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1

[Febrile neutropenia at the emergency department of a cancer hospital].  

PubMed

Febrile neutropenia is an important cause of fever in the cancer patient. When he/she is undergoing chemotherapy, the priority is to exclude that complication because it requires rapid administration of empiric broad-spectrum antibiotics. We have studied the rate and characteristics of febrile neutropenia in cancer patients consulting in a emergency department. We have conducted a retrospective study in the emergency department of a cancer hospital over the year 2008. Every patient with cancer and fever > or = 38 degrees C was included. Over 2.130 consultations, 408 were selected (313 patients) including 21.6% (88) for febrile neutropenia. A focal symptom or physical sign was present in the majority of the cases. 88% were assessed as low risk for severe complications and about half of them received oral antibiotics. There were only a few patients with a nude fever for which it was difficult to make a hypothetical diagnosis in order to administer a probabilistic treatment. The majority of the consultations lead to hospital admission. Over the 80 hospitalisations, 6 deaths occurred. There was no death among the patients who remained ambulatory. In conclusion, our study shows that febrile neutropenia is frequent in ambulatory cancer patients presenting with fever and that in the majority of the cases, it is associated with a low risk. In such a situation, ambulatory management is more and more often considered or, at least, a rapid discharge after a short admission in case of low risk febrile neutropenia. In that context, the role of the general practioner has to be emphasised and to facilitate the outpatient management, we propose an algorithm that requires validation. PMID:21688591

Debey, C; Meert, A-P; Berghmans, T; Thomas, J M; Sculier, J P

2011-01-01

2

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

PubMed Central

Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis. PMID:25525436

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

2014-01-01

3

Febrile neutropenia: a critical review of the initial management.  

PubMed

The present state of the art for management of patients with febrile neutropenia has been reviewed as well as potential ways to improve it in the future. A major advance has been the possibility to predict, accurately and early, the risk of complications and death in those patients. While the algorithm for therapy in low-risk patients is presently straightforward, significant progresses are needed for patients who are at higher risk of presenting severe complications. PMID:20413323

Klastersky, Jean; Awada, Ahmad; Paesmans, Mariane; Aoun, Mickael

2011-06-01

4

Empiric Oral versus Intravenous Antibiotics for Low-Risk Febrile Neutropenia: a Meta-analysis  

Microsoft Academic Search

Empiric intravenous antimicrobial therapy is the current standard of management for patients with febrile neutropenia. The use of oral antibiotic regimens for low-risk febrile neutropenia is a potentially cost-effective alternative if proven to be equally effective as the standard intravenous regimens. It is the objective of the study to determine if oral antibiotic regimens are equally effective as the standard

Marissa M. Alejandria; Mario M. Panaligan; Felice G. Molina; Maria Fe; P. Raymundo

5

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

PubMed Central

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

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

2014-01-01

6

Factors Associated with Hospital Length of Stay among Cancer Patients with Febrile Neutropenia  

PubMed Central

Purpose This study sought to evaluate factors associated with hospital length of stay in cancer patients with febrile neutropenia. Methods A prospective cohort study was performed at a single tertiary referral hospital in southern Brazil from October 2009 to August 2011. All adult cancer patients with febrile neutropenia admitted to the hematology ward were evaluated. Stepwise random-effects negative binomial regression was performed to identify risk factors for prolonged length of hospital stay. Results In total, 307 cases of febrile neutropenia were evaluated. The overall median length of hospital stay was 16 days (interquartile range 18 days). According to multiple negative binomial regression analysis, hematologic neoplasms (P?=?0.003), high-dose chemotherapy regimens (P<0.001), duration of neutropenia (P<0.001), and bloodstream infection involving Gram-negative multi-drug-resistant bacteria (P?=?0.003) were positively associated with prolonged hospital length of stay in patients with febrile neutropenia. The condition index showed no evidence of multi-collinearity effect among the independent variables. Conclusions Hematologic neoplasms, high-dose chemotherapy regimens, prolonged periods of neutropenia, and bloodstream infection with Gram-negative multi-drug-resistant bacteria are predictors of prolonged length hospital of stay among adult cancer patients with febrile neutropenia. PMID:25285790

Rosa, Regis G.; Goldani, Luciano Z.

2014-01-01

7

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

PubMed Central

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

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

2014-01-01

8

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

E-print Network

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

Oakley, Jeremy

9

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

PubMed Central

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

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

2015-01-01

10

Brucellosis: a rare cause of febrile neutropenia in acute myeloblastic leukemia.  

PubMed

Brucellosis is a zoonotic disease and endemically seen in the Middle East, Eastern Europe and continental America. Febrile neutropenia related to Brucellosis has been reported only in a few cases. Brucella was cultured from the bone marrow of a 42-year-old woman who was admitted to hospital with symptoms of fever and fatigue and later diagnosed as acute myeloblastic leukemia (AML). The patient was treated for both AML and Brucellosis without any problems and discharged from the hospital after scheduling her follow-up visits. Brucellosis might be considered in the etiology of febrile neutropenia in endemic regions and must be treated effectively to prevent possible morbidity and mortality during or after chemotherapy. PMID:20169426

Ozbalci, Demircan; Ergene, Ulku; Cetin, Cigdem Banu

2011-03-01

11

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

PubMed Central

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

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

2014-01-01

12

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

PubMed

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

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

2014-09-01

13

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

PubMed

Children with cancer often have fever during chemotherapy-induced neutropenia, but only some develop serious infectious complications. Mannose-binding lectin (MBL) deficiency might increase infection susceptibility in these children. MBL genotype and phenotype were prospectively determined in 110 paediatric oncology patients. During febrile neutropenia, MBL concentrations were measured longitudinally in time. MBL genotype and phenotype were correlated to clinical and laboratory parameters. Structural exon-1 MBL2 mutations and the LX promoter polymorphism lead to deficient MBL concentrations. The capacity to increase MBL concentrations during febrile neutropenia was associated with MBL2 genotype. Infectious parameters did not differ between MBL-deficient and MBL-sufficient neutropenic children (n = 66). In contrast, MBL-sufficient patients had a greater risk of Intensive Care admittance (Relative Risk 1.6, 95% Confidence Interval 1.3-2.0, P = 0.04). MBL-deficient neutropenic children did not have more severe infections. However, most patients (61%) were severely neutropenic (<100 cells/microL), compromising the opsonophagocytic effector function of MBL. MBL substitution might still be beneficial in patients with phagocytic activity. PMID:16517152

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

2006-05-01

14

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

PubMed

The aim of this study was to determine the incidence and causes of fever as a major problem contributing to transplantation related mortality among patients undergoing hematopoietic stem cell transplantation (HSCT) and evaluation of antibiotic use, according to reliable guidelines.We retrospectively reviewed hospital records of 195 adult patients who underwent HSCT between 2009-2011 at hematology-oncology and bone marrow transplantation research center. Baseline information and also data related to fever and neutropenia, patient's outcomes, duration of hospitalization and antibiotic use pattern were documented.A total of 195 patients were analyzed and a total of 268 febrile episodes in 180 patients were recorded (mean 1.5 episodes per patient). About 222 episodes (82%) were associated with neutropenia which one-fourth of them were without any documented infection sources. Microbiologic documents showed that the relative frequencies of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively. The hospital stay duration was directly related to the numbers of fever episodes (P<0.0001).The rate of febrile episodes in autologous stem cell transplantation was significantly higher compared to allogeneic type (P<0.05).It is necessary to determine not only the local profile of microbiologic pattern, but also antibiotic sensitivities in febrile neutropenic patients following hematopoietic stem cell transplantation, and reassess response to antibiotic treatment to establish any necessity for modifications to treatment guidelines in order to prevent any fatal complications from infection. PMID:24658984

Amini, Shahideh; Hadjibabaie, Molouk; Jahangard-Rafsanjani, Zahra; Ashuri, Asieh; Torkamandi, Hassan; Ghavamzadeh, Ardeshir

2014-01-01

15

Variation in policies for the management of febrile neutropenia in United Kingdom Children's Cancer Study Group centres  

PubMed Central

Objective To assess the variation in the current UK management strategies for the treatment of febrile neutropenia in childhood. Design and setting A postal survey of all 21 United Kingdom Children's Cancer Study Group (UKCCSG) centres assessing and collating local policies, protocols or guidelines relating to the management of febrile neutropenia. Further direct contact was undertaken to clarify any uncertainties. Results All 21 centres provided information. The policies used to manage febrile neutropenia in the centres around the UK vary in almost every aspect of management. Definitions of fever ranged from a persistent temperature of >37.5°C to a single reading of >39°C. Neutropenia was inconsistently defined as an absolute neutrophil count of <1×109, <0.75×109 or <0.5×109. Choices of antibiotic approaches, empirical modifications and antistaphylococcal treatment were different in each protocol. The use of risk stratification was undertaken in 11 centres, with six using a policy of reduced intensity therapy in low risk cases. Empirical antifungal treatment was very poorly described and varied even more widely. Conclusions There was a great deal of variation in definitions and treatment of febrile neutropenia in the UKCCSG children's cancer treatment centres. A degree of variation as a result of local microbiological differences is to be expected, but beyond this we should seek to standardise the core of our approach to defining fever and neutropenia, risk stratification and duration of empirical therapy in a way that maintains safety, minimises resource utilisation and maximises quality of life. PMID:17284481

Phillips, Bob; Selwood, Karen; Lane, Sheila M; Skinner, Roderick; Gibson, Faith; Chisholm, Julia C

2007-01-01

16

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

E-print Network

HEDS Discussion Paper: Cost-effectiveness of G-CSFs for febrile neutropenia prophylaxis in non-Hodgkin prophylaxis in non-Hodgkin's lymphoma: Whyte et al - 2 - #12;HEDS Discussion Paper: Cost-effectiveness of G-CSFs for febrile neutropenia prophylaxis in non-Hodgkin's lymphoma: Whyte et al - 3 - Cost

Oakley, Jeremy

17

Empiric monotherapy for febrile neutropenia--a randomized study comparing meropenem with ceftazidime.  

PubMed

In this Swedish multicentre study we compared the efficacy of meropenem with ceftazidime for treatment of febrile neutropenia. 192 patients were randomized and the number of evaluable patients was 92 in the meropenem group and 95 in the ceftazidime group. 40 (43%) patients in the meropenem arm and 49 (52%) in the ceftazidime arm had acute leukaemia. 56 (61%) and 52 (55%) patients respectively had a neutrophil count of < 0.1 x 10(9)/l at randomization and the median duration of neutropenia was 6.5 and 8 d, respectively. Thirty-one (34%) and 28 (29%) patients had a microbiologically defined infection, 14 (15%) and 17 (18%) a clinically defined infection and the remaining 47 (51%) and 50 (53%) had unexplained fever. After 72 h of treatment, 46 (50%) patients in the meropenem arm and 53 (56%) patients in the ceftazidime arm were alive on unmodified monotherapy. 42 (46%) and 47 (49%) of these completed the study on monotherapy alone. Only 2 patients (2%) in each arm had to stop treatment owing to allergic reactions. None of the observed differences were statistically significant and we therefore conclude that meropenem was an effective and safe alternative to ceftazidime for empiric treatment of fever during neutropenia. PMID:9790130

Lindblad, R; Rödjer, S; Adriansson, M; Andreasson, B; Bäckström, B; Johansson, P; Karlsson, K; Rhedin, C; Turesson, I

1998-01-01

18

Prevention of febrile neutropenia in chemotherapy-treated cancer patients: Pegylated versus standard myeloid colony stimulating factors. Do we have a choice?  

PubMed

The pertinent literature on clinical studies comparing the respective value of myeloid colony stimulating factors to pegfilgrastim as a prevention of febrile neutropenia in chemotherapy-treated cancer patients has been reviewed. Pegfilgrastim is definitely not inferior to filgrastim or other myeloid colony stimulating agents with respect to duration of grade IV neutropenia and delivery of full chemotherapy dose on time; several comparative studies indicate a trend to less frequent febrile neutropenia with pegfilgrastim. PMID:20227290

Klastersky, Jean; Awada, Ahmad

2011-04-01

19

The use of chemotherapy regimens carrying a moderate or high risk of febrile neutropenia and the corresponding management of febrile neutropenia: an expert survey in breast cancer and non-Hodgkin's lymphoma  

Microsoft Academic Search

BACKGROUND: The use of chemotherapy regimens with moderate or high risk of febrile neutropenia (defined as having a FN incidence of 10% or more) and the respective incidence and clinical management of FN in breast cancer and NHL has not been studied in Belgium. The existence of a medical need for G-CSF primary and secondary prophylaxis with these regimens was

Laetitia Gerlier; Mark Lamotte; Ahmad Awada; André Bosly; Greet Bries; Véronique Cocquyt; Christian Focan; Stéphanie Henry; Yassine Lalami; Jean-Pascal Machiels; Jeroen Mebis; Nicole Straetmans; Didier Verhoeven; Luc Somers

2010-01-01

20

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

PubMed

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

Nakagawa, Yasunori; Suzuki, Kenshi; Masaoka, Toru

2009-06-01

21

Bloodstream infections and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City.  

PubMed

We assessed the association between bloodstream infections (BSIs) and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City. The estimated length of stay for BSIs was 19 days, which corresponded with a 100% (95% confidence limits, 60%-160%) relative increase in the length of stay compared with patients for whom no pathogen was identified. Feasible options for reducing the length of stay should be considered to alleviate patient and resource burden. PMID:25234044

Avilés-Robles, Martha; Ojha, Rohit P; González, Miriam; Ojeda-Diezbarroso, Karla; Dorantes-Acosta, Elisa; Jackson, Bradford E; Johnson, Kyle M; Caniza, Miguela A

2014-11-01

22

Assessment and management of febrile neutropenia in emergency departments within a regional health authority—a benchmark analysis  

PubMed Central

Objectives Febrile neutropenia is considered an oncologic emergency, for which prompt initiation of antibiotics is essential. Methods We conducted a retrospective cohort study for the 2006 calendar year involving all adult oncology patients presenting with febrile neutropenia to a regional health authority’s emergency departments. The objective was to determine the time from triage to antibiotic administration and its impact on patient outcomes. Results We identified 68 patients presenting with febrile neutropenia, most of whom (76%) were seen in tertiary care centers. Of those patients, 65% were triaged to be seen within 15 minutes of arrival in the emergency room; however, the median time to reassessment was 57 minutes. The median time from triage to antibiotic administration was 5 hours (range: 1.23–22.8 hours). No increased risk of death or increased length of hospital stay was associated with delayed antibiotic administration. Older patients and patients without caregiver support were more likely to experience delayed antibiotic administration (odds ratio: 3.8 and 12.7 respectively). Conclusions We were not able to show a deleterious effect of delay in antibiotic administration, but our analysis identified several points at which patient flow through the emergency room could be improved. PMID:22184489

Szwajcer, D.; Czaykowski, P.; Turner, D.

2011-01-01

23

The safety of full-dose chemotherapy with secondary prophylactic granulocyte colony stimulating factor (G-CSF) following a prior cycle with febrile neutropenia  

Microsoft Academic Search

Secondary prophylactic administration of recombinant human granulocyte colony stimulating factor (G-CSF) following an episode\\u000a of febrile neutropenia is recommended if maintenance of dose-intensity is desired. This policy was adopted in our center in\\u000a patients treated with an intent for cure or durable complete response. The purpose of this study was to evaluate the safety\\u000a and feasibility of this policy. Patients

Nissim Haim; Katerina Shulman; Hadassah Goldberg; Medy Tsalic

2005-01-01

24

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

25

Response of first-line antibiotic therapy in patients with febrile neutropenia during treatment of hematological disorders.  

PubMed

Patients with hematological disorders develop febrile neutropenia (FN); most of these events remain undetermined in origin. We performed a prospective study to determine the microbiological characteristics of infections and their response to the first-line antibiotic therapy in FN. The study was conducted at National Institute of Blood Disease and Bone Marrow Transplant. Two-hundred episodes of FN were assessed for the bacterial growth, antimicrobial susceptibility pattern and response to the first-line treatment of FN. All patients were given Ceftazidime and Amikacin Bosch Pharmaceutical (Pvt. Ltd), as first-line antibiotic in FN. Out of 200 episodes we had 108 clinically and microbiologically documented infections. The isolated frequencies for gram negative and gram positive organisms were n = 52 and 49 (48 and 45 %) respectively. Among gram negative micro-organisms, Escherichia coli (E. coli) was isolated in 15 (28.8 %), Klebsiella pneumonae in 4 (7.6 %) and Pseudomonas aeruginosa in 10 (19.2 %) were in highest frequencies. Methicillin sensitive staphylococci emerged as the frequently isolated gram-positive bacteria. Eight-one episodes (45.3 %) responded to the first-line treatment and death reported in 20 cases (10 %). Our study showed almost equal trend of gram positive and gram negative bacteria isolated from patients suffering from neutropenic fever. Empirical use of Ceftazidime and Amikacin as first-line antibiotics was able to cover the infection only in 45.3 % of episodes suffering from FN. PMID:25825556

Taj, M; Qureshi, R N; Farzana, T; Shamsi, T S; Ahmed, S S

2015-06-01

26

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

PubMed

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

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

2015-01-01

27

Protocol for a systematic review of reductions in therapy for children with low-risk febrile neutropenia  

PubMed Central

Background Febrile neutropenia is a common complication of therapy in children with cancer. Some patients are at low risk of complications, and research has considered reduction in therapy for these patients. A previous systematic review broadly considered whether outpatient treatment and oral antibiotics were safe in this context and concluded that this was likely to be the case. Since that review, there has been further research in this area. Therefore, we aim to provide a more robust answer to these questions and to additionally explore whether the exact timing of discharge, including entirely outpatient treatment, has an impact on outcomes. Methods/design The search will cover MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CDSR, CENTRAL, LILACS, HTA and DARE. A full search strategy is provided. Key conference proceedings and reference lists of included papers will be hand searched. Prominent authors/clinicians in the field will be contacted. We will include randomised and quasi-randomised controlled trials along with prospective single-arm studies that examine the location of therapy and/or the route of administration of antibiotics in children or young adults (aged less than 18 years) who attend paediatric services with fever and neutropenia due to treatment for cancer and are assessed to be at low risk of medical complications. Studies will be screened and data extracted by one researcher and independently checked by a second. All studies will be critically appraised using tools appropriate to the study design. Data from randomised controlled trials (RCTs) will be combined to provide comparative estimates of treatment failure, safety and adequacy. Information from quasi-randomised trials and single-arm studies will provide further data on the safety and adequacy of regimes. Random effects meta-analysis will be used to combine studies. A detailed analysis plan, including assessment of heterogeneity and publication bias, is provided. Discussion This study will aim to specifically define the features of a low-risk strategy that will maintain levels of safety and adequacy equivalent to those of traditional treatments. This will both inform the development of services and provide patients and families with data to help them make an informed decision about care. Systematic review registration PROSPERO CRD42014005817 PMID:25336249

2014-01-01

28

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

PubMed

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

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

2015-03-01

29

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

PubMed Central

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

Rosa, Regis G.

2014-01-01

30

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

PubMed

Febrile neutropenia is the main treatment-related cause of mortality in cancer patients. During June 2012 to April 2014, 97 blood culture samples were collected from patients receiving chemotherapy for hematological malignancy and cancer with febrile neutropenia episodes (FNEs). The samples were examined for the presence of bacteria and fungi using real-time PCR amplification and sequencing of 16S and 18S rRNA genes. Bacteria were identified in 20 of 97 samples (20.6%) by the real-time PCR assay and in 10 of 97 (10.3%) samples by blood culture. In 6 blood culture-positive samples, the real-time PCR assay detected the same type of bacteria. No fungi were detected by the real-time PCR assay or blood culture. During antibiotic therapy, all samples were negative by blood culture, but the real-time PCR assay yielded a positive result in 2 cases of 2 (100%). The bacterial DNA copy number was not well correlated with the serum C-reactive protein titer of patients with FNEs. We conclude that a real-time PCR assay could provide better detection of causative microbes' in a shorter time, and with a smaller blood sample than blood culture. Using a real-time PCR assay in combination with blood culture could improve microbiological documentation of FNEs. PMID:25497674

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

2015-03-01

31

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

PubMed Central

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

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

2015-01-01

32

History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in patients with non-Hodgkin lymphoma not receiving granulocyte colony-stimulating factor prophylaxis.  

