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1

Microbial etiology of febrile neutropenia.  

PubMed

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

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

2010-06-01

2

Malaria Parasitemia Associated with Febrile Neutropenia in African Patients Undergoing Chemotherapy for Haematological Malignancies  

Microsoft Academic Search

Background: Very little is documented in the medical literature on the association between malaria parasitemia and febrile neutropenia in patients undergoing cancer chemotherapy. Methods: This report will concentrate on the clinical presentation and outcome of 3 patients with haematological malignancies undergoing chemotherapy who developed febrile neutropenia and malaria parasitemia concurrently. Results: Three patients infected with documented malaria during a febrile

Bernardo L. Rapoport; Almarie Uys

2008-01-01

3

Variation in Antimicrobial Utilization for Febrile Neutropenia in Cancer Patients  

Microsoft Academic Search

Summary  \\u000a \\u000a Background: No previous study has compared hospitals with respect to the variation of antimicrobial utilization (AU) for cancer patients\\u000a with febrile neutropenia (FNE).\\u000a \\u000a \\u000a \\u000a \\u000a Patients and Methods: We conducted an observational cohort study, carried out in 18 tertiary care centers across nine countries, in order to describe\\u000a AU patterns for cancer patients with FNE and to evaluate whether prescription was

S. Harbarth; M. Viot; I. Beeler; J. Klastersky; T. Szucs

2000-01-01

4

Empirical antifungal therapy in selected patients with persistent febrile neutropenia.  

PubMed

Universal empirical antifungal therapy (EAT) in patients with unexplained persistent febrile neutropenia (PFN) is the standard of care, but EAT could be applied in selected patients on the basis of clinical criteria and risk factors. A prospective interventional study was carried out to analyse the incidence and related mortality of invasive fungal infection (IFI) in patients with PFN according to whether or not EAT was indicated. EAT was indicated according to the following criteria: (a) severe sepsis or septic shock; (b) focused infection: lung, central nervous system, sinus, abdominal or skin; (c) individualized clinical decision in patients at high risk. Sixty-six (19%) of 347 episodes of febrile neutropenia fulfilled PFN criteria, 97% with a haematological malignancy. Just 26 (39.4%) were treated with EAT. The overall IFI incidence was 4.5%. In the group that received EAT, three patients developed IFI (11.5%), in comparison with none in the group that did not receive it (P=0.04, RR 2.7:1.9-3.8). IFI-related mortality was null in the group that did not receive EAT and 8% (two of 26 patients) in the group that received EAT. These data suggest that in patients with PFN, EAT in selected patients may be safe and avoid unnecessary antifungal therapy. PMID:19525983

Aguilar-Guisado, M; Espigado, I; Cordero, E; Noguer, M; Parody, R; Pachón, J; Cisneros, J M

2010-01-01

5

Risk Factors for Febrile Neutropenia during Chemotherapy for HIV-Related Lymphoma  

PubMed Central

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38?; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.

Park, Jinyong; Kim, Tae Min; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Choe, Pyoeng Gyun; Song, Kyoung-ho; Kim, Eu Suk; Park, Sang-Won; Kim, Hong Bin; Kim, Nam Joong; Oh, Myoung-don

2012-01-01

6

Assessment of febrile neutropenia episodes in children with acute leukemia treated with BFM protocols.  

PubMed

The authors overviewed 239 febrile neutropenia (FN) episodes in 82 pediatric leukemia cases treated with BFM treatment protocols. FN was observed mostly during consolidation therapy. Mucositis was the most identified focus; gram-negative microorganisms were the most identified pathogens. Five patients developed invasive fungal infections. Fever resolved after mean 5.3 days and mean antibiotic administration time was 12.7 days. Addition of G-CSF to antimicrobial therapy shortened the duration of neutropenia, but it did not affect duration of fever resolution and antibiotic administration. The duration of neutropenia, fever resolution, and antibiotic administration was significantly longer in children with acute myeloid leukemia. The authors conclude that children with acute leukemia have severe prolonged neutropenia and are in high risk. In these patients, prediction of the risk of bacteremia based on clinical and laboratory features is important for immediate empiric broad-spectrum antimicrobial therapy and for higher survival rate. PMID:18432502

Yilmaz, Sebnem; Oren, Hale; Demircio?lu, Fatih; Irken, Gülersu

2008-01-01

7

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach  

PubMed Central

Background Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients’ risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and Methods This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. Results Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. Conclusions Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials.

Aguilar-Guisado, Manuela; Martin-Pena, Almudena; Espigado, Ildefonso; Ruiz Perez de Pipaon, Maite; Falantes, Jose; de la Cruz, Fatima; Cisneros, Jose M.

2012-01-01

8

Diagnostic Value of PCR Analysis of Bacteria and Fungi from Blood in Empiric-Therapy-Resistant Febrile Neutropenia ?  

PubMed Central

This study aimed to assess the clinical utility of PCR for the analysis of bacteria and fungi from blood for the management of febrile neutropenic patients with hematologic malignancies. Using a PCR system able to detect a broad range of bacteria and fungi, we conducted a prospective pilot study of periodic analyses of blood from patients following intensive chemotherapy. When fever occurred, it was treated with empirical antibiotic therapy, basically without knowledge of the PCR results. In 23 febrile episodes during the neutropenic period, bacteria were detected by PCR in 11 cases, while the same species were identified by blood culture in 3 cases. In 10 out of 11 PCR-positive cases, fever could be managed by empirical therapy. In the empirical-therapy-resistant case, the identification of Stenotrophomonas maltophilia by PCR led to improvement of fever. No fungi were detected by PCR in febrile cases, while Aspergillus fumigatus was detected in one afebrile patient, several days before a clinical diagnosis was made. In subsequent sporadic PCR analyses in 15 cases of febrile neutropenia, bacteria were detected by both PCR and blood culture in 7 cases and by PCR alone in 6. Fungi were not detected. While fever was improved by empirical therapy in 12 out of the 13 PCR-positive cases, the identification of Pseudomonas aeruginosa by PCR in one therapy-resistant case contributed to the successful treatment of persistent fever. Our results indicate that PCR analysis of bacteria from blood provides essential information for managing empirical-therapy-resistant febrile neutropenia.

Nakamura, Akiko; Sugimoto, Yuka; Ohishi, Kohshi; Sugawara, Yumiko; Fujieda, Atsushi; Monma, Fumihiko; Suzuki, Kei; Masuya, Masahiro; Nakase, Kazunori; Matsushima, Yoshiko; Wada, Hideo; Katayama, Naoyuki; Nobori, Tsutomu

2010-01-01

9

Time to antibiotics and outcomes in cancer patients with febrile neutropenia  

PubMed Central

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

2014-01-01

10

Improving efficacy of antifungal therapy by polymerase chain reaction-based strategy among febrile patients with neutropenia and cancer.  

PubMed

Early detection of fungal infections in and corresponding early treatment of febrile patients with neutropenia and cancer have been important issues and continue to be major challenges for clinicians. The use of nested PCR to make therapeutic decisions was studied. Sequential blood samples obtained from 42 patients with neutropenia and cancer were tested by nested PCR and culture. Instead of the empirical antifungal therapy strategy, amphotericin B treatment was initiated only for patients who had 2 consecutive positive results by nested PCR. A reduced mortality rate was observed for febrile patients with neutropenia and cancer who had fungal infections. Thus, this strategy, combined with the nested PCR for early detection of fungal infection in febrile patients with neutropenia, may be used as a guideline for antifungal therapy. PMID:11595977

Lin, M T; Lu, H C; Chen, W L

2001-11-15

11

Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: A systematic review.  

PubMed

Neutropenia with fever (febrile neutropenia [FN]) is a serious consequence of myelosuppressive chemotherapy that usually results in hospitalization and the need for intravenous antibiotics. FN may result in dose reductions, delays, or even discontinuation of chemotherapy, which, in turn, may compromise patient outcomes. It is important to identify which patients are at high risk for developing FN so that patients can receive optimal chemotherapy while their risk for FN is appropriately managed. A systematic review of the literature was performed to gain a comprehensive and updated understanding of FN risk factors. Older age, poor performance status, advanced disease, certain comorbidities, low baseline blood cell counts, low body surface area/body mass index, treatment with myelosuppressive chemotherapies, and specific genetic polymorphisms correlated with the risk of developing FN. Albeit many studies have analyzed FN risk factors, there are several limitations, including the retrospective nature and small sample sizes of most studies. PMID:24434034

Lyman, Gary H; Abella, Esteban; Pettengell, Ruth

2014-06-01

12

Utility of a commercially available multiplex real-time PCR assay to detect bacterial and fungal pathogens in febrile neutropenia.  

PubMed

Infection is the main treatment-related cause of mortality in cancer patients. Rapid and accurate diagnosis to facilitate specific therapy of febrile neutropenia is therefore urgently warranted. Here, we evaluated a commercial PCR-based kit to detect the DNA of 20 different pathogens (SeptiFast) in the setting of febrile neutropenia after chemotherapy. Seven hundred eighty-four serum samples of 119 febrile neutropenic episodes (FNEs) in 70 patients with hematological malignancies were analyzed and compared with clinical, microbiological, and biochemical findings. In the antibiotic-naïve setting, bacteremia was diagnosed in 34 FNEs and 11 of them yielded the same result in the PCR. Seventy-three FNEs were negative in both systems, leading to an overall agreement in 84 of 119 FNEs (71%). During antibiotic therapy, positivity in blood culture occurred only in 3% of cases, but the PCR yielded a positive result in 15% of cases. In six cases the PCR during antibiotic treatment detected a new pathogen repetitively; this was accompanied by a significant rise in procalcitonin levels, suggestive of a true detection of infection. All patients with probable invasive fungal infection (IFI; n = 3) according to the standards of the European Organization for Research and Treatment of Cancer had a positive PCR result for Aspergillus fumigatus; in contrast there was only one positive result for Aspergillus fumigatus in an episode without signs and symptoms of IFI. Our results demonstrate that the SeptiFast kit cannot replace blood cultures in the diagnostic workup of FNEs. However, it might be helpful in situations where blood cultures remain negative (e.g., during antimicrobial therapy or in IFI). PMID:19571034

von Lilienfeld-Toal, Marie; Lehmann, Lutz E; Raadts, Ansgar D; Hahn-Ast, Corinna; Orlopp, Katjana S; Marklein, Günter; Purr, Ingvill; Cook, Gordon; Hoeft, Andreas; Glasmacher, Axel; Stüber, Frank

2009-08-01

13

Micafungin for empirical antifungal therapy in patients with febrile neutropenia: multicenter phase 2 study.  

PubMed

Empirical antifungal therapy is the current standard of care for patients with febrile neutropenia unresponsive to broad-spectrum antimicrobials. Although a number of antifungal agents are currently available, the need remains for effective but less toxic alternatives for this indication. We therefore conducted a phase 2 study of micafungin for 80 patients with hematologic diseases who were suffering from persistent or recurrent fever after at least 96 h of antibacterial therapy. The patients were treated with micafungin at a fixed dose of 150 mg/day. Of the 78 evaluable patients, 54 (69 %) achieved defervescence by the time of neutrophil recovery, and 56 (72 %) completed the treatment in accordance with the provision of the protocol. Four patients developed invasive fungal infection, nine changed antifungal therapy because of lack of efficacy, and three discontinued micafungin because of drug-related adverse events. Based on the composite end point taking account of these, the overall treatment success rate was 60 %, with the lower limit of a 90 % confidence interval (50.3 %) exceeding the predefined threshold success rate (50 %). These findings show the efficacy and safety of micafungin for empirical antifungal therapy in patients with persistent or recurrent febrile neutropenia, warranting further investigation of this drug in a phase 3 study. PMID:23857638

Mizuno, Hiroki; Sawa, Masashi; Yanada, Masamitsu; Shirahata, Mizuho; Watanabe, Masato; Kato, Tomonori; Nagai, Hirokazu; Ozawa, Yukiyasu; Morishita, Takanobu; Tsuzuki, Motohiro; Goto, Emi; Tsujimura, Akane; Suzuki, Ritsuro; Atsuta, Yoshiko; Emi, Nobuhiko; Naoe, Tomoki

2013-08-01

14

Predictive value of interleukin-5 and monocyte chemotactic protein-1 for bacteremia in children with febrile neutropenia.  

PubMed

A variety of clinical and laboratory parameters have been used to predict bacteremia. We hypothesize that the generation of a cytokine profile could be used to identify patients at higher risk of bacteremia at the time of presentation with febrile neutropenia. We prospectively evaluated children with cancer who presented with an episode of febrile neutropenia. A multiplexed flow cytometric assay was performed which measured 15 cytokines and chemokines obtained before the initiation of antibiotics. Fifty-eight episodes of chemotherapy-induced febrile neutropenia were included in this study during which 4 patients (7%) had bacteremia. An interleukin-5 level of >8 pg/dL had a sensitivity of 67% and a specificity of 96% to predict bacteremia. An monocyte chemotactic protein-1 level >1650 pg/dL had a sensitivity of 80% and a specificity of 82% to predict bacteremia. Erythrocyte sedimentation rate, C-reactive protein, protein C, and other cytokines/chemokines were not predictive of bacteremia. Elevations of interleukin-5 and monocyte chemotactic protein-1 are predictive of bacteremia in children with cancer who have febrile neutropenia. Prospective studies should be undertaken to determine whether these parameters retain predictive value in a larger series of patients and can select children for outpatient management or early discharge. PMID:22584776

Aquino, Victor M; Cost, Carrye; Gomez, Ana; Bowers, Daniel C; Ramilo, Octavio; Ahmad, Naveed; Winick, Naomi; Leavey, Patrick J

2012-08-01

15

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

PubMed Central

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

2011-01-01

16

Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma: data from the INC-EU Prospective Observational European Neutropenia Study  

PubMed Central

Myelosuppression, particularly febrile neutropenia (FN), are serious dose-limiting toxicities that occur frequently during the first cycle of chemotherapy. Identifying patients most at risk of developing FN might help physicians to target prophylactic treatment with colony-stimulating factor (CSF), in order to decrease the incidence, or duration, of myelosuppression and facilitate delivery of chemotherapy as planned. We present a risk model for FN occurrence in the first cycle of chemotherapy, based on a subgroup of 240 patients with non-Hodgkin lymphoma (NHL) enroled in our European prospective observational study. Eligible patients had an International Prognostic Index of 0–3, and were scheduled to receive a new myelosuppressive chemotherapy regimen with at least four cycles. Clinically relevant factors significantly associated with cycle 1 FN were older age, increasing planned cyclophosphamide dose, a history of previous chemotherapy, a history of recent infection, and low baseline albumin (<35 g/l). Prophylactic CSF use and higher weight were associated with a significant protective effect. The model had high sensitivity (81%) and specificity (80%). Our model, together with treatment guidelines, may rationalise the clinical decision of whether to support patients with CSF primary prophylaxis based on their risk factor profile. Further validation is required.

Pettengell, Ruth; Bosly, Andre; Szucs, Thomas D; Jackisch, Christian; Leonard, Robert; Paridaens, Robert; Constenla, Manuel; Schwenkglenks, Matthias

2008-01-01

17

An open study of the comparative efficacy and safety of caspofungin and liposomal amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with haematological malignancy.  

PubMed

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2-45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients. PMID:17005784

Ellis, Michael; Frampton, Chris; Joseph, Jose; Alizadeh, Hussain; Kristensen, Jorgen; Hauggaard, Anders; Shammas, Fuad

2006-10-01

18

Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection  

Microsoft Academic Search

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times

A. J. Ullmann; O. A. Cornely; A. Burchardt; R. Hachem; D. P. Kontoyiannis; K. Topelt; R. Courtney; D. Wexler; G. Krishna; M. Martinho; G. Corcoran; I. Raad

2006-01-01

19

Clinical Predictive Models for Chemotherapy-Induced Febrile Neutropenia in Breast Cancer Patients: A Validation Study  

PubMed Central

Background Predictive models for febrile neutropenia (FN) would be informative for physicians in clinical decision making. This study aims to validate a predictive model (Jenkin’s model) that comprises pretreatment hematological parameters in early-stage breast cancer patients. Patients and Methods A total of 428 breast cancer patients who received neoadjuvant/adjuvant chemotherapy without any prophylactic use of colony-stimulating factor were included. Pretreatment absolute neutrophil counts (ANC) and absolute lymphocyte counts (ALC) were used by the Jenkin’s model to assess the risk of FN. In addition, we modified the threshold of Jenkin’s model and generated Model-A and B. We also developed Model-C by incorporating the absolute monocyte count (AMC) as a predictor into Model-A. The rates of FN in the 1st chemotherapy cycle were calculated. A valid model should be able to significantly identify high-risk subgroup of patients with FN rate >20%. Results Jenkin’s model (Predicted as high-risk when ANC?3.1*10?9/L;ALC?1.5*10?9/L) did not identify any subgroups with significantly high risk (>20%) of FN in our population, even if we used different thresholds in Model-A(ANC?4.4*10?9/L;ALC?2.1*10?9/L) or B(ANC?3.8*10?9/L;ALC?1.8*10?9/L). However, with AMC added as an additional predictor, Model-C(ANC?4.4*10?9/L;ALC?2.1*10?9/L; AMC?0.28*10?9/L) identified a subgroup of patients with a significantly high risk of FN (23.1%). Conclusions In our population, Jenkin’s model, cannot accurately identify patients with a significant risk of FN. The threshold should be changed and the AMC should be incorporated as a predictor, to have excellent predictive ability.

Zhu, Liling; Su, Fengxi; Jia, Weijuan; Deng, Xiaogeng

2014-01-01

20

Real-world impact of granulocyte-colony stimulating factor on febrile neutropenia  

PubMed Central

Background Primary prophylaxis with granulocyte colony–stimulating factors (pp-g-csf) is recommended in patients undergoing chemotherapy carrying a febrile neutropenia (fn) risk of 20% or more. In the present study, we examined clinical practice patterns and the impact of pp-g-csf on fn incidence in women with early-stage breast cancer (ebc) treated with modern adjuvant chemotherapy (act). Methods This single-centre retrospective cohort study of women with ebc, who were identified from the pharmacy database and who received at least 1 cycle of modern act from January 2009 to December 2011, was conducted at the Cancer Centre of Southeastern Ontario. Data on patient demographics, pathology, stage distribution, chemotherapy, pp-g-csf use, dose reductions, chemotherapy delays, treatment discontinuation, relative dose intensity, and fn events were collected. Chi-square tests, t-tests, univariate and multivariate logistic regression analyses, and nonparametric Mann–Whitney U-tests were used for data analysis. Results Of the 239 women eligible for analysis, 145 (61%) received pp-g-csf, and 50 (21%) developed at least 1 episode of fn. Use of pp-g-csf was associated with a significantly lower rate of fn (14% vs. 31%, p = 0.002) and trends to fewer dose delays (17% vs. 27%, p = 0.060) and dose reductions (19% vs. 25%, p = 0.28). Among women receiving pp-g-csf, higher fn rates were associated with an age of 65 years or older, taxane-based chemotherapy, and prophylaxis with filgrastim Conclusions Clinical practice patterns at our institution showed that more than 50% of ebc patients treated with modern act received pp-g-csf, which led to fewer fn episodes and increased delivery of planned act. The observed high fn risk despite pp-g-csf was linked to older age, taxane-based chemotherapy, and filgrastim.

Altwairgi, A.K.; Hopman, W.M.; Mates, M.

2013-01-01

21

Self-administered antibiotic therapy for chemotherapy-induced, low-risk febrile neutropenia in patients with nonhematologic neoplasms.  

PubMed

A multicenter prospective nonrandomized trial was conducted to evaluate the efficacy of self-administered oral ofloxacin in the treatment of cancer patients with fever and neutropenia. Patients receiving chemotherapy who either resided far away and were unable to reach the oncology ward within 12 hours of the onset of fever or were unable to afford the expensive inpatient care were eligible for inclusion in the study. Requirements for enrollment included an absolute neutrophil count of < or = 0.5 x 10(9)/L, temperature of > 38 degrees C, and the ability to take oral medications. The patients were instructed to immediately self-administer oral ofloxacin on recognition of fever and to maintain daily telephonic contact with the oncology staff. One-hundred eleven such episodes were evaluable. Neutropenia was mostly of short duration (87% of episodes, < or = 1 week); 92 (83%) of the febrile episodes responded to ofloxacin with resolution of fever and neutropenia (hospitalization was not required). Two episodes resulted in death before the patients could be brought to the hospital; 17 (15%) did not respond to ofloxacin, and the patients required hospitalization. The conditions of all except one improved with parenteral combination antibiotic therapy. No toxicity was observed, and the cost of therapy was negligible. Treatment with oral ofloxacin may possibly serve as an alternative to hospitalization for those who are otherwise at low risk of morbidity and death. PMID:7811873

Malik, I A; Khan, W A; Aziz, Z; Karim, M

1994-09-01

22

Ceftazidime-resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia  

Microsoft Academic Search

Objectives: To evaluate prevalence of ceftazidime-resistant Klebsiella pneumoniae (CRKP) in the pediatric oncology unit of University Hospital, Kuala, Lumpur, and to identify differences between febrile neutropenic pediatric patients with CRKP and ceftazidime-sensitive K. pneumoniae (CSKP) bacteremia.Materials and Methods: Febrile neutropenic patients treated between January 1996 and December 1997 at the pediatric oncology unit of University Hospital, Kuala Lumpur, were prospectively

Hany Ariffin; Parasakthi Navaratnam; Mahfuzah Mohamed; Anusha Arasu; Wan Ariffin Abdullah; Chan Lee Lee; Lin Hai Peng

2000-01-01

23

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

ClinicalTrials.gov

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

2013-07-10

24

Etiology and Clinical Course of Febrile Neutropenia in Children with Cancer  

PubMed Central

Background The etiology, clinical course and outcome of fever and neutropenia (FN) in children with cancer using the current FN guidelines and diagnostic resources in the United States have not been well described. Patients and Methods Medical records of one randomly selected FN episode per patient during 2004–2005 at a pediatric oncology center were reviewed. Patients were managed as per institutional FN guidelines and blood cultures collected in continuously-read BACTEC™ bottles. Results Of 337 FN episodes, infection was proven in 86 (25%) and probable in 75 (22%). 177 episodes (53%) were judged fever of unknown origin (FUO). Bacteremia accounted for most (41) of the proven bacterial episodes, with viridans streptococci (13), Pseudomonas spp (6) and E. coli (6) the most frequently isolated organisms. The median time to positivity of blood cultures was 12 hrs (range 5.4 – 143.7) with 93% positive within 24 hours of incubation. Viral pathogens were identified in 29 (34%) episodes. Compared to other patients, those with FUO had shorter median duration of fever (0.5 vs. 2.0 days; p<0.0001) and hospitalization (3 vs. 6 days; p<0.0001), longer median duration since last chemotherapy (6.0 vs. 4.0 days; p=0.01) and were less likely to have a diagnosis of acute myelogenous leukemia (AML) (11% vs 22%; p=0.009) or develop a clinical complication (5.1% vs 24.4%; p<0.0001). Conclusion Despite currently available diagnostic resources, the majority of patients with FN have FUO marked by a low rate of clinical complications and no infection-related mortality. Emergence of viridans streptococci as the most common blood isolate has affected FN treatment recommendations. Study findings will help further development of strategies for risk stratified management of fever with neutropenia in pediatric patients.

Hakim, Hana; Flynn, Patricia M.; Knapp, Katherine M.; Srivastava, Deo Kumar; Gaur, Aditya

2009-01-01

25

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

Microsoft Academic Search

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

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

2011-01-01

26

Cost-Effectiveness Analysis Comparing Two Approaches for Empirical Antifungal Therapy in Hematological Patients with Persistent Febrile Neutropenia  

PubMed Central

New approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more cost-effective than the EAT approach in the management of PFN in hematological patients.

Gil-Navarro, M. Victoria; Aguilar-Guisado, Manuela; Espigado, Ildefonso; de Pipaon, Maite Ruiz Perez; Falantes, Jose; Pachon, Jeronimo

2013-01-01

27

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

PubMed

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/?l. 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

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

28

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

Microsoft Academic Search

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

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

1998-01-01

29

Deviations from Guideline-Based Therapy for Febrile Neutropenia in Cancer Patients and Their Impact on Outcomes  

PubMed Central

Background Febrile neutropenia (FN) is a common cause of mortality in cancer patients. We examined guideline and non-guideline-based care for patients hospitalized with FN and examined how initial treatment influenced outcomes. Methods The Perspectives database was used to examine the treatment of cancer patients with FN from 2000–2010. To capture initial decision-making, we examined treatment within 48 hours of admission. We determined use of guideline-based antibiotics and non-guideline-based treatments, vancomycin and granulocyte-colony stimulating factors (GCSF). Hierarchical models were developed to examine the factors associated with treatment. Patients were stratified into low and high-risk groups and the effect of initial treatment on outcome (non-routine discharge and death) examined. Findings Among 25,231 admitted with FN, guideline-based antibiotics were administered to 79%, vancomycin to 37%, and GCSF to 63%. Patients treated at high-FN volume hospitals, by high-FN volume physicians and patients managed by hospitalists were more likely to receive guideline-based antibiotics (p<0.05). Vancomycin use increased from 17% in 2000 to 55% in 2010 while GCSF use only decreased from 73% to 55%. Among low-risk patients, prompt initiation of guideline-based antibiotics decreased discharge to a nursing facility (OR=0.77; 95% CI, 0.65–0.92) and death (OR=0.63; 95% CI, 0.42–0.95). Conclusion While use of guideline-based antibiotics is high, use of the non-guideline-based treatments, vancomycin and GCSF, is also high. Physician and hospital factors are the strongest predictors of both guideline and non-guideline-based treatment.

Wright, Jason D.; Neugut, Alfred I.; Ananth, Cande V.; Lewin, Sharyn N.; Wilde, Elizabeth T.; Lu, Yu-Shiang; Herzog, Thomas J.; Hershman, Dawn L.

2013-01-01

30

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

Microsoft Academic Search

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3\\/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and\\/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or

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

2006-01-01

31

Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network  

Microsoft Academic Search

Purpose  We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the\\u000a Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them\\u000a according to MASCC score and Talcott

Edwin Pun Hui; Linda K. S. Leung; Terence C. W. Poon; Frankie Mo; Vicky T. C. Chan; Ada T. W. Ma; Annette Poon; Eugenie K. Hui; So-shan Mak; Maria Lai; Kenny I. K. Lei; Brigette B. Y. Ma; Tony S. K. Mok; Winnie Yeo; Benny C. Y. Zee; Anthony T. C. Chan

32

A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia  

PubMed Central

Introduction Endothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN. Methods This was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome. Results A total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality. Conclusions A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia.

2013-01-01

33

Autoimmune neutropenia.  

PubMed

Autoimmune neutropenia (AIN) is a rare entity caused by antibodies directed against neutrophil-specific antigens. It includes primary and secondary autoimmune neutropenia. Acute autoimmune neutropenia can be related to drug-induced mechanism or viral infections. Chronic autoimmune neutropenias occur in the context of autoimmune diseases, hematological malignancies, such as large granular lymphocyte leukemia, primary immune deficiency syndromes or solid tumors. The therapeutic management depends on the etiology. Granulocyte growth factor is the main therapeutic option, raising the question of their long-term utilization safety. Corticosteroids or immunosuppressive therapy are indicated in infection-related AIN or in case of symptomatic autoimmune disease or LGL leukemia. PMID:24680423

Autrel-Moignet, Aline; Lamy, Thierry

2014-04-01

34

Background and methodology of MONITOR-GCSF, a pharmaco-epidemiological study of the multi-level determinants, predictors, and clinical outcomes of febrile neutropenia prophylaxis with biosimilar granulocyte-colony stimulating factor filgrastim  

Microsoft Academic Search

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of Zarzio® in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates statistical methodologies

Pere Gascón; Matti Aapro; Heinz Ludwig; Nadia Rosencher; Matthew Turner; MinKyoung Song; Karen MacDonald; Christopher Lee; Michael Muenzberg; Ivo Abraham

2011-01-01

35

Economic costs of chemotherapy-induced febrile neutropenia among patients with non-Hodgkin's lymphoma in European and Australian clinical practice  

PubMed Central

Background Economic implications of chemotherapy-induced febrile neutropenia (FN) in European and Australian clinical practice are largely unknown. Methods Data were obtained from a European (97%) and Australian (3%) observational study of patients with non-Hodgkin’s lymphoma (NHL) receiving CHOP (±rituximab) chemotherapy. For each patient, each cycle of chemotherapy within the course, and each occurrence of FN within cycles, was identified. Patients developing FN in a given cycle (“FN patients”), starting with the first, were matched to those who did not develop FN in that cycle (“comparison patients”), irrespective of subsequent FN events. FN-related healthcare costs (£2010) were tallied for the initial FN event as well as follow-on care and FN events in subsequent cycles. Results Mean total cost was £5776 (95%CI £4928-£6713) higher for FN patients (n?=?295) versus comparison patients, comprising £4051 (£3633-£4485) for the initial event and a difference of £1725 (£978-£2498) in subsequent cycles. Among FN patients requiring inpatient care (76% of all FN patients), mean total cost was higher by £7259 (£6327-£8205), comprising £5281 (£4810-£5774) for the initial hospitalization and a difference of £1978 (£1262-£2801) in subsequent cycles. Conclusions Cost of chemotherapy-induced FN among NHL patients in European and Australian clinical practice is substantial; a sizable percentage is attributable to follow-on care and subsequent FN events.

2012-01-01

36

Granulocyte colony-stimulating factor as secondary prophylaxis of febrile neutropenia in the management of advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy: a decision analysis.  

PubMed

Current practice guidelines are unclear regarding the role of secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma despite several small retrospective studies that demonstrate the omission of growth factors to be a safe and economic practice. We used a decision-analytic model to compare secondary prophylaxis with granulocyte colony-stimulating factor (G-CSF) to no G-CSF with the onset of severe neutropenia for a hypothetical cohort of patients with advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). There was a net benefit of 0.017 years and 0.037 quality-adjusted life years for no G-CSF use in severe neutropenia. On microsimulation (10 000 trials), 96% of the simulations showed that the no G-CSF strategy is preferred to the use of G-CSF. This finding was robust across a wide range of sensitivity analyses. Our analysis suggests that G-CSF not be used as secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma. PMID:23597142

Graczyk, Joanna; Cheung, Matthew C; Buckstein, Rena; Chan, Kelvin

2014-01-01

37

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

PubMed Central

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

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

2014-01-01

38

Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors  

PubMed Central

Background Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors. Methods Data from consecutive breast cancer patients receiving chemotherapy with 4–6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles. Results Overall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR?=?0.78 [0.65; 0.93]) and haemoglobin (OR?=?0.81 [0.67; 0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR?=?6.7 [1.04; 43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR?=?1.02 [1.01; 1.03]), carriers of the rs246221 variant C-allele (OR?=?2.0 [1.03; 3.86]) in MRP1 and the rs351855 variant C-allele (OR?=?2.48 [1.13; 5.44]) in FGFR4. Lower height (OR?=?0.62 [0.41; 0.92]) increased risk of FN in the first cycle. Conclusions Both established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings.

2014-01-01

39

A case of an SLE patient with febrile neutropenia who experienced exacerbation of cutaneous manifestations after the administration of G-CSF.  

PubMed

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. Although hematological anomalies are commonly found in SLE, severe polymorphonuclear leukocyte depletion is rare. Most episodes of severe granulocytopenia in SLE patients tend to occur as part of drug toxicity-induced medullar hypoplasia, and recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) has been shown to be effective for treating neutropenia associated with SLE. However, flares of some autoimmune diseases, including flares in six SLE patients, have been reported after G-CSF therapy. This report presents the case of a patient with SLE who experienced exacerbation of skin symptoms after G-CSF therapy. There is sufficient evidence to suggest that G-CSF can exacerbate inflammatory disease. Furthermore, the possibility that several factors other than rhG-CSF may affect the disease activity of SLE should be considered when SLE patients with neutropenia require the administration of rhG-CSF. Therefore rhG-CSF should be used with considerable caution in neutropenic patients with SLE. PMID:22933310

Sakai, Takashi; Hatano, Yutaka; Abe, Itomi; Ishii, Koji; Fujiwara, Sakuhei

2013-11-01

40

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

Microsoft Academic Search

Background and purpose: The empirical use of antibiotic therapy is widely accepted for patients with fever and neutropenia during cancer chemotherapy. The use of intravenous monotherapy with broad-spectrum anti- biotics in patients at high risk for complications is an appropriate alternative. However, few data are available for pediatric patients. The aim of this study was to compare the efficacy and

Carlos Alberto Pires Pereira; Fabianne Altruda Carlesse; Flávio Augusto; Vercillo Luisi

2008-01-01

41

Gene Polymorphisms and Febrile Neutropenia in Acute Leukemia-No Association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 Are Associated with the Disease in Turkish Patients: A Preliminary Study.  

PubMed

Aims: The aim of this study was to investigate the mannose-binding lectin 2 (MBL-2), interleukin (IL)-4, Toll-like receptor 4 (TLR-4), angiotensin converting enzyme (ACE), chemokine receptor 5 (CCR-5), and IL-1 receptor antagonist (RA) gene polymorphisms (GPs) in acute leukemias (ALs) and to evaluate their roles in febrile neutropenia (FN) resulting from chemotherapy. Methods: The study included 60 AL patients hospitalized between the period of July 2001 and August 2006. Polymorphisms for the genes ACE(I/D), CCR-5, IL-1RA, MBL-2, TLR-4, and IL-4 were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymerase. Genotype frequencies for these genes were compared in the patient and control groups. The relationships between the genotypes and the body distribution of infections, pathogens, the duration of neutropenia, and febrile episodes in AL patients were evaluated. Results: No significant differences in either the genotype distribution or the allelic frequencies of TLR-4, IL-4, CCR-5, IL-1RN GPs were observed between patients and healthy controls. The AB/BB genotype (53.3%) in the MBL-2 gene was found to be significantly higher in the AL patients compared with control groups. There were correlations between the presence of MBL-2, TLR-4, and ACE polymorphisms and clinical parameters due to FN. Overall, bacteremia was more common in MBL BB and ACE DD. Gram-positive bacteremia was more common in ACE for ID versus DD genotype. Gram-negative bacteremia was more common for both the MBL-2 AB/BB genotype and TLR-4 AG genotype. Median durations of febrile episodes were significantly shorter in ACE DD and MBL AB/BB. Conclusion: Although TLR-4, ACE, and MBL-2 GPs have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of FN in patients with ALs. As a conclusion, TLR-4, ACE, and MBL-2 genes might play roles in the genetic etiopathogenesis of FN in patients with ALs. PMID:24819208

Pehlivan, Mustafa; Sahin, Handan Haydaro?lu; Ozdilli, Kur?at; Onay, Hüseyin; Ozcan, Ali; Ozkinay, Ferda; Pehlivan, Sacide

2014-07-01

42

Febrile neutropenic events in cancer patients Treatment for fever and neutropenia in young adult patients during intensive chemotherapy for solid tumours  

Microsoft Academic Search

Summary Febrile neutropenic events (FNE) were studied in 90 patients on chemotherapy protocols for solid tumours, from 1986 to 1990. All patients received intensive chemotherapy with a high dose intensity. There were 51 FNE admissions in 31 patients, with an average event rate of 1.6\\/patient. The average periods of granulocytopenia, fever and admission were 3.5, 2.7 and 5.4 days respectively.

Mariëlle Nobbenhuis; Frans J. Cleton

1992-01-01

43

Cyclic and chronic neutropenia.  

PubMed

Patients with severe chronic neutropenia have blood neutrophil level <0.5 × 10(9)/L, predisposing them to increased susceptibility to life-threatening bacterial infections. This chapter focuses on cyclic and congenital neutropenia, two very interesting and rare hematological conditions causing severe chronic neutropenia. Both disorders respond well to treatment with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF). This chapter describes the basic features of these diseases and addresses several current clinical issues regarding their diagnosis and management. Cyclic neutropenia is a rare, inherited autosomal dominant disorder due to mutations in the gene for neutrophil elastase (ELA-2 or ELANE). Usually these patients have regular oscillation of blood neutrophil counts with periods of severe neutropenia occurring every 21 days. During these periods, they have painful mouth ulcers, fevers, and bacterial infections. The most severe consequences are gangrene, bacteremia, and septic shock. Cyclic neutropenia patients respond well to treatment with granulocyte colony-stimulating factor (G-CSF) given by subcutaneous injections on a daily or alternate-day basis. Severe congenital neutropenia is also a rare hematological disease, but it is probably more common than cyclic neutropenia. Blood neutrophils are extremely low on a continuing basis; the levels may be <0.2 × 10(9)/L, and the risk of severe bacterial infections is even greater than in cyclic neutropenia. The majority of cases are due to autosomal dominant inheritance of mutations in the ELA-2 or ELANE gene. Less commonly, mutations in HAX-1, G6PC3, and other genes cause this disorder. Treatment with G-CSF is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of severe congenital neutropenia patients evolve to develop acute myeloid leukemia, necessitating careful clinical monitoring. PMID:21052952

Dale, David C; Welte, Karl

2011-01-01

44

Immediate versus deferred empirical antifungal (IDEA) therapy in high-risk patients with febrile neutropenia: a randomized, double-blind, placebo-controlled, multicenter study.  

PubMed

Empirical antifungal therapy is widely used in high-risk neutropenic hematology patients with fever persisting for more than 4 days. This clinical trial assessed whether immediate empirical therapy with voriconazole could lower the rates of invasive fungal infections (IFIs) compared with this approach. In a double-blind, placebo-controlled, multicenter study, patients with acute leukemia undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) recipients were randomized to broad-spectrum antibacterial therapy plus voriconazole (immediate) or placebo (deferred) after the onset of neutropenic fever. If fever persisted for 96 h, patients were switched to open-label intravenous voriconazole; oral treatment was permitted after 96 h. The primary endpoint was the rate of proven/probable IFIs between Days 2 and 28 after fever onset in the modified intent-to-treat (mITT) complete-case population. One hundred and forty-seven patients were randomized to immediate (n?=?81) or deferred (n?=?66) voriconazole. In the mITT population, six patients in the immediate group and nine in the deferred group developed proven/probable IFI between Days 2 and 28 (p?=?0.258). The safety profiles were similar in both groups. While immediate empirical therapy with voriconazole appears to be safe in febrile neutropenic high-risk patients, it was not associated with a significant reduction in IFIs compared with therapy deferred for 96 h after fever onset. PMID:23271674

Maschmeyer, G; Heinz, W J; Hertenstein, B; Horst, H-A; Requadt, C; Wagner, T; Cornely, O A; Löffler, J; Ruhnke, M

2013-05-01

45

Antibiotic-associated neutropenia.  

PubMed

Neutropenia is an uncommon but potentially serious complication of drug therapy. Many drugs, especially antibiotics, can produce this untoward effect. Typically, drug-induced neutropenia occurs in a patient receiving a semisynthetic penicillin for two weeks or more. The cause is believed to be either a hypersensitivity reaction or a toxic dose-related suppression of white blood cell precursors. Most patients improve after discontinuation of the drug. PMID:1575118

Walbroehl, G S; John, P G

1992-05-01

46

Suramin-induced neutropenia  

Microsoft Academic Search

This paper presents a retrospective review of 6 cases of severe neutropenia attributed to suramin, the response to granulocyte-colony stimulating factor (G-CSF) and the possible mechanism. Plasma suramin concentrations, G-CSF, platelet-derived growth factor-AB (PDGF-AB) and fibroblast growth factor basic (FGF basic) levels were measured and correlated with neutropenic course. The time course of neutropenia was unpredictable and occurred both during

N. A. Dawson; R. M. Lush; S. M. Steinberg; A. C. Tompkins; D. J. Headlee; W. D. Figg

1996-01-01

47

Chemotherapy-Induced Neutropenia in HIV Positive Patients with Lymphoma: Comparison of Pegfilgrastim with Daily Filgrastim Administration  

PubMed Central

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

Teofili, Luciana; Izzi, Immacolata; Nuzzolo, Eugenia Rosa; Scoppettuolo, Giancarlo; Torti, Lorenza; Rossi, Marianna; de Gaetano Donati, Katleen

2012-01-01

48

Febrile Response to Bacterial Pyrogens in Leukemia  

Microsoft Academic Search

T HE INTRAVENOUS INJECTION of a bacterial pyrogen is followed successively by its localization in the buffy coat, transient neutropenia and fever.' These changes, and the discovery by Bennett and Beeson2 of a pyrogen in granubocytes, Suggest that fever could result from interaction between bac- teriab pyrogens and granubocytes. Yet the failure to elicit a diminished febrile reaction in rabbits

ABRAHAM I. BRAUDE; JAY BECK; MARGARET ZALESKY

2010-01-01

49

Febrile Seizures  

MedlinePLUS

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

50

Febrile Seizures  

MedlinePLUS

... to febrile seizures are not considered to have epilepsy, since epilepsy is characterized by recurrent seizures that are not ... be at risk of subsequent seizures without fever (epilepsy). In other words, between 95 and 98 percent ...

