclusion criteria. One trial is still ongoing, leaving a total of 11 trials eligible involving 653 participants. These trials were conducted between 1978 and 2006 and enrolled participants from fairly comparable patient populations. None of the studies included people with neutrophil dysfunction. Ten studies included only adults, and two studies included children and adults. Ten of these studies contained separate data for each arm and were able to be critically appraised. One study re-randomised people and therefore quantitative analysis was unable to be performed. Overall, the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcome estimates being imprecise. All-cause mortality was reported for nine studies (609 participants). There was no difference in all-cause mortality over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (seven studies; 437 participants; RR 0.92, 95% CI 0.63 to 1.36, very low-quality evidence). Mortality due to infection was reported for seven studies (398 participants). There was no difference in mortality due to infection over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (six studies; 286 participants; RR 0.69, 95% CI 0.33 to 1.44, very low-quality evidence). The number of people with localised or systemic bacterial or fungal infections was reported for nine studies (609 participants). There were differences between the granulocyte dose subgroups (test for subgroup differences P = 0.01). There was no difference in the number of people with infections over 30 days between people receiving prophylactic granulocyte transfusions and those that did not in the low-dose granulocyte group (< 1.0 × 1010 granulocytes per day) (four studies, 204 participants; RR 0.84, 95% CI 0.58 to 1.20; very low-quality evidence). There was a decreased number of people with infections over 30 days in the people receiving prophylactic granulocyte transfusions in the intermediate-dose granulocyte group (1.0 × 1010 to 4.0 × 1010 granulocytes per day) (4 studies; 293 participants; RR 0.40, 95% CI 0.26 to 0.63, low-quality evidence). There was a decreased number of participants with bacteraemia and fungaemia in the participants receiving prophylactic granulocyte transfusions (nine studies; 609 participants; RR 0.45, 95% CI 0.30 to 0.65, low-quality evidence). There was no difference in the number of participants with localised bacterial or fungal infection in the participants receiving prophylactic granulocyte transfusions (six studies; 296 participants; RR 0.75, 95% CI 0.50 to 1.14; very low-quality evidence). Serious adverse events were only reported for participants receiving granulocyte transfusions and donors of granulocyte transfusions. Authors’ conclusions In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is low-grade evidence that prophylactic granulocyte transfusions decrease the risk of bacteraemia or fungaemia. There is low-grade evidence that the effect of prophylactic granulocyte transfusions may be dose-dependent, a dose of at least 10 × 1010 per day being more effective at decreasing the risk of infection. There is insufficient evidence to determine any difference in mortality rates due to infection, all-cause mortality, or serious adverse events. PMID:26118415

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

    SciTech Connect

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

    1988-04-08

    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.

  13. Syncope in a febrile state: A case report of Brugada syndrome.

    PubMed

    Martins, Juliana; Braga, Carlos; Arantes, Carina; Ramos, Vítor; Salgado, Alberto; Rebelo, Adília; Correia, Adelino

    2014-12-01

    In 1992, Brugada and Brugada first described a new entity, which became known as Brugada syndrome, that is associated with a high risk of ventricular arrhythmias and sudden cardiac death in patients without structural heart disease. This syndrome is characterized by a distinct electrocardiographic phenotype, type 1 Brugada pattern, consisting of a coved ST-segment elevation (≥0.2 mV) followed by a negative T wave in more than one right precordial lead. This pattern is dynamic, and can be spontaneous or concealed, but is unmasked under certain circumstances, like febrile states. The authors report a case in which the diagnosis of Brugada syndrome was made in the course of etiologic investigation of recurrent syncope in a febrile state. PMID:25448794

  14. [Food matching based on herbal properties of formulas in "Treatise on Febrile Diseases"].

    PubMed

    Yan, Su-rong; Zheng, Hu-zhan; Miao, Su-fen; Wang, Yun

    2015-09-01

    Based on databases for herbal properties of formulas and foods recorded in "Treatise on Febrile Diseases", a case study was conducted for the food matching method according to herbal properties of formulas in "Treatise on Febrile Diseases". The result show that the method was technically feasible once the herbal properties of foods were determined. Moreover, according to herbal properties of target formulas, the compositions of foods were effectively defined. In this study, researchers determined the similarity between the food matching scheme and the target formulas in function and efficacy, provided a quantitative method for food formulation and promote the development of application technology of the herbal property theory and the compatibility theory. PMID:26983218

  15. Why actions for early treatment of febrile illnesses in children are delayed by caregivers.

    PubMed

    Arulogun, Oyedunni S; Adeniyi, Joshua D; Asa, Sola; Adegbenro, Caleb A

    The study explored why actions for early treatment of febrile illnesses in children are delayed by caregivers of children less than five years in five Local Government Areas (LGAs) of southwestern Nigeria using four indicators: caregivers' perception of illness, notion of causation and seriousness, belief in efficacy of selected pathway, and the decision making process. Seven types of febrile illnesses (yellow fever, typhoid fever, ordinary fever/malaria, hot body fever, rain fever, cold fever, and headache fever) were identified and yellow fever was perceived as the most severe type (60.8%). Only 24.2% correctly identified an infected mosquito bite as the cause of ordinary fever/malaria. Use of leftover drugs at home (55.6%) was the main action taken and fathers were the main decisionmakers in all cases. Empowerment of women for improved knowledge on causation, severity, and importance of prompt action for a healthy outcome is recommended. PMID:23353563

  16. High Prevalence of Intermediate Leptospira spp. DNA in Febrile Humans from Urban and Rural Ecuador

    PubMed Central

    Chiriboga, Jorge; Barragan, Verónica; Arroyo, Gabriela; Sosa, Andrea; Birdsell, Dawn N.; España, Karool; Mora, Ana; Espín, Emilia; Mejía, María Eugenia; Morales, Melba; Pinargote, Carmina; Gonzalez, Manuel; Hartskeerl, Rudy; Keim, Paul; Bretas, Gustavo; Eisenberg, Joseph N.S.

    2015-01-01

    Leptospira spp., which comprise 3 clusters (pathogenic, saprophytic, and intermediate) that vary in pathogenicity, infect >1 million persons worldwide each year. The disease burden of the intermediate leptospires is unclear. To increase knowledge of this cluster, we used new molecular approaches to characterize Leptospira spp. in 464 samples from febrile patients in rural, semiurban, and urban communities in Ecuador; in 20 samples from nonfebrile persons in the rural community; and in 206 samples from animals in the semiurban community. We observed a higher percentage of leptospiral DNA–positive samples from febrile persons in rural (64%) versus urban (21%) and semiurban (25%) communities; no leptospires were detected in nonfebrile persons. The percentage of intermediate cluster strains in humans (96%) was higher than that of pathogenic cluster strains (4%); strains in animal samples belonged to intermediate (49%) and pathogenic (51%) clusters. Intermediate cluster strains may be causing a substantial amount of fever in coastal Ecuador. PMID:26583534

  17. 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

  18. A case of Brugada Syndrome unmasked by a postoperative febrile state

    PubMed Central

    Rijal, Jharendra; Giri, Smith; Khanal, Sumesh; Dahal, Khagendra

    2015-01-01

    Background: Brugada Syndrome (BS) is an inherited ion channelopathy characterized by an electrocardiographic (ECG) pattern of a coved type ST segment elevation in right precordial leads with or without right bundle branch block. Case Presentation: A 23-year old male presented with right lower quadrant abdominal pain. Further evaluation revealed a diagnosis of acute appendicitis. The patient developed a febrile episode on second post-operative day of laparoscopic appendectomy. ECG revealed features consistent with BS. Prompt control of temperature in the patient resolved the ST-segment elevation and prevented potentially life-threatening arrhythmias. Conclusion: Febrile episodes in susceptible patients may unmask a concealed BS. Prompt control of temperature is advocated to reduce the risk of life-threatening arrythmias. PMID:26221497

  19. Itraconazole Oral Solution for Primary Prophylaxis of Fungal Infections in Patients with Hematological Malignancy and Profound Neutropenia: a Randomized, Double-Blind, Double-Placebo, Multicenter Trial Comparing Itraconazole and Amphotericin B

    PubMed Central

    Harousseau, J. L.; Dekker, A. W.; Stamatoullas-Bastard, A.; Fassas, A.; Linkesch, W.; Gouveia, J.; De Bock, R.; Rovira, M.; Seifert, W. F.; Joosen, H.; Peeters, M.; De Beule, K.

    2000-01-01

    Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 × 109 neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia. PMID:10858349

  20. Incomplete splicing of neutrophil-specific genes affects neutrophil development in a zebrafish model of poikiloderma with neutropenia

    PubMed Central

    Patil, Prakash; Uechi, Tamayo; Kenmochi, Naoya

    2015-01-01

    Poikiloderma with neutropenia (PN) is a rare inherited disorder characterized by poikiloderma, facial dysmorphism, pachyonychia, short stature and neutropenia. The molecular testing of PN patients has identified mutations in the C16orf57 gene, which encodes a protein referred to as USB1 (U Six Biogenesis 1). In this study, we developed a zebrafish model of PN by the microinjection of morpholino antisense oligos to suppress usb1 gene function. Severe morphological defects, including a bent tail, thin yolk extension and reduced body length, were predominant in the Usb1-suppressed embryos (morphants). We also observed significantly decreased number of neutrophils in the morphants by Sudan Black staining. Interestingly, the splicing of genes involved in neutrophil differentiation and development, such as mpx, ncf1, ela3l and npsn, was aberrant in the morphants. However, the splicing of haematopoietic precursors and erythroid-specific genes was unaltered. Importantly, the neutrophil defects were almost completely rescued by co-injection of ela3l mRNA, the most markedly affected gene in the morphants. Our study demonstrated a possible role of USB1 in modulating the tissue-specific gene splicing that eventually leads to the impaired development of neutrophils. This zebrafish model could serve as a valuable tool to investigate the causative role of USB1 in PN pathogenesis. PMID:25849198

  1. Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells.

    PubMed

    Hiramoto, Takafumi; Ebihara, Yasuhiro; Mizoguchi, Yoko; Nakamura, Kazuhiro; Yamaguchi, Kiyoshi; Ueno, Kazuko; Nariai, Naoki; Mochizuki, Shinji; Yamamoto, Shohei; Nagasaki, Masao; Furukawa, Yoichi; Tani, Kenzaburo; Nakauchi, Hiromitsu; Kobayashi, Masao; Tsuji, Kohichiro

    2013-02-19

    The derivation of induced pluripotent stem (iPS) cells from individuals of genetic disorders offers new opportunities for basic research into these diseases and the development of therapeutic compounds. Severe congenital neutropenia (SCN) is a serious disorder characterized by severe neutropenia at birth. SCN is associated with heterozygous mutations in the neutrophil elastase [elastase, neutrophil-expressed (ELANE)] gene, but the mechanisms that disrupt neutrophil development have not yet been clarified because of the current lack of an appropriate disease model. Here, we generated iPS cells from an individual with SCN (SCN-iPS cells). Granulopoiesis from SCN-iPS cells revealed neutrophil maturation arrest and little sensitivity to granulocyte-colony stimulating factor, reflecting a disease status of SCN. Molecular analysis of the granulopoiesis from the SCN-iPS cells vs. control iPS cells showed reduced expression of genes related to the wingless-type mmtv integration site family, member 3a (Wnt3a)/β-catenin pathway [e.g., lymphoid enhancer-binding factor 1], whereas Wnt3a administration induced elevation lymphoid enhancer-binding factor 1-expression and the maturation of SCN-iPS cell-derived neutrophils. These results indicate that SCN-iPS cells provide a useful disease model for SCN, and the activation of the Wnt3a/β-catenin pathway may offer a novel therapy for SCN with ELANE mutation. PMID:23382209

  2. A Case of Neonatal Alloimmune Neutropenia Associated with Anti-Human Neutrophil Antigen-1a (HNA-1a) Antibody

    PubMed Central

    Han, Tae Hee; Chey, Myoung-Jae

    2006-01-01

    Neonatal alloimmune neutropenia (NAN) is an uncommon disease of the newborn provoked by the maternal production of neutrophil-specific alloantibodies, whereby neutrophil IgG antibodies cross the placenta and induce the destruction of fetal neutrophils. Affected newborns are usually identified by the occurrence of bacterial infections. The most frequent antigens involved in NAN are the human neutrophil antigen-1a (HNA-1a), HNA-1b, and HNA-2a. We report a neonate who was delivered at 36 weeks and had a severe neutropenia but who responded well to recombinant human granulocyte colony-stimulating factor (rhG-CSF). Anti-HNA-1a antibody was identified by mixed passive hemagglutination assay in both the sera of the baby and the mother. The baby had HNA-1a and HNA-1b but the mother had only HNA-1b on granulocytes. This is the first Korean report of NAN in which the specificity of the causative antibody was identified. PMID:16614528

  3. 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. PMID:26063965

  4. [Preliminarily analysis on traditional Chinese medicine advices in Treatise on Febrile Diseases].

    PubMed

    Liu, Tong; Zhai, Hua-qiang; Zhang, Tian; Jin, Shi-yuan

    2015-02-01

    To make a systematic analysis on literatures concerning traditional Chinese medicine (TCM) advices in Treatise on Febrile Diseases, and summarize the main connotations of traditional Chinese medicine advices, relevant TCM advices in Treatise on Febrile Diseases were collected, screened, compared, summarized and analyzed according to TCM dosage form preparation methods, TCM administration methods, medication contraindications and nursing after TCM administration. The literatures concerning medications in Treatise on Febrile Diseases were consulted, summarized and compared to standardize medicine advices and facilitate rational clinical application of TCMs. The standard medicine advices were as follows. The boiling water for TCMs shall be tap water and well water. The decoctions that have effects in promoting blood and meridians can be boiled with wine. The decoctions containing toxic components can be boiled with honey. Some TCMs shall be boiled with special methods, e. g. Herba Ephedra that could be boiled before other medicine and skimmed. Japonica rice could be added in decoctions to measure the duration of decoctions. Different dosages were required for different forms (litre, pill, medicine spoon). Administration times, temperature and frequency shall be adjusted according to target positions, functions and stage of illness. As for dietary contraindications during medication, thick porridges are recommended, where foods impacting medicine efficacy are prohibited. Regarding nursing after medication is important to recover physical functions, particularly warm porridges can go with diaphoretic recipes, while thick porridges can go with purgative recipes. And drug efficacies shall be defined by observing urine and excrements, and blood form. In conclusion, Treatise on Febrile Diseases is the first book that discusses TCM advices and records them in details. In this study, new standard medicine advices were proposed to provide important basis for improving clinical advices of TCMs and supports for developing the TCM dispensing technology. PMID:26137701

  5. First febrile convulsions: inquiry about the knowledge, attitudes and concerns of the patients' mothers.

    PubMed

    Kolahi, Ali-Asghar; Tahmooreszadeh, Shahrokh

    2009-02-01

    In comparison with other diseases, febrile convulsion, despite its excellent prognosis, is a cause of high anxiety among mothers. The objective of our study was to evaluate the knowledge, concerns, attitudes and practices of the mothers of children with first febrile convulsion. A prospective questionnaire-based study was carried out at the Mofid Children's Hospital. One hundred and twenty-six mothers of consecutive children presenting with febrile convulsion were enrolled. Only 58 (46%) mothers recognised the convulsion. Forty-nine (39%) of them interpreted the seizure as death. Others interpreted it as other causes. Eighty-five (68%) parents did not carry out any intervention prior to getting the child to the hospital. The most common cause of concern among parents was the state of their child's health in the future (n=120, 95%), followed by the fear of recurrence (n=83, 66%), mental retardation (n=60, 48%), paralysis (n=39, 31%), physical disability (n=37, 30%) and learning dysfunction (n=28, 22%). In 41 (33%) mothers, there were other causes of concerns, including fear of visual defect, hearing loss, memory loss, brain defect, delay in walking, drug adverse effects, coma and death. Sixty-eight percent of mothers had acceptable information about the measures that should be taken to prevent recurrence. Awareness of preventive measures was higher in mothers with high educational level (P<0.01). Seventy-six percent of mothers did not know anything about the necessary measures in case of recurrence. From this study, we conclude that parental fear of febrile convulsion is a major problem, with serious negative consequences affecting daily familial life. PMID:18461360

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

    PubMed Central

    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.

    2015-01-01

    Abstract 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) (r2?=??0.274, P?=?0.007), negative correlation between TPO-Abs/TG-Abs and C4 (r2?=??0.16, P?=?0.045; r2?=??0.266, P?=?0.001), and CD4+ counts were inversely correlated to T4 and positively to TSH (r2?=??0.274, P?=?0.024; r2?=?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

  7. 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) (r² = -0.274, P = 0.007), negative correlation between TPO-Abs/TG-Abs and C4 (r² = -0.16, P = 0.045; r² = -0.266, P = 0.001), and CD4⁺ counts were inversely correlated to T4 and positively to TSH (r² = -0.274, P = 0.024; r² = 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 TCRγδ+ 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

  8. Cost-Effectiveness of Pre-Referral Antimalarial, Antibacterial, and Combined Rectal Formulations for Severe Febrile Illness

    PubMed Central

    Buchanan, James; Mihaylova, Borislava; Gray, Alastair; White, Nicholas

    2010-01-01

    Background Malaria and bacterial infections account for most infectious disease deaths in developing countries. Prompt treatment saves lives, but rapid deterioration often prevents the use of oral therapies; delays in reaching health facilities providing parenteral interventions are common. Rapidly and reliably absorbed antimalarial/antibacterial rectal formulations used in the community could prevent deaths and disabilities. Rectal antimalarial treatments are currently available; rectal antibacterial treatments are yet to be developed. Assessment of the likely cost-effectiveness of these interventions will inform research priorities and implementation. Methods and Findings The burden of malaria and bacterial infections worldwide and in Sub-Saharan and Southern Africa (SSA) and South and South-East Asia (SEA) was summarised using published data. The additional healthcare costs (US$) per death and per Disability Adjusted Life Year (DALY) avoided following pre-referral treatment of severe febrile illness with rectal antimalarials, antibacterials or combined antimalarial/antibacterials in populations at malaria risk in SSA/SEA were assessed. 46 million severe malaria and bacterial infections and 5 million deaths occur worldwide each year, mostly in SSA/SEA. At annual delivery costs of $0.02/capita and 100% coverage, rectal antimalarials ($2 per dose) would avert 240,000 deaths in SSA and 7,000 deaths in SEA at $5 and $177 per DALY avoided, respectively; rectal antibacterials ($2 per dose) would avert 130,000 deaths in SSA and 27,000 deaths in SEA at $19 and $97 per DALY avoided, respectively. Combined rectal formulations ($2.50 per dose) would avert 370,000 deaths in SSA and 33,000 deaths in SEA at $8 and $79 per DALY avoided, respectively, and are a cost-effective alternative to rectal antimalarials or antibacterials alone. Conclusions Antimalarial, antibacterial and combined rectal formulations are likely to be cost-effective interventions for severe febrile illness in the community. Attention should focus on developing effective rectal antibacterials and ensuring that these lifesaving treatments are used in a cost-effective manner. PMID:21206901

  9. Presumptive self-diagnosis of malaria and other febrile illnesses in Sierra Leone

    PubMed Central

    Ansumana, Rashid; Jacobsen, Kathryn H; Gbakima, Aiah Albert; Hodges, Mary Hamer; Lamin, Joseph Morrison; Leski, Tomasz Andrzej; Malanoski, Anthony Peter; Lin, Baochuan; Bockarie, Moses John; Stenger, David Andrew

    2013-01-01

    Introduction The objective of this study was to evaluate the prevalence of self-diagnosis of malaria and other febrile illnesses in Bo, Sierra Leone. Methods All households in two neighboring sections of Bo were invited to participate in a cross-sectional survey. Results A total of 882 households (an 85% participation rate) that were home to 5410 individuals participated in the study. Of the 910 individuals reported to have had what the household considered to be malaria in the past month, only 41% were diagnosed by a healthcare professional or a laboratory test. Of the 1402 individuals reported to have had any type of febrile illness within the past six months, only 34% had sought a clinical or laboratory diagnosis. Self-diagnosis of influenza, yellow fever, typhoid, and pneumonia was also common. Conclusion Self-diagnosis and presumptive treatment with antimalarial drugs and other antibiotic medications that are readily available without a prescription may compromise health outcomes for febrile adults and children. PMID:24009810

  10. Cost and Predictors of Care-Seeking Behaviors Among Caregivers of Febrile Children-Uganda, 2009.

    PubMed

    Menon, Manoj P; Njau, Joseph D; McFarland, Deborah A

    2016-04-01

    Fever is a major cause of morbidity and mortality among children under 5 years of age in resource-limited countries. Although prevention and treatment of febrile illnesses have improved, the costs-both financial and nonfinancial-remain barriers to care. Using data from the 2009 Uganda Malaria Indicator Survey, we describe the costs associated with the care of a febrile child and assess predictors of care-seeking behavior. Over 80% of caregivers sought care for their febrile child, however less than half did so on either the day of or the day after the development of fever. The odds of seeking care decreased with each additional month of the child's age. Caregivers living in rural areas were more likely to seek care, however were less likely to seek care promptly. Caregivers with at least a primary school education and those familiar with the protective effect of bed nets and the need to seek care promptly were more likely to seek care. Despite government assistance, the majority of caregivers did incur costs (mean 13,173 Ugandan shilling; $6.84 U.S. dollars) associated with medical care. Continued efforts targeting barriers to seeking care, including the economic burden, are necessary. PMID:26880780

  11. Risk Factors for Febrile Status Epilepticus: A Case-Control Study

    PubMed Central

    Hesdorffer, Dale C.; Shinnar, Shlomo; Lewis, Darrell V.; Nordli, Douglas R.; Pellock, John M.; Moshé, Solomon L.; Shinnar, Ruth C.; Litherland, Claire; Bagiella, Emilia; Frank, L. Matthew; Bello, Jacqueline A.; Chan, Stephen; Masur, David; MacFall, James; Sun, Shumei

    2013-01-01

    Objective To identify risk factors for developing a first febrile status epilepticus (FSE) among children with a first febrile seizure (FS). Study design Cases were children with a first FS that was FSE drawn from the Consequences of Prolonged Febrile Seizures in Childhood and Columbia cohorts. Controls were children with a first simple FS and separately, children with a first complex FS that was not FSE. Identical questionnaires were administered to family members of the 3 cohorts. Magnetic resonance imaging protocol and readings were consistent across cohorts, and seizure phenomenology was assessed by the same physicians. Risk factors were analyzed using logistic regression. Results Compared with children with simple FS, FSE was associated with younger age, lower temperature, longer duration (1-24 hours) of recognized temperature before FS, female sex, structural temporal lobe abnormalities, and first-degree family history of FS. Compared with children with other complex FS, FSE was associated with low temperature and longer duration (1-24 hours) of temperature recognition before FS. Risk factors for complex FS that was not FSE were similar in magnitude to those for FSE but only younger age was significant. Conclusions Among children with a first FS, FSE appears to be due to a combination of lower seizure threshold (younger age and lower temperatures) and impaired regulation of seizure duration. Clinicians evaluating FS should be aware of these factors as many episodes of FSE go unnoticed. Further work is needed to develop strategies to prevent FSE. PMID:23809042

  12. Bacteremia among Febrile Ugandan Children Treated with Antimalarials Despite a Negative Malaria Test

    PubMed Central

    Kibuuka, Afizi; Byakika-Kibwika, Pauline; Achan, Jane; Yeka, Adoke; Nalyazi, Joan N.; Mpimbaza, Arthur; Rosenthal, Philip J.; Kamya, Moses R.

    2015-01-01

    Bacteremia may be inappropriately treated as malaria in children admitted with a febrile illness in Africa. We determined the prevalence, clinical features, and spectrum of bacteremia among febrile children younger than 5 years of age admitted with a negative malaria test, but prescribed antimalarials at a referral hospital in Jinja, Uganda. After initial evaluation, a blood sample was drawn from 250 children for a complete blood count and bacterial culture. Of 250 samples cultured, 15 grew organisms presumed to be skin contaminants, and of the remaining 235 samples, 45 (19.1%) had bacteremia. Staphylococcus aureus (42%), non-typhoidal Salmonella (24%), Pseudomonas aeruginosa (11%), and Streptococcus pneumoniae (9%) were the most common bacterial isolates. On multivariate analysis, history of weight loss (odds ratio [OR] = 2.75; 95% confidence interval [CI] = 1.27–5.95), presence of pulmonary crackles (OR = 3.63; 95% CI = 1.40–9.45), and leukocytosis (OR = 2.21; 95% CI = 1.09–4.47) were independent predictors of bacteremia. At a referral hospital in Uganda, bacteremia was a remarkably common finding in children with febrile illness who were treated for malaria despite negative malaria test results. PMID:26055736

  13. Association of Interleukin-1 Gene Cluster and Interleukin-1 Receptor Polymorphisms With Febrile Seizures.

    PubMed

    Soltani, Samaneh; Zare-Shahabadi, Ameneh; Shahrokhi, Amin; Rezaei, Arezou; Zoghi, Samaneh; Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Rezaei, Nima

    2016-05-01

    Interleukin-1 (IL-1) plays a key role in inflammation, has an effect on a wide variety of cells, and often leads to tissue destruction. While the ratio between IL-1 and IL-1Ra could influence the development of different diseases of the central nervous system, its gene polymorphisms were investigated in a group of patients with febrile seizures. Ninety patients with febrile seizures were enrolled and compared with 140 controls. The allele and genotype frequency of single nucleotide polymorphisms within the IL-1α, β, IL-1 R and IL-1Ra gene were determined. The frequency of the IL-1Ra/C allele at position Mspa-I 11100 was decreased significantly (P= .002) and the IL-1Ra/T frequency was significantly increased in patients (P= .002). In addition, the CT genotype frequency at the same position was significantly overrepresented in controls compared to patients (P= .001). Certain alleles and genotypes in the IL-1 gene were overrepresented in patients with febrile seizures, which possibly could predispose individuals to this disease. PMID:26500244

  14. Bacteremia Among Febrile Ugandan Children Treated with Antimalarials Despite a Negative Malaria Test.

    PubMed

    Kibuuka, Afizi; Byakika-Kibwika, Pauline; Achan, Jane; Yeka, Adoke; Nalyazi, Joan N; Mpimbaza, Arthur; Rosenthal, Philip J; Kamya, Moses R

    2015-08-01

    Bacteremia may be inappropriately treated as malaria in children admitted with a febrile illness in Africa. We determined the prevalence, clinical features, and spectrum of bacteremia among febrile children younger than 5 years of age admitted with a negative malaria test, but prescribed antimalarials at a referral hospital in Jinja, Uganda. After initial evaluation, a blood sample was drawn from 250 children for a complete blood count and bacterial culture. Of 250 samples cultured, 15 grew organisms presumed to be skin contaminants, and of the remaining 235 samples, 45 (19.1%) had bacteremia. Staphylococcus aureus (42%), non-typhoidal Salmonella (24%), Pseudomonas aeruginosa (11%), and Streptococcus pneumoniae (9%) were the most common bacterial isolates. On multivariate analysis, history of weight loss (odds ratio [OR] = 2.75; 95% confidence interval [CI] = 1.27-5.95), presence of pulmonary crackles (OR = 3.63; 95% CI = 1.40-9.45), and leukocytosis (OR = 2.21; 95% CI = 1.09-4.47) were independent predictors of bacteremia. At a referral hospital in Uganda, bacteremia was a remarkably common finding in children with febrile illness who were treated for malaria despite negative malaria test results. PMID:26055736

  15. Emergency Department Crowding and Time to Antibiotic Administration in Febrile Infants

    PubMed Central

    Light, Jennifer K.; Hoelle, Robyn M.; Herndon, Jill Boylston; Hou, Wei; Elie, Marie-Carmelle; Jackman, Kelly; Tyndall, J. Adrian; Carden, Donna L.