PubMed

We conducted a cohort study to examine the association between a wide variety of chronic comorbidities and risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma (NHL) from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California. History of comorbidities and FN events were identified using electronic medical records. Cox model adjusting for propensity score was used to determine the association between a comorbid condition and FN. Models that additionally adjusted for cancer stage, baseline absolute neutrophil count, chemotherapy regimen and dose reduction were also evaluated. A total of 2480 patients with NHL were included, and 60% received CHOP/R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone, with or without rituximab). In total, 236 (9.5%) patients developed FN in the first chemotherapy cycle. Anemia (adjusted hazard ratio [HR] = 1.6, 95% confidence interval [1.2-2.2]), HIV infection (HR = 3.8 [2.0-6.7]) and rheumatoid diseases (HR = 2.4 [1.3-4.0]) were associated with significantly increased risk of FN. These results provide evidence that chronic comorbidity increases the risk of FN. PMID:24684228

Chao, Chun; Rodriguez, Roberto; Page, John H; Yang, Su-Jau; Huynh, Julie; Chia, Victoria M

2015-01-01

33

Healthcare utilisation in patients with breast cancer or non-Hodgkin lymphoma who experienced febrile neutropenia in the Netherlands: a retrospective matched control study using the PHARMO database.  

PubMed

Few data have been published on healthcare resource utilisation associated with chemotherapy-induced febrile neutropenia (FN) in Europe. Using the PHARMO record linkage system, we identified incident adult patients with a primary hospital discharge diagnosis of breast cancer (BC) or non-Hodgkin lymphoma (NHL) from 1998 to 2008. Patients who experienced FN were matched 1:2 non-FN reference patients. Of 1033 BC patients, 80 (8%) had FN and were matched with 160 reference patients; and of 486 NHL patients, 95 (20%) had FN and 89 were matched with 178 reference patients. Significantly more FN patients were hospitalised for any cause than reference patients: BC, 81% vs. 24% (OR 12.6; 95% CI 5.7-27.8); NHL, 82% vs. 44% (OR 6.7; 95% CI 3.3-13.9). Median length of all-cause hospitalisation stay was higher for FN patients: BC, 4.0 vs. 1.0 days; NHL, 8.5 vs. 1.8 days. The median (interquartile range) number of medication treatments was higher for FN patients: BC, 5.5 (4.0-7.5) vs. 2.0 (2.0-4.0); NHL, 8.0 (5.0-11.0) vs. 3.0 (2.0-4.0). In conclusion, FN in patients with BC or NHL had increased healthcare utilisation compared with non-FN patients; thus, efforts to reduce FN are warranted to reduce cost and improve outcomes. PMID:24528512

Issa, D E; Gelderblom, H; Lugtenburg, P J; van Herk-Sukel, M P; Houweling, L M A; De La Orden, M; van der Werf-Langenberg, M E; Nortier, J W R; de Jong, F A

2015-03-01

34

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. PMID:25018856

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

2014-01-01

35

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

PubMed

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

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

2015-02-01

36

Influenza B, Q fever, and the consequences of febrile illness occurring during jungle warfare training: a clinical and serological study.  

PubMed

Seventy-one Royal Marines undergoing jungle warfare training were studied clinically and serologically to determine the incidence and consequences of febrile illness. During acclimatization and the early part of the deployment the incidence of illness having an impact on training was low; during the latter part an outbreak of influenza B occurred, with 25 cases diagnosed clinically. Only 12 of these were confirmed serologically, probably because the outbreak was still in progress when the second samples were taken. A further four subclinical cases were uncovered by the serological study. Five cases of heat exhaustion occurred, one Marine suffering two episodes. Four patients required case-vac from the jungle. Three Marines were found to have serological evidence of previous acute Q fever, including the patient who had two episodes of heat exhaustion. This incidence is higher than expected, and warrants further investigation. PMID:2600890

Wale, M C

1989-01-01

37

Febrile seizures  

PubMed Central

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

2014-01-01

38

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

PubMed Central

Background Febrile neutropenia is an important cause of mortality and morbidity in hematology–oncology patients undergoing chemotherapy. The management of febrile neutropenia is typically algorithm-driven. The aim of this study was to assess the results of a standardized protocol for the treatment of febrile neutropenia. Methods A retrospective cohort study (2011–2012) was conducted of patients with high-risk neutropenia in a hematology–oncology service. Results Forty-four episodes of 17 patients with a median age of 48 years (range: 18–78 years) were included. The incidence of febrile neutropenia was 61.4%. The presence of febrile neutropenia was associated with both the duration and severity of neutropenia. Microbiological agents were isolated from different sources in 59.3% of the episodes with bacteremia isolated from blood being the most prevalent (81.3%). Multiple drug-resistant gram-negative bacilli were isolated in 62.5% of all microbiologically documented infections. Treatment of 63% of the episodes in which the initial treatment was piperacillin/tazobactam needed to be escalated to meropenem. The mortality rate due to febrile neutropenia episodes was 18.5%. Conclusion The high rate of gram-negative bacilli resistant to piperacillin/tazobactam (front-line antibiotics in our protocol) and the early need to escalate to carbapenems raises the question as to whether it is necessary to change the current protocol. PMID:25638764

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

2014-01-01

39

Febrile Seizures  

MedlinePLUS

... term impact that febrile seizures might have on intelligence, behavior, school achievement, and the development of epilepsy. ... and especially very long seizures, on measures of intelligence and on the development of epilepsy. In particular ...

40

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

PubMed

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

Kanai, Hiroaki; Sato, Hiroki; Takei, Yoshichika

2015-03-01

41

[Use of granulocyte-colony stimulating factor(G-CSF)in patients with cancer at high risk of febrile neutropenia on the basis of high age and complications, recommendations for patients receiving radiotherapy, and adverse events because of G-CSF].  

PubMed

Neutropenic complications are the primary dose-limiting toxic effects observed in patients treated with systemic cancer chemotherapy. Broad-spectrum antibiotic therapy should be promptly administered to patients with febrile neutropenia(FN). The risk assessment of FN includes the disease characteristics, chemotherapy regimen, individual patient risk factors, and treatment intent. After considering such risk factors of FN, clinicians should appropriately consider the use of granulocytecolony stimulating factor(G-CSF)as a prophylactic or therapeutic measure. Some types of lymphoma can be cured with chemotherapy. The incidence of FN in patients receiving the standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP)regimen is approximately 20%. Primary prophylactic use of G-CSF is recommended for patients agedB 65 years having diffuse aggressive lymphoma and treated with curative chemotherapy in an effort to improve their quality of life(QOL). Primary prophylaxis is recommended for the prevention of FN in patients at high risk, on the basis of factors other than age. G-CSF should be avoided in patients receiving concomitant chemotherapy and radiation therapy, particularly in those with cancer involving the mediastinum. The adverse events of G-CSF are generally graded mild to moderate; however, rare life-threatening adverse effects have been published in the literature. A clinical practice guideline for the use of G-CSF was published by the Japan Society of Clinical Oncology in 2013. On the basis of this guideline, the above issues have been discussed in this paper. PMID:25129083

Hanada, Naoyuki; Tanaka, Satoshi; Takahata, Takenori; Sato, Atsushi

2014-06-01

42

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

PubMed

Neutropenic sepsis remains a potentially life-threatening complication of anticancer chemotherapy. However, it is possible to identify patients who are at low risk for serious complications and for whom less-intensive, more-convenient treatment may be appropriate. The aim of this study was to assess the efficacy and safety of oral antibiotics in conjunction with early hospital discharge in comparison with standard in-patient intravenous antibiotics in patients with low-risk neutropenic fever. In all, 126 episodes of low-risk neutropenic fever occurred in 102 patients. Patients were randomised to receive either: an oral regimen of ciprofloxacin (750 mg 12 hourly) plus amoxicillin-clavulanate (675 mg 8 hourly) for a total of 5 days, or a standard intravenous regimen of gentamicin and tazocin (piperacillin/tazobactam) until hospital discharge. Patients randomised to oral antibiotics were eligible for discharge following 24 h of hospitalisation, if clinically stable and symptomatically improved. The efficacy of the two arms was similar: initial treatment was successful without antibiotic modification in 90% of episodes in the intravenous arm and 84.8% of episodes in the oral arm, P=0.55, absolute difference between the groups 5.2%; 95% confidence interval (CI) for the difference -7 to 17.3%. Only one episode in the oral arm was associated with significant clinical deterioration: this occurred within the initial in-patient assessment period. The median in-patient stay was 4 days in the intravenous arm (range 2-8) and 2 days in the oral arm (range 1-16 days), P&<0.0005. The reduction in hospital stay led to significant cost-savings in the oral arm. In conclusion, this study suggests that oral antibiotics in conjunction with early hospital discharge for patients who remain stable after a 24 h period of in-patient monitoring offers a feasible and cost-effective alternative to conventional management of low-risk neutropenic fever. PMID:12838298

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

2003-07-01

43

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

PubMed

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

Ratti, Margherita; Tomasello, Gianluca

2015-01-01

44

Plasma levels of procalcitonin and eight additional inflammatory molecules in febrile neutropenic patients  

PubMed Central

OBJECTIVE: This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia. METHOD: We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-?), two soluble TNF-? receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2–3 ml of plasma was obtained from each blood sample and stored at -80°C. RESULTS: The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1. CONCLUSION: Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints. PMID:22012040

Neuenschwander, Letícia Carvalho; Bittencourt, Henrique; Tibúrcio Ribeiro, Ana Flávia; Teixeira, Antônio Lúcio; Teixeira, Mauro M.; Teixeira, Jairo Cerqueira; Nobre, Vandack

2011-01-01

45

Incidence of chemotherapy-induced neutropenia and current practice of prophylaxis with granulocyte colony-stimulating factors in cancer patients in Spain: a prospective, observational study.  

PubMed

We aimed to describe the incidence of neutropenia in breast cancer and lymphoma patients and granulocyte colony-stimulating factors (G-CSF) use in clinical practice. We conducted a multicentre, prospective, observational study including breast cancer and lymphoma patients initiating chemotherapy (? 10% febrile neutropenia risk). We included 734 patients with breast cancer and 291 with lymphoma. Over the first four chemotherapy cycles, patients had an incidence of 11.0% grade 3-4 neutropenia (absolute neutrophil count <1.0 × 10(9) /L) and 4.3% febrile neutropenia (absolute neutrophil count <0.5 × 10(9) /L and fever ? 38 °C) in the breast cancer cohort, and 40.5% and 14.8% in the lymphoma cohort. Full dose on schedule (>85% of planned chemotherapy dose and ? 3 days delay) was achieved by 85.6% of breast cancer and 68.9% of lymphoma patients. Hospitalisation due to febrile neutropenia was required in 2.0% and 12.0% of breast cancer and lymphoma patients respectively. G-CSF was administered to 70.0% of breast cancer and 83.8% of lymphoma patients, and initiated from the first chemotherapy cycle (primary prophylaxis) in 60.6% and 64.2% of cases. Severe neutropenia affects approximately one in 10 breast cancer patients and one in two lymphoma patients receiving chemotherapy with moderate or greater risk of febrile neutropenia. Most patients received treatment with G-CSF in Spanish clinical practice. PMID:23730920

Jolis, L; Carabantes, F; Pernas, S; Cantos, B; López, A; Torres, P; Funes, C; Caballero, D; Benedit, P; Salar, A

2013-07-01

46

Febrile seizures  

MedlinePLUS

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

47

Drug-induced immune neutropenia/agranulocytosis.  

PubMed

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

Curtis, Brian R

2014-01-01

48

A pilot study of outpatient management of febrile neutropenic children with cancer at low risk of bacteremia  

Microsoft Academic Search

Febrile neutropenic children with cancer were eligible for outpatient management with intravenous ceftriaxone therapy if they displayed selected low-risk criteria. Nineteen children were enrolled. All patients had sterile blood cultures, and only one of them was hospitalized because of persistent fever. This pilot study suggests that selected children with febrile neutropenia might be successfully managed without hospitalization. (J PEDIATR 1996;128:847-9)

Mahmoud M. Mustafa; Victor M. Aquino; Alberto Pappo; Isabelle Tkaczewski; George R. Buchanan

1996-01-01

49

Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis.  

PubMed

Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entrée for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host-microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapy-induced tissue damage in order to reduce fever in neutropenic patients with cancer. PMID:25196917

van der Velden, Walter J F M; Herbers, Alexandra H E; Netea, Mihai G; Blijlevens, Nicole M A

2014-11-01

50

A pilot study of the efficacy and safety of empiric daptomycin therapy in oncology patients with fever and severe neutropenia  

PubMed Central

Objectives: Patients with extended periods of time spent with low or absent absolute neutrophil counts (ANCs) are at risk for bacterial infections. Febrile neutropenia is a complication in this patient population, requiring administration of antibiotics. The use of daptomycin in treating patients with febrile neutropenia is not well described. Our objective was to describe the clinical course of febrile neutropenic patients that received daptomycin therapy. Methods: This was an open-labeled, pilot study of 30 patients with documented febrile neutropenia treated with empiric daptomycin. Eligible patients received daptomycin 6?mg/kg/day, in addition to concomitant broad-spectrum antimicrobials. The Kaplan–Meier method was used to estimate the median days to reach an afebrile state and negative bacterial cultures. Results: A total of 30 febrile neutropenic patients were enrolled and received daptomycin as part of an empiric antimicrobial regimen. All patients had severe neutropenia with ANC <100 cells/mm3. Two patients were removed from study due to the development of pneumonia. Clinically, 87% patients improved on daptomycin in combination with Gram-negative coverage, with 73% of patients succeeding therapy. A total of 18 of 19 (95%) subjects with positive blood cultures had microbiological eradication, with the median time to reach an afebrile state of 4.3 days (range 1–13). Four patients were discontinued from daptomycin due to a suspected related adverse event or to clinical failure. Conclusions: This pilot study supports future evaluation of the use of empiric daptomycin therapy in combination with Gram-negative coverage compared with vancomycin in patients with neutropenic fever in a large, randomized controlled trial. PMID:25165552

Kullar, Ravina; Maziarz, Richard T.

2013-01-01

51

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

PubMed Central

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

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

2015-01-01

52

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. PMID:18317581

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

2008-01-01

53

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

54

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

55

Leukopenia and neutropenia induced by quetiapine.  

PubMed

Leukopenia and neutropenia are recognised as side effects of antipsychotic medication, notably clozapine. A case is presented in which a female Caucasian patient who had previously developed these side effects with clozapine also developed them with quetiapine in conjunction with semisodium valproate. There was no such reaction to zuclopenthixol, sulpiride, olanzapine and aripiprazole. It is concluded that caution should be exercised when treating with quetiapine especially where there has been neutropenia with a previous antipsychotic agent. PMID:16930797

Cowan, Colin; Oakley, Clare

2007-01-30

56

Infections in acute leukemia: an analysis of 240 febrile episodes.  

PubMed

Infections are the major cause of morbidity and mortality in acute leukemia patients. Case records of 91 consecutive patients (AML-48, ALL-40, RAEB-t/AML-3) treated between January 1997 and July 1999 were studied to determine the type, frequency and severity of infections. Patients' median age was 36 y (range 6-66) and male to female ratio was 2.5:1. A total of 240 febrile episodes were recorded; of them, 162 were associated with neutropenia (absolute neutrophil count, ANC<500/mm3) and 78 were without neutropenia. Among the neutropenic episodes, an infectious etiology could be documented in 52%; the remainder (48%) were defined as isolated febrile episodes. Chest was the most common site of infection (35. 7%) followed by skin, soft tissue (13%), GIT (7%) and genitourinary tract (6%) infections in order of decreasing frequency. Microbiologically, gram positive organisms (staphylococcus aureus, coagulase negative staphylococcus, streptococcus, enterococcus) were the most common isolates (52.8%) followed by gram negative organisms (E. coli, klebsiella, pseudomonas) in 42.8% of isolates. Two patients had pulmonary tuberculosis and three patients had fungal infections (candida-2, aspergillus-1). Among non-neutropenic patients, infection could be documented in 36%; the remaining 64% were isolated febrile episodes. Gram negative infections were documented in 50%, gram positive in 30% and fungal infections (candida-4, aspergillus-1, mucormycosis-1) in 20% of them. A combination of third generation cephalosporin and an aminoglycoside were used in 79% of episodes initially; a combination of a newer penicillin and aminoglycoside (4.6%), double betalactums (4.1%), oral antibiotics (9.8%) and others were used in the remaining episodes. Fever resolved in 38% of episodes using the above combinations; in the remainder second line antibiotics (mainly vancomycin) and antifungals (amphotericin-B) were added empirically or depending on culture and sensitivity. In 52.5% of episodes fever resolved after addition of second line antibiotics and antifungals. 11 of 91 patients died of infectious complications in this study. There is a need for improvised diagnostic tests to detect infections early as well as for new therapies to overcome antimicrobial resistance. PMID:10871816

Jagarlamudi, R; Kumar, L; Kochupillai, V; Kapil, A; Banerjee, U; Thulkar, S

2000-05-01

57

Fungal infections in patients with neutropenia: challenges in prophylaxis and treatment.  

PubMed

Fungal infections are a leading cause of mortality in patients with neutropenia. Candidiasis and aspergillosis account for most invasive fungal infections. General prophylactic measures include strict hygiene and environmental measures. Haemopoietic growth factors shorten the duration of neutropenia and thus may reduce the incidence of fungal infections. Fluconazole is appropriate for antifungal prophylaxis and should be offered to patients with prolonged neutropenia, such as high-risk patients with leukaemia undergoing remission induction or consolidation therapy and high-risk stem cell transplant recipients. Empirical antifungal therapy is mandatory in patients with persistent febrile neutropenia who fail to respond to broad-spectrum antibacterials. Intravenous amphotericin B at a daily dose of 0.6 to 1 mg/kg is preferred whenever aspergillosis cannot be ruled out. Lipid formulations of amphotericin B have demonstrated similar efficacy and are much better tolerated. Fluconazole is the best choice for acute candidiasis in stable patients; amphotericin B should be used in patients with unstable disease. Use of fluconazole is restricted by the existence of resistant strains (Candida krusei and, to a lesser extent, C. glabrata). Amphotericin B still remains the gold standard for invasive aspergillosis. Lipid formulations of amphotericin B are effective in aspergillosis and because they are less nephrotoxic are indicated in patients with poor renal function. Itraconazole is an alternative in patients who have good intestinal function and are able to eat. Mucormycosis, trichosporonosis, fusariosis and cryptococcosis are less common but require specific management. New antifungal agents, especially new azoles, are under development. Their broad in vitro spectrum and preliminary clinical results are promising. PMID:11190415

Herbrecht, R; Neuville, S; Letscher-Bru, V; Natarajan-Amé, S; Lortholary, O

2000-11-01

58

Febrile Seizure: Demographic Features and Causative Factors  

PubMed Central

Objective Because of geographical and periodical variation, we prompted to determine the demographic features and causative factors for febrile seizure in Rasht. Materials & Methods In this cross-sectional study, all 6–month- to 6-year-old children with the diagnosis of febrile seizure admitted to 17 Shahrivar hospital in Rasht, from August, 2009 to August, 2010 were studied. Age, sex, family history of the disease, seizure types, body temperature upon admission and infectious causes of the fever were recorded. All statistical analysis was performed with SPSS software, version 16. Results Of the 214 children (mean age, 25.24±15.40 months), 124 were boys and 109 had a positive family history. Complex seizures were seen in 39 cases. In patients with a complex febrile seizure, 59% had the repetitive type, 20.5% had the focal type and 20.5% had more than 15 minutes duration of seizures. Most of the repetitive seizures (78.3%) occurred in patients under 2 years old; the difference between under and over 2-year-old patients was statistically significant. Study results did not show significant differences between the two genders for simple or complex seizures. The mean body temperature upon admission was 38.2±1.32?C (38.31±0.82 degrees in boys and 38.04±1.78 in girls). Upper respiratory infections were seen in most patients (74.29%). All cases of lower respiratory infections were boys. There was a statistically significant difference between boys and girls in causes of fever. Conclusion Most of the children had a positive family history and the most common causative factor was upper respiratory infection. PMID:24665278

ESMAILI GOURABI, Hamed; BIDABADI, Elham; CHERAGHALIPOUR, Fatemeh; AARABI, Yasaman; SALAMAT, Fatemeh

2012-01-01

59

Refractory Thrombocytopenia and Neutropenia: a Diagnostic Challenge  

PubMed Central

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

Gyan, Emmanuel; Dreyfus, François; Fenaux, Pierre

2015-01-01

60

Are febrile seizures an indication for intermittent benzodiazepine treatment, and if so, in which cases?  