51

Antibiotic Rotation for Febrile Neutropenic Patients with Hematological Malignancies: Clinical Significance of Antibiotic Heterogeneity  

PubMed Central

Background Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum ?-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance. Methods This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis. Results In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods. Conclusions We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia.

Chong, Yong; Shimoda, Shinji; Yakushiji, Hiroko; Ito, Yoshikiyo; Miyamoto, Toshihiro; Kamimura, Tomohiko; Shimono, Nobuyuki; Akashi, Koichi

2013-01-01

52

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 ...

53

An infant with chronic severe neutropenia.  

PubMed

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

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

2014-01-01

54

Colony-Stimulating Factors for Febrile Neutropenia during Cancer Therapy  

PubMed Central

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?

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

2014-01-01

55

Autoimmune neutropenia in adults.  

PubMed

Autoimmune neutropenias (AIN) in adults are a heterogeneous group of diseases with clinical manifestations varying from being asymptomatic to having infectious complications with considerable morbidity and mortality. They are characterized by autoantibodies directed against neutrophils, resulting in destruction of neutrophils. AIN can be divided into two forms. In primary AIN, neutropenia is usually the sole hematologic abnormality and it is more common in children. Secondary AIN, which is more prevalent in adults, is associated with underlying autoimmune diseases, malignancies, infections, particularly viral, neurological diseases or drug exposure. This article is an overview of these conditions with emphasis on secondary AIN; it also discusses the available serological methods for antibody detection and recent therapeutic developments including colony stimulating factors, rituximab and Campath-1H. PMID:19293004

Akhtari, Mojtaba; Curtis, Brian; Waller, Edmund K

2009-09-01

56

Evaluation and Management of Patients with Isolated Neutropenia  

PubMed Central

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

Newburger, Peter E.; Dale, David C.

2013-01-01

57

Severe neutropenia in dengue patients: prevalence and significance.  

PubMed

Studies on severe neutropenia in dengue are scarce, and its clinical significance is uncertain. We analyzed a cohort of 1,921 reverse transcription polymerase chain reaction-confirmed adult dengue patients admitted to the Communicable Disease Center in Singapore between 2005 and 2008. Time trend analyses for daily absolute neutrophil counts (ANCs) were done using Bayesian hierarchical and Markov models. We found that severe neutropenia, defined as ANC ? 0.5 × 10(9)/L, was found in 11.8% with a median duration of 1 day. ANC nadir occurred on illness day 5. Severe neutropenia was not predictive of more severe disease and not associated with secondary bacterial infections, prolonged hospital stay, prolonged fever, or fatal outcome. We concluded that prophylactic antibiotics are not indicated in patients with severe neutropenia without indication for bacterial infection. PMID:24732460

Thein, Tun-Linn; Lye, David C; Leo, Yee-Sin; Wong, Joshua G X; Hao, Ying; Wilder-Smith, Annelies

2014-06-01

58

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.  

PubMed

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment. PMID:11112678

Shenep, J L; Flynn, P M; Baker, D K; Hetherington, S V; Hudson, M M; Hughes, W T; Patrick, C C; Roberson, P K; Sandlund, J T; Santana, V M; Sixbey, J W; Slobod, K S

2001-01-01

59

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 ...

60

Neutropenia in patients with primary antibody deficiency disorders.  

PubMed

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7+/-5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient. PMID:17301396

Rezaei, Nima; Farhoudi, Abolhassan; Pourpak, Zahra; Aghamohammadi, Asghar; Moin, Mostafa; Gharagozlou, Mohammad; Movahedi, Masoud; Mirsaeid Ghazi, Bahram; Atarod, Lida; Mahmoudi, Maryam; Ahmadi Afshar, Akefeh; Bazargan, Nasrin; Isaeian, Anna; Nabavi, Mohammad; Chavoshzadeh, Zahra; Heydarzadeh, Marzieh; Bemanian, Mohammad Hassan; Fazlollahi, Mohammad Reza

2004-06-01

61

Diagnostic criteria for autoimmune neutropenia.  

PubMed

Autoimmune neutropenia denotes that the number of circulating polymorphonuclear neutrophils is below 1.5×10(9)/L. This encompasses a wide range of disorders from primary conditions to complications of systemic autoimmune diseases or hematological neoplasms. Antineutrophil autoantibodies are particularly difficult to detect, and their amount does not correlate with the degree of neutropenia. Granulocyte colony-stimulating factor is the first-line therapy, but should be restricted to patients with total absence of neutrophils and/or severe infections. PMID:24418296

Youinou, Pierre; Jamin, Christophe; Le Pottier, Laëtitia; Renaudineau, Yves; Hillion, Sophie; Pers, Jacques-Olivier

2014-01-01

62

Fever, febrile seizures and epilepsy  

PubMed Central

Seizures induced by fever (febrile seizures) are the most common type of pathological brain activity in infants and children. These febrile seizures and their potential contribution to the mechanisms of limbic (temporal lobe) epilepsy have been a topic of major clinical and scientific interest. Key questions include the mechanisms by which fever generates seizures, the effects of long febrile seizures on neuronal function and the potential contribution of these seizures to epilepsy. This review builds on recent advances derived from animal models and summarizes our current knowledge of the mechanisms underlying febrile seizures and of changes in neuronal gene expression and function that facilitate the enduring effects of prolonged febrile seizures on neuronal and network excitability. The review also discusses the relevance of these findings to the general mechanisms of epileptogenesis during development and points out gaps in our knowledge, including the relationship of animal models to human febrile seizures and epilepsy.

Dube, Celine M.; Brewster, Amy L.; Richichi, Cristina; Zha, Qinqin; Baram, Tallie Z.

2009-01-01

63

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

PubMed Central

Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined.

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

2008-01-01

64

Intermittent neutropenia as an early feature of mild mevalonate kinase deficiency.  

PubMed

A 15-month-old boy, born to Iranian consanguineous parents presented with intermittent neutropenia interspersed with episodes of fever and leukocytosis since early infancy. No ELA2 mutations were found and the bone marrow study was normal. At age 4 years he progressed to more typical attacks of periodic attacks of fever, abdominal pain, oral aphthous ulcers, cutaneous rash and leukocytosis. The clinical and laboratory features were compatible with the mild form of mevalonate kinase deficiency, usually named "Hyper-IgD and periodic fever syndrome" (HIDS). Genomic sequencing of the mevalonate kinase (MVK) gene revealed homozygous missense mutation (p.Val377Ile). On demand dexamethasone resulted in a rapid amelioration of febrile episodes. The presentation of intermittent neutropenia has not been reported in HIDS and deserves more attention in large patient cohorts. PMID:24177804

Parvaneh, Nima; Ziaee, Vahid; Moradinejad, Mohammad-Hassan; Touitou, Isabelle

2014-01-01

65

Periodontal changes associated with chronic idiopathic neutropenia  

Microsoft Academic Search

This case report focuses on the periodontal status of a young patient with chronic idiopathic neutropenia. A four- year clinical course is presented. Chronic idiopatin'c neutropenia is a relatively rare blood dyscrasia characterized by a severe decrease in the number of circulating neutrophils. Young individuals exin'biting tins problem experience rapid destruction of periodontal structures. A review of related literature reveals

Kenneth L. Kalkwarf; Dennis P. Gutz

1981-01-01

66

Pulmonary hypertension, heart failure and neutropenia due to diazoxide therapy  

Microsoft Academic Search

Primary persistent hyperinsulinaemic hypoglycaemia is characterised by clinical symptoms that occur when blood glucose levels\\u000a drop below the normal range. Diazoxide treatment remains the mainstay of medical therapy. Tolerance of diazoxide is usually\\u000a excellent, but several side effects of this drug have been described. We present a 4-month-old girl who developed pulmonary\\u000a hypertension, heart failure and neutropenia during diazoxide therapy.

Dincer Yildizdas; Sevcan Erdem; Osman Küçükosmano?lu; Mustafa Yilmaz; Bilgin Yüksel

2008-01-01

67

Genetic background of febrile seizures.  

PubMed

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 1? (IL-1?) 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-1?, 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

Saghazadeh, Amene; Mastrangelo, Mario; Rezaei, Nima

2014-01-01

68

Experiencing neutropenia: Quality of life interviews with adult cancer patients  

Microsoft Academic Search

BACKGROUND: Neutropenia is a common toxicity in chemotherapy but detailed information about how neutropenia is associated with changes in patients' quality of life is not readily available. This prospective study interviewed patients with grade 4 neutropenia to provide qualitative information on patients' experience of developing and coping with grade 4 neutropenia during a cycle of chemotherapy. METHODS: A sample of

Barry V Fortner; Kurt W Tauer; Ted Okon; Arthur C Houts; Lee S Schwartzberg

2005-01-01

69

Food-borne bacteremic illnesses in febrile neutropenic children.  

PubMed

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

Lee, Anselm Chi-Wai; Siao-Ping Ong, Nellie Dawn

2011-08-31

70

Randomized comparison between antibiotics alone and antibiotics plus granulocyte-macrophage colony-stimulating factor ( Escherichia coli-derived) in cancer patients with fever and neutropenia  

Microsoft Academic Search

purpose: A prospective, randomized study was conducted to determine if recombinant human granulocyte-macrophage colony-stimulating factor (rh-GMCSF) (Escherichia coli-derived) could improve response rates to antibiotic therapy and shorten the duration of neutropenia in cancer patients.patients and methods: A total of 107 febrile neutropenic cancer patients were randomly assigned to empiric therapy with ticarcillin-clavulanate (4 g ticarcillin + 0.1 g clavulanate IV

Elias J Anaissie; Shahe Vartivarian; Gerald P Bodey; Catherine Legrand; Hagop Kantarjian; Dima Abi-Said; Cynthia Karl; Saroj Vadhan-Raj

1996-01-01

71

Two cases of bacteremia caused by Leptotrichia trevisanii in patients with febrile neutropenia.  

PubMed

We present two cases of bacteremia caused by Leptotrichia trevisanii: a 12-year-old girl with recurrent myeloid leukemia of the mandible and a 66-year-old man with esophageal carcinoma. As this filamentous bacillus showed indefinite Gram staining and the identification based on biochemical enzymatic reactions was not definitive, identification required 16s rRNA analysis. For this organism, drug sensitivity testing showed susceptiblity to each ?-lactam antibiotics and clindamycin, but resistance to fluoroquinolone and erythromycin. This filamentous bacillus needs careful identification and appropriate antibiotic treatment. PMID:23584842

Higurashi, Yoshimi; Tatsuno, Keita; Fujimoto, Fumie; Kobayashi, Ito; Ida, Kohmei; Seto, Yasuyuki; Ohkusu, Kiyofumi; Ezaki, Takayuki; Okugawa, Shu; Moriya, Kyoji

2013-12-01

72

Atypical Febrile Seizures, Mesial Temporal Lobe Epilepsy, and Dual Pathology  

PubMed Central

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE.

Sanon, Nathalie T.; Desgent, Sebastien; Carmant, Lionel

2012-01-01

73

A case of cyclic neutropenia in adults.  

PubMed

A 22 years old patient presented with recurrent episodes of diarrhoea, pharyngitis, apthous ulcers and fever for the past 6 months. The episodes lasted a week each time. The patient was admitted and blood studies revealed neutropenia with increased number of Large Granular Lymphocytes. Later on it was found out that his neutrophil count dropped to less than 0.2 x 10(9)/L after every 3 weeks. Bone marrow study revealed decreases neutrophil precursors during these episodes. He was diagnosed with adult onset cyclic neutropenia and his episodes were treated with G-CSF and Ceftriaxone. PMID:22764469

Mansoor, Muhammad Sohail; Khan, Muhammad Bilal Salman

2012-03-01

74

The mild inflammatory response in febrile neutropenic lymphoma patients with low risk of complications is more pronounced in patients receiving tobramycin once daily compared with three times daily.  

PubMed

We evaluated inflammatory markers in febrile neutropenic lymphoma patients undergoing high-dose chemotherapy with autologous stem cell support. Based on MASCC scores, our patients had a low risk of serious complications and a perspective of a benign initial clinical course of the febrile neutropenia. We also studied the impact of tobramycin given once versus three times daily on these immune markers. Sixty-one patients participating in a Norwegian multicentre prospective randomized clinical trial, comparing tobramycin once daily versus three times daily, given with penicillin G to febrile neutropenic patients, constituted a clinically homogenous group. Four patients had bacteraemia, all isolates being Gram-positive. Thirty-two patients received tobramycin once daily, and 29 patients received tobramycin three times daily. Blood samples were taken at the onset of febrile neutropenia and 1-2 days later. All samples were frozen at -70 °C and analysed at the end of the clinical trial for C-reactive protein (CRP), procalcitonin (PCT), complement activation products, mannose-binding lectin (MBL) and 17 cytokines. We found a mild proinflammatory response in this series of patients. CRP was non-specifically elevated. Ten patients with decreased MBL levels showed the same mild clinical and proinflammatory response. Patients receiving tobramycin once daily showed a more pronounced proinflammatory response compared with patients receiving tobramycin three times daily. Overall, febrile neutropenic cancer patients with a benign clinical course show a mild proinflammatory immune response. PMID:21883353

Torfoss, D; Sandstad, B; Mollnes, T E; Høiby, E A; Holte, H; Bjerner, J; Bjøro, T; Gaudernack, G; Kvalheim, G; Kvaløy, S

2011-12-01

75

The Infectious Diseases Society of America 2002 Guidelines for the Use of Antimicrobial Agents in Patients with Cancer and Neutropenia: Salient Features and Comments  

Microsoft Academic Search

Infection remains the most common complication of chemotherapy-induced neutropenia. Bacterial infections predominate initially. Invasive fungal infections occur in patients with prolonged neutropenia. Chemopro- phylaxis is recommended only for patients at high risk. Initial empirical therapy is based on local epidemiology and drug-susceptibility patterns. Patients at low risk can be treated as outpatients. Other patients need hospital- based, parenteral therapy. Several

2004-01-01

76

Neutrophil elastase in cyclic and severe congenital neutropenia  

Microsoft Academic Search

Mutations in ELA2 encoding the neutro- phil granule protease, neutrophil elastase (NE), are the major cause of the 2 main forms of hereditary neutropenia, cyclic neutropeniaandseverecongenitalneutro- penia (SCN). Genetic evaluation of other forms of neutropenia in humans and model organisms has helped to illumi- nate the role of NE. A canine form of cyclic neutropenia corresponds to hu- man Hermansky-Pudlak

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

2007-01-01

77

Severe congenital neutropenia: new lane for ELANE.  

PubMed

In this issue of Blood, Tidwell et al1 demonstrate that mutations in the start codon (protein synthesis is initiated at the codon ATG) of neutrophil elastase (ELANE) result in the production of N-terminally truncated elastase, which mislocates to the nucleus and results in severe congenital neutropenia (SCN). PMID:24458273

Borregaard, Niels

2014-01-23

78

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

SciTech Connect

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.

Okada, Yuji; Kawagishi, Mayumi; Kusaka, Masaru (Kirin Brewery Co., Ltd., Gunma (Japan))

1990-01-01

79

Hepatosplenic candidiasis: an overlooked cause of prolonged fever during recovery from an episode of neutropenia.  

PubMed

Two cases of hepatosplenic candidiasis (HSC) are reported occurring after protracted episodes of neutropenia, induced by chemotherapy for acute leukemia in one case and drug hypersensitivity in the other. The disease presented with persistent or recurrent fever after correction of the neutropenia and with splenomegaly. The alkaline phosphatases were elevated. The diagnosis was strongly suggested by abdominal ultrasonography, CT scan and MRI, which showed multiple hepatosplenic defects. It was confirmed by serologic tests for candidiasis, the presence, in 1 case, of circulating candida antigens, and the rapid response to amphotericin B. The diagnosis of HSC should be considered in patients with persistent fever after an episode of neutropenia. Ideally, histologic confirmation is desirable, but this is often obtainable only by open liver biopsy, an aggressive procedure in such patients. Failing this, our 2 cases stress the diagnostic value of noninvasive imaging techniques, serological testing (in particular the discovery of circulating candida antigens) and the response to amphotericin B. PMID:2644620

Fenaux, P; Lemaitre, L; Ajana, F; Colcher-Plantier, I; Jouet, J P; Bauters, F

1989-01-01

80

Evidence on the use of paracetamol in febrile children.  

PubMed Central

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.

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

2003-01-01

81

[Significance of the antimicrobial drug used to prevent febrile infection following prostate needle biopsy].  

PubMed

The rate of incidence of febrile infection and the antimicrobial drug used at the time of prostate needle biopsy was examined retrospectively. SPFX (sparfloxacin) 400 mg (January 2007 to March 2010) and LVFX (levofloxacin) 500 mg (April 2010, onward) were administered prophylactically in 1,034 patients undergoing transrectal or transperineal prostate biopsy. One febrile infection occurred and resolved in each group. A single dose of LVFX 500 mg before the procedure effectively prevented febrile infection in both transrectal and transperineal prostate needle biopsy. PMID:24894858

Kobayashi, Satoshi; Maki, Tomoko; Kobayashi, Takeshi; Hamaguchi, Masumitsu; Yoshikawa, Masahiro; Sakamoto, Naotaka; Iguchi, Atushi

2014-05-01

82

Osmolality and electrolytes in cerebrospinal fluid and serum of febrile children with and without seizures  

Microsoft Academic Search

Abstract  During acute febrile diseases mild disturbances of water and electrolyte balance occur frequently. It has been suggested that\\u000a changes in electrolyte balance, in particular hyponatraemia, might predispose a child to convulsions during febrile illness;\\u000a however, the changes of electrolytes in the CSF are not known.\\u000a \\u000a We have studied the effects of fever and convulsions on water and electrolyte balance in

Tiula Kiviranta; Leena Tuomisto; Eila M. Airaksinen

1996-01-01

83

Cardiomyopathy in a male patient with neutropenia and growth delay.  

PubMed

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

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

84

Cardiomyopathy in a male patient with neutropenia and growth delay  

PubMed Central

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.

2014-01-01

85

Neutrophil antibody specificity in different types of childhood autoimmune neutropenia.  

PubMed

Autoimmune neutropenia (AIN) in children can be divided into 2 forms. In primary AIN, neutropenia is the sole abnormality, and although neutrophil counts are generally below 500 microL(-1), mild bacterial infections occur. Primary AIN is mostly seen in young children and shows a self-limited course. AIN occurring in association with autoimmune diseases (secondary AIN) often shows more severe infectious complications. We analyzed clinical and serological data from 28 pediatric patients with AIN to evaluate whether there is a possible relationship between specificity of the neutrophil autoantibodies and the clinical course of the disease. Specificity of the circulating antibodies was determined with the indirect granulocyte immunofluorescence test (GIFT) and a panel of phenotyped donor neutrophils. The samples were further analyzed in the monoclonal antibody immobilization of granulocyte antigens assay (MAIGA) for neutrophil antigen (NA)1, NA2, CD11a, and CD11b specificity. With the indirect GIFT, an antibody specificity was deduced in 26 of the 28 analyzed samples. In all but 3 sera from patients with primary AIN, NA1-(76%) or NA2-(10%) specific antibodies were detected with the indirect GIFT. In 2 samples, the reactivity in the indirect GIFT was too weak to draw conclusions, but the MAIGA showed NA1 and/or NA2 specificity of the antibodies. One serum, from a patient with primary AIN with a persistent neutropenia for more than 6 years, contained NA1, possibly pan-FcgammaRIIIb, and CD11a antibodies. In 4 sera from patients with primary AIN, weak antibodies with CD11a or CD11b specificity were detected with the MAIGA. Sera from 7 patients with secondary AIN contained in all cases antibodies with pan-FcgammaRIIIb specificity, as deduced from the indirect GIFT results and absorbance/elution experiments performed with 2 sera. The MAIGA confirmed this for only 1 of the 5 tested sera. Furthermore, CD11a antibodies were detected in 1 of the 5 tested sera. In conclusion, our results indicate that primary AIN is usually associated with NA-specific antibodies, whereas secondary AIN seems to be associated with pan-FcgammaRIIIb antibodies. Thus, characterization of the antibodies in sera from children with AIN discriminates patients with primary AIN from those with secondary AIN. PMID:10477706

Bruin, M C; von dem Borne, A E; Tamminga, R Y; Kleijer, M; Buddelmeijer, L; de Haas, M

1999-09-01

86

Febrile seizures: Mechanisms and relationship to epilepsy  

PubMed Central

Studies of febrile seizures have been driven by two major enigmas: first, how these most common of human seizures are generated by fever has not been known. Second, epidemiological studies have linked prolonged febrile seizures with the development of temporal lobe epilepsy, yet whether long or recurrent febrile seizures cause temporal lobe epilepsy has remained unresolved. To investigate these questions, a model of prolonged (complex) febrile seizures was developed in immature rats and mice, permitting mechanistic examination of the potential causal relationships of fever and seizures, and of febrile seizures and limbic epilepsy. Although the model relied on hyperthermia, it was discovered that the hyperthermia-induced secretion of endogenous fever mediators including interleukin-1?, which contributed to the generation of these ‘febrile’ seizures. In addition, prolonged experimental febrile seizures provoked epilepsy in a third of the animals. Investigations of the mechanisms of this epileptogenesis demonstrated that expression of specific ion (HCN) channels and of endocannabinoid signaling, may be involved. These may provide novel drug targets for intervention in the epileptogenic process.

Dube, Celine M.; Brewster, Amy L.; Baram, Tallie Z.

2009-01-01

87

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

PubMed Central

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

Deepak, Desh; Garg, Rakesh; Pawar, Mridula; Banerjee, Neerja; Solanki, Rakesh; Maurya, Indubala

2011-01-01

88

Two Cases of Severe Neutropenia Associated with Ticlopidine  

Microsoft Academic Search

Ticlopidine is a powerful inhibitor of platelet aggregation which is induced by adenosine diphosphate. Ticlopi- dine has been shown to be effective in reducing combined stroke, myocardial infarction, reocclusion of coronary stent. The principal side effects of ticlopidine are severe neutropenia, rash and gastrointestinal upset. Recently, we experienced two cases of severe neutropenia associated with ticlopidine. One was administered ticlopidine

Seong Tae Kim; Jung Gu Lee; Chan Jong Seo; Eak Kyun Shin

1999-01-01

89

Assessment of febrile seizures in children  

Microsoft Academic Search

Febrile seizures are the most common form of childhood seizures, affecting 2–5% of all children and usually appearing between\\u000a 3 months and 5 years of age. Despite its predominantly benign nature, a febrile seizure (FS) is a terrifying experience for\\u000a most parents. The condition is perhaps one of the most prevalent causes of admittance to pediatric emergency wards worldwide.\\u000a FS, defined as

Arne Fetveit

2008-01-01

90

Congenital neutropenia: diagnosis, molecular bases and patient management  

PubMed Central

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.

2011-01-01

91

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

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

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

2013-01-01

92

Cerebrospinal fluid zinc concentrations in febrile convulsions.  

PubMed Central

Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal fluid GABA values have been reported in association with several seizure disorders, including febrile convulsions. It is also known that fever and/or infections may cause a reduction in serum zinc concentrations. In this study the hypothesis that febrile convulsions are related to low cerebrospinal fluid zinc was tested. Cerebrospinal fluid zinc concentrations were measured in 66 febrile children: 32 with febrile convulsions, 18 with fever but without convulsions, and 16 with aseptic (viral) meningitis. There was no statistically significant difference in the cerebrospinal fluid zinc between the three groups of children, and the mean concentration was 26.2 micrograms/l. No significant relationship was found between either age, gender, maximal temperature, type of infection, or time of performance of the lumbar puncture and cerebrospinal fluid zinc concentration. These results do not support the hypothesis that febrile convulsions are related to reduced cerebrospinal fluid zinc concentrations.

Garty, B Z; Olomucki, R; Lerman-Sagie, T; Nitzan, M

1995-01-01

93

Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma  

PubMed Central

A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma.

Vakkalanka, Bhanu; Link, Brian K.

2011-01-01

94

Antibodies to Myeloid Precursor Cells in Autoimmune Neutropenia.  

National Technical Information Service (NTIS)

Antibodies to mature blood neutrophils and to bone marrow myeloid cells have been described in the sera of some patients with apparent autoimmune neutropenia. To further explore the prevalence and specificities of antibodies to myeloid precursor cells, we...

K. R. Hartman V. F. LaRussa S. Rothwell T. O. Atolagbe F. T. Ward

1994-01-01

95

Issues in febrile urinary tract infection management.  

PubMed

Urinary tract infections are common occurrences in the pediatric age group and are a cause of significant morbidity and expense. The understanding of the consequences and sequelae of febrile urinary tract infections led to revision of standard protocols initiated by the American Academy of Pediatrics (AAP) in 1999. A less invasive protocol of radiologic evaluation has been the major outcome of the revised AAP guidelines. Emphasis on prevention of recurrent febrile urinary tract infections has also led to therapeutic programs that are centered less around the use of prophylactic antibiotics than has previously been the practice. PMID:22857837

Koyle, Martin A; Shifrin, Donald

2012-08-01

96

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

PubMed

Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p <0001) whereas serum creatinine >2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation. PMID:23607363

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

2014-02-01

97

?-Herpesviruses in Febrile Children with Cancer  

PubMed Central

We conducted a cross-sectional study of ?-herpesviruses in febrile pediatric oncology patients (n = 30), with a reference group of febrile pediatric solid-organ transplant recipients (n = 9). One (3.3%) of 30 cancer patients and 3 (33%) of 9 organ recipients were PCR positive for cytomegalovirus. Four (13%) of 30 cancer patients and 3 (33%) of 9 transplant recipients had human herpesvirus 6B (HHV-6B) DNAemia, which was more common within 6 months of initiation of immune suppression (4 of 16 vs. 0 of 14 cancer patients; p = 0.050). HHV-6A and HHV-7 were not detected. No other cause was identified in children with HHV-6B or cytomegalovirus DNAemia. One HHV-6B–positive cancer patient had febrile disease with concomitant hepatitis. Other HHV-6B–positive children had mild “viral” illnesses, as did a child with primary cytomegalovirus infection. Cytomegalovirus and HHV-6B should be included in the differential diagnosis of febrile disease in children with cancer.

Yee-Guardino, Stephanie; Gowans, Kate; Yen-Lieberman, Belinda; Berk, Pamela; Kohn, Debra; Wang, Fu-Zhang; Danziger-Isakov, Lara; Sabella, Camille; Worley, Sarah; Goldfarb, Johanna

2008-01-01

98

Febrile Seizures and Epilepsy: Possible Outcomes  

MedlinePLUS

... 10.1212/WNL.0b013e31826aa902 2012;79;e80-e82 Neurology Jacqueline A. French Febrile seizures: Possible outcomes This ... current as of August 27, 2012 http://www.neurology.org/content/79/9/e80.full.html located ...

99

Astrovirus MLB2 Viremia in Febrile Child  

PubMed Central

Astroviruses cause diarrhea, but it is not known whether they circulate in human plasma. Astrovirus MLB2 was recently discovered in diarrhea samples from children. We detected MLB2 in the plasma of a febrile child, which suggests that MLB2 has broader tropism than expected and disease potential beyond the gastrointestinal tract.

Holtz, Lori R.; Wylie, Kristine M.; Sodergren, Erica; Jiang, Yanfang; Franz, Carl J.; Weinstock, George M.; Storch, Gregory A.

2011-01-01

100

Cutaneous Infrared Thermometry for Detecting Febrile Patients  

PubMed Central

We assessed the accuracy of cutaneous infrared thermometry, which measures temperature on the forehead, for detecting patients with fever in patients admitted to an emergency department. Although negative predictive value was excellent (0.99), positive predictive value was low (0.10). Therefore, we question mass detection of febrile patients by using this method.

Zhao, Yan; Defrenne, Stephanie; Bonnet, Pascale; Riou, Bruno

2008-01-01

101

Iron status in children with febrile seizure.  

PubMed

This hospital based cross sectional analytic study was carried out in department of Pediatrics Dhaka Medical College Hospital and Combined Military Hospital from July 2009 to June 2010 to find out the relationship of iron status with febrile seizure in children. Sixty children aged 6 months to 5 years having febrile seizure were enrolled as cases after taking proper consent by purposive sampling. Sixty age matched children with fever but no seizures were taken as control after taking proper consent. Children having a febrile seizure, developmental delay, hemorrhagic disorder, severe malnutrition or micronutrient deficiency and abnormal CSF findings were excluded from the study. In cases after control of seizure 2 ml of CSF was taken for cytology, biochemistry, Gram & AFB staining. Two milliliter of blood from cases as well as control was collected, released to EDTA bottle for Hb, MCV and MCHC. Again 2 ml of blood was taken in plain test tube for testing serum iron, TIBC and for serum ferritin. Serum iron, TIBC, serum ferritin was estimated by automated analyzer (PENTRA for serum iron, DADE BEHRING for TIBC, IMMULITE 1000 for serum ferritin). There was no significant difference between two groups regarding age (p>0.05), sex (p>0.05). High fever (p<0.001) and continuous fever (p<0.001) was significantly associated with febrile seizure. Seizure was generalized in all with positive family history in 83.3% cases. The Mean±SD of blood Hb (Case 9.8±1.6; Control 10.7±0.9), MCH (Case 22.1±2.3; Control 24.3±3.6) & serum ferritin (Case 55.1±29.3; Control 99.6±81.9) level were significantly low associated with febrile seizure (p<0.05). No significant difference was found between cases and control regarding MCV, serum iron and serum TIBC. PMID:23715348

Choudhury, M A; Zaman, M; Mollah, A H; Hoque, M A; Fatmi, L E; Islam, M N; Bhuiyan, K J; Hossain, M A

2013-04-01

102

Trends in Neutropenia-Related Inpatient Events  

PubMed Central

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

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

2012-01-01

103

Oral health comparison between children with neutropenia and healthy controls.  

PubMed

The purpose of this cross-sectional study was to assess and compare the oral health of children with neutropenia, who are under the active care of a hematologist in a designated marrow failure and myelodysplasia program, to a healthy control group. Children aged 6-18 with neutropenia attending the Marrow Failure and Myelodysplasia Program at SickKids Hospital and controls attending the Children's Clinic, Faculty of Dentistry, University of Toronto were asked to participate in the study consisting of a patient questionnaire followed by a dental and radiographic examination. Fifteen patients with neutropenia (mean age 12.14 ± 4.04 years) and 26 healthy controls (mean age 11.61 ± 3.82 years) participated in this study. Patients with neutropenia reported significantly increased mouth sores (p < .008) and bleeding gums while brushing (p < .001). The dmft/t score was significantly lower for the neutropenia group (p < .009). The clinical examination also showed that there were no statistically significant differences with respect to ulcerations, gingival recession, tooth mobility, gingival inflammation, periodontal bone loss, DMFT/T scores, plaque, and calculus levels. Preliminary data demonstrates that pediatric patients who are under the active care of a hematologist do not present with an increased risk of oral diseases. PMID:24382366

Park, Michael S; Tenenbaum, Howard C; Dror, Yigal; Gloguaer, Michael

2014-01-01

104

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

PubMed Central

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

Yu, Donghui T; Seger, Diane L; Peterson, Josh F; Kumar, Ritesh N; Bates, David W

2006-01-01

105

Inheritance of febrile seizures in sudden unexplained death in toddlers.  

PubMed

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

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

2012-04-01

106

Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers  

PubMed Central

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.

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

2014-01-01

107

Predictive value for infection of febrile morbidity after vaginal surgery  

Microsoft Academic Search

Objective: To determine the screening value of febrile morbidity for detecting infections after vaginal surgery.Methods: A cohort of 431 consecutive women had vaginal surgery at the M. S. Hershey Medical Center from September 1988 through June 1995. Outcomes of febrile morbidity and infection were analyzed.Results: Fifty-four of 431 patients (12.5%) had febrile morbidity. Thirty-five infections (8.1%) were identified, of which

D. Paul Shackelford; M. K Hoffman; M. F Davies; P. F Kaminski

1999-01-01

108

Gingivo-periodontal manifestations in chronic benign neutropenia.  

PubMed

A case of chronic benign neutropenia in a 7-year-old Caucasian male is reported. The predominant clinical symptoms were persistent gingivitis and periodontitis. The clinical, hematological, oral radiographical, histological, and therapeutical features of this uncommon disease are discussed. PMID:276530

Reichart, P A; Dornow, H

1978-02-01

109

Hematopoetic Stem Cell Transplantation in Neutrophil Disorders: Severe Congenital Neutropenia, Leukocyte Adhesion Deficiency and Chronic Granulomatous Disease  

Microsoft Academic Search

Until further progress will occur in the field of gene therapy, the only curative treatment available in severe congenital\\u000a neutropenia, leukocyte adhesion deficiency, and chronic granulomatous disease is allogeneic hematopoietic stem cell transplantation\\u000a (HSCT). This review summarizes the current data regarding indications for transplantation in each disease, treatment results\\u000a using related and unrelated donors, as well as toxicity of HSCT

Ronit Elhasid; Jacob M. Rowe

2010-01-01

110

Repeated Lentivirus-Mediated Granulocyte Colony-Stimulating Factor Administration to Treat Canine Cyclic Neutropenia  

PubMed Central

Abstract Cyclic neutropenia occurs in humans and gray collie dogs, is characterized by recurrent neutropenia, and is treated by repeated injections of recombinant granulocyte colony-stimulating factor (rG-CSF). As dose escalation of lentivirus may be clinically necessary, we monitored the outcome of four sequential intramuscular injections of G-CSF-lentivirus (3×107 IU/kg body weight) to a normal dog and a gray collie. In the normal dog absolute neutrophil counts were significantly increased after each dose of virus, with mean levels of 27.75±3.00, 31.50±1.40, 35.05±1.68, and 43.88±2.94×103 cells/?l, respectively (p<0.001), and elevated neutrophil counts of 31.18±7.81×103 cells/?l were maintained for more than 6 years with no adverse effects. A gray collie dog with a mean count of 1.94±1.48×103 cells/?l received G-CSF-lentivirus and we observed sustained elevations in neutrophil levels for more than 5 months with a mean of 26.00±11.00×103 cells/?l, significantly increased over the pretreatment level (p<0.001). After the second and third virus administrations mean neutrophil counts of 15.80±6.14 and 11.52±4.90×103 cells/?l were significantly reduced compared with cell counts after the first virus administration (p<0.001). However, after the fourth virus administration mean neutrophil counts of 15.21±4.50×103 cells/?l were significantly increased compared with the previous administration (p<0.05). Throughout the nearly 3 years of virus administrations the dog gained weight, was healthy, and showed neutrophil counts significantly higher than pretreatment levels (p<0.001). These studies suggest that patients with cyclic and other neutropenias may be treated with escalating doses of G-CSF-lentivirus to obtain a desired therapeutic neutrophil count.

Yanay, Ofer; Dale, David C.

2012-01-01

111

Iron Deficiency and Iron Deficiency Anemia in Children with Febrile Seizure  

PubMed Central

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 ?g/dl vs. 75.13 ± 35.57 ?g/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.

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

2013-01-01

112

Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures  

ERIC Educational Resources Information Center

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…

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

2012-01-01

113

Dengue fever in febrile returning travellers to a UK regional infectious diseases unit  

Microsoft Academic Search

Background. Dengue occurs in many tourist destinations, and is increasingly imported by returning travellers. We review the epidemiology and clinical features of confirmed dengue in returning travellers presenting to a UK regional infectious diseases unit.Methods. A retrospective, case-record review of febrile returning travellers, admitted to Leicester Royal Infirmary during 2000–2002. The presenting clinical features of patients with positive dengue serology

Iain Stephenson; John Roper; Maria Fraser; Karl Nicholson; Martin Wiselka

2003-01-01

114

Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following FOLFOX4 failure in elderly patients with metastatic colorectal cancer  

PubMed Central

Previous studies have reported improved outcomes for elderly patients with metastatic colorectal cancer (mCRC) treated with oxaliplatin or irinotecan as first-line chemotherapy. However, few studies regarding second-line chemotherapy with oxaliplatin or irinotecan are currenlty available. We analyzed retrospectively the efficacy and toxicity in elderly patients (median age, 74 years) treated with second-line FOLFIRI following first-line FOLFOX4 failure. From March 2005 to January 2008, 35 elderly patients with mCRC received first-line FOLFOX4 comprising leucovorin, 5-FU and oxaliplatin followed by second-line FOLFIRI comprising leucovorin, 5-FU and irinotecan. The median number of treatment courses with FOLFIRI was 5 (range 2–32). One patient responded to the treatment. The disease control rate was 38.2%. The median time to treatment failure was 3 months, and the median overall survival (OS) time from the beginning of first-line chemotherapy was 20.7 months. The incidence of grade 3/4 neutropenia was 71.4%, while febrile neutropenia was 11.4%. The incidence of non-hematological toxicity was low. The use of the three active drugs, 5-FU, oxaliplatin and irinotecan, in mCRC produced the longest OS in elderly as well as in younger patients. However, the elderly patients treated with second-line FOLFIRI had a high rate of hematological toxicity. Second-line FOLFIRI may therefore be used with caution in the elderly.

KUBOKI, YASUTOSHI; MIZUNUMA, NOBUYUKI; OZAKA, MASATO; OGURA, MARIKO; SUENAGA, MITSUKUNI; SHINOZAKI, EIJI; MATSUSAKA, SATOSHI; CHIN, KEISHOU; MATSUURA, MASAAKI; HATAKE, KIYOHIKO

2011-01-01

115

Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following FOLFOX4 failure in elderly patients with metastatic colorectal cancer.  

PubMed

Previous studies have reported improved outcomes for elderly patients with metastatic colorectal cancer (mCRC) treated with oxaliplatin or irinotecan as first-line chemotherapy. However, few studies regarding second-line chemotherapy with oxaliplatin or irinotecan are currenlty available. We analyzed retrospectively the efficacy and toxicity in elderly patients (median age, 74 years) treated with second-line FOLFIRI following first-line FOLFOX4 failure. From March 2005 to January 2008, 35 elderly patients with mCRC received first-line FOLFOX4 comprising leucovorin, 5-FU and oxaliplatin followed by second-line FOLFIRI comprising leucovorin, 5-FU and irinotecan. The median number of treatment courses with FOLFIRI was 5 (range 2-32). One patient responded to the treatment. The disease control rate was 38.2%. The median time to treatment failure was 3 months, and the median overall survival (OS) time from the beginning of first-line chemotherapy was 20.7 months. The incidence of grade 3/4 neutropenia was 71.4%, while febrile neutropenia was 11.4%. The incidence of non-hematological toxicity was low. The use of the three active drugs, 5-FU, oxaliplatin and irinotecan, in mCRC produced the longest OS in elderly as well as in younger patients. However, the elderly patients treated with second-line FOLFIRI had a high rate of hematological toxicity. Second-line FOLFIRI may therefore be used with caution in the elderly. PMID:22866109

Kuboki, Yasutoshi; Mizunuma, Nobuyuki; Ozaka, Masato; Ogura, Mariko; Suenaga, Mitsukuni; Shinozaki, Eiji; Matsusaka, Satoshi; Chin, Keishou; Matsuura, Masaaki; Hatake, Kiyohiko

2011-05-01

116

Optimum management of pediatric patients with fever and neutropenia  

Microsoft Academic Search

Fever with neutropenia is a common clinical problem in patients receiving cancer treatment. Prevention and optimum management\\u000a of infectious complications is critical to the overall success of cancer therapy. This article provides an overview of the\\u000a current status of this evolving subject. While the basic principles of rapid institution of broad spectrum antibiotics, early\\u000a intervention with empiric antifungal therapy and

Aditya H. Gaur; Patricia M. Flynn; Jerry L. Shenepu

2004-01-01

117

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

PubMed Central

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

2013-01-01

118

Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature.  