    2013-01-01

    Introduction: Early antibiotic administration is recommended in newborns presenting with febrile illness to emergency departments (ED) to avert the sequelae of serious bacterial infection. Although ED crowding has been associated with delays in antibiotic administration in a dedicated pediatric ED, the majority of children that receive emergency medical care in the United States present to EDs that treat both adult and pediatric emergencies. The purpose of this study was to examine the relationship between time to antibiotic administration in febrile newborns and crowding in a general ED serving both an adult and pediatric population. Methods: We conducted a retrospective chart review of 159 newborns presenting to a general ED between 2005 and 2011 and analyzed the association between time to antibiotic administration and ED occupancy rate at the time of, prior to, and following infant presentation to the ED. Results: We observed delayed and variable time to antibiotic administration and found no association between time to antibiotic administration and occupancy rate prior to, at the time of, or following infant presentation (p>0.05). ED time to antibiotic administration was not associated with hospital length of stay, and there was no inpatient mortality. Conclusion: Delayed and highly variable time to antibiotic treatment in febrile newborns was common but unrelated to ED crowding in the general ED study site. Guidelines for time to antibiotic administration in this population may reduce variability in ED practice patterns. PMID:24106552

  16. Central mediators involved in the febrile response: effects of antipyretic drugs

    PubMed Central

    Zampronio, Aleksander R; Soares, Denis M; Souza, Glória E P

    2015-01-01

    Fever is a complex signal of inflammatory and infectious diseases. It is generally initiated when peripherally produced endogenous pyrogens reach areas that surround the hypothalamus. These peripheral endogenous pyrogens are cytokines that are produced by leukocytes and other cells, the most known of which are interleukin-1β, tumor necrosis factor-α, and interleukin-6. Because of the capacity of these molecules to induce their own synthesis and the synthesis of other cytokines, they can also be synthesized in the central nervous system. However, these pyrogens are not the final mediators of the febrile response. These cytokines can induce the synthesis of cyclooxygenase-2, which produces prostaglandins. These prostanoids alter hypothalamic temperature control, leading to an increase in heat production, the conservation of heat, and ultimately fever. The effect of antipyretics is based on blocking prostaglandin synthesis. In this review, we discuss recent data on the importance of prostaglandins in the febrile response, and we show that some endogenous mediators can still induce the febrile response even when known antipyretics reduce the levels of prostaglandins in the central nervous system. These studies suggest that centrally produced mediators other than prostaglandins participate in the genesis of fever. Among the most studied central mediators of fever are corticotropin-releasing factor, endothelins, chemokines, endogenous opioids, and substance P, which are discussed herein. Additionally, recent evidence suggests that these different pathways of fever induction may be activated during different pathological conditions. PMID:27227071

  17. Association between the low-dose irinotecan regimen-induced occurrence of grade 4 neutropenia and genetic variants of UGT1A1 in patients with gynecological cancers.

    PubMed

    Moriya, Hiroyuki; Saito, Katsuhiko; Helsby, Nuala; Sugino, Shigekazu; Yamakage, Michiaki; Sawaguchi, Takeru; Takasaki, Masahiko; Kato, Hidenori; Kurosawa, Nahoko

    2014-06-01

    The occurrence of severe neutropenia during treatment with irinotecan (CPT-11) is associated with the *6 and *28 alleles of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). However, the correlation between these variants and the occurrence of severe neutropenia in a low-dose CPT-11 regimen for the treatment of gynecological cancers has not been extensively studied. There are also no studies regarding the association between the 421C>A mutation in ATP-binding cassette sub-family G member 2 (ABCG2) and the occurrence of severe neutropenia in CPT-11-treated patients with gynecological cancers. The present study was designed to determine the factors associated with the occurrence of grade 4 neutropenia during chemotherapy for gynecological cancers with combinations of CPT-11 and cisplatin or mitomycin C. In total, 44 patients with gynecological cancer were enrolled in the study. The association between the absolute neutrophil count (ANC) nadir values, the total dose of CPT-11 and the genotypes of UGT1A1 or ABCG2 was studied. No correlation was observed between the ANC nadir values and the total dose of CPT-11. The ANC nadir values in the UGT1A1*6/*28 and *6/*6 groups were significantly lower compared with those in the *1/*1 group (P<0.01). Univariate analysis showed no association between the occurrence of grade 4 neutropenia and the ABCG2 421C>A mutation. Subsequent to narrowing the factors by univariate analysis, multivariate logistic regression analysis only detected significant correlations between the occurrence of grade 4 neutropenia and the UGT1A1*6/*6 and *6/*28 groups (P=0.029; odds ratio, 6.90; 95% confidence interval, 1.22-38.99). No associations were detected between the occurrence of grade 4 neutropenia and the heterozygous variant (*1/*6 or *1/*28) genotype, type of regimen or age. In conclusion, the UGT1A1*6/*28 and *6/*6 genotypes were found to be associated with the occurrence of severe neutropenia in the low-dose CPT-11 regimen for gynecological cancers. This finding indicates that the determination of UGT1A1 variants may be as useful in CPT-11 chemotherapy for gynecological conditions as it is in colorectal and lung cancer patients treated with this drug. PMID:24932285

  18. Arboviral Etiologies of Acute Febrile Illnesses in Western South America, 20002007

    PubMed Central

    Forshey, Brett M.; Guevara, Carolina; Laguna-Torres, V. Alberto; Cespedes, Manuel; Vargas, Jorge; Gianella, Alberto; Vallejo, Efrain; Madrid, Csar; 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

  19. Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus.

    PubMed

    Goldberg-Stern, Hadassa; Aharoni, Sharon; Afawi, Zaid; Bennett, Odeya; Appenzeller, Silke; Pendziwiat, Manuela; Kuhlenbäumer, Gregor; Basel-Vanagaite, Lina; Shuper, Avinoam; Korczyn, Amos D; Helbig, Ingo

    2014-02-01

    Genetic (generalized) epilepsy with febrile seizures plus is a familial epilepsy syndrome with marked phenotypic heterogeneity ranging from simple febrile seizure to severe phenotypes. Here we report on a large Israeli family with genetic (generalized) epilepsy with febrile seizures plus and 14 affected individuals. A novel SCN1A missense mutation in exon 21 (p.K1372E) was identified in all affected individuals and 3 unaffected carriers. The proband had Dravet syndrome, whereas febrile seizure plus phenotypes were present in all other affected family members. Simple febrile seizures were not observed. Phenotypes were found at both extremes of the genetic (generalized) epilepsy with febrile seizures plus spectrum and distribution of phenotypes suggested modifying familial, possibly genetic factors. We suggest that families with extreme phenotype distributions can represent prime candidates for the identification of genetic or environmental modifiers. PMID:24257433

  20. 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

  1. The importance of the recognition of benign ethnic neutropenia in black patients during treatment with clozapine: case reports and database study.

    PubMed

    Whiskey, Eromona; Olofinjana, Olubanke; Taylor, David

    2011-06-01

    Clozapine is the treatment of choice in refractory schizophrenia. Its more extensive use is limited by adverse effects and the need for regular blood monitoring. However, black patients are disadvantaged with respect to clozapine usage. Lower baseline Absolute Neutrophil Count compared with Whites leads to a greater frequency of blood testing, treatment interruptions and discontinuation. This may in part be explained by Benign Ethnic Neutropenia, but too few black patients are thus registered. The four cases described in this report underline some of the difficulties if this problem is under-recognized. Moreover, in our sample of 191 clozapine recipients in an inner London hospital, black patients account for approximately half, but only a small proportion, 8/95 (8.4%) are registered as having Benign Ethnic Neutropenia. None of the Benign Ethnic Neutropenia-registered patients discontinued treatment for haematological reasons. To optimize clozapine treatment and improve long-term outcomes, a significantly greater proportion of Black patients should be registered as having Benign Ethnic Neutropenia. PMID:20305043

  2. Myasis occuring in a neonate.

    PubMed

    Obasa, Temitope O; Sowunmi, Funmilola Olusola

    2012-12-01

    Myasis is the infestation of skin by larvae or maggots of a variety of flies. It is a condition that occurs more commonly in adults who are living and/or have visited tropical countries. It rarely occurs in neonates, and even when seen, only few larvae are extracted. This case report describes myasis occurring in an 11-day-old female who had 47 larvae in her skin. PMID:23355934

  3. Myasis occuring in a neonate

    PubMed Central

    Obasa, Temitope O.; Sowunmi, Funmilola Olusola

    2012-01-01

    Myasis is the infestation of skin by larvae or maggots of a variety of flies. It is a condition that occurs more commonly in adults who are living and/or have visited tropical countries. It rarely occurs in neonates, and even when seen, only few larvae are extracted. This case report describes myasis occurring in an 11-day-old female who had 47 larvae in her skin. PMID:23355934

  4. Maternal Use of Antibiotics and the Risk of Childhood Febrile Seizures: A Danish Population-Based Cohort

    PubMed Central

    Miller, Jessica E.; Pedersen, Lars Henning; Vestergaard, Mogens; Olsen, Jrn

    2013-01-01

    Objective In a large population-based cohort in Denmark to examine if maternal use of antibiotics during pregnancy, as a marker of infection, increases the risk of febrile seizures in childhood in a large population-based cohort in Denmark. Methods All live-born singletons born in Denmark between January 1, 1996 and September 25, 2004 and who were alive on the 90th day of life were identified from the Danish National Birth Registry. Diagnoses of febrile seizures were obtained from the Danish National Hospital Register and maternal use of antibiotics was obtained from the National Register of Medicinal Product Statistics. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazard regression models. Results We followed 551,518 singletons for up to 5 years and identified a total of 21,779 children with a diagnosis of febrile seizures. Slightly increased hazard ratios were observed among most exposure groups when compared to the unexposed group, ex. HR 1.08 95% CI: 1.051.11 for use of any systemic antibiotic during pregnancy. Conclusion We found weak associations between the use of pharmacologically different antibiotics during pregnancy and febrile seizures in early childhood which may indicate that some infections, or causes or effects of infections, during pregnancy could affect the fetal brain and induce susceptibility to febrile seizures. PMID:23613800

  5. Mold colonization of fiberglass insulation of the air distribution system: effects on patients with hematological malignancies.

    PubMed

    Takuma, Takahiro; Okada, Kaoru; Yamagata, Akihiro; Shimono, Nobuyuki; Niki, Yoshihito

    2011-02-01

    We investigated mold colonization of air handling units (AHUs) of heating, ventilating, and air conditioning (HVAC) systems and its effects, including invasive pulmonary mycoses and febrile neutropenia, in patients with hematological malignancies. Sample collection with transparent adhesive tape and culture swabs revealed that AHUs were heavily colonized with molds, including thermotolerant, variously distributed Penicillium spp. Cases of nosocomial invasive pulmonary mycosis were not clustered in specific patient rooms but did occur frequently when the HVAC systems were not in use, prior to intervention (i.e., sealing and disuse of AHUs in private room), and during construction of a new hospital building. Multivariate logistic regression analysis of initial episodes of febrile neutropenia showed that the rate of febrile neutropenia was significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239-0.902). An evaluation of private rooms showed that female patients also had a lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The reduced rate of febrile neutropenia after intervention suggests that mold colonization of AHUs had adverse effects on patients with hematological malignancies. PMID:20807030

  6. Distinct Inflammatory Mediator Patterns Characterize Infectious and Sterile Systemic Inflammation in Febrile Neutropenic Hematology Patients

    PubMed Central

    Wennerås, Christine; Hagberg, Lars; Andersson, Rune; Hynsjö, Lars; Lindahl, Anders; Okroj, Marcin; Blom, Anna M.; Johansson, Peter; Andreasson, Björn; Gottfries, Johan; Wold, Agnes E.

    2014-01-01

    Background Invasive infections and sterile tissue damage can both give rise to systemic inflammation with fever and production of inflammatory mediators. This makes it difficult to diagnose infections in patients who are already inflamed, e.g. due to cell and tissue damage. For example, fever in patients with hematological malignancies may depend on infection, lysis of malignant cells, and/or chemotherapy-induced mucosal damage. We hypothesized that it would be possible to distinguish patterns of inflammatory mediators characterizing infectious and non-infectious causes of inflammation, respectively. Analysis of a broad range of parameters using a multivariate method of pattern recognition was done for this purpose. Methods In this prospective study, febrile (>38°C) neutropenic patients (n = 42) with hematologic malignancies were classified as having or not having a microbiologically defined infection by an infectious disease specialist. In parallel, blood was analyzed for 116 biomarkers, and 23 clinical variables were recorded for each patient. Using O-PLS (orthogonal projection to latent structures), a model was constructed based on these 139 variables that could separate the infected from the non-infected patients. Non-discriminatory variables were discarded until a final model was reached. Finally, the capacity of this model to accurately classify a validation set of febrile neutropenic patients (n = 10) as infected or non-infected was tested. Results A model that could segregate infected from non-infected patients was achieved based on discrete differences in the levels of 40 variables. These variables included acute phase proteins, cytokines, measures of coagulation, metabolism, organ stress and iron turn-over. The model correctly identified the infectious status of nine out of ten subsequently recruited febrile neutropenic hematology patients. Conclusions It is possible to separate patients with infectious inflammation from those with sterile inflammation based on inflammatory mediator patterns. This strategy could be developed into a decision-making tool for diverse clinical applications. PMID:24642872

  7. Q Fever, Spotted Fever Group, and Typhus Group Rickettsioses Among Hospitalized Febrile Patients in Northern Tanzania

    PubMed Central

    Prabhu, Malavika; Nicholson, William L.; Roche, Aubree J.; Kersh, Gilbert J.; Fitzpatrick, Kelly A.; Oliver, Lindsay D.; Massung, Robert F.; Morrissey, Anne B.; Bartlett, John A.; Onyango, Jecinta J.; Maro, Venance P.; Kinabo, Grace D.; Saganda, Wilbrod

    2011-01-01

    Background. The importance of Q fever, spotted fever group rickettsiosis (SFGR), and typhus group rickettsiosis (TGR) as causes of febrile illness in sub-Saharan Africa is unknown; the putative role of Q fever as a human immunodeficiency virus (HIV) coinfection is unclear. Methods. We identified febrile inpatients in Moshi, Tanzania, from September 2007 through August 2008 and collected acute- and convalescent-phase serum samples. A ≥4-fold increase in immunoglobulin (Ig) G immunfluorescence assay (IFA) titer to Coxiella burnetii phase II antigen defined acute Q fever. A ≥4-fold increase in IgG IFA titer to Rickettsia conorii or Rickettsia typhi antigen defined SFGR and TGR, respectively. Results. Among 870 patients, 483 (55.5%) were tested for acute Q fever, and 450 (51.7%) were tested for acute SFGR and TGR. Results suggested acute Q fever in 24 (5.0%) patients and SFGR and TGR in 36 (8.0%) and 2 (0.5%) patients, respectively. Acute Q fever was associated with hepato- or splenomegaly (odds ratio [OR], 3.1; P = .028), anemia (OR, 3.0; P = .009), leukopenia (OR, 3.9; P = .013), jaundice (OR, 7.1; P = .007), and onset during the dry season (OR, 2.7; P = .021). HIV infection was not associated with acute Q fever (OR, 1.7; P = .231). Acute SFGR was associated with leukopenia (OR, 4.1; P = .003) and with evidence of other zoonoses (OR, 2.2; P = .045). Conclusions. Despite being common causes of febrile illness in northern Tanzania, Q fever and SFGR are not diagnosed or managed with targeted antimicrobials. C. burnetii does not appear to be an HIV-associated co-infection. PMID:21810740

  8. Sequence Analysis of the Human Virome in Febrile and Afebrile Children

    PubMed Central

    Wylie, Kristine M.; Mihindukulasuriya, Kathie A.; Sodergren, Erica; Weinstock, George M.; Storch, Gregory A.

    2012-01-01

    Unexplained fever (UF) is a common problem in children under 3 years old. Although virus infection is suspected to be the cause of most of these fevers, a comprehensive analysis of viruses in samples from children with fever and healthy controls is important for establishing a relationship between viruses and UF. We used unbiased, deep sequencing to analyze 176 nasopharyngeal swabs (NP) and plasma samples from children with UF and afebrile controls, generating an average of 4.6 million sequences per sample. An analysis pipeline was developed to detect viral sequences, which resulted in the identification of sequences from 25 viral genera. These genera included expected pathogens, such as adenoviruses, enteroviruses, and roseoloviruses, plus viruses with unknown pathogenicity. Viruses that were unexpected in NP and plasma samples, such as the astrovirus MLB-2, were also detected. Sequencing allowed identification of virus subtype for some viruses, including roseoloviruses. Highly sensitive PCR assays detected low levels of viruses that were not detected in approximately 5 million sequences, but greater sequencing depth improved sensitivity. On average NP and plasma samples from febrile children contained 1.5- to 5-fold more viral sequences, respectively, than samples from afebrile children. Samples from febrile children contained a broader range of viral genera and contained multiple viral genera more frequently than samples from children without fever. Differences between febrile and afebrile groups were most striking in the plasma samples, where detection of viral sequence may be associated with a disseminated infection. These data indicate that virus infection is associated with UF. Further studies are important in order to establish the range of viral pathogens associated with fever and to understand of the role of viral infection in fever. Ultimately these studies may improve the medical treatment of children with UF by helping avoid antibiotic therapy for children with viral infections. PMID:22719819

  9. Childhood febrile illness and the risk of myopia in UK Biobank participants.

    PubMed

    Guggenheim, J A; Williams, C

    2016-04-01

    PurposeHistorical reports suggest febrile illness during childhood is a risk factor for myopia. The establishment of the UK Biobank provided a unique opportunity to investigate this relationship.Patients and methodsWe studied a sample of UK Biobank participants of White ethnicity aged 40-69 years old who underwent autorefraction (N=91 592) and were classified as myopic (≤-0.75 Dioptres (D)), highly myopic (≤-6.00 D), or non-myopic (>-0.75 D). Self-reported age at diagnosis of past medical conditions was ascertained during an interview with a nurse at a Biobank assessment centre. Logistic regression analysis was used to calculate the odds ratio (OR) for myopia or high myopia associated with a diagnosis before age 17 years of each of nine febrile illnesses, after adjusting for potential confounders (age, sex, highest educational qualification, and birth order).ResultsRubella, mumps, and pertussis were associated with myopia: rubella, OR=1.38, 95% CI: 1.03-1.85, P=0.030; mumps, OR=1.32, 95% CI: 1.07-1.64, P=0.010; and pertussis, OR=1.39, 95% CI 1.03-1.87, P=0.029. Measles, rubella, and pertussis were associated with high myopia: measles, OR=1.48, 95% CI: 1.07-2.07, P=0.019; rubella, OR=1.94, 95% CI: 1.12-3.35, P=0.017; and pertussis, OR=2.15, 95% CI: 1.24-3.71, P=0.006. The evidence did not support an interaction between education and febrile illness in explaining the above risks.ConclusionA history of childhood measles, rubella, or pertussis was associated with high myopia, whereas a history of childhood rubella, mumps, or pertussis was associated with any myopia. The reasons for these associations are unclear. PMID:26846593

  10. Childhood febrile illness and the risk of myopia in UK Biobank participants

    PubMed Central

    Guggenheim, Jeremy A.; Williams, Cathy

    2016-01-01

    Purpose Historical reports suggest febrile illness during childhood is a risk factor for myopia. The establishment of the UK Biobank provided a unique opportunity to investigate this relationship. Methods We studied a sample of UK Biobank participants of White ethnicity aged 40-69 years-old who underwent autorefraction (N=91,592) and were classified as myopic (<= −0.75 Dioptres [D]), highly-myopic (<= −6.00 D) or non-myopic (> −0.75 D). Self-reported age-at-diagnosis of past medical conditions was ascertained during an interview with a nurse at a Biobank assessment centre. Logistic regression analysis was used to calculate the odds ratio (OR) for myopia or high myopia associated with a diagnosis prior to age 17 years of each of nine febrile illnesses, after adjusting for potential confounders (age, sex, highest educational qualification, and birth order). Results Rubella, mumps and pertussis were associated with myopia: rubella, OR=1.38, 95% CI 1.03 to 1.85, P=0.030; mumps, OR=1.32, 95% CI 1.07 to 1.64, P=0.010; pertussis, OR=1.39, 95% CI 1.03 to 1.87, P=0.029. Measles, rubella and pertussis were associated with high myopia: Measles, OR=1.48, 95% CI 1.07 to 2.07, P=0.019; rubella, OR=1.94, 95% CI 1.12 to 3.35, P=0.017; pertussis, OR=2.15, 95% CI 1.24 to 3.71, P=0.006. The evidence did not support an interaction between education and febrile illness in explaining the above risks. Conclusion A history of childhood measles, rubella or pertussis was associated with high myopia, while a history of childhood rubella, mumps or pertussis was associated with any myopia. The reason for these associations are unclear. PMID:26846593

  11. 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

  12. NEW PERSPECTIVES IN THE DIAGNOSIS AND THE TREATMENT OF CHILDHOOD FEBRILE EXANTHEMAS.

    PubMed

    Luca, Mihaela Cătălina; Vâţă, A; St Luca, A; Dorobăţ, Carmen Mihaela; Brănişteanu, Daciana Elena

    2015-01-01

    A child with a febrile exanthema is a complex medical problem involving diagnostic challenges, epidemiological threats and a great concern for the parents and any physician, should be prepared to deal with it. Many of the classical ones (measles, rubella, chickenpox) have now a decreased incidence due to a high vaccine coverage, which makes even harder for the physician to establish an early diagnosis. To the untrained eye most of them are difficult to differentiate. Their prompt recognition is necessary in order to manage them adequately and to prevent spreading of the disease. PMID:26204631

  13. High dengue NS1 antigenemia in febrile patients in Ibadan, Nigeria.

    PubMed

    Oyero, Olufunmilayo G; Ayukekbong, James A

    2014-10-13

    We conducted a dengue seroprevalence survey among febrile patients positive or negative for malaria in Ibadan, Nigeria. Dengue IgG and NS1 seroprevalence of 73% and 35%, respectively, was observed, and 43% of those with malaria had acute dengue infection (NS1 determination). On the other hand, all participants with malaria were IgG dengue seropositive consistent with the endemicity of both arthropod-borne infections in the region. These data indicate that dengue is emerging as a major and neglected cause of fever in Nigeria. PMID:25087878

  14. Febrile convulsions in an adult as presenting symptom of intracranial dermoid cyst: a case report.

    PubMed

    Berginer, V M; Tiberin, P; Hirsch, M; Berginer, J

    1988-01-01

    A 32-year-old man had generalized tonic-clonic epileptic seizures associated with episodes of recurrent high fever for 6 years. Repeated physical examinations including neurological status, EEG and nuclear brain scan were negative. Brain CT showed a non-homogeneous parasellar cyst of low density and fat-fluid levels in the lateral ventricles. The diagnosis of intracranial dermoid cyst was confirmed at surgery and histopathologically. Recurrent febrile convulsions and chemical meningitis may be the only clinical manifestations of ruptured dermoid cyst. The CT features of intracranial dermoid cyst are pathognomonic. PMID:3197687

  15. Hematological toxicity of doxorubicin-containing protocols in dogs with spontaneously occurring malignant tumors.

    PubMed

    Ahaus, E A; Couto, C G; Valerius, K D

    2000-01-01

    The medical records of 49 dogs with spontaneously occurring malignant tumors treated with doxorubicin-based chemotherapy protocols were evaluated for hematological toxicity. Protocols included vincristine, doxorubicin, and cyclophosphamide (VAC); 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); doxorubicin and cyclophosphamide (AC); and doxorubicin and dacarbazine (ADIC). Prevalence of Grades 1, 2, or 3 toxicities were less than 30%, and the prevalence of Grade 4 toxicity alone was less than 5%. The frequency of sepsis was less than 2.5% in dogs treated with VAC, FAC, or AC, and it was 15% in dogs treated with ADIC. There were no significant differences in the prevalence or severity of hematological toxicity caused by VAC or AC. Five-fluorouracil, doxorubicin, and cyclophosphamide caused significantly more severe neutropenia than VAC or AC. The low prevalence of hematological complications makes these protocols acceptable for use in practice. PMID:10997518

  16. The aetiology of non-malarial febrile illness in children in the malaria-endemic Niger Delta Region of Nigeria

    PubMed Central

    Pondei, Kemebradikumo; Kunle-Olowu, Onyaye E.; Peterside, Oliemen

    2013-01-01

    Objective Febrile illnesses are common in childhood and differentiating the causes could be challenging in areas of perennial malaria transmission. To determine the proportion of non-malarial febrile illness in children, the aetiological agents and their antimicrobial sensitivity pattern. Methods Blood, urine, throat swab and ear swab samples were obtained from 190 febrile children aged 6 months to 11 years. Malaria parasite was detected by microscopic examination of thick and thin Giemsa-stained films. Smears from ear and throat swabs and urine specimen were cultured on appropriate media. Bacterial isolates were identified by Gram staining, morphology and biochemical tests. Antibiotic susceptibility was tested using the Kirby-Bauer disc diffusion method. Results The prevalence of non-malarial febrile illnesses was 45.26% (95% CI: 38.21-52.31). Twenty-four patients (12.6%) had at least one sample that was bacterial culture positive. Samples from 62 patients (32.6%) were negative for both malaria parasite and bacterial culture. Urinary tract infection was responsible for 8.42%, otitis media 7.89% and pharyngitis 5.78% of the fevers. E.coli, S. aureus and S. pneumoniae were the commonest isolates from urine, ear swab and throat swab samples respectively. S. pneumoniae was responsible for all the positive throat cultures. Bacterial isolates exhibited different degrees of susceptibility to the antibiotics tested, but susceptibility of most of the isolates to oxacillin and cloxacillin was generally poor. Conclusions Bacterial infections are responsible for a significant proportion of non-malarial febrile illnesses, and diagnostic facilities should be strengthened to detect other causes of febrile illness outside malaria.

  17. Utility of the Multinational Association for Supportive Care in Cancer (MASCC) Risk Index Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors

    PubMed Central

    Bitar, Roger A

    2015-01-01

    Objectives: This retrospective study was initiated in febrile neutropenic inpatients with solid tumors in 4 community hospitals, to discover how the Multinational Association for Supportive Care in Cancer (MASCC) risk index score (RIS) of 21 or greater correlated with complications occurring in 198 episodes: whether it could help determine which patients not to admit, the savings of not admitting patients without complications, and whether an algorithm could facilitate management of those not admitted. Methods: Febrile neutropenic episodes in patients with solid tumors were identified electronically between October 1, 2008, and November 15, 2010. Electronic charts were reviewed manually for inclusion criteria and data extraction. Episodes were stratified by an MASCC RIS below 21 or 21 or greater. Complications were correlated with the index. Results: Inclusion criteria were met in 198 episodes. Sensitivity, specificity, and positive and negative predictive values of the MASCC RIS vs complications were 94%, 29.6%, 57.7%, and 82.9%, respectively. In episodes with an RIS 21 or greater, 42.3% had complications, misclassifying to low risk 69 episodes with complications. “Unable to eat” correlated with complications in 84% of episodes. In 3 patients stratified to no complication, a complication developed 24 hours after admission. Conclusions: An MASCC RIS of 21 or greater could not be used as a criterion for “no complication/do not admit.” Inability to eat should be an admission criterion. Savings of approximately $1 million per 100 uncomplicated admissions could be realized if appropriate criteria for nonadmission could be devised. An algorithm to facilitate outpatient management is suggested. PMID:26176568

  18. Role of the sodium channel SCN9A in genetic epilepsy with febrile seizures plus and Dravet syndrome.

    PubMed

    Mulley, John C; Hodgson, Bree; McMahon, Jacinta M; Iona, Xenia; Bellows, Susannah; Mullen, Saul A; Farrell, Kevin; Mackay, Mark; Sadleir, Lynette; Bleasel, Andrew; Gill, Deepak; Webster, Richard; Wirrell, Elaine C; Harbord, Michael; Sisodiya, Sanyjay; Andermann, Eva; Kivity, Sara; Berkovic, Samuel F; Scheffer, Ingrid E; Dibbens, Leanne M

    2013-09-01

    Mutations of the SCN1A subunit of the sodium channel is a cause of genetic epilepsy with febrile seizures plus (GEFS(+) ) in multiplex families and accounts for 70-80% of Dravet syndrome (DS). DS cases without SCN1A mutation inherited have predicted SCN9A susceptibility variants, which may contribute to complex inheritance for these unexplained cases of DS. Compared with controls, DS cases were significantly enriched for rare SCN9A genetic variants. None of the multiplex febrile seizure or GEFS(+) families could be explained by highly penetrant SCN9A mutations. PMID:23895530

  19. Detection of abnormalities in febrile AIDS patients with In-111-labeled leukocyte and Ga-67 scintigraphy

    SciTech Connect

    Fineman, D.S.; Palestro, C.J.; Kim, C.K.; Needle, L.B.; Vallabhajosula, S.; Solomon, R.W.; Goldsmith, S.J.