PubMed

Febrile seizures occur in ?4% of children. After a first febrile seizure, the risk of recurrence is ?40%, but excellent studies document that febrile seizures do not cause brain damage or deficits in cognition or behaviour. The risk of subsequent epilepsy is 2-4%. Prolonged febrile seizures are of concern because a child may later develop mesial temporal sclerosis and intractable epilepsy in rare cases. Most prolonged febrile seizures represent the first febrile seizure and cannot be anticipated. A first prolonged febrile seizure does not increase the risk of recurrence, but if there is a recurrence, it is more likely to be prolonged. Prevention of recurrent febrile seizures is difficult. Antipyretics are ineffective. Daily AED treatment is not often justified. Intermittent oral diazepam at the time of illness is not very successful and has significant side effects. The most optimistic study found that the number of subjects required to treat in order to prevent one recurrence was 14. Intermittent clobazam has fewer side effects than diazepam and may be somewhat effective. Rescue benzodiazepines given outside health care facilities may be effective in selected patients to prevent prolonged recurrences, although this has not been proven with rectal diazepam which has been more extensively studied than buccal or nasal midazolam. Currently, we suggest that, for children with febrile seizures, candidates for consideration for rescue benzodiazepines are those with a prolonged febrile seizure or poor access to medical care. It is possible that the use of a rescue benzodiazepine may alleviate severe parental anxiety, but this remains to be established. PMID:25299426

Camfield, Peter; Camfield, Carol

2014-10-01

61

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. PMID:24887148

2014-01-01

62

Neutropenia in type Ib glycogen storage disease  

PubMed Central

Purpose of review Glycogen storage disease type Ib (GSD-Ib), characterized by disturbed glucose homeostasis, neutropenia, and neutrophil dysfunction, is caused by a deficiency in a ubiquitously expressed glucose-6-phosphate transporter (G6PT). G6PT translocates glucose-6-phosphate (G6P) from the cytoplasm into the lumen of the endoplasmic reticulum, where it is hydrolyzed to glucose either by a liver/kidney/intestine-restricted glucose-6-phosphatase-? (G6Pase-?) or by a ubiquitously expressed G6Pase-?. The role of the G6PT/G6Pase-? complex is well established and readily explains why G6PT disruptions disturb interprandial blood glucose homeostasis. However, the basis for neutropenia and neutrophil dysfunction in GSD-Ib are poorly understood. Recent studies that are now starting to unveil the mechanisms are presented in this review. Recent Findings Characterization of G6Pase-? and generation of mice lacking either G6PT or G6Pase-? have shown that neutrophils express the G6PT/G6Pase-? complex capable of producing endogenous glucose. Loss of G6PT activity leads to enhanced ER stress, oxidative stress, and apoptosis that underlie neutropenia and neutrophil dysfunction in GSD-Ib. Summary Neutrophil function is intimately linked to the regulation of glucose and G6P metabolism by the G6PT/G6Pase-? complex. Understanding the molecular mechanisms that govern energy homeostasis in neutrophils has revealed a previously unrecognized pathway of intracellular G6P metabolism in neutrophils. PMID:19741523

Chou, Janice Y.; Jun, Hyun Sik; Mansfield, Brian C.

2011-01-01

63

Prevalence, phenotype and inheritance of benign neutropenia in Arabs  

PubMed Central

Background Benign neutropenia, i.e., neutropenia not associated with an increased risk of infection, may result in serious medical consequences when a 'standard' definition of neutropenia (absolute neutrophil count (ANC) < 1.5 × 109cells/L) is universally applied to all races. The aims of this study were to determine the prevalence of benign neutropenia among healthy Arabs and evaluate its mode of inheritance. Methods ANCs were studied prospectively amongst a healthy indigenous population (n = 1032) from the United Arab Emirates undergoing a nation-wide sickle-cell and thalassemia screening program. The mean neutrophil count and the prevalence of benign neutropenia were compared by age, sex and amongst various tribes. Results The mean neutrophil count (× 109cells/L) was 3.3 (range 0.95–7.6). Benign neutropenia was present in 110 (10.7%) subjects of whom 24 (2.3%) individuals had moderate neutropenia (ANC 0.5 – 1.0 × 109 cells/L). In the 22 tribe-family groups, the prevalence of benign neutropenia varied between 0% and 38%. Benign neutropenia showed no difference in the frequency amongst the sexes (p = 0.23) and it was independent of age (Spearman's rho = 0.05, p = 0.13). The age-related mean neutrophil count was the lowest in Arabs when compared with other ethnic groups (Blacks, Europeans and Mexicans). The inheritance of benign neutropenia was consistent with an autosomal dominant pattern; however, the diversity of observed phenotypes suggested the presence of more than one genetic variant for this trait. Conclusion Arabs have a high prevalence of benign neutropenia that may be inherited as an autosomal dominant trait. PMID:19323844

Denic, Srdjan; Showqi, Saad; Klein, Christoph; Takala, Mohamed; Nagelkerke, Nicollas; Agarwal, Mukesh M

2009-01-01

64

Febrile Seizures and Epilepsy: Possible Outcomes  

MedlinePLUS

... more complex features. WHAT IS THE CONNECTION BETWEEN FE- BRILE SEIZURES AND LATER DEVELOPMENT OF EPILEPSY? Overall, ... more febrile seizures. WHAT IS THE CONNECTION BETWEEN FE- BRILE SEIZURES AND LATER DEVELOPMENT OF SPECIFIC TYPES ...

65

A case of onycotricodysplasia with intellectual disability, without neutropenia.  

PubMed

Onychotrichodysplasia, a rare autosomal recessive disorder, presents with hypoplastic fingernails, trichorrhexis, chronic neutropenia, and psychomotor retardation. Here, we describe a rare presentation of a child with onycotrichodysplasia associated with intellectual disability, but without neutropenia. He had sparse, short, dry, curly hair, dysplastic nails and intellectual disability. In contrast to cases described earlier, our patient had normal neutrophil count. PMID:23072187

Ikbal, M; Eker, H K; Tos, T; Alp, M Y; Cebi, A H

2012-01-01

66

Dose Schedule Optimization and the Pharmacokinetic Driver of Neutropenia  

PubMed Central

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

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

2014-01-01

67

Safety, tolerability, and pharmacokinetics of Micafungin (FK463) in febrile neutropenic pediatric patients.  

PubMed

Micafungin (FK463) is a new parenteral echinocandin. A multicenter, phase I, open-label, sequential-group dose escalation study was conducted to assess the safety, tolerability, and pharmacokinetics of micafungin in neutropenic pediatric patients. A total of 77 patients stratified by age (2 to 12 and 13 to 17 years) received micafungin. Therapy was initiated at 0.5 mg/kg per day and escalated to higher dose levels of 1.0, 1.5, 2.0, 3.0, and 4.0 mg/kg per day. Micafungin was administered within 24 h of initiating broad-spectrum antibacterial antibiotics for the new onset of fever and neutropenia. The most common overall adverse events in the study population were diarrhea (19.5%), epistaxis (18.2%), abdominal pain (16.9%), and headache (16.9%). Nine patients (12%) experienced adverse events considered by the investigator to be possibly related to the study drug. The most common related events were diarrhea, vomiting, and headache, all occurring in two patients each. There was no evidence of a dose-limiting toxicity as defined within the prespecified criteria of this clinical protocol. There was one death during the study due to septic shock. The pharmacokinetic profiles for micafungin over the 0.5- to 4.0-mg/kg dose range demonstrated dose linearity. Clearance, volume of distribution, and half-life remained relatively constant over the dose range and did not change with repeated administration. The overall plasma pharmacokinetic profile was similar to that observed in adults. However, there was an inverse relation between age and clearance. For patients 2 to 8 years old, clearance was approximately 1.35 times that of patients >/=9 years of age. In summary, micafungin over a dosage range between 0.5 and 4.0 mg/kg/day in 77 febrile neutropenic pediatric patients displayed linear pharmacokinetics and increased clearance as a function of decreasing age. PMID:16048942

Seibel, Nita L; Schwartz, Cindy; Arrieta, Antonio; Flynn, Patricia; Shad, Aziza; Albano, Edith; Keirns, James; Lau, Wendi M; Facklam, David P; Buell, Donald N; Walsh, Thomas J

2005-08-01

68

Safety, Tolerability, and Pharmacokinetics of Micafungin (FK463) in Febrile Neutropenic Pediatric Patients  

PubMed Central

Micafungin (FK463) is a new parenteral echinocandin. A multicenter, phase I, open-label, sequential-group dose escalation study was conducted to assess the safety, tolerability, and pharmacokinetics of micafungin in neutropenic pediatric patients. A total of 77 patients stratified by age (2 to 12 and 13 to 17 years) received micafungin. Therapy was initiated at 0.5 mg/kg per day and escalated to higher dose levels of 1.0, 1.5, 2.0, 3.0, and 4.0 mg/kg per day. Micafungin was administered within 24 h of initiating broad-spectrum antibacterial antibiotics for the new onset of fever and neutropenia. The most common overall adverse events in the study population were diarrhea (19.5%), epistaxis (18.2%), abdominal pain (16.9%), and headache (16.9%). Nine patients (12%) experienced adverse events considered by the investigator to be possibly related to the study drug. The most common related events were diarrhea, vomiting, and headache, all occurring in two patients each. There was no evidence of a dose-limiting toxicity as defined within the prespecified criteria of this clinical protocol. There was one death during the study due to septic shock. The pharmacokinetic profiles for micafungin over the 0.5- to 4.0-mg/kg dose range demonstrated dose linearity. Clearance, volume of distribution, and half-life remained relatively constant over the dose range and did not change with repeated administration. The overall plasma pharmacokinetic profile was similar to that observed in adults. However, there was an inverse relation between age and clearance. For patients 2 to 8 years old, clearance was approximately 1.35 times that of patients ?9 years of age. In summary, micafungin over a dosage range between 0.5 and 4.0 mg/kg/day in 77 febrile neutropenic pediatric patients displayed linear pharmacokinetics and increased clearance as a function of decreasing age. PMID:16048942

Seibel, Nita L.; Schwartz, Cindy; Arrieta, Antonio; Flynn, Patricia; Shad, Aziza; Albano, Edith; Keirns, James; Lau, Wendi M.; Facklam, David P.; Buell, Donald N.; Walsh, Thomas J.

2005-01-01

69

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

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

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

2013-12-01

70

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. PMID:21595885

2011-01-01

71

Water Extract of Deer Bones Activates Macrophages and Alleviates Neutropenia  

PubMed Central

Extracts from deer bones, called nok-gol in Korean, have long been used to invigorate Qi. While neutropenia is not well detected in normal physiological condition, it could be a cause of severe problems to develop diseases such as infectious and cancerous diseases. Thus, a prevention of neutropenia in normal physiology and pathophysiological states is important for maintaining Qi and preventing disease progress. In cell biological aspects, activated macrophages are known to prevent neutropenia. In this study, we demonstrate that water extract of deer bone (herein, NG) prevents neutropenia by activating macrophages. In mouse neutropenia model system in vivo where ICR mice were treated with cyclophosphamide to immunosuppress, an oral administration of NG altered the number of blood cells including lymphocytes, neutrophils, basophils, and eosinophils. This in vivo effect of NG was relevant to that of granulocyte colony stimulating factor (G-CSF) that was known to improve neutropenia. Our in vitro studies further showed that NG treatment increased intracellular reactive oxygen species (ROS) and promoted macrophagic differentiation of mouse monocytic Raw264.7 cells in a dose-dependent manner. In addition, NG enhanced nitric oxide (NO) synthesis and secretions of cytokines including IL-6 and TNF-?. Consistently, NG treatment induced phosphorylation of ERK, JNK, IKK, I?B?, and NF-?B in Raw264.7 cells. Thus, our data suggest that NG is helpful for alleviating neutropenia. PMID:23840259

Choi, Han-Seok; Kim, Soon Re; Hong, Se Hyang; Ku, Jin Mo; Kim, Min Kyoung; Seo, Hye Sook; Cho, Sung-Gook; Shin, Sangtae; Shin, Yong Cheol; Ko, Seong-Gyu

2013-01-01

72

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. PMID:7492199

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

1995-01-01

73

Tocilizumab-induced neutropenia in rheumatoid arthritis patients with previous history of neutropenia: case series and review of literature.  

PubMed

One of the adverse events of tocilizumab (TCZ) is a transient, dose-dependent neutropenia. The recommendations of the Summary of Product Characteristics state that this neutropenia should be managed according to the absolute neutrophil count (ANC). However, the approach to a patient who had a history of neutropenia induced by previous DMARDs and developed TCZ-induced neutropenia remains unclear. We would like to report a series of four patients with rheumatoid arthritis who developed Grade 2 neutropenia (ANC 1-1.5 × 10(9)/L) following intravenous TCZ treatment at a dose of 8 mg/kg. All of them had a previous history of neutropenia (Grade 2 or Grade 3) due to Etanercept (three patients) and Sulfasalazine (one patient). Therefore, we decided to decrease the TCZ dosage by 10-20% approximately. Reducing of the dosage did not have any influence on the efficacy of TCZ, and all of our patients remained in clinical remission. The mechanisms underlying neutropenia induced by Tocilizumab, Etanercept and Sulfasalazine are also discussed in this article. PMID:25403696

Shovman, O; Shoenfeld, Y; Langevitz, P

2015-02-01

74

Febrile urinary tract infections: clinical and laboratory diagnosis, imaging, and prognosis.  

PubMed

According to the literature, febrile urinary tract infections (UTIs) are among the most common severe bacterial infections occurring in childhood, with potential serious long-term consequences. In recent years, there have been significant developments in our understanding of the pathophysiology and clinical and laboratory issues of febrile UTIs. Studies are focusing on the role of predisposing host factors related to genes regulating immune response, inflammation and fibrosis in the development of acute renal damage and subsequent processes leading to renal scars. All the available guidelines underline the importance of a correct diagnosis of febrile UTI to allow a more rational use of antibiotics and imaging. As a consequence, a shift from aggressive imaging studies to a more restrictive and targeted approach has been recently observed. Regarding the prognosis of febrile UTI, the introduction of prenatal ultrasound studies revealed that a great portion of the alterations at imaging (and thus of the clinical complications), previously attributed to postinfection scarring, were because of congenital kidney and urinary tract abnormalities. Although the long-term consequences of febrile UTIs are difficult to ascertain, it seems that children with febrile UTI, normal renal function and normal kidneys at start present a very low risk of developing decreased renal function or hypertension during follow-up. However, high body temperature and high procalcitonin levels during the acute phase of disease, which are indicative of severe inflammation, and the finding of renal scarring on imaging with DMSA scintigraphy 6 months after febrile UTI, together with the detection of congenital kidney and urinary tract abnormalities, indicate "kidney at risk" in UTI. PMID:24484749

Edefonti, Alberto; Tel, Francesca; Testa, Sara; De Palma, Diego

2014-03-01

75

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

PubMed

Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-?), soluble TNF-? I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1? (MIP-1? or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48 h before the onset of fever and within 24?h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11 h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514 pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients. PMID:23369970

Ribeiro, A F Tibúrcio; Nobre, V; Neuenschwander, L C; Teixeira, A L; Xavier, S G; Paula, F D F; Teixeira, M M; Teixeira, J C A; Bittencourt, H

2013-02-01

76

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

PubMed Central

Febrile neutropenia remains a frequent complication in onco-hematological patients, and changes in the circulating level of inflammatory molecules (IM) may precede the occurrence of fever. The present observational prospective study was carried out to evaluate the behavior of plasma tumor necrosis factor alpha (TNF-?), soluble TNF-? I and II receptors (sTNFRI and sTNFRII), monocyte chemoattractant protein-1 [MCP-1 or chemokine (c-c motif) ligand 2 (CCL2)], macrophage inflammatory protein-1? (MIP-1? or CCL3), eotaxin (CCL11), interleukin-8 (IL-8 or CXCL8), and interferon-inducible protein-10 (IP-10 or CXCL10) in 32 episodes of neutropenia in 26 onco-hematological patients. IM were tested on enrollment and 24-48?h before the onset of fever and within 24?h of the first occurrence of fever. Eight of 32 episodes of neutropenia did not present fever (control group) and the patients underwent IM tests on three different occasions. sTNFRI levels, measured a median of 11?h (1-15) before the onset of fever, were significantly higher in patients presenting fever during follow-up compared to controls (P = 0.02). Similar results were observed for sTNFRI and CCL2 levels (P = 0.04 for both) in non-transplanted patients. A cut-off of 1514?pg/mL for sTNFRI was able to discriminate between neutropenic patients with or without fever during follow-up, with 65% sensitivity, 87% specificity, and 93% positive predictive value. Measurement of the levels of plasma sTNFRI can be used to predict the occurrence of fever in neutropenic patients. PMID:23369970

Ribeiro, A.F. Tibúrcio; Nobre, V.; Neuenschwander, L.C.; Teixeira, A.L.; Xavier, S.G.; Paula, F.D.F.; Teixeira, M.M.; Teixeira, J.C.A.; Bittencourt, H.

2013-01-01

77

Frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria.  

PubMed

6 out of 7 patients with severe neutropenia associated with the use of amodiaquine for malaria prophylaxis amodiaquine (400 mg weekly) plus proguanil (200 mg daily); 1 of these patients had also taken cotrimoxazole and another had taken sulphaguanidine. The 7th patient had taken amodiaquine alone, but at a higher dose. A retrospective analysis suggests that the frequency of severe neutropenia complicating amodiaquine taken prophylactically may be as high as 1 in 2000. PMID:2868340

Hatton, C S; Peto, T E; Bunch, C; Pasvol, G; Russell, S J; Singer, C R; Edwards, G; Winstanley, P

1986-02-22

78

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

PubMed Central

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reported GATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. PMID:23223431

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

2013-01-01

79

Neutrophil elastase in cyclic and severe congenital neutropenia  

PubMed Central

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

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

2007-01-01

80

Systematic search for neutropenia should be part of the first screening in patients with poikiloderma.  