PubMed

Rituximab is a chimeric monoclonal antibody against CD20 that is used mainly for the treatment of CD20-positive lymphoma. Recently, its use has been expanded to include treatment of other nonmalignant diseases such as rheumatologic diseases and autoimmune cytopenia. Correlating with the increased use of rituximab has been an increased number of reports of its late adverse effects. One of these is late-onset neutropenia (LON). Most investigators define LON as grade III-IV neutropenia occurring 3-4 weeks after the last treatment with rituximab, in the absence of an alternative explanation for the neutropenia.We report 6 cases of LON identified in our institution. Four patients were treated for diffuse large B-cell lymphoma, and 2 patients for follicular lymphoma. Median patient age was 68 years (range, 33-83 yr); LON appeared after a median interval of 77 days (range, 42-153 d) and lasted for a median of 5 days (range, 1-45 d). Five of the 6 patients presented with infectious complications, and 4 patients experienced recurrent episodes of neutropenia. One patient presented with LON and concomitant subacute pulmonary disease that was attributed to rituximab therapy.In addition to our own case series we present a systematic review of the literature, which we performed to compile data to describe better the syndrome of LON. Systematic studies, case series, and case reports were extracted. Most studies dealing with LON are retrospective by design and are limited by the heterogeneous populations included in the analysis. The incidence of LON is generally reported to be in the range of 3%-27%. Data regarding populations at risk are not consistent, and in some instances are conflicting.Patients considered at increased risk of LON include patients after autologous stem cell transplantation, patients treated for acquired immunodeficiency syndrome (AIDS)-related lymphoma, and patients treated with purine analogues. Patients who received previous cytotoxic treatment as well as those treated with more intensive chemotherapy or with chemotherapy in combination with radiotherapy are also considered to be at risk of LON. In addition, advanced stages of disease and having received multiple doses of rituximab are risk factors for LON.The mechanism of LON is poorly understood. Direct toxicity is very unlikely. Some speculate that there may be an infectious etiology involved, as well as an antibody-mediated process, but these ideas have not been substantiated. The concept of a lymphocyte subpopulation imbalance leading to LON has been presented based on the demonstration of T-LGL in peripheral blood and bone marrow of patients with LON. Perturbations in stromal-derived factor-1 and in the BAFF cytokine have also been discussed as potential players in the pathogenesis of LON. A recent study correlated specific polymorphism in the immunoglobulin G Fc receptor FC?RIIIa 158 V/F with increased rates of LON.The clinical significance of LON is important because it may affect treatment strategies. Of note, infectious complications are not very frequent and not very severe. Pooling data from the major retrospective studies reveals an infection rate of 16.9%. Most infections were mild and resolved promptly. One death occurred from infection during neutropenia. Repeated episodes of LON are not uncommon, but it is so far impossible to identify those patients at risk of these relapsing episodes of LON. Re-treatment with rituximab after LON may result in recurrent episodes, but the implications and risks are uncertain at the present time. The role of growth factors once LON appears is ill defined, and the decision to use them should be made on a case-by-case basis. PMID:20827108

Wolach, Ofir; Bairey, Osnat; Lahav, Meir

2010-09-01

119

Corneal and Scleral Dellen after an Uneventful Pterygium Surgery and a Febrile Episode  

PubMed Central

Introduction We describe a patient with corneal and scleral dellen, which occurred after an uneventful pterygium excision without adjunctive therapy and a subsequent febrile episode. Case Report A 43-year-old woman presented with a history of recurrent irritation in her right eye and a diagnosis of pterygium. The pterygium was excised under local anesthesia with the bare scleral technique and without the use of antimetabolites. No complications occurred until 14 days after surgery when corneal and sclera dellen appeared; this was 2 days after a concomitant febrile episode (39°C). Tobramycin and dexamethasone eye drops given after surgery were withdrawn and topical lubricants and antibiotic ointment, in combination with oral L-amino acids, were administered along with eye patching. One week later, the corneal dellen had completely healed and, 4 weeks later, the thinned sclera appeared regularly thick and white in color. Three months after surgery, a small recurrent pterygium was diagnosed, which remained stable without signs of inflammation for additional 18 months. Conclusions Corneal and scleral dellen might be a late complication of uneventful pterygium surgery without antimetabolites and a subsequent febrile episode.

Accorinti, Massimo; Gilardi, Marta; Giubilei, Marco; De Geronimo, Daniele; Iannetti, Ludovico

2014-01-01

120

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

PubMed Central

Background Nivestim™ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia and febrile neutropenia induced by myelosuppressive chemotherapy. Nivestim™ has been studied in phase 2 and 3 clinical trials where its efficacy and safety was found to be similar to its reference product, Neupogen®. Follow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV studies that are evaluating the safety profile of Nivestim™ for the prevention and treatment of febrile neutropenia (FN) in patients treated with cytotoxic chemotherapy in general clinical practice. Methods/Design The NEXT (Tolérance de Nivestim chez les patiEnts traités par une chimiothérapie anticancéreuse cytotoXique en praTique courante) and VENICE (VErträglichkeit von NIvestim unter zytotoxischer Chemotherapie in der Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies evaluating the safety profile of Nivestim™ in 'real-world’ clinical practice. Inclusion criteria include patients undergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis (NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union pharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestim™ by gathering data on adverse events in all system organ classes. Secondary objectives include obtaining information on patient characteristics, efficacy of Nivestim™ therapy (including chemotherapy dose intensity), patterns of use of Nivestim™, and physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestim™. Data will be gathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of chemotherapy. Recruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment in July 2013 with 407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each study will be December 2013 and March 2014 respectively. Discussion The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in patients receiving Nivestim™ to support myelosuppressive chemotherapy in real world clinical practice. These data will improve our understanding of the performance of Nivestim™ in patients encountered in the general patient population. Trial registration NEXT NCT01574235, VENICE NCT01627990

2013-01-01

121

Adjuvant Chemotherapy for Breast Cancer in a Patient with Primary Autoimmune Neutropenia  

PubMed Central

We report an extremely rare and complex case of a 44-year-old woman diagnosed with an early stage triple negative breast cancer in the setting of primary autoimmune neutropenia with a pre-existing severe neutropenia. This case-report demonstrates that adjuvant chemotherapy for breast cancer can be administered in a patient with severe neutropenia. The management is however complicated and requires careful monitoring of side-effects related to both chemotherapy and treatment of autoimmune neutropenia. The role of chemotherapy in the treatment of triple negative breast cancer, the approach to autoimmune neutropenia and potential interactions are reviewed. To our knowledge, this is the first case reporting on the use of chemotherapy in a patient with severe pre-existing primary autoimmune neutropenia.

Trus, Michael; Dhamanaskar, Kavita; Potts, Jayson; Wasi, Parveen; Bains, Satvir; Bordeleau, Louise

2013-01-01

122

Risk of myelodysplastic syndrome and acute myeloid leukemia in congenital neutropenias  

Microsoft Academic Search

Granulocyte colony-stimulating factor (G-CSF) has had a major impact on the management of “severe chronic neutropenia” (SCN), a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia and Shwachman-Diamond syndrome (SDS) have developed myelodysplastic syndrome and acute myeloid leukemia (MDS\\/AML), which

Melvin H. Freedman; Blanche P. Alter

2002-01-01

123

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

Microsoft Academic Search

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

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

2000-01-01

124

Cost Effective Screening for UTI in Febrile Children.  

National Technical Information Service (NTIS)

Emergency department physicians should have a low threshold for screening for urinary tract infection (UTI) since it is often present and its sequelae are severe. While there is little consistent information about the prevalence of UTI among febrile pedia...

K. Shaw

1999-01-01

125

Laboratory predictors of dengue shock syndrome during the febrile stage.  

PubMed

The clinical manifestations of dengue hemorrhagic fever (DHF) consist of three successive stages: febrile, toxic and convalescent. The toxic stage is the critical period, which may manifestas circulatory disturbance or even profound shock in some patients. We attempted to determine predictors for the risk of dengue shock syndrome (DSS) during the febrile stage. One hundred one children with acute febrile illness were enrolled in the study, with a mean age of 11 years old. The diagnosis included dengue fever (DF) 21 cases, DHF grade I 30 cases, DHF grade II 33 cases, DHF grades III and IV 10 cases; children with other febrile illnesses (OFI) 7 cases were used as controls. Complete blood counts, coagulation tests, von Willebrand factor antigens (VWF:Ag) and ristocetin cofactor activity (VWF:Rcof) were determined daily during hospitalization and 2-4 weeks after discharge from the hospital. The results revealed any one of the following abnormal laboratory findings during the febrile stage served as a predictor for risk of DSS: increase in hematocrit > 25%, a platelet count < 40,000/microl, an activated partial thromboplastin time >44 seconds, a prothrombin time >14 seconds, a thrombin time >16 seconds or a VWF:Ag or VWF:Rcof > 210%. The relative risk ranged from 4.8 to 10.9. Simple laboratory investigations with complete blood count, coagulation test or the more sophisticated von Willebrand factor, are helpful in predicting the risk for DSS during the febrile stage. PMID:20578515

Chuansumrit, Ampaiwan; Puripokai, Chartchai; Butthep, Punnee; Wongtiraporn, Wanida; Sasanakul, Werasak; Tangnararatchakit, Kanchana; Chunhakan, Sirichan; Yoksan, Sutee

2010-03-01

126

Risk Factors for Neutropenia in Clozapine-Treated Children and Adolescents with Childhood-Onset Schizophrenia  

PubMed Central

Abstract Objective The purpose of this study was to retrospectively analyze rates of neutropenia and risk factors for neutropenia in hospitalized children and adolescents treated with clozapine. Methods A retrospective chart review was conducted for all patients who received clozapine at any time during a hospitalization at the National Institute of Mental Health (NIMH) between 1990 and 2011. All patients satisfied screening criteria for the NIMH childhood-onset schizophrenia study, including onset of psychosis before the age of 13 years. Absolute neutrophil count (ANC) values recorded during inpatient hospitalization were extracted for 87 eligible patients with a mean age of 13.35±2.46 years at hospitalization and a mean length of stay of 117±43 days. Results Mild neutropenia only (lowest ANC<2000/mm3 but>1500/mm3) was observed in 27 (31%) patients and moderate neutropenia (any ANC<1500/mm3) was observed in 17 (20%) patients. There were no cases of agranulocytosis or severe infection. Significant risk factors for mild neutropenia compared with no hematologic adverse effects (HAEs) were male gender (p=0.012) and younger age (p<0.001). Male gender was also a significant risk factor for moderate neutropenia compared with no HAEs (p=0.003). If a child of African American ethnicity developed neutropenia during hospitalization at all that child was significantly more likely to develop moderate neutropenia than mild neutropenia only (p=0.017). African American boys had the highest rate of moderate neutropenia at 47%. Sixteen of the 17 patients exhibiting moderate neutropenia were successfully treated with clozapine by the time of discharge; 8 of these 16 required adjunctive lithium carbonate administration to maintain ANC>2000/mm3. Conclusions Our study shows that the rates of neutropenia in clozapine-treated children and adolescents are considerably higher than in the adult population. Younger age, African American ethnicity, and male gender were significant risk factors. These are also risk factors for benign neutropenia in healthy children and adolescents. Despite these high rates of neutropenia, all but one of the patients with neutropenia during hospitalization were successfully discharged on clozapine.

Maher, Kristin N.; Tan, Marcus; Tossell, Julia W.; Weisinger, Brian; Gochman, Peter; Miller, Rachel; Greenstein, Deanna; Overman, Gerald P.; Rapoport, Judith L.

2013-01-01

127

Febrile illness experience among Nigerian nomads  

PubMed Central

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.

2012-01-01

128

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

PubMed

Severe congenital neutropenia (SCN) is a heterogeneous group of disorders with a defect in granulopoiesis causing marked neutropenia and severe bacterial infections. A 17-month-old girl (patient 1) was admitted due to cervical lymphadenitis caused by methicillin-resistant Staphylococcus aureus, with neutropenia. She had Pseudomonas aeruginosa sepsis and peritonitis with perforated appendicitis at 8-month of age. Her sister, a 37-month-old girl (patient 2), had recurrent stomatitis with profound neutropenia, and her mother, a 32-yr-old woman (patient 3), had had recurrent stomatitis until her early 20s with neutropenia. We found an ELANE gene mutation (c.597+1G > A) from them in direct DNA sequencing analysis. Patients 1 and 2 did not respond to granulocyte colony stimulating factor and patient 1 was treated with prolonged antibiotics and excision. We demonstrated inherited SCN cases showing different severity even with the same mutation of the ELANE gene in a family. PMID:24616599

Cho, Hye-Kyung; Jeon, In Sang

2014-03-01

129

Diazepam Versus Clobazam for Intermittent Prophylaxis of Febrile Seizures  

Microsoft Academic Search

Objective  To compare the effectiveness of intermittent clobazam versus diazepam therapy in preventing the recurrence of febrile seizures\\u000a and assess adverse effects of each drug.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  This prospective randomized controlled trial was performed on neurologically normal children aged from 6 months to 5 years\\u000a with a history of simple febrile seizures and normal electroencephalogram without any evidence of acute central nervous system\\u000a infection. The

Nahid Khosroshahi; Fatemeh Faramarzi; Payman Salamati; Seeid Mohammad Ogaghi Haghighi; Kamyar Kamrani

2011-01-01

130

ELANE Mutations in Cyclic and Severe Congenital Neutropenia--Genetics and Pathophysiology  

PubMed Central

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

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

2012-01-01

131

The Long-Term Risk of Epilepsy after Febrile Seizures in Susceptible Subgroups  

Microsoft Academic Search

A family history of seizures, preexisting brain damage, or birth complications may modify the long-term risk of epilepsy after febrile seizures. The authors evaluated the association between febrile seizures and epilepsy in a population-based cohort of 1.54 million persons born in Denmark (1978-2002), including 49,857 persons with febrile seizures and 16,481 persons with epilepsy. Overall, for children with febrile seizures

Mogens Vestergaard; Carsten Bøcker Pedersen; Per Sidenius; Jørn Olsen; Jakob Christensen

2007-01-01

132

Review of clinical profile and bacterial spectrum and sensitivity patterns of pathogens in febrile neutropenic patients in hematological malignancies: A retrospective analysis from a single center  

PubMed Central

Background: The aim of this study was to study clinical profile with bacterial spectrum and susceptibility patterns of pathogens in culture positive febrile neutropenic (FN) patients of hematological malignancies. Materials and Methods: We retrospectively reviewed the medical records of 23 hematological malignancy patients admitted with chemotherapy induced febrile neutropenia with culture positive results, at our institute between June 2011 and December 2011. Results: A total of 23 patients were studied 12 males and 11 females, with a median age of 35 years. Most common diagnosis was acute leukemia (78%) with the majority of patients developing febrile neutropenia during the induction phase of treatment. Most common presenting symptoms were fever, cough, dyspnea, and diarrhea. Primary site of infection was not found in 47% of patients while the rest had lung, gastro-intestinal and skin/soft-tissue infection. Overall 23 organisms were isolated during the study period, from blood (56%), sputum (46%), stool (23%), and nasal swab from one patient. Gram negative bacteria accounted for 78% of organisms while gram positive organisms accounted for 22% of the total isolates. The most common organisms were: Escherichia coli (43%), Staphylococcus aureus (22%), Pseudomonas aeruginosa (17.4%) and Klebsiella pneumonia (17.4%). Antibiotic sensitivity patterns of these bacteria were studied. Gram negative bacterial infections were associated with higher mortality (89%). Conclusions: Induction phase of treatment in acute leukemia is the major cause of FN in hematological malignancies at our institute and gram negative organisms are the predominant organisms with E. coli as major isolate while S. aureus represents the most common gram positive organism. Amikacin and cefoperazone/sulbactum appears to be initial antibiotic appropriate to cover most gram negative pathogens while vancomycin to be added for suspected gram positive infections. FN represents a major cause of morbidity and mortality in hematological malignancy patients, high index of suspicion and early empirical antibiotics with supportive care are main interventions to reduce high mortality for these patients. Antibiotics should be modified according to culture sensitive report as soon as possible.

Karanwal, Arun B.; Parikh, Bharat J.; Goswami, Parijat; Panchal, Harsha P.; Parekh, Bhavesh B.; Patel, Kaushal B.

2013-01-01

133

Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome.  

PubMed

Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund-Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome. PMID:15558713

Van Hove, Johan L K; Jaeken, Jaak; Proesmans, Marijke; Boeck, Kris De; Minner, Kristin; Matthijs, Gert; Verbeken, Eric; Demunter, Anouk; Boogaerts, Marc

2005-01-15

134

Serum Zinc Level in Children Presenting with Febrile Seizures.  

PubMed

Objective: To determine the frequency of low serum zinc level in children presenting with febrile seizures at The Children's Hospital and the Institute of Child Health (CH/ICH) Multan. Methods: This is an observational cross sectional study conducted at the Department of Pediatric Medicine, The Children's Hospital and the Institute of Child Health, Multan from September 2010 to March 2011. Children (6 months to 6 years of age) presenting with febrile seizures who satisfied inclusion and exclusion criteria were enrolled for the study. Cause of fever was determined after detailed history, physical examination and relevant investigations. Four milliliters centrifuged blood sample was preserved in acid washed test tube. Separated serum was used to measure serum zinc level by employing Randox kit on auto-analyzer in all cases. The outcome variable (serum zinc level) was recorded on a predesigned proforma. Results: Out of 100 enrolled children, there were 66 (66%) male with male to female ratio of 1:0.52. Mean age of the children was 23.97±14.45 months. Upper respiratory tract infection was the most frequent cause of fever apparent in 24 children (24%) followed by tonsillitis 17 (17%), pneumonia 16 (16%), urinary tract infection 16 (16%), otitis media 15 (15%), and bronchiolitis 12 (12%). Frequency of low serum zinc level was 26% in children with febrile seizures. Conclusion: Zinc deficiency could be a potential risk factor for febrile seizure in children. PMID:24353677

Waqar Rabbani, Muhammad; Ali, Ibad; Zahid Latif, Hafiz; Basit, Abdul; Rabbani, Muhammad Ali

2013-07-01

135

Recurrent febrile syndromes—what a rheumatologist needs to know  

Microsoft Academic Search

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

Anna Simon; Hal M. Hoffman

2009-01-01

136

Serum Zinc Level in Children Presenting with Febrile Seizures  

PubMed Central

Objective: To determine the frequency of low serum zinc level in children presenting with febrile seizures at The Children’s Hospital and the Institute of Child Health (CH/ICH) Multan. Methods: This is an observational cross sectional study conducted at the Department of Pediatric Medicine, The Children’s Hospital and the Institute of Child Health, Multan from September 2010 to March 2011. Children (6 months to 6 years of age) presenting with febrile seizures who satisfied inclusion and exclusion criteria were enrolled for the study. Cause of fever was determined after detailed history, physical examination and relevant investigations. Four milliliters centrifuged blood sample was preserved in acid washed test tube. Separated serum was used to measure serum zinc level by employing Randox kit on auto-analyzer in all cases. The outcome variable (serum zinc level) was recorded on a predesigned proforma. Results: Out of 100 enrolled children, there were 66 (66%) male with male to female ratio of 1:0.52. Mean age of the children was 23.97±14.45 months. Upper respiratory tract infection was the most frequent cause of fever apparent in 24 children (24%) followed by tonsillitis 17 (17%), pneumonia 16 (16%), urinary tract infection 16 (16%), otitis media 15 (15%), and bronchiolitis 12 (12%). Frequency of low serum zinc level was 26% in children with febrile seizures. Conclusion: Zinc deficiency could be a potential risk factor for febrile seizure in children.

Waqar Rabbani, Muhammad; Ali, Ibad; Zahid Latif, Hafiz; Basit, Abdul; Rabbani, Muhammad Ali

2013-01-01

137

Neutropenia in a patient treated with ipilimumab (anti-CTLA-4 antibody).  

PubMed

A 42-year-old white woman with a diagnosis of metastatic melanoma developed severe neutropenia during treatment with ipilimumab (anticytotoxic T-lymphocyte-associated antigen-4 antibody). Bone marrow aspiration and biopsy specimens revealed marked myeloid hypoplasia, with unremarkable erythropoiesis and megakaryopoiesis. The patient's neutropenia did not respond to therapy with a combination of colony stimulating factors and steroids; however, it rapidly improved after administration of intravenous immunoglobulin. Treatment with ipilimumab has not been reported to be associated with hematologic toxicities, and to our knowledge, no case of neutropenia has previously been reported. This report of acute grade 4 neutropenia associated with ipilimumab and clinically consistent with an autoimmune process emphasizes the importance of monitoring complete blood count during treatment with this new monoclonal antibody. PMID:19242368

Akhtari, Mojtaba; Waller, Edmund K; Jaye, David L; Lawson, David H; Ibrahim, Ramy; Papadopoulos, Nicholas E; Arellano, Martha L

2009-04-01

138

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

ClinicalTrials.gov

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

2012-09-20

139

Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia  

Microsoft Academic Search

Congenital neutropenia and cyclic neu- tropenia are disorders of neutrophil pro- duction predisposing patients to recur- rent bacterial infections. Recently the locus for autosomal dominant cyclic neutropenia was mapped to chromo- some 19p13.3, and this disease is now attrib- utable to mutations of the gene encoding neutrophil elastase (the ELA2 gene). The authors hypothesized that congenital neu- tropenia is also

David C. Dale; Richard E. Person; Audrey Anna Bolyard; Andrew G. Aprikyan; Cindy Bos; Mary Ann Bonilla; Laurence A. Boxer; George Kannourakis; Cornelia Zeidler; Karl Welte; Kathleen F. Benson; Marshall Horwitz

2000-01-01

140

Autoimmune Neutropenia of Infancy with Multiple Brain Abscesses during the Course of Human Herpesvirus6 Infection  

Microsoft Academic Search

Autoimmune neutropenia of infancy is characterized by recurrent infections such as pneumonia, otitis media, impetigo, purulent\\u000a skin regions, gastritis, and upper respiratory infection. However, severe bacterial infection is uncommon. This report documents\\u000a a 9-month-old boy presenting with autoimmune neutropenia in association with multiple brain abscesses during the course of\\u000a human herpesvirus (HHV)-6 infection. HHV-6 has a tendency of neurovirulence, which

Miyoko Tokushima-Imayoshi; Tomoko Onoue; Muneaki Matsuo; Nobuyuki Yoshida; Takashi Sato; Masao Kobayashi; Yuhei Hamasaki; Eiichi Ishii

2006-01-01

141

Progenitor Cell Self-renewal and Cyclic Neutropenia  

PubMed Central

Cyclic neutropenia (CN) is a rare genetic disorder where patients experience regular cycling of neutrophils and various other hematopoietic lineages. The nadir in the neutrophil count is the main source of problems due to the risk of life-threatening infections. Patients with CN benefit from G-CSF therapy although cycling persists. Mutations in the neutrophil elastase gene (ELA2) have been found in more than half of the patients with CN. However, neither the connection between phenotypic expression of ELA2 and CN nor the mechanism of cycling are known. Recently a multi-compartment model of hematopoiesis that couples stem cell replication with marrow output was proposed. In the following, we couple this model of hematopoiesis with a linear feedback mechanism via G-CSF. We propose that the phenotypic effect of ELA2 mutations leads to a reduction in self-renewal of granulocytic progenitors. The body responds by an overall relative increase of G-CSF and increasing progenitor cell self-renewal leading to cell count cycling. The model is compatible with the available experimental data and makes testable predictions.

Dingli, David; Antal, Tibor; Traulsen, Arne; Pacheco, Jorge M.

2009-01-01

142

A computerized system for the identification of alloimmune neutropenia in neonates.  

PubMed

In an attempt to determine the incidence of alloimmune neonatal neutropenia, a systematic study was initiated during a period of six months. Complete blood count, differential and absolute neutrophil count of all the newborns were determined to identify the newborns with neutropenia and those with persistent neutropenia were evaluated for the presence of maternal neutrophil antibodies. This resulted in the design and use of a computerized system which was successfully employed to identify several neonates born with this disorder. The system includes a main program and eight functional options, and is operated under a secret authority code so that patients' data are accessible only to the investigators. The major functional options are: create, display, update and delete a record for the newborn; display most recent neutropenic babies; search all records and display name and ID number; search all records for a given year and display data; and perform statistics. The statistical analysis includes the total number of babies, both normal and those with neutropenia, the total number of babies with neutropenia and with/without sepsis, and those with persistent neutropenia. Also included are the hematological data consisting of complete blood count and differential of all of the newborns. Several possibilities exist to expand and extend the program for additional research-related purposes. PMID:3899502

Madyastha, P R; Glassman, A B; Groves, W E; Levine, D H; Davidson, R

1985-08-01

143

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

PubMed

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

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

2013-08-14

144

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

PubMed Central

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

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

2013-01-01

145

Prevalence of Coxiella burnetii Antibodies Among Febrile Patients in Croatia, 2008-2010  

PubMed Central

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.

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

2012-01-01

146

Proton pump inhibitor-induced neutropenia: possible cross-reactivity between omeprazole and pantoprazole.  

PubMed

Proton pump inhibitors (PPIs) are widely used drugs in the treatment or prophylaxis of peptic ulcer and gastro-oesophageal reflux disease. In addition to their well documented efficacy, these drugs are generally well tolerated with only rare serious adverse effects having been reported. Neutropenia and agranulocytosis are rare adverse events associated with PPI treatment. All previously published cases of isolated neutropenia have involved omeprazole, but leukopenia is labelled as a possible adverse effect in the summary of product characteristics of the other PPIs. In this report, we describe a case of omeprazole-induced neutropenia with further recurrence upon pantoprazole treatment. A 60-year-old man with chronic alcoholism and a medical history of pulmonary tuberculosis, untreated chronic C hepatitis, peripheral artery disease, chronic obstructive pulmonary disease and stable stage 3 chronic kidney disease was admitted with dehydration and malnutrition. Omeprazole 20 mg/day and sucralfate 3 g/day were started for diffuse gastritis on gastric endoscopy. While the patient's blood cell count had been within the normal range before this treatment, routine laboratory examination revealed moderate neutropenia (0.9 x 109/L) after 9 days of treatment. His blood cell count returned to the normal range after discontinuation of omeprazole and no further episodes of neutropenia were noted in the following months. One year later, oesophago-gastroscopy revealed a hiatal hernia with an extensive zone of Barrett's oesophagus. As the lesions did not improve with ranitidine and sucralfate therapy, the patient was started on pantoprazole 40 mg/day. His initial white blood cell count was normal, but moderate neutropenia (0.8 x 109/L) was again noted after only 2 days of pantoprazole treatment. Complete and further stable normalization was obtained within 3 days after replacement of pantoprazole with ranitidine. Toxic and immune-mediated mechanisms are the two commonly proposed mechanisms to explain the pathogenesis of drug-induced neutropenia. This report suggests that PPI-induced neutropenia is immune mediated and argues for a possible cross-reactivity between the two PPIs, as has already been described for PPI-induced hypersensitivity reactions. The report also indicates that patients with a history of neutropenia induced by one PPI may be at risk of recurrence of neutropenia if given another member of this drug class. In these patients, close haematological monitoring is proposed. PMID:20586518

Gouraud, Aurore; Vochelle, Véronique; Descotes, Jacques; Vial, Thierry

2010-01-01

147

Neutropenia induced by systemic infusion of 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid: correlation with its in vitro effects upon neutrophils.  

PubMed Central

5(S), 12(S)-Dihydroxy-cis-14,trans-6,8,10-eicosatetraenoate (compound I), 5(S),12(R)-dihydroxy-cis-14,trans-6,8,10-eicosatetraenoate (compound II), and 5(S),12(R)-dihydroxy-cis-6,14,trans-8,10-eicosatetraenoate (compound III) were prepared from rabbit peritoneal neutrophils challenged with arachidonic acid plus ionophore A23187. Each arachidonate metabolite caused rabbit neutrophils to aggregate and, in cells treated with cytochalasin B, release granule-bound enzymes. Compound III was 10- to 100-fold more potent than compounds II and I. When intravenously infused into rabbits at doses of 100--1,000 ng/kg, compound III induced abrupt, profound, transient neutropenia associated with a rapidly reversing accumulation of neutrophils in the pulmonary circulation. This in vivo action correlated closely with the ability of the fatty acid to activate neutrophils in vitro: neutropenia, aggregation, and degranulation occurred at similar doses of stimulus and the rapid, reversing kinetics of the neutropenic response paralleled the equally rapid, reversing formation of aggregates. The fatty acid did not alter the circulating levels of lymphocytes or platelets and did not aggregate platelets in vitro. At comparable doses (i.e., 100--1,000 ng/kg), compounds I and II did not cause neutropenia. Thus, compound III possesses a high degree of structural and target-cell specificity in stimulating neutrophils in vitro and in vivo. Clinical and experimental syndromes associating neutropenia with increased levels of circulating arachidonate metabolites may involve compound III as a mediator of neutrophil sequestration in lung.

O'Flaherty, J T; Thomas, M J; Cousart, S L; Salzer, W L; McCall, C E

1982-01-01

148

Hemorrhagic fever with renal syndrome and Crimean-Congo hemorrhagic fever as causes of acute undifferentiated febrile illness in Bulgaria.  

PubMed

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are the 2 widespread viral hemorrhagic fevers occurring in Europe. HFRS is distributed throughout Europe, and CCHF has been reported mainly on the Balkan Peninsula and Russia. Both hemorrhagic fevers are endemic in Bulgaria. We investigated to what extent acute undifferentiated febrile illness in Bulgaria could be due to hantaviruses or to CCHF virus. Using enzyme-linked immunosorbent assays (ELISAs), we tested serum samples from 527 patients with acute febrile illness for antibodies against hantaviruses and CCHF virus. Immunoglobulin M (IgM) antibodies against hantaviruses were detected in 15 (2.8%) of the patients. Of the 15 hantavirus-positive patients, 8 (1.5%) were positive for Dobrava virus (DOBV), 5 (0.9%) were positive for Puumala virus (PUUV), and the remaining 2 were positive for both hantaviruses. A plaque reduction neutralization test (PRNT) confirmed 4 of the 10 DOBV-positive samples. PRNT was negative for all PUUV-positive samples. Serologic evidence of recent CCHF virus infection was found in 13 (2.5%) of the patients. Interestingly, HFRS and CCHF were not only detected in well-known endemic areas of Bulgaria but also in nonendemic regions. Our results suggested that in endemic countries, CCHF and/or HFRS might appear as a nonspecific febrile illness in a certain proportion of patients. Physicians must be aware of possible viral hemorrhagic fever cases, even if hemorrhages or renal impairment are not manifested. PMID:23421884

Christova, Iva; Younan, Rasha; Taseva, Evgenia; Gladnishka, Teodora; Trifonova, Iva; Ivanova, Vladislava; Spik, Kristin; Schmaljohn, Connie; Mohareb, Emad

2013-03-01

149

Human febrile illness caused by encephalomyocarditis virus infection, Peru.  

PubMed

Etiologic studies of acute febrile disease were conducted in sites across South America, including Cusco and Iquitos, Peru. Patients' clinical signs and symptoms were recorded, and acute- and convalescent-phase serum samples were obtained for serologic examination and virus isolation in Vero E6 and C6/36 cells. Virus isolated in Vero E6 cells was identified as encephalomyocarditis virus (EMCV) by electron microscopy and by subsequent molecular diagnostic testing of samples from 2 febrile patients with nausea, headache, and dyspnea. The virus was recovered from acute-phase serum samples from both case-patients and identified with cardiovirus-specific reverse transcription-PCR and sequencing. Serum samples from case-patient 1 showed cardiovirus antibody by immunoglobulin M ELISA (acute phase <8, convalescent phase >1,024) and by neutralization assay (acute phase <10, convalescent phase >1,280). Serum samples from case-patient 2 did not contain antibodies detectable by either assay. Detection of virus in serum strongly supports a role for EMCV in human infection and febrile illness. PMID:19331761

Oberste, M Steven; Gotuzzo, Eduardo; Blair, Patrick; Nix, W Allan; Ksiazek, Thomas G; Comer, James A; Rollin, Pierre; Goldsmith, Cynthia S; Olson, James; Kochel, Tadeusz J

2009-04-01

150

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

PubMed Central

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.

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

2013-01-01

151

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

PubMed

Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. Neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose. PMID:21255689

Newman, Kam A; Akhtari, Mojtaba

2011-05-01

152

Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor.  

PubMed

Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10 micrograms/kg/day for 30 d, which caused an initial neutrophilia, followed by a prolonged period of chronic neutropenia. A control dog treated with recombinant canine G-CSF (rcG-CSF) showed persistent neutrophilia over 3 mo. Serum from dogs during neutropenia contained an antibody to rhG-CSF, which neutralized the stimulatory effects of both rhG-CSF and rcG-CSF on dog marrow neutrophilic progenitor cell growth and on NFS-60 cell proliferation. 4 mo after discontinuation of rhG-CSF, the dogs' neutrophil counts returned to the normal range. Rechallenge with the rhG-CSF re-induced severe neutropenia in 1 wk. Neutropenia was transferred by plasma infusion from a neutropenic dog to a previously normal dog. These data suggest that human rhG-CSF immunizes normal dogs and thereby induces neutralization of endogenous canine G-CSF and neutropenia. This model system should allow more precise definition of the in vivo role of G-CSF. PMID:1704019

Hammond, W P; Csiba, E; Canin, A; Hockman, H; Souza, L M; Layton, J E; Dale, D C

1991-02-01

153

Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor.  

PubMed Central

Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10 micrograms/kg/day for 30 d, which caused an initial neutrophilia, followed by a prolonged period of chronic neutropenia. A control dog treated with recombinant canine G-CSF (rcG-CSF) showed persistent neutrophilia over 3 mo. Serum from dogs during neutropenia contained an antibody to rhG-CSF, which neutralized the stimulatory effects of both rhG-CSF and rcG-CSF on dog marrow neutrophilic progenitor cell growth and on NFS-60 cell proliferation. 4 mo after discontinuation of rhG-CSF, the dogs' neutrophil counts returned to the normal range. Rechallenge with the rhG-CSF re-induced severe neutropenia in 1 wk. Neutropenia was transferred by plasma infusion from a neutropenic dog to a previously normal dog. These data suggest that human rhG-CSF immunizes normal dogs and thereby induces neutralization of endogenous canine G-CSF and neutropenia. This model system should allow more precise definition of the in vivo role of G-CSF.

Hammond, W P; Csiba, E; Canin, A; Hockman, H; Souza, L M; Layton, J E; Dale, D C

1991-01-01

154

[Granulocyte colony-stimulating factor in neutropenia secondary to lymphoid bone marrow infiltration].  

PubMed

In patients with low-grade lymphoid malignancy, severe neutropenia due to massive bone marrow infiltration of lymphocytes increases the risk of infection, especially after myelosuppressive chemotherapy. Three patients (two with chronic lymphocytic leukemia and one with follicular lymphoma) with massive bone marrow infiltration and neutropenia not caused by short-term effects of chemotherapy, were treated with G-CSF for five two-week periods, to find out if the neutropenia was reversible. All three patients initially responded to G-CSF with an increase of neutrophil counts into the normal range or above. In one patient, G-CSF administered after a subsequent course of myelosuppressive chemotherapy apparently prevented severe chemotherapy-induced neutropenia. Retreatment of a previous responder in a later, preterminal stage of the disease produced very little response in terms of neutrophil counts. G-CSF can increase peripheral blood neutrophil counts to normal levels in patients with severe neutropenia induced by lymphoid bone marrow infiltration. PMID:8644050

Hammerstrøm, J

1996-02-10

155

Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits  

Microsoft Academic Search

Febrile (fever-induced) seizures affect 3–5% of infants and young children. Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial. Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic

Kang Chen; Tallie Z. Baram; Ivan Soltesz

1999-01-01

156

Immunomodulatory derivatives induce PU.1 down-regulation, myeloid maturation arrest, and neutropenia.  

PubMed

The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide yield high response rates in patients with multiple myeloma, but the use of IMiDs in multiple myeloma is associated with neutropenia and increased risk for venous thromboembolism (VTE) by mechanisms that are unknown. We show that IMiDs down-regulate PU.1, a key transcription factor involved in granulocyte differentiation in vitro and in patients treated with lenalidomide. Loss of PU.1 results in transient maturation arrest with medullary accumulation of immature myeloid precursors and subsequent neutropenia. Accumulation of promyelocytes leads to high levels of the platelet aggregation agonist, cathepsin G stored in the azurophilic granules of promyelocytes. High levels of cathepsin G subsequently may increase the risk of VTE. To our knowledge, this is the first report investigating the underlying mechanism of IMiD-induced neutropenia and increased risk of VTE in multiple myeloma. PMID:19965623

Pal, Rekha; Monaghan, Sara A; Hassett, Andrea Cortese; Mapara, Markus Y; Schafer, Peter; Roodman, G David; Ragni, Margaret V; Moscinski, Lynn; List, Alan; Lentzsch, Suzanne

2010-01-21

157

The long-term risk of epilepsy after febrile seizures in susceptible subgroups.  

PubMed

A family history of seizures, preexisting brain damage, or birth complications may modify the long-term risk of epilepsy after febrile seizures. The authors evaluated the association between febrile seizures and epilepsy in a population-based cohort of 1.54 million persons born in Denmark (1978-2002), including 49,857 persons with febrile seizures and 16,481 persons with epilepsy. Overall, for children with febrile seizures compared with those without such seizures, the rate ratio for epilepsy was 5.43 (95% confidence interval: 5.19, 5.69). The risk remained high during the entire follow-up but was particularly high shortly after the first febrile seizure, especially in children who experienced early (<1 year of age) or late (>3 years of age) onset of febrile seizures. At 23 years of follow-up, the overall cumulative incidence of epilepsy after febrile seizures was 6.9% (95% confidence interval: 6.5, 7.3). In conclusion, persons with a history of febrile seizures had a higher rate of epilepsy that lasted into adult life, but less than 7 percent of children with febrile seizures developed epilepsy during 23 years of follow-up. The risk was higher for those who had a family history of epilepsy, cerebral palsy, or low Apgar scores at 5 minutes. PMID:17267419

Vestergaard, Mogens; Pedersen, Carsten Bøcker; Sidenius, Per; Olsen, Jørn; Christensen, Jakob

2007-04-15

158

Dimensions of neutropenia in adult cancer patients: expanding conceptualizations beyond the numerical value of the absolute neutrophil count.  

PubMed

Neutropenia is a common and dangerous toxicity of cancer therapy that profoundly affects patients' lives. Neutropenia is typically defined by the numerical value of the absolute neutrophil count. However, considering neutropenia exclusively as the numerical value of the absolute neutrophil count limits its conceptualizations to physiologically related aspects, minimizes its complexities, and neglects dimensions of human response and the patient experience. This article offers a dimensional analysis of neutropenia derived from 42 research and clinical articles. Schatzman's dimensional analysis methods were applied to the literature to identify aspects of this phenomenon lying beyond its numerical boundaries. Dimensions of neutropenia that emerged were sorted into categories of perspective, context, conditions, processes, and consequences. The presence of the same dimension in more than 1 category and the circuitous relationships among categories begin to explicate the complexity and gravity of neutropenia. Articulation of these dimensions is necessary to assemble the beginnings of a theoretical understanding of neutropenia, which is crucial for the development and application of knowledge to research and practice. Limitations evident in the literature illuminate the urgent need for research into the psychosocial as well as physiologic dimensions of neutropenia. PMID:15292722

Crighton, Margaret H

2004-01-01

159

Impaired granulocytopoiesis in patients with chronic idiopathic neutropenia is associated with increased apoptosis of bone marrow myeloid progenitor cells  

Microsoft Academic Search

To probe the pathophysiologic mecha- nisms underlying neutropenia in patients with chronic idiopathic neutropenia (CIN) with hypoplastic and left-shifted granulo- cytic series in the bone marrow (BM), we have studied granulocytopoiesis in 32 adults with CIN by evaluating the number and survival characteristics of cells in several stages of granulocyte differentia- tion using flow cytometry and BM culture assays. We

Helen A. Papadaki; Aristides G. Eliopoulos; Theodoros Kosteas; Claudia Gemetzi; Athina Damianaki; Helen Koutala; Juergen Bux; George D. Eliopoulos; Crete Heraklion

2003-01-01

160

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

PubMed

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

Belfonte, Cassius D; Shanmugam, Victoria K; Kieffer, Nicole; Coker, Shodeinde; Boucree, Suelyn; Kerr, Gail

2013-10-01

161

Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: A randomized, placebo-controlled trial  

Microsoft Academic Search

Background. Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapyinduced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. Methods. We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for ?10 days. Patients were randomized to

Lennert Slobbe; Bob Löwenberg; Arnold Vulto

2008-01-01

162

Cyclic Neutropenia : The Relationship Between Urine Granulocyte Colony Stimulating Activity and Neutrophil Count  

Microsoft Academic Search

Urinary colony stimulating activity be highest when the granulocyte count (CSA) has been studied in a 70-yr-old was high or falling. It is suggested, female with chronic cyclic neutropenia on the basis of this and other data, of unknown cause. Changes in urinary that granulopoiesis, at least in part, CSA were correlated with absolute may be regulated by a positive

Aroop Mangalik; W. A. Robinson

1973-01-01

163

A predictive model to estimate the risk of serious bacterial infections in febrile infants  

Microsoft Academic Search

Low risk criteria have been defined to identify febrile infants unlikely to have serious bacterial infection (SBI). Using these criteria approximately 40% of all febrile infants can be defined as being at low risk. Of the remaining infants (60%) only 10%–20% have an SBI. No adequate criteria exist to identify these infants. All infants aged 2 weeks-1 year, presenting during

R. M. F. Berger; M. Y. Berger; H. A. van Steensel-Moll; G. Dzoljic-Danilovic; G. Derksen-Lubsen

1996-01-01

164

Seizure-Induced Neuronal Injury: Vulnerability to Febrile Seizures in an Immature Rat Model  

Microsoft Academic Search

Febrile seizures are the most common seizure type in young children. Whether they induce death of hippocampal and amyg- dala neurons and consequent limbic (temporal lobe) epilepsy has remained controversial, with conflicting data from prospec- tive and retrospective studies. Using an appropriate-age rat model of febrile seizures, we investigated the acute and chronic effects of hyperthermic seizures on neuronal integrity

Zsolt Toth; Xiao-Xin Yan; Suzie Haftoglou; Charles E. Ribak; Tallie Z. Baram

1998-01-01

165

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

ERIC Educational Resources Information Center

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…

Deonna, Thierry

2012-01-01

166

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

ERIC Educational Resources Information Center

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…

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

167

Infections in acute myeloid leukemia. Study of 184 febrile episodes.  