    1989-03-01

    Thirty-six patients with acquired immunodeficiency syndrome (AIDS), who were febrile but without localizing signs, underwent indium-111 leukocyte scintigraphy 24 hours after injection of labeled white blood cells (WBCs) and were restudied 48 hours after injection of gallium-67 citrate. Fifty-six abnormalities were identified as possible sources of the fever; 27 were confirmed with biopsy. Of these 27, 15 were identified only on In-111 WBC scans (including colitis, sinusitis, and focal bacterial pneumonia); six, only on Ga-67 scans (predominantly Pneumocystis carinii pneumonia and lymphadenopathy); and six, on both studies (predominantly pulmonary lesions). In-111 WBC scanning revealed 21 of 27 abnormalities (78%) and gallium scanning, 12 of 27 (44%). If only one scintigraphic study has been performed, particularly with Ga-67, a significant number of lesions would not have been detected. The authors believe radionuclide evaluation of the febrile AIDS patient without localizing signs should begin with In-111 WBC scintigraphy. Gallium scanning may be used depending on results of In-111 WBC scans or if there is a high index of suspicion for P carinii pneumonia.

  20. Serological Evidence of Chikungunya Virus among Acute Febrile Patients in Southern Mozambique

    PubMed Central

    Gudo, Eduardo Samo; Pinto, Gabriela; Vene, Sirkka; Mandlaze, Arcildo; Muianga, Argentina Felisbela; Cliff, Julie; Falk, Kerstin

    2015-01-01

    Background In the last two decades, chikungunya virus (CHIKV) has rapidly expanded to several geographical areas, causing frequent outbreaks in sub-Saharan Africa, South East Asia, South America, and Europe. Therefore, the disease remains heavily neglected in Mozambique, and no recent study has been conducted. Methods Between January and September 2013, acute febrile patients with no other evident cause of fever and attending a health center in a suburban area of Maputo city, Mozambique, were consecutively invited to participate. Paired acute and convalescent serum samples were requested from each participant. Convalescent samples were initially screened for anti-CHIKV IgG using a commercial indirect immunofluorescence test, and if positive, the corresponding acute sample was screened using the same test. Results Four hundred patients were enrolled. The median age of study participants was 26 years (IQR: 21–33 years) and 57.5% (224/391) were female. Paired blood samples were obtained from 209 patients, of which 26.4% (55/208) were presented anti-CHIKV IgG antibodies in the convalescent sample. Seroconversion or a four-fold titer rise was confirmed in 9 (4.3%) patients. Conclusion The results of this study strongly suggest that CHIKV is circulating in southern Mozambique. We recommend that CHIKV should be considered in the differential diagnosis of acute febrile illness in Mozambique and that systematic surveillance for CHIKV should be implemented. PMID:26473605

  1. Murine typhus is a common cause of febrile illness in Bedouin children in Israel.

    PubMed

    Shalev, Hanna; Raissa, Rotkane; Evgenia, Zislin; Yagupsky, Pablo

    2006-01-01

    Murine typhus is known to be endemic among populations living in poverty and exposed to rats and their fleas. A prospective 2-y study was conducted to determine the contribution of murine typhus to undifferentiated febrile illnesses among Bedouin children attending an outpatient clinic in southern Israel. Children with fever > or = 38.5 degrees C lasting for > or = 3 d were enrolled in the study. Murine typhus was serologically confirmed by the microimmunofluorescence test. A total of 549 children met the inclusion criteria of whom 76 (13.8%) had serologically-confirmed murine typhus. The disease was diagnosed in 27 of 434 (6.2%) patients aged < 5 y and in 49 of 115 (42.6%) older children (p<0.001). Murine typhus was diagnosed in 54 of 288 (18.8%) patients between June and November and in 22 of 261 (8.4%) between December and May (p<0.001). Patients with murine typhus had significantly higher prevalence of anaemia, leukopenia, hyponatraemia, and elevated liver enzymes compared to children without the disease. A single child was hospitalized and all 76 patients recovered without complications. Murine typhus is an important cause of febrile illnesses among Bedouin children > or = 5 y of age living in southern Israel and usually runs a benign clinical course. PMID:16798692

  2. Comparison of renal ultrasonography and dimercaptosuccinic acid renal scintigraphy in febrile urinary tract infection.

    PubMed

    Ayazi, Parviz; Mahyar, Abolfazl; Noroozian, Elham; Esmailzadehha, Neda; Barikani, Ameneh

    2015-12-01

    Accurate and early diagnosis and appropriate treatment of patient with urinary tract infection (UTI) are essential for the prevention or restriction of permanent damage to the kidneys in children. The aim of this study was to compare renal ultrasonography (US) and dimercaptosuccinic acid (DMSA) renal scan in the diagnosis of patients with febrile urinary tract infection. This study involved the medical records of children with febrile urinary tract infection who were admitted to the children's hospital in Qazvin, Iran. Pyelonephritis was diagnosed on the basis of clinical symptoms, laboratory tests and abnormal DMSA renal scans. The criteria for abnormality of renal US were an increase or a decrease in diffuse or focal parenchymal echogenicity, loss of corticomedullary differentiation, kidney position irregularities, parenchymal reduction and increased kidney size. Of the 100 study patients, 23% had an abnormal US and 46% had an abnormal DMSA renal scan. Of the latter patients, 15 had concurrent abnormal US (P value ≤ 0.03, concordance rate: 18%). Renal US had a sensitivity of 32%, specificity of 85%, positive predictive value of 65% and negative predictive value of 60%. Of the 77 patients with normal US, 31 (40.2%) had an abnormal DMSA renal scan. Despite the benefits and accessibility of renal US, its value in the diagnosis of pyelonephritis is limited. PMID:26700082

  3. Chikungunya and Dengue Fever among Hospitalized Febrile Patients in Northern Tanzania

    PubMed Central

    Hertz, Julian T.; Munishi, O. Michael; Ooi, Eng Eong; Howe, Shiqin; Lim, Wen Yan; Chow, Angelia; Morrissey, Anne B.; Bartlett, John A.; Onyango, Jecinta J.; Maro, Venance P.; Kinabo, Grace D.; Saganda, Wilbrod; Gubler, Duane J.; Crump, John A.

    2012-01-01

    Consecutive febrile admissions were enrolled at two hospitals in Moshi, Tanzania. Confirmed acute Chikungunya virus (CHIKV), Dengue virus (DENV), and flavivirus infection were defined as a positive polymerase chain reaction (PCR) result. Presumptive acute DENV infection was defined as a positive anti-DENV immunoglobulin M (IgM) enzyme-linked immunsorbent assay (ELISA) result, and prior flavivirus exposure was defined as a positive anti-DENV IgG ELISA result. Among 870 participants, PCR testing was performed on 700 (80.5%). Of these, 55 (7.9%) had confirmed acute CHIKV infection, whereas no participants had confirmed acute DENV or flavivirus infection. Anti-DENV IgM serologic testing was performed for 747 (85.9%) participants, and of these 71 (9.5%) had presumptive acute DENV infection. Anti-DENV IgG serologic testing was performed for 751 (86.3%) participants, and of these 80 (10.7%) had prior flavivirus exposure. CHIKV infection was more common among infants and children than adults and adolescents (odds ratio [OR] 1.9, P = 0.026) and among HIV-infected patients with severe immunosuppression (OR 10.5, P = 0.007). CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania. DENV or other closely related flaviviruses are likely also circulating. PMID:22232469

  4. Cognitive Dysfunction and Hippocampal Damage Induced by Hypoxic-Ischemic Brain Injury and Prolonged Febrile Convulsions in Immature Rats

    PubMed Central

    Byeon, Jung Hye; Kim, Gun-Ha; Kim, Joo Yeon; Sun, Woong; Kim, Hyun

    2015-01-01

    Objective Perinatal hypoxic-ischemic encephalopathy (HIE) and prolonged febrile seizures (pFS) are common neurologic problems that occur during childhood. However, there is insufficient evidence from experimental studies to conclude that pFS directly induces hippocampal injury. We studied cognitive function and histological changes in a rat model and investigated which among pFS, HIE, or a dual pathologic effect is most detrimental to the health of children. Methods A rat model of HIE at postnatal day (PD) 7 and a pFS model at PD10 were used. Behavioral and cognitive functions were investigated by means of weekly open field tests from postnatal week (PW) 3 to PW7, and by daily testing with the Morris water maze test at PW8. Pathological changes in the hippocampus were observed in the control, pFS, HIE, and HIE+pFS groups at PW9. Results The HIE priming group showed a seizure-prone state. The Morris water maze test revealed a decline in cognitive function in the HIE and HIE+pFS groups compared with the pFS and control groups. Additionally, the HIE and HIE+pFS groups showed significant hippocampal neuronal damage, astrogliosis, and volume loss, after maturation. The pFS alone induced minimal hippocampal neuronal damage without astrogliosis or volume loss. Conclusion Our findings suggest that pFS alone causes no considerable memory or behavioral impairment, or cellular change. In contrast, HIE results in lasting memory impairment and neuronal damage, gliosis, and tissue loss. These findings may contribute to the understanding of the developing brain concerning conditions caused by HIE or pFS. PMID:26279809

  5. A randomized, crossover comparison of standard-dose versus low-dose lenograstim in the prophylaxis of post-chemotherapy neutropenia.

    PubMed

    Juan, O; Campos, J M; Carañana, V; Sanchez, J J; Casañ, R; Alberola, V

    2001-06-01

    The aim of this trial was to compare the severity of neutropenia, the frequency of hospital admission for fever or infection, and the use of antibiotics among patients treated with a standard dose of lenograstim (263 microg/day of Euprotin) and others treated with half of this dose (131.5 microg/day) and the cost-effectiveness of each of the two doses. In this single-center study, 44 patients with solid tumors, who were all receiving standard-dose chemotherapy regimens following previous neutropenia or were at high risk of neutropenia, were randomized to receive lenograstim at a dose of 263 microg or 131.5 microg daily in the first cycle and then crossed over to the alternate dose for the following cycle. Crossover to the alternate dose was repeated for patients who received more than two cycles. Lenograstim was administered from day +5 to day +14. The absolute neutrophil count (ANC) was assessed on days +5, +8, +12 and +15 of each cycle. Statistical analysis was performed using a general lineal model for repeated samples. In all, 120 cycles were administered, with a median of 3 cycles (range 1-6). Only 4 patients received only 1 cycle. No statistically significant difference (P=0.324) in ANC was observed between standard-dose (mean 5.3, 10.7, 8.3, 11.4 x 10(9)/l) and low-dose (5.0, 8.6, 5.4, 7.5 x 10(9)/l) treatment at days +5, +8, +12 and + 15. Neutropenia grade III-IV was more common in patients receiving the low than in those receiving the standard dose of lenograstim (20% vs 12%, respectively), but the difference did not reach statistical significance (P=0.1). The incidence of fever and frequency of hospital admission were not affected by the dose of lenograstim: 3 patients presented with fever with the standard dose (all of those were admitted to hospital) and 2 patients with the low dose (1 was admitted). ANC in both groups (standard and low doses) was independent of chemotherapy line (first versus second or more). Lenograstim at a dose of 131.5 microg/day is as effective as the standard dose in limiting the severity of neutropenia and in preventing episodes of fever and hospital admissions after chemotherapy for solid tumors. The lower dose of lenograstim is cost-effective in neutropenia prophylaxis. Starting its administration on day +5 reduces costs while maintaining efficacy. PMID:11430419

  6. 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.

  7. The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib: A Prisma-Compliant Systematic Review and Meta-Analysis.

    PubMed

    Zhou, Jian-Guo; Tian, Xu; Cheng, Long; Zhou, Quan; Liu, Yuan; Zhang, Yu; Bai, Yu-ju; Ma, Hu

    2015-10-01

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21-0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11-0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinib with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78-1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34-1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07-0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01-0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined to detect an RR of 0.38 for neutropenia, and 78.03% for an RR of 0.32 for leukopenia. The present meta-analysis suggested that erlotinib could decrease the incidence of neutropenia and leukopenia in patients with advanced NSCLC undergoing erlotinib regardless of whether combined with CT or not. The subgroup analysis revealed that erlotinib combine with CT did not affect the incidence; however, erlotinib alone could significantly decrease the incidence of neutropenia and leukopenia compared with CT alone. PMID:26448029

  8. An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients

    PubMed Central

    Ichikawa, W; Uehara, K; Minamimura, K; Tanaka, C; Takii, Y; Miyauchi, H; Sadahiro, S; Fujita, K; Moriwaki, T; Nakamura, M; Takahashi, T; Tsuji, A; Shinozaki, K; Morita, S; Ando, Y; Okutani, Y; Sugihara, M; Sugiyama, T; Ohashi, Y; Sakata, Y

    2015-01-01

    Background: In Asians, the risk of irinotecan-induced severe toxicities is related in part to UGT1A1*6 (UGT, UDP glucuronosyltransferase) and UGT1A1*28, variant alleles that reduce the elimination of SN-38, the active metabolite of irinotecan. We prospectively studied the relation between the UGT1A1 genotype and the safety of irinotecan-based regimens in Japanese patients with advanced colorectal cancer, and then constructed a nomogram for predicting the risk of severe neutropenia in the first treatment cycle. Methods: Safety data were obtained from 1312 patients monitored during the first 3 cycles of irinotecan-based regimen in a prospective observational study. In development of the nomogram, multivariable logistic regression analysis was used to test the associations of candidate factors to severe neutropenia in the first cycle. The final nomogram based on the results of multivariable analysis was constructed and validated internally using a bootstrapping technique and externally in an independent data set (n=350). Results: The UGT1A1 genotype was confirmed to be associated with increased risks of irinotecan-induced grade 3 or 4 neutropenia and diarrhoea. The final nomogram included type of regimen, administered dose of irinotecan, gender, age, UGT1A1 genotype, Eastern Cooperative Oncology Group performance status, pre-treatment absolute neutrophil count, and total bilirubin level. The model was validated both internally (bootstrap-adjusted concordance index, 0.69) and externally (concordance index, 0.70). Conclusions: Our nomogram can be used before treatment to accurately predict the probability of irinotecan-induced severe neutropenia in the first cycle of therapy. Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan. PMID:25880011

  9. Foliicolous microfungi occurring on Encephalartos.

    PubMed

    Crous, P W; Wood, A R; Okada, G; Groenewald, J Z

    2008-12-01

    Species of Encephalartos, commonly known as bread trees, bread palms or cycads are native to Africa; the genus encompasses more than 60 species and represents an important component of the indigenous African flora. Recently, a leaf blight disease was noted on several E. altensteinii plants growing at the foot of Table Mountain in the Kirstenbosch Botanical Gardens of South Africa. Preliminary isolations from dead and dying leaves of E. alten-steinii, E. lebomboensis and E. princeps, collected from South Africa, revealed the presence of several novel microfungi on this host. Novelties include Phaeomoniella capensis, Saccharata kirstenboschensis, Teratosphaeria altensteinii and T. encephalarti. New host records of species previously only known to occur on Proteaceae include Cladophialophora proteae and Catenulostroma microsporum, as well as a hyperparasite, Dactylaria leptosphaeriicola, occurring on ascomata of T. encephalarti. PMID:20396583

  10. Evaluation of Bax and Bcl-2 Proteins Expression in the Rat Hippocampus due to Childhood Febrile Seizure

    PubMed Central

    SAEEDI BORUJENI, Mohammad Javad; HAMI, Javad; HAGHIR, Hossein; RASTIN, Maryam; SAZEGAR, Ghasem

    2016-01-01

    Objective Simple Febrile Seizure (SFS) is the most common seizure disorder in childhood, and is frequently described as inoffensive disorder. Nevertheless, there is evidence suggesting the association between neonatal febrile seizures and hippocampal abnormalities in adulthood. This study was conducted at evaluating the hippocampal expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins following SFS induction in rat neonates. Materials & Methods Febrile seizure was modeled by hyperthermia-induced seizure in 22-dayold male rats by a hot water bath. The animals were divided into two groups based on the presence or absence of seizure behaviors: Hyperthermia without seizure (n=10) and hyperthermia with seizure (n=10). To control the effects of environmental stress a sham-control group was also added (n=10). The rats’ hippocampi were dissected 2 or 15 days after hyperthermia. The expression of Bax and Bcl-2 proteins were measured using Western Blotting technique. Results The hippocampal expression of Bcl-2 protein was significantly lower in the hyperthermia with seizure animals than that of the sham-control and hyperthermia without seizure groups. The expression of pro-apoptotic Bax protein also significantly increased in the hippocampus of hyperthermia with seizure group rats compared to the sham-control and hyperthermia without seizure animals. Conclusion The simple febrile seizure markedly disturbed the hippocampal expression of both Bcl2 and Bax proteins, resulting in apoptosis promotion in hippocampi of juvenile rats, which were measurable for at least 15 days. PMID:27057189

  11. Roles of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 in acute encephalopathy following prolonged febrile seizures.

    PubMed

    Suenaga, Naoko; Ichiyama, Takashi; Kubota, Masaya; Isumi, Hiroshi; Tohyama, Jun; Furukawa, Susumu

    2008-03-15

    Prolonged febrile seizures may be followed by acute encephalopathy with neurological sequelae. To investigate the function of the blood-brain-barrier (BBB) in acute encephalopathy following prolonged febrile seizures with neurological sequelae (AEPFS), the concentrations of serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) were measured by ELISA in 10 children with AEPFS, 16 with prolonged febrile seizures without encephalopathy (PFS), 20 with simple febrile seizures (SFS), 23 with convulsive status epilepticus (CSE), and 18 with West syndrome. Serum MMP-9 levels in AEPFS and PFS patients were significantly higher than those in SPS and West syndrome patients and in controls, and those in CSE patients were significantly higher than in controls. Serum TIMP-1 levels in AEPFS patients were significantly lower than those in PFS, SFS, CSE and West syndrome patients and in controls. Serum MMP-9 levels and MMP-9/TIMP-1 ratios in AEPFS patients with motor paralysis were significantly higher than for those without motor paralysis. Our results suggest that prolonged seizures are related to high serum MMP-9 levels, and that an increased MMP-9/TIMP-1 ratio in AEPFS might induce dysfunction of the BBB. Furthermore, an imbalance of serum MMP-9 and TIMP-1 levels in patients with AEPFS may be associated with severe neurological sequelae. PMID:17928006

  12. 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

  13. Carcinogens occurring naturally in foods.

    PubMed

    Miller, J A; Miller, E C

    1976-05-01

    Humans are susceptible to the carcinogenic action of a small group of organic and inorganic chemicals in certain industrial, medical, and social habit exposures. A larger number and wider variety of chemical carcinogens, primarily organic compounds, are known for experimental animals. Chemical carcinogens are also found among the metabolites of living cells. No common structure is evident among chemical carcinogens, and a majority of these agents are precarcinogens that require metabolic activation into reactive electrophilic ultimate carcinogens. These strong electrophiles combine covalently with nucleophilic sites in DNAs, RNAs, and proteins in target tissues. One or more of these adducts appear to initiate carcinogenesis. About 20 naturally occurring organic chemical carcinogens, primarily metabolites of green plants and fungi, are known; some occur in some human foods. Many other naturally chemical carcingens doubtless exist among the vast number of uncharacterized nonnutritive minor components of living systems, some of which are sources of human foods. The electrophilic forms of chemical carcinogens are mutagenic, and mammalian tissue-mediated mutagenicity assays appear promising in the detection of potential chemical carcinogens. These assays should serve at least as a prescreen for conventional lifetime tests in rodents for the carcinogenic activity of food components and contaminants. Epidemiological approaches appear necessary to evaluate the importance of the naturally occurring chemical carcinogens in the occurrence of human cancer. PMID:770205

  14. Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans.

    PubMed

    Foster, Josh; Mauger, Alexis; Thomasson, Katie; White, Stephanie; Taylor, Lee

    2016-01-01

    In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin temperature, heart rate, or thermal sensation between the acetaminophen and placebo trials (p > 0.05). The results indicate oral acetaminophen reduces core temperature of humans exposed to an environment beneath the thermal neutral zone. These results suggest that acetaminophen may inhibit the thermogenic mechanisms required to regulate core temperature during exposure to sub-neutral environments. PMID:27014068

  15. 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, Henritte 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

  16. Aetiology of Acute Febrile Episodes in Children Attending Korogwe District Hospital in North-Eastern Tanzania

    PubMed Central

    Mahende, Coline; Ngasala, Billy; Lusingu, John; Butichi, Allvan; Lushino, Paminus; Lemnge, Martha; Premji, Zul

    2014-01-01

    Introduction Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH). Methods A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was performed in selected cases to test for bacterial infection and a chest radiograph was requested if pneumonia was suspected. Diagnosis was based on both clinical and laboratory investigations. Results A total of 867 patients with a median age of 15.1 months (Interquartile range 8.6–29.9) were enrolled from January 2013 to October 2013. Respiratory tract infections were the leading clinical diagnosis with 406/867 (46.8%) of patients diagnosed with upper respiratory tract infection and 130/867 (15.0%) with pneumonia. Gastroenteritis was diagnosed in 184/867 (21.2%) of patients. Malaria infection was confirmed in 72/867 (8.3%) of patients. Bacterial infection in blood and urine accounted for 26/808 (3.2%) infections in the former, and 66/373 (17.7%) infections in the latter. HIV infection was confirmed in 10/824 (1.2%) of patients. Respiratory tract infections and gastroenteritis were frequent in patients under 36 months of age (87.3% and 91.3% respectively). Co-infections were seen in 221/867 (25.5%) of patients. The cause of fever was not identified in 65/867 (7.5%) of these patients. Conclusions The different proportions of infections found among febrile children reflect the causes of fever in the study area. These findings indicate the need to optimise patient management by developing malaria and non-malaria febrile illnesses management protocols. PMID:25090651

  17. Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

    PubMed Central

    Foster, Josh; Mauger, Alexis; Thomasson, Katie; White, Stephanie; Taylor, Lee

    2016-01-01

    In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin temperature, heart rate, or thermal sensation between the acetaminophen and placebo trials (p > 0.05). The results indicate oral acetaminophen reduces core temperature of humans exposed to an environment beneath the thermal neutral zone. These results suggest that acetaminophen may inhibit the thermogenic mechanisms required to regulate core temperature during exposure to sub-neutral environments. PMID:27014068

  18. PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) augments the therapeutic effect of pegfilgrastim on gemcitabine-induced neutropenia.

    PubMed

    Yoo, Nina; Lee, Ha-Reum; Shin, Su-Hyun; Sohn, Ki-Young; Kim, Heung-Jae; Han, Yong-Hae; Chong, Saeho; Kim, Myung-Hwan; Yoon, Sun Young; Kim, Jae Wha

    2016-07-10

    Granulocyte colony-stimulating factor (G-CSF) is widely used for preventing neutropenia during chemotherapy. Polyethylene glycol-conjugated granulocyte colony-stimulating factor (PEG-G-CSF, pegfilgrastim) serves the same purpose but has a longer half-life and greater stability than G-CSF. In this study, we investigated whether 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride (PLAG), augments the therapeutic effect of pegfilgrastim on chemotherapy-induced neutropenia. We compared neutrophil counts in four groups of mice: control mice, gemcitabine-treated mice, gemcitabine/pegfilgrastim-treated mice, and gemcitabine/pegfilgrastim/PLAG-treated mice. PLAG (50 mg/kg) was orally administered every day during the treatment course. CBC analysis showed that the group treated with PLAG experienced a dramatically increased neutrophil counts on the third day following pegfilgrastim treatment. PLAG had no effect on blood cell apoptosis and neutrophil release from bone marrow. Additionally, pegfilgrastim-induced CXCR2 expression in neutrophils was markedly decreased in PLAG-treated animals. These results suggest that PLAG plays a role in inhibiting neutrophil extravasation, giving rise to an increased number of circulating neutrophils when used with pegfilgrastim during gemcitabine treatment. These data support the potential for PLAG to be used with pegfilgrastim to treat or prevent chemotherapy-induced neutropenia by modulating neutrophil transmigration. PMID:27105612

  19. Neutropenia in HIV-Infected Kenyan Women Receiving Triple Antiretroviral Prophylaxis to Prevent Mother-to-Child HIV Transmission Is Not Associated with Serious Clinical Sequelae

    PubMed Central

    Iuliano, A. Danielle; Weidle, Paul J.; Brooks, John T.; Masaba, Rose; Girde, Sonali; Ndivo, Richard; Ogindo, Paul; Omolo, Paul; Zeh, Clement; Thomas, Timothy K.

    2015-01-01

    Background Absolute neutrophil counts (ANCs) are lower in East African adults. To assess the impact of lower ANCs, we reviewed data from HIV-infected Kenyan women receiving antiretroviral therapy antepartum and postpartum. Methods The Kisumu Breastfeeding Study (KiBS) participants received an antiretroviral regimen from 34 weeks’ gestation through 6 months postpartum. Measured ANCs and subsequent illnesses were reviewed. Adverse events (AEs) potentially attributable to neutropenia were identified, and ANCs were graded using the 2004 Division of AIDS table for Grading the Severity of AEs. Results Among 478 women with ≥ 1 postpartum ANC measured, 298 (62.1%) women met criteria for an AE (<1.3 × 109 cells/L). Of those, 38 (12.5%) women experienced a nonlife-threatening illness potentially attributable to neutropenia. Conclusion More than half of KiBS women met criteria for neutropenia. The mild clinical experience of most participants with low ANCs supports that these values might be typical for this population and may not result in adverse clinical sequelae. PMID:24080477

  20. 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

  1. Functional analysis of mutations in a severe congenital neutropenia syndrome caused by glucose-6-phosphatase-β deficiency

    PubMed Central

    Lin, Su Ru; Pan, Chi-Jiunn; Mansfield, Brian C.; Chou, Janice Yang

    2016-01-01

    Glucose-6-phosphatase-β (G6Pase-β or G6PC3) deficiency is characterized by neutropenia and dysfunction in both neutrophils and macrophages. G6Pase-β is an enzyme embedded in the endoplasmic reticulum membrane that catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate. To date, 33 separate G6PC3 mutations have been identified in G6Pase-β-deficient patients but only the p.R253H and p.G260R missense mutations have been characterized functionally for pathogenicity. Here we functionally characterize 16 of the 19 known missense mutations using a sensitive assay, based on a recombinant adenoviral vector-mediated expression system, to demonstrate pathogenicity. Fourteen missense mutations completely abolish G6Pase-β enzymatic activity while the p.S139I and p.R189Q mutations retain 49% and 45%, respectively of wild type G6Pase-β activity. A database of residual enzymatic activity retained by the G6Pase-β mutations will serve as a reference for evaluating genotype-phenotype relationships. PMID:25492228

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

    PubMed Central

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

    2015-01-01

    Chemotherapy-induced neutropenia (CIN) reportedly indicated better prognosis for some cancers. We retrospectively analyzed 150 evaluable metastatic gastric cancer (MGC) patients who had received first-line EOF5 (combination regimen of epirubicin, oxaliplatin and 5-day continuous infusion of 5-fluorouracil) treatment. We divided patients into three groups according to the worst grade of CIN: absent group (grade 0), moderate group (grade 1–2) and severe group (grade 3–4). Multivariate analyses of overall survival (OS) proved moderate and severe CIN were important prognostic factors whether regarding CIN as a time-varying covariate (TVC) or not. Compared with absent CIN, hazard ratio (HR) for moderate and severe CIN were 0.31 (95% confidential interval (CI): 0.17–0.55; P < 0.001) and 0.36 (95% CI: 0.20–0.64; P = 0.001) respectively with TVC; and were 0.31 (95% CI: 0.17–0.56; P < 0.001) and 0.34 (95% CI: 0.19–0.61; P < 0.001) respectively without TVC. In progression-free survival (PFS) analyses, moderate and severe CIN showed similar results. In the landmark group (n = 122 patients) analyses with TVC, moderate and severe CIN remained prognostic factors for PFS, while only moderate CIN was prognostic factor for OS. CIN predicted longer OS and PFS in MGC patients treated with first-line EOF5 chemotherapy. PMID:26528696

  3. Functional analysis of mutations in a severe congenital neutropenia syndrome caused by glucose-6-phosphatase-β deficiency.