PubMed

Poikiloderma occurs in a number of hereditary syndromes, the best known of which is Rothmund-Thomson syndrome (RTS). Differential diagnoses include Dyskeratosis Congenita (DC) with high genetic heterogeneity and Clericuzio-type Poikiloderma with Neutropenia (CPN) due to mutations in the C16orf57 gene. Mutations in the RECQL4 gene are only observed in two thirds of RTS patients. In this study, 10 patients referred for syndromic poikiloderma and negative for RECQL4 sequencing analysis were investigated for C16orf57 mutations. Two C16orf57 heterozygous nonsense mutations (p.W81X and p.Y89X) were identified in a 5-year-old female child presenting with generalized poikiloderma, dental dysplasia, gingivitis, nail dystrophy, palmoplantar keratoderma and pachyonychia of the great toenails. Previously undetected and silent neutropenia was evidenced after C16orf57 molecular analysis. Neutropenia was absent in the C16orf57-negative patients. This report confirms that neutrophil count should be performed in all patients with poikiloderma to target the C16orf57 gene sequencing analysis, prior to RECQL4 analysis. PMID:21872685

Piard, Juliette; Holder-Espinasse, Muriel; Aral, Bernard; Gigot, Nadège; Rio, Marlène; Tardieu, Marc; Puzenat, Eve; Goldenberg, Alice; Toutain, Annick; Franques, Jerôme; MacDermot, Kay; Bessis, Didier; Boute, Odile; Callier, Patrick; Gueneau, Lucie; Huet, Frédéric; Vabres, Pierre; Catteau, Benoît; Faivre, Laurence; Thauvin-Robinet, Christel

2012-01-01

81

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

PubMed

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

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

2015-02-01

82

Hippocampal Sclerosis After Febrile Status Epilepticus: The FEBSTAT Study  

PubMed Central

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

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

2014-01-01

83

Amphotericin B deoxycholate (d-AMB) use in cases with febrile neutropenia and fungal infections: lower toxicity with suitable premedication.  

PubMed

In spite of the development of new antifungal drugs, amphotericin B deoxycholate (d-AMB) remains the gold standard in the treatment of severe fungal infections in immunosuppressed hosts. However, d-AMB is a toxic drug, the most important dose-limiting toxicities being nephrotoxicity and infusion-related allergic reactions. Lipid and liposomal formulations of d-AMB have relatively lower toxicity and are considered alternative choices. However, the routine use of these formulations is limited by their higher cost. Using retrospective analysis, we explored the incidence of nephrotoxicity and allergic reactions requiring the cessation of conventional d-AMB in 113 cases treated with the drug. In contrast to knowledge in the relevant literature, we did not detect significant toxicity, which would have required discontinuation of the d-AMB treatment. Mean serum creatinine levels were 0.72 +/- 0.25 and 0.84 +/- 0.31 mg dl(-1) before and after therapy, respectively. Although the difference between creatinine levels before and after d-AMB is statistically significant, the creatinine level increased twofold in only eight cases. Mean serum potassium levels were 3.8 +/- 0.54 and 3.6 +/- 0.7 mmol l(-1) before and after d-AMB respectively. Potassium levels below 3 mmol l(-1) were found in 7 and 17 cases before and after d-AMB respectively. Potassium levels were statistically lower in cases with fungal mucositis. Severe infusion-related allergic reactions were observed in three cases. Antihistamine and corticosteroid were added to the treatment in these cases. With these findings, we can conclude that d-AMB is a tolerable, low cost drug which can be safely used provided there is suitable premedication and monitoring of blood urea nitrogen, serum potassium and magnesium levels. PMID:17305778

Oto, Ozgur Akin; Paydas, Semra; Disel, Umut; Yavuz, Sinan; Seydaoglu, Gulsah

2007-03-01

84

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. PMID:22942808

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

2012-01-01

85

Factors associated with severe sepsis: prospective study of 94 neutropenic febrile episodes.  

PubMed

Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion abnormalities predispose to septic shock and increased mortality in neutropenic setting. We aimed at determining predictors of severe sepsis in neutropenic patients. Between 1 October and 31 December 2007, 41 patients (21 with acute myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem cell transplantation for a mantle cell lymphoma) with chemotherapy-induced neutropenia (<0.5 x 10(9)/l) lasting for more than 7 days were included in this study. The median age was 28 years (range: 3-58 years). All patients were on oral antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B) prophylaxis. The first neutropenic febrile episode was treated with piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h from the start of this first line of treatment, amphotericin B i.v. is added. Imipenem was introduced in the case of non-response and finally glycopeptides were introduced according to the IDSA criteria. Severe sepsis and septic shock are defined according to the criteria of the consensus conference of the ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic. Ninety-four febrile episodes were observed: 27 microbiologically documented (28.7%), six clinically documented (6.3%) and 61 fever of unknown origin (65%). Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram-positive organisms and three combined (Gram+ and -). Clinically documented infections were pneumonia (two), neutropenic enterocolitis (one), sinuses infection (one) and cutaneous infection (two). Severe sepsis accounted for 22 febrile episodes. Factors associated with the occurrence of severe sepsis were: hypophosphatemia (<0.8 mmol/l; p=0.05, OR=3.9, 95% CI: 1.3-45.7), hypoproteinemia (<62 g/l; p=0.006, OR=4.1, 95% CI: 1.4-11.4) and non-adapted antibiotherapy at the onset of severe sepsis (p=0.019, OR=2.7, 95% CI: 1.02-7.39). However, heart rate/systolic blood pressure ratio <1.1 (p<0.001, OR=0.1, 95% CI: 0.03-0.31) and Creactive protein <80 mg (p=0.001, OR=0.14, 95% CI: 0.04-0.54) were not predictive. PMID:20132659

Jeddi, Ramzi; Achour, Mériem; Amor, Ramzi Ben; Aissaoui, Lamia; Bouterâa, Walid; Kacem, Karima; Lakhal, Raihane Ben; Abid, Héla Ben; BelHadjAli, Zaher; Turki, Amel; Meddeb, Balkis

2010-02-01

86

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

87

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. PMID:22490769

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

2014-01-01

88

Intermittent clobazam therapy in febrile seizures  

Microsoft Academic Search

Objective: To evaluate the efficacy of intermittent clobazam therapy in preventing the recurrence of febrile seizures and to assess\\u000a its safety.Methods: The study was a prospective, randomized, double-blind placebo-controlled trial conducted in the Department of Child Health,\\u000a Christian Medical College Hospital, Vellore between July 2001 and September 2002. Neurologically normal children between 6\\u000a months and 3 years of age with

Winsley Rose; Chellam Kirubakaran; Julius Xavier Scott

2005-01-01

89

Failure of phenobarbitone to prevent febrile convulsions.  

PubMed Central

One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage. PMID:1260273

Heckmatt, J Z; Houston, A B; Clow, D J; Strephenson, J B; Dodd, K L; Lealman, G T; Logan, R W

1976-01-01

90

Interventional antimicrobial therapy in febrile neutropenic patients  

Microsoft Academic Search

Summary In this prospective multicenter trial, treatment strategies for 1573 patients with neutropenia n=258): 74.4%, CEPH\\/AMG (n=252): 73.4%; PEN\\/CEPH (n=290): 70.0%. Total response rate was 72.5%. In phase II, patients not responding after 3 days received PEN\\/CEPH\\/vancomycin (n=70) or PEN\\/CEPH\\/AMG (n=74). The respective response rates were 52.9% and 55.4%, total 54.2%. If fever did not resolve, the patients received either

H. Link; G. Maschmeyer; P. Meyer; W. Hiddemann; W. Stille; M. Helmerking

1994-01-01

91

Micafungin compared with caspofungin for the treatment of febrile episodes in neutropenic patients with hematological malignancies: A retrospective study  

PubMed Central

BACKGROUND: Invasive fungal infections are associated with morbidity and mortality in neutropenia secondary to hematological malignancies. Empirical antifungal agents are used to reduce their consequences. Caspofungin is the only echinocandin approved for this indication. Micafungin was compared with caspofungin for the treatment of patients with hematological malignancies and prolonged neutropenia. METHODS: A retrospective cohort study was conducted involving patients who had hematological malignancies with profound neutropenia for a minimum of 10 days, and received empirical micafungin or caspofungin for a minimum of five days, between April 2005 and November 2009. Successful outcome was based on a composite end point: survival for a minimum of seven days following antifungal cessation, successful treatment of baseline fungal infection, absence of adverse events and absence of breakthrough fungal infection. Fungal infections were defined according to revised definitions of invasive fungal disease from the 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) criteria, with modification of the diagnostic imaging criteria. RESULTS: Micafungin had similar overall success to caspofungin (60.4% [29 of 48] versus 57.3% [47 of 82], respectively; P=0.729). Survival was higher in the micafungin group compared with the caspofungin group (100% [48 of 48] versus 89% [73 of 82]; P=0.02). No baseline invasive fungal infections were identified in the micafungin group, compared with three proven infections treated successfully with caspofungin (3.7%; P=0.18). Three proven breakthrough infections were observed in the micafungin group (three of 48 [27.3%]) compared with none in the caspofungin group (zero of 82; P=0.02). CONCLUSION: Micafungin has similar efficacy to caspofungin as empirical antifungal therapy in febrile neutropenic patients with hematological malignancies. Verification of these results in a prospective trial is warranted. PMID:25587291

Shalhoub, Sarah; Wang, Luchen; Ching, Arthur; Husain, Shahid; Rotstein, Coleman

2014-01-01

92

The cause of fever following resolution of neutropenia in patients with acute leukemia.  

PubMed

Many studies have examined the etiology of fever complicating neutropenia. Little is known about the etiology of fever occurring immediately following recovery from myelosuppression. We reviewed 165 episodes of fever in patients who were admitted to the University of Pennsylvania Medical Center (Philadelphia) between 1 August 1992 and 15 August 1994 for the treatment of acute leukemia. We included patients who had episodes of fever (temperature of > or = 38 degrees C) for > or = 48 hours within 10 days after an absolute neutrophil count of < or = 500 cells/mm3 was determined. Twenty-nine (20%) of 145 episodes met these criteria. In 5 (17%) of 29 episodes the cause of fever was a bacterial infection, in 6 (21%) of 29 episodes the cause of fever was noninfectious, and in 12 (41%) of 29 episodes the cause of fever was unknown. Six (21%) of 29 episodes were due to documented or suspected fungal infection, four were due to suspected pulmonary aspergillosis, and two were due to systemic candidal infections. Fever following recovery from chemotherapy-induced neutropenia is common. Fungal infections occur frequently after recovery from myelosuppression despite widespread use of empirical and prophylactic antifungal therapy. Improved strategies for diagnosing and preventing fungal infections in patients who have fever following recovery from myelosuppression are clearly needed. PMID:8783711

Barton, T D; Schuster, M G

1996-06-01

93

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. PMID:24575264

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

2013-01-01

94

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

95

ORIGINAL CONTRIBUTION A Novel Locus for Generalized Epilepsy With Febrile  

E-print Network

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

Boyer, Edmond

96

Methimazole associated neutropenia in a preterm neonate treated for hyperthyroidism.  

PubMed

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

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

2015-01-01

97

Methimazole Associated Neutropenia in a Preterm Neonate Treated for Hyperthyroidism  

PubMed Central

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

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

2015-01-01

98

Study design: two long-term observational studies of the biosimilar filgrastim Nivestim™ (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 PMID:24237790

2013-01-01

99

The role of interleukin-1? in febrile seizures  

PubMed Central

Febrile seizures (FS) occur in children as a result of fever. Despite their prevalence, the pathophysiology of FS has remained unclear. Recent evidence from clinical and experimental studies has highlighted a potential role of immune generated products in the genesis of FS. Of particular interest are the pro-inflammatory cytokine, interleukin 1beta (IL-1?) and its naturally occurring antagonist, interleukin 1 receptor antagonist (IL-1ra). Using a novel animal model of FS, involving the generation of physiological fever, we investigated the role of the IL-1?/IL-1ra system in the genesis of FS. We found that animals with FS had increased hippocampal and hypothalamic IL-1? compared to equally treated animals without FS, which was first evident at onset of FS in the hippocampus. There were no differences in IL-1ra levels. ICV IL-1? increased the number of animals with FS while IL-1ra had an opposite anti-convulsant effect. The data from these studies, in combination with recent results from other laboratories, have established a putative role for the IL-1?/IL-1ra system in the genesis of FS. PMID:19217733

HEIDA, James G.; MOSHÉ, Solomon L.; PITTMAN, Quentin J.

2009-01-01

100

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

PubMed Central

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

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

2014-01-01

101

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

PubMed

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

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

2014-01-01

102

Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia  

PubMed Central

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

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

2015-01-01

103

Undifferentiated Febrile Illness in Kathmandu, Nepal  

PubMed Central

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

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

2015-01-01

104

Undifferentiated febrile illness in kathmandu, Nepal.  

PubMed

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

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

2015-04-01

105

Empirical voriconazole therapy for febrile neutropenic patients with hematological disorders: a prospective multicenter trial in Japan.  

PubMed

An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. In addition, to find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. Plasma (1-3)-?-D-glucan and Aspergillus PCR in blood were also measured to improve the diagnostic accuracy. A total of 103 patients (median age, 59 years), including 25 undergoing induction chemotherapies and 19 allogeneic hematopoietic cell transplants, were evaluable. Sixty-nine percent of the patients achieved resolution of clinical symptoms and 31% achieved treatment success, defined as fulfilling the previously described five-part composite endpoint. Although VRCZ was discontinued in 9.7% of the patients because of adverse effects, all the patients recovered soon after discontinuation of VRCZ. The treatment success rate of VRCZ appeared to be higher in patients categorized as "not classified" compared with "possible invasive fungal disease" according to the EORTC/MSG criteria. Moreover, six "not classified" patients were positive for either plasma (1-3)-?-D-glucan (n = 5) or Aspergillus PCR in blood (n = 2). The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. Additionally, (1-3)-?-D-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections. PMID:23813092

Koh, Hideo; Hino, Masayuki; Ohta, Kensuke; Iino, Masaki; Urase, Fumiaki; Yamaguchi, Masaki; Yamanouchi, Jun; Usui, Noriko; Yoshida, Minoru; Tanimoto, Mitsune; Ohyashiki, Kazuma; Urabe, Akio; Tamura, Kazuo; Kanamaru, Akihisa; Masaoka, Tohru

2013-12-01

106

Managing oncology neutropenia and sepsis in the intensive care unit.  

PubMed

Neutropenic sepsis results as a post-cancer treatment complications and is considered an oncologic emergency. Neutropenic sepsis can result in mortality, especially if it is not identified at an early stage. Septic syndrome is the leading cause of nonrelapse mortality in patients with hematologic malignancies and solid tumors. Therefore, intensive care unit (ICU) nurses must possess a thorough understanding of cancer treatments, hematopoiesis, neutropenia, sepsis, risk factors, and the ability to perform a comprehensive assessment of the oncology patient. Each of these components plays a vital role in the patient's overall management following treatments with chemotherapy, radiation, and stem cell transplantation. The ICU nurse who encompasses this understanding will be able to identify neutropenic sepsis in a timely manner. The early identification of neutropenic sepsis will enable the ICU nurse to expeditiously implement preventive treatment and management to prevent mortality. PMID:25741957

Vioral, Anna N; Wentley, Dawn

2015-01-01

107

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. PMID:23351986

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

2012-01-01

108

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

PubMed

X-linked agammaglobulinemia (XLA) is a primary B-cell deficiency syndrome with an incidence of 5 to 10 cases per million. The current treatment approach includes intravenous immunoglobulin and aggressive antibiotic regimens for infections. Besides recurrent infections, XLA patients may present with other manifestations, such as alopecia, enteropathy, amyloidosis, and neutropenia. Neutropenia, which has been shown in up to 25% of affected patients, might also contribute to the degree of severity of bacterial infections that have been reported in these cases. Here we present our experience with the granulocyte colony-stimulant factor, filgrastim (Neupogen), in the treatment of neutropenia in a 14-month-old child with XLA. PMID:18799945

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

2008-08-01

109

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

PubMed Central

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

Dufour, Carlo

2015-01-01

110

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis  

Microsoft Academic Search

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we

Sebastian Schuchmann; Dietmar Schmitz; Claudio Rivera; Sampsa Vanhatalo; Benedikt Salmen; Ken Mackie; Sampsa T Sipilä; Juha Voipio; Kai Kaila

2006-01-01

111

RESEARCH Open Access Management of uncomplicated malaria in febrile  

E-print Network

RESEARCH Open Access Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests Arsène Ratsimbasoa1 Background: Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria

Boyer, Edmond

112

[Mycoplasma pneumoniae: a cause of febrile hemolytic anemia in travelers].  

PubMed

Mycoplasma pneumoniae can cause varied hematologic manifestations that are frequently associated with lower respiratory tract infections. Acute febrile hemolysis without respiratory symptoms is quite rare. We describe the case of a 25-year-old man, admitted for acute fever with hemolysis, after returning from Djibouti. M. pneumoniae infection was proved by serological testing. A favorable outcome followed macrolide treatment. PMID:23352983

Ficko, C; Andriamanantena, D; Flateau, F; Mangouka, L; Soler, C; Carmoi, T; Rapp, C

2012-01-01

113

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

114

Influences of nutrition and stress on people at risk for neutropenia: nursing implications.  

PubMed

Neutropenia may be influenced by malignancy type, treatment, age extremes, inadequate nutrition, or psychological stress. Of these five factors, only nutrition and stress are amenable to nursing intervention and management. The increasing trend of providing treatment in the outpatient setting and managing the patient with neutropenia in the home challenges nurses to develop innovative methods of care. This article offers suggestions to assist nurses in the creative management of individuals at risk for neutropenia by maximizing nutrition and minimizing psychological stress. This discussion addresses the physiology of the inflammatory immune response; pathophysiology of neutropenia; factors that may influence the risk of infection, such as sustained stress, dietary fiber, antioxidant vitamins, and food-borne bacteria; and interventions that reduce the potential for neutropenic sepsis. Nursing implications that reduce the risk of neutropenic infection include patient education related to nutrition, stress management, and self-care. PMID:8415151

Carter, L W

1993-09-01

115

[Epilepsy after febrile seizures. Predisposing factors and role of phenobarbital in its prophylaxis (author's transl)].  

PubMed

Authors studied two different groups of patients. One of them with febrile seizures and the other febrile seizures associated to epilepsy, in order to find risk factors for the presentation of this one. They conclude that epilepsy has a presentation rate of 9,6% in patients with previous febrile seizures, having the highest risk when they show previous familial seizures, neonatal pathology and altered EEG after the first febrile convulsion. They study the role of phenobarbital taken after febrile seizures, as prophylaxis. No effect was observed in the prevention of following epilepsy. PMID:7337301

Palencia Luances, R; Díez, J M; Tresierra, F; Sánchez-Villares, S

1981-10-01

116

Congenital neutropenia and primary immunodeficiency disorders: a survey of 26 Iranian patients.  