PubMed

We analysed the case records of 75 patients with acute myeloid leukaemia treated at our institute from January 1984 to December 1988 to see the pattern and severity of infections and their relationship with granulocytopenia. A total of 184 febrile episodes (mean 2.45) were recorded; 153 (83.15%) were associated with granulocytopenia while 31 (16.84%) were without granulocytopenia. Among granulocytopenic patients, infections could be documented microbiologically in 58.2% and clinically in 30.0% of episodes. In the remaining 41.8% of episodes, no clinical, radiological or microbiological evidence could be found out. The various sites of infection were: septicaemia 21 (13.72%), disseminated fungal infections 4 (2.6%), upper respiratory tract 21 (13.7%), chest 58 (37.9%), gastrointestinal tract 8 (5.2%), genitourinary (7.2%), soft tissues 5 (3.2%) and skin cellulitis 7 (4.6%). Microbiologically, gram negative organisms (Klebsiella pneumoniae, E coli, Pseudomonas aeruginosa) were most common, followed by gram positive (Streptococcal faecalis, Staphylococcus aureus, Staph albus, Staph epidermidis). Four patients had disseminated fungal infection: candida 2, aspergillus *1, mucormycosis *1. Among non neutropenic febrile episodes, the sites infected were: septicemia 2 (6.4%), chest 9(29.0%), upper respiratory tract 1 (3.2%), gastrointestinal 1 (3.2%), soft tissue 1 (3.2%), drug fever 3 (9.6%) and fever of unknown origin 14 (45.2%). PMID:1634456

Kumar, L; Kochupillai, V; Bhujwala, R A

1992-01-01

168

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

PubMed

Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count <0.5 ×?10(9) /L and recurrent bacterial infections. Homozygous mutations of either HAX-1 or ELA-2 have been described. We report the case of a premature male infant with congenital neutropenia, associated with multiple infections, refractory to treatment with granulocyte colony stimulating factor who subsequently underwent matched sibling donor stem-cell transplant. He was found to be heterozygous for the M1V variant of the ELA-2 gene that we postulate to be causative for his severe neutropenia PMID:21618407

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

2011-09-01

169

Interleukin–8 Serum Levels at Fever Onset in Patients with Neutropenia Predict Early Medical Complications  

Microsoft Academic Search

Background: Previous studies have shown that interleukin-8 serum levels in febrile neutropenic patients are significantly higher in patients with gram-negative bacteremia than in patients with other causes of fever and may indicate unfavorable outcomes. We assessed the value of interleukin-8 serum levels at fever onset to predict clinical complications in order to confirm these earlier findings. Patients and Methods: In

A. Engel; Stefanie Knoll; P. Kern; W. V. Kern

2005-01-01

170

[Characteristics of acupuncture in Shanghan Lun (Treatise on Febrile Diseases)].  

PubMed

Through summarization and analysis on etiology, pathology and acupoint selection in chapters about acupuncture in Shanghan Lun (Treatise on Febrile Diseases), written by ZHANG Zhong-jing, famous physician of the Eastern Han Dynasty, five features of acupuncture in the book are concluded: to cut off the pathway of pathogenic factors to prevent progress of diseases; to adopt both acupuncture and herbal medicine to give full play to their respective advantages in treatment; to distinguish pathogenesis carefully and select the proper acupoints; to observe the progressing tendency of diseases to give treatment accordingly; and to understand that yang channels are appropriate for acupuncture, while yin channels can also be selected in treatment. In this way, the law of acupuncture of ZHANG Zhong-jing is expected to be better understood. PMID:20862948

Zeng, Zi-Yu; Chen, Shu-Kai; Guo, Chang-Qing; Liu, Nai-Gang

2010-07-01

171

Association of IL6 single nucleotide polymorphisms with febrile seizures.  

PubMed

Febrile seizures (FSs) are the most common convulsive event in children. Inflammatory elements and genetics have major roles in their pathogenesis. As of the importance of interleukin-6 (IL-6) in FS, this study was performed to assess IL6 single nucleotide polymorphisms (SNPs) in a group of patients with FS. IL6 gene (-174 and +565) SNPs were studied on genomic DNAs of 90 children with FS, using PCR-SSP method. The results were compared to 139 healthy individuals. The presence of the G allele or the GG genotype at +565 position reduced risk of FS, while the A allele at +565 position of the promoter regions was a constituted risk factor for developing FS. This study could support the idea that IL6 SNPs play a role in the pathogenesis of FS. PMID:24834995

Shahrokhi, Amin; Zare-Shahabadi, Ameneh; Soltani, Samaneh; Ashrafi, Mahmoud Reza; Zoghi, Samaneh; Hosseini, Seyed Ahmad; Heidari, Moreteza; Yaghmaei, Bahareh; Pourakbari, Babak; Rezaei, Nima

2014-07-15

172

Early postictal electroencephalography and correlation with clinical findings in children with febrile seizures  

PubMed Central

Purpose Electroencephalography (EEG) is frequently ordered for patients with febrile seizures despite its unclear diagnostic value. We evaluated the prevalence of abnormal EEGs, the association between clinical findings and abnormal EEGs, and the predictive value of EEG for the recurrence of febrile seizures. Methods Data were collected on 230 children who were treated for febrile seizures at Kyung Hee University Medical Center from 2005 to 2009. EEGs were recorded after 1-2 days of hospitalization when children became afebrile. EEG patterns were categorized as normal, epileptiform, or nonspecific relative to abnormalities. The patients' medical records were reviewed, and telephone interviews with the families of the children were conducted to inquire about seizure recurrence. The relationships between clinical variables, including seizure recurrence, and EEG abnormalities were evaluated. Results Of the 131 children included, 103 had simple and 28 had complex febrile seizures. EEG abnormalities were found in 41 children (31%). EEG abnormalities were more common in children with complex than simple febrile seizures (43% vs. 28%), but the difference was not statistically significant. Logistical regression analysis showed that having multiple seizures in a 24-hour period was significantly predictive of abnormal EEG (odds ratio, 2.98; 95% confidence interval, 1.0 to 88; P=0.048). The frequency of recurrence did not differ significantly in the normal (31%) and abnormal (23%) EEG groups. Conclusion Multiple seizures within 24 hours were predictive of abnormal EEG in children with febrile seizures. Abnormal EEG was not predictive of febrile seizure recurrence.

Jeong, Kyung A; Han, Myung Hee; Lee, Eun Hye

2013-01-01

173

Comparison of Serum Zinc Levels Measured by Inductively Coupled Plasma Mass Spectrometry in Preschool Children with Febrile and Afebrile Seizures  

PubMed Central

Background Changes in levels of trace elements have been proposed to underlie febrile seizures. Particularly, low zinc levels have been proposed as related factor of febrile seizure. In this study, we investigated whether mean serum zinc levels differed between children with febrile seizure and afebrile seizure. Methods Using inductively coupled plasma mass spectrometry, serum zinc levels were measured in 288 children who had been diagnosed with febrile seizures (N=248) and afebrile seizures (N=40). Mean serum zinc levels were compared between the 2 groups. Results Mean serum zinc level was 60.5±12.7 µg/dL in the febrile seizure group and 68.9 ±14.5 µg/dL in the afebrile seizure group. A significant difference in serum zinc levels was observed between the febrile and afebrile seizure groups (P<0.001). Conclusions Zinc levels in children with febrile seizure were significantly lower than those in children with afebrile seizure.

Lee, Jun-Hwa

2012-01-01

174

The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance).  

PubMed

Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients. PMID:23188068

Lewis, Lionel D; Miller, Antonius A; Owzar, Kouros; Bies, Robert R; Markova, Svetlana; Jiang, Chen; Kroetz, Deanna L; Egorin, Merrill J; McLeod, Howard L; Ratain, Mark J

2013-01-01

175

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

PubMed Central

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.

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

2010-01-01

176

Poikiloderma with neutropenia: report of three cases including one with calcinosis cutis.  

PubMed

Poikiloderma with neutropenia (PN), Clericuzio type (OMIM #604173) is a new, unique genodermatosis first described by Clericuzio et al (Am J Med Genet A, 2011, 155, 337) in Navajo Indian population. This disease is characterized by poikiloderma that usually develops in the first year of life and is associated with nail abnormality, palmoplantar hyperkeratosis, chronic neutropenia, and recurrent infections. The rash typically starts from the extremities and spreads centripetally to involve the trunk, face, and ears. Recently, a homozygous mutation in the C16orf57 gene on chromosome 16q13 was identified as a strong candidate as the gene responsible for PN. We report three cases of PN whose clinical presentations, laboratory investigations, and C16orf57 mutation support the diagnosis of PN. One child has developed multiple painful calcinosis cutis lesions. Early-onset poikiloderma should prompt a complete blood count as a screening test. PMID:21967010

Chantorn, Rattanavalai; Shwayder, Tor

2012-01-01

177

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

PubMed Central

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

Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry

2011-01-01

178

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

PubMed

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

Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry

2011-10-01

179

Mutations in the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia  

Microsoft Academic Search

Previously, nonsense mutations in the gene encoding the granulocyte colony-stimulating factor receptor (G-CSF-R) have been described in three patients with severe congenital neutropenia (SCN) (Proc Natl Acad Sci USA 1994; 91: 4480; New Engl J Med 1995; 333: 487). The mutations resulted in the truncation of the carboxy-terminal region of G-CSF-R essential for transduction of maturation signals. Two of these

F. Dong; D. C. Dale; M. A. Bonilla; M. Freedman; A. Fasth; H. J. Neijens; J. Palmblad; G. L. Briars; G Carlsson; A. J. P. Veerman; K. Welte; B. Löwenberg; I. P. Touw

1997-01-01

180

High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann’s syndrome)  

Microsoft Academic Search

Objective: Clinical observation of bone pain, unusual fractures in two patients, and diffuse osteopenia\\/osteoporosis led us to assess bone mineral content and density in 30 patients with severe congenital neutropenia who were treated with recombinant-methionyl-human granulocyte colony-stimulating factor (r-metHuG-CSF).Study design: We reviewed roentgenograms in 29 of these 30 patients to evaluate bone loss before and during treatment. In addition, in

Elif Yakisan; Eckart Schirg; Cornelia Zeidler; Nick J. Bishop; Alfred Reiter; A. Hirt; Hansjörg Riehm; Karl Welte

1997-01-01

181

Neutropenia, thrombocytopenia and hepatic injury associated with dexketoprofen trometamol therapy in a previously healthy 35-year-old woman.  

PubMed

This case report describes a previously healthy 35-year-old woman, with an episode of fever, neutropenia, thrombocytopenia and elevation of biochemical markers of liver injury, 10 days after beginning drug therapy with dexketoprofen trometamol. Infectious and autoimmune causes of neutropenia, and viral or autoimmune hepatitis were excluded. The resolution following withdrawal of dexketoprofen trometamol confirms the possibility of an adverse drug reaction. PMID:18211621

Zabala, S; Calpe, M J; Pérez, G; Lerín, F J; Mouronval, L

2008-02-01

182

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

Microsoft Academic Search

BACKGROUND: Patients with cancer must make frequent visits to the clinic not only for chemotherapy but also for the management of treatment-related adverse effects. Neutropenia, the most common dose-limiting toxicity of myelosuppressive chemotherapy, has substantial clinical and economic consequences. Colony-stimulating factors such as filgrastim and pegfilgrastim can reduce the incidence of neutropenia, but the clinic visits for these treatments can

Barry V Fortner; Kurt Tauer; Ling Zhu; Theodore A Okon; Kelley Moore; Davis Templeton; Lee Schwartzberg

2004-01-01

183

Targeted Next-Generation Sequencing Appoints C16orf57 as Clericuzio-Type Poikiloderma with Neutropenia Gene  

Microsoft Academic Search

Next-generation sequencing is a straightforward tool for the identification of disease genes in extended genomic regions. Autozygosity mapping was performed on a five-generation inbred Italian family with three siblings affected with Clericuzio-type poikiloderma with neutropenia (PN [MIM %604173]), a rare autosomal-recessive genodermatosis characterised by poikiloderma, pachyonychia, and chronic neutropenia. The siblings were initially diagnosed as affected with Rothmund-Thomson syndrome (RTS

Ludovica Volpi; Gaia Roversi; Elisa Adele Colombo; Nico Leijsten; Daniela Concolino; Andrea Calabria; Maria Antonietta Mencarelli; Michele Fimiani; Fabio Macciardi; Rolph Pfundt; Eric F. P. M. Schoenmakers; Lidia Larizza

2010-01-01

184

Identification of a Nonsense Mutation in the Granulocyte-Colony-Stimulating Factor Receptor in Severe Congenital Neutropenia  

Microsoft Academic Search

Severe congenital neutropenia (Kostmann syndrome) is characterized by profound absolute neutropenia and a maturation arrest of marrow progenitor cells at the promyelocyte-myelocyte stage. Marrow cells from such patients frequently display a reduced responsiveness to granulocyte-colony- stimulating factor (G-CSF). G-CSF binds to and activates a specific receptor which transduces signals critical for the proliferation and maturation of granulocytic progenitor cells. Here

Fan Dong; Lies H. Hoefsloot; Anita M. Schelen; Lianne C. A. M. Broeders; Yolande Meijer; Anjo J. P. Veerman; Ivo P. Touw; Bob Lowenberg

1994-01-01

185

Leukocyte integrin activation mediates transient neutropenia after G-CSF administration  

PubMed Central

After administration of granulocyte colony-stimulating factor (G-CSF), there is a marked, albeit transient, drop in circulating neutrophils. To determine the role of leukocyte integrins in this disappearance, a dog having canine leukocyte adhesion deficiency (CLAD) or CLAD dogs who had undergone gene correction either by matched littermate allogeneic transplant or autologous gene therapy were evaluated. Shortly after G-CSF administration, a dramatic, yet transient, neutropenia was observed in the control littermates. This neutropenia was not as marked in the CLAD dogs. In all instances, it was CD18+ neutrophils that preferentially egressed from the circulation. The association of CD18 with this rapid loss suggested leukocyte integrin activation after G-CSF administration. To determine the activation status of the integrin, a monoclonal antibody recognizing the activated ?-subunit cation binding domain (mAb24) was used to evaluate human leukocytes after G-CSF administration. Mirroring the dramatic decrease in circulating neutrophil numbers, there was a dramatic and specific increase in the activation of the ?-subunit after G-CSF expression on polymorphonuclear leukocytes. This activation, like the drop in neutrophil count, was transient. These results demonstrate that the leukocyte integrin on circulating neutrophils is transiently activated after G-CSF administration and mediates the transient neutropenia observed after G-CSF administration.

Tuschong, Laura; Bauer, Thomas R.; Yau, Yu Ying; Leitman, Susan F.; Hickstein, Dennis D.

2011-01-01

186

Acute lymphoblastic leukemia following severe congenital neutropenia or de novo ALL?  

PubMed

Acute lymphoblastic leukemia (ALL) presenting with neutropenia alone is very rare. We describe a newborn with an early life-threatening infection, severe neutropenia and bone marrow findings compatible with severe congenital neutropenia (SCN). She was treated with granulocyte colony-stimulating factor (G-CSF) with complete neutrophil recovery. Three months later she developed a pro-B ALL. We identified a rare loss of 5'-MLL present at the diagnosis of SCN and ALL by FISH analysis using two different MLL (11q23) probes. Molecular analyses for SCN causing mutations (ELA-2, HAX-1 and G6PC3) and for somatic mutations of the CSF3R gene were negative. The early presence of 5'-MLL loss in bone marrow samples may favor the diagnosis of de novo ALL. Nevertheless, the genetic background for SCN is heterogeneous and a non-described mutation for SCN followed by a secondary ALL cannot be excluded. Further genetic investigation may be useful to gain insight into this rare condition in children. PMID:19398129

Valera, Elvis Terci; Brassesco, María Sol; Germeshausen, Manuela; Silveira, Vanessa da Silva; Queiroz, Rosane Gomes de Paula; Roxo, Pérsio; Scrideli, Carlos Alberto; de Menezes, Ullissis Pádua; Ferriani, Virgínia; Tone, Luiz Gonzaga

2009-09-01

187

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

National Technical Information Service (NTIS)

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 he...

B. M. Forshey C. Guevara J. Vargas M. Cespedes V. A. Laguna-Torres

2010-01-01

188

Anterior Urethral Valve and Diverticulum in a Neonate with Febrile Urinary Tract Infection  

PubMed Central

Anterior urethral valve is a rare congenital anomaly that can cause obstructive uropathy. Herein, we report a case of an anterior urethral valve that led to the development of febrile urinary tract infection in a neonate.

Song, Jin Hyun; Lee, Min Ho; Lee, Ji Hye; Lee, Chang Ho; Jeon, Youn Soo; Lee, Nam Kyu

2012-01-01

189

Role of Fluorine18Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients  

Microsoft Academic Search

Objective and Methods: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.Results: Our data

Jonas F. Santiago; Suman Jana; Holly M. Gilbert; Shahenda Salem; Paul Curtis Bellman; Ricky K. S. Hsu; Sleiman Naddaf; Hussein M. Abdel-Dayem

1999-01-01

190

Sudden Death, Febrile Seizures, and Hippocampal and Temporal Lobe Maldevelopment in Toddlers: A New Entity  

PubMed Central

Recently, we reported hippocampal and temporal lobe abnormalities in 5 toddlers with sudden unexplained death in childhood (SUDC). The association of these anomalies with a high incidence (40%) of individual/ family histories of simple febrile seizures in the cases raised concern that febrile seizures can be associated with death. In a series of 64 toddlers with sudden death, we tested the hypothesis that an SUDC subset is characterized by hippocampal and temporal lobe maldevelopment and an individual and/or family history of simple familial seizures. Cases of sudden and unexplained death in children aged 1.0 to 5.9 years (median 1.7 years) were divided into groups based upon a history of febrile or nonfebrile seizures, familial febrile seizures, and autopsy classification of cause of death. Forty-nine of the 64 cases (77%) were classified as SUDC, of which 40% had an individual/family history of febrile seizures. Of the 26 SUDC cases with available hippocampal sections, 62% (16/26) had hippocampal and temporal lobe anomalies, including 82% (9/11) of cases with an individual/family history of febrile seizures. Cases with these anomalies were all found dead during a sleep period, typically in the prone (87%) position. We conclude that a potential new entity may account for the majority of SUDC in toddlers, defined by sleep-related death in the prone position, individual/family history of febrile seizures, and hippocampal and temporal lobe anomalies. The mechanism of death appears analogous to sudden death in (temporal lobe) epilepsy, with a putative unwitnessed seizure during sleep leading to airway occlusion and death. This study mandates further research into the potential link between simple febrile seizures and death.

Kinney, Hannah C.; Chadwick, Amy E.; Crandall, Laura A.; Grafe, Marjorie; Armstrong, Dawna L.; Kupsky, William J.; Trachtenberg, Felicia L.; Krous, Henry F.

2012-01-01

191

Febrile Convulsions in 220 Children – Neurological Sequelae at 12 Years Follow-Up  

Microsoft Academic Search

We report a 12-year follow-up study of children with febrile convulsions (FCs). The National General Practice Study of Epilepsy (NGPSE) is a large prospective community-based cohort study of 1,195 patients of all ages from first presentation with an identified seizure. Two hundred and twenty children with a first febrile convulsion were identified from the above study between 1984 and 1987.

Bridget K. MacDonald; Anthony L. Johnson; Josemir W. A. S. Sander; Simon D. Shorvon

1999-01-01

192

Febrile illness in successive cohorts of tourists at a hotel on the Italian Adriatic coast: evidence for a persistent focus of Legionella infection.  

PubMed

Outbreaks of febrile illness consistent with legionellosis occurred in successive groups of vacationers at an Adriatic resort in 1980. Illness was associated with one of two hotels used by the groups. A cohort study of guests of the suspect hotel revealed 23 cases of febrile illness with pulmonary symptoms, significant antibody titers to Legionella pneumophila, or both, among 291 persons at risk. Two patients died. Attack rates ranged from 0-19% in the nine cohorts of vacationers and were highest among the most elderly. Febrile illness in the last two cohorts of the season was associated with an antibody titer greater than or equal to 128. L. pneumophila was isolated from shower heads in the suspect hotel, but no association was found between showering and illness or seropositivity. Bacteria identified as L. pneumophila by direct immunofluorescence were also found in water from an adjacent hotel and from the outflow from a common well. No cases were associated with the adjacent hotel. PMID:6691329

Rosmini, F; Castellani-Pastoris, M; Mazzotti, M F; Forastiere, F; Gavazzoni, A; Greco, D; Ruckdeschel, G; Tartagni, E; Zampieri, A; Baine, W B

1984-01-01

193

Gene expression profiles in febrile children with defined viral and bacterial infection  

PubMed Central

Viral infections are common causes of fever without an apparent source in young children. Despite absence of bacterial infection, many febrile children are treated with antibiotics. Virus and bacteria interact with different pattern recognition receptors in circulating blood leukocytes, triggering specific host transcriptional programs mediating immune response. Therefore, unique transcriptional signatures may be defined that discriminate viral from bacterial causes of fever without an apparent source. Gene expression microarray analyses were conducted on blood samples from 30 febrile children positive for adenovirus, human herpesvirus 6, or enterovirus infection or with acute bacterial infection and 22 afebrile controls. Blood leukocyte transcriptional profiles clearly distinguished virus-positive febrile children from both virus-negative afebrile controls and afebrile children with the same viruses present in the febrile children. Virus-specific gene expression profiles could be defined. The IFN signaling pathway was uniquely activated in febrile children with viral infection, whereas the integrin signaling pathway was uniquely activated in children with bacterial infection. Transcriptional profiles classified febrile children with viral or bacterial infection with better accuracy than white blood cell count in the blood. Similarly accurate classification was shown with data from an independent study using different microarray platforms. Our results support the paradigm of using host response to define the etiology of childhood infections. This approach could be an important supplement to highly sensitive tests that detect the presence of a possible pathogen but do not address its pathogenic role in the patient being evaluated.

Hu, Xinran; Yu, Jinsheng; Crosby, Seth D.; Storch, Gregory A.

2013-01-01

194

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

PubMed

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

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

195

A prospective survey of febrile events in hematological malignancies.  

PubMed

The Hema e-Chart prospectively collected data on febrile events (FEs) in hematological malignancy patients (HMs). The aim of the study was to assess the number, causes and outcome of HM-related FEs. Data were collected in a computerized registry that systematically approached the study and the evolution of FEs developing in a cohort of adult HMs who were admitted to 19 hematology departments in Italy from March 2007 to December 2008. A total of 869 FEs in 3,197 patients with newly diagnosed HMs were recorded. Fever of unidentified origin (FUO) was observed in 386 cases (44.4%). The other causes of FE were identified as noninfectious in 48 cases (5.5%) and infectious in 435 cases (50.1%). Bacteria were the most common cause of infectious FEs (301 cases), followed by fungi (95 cases), and viruses (7 cases). Mixed agents were isolated in 32 episodes. The attributable mortality rate was 6.7% (58 FEs). No deaths were observed in viral infection or in the noninfectious groups, while 25 deaths were due to FUO, 16 to bacterial infections, 14 to fungal infections, and three to mixed infections. The Hema e-Chart provided a complete system for the epidemiological study of infectious complications in HMs. PMID:22124621

Pagano, L; Caira, M; Rossi, G; Tumbarello, M; Fanci, R; Garzia, M G; Vianelli, N; Filardi, N; De Fabritiis, P; Beltrame, A; Musso, M; Piccin, A; Cuneo, A; Cattaneo, C; Aloisi, T; Riva, M; Rossi, G; Salvadori, U; Brugiatelli, M; Sannicolò, S; Morselli, M; Bonini, A; Viale, P; Nosari, A; Aversa, F

2012-05-01

196

Ring chromosome 18 in a child with febrile seizures.  

PubMed

Ring chromosomes are uncommon cytogenetic findings but have meanwhile been reported for nearly all human chromosomes. Among the rare observations of ring chromosomes in man, the diagnosis of ring chromosome 18 represents a prominent group. We here describe on the cytogenetic analysis results obtained for a 9 years old male patient of non-consanguineous parents. He had growth and developmental delay, mental and motor retardation, microcephaly, microphtalmia, triangle face, small dysplastic ears, strabismus, epicanthal folds on the left, short stature, cryptorchidism, spasticity, pes equinovarus, pes planus, hypothroidism, stereotypic movements and febrile seizures. Also he had hypomyelinization and multiple hyperintense focuses within the white matter on the MRI. The generalized epileptiform abnormality originated from bilateral Centroparietal region. The metabolic investigations including blood and urine amino acids and lysosomal screening tests were normal. The chromosome analysis identified [46,XY,r(18)/46,XY] in 35% of cells a ring 18 and in 65% of cells normal karyotype in peripheral blood cells examined by standard G-bands by Trypsin using Giemsa (GTG) analysis. The dysmorphic features of the presented patient are discussed to the identification of the genotype-phenotype correlation related to his karyotype. PMID:21848009

Celep, F; Sonmez, F M; Kul, S; Ucar, F; Karaguzel, A

2011-01-01

197

Diagnostic significance of indium-111 granulocyte scintigraphy in febrile patients  

SciTech Connect

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

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

1987-02-01

198

Premedication with midazolam for urethral catheterization of febrile infants.  

PubMed

Febrile infants undergoing urethral catheterization (UC) are often not treated for pain and distress. The aim was to evaluate the effectiveness of midazolam premedication. We compared a convenience sample of infants who underwent UC with midazolam with those who did not receive midazolam. Outcome measures were Visual Analog Scale assessment, duration of cry, and emergency department length of stay. Thirty-two study participants and 18 controls were prospectively enrolled. Midazolam premedication showed a 53% decrease in the mean Visual Analog Scale score when parents assessed distress (33.6 vs. 71.7, P<0.0001) and a 48% decrease when nurses assessed distress (28.7 vs. 55.5, P<0.0002); the median cry duration was significantly shorter (0 vs. 240 s). Serious adverse events were not observed during sedation and at 48 h after discharge. Study participants had longer emergency department length of stay compared with the controls (191.5 vs. 139 min, P<0.017). In this cohort, midazolam significantly reduced the distress associated with UC without causing serious adverse events. PMID:24323046

Weiser, Giora; Cohen, Dana; Krauss, Baruch; Galbraith, Roger; Shavit, Itai

2014-08-01

199

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

PubMed Central

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.

GHASEMI, Fateme; VALIZADEH, Fateme; TAEE, Nadere

2014-01-01

200

A diagnostic algorithm combining clinical and molecular data distinguishes Kawasaki disease from other febrile illnesses  

PubMed Central

Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Methods Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Results Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. Conclusions A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.

2011-01-01

201

Estimating risk factors and causes for postpartum febrile morbidity in teenage mothers.  

PubMed

In this cohort study, our objective was to identify potentially modifiable risk factors and causes for febrile morbidity in teenage mothers. We identified all cases of febrile morbidity using the United States Joint Commission on Maternal Welfare definition in a cohort of teenage deliveries over a 4-year period at one institution. Of the 730 included teenage deliveries, 49 (7%) women suffered postpartum febrile morbidity. Higher maternal pre-pregnancy body mass index (BMI: 34.0 ± 8.6 vs 30.3 ± 6.0 kg/m(2), p = 0.0001), caesarean delivery (RR 21.3, 95% CU 8.9-54.9) and postpartum haemorrhage (RR 3.0, 95% CI 1.1-6.7) were associated with postpartum febrile morbidity. Risk factors for febrile morbidity in the teenage parturient include obesity, caesarean delivery and postpartum haemorrhage. Considering the increasing rates of teenage obesity and overall caesarean delivery rates, attention must be focused on these modifiable risk factors to avoid this complication during a tenuous time for the teenage parent. PMID:23445136

Haeri, S; Baker, A M

2013-02-01

202

Assessment of Febrile Neonates According to Low Risk Criteria for Serious Bacterial Infection  

PubMed Central

Objective It is propounded that febrile neonates with low risk criteria (LRC) can be carefully observed without parenteral antimicrobial therapy; but yet, reliability of LRC to exclude serious bacterial infection (SBI) is uncertain. Methods The records of all febrile term neonates, seen in the emergency room and admitted in neonatal ward of 17 Shahrivar children's hospital of Rasht, Iran from January 2004 to January 2009 were reviewed. All of them underwent full sepsis workup. The prevalence of SBI in total population and LRC positive and negative neonates were calculated Findings A total of 202 records of previously healthy febrile neonates were evaluated. SBI was shown in 38 (18.8%). The most common type of SBI was urinary tract infection (UTI). Sixty-two (31%) neonates had LRC, and only one (1.6%) had SBI (UTI with E. coli). SBI was significantly more common in neonates without LRC (26.6% versus 1.6%, P<0.001). The negative predictive value (NPV) of LRC to exclude SBI was 98.4% (95%confidence interval: 96.7% to 100%). Conclusion These findings suggest that LRC may be relied upon to exclude SBI in febrile neonates. We propose that all febrile neonates be admitted, ill or LRC negative neonates should undergo a full sepsis work up and be administered systemic antibiotics immediately. LRC positive neonates should be under close observation.

Zarkesh, Marjaneh; Hashemian, Houman; Momtazbakhsh, Mohammad; Rostami, Tahereh

2011-01-01

203

Incidence of and risk factors for febrile morbidity after laparoscopic-assisted vaginal hysterectomy  

PubMed Central

Background The purpose of this study was to assess the incidence of and risk factors for postoperative febrile morbidity after laparoscopic-assisted vaginal hysterectomy (LAVH). Methods This retrospective study was carried out using the medical records of women with benign gynecologic conditions who underwent LAVH between June 2007 and May 2012 at Srinagarind Hospital in Thailand. Data were collected to assess baseline patient characteristics, occurrence of body temperature ?38°C on two occasions at least 6 hours apart in the 24 hours following the surgical procedure, and possible risk factors related to postoperative febrile morbidity. Results In total, 199 women underwent LAVH during the study period. They had a mean age of 46±6 years, a mean body mass index of 24.0±3.2 kg/m2, a mean surgical duration of 134±52 minutes, median estimated blood loss of 200 mL, a mean total hospital stay of 5±2 days, and a mean postoperative hospital stay of 3±2 days. Postoperative febrile morbidity was documented in 31 cases (15.6%). The cause of postoperative fever was unknown in most cases, with only two cases having an identifiable cause. The risk of postoperative febrile morbidity was highest in women treated with more than two antibacterial agents and with a regimen of more than 3 days. Conclusion This study shows a moderately high rate of febrile morbidity after LAVH, for which the main risk factors were use of multiple drugs and doses for antibiotic prophylaxis.

Wongpia, Iyara; Thinkhamrop, Jadsada; Seejorn, Kanok; Buppasiri, Pranom; Luanratanakorn, Sanguanchoke; Temtanakitpaisan, Teerayut; Khampitak, Kovit

2014-01-01

204

Bilateral hippocampal atrophy in temporal lobe epilepsy: Effect of depressive symptoms and febrile seizures  

PubMed Central

Summary Purpose Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reductions in patients with temporal lobe epilepsy (TLE). Methods We used radial atrophy mapping (RAM), a three-dimensional (3D) surface modeling tool, to measure hippocampal atrophy in 40 patients with unilateral TLE, with or without a history of febrile seizures and symptoms of depression. Multiple linear regression was used to single out the effects of covariates on local atrophy. Key Findings Subjects with a history of febrile seizures (n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures (n = 25). Subjects with Beck Depression Inventory II (BDI-II) score ?14 (n = 11) had atrophy in the superoanterior portion of the CHC compared to subjects with BDI-II <14 (n = 29). Significance Contralateral hippocampal atrophy in TLE may be related to febrile seizures or depression.

Finegersh, Andrey; Avedissian, Christina; Shamim, Sadat; Dustin, Irene; Thompson, Paul M.; Theodore, William H.

2011-01-01

205

Single infusion of myeloid progenitors reduces death from Aspergillus fumigatus following chemotherapy-induced neutropenia.  

PubMed

Hematopoietic progenitors committed to the myeloid lineage, the common myeloid and granulocyte-monocyte progenitors (CMP/GMP), have been shown to protect against opportunistic pathogens following myeloablative radiation; however, the efficacy of this approach has not been studied in the setting of chemotherapy-induced neutropenia. In this mouse model, the infusion of CMP/GMP on the day after 5-fluorouracil (5-FU) administration (D+1) resulted in a significant increase in the number of splenic neutrophils by D+8 when compared with 5-FU-only controls (P = .02), the majority of which were CMP/GMP-derived (54%). Moreover, 19% and 28% of neutrophils in the blood and bone marrow, respectively, were CMP/GMP-derived. Survival following intranasal challenge with the fungus Aspergillus fumigatus was significantly higher in CMP/GMP-infused mice than the controls (56% and 33% respectively; P = .019). Thus, a single infusion of CMP/GMP enhances tissue neutrophil content and increases survival against a lethal challenge with A fumigatus in the setting of chemotherapy-induced neutropenia. PMID:15576478

BitMansour, Andrew; Cao, Thai M; Chao, Stephanie; Shashidhar, Sumana; Brown, Janice M Y

2005-05-01

206

Granulocyte transfusions for children with infection and neutropenia or granulocyte dysfunction.  

PubMed

Transfusions of granulocytes can be used as an adjunct therapy to antimicrobials in patients with infection and neutropenia or granulocyte dysfunction. However, there is a lack of strong clinical evidence to support the use of this treatment strategy, particularly in children. We retrospectively reviewed the medical records of children who received granulocytes at our institution from April 2009 to October 2012, with emphasis on primary indication for the transfusion and clinical outcome in terms of infection. The patients had granulocyte dysfunction or severe neutropenia, defined as absolute neutrophil count (ANC) < 500 cells/mm(3) due to chemotherapy or hematopoietic stem cell transplant (HSCT), and reasonable hope for bone marrow recovery or engraftment. Eighteen children received granulocytes during 20 distinct episodes: 62% (n = 13) for acute infection, 29% (n = 5) for unresolved chronic infection during the time of HSCT, and 9% (n = 2) for other clinical conditions such as typhilitis and appendectomy. Overall, 92% (n = 12) of the episodes of acute infection had complete or partial resolution, as determined by review of vital signs, physical exam findings and discontinuation of antimicrobials. A substantial number (46%) of children who received granulocytes for acute infection developed respiratory adverse events, but all of these recovered. We conclude that granulocyte transfusions continue to be primarily used in neutropenic patients with acute infections, and that its use in this group of patients is reasonable. However, a prospective randomized clinical trial is needed to evaluate safety and whether the use of granulocytes is superior to antimicrobial-only therapy. PMID:24383443

Díaz, Rosa; Soundar, Esther; Hartman, S Kate; Dreyer, ZoAnn; Teruya, Jun; Hui, Shiu-Ki Rocky

2014-08-01

207

Different pattern of gene mutations in Iranian patients with severe congenital neutropenia (including 2 new mutations).  

PubMed

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease. Different genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3. The aim of this study was to find different gene mutations responsible for SCN in Iranian patients. Twenty-seven patients with SCN referred to Immunology, Asthma and Allergy Research Institute during a five year priod 5 years (May 2007 and May 2012), were included in this study. Neutropenia related exons and flanking regions of ELA2, HAX1, WAS, GFI1, G-CSFR and G6PC3 were amplified by PCR and the sequences were analyzed. The results showed different mutations including 4 ELANE mutations, 11 HAX1 mutations and 2 G6PC3 mutations. None of the patients had GFI1 mutation and also one mutation was found in G-CSFR in a patient with ELANE mutation. Ten patients had unknown genetic diagnosis which was compatible with other studies. According to these results, most of the patients showed HAX1 mutations and this finding which significantly differed from other reports, might be related to differences in Iranian ethnicity and also in high rate of consanguineous marriages in Iran. PMID:23454784

Alizadeh, Zahra; Fazlollahi, Mohammad Reza; Houshmand, Massoud; Maddah, Marzieh; Chavoshzadeh, Zahra; Hamidieh, Amir Ali; Shamsian, Bibi Shahin; Eshghi, Payman; Bolandghamat Pour, Samaneh; Sadaaie Jahromi, Hoda; Mansouri, Mahboobeh; Movahedi, Masoud; Nayebpour, Mohsen; Pourpak, Zahra; Moin, Mostafa

2013-03-01

208

Multistability in an age-structured model of hematopoiesis: Cyclical neutropenia.  

PubMed

Cyclical neutropenia (CN) is a rare hematopoietic disorder in which the patient's neutrophil level drops to extremely low levels for a few days approximately every three weeks. CN is effectively treated with granulocyte colony stimulating factor (G-CSF), which is known to interfere with apoptosis in neutrophil precursors and to consequently increase the circulating neutrophil level. However, G-CSF treatment usually fails to eliminate the oscillation. In this study, we establish an age-structured model of hematopoiesis, which reduces to a set of four delay differential equations with specific forms of initial functions. We numerically investigate the possible stable solutions of the model equations with respect to changes in the parameters as well as the initial conditions. The results show that the hematopoietic system possesses multistability for parameters typical of the normal healthy state. From our numerical results, decreasing the proliferation rate of neutrophil precursors or increasing the stem cell death rate are two possible mechanisms to induce cyclical neutropenia, and the periods of the resulting oscillations are independent of the changing parameters. We also discuss the dependence of the model solution on the initial condition at normal parameter values corresponding to a healthy state. Using insight from our results we design a hybrid treatment method that is able to abolish the oscillations in CN. PMID:21094168

Lei, Jinzhi; Mackey, Michael C

2011-02-01

209

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

PubMed Central

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.

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

210

[Guideline for febrile children in the hospital setting; relevance for general practitioners and paediatricians].  

PubMed

- Febrile children pose the diagnostic dilemma of distinguishing those with serious infections from the vast majority with self-limiting diseases at an early stage.- Alarm symptoms can aid in assessing the probability of serious infections in febrile children.- The combined absence of alarm symptoms is useful in ruling out serious infections.- CRP and PCT values are important diagnostic markers in febrile children in hospital settings.- Children without any alarm symptoms and low inflammatory markers can be treated conservatively, provided there are good instructions on reassessment.- Children with amber alarm symptoms or mildly elevated inflammatory markers in whom a serious infection cannot be ruled out require clinical observation or ambulant follow-up; empirical parenteral antibiotic treatment should also be considered and easily accessible.- Children with red alarm symptoms or highly elevated inflammatory markers deserve clinical observation. In children < 3 months, empirical parenteral antibiotic treatment is also indicated. PMID:25027213

Nijman, R G; Oteman, N; Oostenbrink, R

2014-01-01

211

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

PubMed

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

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

2014-01-01

212

Hospital-Based Prevalence of Malaria and Dengue in Febrile Patients in Bangladesh  

PubMed Central

We conducted a nationwide study at six tertiary hospitals from December 2008 through November 2009 to investigate etiologies of febrile illnesses in Bangladesh. Febrile patients meeting a clinical case definition were enrolled from inpatient and outpatient medicine and pediatric units. We assessed 720 febrile patients over 12 months; 69 (9.6%) were positive for IgM antibodies against dengue virus by enzyme-linked immunosorbent assay, and four malaria patients (0.56%) were confirmed with immuno-chromatography and microscopic slide tests. We identified dengue cases throughout the year from rural (49%) and urban areas (51%). We followed-up 55 accessible dengue-infected patients two months after their initial enrollment: 45 (82%) patients had fully recovered, 9 (16%) reported ongoing jaundice, fever and/or joint pain, and one died. Dengue infection is widespread across Bangladesh, but malaria is sufficiently uncommon that it should not be assumed as the cause of fever without laboratory confirmation.