    PubMed

    Lin, Su Ru; Pan, Chi-Jiunn; Mansfield, Brian C; Chou, Janice Yang

    2015-01-01

    Glucose-6-phosphatase-β (G6Pase-β or G6PC3) deficiency is characterized by neutropenia and dysfunction in both neutrophils and macrophages. G6Pase-β is an enzyme embedded in the endoplasmic reticulum membrane that catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate. To date, 33 separate G6PC3 mutations have been identified in G6Pase-β-deficient patients but only the p.R253H and p.G260R missense mutations have been characterized functionally for pathogenicity. Here we functionally characterize 16 of the 19 known missense mutations using a sensitive assay, based on a recombinant adenoviral vector-mediated expression system, to demonstrate pathogenicity. Fourteen missense mutations completely abolish G6Pase-β enzymatic activity while the p.S139I and p.R189Q mutations retain 49% and 45%, respectively of wild type G6Pase-β activity. A database of residual enzymatic activity retained by the G6Pase-β mutations will serve as a reference for evaluating genotype-phenotype relationships. PMID:25492228

  4. 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

  5. Epidemiological and clinical features of dengue versus other acute febrile illnesses amongst patients seen at government polyclinics.

    PubMed

    Mustafa, B; Hani, A W Asmah; Chem, Y K; Mariam, M; Khairul, A H; Abdul Rasid, K; Chua, K B

    2010-12-01

    Classical dengue fever is characterized by the clinical features of fever, headache, severe myalgia and occasionally rash, which can also be caused by a number of other viral and bacterial infections. Five hundred and fifty eight patients who fulfilled the criteria of clinical diagnosis of acute dengue from 4 government outpatient polyclinics were recruited in this prospective field study. Of the 558 patients, 190 patients were categorized as acute dengue fever, 86 as recent dengue and 282 as non-dengue febrile illnesses based on the results of a number of laboratory tests. Epidemiological features of febrile patients showed that the mean age of patients in the dengue fever group was significantly younger in comparison with patients in the non-dengue group. There was no significant difference between the two groups with respect to gender but there was significant ethnic difference with foreign workers representing a higher proportion in the dengue fever group. Patients with acute dengue fever were more likely to have patient-reported rash and a history of dengue in family or neighbourhood but less likely to have respiratory symptoms, sore-throat and jaundice in comparison to patients with non-dengue febrile illnesses. As with patients with dengue fever, patients in the recent dengue group were more likely to have history of patient-reported rash and a history of dengue contact and less likely to have respiratory symptoms in comparison to patients with non-dengue febrile illnesses. In contrast to patients with dengue fever, patients in the recent dengue group were more likely to have abdominal pain and jaundice in comparison to non-dengue febrile patients. The finding strongly suggests that a proportion of patients in the recent dengue group may actually represent a subset of patients with acute dengue fever at the late stage of illness. PMID:21901948

  6. Novel mutation of SCN1A in familial generalized epilepsy with febrile seizures plus.

    PubMed

    Li, Nan; Zhang, Jie; Guo, Ji-feng; Yan, Xin-xiang; Xia, Kun; Tang, Bei-sha

    2010-08-23

    Generalized epilepsy with febrile seizures plus (GEFS+) is an epileptic syndrome inherited in autosomal dominant mode. Of all the identified causative GEFS+ genes, voltage-gated sodium channel alpha1 subunit gene (SCN1A) is the most clinically relevant one. We describe here the clinical and molecular characterization of a GEFS+ family. A novel heterozygous mutation c.5383G>A was revealed by direct sequencing of the SCN1A gene for both affected and unaffected individuals. It is speculated that the function of the sodium channel could be compromised by the substitution of lysine for a highly conserved residue glutamic acid at position 1795 within the C-terminus of alpha1 subunit. Our finding extends the spectrum of SCN1A mutations related to GEFS+ and further confirms the contribution of the sodium channel genes to the etiology of idiopathic epilepsies. PMID:20600615

  7. Outbreak of acute respiratory febrile illness among college students--Acapulco, Mexico, March 2001.

    PubMed

    2001-04-13

    On March 30, 2001, CDC was notified by Pennsylvania Department of Health (PDH) of an acute respiratory febrile illness in 44 students from two colleges who traveled to Acapulco, Mexico, for spring break vacation during March 3-18. Within 7-14 days of their return from Acapulco, 21 students presented to health-care providers with illness characterized by fever, chills, dry cough, chest pain, and headache. Two students were hospitalized. On the basis of clinical symptoms and chest radiographs that revealed bilateral, nodular patchy infiltrates, acute pulmonary histoplasmosis was the suspected illness. While in Acapulco, most of the students stayed at the Calinda Beach Hotel and participated in group activities at other recreational locations. PMID:11411829

  8. Viral Hemorrhagic Fever Cases in the Country of Georgia: Acute Febrile Illness Surveillance Study Results

    PubMed Central

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

    2014-01-01

    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

  9. Acute febrile neutrophilic dermatosis associated with JAK-2 positive myeloproliferative disorder.

    PubMed

    Smyth, Dean; Selwyn, Jey

    2016-01-01

    We present a case of a 77-year-old man with a history of myeloproliferative disorder. He was admitted with a 2-week history of erythaema, swelling and significant pain of the right forearm following a mechanical fall at home, which had caused a skin laceration. During his admission, he developed ongoing intermittent fever and persistently elevated C reactive protein, and total white cell count. Initially, he was treated with antibiotics for suspected cellulitis. However, symptoms continued to progress, making a suitable management plan challenging. Wound swabs, blood cultures and viral PCR did not confirm infection. A punch biopsy of a skin lesion on the forearm was performed. The histology demonstrated a dense infiltrate of neutrophils and neutrophilic debris in keeping with acute febrile neutrophilic dermatosis (Sweet's syndrome). He was treated with oral steroids and after that he had a complete resolution of symptoms. However, he required a period of rehabilitation before returning home. PMID:27118753

  10. Unsuspected Dengue and Acute Febrile Illness in Rural and Semi-Urban Southern Sri Lanka

    PubMed Central

    Bodinayake, Champika; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara-Arachichi, Wasantha; Strouse, John J.; Broadwater, Anne; Østbye, Truls; de Silva, Aravinda; Woods, Christopher W.

    2012-01-01

    Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults. PMID:22304972

  11. Rickettsial Infections in Southeast Asia: Implications for Local Populace and Febrile Returned Travelers

    PubMed Central

    Aung, Ar Kar; Spelman, Denis W.; Murray, Ronan J.; Graves, Stephen

    2014-01-01

    Rickettsial infections represent a major cause of non-malarial febrile illnesses among the residents of Southeast Asia and returned travelers from that region. There are several challenges in recognition, diagnosis, and management of rickettsioses endemic to Southeast Asia. This review focuses on the prevalent rickettsial infections, namely, murine typhus (Rickettsia typhi), scrub typhus (Orientia tsutsugamushi), and members of spotted fever group rickettsiae. Information on epidemiology and regional variance in the prevalence of rickettsial infections is analyzed. Clinical characteristics of main groups of rickettsioses, unusual presentations, and common pitfalls in diagnosis are further discussed. In particular, relevant epidemiologic and clinical aspects on emerging spotted fever group rickettsiae in the region, such as Rickettsia honei, R. felis, R. japonica, and R. helvetica, are presented. Furthermore, challenges in laboratory diagnosis and management aspects of rickettsial infections unique to Southeast Asia are discussed, and data on emerging resistance to antimicrobial drugs and treatment/prevention options are also reviewed. PMID:24957537

  12. Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic Anemia.

    PubMed

    Hashiba, Masamitsu; Tomino, Atsutoshi; Takenaka, Nobuyoshi; Hattori, Tomonori; Kano, Hideki; Tsuda, Masanobu; Takeyama, Naoshi

    2016-01-01

    BACKGROUND Clostridium perfringens (C. perfringens) can cause various infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. CASE REPORT We present the case of a male patient with diabetes who developed a fatal liver abscess with massive intravascular hemolysis and septic shock caused by toxigenic C. perfringens. The peripheral blood smear showed loss of central pallor, with numerous spherocytes. Multiplex PCR only detected expression of the cpa gene, indicating that the pathogen was C. perfringens type A. CONCLUSIONS C. perfringens infection should be considered in a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed blood sample, and negative Coombs test. The characteristic peripheral blood smear findings may facilitate rapid diagnosis. PMID:27049736

  13. Translation of clinical prediction rules for febrile children to primary care practice: an observational cohort study

    PubMed Central

    van Ierland, Yvette; Elshout, Gijs; Berger, Marjolein Y; Vergouwe, Yvonne; de Wilde, Marcel; van der Lei, Johan; Mol, Henriëtte A; Oostenbrink, Rianne

    2015-01-01

    Background Clinical prediction rules (CPRs) to identify children with serious infections lack validation in low-prevalence populations, which hampers their implementation in primary care practice. Aim To evaluate the diagnostic value of published CPRs for febrile children in primary care. Design and setting Observational cohort study among febrile children (<16 years) who consulted five GP cooperatives (GPCs) in the Netherlands. Method Alarm signs of serious infection and clinical management were extracted from routine clinical practice data and manually recoded with a structured electronic data-entry program. Eight CPRs were selected from literature. CPR-variables were matched with alarm signs and CPRs were applied to the GPC-population. ‘Referral to emergency department (ED)’ was used as a proxy outcome measure for ‘serious infection’. CPR performance was assessed by calibration analyses, sensitivity, specificity, and area under the ROC-curve (ROC-area). Results A total of 9794 GPC-contacts were eligible, 54% male, median age 2.3 years (interquartile range 1.0–4.6 years) and 8.1% referred to ED. Frequencies of CPR-variables varied from 0.5% (cyanosis, drowsy) to 25% (temperature ≥40°C). Alarm signs frequently included in CPRs were ‘ill appearance’, ‘inconsolable’, and ‘abnormal circulatory or respiratory signs’. The height of the CPR’s predicted risks generally corresponded with being (or not being) referred to the ED in practice. However, calibration-slopes indicated that three CPRs underestimated the risk of serious infection in the GPC-population. Sensitivities ranged from 42% to 54%, specificities from 68% to 89%. ROC-areas ranged from 0.52 to 0.81, with best performance of CPRs for children aged <3 months. Conclusion Published CPRs performed moderately well in the primary out-of-hours care population. Advice is given on how to improve translation of CPRs to primary care practice. PMID:25824182

  14. Frequency of Epstein - Barr Virus in Patients Presenting with Acute Febrile Illness in Kenya

    PubMed Central

    Masakhwe, Clement; Ochanda, Horace; Nyakoe, Nancy; Ochiel, Daniel; Waitumbi, John

    2016-01-01

    Background Most acute febrile illnesses (AFI) are usually not associated with a specific diagnosis because of limitations of available diagnostics. This study reports on the frequency of EBV viremia and viral load in children and adults presenting with febrile illness in hospitals in Kenya. Methodology/Principal Findings A pathogen surveillance study was conducted on patients presenting with AFI (N = 796) at outpatient departments in 8 hospitals located in diverse regions of Kenya. Enrollment criterion to the study was fever without a readily diagnosable infection. All the patients had AFI not attributable to the common causes of fever in Kenyan hospitals, such as malaria or rickettsiae, leptospira, brucella and salmonella and they were hence categorized as having AFI of unknown etiology. EBV was detected in blood using quantitative TaqMan-based qPCR targeting a highly conserved BALF5 gene. The overall frequency of EBV viremia in this population was 29.2%, with significantly higher proportion in younger children of <5years (33.8%, p = 0.039) compared to patients aged ≥5 years (26.3% for 5–15 years or 18.8% for >15 years). With respect to geographical localities, the frequency of EBV viremia was higher in the Lake Victoria region (36.4%), compared to Kisii highland (24.6%), Coastal region (22.2%) and Semi-Arid region (25%). Furthermore, patients from the malaria endemic coastal region and the Lake Victoria region presented with significantly higher viremia than individuals from other regions of Kenya. Conclusions/Significance This study provides profiles of EBV in patients with AFI from diverse eco-regions of Kenya. Of significant interest is the high frequency of EBV viremia in younger children. The observed high frequencies of EBV viremia and elevated viral loads in residents of high malaria transmission areas are probably related to malaria induced immune activation and resultant expansion of EBV infected B-cells. PMID:27163791

  15. Value of Ultrasound in Detecting Urinary Tract Anomalies After First Febrile Urinary Tract Infection in Children.

    PubMed

    Ghobrial, Emad E; Abdelaziz, Doaa M; Sheba, Maha F; Abdel-Azeem, Yasser S

    2016-05-01

    Background Urinary tract infection (UTI) is an infection that affects part of the urinary tract. Ultrasound is a noninvasive test that can demonstrate the size and shape of kidneys, presence of dilatation of the ureters, and the existence of anatomic abnormalities. The aim of the study is to estimate the value of ultrasound in detecting urinary tract anomalies after first attack of UTI. Methods This study was conducted at the Nephrology Clinic, New Children's Hospital, Faculty of Medicine, Cairo University, from August 2012 to March 2013, and included 30 children who presented with first attack of acute febrile UTI. All patients were subjected to urine analysis, urine culture and sensitivity, serum creatinine, complete blood count, and imaging in the form of renal ultrasound, voiding cysto-urethrography, and renal scan. Results All the patients had fever with a mean of 38.96°C ± 0.44°C and the mean duration of illness was 6.23 ± 5.64 days. Nineteen patients (63.3%) had an ultrasound abnormality. The commonest abnormalities were kidney stones (15.8%). Only 2 patients who had abnormal ultrasound had also vesicoureteric reflux on cystourethrography. Sensitivity of ultrasound was 66.7%, specificity was 37.5%, positive predictive value was 21.1%, negative predictive value was 81.8%, and total accuracy was 43.33%. Conclusion We concluded that ultrasound alone was not of much value in diagnosing and putting a plan of first attack of febrile UTI. It is recommended that combined investigations are the best way to confirm diagnosis of urinary tract anomalies. PMID:26084536

  16. Emergency Management of Febrile Status Epilepticus: Results of the FEBSTAT study

    PubMed Central

    Seinfeld, Syndi; Shinnar, Shlomo; Sun, Shumei; Hesdorffer, Dale C; Deng, Xiaoyan; Shinnar, Ruth C; OHara, Kathryn; Nordli, Douglas R; Frank, L Matthew; Gallentine, William; Mosh, Solomon L; Pellock, John M

    2014-01-01

    Objective Treatment of seizures varies by region with no standard emergency treatment protocol. Febrile status epilepticus (FSE) is often a childs first seizure; therefore, families are rarely educated about emergency treatment. Methods From 2002 to 2010, 199 subjects, age 1 month to 6 years, were recruited as part of a prospective, multicenter study of consequences of FSE. FSE was defined as a febrile seizure or series of seizures lasting >30 minutes. The patients charts were reviewed. No standardized treatment protocol was implemented for this observational study. Results 179 received at least one antiepileptic drug (AED) to terminate FSE and more than one AED was required in 140 patients (70%). Median time from the seizure onset to first AED by EMS or ED was 30 minutes. Mean seizure duration was 81 minutes for subjects given medication prior to ED and 95 minutes for those who did not (p=0.1). Median time from the first dose of AED to end of seizure was 38 minutes. Initial dose of lorazepam or diazepam was suboptimal in 32 of 166 patients (19%). Ninety-five (48%) subjects received respiratory support by EMS or ED. Median seizure duration for respiratory support group was 83 minutes; for non-respiratory support group was 58 minutes (p-value < 0.001). Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration. Significance FSE rarely stops spontaneously, is fairly resistant to medications and even with treatment persists for a significant period of time. The total seizure duration is composed of two separate factors; the time from seizure onset to AED initiation, and the time from first AED to seizure termination. Earlier onset of treatment results in shorter total seizure duration. A standard pre-hospital treatment protocol should be used nationwide and education of EMS responders is necessary. PMID:24502379

  17. Urinary Colorimetric Sensor Array and Algorithm to Distinguish Kawasaki Disease from Other Febrile Illnesses

    PubMed Central

    Jin, Bo; Deng, Xiaohong; Hu, Guang; Liu, Xiaodan; Zhang, Jie; Jin, Hua; Huang, Min; Kanegaye, John T.; Tremoulet, Adriana H.; Burns, Jane C.; Wu, Jianmin; Cohen, Harvey J.; Ling, Xuefeng B.

    2016-01-01

    Objectives Kawasaki disease (KD) is an acute pediatric vasculitis of infants and young children with unknown etiology and no specific laboratory-based test to identify. A specific molecular diagnostic test is urgently needed to support the clinical decision of proper medical intervention, preventing subsequent complications of coronary artery aneurysms. We used a simple and low-cost colorimetric sensor array to address the lack of a specific diagnostic test to differentiate KD from febrile control (FC) patients with similar rash/fever illnesses. Study Design Demographic and clinical data were prospectively collected for subjects with KD and FCs under standard protocol. After screening using a genetic algorithm, eleven compounds including metalloporphyrins, pH indicators, redox indicators and solvatochromic dye categories, were selected from our chromatic compound library (n = 190) to construct a colorimetric sensor array for diagnosing KD. Quantitative color difference analysis led to a decision-tree-based KD diagnostic algorithm. Results This KD sensing array allowed the identification of 94% of KD subjects (receiver operating characteristic [ROC] area under the curve [AUC] 0.981) in the training set (33 KD, 33 FC) and 94% of KD subjects (ROC AUC: 0.873) in the testing set (16 KD, 17 FC). Color difference maps reconstructed from the digital images of the sensing compounds demonstrated distinctive patterns differentiating KD from FC patients. Conclusions The colorimetric sensor array, composed of common used chemical compounds, is an easily accessible, low-cost method to realize the discrimination of subjects with KD from other febrile illness. PMID:26859297

  18. Antibiotic use among patients with febrile illness in a low malaria endemicity setting in Uganda

    PubMed Central

    2011-01-01

    Background Uganda embraced the World Health Organization guidelines that recommend a universal 'test and treat' strategy for malaria, mainly by use of rapid diagnostic test (RDT) and microscopy. However, little is known how increased parasitological diagnosis for malaria influences antibiotic treatment among patients with febrile illness. Methods Data collection was carried out within a feasibility trial of presumptive diagnosis of malaria (control) and two diagnostic interventions (microscopy or RDT) in a district of low transmission intensity. Five primary level health centres (HCs) were randomized to each diagnostic arm (diagnostic method in a defined group of patients). All 52,116 outpatients (presumptive 16,971; microscopy 17,508; and RDT 17,638) aged 5 months to ninety five years presenting with fever (by statement or measured) were included. Information from outpatients and laboratory registers was extracted weekly from March 2010 to July 2011. The proportion of patients who were prescribed antibiotics was calculated among those not tested for malaria, those who tested positive and in those who tested negative. Results Seven thousand and forty (41.5%) patients in the presumptive arm were prescribed antibiotics. Of the patients not tested for malaria, 1,537 (23.9%) in microscopy arm and 810 (56.2%) in RDT arm were prescribed antibiotics. Among patients who tested positive for malaria, 845 (25.8%) were prescribed antibiotics in the RDT and 273(17.6%) in the microscopy arm. Among patients who tested negative for malaria, 7809 (61.4%) were prescribed antibiotics in the RDT and 3749 (39.3%) in the microscopy arm. Overall the prescription of antibiotics was more common for children less than five years of age 5,388 (63%) compared to those five years and above 16798 (38.6%). Conclusion Prescription of antibiotics in patients with febrile illness is high. Testing positive for malaria reduces antibiotic treatment but testing negative for malaria increases use of antibiotics. Trial Registration ClinicalTrials.gov: NCT00565071 PMID:22183039

  19. Evaluation of new American Academy of Pediatrics guideline for febrile urinary tract infection

    PubMed Central

    Choi, Da Min; Heo, Tae Hoon; Yoo, Kee Hwan

    2015-01-01

    Purpose To evaluate the practical applications of the diagnosis algorithms recommended by the American Academy of Pediatrics urinary tract infection (UTI) guideline. Methods We retrospectively reviewed the medical records of febrile UTI patients aged between 2 and 24 months. The patients were divided into 3 groups: group I (patients with positive urine culture and urinalysis findings), group II (those with positive urine culture but negative urinalysis findings), and group III (those with negative urine culture but positive urinalysis findings). Clinical, laboratory, and imaging results were analyzed and compared between the groups. Results A total of 300 children were enrolled. The serum C-reactive protein level was lower in children in group II than in those in groups I and III (P<0.05). Children in group I showed a higher frequency of hydronephrosis than those in groups II and III (P<0.05). However, the frequencies of acute pyelonephritis (APN), vesicoureteral reflux (VUR), renal scar, and UTI recurrence were not different between the groups. In group I, recurrence of UTI and presence of APN were associated with the incidence of VUR (recurrence vs. no recurrence: 40% vs.11.4%; APN vs. no APN: 23.3% vs. 9.2%; P<0.05). The incidence of VUR and APN was not related to the presence of hydronephrosis. Conclusion UTI in febrile children cannot be ruled out solely on the basis of positive urinalysis or urine culture findings. Recurrence of UTI and presence of APN may be reasonable indicators of the presence of VUR. PMID:26512260

  20. 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

  1. 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. PMID:26114067

  2. Detecting change as it occurs

    SciTech Connect

    Radok, U.; Brown, T.J.

    1992-01-01

    Traditionally climate changes have been detected from long series of observations and long after they have happened. Our inverse sequential procedure, for detecting change as soon as it occurs, describes the existing or most recent data by their frequency distribution. Its parameter(s) are estimated both from the existing set of observations and from the same set augmented by 1,2,....j new observations. Individual-value probability products (likelihoods) are used to form ratios which yield two probabilities for erroneously accepting the existing parameter(s) as valid for the augmented data set, and vice versa. A genuine parameter change is signaled when these probabilities (or a more stable compound probability) show a progressive decrease. New parameter values can then be estimated from the new observations alone using standard statistical techniques. The inverse sequential procedure will be illustrated for global annual mean temperatures (assumed normally distributed), and for annual numbers of North Atlantic hurricanes (assumed to represent Poisson distributions). The procedure was developed, but not yet tested, for linear or exponential trends, and for chi-squared means or degrees of freedom, a special measure of autocorrelation.

  3. Detecting change as it occurs

    NASA Technical Reports Server (NTRS)

    Radok, Uwe; Brown, Timothy J.

    1992-01-01

    Traditionally climate changes have been detected from long series of observations and long after they have happened. Our 'inverse sequential' procedure, for detecting change as soon as it occurs, describes the existing or most recent data by their frequency distribution. Its parameter(s) are estimated both from the existing set of observations and from the same set augmented by 1,2,....j new observations. Individual-value probability products ('likelihoods') are used to form ratios which yield two probabilities for erroneously accepting the existing parameter(s) as valid for the augmented data set, and vice versa. A genuine parameter change is signaled when these probabilities (or a more stable compound probability) show a progressive decrease. New parameter values can then be estimated from the new observations alone using standard statistical techniques. The inverse sequential procedure will be illustrated for global annual mean temperatures (assumed normally distributed), and for annual numbers of North Atlantic hurricanes (assumed to represent Poisson distributions). The procedure was developed, but not yet tested, for linear or exponential trends, and for chi-squared means or degrees of freedom, a special measure of autocorrelation.

  4. Molecular Detection of Streptococcus pneumoniae on Dried Blood Spots from Febrile Nigerian Children Compared to Culture

    PubMed Central

    Iroh Tam, Pui-Ying; Hernandez-Alvarado, Nelmary; Schleiss, Mark R.; Hassan-Hanga, Fatimah; Onuchukwu, Chuma; Umoru, Dominic; Obaro, Stephen K.

    2016-01-01

    Background Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture. Methods Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples. Results A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4–90.1%) and 62.5% (95% CI 24.5–91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture. Conclusions Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens. PMID:27007889

  5. Association between use of air-conditioning or fan and survival of elderly febrile patients: a prospective study.

    PubMed

    Theocharis, G; Tansarli, G S; Mavros, M N; Spiropoulos, T; Barbas, S G; Falagas, M E

    2013-09-01

    Elderly individuals are more susceptible to excess summer heat. We sought to examine whether the use of cooling systems (air-conditioning or fan) affected the clinical outcomes of elderly febrile patients. We prospectively followed elderly (≥ 75 years old) febrile patients requesting the medical services of the SOS Doctors (a network of physicians performing house-call visits) from July 10 to August 20, 2011. Patients who used cooling systems ("users") were compared with those who did not ("non-users") regarding mortality, clinical outcome of primary illness (improvement or deterioration), and emergency hospitalization. Prospectively collected data were available for 339 individual elderly febrile patients. "Users" had lower mortality (10 % vs. 19 %, p < 0.05) than "non-users"; no difference was noted on clinical improvement (85 % vs. 76 %, p = 0.11) and emergency hospitalization rates (21 % vs. 30 %, p = 0.16). No difference was noted between users of air-conditioning and fan regarding mortality or clinical improvement, but fan use was associated with more hospitalizations (37 % vs. 19 %, p < 0.05). On multivariate analysis (assessing daily ambient temperature, use of cooling systems, patient age, and living conditions), the sole variable significantly associated with mortality was the non-use of cooling systems [odds ratio (OR): 2.18, 95 % confidence interval (CI): 1.06-4.50]. The use of air-conditioning or fan during hot summer periods appeared to be beneficial for elderly febrile patients living in a large city. Large prospective studies are warranted in order to provide further insight into potential individual and public health initiatives aiming to alleviate the impact of excess summer heat on the health of elderly patients. PMID:23532568

  6. Are Clinical, Laboratory, and Imaging Markers Suitable Predictors of Vesicoureteral Reflux in Children With Their First Febrile Urinary Tract Infection?

    PubMed Central

    Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

    2014-01-01

    Purpose This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. Materials and Methods One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Results Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38℃, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2℃ and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. Conclusions This study revealed fever>38.2℃ and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux. PMID:25132949

  7. A Study on the Serum Adenosine Deaminase Activity in Patients with Typhoid Fever and Other Febrile Illnesses

    PubMed Central

    Ketavarapu, Sameera; Ramani G., Uma; Modi, Prabhavathi

    2013-01-01

    Background: Adenosine Deaminase (ADA) has been suggested to be an important enzyme which is associated with the cell mediated immunity, but its clinical significance in typhoid fever has not yet been characterized. The present study was taken up to evaluate the serum ADA activity in patients of typhoid fever. The levels of ADA were also measured in the patients who were suffering from other febrile illnesses. Material and Method: This was a case control study. The subjects who were included in this study were divided into 3 groups. Group A consisted of 50 normal healthy individuals who served as the controls. Group B consisted of 50 patients, both males and females of all age groups, who were suffering from culture positive typhoid fever. Group C consisted of 50 patients who were suffering from febrile illnesses other than typhoid fever like viral fever, gastro enteritis, malaria, tonsillitis, upper respiratory tract infections, etc. The serum levels of ADA were estimated in all the subjects who were under study. Results: The serum ADA level was found to be increased in the patients of typhoid fever as compared to that in those with other febrile illnesses and in the controls. Conclusion: From the present study, it can be concluded that there was a statistically significant increase in the serum ADA levels in the patients with typhoid. PMID:23730630

  8. Generalized epilepsy with febrile seizures plus (GEFS+) spectrum: clinical manifestations and SCN1A mutations in Indonesian patients.