PubMed

Inherited neutropenia is characterized by a decrease in the absolute number of circulating neutrophils and an increased susceptibility to infections. The current study was performed to determine the clinical and laboratory findings of Iranian patients with inherited neutropenias. Records of 26 patients (14 male, 12 female) with inherited neutropenia were reviewed in this study. The patients had been referred to Children's Medical Center, a referral center for immunodeficiency disorders in Iran, during a 22-year period (1981-2003). Primary immunodeficiency disorders of these patients were as follows: cyclic neutropenia (8 patients), Shwachman-Diamond syndrome (7 patients), Kostmann syndrome (6 patients), and Chediak-Higashi syndrome (5 patients). The mean absolute neutrophil count of patients was 398.2 +/- 259.3 cells/mm (range 74-1,152/mm) at the first visit. Twenty-one patients showed severe, four moderate, and one mild neutropenia. Sixteen of these patients had leukopenia, seven anemia, two thrombocytopenia, and one monocytosis. The most common presenting complaints in these patients were oral ulcer, otitis, pneumonia, diarrhea, cutaneous abscess, and oral candidiasis. The patients first manifested symptoms of infection suggesting neutropenia at a median age of 7.5 months (range 1 month to 10 years). During follow-up, respiratory infections developed in 24 cases, oral manifestations in 20 patients. The most common infections, in descending order of frequency, were otitis media, abscesses, pneumonia, oral ulcers, acute diarrhea, cutaneous infections, oral candidiasis, and periodontitis. Less frequent infections were sinusitis, cystitis, conjunctivitis, meningitis, and osteomyelitis. Nonspecific symptoms (hepatomegaly and splenomegaly) were also detected in 10 patients and 1 patient, respectively. Three patients died of recurrent infections. The infectious manifestations both at presentation and during follow-up in inherited neutropenia were similar. Although inherited neutropenias are rare, recurrent infections always deserves further evaluation for detecting such disorders. PMID:16012323

Rezaei, Nima; Farhoudi, Abolhasan; Ramyar, Asghar; Pourpak, Zahra; Aghamohammadi, Asghar; Mohammadpour, Behzad; Moin, Mostafa; Gharagozlou, Mohammad; Movahedi, Masoud; Ghazi, Bahram Mirsaeid; Izadyar, Mina; Mahmoudi, Maryam

2005-07-01

117

Central involvement of kinin B1 and B2 receptors in the febrile response induced by endotoxin in rats  

PubMed Central

The effect of central injection of selective kinin B1 and B2 receptor antagonists on the febrile response induced by endotoxin (E. coli lipopolysaccharide, LPS) in rats was investigated. Intracerebroventricular (i.c.v.) injection of a selective B2 receptor antagonist (Hoe-140, 8?nmol) reduced the early (0–2?h), but increased the late phase (4–6?h) of the febrile response induced by intravenous (i.v.) injection of LPS (0.5??g?kg?1). Co-administration of Hoe-140 (8?nmol, i.c.v.) with LPS (0.5??g?kg?1, i.v.), followed 2.5?h later by the i.c.v. injection of a selective B1 receptor antagonist [des-Arg9-Leu8]-bradykinin (BK, 8?nmol), significantly reduced the febrile response induced by LPS throughout the whole experimental period. Intravenous injection of Hoe-140 (1?mg?kg?1) significantly reduced the febrile response induced by LPS (0.5??g?kg?1, i.p.). Pretreatment (24?h) with LPS (0.5??g?kg?1, i.v.) reduced the febrile response induced by BK or [Tyr8]-BK (both, 5?nmol, i.c.v.), but markedly increased the febrile response induced by [des-Arg9]-BK (5?nmol, i.c.v.). The response induced by [des-Arg9]-BK in LPS-pretreated rats was significantly inhibited by co-injection of [des-Arg9-Leu8]-BK (15?nmol, i.c.v.). The results suggest that kinins are involved in the induction of LPS-induced fever and that central B2 and B1 receptors are activated during the initial and late phase of this response, respectively. The results also suggest that downregulation and/or desensitization of B2 receptors and induction and/or upregulation of B1 receptors in LPS-pretreated animals may have a significant pathophysiologcal role in the induction and maintenance of fever. These observations may be specifically important in the case of chronic inflammatory conditions, because the BK metabolite [des-Arg9]-BK, so far considered an inactive metabolite, acquires an active and relevant role with the progressive expression of B1 receptors that occurs in such states. PMID:9154340

Coelho, M M; Oliveira, C R; Pajolla, G P; Calixto, J B; Pelá, I R

1997-01-01

118

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

119

rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU.  

PubMed Central

Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas. PMID:8123485

Rampling, R.; Steward, W.; Paul, J.; Macham, M. A.; Harvey, E.; Eckley, D.

1994-01-01

120

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

PubMed Central

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

2015-01-01

121

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

PubMed Central

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

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

2014-01-01

122

Febrile seizure recurrence reduced by intermittent oral levetiracetam  

PubMed Central

Objective Febrile seizure (FS) is the most common form of childhood seizure disorders. FS is perhaps one of the most frequent causes of admittance to pediatric emergency wards worldwide. We aimed to identify a new, safe, and effective therapy for preventing FS recurrence. Methods A total of 115 children with a history of two or more episodes of FS were randomly assigned to levetiracetam (LEV) and control (LEV/control ratio = 2:1) groups. At the onset of fever, LEV group was orally administered with a dose of 15–30 mg/kg per day twice daily for 1 week. Thereafter, the dosage was gradually reduced until totally discontinued in the second week. The primary efficacy variable was seizure frequency associated with febrile events and FS recurrence rate (RR) during 48-week follow-up. The second outcome was the cost effectiveness of the two groups. Results The intention-to-treat analysis showed that 78 children in LEV group experienced 148 febrile episodes. Among these 78 children, 11 experienced 15 FS recurrences. In control group, 37 children experienced 64 febrile episodes; among these 37 children, 19 experienced 32 FS recurrences. A significant difference was observed between two groups in FS RR and FS recurrence/fever episode. The cost of LEV group for the prevention of FS recurrence is lower than control group. During 48-week follow-up period, one patient in LEV group exhibited severe drowsiness. No other side effects were observed in the same patient and in other children. Interpretation Intermittent oral LEV can effectively prevent FS recurrence and reduce wastage of medical resources. PMID:25356397

Hu, Lin-Yan; Zou, Li-Ping; Zhong, Jian-Min; Gao, Lei; Zhao, Jian-Bo; Xiao, Nong; Zhou, Hong; Zhao, Meng; Shi, Xiu-Yu; Liu, Yu-Jie; Ju, Jun; Zhang, Wei-Na; Yang, Xiao-Fan; Kwan, Patrick

2014-01-01

123

Uncommon clinical pattern of FMF: protracted febrile myalgia syndrome  

Microsoft Academic Search

Familial Mediterranean fever (FMF) is a genetic multisystem disorder of unknown etiology characterized by recurrent episodes\\u000a of fever and pain due to acute inflammation of the peritoneum, synovia, or pleura. Up to 25% of patients with FMF report muscle\\u000a pain. Myalgia may be a spontaneous pattern, exercise-induced pattern, or protracted febrile myalgia syndrome (PFMS). PFMS\\u000a is characterized by severe paralyzing

Gülnihal Tufan; Serap Demir

2010-01-01

124

Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.  

PubMed

Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia. PMID:20558844

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

2010-07-01

125

Sulfur mustard-induced neutropenia: treatment with granulocyte colony-stimulating factor.  

PubMed

Although best known as a blistering agent, sulfur mustard (HD) can also induce neutropenia in exposed individuals, increasing their susceptibility to infection. Granulocyte colony-stimulating factor (G-CSF) and pegylated G-CSF (peg-G-CSF) have been approved by the U.S. Food and Drug Administration as hematopoietic growth factors to treat chemotherapy-induced neutropenia. The goal of this study was to determine the effectiveness of G-CSF and peg-G-CSF in ameliorating HD-induced neutropenia. African green monkeys (Chlorocebus aethiops) were challenged with HD and, at 1, 3, 5, or 7 days after exposure, G-CSF therapy (10 microg/kg per day for 21 days) was initiated. Peg-G-CSF (300 microg/kg, single treatment) was similarly tested, with treatment given at 3 days after exposure. Untreated HD-exposed animals recovered from neutropenia 28 days after exposure, whereas G-CSF- or peg-G-CSF-treated animals recovered 8 to 19 days after exposure (p < 0.05). These results indicate that G-CSF or peg-G-CSF may provide Food and Drug Administration-approved treatments that will reduce the duration of HD-induced neutropenia. PMID:16761898

Anderson, Dana R; Holmes, Wesley W; Lee, Robyn B; Dalal, Stephen J; Hurst, Charles G; Maliner, Beverly I; Newmark, Jonathan; Smith, William J

2006-05-01

126

Intermittent prophylaxis of recurrent febrile seizures with clobazam versus diazepam.  

PubMed

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

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

2014-10-01

127

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

PubMed

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

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

2015-03-01

128

Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures  

PubMed Central

Purpose Childhood convulsive status epilepticus (CSE), in particular prolonged febrile seizures (PFS), has been linked with mesial temporal sclerosis (MTS). Previous studies have shown that hippocampal injury occurs in the acute phase immediately following CSE, but little is known about the longer term evolution of such injury. This study aimed to investigate the longer term outcome of childhood CSE with sequential magnetic resonance imaging (MRI) looking for progressive hippocampal injury during the first year post-CSE. Methods Eighty children (0.18–15.5 years) underwent brain MRI 1 month post-CSE, 50 with a repeat MRI at 6 months and 46 with repeat MRI at 12 months post-CSE. Thirty-one control subjects without neurologic problems had a single brain MRI for comparison. Hippocampal volumes were measured from each MRI scan by two independent observers, and hippocampal growth rates were estimated in each patient with suitable imaging. Key Findings Hippocampal volume loss was found in 20–30% of patients and was not associated with the etiology or clinical features of CSE, including seizure duration or focality. A borderline association was found between a history of previous seizures (p = 0.063) and the number of previous febrile seizures (p = 0.051), suggesting that multiple insults may be important in the pathogenesis of progressive hippocampal injury. Significance It is apparent that progressive hippocampal damage can occur after CSE of any etiology and is not limited to PFS. Repeated seizures may play an important role, but further follow-up is needed to determine any other risk factors and proportion of children showing initial volume loss progress to clinical MTS and temporal lobe epilepsy. PMID:24304434

Yoong, Michael; Martinos, Marina M; Chin, Richard F; Clark, Christopher A; Scott, Rodney C

2013-01-01

129

Cyclic neutropenia in animals To the editor: Pacheco et al. [1] recently published in these pages an allo-  

E-print Network

Cyclic neutropenia in animals To the editor: Pacheco et al. [1] recently published in these pages the genetic defects in man and dog may share common downstream mecha- nisms involving elastase trafficking;108:362­ 369. Cyclic neutropenia in animals To the editor: We thank Dr. Newburger for his comments regarding

Traulsen, Arne

130

Mechanism-based pharmacokinetic\\/pharmacodynamic model for troxacitabine-induced neutropenia in cancer patients  

Microsoft Academic Search

Purposes  The objective of this study was to develop a mechanism-based population pharmacokinetic\\/pharmacodynamic (PK\\/PD) model in describing\\u000a troxacitabine-induced neutropenia in patients with cancer.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 727 PK\\/PD samples from 31 patients with cancer were included in the analysis. A mechanism-based population PD model\\u000a was developed to describe neutropenia and the final model consisted of (1) a drug-sensitive uncommitted progenitor cell

Chee M. Ng; A. Patnaik; M. Beeram; C. C. Lin; C. H. Takimoto

2011-01-01

131

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

PubMed Central

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

Bagby, G C; Gabourel, J D

1979-01-01

132

Involvement of brain cytokines in zymosan-induced febrile response.  

PubMed

This study compared the involvement of interleukin-1? (IL-1?), IL-6, and tumor necrosis factor-? (TNF-?) within the central nervous system (CNS) in the febrile response induced by zymosan (zym) and lipopolysaccharide (LPS). In addition, we investigated whether zym could activate important regions related to fever; namely, the vascular organ of the laminae terminalis (OVLT) and the median preoptic nucleus (MnPO). Intraperitoneal injection of zym (1, 3, and 10 mg/kg) induced a dose-related increase in core temperature. Zym (3 mg/kg) also reduced tail skin temperature, suggesting the activation of heat conservation mechanisms, as expected, during fever. LPS increased plasma levels of TNF-? measured at 1 h, IL-1? measured at 2 h, and IL-6 measured at 3 h after injection. Zym increased circulating levels of IL-6 but not those of TNF-? or IL-1? at the same time points. In addition, an intracerebroventricular injection of antibodies against TNF-? (2.5 ?g) and IL-6 (10 ?g) or the IL-1 receptor antagonist (160 ng) reduced the febrile response induced by zym and LPS. Zym (100 ?g/ml) also increased intracellular calcium concentration in the OVLT and MnPO from rat primary neuroglial cultures and increased release of TNF-? and IL-6 into the supernatants of these cultures. Together, these results suggest that TNF-?, IL-1?, and IL-6 within the CNS participate in the febrile response induced by zym. However, the time course of release of these cytokines may be different from that of LPS. In addition, zym can directly activate the brain areas related to fever. PMID:24651990

Bastos-Pereira, Amanda L; Fraga, Daniel; Ott, Daniela; Simm, Björn; Murgott, Jolanta; Roth, Joachim; Zampronio, Aleksander R

2014-05-01

133

Subacute Sclerosing Panencephalitis in a Child with Recurrent Febrile Seizures  

PubMed Central

Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recurrent febrile seizures. The disease progressed with an appearance of myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis.

Kartal, Ay?e; Ç?tak Kurt, Ay?egül Ne?e; Hirfano?lu, Tu?ba; Ayd?n, Kür?ad; Serdaro?lu, Ay?e

2015-01-01

134

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

PubMed

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

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

2015-02-01

135

The acute phase nature of interleukin 6: studies in Kawasaki disease and other febrile illnesses.  

PubMed

Interleukin 6 (IL-6) has manifold biological functions involved in the immune or inflammatory responses of the host to various stimuli. Here we asked whether IL-6 might be responsible for manifestations of Kawasaki disease (KD), such as immunoglobulin hypersecretion, lymphocyte activation and systemic vasculitis. IL-6 activity in the serum was determined by a sensitive colorimetric assay using an IL-6-dependent murine hybridoma clone. Usually sera from healthy or afebrile donors contained only negligible levels of IL-6 activity below the detection threshold of the assay. Importantly it was found that serum IL-6 was markedly elevated in all patients with acute KD. Serum levels of IL-6 activity gradually diminished during the course of the disease and reached undetectable or lower levels at the convalescent phase. However, such elevated levels of serum IL-6 activity were also observed in the majority of other febrile diseases, such as bacterial or viral infections, indicating that the appearance of IL-6 in the serum could generally occur in febrile or inflammatory disease conditions. Serum IL-6 activity correlated with serum concentrations of some acute phase proteins (APP), such as C-reactive protein, haptoglobin and alpha 1-acid glycoprotein, implying its role for modulating induction of APP in vivo. IL-6 is well known to be secreted by a variety of cell types. Further studies, including immunohistochemical analysis using anti-IL-6 antibody, will be necessary to examine whether the source of serum IL-6 in KD might be different from that seen in other diseases. PMID:2473858

Ueno, Y; Takano, N; Kanegane, H; Yokoi, T; Yachie, A; Miyawaki, T; Taniguchi, N

1989-06-01

136

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

137

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

PubMed Central

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

Yang, T. J.

1978-01-01

138

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

PubMed Central

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

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

2014-01-01

139

Piperacillin/tazobactam-induced neutropenia, thrombocytopenia, and fever during treatment of a diabetic foot infection.  

PubMed

Piperacillin/tazobactam (PTZ) is frequently used in patients with diabetic foot infections. Herein, we report a patient who developed severe neutropenia, thrombocytopenia, and fever while receiving PTZ for a diabetic foot infection. We recommend vigilance when long-term PTZ use is planned in patients with diabetic foot infections. PMID:22746695

Uzun, Günalp; Onem, Yalçin; Hatipoglu, Mustafa; Turhan, Vedat; Mutluoglu, Mesut; Ay, Hakan

2013-01-01

140

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

PubMed

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

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

2014-12-01

141

Leptospirosis among Hospitalized Febrile Patients in Northern Tanzania  

PubMed Central

We enrolled consecutive febrile admissions to two hospitals in Moshi, Tanzania. Confirmed leptospirosis was defined as a ? 4-fold increase in microscopic agglutination test (MAT) titer; probable leptospirosis as reciprocal MAT titer ? 800; and exposure to pathogenic leptospires as titer ? 100. Among 870 patients enrolled in the study, 453 (52.1%) had paired sera available, and 40 (8.8%) of these met the definition for confirmed leptospirosis. Of 832 patients with ? 1 serum sample available, 30 (3.6%) had probable leptospirosis and an additional 277 (33.3%) had evidence of exposure to pathogenic leptospires. Among those with leptospirosis the most common clinical diagnoses were malaria in 31 (44.3%) and pneumonia in 18 (25.7%). Leptospirosis was associated with living in a rural area (odds ratio [OR] 3.4, P < 0.001). Among those with confirmed leptospirosis, the predominant reactive serogroups were Mini and Australis. Leptospirosis is a major yet underdiagnosed cause of febrile illness in northern Tanzania, where it appears to be endemic. PMID:21813847

Biggs, Holly M.; Bui, Duy M.; Galloway, Renee L.; Stoddard, Robyn A.; Shadomy, Sean V.; Morrissey, Anne B.; Bartlett, John A.; Onyango, Jecinta J.; Maro, Venance P.; Kinabo, Grace D.; Saganda, Wilbrod; Crump, John A.

2011-01-01

142

Brucellosis among Hospitalized Febrile Patients in Northern Tanzania  

PubMed Central

Acute and convalescent serum samples were collected from febrile inpatients identified at two hospitals in Moshi, Tanzania. Confirmed brucellosis was defined as a positive blood culture or a ? 4-fold increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer ? 160. Among 870 participants enrolled in the study, 455 (52.3%) had paired sera available. Of these, 16 (3.5%) met criteria for confirmed brucellosis. Of 830 participants with ? 1 serum sample, 4 (0.5%) met criteria for probable brucellosis. Brucellosis was associated with increased median age (P = 0.024), leukopenia (odds ratio [OR] 7.8, P = 0.005), thrombocytopenia (OR 3.9, P = 0.018), and evidence of other zoonoses (OR 3.2, P = 0.026). Brucellosis was never diagnosed clinically, and although all participants with brucellosis received antibacterials or antimalarials in the hospital, no participant received standard brucellosis treatment. Brucellosis is an underdiagnosed and untreated cause of febrile disease among hospitalized adult and pediatric patients in northern Tanzania. PMID:23091197

Bouley, Andrew J.; Biggs, Holly M.; Stoddard, Robyn A.; Morrissey, Anne B.; Bartlett, John A.; Afwamba, Isaac A.; Maro, Venance P.; Kinabo, Grace D.; Saganda, Wilbrod; Cleaveland, Sarah; Crump, John A.

2012-01-01

143

Prolonged sleep fragmentation of mice exacerbates febrile responses to lipopolysaccharide  

PubMed Central

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

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

2013-01-01

144

Prevention and control of infections in patients with severe congenital neutropenia; a follow up study.  

PubMed

Severe congenital neutropenia is one of primary immunodeficiency disorders that characterized by severe neutropenia and is associated with severe systemic bacterial infections from early infancy. Granulocyte colony stimulating factor (GCSF) is clinically used as a treatment for congenital and acquired neutropenia. The aim of this study was evaluation of GCSF (PD- Grastim) in treatment of these patients. Patients with severe congenital neutropenia referred to Immunology, Asthma and Allergy Research Institute between Jan 2007 and Dec 2010 enrolled the study. Other causes of neutropenia were excluded by serial CBC and bone marrow studies, medical and drug histories and immunological tests. Patients were visited and examined monthly to evaluate their CBC and ANC (absolute neutrophil count), GCSF side effects and dosage adjustment. Cytogenetic studies were being done for all the patients for early detection of progression to AML/MDS. From twenty two patients who enrolled this study, 16 patients regularly evaluated. They were ten males and six females, range in age from 2 to 18 years old. Two patients failed to continue our follow up unfortunately and four patients died due to disease complications. Patients were followed for 24 to 48 months. In a period of 12-24 months before treatment, the mean of hospitalization frequency was 3.1 times and duration was 10 days; while during receiving treatment, they decreased to 0.2 times and 3 days, respectively (p<0.01). Also significant increase in mean ANC was observed during follow up (315/µl before treatment versus 1749/µl after 12 month regular treatment). Bone pain was the most common side effect. There have been no evidences of developing AML/MDS up to present time. Treatment with GCSF significantly reduced the duration and the frequency of hospitalization. Because of plausible progression to AML/MDS, regular follow-up of patients should be continued. PMID:22427476

Salehi, Tahmineh; Fazlollahi, Mohammad Reza; Maddah, Marzieh; Nayebpour, Mohsen; Tabatabaei Yazdi, Mojtaba; Alizadeh, Zahra; Eshghi, Peyman; Chavoshzadeh, Zahra; Movahedi, Masoud; Hamidieh, Amir Ali; Cheraghi, Taher; Pourpak, Zahra; Moin, Mostafa

2012-03-01

145

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

PubMed Central

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

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

2014-01-01

146

PRRT2 mutations are related to febrile seizures in epileptic patients.  