Faruque, Labib I.; Zaman, Rashid Uz; Alamgir, A. S. M.; Gurley, Emily S.; Haque, Rashidul; Rahman, Mahmudur; Luby, Stephen P.

2012-01-01

213

Identification of Bartonella Infections in Febrile Human Patients from Thailand and Their Potential Animal Reservoirs  

PubMed Central

To determine the role of Bartonella species as causes of acute febrile illness in humans from Thailand, we used a novel strategy of co-cultivation of blood with eukaryotic cells and subsequent phylogenetic analysis of Bartonella-specific DNA products. Bartonella species were identified in 14 blood clots from febrile patients. Sequence analysis showed that more than one-half of the genotypes identified in human patients were similar or identical to homologous sequences identified in rodents from Asia and were closely related to B. elizabethae, B. rattimassiliensis, and B. tribocorum. The remaining genotypes belonged to B. henselae, B. vinsonii, and B. tamiae. Among the positive febrile patients, animal exposure was common: 36% reported owning either dogs or cats and 71% reported rat exposure during the 2 weeks before illness onset. The findings suggest that rodents are likely reservoirs for a substantial portion of cases of human Bartonella infections in Thailand.

Kosoy, Michael; Bai, Ying; Sheff, Kelly; Morway, Christina; Baggett, Henry; Maloney, Susan A.; Boonmar, Sumalee; Bhengsri, Saithip; Dowell, Scott F.; Sitdhirasdr, Anussorn; Lerdthusnee, Kriangkrai; Richardson, Jason; Peruski, Leonard F.

2010-01-01

214

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

PubMed Central

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

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

2014-01-01

215

A Randomized Controlled Phase I11 Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia  

Microsoft Academic Search

EVERE CHRONIC neutropenia includes a heteroge- S neous group of hematologic diseases characterized by a selective decrease in circulating neutrophils to levels often associated with recurrent fevers, chronic oropharyngeal in- flammation, and severe infections.',' Severe chronic neutro- penia has been divided into three main syndromes: idiopathic neutr~penia,~.~ cyclic neutropenia,'-' and Congenital forms of Diagnosis of these separate entities requires a

David C. Dale; Mary Ann Bonilla; Mark W. Davis; Arline M. Nakanishi; William P. Hammond; Joanne Kurtzberg; Winfred Wang; Ann Jakubowski; Elliott Winton; Parviz Lalezari; William Robinson; John A. Glaspy; Steve Emerson; Janice Gabrilove; Martha Vincent; Laurence A. Boxer

216

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

PubMed

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

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

217

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

PubMed Central

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.

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

2013-01-01

218

Commonly Occurring VHL Manifestations  

MedlinePLUS

... Most Common Ages at DX Frequency in Patients CNS Retinal hemangioblastomas 0-68 yrs 12-25 yrs ... Occurring VHL Manifestations Kidney Brain and Spinal Cord / CNS Retina Pancreas Inner Ear Pheochromocytoma / Paraganglioma Reproductive Organs ...

219

Diagnosis and Management of Febrile Infants (0-3 months): Executive Summary. Evidence Report/Technology Assessment Number 205.  

National Technical Information Service (NTIS)

The febrile infant is a common clinical problem that accounts for a large number of ambulatory care visits. Young febrile infants (ages 0-3 months) often present with nonspecific symptoms and it is difficult to distinguish between infants with a viral syn...

2012-01-01

220

Diagnosis and Management of Febrile Infants (0-3 Months) Evidence Report/Technology Assessment Number 205.  

National Technical Information Service (NTIS)

The febrile infant is a common clinical problem that accounts for a large number of ambulatory care visits. Young febrile infants (ages 0-3 months) often present with nonspecific symptoms and it is difficult to distinguish between infants with a viral syn...

A. Tsertsvadze A. C. Tricco C. Hui F. Yazdi G. Neto

2012-01-01

221

[Febrile episodes of unknown origin, elevated level of plasma ferritin and rapidly developed multiorgan dysfunction].  

PubMed

A previously healthy 40-year-old man developed febrile episodes of unknown origin, articular symptoms, venous occlusion of the lower limb and transient elevation of hepatic enzymes, and cutaneous symptoms. Computed tomography scanning revealed enlarged lymph nodes, but no sample was collected. In addition to microcytic anemia, a high serum ferritin level and an increased IL-2 receptor value in serum were found. Drug therapy against tuberculosis and borreliosis was started, but febrile episodes continued and in a few days the patient developed multiorgan dysfunction. Hemophagocytic lymphohistiocytosis associated with T-cell lymphoma was revealed as the underlying condition. PMID:24660387

Jantunen, Esa; Siitonen, Sanna; Karjalainen-Lindsberg, Marja-Liisa

2014-01-01

222

Febrile cholestatic disease as an initial presentation of nodular lymphocyte-predominant Hodgkin lymphoma  

PubMed Central

Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma (HL). The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subtype of HL, a nodular lymphocyte-predominant HL (NLPHL). Liver involvement in the early stage of the usually indolent NLPHL’s clinical course suggests an aggressiveness and unfavorable outcome. Emphasizing a liver biopsy early in the diagnostic algorithm enables accurate diagnosis and appropriate treatment. Although rare, HL should be considered in the differential diagnosis of cholestasis.

Mrzljak, Anna; Gasparov, Slavko; Kardum-Skelin, Ika; Colic-Cvrlje, Vesna; Ostojic-Kolonic, Slobodanka

2010-01-01

223

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

PubMed Central

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.

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

2012-01-01

224

Dyskeratosis congenita with isolated neutropenia and granulocyte colony-stimulating factor treatment.  

PubMed

A 3-year-old Turkish boy with a history of chronic cough, recurrent bronchopneumonia, and a borderline sweat chloride test (40 mEq/L) was referred for further evaluation to our department. He was born at term (2100 g) to a marriage with no consanguinity. His mother and father were 40 and 46 years old, respectively. Physical examination (Fig. 1) revealed hypopigmented, atrophic, and hyperkeratotic skin lesions surrounded by reticulate hyperpigmentation on the entire body, predominantly on the face, neck, arms, shoulders, and legs, which had been noticed initially at the age of 18 months. Dystrophic toenails, sparse and thin hair, and phimosis were also observed. Laboratory tests disclosed an isolated neutropenia (white blood cell count, 1800/mm3). Bone marrow (BM) aspiration showed a decreased myelopoiesis without myelodysplastic changes, but normal erythropoiesis, megakaryopoiesis, and normal stroma. Lymphocyte subgroups containing CD4, CD5, CD6, CD8, CD19, CD23, and CD25, and immunoglobulin G (IgG), IgM, IgA, and IgE, were in the normal range; hemoglobin F (HbF), 2.8%. Spontaneous and clastogen-induced chromosome breaks were not increased. A skin biopsy showed increased pigmentation at the basal layer, dyskeratotic epidermal cells, and marked IgM deposition and cytoid bodies and mild IgA and IgG deposits at the dermo-epidermal junction. Lactate response to glucose challenge, amino acid chromatography, and urine organic acid analysis were normal. A diagnosis of dyskeratosis congenita (DC) was made with typical skin lesions, dystrophic toenails, thin and sparse hair, and neutropenia with decreased myelopoiesis in BM. Treatment with granulocyte colony-stimulating factor (G-CSF) was considered for the neutropenia. As the increase in neutrophil count at a dose of 5 microg/kg was not adequate, 10 microg/kg G-CSF was tried (Fig. 2). With 10 microg/kg once to three times a week, a 1.8-4.8-fold increase in the absolute neutrophil count (ANC) was achieved with no side-effects. Treatment was more frequent during infection (days 22-28). PMID:12010344

Yilmaz, Kutluhan; Inalöz, H Serhat; Unal, Bünyamin; Güler, Elif

2002-03-01

225

Viridans streptococci bacteraemia in children with fever and neutropenia: a case–control study of predisposing factors  

Microsoft Academic Search

Viridans streptococci (VS) are an increasing cause of bacteraemia in neutropenic patients with cancer. Case–control studies of predisposing factors for acquisition of this infection in children are not published. Between January 1989 and December 1999, 168 episodes of bacteraemia in 161 children with fever and neutropenia of haemato-oncology origin were analysed. 15 cases (9%) in 15 patients were caused by

H. Paganini; V Staffolani; P. Zubizarreta; L. Casimir; H. Lopardo; V. Luppino

2003-01-01

226

Co-Occurring Disorders  

MedlinePLUS

... and mental health problems. For people struggling with co-occurring mental health and substance abuse disorders, physical safety and overall health risks are greater; the impairment of life skills is greater; and the chances for successful treatment are much less - all of which contribute to ...

227

[Pure red cell aplasia and neutropenia associated with chronic monoclonal T-lymphocytosis].  

PubMed

We report a patient with nonregenerative anemia and neutropenia associated with an increment of circulating large granular lymphocytes (LGL). The anemia was secondary to the absence of erythroid precursors in the bone marrow or pure red blood cell aplasia associated with moderate lymphoid infiltration by LGL. Myeloid (CFU-GM) or erythroid (CFU-E, BFU-E) precursors were not detected by bone marrow culture. A high number of T colonies was found. The lymphoid population had a cytotoxic/suppressor phenotype (CD2+, CD4-, CD8+). Virologic studies (including search for HTLV1) were carried out with negative results. A clonal origin was demonstrated by DNA analysis with probes of those genes encoding T receptor (TRc). After cytostatic therapy with cyclophosphamide and low doses of prednisone a clinical and laboratory remission was achieved. We review the literature, with a discussion of the clinical, phenotypic and molecular features of this disease as well as its response to therapy. PMID:2109163

Palomera Bernal, L; García Díez, I

1990-02-24

228

Identification of a novel C16orf57 mutation in Athabaskan patients with Poikiloderma with Neutropenia.  

PubMed

Poikiloderma with Neutropenia (PN), Clericuzio-Type (OMIM #604173) is characterized by poikiloderma, chronic neutropenia, recurrent sinopulmonary infections, bronchiectasis, and nail dystrophy. First described by Clericuzio in 1991 in 14 patients of Navajo descent, it has since also been described in non-Navajo patients. C16orf57 has recently been identified as a causative gene in PN. The purpose of our study was to describe a spectrum of C16orf57 mutations in a cohort of PN patients including five patients of Athabaskan (Navajo and Apache) ancestry. Eleven patients from eight kindreds were enrolled in an IRB-approved study at Baylor College of Medicine. Five patients were of Athabaskan ancestry. PCR amplification and sequencing of the entire coding region of the C16orf57 gene was performed on genomic DNA. We identified biallelic C16orf57 mutations in all 11 PN patients in our cohort. The seven new deleterious mutations consisted of deletion (2), nonsense (3), and splice site (2) mutations. The patients of Athabaskan ancestry all had a common deletion mutation (c.496delA) which was not found in the six non-Athabaskan patients. Mutations in the C16orf57 gene have been identified thus far in all patients studied with a clinical diagnosis of PN. We have identified seven new mutations in C16orf57 in PN patients. One of these is present in all patients of Athabaskan descent, suggesting that c.496delA represents the PN-causative mutation in this subpopulation. PMID:21271650

Clericuzio, Carol; Harutyunyan, Karine; Jin, Weidong; Erickson, Robert P; Irvine, Alan D; McLean, W H Irwin; Wen, Yaran; Bagatell, Rochelle; Griffin, Thomas A; Shwayder, Tor A; Plon, Sharon E; Wang, Lisa L

2011-02-01

229

Identification of a Novel C16orf57 Mutation in Athabaskan Patients with Poikiloderma with Neutropenia  

PubMed Central

Poikiloderma with Neutropenia (PN), Clericuzio-Type (OMIM #604173) is characterized by poikiloderma, chronic neutropenia, recurrent sinopulmonary infections, bronchiectasis, and nail dystrophy. First described by Clericuzio in 1991 in 14 patients of Navajo descent, it has since also been described in non-Navajo patients. C16orf57 has recently been identified as a causative gene in PN. The purpose of our study was to describe a spectrum of C16orf57 mutations in a cohort of PN patients including five patients of Athabaskan (Navajo and Apache) ancestry. Eleven patients from eight kindreds were enrolled in an IRB-approved study at Baylor College of Medicine. Five patients were of Athabaskan ancestry. PCR amplification and sequencing of the entire coding region of the C16orf57 gene was performed on genomic DNA. We identified biallelic C16orf57 mutations in all eleven PN patients in our cohort. The seven new deleterious mutations consisted of deletion (2), nonsense (3), and splice site (2) mutations. The patients of Athabaskan ancestry all had a common deletion mutation (c.496delA) which was not found in the six non-Athabaskan patients. Mutations in the C16orf57 gene have been identified thus far in all patients studied with a clinical diagnosis of PN. We have identified seven new mutations in C16orf57 in PN patients. One of these is present in all patients of Athabaskan descent, suggesting that c.496delA represents the PN-causative mutation in this subpopulation.

Clericuzio, Carol; Harutyunyan, Karine; Jin, Weidong; Erickson, Robert P.; Irvine, Alan D.; McLean, W.H. Irwin; Wen, Yaran; Bagatell, Rochelle; Griffin, Thomas A.; Shwayder, Tor A.; Plon, Sharon E.; Wang, Lisa L.

2010-01-01

230

Accidental ingestion of Ecstasy by a toddler: unusual cause for convulsion in a febrile child.  

PubMed Central

The case is reported of a toddler who presented with an apparent febrile convulsion. The final diagnosis was that of accidental ingestion of Ecstasy. The child made an uneventful recovery. Ecstasy toxicity should be added to the list of differential diagnoses in a child presenting with fever and an unexplained seizure.

Cooper, A J; Egleston, C V

1997-01-01

231

Topiramate as a neuroprotectant in the experimental model of febrile seizures  

Microsoft Academic Search

Purpose: The aim of the study wad to estimate a poten- tially neuroprotective effect of topiramate (TPM) in the experi- mental model of FS. Material and methods: 24 young male rats divided in 4 groups were involved in the study. Febrile seizures were induced by placing the animals in 45°C warm water bath for four consecutive days. TPM at the

Sobaniec W

232

Febrile seizures: an appropriate-aged model suitable for long-term studies  

Microsoft Academic Search

Seizures induced by fever are the most prevalent age-specific seizures in infants and young children. Whether they result in long-term sequelae such as neuronal loss and temporal lobe epilepsy is controversial. Prospective studies of human febrile seizures have found no adverse effects on the developing brain. However, adults with temporal lobe epilepsy and associated limbic cell loss frequently have a

Tallie Z. Baram; Angelika Gerth; Linda Schultz

1997-01-01

233

VENEZUELAN EQUINE ENCEPHALITIS FEBRILE CASES AMONG HUMANS IN THE PERUVIAN AMAZON RIVER REGION  

Microsoft Academic Search

A survey was conducted from October 1, 1993 to June 30, 1995 to determine the arboviral etiologies of febrile illnesses in the city of Iquitos in the Amazon River Basin of Peru. The study subjects were patients who were enrolled at medical care clinics or in their homes by Peruvian Ministry of Health (MOH) workers as part of the passive

DOUGLAS M. WATTS; JOHNNY CALLAHAN; CINDY ROSSI; M. STEVEN OBERSTE; J. T. ROEHRIG; MARK T. WOOSTER; JONATHAN F. SMITH; C. B. CROPP; ELMER M. GENTRAU; NICK KARABATSOS; DUANE GUBLER; CURT G. HAYES

234

Detection of bacterial DNA in blood samples from febrile patients: underestimated infection or emerging contamination?  

Microsoft Academic Search

We applied real-time broad-range polymerase chain reaction (PCR) to detect bacteraemia in blood from febrile patients. Interpretation of amplification results in relation to clinical data and blood culture outcome was complex, although the reproducibility of the PCR results was good. Sequencing analysis of the PCR products revealed the presence of Burkholderia species DNA while no Burkholderia species grew in culture.

Remco P. H. Peters; Tamimount Mohammadi; Christina M. J. E. Vandenbroucke-Grauls; Sven A. Danner; Michiel A. van Agtmael; Paul H. M. Savelkoul

2004-01-01

235

Ocular Involvement in Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome): New Cases and Review of the Literature  

Microsoft Academic Search

Sweet syndrome (acute febrile neutrophilic dermatosis) is a dermatologic disorder with accompanying features of systemic inflammation. It is commonly associated with conjunctivitis, but a variety of types of ocular inflammation have been reported. The ocular manifestations of Sweet syndrome include periorbital and orbital inflammation, dacryoadenitis, conjunctivitis, episcleritis, scleritis, limbal nodules, peripheral ulcerative keratitis, iritis, glaucoma, and choroiditis. The ocular inflammation

Chloe C. Gottlieb; Aditya Mishra; Dan Belliveau; Peter Green; J. Godfrey Heathcote

2008-01-01

236

Unsuspected Rickettsioses among Patients with Acute Febrile Illness, Sri Lanka, 2007  

PubMed Central

We studied rickettsioses in southern Sri Lanka. Of 883 febrile patients with paired serum samples, 156 (17.7%) had acute rickettsioses; rickettsioses were unsuspected at presentation. Additionally, 342 (38.7%) had exposure to spotted fever and/or typhus group rickettsioses and 121 (13.7%) scrub typhus. Increased awareness of rickettsioses and better tests are needed.

Bodinayake, Champica; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara-Arachichi, Wasantha; Strouse, John J.; Flom, Judith E.; ?stbye, Truls; Woods, Christopher W.; Dumler, J. Stephen

2012-01-01

237

Rift Valley fever among febrile patients at New Halfa hospital, eastern Sudan  

Microsoft Academic Search

BACKGROUND: Since the first isolation of the Rift Valley Fever virus (RVFV) in 1930s, there have been several epizootics outbreaks in the tropic mainly in Africa including Sudan. Recognition of cases and diagnosis of RVF are critical for management and control of the disease. AIMS: To investigate the seroprevalence and risk factors for seropostive to RVFV IgG among febrile patients.

Ahmed M Hassanain; Waleed Noureldien; Mubarak S Karsany; El najeeb S Saeed; Imadeldin E Aradaib; Ishag Adam

2010-01-01

238

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

ERIC Educational Resources Information Center

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…

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

2009-01-01

239

"Naturally occurring asbestos  

NASA Astrophysics Data System (ADS)

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.

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

2012-04-01

240

Costs and Infant Outcomes After Implementation of a Care Process Model for Febrile Infants  

PubMed Central

OBJECTIVE: Febrile infants in the first 90 days may have life-threatening serious bacterial infection (SBI). Well-appearing febrile infants with SBI cannot be distinguished from those without by examination alone. Variation in care resulting in both undertreatment and overtreatment is common. METHODS: We developed and implemented an evidence-based care process model (EB-CPM) for the management of well-appearing febrile infants in the Intermountain Healthcare System. We report an observational study describing changes in (1) care delivery, (2) outcomes of febrile infants, and (3) costs before and after implementation of the EB-CPM in a children’s hospital and in regional medical centers. RESULTS: From 2004 through 2009, 8044 infants had 8431 febrile episodes, resulting in medical evaluation. After implementation of the EB-CPM in 2008, infants in all facilities were more likely to receive evidence-based care including appropriate diagnostic testing, determination of risk for SBI, antibiotic selection, decreased antibiotic duration, and shorter hospital stays (P < .001 for all). In addition, more infants had a definitive diagnosis of urinary tract infection or viral illness (P < .001 for both). Infant outcomes improved with more admitted infants positive for SBI (P = .011), and infants at low risk for SBI were more often managed without antibiotics (P < .001). Although hospital admissions were shortened by 27%, there were no cases of missed SBI. Health Care costs were also reduced, with the mean cost per admitted infant decreasing from $7178 in 2007 to $5979 in 2009 (?17%, P < .001). CONCLUSIONS: The EB-CPM increased evidence-based care in all facilities. Infant outcomes improved and costs were reduced, substantially improving value.

Reynolds, Carolyn C.; Korgenski, Kent; Sheng, Xiaoming; Valentine, Karen J.; Nelson, Richard E.; Daly, Judy A.; Osguthorpe, Russell J.; James, Brent; Savitz, Lucy; Pavia, Andrew T.; Clark, Edward B.

2012-01-01

241

Sweet's syndrome - a comprehensive review of an acute febrile neutrophilic dermatosis  

PubMed Central

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.

Cohen, Philip R

2007-01-01

242

Naturally occurring triterpenoid saponins.  

PubMed

Naturally occurring new triterpenoid saponins reported from mid-1996 to March, 2007 are reviewed including their physical constants and plant sources, and are compiled in Table 1. New saponins are arranged in Table 1 on the basis of the skeletal structures of their aglycones, e.g., oleanane type, ursane type, lupane type, hopane type, taraxastane type, cycloartane type, lanostane type, tirucallane type, dammarane type, cucurbitane type, and holostane type. The known triterpenoid saponins and prosapogenins of the new saponins, the biological and pharmacological activities of which were published during 1996-2007, are also reviewed together with their plant sources listed in Table 2 according to the skeletal structures of their aglycones in the same fashion as in Table 1. The plant and animal sources of both new and known bioactive triterpenoid saponins are collected in Table 3 in alphabetical order. The biological and pharmacological activities such as antiallergic, antiatherosclerosis and antiplatelet, antibacterial, anticomplementary, antidiabetic, contraceptive, antifungal, anti-inflammatory, antileishmanial, antimalarial/antiplasmodial, anti-obesity, anti-proliferative, antipsoriatic, antispasmodic, antisweet, antiviral, cytotoxic/antitumor, detoxication, gastroprotective, haemolytic, hepatoprotective, immunomodulatory, anti-enzyme, anti-osteoporotic, insecticidal, insulin-like, membrane-porosity, molluscicidal, neuropharmacological, anti-endothelial dysfunction, snake venom antidote, and sweet activities of these saponins or derived prosapogenins are discussed briefly after Table 3. PMID:20963775

Dinda, Biswanath; Debnath, Sudhan; Mohanta, Bikas Chandra; Harigaya, Yoshihiro

2010-10-01

243

Naturally occurring cardiac glycosides.  

PubMed

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

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

1986-05-12

244

Characteristics of T-cell large granular lymphocyte proliferations associated with neutropenia and inflammatory arthropathy  

PubMed Central

Introduction The purpose of this study was to analyze the data of patients with T-cell large granular lymphocyte (T-LGL) lymphocytosis associated with inflammatory arthropathy or with no arthritis symptoms. Methods Clinical, serological as well as histopathological, immuhistochemical, and flow cytometric evaluations of blood/bone marrow of 21 patients with T-LGL lymphocytosis were performed. The bone marrow samples were also investigated for T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangements by polymerase chain reaction with heteroduplex analysis. Results Neutropenia was observed in 21 patients, splenomegaly in 10, autoimmune diseases such as rheumatoid arthritis (RA) in 9, unclassified arthritis resembling RA in 2, and autoimmune thyroiditis in 5 patients. T-LGL leukemia was recognized in 19 cases. Features of Felty syndrome were observed in all RA patients, representing a spectrum of T-LGL proliferations from reactive polyclonal through transitional between reactive and monoclonal to T-LGL leukemia. Bone marrow trephines from T-LGL leukemia patients showed interstitial clusters and intrasinusoidal linear infiltrations of CD3+/CD8+/CD57+/granzyme B+ lymphocytes, reactive lymphoid nodules, and decreased or normal granulocyte precursor count with left-shifted maturation. In three-color flow cytometry (FCM), T-LGL leukemia cells demonstrated CD2, CD3, and CD8 expression as well as a combination of CD16, CD56, or CD57. Abnormalities of other T-cell antigen expressions (especially CD5, CD7, and CD43) were also detected. In patients with polyclonal T-LGL lymphocytosis, T cells were dispersed in the bone marrow and the expression of pan-T-cell antigens in FCM was normal. Molecular studies revealed TCRB and TCRG gene rearrangements in 13 patients and TCRB, TCRG, and TCRD in 4 patients. The most frequently rearranged regions of variable genes were V?-J?1, J?2 and V? If V?10-J?. Moreover, in 4 patients, additional rearrangements of IG kappa and lambda variable genes of B cells were also observed. Conclusion RA and neutropenia patients represented a continuous spectrum of T-LGL proliferations, although monoclonal expansions were most frequently observed. The histopathological pattern and immunophenotype of bone marrow infiltration as well as molecular characteristics were similar in T-LGL leukemia patients with and without arthritis.

Prochorec-Sobieszek, Monika; Rymkiewicz, Grzegorz; Makuch-Lasica, Hanna; Majewski, Miroslaw; Michalak, Katarzyna; Rupinski, Robert; Warzocha, Krzysztof; Maryniak, Renata

2008-01-01

245

Simultaneous treatment with carbimazole and granulocyte-colony stimulating factor in a patient with thyrotoxicosis and carbimazole induced neutropenia  

Microsoft Academic Search

We describe a patient who was admitted with uncontrolled thyrotoxicosis and carbimazole induced neutropenia. She required\\u000a 80 mg of carbimazole daily. The patient declined radio-iodine treatment because she had a little child and wished to have\\u000a thyroid surgery. She received four doses of filgrastim (Granulocyte-colony stimulating factor) which maintained the neutrophil\\u000a count within a reasonable level while she continued to

Indrajit Talapatra; Vengal Reddy Nagareddy; Manju Bhavnani; David James Tymms

2006-01-01

246

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

PubMed Central

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.

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

2014-01-01

247

Applying Outpatient Protocols in Febrile Infants 1-28 Days of Age: Can the Threshold Be Lowered?  

Microsoft Academic Search

The purpose of this study was to determine the applicability of two accepted outpatient management protocols for the febrile infant 1-2 months of age (Boston and Philadelphia protocols) in febrile infants 1-28 days of age. We retrospectively reviewed charts of patients 1-28 days of age with a temperature greater than or equal to 38.00C. Criteria from each of the above-cited

Howard A. Kadish; Brian Loveridget; John Tobeyt; Robert G. Bolte; Howard M. Corneli

2000-01-01

248

Relative pharmacokinetics of three amikacin brands in onco-hemotologic pediatric patients experiencing febrile neutropeina  

Microsoft Academic Search

Summary  Three commercially available brands of amikacin were investigated in aparallel study design for the assessment of comparative\\u000a pharmacokinetics in pediatric oncology patients with chemotherapy-induced neutropenic febrile episode. Amikacin concentration\\u000a in serum samples was determined by fluorescence polarization immunoassay method using Abbott TDx system. Computer software,\\u000a PK II was used for computation of pharmacokinetic parameters of amikacin. The serum concentration of

Muhammad Jamshaid; Samia Yousuf; Nadeem Irfan Bukhari; Amir Ali Rizvi

2003-01-01

249

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

Microsoft Academic Search

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

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

1999-01-01

250

Congenital neutropenia with retinopathy, a new phenotype without intellectual deficiency or obesity secondary to VPS13B mutations.  

PubMed

Over one hundred VPS13B mutations are reported in Cohen syndrome (CS). Most cases exhibit a homogeneous phenotype that includes intellectual deficiency (ID), microcephaly, facial dysmorphism, slender extremities, truncal obesity, progressive chorioretinal dystrophy, and neutropenia. We report on a patient carrying two VPS13B splicing mutations with an atypical phenotype that included microcephaly, retinopathy, and congenital neutropenia, but neither obesity nor ID. RNA analysis of the IVS34+2T_+3AinsT mutation did not reveal any abnormal splice fragments but mRNA quantification showed a significant decrease in VPS13B expression. RNA sequencing analysis up- and downstream from the IVS57+2T>C mutation showed abnormal splice isoforms. In contrast to patients with typical CS, who express only abnormal VPS13B mRNA and truncated protein, a dose effect of residual normal VPS13B protein possibly explains the incomplete phenotype in the patient. This observation emphasizes that VPS13B analysis should be performed in cases of congenital neutropenia associated with retinopathy, even in the absence of ID, therefore extending the VPS13B phenotype spectrum. PMID:24311531

Gueneau, Lucie; Duplomb, Laurence; Sarda, Pierre; Hamel, Christian; Aral, Bernard; Chehadeh, Salima El; Gigot, Nadège; St-Onge, Judith; Callier, Patrick; Thevenon, Julien; Huet, Frédéric; Carmignac, Virginie; Droin, Nathalie; Faivre, Laurence; Thauvin-Robinet, Christel

2014-02-01

251

Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis  

PubMed Central

Mutations in more than 15 genes are now known to cause severe congenital neutropenia (SCN); however, the pathologic mechanisms of most genetic defects are not fully defined. Deficiency of G6PC3, a glucose-6-phosphatase, causes a rare multisystem syndrome with SCN first described in 2009. We identified a family with 2 children with homozygous G6PC3 G260R mutations, a loss of enzymatic function, and typical syndrome features with the exception that their bone marrow biopsy pathology revealed abundant neutrophils consistent with myelokathexis. This pathologic finding is a hallmark of another type of SCN, WHIM syndrome, which is caused by gain-of-function mutations in CXCR4, a chemokine receptor and known neutrophil bone marrow retention factor. We found markedly increased CXCR4 expression on neutrophils from both our G6PC3-deficient patients and G6pc3?/? mice. In both patients, granulocyte colony-stimulating factor treatment normalized CXCR4 expression and neutrophil counts. In G6pc3?/? mice, the specific CXCR4 antagonist AMD3100 rapidly reversed neutropenia. Thus, myelokathexis associated with abnormally high neutrophil CXCR4 expression may contribute to neutropenia in G6PC3 deficiency and responds well to granulocyte colony-stimulating factor.

De Ravin, Suk See; Jun, Hyun Sik; Liu, Qian; Priel, Debra A. Long; Noel, Pierre; Takemoto, Clifford M.; Ojode, Teresa; Paul, Scott M.; Dunsmore, Kimberly P.; Hilligoss, Dianne; Marquesen, Martha; Ulrick, Jean; Kuhns, Douglas B.; Chou, Janice Y.; Malech, Harry L.; Murphy, Philip M.

2010-01-01

252

Methods for detection of immune-mediated neutropenia in horses, using antineutrophil serum of rabbit origin.  

PubMed

Equine neutrophil antibody was raised in rabbits inoculated with equine neutrophils isolated to purity greater than 99.0%, using Percoll density-gradient sedimentation. Neutrophil antibody was detected by use of agar gel diffusion, leukoagglutination, indirect immunofluorescence, staphylococcal protein A and streptococcal protein G binding, and phagocytic inhibition techniques. Precipitin lines and leukoagglutination were seen in antiserum dilutions of 1:4 and 1:64, respectively. The specific nature of leukoagglutination was characterized by the formation of rosette-like clumps of neutrophils. Specific bright membranous fluorescence was seen in neutrophils treated with the antiserum and exposed to fluorescein-conjugated goat anti-rabbit immunoglobulin, and staphylococcal protein A and streptococcal protein G. Whereas the indirect immunofluorescence and protein G-binding tests were equally sensitive and resulted in titer of 1:256, the protein A-binding test was less sensitive and resulted in titer of only 1:32. Nonspecific binding of protein A and protein G was noticed as uniform or patchy cellular fluorescence in a small number of neutrophils. Treatment of neutrophils with antiserum up to dilution of 1:8 resulted in a significant (P less than 0.05) suppression of phagocytosis of opsonized zymosan particles. Thus, protein G-binding and indirect immunofluorescence tests are highly sensitive to detect neutrophil antibody and may be used to diagnose immune-mediated neutropenias in horses and, possibly, in other animal species. PMID:2117866

Jain, N C; Vegad, J L; Kono, C S

1990-07-01

253

Poikiloderma with neutropenia: a novel C16orf57 mutation and clinical diagnostic criteria.  

PubMed

A new syndrome with poikiloderma was described by Clericuzio et al. in 1991.(1) They reported 14 Navajo native Americans, including eight siblings, developing in the first year of life an erythematous rash, which started on the limbs and spread over the trunk and the face. This rash evolved into poikiloderma. All patients had recurrent bacterial infections. First published as Navajo poikiloderma this syndrome is now known as poikiloderma with neutropenia (PN, OMIM 604173). The inheritance is autosomal recessive, and mutations in a new gene, C16orf57, were recently described in two kindreds.(2) Because of the phenotypic overlap between Rothmund-Thomson syndrome (RTS) and PN, a few patients have been reclassified as mutations in the RECQL4 gene for RTS were absent.(2-5) Until now 27 patients have been described with clinical PN.(1-3,5-8) Here, we report the sixth family with PN outside the Navajo population. We found the previously unreported mutation c.243G>A, p.W81X in the C16orf57 gene, thus confirming the relation of this gene to the disease.(2,6) Because the molecular genetic diagnosis is not always available, we propose clinical and laboratory diagnostic criteria for PN. PMID:20618321

Arnold, A W; Itin, P H; Pigors, M; Kohlhase, J; Bruckner-Tuderman, L; Has, C

2010-10-01

254

Open randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients.  

PubMed Central

An open-label randomized trial comparing the efficacy and safety of cefepime versus piperacillin plus gentamicin (P+G) given intravenously for the treatment of febrile episodes in neutropenic patients with underlying malignancy was conducted at two oncology centers. Over a 30-month period 111 patients were enrolled and 99 patients were found to be suitable for evaluation. At the 72-h time of evaluation, cefepime monotherapy and P+G combination therapy produced comparable clinical response rates (78% for both). P+G and cefepime produced comparable response rates in microbiologically documented (78 versus 71%), clinically documented (100 versus 100%), and possible (75 versus 79%) infections. The P+G and cefepime treatments achieved comparable microbiological eradication of gram-negative (100 versus 71%) (P = 0.09) and gram-positive (44 versus 70%) (P = 0.37) organisms. There were no statistically significant differences in the rates of superinfection between the groups; however, more superinfections of fungal origin were noted in the P+G group. Cefepime was demonstrated to be an effective and safe treatment for febrile episodes in neutropenic patients with malignancies, and its lack of nephrotoxicity compared to P+G was noteworthy. Cefepime appears to be a candidate for monotherapy in febrile neutropenic cancer patients.

Yamamura, D; Gucalp, R; Carlisle, P; Cimino, M; Roberts, J; Rotstein, C

1997-01-01

255

Emergency Department Crowding and Time to Antibiotic Administration in Febrile Infants  

PubMed Central

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.

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

256

Emergency cranial computed tomography in the management of acute febrile encephalopathy in children.  

PubMed Central

OBJECTIVE: Evaluation of the influence of emergency cranial computed tomography on the management of acute febrile encephalopathy in children. METHODS: A retrospective study in children with acute febrile encephalopathy who underwent emergency cranial computed tomography within 12 hours of admission to the paediatric intensive care unit. All scans were evaluated by two independent radiologists. RESULTS: Thirty nine children were included. Fourteen scans were abnormal and two had clinically insignificant incidental findings. Four children with focal neurological signs had scans demonstrating extra-axial collections. None required neurosurgical intervention. Clinically, raised intracranial pressure was present in 10 patients. Only five had cerebral oedema on computed tomography; these five children died. Emergency cranial computed tomography influenced subsequent management in no child without focal neurological signs and in only one child with focal neurology. CONCLUSION: Emergency cranial computed tomography in acute febrile encephalopathy in children without focal neurological signs has little influence on subsequent management. Where cranial computed tomography is thought to be necessary, it should be carried out when the child's clinical condition has been stabilised.

Nadel, S; Joarder, R; Gibson, M; Stevens, J; Britto, J; Habibi, P; Owens, C

1999-01-01

257

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

PubMed

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

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

2008-04-01

258

Outbreak of febrile respiratory illness associated with human adenovirus type 14p1 in Gansu Province, China  

PubMed Central

ObjectivesHuman adenovirus (HAdV) type 14 had been infrequently associated with outbreaks of febrile respiratory illness (FRI) until the HAdV-14p1 emerged in 2006 and rapidly spread in the United States. Here, we report an outbreak of FRI caused by HadV-14p1 that occurred in 2011 at a primary and middle school in China. DesignThe basic information of the outbreak was recored; throat swabs were collected from 17 patients, polymerase chain reaction, A549 cell culture, and sequencing were used to identify the pathogen of the outbreak.. ResultsTotal of 43 students were infected in this outbreak. Boys were more than girls. We identified 11 HAdV-positive specimens and 6 HAdV isolates. Genetic analysis showed that the complete hexon, fiber, and E1A sequences of isolates were nearly 100% identical with other HAdV-14p1 sequences deposited in GenBank. ConclusionsHadV-14p1 has caused outbreaks of pneumonia and mortality among adults in the United States and Europe. It may cause similar conditions among Chinese adults due to poor hygiene and sanitation. It seems prudent for China to develop a national surveillance system to determine the etiology of severe respiratory diseases and deaths among adults and school-aged children.

Huang, Guohong; Yu, Deshan; Zhu, Zhen; Zhao, Hai; Wang, Peng; Gray, Gregory C; Meng, Lei; Xu, Wenbo

2013-01-01

259

Genomic analysis of HAdV-B14 isolate from the outbreak of febrile respiratory infection in China.  

PubMed

Human adenovirus type 14 (HAdV-B14) was first reported in 1955 from the Netherlands and since then had been associated with outbreaks of febrile respiratory illness (FRI). In China, sporadic HAdV-B14 infections were first identified in 2010, in Guangzhou and Beijing. In 2012, an outbreak of FRI occurred in Beijing and the etiological agent was determined to be HAdV-B14. We present a complete HAdV-B14 genome sequence isolated from this recent FRI outbreak. Virus in 30 throat swab samples was detected using polymerase chain reaction assays, and confirmed by sequencing of the fiber, hexon and penton genes. Comparative genomics and phylogenetic analysis showed that the newly isolated HAdV-B14 (HAdV-B14 CHN) shared highest sequence homology with a 2006 isolate from the United States and clustered closely with other HAdV-B14 strains. It is expected that data from the present study will help in devising better protocols for virus surveillance, and in developing preventative measures. PMID:24055951

Mi, Zhiqiang; Butt, Azeem Mehmood; An, Xiaoping; Jiang, Tao; Liu, Wei; Qin, Chengfeng; Cao, Wu-Chun; Tong, Yigang

2013-01-01

260

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

PubMed Central

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

2014-01-01

261

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

PubMed

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

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

2003-04-01

262

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

PubMed Central

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

Mroczek, Seweryn; Krwawicz, Joanna; Kutner, Jan; Lazniewski, Michal; Kucinski, Iwo; Ginalski, Krzysztof; Dziembowski, Andrzej

2012-01-01

263

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

PubMed Central

Background In August 2002, the antifungal prophylaxis algorithm for neutropenic hematology/oncology (NHO) patients at the Medical Center was changed from conventional amphotericin (AMB) to an azole (AZ) based regimen (fluconazole [FLU] in low-risk and voriconazole [VOR] in high-risk patients). The aim of our study was to compare outcomes associated with the two regimens, including breakthrough fungal infection, adverse drug events, and costs. Methods Adult, non-febrile, NHO patients who received prophylactic AMB from 8/01/01-7/30/02 or AZ from 8/01/02-7/30/03 were retrospectively evaluated. Results A total of 370 patients (AMB: n = 181; AZ: n = 216) associated with 580 hospitalizations (AMB: n = 259; AZ: n = 321) were included. The incidence of probable/definite breakthrough Aspergillus infections was similar among regimens (AMB: 1.9% vs AZ: 0.6%; p=0.19). A greater incidence of mild/moderate (24.7% vs. 5.3%; p < 0.0001) and severe renal dysfunction (13.5% vs. 4.4%; p < 0.0012) was observed with AMB. In contrast, patients treated with VOR were found to have an increased rate of severe hepatic toxicity (32.5%) compared with patients treated with either AMB (22.6%) or FLU (21.4%) (p = 0.05). While the AZ period was associated with a >$9,000 increase in mean total costs/hospitalization, the mean acquisition cost associated with AZ was only $947/hospitalization more than AMB. Conclusion While an AZ-based regimen is associated with increased cost, the reduced rate of nephrotoxicity and availability of oral dosage forms, suggests that azoles be used preferentially over AMB. However, an increased rate of severe hepatic toxicity may be associated with VOR.

Riedel, Amy; Choe, Lan; Inciardi, John; Yuen, Courtney; Martin, Thomas; Guglielmo, B Joseph

2007-01-01

264

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

PubMed Central

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: 1.05–1.11 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.