    PubMed

    Herini, Elisabeth Siti; Gunadi; Harahap, Indra Sari Kusuma; Yusoff, Surini; Morikawa, Satoru; Patria, Suryono Yudha; Nishimura, Noriyuki; Sunartini; Sutaryo; Takada, Satoshi; Matsuo, Masafumi; Nishio, Hisahide

    2010-06-01

    Generalized epilepsy with febrile seizures plus (GEFS+) is a childhood genetic epilepsy syndrome. GEFS+ includes a wide spectrum of clinical manifestations, and SCN1A mutations have frequently been reported among the GEFS+-related gene abnormalities. In this study, to clarify the distributions of the clinical subtypes, we analyzed 34 families with GEFS+ in Indonesia using the hospital records of the patients and questionnaires for the family members. The number of patients with febrile seizures plus (FS+), FS+ and afebrile generalized/partial seizures, borderline severe myoclonic epilepsy in infancy (SMEB) and severe myoclonic epilepsy in infancy (SMEI) were 9, 11, 7, and 7, respectively. Most patients had a family history of febrile seizures. Next, we performed molecular analyses to clarify the contributions of SCN1A mutations to the development of the GEFS+ subtypes. Only 3 of 34 probands showed SCN1A mutations. These mutations were two missense mutations, p.V1612I and p.C1756G, in two patients with SMEI and SMEB, and one silent mutation, p.G1762G, in a patient with FS+ and afebrile partial seizures. In conclusion, the majority of GEFS+ patients in Indonesia were not associated with SCN1A mutations. To detect the GEFS+-causing mutations, we must search and analyze other genes in these patients. PMID:20452746

  9. Serum interleukin -8 is not a reliable marker for prediction of vesicoureteral reflux in children with febrile urinary tract infection

    PubMed Central

    Mahyar, Abolfazl; Ayazi, Parviz; Yarigarravesh, Mohammad Hadi; Khoeiniha, Mohammad Hossein; Oveisi, Sonia; Sahmani, Ahmad Ali; Esmaeily, Shiva

    2015-01-01

    ABSTRACT Objective: In view of the side effects of voiding cystourethrography (VCUG), identification of noninvasive markers predicting the presence of vesicoureteral reflux (VUR) is important. This study was conducted to determine the predictive value of serum interleukin-8 (IL-8) in diagnosis of VUR in children with first febrile urinary tract infection (UTI). Materials and Methods: Eighty children with first febrile UTI were divided into two groups, with and without VUR, based on the results of VCUG. The sensitivity, specificity, positive and negative predictive value positive and negative likelihood ratio, and accuracy of IL-8 for prediction of VUR were investigated. Results: Of the 80 children with febrile UTI, 30 (37.5%) had VUR. There was no significant difference between the children with and without VUR and also between low and high-grade VUR groups in terms of serum concentration of IL-8 (P>0.05). Based on ROC curve, the sensitivity, specificity, likelihood ratio positive, and accuracy of serum IL-8 was lower than those of erythrocyte sedimentation rate and C-reactive protein. Multivariate logistic regression analysis showed significant positive correlation only between erythrocyte sedimentation rate and VUR. Conclusions: This study showed no significant difference between the children with and without VUR in terms of the serum concentration of IL-8. Therefore, it seems that serum IL-8 is not a reliable marker for prediction of VUR. PMID:26742975

  10. Factors associated with mortality in febrile patients in a government referral hospital in the Kenema district of Sierra Leone.

    PubMed

    Roth, Prerana J; Grant, Donald S; Ngegbai, Amara S; Schieffelin, John; McClelland, R Scott; Jarrett, Olamide D

    2015-01-01

    There is a paucity of data on the etiologies and outcomes of febrile illness in rural Sierra Leone, especially in the Lassa-endemic district of Kenema. We conducted a retrospective study of patients with subjective or documented fever (T ≥ 38.0°C) who were admitted to a rural tertiary care hospital in Kenema between November 1, 2011 and October 31, 2012. Of 854 patients admitted during the study period, 429 (50.2%) patients had fever on admission. The most common diagnoses were malaria (27.3%), pneumonia (5.1%), and Lassa fever (4.9%). However, 53.4% of febrile patients had no diagnosis at discharge. The in-hospital mortality rate was 18.9% and associated with documented temperature ≥ 38.0°C (adjusted odds ratio [AOR] = 2.89, P = 0.001) and lack of diagnosis at discharge (AOR = 2.04, P = 0.03). Failure to diagnose the majority of febrile adults and its association with increased mortality highlight the need for improved diagnostic capacity to improve patient outcomes. PMID:25404077

  11. Identification of a Premature Termination Mutation in the Proline-Rich Transmembrane Protein 2 Gene in a Chinese Family with Febrile Seizures.

    PubMed

    Zheng, Wen; Zhang, Jie; Deng, Xiong; Xiao, Jingjing; Yuan, Lamei; Yang, Yan; Guan, Liping; Song, Zhi; Yang, Zhijian; Deng, Hao

    2016-03-01

    Febrile seizures (FS), the most frequent type of seizures in children, occur in neurologically normal infants and children between the ages of 3 months and 5 years with genetic predisposition. The aim of this study was to identify the responsible gene in a four-generation Chinese Han pedigree with autosomal dominant FS. Seven family members (three affected and four unaffected) were enrolled in this study. Exome sequencing was conducted and a duplication mutation c.649dupC (p.R217Pfs*8) in the proline-rich transmembrane protein 2 gene (PRRT2) was identified. The mutation co-segregated with the disorder and was absent in normal controls. To our knowledge, this is the first report of a pedigree with complete penetrance of FS, which is caused by mutation in the PRRT2 gene. FS is a novel phenotype of the c.649dupC (p.R217Pfs*8) mutation. Our discovery broadens the spectrum of genetic causes of FS and the spectrum of phenotypes linked to mutation in the PRRT2 gene. PMID:25502464

  12. Performance of Serum Biomarkers for the Early Detection of Invasive Aspergillosis in Febrile, Neutropenic Patients: A Multi-State Model

    PubMed Central

    Schwarzinger, Michaël; Sagaon-Teyssier, Luis; Cabaret, Odile; Bretagne, Stéphane; Cordonnier, Catherine; Pautas, Cécile; Maury, Sébastien; Hicheri, Yosr; Botterel, Françoise; Foulet, Francoise; Vekhoff, Anne; Chaoui, Driss; Cornet, Muriel; Agnamey, Patrice; Farhat, Hassan; Castaigne, Sylvie; Eloy, Odile; Suarez, Felipe; Buzyn, Agnès; Delarue, Richard; Challier, Svetlana; Dhedin, Nathalie; Aljijakli, Ahmad; Delabesse, Emmanuelle; Datry, Annick; Isnard, Françoise; Fouillard, Loic; Poirot, Jean-Yves; Meliani, Leila; Adès, Lionel; Bouges-Michel, Claire; Deniau, Michèle; Kuhnowski, Frédérique; Dreyfus, François; Paugam, André; Baixench, Marie-Thérèse; Leclercq, Roland; Reman, Oumady; Duhamel, Chantal; Bourrhis, Jean-Henri; Chehata, Sami; Chachati, Isabelle; Foissaud, Vincent; Macnab, Christine; Tilly, Hervé; Leprêtre, Stéphane; Gray, Christian; Raffoux, Emmanuel; Lacroix, Claire; Goldhaber-Fiebert, Jeremy D; Bendavid, Eran; Farley, Brandon J

    2013-01-01

    Background The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking. Methods We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3)- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus. Results The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010), independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53). Conclusions The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay. PMID:23799048

  13. 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

  14. Hantavirus infection among children hospitalized for febrile illness suspected to be dengue in Barbados.

    PubMed

    Kumar, Alok; Krishnamurthy, Kandamaran; Nielsen, Anders L

    2016-01-01

    Emerging picture of hantavirus infection in the South America is characterized by greater proportion of childhood infection and wider spectrum of disease from mild asymptomatic to lethal cardiopulmonary disease. Barbados is endemic for dengue and leptospirosis, both of which share clinical features with hantavirus infection and in many cases neither of these diagnosis could be confirmed. We investigate whether some of the children hospitalized with suspected dengue could indeed have been hantavirus infections. In this prospective study children hospitalized with suspected dengue were tested for hantavirus infection using ELISA for the IgM antibodies. Thirty-eight children tested positive for hantavirus infection. They presented with fever, headache and mild respiratory and gastrointestinal symptoms and signs. None of them had features suggestive of hantavirus cardiopulmonary syndrome. Blood count values ranged from low to normal to high for their age. There were no deaths. Hantavirus infection is prevalent in this Caribbean country. It predominantly presents with milder disease and is responsible for some of the nonspecific febrile illnesses in children. PMID:26153080

  15. Rapid, Coordinate Inflammatory Responses after Experimental Febrile Status Epilepticus: Implications for Epileptogenesis1,2,3

    PubMed Central

    Patterson, Katelin P.; Kinney-Lang, Eli; Dubé, Celine; Rashid, Faisal; Ly, Catherine; Obenaus, Andre

    2015-01-01

    Abstract Epilepsy is a common neurological disorder with many causes. For temporal lobe epilepsy, antecedent insults are typically found. These risk factors include trauma or history of long fever-associated seizures (febrile status epilepticus) in childhood. Whereas the mechanisms by which such insults promote temporal lobe epilepsy are unknown, an extensive body of work has implicated inflammation and inflammatory mediators in both human and animal models of the disorder. However, direct evidence for an epileptogenic role for inflammation is lacking. Here we capitalized on a model where only a subgroup of insult-experiencing rodents develops epilepsy. We reasoned that if inflammation was important for generating epilepsy, then early inflammation should be more prominent in individuals destined to become epileptic compared with those that will not become epileptic. In addition, the molecular and temporal profile of inflammatory mediators would provide insights into which inflammatory pathways might be involved in the disease process. We examined inflammatory profiles in hippocampus and amygdala of individual rats and correlated them with a concurrent noninvasive, amygdalar magnetic resonance imaging epilepsy-predictive marker. We found significant individual variability in the expression of several important inflammatory mediators, but not in others. Of interest, a higher expression of a subset of hippocampal and amygdalar inflammatory markers within the first few hours following an insult correlated with the epilepsy-predictive signal. These findings suggest that some components of the inflammatory gene network might contribute to the process by which insults promote the development of temporal lobe epilepsy. PMID:26730400

  16. Changing Epidemiology of Serious Bacterial Infections in Febrile Infants without Localizing Signs

    PubMed Central

    Watt, Kevin; Waddle, Erica; Jhaveri, Ravi

    2010-01-01

    Objective Historically, management of infants with fever without localizing signs (FWLS) has generated much controversy, with attempts to risk stratify based on several criteria. Advances in medical practice may have altered the epidemiology of serious bacterial infections (SBIs) in this population. We conducted this study to test the hypothesis that the rate of SBIs in this patient population has changed over time. Patients and Methods We performed a retrospective review of all infants meeting FWLS criteria at our institution from 1997–2006. We examined all clinical and outcome data and performed statistical analysis of SBI rates and ampicillin resistance rates. Results 668 infants met criteria for FWLS. The overall rate of SBIs was 10.8%, with a significant increase from 2002–2006 (52/361, 14.4%) compared to 1997–2001 (20/307, 6.5%) (p = 0.001). This increase was driven by an increase in E. coli urinary tract infections (UTI), particularly in older infants (31–90 days). Conclusions We observed a significant increase in E. coli UTI among FWLS infants with high rates of ampicillin resistance. The reasons are likely to be multifactorial, but the results themselves emphasize the need to examine urine in all febrile infants <90days and consider local resistance patterns when choosing empiric antibiotics. PMID:20805983

  17. Unsuspected Leptospirosis Is a Cause of Acute Febrile Illness in Nicaragua

    PubMed Central

    Reller, Megan E.; Wunder, Elsio A.; Miles, Jeremy J.; Flom, Judith E.; Mayorga, Orlando; Woods, Christopher W.; Ko, Albert I.; Dumler, J. Stephen; Matute, Armando J.

    2014-01-01

    Background Epidemic severe leptospirosis was recognized in Nicaragua in 1995, but unrecognized epidemic and endemic disease remains unstudied. Methodology/Principal Findings To determine the burden of and risk factors associated with symptomatic leptospirosis in Nicaragua, we prospectively studied patients presenting with fever at a large teaching hospital. Epidemiologic and clinical features were systematically recorded, and paired sera tested by IgM-ELISA to identify patients with probable and possible acute leptospirosis. Microscopic Agglutination Test and PCR were used to confirm acute leptospirosis. Among 704 patients with paired sera tested by MAT, 44 had acute leptospirosis. Patients with acute leptospirosis were more likely to present during rainy months and to report rural residence and fresh water exposure. The sensitivity of clinical impression and acute-phase IgM detected by ELISA were poor. Conclusions/Significance Leptospirosis is a common (6.3%) but unrecognized cause of acute febrile illness in Nicaragua. Rapid point-of-care tests to support early diagnosis and treatment as well as tests to support population-based studies to delineate the epidemiology, incidence, and clinical spectrum of leptospirosis, both ideally pathogen-based, are needed. PMID:25058149

  18. The Optimal Management of Acute Febrile Encephalopathy in the Aged Patient: A Systematic Review

    PubMed Central

    Sheybani, Fereshte; Naderi, HamidReza; Sajjadi, Sareh

    2016-01-01

    The elderly comprise less than 13 percent of world population. Nonetheless, they represent nearly half of all hospitalized adults. Acute change in mental status from baseline is commonly seen among the elderly even when the main process does not involve the central nervous system. The term “geriatric syndrome” is used to capture those clinical conditions in older people that do not fit into discrete disease categories, including delirium, falls, frailty, dizziness, syncope, and urinary incontinence. Despite the growing number of elderly population, especially those who require hospitalization and the high burden of common infections accompanied by encephalopathy among them, there are several unresolved questions regarding the optimal management they deserve. The questions posed in this systematic review concern the need to rule out CNS infection in all elderly patients presented with fever and altered mental status in the routine management of febrile encephalopathy. In doing so, we sought to identify all potentially relevant articles using searches of web-based databases with no language restriction. Finally, we reviewed 93 research articles that were relevant to each part of our study. No prospective study was found to address how should AFE in the aged be optimally managed. PMID:26989409

  19. Loss of synaptic Zn2+ transporter function increases risk of febrile seizures

    PubMed Central

    Hildebrand, Michael S.; Phillips, A. Marie; Mullen, Saul A.; Adlard, Paul A.; Hardies, Katia; Damiano, John A.; Wimmer, Verena; Bellows, Susannah T.; McMahon, Jacinta M.; Burgess, Rosemary; Hendrickx, Rik; Weckhuysen, Sarah; Suls, Arvid; De Jonghe, Peter; Scheffer, Ingrid E.; Petrou, Steven; Berkovic, Samuel F.; Reid, Christopher A.

    2015-01-01

    Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn2+) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn2+ homeostasis contributes to susceptibility is unknown. Synaptic Zn2+ is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn2+ into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn2+ increases the risk of FS and more broadly support the idea that impaired synaptic Zn2+ homeostasis can contribute to neuronal hyperexcitability. PMID:26647834

  20. Rapid, Coordinate Inflammatory Responses after Experimental Febrile Status Epilepticus: Implications for Epileptogenesis(1,2,3).

    PubMed

    Patterson, Katelin P; Brennan, Gary P; Curran, Megan; Kinney-Lang, Eli; Dubé, Celine; Rashid, Faisal; Ly, Catherine; Obenaus, Andre; Baram, Tallie Z

    2015-01-01

    Epilepsy is a common neurological disorder with many causes. For temporal lobe epilepsy, antecedent insults are typically found. These risk factors include trauma or history of long fever-associated seizures (febrile status epilepticus) in childhood. Whereas the mechanisms by which such insults promote temporal lobe epilepsy are unknown, an extensive body of work has implicated inflammation and inflammatory mediators in both human and animal models of the disorder. However, direct evidence for an epileptogenic role for inflammation is lacking. Here we capitalized on a model where only a subgroup of insult-experiencing rodents develops epilepsy. We reasoned that if inflammation was important for generating epilepsy, then early inflammation should be more prominent in individuals destined to become epileptic compared with those that will not become epileptic. In addition, the molecular and temporal profile of inflammatory mediators would provide insights into which inflammatory pathways might be involved in the disease process. We examined inflammatory profiles in hippocampus and amygdala of individual rats and correlated them with a concurrent noninvasive, amygdalar magnetic resonance imaging epilepsy-predictive marker. We found significant individual variability in the expression of several important inflammatory mediators, but not in others. Of interest, a higher expression of a subset of hippocampal and amygdalar inflammatory markers within the first few hours following an insult correlated with the epilepsy-predictive signal. These findings suggest that some components of the inflammatory gene network might contribute to the process by which insults promote the development of temporal lobe epilepsy. PMID:26730400

  1. Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

    PubMed

    Tao, K; Ichikawa, J; Matsuki, N; Ikegaya, Y; Koyama, R

    2016-03-24

    Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function. PMID:26794590

  2. Role of antineuronal antibodies in children with encephalopathy and febrile status epilepticus.

    PubMed

    Lin, Kuang-Lin; Wang, Huei-Shyong

    2014-06-01

    Status epilepticus in childhood is more common, with a different range of causes and a lower risk of death, than convulsive status epilepticus in adults. Acute central nervous system infections appear to be markers for morbidity and mortality. Nevertheless, central nervous infection is usually presumed in these conditions. Many aspects of the pathogenesis of acute encephalitis and acute febrile encephalopathy with status epilepticus have been clarified in the past decade. The pathogenesis is divided into direct pathogens invasion or immune-mediated mechanisms. Over the past few decades, the number of antineuronal antibodies to ion channels, receptors, and other synaptic proteins described in association with central nervous system disorders has increased dramatically, especially their role in pediatric encephalitis and status epilepticus. These antineuronal antibodies are divided according to the location of their respective antigens: (1) intracellular antigens, including glutamic acid decarboxylase and classical onconeural antigens such as Hu (antineuronal nuclear antibody 1, ANNA1), Ma2, Yo (Purkinje cell autoantibody, PCA1), Ri (antineuronal nuclear antibody 2, ANNA2), CV2/CRMP5, and amphiphysin; and (2) cell membrane ion channels or surface antigens including voltage-gated potassium channel receptor, N-methyl-d-aspartate receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, γ-aminobutyric acid(B) receptor, leucine-rich glioma-inactivated protein 1, and contactin-associated protein-like 2. Identifying the mechanism of the disease may have important therapeutic implications. PMID:24050844

  3. Cognitive outcomes in febrile infection-related epilepsy syndrome treated with the ketogenic diet.

    PubMed

    Singh, Rani K; Joshi, Sucheta M; Potter, Denise M; Leber, Steve M; Carlson, Martha D; Shellhaas, Rene A

    2014-11-01

    Febrile infection-related epilepsy syndrome (FIRES) is a newly recognized epileptic encephalopathy in which previously healthy school-aged children present with prolonged treatment-resistant status epilepticus (SE). Survivors are typically left with pharmacoresistant epilepsy and severe cognitive impairment. Various treatment regimens have been reported, all with limited success. The ketogenic diet (KD) is an alternative treatment of epilepsy and may be an appropriate choice for children with refractory SE. We report 2 previously healthy children who presented with FIRES and were placed on the KD during the acute phase of their illness. Both children experienced resolution of SE and were maintained on the KD, along with other anticonvulsant medications, for several months. Both were able to return to school, with some academic accommodations. These cases highlight the potential value of the KD as a preferred treatment in FIRES, not only in the acute setting but also for long-term management. Early KD treatment might optimize both seizure control and cognitive outcome after FIRES. PMID:25332495

  4. Virus identification in unknown tropical febrile illness cases using deep sequencing.

    PubMed

    Yozwiak, Nathan L; Skewes-Cox, Peter; Stenglein, Mark D; Balmaseda, Angel; Harris, Eva; DeRisi, Joseph L

    2012-01-01

    Dengue virus is an emerging infectious agent that infects an estimated 50-100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ?40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness. PMID:22347512

  5. 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

  6. Etiology of acute undifferentiated febrile illness in the Amazon basin of Ecuador.

    PubMed

    Manock, Stephen R; Jacobsen, Kathryn H; de Bravo, Narcisa Brito; Russell, Kevin L; Negrete, Monica; Olson, James G; Sanchez, Jos L; Blair, Patrick J; Smalligan, Roger D; Quist, Brad K; Espn, Juan Freire; Espinoza, Willan R; MacCormick, Fiona; Fleming, Lila C; Kochel, Tadeusz

    2009-07-01

    We conducted a longitudinal observational study of 533 patients presenting to two hospitals in the Ecuadorean Amazon basin with acute undifferentiated febrile illness (AUFI) from 2001 through 2004. Viral isolation, reverse transcription-polymerase chain reaction (RT-PCR), IgM seroconversion, and malaria smears identified pathogens responsible for fever in 122 (40.1%) of 304 patients who provided both acute and convalescent blood samples. Leptospirosis was found in 40 (13.2%), malaria in 38 (12.5%), rickettsioses in 18 (5.9%), dengue fever in 16 (5.3%), Q fever in 15 (4.9%), brucellosis in 4 (1.3%), Ilhus infection in 3 (1.0%), and Venezuelan equine encephalitis (VEE), Oropouche, and St. Louis encephalitis virus infections in less than 1% of these patients. Viral isolation and RT-PCR on another 229 participants who provided only acute samples identified 3 cases of dengue fever, 2 of VEE, and 1 of Ilhus. None of these pathogens, except for malaria, had previously been detected in the study area. PMID:19556580

  7. What is your diagnosis? Subcutaneous mass fluid from a febrile dog.

    PubMed

    Bulla, Camilo; Thomas, Jennifer S

    2009-09-01

    A 10-month-old spayed female Doberman Pinscher was presented for lameness. On physical examination, the dog was lethargic and febrile and had a 2-cm raised subcutaneous mass at the base of the left ear. Fluid from the mass was drained. Direct smears of the fluid, stained with modified Wright's and new methylene blue, were highly cellular and contained large numbers of degenerate neutrophils with moderate numbers of macrophages. Large numbers of round yeast organisms, 8-20 mum in diameter, were observed extracellularly. The organisms had a thick blue wall and granular internal contents and broad-based budding was seen frequently. Branching hyphae or pseudohyphae, with parallel sides and 2-4 mum in diameter, appeared to extend from the surface of the yeast. The morphology of the yeast organisms was consistent with Blastomyces dermatitidis, with atypical hyphae formation. Culture results were not definitive because it was not possible to induce transition from the mycelial to the yeast form at 37 degrees C and because the morphology of the mycelial form of B. dermatitidis could not be differentiated from that of Emmonsia parvae. The organism was confirmed as Ajellomyces dermatitidis (the mycelial form of B. dermatitidis) using 18S ribosome RNA gene sequencing and comparison with an available databank. The mycelial form of B. dermatitidis is rarely found in the tissue of dogs, and may have been induced in this case by low environmental temperatures and the time delay between sample collection and slide preparation. PMID:19351342

  8. Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic Anemia

    PubMed Central

    Hashiba, Masamitsu; Tomino, Atsutoshi; Takenaka, Nobuyoshi; Hattori, Tomonori; Kano, Hideki; Tsuda, Masanobu; Takeyama, Naoshi

    2016-01-01

    Patient: Male, 82 Final Diagnosis: Clostridium perfringens infection Symptoms: Anemia • fever • shock Medication: — Clinical Procedure: Antimicrobial chemotherapy Specialty: Infectious Diseases Objective: Rare disease Background: Clostridium perfringens (C. perfringens) can cause various infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. Case Report: We present the case of a male patient with diabetes who developed a fatal liver abscess with massive intravascular hemolysis and septic shock caused by toxigenic C. perfringens. The peripheral blood smear showed loss of central pallor, with numerous spherocytes. Multiplex PCR only detected expression of the cpa gene, indicating that the pathogen was C. perfringens type A. Conclusions: C. perfringens infection should be considered in a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed blood sample, and negative Coombs test. The characteristic peripheral blood smear findings may facilitate rapid diagnosis. PMID:27049736

  9. Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection

    PubMed Central

    Han, Song Yi; Lee, I Re; Park, Se Jin; Kim, Ji Hong

    2016-01-01

    Purpose Acute pyelonephritis (APN) is a serious bacterial infection that can cause renal scarring in children. Early identification of APN is critical to improve treatment outcomes. The neutrophil-lymphocyte ratio (NLR) is a prognostic marker of many diseases, but it has not yet been established in urinary tract infection (UTI). The aim of this study was to determine whether NLR is a useful marker to predict APN or vesicoureteral reflux (VUR). Methods We retrospectively evaluated 298 pediatric patients (age≤36 months) with febrile UTI from January 2010 to December 2014. Conventional infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and NLR were measured. Results WBC, CRP, ESR, and NLR were higher in APN than in lower UTI (P<0.001). Multiple logistic regression analyses showed that NLR was a predictive factor for positive dimercaptosuccinic acid (DMSA) defects (P<0.001). The area under the receiver operating characteristic (ROC) curve was high for NLR (P<0.001) as well as CRP (P<0.001) for prediction of DMSA defects. NLR showed the highest area under the ROC curve for diagnosis of VUR (P<0.001). Conclusion NLR can be used as a diagnostic marker of APN with DMSA defect, showing better results than those of conventional markers for VUR prediction. PMID:27186221

  10. Teicoplanin as modification of initial empirical therapy in febrile granulocytopenic patients.

    PubMed

    Nováková, I R; Donnelly, J P; Verhagen, C S; De Pauw, B E

    1990-06-01

    Teicoplanin at a dose of 400 mg per day was added to the initial empirical therapy of 65 of 202 febrile granulocytopenic episodes. Of 53 cases evaluable for outcome 23 (43%) responded. Responders and nonresponders were comparable in terms of time of starting teicoplanin treatment, duration of therapy and of granulocytopenia, number of granulocytopenic days after therapy was stopped and peak and through concentrations of the drug. Teicoplanin was given most often because of persistent fever or initial Gram-positive bacteraemia and only one-third of these cases responded. However, when teicoplanin was given because of proven or presumed Gram-positive infection 67% of cases were treated successfully. Patients with skin and soft tissue infections achieved a 78% response rate. The development of a lung infiltrate was the most common reason for failure to respond, although in most instances the aetiology was not determined. Serum concentrations of teicoplanin were predictable; peak and trough concentrations on the fourth day were 30.4 +/- 5.0 mg/l and 9.8 +/- 1.7 mg/l, respectively. Concentrations achieved in individual patients did not correspond to outcome. Hearing loss of 20 dB at 800 Hz was noted in one of 15 cases and transient liver or kidney disturbances attributable to the drug were observed in 4% of cases. Teicoplanin therapy was safe but only effective when used to treat infective episodes with a high probability of being due to Gram-positive bacteria. PMID:2142486

  11. Longitudinal assessment of skill development in children with first febrile seizure

    PubMed Central

    Leaffer, Emily B.; Hinton, Veronica J.; Hesdorffer, Dale C.

    2013-01-01

    To determine whether first febrile seizure (FS) has detrimental effects on development, 159 children (6 months to 5 years) with FS were compared to 142 controls on measures of cognition, motor ability, and adaptive behavior. Participants were identified through the emergency department in an urban, low income community. Children were evaluated within one month of the ED visit and one year later, and difference in performance over one year was examined. Performance did not differ between cases and controls on measures of cognition (baseline: p=0.5, one year: p=0.2, change over time: p=0.1) or motor skills (baseline: p=0.9, one year: p=0.7, change over time, p=0.6). The adaptive behavior composite score did not differ by FS case status at baseline (p=0.2) or one year later (p=0.6), however between group differences over time approached significance (p=0.05). Findings support that first FS does not pose more developmental or behavioral consequences than low socioeconomic environment. PMID:23669493

  12. 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

  13. Deficiency of the ribosome biogenesis gene Sbds in hematopoietic stem and progenitor cells causes neutropenia in mice by attenuating lineage progression in myelocytes

    PubMed Central

    Zambetti, Noemi A.; Bindels, Eric M. J.; Van Strien, Paulina M. H.; Valkhof, Marijke G.; Adisty, Maria N.; Hoogenboezem, Remco M.; Sanders, Mathijs A.; Rommens, Johanna M.; Touw, Ivo P.; Raaijmakers, Marc H. G. P.