PubMed

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

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

2014-01-01

147

PRRT2 Mutations Are Related to Febrile Seizures in Epileptic Patients  

PubMed Central

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

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

2014-01-01

148

Prostaglandin E as the neural mediator of the febrile response.  

PubMed Central

The evidence favoring a role for prostaglandin E (PGE) as the neural mediator of the febrile response is reviewed and considered under five different essential criteria which would need to be satisfied, if such a role is to be accepted. These criteria are: the ability of intracerebrally microinjected exogenous PGE to cause fever; the detection of increased levels of endogenous PGE in the brain during the normal production of fever; the ability of substances that inhibit the production and release of PGE to block normal fevers; the ability of substances that are specific PGE antagonists to inhibit normal fevers; and the identification of a specific site and cell type for the release of PGE in response to the action of pyrogens. Evidence from the literature that supports these criteria is reviewed and presented in this format, and the conclusion is drawn that the evidence available is more than sufficient to support the initial hypothesis. PMID:3739372

Stitt, J. T.

1986-01-01

149

[Efficacy and failure of phenobarbital in the prevention of febrile convulsions. Importance of familial antecedents].  

PubMed

The authors analyze the value of phenobarbital for prophylaxis of new convulsions in a group of 370 patients who had previously had febrile seizures. Percentage of recurrences in phenobarbital treated cases (4 +/- 0,6 mg/Kg/d) was 18,67%, versus 55,89% in untreated children (p less than 0.001). The presence of family history of epileptic or febrile seizures is a risk factor (p less than 0.01) that facilitates failure of phenobarbital prophilaxis in future febrile seizures. PMID:6683949

Palencia, R; Cilleruelo, M L; Tresierra, F; Blanco, A

1983-02-01

150

Epidemiological study of severe febrile reactions in young children in Western Australia caused by a 2010 trivalent inactivated influenza vaccine  

PubMed Central

Background The 2010 influenza vaccination program for children aged 6?months to 4?years in Western Australia (WA) was suspended following reports of severe febrile reactions, including febrile convulsions, following vaccination with trivalent inactivated influenza vaccine (TIV). Methods To investigate the association between severe febrile reactions and TIV, three studies were conducted: (i) rates of febrile convulsions within 72?h of receiving TIV in 2010 were estimated by vaccine formulation and batch; (ii) numbers of children presenting to hospital emergency departments with febrile convulsions from 2008 to 2010 were compared; and (iii) a retrospective cohort study of 360 children was conducted to compare the reactogenicity of available TIV formulations. Findings In 2010, an estimated maximum of 18?816 doses of TIV were administered and 63 febrile convulsions were recorded, giving an estimated rate of 3.3 (95% CI 2.6 to 4.2) per 1000 doses of TIV administered. The odds of a TIV-associated febrile convulsion was highly elevated in 2010 (p<0.001) and was associated with the vaccine formulations of one manufacturer—Fluvax and Fluvax Junior (CSL Biotherapies). The risk of both febrile convulsions (p<0.0001) and other febrile reactions (p<0.0001) was significantly greater for Fluvax formulations compared to the major alternate brand. The risk of febrile events was not associated with prior receipt of TIV or monovalent 2009 H1N1 pandemic vaccine. The biological cause of the febrile reactions is currently unknown. Interpretation One brand of influenza vaccine was responsible for the increase in febrile reactions, including febrile convulsions. Until the biological reason for this is determined and remediation undertaken, childhood influenza vaccination programs should not include Fluvax-type formulations and enhanced surveillance for febrile reactions in children receiving TIV should be undertaken. PMID:22021725

Dowse, G K; Effler, P V; Carcione, D; Blyth, C C; Richmond, P C; Geelhoed, G C; Mascaro, F; Scully, M; Weeramanthri, T S

2011-01-01

151

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

152

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

PubMed Central

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

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

2015-01-01

153

Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation  

PubMed Central

We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN. PMID:20803142

Verhard, Els M.; Tool, Anton J. T.; de Visser, Adriëtte W.; Kuijpers, Taco W.; Hiemstra, Pieter S.; van Dissel, Jaap T.

2010-01-01

154

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

PubMed

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

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

2015-02-01

155

Transient restricted diffusion of corpus callosum and subcortical white matter following febrile status epilepticus.  

PubMed

We describe the case of a 4½-year-old girl with prolonged febrile status followed by abnormal behavior and loss of speech. Interesting findings on diffusion-restricted imaging were noted. The clinicoradiologic possibilities are discussed. PMID:24850571

Jain, Puneet; Sharma, Suvasini; Dhingra, Dhulika; Aneja, Satinder

2015-05-01

156

Pharmacokinetics of gentamicin following single dose intravenous administration in normal and febrile goats.  

PubMed

A pharmacokinetic study of gentamicin (5 mg/kg intravenous (i.v.)) was conducted first in clinically healthy female goats and then in the same goats after induction of fever by Escherichia coli endotoxin (0.2 microgram/kg i.v.). Rectal temperature increased 1 degrees to 1.5 degrees C in febrile goats. Differences in the blood serum concentrations of gentamicin were not observed at any time between febrile and normal goats. The disposition kinetics of gentamicin were described by a biexponential expression CP = Ae-alpha t + Be-beta t. Median values for the half-lives of gentamicin were 103.6 min in normal and 136.0 min in febrile goats. The apparent volume of distribution (Vd) was 263.3 ml/kg in the febrile goats which was not different from that in the normal goats (240.6 ml/kg). The volume of the central compartment (Vc) was almost identical in normal and febrile goats. The body clearance (Cl beta) was observed to be 1.7 and 1.6 ml/min.kg in normal and febrile goats, respectively. Dosage regimens for gentamicin were calculated on the basis of median kinetic data. PMID:7853462

Ahmad, A H; Bahga, H S; Sharma, L D

1994-10-01

157

Transcriptome analysis of the hippocampus in novel rat model of febrile seizures.  

PubMed

Febrile seizures (FS) are the most common type of convulsive events in infants and young children, but the precise underlying genetic mechanism remains to be explored. To investigate the underlying pathogenic factors in FS and subsequent epilepsy, alterations in gene expression between the two new strains of rats (hyperthermia-prone [HP] vs hyperthermia-resistant [HR]), were investigated by using the Whole Rat Genome Oligo Microarray. This process identified 1,140 differentially expressed genes (DEGs; 602 upregulated and 538 downregulated), which were analyzed to determine significant Gene Ontology (GO) categories, signaling pathways and gene networks. Based on the GO analyses, the modified genes are closely related to various FS pathogenesis factors, including immune and inflammatory responses and ion transport. Certain DEGs identified have not been previously examined in relation to FS pathogenesis. Among these genes is dipeptidyl peptidase 4 (DPP4), a gene closely linked to interleukin 6 (IL-6), which played a key role in the gene network analysis. Furthermore, sitagliptin, a DPP4 inhibitor significantly decreased epileptic discharge in rats, observed via electroencephalogram, suggesting an important role for DPP4 in FS. The effectiveness of sitagliptin in reducing seizure activity may occur through a mechanism that stabilizes cellular Ca2+ homeostasis. In addition, DPP4 expression may be regulated by DNA methylation. The hippocampal gene expression profiles in novel rat models of FS provides a large database of candidate genes and pathways, which will be useful for researchers interested in disorders of neuronal excitability. PMID:24736375

Wang, Zhongcheng; Fan, Yuanteng; Xu, Jian; Li, Liang; Heng, Duanhe; Han, Song; Yin, Jun; Peng, Biwen; Liu, Wanhong; He, Xiaohua

2014-01-01

158

Acute oral candidiasis during febrile episodes in immunocompromised patients with haematologic malignancies.  

PubMed

To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long-lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum. PMID:2196672

Bergmann, O J; Andersen, P L

1990-01-01

159

Transcriptome Analysis of the Hippocampus in Novel Rat Model of Febrile Seizures  

PubMed Central

Febrile seizures (FS) are the most common type of convulsive events in infants and young children, but the precise underlying genetic mechanism remains to be explored. To investigate the underlying pathogenic factors in FS and subsequent epilepsy, alterations in gene expression between the two new strains of rats (hyperthermia-prone [HP] vs hyperthermia-resistant [HR]), were investigated by using the Whole Rat Genome Oligo Microarray. This process identified 1,140 differentially expressed genes (DEGs; 602 upregulated and 538 downregulated), which were analyzed to determine significant Gene Ontology (GO) categories, signaling pathways and gene networks. Based on the GO analyses, the modified genes are closely related to various FS pathogenesis factors, including immune and inflammatory responses and ion transport. Certain DEGs identified have not been previously examined in relation to FS pathogenesis. Among these genes is dipeptidyl peptidase 4 (DPP4), a gene closely linked to interleukin 6 (IL-6), which played a key role in the gene network analysis. Furthermore, sitagliptin, a DPP4 inhibitor significantly decreased epileptic discharge in rats, observed via electroencephalogram, suggesting an important role for DPP4 in FS. The effectiveness of sitagliptin in reducing seizure activity may occur through a mechanism that stabilizes cellular Ca2+ homeostasis. In addition, DPP4 expression may be regulated by DNA methylation. The hippocampal gene expression profiles in novel rat models of FS provides a large database of candidate genes and pathways, which will be useful for researchers interested in disorders of neuronal excitability. PMID:24736375

Xu, Jian; Li, Liang; Heng, Duanhe; Han, Song; Yin, Jun; Peng, Biwen; Liu, Wanhong; He, Xiaohua

2014-01-01

160

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

PubMed Central

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

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

2014-01-01

161

Kidney imaging in management of delayed febrile urinary tract infection.  

PubMed

We report a cross-sectional study performed to evaluate the imaging findings of 40 children, aged one month to five years (16.65 ± 14.97 months), who presented with protracted fever of more than 48 hours due to urinary tract infection (UTI). About 85% of the patients had positive Tc99-Dimercaptosuccinic acid (DMSA) scan and 58% had vesicoureteral reflux (VUR). Kidney sonography aided in the diagnosis and treatment in 10% of the patients. Age, sex, presence or laterality of VUR did not contribute to defective DMSA scan (pyelonephritis) (P > 0.05). Delayed diagnosis and treatment of febrile UTI is associated with a high incidence of positive findings of DMSA scan irrespective of age, sex or presence/absence of VUR. In mild VUR, the DMSA scan may be normal while in patients with moderate and severe VUR the DMSA scan is almost always abnormal. Thus, our study shows that a normal DMSA scan can help in ruling out moderate to severe forms of VUR and that cystography remains an excellent and standard tool for the diagnosis of VUR. PMID:22089774

Sayedzadeh, Sayed Abolhassan; Malaki, Majid; Shoaran, Maryam; Nemati, Massood

2011-11-01

162

Protective effect of carnosine on febrile seizures in immature mice.  

PubMed

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

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

2015-02-19

163

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

164

Cefozopran, meropenem, or imipenem-cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: A multicenter prospective randomized trial.  

PubMed

We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ? 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462). PMID:25239059

Nakane, Takahiko; Tamura, Kazuo; Hino, Masayuki; Tamaki, Toshiharu; Yoshida, Isao; Fukushima, Toshihiro; Tatsumi, Youichi; Nakagawa, Yasuaki; Hatanaka, Kazuo; Takahashi, Tsutomu; Akiyama, Nobu; Tanimoto, Mitsune; Ohyashiki, Kazuma; Urabe, Akio; Masaoka, Toru; Kanamaru, Akihisa

2015-01-01

165

JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.  

PubMed

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

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

2014-09-01

166

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

PubMed

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

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

2014-11-23

167

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

PubMed Central

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

Kasperavi?i?t?, Dalia; Catarino, Claudia B.; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Bárbara; Hessel, Ellen V. S.; Hallmann, Kerstin; Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P.; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J.; Zumsteg, Dominik; Duncan, Susan; Kälviäinen, Reetta K.; Eriksson, Kai J.; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M.; Stogmann, Elisabeth; Zimprich, Fritz; Théâtre, Emilie; Smith, Colin; O’Brien, Terence J.; Meng Tan, K.; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R.; Buono, Russell J.; Hakonarson, Hakon; Chaves, João; Costa, Paulo P.; Silva, Berta M.; da Silva, António M.; de Graan, Pierre N. E.; Koeleman, Bobby P. C.; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S.; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo M.; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E.; Berkovic, Samuel F.; Weale, Michael E.; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L.; Kunz, Wolfram S.

2013-01-01

168

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

PubMed

In a prospective randomised study, 289 children admitted consecutively to hospital with their first febrile seizure were allocated, by date of admission, to short term diazepam prophylaxis (n = 152) or to no prophylaxis (n = 137) and followed for 18 months. In untreated children, five major risk factors for recurrent febrile convulsions were identified: age 15 months or less at the time of the first febrile seizure, epilepsy in first degree relatives, febrile convulsions in first degree relatives, a first complex febrile seizure, and day nursery care. The 18 month recurrence rate was 80 to 100% if three to five risk factors were present, 50% if two factors were identified, 25% where one factor was found, and 12% if there were no predictors. During prophylaxis the recurrence rate was uniformly low (mean 12%) in all risk groups. In high (three or more factors) and intermediate (two factors) risk children prophylaxis provided effective seizure control and reduced the recurrence rate from 80%, or more, to 12% and 50% to 12%, respectively. In children with one risk factor 50% of all recurrences were prevented (25% to 12%). Prophylaxis was ineffective in very low risk children (12% to 12%). PMID:3907504

Knudsen, F U

1985-11-01

169

Planctomycetes DNA in Febrile Aplastic Patients with Leukemia, Rash, Diarrhea, and Micronodular Pneumonia  

PubMed Central

We found Planctomycetes DNA in 2 out of 100 blood samples from patients suffering from leukemia with neutropenia induced by chemotherapy, as well as fever, rash, pneumonia, and diarrhea. Antibiotic-resisting Planctomycetes may be pathogenic in these patients. PMID:24920769

Prebet, T.; Aghnatios, R.; Edouard, S.; Cayrou, C.; Henry, M.; Blaise, D.; Raoult, D.

2014-01-01

170

Quality of Life and neutropenia in patients with early stage Breast cancer: A Randomized pilot study comparing Additional Treatment with Mistletoe extract to chemotherapy Alone  

Microsoft Academic Search

Background: Chemotherapy for breast cancer often deteriorates quality of life, augments fatigue, and induces neutropenia. Mistletoe preparations are frequently used by cancer patients in Central Europe. Physicians have reported better quality of life in breast cancer patients additionally treated with mistletoe preparations during chemotherapy. Mistletoe preparations also have immunostimulant prop- erties and might therefore have protective effects against chemotherapy-induced neutropenia.

Wilfried Tröger; Svetlana Jezdi?; Zdravko Ždrale

2009-01-01

171

Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia  

PubMed Central

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

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

2015-01-01

172

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

PubMed Central

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

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

2014-01-01

173

The clinical, immunohematological, and molecular study of Iranian patients with severe congenital neutropenia.  

PubMed

Severe congenital neutropenia (SCN) is a rareE primary immunodeficiency disorder characterized by early onset recurrent infections in association with persistent severe agranulocytosis. To identify the clinical, immunohematological, and molecular characteristics of patients with SCN, 18 Iranian patients with the mean age of 8.8 +/- 5.8 years were investigated in this study. All of these patients experienced severe neutropenia; the mean of absolute neutrophil count was 281.4 +/- 137.7 cells/mm3. Bone marrow findings were typified by a myeloid maturation arrest at the promyelocyte-myelocyte stage in these patients. Molecular analysis revealed different mutations in the ELA-2 gene of one patient and in the HAX-1 gene of another three patients. The most common presenting complaints in these patients were superficial abscesses, oral ulcers, cutaneous infections, omphalitis, and pneumonia. During the course of illness, all patients developed mucocutaneous manifestations, and 16 cases had respiratory infections. The most commonly manifestations were abscesses, oral ulcers, pneumonia, periodontitis, otitis media, cutaneous infections, mucocutaneous candidiasis, and acute diarrhea. Three patients died because of a severe infection. Although SCN is a rare disorder, early onset of severe and recurrent infections should always raise a suspicion, which deserves further evaluation for detecting such disorder. PMID:17587155

Rezaei, Nima; Moin, Mostafa; Pourpak, Zahra; Ramyar, Asghar; Izadyar, Mina; Chavoshzadeh, Zahra; Sherkat, Roya; Aghamohammadi, Asghar; Yeganeh, Mehdi; Mahmoudi, Maryam; Mahjoub, Fatemeh; Germeshausen, Manuela; Grudzien, Magda; Horwitz, Marshall S; Klein, Christoph; Farhoudi, Abolhassan

2007-09-01

174

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 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

175

Hyperthermia in the febrile range induces HSP72 expression proportional to exposure temperature but not to HSF-1 DNA-binding activity in human lung epithelial A549 cells  

Microsoft Academic Search

Expression of heat shock proteins (HSPs) is classically activated at temperatures above the physiologic range (?42°C) via\\u000a activation of the stress-activated transcription factor, heat shock factor-1 (HSF-1). Several studies suggest that less extreme\\u000a hyperthermia, especially within the febrile range, as occurs during fever and exertional\\/environmental hyperthemia, can also\\u000a activate HSF-1 and enhance HSP expression. We compared HSP72 protein and mRNA

Mohan E. Tulapurkar; Benedict E. Asiegbu; Ishwar S. Singh; Jeffrey D. Hasday

2009-01-01

176

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

PubMed Central

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

177

Complicated malaria and other severe febrile illness in a pediatric ward in Libreville, Gabon  

PubMed Central

Background Although a substantial decline of Plasmodium falciparum infection is observed in Africa following implementation of new control strategies, malaria is still considered as the major cause of febrile illness in hospitalized African children. The present study was designed to assess the management of febrile illness and to determine the proportion of children with febrile illness hospitalized for primary diagnosis of malaria who had confirmed complicated malaria after implementation of new malaria control strategies in Libreville, Gabon. Methods Demographic, clinical and biological data from hospitalized children with fever or a history of fever, with a primary diagnosis of clinical malaria, aged less than 18?years old, who benefited from hematological measurements and microscopic malaria diagnosis, were recorded and analyzed during a prospective and observational study conducted in 2008 in the Centre Hospitalier de Libreville. Results A total of 418 febrile children were admitted at hospital as malaria cases. Majority of them (79.4%) were aged below five years. After medical examination, 168 were diagnosed and treated as clinical malaria and, among them, only 56.7% (n?=?95) had Plasmodium falciparum positive blood smears. Age above five years, pallor, Blantyre Coma Score ?2 and thrombocytopenia were predictive of malaria infection. Respiratory tract infections were the first leading cause of hospitalization (41.1%), followed by malaria (22.7%); co-morbidities were frequent (22%). Less than 5% of suspected bacterial infections were confirmed by culture. Global case fatality rate was 2.1% and 1% for malaria. Almost half (46%) of the children who received antimalarial therapy had negative blood smears. Likewise, antibiotics were frequently prescribed without bacteriological confirmation. Conclusions The use of clinical symptoms for the management of children febrile illness is frequent in Gabon. Information, training of health workers and strengthening of diagnosis tools are necessary to improve febrile children care. PMID:22973831

2012-01-01

178

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. PMID:24277604

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

2013-01-01

179

Serum interleukin-1beta and tumor necrosis factor-alpha in febrile seizures: is there a link?  