Miller, Jessica E.; Pedersen, Lars Henning; Vestergaard, Mogens; Olsen, J?rn

2013-01-01

265

Leptospirosis and Human Immunodeficiency Virus Co-Infection Among Febrile Inpatients in Northern Tanzania  

PubMed Central

Abstract Background Leptospirosis and human immunodeficiency virus (HIV) infection are prevalent in many areas, including northern Tanzania, yet little is known about their interaction. Methods We enrolled febrile inpatients at two hospitals in Moshi, Tanzania, over 1 year and performed HIV antibody testing and the microscopic agglutination test (MAT) for leptospirosis. Confirmed leptospirosis was defined as ?four-fold rise in MAT titer between acute and convalescent serum samples, and probable leptospirosis was defined as any reciprocal MAT titer ?800. Results Confirmed or probable leptospirosis was found in 70 (8.4%) of 831 participants with at least one serum sample tested. At total of 823 (99.0%) of 831 participants had HIV testing performed, and 203 (24.7%) were HIV infected. Among HIV-infected participants, 9 (4.4%) of 203 had confirmed or probable leptospirosis, whereas among HIV-uninfected participants 61 (9.8%) of 620 had leptospirosis. Leptospirosis was less prevalent among HIV-infected as compared to HIV-uninfected participants [odds ratio (OR) 0.43, p=0.019]. Among those with leptospirosis, HIV-infected patients more commonly presented with features of severe sepsis syndrome than HIV-uninfected patients, but differences were not statistically significant. Among HIV-infected patients, severe immunosuppression was not significantly different between those with and without leptospirosis (p=0.476). Among HIV-infected adolescents and adults, median CD4 percent and median CD4 count were higher among those with leptospirosis as compared to those with other etiologies of febrile illness, but differences in CD4 count did not reach statistical significance (p=0.015 and p=0.089, respectively). Conclusions Among febrile inpatients in northern Tanzania, leptospirosis was not more prevalent among HIV-infected patients. Although some indicators of leptospirosis severity were more common among HIV-infected patients, a statistically significant difference was not demonstrated. Among HIV-infected patients, those with leptospirosis were not more immunosuppressed relative to those with other etiologies of febrile illness.

Biggs, Holly M.; Galloway, Renee L.; Bui, Duy M.; Morrissey, Annie B.; Maro, Venance P.

2013-01-01

266

Baseline Platelet Count and Creatinine Clearance Rate Predict the Outcome of Neutropenia-Related Invasive Aspergillosis  

PubMed Central

Background.?Invasive aspergillosis (IA) is a life-threatening infection for immunocompromised patients. Improvement in IA outcome has been hampered by lack of early prognostic factors, namely, those available before starting chemotherapy (baseline) or early in the course of IA (nonbaseline). We hypothesized that prognostic factors can be identified before chemotherapy, ?7 days from the first positive serum Aspergillus galactomannan index (s-GMI). Methods.?We analyzed 98 patients with multiple myeloma who developed neutropenia-related IA and had a positive s-GMI. Three response criteria were used: kinetics of s-GMI, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions, and 6-week survival. Baseline and nonbaseline variables were analyzed separately. Results.?Independent response predictors at baseline were a platelet count ?65,000 platelets/mm3 (odds ratio [OR], 1.009; 95% confidence interval [CI], 1.001–1.017; P = .03) by s-GMI kinetics, and a platelet count ?65,000 platelets/mm3 (OR, 1.009; 95% CI, 1.002–1.017; P = .01) and a creatinine clearance rate ?53 mL/min (OR, 1.024; 95% CI, 1.006–1.042; P = .009) by EORTC/MSG criteria, with response rates of 83% and 28% when both variables were above or below these cutoffs, respectively (P < .001). Only baseline creatinine clearance rate ?53 mL/min predicted 6-week survival (P = .003). Normalization of the s-GMI ?7 days after the first positive s-GMI and neutrophil recovery were the nonbaseline factors associated with positive outcomes. Conclusions.?Two simple, inexpensive to measure, widely available, and routinely collected prechemotherapy values, platelet count and creatinine clearance rate, predict IA outcome and stratify patients into low-, intermediate-, and high-risk categories, while early evaluation of s-GMI allows timely treatment modification. These findings may improve patient outcomes by optimizing management strategies for this serious infection and may prove valuable in designing clinical trials of interventions to improve IA outcomes.

Nouer, Simone Aranha; Nucci, Marcio; Kumar, Naveen Sanath; Grazziutti, Monica; Restrepo, Alejandro; Anaissie, Elias

2012-01-01

267

Segregation of a haplotype encompassing FEB1 with genetic epilepsy with febrile seizures plus in a Colombian family.  

PubMed

Febrile seizures and epilepsy are believed to be linked and some forms of epilepsy are associated with a history of febrile seizures (FS). Linkage analysis to seven known loci for FS and/or genetic epilepsy with febrile seizures plus (GEFS plus) was performed in a small Colombian family. Short tandem repeat (STR) markers were genotyped and two-point linkage analysis and haplotype reconstruction were conducted. A maximum LOD score of 0.75 at marker D8S533 for FEB1 at a recombination fraction (?) of 0 and a segregating haplotype were identified. FEB1 was the first locus to be associated with FS and this is the second report to describe this association. Two genes in this region, CRH and DEPDC2, are good putative candidate genes that may play a role in FS and/or GEFS plus. PMID:23773973

Caro-Gomez, Maria-Antonieta; Carrizosa, Jaime; Moreno, Johanna Tejada; Cabrera, Dagoberto; Bedoya, Gabriel; Ruiz-Linares, Andres; Franco, Andres; Gomez-Castillo, Christhian; Cornejo, William; Pineda-Trujillo, Nicolas

2013-06-01

268

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

PubMed Central

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.

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

2013-01-01

269

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

PubMed Central

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

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

2014-01-01

270

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

Microsoft Academic Search

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

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

2011-01-01

271

Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials  

Microsoft Academic Search

Summary Background Although fever is part of the normal inflammatory process after immunisation, prophylactic antipyretic drugs are sometimes recommended to allay concerns of high fever and febrile convulsion. We assessed the effect of prophylactic administration of paracetamol at vaccination on infant febrile reaction rates and vaccine responses. Methods In two consecutive (primary and booster) randomised, controlled, open-label vaccination studies, 459

Roman Prymula; Claire-Anne Siegrist; Roman Chlibek; Helena Zemlickova; Marie Vackova; Jan Smetana; Patricia Lommel; Eva Kaliskova; Dorota Borys; Lode Schuerman

2009-01-01

272

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

PubMed

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

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

273

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

SciTech Connect

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.

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

1989-03-01

274

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

PubMed Central

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

Kaya, Zuhre; Kucukcongar, Aynur; Vurall?, Dogus; Emeksiz, Hamdi Cihan; Gursel, Turkiz

2014-01-01

275

Leukocyte count and erythrocyte sedimentation rate as diagnostic factors in febrile convulsion.  

PubMed

Febrile convulsion (FC) is the most common seizure disorder in childhood. white blood cell (WBC) and erythrocyte sedimentation rate (ESR) are commonly measured in FC. Trauma, vomiting and bleeding can also lead to WBC and ESR so the blood tests must carefully be interpreted by the clinician. In this cross sectional study 410 children(163 with FC), aged 6 months to 5 years, admitted to Bahrami Children hospital in the first 48 hours of their febrile disease, either with or without seizure, were evaluated over an 18 months period. Age, sex, temperature; history of vomiting, bleeding or trauma; WBC, ESR and hemoglobin were recorded in all children. There was a significant increase of WBC (P<0.001) in children with FC so we can deduct that leukocytosis encountered in children with FC can be due to convulsion in itself. There was no significant difference regarding ESR (P=0.113) between the two groups. In fact, elevated ESR is a result of underlying pathology. In stable patients who don't have any indication of lumbar puncture, there's no need to assess WBC and ESR as an indicator of underlying infection. If the patient is transferred to pediatric ward and still there's no reason to suspect a bacterial infection, there is no need for WBC test. PMID:21960077

Rahbarimanesh, Ali Akbar; Salamati, Peyman; Ashrafi, Mohammadreza; Sadeghi, Manelie; Tavakoli, Javad

2011-01-01

276

Persistence of febrile response to pyrogens after PO/AH lesions in squirrel monkeys.  

PubMed

Observation of a patient who developed fever in spite of severe CNS sarcoidosis led us to test the idea that febrile responses require mediation by neurons in the preoptic/anterior hypothalamic (PO/AH) region. Changes in rectal and skin temperatures and oxygen consumption were recorded after intravenous and intracerebroventricular injections of endotoxin, after intracerebroventricular prostaglandin E1 (PGE1), and after intravenous injections of leukocyte pyrogens in animals in which the PO/AH region had been destroyed. The capacity to develop fever persisted after PO/AH destruction, and the patterns of heat production and heat loss were unchanged. Pyrogens were still effective after intracerebroventricular 6-hydroxydopamine and intraperitoneal reserpine given to reduce brain amines in monkeys with PO/AH lesions. It is unlikely that a secondary control in the medulla oblongata is responsible for the persisting sensitivity to pyrogens, since multiple injections of endotoxin into this region did not cause fever either before or after the PO/AH region was destroyed. The results do not support the idea that control of fever is localized in the PO/AH region alone. Rather, it appears that in the brains of primates there is either multiple central representation of fever control or an inherent capacity to develop sensitivity to pyrogens and to produce coordinated febrile responses. PMID:827212

Lipton, J M; Trzcinka, G P

1976-12-01

277

Reversible splenic lesion in a patient with Febrile Infection-Related Epilepsy Syndrome (FIRES).  

PubMed

Febrile infection-related epilepsy syndrome (FIRES) is a severe epileptic syndrome that manifests with refractory seizures or status epilepticus in previously healthy children after banal febrile illness. The neuroimaging findings in the acute phase of FIRES are nonspecific or normal. We report the case of a 7-year-old boy with FIRES who presented with a reversible lesion in the splenium of the corpus callosum on brain magnetic resonance imaging (MRI). The patient developed clusters of clonic seizures with a deviation of the eyes after a 3-day history of fever. A reversible splenial lesion was observed on brain MRI and, therefore, the initial diagnosis was mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). However, the intractable complex partial seizures necessitated a long-term midazolam infusion, indicating that FIRES was a more likely diagnosis than MERS. All other findings of this patient met the diagnostic criteria for FIRES. With this diagnosis, a high-dose phenobarbital was administrated, and the seizures were successfully controlled. This case indicated that FIRES should be considered even in patients with a reversible splenial lesion associated with encephalitis/encephalopathy. PMID:23794447

Nozaki, Fumihito; Kumada, Tomohiro; Miyajima, Tomoko; Kusunoki, Takashi; Hiejima, Ikuko; Hayashi, Anri; Fujii, Tatsuya

2013-10-01

278

Febrile seizures  

MedlinePLUS

... does not have a history of seizure disorders ( epilepsy ). In infants and young children, it is important ... no evidence that they cause death, brain damage, epilepsy, a decrease in IQ, or learning problems. Most ...

279

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

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.

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

280

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

PubMed

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)/?-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/?-catenin pathway may offer a novel therapy for SCN with ELANE mutation. PMID:23382209

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

281

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

PubMed Central

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)/?-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/?-catenin pathway may offer a novel therapy for SCN with ELANE mutation.

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

2013-01-01

282

Evaluation of single-drug and combination antifungal therapy in an experimental model of candidiasis in rabbits with prolonged neutropenia.  

PubMed

We developed an experimental model of candidiasis in rabbits with prolonged neutropenia. Rabbits were made neutropenic with cytosine arabinoside (Ara-C) administered through an indwelling silastic catheter that had been surgically implanted in the external jugular vein. Neutropenia was sustained with intravenous Ara-C, and bacterial complications were prevented with parenteral ceftazidime plus ampicillin. Candidiasis was established by intravenously administering Candida albicans or Candida tropicalis (1-2 x 10(5) colony-forming units) and resulted in hepatic and splenic lesions that mimicked those associated with hepatosplenic candidiasis in humans. The kidney proved to be the site most refractory to eradication of Candida spp. and offered a target organ for assessing antifungal therapy. We evaluated amphotericin B, 5-flucytosine, ketoconazole, and rifampin, alone and in combination. Although each agent reduced the colony counts of Candida in the liver, spleen, and lung, the combination of amphotericin B and 5-flucytosine was the only regimen effective in eradicating renal candidiasis. PMID:3392423

Thaler, M; Bacher, J; O'Leary, T; Pizzo, P A

1988-07-01

283

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

PubMed Central

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

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

2014-01-01

284

Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963).  

PubMed

Circadian clocks control cellular proliferation and drug metabolism over the 24?h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N?=?556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p?Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p?=?.36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR?=?0.56; p = .015), and worse survival on chronoFLO4 (HR?=?1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy. PMID:21859417

Innominato, Pasquale F; Giacchetti, Sylvie; Moreau, Thierry; Smaaland, Rune; Focan, Christian; Bjarnason, Georg A; Garufi, Carlo; Iacobelli, Stefano; Tampellini, Marco; Tumolo, Salvatore; Carvalho, Carlos; Karaboué, Abdoulaye; Lévi, Francis

2011-08-01

285

Incidence of Neutropenia and Infections During Combination Treatment of Chronic Hepatitis C with Pegylated Interferon Alfa-2a or Alfa-2b Plus Ribavirin  

Microsoft Academic Search

Background:  Combination therapy with pegylated interferon (peginterferon) plus ribavirin is associated with several side effects, including\\u000a neutropenia and infection.\\u000a \\u000a \\u000a \\u000a Aims:  To evaluate the incidence of neutropenia and infection between all consecutive patients with hepatitis C who were treated\\u000a in two centers with peginterferon-alfa-2a and peginterferon-alfa-2b, in combination with ribavirin and actively monitored\\u000a for occurrence of any infection. \\u000a \\u000a \\u000a \\u000a Methods:  A total of 319 consecutive

M. G. Antonini; S. Babudieri; I. Maida; C. Baiguera; B. Zanini; L. Fenu; G. Dettori; D. Manno; M. S. Mura; G. Carosi; M. Puoti

2008-01-01

286

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

PubMed Central

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.

MORIYA, HIROYUKI; SAITO, KATSUHIKO; HELSBY, NUALA; SUGINO, SHIGEKAZU; YAMAKAGE, MICHIAKI; SAWAGUCHI, TAKERU; TAKASAKI, MASAHIKO; KATO, HIDENORI; KUROSAWA, NAHOKO

2014-01-01

287

Myasis occuring in a neonate  

PubMed Central

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.

Obasa, Temitope O.; Sowunmi, Funmilola Olusola

2012-01-01

288

Severe febrile illness in adult hospital admissions in Tanzania: a prospective study in an area of high malaria transmission.  

PubMed

Severe febrile illness is a major cause of adult hospital admission in Africa. Studies of non-malarial fever come largely from children or from high HIV prevalence settings. This prospective study of adult admissions with severe febrile illness in a malaria-endemic area with moderate/low HIV prevalence investigated admission diagnosis as well as final diagnosis based on results of investigations. Severe malaria was the admission diagnosis in 148/198 (74.7%) cases. Plasmodium falciparum was identified in 38/188 (20.2%) admissions and 26/198 (13.1%) were bacteraemic, with 13/25 (52%) prescribed empirical antibiotics. HIV was equally common among those with (16/37; 43.2%) and without P. falciparum (50/138; 36.2%) (p=0.44). In 6/22 (27.3%) deaths, blood cultures were positive for a pathogen, with Streptococcus pneumoniae, Escherichia coli and non-Typhi Salmonella predominating. Chest radiography was suspicious for bacterial/mycobacterial disease in 5/22 additional deaths. Systemic inflammatory response syndrome criteria were more sensitive but less specific than WHO severe malaria criteria for predicting mortality. Malaria is overdiagnosed in adults with severe febrile illness and was not associated with mortality in the absence of co-infection in this high-incidence setting. Adults with severe febrile illness should be tested for malaria and HIV using rapid, sensitive tests. Early antibiotic use should be promoted. Improved diagnostics for invasive bacterial disease are needed. PMID:23022040

Nadjm, Behzad; Mtove, George; Amos, Ben; Walker, Naomi F; Diefendal, Helmut; Reyburn, Hugh; Whitty, Christopher J M

2012-11-01

289

Serum procalcitonin measurement as diagnostic and prognostic marker in febrile adult patients presenting to the emergency department  

Microsoft Academic Search

INTRODUCTION: Identification of bacterial infections is crucial if treatment is to be initiated early and antibiotics used rationally. The primary objective of this study was to test the efficiency of procalcitonin (PCT) in identifying bacterial\\/parasitic episodes among febrile adult patients presenting to an emergency department. Secondary objectives were to identify clinical or biological variables associated with either bacterial\\/parasitic infection or

Pierre Hausfater; Gaëlle Juillien; Beatrice Madonna-Py; Julien Haroche; Maguy Bernard; Bruno Riou

2007-01-01

290

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

Microsoft Academic Search

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

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

2010-01-01

291

Degree of hippocampal atrophy is not related to a history of febrile seizures in patients with proved hippocampal sclerosis  

Microsoft Academic Search

OBJECTIVESTo examine the degree of hippocampal atrophy in patients with temporal lobe epilepsy and proved hippocampal sclerosis to determine whether or not patients with febrile seizures have more severe hippocampal atrophy. To determine whether or not there is a relation between age of seizure onset, duration of temporal lobe epilepsy, or seizure frequency, and severity of hippocampal atrophy.METHODSHippocampal volumes were

Simon P C Bower; Christine J Kilpatrick; Simon J Vogrin; Kevin Morris; Mark J Cook

2000-01-01

292

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

PubMed Central

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.

2012-01-01

293

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

PubMed Central

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.

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

294

Measurements of procalcitonin facilitate targeting of endotoxin adsorption treatment in febrile neutropenic patients suffering from shock.  

PubMed

Immediate initiation of hemoperfusion treatment with polymixin B immobilized fiber (PMX-DHP) is a potent strategy to improve hemodynamics in septic patients with critical circulatory failure. However, it is often difficult to accurately and rapidly differentiate between bacterial infections and non-infectious causes of shock in acutely critically-ill patients. Procalcitonin (PCT) measurements may assist in the early identification of bacterial infection/sepsis and determination of severity in such patients. We present two febrile neutropenic (FN) patients who developed severe shock after chemotherapy for hematological malignancies. PCT levels were markedly elevated in both patients (? 10 ng/ml), suggesting a high likelihood of bacterial infectious etiology as the cause of their shock, and thus they were promptly treated with PMX-DHP. Measurements of PCT may facilitate targeting of PMX-DHP treatment among FN patients suffering from shock, which may lead to better prognosis. PMID:22909782

Hara, Masaki; Tsuchiya, Ken; Nitta, Kosaku; Ando, Minoru

2014-01-01

295

Facial emotion recognition in childhood: the effects of febrile seizures in the developing brain.  

PubMed

It has been documented that anteromedial temporal lobe dysfunction can cause impairment in emotional intelligence. In particular, medial temporal lobe epilepsy (MTLE) is associated with disorders in emotion recognition from facial expressions. About one-third of patients with MTLE experienced febrile seizures (FSs) during childhood. In the present study, we investigated facial emotion recognition ability in a group of 38 school-aged children with antecedent FSs and in an age- and sex-matched control group. Children with abnormal general visuoperceptual abilities were excluded. Children with FSs showed lower recognition scores versus controls in both matching (28.64 vs 33.47; p<.0001) and labeling (21.25 vs 23.03; p=.001) facial emotions. Our findings support the hypothesis that FSs can be associated during childhood with a dysfunction within the neural network subserving the processing of facial expressions of the basic emotions. PMID:23994831

Cantalupo, Gaetano; Meletti, Stefano; Miduri, Alessia; Mazzotta, Silvia; Rios-Pohl, Loreto; Benuzzi, Francesca; Pisani, Francesco; Tassinari, Carlo Alberto; Cossu, Giuseppe

2013-10-01

296

Pronounced increase in breathing rate in the "hair dryer model" of experimental febrile seizures.  

PubMed

In a study using a heated chamber for induction of experimental febrile seizures (eFS) in rat pups, ictal activity was shown to be precipitated by a respiratory alkalosis (Schuchmann et al., 2006). In sharp contrast to this, in a recent review Dubé et al., (2007) suggest that the respiratory alkalosis is model specific, and that no increase in respiratory rate is observed in the widely used "hair dryer model" of eFS. The data in the present work, based on well-established techniques for measuring respiratory rates in rat pups, show a pronounced increase in the "hair dryer model" with values that are slightly higher than those recorded in the heated chamber model. Hence, a temperature-evoked increase in respiration is a common feature of these two models of eFS. PMID:18325016

Schuchmann, Sebastian; Tolner, Else A; Marshall, Pepin; Vanhatalo, Sampsa; Kaila, Kai

2008-05-01

297

Septic, CD-30 positive febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta.  

PubMed

We report life-threatening febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta in an 8-year-old girl. Hemorrhagic-crusted papules and plaques covered over 90% of the patient's body, leaving her susceptible to Pseudomonas aeruginosa and Staphylococcus epidermidis bacteremia as well as Candida parapsilosis fungemia. Sepsis delayed definitive treatment of the underlying cutaneous disease for 2 weeks. Combined therapy with methotrexate and cyclosporin caused remission of the process. Although immunohistochemistry revealed CD-30 positive cells, suggesting the diagnosis of lymphomatoid papulosis, the histopathology was most compatible with pityriasis lichenoides et varioliformis acuta. A partial loss of CD2 and CD5 in the predominant CD3 T-cell lymphocytes suggested a clonal proliferation. Elevated soluble interleukin-2 receptor levels reflected marked T-cell activation, and the downward trend of the levels during treatment coincided with clinical regression of this inflammatory dermatosis. PMID:16060878

Herron, Mark D; Bohnsack, John F; Vanderhooft, Sheryll L

2005-01-01

298

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

Microsoft Academic Search

BACKGROUND: For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM) to induce neutropenia. Although high doses (350–450 mg\\/kg) are still used and their effects on mouse leukocytes have been described, a lower dose

Andres F Zuluaga; Beatriz E Salazar; Carlos A Rodriguez; Ana X Zapata; Maria Agudelo; Omar Vesga

2006-01-01

299

Medium adsorbance fraction of reticulocyte and myeloperoxidase index may individuate a patient subset with a low risk of chemotherapy-related neutropenia.  

PubMed

In neoplastic patients chemotherapy frequently involves severe myeloid suppression. Sometimes myeloid suppression is the main cause of therapy recycling delay with severe and prolonged neutropenia, anaemia and thrombocytopenia. Our study aimed to verify whether there is a correlation between reticulocyte fractions, reticulocyte indices, myeloperoxidase index (MPXI) and post-chemotherapy myelopoietic function and severe post-chemotherapy neutropenia. A cohort of 112 patients was identified, 30 with lymphoma or myeloma and 82 with solid neoplasms with bone marrow micrometastases. The patients were treated with chemotherapy (CT). After CT, 60 patients had neutropenia (ANC <500/mcl) for a median of 7 days (range 3-21). Before CT, myelopoietic function was assessed by the above-mentioned parameters using a hematologic automated analyzer. We assigned patients with an MPXI-positive value and medium adsorbance fraction of reticulocyte (MFR) >10.7% a score of 1, and a score of 0 was assigned to the remaining patients. Patients with a score of 1 showed a lower number of neutropenic events (only 9 out of 36 patients) than those with a score of 0 (51 out of 76 patients), p<0.0001. MPXI and MFR may be used in the assessment of myelopoiesis before CT administration, independently of the type of tumor, CT regimen and number of CT cycle, with the aim of identifying a patient subset with a lower risk of developing neutropenia post-CT. PMID:19082461

Giordano, Giulio; Ferrucci, Pier Francesco; Nicci, Chiara; Grafone, Tiziana; Tambaro, Rosa; Papini, Stefano; Farina, Giuliana; Piano, Silvia; Zappacosta, Bruno; Storti, Sergio

2009-01-01

300

Detection of Bacteraemia in Patients with Fever and Neutropenia Using 16S rRNA Gene Amplification by Polymerase Chain Reaction  

Microsoft Academic Search

Episodes of fever and neutropenia are common complications of treatment for cancer. The use of prophylactic and early empirical antibiotics has reduced mortality but decreases the sensitivity of diagnostic tests based on culture. The aim of this study was to determine the potential of a broad diagnostic approach (eubacterial) based on 16S rRNA gene amplification and sequencing to augment cultural

B. E. Ley; C. J. Linton; D. M. C. Bennett; H. Jalal; A. B. M. Foot; M. R. Millar

1998-01-01

301

Detection of bacteraemia in patients with fever and neutropenia using 16S rRNA gene amplification by polymerase chain reaction  

Microsoft Academic Search

Episodes of fever and neutropenia are common complications of treatment for cancer. The use of prophylactic and early empirical antibiotics has reduced mortality but decreases the sensitivity of diagnostic tests based on culture. The aim of this study was to determine the potential of a broad diagnostic approach (eubacterial) based on 16S rRNA gene amplification and sequencing to augment cultural

B. E. Ley; C. J. Linton; D. M. C. Bennett; H. Jalal; A. B. M. Foot; M. R. Millar

1998-01-01

302

Antibiotic use among patients with febrile illness in a low malaria endemicity setting in Uganda  

PubMed Central

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

2011-01-01

303

Role of rapid diagnostic tests for guiding outpatient treatment of febrile illness in Liaquat University Hospital  

PubMed Central

Objectives: To assess the validity /strength of clinical diagnosis of Malaria on the basis of IMNCI algorithm by slide microscopy (gold standard) and to compare the effectiveness of Rapid Diagnostic Test (RDT )against slide microscopy. Methods : It is a descriptive cross sectional study of 6 month duration conducted at Pediatric Outpatient Department LUH Hyderabad from June-Dec. 2010. Sample of 400{the minimum required sample was 385 with malaria prevalence 5% (0.05) with margin of error of 3% (0.03, frequency vary from 2—8 % among different studies)} febrile children under 5 years classified as Suspected Clinical Malaria according to algorithm of IMNCI were included; The operational definition for Suspected Clinical Malaria was; fever for more than 2 days with no runny nose, no measel rash and no other cause of fever. Hyderabad was considered as low risk area. Rapid diagnostic test (RDT) and slide microscopy were done, and only confirmed cases were treated according to current guidelines given by National Malaria Program/updated IMNCI. Results: Total 2000 patients under 5 years presented with fever and were evaluated. From 2000 cases 20% (400) were diagnosed as suspected clinical Malaria according to IMNCI algorithm; and only 40 cases (10%) have shown positive results for malaria parasite on slide microscopy and 38 cases on RDT. Regarding the plasmodium species 70% were vivax and 30% were falciparum. As regards the effectiveness, RDT has shown 95% sensitivity for the detection of plasmodium antigens in the febrile clinically suspected cases of malaria. Conclusion: Prompt and accurate diagnosis of malaria is needed for implementation of appropriate treatment to reduce unnecessary anti-malarial prescription. RDT is as effective as slide microscopy for the diagnosis of malaria especially in resource poor countries.

Shaikh, Salma; Memon, Shazia; Memon, Hafeezullah; Ahmed, Imran

2013-01-01

304

Febrile-range hyperthermia accelerates caspase-dependent apoptosis in human neutrophils1  

PubMed Central

Human neutrophilic polymorphonuclear leukocytes (PMNs) are central to innate immunity and are responsible for clearance of pathogens. PMNs undergo a tightly regulated apoptosis program that allows for timely clearance of PMNs without extravasation of toxic intracellular contents. We investigated the rate of spontaneous apoptosis of human peripheral blood PMNs cultured at basal (37°C) and febrile-range (39.5°C) temperatures (FRT). We found that PMN apoptosis is accelerated at FRT, reaching ~90% completion by 8 h at 39.5°C vs. 18 h at 37°C based on morphologic criteria. Caspase-8 activation peaked within 15 minutes of PMN exposure to FRT and subsequent activation of caspase-3 and -9, cleavage of the BH3 only protein Bid, and mitochondrial release of cytochrome c were also greater in FRT-exposed PMNs. Inhibition of caspase-3, -8, and -9 conferred comparable protection from apoptosis in FRT-exposed PMNs. These results demonstrate that exposure to FRT enhances caspase-8 activation and subsequent mitochondrial-dependent and mitochondrial–independent apoptosis pathways. The PMN survival factors G-CSF, GM-CSF, and IL-8, each prolonged PMN survival at 37°C and 39.5°C, but did reduce the difference in survival at the two temperatures. In a mouse model of intratracheal endotoxin-induced alveolitis, co-exposure to FRT (core temperature ~39.5°C) doubled the proportion of bronchoalveolar PMNs undergoing apoptosis compared with euthermic mice. This process may play an important role in limiting inflammation and tissue injury during febrile illnesses.

Nagarsekar, Ashish; Greenberg, Rachel S.; Shah, Nirav G.; Singh, Ishwar S.; Hasday, Jeffrey D.

2010-01-01

305

Human Herpesvirus 6 and 7 in Febrile Status Epilepticus: The FEBSTAT study  

PubMed Central

SUMMARY Purpose In a prospective study of the consequences of prolonged febrile seizures (FEBSTAT), we determined the frequency of Human Herpesvirus (HHV)-6 and HHV-7 infection as a cause of febrile status epilepticus (FSE). Methods Children ages 1 month to 5 years presenting with FSE were enrolled within 72 hours and received a comprehensive assessment including specimens for HHV-6 and HHV-7. The presence of HHV-6A, HHV-6B or HHV-7 DNA and RNA (amplified across a spliced junction) determined using quantitative polymerase chain reaction (qPCR) at baseline indicated viremia. Antibody titers to HHV-6 and HHV-7 were used in conjunction with the PCR results to distinguish primary infection from reactivated or prior infection Key findings Of 199 children evaluated, HHV-6 or HHV-7 status could be determined in 169 (84.9%). HHV-6B viremia at baseline was found in 54 subjects (32.0%), including 38 with primary infection and 16 with reactivated infection. No HHV-6A infections were identified. HHV-7 viremia at baseline was observed in 12 (7.1%) subjects, including 8 with primary infection and 4 with reactivated infection. Two subjects had HHV-6/HHV-7 primary co-infection at baseline. There were no differences in age, characteristics of illness or fever, seizure phenomenology or the proportion of acute EEG or imaging abnormalities in children presenting with FSE with or without HHV infection. Significance HHV-6B infection is commonly associated with FSE. HHV-7 infection is less frequently associated with FSE. Together, they account for one third of FSE, a condition associated with an increased risk of both hippocampal injury and subsequent temporal lobe epilepsy.

Epstein, Leon G.; Shinnar, Shlomo; Hesdorffer, Dale C.; Nordli, Douglas R.; Hamidullah, Aaliyah; Benn, Emma K.T.; Pellock, John M.; Frank, L. Matthew; Lewis, Darrell V; Moshe, Solomon L.; Shinnar, Ruth C.; Sun, Shumei

2012-01-01

306

Does Lupus Occur in Men?  

MedlinePLUS

... Home > Get Answers > Topic: Understanding lupus Understanding lupus Does lupus occur in men? As a man with ... Related topics men living well Related questions How does smoking affect people with lupus? Are flu and ...

307

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

PubMed

This report describes an international prevalidation study conducted to optimise the Standard Operating Procedure (SOP) for detecting myelosuppressive agents by CFU-GM assay and to study a model for predicting (by means of this in vitro hematopoietic assay) the acute xenobiotic exposure levels that cause maximum tolerated decreases in absolute neutrophil counts (ANC). In the first phase of the study (Protocol Refinement), two SOPs were assessed, by using two cell culture media (Test A, containing GM-CSF; and Test B, containing G-CSF, GM-CSF, IL-3, IL-6 and SCF), and the two tests were applied to cells from both human (bone marrow and umbilical cord blood) and mouse (bone marrow) CFU-GM. In the second phase (Protocol Transfer), the SOPs were transferred to four laboratories to verify the linearity of the assay response and its interlaboratory reproducibility. After a further phase (Protocol Performance), dedicated to a training set of six anticancer drugs (adriamycin, flavopindol, morpholino-doxorubicin, pyrazoloacridine, taxol and topotecan), a model for predicting neutropenia was verified. Results showed that the assay is linear under SOP conditions, and that the in vitro endpoints used by the clinical prediction model of neutropenia are highly reproducible within and between laboratories. Valid tests represented 95% of all tests attempted. The 90% inhibitory concentration values (IC(90)) from Test A and Test B accurately predicted the human maximum tolerated dose (MTD) for five of six and for four of six myelosuppressive anticancer drugs, respectively, that were selected as prototype xenobiotics. As expected, both tests failed to accurately predict the human MTD of a drug that is a likely protoxicant. It is concluded that Test A offers significant cost advantages compared to Test B, without any loss of performance or predictive accuracy. On the basis of these results, we proposed a formal Phase II validation study using the Test A SOP for 16-18 additional xenobiotics that represent the spectrum of haematotoxic potential. PMID:11698175

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

2001-12-01

308

Predictive ability of a semi-mechanistic model for neutropenia in the development of novel anti-cancer agents: two case studies.  

PubMed

In cancer chemotherapy neutropenia is a common dose-limiting toxicity. An ability to predict the neutropenic effects of cytotoxic agents based on proposed trial designs and models conditioned on previous studies would be valuable. The aim of this study was to evaluate the ability of a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for myelosuppression to predict the neutropenia observed in Phase I clinical studies, based on parameter estimates obtained from prior trials. Pharmacokinetic and neutropenia data from 5 clinical trials for diflomotecan and from 4 clinical trials for indisulam were used. Data were analyzed and simulations were performed using the population approach with NONMEM VI. Parameter sets were estimated under the following scenarios: (a) data from each trial independently, (b) pooled data from all clinical trials and (c) pooled data from trials performed before the tested trial. Model performance in each of the scenarios was evaluated by means of predictive (visual and numerical) checks. The semi-mechanistic PK/PD model for neutropenia showed adequate predictive ability for both anti-cancer agents. For diflomotecan, similar predictions were obtained for the three scenarios. For indisulam predictions were better when based on data from the specific study, however when the model parameters were conditioned on data from trials performed prior to a specific study, similar predictions of the drug related-neutropenia profiles and descriptors were obtained as when all data were used. This work provides further indication that modeling and simulation tools can be applied in the early stages of drug development to optimize future trials. PMID:20449627

Soto, Elena; Keizer, Ron J; Trocóniz, Iñaki F; Huitema, Alwin D R; Beijnen, Jos H; Schellens, Jan H M; Wanders, Jantien; Cendrós, Josep María; Obach, Rosendo; Peraire, Concepción; Friberg, Lena E; Karlsson, Mats O

2011-10-01

309

The impact of cefepime as first line therapy for neutropenic fever on Clostridium difficile rates among hematology and oncology patients.  

PubMed

After changing empiric treatment of febrile neutropenia from meropenem to cefepime, the effect on Clostridium difficile infection (CDI) was investigated. The change was assessed using an autoregressive model. A significant increase in CDI rates occurred following the introduction of cefepime. There may be an association between increased cefepime usage and CDI. PMID:24140078

Muldoon, Eavan G; Epstein, Lauren; Logvinenko, Tanya; Murray, Susan; Doron, Shira I; Snydman, David R

2013-12-01

310

Repetition Blindness Occurs in Nonwords  

ERIC Educational Resources Information Center

Theorists have predicted that repetition blindness (RB) should be absent for nonwords because they do not activate preexisting mental types. The authors hypothesized that RB would be observed for nonwords because RB can occur at a sublexical level. Four experiments showed that RB is observed for word-nonword pairs (noon noof), orthographically…

Harris, Catherine L.; Morris, Alison L.

2004-01-01

311

Can Photosynthesis Occur At Saturn?  

NSDL National Science Digital Library

This is an activity about photosynthesis. Learners will use the basic principle of photosynthesis and investigate how light intensity diminishes as a function of distance from the light source. Questions help them connect these two ideas to determine if photosynthesis could occur at Saturn.

312

Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011.  

PubMed

In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24 h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010-2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0-1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. Sequential statistical methods were employed to account for repeated analyses of accumulating data. Signals for seizures based on computerized data were identified in mid November 2010 using a current vs. historical design and in late December 2010 using a self-controlled risk interval design. Further signal evaluation was conducted with chart-confirmed febrile seizure cases using only data from the primary approach (i.e. self-controlled risk interval design). The magnitude of the incidence rate ratio and risk difference comparing risk of seizures in the 0-1 days vs. 14-20 days following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate vaccine (PCV13). Among children 6-59 months of age, the incidence rate ratio (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest estimates occurring at 59 months (1.1 per 100,000 doses for TIV without concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and 4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and risk difference estimates were lower for children receiving TIV without concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of preventing influenza and pneumococcal infections and associated complications, our findings should be placed in a benefit-risk framework to ensure that population health benefits are maximized. PMID:22361304

Tse, Alison; Tseng, Hung Fu; Greene, Sharon K; Vellozzi, Claudia; Lee, Grace M

2012-03-01

313

Diversity of Naturally Occurring Prokaryotes  

Microsoft Academic Search

Understanding the patterns of naturally occurring microbial diversity, how these patterns vary in space and time, and how\\u000a they relate to ecosystem structure and function, remains a significant challenge for microbiologists. A variety of levels\\u000a of microbial diversity are important and relevant from the perspective of microbial ecology, including trophic, physiological\\u000a or functional diversity, intraspecific genetic diversity, or phylogenetic diversity

E. F. Long

314

Naturally occurring anhydrovitamin A2  

PubMed Central

1. `Naturally occurring anhydrovitamin A2' obtained from the liver oil of freshwater fish Bagarius bagarius yielded, after six-stage chromatography, a pure product showing characteristic bands at 350, 368 (E1%1cm. 1006) and 390m? in ethanol, and producing a green colour with antimony trichloride (E1%1cm. 1884 at 693m?). 2. On distribution of the material between light petroleum and 95% methanol, 70% of it is found in methanol, which points to its hydroxylic character. 3. It gives an acetyl derivative, from which the original hydroxy compound can be regenerated on hydrolysis. 4. The infrared spectrum shows, besides other bands, one at 3460cm.?1 attributable to a hydroxy group. 5. On passing a light-petroleum solution of naturally occurring anhydrovitamin A2 through manganese dioxide a 6% conversion into retinene2 is observed. 6. A 3-hydroxyanhydroretinol structure is proposed for naturally occurring anhydrovitamin A2 and a mechanism of its transformation into retinene2 on this basis is suggested.

Barua, R. K.; Nayar, P. G.

1966-01-01

315

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

Microsoft Academic Search

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

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

2008-01-01

316

A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation.  

PubMed

Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl(-) extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures. PMID:24668262

Puskarjov, Martin; Seja, Patricia; Heron, Sarah E; Williams, Tristiana C; Ahmad, Faraz; Iona, Xenia; Oliver, Karen L; Grinton, Bronwyn E; Vutskits, Laszlo; Scheffer, Ingrid E; Petrou, Steven; Blaesse, Peter; Dibbens, Leanne M; Berkovic, Samuel F; Kaila, Kai

2014-06-01

317

High prevalence of stress hyperglycaemia in children with febrile seizures and traumatic injuries.  