    2015-01-01

    Shwachman-Diamond syndrome is a congenital bone marrow failure disorder characterized by debilitating neutropenia. The disease is associated with loss-of-function mutations in the SBDS gene, implicated in ribosome biogenesis, but the cellular and molecular events driving cell specific phenotypes in ribosomopathies remain poorly defined. Here, we established what is to our knowledge the first mammalian model of neutropenia in Shwachman-Diamond syndrome through targeted downregulation of Sbds in hematopoietic stem and progenitor cells expressing the myeloid transcription factor CCAAT/enhancer binding protein α (Cebpa). Sbds deficiency in the myeloid lineage specifically affected myelocytes and their downstream progeny while, unexpectedly, it was well tolerated by rapidly cycling hematopoietic progenitor cells. Molecular insights provided by massive parallel sequencing supported cellular observations of impaired cell cycle exit and formation of secondary granules associated with the defect of myeloid lineage progression in myelocytes. Mechanistically, Sbds deficiency activated the p53 tumor suppressor pathway and induced apoptosis in these cells. Collectively, the data reveal a previously unanticipated, selective dependency of myelocytes and downstream progeny, but not rapidly cycling progenitors, on this ubiquitous ribosome biogenesis protein, thus providing a cellular basis for the understanding of myeloid lineage biased defects in Shwachman-Diamond syndrome. PMID:26185170

  14. The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64.

    PubMed

    McCarthy, Desmond A; Macey, Marion G; Streetly, Matthew; Schey, Stephen A; Brown, K Alun

    2006-07-01

    A major limitation to the treatment of multiple myeloma by the thalidomide analogue CC-4047 (Actimid) is the development of a severe neutropenia. We investigated the hypothesis that this effect may have been due to CC-4047 enhancing the removal of neutrophils from the circulation by altering the expression of surface adhesion molecules required for endothelial binding, by binding to platelets, or by enhancing apoptosis. Flow cytometric analysis was used to examine the expression of neutrophil surface molecules, platelet binding and apoptosis in whole blood samples from 19 patients with multiple myeloma who were assigned to receive either 1, 2, 5 or 10 mg of CC-4047 every other day (e.o.d.) for 28 days. CC-4047 induced dose-related decreases in neutrophil numbers and increases in the percentage of CD64-positive neutrophils, but had little, or no effect on the expression of CD11b, CD62L or CD162, neutrophil-platelet binding, or apoptosis. Relative decreases in the neutrophil count were inversely associated with relative increases in the intensity of CD64 expression on neutrophils (r=- 0.307; p=0.028). Although seven patients developed severe neutropenia, none suffered severe or recurrent bacterial infections. The percentage of CD64-positive neutrophils was still increased in eight patients who continued receiving 1-5 mg CC-4047 e.o.d. for several months afterwards, but neutrophil counts were similar to pre-treatment values. PMID:16714224

  15. Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients.

    PubMed

    Atasilp, Chalirmporn; Chansriwong, Pichai; Sirachainan, Ekapob; Reungwetwattana, Thanyanan; Chamnanphon, Montri; Puangpetch, Apichaya; Wongwaisayawan, Sansanee; Sukasem, Chonlaphat

    2016-02-01

    UDP-glucuronosyltransferase1A1 (UGT1A1) polymorphisms have been related with irinotecan toxicity. The purpose of this study was to determine the associations between UGT1A1(*)28 and (*)6 polymorphisms and irinotecan toxicity in Thai patients with metastatic colorectal cancer. 44 metastatic colorectal cancer patients received irinotecan-based chemotherapy. Hematologic toxicities were determined in the first and second cycles of treatment. The genotypes of UGT1A1(*)28 and (*)6 were analyzed by pyrosequencing technique. The frequencies of genetic testing for UGT1A1(*)28 and (*)6 polymorphisms were 22.8% (TA6/TA7; 20.5%, TA7/TA7; 2.3%) and 15.9% (GA), respectively. No patients had the homozygous UGT1A1(*)6 (AA). Neither UGT1A1(*)28 nor UGT1A1(*)6 polymorphisms were significantly associated with severe hematologic toxicities. However, analysis of UGT1A1(*)28 and (*)6 in combination revealed an association with severe neutropenia in the first and second cycles (P = 0.044, P = 0.017, respectively). Both UGT1A1(*)28 and (*)6 polymorphisms may have an increased risk of irinotecan-induced neutropenia in Thai colorectal cancer patients. PMID:26830078

  16. Postnatal interleukin-1β administration after experimental prolonged febrile seizures enhances epileptogenesis in adulthood.

    PubMed

    Fukuda, Mitsumasa; Ito, Masanori; Yano, Yoshiaki; Takahashi, Hisaaki; Motoie, Ryota; Yano, Akiko; Suzuki, Yuka; Ishii, Eiichi

    2015-06-01

    It remains unclear whether prolonged febrile seizures (pFS) in childhood facilitate mesial temporal lobe epilepsy (MTLE) in adulthood. Interleukin (IL)-1β is associated with seizures in children and immature animal models. Here, we use a rat model of pFS to study the effects of IL-1β on adult epileptogenesis, hippocampal damage, and cognition. We produced prolonged hyperthermia-induced seizures on postnatal days (P) 10-11 and administered IL-1β or saline intranasally immediately after the seizures. Motor and cognitive functions were assessed at P85 using rotarod and passive avoidance tests. Electroencephalogram recordings were conducted at P90 and P120. Hippocampal CA1 and CA3 neurons and gliosis were quantified at the end of the experiment. Spontaneous seizure incidence was significantly greater in rats that had received IL-1β than in those that had received saline or those without hyperthermia-induced seizures (p < 0.05). Seizure frequency did not differ significantly between the three groups and no motor deficits were observed. Passive avoidance learning was impaired in rats that received IL-1β compared with controls (p < 0.05), but was not different from that in rats that received saline. Hippocampal cell numbers and gliosis did not differ between the three groups. These results indicate that neuronal loss and gliosis are not prerequisites for the epileptogenic process that follows pFS. Our results suggest that infantile pFS combined with IL-1β overproduction can enhance adulthood epileptogenesis, and might contribute to the development of MTLE. PMID:25575695

  17. [Difficulties in diagnosing febrile states in 21-month-old patient: case report].

    PubMed

    Pilch, Bozena; Legutko, Magdalena; Pietrys, Danuta; Pietrzyk, Jacek J

    2007-01-01

    A 21-month-old girl was admitted to our Department of Pediatrics to diagnose febrile states lasting for previous two weeks, anemia and increased erythrocyte sedimentation rate (ESR - erythrocyte sedimentation rate). The physical examination revealed the paleness of skin and oral mucosa, silent systolic murmur and hypotrophic constitution. The laboratory tests confirmed anemia and showed increased ESR and moderately increased C Reactive Protein (CRP - C Reactive Protein). The blood culture, the urine culture, the stool culture, the tests of the stool in direction of parasites and the serologic tests carried out in direction of infection caused by Toxoplasma ghondi, Mycoplasma pneumoniae, HAV, HCV, CMV, EBV and Parvovirus B19 were all negative. The chest X-ray picture and ultrasonographic examination of abdomen showed no abnormality. The consulting hematologist carried the bone marrow biopsy out--the bone marrow was poorly cellular. The urinary level of catecholamines and plasma level of neuron-specific enolase (NSE) were greatly increased. The computer tomography scan of head, neck, thorax and abdomen did not confirmed the presence of the tumor. Nevertheless the bone scintigraphy demonstrated the presence of foci of abnormally increased activity in left femur and the right hip-bone--pathognomonic of metastatic disease. During the hospitalization we did not observe the fever, but only the deepening anemia, weakness, irritability, limping and the presence of spectacle-shaped hematomas. The blood parameters temporarily were normal after blood transfusion. The patient was transmitted to the Department of Children's Oncology and Hematology. The trepanobiopsy of the bone marrow showed the presence of metastases of neuroblastoma. The magnetic resonance imaging (MRI) was made, but it did not revealed the presence of the primary tumor. The patient underwent a course of chemotherapy. PMID:18434975

  18. "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to Germany from Vacation in Southern Africa.

    PubMed

    Fingerle, Volker; Pritsch, Michael; Wächtler, Martin; Margos, Gabriele; Ruske, Sabine; Jung, Jette; Löscher, Thomas; Wendtner, Clemens; Wieser, Andreas

    2016-03-01

    A 26 year-old female patient presented to the Tropical Medicine outpatient unit of the Ludwig Maximilians-University in Munich with febrile illness after returning from Southern Africa, where she contracted a bite by a large mite-like arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained blood smears and treatment was started with doxycycline for suspected tick-borne relapsing fever. The patient eventually recovered after developing a slight Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA-blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia duttonii, and B. parkeri. Further sequences obtained from the flagellin gene (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B. duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of 0.086 to B. hermsii in genetic analysis and only distant relations with classic Old World relapsing fever species. This revealed the presence of a novel species of tick-borne relapsing fever spirochetes that we propose to name "Candidatus Borrelia kalaharica", as it was contracted from an arthropod bite in the Kalahari Desert belonging to both, Botswana and Namibia, a region where to our knowledge no relapsing fever has been described so far. Interestingly, the novel species shows more homology to New World relapsing fever Borrelia such as B. parkeri or B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. PMID:27031729

  19. "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to Germany from Vacation in Southern Africa

    PubMed Central

    Wächtler, Martin; Margos, Gabriele; Ruske, Sabine; Jung, Jette; Löscher, Thomas; Wendtner, Clemens; Wieser, Andreas

    2016-01-01

    A 26 year-old female patient presented to the Tropical Medicine outpatient unit of the Ludwig Maximilians-University in Munich with febrile illness after returning from Southern Africa, where she contracted a bite by a large mite-like arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained blood smears and treatment was started with doxycycline for suspected tick-borne relapsing fever. The patient eventually recovered after developing a slight Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA-blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia duttonii, and B. parkeri. Further sequences obtained from the flagellin gene (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B. duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of 0.086 to B. hermsii in genetic analysis and only distant relations with classic Old World relapsing fever species. This revealed the presence of a novel species of tick-borne relapsing fever spirochetes that we propose to name “Candidatus Borrelia kalaharica”, as it was contracted from an arthropod bite in the Kalahari Desert belonging to both, Botswana and Namibia, a region where to our knowledge no relapsing fever has been described so far. Interestingly, the novel species shows more homology to New World relapsing fever Borrelia such as B. parkeri or B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. PMID:27031729

  20. Searsia chirindensis reverses the potentiating effect of prenatal stress on the development of febrile seizures and decreased plasma interleukin-1β levels.

    PubMed

    Qulu, Lihle; Daniels, Willie M U; Russell, Vivienne; Mabandla, Musa V

    2016-02-01

    It is estimated that more than 80% of patients with epilepsy live in developing countries with 50-60% of them being children. This high prevalence is perpetuated by low socio-economic challenges, poor health care facilities and lack of drug affordability. Searsia chirindensis formerly known as rhus chirindensis and commonly known as 'Red Current' is a popular traditional medicinal plant, which has been used to treat a number of illnesses such as heart complaints and neurological disorders. The aim of this study is to investigate the effects of S. chirindensis on the development of febrile seizure in a prenatally stressed rat. Febrile seizures were induced by administering lipopolysaccharide to 14-day-old rat pups followed by kainic acid. A subset of the rats was treated with Searsia after induction of febrile seizures. Interleukin-1β (IL-1β) levels were measured in plasma. Lipid peroxidation was determined in liver tissue. Our data shows that treatment with Searsia reduced interleukin-1β levels in plasma of the febrile seizure rats and prevented lipid oxidation in the liver. Prenatal stress is dampened by the beneficial effects of Searsia on seizure development in rat pups. These results highlight the potentiating effects of Searsia in the reversal of febrile seizures and prenatal stress effects. PMID:26320878

  1. Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis

    PubMed Central

    Oguri, Masayoshi; Saito, Yoshiaki; Fukuda, Chisako; Kishi, Kazuko; Yokoyama, Atsushi; Lee, Sooyoung; Torisu, Hiroyuki; Toyoshima, Mitsuo; Sejima, Hitoshi; Kaji, Shunsaku; Hamano, Shin-ichiro; Okanishi, Toru; Tomita, Yutaka; Maegaki, Yoshihiro

    2016-01-01

    Background To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. Methods We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. Results Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. Conclusion Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD. PMID:27046946

  2. Acute respiratory infection and bacteraemia as causes of non-malarial febrile illness in African children: a narrative review

    PubMed Central

    Muro, Florida; Reyburn, Rita; Reyburn, Hugh

    2015-01-01

    The replacement of “presumptive treatment for malaria” by “test before treat” strategies for the management of febrile illness is raising awareness of the importance of knowing more about the causes of illness in children who are suspected to have malaria but return a negative parasitological test. The most common cause of non-malarial febrile illness (NMFI) in African children is respiratory tract infection. Whilst the bacterial causes of NMFI are well known, the increasing use of sensitive techniques such as polymerase chain reaction (PCR) tests is revealing large numbers of viruses that are potential respiratory pathogens. However, many of these organisms are commonly present in the respiratory tract of healthy children so causality and risk factors for pneumonia remain poorly understood. Infection with a combination of viral and bacterial pathogens is increasingly recognised as important in the pathogenesis of pneumonia. Similarly, blood stream infections with organisms typically grown by aerobic culture are well known but a growing number of organisms that can be identified only by PCR, viral culture, or serology are now recognised to be common pathogens in African children. The high mortality of hospitalised children on the first or second day of admission suggests that, unless results are rapidly available, diagnostic tests to identify specific causes of illness will still be of limited use in guiding the potentially life saving decisions relating to initial treatment of children admitted to district hospitals in Africa with severe febrile illness and a negative test for malaria. Malaria control and the introduction of vaccines against Haemophilus influenzae type b and pneumococcal disease are contributing to improved child survival in Africa. However, increased parasitological testing for malaria is associated with increased use of antibiotics to which resistance is already high. PMID:26594615

  3. Rapid Diagnostic Tests for Dengue Virus Infection in Febrile Cambodian Children: Diagnostic Accuracy and Incorporation into Diagnostic Algorithms

    PubMed Central

    Carter, Michael J.; Emary, Kate R.; Moore, Catherine E.; Parry, Christopher M.; Sona, Soeng; Putchhat, Hor; Reaksmey, Sin; Chanpheaktra, Ngoun; Stoesser, Nicole; Dobson, Andrew D. M.; Day, Nicholas P. J.; Kumar, Varun; Blacksell, Stuart D.

    2015-01-01

    Background Dengue virus (DENV) infection is prevalent across tropical regions and may cause severe disease. Early diagnosis may improve supportive care. We prospectively assessed the Standard Diagnostics (Korea) BIOLINE Dengue Duo DENV rapid diagnostic test (RDT) to NS1 antigen and anti-DENV IgM (NS1 and IgM) in children in Cambodia, with the aim of improving the diagnosis of DENV infection. Methodology and principal findings We enrolled children admitted to hospital with non-localised febrile illnesses during the 5-month DENV transmission season. Clinical and laboratory variables, and DENV RDT results were recorded at admission. Children had blood culture and serological and molecular tests for common local pathogens, including reference laboratory DENV NS1 antigen and IgM assays. 337 children were admitted with non-localised febrile illness over 5 months. 71 (21%) had DENV infection (reference assay positive). Sensitivity was 58%, and specificity 85% for RDT NS1 and IgM combined. Conditional inference framework analysis showed the additional value of platelet and white cell counts for diagnosis of DENV infection. Variables associated with diagnosis of DENV infection were not associated with critical care admission (70 children, 21%) or mortality (19 children, 6%). Known causes of mortality were melioidosis (4), other sepsis (5), and malignancy (1). 22 (27%) children with a positive DENV RDT had a treatable other infection. Conclusions The DENV RDT had low sensitivity for the diagnosis of DENV infection. The high co-prevalence of infections in our cohort indicates the need for a broad microbiological assessment of non-localised febrile illness in these children. PMID:25710684

  4. Investigating the presence of fungal agents in febrile neutropenic patients with hematological malignancies using different microbiological, serological, and molecular methods

    PubMed Central

    Sönmez, Ahu; Eksi, Fahriye; Pehlivan, Mustafa; Sahin, Handan Haydaroglu

    2015-01-01

    This study aimed to investigate fungal agents in febrile neutropenic patients with hematological malignancies. Direct microscopy and cultures were performed on clinical samples collected from febrile neutropenic episodes. The galactomannan (GM) antigen was tested using enzyme-linked immunosorbent assays, and Aspergillus fumigatus and Candida albicans deoxyribonucleic acid (DNA) assessed using real-time polymerase chain reaction (PCR) in consecutive serum samples. Of the 199 episodes investigated, 1.5% were classified as definite invasive aspergillosis (IA), 4.0% as IA with high probability, and 4.0% as IA with low probability. Additionally, candidaemia was detected in eight episodes (4.1%). The GM antigen was found negative for 86.4% of episodes, as one positive for 7.0% of episodes, as two or more consecutive positives for 5.5% of episodes, and as positive in any two serum samples in 1.0% of episodes. While no C. albicans DNA was detected in 98.5% of 199 ­episodes, one positive result was obtained in 1.0% of episodes, and two or more consecutive positives in 0.5% of episodes. A. fumigatus PCR results were found negative in 81.9% of episodes, as one positive in 16.1% of episodes, as positive in any two serum samples in 1.0% of episodes, and consecutively positive in 1.0% of episodes. GM antigen tests were found consecutively positive in all three patients diagnosed as having definite IA. These findings indicate that conventional, serological, and molecular methods should be used in combination to detect fungal agents in febrile neutropenic patients. PMID:26295293

  5. Risk of febrile seizures after first dose of measles–mumps–rubella–varicella vaccine: a population-based cohort study

    PubMed Central

    MacDonald, Shannon E.; Dover, Douglas C.; Simmonds, Kimberley A.; Svenson, Lawrence W.

    2014-01-01

    Background: The combination measles–mumps–rubella–varicella (MMRV) vaccine currently used in Canada (Priorix-Tetra) may increase the risk of febrile seizures relative to the separate vaccines (MMR and varicella) previously administered. We determined the risk of febrile seizure after the first dose of MMRV, as well as any additional risk for children at high risk for seizures because of pre-existing medical conditions. Methods: In this retrospective, population-based cohort study, we compared the risk of seizures after the first dose of MMRV with the risk after same-day administration of separate MMR and varicella vaccines (MMR+V) in children 12 to 23 months of age in the province of Alberta. We deterministically linked vaccination data to health service utilization data for seizures. We used Poisson regression, with adjustment for age and calendar year, to determine the risk for the full cohort and for high-risk children. Results: The risk of seizures 7 to 10 days after vaccination was twice as high with MMRV as with MMR+V (relative risk [RR] 1.99, 95% confidence interval [CI] 1.30–3.05). The excess absolute risk of seizures was 3.52 seizures per 10 000 doses of MMRV relative to MMR+V. In high-risk children, the risk was not differentially higher for MMRV (RR 1.30, 95% CI 0.60–2.79). Interpretation: Despite an increased risk of febrile seizures following MMRV (compared with MMR+V), the absolute level of risk was small. Policy-makers need to balance these findings with the potential benefits of administering the combination vaccine or determine whether the choice of vaccine rests with clinicians and/or parents. PMID:24914115

  6. Febrile seizures in one-five aged infants in tropical practice: Frequency, etiology and outcome of hospitalization

    PubMed Central

    Assogba, Komi; Balaka, Bahoura; Touglo, Fidato A.; Apetsè, Kossivi M.; Kombaté, Damelan

    2015-01-01

    Background: Convulsive seizures are the common neurological emergencies in developing regions. Objectives: The aim was to determine the prevalence, causes and outcome of seizures in childhood. Patients and Methods: Participants were children aged 1–5 years old, admitted consecutively with a history of febrile convulsions or were presented seizures with fever during hospitalization, in two pediatric university hospitals. The prospective study covered a period from January to December 2013. At admission, emergency care and resuscitation procedures were provided according to the national guidelines. The history included the number and a parental description of seizures. Children with epilepsy, any central nervous system infections and other disease were excluded. Results: We have recorded 3647 children. Among them, 308 (8.4%) infants had presented with febrile seizures including 174 males and 134 females admitted to both pediatric hospitals (Tokoin University Teaching Hospitals: 206/3070, Campus University Teaching Hospitals: 102/577). Infants from 1 to 3 years age were the most common affected and constituted 65.9% of all patients. The months of September, December and January had recorded the high frequency of admission due to seizures. Regarding the seizures type, generalized tonic-clonic seizures were predominant (46.4%) followed by tonic seizures (17.2%) and status epilepticus in 9%. The etiologies were marked by falciparum malaria (52.3%), and other infections in 47.7%. At discharge, we have noted 11% (34/308) with neurodevelopmental disabilities, 6.7% of epilepsy and 9.7% (30/308) of death. Conclusion: The febrile seizure in child younger 5 years is an indicator of severe malaria in tropical nations. The campaign for “roll back malaria” must continue in developing countries to avoid long-term gross neurological deficits. PMID:25878734

  7. Stroke-Like Presentation Following Febrile Seizure in a Patient with 1q43q44 Deletion Syndrome

    PubMed Central

    Robinson, J. Elliott; Wolfe, Stephanie M.; Kaiser-Rogers, Kathleen; Greenwood, Robert S.

    2016-01-01

    Hemiconvulsion–hemiplegia–epilepsy syndrome (HHE) is a rare outcome of prolonged hemiconvulsion that is followed by diffuse unilateral hemispheric edema, hemiplegia, and ultimately hemiatrophy of the affected hemisphere and epilepsy. Here, we describe the case of a 3-year-old male with a 1;3 translocation leading to a terminal 1q43q44 deletion and a terminal 3p26.1p26.3 duplication that developed HHE after a prolonged febrile seizure and discuss the pathogenesis of HHE in the context of the patient’s complex genetic background. PMID:27199890

  8. Prediction of Cortical Defect Using C-Reactive Protein and Urine Sodium to Potassium Ratio in Infants with Febrile Urinary Tract Infection

    PubMed Central

    Jung, Su Jin

    2016-01-01

    Purpose We investigated whether C-reactive protein (CRP) levels, urine protein-creatinine ratio (uProt/Cr), and urine electrolytes can be useful for discriminating acute pyelonephritis (APN) from other febrile illnesses or the presence of a cortical defect on 99mTc dimercaptosuccinic acid (DMSA) scanning (true APN) from its absence in infants with febrile urinary tract infection (UTI). Materials and Methods We examined 150 infants experiencing their first febrile UTI and 100 controls with other febrile illnesses consecutively admitted to our hospital from January 2010 to December 2012. Blood (CRP, electrolytes, Cr) and urine tests [uProt/Cr, electrolytes, and sodium-potassium ratio (uNa/K)] were performed upon admission. All infants with UTI underwent DMSA scans during admission. All data were compared between infants with UTI and controls and between infants with or without a cortical defect on DMSA scans. Using multiple logistic regression analysis, the ability of the parameters to predict true APN was analyzed. Results CRP levels and uProt/Cr were significantly higher in infants with true APN than in controls. uNa levels and uNa/K were significantly lower in infants with true APN than in controls. CRP levels and uNa/K were relevant factors for predicting true APN. The method using CRP levels, u-Prot/Cr, u-Na levels, and uNa/K had a sensitivity of 94%, specificity of 65%, positive predictive value of 60%, and negative predictive value of 95% for predicting true APN. Conclusion We conclude that these parameters are useful for discriminating APN from other febrile illnesses or discriminating true APN in infants with febrile UTI. PMID:26632389

  9. Effects of timing of vaccination (day 0 versus day 14 of a receiving period) with a modified-live respiratory viral vaccine on performance, feed intake, and febrile response of beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to evaluate the effects of timing of the administration of a modified-live respiratory viral vaccine on day 0 or on day 14 of a receiving period on performance, feed intake, and febrile response in beef heifers. Our hypothesis was vaccine timing will alter febrile res...

  10. Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome

    PubMed Central

    Jun, Hyun Sik; Lee, Young Mok; Cheung, Yuk Yin; McDermott, David H.; Murphy, Philip M.; De Ravin, Suk See; Mansfield, Brian C.

    2010-01-01

    G6PC3 deficiency, characterized by neutropenia and neutrophil dysfunction, is caused by deficiencies in the endoplasmic reticulum (ER) enzyme glucose-6-phosphatase-β (G6Pase-β or G6PC3) that converts glucose-6-phosphate (G6P) into glucose, the primary energy source of neutrophils. Enhanced neutrophil ER stress and apoptosis underlie neutropenia in G6PC3 deficiency, but the exact functional role of G6Pase-β in neutrophils remains unknown. We hypothesized that the ER recycles G6Pase-β–generated glucose to the cytoplasm, thus regulating the amount of available cytoplasmic glucose/G6P in neutrophils. Accordingly, a G6Pase-β deficiency would impair glycolysis and hexose monophosphate shunt activities leading to reductions in lactate production, adenosine-5′-triphosphate (ATP) production, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Using annexin V–depleted neutrophils, we show that glucose transporter-1 translocation is impaired in neutrophils from G6pc3−/− mice and G6PC3-deficient patients along with impaired glucose uptake in G6pc3−/− neutrophils. Moreover, levels of G6P, lactate, and ATP are markedly lower in murine and human G6PC3-deficient neutrophils, compared with their respective controls. In parallel, the expression of NADPH oxidase subunits and membrane translocation of p47phox are down-regulated in murine and human G6PC3-deficient neutrophils. The results establish that in nonapoptotic neutrophils, G6Pase-β is essential for normal energy homeostasis. A G6Pase-β deficiency prevents recycling of ER glucose to the cytoplasm, leading to neutrophil dysfunction. PMID:20498302

  11. Hospital-Based Surveillance for Infectious Etiologies Among Patients with Acute Febrile Illness in Georgia, 2008-2011.

    PubMed

    Kuchuloria, Tinatin; Imnadze, Paata; Mamuchishvili, Nana; Chokheli, Maiko; Tsertsvadze, Tengiz; Endeladze, Marina; Mshvidobadze, Ketevan; Gatserelia, Lana; Makhviladze, Manana; Kanashvili, Marine; Mikautadze, Teona; Nanuashvili, Alexander; Kiknavelidze, Khatuni; Kokaia, Nora; Makharadze, Manana; Clark, Danielle V; Bautista, Christian T; Farrell, Margaret; Fadeel, Moustafa Abdel; Maksoud, Mohamed Abdel; Pimentel, Guillermo; House, Brent; Hepburn, Matthew J; Rivard, Robert G

    2016-01-01

    Information on the infectious causes of undifferentiated acute febrile illness (AFI) in Georgia is essential for effective treatment and prevention. In May 2008, a hospital-based AFI surveillance was initiated at six hospitals in Georgia. Patients aged ≥ 4 years with fever ≥ 38°C for ≥ 48 hours were eligible for surveillance. Blood culture and serologic testing were conducted for Leptospira spp., Brucella spp., West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus, Coxiella burnetii, tick-borne encephalitis virus (TBEV), hantavirus, Salmonella enterica serovar Typhi (S. Typhi), and Rickettsia typhi. Of 537 subjects enrolled, 70% were outpatients, 54% were males, and the mean age was 37 years. Patients reported having fatigue (89%), rigors (87%), sweating (83%), pain in joints (49%), and sleep disturbances (42%). Thirty-nine (7%) patients were seropositive for R. typhi, 37 (7%) for Brucella spp., 36 (7%) for TBEV, 12 (2%) for Leptospira spp., 10 (2%) for C. burnetii, and three (0.6%) for S. Typhi. None of the febrile patients tested positive for WNV antibodies. Of the patients, 73% were negative for all pathogens. Our results indicate that most of the targeted pathogens are present in Georgia, and highlight the importance of enhancing laboratory capacity for these infectious diseases. PMID:26438032

  12. Dengue: etiology of acute febrile illness in Abidjan, Côte d'Ivoire, in 2011–2012

    PubMed Central

    L'Azou, Maïna; Succo, Tiphanie; Kamagaté, Mamadou; Ouattara, Abdoulaye; Gilbernair, Elia; Adjogoua, Edgar; Luxemburger, Christine

    2015-01-01

    Background The burden of dengue in Africa is not well understood. A prospective study was conducted in Abidjan, Côte d'Ivoire from December 2011 to December 2012 to estimate the proportion of dengue and malaria cases among febrile patients during a period when dengue was not known to be circulating in the region, and to describe the clinical and virological characteristics of laboratory-diagnosed dengue cases. Methods Blood samples were taken from febrile patients (body temperature ≥38°C) at two study sites. Patients with fever lasting more than 7 days, with fever of known origin and with jaundice were excluded. Thick blood film tests, ELISA for anti-dengue IgM and reverse transcription-PCR (RT-PCR) were performed. Results A total of 812 patients were enrolled (51.7% male [48.3% female]; 46.4% aged <10 years) of whom 796 (98.0%) provided IgM ELISA and RT-PCR data, and 807 (99.4%) had thick blood film results. Three (0.4%) patients had laboratory-diagnosed dengue (one with DENV-3 serotype), none of whom were diagnosed clinically, and 234 (28.8%) had confirmed malaria. Conclusions This study suggests that dengue virus circulates in Abidjan outside an epidemic and that there should be an increase in awareness of dengue as a possible diagnosis in cases of undifferentiated fever. These results stress the importance of implementing laboratory capacity to assess dengue burden in Africa. PMID:26385938

  13. Prevalence of malaria among acute febrile patients clinically suspected of having malaria in the Zeway Health Center, Ethiopia.