PubMed Central

Purpose Febrile seizures are induced by fever and are the most common type of seizures in children. Although numerous studies have been performed on febrile seizures, their pathophysiology remains unclear. Recent studies have shown that cytokines may play a role in the pathogenesis of febrile seizures. The present study was conducted to identify potential links between serum interleukin-1beta (IL-1?), tumor necrosis factor-alpha (TNF-?), and febrile seizures. Methods Ninety-two patients with simple or complex febrile seizures (46 patients per seizure type), and 46 controls with comparable age, sex, and severity of temperature were enrolled. Results The median concentrations of serum IL-1? in the simple, complex febrile seizure, and control groups were 0.05, 0.1, and 0.67 pg/mL, respectively (P=0.001). Moreover, the median concentrations of TNF-? in the simple, complex febrile seizure, and control groups were 2.5, 1, and 61.5 pg/mL, respectively (P=0.001). Furthermore, there were significant differences between the case groups in serum IL-1? and TNF-? levels (P<0.05). Conclusion Unlike previous studies, our study does not support the hypothesis that increased IL-1? and TNF-? production is involved in the pathogenesis of febrile seizures. PMID:25379044

Ayazi, Parviz; Orangpour, Reza; Daneshi-Kohan, Mohammad Mahdi; Sarokhani, Mohammad Reza; Javadi, Amir; Habibi, Morteza; Talebi-Bakhshayesh, Mousa

2014-01-01

180

Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia  

PubMed Central

Neutropenia and related infections are the most important dose-limiting toxicities in anticancer chemotherapy and radiotherapy. In this study, we explored a new strategy for augmenting host defense in neutropenia-related pneumonia. Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) signaling in neutrophils was elevated by depleting PTEN, a phosphatidylinositol 3?-phosphatase that hydrolyzes PtdIns(3,4,5)P3. In myeloid-specific PTEN knockout mice, significantly more neutrophils were recruited to the inflamed lungs during neutropenia-associated pneumonia. Using an adoptive transfer technique, we demonstrated that this enhancement could be caused directly by PTEN depletion in neutrophils. In addition, disruption of PTEN increased the recruitment of macrophages and elevated proinflammatory cytokines/chemokine levels in the inflamed lungs, which could also be responsible for the enhanced neutrophil recruitment. Depleting PTEN also significantly delayed apoptosis and enhanced the bacteria-killing capability of the recruited neutrophils. Finally, we provide direct evidence that enhancement of neutrophil function by elevating PtdIns(3,4,5)P3 signaling can alleviate pneumonia-associated lung damage and decrease pneumonia-elicited mortality. Collectively, these results not only provide insight into the mechanism of action of PTEN and PtdIns(3,4,5)P3 signaling pathway in modulating neutrophil function during lung infection and inflammation, but they also establish PTEN and related pathways as potential therapeutic targets for treating neutropenia-associated pneumonia. PMID:19286998

Li, Yitang; Jia, Yonghui; Pichavant, Muriel; Loison, Fabien; Sarraj, Bara; Kasorn, Anongnard; You, Jian; Robson, Bryanne E.; Umetsu, Dale T.; Mizgerd, Joseph P.; Ye, Keqiang

2009-01-01

181

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

PubMed Central

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

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

2010-01-01

182

DMSA study performed during febrile urinary tract infection: a predictor of patient outcome?  

Microsoft Academic Search

Technetium-99m dimercaptosuccinic acid (DMSA) study has been advocated as a method for the assessment of renal sequelae after acute febrile urinary tract infection (UTI). However, it is not known whether DMSA scintigraphy performed during acute UTI has any prognostic value for outcome assessment. The objective of this study was to evaluate the usefulness of DMSA scintigraphy performed during UTI as

V. Camacho; M. Estorch; G. Fraga; E. Mena; J. Fuertes; M. A. Hernández; A. Flotats; I. Carrió

2004-01-01

183

Reliability of the Urinalysis for Predicting Urinary Tract Infections in Young Febrile Children  

Microsoft Academic Search

Background: Urinary tract infections (UTIs) are a com- mon source of bacterial infection among young febrile children. Clinical variables affecting the sensitivity of the urinalysis (UA) as a screen for UTI have not been pre- viously investigated. The limited sensitivity of the UA for detecting a UTI requires that a urine culture be ob- tained in some children regardless of

Richard Bachur; Marvin B. Harper

2001-01-01

184

Association of IL4 single-nucleotide polymorphisms with febrile seizures.  

PubMed

As of importance of interleukin-4 (IL-4) in inhibiting the production of proinflammatory cytokines, the IL4 gene polymorphisms were investigated in patients with febrile seizure. This association has not been investigated yet, except 1 study which has been done in Japanese population. Eighty-two patients with febrile seizure were enrolled in this study, compared with 139 controls. The allele and genotype frequency of 3 single-nucleotide polymorphisms of IL4 gene were determined. Frequency of the IL4-590/C allele in the patient group was significantly higher than in the control group (P < .0001). Frequency of the following genotypes was significantly lower in patients compared to controls: IL-4 (-590) TC (P = .0001) and IL-4 (-33) TC (P = .001). The most frequent IL-4 haplotype in the patient group was TCC (P = .00) haplotype. In contrast, frequencies of GCC (P = .01), TTT (P = .009), and TTC (P = .0007) haplotypes were significantly lower in febrile seizure patients. Certain alleles, genotypes, and haplotypes in the IL4 gene were overrepresented in Iranian patients with febrile seizure, which could predispose individuals to this disease, and further investigations in other ethnicities are required. PMID:25330798

Zare-shahabadi, Ameneh; Soltani, Samaneh; Ashrafi, Mahmoud Reza; Shahrokhi, Amin; Zoghi, Samaneh; Pourakbari, Babak; Zamani, Gholam Reza; Mohammadi, Mahmoud; Rezaei, Nima

2015-03-01

185

Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes  

Microsoft Academic Search

Summary The clinical and genetic relationships of febrile seizures myoclonic seizures, FS 1 and atonic seizures, and the most severely affected individual had myoclonic-astatic epilepsy and the generalized epilepsies are poorly understood. We ascertained a family with genealogical information in 2000 (MAE). The pattern of inheritance was autosomal dominant. The large variation in generalized epilepsy phenotypes was individuals where there

Ingrid E. Scheffer; Samuel F. Berkovic

1997-01-01

186

Vesicoureteric reflux in Kuwaiti children with first febrile urinary tract infection  

Microsoft Academic Search

The prevalence of vesicoureteric reflux (VUR) in children with urinary tract infection (UTI) varies among different racial groups. The purpose of this study was to determine the frequency of VUR and associated renal changes in a group of Arab Kuwaiti children with their first documented febrile UTI and to compare our findings with those reported from other racial groups. One

Mohamed Zaki; Ghalia AL Mutari; Mona Badawi; Dina Ramadan; Emad Al deen Hanafy

2003-01-01

187

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

PubMed Central

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

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

2013-01-01

188

Aspergillus Tracheobronchitis and Influenza A Co-infection in a Patient with AIDS and Neutropenia  

PubMed Central

Aspergillus tracheobronchitis (AT), an unusual form of invasive pulmonary aspergillosis (IPA), is characterized by pseudomembrane formation, ulcer or obstruction that is predominantly confined to tracheobronchial tree. Hematologic malignancies, neutropenia, solid organ transplantation, chronic corticosteroid therapy and acquired immunodeficiency syndrome (AIDS) are known to be major predisposing conditions. However, since the introduction of highly active antiretroviral therapy, there is only one reported case of AT in AIDS patient. After pandemic of influenza A/H1N1 2009, there are several reports of IPA in patient with influenza and most of them received corticosteroid or immunosuppressive therapy before the development of IPA. We present a 45 year-old AIDS patient with influenza A infection who developed pseudomembranous AT without corticosteroid use or immunosuppressive therapy. PMID:25298912

Lee, Ji-Yong; Yeom, Joon-Sup; Song, Jae-Uk; Yim, Seo-Hyung; Shin, Dong-Suk; Yu, Jung-Hee; Ju, Deok-Yun; Yim, Jae-Wan; Song, Young-Seok; Sohn, Yoon-Jeong; Do, Sung-Im

2014-01-01

189

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. PMID:22732178

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

190

Co-Occurring Disorders  

MedlinePLUS

... are much less - all of which contribute to stigma. This area of the Mental Health America website is designed to assist mental health advocates in increasing their understanding of key issues in the area of substance abuse and co-occurring disorders. We are committed to providing accurate and timely ...

191

RNA Transcriptional Biosignature Analysis for Identifying Febrile Infants With Serious Bacterial Infections in the Emergency Department  

PubMed Central

Objectives To develop the infrastructure and demonstrate the feasibility of conducting microarray-based RNA transcriptional profile analyses for the diagnosis of serious bacterial infections in febrile infants 60 days and younger in a multicenter pediatric emergency research network. Methods We designed a prospective multicenter cohort study with the aim of enrolling more than 4000 febrile infants 60 days and younger. To ensure success of conducting complex genomic studies in emergency department (ED) settings, we established an infrastructure within the Pediatric Emergency Care Applied Research Network, including 21 sites, to evaluate RNA transcriptional profiles in young febrile infants. We developed a comprehensive manual of operations and trained site investigators to obtain and process blood samples for RNA extraction and genomic analyses. We created standard operating procedures for blood sample collection, processing, storage, shipping, and analyses. We planned to prospectively identify, enroll, and collect 1 mL blood samples for genomic analyses from eligible patients to identify logistical issues with study procedures. Finally, we planned to batch blood samples and determined RNA quantity and quality at the central microarray laboratory and organized data analysis with the Pediatric Emergency Care Applied Research Network data coordinating center. Below we report on establishment of the infrastructure and the feasibility success in the first year based on the enrollment of a limited number of patients. Results We successfully established the infrastructure at 21 EDs. Over the first 5 months we enrolled 79% (74 of 94) of eligible febrile infants. We were able to obtain and ship 1 mL of blood from 74% (55 of 74) of enrolled participants, with at least 1 sample per participating ED. The 55 samples were shipped and evaluated at the microarray laboratory, and 95% (52 of 55) of blood samples were of adequate quality and contained sufficient RNA for expression analysis. Conclusions It is possible to create a robust infrastructure to conduct genomic studies in young febrile infants in the context of a multicenter pediatric ED research setting. The sufficient quantity and high quality of RNA obtained suggests that whole blood transcriptional profile analysis for the diagnostic evaluation of young febrile infants can be successfully performed in this setting. PMID:25526020

Mahajan, Prashant; Kuppermann, Nathan; Suarez, Nicolas; Mejias, Asuncion; Casper, Charlie; Dean, J. Michael; Ramilo, Octavio

2015-01-01

192

Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions.  

PubMed

Peripheral blood mononuclear cells (MNC) from 27 children with a febrile convulsion were tested for production of interleukin-1 (IL-1) in culture. MNC stimulated with lipopolysaccharide (LPS) showed a significantly increased production of IL-1 when compared to MNC from children without convulsions but with bacterial infections (p less than 0.001), viral infections (p less than 0.005) or no infection (p less than 0.005). Children who had experienced a febrile convulsion were retested several months later; this time the IL-1 production from LPS-stimulated MNC was not different from controls. These results demonstrate that MNC at the time of febrile convulsions have increased sensitivity to LPS and possibly to other IL-1 inducers; the resulting enhanced IL-1 response from sensitized MNC may have a role in the pathogenesis of febrile convulsions. PMID:2239277

Helminen, M; Vesikari, T

1990-01-01

193

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

Microsoft Academic Search

Summary  In cancer chemotherapy neutropenia is a common dose-limiting toxicity. An ability to predict the neutropenic effects of cytotoxic\\u000a agents based on proposed trial designs and models conditioned on previous studies would be valuable. The aim of this study\\u000a was to evaluate the ability of a semi-mechanistic pharmacokinetic\\/pharmacodynamic (PK\\/PD) model for myelosuppression to predict\\u000a the neutropenia observed in Phase I clinical

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

194

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

Microsoft Academic Search

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

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

1997-01-01

195

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. PMID:24852787

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

2014-01-01

196

"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

197

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

PubMed

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

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

2015-05-01

198

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

199

The association between acetaminophen concentrations in the cerebrospinal fluid and temperature decline in febrile infants.  

PubMed

The objective of this study consisting of a prospective cohort of febrile infants was to describe the correlation between cerebrospinal fluid (CSF) acetaminophen (paracetamol) concentrations and changes in body temperature in febrile infants. Infants, one week to one year of age, with rectal temperature >or=38.0 degrees C, treated with acetaminophen were studied if they underwent a lumbar puncture (LP). Patients received 15 mg/kg of acetaminophen 30 minutes to 4 hours before lumbar puncture was performed. Rectal temperature was documented before acetaminophen administration and at the time of lumbar puncture. Plasma and CSF acetaminophen levels were determined using high-pressure liquid chromatography. Thirty-one infants were studied. In a nonlinear regression, the relationship among acetaminophen concentrations in the CSF, time, and temperature differences is best described by a Lorentzian distribution. The model suggests that a peak effect on temperature is achieved at CSF concentration of 11.9 microg/mL and 182 minutes after acetaminophen administration (P<0.001 and P<0.001, respectively r=0.9 adjusted r square=0.78). Temperature decrement in young febrile infants, treated with acetaminophen, correlates with time and acetaminophen concentrations in the CSF. High concentrations of acetaminophen in the CSF, exceeding a certain level, are not associated with greater temperature decrement. PMID:18043482

Kozer, Eran; Hahn, Yuval; Berkovitch, Matitiahu; Chaim, Adina Bar; Brandriss, Norit; Verjee, Zul; Mor, Anat; Goldman, Michael

2007-12-01

200

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

PubMed Central

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

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

2013-01-01

201

Roles of two preoptic cell groups in tonic and febrile control of rat tail sympathetic fibers.  

PubMed

In response to cold and in fever, heat dissipation from the skin is reduced by sympathetic vasoconstriction. The preoptic region has been implicated in regulating basal, thermal, and febrile vasoconstriction of cutaneous vessels such as the rat's tail, but the neurons responsible for these functions have not been well localized. We recorded activity from single sympathetic nerve fibers supplying tail vessels in urethane-anesthetized rats, while microinjections of GABA (300 mM, 15-30 nl) were used to inhibit neurons in different parts of the preoptic region. Tail fiber activity increased promptly after GABA injections in two distinct regions: a rostromedial preoptic region (RMPO) centered around the organum vasculosum of the lamina terminalis, and a second region centered approximately 1 mm caudolaterally (CLPO). Responses to GABA within each region were similar. The febrile mediator, PGE(2) (0.2 or 1 ng in 15 nl) was then microinjected into GABA-sensitive preoptic sites. Injections of PGE(2) into the RMPO induced a rapid increase in tail fiber activity followed by a rise in core temperature; injections into the rostromedial part of CLPO gave delayed tail fiber responses; injections into the central and caudal parts of CLPO were without effect. These results indicate that neurons in two distinct preoptic regions provide tonic inhibitory drive to the tail vasoconstrictor supply, but febrile vasoconstriction is mediated by PGE(2) selectively inhibiting neurons in the rostromedial region. PMID:19211726

Tanaka, Mutsumi; McKinley, Michael J; McAllen, Robin M

2009-04-01

202

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. PMID:24106552

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

203

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

PubMed Central

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

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

2013-01-01

204

Triage of febrile children at a GP cooperative: determinants of a consultation  

PubMed Central

Background Most febrile children contacting a GP cooperative are seen by a GP, although the incidence of serious illness is low. The guidelines for triage might not be suitable in primary care. Aim To investigate the determinants related to the outcome of triage in febrile children. Design of study Cross-sectional study. Setting Dutch GP cooperative. Method Receptionists filled out a triage questionnaire when parents called regarding their febrile child (aged between 3 months and 6 years) and estimated the level of concern of the parents. The outcome was either telephone advice, a consultation, or a home visit. Children were divided in subgroups based on age <18 months or ?18 months, and prognostic models for a consultation were constructed. Results Of 422 children, 73% were seen by a GP. Children aged <18 months were more likely to be seen when their parents reported less drinking or shortness of breath. In children aged ?18 months, a duration of fever of ?3 days, drowsiness, or a pale, ashen, or mottled skin were predictors of consultation. Children with alarm symptoms were seen according to the guideline. In both subgroups, children without alarm symptoms were more likely to be seen when their parents were concerned. Conclusion The available guideline was followed to a large extent at a GP cooperative. Because, surprisingly, most children were reported to have alarm symptoms, the validity of the triage questions asking parents about alarm symptoms is questionable. PMID:18494175

Monteny, Miriam; Berger, Marjolein Y; van der Wouden, Johannes C; Broekman, Berth J; Koes, Bart W

2008-01-01

205

Characteristics and treatment of temporal lobe epilepsy with a history of complicated febrile convulsion  

PubMed Central

This study aimed to examine the close correlation between complicated febrile convulsions (CFC) and medial temporal lobe epilepsy and to delineate characteristics of temporal lobe epilepsy with CFC. Patients with temporal lobe epilepsy were divided into those with a prior episode of CFC (n=52), those with febrile convulsions other than CFC, and those witout either (n=345). Clinical constellations, neuroimaging, drug resistance, and effects of temporal lobectomy of the three groups were compared. A close association between CFC and temporal lobe epilepsy was confirmed. The salient features of temporal lobe epilepsy with CFC were early age at onset of habitual seizures (about 10 years), the predominance of autonomic auras, and a high incidence of MRI evidence of unilateral medial temporal sclerosis. Patients with temporal lobe epilepsy with prior CFC had an excellent outcome after surgery, by contrast with an unfavourable response to drug therapy. The surgical results were discouraging in patients with temporal lobe epilepsy without history of any febrile convulsions and without solid brain tumours. These results indicate surgical intervention as the choice of therapy in a substantial number of patients with temporal lobe epilepsy with a history of CFC.?? PMID:9489540

Kanemoto, K.; Takuji, N.; Kawasaki, J.; Kawai, I.

1998-01-01

206

Effect of neutropenia and treatment delay on the response to antifungal agents in experimental disseminated candidiasis.  