PubMed

Although hyperglycaemia is relatively frequent in the course of severe illnesses and may be looked upon as the possible result of an uncoordinated insulin response to the increased glucose that the body may need during periods of stress, it is generally agreed that it does not constitute a prediabetic condition. Numerous studies have aimed to explain the pathophysiology of this occurrence but none has looked at which conditions are more prone to develop stress hyperglycaemia (SH). Therefore, the aim of this study was to evaluate the main clinical conditions that may be associated with SH in children. A total of 1199 children was studied: 833 children (439 M, 394 F, mean age 5.2 +/- 4.5 y) admitted for an acute illness or injury constituted the stress-exposed group, while 366 children (222 M, 144 F, mean age 6.2 +/- 4.6 y) admitted for elective minor surgery represented the stress-unexposed group and were considered as the control group. SH was defined as plasma glucose concentrations > or = 8.3 mmol l(-1) during an acute illness. Stress-exposed patients had significantly higher glycaemic levels than controls (5.6 +/- 1.4 vs 4.7 +/- 0.7 mmol l(-1); p < 0.0001). SH was found in 41 (4.9%) stress-exposed patients and in none of the controls. SH was significantly more prevalent in children affected by febrile seizures (12.9%) or traumatic injuries (11.7%; p < 0.008 and p < 0.02, respectively, vs other diagnoses). A significant correlation was found between glycaemia and systolic pressure (r = 0.1; p < 0.01), white cell count (r = 0.12; p < 0.0003) and body temperature (r = 0.16; p < 0.0001). SH was more frequent in patients with body temperature > 39 degrees C (14%) than in those with a temperature < or = 39 degrees C (4%; p < 0.0008). SH was more prevalent in clinical conditions of fever associated with seizures or pain (12.9% and 12.5%, respectively) than fever alone (4.4%). After a mean period of 3.5 +/- 0.6 y of follow-up none of the hyperglycaemic patients had developed diabetes mellitus. Conclusion: Traumatic injuries, febrile seizures or conditions in which an elevated body temperature may be found are frequently associated with SH in children. In the presence of these conditions specific studies directed towards unmasking a prediabetic state may be unnecessary. PMID:11440092

Valerio, G; Franzese, A; Carlin, E; Pecile, P; Perini, R; Tenore, A

2001-06-01

318

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

Microsoft Academic Search

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

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

1999-01-01

319

Effects of nitric oxide synthase inhibitors on the febrile response to muramyl dipeptide and lipopolysaccharide in rats  

Microsoft Academic Search

We have administered aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase, and N-nitro-L-arginine methyl ester (L-NAME), an unspecific nitric oxide synthase inhibitor, to rats made febrile with the gram-positive pyrogen, muramyl dipeptide and gram-negative pyrogen, lipopolysaccharide. Sprague-Dawley rats, housed individually at ~25 °C with a 12:12 h light:dark cycle (lights on 0700 hours), were injected (at 0900 hours)

P. R. Kamerman; D. Mitchell; H. Laburn

2002-01-01

320

Prevalence and risk factors for quinolone resistance among Escherichia coli strains isolated from males with community febrile urinary tract infection  

Microsoft Academic Search

The purpose of this study was to evaluate the prevalence and clinical risk factors for quinolone resistance (QR) in E. coli strains from males with febrile urinary tract infection (FUTI). An ambispective cross-sectional study was performed in which\\u000a we evaluated 153 males with a community FUTI caused by E. coli. Among the 153 FUTI episodes, 101 (66%) were due to

A. Smithson; C. Chico; J. Ramos; C. Netto; M. Sanchez; J. Ruiz; R. Porron; M. T. Bastida

321

Antibodies to Orientia tsutsugamushi, Rickettsia typhi and spotted fever group rickettsiae among febrile patients in rural areas of Malaysia  

Microsoft Academic Search

A serosurvey was conducted in 1995–1997 among 1596 febrile patients from 8 health centres in Malaysia for antibodies against Orientia tsutsugamushi (OT), Rickettsia typhi (RT) and TT118 spotted fever group rickettsiae (SFGR) by using an indirect immunoperoxidase assay. A total of 51·4% patients had antibody against at least 1 of those rickettsiae. Antibody to SFGR was most prevalent (42.5%), followed

S. T. Tay; T. M. Ho; M. Y. Rohani; S. Devi

2000-01-01

322

Naturally Occurring Carboxypeptidase A6 Mutations  

PubMed Central

Carboxypeptidase A6 (CPA6) is a member of the A/B subfamily of M14 metallocarboxypeptidases that is expressed in brain and many other tissues during development. Recently, two mutations in human CPA6 were associated with febrile seizures and/or temporal lobe epilepsy. In this study we screened for additional CPA6 mutations in patients with febrile seizures and focal epilepsy, which encompasses the temporal lobe epilepsy subtype. Mutations found from this analysis as well as CPA6 mutations reported in databases of single nucleotide polymorphisms were further screened by analysis of the modeled proCPA6 protein structure and the functional role of the mutated amino acid. The point mutations predicted to affect activity and/or protein folding were tested by expression of the mutant in HEK293 cells and analysis of the resulting CPA6 protein. Common polymorphisms in CPA6 were also included in this analysis. Several mutations resulted in reduced enzyme activity or CPA6 protein levels in the extracellular matrix. The mutants with reduced extracellular CPA6 protein levels showed normal levels of 50-kDa proCPA6 in the cell, and this could be converted into 37-kDa CPA6 by trypsin, suggesting that protein folding was not greatly affected by the mutations. Interestingly, three of the mutations that reduced extracellular CPA6 protein levels were found in patients with epilepsy. Taken together, these results provide further evidence for the involvement of CPA6 mutations in human epilepsy and reveal additional rare mutations that inactivate CPA6 and could, therefore, also be associated with epileptic phenotypes.

Sapio, Matthew R.; Salzmann, Annick; Vessaz, Monique; Crespel, Arielle; Lyons, Peter J.; Malafosse, Alain; Fricker, Lloyd D.

2012-01-01

323

A Study on the Serum Adenosine Deaminase Activity in Patients with Typhoid Fever and Other Febrile Illnesses  

PubMed Central

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.

Ketavarapu, Sameera; Ramani G., Uma; Modi, Prabhavathi

2013-01-01

324

A novel SCN1A mutation in a cytoplasmic loop in intractable juvenile myoclonic epilepsy without febrile seizures.  

PubMed

Generalised (genetic) epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with various phenotypes. The majority of individuals with GEFS+ have generalised seizure types, in addition to febrile seizures (FS) or febrile seizures plus (FS+), defined as either continued FS after 6 years of age or afebrile seizures following FS. A 27-year-old man with no history of FS/FS+ experienced intractable generalised convulsive seizures. The patient's father had a history of similar seizures during puberty and the patient's siblings had only FS. No individual in the family had both generalised seizures and FS/FS+, although GEFS+ might be considered to be present in the family. Analysis of SCN1A, a sodium channel gene, revealed a novel mutation (c.3250A>T [S1084C]) in the cytoplasmic loop 2 of SCN1A in both the patient and his father. Most previously reported SCN1A mutations in GEFS+ patients are located in the conserved homologous domains of SCN1A, whereas mutations in the cytoplasmic loops are very rare. SCN1A gene analysis is not commonly performed in subjects with generalised seizures without FS. SCN1A mutation may be a clinically-useful genetic marker in order to distinguish GEFS+ patients from those with classic idiopathic generalised epilepsy, even if they present an atypical clinical picture. PMID:24842605

Jingami, Naoto; Matsumoto, Riki; Ito, Hirotaka; Ishii, Atsushi; Ihara, Yukiko; Hirose, Shinichi; Ikeda, Akio; Takahashi, Ryosuke

2014-06-01

325

The effect of educational program on knowledge, attitude and practice of mothers regarding prevention of febrile seizure in children  

PubMed Central

Background: Febrile convulsion is one of the most common problems in children aged 5 months to 6 years. The aim of this study was to explore the effectiveness of an educational program on mothers for prevention of febrile seizure in children. Materials and Methods: In this clinical trial study, 88 mothers were chosen who were divided into intervention and control groups, randomly. Data of the control and intervention groups were collected in two stages, before intervention and 1 month after intervention, by a validated and reliable questionnaire. The intervention consisted of three educational sessions, each one lasting for 60 min. Data were analyzed using chi-square, t-test and paired t-test. Findings: Age average of subjects in the intervention group and in the control group was 26.75 and 26.84 years, respectively. The results showed a significant increase in the knowledge (P < 0.001), attitude (P = 0.04) and practice (P = 0.01) in the intervention group 1 month after intervention compared with that before intervention, while such an increase was not seen in the control group. Conclusion: This study confirmed the efficiency of educational interventions in improving mother's knowledge, attitude and practice regarding prevention of febrile seizure in children.

Najimi, Arash; Dolatabadi, Nayereh Kasiri; Esmaeili, Ahmad Ali; Sharifirad, Gholam Reza

2013-01-01

326

Evaluation of Cytopenias Occurring in Imatinib Treated Chronic Myeloid Leukemia (CML) Patients  

PubMed Central

Imatinib Mesylate, a Tyrosine Kinase inhibitor, is presently the drug of choice for Chronic myeloid leukemia (CML). During therapy, a few patients develop myelosuppression and present with cytopenias. To study the bone marrow morphology in imatinib treated CML patients presenting with persistent cytopenias. The cases were retrieved from the Hematopathology record files, Department of Pathology; the study period being January 2008–June 2009. Cases of CML on Imatinib presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenias with bone marrow studies, were included in the study. The morphology of all cases was reviewed with cytogenetic studies. Follow-up details were obtained from the Medical Oncology records. During the study period, 683 Imatinib treated CML patients had bone marrow studies as part of their follow-up investigations. Of these, 60 patients (9%) had some form of persistent cytopenia. The patients ranged from 21 to 75 years of age with a median age of 38 years. The male:female ratio was 1:1. There were 46 patients with ?grade 2 anemia, 25 patients with ?grade 2 neutropenia and 37 patients with ?grade 2 thrombocytopenia. Of these, 18 patients had bicytopenia and 13 cases had pancytopenia. The marrow evaluation revealed morphologic response in 30 patients, persistent marrow disease in five patients, marrow hypoplasia in six patients, extensive stromal changes including fibrosis in five patients, megaloblastic erythropoiesis in 11 patients and disease progression to accelerated or blast crisis in three patients. Various degrees of cytopenias may occur in few patients of CML on imatinib therapy. Regular hematologic follow-up is required so that the drug may be stopped or dose modified as per the individual’s needs.

Uppin, Shantveer G.; Uppin, Megha S.; Jacob, Rachel T.; Rao, D. Raghunadha; Rajappa, Senthil J.

2010-01-01

327

Evaluation of Cytopenias Occurring in Imatinib Treated Chronic Myeloid Leukemia (CML) Patients.  

PubMed

Imatinib Mesylate, a Tyrosine Kinase inhibitor, is presently the drug of choice for Chronic myeloid leukemia (CML). During therapy, a few patients develop myelosuppression and present with cytopenias. To study the bone marrow morphology in imatinib treated CML patients presenting with persistent cytopenias. The cases were retrieved from the Hematopathology record files, Department of Pathology; the study period being January 2008-June 2009. Cases of CML on Imatinib presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenias with bone marrow studies, were included in the study. The morphology of all cases was reviewed with cytogenetic studies. Follow-up details were obtained from the Medical Oncology records. During the study period, 683 Imatinib treated CML patients had bone marrow studies as part of their follow-up investigations. Of these, 60 patients (9%) had some form of persistent cytopenia. The patients ranged from 21 to 75 years of age with a median age of 38 years. The male:female ratio was 1:1. There were 46 patients with ?grade 2 anemia, 25 patients with ?grade 2 neutropenia and 37 patients with ?grade 2 thrombocytopenia. Of these, 18 patients had bicytopenia and 13 cases had pancytopenia. The marrow evaluation revealed morphologic response in 30 patients, persistent marrow disease in five patients, marrow hypoplasia in six patients, extensive stromal changes including fibrosis in five patients, megaloblastic erythropoiesis in 11 patients and disease progression to accelerated or blast crisis in three patients. Various degrees of cytopenias may occur in few patients of CML on imatinib therapy. Regular hematologic follow-up is required so that the drug may be stopped or dose modified as per the individual's needs. PMID:21629637

Paul, T Roshni; Uppin, Shantveer G; Uppin, Megha S; Jacob, Rachel T; Rao, D Raghunadha; Rajappa, Senthil J

2010-06-01

328

Increased CPA6 promoter methylation in focal epilepsy and in febrile seizures.  

PubMed

Focal epilepsy (FE) is one of the most common forms of adult epilepsy and is usually regarded as a multifactorial disorder. Febrile seizures (FS) often appear during childhood in a subtype of FE patients, i.e. with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). FS are the most common human convulsive event associated with fever. Genetic evidences for FS have suggested a complex mode of inheritance. Until now, to investigate genes at the genomic level, linkage analysis of familial forms and association studies have been performed, but nothing conclusive has been clearly related to FE and FS. As complex disorders, environmental factors might play a crucial role through epigenetic modification of key candidate genes such as CPA6, which encodes Carboxypeptidase A6, an extracellular protein. Therefore, we assessed DNA methylation in promoter of CPA6. In 186 FE patients and 92 FS patients compared to 93 healthy controls and 42 treated controls with antiepileptic drugs (AEDs), we found significant higher levels of methylation for epileptic patients. Methylation status were 3.4% (±3.2%) for FE cases and 4.3% (±3.5%) for FS cases, whereas healthy individuals and treated controls with AEDs showed a level of 0.8% (±2.9%) and 1.5% (±3.9%), respectively (p?0.001 for all comparisons). These results let growing evidence for DNA methylation involvment in FE and FS. PMID:24290490

Belhedi, N; Perroud, N; Karege, F; Vessaz, M; Malafosse, A; Salzmann, A

2014-01-01

329

Infection and immunity for human parvovirus B19 in patients with febrile exanthema.  

PubMed

The contribution of parvovirus B19 (B19V) as a causative agent of febrile exanthema (FE) in Cordoba, Argentina, was analysed by detection of viral DNA, and specific IgM and IgG. Serum from 141 patients with FE who were negative for measles and rubella, collected during 2005-2009, plus serum from 31 healthy individuals, were assayed. B19V was the aetiological agent in 14·9% of all FE cases, and in 39·1% in an epidemic year (2007). B19V DNA was detected in 47·6% of IgM-positive FE patients, 30·2% of IgM-negative/IgG-positive FE patients, and 9·7% of healthy controls, indicating B19V long-term infection in ~10% of immunocompetent individuals. Persistent B19V DNA was significantly more frequent in children than adults and in males than females. All patients with acute B19V infection had rash and fever, 85·7% had adenopathy, and only 14·3% had arthropathy. This is the first follow-up study of markers of infection and immunity for B19V infection in Argentina. PMID:21676356

Pedranti, M S; Barbero, P; Wolff, C; Ghietto, L M; Zapata, M; Adamo, M P

2012-03-01

330

Familial History and Recurrence of Febrile Seizures; a Systematic Review and Meta-Analysis  

PubMed Central

Objective Febrile seizure (FS) as the most common form of seizures in childhood, affects 2-5% of all children across the world. The present study reviews available reports on FS recurrence frequency and evaluates its associated risk factors in Iran. Methods We searched the Persian database such as: SID, MagIran, Medlip, Irandoc, Iranmedex as well as English databases PubMed, ISI, and Scopus. Random effects models were used to calculate 95% confidence intervals. Meta regression was introduced to explore the heterogeneity between studies. Findings The overall FS recurrence rate was 20.9% [95% confidence interval (CI): 12.3-29.5%]. The frequency of FS simple and complex types was 69.3% (95% CI: 59.5-79.0) and 25.3% (95% CI: 19.6-31.0), respectively. A positive familial history of 28.8% (95% CI: 19.3-38.4%) was observed for childhood FS including 36.2% (95% CI: 27.3-39.6%) for the simple and 29.4% (95% CI: 23.1-33.5%) for the complex type. The heterogeneity of recurrent FS was significantly affected by sample size (P=0.026). Conclusion Almost one-third of FS children had a positive familial history. The increased risk of recurrence in patients with symptomatic seizures needs to be fully considered by parents, physicians, nurses and health policy makers.

Veisani, Yousef; Delpisheh, Ali; Sayehmiri, Kourosh

2013-01-01

331

Longitudinal assessment of skill development in children with first febrile seizure.  

PubMed

To determine whether first febrile seizure (FS) has detrimental effects on development, 159 children (aged 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 the idea that first FS does not pose developmental or behavioral consequences in a low socioeconomic environment. PMID:23669493

Leaffer, Emily B; Hinton, Veronica J; Hesdorffer, Dale C

2013-07-01

332

Unsuspected Leptospirosis Is a Cause of Acute Febrile Illness in Nicaragua  

PubMed Central

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.

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

333

Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing  

PubMed Central

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.

Balmaseda, Angel; Harris, Eva; DeRisi, Joseph L.

2012-01-01

334

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

PubMed

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

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

2010-08-01

335

Seroprevalence of Antibodies against Chikungunya, Dengue, and Rift Valley Fever Viruses after Febrile Illness Outbreak, Madagascar  

PubMed Central

In October 2009, two–3 months after an outbreak of a febrile disease with joint pain on the eastern coast of Madagascar, we assessed serologic markers for chikungunya virus (CHIKV), dengue virus (DENV), and Rift Valley fever virus (RVFV) in 1,244 pregnant women at 6 locations. In 2 eastern coast towns, IgG seroprevalence against CHIKV was 45% and 23%; IgM seroprevalence was 28% and 5%. IgG seroprevalence against DENV was 17% and 11%. No anti-DENV IgM was detected. At 4 locations, 450–1,300 m high, IgG seroprevalence against CHIKV was 0%–3%, suggesting CHIKV had not spread to higher inland-altitudes. Four women had IgG against RVFV, probably antibodies from a 2008 epidemic. Most (78%) women from coastal locations with CHIKV-specific IgG reported joint pain and stiffness; 21% reported no symptoms. CHIKV infection was significantly associated with high bodyweight. The outbreak was an isolated CHIKV epidemic without relevant DENV co-transmission.

Girmann, Mirko; Randriamampionona, Njary; Bialonski, Alexandra; Maus, Deborah; Krefis, Anne Caroline; Njarasoa, Christine; Rajanalison, Jeanne Fleury; Ramandrisoa, Herly Daniel; Randriarison, Maurice Lucien; May, Jurgen; Schmidt-Chanasit, Jonas; Rakotozandrindrainy, Raphael

2012-01-01

336

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

PubMed

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

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

2014-07-01

337

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

SciTech Connect

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.

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

1987-05-01

338

Human Procaspase-1 Variants with Decreased Enzymatic Activity Are Associated with Febrile Episodes and May Contribute to Inflammation via RIP2 and NF-?B Signaling.  

PubMed

The proinflammatory enzyme caspase-1 plays an important role in the innate immune system and is involved in a variety of inflammatory conditions. Rare naturally occurring human variants of the caspase-1 gene (CASP1) lead to different protein expression and structure and to decreased or absent enzymatic activity. Paradoxically, a significant number of patients with such variants suffer from febrile episodes despite decreased IL-1? production and secretion. In this study, we investigate how variant (pro)caspase-1 can possibly contribute to inflammation. In a transfection model, such variant procaspase-1 binds receptor interacting protein kinase 2 (RIP2) via Caspase activation and recruitment domain (CARD)/CARD interaction and thereby activates NF-?B, whereas wild-type procaspase-1 reduces intracellular RIP2 levels by enzymatic cleavage and release into the supernatant. We approach the protein interactions by coimmunoprecipitation and confocal microscopy and show that NF-?B activation is inhibited by anti-RIP2-short hairpin RNA and by the expression of a RIP2 CARD-only protein. In conclusion, variant procaspase-1 binds RIP2 and thereby activates NF-?B. This pathway could possibly contribute to proinflammatory signaling. PMID:24706726

Heymann, Michael C; Winkler, Stefan; Luksch, Hella; Flecks, Silvana; Franke, Marcus; Ruß, Susanne; Ozen, Seza; Yilmaz, Engin; Klein, Christoph; Kallinich, Tilmann; Lindemann, Dirk; Brenner, Sebastian; Ganser, Gerd; Roesler, Joachim; Rösen-Wolff, Angela; Hofmann, Sigrun R

2014-05-01

339

Kinetics and correlation with body temperature of circulating interleukin-6, interleukin-8, tumor necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia  

Microsoft Academic Search

Summary Interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF) are important mediators of fever and inflammation, and are involved in the pathogenesis of sepsis. There is only limited data on serum concentrations of these proinflammatory cytokines in patients with fever and neutropenia, and their interrelationship and correlation with body temperature and clinical disease early in

A. Engel; W. V. Kern; G. Mürdter; P. Kern

1994-01-01

340

Late-onset epilepsy in children with acute febrile encephalopathy with prolonged convulsions: A clinical and encephalographic study.  

PubMed

The aim of this study is to analyze the characteristics of epilepsies as the sequelae of acute febrile encephalopathy with prolonged convulsions during childhood. Sixteen patients (M:F=9:7) aged 2-13years (mean 6.1years) with history of febrile acute encephalopathy were retrospectively reviewed. These patients experienced febrile encephalopathy at the age of 11months to 4years, with 11 individuals presenting with findings of a biphasic clinical course (n=5), frontal predominant (n=8) lesions, and/or reduced diffusivity in the cerebral white matter on magnetic resonance imaging (MRI; n=3). The remaining 5 patients had unilateral lesions that manifested the phenotype of hemiconvulsion-hemiplegia-epilepsy syndrome (HHES). Epilepsy emerged with a latent period of 2months to 2years after the acute phase of febrile encephalopathy. Head nodding or spasm with subsequent motion arrest and brief tonic seizures were the main seizure phenotypes. Ictal records of epileptic seizures were available in 9 patients. Epileptiform discharges with a focal or uneven distribution appeared at the seizure onset and lasted less than 1s in all patients; these were followed by either generalized attenuation or fast activity in 8 patients with head nodding, spasm, or brief tonic seizures, and by localized fast activity in 1 patient with versive tonic seizures. Notably, the seizure onset area was often located outside the severe lesions on MRI, i.e., in the parietal areas in patients with frontal predominant lesions, and in the spared hemisphere of HHES. Although phenobarbital, zonisamide, carbamazepine, clobazam, clonazepam, and clorazepate were partially effective in some patients, daily seizures persisted in 11 patients. Callosotomy was performed in 2 patients, and beneficial effects were observed in both. These characteristics suggested a broad distribution of augmented excitability in these patients, resulting in the rapid propagation of epileptic activity in the initial phase of ictal phenomena. Thus, this study investigates the most severe subgroup of epilepsy following febrile acute encephalopathy and provides the basis for further exploration of the pathogenesis and treatment of characteristic seizures in this population. PMID:22982002

Saito, Takashi; Saito, Yoshiaki; Sugai, Kenji; Nakagawa, Eiji; Komaki, Hirofumi; Okazaki, Tetsuya; Ishido, Yusaku; Kaneko, Yuu; Kaido, Takanobu; Takahashi, Akio; Ohtsuki, Taisuke; Sakuma, Hiroshi; Sasaki, Masayuki

2013-06-01

341

Naturally occurring methyl salicylate glycosides.  

PubMed

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

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

2014-01-01

342

Late-onset neutropenia (LON) after low-dose rituximab treatment in living related kidney transplantation--single-center study.  

PubMed

We have performed more than 200 ABO-incompatible and HLA-incompatible transplantations, by using low-dose rituximab (Rit) as one of the B cell-depleting strategies. It has been revealed that a significant number of such patients who receive rituximab treatment develop late-onset neutropenia (LON). To obtain insights into the mechanism underlying the development of LON, we evaluated the kinetics of various cytokines involved in B-cell and granulocyte homeostases. The subjects of this study could be categorized into five groups, as follows; group 1: Rit(+)LON(+), N=22; group 2: Rit(+)LON(-), N=30; group 3: Rit(-)LON(+), N=15; group 4: Rit(-)LON(-), N=53; and group5: CKD5 patients (N=10). Serum levels of the cytokines were examined pre-RTx, 6months after RTx, 12months after RTx and 1.5years after RTx. We investigated the association between the serum levels of the B cell-related cytokines and the incidence of acute rejection. Serum levels of BAFF were significantly elevated in groups 1, 2 and 3; in particular, group 1 patients showed marked elevation of the serum BAFF at 6 and 12months after RTx. No correlations were observed between the serum BAFF and the incidence of acute rejection. Transplant recipients treated with low-dose Rit and presenting with LON showed a marked elevation of the serum BAFF levels. PMID:23353568

Ishida, Hideki; Inui, Masashi; Furusawa, Miyuki; Tanabe, Kazunari

2013-03-01

343

Performance of Serum Biomarkers for the Early Detection of Invasive Aspergillosis in Febrile, Neutropenic Patients: A Multi-State Model  

PubMed Central

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)- ?-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 ?-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 ?-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.

Schwarzinger, Michael; Sagaon-Teyssier, Luis; Cabaret, Odile; Bretagne, Stephane; Cordonnier, Catherine; Pautas, Cecile; Maury, Sebastien; Hicheri, Yosr; Botterel, Francoise; Foulet, Francoise; Vekhoff, Anne; Chaoui, Driss; Cornet, Muriel; Agnamey, Patrice; Farhat, Hassan; Castaigne, Sylvie; Eloy, Odile; Suarez, Felipe; Buzyn, Agnes; Delarue, Richard; Challier, Svetlana; Dhedin, Nathalie; Aljijakli, Ahmad; Delabesse, Emmanuelle; Datry, Annick; Isnard, Francoise; Fouillard, Loic; Poirot, Jean-Yves; Meliani, Leila; Ades, Lionel; Bouges-Michel, Claire; Deniau, Michele; Kuhnowski, Frederique; Dreyfus, Francois; Paugam, Andre; Baixench, Marie-Therese; Leclercq, Roland; Reman, Oumady; Duhamel, Chantal; Bourrhis, Jean-Henri; Chehata, Sami; Chachati, Isabelle; Foissaud, Vincent; Macnab, Christine; Tilly, Herve; Lepretre, Stephane; Gray, Christian; Raffoux, Emmanuel; Lacroix, Claire; Goldhaber-Fiebert, Jeremy D; Bendavid, Eran; Farley, Brandon J

2013-01-01

344

Detecting change as it occurs  

NASA Technical Reports Server (NTRS)

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.

Radok, Uwe; Brown, Timothy J.

1992-01-01

345

Cost-effectiveness of leucoreduction for prevention of febrile non-haemolytic transfusion reactions  

PubMed Central

Background The cost-effectiveness of universal leucoreduction of blood components remains unclear. When using leucoreduced red blood cells, the decrease in the rate of febrile non-haemolytic transfusion reactions (FNHTR) is the only proven, meaningful clinical benefit, whose relationship to costs can be calculated relatively easily. The aim of this study was to evaluate the cost-effectiveness of leucoreduction in avoiding FNHTR. Materials and methods Data were obtained from two large tertiary hospitals in Athens, Greece, over a 4-year period (2009–2012). The incidence of FNHTR in patients transfused with leucoreduced or non-leucodepleted red blood cells, the additional cost of leucoreduction and the cost to treat the FNHTR were estimated. The incremental cost-effectiveness ratio (ICER), which is the ratio of the change in costs to the incremental benefits of leucoreduction, was calculated. Results In total, 86,032 red blood cell units were transfused. Of these, 53,409 were leucodepleted and 32,623 were non-leucoreduced. Among patients transfused with leucodepleted units, 25 cases (0.047%) met the criteria for having a FNHTR, while in patients treated with non-leucoreduced components, 134 FNHTR were observed (0.411%). The ICER of leucoreduction was € 6,916 (i.e., the cost to prevent one case of FNHTR). Conclusions Leucoreduction does not have a favourable cost-effectiveness ratio in relation to the occurrence of FNHTR. However, many factors, which could not be easily and accurately assessed, influence the long-term costs of transfusion. It is imperative to undertake a series of large, meticulously designed clinical studies across the entire spectrum of blood transfusion settings, to investigate most of the parameters involved.

Tsantes, Argirios E.; Kyriakou, Elias; Nikolopoulos, Georgios K.; Stylos, Dimitrios; Sidhom, Marlene; Bonovas, Stefanos; Douramani, Panagiota; Kalantzis, Dimitrios; Kokoris, Styliani; Valsami, Serena; Stamoulis, Konstantinos; Politou, Marianna; Foudoulaki-Paparizos, Leontini

2014-01-01

346

ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus  

PubMed Central

Objective: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures, leaving neurologic sequelae in many patients. However, its pathogenesis remains unclear. In this study, we clarified that genetic variation in the adenosine A2A receptor (ADORA2A), whose activation is involved in excitotoxicity, may be a predisposing factor of AESD. Methods: We analyzed 4 ADORA2A single nucleotide polymorphisms in 85 patients with AESD. The mRNA expression in brain samples, mRNA and protein expression in lymphoblasts, as well as the production of cyclic adenosine monophosphate (cAMP) by lymphoblasts in response to adenosine were compared among ADORA2A diplotypes. Results: Four single nucleotide polymorphisms were completely linked, which resulted in 2 haplotypes, A and B. Haplotype A (C at rs2298383, T at rs5751876, deletion at rs35320474, and C at rs4822492) frequency in patients was significantly higher than in controls (p = 0.005). Homozygous haplotype A (AA diplotype) had a higher risk of developing AESD (odds ratio 2.32, 95% confidence interval 1.32–4.08; p = 0.003) via a recessive model. mRNA expression was significantly higher in AA than AB and BB diplotypes, both in the brain (p = 0.003 and 0.002, respectively) and lymphoblasts (p = 0.035 and 0.003, respectively). In lymphoblasts, ADORA2A protein expression (p = 0.024), as well as cellular cAMP production (p = 0.0006), was significantly higher in AA than BB diplotype. Conclusions: AA diplotype of ADORA2A is associated with AESD and may alter the intracellular adenosine/cAMP cascade, thereby promoting seizures and excitotoxic brain damage in patients.

Shinohara, Mayu; Nishizawa, Daisuke; Ikeda, Kazutaka; Hirose, Shinichi; Takanashi, Jun-ichi; Takita, Junko; Kikuchi, Kenjiro; Kubota, Masaya; Yamanaka, Gaku; Shiihara, Takashi; Kumakura, Akira; Kikuchi, Masahiro; Toyoshima, Mitsuo; Goto, Tomohide; Yamanouchi, Hideo; Mizuguchi, Masashi

2013-01-01

347

Overdiagnosis of malaria in patients with severe febrile illness in Tanzania: a prospective study  

PubMed Central

Objective To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission. Design Prospective observational study of children and adults over the course a year. Setting 10 hospitals in north east Tanzania. Participants 17 313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease. Main outcome measure Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system. Results Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged ? 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children. Conclusions In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.

Reyburn, Hugh; Mbatia, Redepmta; Drakeley, Chris; Carneiro, Ilona; Mwakasungula, Emmanuel; Mwerinde, Ombeni; Saganda, Kapalala; Shao, John; Kitua, Andrew; Olomi, Raimos; Greenwood, Brian M; Whitty, Christopher J M

2004-01-01

348

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

PubMed Central

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

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

2011-01-01

349

Nav 1.1 dysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome.  

PubMed

Relatively few SCN1A mutations associated with genetic epilepsy with febrile seizures-plus (GEFS+) and Dravet syndrome (DS) have been functionally characterized. In contrast to GEFS+, many mutations detected in DS patients are predicted to have complete loss of function. However, functional consequences are not immediately apparent for DS missense mutations. Therefore, we performed a biophysical analysis of three SCN1A missense mutations (R865G, R946C and R946H) we detected in six patients with DS. Furthermore, we compared the functionality of the R865G DS mutation with that of a R859H mutation detected in a GEFS+ patient; the two mutations reside in the same voltage sensor domain of Na(v) 1.1. The four mutations were co-expressed with ?1 and ?2 subunits in tsA201 cells, and characterized using the whole-cell patch clamp technique. The two DS mutations, R946C and R946H, were nonfunctional. However, the novel voltage sensor mutants R859H (GEFS+) and R865G (DS) produced sodium current densities similar to those in wild-type channels. Both mutants had negative shifts in the voltage dependence of activation, slower recovery from inactivation, and increased persistent current. Only the GEFS+ mutant exhibited a loss of function in voltage-dependent channel availability. Our results suggest that the R859H mutation causes GEFS+ by a mixture of biophysical defects in Na(v) 1.1 gating. Interestingly, while loss of Na(v) 1.1 function is common in DS, the R865G mutation may cause DS by overall gain-of-function defects. PMID:21864321

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

2011-10-01

350

Effects of peripheral cold application on core body temperature and haemodynamic parameters in febrile patients.  

PubMed

This study designed to assess the effects of peripheral cold application (PCA) on core body temperature and haemodynamic parameters in febrile patients. This study was an experimental, repeated-measures performed in the neurosurgical intensive-care unit. The research sample included all patients with fever in postoperative period. PCA was performed for 20 min. During fever, systolic blood pressure, mean arterial blood pressure and arterial oxygen saturation (O2 Sat) decreased by 5.07 ± 7.89 mm Hg, 0.191 ± 6.00 mm Hg and 0.742% ± 0.97%, respectively, whereas the pulse rate and diastolic blood pressure increased by 8.528 ± 4.42 beats/ min and 1.842 ± 6.9 mmHg, respectively. Immediately after PCA, core body temperature and pulse rate decreased by 0.3°C, 3.3 beats/min, respectively, whereas systolic, diastolic, mean arterial blood pressure and O2 Sat increased by, 1.40 mm Hg, 1.87 mm Hg, 0.98 mmHg and 0.27%, respectively. Thirty minutes after the end of PCA, core body temperature, diastolic, mean arterial blood pressure and pulse rate decreased by 0.57°C, 0.34 mm Hg, 0.60 mm Hg and 4.5 beats/min, respectively, whereas systolic blood pressure and O2 Sat increased by 0.98 mm Hg and 0.04%, respectively. The present results showed that PCA increases systolic, diastolic, mean arterial blood pressure and O2 Sat, and decreases core body temperature and pulse rate. PMID:24713012

Asgar Pour, Hossein; Yavuz, Meryem

2014-04-01

351

Low-Dose Amphotericin B Lipid Complex for the Treatment of Persistent Fever of Unknown Origin in Patients with Hematologic Malignancies and Prolonged Neutropenia  

Microsoft Academic Search

We studied the safety of low-dose amphotericin B lipid complex (ABLC, at 1 mg\\/kg\\/day) in 30 persistently febrile (>38°C for at least 5 days or with recurrent fever after 3 days of apyrexia) and neutropenic (<0.5 × 109\\/l) adult patients with hematologic malignancies. The median age was 45 years (range 18–67), most (60%) had an acute leukemia and all had

Rodrigo Martino; Maricel Subirá; Andreu Domingo-Albós; Anna Sureda; Salut Brunet; Jordi Sierra

1999-01-01

352

Subcutaneous 5-Azacitidine Treatment of Naturally Occurring Canine Urothelial Carcinoma: A Novel Epigenetic Approach to Human Urothelial Carcinoma Drug Development  

PubMed Central

Purpose We determined the efficacy, biological activity, pharmacokinetics and safety of the hypomethylating agent 5-azacitidine (Celgene Corp., Summit, New Jersey) in dogs with naturally occurring invasive urothelial carcinoma. Materials and Methods We performed a preclinical phase I trial in dogs with naturally occurring invasive urothelial carcinoma to examine once daily subcutaneous administration of 5-azacitidine in 28-day cycles at doses of 0.10 to 0.30 mg/kg per day according to 2 dose schedules, including days 1 to 5 (28-day cohort) or days 1 to 5 and 15 to 19 (14-day cohort). Clinical efficacy was assessed by serial cystosonography, radiography and cystoscopy. Urinary 5-azacitidine pharmacokinetic analysis was also done. Pretreatment and posttreatment peripheral blood mononuclear cell and invasive urothelial carcinoma DNA, respectively, was analyzed for global and gene specific [CDKN2A (p14ARF)] methylation changes. Results Enrolled in the study were 19 dogs with naturally occurring invasive urothelial carcinoma. In the 28-day cohort the maximum tolerated dose was 0.20 mg/kg per day with higher doses resulting in grade 3 or 4 neutropenia in 4 of 6 dogs. In the 14-day cohort the maximum tolerated dose was 0.10 mg/kg per day with grade 3 or 4 neutropenia seen in 2 of 3 dogs treated at higher doses. No grade 3 or 4 nonhematological toxicity was observed during either dosing schedule. Of 18 dogs evaluable for tumor response partial remission, stable disease and progressive disease were observed in 4 (22.2%), 9 (50.0%) and 4 (22.2%), respectively. Consistent 5-azacitidine levels (205 to 857 ng/ml) were detected in urine. Pretreatment and posttreatment methylation analysis revealed no significant correlation with clinical response. Conclusions Subcutaneous 5-azacitidine showed promising clinical activity in a canine invasive urothelial carcinoma model, thus meriting further development in humans with urothelial carcinoma.

Hahn, Noah M.; Bonney, Patty L.; Dhawan, Deepika; Jones, David R.; Balch, Curtis; Guo, Zhongmin; Hartman-Frey, Corie; Fang, Fang; Parker, Heidi G.; Kwon, Erika M.; Ostrander, Elaine A.; Nephew, Kenneth P.; Knapp, Deborah W.

2012-01-01

353

Temperature-Sensitive Cav1.2 Calcium Channels Support Intrinsic Firing of Pyramidal Neurons and Provide a Target for the Treatment of Febrile Seizures  

PubMed Central

Febrile seizures are associated with increased brain temperature and are often resistant to treatments with antiepileptic drugs, such as carbamazepine and phenytoin, which are sodium channel blockers. Although they are clearly correlated with the hyperthermic condition, the precise cellular mechanisms of febrile seizures remain unclear. We performed patch-clamp recordings from pyramidal cells in acute rat brain slices at temperatures up to 40°C and found that, at ?37°C, L-type calcium channels are active at unexpectedly hyperpolarized potentials and drive intrinsic firing, which is also supported by a temperature-dependent, gadolinium-sensitive sodium conductance. Pharmacological data, RT-PCR, and the current persistence in Cav1.3 knock-out mice suggested a critical contribution of Cav1.2 subunits to the temperature-dependent intrinsic firing, which was blocked by nimodipine. Because intrinsic firing may play a critical role in febrile seizures, we tested the effect of nimodipine in an in vivo model of febrile seizures and found that this drug dramatically reduces both the incidence and duration of febrile seizures in rat pups, suggesting new possibilities of intervention for this important pathological condition.

Radzicki, Daniel; Yau, Hau-Jie; Pollema-Mays, Sarah L.; Mlsna, Lauren; Cho, Kangho; Koh, Sookyong

2013-01-01

354

Bortezomib inhibits STAT5-dependent degradation of LEF-1, inducing granulocytic differentiation in congenital neutropenia CD34+ cells.  

PubMed

The transcription factor lymphoid enhancer-binding factor 1 (LEF-1), which plays a definitive role in granulocyte colony-stimulating factor (G-CSF) receptor-triggered granulopoiesis, is downregulated in granulocytic progenitors of severe congenital neutropenia (CN) patients. However, the exact mechanism of LEF-1 downregulation is unclear. CN patients are responsive to therapeutically high doses of G-CSF and are at increased risk of developing acute myeloid leukemia. The normal expression of LEF-1 in monocytes and lymphocytes, whose differentiation is unaffected in CN, suggests the presence of a granulopoiesis-specific mechanism downstream of G-CSF receptor signaling that leads to LEF-1 downregulation. Signal transducer and activator of transcription 5 (STAT5) is activated by G-CSF and is hyperactivated in acute myeloid leukemia. Here, we investigated the effects of activated STAT5 on LEF-1 expression and functions in hematopoietic progenitor cells. We demonstrated that constitutively active STAT5a (caSTAT5a) inhibited LEF-1-dependent autoregulation of the LEF-1 gene promoter by binding to the LEF-1 protein, recruiting Nemo-like kinase and the E3 ubiquitin-ligase NARF to LEF-1, leading to LEF-1 ubiquitination and a reduction in LEF-1 protein levels. The proteasome inhibitor bortezomib reversed the defective G-CSF-triggered granulocytic differentiation of CD34(+) cells from CN patients in vitro, an effect that was accompanied by restoration of LEF-1 protein levels and LEF-1 messenger RNA autoregulation. Taken together, our data define a novel mechanism of LEF-1 downregulation in CN patients via enhanced ubiquitination and degradation of LEF-1 protein by hyperactivated STAT5. PMID:24394665

Gupta, Kshama; Kuznetsova, Inna; Klimenkova, Olga; Klimiankou, Maksim; Meyer, Johann; Moore, Malcolm A S; Zeidler, Cornelia; Welte, Karl; Skokowa, Julia

2014-04-17

355

Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis.  

PubMed

Severe congenital neutropenia (CN) is a preleukemic bone marrow failure syndrome with a 20% risk of evolving into leukemia or myelodysplastic syndrome (MDS). Patterns of acquisition of leukemia-associated mutations were investigated using next-generation deep-sequencing in 31 CN patients who developed leukemia or MDS. Twenty (64.5%) of the 31 patients had mutations in RUNX1. A majority of patients with RUNX1 mutations (80.5%) also had acquired CSF3R mutations. In contrast to their high frequency in CN patients who developed leukemia or MDS, RUNX1 mutations were found in only 9 of 307 (2.9%) patients with de novo pediatric acute myeloid leukemia. A sequential analysis at stages prior to overt leukemia revealed RUNX1 mutations to be late events in leukemic transformation. Single-cell analyses in 2 patients showed that RUNX1 and CSF3R mutations were present in the same malignant clone. Functional studies demonstrated elevated granulocyte colony-stimulating factor (G-CSF)-induced proliferation with diminished myeloid differentiation of hematopoietic CD34(+) cells coexpressing mutated forms of RUNX1 and CSF3R. The high frequency of cooperating RUNX1 and CSF3R mutations in CN patients suggests a novel molecular pathway of leukemogenesis: mutations in the hematopoietic cytokine receptor (G-CSFR) in combination with the second mutations in the downstream hematopoietic transcription fator (RUNX1). The detection of both RUNX1 and CSF3R mutations could be used as a marker for identifying CN patients with a high risk of progressing to leukemia or MDS. PMID:24523240

Skokowa, Julia; Steinemann, Doris; Katsman-Kuipers, Jenny E; Zeidler, Cornelia; Klimenkova, Olga; Klimiankou, Maksim; Unalan, Murat; Kandabarau, Siarhei; Makaryan, Vahagn; Beekman, Renee; Behrens, Kira; Stocking, Carol; Obenauer, Julia; Schnittger, Susanne; Kohlmann, Alexander; Valkhof, Marijke G; Hoogenboezem, Remco; Göhring, Gudrun; Reinhardt, Dirk; Schlegelberger, Brigitte; Stanulla, Martin; Vandenberghe, Peter; Donadieu, Jean; Zwaan, C Michel; Touw, Ivo P; van den Heuvel-Eibrink, Marry M; Dale, David C; Welte, Karl

2014-04-01

356

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

PubMed Central

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.