    PubMed

    Feleke, Sendeaw M; Animut, Abebe; Belay, Mulugeta

    2015-01-01

    Malaria diagnosis is a common challenge in developing countries with limited diagnostic services. Common febrile illnesses were assessed in 280 malaria-suspected patients, and each case was subjected to clinical and laboratory examinations for malaria, relapsing fever, typhoid fever, typhus, and brucellosis. Data were entered and analyzed using Epi Info version 3.1 software. Malaria accounted for 17% (CI, 12.6-21.4%) of febrile illnesses. The remaining cases were associated with typhoid fever (18.5%; CI, 13.95-23.05%), typhus (17.8%; CI, 13.32-22.28%), brucellosis (1%; CI, -0.17-2.17%), relapsing fever (2%; CI, 0.36-3.64%), and unknown causes (44%). Approximately 7% of patients had coinfections, and 2% of patients treated as monoinfections. Approximately 1.4% of the nonmalarial patients received antimalarial treatment. The sensitivity and specificity of the CareStart Pf/pan rapid diagnostic tests in comparison with those of microscopy were 100% and 91%, respectively, with positive- and negative-predictive values of 94% and 100%, respectively. Compared with microscopy, the positive-predictive value of each malaria symptom was much lower than that of the symptoms combined: fever, 17%; sweating, 30%; headache, 18%; general body ache, 22%; loss of appetite, 21%. The study findings revealed a high proportion of nonmalarial illnesses were clinically categorized as malaria. Parasite-based diagnosis is recommended for the management of malarial and nonmalarial cases. PMID:25420658

  14. pap genotype and P fimbrial expression in Escherichia coli causing bacteremic and nonbacteremic febrile urinary tract infection.

    PubMed

    Otto, G; Magnusson, M; Svensson, M; Braconier, J; Svanborg, C

    2001-06-01

    Escherichia coli strains from patients with febrile urinary tract infections (n=73) were examined for pap genotype and P fimbrial expression in relation to bacteremia and patients' background variables. Most isolates were pap(+) by DNA hybridization (n=51), and 36 were papG(IA2)(+) and 18 prsG(J96)(+) by polymerase chain reaction. The pap and papG genotypes of the infecting strain were shown to vary with host compromise, sex, and age. Bacteremia in noncompromised patients was caused by papG(IA2)(+) strains, but compromised hosts carried a mixture of papG(IA2)(+), prsG(J96)(+), and pap(-) strains. Women of all ages were infected with papG(IA2)(+) strains. Infected men carried prsG(J96)(+) or pap(-) strains and were older, and most had compromising conditions. papG(IA2)(+) strains predominated among patients with medical illness, whereas prsG(J96)(+) strains predominated among patients with urinary tract abnormalities. These findings emphasize the strong influence of host factors on the selection of E. coli strains causing febrile urinary tract infections. PMID:11340521

  15. Endotoxin exposure during late pregnancy alters ovine offspring febrile and hypothalamic-pituitary-adrenal axis responsiveness later in life.

    PubMed

    Fisher, Rebecca E; Karrow, Niel A; Quinton, Margaret; Finegan, Esther J; Miller, Stephan P; Atkinson, Jim L; Boermans, Herman J

    2010-07-01

    A growing number of studies indicate that maternal infection during pregnancy is associated with adverse fetal development and neonatal health. In this study, late gestating sheep (day 135) were challenged systemically with saline (0.9%) or Escherichia coli lipopolysaccharide endotoxin (400 ng/kg x 3 consecutive days, or 1.2 microg/kg x 1 day) in order to assess the impact of maternal endotoxemia on the developing fetal neuroendocrine-immune system. During adulthood, cortisol secretion and febrile responses of female offspring and the cortisol response of the male offspring to endotoxin (400 ng/kg), as well as the female cortisol response to adrenocorticotropic hormone (ACTH) challenge, were measured to assess neuroendocrine-immune function. These studies revealed that maternal endotoxin treatment during late gestation altered the female febrile and male and female cortisol response to endotoxin exposure later in life; however, the response was dependent on the endotoxin treatment regime that the pregnant sheep received. The follow-up ACTH challenge suggests that programing of the adrenal gland may be altered in the female fetus during maternal endotoxemia. The long-term health implications of these changes warrant further investigation. PMID:20536335

  16. Drugs indicated for mitochondrial dysfunction as treatments for acute encephalopathy with onset of febrile convulsive status epileptics.

    PubMed

    Omata, Taku; Fujii, Katsunori; Takanashi, Jun-Ichi; Murayama, Kei; Takayanagi, Masaki; Muta, Kaori; Kodama, Kazuo; Iida, Yukiko; Watanabe, Yoshimi; Shimojo, Naoki

    2016-01-15

    We studied the efficacy of drugs indicated for mitochondrial dysfunction in the treatment of 21 patients with acute encephalopathy with onset of febrile convulsive status epilepticus at our hospital from January 2006 to December 2014. Among them, 11 patients had been treated with a mitochondrial drug cocktail consisting of vitamin B1, vitamin C, biotin, vitamin E, coenzyme Q10, and l-carnitine (prescription group) and 10 patients were not treated with the cocktail (non-prescription group). We retrospectively reviewed age, trigger, clinical form, treatment start time, and sequelae. Clinical form was classified into a biphasic group presenting acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and a monophasic group. Sequelae were classified as (A) no sequelae group or (B) sequelae group, and differences in the interval between diagnosis and treatment were also evaluated. The sequelae were not different between the mitochondrial drug cocktail prescription and non-prescription groups, but significantly better in the group administered the mitochondrial drug cocktail within 24h (P=0.035). We expect that early treatment with a mitochondrial drug cocktail could prevent sequelae in acute encephalopathy with onset of febrile convulsive status epilepticus. PMID:26723974

  17. Aetiologies of Acute Undifferentiated Febrile illness in Adult Patients – an Experience from a Tertiary Care Hospital in Northern India

    PubMed Central

    Ahmad, Sohaib; Agarwal, R K; Dhar, Minakshi; Mittal, Manish; Sharma, Shiwani

    2015-01-01

    Introduction Acute undifferentiated febrile illness (AUFI) is a common clinical entity in most of the hospitals. The fever can be potentially fatal if the aetiology is not recognized and appropriately treated early. Aim To describe the aetiology of fever among patients in a tertiary care hospital in Northern India. Materials and Methods A one-year retro-prospective, observational study was conducted in adults (age>18years) presenting with undifferentiated febrile illness (of duration 5-14 days). Diagnosis was confirmed by suitable laboratory tests after exhaustive clinical examination. Results A total of 2547 patients with AUFI were evaluated. Of these, 1663 (65.3%) were males and 884 (34.7%) were females. Dengue (37.54%); enteric fever (16.5%); scrub typhus (14.42%); bacterial sepsis (10.3%); malaria (6.8%); hepatitis A (1.9%); hepatitis E (1.4%); leptospirosis (0.14%); were the main infections while no specific diagnosis could be delineated in 11%. Mixed infections were noted in 48 (1.9%) patients. Conclusion A good clinical acumen supported by the basic investigations can help diagnose the cause of fever with reasonable certainty. PMID:26816892

  18. Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer

    PubMed Central

    Di Lorenzo, Giuseppe; Bracarda, Sergio; Gasparro, Donatello; Gernone, Angela; Messina, Caterina; Zagonel, Vittorina; Puglia, Livio; Bosso, Davide; Dondi, Davide; Sonpavde, Guru; Lucarelli, Giuseppe; De Placido, Sabino; Buonerba, Carlo

    2016-01-01

    Abstract Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3–4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed “per cycle” incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel. The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis. “Per cycle” incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86–0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34–0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86–1; P = 0.07). Patients with a body surface area >2 m2 presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86–1; P = 0.07), but decreased odds of having G3 to 4 anemia. Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment. PMID:26765406

  19. The role of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the diagnosis of childhood febrile urinary tract infections

    PubMed Central

    İlarslan, Nisa Eda Çullas; Fitöz, Ömer Suat; Öztuna, Derya Gökmen; Küçük, Nuriye Özlem; Yalçınkaya, Fatma Fatoş

    2015-01-01

    Aim: This study assessed the ability of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the detection of childhood febrile urinary tract infections in comparison with the gold standard reference method: Tc-99m dimercaptosuccinicacid renal cortical scintigraphy. Material and Methods: This prospective study included 60 patients who were hospitalized with a first episode of febrile urinary tract infections. All children were examined with dimercaptosuccinicacid scan and tissue harmonic imaging ultrasound combined with power Doppler ultrasound within the first 3 days of admission. Results: Signs indicative of acute infection were observed in 29 patients according to the results of tissue harmonic imaging ultrasound combined with power Doppler ultrasound while dimercaptosuccinicacid scan revealed abnormal findings in 33 patients. The sensitivity, specificity, positive predictive value and negative predictive value of tissue harmonic imaging combined with power Doppler ultrasound using dimercaptosuccinicacid scintigraphy as the reference method in patients diagnosed with first episode febrile urinary tract infections were calculated as 57.58% (95% confidence interval: 40.81%–72.76%); 62.96% (95% confidence interval: 44.23%–78.47%); 65.52% (95% confidence interval: 52.04%–77%); 54.84% (95% confidence interval: 41.54%–67.52%); respectively. Conclusions: Although current results exhibit inadequate success of power Doppler ultrasound, this practical and radiation-free method may soon be comprise a part of the routine ultrasonographic evaluation of febrile urinary tract infections of childhood if patients are evaluated early and under appropriate sedation. PMID:26265892

  20. A comparison of lipopolysacchardie-induced febrile responses across heat-tolerant and -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...

  1. 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...

  2. Seasonal and geographic differences in treatment-seeking and household cost of febrile illness among children in Malawi

    PubMed Central

    2011-01-01

    Background Households in malaria endemic countries experience considerable costs in accessing formal health facilities because of childhood malaria. The Ministry of Health in Malawi has defined certain villages as hard-to-reach on the basis of either their distance from health facilities or inaccessibility. Some of these villages have been assigned a community health worker, responsible for referring febrile children to a health facility. Health facility utilization and household costs of attending a health facility were compared between individuals living near the district hospital and those in hard-to-reach villages. Methods Two cross-sectional household surveys were conducted in the Chikhwawa district of Malawi; one during each of the wet and dry seasons. Half the participating villages were located near the hospital, the others were in areas defined as hard-to-reach. Data were collected on attendance to formal health facilities and economic costs incurred due to recent childhood febrile illness. Results Those living in hard-to-reach villages were less likely to attend a formal health facility compared to those living near the hospital (Dry season: OR 0.35, 95%CI0.18-0.67; Wet season: OR 0.46, 95%CI0.27-0.80). Analyses including community health workers (CHW) as a source of formal health-care decreased the strength of this relationship, and suggested that consulting a CHW may reduce attendance at health facilities, even if indicated. Although those in hard-to-reach villages were still less likely to attend in both the dry (OR 0.53, 95%CI 0.25-1.11) and wet (OR 0.60, 95%CI 0.37-0.98) seasons. Household costs for those who attended a health facility were greater for those in HTR villages (Dry: USD5.24; Wet: USD5.60) than for those living near the district hospital (Dry: USD3.45; Wet: USD4.46). Conclusion Those living in hard-to-reach areas were less likely to attend a health facility for a childhood febrile event and experienced greater associated household costs. Consulting CHWs was infrequent, but appeared to reduce attendance at a health facility, even when indicated. Health service planners must consider geographic and financial barriers to accessing public health facilities in designing appropriate interventions. PMID:21303538

  3. WHERE DOES WATERBORNE GIARDIASIS OCCUR, AND WHY

    EPA Science Inventory

    Over 60 outbreaks of waterborne giardiasis occurred in the United States between 1965 and 1982, mainly in the Northeast, the Rocky Mountain states, and the Pacific states. Outbreaks most often occurred as a result of inadequate or interrupted treatment. Disinfection problems and ...

  4. A case of febrile ulceronecrotic Mucha-Habermann disease requiring debridement of necrotic skin and epidermal autograft.

    PubMed

    Yanaba, K; Ito, M; Sasaki, H; Inoue, M; Nobeyama, Y; Yonemoto, H; Ishiji, T; Tanaka, H; Kamide, R; Niimura, M

    2002-12-01

    We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization. PMID:12452879

  5. Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar – Aetiologies, Antibiotic Treatment and Outcome

    PubMed Central

    Elfving, Kristina; Shakely, Deler; Andersson, Maria; Baltzell, Kimberly; Ali, Abdullah S.; Bachelard, Marc; Falk, Kerstin I.; Ljung, Annika; Msellem, Mwinyi I.; Omar, Rahila S.; Parola, Philippe; Xu, Weiping; Petzold, Max; Trollfors, Birger; Björkman, Anders; Lindh, Magnus; Mårtensson, Andreas

    2016-01-01

    Background Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. Methods We prospectively studied the aetiology of febrile illness in 677 children aged 2–59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. Findings NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. Conclusions This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low. PMID:26821179

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

    PubMed Central

    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

  7. Update: outbreak of acute febrile illness among athletes participating in Eco-Challenge-Sabah 2000--Borneo, Malaysia, 2000.

    PubMed

    2001-01-19

    During September 7-11, 2000, CDC was notified by the Idaho Department of Health, the Los Angeles County Department of Health Services, and the GeoSentinel Global Surveillance Network of at least 20 cases of acute febrile illness in three countries; all ill patients had participated in the Eco-Challenge-Sabah 2000 multisport expedition race in Borneo, Malaysia, during August 21-September 3, 2000. Participants included athletes from 29 U.S. states and 26 countries. This report updates the ongoing investigation of this outbreak through December 2, which suggests that Leptospira were the cause of illness and that water from the Segama River was the primary source of infection. Participants in adventure sports and exotic tourism should be aware of potential exposure to unusual and emerging infectious agents. PMID:11215718

  8. Challenges in the Etiology and Diagnosis of Acute Febrile Illness in Children in Low- and Middle-Income Countries.

    PubMed

    Iroh Tam, Pui-Ying; Obaro, Stephen K; Storch, Gregory

    2016-06-01

    Acute febrile illness is a common cause of hospital admission, and its associated infectious causes contribute to substantial morbidity and death among children worldwide, especially in low- and middle-income countries. Declining transmission of malaria in many regions, combined with the increasing use of rapid diagnostic tests for malaria, has led to the increasing recognition of leptospirosis, rickettsioses, respiratory viruses, and arboviruses as etiologic agents of fevers. However, clinical discrimination between these etiologies can be difficult. Overtreatment with antimalarial drugs is common, even in the setting of a negative test result, as is overtreatment with empiric antibacterial drugs. Viral etiologies remain underrecognized and poorly investigated. More-sensitive diagnostics have led to additional dilemmas in discriminating whether a positive test result reflects a causative pathogen. Here, we review and summarize the current epidemiology and focus particularly on children and the challenges for future research. PMID:27059657

  9. Evidence of a Major Reservoir of Non-Malarial Febrile Diseases in Malaria-Endemic Regions of Bangladesh

    PubMed Central

    Swoboda, Paul; Fuehrer, Hans-Peter; Ley, Benedikt; Starzengruber, Peter; Ley-Thriemer, Kamala; Jung, Mariella; Matt, Julia; Fally, Markus A.; Mueller, Milena K. S.; Reismann, Johannes A. B.; Haque, Rashidul; Khan, Wasif A.; Noedl, Harald

    2014-01-01

    In malaria-endemic regions any febrile case is likely to be classified as malaria based on presumptive diagnosis largely caused by a lack of diagnostic resources. A district-wide prevalence study assessing etiologies of fever in 659 patients recruited in rural and semi-urban areas of Bandarban district in southeastern Bangladesh revealed high proportions of seropositivity for selected infectious diseases (leptospirosis, typhoid fever) potentially being misdiagnosed as malaria because of similarities in the clinical presentation. In an area with point prevalences of more than 40% for malaria among fever cases, even higher seroprevalence rates of leptospirosis and typhoid fever provide evidence of a major persistent reservoir of these pathogens. PMID:24420774

  10. Febrile ulceronecrotic Mucha-Habermann disease following suspected hemorrhagic chickenpox infection in a 20-month-old boy.

    PubMed

    Lode, H N; Döring, P; Lauenstein, P; Hoeger, P; Dombrowski, F; Bruns, R

    2015-10-01

    We present the youngest pediatric patient so far with febrile ulcerative Mucha-Haberman disease (FUMHD) after an admitting clinical picture of hemorrhagic varicella infection. With a time to diagnosis of 25 days, the 20-month-old boy responded to low dose cyclosporine and prednisolone given for 3 months and is free of disease after 4 years of follow up. We describe a polyclonal CD8+ T cell response with elevated pro-inflammatory cytokines and a fivefold upregulation of the high-affinity Fc receptor type I (CD64) on granulocytes. Early consideration of FUMHD in the differential diagnosis of a systemic inflammatory disease combined with a generalized necrotizing rash is important for early and adequate management of children with this rare and challenging disease. PMID:25627543

  11. Alarming Signs and Symptoms in Febrile Children in Primary Care: An Observational Cohort Study in The Netherlands

    PubMed Central

    Bohnen, Arthur M.; de Wilde, Marcel; Moll, Henritte A.; Oostenbrink, Rianne; Berger, Marjolein Y.

    2014-01-01

    Context Febrile children in primary care have a low risk for serious infection. Although several alarming signs and symptoms are proposed to have predictive value for serious infections, most are based on research in secondary care. The frequency of alarming signs/symptoms has not been established in primary care; however, in this setting differences in occurrence may influence their predictive value for serious infections. Objective To determine the frequency of alarming signs/symptoms in febrile children in primary care. Design Observational cohort study. Clinical information was registered in a semi-structured way and manually recoded. Setting General practitioners' out-of-hours service. Subjects Face-to-face patient contacts concerning children (aged ?16 years) with fever were eligible for inclusion. Main outcome measures Frequency of 18 alarming signs and symptoms as reported in the literature. Results A total of 10,476 patient contacts were included. The frequency of alarming signs/symptoms ranged from n?=?1 (ABC instability; <0.1%) to n?=?2,207 (vomiting & diarrhea; 21.1%). Of all children, 59.7% had one or more alarming signs and/or symptoms. Several alarming signs/symptoms were poorly registered with the frequency of missing information ranging from 1,347 contacts (temperature >40C as reported by the parents; 12.9%) to 8,647 contacts (parental concern; 82.5%). Conclusion Although the prevalence of specific alarming signs/symptoms is low in primary care, ?50% of children have one or more alarming signs/symptoms. There is a need to determine the predictive value of alarming signs/symptoms not only for serious infections in primary care, but as well for increased risk of a complicated course of the illness. PMID:24586305

  12. Utility of adding Pneumocystis jirovecii DNA detection in nasopharyngeal aspirates in immunocompromised adult patients with febrile pneumonia.

    PubMed

    Guigue, Nicolas; Alanio, Alexandre; Menotti, Jean; Castro, Nathalie De; Hamane, Samia; Peyrony, Olivier; LeGoff, Jérôme; Bretagne, Stéphane

    2015-04-01

    Detection of viral and bacterial DNA in nasopharyngeal aspirates (NPAs) is now a routine practice in emergency cases of febrile pneumonia. We investigated whether Pneumocystis jirovecii DNA could also be detected in these cases by conducting retrospective screening of 324 consecutive NPAs from 324 adult patients (198 or 61% were immunocompromised) admitted with suspected pulmonary infections during the 2012 influenza epidemic season, using a real-time quantitative polymerase chain reaction (PCR) assay (PjqPCR), which targets the P. jirovecii mitochondrial large subunit ribosomal RNA gene. These NPAs had already been tested for 22 respiratory pathogens (18 viruses and 4 bacteria), but we found that 16 NPAs (4.9%) were PjqPCR-positive, making P. jirovecii the fourth most prevalent of the 23 microorganisms in the screen. Eleven of the 16 PjqPCR-positive patients were immunocompromised, and five had underlying pulmonary conditions. Nine NPAs were also positive for another respiratory pathogen. Six had PjqPCR-positive induced sputa less than 3 days after the NPA procedure, and five were diagnosed with pneumocystis pneumonia (four with chronic lymphoproliferative disorders and one AIDS patient). In all six available pairs quantification of P. jirovecii DNA showed fewer copies in NPA than in induced sputum and three PjqPCR-negative NPAs corresponded to PjqPCR-positive bronchoalveolar lavage fluids, underscoring the fact that a negative PjqPCR screen does not exclude a diagnosis of pneumocystosis. Including P. jirovecii DNA detection to the panel of microorganisms included in screening tests used for febrile pneumonia may encourage additional investigations or support use of anti-pneumocystis pneumonia prophylaxis in immunocompromised patients. PMID:25550391

  13. Estimating the Burden of Leptospirosis among Febrile Subjects Aged below 20 Years in Kampong Cham Communities, Cambodia, 2007-2009

    PubMed Central

    Hem, Sopheak; Ly, Sowath; Votsi, Irene; Vogt, Florian; Asgari, Nima; Buchy, Philippe; Heng, Seiha; Picardeau, Mathieu; Sok, Touch; Ly, Sovann; Huy, Rekol; Guillard, Bertrand; Cauchemez, Simon; Tarantola, Arnaud

    2016-01-01

    Background Leptospirosis is an emerging but neglected public health challenge in the Asia/Pacific Region with an annual incidence estimated at 10–100 per 100,000 population. No accurate data, however, are available for at-risk rural Cambodian communities. Method We conducted anonymous, unlinked testing for IgM antibodies to Leptospira spp. on paired sera of Cambodian patients <20 years of age between 2007–2009 collected through active, community-based surveillance for febrile illnesses in a convenience sample of 27 rural and semi-rural villages in four districts of Kampong Cham province, Cambodia. Leptospirosis testing was done on paired serological samples negative for Dengue, Japanese encephalitis and Chikungunya viruses after random selection. Convalescent samples found positive while initial samples were negative were considered as proof of acute infection. We then applied a mathematical model to estimate the risk of fever caused by leptospirosis, dengue or other causes in rural Cambodia. Results A total of 630 samples are coming from a randomly selected subset of 2358 samples. IgM positive were found on the convalescent serum sample, among which 100 (15.8%) samples were IgM negative on an earlier sample. Seventeen of these 100 seroconversions were confirmed using a Microagglutination Test. We estimated the probability of having a fever due to leptospirosis at 1. 03% (95% Credible Interval CI: 0. 95%–1. 22%) per semester. In comparison, this probability was 2. 61% (95% CI: 2. 55%, 2. 83%) for dengue and 17. 65% (95% CI: 17. 49%, 18. 08%) for other causes. Conclusion Our data from febrile cases aged below 20 years suggest that the burden of leptospirosis is high in rural Cambodian communities. This is especially true during the rainy season, even in the absence of identified epidemics. PMID:27043016

  14. ST elevation occurring during stress testing

    PubMed Central

    Malouf, Diana; Mugmon, Marc

    2016-01-01

    A case is presented of significant reversible ST elevation occurring during treadmill testing, and the coronary anatomy and subsequent course are described, indicating that ischemia is a potential cause of this electrocardiographic finding. PMID:27124164

  15. Inflammatory myofibroblastic tumor occurs in the mediastinum.

    PubMed

    Meng, Xiangjiao; Wang, Renben

    2013-01-01

    Inflammatory myofibroblastic tumor (IMT) is a rare disease. We report a rare case of inflammatory myofibroblastic tumor occurs in the mediastinum. Chest contrast-enhanced computed tomography (CT) showed a heterogeneously enhanced irregular mass in the anterior mediastinum; a small pericardial effusion was also noted. The diagnosis was confirmed by histopathology and immunohistochemical study. PMID:24518726

  16. 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…

  17. Young Children's Reports of when Learning Occurred

    ERIC Educational Resources Information Center

    Tang, Connie M.; Bartsch, Karen; Nunez, Narina

    2007-01-01

    This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about…

  18. Young Children's Reports of when Learning Occurred

    ERIC Educational Resources Information Center

    Tang, Connie M.; Bartsch, Karen; Nunez, Narina

    2007-01-01

    This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about

  19. Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania

    PubMed Central

    2012-01-01

    Background In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania. Methods From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages. Results A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025) and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4% resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to meropenem, ciprofloxacin and ceftriaxone respectively. Conclusion Urinary tract infection caused by multi drug resistant Escherichia coli was the common cause of febrile illness in our setting. Improvement of malaria diagnosis and its differential diagnosis from other causes of febrile illnesses may provide effective management of febrile illnesses among children in Tanzania PMID:22958592

  20. Naturally Occuring Fish Poisons from Plants

    NASA Astrophysics Data System (ADS)

    Cannon, Jonathan G.; Burton, Robert A.; Wood, Steven G.; Owen, Noel L.

    2004-10-01

    Since prehistoric times, cultures throughout the world have used piscicidal (fish poisoning) plants for fishing. In recent times, scientists have identified many of the plant compounds responsible for killing the fish and have found that these compounds possess other important biological properties, such as insecticidal and anti-cancer activities. This article reviews some of the chemical research that has been performed on naturally occurring fish poisons, including plant sources, methods of use, toxicity, and mechanisms of action of piscicides.

  1. Trypanosomiasis in mice with naturally occurring immunodeficiencies.

    PubMed Central

    Jones, J F; Hancock, G E

    1983-01-01

    By using mice with naturally occurring defects, we have shown that an intact macrophage system is crucial to survival with the pathogenic protozoan Trypanosoma rhodesiense, since a defect in these cells decreased survival by half. Deficiencies in natural killer cell function or complement levels had no effect on survival. However, the capacity to survive trypanosomiasis was not related to the levels of parasitemia achieved during infection. PMID:6605927

  2. Can Superflares Occur on Our Sun?

    NASA Astrophysics Data System (ADS)

    Shibata, Kazunari; Isobe, Hiroaki; Hillier, Andrew; Choudhuri, Arnab Rai; Maehara, Hiroyuki; Ishii, Takako T.; Shibayama, Takuya; Notsu, Shota; Notsu, Yuta; Nagao, Takashi; Honda, Satoshi; Nogami, Daisaku

    2013-06-01

    Recent observations of Sun-like stars, similar to our Sun in their surface temperature (5600-6000 K) and slow rotation (rotational period > 10 d), using the Kepler satellite by Maehara et al. (2012, Nature, 485, 478) have revealed the existence of superflares (with energy of 1033-1035 erg). From statistical analyses of these superflares, it was found that superflares with energy of 1034 erg occur once in 800 yr, and superflares with 1035 erg occur once in 5000 yr. In this paper, we examine whether superflares with energy of 1033-1035 erg could occur on the present Sun through the use of simple order-of-magnitude estimates based on current ideas related to the mechanisms of the solar dynamo. If magnetic flux is generated by differential rotation at the base of the convection zone, as assumed in typical dynamo models, it is possible that the present Sun would generate a large sunspot with a total magnetic flux of ˜2 × 1023 Mx (= G cm2) within one solar cycle period, and lead to superflares with an energy of 1034 erg. To store a total magnetic flux of ˜1024 Mx, necessary for generating 1035 erg superflares, it would take ˜40 yr. Hot Jupiters have often been argued to be a necessary ingredient for the generation of superflares, but we found that they do not play any essential role in the generation of magnetic flux in the star itself, if we consider only the magnetic interaction between the star and the hot Jupiter. This seems to be consistent with Maehara et al.'s finding of 148 superflare-generating solar-type stars that do not have a hot Jupiter-like companion. Altogether, our simple calculations, combined with Maehara et al.'s analysis of superflares on Sun-like stars, show that there is a possibility that superflares of 1034 erg would occur once in 800 yr on our present Sun.