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

2014-01-01

357

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

PubMed Central

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

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

2009-01-01

358

An Analysis of Hematological Parameters as a Diagnostic test for Malaria in Patients with Acute Febrile Illness: An Institutional Experience  

PubMed Central

Objectives Hematological changes are among the most common complications encountered in malaria. This study analyzes and statistically evaluates the hematological changes as a diagnostic test for malaria in patients with acute febrile illness and whether these could guide the physician to institute specific antimalarial treatment. Methods The present study was an observational study, conducted from January to December 2012. A total of 723 patients presenting with acute febrile illness at our hospital were evaluated. A complete blood count and malarial parasite microscopy were performed for each patient. Results The findings showed that 172 out of 723 patients (24%) were diagnosed to have malaria by positive smear report. There were 121 males and 51 females with a male to female ratio of 2.3:1. Maximum number of cases were seen in the 20-30 years age group. There was a statistically significant reduction in hemoglobin (p<0.005), platelet count (p<0.001) and total leukocyte count (p<0.001) levels in patients with malaria compared to those without the disease. Likelihood ratios for a positive result of platelets (6.2) and total leukocyte count (3.4) was relevant as compared to hemoglobin (1.61) and Red cell distribution width (1.79). The negative predictive values for hemoglobin (79%), total leukocyte count (86%), platelets (94%) and Red cell distribution width (93%) were significant. Red cell distribution width values were found to be higher in patients with malaria than in patients without malaria (p<0.001). Conclusion This study revealed that routinely used laboratory findings such as hemoglobin, leukocytes, platelet counts and even red cell distribution width values can provide a diagnostic clue in a patient with acute febrile illness in endemic areas, thus increasing the probability of malaria and enhancing prompt initiation of treatment.

Jairajpuri, Zeeba Shamim; Rana, Safia; Hassan, Mohd Jaseem; Nabi, Farhat; Jetley, Sujata

2014-01-01

359

Population Pharmacokinetic Study of Amikacin Administered Once or Twice Daily to Febrile, Severely Neutropenic Adults  

PubMed Central

Once-daily (o.d.) administration of 20 mg of amikacin per kg of body weight to neutropenic patients has been validated by clinical studies, but amikacin pharmacokinetics have been documented only for the 7.5-mg/kg twice-daily (b.i.d.) regimen in this population. In order to determine in neutropenic patients (i) the influence of the dosing regimen on the kinetics of amikacin, (ii) the linearity of kinetics of amikacin in the range of 7.5 to 20 mg/kg, and (iii) the influence of patient characteristics on the disposition of amikacin and (iv) to provide a rationale for dosing recommendations, we evaluated the population pharmacokinetics of amikacin administered to 57 febrile neutropenic adults (neutrophil count, <500/mm3) being treated for a hematological disorder and receiving amikacin at 7.5 mg/kg b.i.d. (n = 29) or 20 mg/kg o.d. (n = 28) and administered intravenously over 0.5 h. A total of 278 blood samples were obtained (1 to 14 samples per patient) during one or several administration intervals (1 to 47). Serum amikacin levels were measured by the enzyme-multiplied immunoassay technique. A mixed-effect modeling approach was used to fit a bicompartmental model to the data (NONMEM software). The influences of the dosing regimen and the demographic and biological indices on the pharmacokinetic parameters of amikacin were evaluated by the maximum-likelihood ratio test on the population model. The dosing regimen had no influence on amikacin pharmacokinetic parameters, i.e., the kinetics of amikacin were linear over the range of 7.5 to 20 mg/kg. Amikacin elimination clearance (CL) was only correlated with creatinine clearance or its covariates, namely, sex, age, body weight, and serum creatinine level. The interindividual variability of CL was 21%, while those of the central volume of distribution, the distribution clearance, and the tissue volume of distribution were 15, 30, and 25%, respectively. On the basis of the expected distribution of amikacin concentrations in this population, dosing recommendations as a function of creatinine clearance (CLCR) are proposed: for patients with normal renal function (CLCR of 80 to 130 ml/min), 20 mg/kg o.d. is recommended, whereas for patients with severe renal impairment (CLCR, 10 to 20 ml/min), a dosage of 17 mg/kg every 48 h is recommended.

Tod, Michel; Lortholary, Olivier; Seytre, Delphine; Semaoun, Remi; Uzzan, Bernard; Guillevin, Loic; Casassus, Philippe; Petitjean, Olivier

1998-01-01

360

Molecular Analysis of Anaplasma phagocytophilum Isolated from Patients with Febrile Diseases of Unknown Etiology in China  

PubMed Central

Although anaplasmosis cases have been nationally identified in China, no human isolates of A. phagocytophilum have been obtained, which limits the analysis of any molecular and genetic contributions to patients' severe clinical manifestations and the study of the bacteria's pathogeneses in China. Given this situation, a joint project was conducted in 2009–2010. A total of 421 febrile cases of unknown etiology were collected and the patients' blood samples were collected for laboratory diagnoses including serologic diagnosis based on the four-fold rise in the anti- A. phagocytophilum IgG titer by indirect micro-immunofluorescence assay (IFA), positive PCR assay and confirmation of A. phagocytophilum DNA and positive culture of A. phagocytophilum and confirmed by amplification and sequencing of the 16S rRNA and ank A genes of the A. phagocytophilum isolates. A total of 570 ticks were collected from the patients' domestic animals (456) and from wild fields (114) for culturing and amplifying and sequencing the 16S rRNA gene of A. phagocytophilum. Phylogenetic analyses were performed on the 16S rRNA and ank A gene sequences of the isolates and the ticks tested in the study. A total of 46 (10.9%) confirmed and 16 (3.8%) probable cases were diagnosed and severe clinical features and higher mortality rates were observed in these Chinese patients. Five isolates were obtained and the 16S rRNA genes of the 5 isolates were conserved but variety for ank A genes. Two human isolates and 1 tick isolate from Shandong Peninsula, where all patients exhibited severe clinical manifestations, were grouped as one clan based on the phylogenetic analyses, while 2 other human isolates were clustered in a second clan. 43.5% of H. longicornis were infected with A. phagocytophilum.The present study is the first to obtain clinical isolates of A. phagocytophilum in China. The diversity of the ank A genes of Chinese isolates will help us to further discern the relationship between the variations in the ank A genes and the severity of the disease's clinical manifestations in China.

Li, Jun; Long, Bo; Yu, Hong; Zhang, Zhilun; He, Jing; Qu, Zhangyi; Yu, Jiguang; Liu, Yuanni; Dong, Tuo; Yao, Na; Wang, Yong; Cheng, Xueqin; Xu, Jianguo

2013-01-01

361

Neuronal voltage-gated ion channels are genetic modifiers of generalized epilepsy with febrile seizures plus  

PubMed Central

Mutations in the neuronal voltage-gated sodium channel genes SCN1A and SCN2A are associated with inherited epilepsies, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (severe myoclonic epilepsy of infancy). The clinical presentation and severity of these epilepsies vary widely, even in people with the same mutation, suggesting the action of environmental or genetic modifiers. To gain support for the hypothesis that genetic modifiers can influence clinical presentation in patients with SCN1A-derived GEFS+, we used mouse models to study the effect of combining the human GEFS+ mutation SCN1A-R1648H with SCN2A, KCNQ2, and SCN8A mutations. Knock-in mice heterozygous for the R1648H mutation (Scn1aRH/+) have decreased thresholds to induced seizures and infrequent spontaneous seizures, whereas homozygotes display spontaneous seizures and premature lethality. Scn2aQ54 transgenic mice have a mutation in Scn2a that results in spontaneous, adult-onset partial motor seizures, and mice carrying the Kcnq2-V182M mutation exhibit increased susceptibility to induced seizures, and rare spontaneous seizures as adults. Combining the Scn1a-R1648H allele with either Scn2aQ54 or Kcnq2V182M/+ results in early-onset, generalized tonic-clonic seizures and juvenile lethality in double heterozygous mice. In contrast, Scn8a mutants exhibit increased resistance to induced seizures. Combining the Scn1a-R1648H and Scn8a-med-jo alleles restores normal thresholds to flurothyl-induced seizures in Scn1aRH/+ heterozygotes and improved survival of Scn1aRH/RH homozygotes. Our results demonstrate that variants in Scn2a, Kcnq2, and Scn8a can dramatically influence the phenotype of mice carrying the Scn1a-R1648H mutation and suggest that ion channel variants may contribute to the clinical variation seen in patients with monogenic epilepsy.

Hawkins, Nicole A.; Martin, Melinda S.; Frankel, Wayne N.; Kearney, Jennifer A.; Escayg, Andrew

2010-01-01

362

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

PubMed Central

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

2012-01-01

363

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

PubMed Central

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

G?tzsche, P. C.; Johansen, H. K.

1997-01-01

364

Endotoxin, cytokines, and procalcitonin in febrile patients admitted to the hospital: identification of subjects at high risk of mortality.  

PubMed

We prospectively examined 464 febrile patients (median age, 61 years) for predictors of in-hospital death, by use of univariate and multivariate logistic regression using clinical data (age, underlying disease, duration of fever, chills, and shock on admission) and plasma endotoxin, TNF-alpha, IL-6, IL-10, and procalcitonin levels. The mortality rate was 4.6-fold higher (95% confidence interval [CI], 1.8-12) in 31 patients with shock on admission, 7 of whom died; the strongest association with mortality was the endotoxin concentration (relative risk, 13.7; 95% CI, 1. 4-136), which predicted 5 of the deaths with a 5% false-positive rate. For 433 patients without shock on admission, mortality (26 deaths) was associated with age and underlying disease: clinical data predicted 30% of the deaths, whereas IL-6 and procalcitonin levels identified an extra 10% with a 5% false-positive rate. When febrile patients are screened on hospital admission to identify those with a high risk for mortality, clinical judgment on the basis of age, underlying disease, and recent history outweighs the predictive value of endotoxin, cytokine, and procalcitonin levels. Only in patients who present with shock will measurement of endotoxin levels help predict those who will likely die at the cost of few false-positive results. PMID:11096000

van Langevelde, P; Joop, K; van Loon, J; Frölich, M; Groeneveld, P H; Westendorp, R G; van Dissel, J T

2000-12-01

365

Role of Fluorine-18-Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients. Experience with Dual Head Coincidence Imaging.  

PubMed

OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner. PMID:14516612

Santiago, Jonas F.; Jana, Suman; Gilbert, Holly M.; Salem, Shahenda; Bellman, Paul Curtis; Hsu, Ricky K.S.; Naddaf, Sleiman; Abdel-Dayem, Hussein M.

1999-11-01

366

Endotoxin exposure during late pregnancy alters ovine offspring febrile and hypothalamic-pituitary-adrenal axis responsiveness later in life.  

PubMed

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

Fisher, Rebecca E; Karrow, Niel A; Quinton, Margaret; Finegan, Esther J; Miller, Stephan P; Atkinson, Jim L; Boermans, Herman J

2010-07-01

367

Blood Glucose as a Predictor of Mortality in Children Admitted to the Hospital with Febrile Illness in Tanzania  

PubMed Central

Data from a prospective study of 3,319 children ages 2 months to 5 years admitted with febrile illness to a Tanzanian district hospital were analyzed to determine the relationship of blood glucose and mortality. Hypoglycemia (blood sugar < 2.5 mmol/L and < 45 mg/dL) was found in 105 of 3,319 (3.2%) children at admission, and low-normal blood glucose (2.5–5 mmol/L and 45–90 mg/dL) was found in 773 of 3,319 (23.3%) children. Mortality was inversely related to admission blood sugar; compared with children with an admission blood glucose of > 5 mmol/L, the adjusted odds of dying were 3.3 (95% confidence interval = 2.1–5.2) and 9.8 (95% confidence interval = 5.1–19.0) among children with admission blood glucose 2.5–5 and < 2.5 mmol/L, respectively. Receiver operating characteristic (ROC) analysis suggested an optimal cutoff for admission blood sugar of < 5 mmol/L in predicting mortality (sensitivity = 57.7%, specificity = 75.2%). A cutoff for admission blood glucose of < 5 mmol/L represents a simple and clinically useful predictor of mortality in children admitted with severe febrile illness to hospital in resource-poor settings.

Nadjm, Behzad; Mtove, George; Amos, Ben; Hildenwall, Helena; Najjuka, Anne; Mtei, Frank; Todd, Jim; Reyburn, Hugh

2013-01-01

368

Homozygosity Mapping and Whole Exome Sequencing to Detect SLC45A2 and G6PC3 Mutations in a Single Patient with Oculocutaneous Albinism and Neutropenia  

PubMed Central

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

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

2011-01-01

369

Scrub Typhus Is an Under-recognized Cause of Acute Febrile Illness with Acute Kidney Injury in India  

PubMed Central

Background Infection-related acute kidney injury (AKI) is an important preventable cause of morbidity and mortality in the tropical region. The prevalence and outcome of kidney involvement, especially AKI, in scrub typhus is not known. We investigated all patients with undiagnosed fever and multisystem involvement for scrub typhus and present the pattern of renal involvement seen. Methods From September 2011 to November 2012, blood samples of all the patients with unexplained acute febrile illness and/or varying organ involvement were evaluated for evidence of scrub typhus. A confirmed case of scrub typhus was defined as one with detectable Orientia tsutsugamushi deoxyribonucleic acid (DNA) in patient's blood sample by nested polymerase chain reaction (PCR) targeting the gene encoding 56-kDa antigen and without any alternative etiological diagnosis. Renal involvement was defined by demonstration of abnormal urinalysis and/or reduced glomerular filtration rate. AKI was defined as per Kidney Disease: Improving Global Outcomes (KDIGO) definition. Results Out of 201 patients tested during this period, 49 were positive by nested PCR for scrub typhus. Mean age of study population was 34.1±14.4 (range 11–65) years. Majority were males and a seasonal trend was evident with most cases following the rainy season. Overall, renal abnormalities were seen in 82% patients, 53% of patients had AKI (stage 1, 2 and 3 in 10%, 8% and 35%, respectively). The urinalysis was abnormal in 61%, with dipstick positive albuminuria (55%) and microscopic hematuria (16%) being most common. Acute respiratory distress syndrome (ARDS) and shock were seen in 57% and 16% of patients, respectively. Hyperbilirubinemia was associated with AKI (p?=?0.013). A total of 8 patients (including three with dialysis dependent AKI) expired whereas rest all made uneventful recovery. Jaundice, oliguria, ARDS and AKI were associated with mortality. However, after multivariate analysis, only oliguric AKI remained a significant predictor of mortality (p?=?0.002). Conclusions Scrub typhus was diagnosed in 24% of patients presenting with unexplained febrile illness according to a strict case definition not previously used in this region. Renal abnormalities were seen in almost 82% of all patients with evidence of AKI in 53%. Our finding is contrary to current perception that scrub typhus rarely causes renal dysfunction. We suggest that all patients with unexplained febrile illness be investigated for scrub typhus and AKI looked for in scrub typhus patients.

Kumar, Vivek; Kumar, Vinod; Yadav, Ashok K.; Iyengar, Sreenivasa; Bhalla, Ashish; Sharma, Navneet; Aggarwal, Ritesh; Jain, Sanjay; Jha, Vivekanand

2014-01-01

370

Seasonal and geographic differences in treatment-seeking and household cost of febrile illness among children in Malawi  

PubMed Central

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.

2011-01-01

371

High incidence of co-infection with Malaria and Typhoid in febrile HIV infected and AIDS patients in Ekpoma, Edo State, Nigeria.  

PubMed

This survey was designed to determine the prevalence of Plasmodium falciparum and Salmonella Typhi among febrile HIV/AIDS patients in Ekpoma. Malaria and typhoid risk factors in Ekpoma included occupation, poor health facilities and poor sanitation. Malaria and typhoid are highly prevalent among Ekpoma HIV/AIDS patients. PMID:24031367

Agwu, E; Ihongbe, J C; Okogun, G R A; Inyang, N J

2009-04-01

372

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

Microsoft Academic Search

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

C M Verity; N R Butler; J Golding

1985-01-01

373

Serologic surveillance for West Nile virus and other flaviviruses in febrile patients, encephalitic patients, and asymptomatic blood donors in northern Mexico.  

PubMed

A clinical and serological investigation was performed to determine the presence of West Nile virus (WNV) among febrile and encephalitic patients in northern Mexico. In addition, asymptomatic blood donors were serologically assayed for WNV to determine the seroprevalence of WNV in the general population. The study cohort consisted of 1432 individuals (588 febrile patients, 44 encephalitic patients, and 800 asymptomatic blood donors). All subjects were negative for WNV IgM. Sixty subjects were reactive for dengue virus (DENV) IgM (16 blood donors and 44 febrile patients). A subset (n = 425) of individuals was also screened by ELISA for flavivirus IgG. The prevalence of flavivirus IgG in febrile patients, encephalitic patients, and blood donors ranged from 40% to 59%. A subset (n = 147) of sera reactive for flavivirus IgG was further tested by plaque reduction neutralization test. Six individuals with no history of travel during the preceding 12 months were seropositive for WNV. Another 65 individuals were seropositive for DENV1 and 24 were seropositive for DENV2. The high prevalence of dengue antibodies in northern Mexico appears to limit the incidence of WNV infection in this region. Article Summary Line: Antibodies to WNV, DENV-1, and DENV-2 were identified in humans in northern Mexico. PMID:19492946

Rodríguez, María de Lourdes Garza; Rodriguez, Diana R Rodríguez; Blitvich, Bradley J; López, Miguel A Reyes; Fernández-Salas, Ildefonso; Jimenez, Javier Ramos; Farfán-Ale, José A; Tamez, Rogelio Cazares; Longoria, César Martinez; Aguilar, Maria I Tavitas; Rivas-Estilla, Ana Maria

2010-03-01

374

Serologic Surveillance for West Nile Virus and Other Flaviviruses in Febrile Patients, Encephalitic Patients, and Asymptomatic Blood Donors in Northern Mexico  

PubMed Central

Abstract A clinical and serological investigation was performed to determine the presence of West Nile virus (WNV) among febrile and encephalitic patients in northern Mexico. In addition, asymptomatic blood donors were serologically assayed for WNV to determine the seroprevalence of WNV in the general population. The study cohort consisted of 1432 individuals (588 febrile patients, 44 encephalitic patients, and 800 asymptomatic blood donors). All subjects were negative for WNV IgM. Sixty subjects were reactive for dengue virus (DENV) IgM (16 blood donors and 44 febrile patients). A subset (n?=?425) of individuals was also screened by ELISA for flavivirus IgG. The prevalence of flavivirus IgG in febrile patients, encephalitic patients, and blood donors ranged from 40% to 59%. A subset (n?=?147) of sera reactive for flavivirus IgG was further tested by plaque reduction neutralization test. Six individuals with no history of travel during the preceding 12 months were seropositive for WNV. Another 65 individuals were seropositive for DENV1 and 24 were seropositive for DENV2. The high prevalence of dengue antibodies in northern Mexico appears to limit the incidence of WNV infection in this region. Article Summary Line Antibodies to WNV, DENV-1, and DENV-2 were identified in humans in northern Mexico.

Rodriguez, Maria de Lourdes Garza; Rodriguez Rodriguez, Diana R.; Blitvich, Bradley J.; Lopez, Miguel A. Reyes; Fernandez-Salas, Ildefonso; Jimenez, Javier Ramos; Farfan-Ale, Jose A.; Tamez, Rogelio Cazares; Longoria, Cesar Martinez; Aguilar, Maria I. Tavitas

2010-01-01

375

Radiographic Evaluation of Children with Febrile Urinary Tract Infection: Bottom-Up, Top-Down, or None of the Above?  

PubMed Central

The proper algorithm for the radiographic evaluation of children with febrile urinary tract infection (FUTI) is hotly debated. Three studies are commonly administered: renal-bladder ultrasound (RUS), voiding cystourethrogram (VCUG), and dimercapto-succinic acid (DMSA) scan. However, the order in which these tests are obtained depends on the methodology followed: bottom-up or top-down. Each strategy carries advantages and disadvantages, and some groups now advocate even less of a workup (none of the above) due to the current controversies about treatment when abnormalities are diagnosed. New technology is available and still under investigation, but it may help to clarify the interplay between vesicoureteral reflux, renal scarring, and dysfunctional elimination in the future.

Prasad, Michaella M.; Cheng, Earl Y.

2012-01-01

376

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

PubMed

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

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

2012-01-01

377

Staphylococcus aureus and repeat bacteremia in febrile patients as early signs of sternal wound infection after cardiac surgery  

PubMed Central

Background Sternal wound infection is a devastating complication of cardiothoracic surgery that carries high postoperative morbidity and mortality rates. We explored whether our current program of extensive bacteriological examination including repeat blood cultures may contribute to the early diagnosis of sternal wound infection. Methods We retrospectively analyzed 112 patients who were subjected to our bacteriological examination protocol including within 90 days after cardiothoracic surgery. Univariate and multivariate analyses were made in order to identify risk factors for sternal infection. Results The median patient age was 75 years, and 65 patients were male. In 35 cases (31.2%) the blood cultures showed the presence of bacterial infection with the following frequencies: Staphylococcus aureus, 18 cases; Coagulase-negative Staphylococcus, 7 cases; other organisms, 10 cases. Eleven patients presented repeat bacteremia on at least 2 different occasions. Twenty patients (17.8%) presented sternal wound infections. There was no difference in operative mortality between the patients with and without sternal wound infection. Univariate and multivariate analyses demonstrated that bilateral mammary artery use (OR, 13.68, 95% CI, 1.09-167.36, p?=?0.043), positive blood culture for Staphylococcus aureus (OR, 19.51, 95% CI, 4.46-104.33, p?febrile patients appear to be useful for the early detection of Staphylococcus aureus and repeat bacteremia, and these were associated with sternal wound infection. Bilateral internal mammary artery use was another risk factor of sternal wound infection in febrile patients. These factors may identify patients suitable for expeditious radiological examination and aggressive treatments.

2014-01-01

378

Toll-like receptor agonists and febrile range hyperthermia synergize to induce heat shock protein 70 expression and extracellular release.  

PubMed

Heat shock protein (Hsp) 70 expression can be stimulated by febrile range temperature (FRT). Hsp70 has been shown to be elevated in serum of patients with sepsis, and when released from cells, extracellular Hsp70 exerts endotoxin-like effects through Toll-like receptor 4 (TLR4) receptors. Circulating TLR agonists and fever both persist for the first several days of sepsis, and each can activate Hsp70 expression; however, the effect of combined exposure to FRT and TLR agonists on Hsp70 expression is unknown. We found that concurrent exposure to FRT (39.5 °C) and agonists for TLR4 (LPS), TLR2 (Pam3Cys), or TLR3 (poly(IC)) synergized to increase Hsp70 expression and extracellular release in RAW264.7 macrophages. The increase in Hsp70 expression was associated with activation of p38 and ERK MAP kinases, phosphorylation of histone H3, and increased recruitment of HSF1 to the Hsp70 promoter. Pretreatment with the p38 MAPK inhibitor SB283580 but not the ERK pathway inhibitor UO126 significantly reduced Hsp70 gene modification and Hsp70 expression in RAW cells co-exposed to LPS and FRT. In mice challenged with intratracheal LPS and then exposed to febrile range hyperthermia (core temperature, ?39.5 °C), Hsp70 levels in lung tissue and in cell-free lung lavage were increased compared with mice exposed to either hyperthermia or LPS alone. We propose a model of how enhanced Hsp70 expression and extracellular release in patients concurrently exposed to fever and TLR agonists may contribute to the pathogenesis of sepsis. PMID:23212905

Gupta, Aditi; Cooper, Zachary A; Tulapurkar, Mohan E; Potla, Ratnakar; Maity, Tapan; Hasday, Jeffrey D; Singh, Ishwar S

2013-01-25

379

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release*  

PubMed Central

Heat shock protein (Hsp) 70 expression can be stimulated by febrile range temperature (FRT). Hsp70 has been shown to be elevated in serum of patients with sepsis, and when released from cells, extracellular Hsp70 exerts endotoxin-like effects through Toll-like receptor 4 (TLR4) receptors. Circulating TLR agonists and fever both persist for the first several days of sepsis, and each can activate Hsp70 expression; however, the effect of combined exposure to FRT and TLR agonists on Hsp70 expression is unknown. We found that concurrent exposure to FRT (39.5 °C) and agonists for TLR4 (LPS), TLR2 (Pam3Cys), or TLR3 (poly(IC)) synergized to increase Hsp70 expression and extracellular release in RAW264.7 macrophages. The increase in Hsp70 expression was associated with activation of p38 and ERK MAP kinases, phosphorylation of histone H3, and increased recruitment of HSF1 to the Hsp70 promoter. Pretreatment with the p38 MAPK inhibitor SB283580 but not the ERK pathway inhibitor UO126 significantly reduced Hsp70 gene modification and Hsp70 expression in RAW cells co-exposed to LPS and FRT. In mice challenged with intratracheal LPS and then exposed to febrile range hyperthermia (core temperature, ?39.5 °C), Hsp70 levels in lung tissue and in cell-free lung lavage were increased compared with mice exposed to either hyperthermia or LPS alone. We propose a model of how enhanced Hsp70 expression and extracellular release in patients concurrently exposed to fever and TLR agonists may contribute to the pathogenesis of sepsis.

Gupta, Aditi; Cooper, Zachary A.; Tulapurkar, Mohan E.; Potla, Ratnakar; Maity, Tapan; Hasday, Jeffrey D.; Singh, Ishwar S.

2013-01-01

380

Rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in Tanzania: randomised trial  

PubMed Central

Objective To compare rapid diagnostic tests (RDTs) for malaria with routine microscopy in guiding treatment decisions for febrile patients. Design Randomised trial. Setting Outpatient departments in northeast Tanzania at varying levels of malaria transmission. Participants 2416 patients for whom a malaria test was requested. Intervention Staff received training on rapid diagnostic tests; patients sent for malaria tests were randomised to rapid diagnostic test or routine microscopy Main outcome measure Proportion of patients with a negative test prescribed an antimalarial drug. Results Of 7589 outpatient consultations, 2425 (32%) had a malaria test requested. Of 1204 patients randomised to microscopy, 1030 (86%) tested negative for malaria; 523 (51%) of these were treated with an antimalarial drug. Of 1193 patients randomised to rapid diagnostic test, 1005 (84%) tested negative; 540 (54%) of these were treated for malaria (odds ratio 1.13, 95% confidence interval 0.95 to 1.34; P=0.18). Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides (P=0.003). Patients with a negative test by any method were more likely to be prescribed an antibiotic (odds ratio 6.42, 4.72 to 8.75; P<0.001). More than 90% of prescriptions for antimalarial drugs in low-moderate transmission settings were for patients for whom a test requested by a clinician was negative for malaria. Conclusions Although many cases of malaria are missed outside the formal sector, within it malaria is massively over-diagnosed. This threatens the sustainability of deployment of artemisinin combination treatment, and treatable bacterial diseases are likely to be missed. Use of rapid diagnostic tests, with basic training for clinical staff, did not in itself lead to any reduction in over-treatment for malaria. Interventions to improve clinicians' management of febrile illness are essential but will not be easy. Trial registration Clinical trials NCT00146796.

Mbakilwa, Hilda; Mwangi, Rose; Mwerinde, Ombeni; Olomi, Raimos; Drakeley, Chris; Whitty, Christopher J M

2007-01-01

381

Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children  

PubMed Central

Objective: Paracetamol and ibuprofen are widely used for fever in children as monotherapy and as combined therapy. None of the treatments is proven clearly superior to others. Hence, the study was planned to compare the efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Materials and Methods: This was an investigator blind, randomized, comparative, parallel clinical trial conducted in 99 febrile children, 6 months to 12 years of age, allocated to three groups. First group received paracetamol 15 mg/kg, second group received ibuprofen 10 mg/kg and third group received both paracetamol and ibuprofen, all as a single dose by the oral route. Patients were followed-up at intervals of 1, 2, 3 and 4 h post dose by tympanic thermometry. Results: Mean tympanic temperature after 4 h of drug administration was significantly lower in the combination group compared with paracetamol group (P < 0.05); however, the difference was not clinically significant (<1°C). The rate of fall of temperature was highest in the combination group. Number of afebrile children any time post dose until 4 h was highest in the combination group. Difference between combination and paracetamol was significant for the 1st h (P = 0.04). Highest fall of temperature was noted in the 1st h of drug administration in all the groups. No serious adverse events were observed in any of the groups. Conclusion: Paracetamol and ibuprofen combination caused quicker temperature reduction than either paracetamol or ibuprofen alone. If quicker reduction of body temperature is the desired goal of therapy, the use of combination of paracetamol + ibuprofen may be advocated.

Vyas, Falgun Indravadan; Rana, Devang Ashwinkumar; Patel, Piyush M.; Patel, Varsha Jitendra; Bhavsar, Rekha H.

2014-01-01

382

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

PubMed Central

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

2013-01-01

383

Observation of Patients with Vesicoureteral Reflux Off Antibiotic Prophylaxis: Physician Bias on Patient Selection and Risk Factors for Recurrent Febrile Urinary Tract Infection  

PubMed Central

Purpose Observation off continuous antibiotic prophylaxis is an option for vesicoureteral reflux. We evaluated the characteristics of patients observed off continuous antibiotic prophylaxis and risk factors for febrile urinary tract infection. Materials and Methods We identified children 1 to 18 years old with primary vesicoureteral reflux between January 1, 2010 and December 31, 2010. We excluded patients with prior surgical correction from analysis. We recorded age, gender, race/ethnicity, primary language, insurance carrier, age at vesicoureteral reflux diagnosis, initial presentation and vesicoureteral reflux severity. We quantified bladder and bowel dysfunction with a validated questionnaire if toilet trained. We compared patients off vs on continuous antibiotic prophylaxis with the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. We used a univariate Cox proportional hazards model to assess predictors of febrile urinary tract infection during observation off continuous antibiotic prophylaxis. Results Of 529 eligible patients 224 were observed off continuous antibiotic prophylaxis. Patients off continuous antibiotic prophylaxis tended to be older (p < 0.001), to be older at diagnosis (p < 0.001), to have an initial presentation other than febrile urinary tract infection (p = 0.05), to have nondilating vesicoureteral reflux on most recent cystogram (p <0.001) and to have lower bladder/bowel dysfunction scores if toilet trained (p < 0.001). Of the patients off continuous antibiotic prophylaxis a febrile urinary tract infection developed in 19 (8.5%). Risk factors associated with febrile urinary tract infection included initial presentation of multiple febrile urinary tract infections (p = 0.03), older age at diagnosis (p = 0.03) and older age starting observation off continuous antibiotic prophylaxis (p = 0.0003). Conclusions Criteria to select patients with vesicoureteral reflux for observation off continuous antibiotic prophylaxis remain poorly defined in the literature. Observation will fail in a subset of patients with vesicoureteral reflux. Physician biases regarding patient selection for observation off continuous antibiotic prophylaxis should be considered when interpreting studies that evaluate treatment strategies.

Drzewiecki, Beth A.; Thomas, John C.; Pope, John C.; Adams, Mark C.; Brock, John W.; Tanaka, Stacy T.

2012-01-01

384

PCR-Restriction Enzyme Analysis for Detection of Candida DNA in Blood from Febrile Patients with Hematological Malignancies  

PubMed Central

Blood samples were drawn daily from 72 patients who had hematological malignancies, neutropenia, and fever and who had failed to respond to broad-spectrum antibiotics. Each sample was used for conventional fungal blood cultures and for detection and identification of Candida DNA by a PCR method with subsequent restriction enzyme analysis (REA) recently developed in our laboratory. The PCR method was able to detect five CFU of Candida spp. per ml of blood, and subsequent REA of the amplicons allowed the identification of the Candida species most commonly implicated in cases of candidiasis. Thirty-one patients were PCR-REA positive, and four of these patients were also culture positive. The ultimate diagnosis for 13 of these patients and 1 patient who was PCR-REA negative was disseminated candidiasis (confirmed by clinical data, multiple cultures, histology, autopsy, and/or ultrasonographic evidence of hepatosplenic candidiasis). The molecular method is significantly more sensitive than conventional fungal blood cultures and has a high negative predictive value (97.5%) for the development of disseminated candidiasis in neutropenic patients.

Morace, Giulia; Pagano, Livio; Sanguinetti, Maurizio; Posteraro, Brunella; Mele, Luca; Equitani, Francesco; D'Amore, Giuseppina; Leone, Giuseppe; Fadda, Giovanni

1999-01-01

385

PCR-restriction enzyme analysis for detection of Candida DNA in blood from febrile patients with hematological malignancies.  

PubMed

Blood samples were drawn daily from 72 patients who had hematological malignancies, neutropenia, and fever and who had failed to respond to broad-spectrum antibiotics. Each sample was used for conventional fungal blood cultures and for detection and identification of Candida DNA by a PCR method with subsequent restriction enzyme analysis (REA) recently developed in our laboratory. The PCR method was able to detect five CFU of Candida spp. per ml of blood, and subsequent REA of the amplicons allowed the identification of the Candida species most commonly implicated in cases of candidiasis. Thirty-one patients were PCR-REA positive, and four of these patients were also culture positive. The ultimate diagnosis for 13 of these patients and 1 patient who was PCR-REA negative was disseminated candidiasis (confirmed by clinical data, multiple cultures, histology, autopsy, and/or ultrasonographic evidence of hepatosplenic candidiasis). The molecular method is significantly more sensitive than conventional fungal blood cultures and has a high negative predictive value (97.5%) for the development of disseminated candidiasis in neutropenic patients. PMID:10325339

Morace, G; Pagano, L; Sanguinetti, M; Posteraro, B; Mele, L; Equitani, F; D'Amore, G; Leone, G; Fadda, G

1999-06-01

386

Randomized trial of the effect of intravenous paracetamol on inflammatory biomarkers and outcome in febrile critically ill adults  

PubMed Central

Background and the purpose of the study The febrile reaction is a complex response involving immunologic and other physiologic systems. Antipyretics are commonly used in critically ill patients with fever. We investigated the inflammatory responses following application of antipyretic therapy in febrile critically ill patients with Systemic Inflammatory Response Syndrome (SIRS). Patients and methods In a prospective, randomized controlled study, critically ill patients with fever (T???38.3°C), SIRS diagnosed within 24 hours of Intensive Care Unit (ICU) admission and Acute Physiology and Chronic Health Evaluation II (APACHE II) score ?10 were randomized into two groups. Upon appearance of fever, one group received intravenous paracetamol 650?mg every 6 hours for 10?days and other group received no treatment unless temperature reached 40°C. Body temperature, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality and infectious complications were recorded. Levels of Interleukin-1 alpha (IL-1?), IL-6, IL-10, Tumour Necrosis Factor alpha (TNF?) and High-Sensitive C-Reactive Protein (HS-CRP) were assessed at baseline and 2, 6 and 24 hours after intervention. Results and discussion During a period of 15-month screening, 20 patients met the criteria and randomized to the control or paracetamol group. Body temperature decreased significantly in the paracetamol group (p?=?0.004) and control group (p?=?0.001) after 24 hours, but there was no significant difference between two groups at this time point (p?=?0.649). Levels of IL-6 and IL-10 decreased significantly (p?=?0.025 and p?=?0.047, respectively) in the paracetamol group at 24 hours but this was not of statistical significance in control group. No patterns over time in each group or differences across two groups were found for HS-CRP, TNF?, and IL-1? (p?>?0.05). There were no differences regarding ICU length of stay, mortality and infectious complications between both groups. Conclusion These results suggest that antipyretic therapy may not be indicated in all ICU patients. Allowing fever to take its natural course does not appear to have detrimental effects on critically ill patients with SIRS and may avoid unnecessary expenses.

2012-01-01

387

Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty  

PubMed Central

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-1?, IL-6, TNF-?, 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-1? (> 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?

2014-01-01

388

Health-related quality of life for pediatric emergency department febrile illnesses: an Evaluation of the Pediatric Quality of Life Inventory™ 4.0 generic core scales  

Microsoft Academic Search

OBJECTIVE: We sought to assess the validity and short-term responsiveness of the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL™) for febrile illnesses evaluated in the pediatric emergency department (ED). DESIGN: Prospective cohort study of children 2–18 years discharged after ED evaluation for fever (? 38°C). Self-administered, parent-report of health-related quality of life (HRQOL) was assessed using the

Rakesh D Mistry; Molly W Stevens; Marc H Gorelick

2009-01-01

389

ANTIBODY PREVALENCE OF ORIENTIA TSUTSUGAMUSHI, RICKETTSIA TYPHI AND TT118 SPOTTED FEVER GROUP RICKETTSIAE AMONG MALAYSIAN BLOOD DONORS AND FEBRILE PATIENTS IN THE URBAN AREAS  

Microsoft Academic Search

The seroprevalence of Orientia tsutsugamushi (OT), Rickettsia typhi (RT) and TT118 spotted fever group rickettsiae (SFGR) among blood donors and febrile Malaysian patients in the urban areas was determined. Of the 240 blood donors, 5.4%, 9.2% and 1.7% had either present or previous exposure to OT, RT and SFG rickettsiae, respectively. Patients admitted to an urban hospital had high seroprevalences

ST Tay; M Kamalanathan; Jalan Pahang

390

Treatment duration of febrile urinary tract infection (FUTIRST trial): a randomized placebo-controlled multicenter trial comparing short (7 days) antibiotic treatment with conventional treatment (14 days)  

Microsoft Academic Search

BACKGROUND: Current guidelines on the management of urinary tract infection recommend treating febrile urinary tract infection or acute pyelonephritis with antimicrobials for at least 14 days. Few randomized trials showed the effectiveness of treatment durations of 5 to 7 days but this has only been studied in young previously healthy women. METHODS\\/DESIGN: A randomized placebo-controlled double-blind multicenter non-inferiority trial in

Cees van Nieuwkoop; Jan W van't Wout; Willem JJ Assendelft; Henk W Elzevier; Ted Koster; G Hanke Wattel-Louis; Nathalie M Delfos; Hans C Ablij; Ed J Kuijper; Jan Pander; Jeanet W Blom; Ida C Spelt; Jaap T van Dissel

2009-01-01

391

Comparative pharmacokinetic study of chlorogenic acid after oral administration of Lonicerae Japonicae Flos and Shuang-Huang-Lian in normal and febrile rats.  

PubMed

Shuang-Huang-Lian (SHL), a famous traditional Chinese medicine recipe containing Lonicerae Japonicae Flos (LJF), Forsythiae Fructus, and Scutellariae Radix, is clinically used for the treatment of fever and acute upper respiratory tract infection. In this research, a comparative study was conducted to compare the pharmacokinetic difference of chlorogenic acid (ChA) after oral administration of LJF and SHL to normal and febrile rats with approximately the same dose of 60 mg/kg, and the antipyrexia effect of LJF and SHL on rectal temperature changes induced by Baker's yeast was investigated. The results indicated that AUC(0-t) and plasma concentrations of ChA in the febrile rats were significantly higher than normal rats whether in the extract of LJF or SHL. In addition, SHL increased the values of AUC of ChA in both febrile and normal rats compared with LJF alone (p < 0.05), and SHL showed better antipyrexia effect than LJF. These results indicate that fever could play an important role in pharmacokinetic process of ChA. Meanwhile, the combined formula SHL exhibits higher bioavailability of ChA and superior antipyrexia effect than the single herb. PMID:23447366

Gao, Ru; Lin, Yining; Liang, Ge; Yu, Boyang; Gao, Yuan

2014-01-01

392

Placenta increta occurring in a blighted ovum.  

PubMed

We present a rare case of placenta increta, confirmed postoperatively by pathologic analysis, occurring before 20 weeks' gestation in a blighted ovum. Hysterectomy was necessary for control of hemorrhage. PMID:8638190

Gist, R S; Vuong, V; Brody, S; Rees, P; Landry, A D

1996-05-01

393

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

PubMed

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

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

2010-01-01