  3. Synthesis of Naturally Occurring Tropones and Tropolones

    PubMed Central

    Liu, Na; Song, Wangze; Schienebeck, Casi M.; Zhang, Min; Tang, Weiping

    2014-01-01

    Tropones and tropolones are an important class of seven-membered non-benzenoid aromatic compounds. They can be prepared directly by oxidation of seven-membered rings. They can also be derived from cyclization or cycloaddition of appropriate precursors followed by elimination or rearrangement. This review discusses the types of naturally occurring tropones and tropolones and outlines important methods developed for the synthesis of tropone and tropolone natural products. PMID:25400298

  4. The Relationship between Poverty and Healthcare Seeking among Patients Hospitalized with Acute Febrile Illnesses in Chittagong, Bangladesh.

    PubMed

    Herdman, M Trent; Maude, Richard James; Chowdhury, Md Safiqul; Kingston, Hugh W F; Jeeyapant, Atthanee; Samad, Rasheda; Karim, Rezaul; Dondorp, Arjen M; Hossain, Md Amir

    2016-01-01

    Delays in seeking appropriate healthcare can increase the case fatality of acute febrile illnesses, and circuitous routes of care-seeking can have a catastrophic financial impact upon patients in low-income settings. To investigate the relationship between poverty and pre-hospital delays for patients with acute febrile illnesses, we recruited a cross-sectional, convenience sample of 527 acutely ill adults and children aged over 6 months, with a documented fever ≥38.0°C and symptoms of up to 14 days' duration, presenting to a tertiary referral hospital in Chittagong, Bangladesh, over the course of one year from September 2011 to September 2012. Participants were classified according to the socioeconomic status of their households, defined by the Oxford Poverty and Human Development Initiative's multidimensional poverty index (MPI). 51% of participants were classified as multidimensionally poor (MPI>0.33). Median time from onset of any symptoms to arrival at hospital was 22 hours longer for MPI poor adults compared to non-poor adults (123 vs. 101 hours) rising to a difference of 26 hours with adjustment in a multivariate regression model (95% confidence interval 7 to 46 hours; P = 0.009). There was no difference in delays for children from poor and non-poor households (97 vs. 119 hours; P = 0.394). Case fatality was 5.9% vs. 0.8% in poor and non-poor individuals respectively (P = 0.001)-5.1% vs. 0.0% for poor and non-poor adults (P = 0.010) and 6.4% vs. 1.8% for poor and non-poor children (P = 0.083). Deaths were attributed to central nervous system infection (11), malaria (3), urinary tract infection (2), gastrointestinal infection (1) and undifferentiated sepsis (1). Both poor and non-poor households relied predominantly upon the (often informal) private sector for medical advice before reaching the referral hospital, but MPI poor participants were less likely to have consulted a qualified doctor. Poor participants were more likely to attribute delays in decision-making and travel to a lack of money (P<0.001), and more likely to face catastrophic expenditure of more than 25% of monthly household income (P<0.001). We conclude that multidimensional poverty is associated with greater pre-hospital delays and expenditure in this setting. Closer links between health and development agendas could address these consequences of poverty and streamline access to adequate healthcare. PMID:27054362

  5. The Relationship between Poverty and Healthcare Seeking among Patients Hospitalized with Acute Febrile Illnesses in Chittagong, Bangladesh

    PubMed Central

    Herdman, M. Trent; Maude, Richard James; Chowdhury, Md. Safiqul; Kingston, Hugh W. F.; Jeeyapant, Atthanee; Samad, Rasheda; Karim, Rezaul; Dondorp, Arjen M.; Hossain, Md. Amir

    2016-01-01

    Delays in seeking appropriate healthcare can increase the case fatality of acute febrile illnesses, and circuitous routes of care-seeking can have a catastrophic financial impact upon patients in low-income settings. To investigate the relationship between poverty and pre-hospital delays for patients with acute febrile illnesses, we recruited a cross-sectional, convenience sample of 527 acutely ill adults and children aged over 6 months, with a documented fever ≥38.0°C and symptoms of up to 14 days’ duration, presenting to a tertiary referral hospital in Chittagong, Bangladesh, over the course of one year from September 2011 to September 2012. Participants were classified according to the socioeconomic status of their households, defined by the Oxford Poverty and Human Development Initiative’s multidimensional poverty index (MPI). 51% of participants were classified as multidimensionally poor (MPI>0.33). Median time from onset of any symptoms to arrival at hospital was 22 hours longer for MPI poor adults compared to non-poor adults (123 vs. 101 hours) rising to a difference of 26 hours with adjustment in a multivariate regression model (95% confidence interval 7 to 46 hours; P = 0.009). There was no difference in delays for children from poor and non-poor households (97 vs. 119 hours; P = 0.394). Case fatality was 5.9% vs. 0.8% in poor and non-poor individuals respectively (P = 0.001)—5.1% vs. 0.0% for poor and non-poor adults (P = 0.010) and 6.4% vs. 1.8% for poor and non-poor children (P = 0.083). Deaths were attributed to central nervous system infection (11), malaria (3), urinary tract infection (2), gastrointestinal infection (1) and undifferentiated sepsis (1). Both poor and non-poor households relied predominantly upon the (often informal) private sector for medical advice before reaching the referral hospital, but MPI poor participants were less likely to have consulted a qualified doctor. Poor participants were more likely to attribute delays in decision-making and travel to a lack of money (P<0.001), and more likely to face catastrophic expenditure of more than 25% of monthly household income (P<0.001). We conclude that multidimensional poverty is associated with greater pre-hospital delays and expenditure in this setting. Closer links between health and development agendas could address these consequences of poverty and streamline access to adequate healthcare. PMID:27054362

  6. Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty

    PubMed Central

    2014-01-01

    Background An estimated one-third of children younger than 5 years in low- and middle-income countries fail to meet their full developmental potential. The first year of life is a period of critical brain development and is also when most of the morbidity from infection is suffered. We aimed to determine if clinical and biological markers of inflammation in the first year of life predict cognitive, language, and motor outcomes in children living in an urban slum in Bangladesh. Methods Children living in Dhaka, Bangladesh were observed from birth until 24 months of age. Febrile illness was used as a clinical marker of inflammation and elevated concentrations of inflammation-related cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10) in sera collected from a subset of the cohort (N = 127) at 6 months of age were used as biomarkers of inflammation. Psychologists assessed cognitive, language, and motor development using a culturally adapted version of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 12 (N = 398) and 24 months of age (N = 210). We tested for the ability of febrile illness and elevated cytokine levels to predict developmental outcomes, independent of known predictors of stunting, family income, and maternal education. Results Every additional 10 days of fever was associated with a 1.9 decrease in language composite score and a 2.1 decrease in motor composite score (p = 0.005 and 0.0002, respectively). Elevated levels of the pro-inflammatory cytokines IL-1β (> 7.06 pg/mL) and IL-6 (> 10.52 pg/mL) were significantly associated with a 4.9 and 4.3 decrease in motor score, respectively. Conversely, an elevated level of the Th-2 cytokine IL-4 (> 0.70 pg/mL) was associated with a 3.6 increase in cognitive score (all p < 0.05). Conclusions Clinical and biological markers of inflammation in the first year of life were significantly associated with poor neurodevelopmental outcomes. Conversely, a Th2-like response was associated with a better outcome. These findings suggest that markers of inflammation could serve as prognostic indicators and potentially lead to immune-based therapies to prevent developmental delays in at-risk children. PMID:24548288

  7. Acute Febrile Illness and Influenza Disease Burden in a Rural Cohort Dedicated to Malaria in Senegal, 2012–2013

    PubMed Central

    Thiam, Diamilatou; Dia, Ndongo; Badiane, Abdoulaye; Ndao, A. B.; Sokhna, Cheikh; Spiegel, André; Richard, Vincent

    2015-01-01

    Background African populations are considered to be particularly vulnerable to fever illnesses, including malaria, and acute respiratory disease, owing to limited resources and overcrowding. However, the overall burden of influenza in this context is poorly defined and incidence data for African countries are scarce. We therefore studied the fever syndrome incidence and more specifically influenza incidence in a cohort of inhabitants of Dielmo and Ndiop in Sokone district, Senegal. Methods Daily febrile-illness data were prospectively obtained from January 2012 to December 2013 from the cohort of the villages of Dielmo and Ndiop, initially dedicated to the study of malaria. Nasopharyngeal swabs were collected from, and malaria diagnosis tests (thick blood smears) carried out on, every febrile individual during clinical visits; reverse transcriptase-polymerase chain reaction was used to identify influenza viruses in the samples. Binomial negative regression analysis was used to study the relationship between the monthly incidence rate and various covariates. Results In Dielmo and Ndiop, the incidence of malaria has decreased, but fever syndromes remain frequent. Among the 1036 inhabitants included in the cohort, a total of 1,129 episodes of fever were reported. Influenza was present all year round with peaks in October-December 2012 and August 2013. The fever, ILI and influenza incidence density rates differed significantly between age groups. At both sites, the adjusted incidence relative risks for fever syndromes and ILI were significantly higher in the [6–24 months) than other age groups: 7.3 (95%CI: [5.7–9.3]) and 16.1 (95%CI: [11.1–23.3]) respectively. The adjusted incidence relative risk for influenza was significantly higher for the [0–6 months) than other age groups: 9.9 (95%CI: [2.9–33.6]). At both sites, incidence density rates were lowest among adults > = 50 years. Conclusions In this rural setting in Senegal, influenza was most frequent among the youngest children. Preventive strategies targeting this population should be implemented. PMID:26679177

  8. 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

  9. 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), α-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 (4 mg) injection. Rectal temperatures were measured with a telethermometer. The administration of IL-1ra (200 µg), sTNFRI (500 ng), and AbIL-6 (5 µg) attenuated body temperature elevations after a zymosan injection. The administration of BQ-788 (3 pmol), BQ-123 (3 pmol), and α-helical CRF9-41 (25 µg) 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-α, IL-1β, and IL-6, but does not depend on either CRF or ET-1. PMID:25819555

  10. 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

  11. 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

  12. Initial assessment of impact of adenovirus type 4 and type 7 vaccine on febrile respiratory illness and virus transmission in military basic trainees, March 2012.

    PubMed

    Hoke, Charles H; Hawksworth, Anthony; Snyder, Clifford E

    2012-03-01

    After a 12-year hiatus, military recruit training centers resumed administration of adenovirus type 4 and type 7 vaccine, live, oral (adenovirus vaccine) to trainees beginning in October of 2011. Subsequently, rates of febrile respiratory illnesses (FRI) and adenovirus isolations markedly declined. These findings are consistent with those of a placebo-controlled efficacy trial conducted prior to the vaccine's licensure by the U.S. Food and Drug Administration. Continued surveillance will clarify the longer term impact of vaccine use. PMID:22452712

  13. Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests

    PubMed Central

    2012-01-01

    Background Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria, are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria, reduce mortality and limit malaria transmission. The purpose of this study was to assess the performance of the malaria rapid diagnostic tests (RDTs) used by community health workers (CHWs) by comparing RDT results with two reference methods (microscopy and Polymerase Chain Reaction, PCR). Methods Eight CHWs in two districts, each with a different level of endemic malaria transmission, were trained to use RDTs in the management of febrile children under five years of age. RDTs were performed by CHWs in all febrile children who consulted for fever. In parallel, retrospective parasitological diagnoses were made by microscopy and PCR. The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs. The stability of the RDTs stored by CHWs was also evaluated. Results Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010, 89.5% were found to be positive for malaria parasites by PCR, 51.6% were positive by microscopy and 55.8% were positive by RDT. The performance accuracy of the RDTs used by CHWs in terms of sensitivity, specificity, positive and negative predictive values was greater than 85%. Concordance between microscopy and RDT, estimated by the Kappa value was 0.83 (95% CI: 0.75-0.91). RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/μl. Conclusion Introduction of easy-to-use diagnostic tools, such as RDTs, at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs. PMID:22443344

  14. A comparison of resource utilization following chemotherapy for acute myeloid leukemia in children discharged versus children that remain hospitalized during neutropenia

    PubMed Central

    Getz, Kelly D; Miller, Tamara P; Seif, Alix E; Li, Yimei; Huang, Yuan-Shung; Bagatell, Rochelle; Fisher, Brian T; Aplenc, Richard

    2015-01-01

    Comparisons of early discharge and outpatient postchemotherapy supportive care in pediatric acute myeloid leukemia (AML) patients are limited. We used data from the Pediatric Health Information System on a cohort of children treated for newly diagnosed AML to compare course-specific mortality and resource utilization in patients who were discharged after chemotherapy to outpatient management during neutropenia relative to patients who remained hospitalized. Patients were categorized at each course as early or standard discharge. Discharges within 3 days after chemotherapy completion were considered “early”. Resource utilization was determined based on daily billing data and reported as days of use per 1000 hospital days. Inpatient mortality, occurrence of intensive care unit (ICU)-level care, and duration of hospitalization were compared using logistic, log-binomial and linear regression methods, respectively. Poisson regression with inpatient days as offset was used to compare resource use by discharge status. The study population included 996 patients contributing 2358 treatment courses. Fewer patients were discharged early following Induction I (7%) than subsequent courses (22–24%). Across courses, patients discharged early experienced high readmission rates (69–84%), yet 9–12 fewer inpatient days (all P < 0.001). Inpatient mortality was low across courses and did not differ significantly by discharge status. The overall risk for ICU-level care was 116% higher for early compared to standard discharge patients (adjusted risk ratio: 2.16, 95% confidence interval: 1.50, 3.11). Rates of antibiotic, vasopressor, and supplemental oxygen use were consistently elevated for early discharge patients. Despite similar inpatient mortality to standard discharge patients, early discharge patients may be at greater risk for life-threatening chemotherapy-related complications, including infections. PMID:26105201

  15. A comparison of resource utilization following chemotherapy for acute myeloid leukemia in children discharged versus children that remain hospitalized during neutropenia.

    PubMed

    Getz, Kelly D; Miller, Tamara P; Seif, Alix E; Li, Yimei; Huang, Yuan-Shung; Bagatell, Rochelle; Fisher, Brian T; Aplenc, Richard

    2015-09-01

    Comparisons of early discharge and outpatient postchemotherapy supportive care in pediatric acute myeloid leukemia (AML) patients are limited. We used data from the Pediatric Health Information System on a cohort of children treated for newly diagnosed AML to compare course-specific mortality and resource utilization in patients who were discharged after chemotherapy to outpatient management during neutropenia relative to patients who remained hospitalized. Patients were categorized at each course as early or standard discharge. Discharges within 3 days after chemotherapy completion were considered "early". Resource utilization was determined based on daily billing data and reported as days of use per 1000 hospital days. Inpatient mortality, occurrence of intensive care unit (ICU)-level care, and duration of hospitalization were compared using logistic, log-binomial and linear regression methods, respectively. Poisson regression with inpatient days as offset was used to compare resource use by discharge status. The study population included 996 patients contributing 2358 treatment courses. Fewer patients were discharged early following Induction I (7%) than subsequent courses (22-24%). Across courses, patients discharged early experienced high readmission rates (69-84%), yet 9-12 fewer inpatient days (all P < 0.001). Inpatient mortality was low across courses and did not differ significantly by discharge status. The overall risk for ICU-level care was 116% higher for early compared to standard discharge patients (adjusted risk ratio: 2.16, 95% confidence interval: 1.50, 3.11). Rates of antibiotic, vasopressor, and supplemental oxygen use were consistently elevated for early discharge patients. Despite similar inpatient mortality to standard discharge patients, early discharge patients may be at greater risk for life-threatening chemotherapy-related complications, including infections. PMID:26105201

  16. Electronic Nose Technology for Detection of Invasive Pulmonary Aspergillosis in Prolonged Chemotherapy-Induced Neutropenia: a Proof-of-Principle Study

    PubMed Central

    van der Schee, Marc P.; Zwinderman, Koos; van den Berk, Inge A. H.; Visser, Caroline Elisabeth; van Oers, Rien; Sterk, Peter J.

    2013-01-01

    Although the high mortality rate of pulmonary invasive aspergillosis (IA) in patients with prolonged chemotherapy-induced neutropenia (PCIN) can be reduced by timely diagnosis, a diagnostic test that reliably detects IA at an early stage is lacking. We hypothesized that an electronic nose (eNose) could fulfill this need. An eNose can discriminate various lung diseases through the analysis of exhaled volatile organic compounds (VOCs). An eNose is cheap and noninvasive and yields results within minutes. In a single-center prospective cohort study, we included patients who were treated with chemotherapy expected to result in PCIN. Based on standardized indications, a full diagnostic workup was performed to confirm invasive aspergillosis or to rule it out. Patients with no aspergillosis were considered controls, and patients with probable or proven aspergillosis were considered index cases. Exhaled breath was examined with a Cyranose 320 (Smith Detections, Pasadena, CA). The resulting data were analyzed using principal component reduction. The primary endpoint was cross-validated diagnostic accuracy, defined as the percentage of patients correctly classified using the leave-one-out method. Accuracy was validated by 100,000 random classifications. We included 46 subjects who underwent 16 diagnostic workups, resulting in 6 cases and 5 controls. The cross-validated accuracy of the eNose in diagnosing IA was 90.9% (P = 0.022; sensitivity, 100%; specificity, 83.3%). Receiver operating characteristic analysis showed an area under the curve of 0.93. These preliminary data indicate that PCIN patients with IA have a distinct exhaled VOC profile that can be detected with eNose technology. The diagnostic accuracy of the eNose for invasive aspergillosis warrants validation. PMID:23467602

  17. Naturally occurring antimicrobials for minimally processed foods.

    PubMed

    Davidson, P Michael; Critzer, Faith J; Taylor, T Matthew

    2013-01-01

    Natural antimicrobials are gaining increased interest from researchers and food manufacturers alike seeking to discover label-friendly alternatives to the widely implemented synthetic compounds. Naturally occurring antimicrobials can be applied directly to food to protect food quality, extend food shelf life by inhibiting or inactivating spoilage microorganisms, and improve food safety by inhibiting or inactivating food-borne pathogens. There are a great number of natural antimicrobials derived from animal, plant, and microbial sources. This manuscript reviews their efficacy against spoilage and pathogenic organisms, their methods of evaluation, and their application in various foods as well as the development of novel delivery systems and incorporation with other hurdles. PMID:23244398

  18. Multiple epidermal cysts occurring in a tattoo.

    PubMed

    Koh, M J A; Teo, R Y L; Liu, T T

    2009-11-01

    In decorative tattooing, pigment is introduced into the skin with needles or a tattoo gun to create a picture, motif or symbol. Various skin reactions have been reported in association with tattoos. These include acute inflammatory reactions, eczematous hypersensitivity reactions, pseudolymphomatous reactions and skin infections. We present a 24-year-old Malay man who developed multiple epidermal cysts a month after tattooing. To the best of our knowledge, this is the first case in the literature of epidermal cysts occurring after skin tattooing. PMID:19960148

  19. 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

  20. Do Unexpected Panic Attacks Occur Spontaneously?

    PubMed Central

    Meuret, Alicia E.; Rosenfield, David; Wilhelm, Frank H.; Zhou, Enlu; Conrad, Ansgar; Ritz, Thomas; Roth, Walton T.

    2012-01-01

    Background Spontaneous or unexpected panic attacks, per definition, occur out-of-the blue, in absence of cues or triggers. Accordingly, physiological arousal or instability should occur at the onset of or during the attack, but not preceding it. To test this hypothesisweexaminedif points of significant autonomic changes preceded the onset of spontaneous panic attacks. Methods Forty-three panic disorder patients underwent repeated 24-hour ambulatory monitoring. Thirteen naturally panic attacks were recorded during 1,960 hours of monitoring. Minute-by-minute epochs beginning 60 minutes before, and continuing to 10 minutes after, the onset of individual attacks were examined for respiration, heart rate, and skin conductance level. Measures were controlled for physical activity and vocalization, and compared to time matched control periods within the same person. Results Significant patterns of instability across a numberof autonomic and respiratory variables were detected as early as 47 minutes before panic onset. The final minutes prior to onset were dominated by respiratory changes, with significant decreases in tidal volume followed by abrupt PCO2 increases. Panic attack onset was characterized by heart rate and tidal volume increases and a drop in PCO2. Symptom report was consistent with these changes. Skin conductance levels were generally elevated in the hour before and duringthe attacks. Changes in the matched control periods were largely absent. Conclusions Significant autonomic irregularities preceded the onset of attacks that were reported as abrupt and unexpected. The findings invite reconsideration of the current diagnostic distinction betweenuncuedand cued panic attacks. PMID:21783179

  1. Nipah virus entry can occur by macropinocytosis

    SciTech Connect

    Pernet, Olivier; Pohl, Christine; Ainouze, Michelle; Kweder, Hasan; Buckland, Robin

    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.

  2. Aetiology of Bacteraemia as a Risk Factor for Septic Shock at the Onset of Febrile Neutropaenia in Adult Cancer Patients

    PubMed Central

    Rosa, Regis Goulart; Goldani, Luciano Zubaran

    2014-01-01

    Septic shock (SS) at the onset of febrile neutropaenia (FN) is an emergency situation that is associated with high morbidity and mortality. The impact of the specific aetiology of bloodstream infections (BSIs) in the development of SS at the time of FN is not well established. The aim of this study was to evaluate the association between the aetiology of BSIs and SS at the time of FN in hospitalised adult cancer patients. This prospective cohort study was performed at a single tertiary hospital from October 2009 to August 2011. All adult cancer patients admitted consecutively to the haematology ward with FN were evaluated. A stepwise logistic regression was conducted to verify the association between the microbiological characteristics of BSIs and SS at the onset of FN. In total, 307 cases of FN in adult cancer patients were evaluated. There were 115 cases with documented BSI. A multivariate analysis showed that polymicrobial bacteraemia (P = 0.01) was associated with SS. The specific blood isolates independently associated with SS were viridans streptococci (P = 0.02) and Escherichia coli (P = 0.01). Neutropaenic cancer patients with polymicrobial bacteraemia or BSI by viridans streptococci or Escherichia coli are at increased risk for SS at the time of FN. PMID:24804223

  3. Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling

    PubMed Central

    Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Cenglin; Wang, Yi; Dai, Yunjian; Wu, Dengchang; Zhu, Junmin; Wang, Shuang; Zhou, Yudong; Shi, Liyun; Hu, Weiwei; Zhang, Xia; Chen, Zhong

    2016-01-01

    It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS. PMID:26902320

  4. 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

  5. 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

  6. Disruption of Fgf13 Causes Synaptic Excitatory–Inhibitory Imbalance and Genetic Epilepsy and Febrile Seizures Plus

    PubMed Central

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

    2015-01-01

    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

  7. Diagnosis and management of febrile children using the WHO/UNICEF guidelines for IMCI in Dhaka, Bangladesh.

    PubMed Central

    Factor, S. H.; Schillinger, J. A.; Kalter, H. D.; Saha, S.; Begum, H.; Hossain, A.; Hossain, M.; Dewitt, V.; Hanif, M.; Khan, N.; Perkins, B.; Black, R. E.; Schwartz, B.

    2001-01-01

    OBJECTIVE: To determine whether the fever module in the WHO/UNICEF guidelines for the integrated management of childhood illness (IMCI) identifies children with bacterial infections in an area of low malaria prevalence. METHODS: Physicians assessed a systematic sample of 669 sick children aged 2-59 months who presented to the outpatient department of Dhaka Shishu Hospital, Bangladesh. FINDINGS: Had IMCI guidelines been used to evaluate the children, 78% of those with bacterial infections would have received antibiotics: the majority of children with meningitis (100%), pneumonia (95%), otitis media (95%) and urinary tract infection (83%); and 50% or less of children with bacteraemia (50%), dysentery (48%), and skin infections (30%). The current fever module identified only one additional case of meningitis. Children with bacteraemia were more likely to be febrile, feel hot, and have a history of fever than those with dysentery and skin infections. Fever combined with parental perception of fast breathing provided a more sensitive fever module for the detection of bacteraemia than the current IMCI module. CONCLUSIONS: In an area of low malaria prevalence, the IMCI guidelines provide antibiotics to the majority of children with bacterial infections, but improvements in the fever module are possible. PMID:11799441

  8. Clinical usefulness of serum 2'-5'-oligoadenylate synthetase for early diagnosis of viral infections among febrile adult patients.

    PubMed

    Yanai, Mitsuru; Gon, Yasuhiro; Suzuki, Kiyozumi; Hayashi, Yuta; Hasumi, Sadayuki; Otsuka, Hiromasa; Soma, Masayoshi

    2016-05-01

    Background This study aimed to evaluate the clinical usefulness of serum 2'-5'-oligoadenylate synthetase (2-5AS) levels in diagnosing viral infection. Methods 2-5AS, procalcitonin (PCT) and C-reactive protein (CRP) serum levels and leukocyte counts were evaluated in 104 febrile patients (26 viral and 55 bacterial infections, 23 non-infectious diseases). Results Assessment of areas under the receiver-operator characteristic curves revealed that 2-5AS and CRP levels and the age of the patient differentiated between viral and bacterial infections, 2-5AS levels differentiated between viral infection and non-infectious disease and PCT levels differentiated between bacterial infection and non-infectious disease. The decision tree constructed according to the results correctly classified the origin of fever in 88 of 104 patients (85%). Conclusions 2-5AS is a useful diagnostic biomarker for viral infections and combining it with the PCT and CRP levels and leukocyte counts improves determination of causes of fever. PMID:26624960

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

    SciTech Connect

    Poulsen, Michael Walpole, Euan; Harvey, Jennifer; Dickie, Graeme; O'Brien, Peter; Keller, Jacqui; Tpcony, Lee; Rischin, Danny

    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.

  10. Cocaine as a naturally occurring insecticide.

    PubMed Central

    Nathanson, J A; Hunnicutt, E J; Kantham, L; Scavone, C

    1993-01-01

    Although cocaine has a fascinating and complex medicinal history in man, its natural function in plants is unknown. The present studies demonstrate that cocaine exerts insecticidal effects at concentrations which occur naturally in coca leaves. Unlike its known action on dopamine reuptake in mammals, cocaine's pesticidal effects are shown to result from a potentiation of insect octopaminergic neurotransmission. Amine-reuptake blockers of other structural classes also exert pesticidal activity with a rank order of potency distinct from that known to affect vertebrate amine transporters. These findings suggest that cocaine functions in plants as a natural insecticide and that octopamine transporters may be useful sites for targeting pesticides with selectivity toward invertebrates. Images Fig. 3 PMID:8415755

  11. Pilomyxoid Astrocytoma Occurring in the Third Ventricle

    PubMed Central

    Kim, Sanghyeon; Kang, Myongjin; Choi, Sunseob; Kim, Dae Cheol

    2015-01-01

    Pilomyxoid astrocytoma (PMA) is a rare central nervous system tumor that has been included in the 2007 World Health Organization Classification of Tumors of the Central Nervous System. Due to its more aggressive behavior, PMA is classified as Grade II neoplasm by the World Health Organization. PMA predominantly affects the hypothalamic/chiasmatic region and occurs in children (mean age of occurrence = 10 months). We report a case of a 24-year-old man who presented with headache, nausea, and vomiting. Brain CT and MRI revealed a mass occupying only the third ventricle. We performed partial resection. Histological findings, including monophasic growth with a myxoid background, and absence of Rosenthal fibers or eosinophilic granular bodies, as well as the strong positivity for glial fibrillary acidic protein were consistent with PMA. PMID:26312139

  12. Febrile Illness in an Infant With an Intracardiac Inflammatory Myofibroblastic Tumor.

    PubMed

    Pang, Renée; Merritt, Neil H; Shkrum, Michael J; Tijssen, Janice A

    2016-02-01

    We report a case of a child with a right ventricular inflammatory myofibroblastic tumor (IMT) who presented with fever, viral symptoms, and abdominal discomfort. Including this case, 49 intracardiac tumors have been previously reported in all age groups. The majority of intracardiac IMTs occur in pediatric patients, with approximately half presenting in children aged <12 months. Intracardiac IMTs are generally described as benign tumors; however, depending on their location, the initial presentation may involve heart failure or sudden death.(1) In addition to cardiac signs and symptoms, the clinical presentation of IMTs may also include constitutional signs such as fever, anemia, an