PubMed

Disseminated candidiasis is associated with a high rate of morbidity and mortality. The presence of neutrophils and the timely administration of antifungal agents are likely to be critical factors for a favorable therapeutic outcome of this syndrome. The effect of neutropenia on the temporal profile of the burden of Candida albicans in untreated mice and those treated with amphotericin B was determined using a pharmacodynamic model of disseminated candidiasis. A mathematical model was developed to describe the rate and extent of the C. albicans killing attributable to neutrophils and to amphotericin B. The consequences of a delay in the administration of amphotericin B, flucytosine, or micafungin were studied by defining dose-response relationships. Neutrophils caused a logarithmic decline in fungal burden in treated and untreated mice. The combination of amphotericin B and neutrophils resulted in a high rate of Candida killing and a sustained anti-C. albicans effect. In neutropenic mice, 5 mg/kg of body weight of amphotericin B was required to prevent progressive logarithmic growth. An increased delay in drug administration resulted in a reduction in the maximum effect to a point at which no drug effect could be observed. Neutrophils and the timely initiation of antifungal agents are critical determinants in the treatment of experimental disseminated candidiasis. PMID:17088486

Hope, William W; Drusano, George L; Moore, Caroline B; Sharp, Andrew; Louie, Arnold; Walsh, Thomas J; Denning, David W; Warn, Peter A

2007-01-01

207

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

PubMed

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

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

2015-03-01

208

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

209

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. PMID:22899009

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

2012-01-01

210

Naturally Occurring Food Toxins  

PubMed Central

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

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

2010-01-01

211

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

PubMed Central

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 their first febrile convulsion, children who had had a febrile convulsion did not differ at age 5 from their peers who had not had febrile convulsions in their behaviour, height, head circumference, or performance in simple intellectual tests. PMID:3922470

Verity, C M; Butler, N R; Golding, J

1985-01-01

212

Febrile-Range Hyperthermia Augments Lipopolysaccharide-Induced Lung Injury by a Mechanism of Enhanced Alveolar Epithelial Apoptosis  

PubMed Central

Fever is common in critically ill patients and is associated with worse clinical outcomes, including increased intensive care unit mortality. In animal models, febrile-range hyperthermia (FRH) worsens acute lung injury, but the mechanisms by which this occurs remain uncertain. We hypothesized that FRH augments the response of the alveolar epithelium to TNF-? receptor family signaling. We found that FRH augmented LPS-induced lung injury and increased LPS-induced mortality in mice. At 24 h, animals exposed to hyperthermia and LPS had significant increases in alveolar permeability without changes in inflammatory cells in bronchoalveolar lavage fluid or lung tissue as compared with animals exposed to LPS alone. The increase in alveolar permeability was associated with an increase in alveolar epithelial apoptosis and was attenuated by caspase inhibition with zVAD.fmk. At 48 h, the animals exposed to hyperthermia and LPS had an enhanced lung inflammatory response. In murine lung epithelial cell lines (MLE-15, LA-4) and in primary type II alveolar epithelial cells, FRH enhanced apoptosis in response to TNF-? but not Fas ligand. The increase in apoptosis was caspase-8 dependent and associated with suppression of NF-?B activity. The FRH-associated NF-?B suppression was not associated with persistence of I?B-?, suggesting that FRH-mediated suppression of NF-?B occurs by means other than alteration of I?B-? kinetics. These data show for the first time that FRH promotes lung injury in part by increasing lung epithelial apoptosis. The enhanced apoptotic response might relate to FRH-mediated suppression of NF-?B activity in the alveolar epithelium with a resultant increase in susceptibility to TNF-?–mediated cell death. PMID:20200273

Lipke, Anne B.; Matute-Bello, Gustavo; Herrero, Raquel; Kurahashi, Kiyoyasu; Wong, Venus A.; Mongovin, Stephen M.; Martin, Thomas R.

2010-01-01

213

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

PubMed Central

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

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

2011-01-01

214

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

PubMed Central

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

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

2013-01-01

215

Sequence Analysis of the Human Virome in Febrile and Afebrile Children  

PubMed Central

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

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

2012-01-01

216

Can Procalcitonin Reduce Unnecessary Voiding Cystoureterography in Children with First Febrile Urinary Tract Infection?  

PubMed Central

Objective: Recently, new predictors of vesicoureteral reflux (VUR) in children with a first febrile UTI such as Procalcitonin (PCT) were introduced as selective approaches for cystography. This study wants to show the capability of PCT in predicting presence of VUR at the first febrile UTI in children. Methods: Patients between 1 month and 15 years of age with febrile UTI were included in this prospective study. PCT values were measured through a semi-quantitative method in four grades comprising values less than 0.5, 0.5-2.0, 2.0-10.0 and above 10.0 ng/ml. The independence of PCT levels in predicting VUR were assessed after adjustment for all potential confounders using a logistic-regression model. Findings: A total of 68 patients, 54 (79.4%) girls and 14 (20.6%) boys were evaluated. PCT level demonstrated a significant difference between patients with positive VUR and those with negative VUR (P=0.012). To calculate the independent factors that may predict the presence of VUR, all included variables were adjusted for age and sex. Results of logistic regression showed that a PCT level between 2.0 and 10.0 ng/mL could independently predict presence of VUR (Odds ratio=6.11, CI 95%= 1.22-30.77, P=0.03). Conclusion: Our finding in this study showed that readily available semi-quantitative measures for PCT are feasible for detecting patients with VUR. We suggest that in semi-quantitative measurements of PCT, levels between 2.0 and 10.0 ng/ml could be an independent predictor of positive VUR. PMID:25755864

Halimi-asl, Aliasghar; Hosseini, Amir Hossein; Nabavizadeh, Pooneh

2014-01-01

217

Protracted febrile myalgia syndrome in a kidney transplant recipient with familial mediterranean Fever.  

PubMed

Drug-induced toxic myopathy is a complication of familial Mediterranean fever in patients who receive colchicine, especially when combined with cyclosporine. Protracted febrile myalgia syndrome is a severe form of familial Mediterranean fever. A 34-year-old man who had familial Mediterranean fever for > 15 years developed kidney failure because of secondary amyloidosis. He received living-unrelated-donor kidney transplant that functioned normally. He was on colchicine prophylaxis that was continued after transplant, and he received immuno-suppression induction with antithymocyte globulin and maintenance with prednisolone, mycophenolate mofetil, and cyclosporine. After 2 months, he presented with severe myopathy and elevated creatine kinase. Muscle biopsy showed evidence of drug-induced toxic myopathy, most likely caused by cyclosporine in combination with colchicine. Cyclosporine was replaced with sirolimus and colchicine was stopped. Symptoms partially improved and creatine kinase decreased to normal. The prednisolone dosage was reduced gradually to 5 mg daily. At 8 months after transplant, he was readmitted because of severe arthralgia, prolonged fever, pleuritic chest pain, diffuse abdominal pain, purpuric rash, macroscopic hematuria, proteinuria, and diarrhea. The C-reactive protein and erythrocyte sedimentation rate were elevated. The clinical diagnosis was recurrent familial Mediterranean fever presenting as protracted febrile myalgia syndrome. Despite the history of toxic myopathy, he was restarted on colchicine (0.5 mg, twice daily), and colchicine was well tolerated. There was marked improvement of most symptoms within several days. Follow-up 5 years later showed normal kidney graft function and no familial Mediterranean fever activity on colchicine prophylaxis. In summary, familial Mediterranean fever reactivation and protracted febrile myalgia syndrome after kidney transplant may be treated with colchicine and modulation of immunosuppressive therapy. PMID:24650330

Abdel Halim, Medhat M; Al-Otaibi, Torki; Donia, Farouk; Gheith, Osama; Asif, Ponnambath; Nawas, Moideen; Rashad, Rashad H; Said, Tarek; Nair, Prasad; Nampoory, Narayanan

2015-04-01

218

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

PubMed Central

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

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

2014-01-01

219

Clinical value of soluble IgG Fc receptor type III in plasma from patients with chronic idiopathic neutropenia.  

PubMed

Previous studies have shown that the plasma level of soluble IgG Fc receptor type III (sFcgammaRIII) is a measure of the total body neutrophil mass. The aim of this study was to determine whether the plasma level sFcgammaRIII is associated with the risk of contracting bacterial infections in patients with neutropenia. We collected blood from 66 patients suffering from acquired idiopathic neutropenia, whose blood was sent to our laboratory for diagnostic evaluation of neutropenia (neutrophil count <1,500 cells/microL). Soluble FcgammaRIII levels were measured in plasma. Genotype distibutions of FcgammaR polymorphisms were determined. Clinical data were obtained from the patient files. Patients were assessed as to whether or not they had suffered from a bacterial infection 3 months before to 3 months after a single sFcgammaRIII measurement. In addition, longitudinal data were obtained from 21 patients. Of the 66 neutropenic patients who were included, 15 had suffered from a bacterial infection in the period 3 months before to 3 months after sFcgammaRIII measurement. The age and sex distribution was equal among the groups with and without infections, as were the genotype frequencies of neutrophil FcgammaR polymorphisms. Both neutrophil count and plasma level sFcgammaRIII were significantly lower in the patient group with infections, compared with the noninfected group (P = .03 and P < .0001, respectively). No infections were reported for patients who had plasma sFcgammaRIII levels above 100 arbitrary units (AU; normal value, 30 to 200). After matching each infected patient with two noninfected patients having the same neutrophil count, sFcgammaRIII plasma levels remained significantly lower in the group with infections (P = . 0001). For the patients who were followed in time, no infections were reported when sFcgammaRIII levels were above 100 AU. In conclusion, our population of patients with chronic idiopathic neutropenia with plasma sFcgammaRIII levels above 100 AU did not show an increased risk of contracting bacterial infections. PMID:9573035

Koene, H R; de Haas, M; Kleijer, M; Huizinga, T W; Roos, D; von dem Borne, A E

1998-05-15

220

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. PMID:23663165

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

2013-01-01

221

Does endogenous peripheral arginine vasopressin have a role in the febrile responses of conscious rabbits?  

PubMed Central

1. The actions of peripheral arginine vasopressin (AVP) on the febrile responses of conscious rabbits induced by peripherally administered polyinosinic:polycytidylic acid (poly(I).poly(C)) have been studied using an AVP V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin). 2. Temperature responses were monitored continuously using rectal thermistor probes. Test substances were administered intravenously (i.v.). Blood samples were taken at timed intervals from a marginal ear vein and plasma PGE2 and PGF2 alpha levels determined by radioimmunoassay. 3. Poly(I).poly(C) (2.5 micrograms/kg) stimulated a reproducible biphasic rise in body temperature with a lag phase of 45-60 min and peaks at 90 and 225 min. The febrile response was accompanied by a 5-fold rise in circulating immunoreactive (ir) PGE2, which peaked after 90 min and remained elevated up to 300 min. Poly(I).poly(C) also stimulated a 2.5-fold rise in circulating irPGF2 alpha, which peaked after 150 min and was followed by a return to basal levels after 300 min. 4. The overall magnitude of the febrile response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. 5. The irPGE2 response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. The irPGF2 alpha response was only reduced at the peak 150 min time point measurement. 6. In conclusion, these results show a modulatory role for a peripherally administered AVP V1 antagonist in the febrile responses to poly(I).poly(C), suggesting a possible propyretic role for endogenous peripheral AVP. This modulatory role appears to be mediated via actions on prostaglandin E2. PMID:8271213

Milton, N G; Hillhouse, E W; Milton, A S

1993-01-01

222

Long-term effect of phenobarbital on cognitive function in children with febrile convulsions.  

PubMed

Psychometric tests were performed on 50 children with a history of febrile convulsions. Twenty-five of these had received daily phenobarbital for a mean of 35 months; 25 had received no phenobarbital. The two groups were matched for sex, age at the time of testing, race, and socioeconomic status. The tests used were the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), the Matching Familiar Figures Test, and the Children's Embedded Figures Test. There were no significant differences in test results between the two groups. PMID:7322717

Wolf, S M; Forsythe, A; Stunden, A A; Friedman, R; Diamond, H

1981-12-01

223

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

PubMed Central

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

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

2013-01-01

224

Altered Pharmacokinetics of Piperacillin in Febrile Neutropenic Patients with Hematological Malignancy  

PubMed Central

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

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

2014-01-01

225

Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel ß1 subunit gene SCN1B  

Microsoft Academic Search

Febrile seizures affect approximately 3% of all children under six years of age and are by far the most common seizure disorder. A small proportion of children with febrile seizures later develop ongoing epilepsy with afebrile seizures. Segregation analysis suggests the majority of cases have complex inheritance but rare families show apparent autosomal dominant inheritance. Two putative loci have been

Robyn H. Wallace; Dao W. Wang; Rita Singh; Ingrid E. Scheffer; Alfred L. George; Hilary A. Phillips; Kathrin Saar; Andre Reis; Eric W. Johnson; Grant R. Sutherland; Samuel F. Berkovic; John C. Mulley

1998-01-01

226

Complex Febrile Seizures Followed by Complete Recovery in an Infant with High-Titer 2009 Pandemic Influenza A (H1N1) Virus Infection?  

PubMed Central

We describe a 2009 H1N1 virus infection with a high viral load in a previously healthy infant who presented with complex febrile seizures and improved on oseltamivir without neurologic sequelae. Febrile seizures may be a complication in young children experiencing infection with high viral loads of 2009 H1N1 influenza virus. PMID:20702660

O'Leary, Mandy F.; Chappell, James D.; Stratton, Charles W.; Cronin, Robert M.; Taylor, Mary B.; Tang, Yi-Wei

2010-01-01

227

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

228

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

229

Hyperventilation in febrile Nigerian children without pneumonia: an evaluation of the influence of anaemia.  

PubMed

A total of 225 pre-school Nigerians were studied to evaluate the effect of anaemia on the respiratory rate of febrile children, and the influence of this on the reliability of the WHO criteria for the clinical diagnosis of pneumonia in the primary health care setting. Malaria was the commonest cause of febrile illness (63.1 pc). The prevalence of severe anaemia was 28.0 pc. The mean respiratory rate of anaemic children (53.9 +/- 12.8/min) was significantly higher than that of the non-anaemic (48.4 +/- 12.7/min; p = 0.011). Mean body temperature was not significantly different in both groups. Haematocrit was negatively correlated with respiratory rate. The positive correlation observed between temperature and respiratory rate was enhanced by decreasing haematocrit. More of the severely anaemic children (68.6 pc) exceeded the WHO respiratory rate threshold for diagnosis of pneumonia than the moderately anaemic (55.4 pc) or non-anaemic (36.1 pc). The specificity of the WHO criteria for clinical diagnosis of pneumonia decreased with decreasing haematocrit. PMID:7585912

Meremikwu, M M; Asindi, A A; Ezedinachi, E N; Imananagha, L; Etim, B; Oyo-Ita, A; Tomkins, M

1995-08-01

230

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

231

Chikungunya and Dengue Fever among Hospitalized Febrile Patients in Northern Tanzania  

PubMed Central

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

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

2012-01-01

232

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

E-print Network

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

Goldin, Alan L.

233

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

PubMed Central

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

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

2015-01-01

234

Rapid Diagnostic Tests Compared with Malaria Microscopy for Guiding Outpatient Treatment of Febrile Illness in Tanzania: Randomised Trial  

Microsoft Academic Search

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

Hugh Reyburn; Hilda Mbakilwa; Rose Mwangi; Ombeni Mwerinde; Raimos Olomi; Chris Drakeley; Christopher J. M. Whitty; Talisuna; Meya

2007-01-01

235

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

PubMed Central

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

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

2014-01-01

236

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. PMID:23936565

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

237

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. PMID:23009155

2012-01-01

238

Intermittent granulocyte colony-stimulating factor for neutropenia management in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone.  

PubMed

Neutropenia is a major dose-limiting toxicity associated with lenalidomide in relapsed/refractory multiple myeloma (MM). The optimal dosing schedule of granulocyte colony-stimulating factor (G-CSF) is unclear. We developed an intermittent G-CSF schedule (4-6 doses per cycle) initiated upon onset of grade 3-4 neutropenia. Of 216 patients with relapsed/refractory MM treated at our center with lenalidomide/dexamethasone on an Expanded Access Program, there was a high incidence of grade 3-4 neutropenia (61%) and grade 3-4 infections (37%). Despite intermittent G-CSF use in 117 patients, recurrent grade 3-4 neutropenia was common (59%), and dose reductions were required in 40% of G-CSF recipients, most due to thrombocytopenia. G-CSF recipients had a longer duration on therapy and achieved a higher rate and depth of response. Intermittent G-CSF may be an effective approach for lenalidomide dose-preservation, which may lead to improved outcomes, although it does not prevent infections or thrombocytopenia-related dose limitations. PMID:24738975

Sun, Haowei Linda; Atenafu, Eshetu G; Yeboah, Elizabeth; Reece, Donna E; Trudel, Suzanne; Kukreti, Vishal; Masih-Khan, Esther; Winter, Andrew; Chen, Christine

2015-02-01

239

Management of sepsis in neutropenia: guidelines of the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO)  

Microsoft Academic Search

These guidelines from the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO) give recommendations for the management of adults with neutropenia and the diagnosis of sepsis. The guidelines are written for clinicians and focus on pathophysiology, diagnosis, and treatment of sepsis. The manuscript contains evidence-based recommendations for the assessment of the quality and strength

Olaf Penack; Thomas Beinert; Dieter Buchheidt; Hermann Einsele; Holger Hebart; Michael G. Kiehl; Gero Massenkeil; Xaver Schiel; Jan Schleicher; Philipp B. Staber; Stefan Wilhelm; Hans-Heinrich Wolf; Helmut Ostermann

2006-01-01

240

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

241

Abnormal Dimercaptosuccinic Acid Scan May Be Related to Persistence of Vesicoureteral Reflux in Children with Febrile Urinary Tract Infection  

PubMed Central

Purpose This study assessed whether 99mtechnetium dimercaptosuccinic acid (DMSA) scintigraphy used for the assessment of renal sequelae after febrile urinary tract infection (UTI) has any prognostic value for outcome measurement of vesicoureteral reflux (VUR) by retrospectively evaluating the correlation between abnormal DMSA scintigraphy results and persistence of VUR in children with febrile UTI. Materials and Methods The medical records of 142 children (57 boys, 85 girls) admitted with febrile UTI from January 2004 to December 2006 and who were followed up for more than 1 year were retrospectively reviewed. At the initial and follow-up visits, renal ultrasound and DMSA scans were performed within 7 days from the diagnosis and voiding cystourethrography (VCUG) was performed within 1 month in all case and follow-up evaluations. Results The children's mean age was 4.8±3.6 years (range, 0.3 to 14 years). The mean follow-up was 28.2±4.8 months. At the initial examination, VUR was more often associated with an abnormal DMSA scan result (83.3%) than with a normal DMSA scan result (16.7%, p=0.02). The frequency of VUR with an abnormal DMSA scan during acute UTI was significantly higher than the frequency of VUR with a normal DMSA scan (38.8% vs, 25.8%, respectively, p=0.004). Also, high-grade VUR was associated with an abnormal DMSA scan result (32.5%) more often than with a normal DMSA scan result (0%, p=0.01). Children with an abnormal DMSA scan had a lower resolution rate of VUR (17.5%) than did children with a normal DMSA scan (75.0%) at the follow-up VCUG (p=0.02). Conclusions An abnormal result on a DMSA scan during febrile UTI is associated with high-grade and persistent VUR. DMSA scans performed during febrile UTI are useful in reflux resolution in childhood. PMID:23136633

Ki, Hyun Chong; Yoo, Dong Hun; Hwang, In Sang; Hwang, Eu Chang; Oh, Kyung Jin; Jung, Seung Il; Kang, Taek Won; Kwon, Dongdeuk; Park, Kwangsung; Ryu, Soo Bang

2012-01-01

242

Rickettsial infections in Southeast Asia: implications for local populace and febrile returned travelers.  

PubMed

Rickettsial infections represent a major cause of non-malarial febrile illnesses among the residents of Southeast Asia and returned travelers from that region. There are several challenges in recognition, diagnosis, and management of rickettsioses endemic to Southeast Asia. This review focuses on the prevalent rickettsial infections, namely, murine typhus (Rickettsia typhi), scrub typhus (Orientia tsutsugamushi), and members of spotted fever group rickettsiae. Information on epidemiology and regional variance in the prevalence of rickettsial infections is analyzed. Clinical characteristics of main groups of rickettsioses, unusual presentations, and common pitfalls in diagnosis are further discussed. In particular, relevant epidemiologic and clinical aspects on emerging spotted fever group rickettsiae in the region, such as Rickettsia honei, R. felis, R. japonica, and R. helvetica, are presented. Furthermore, challenges in laboratory diagnosis and management aspects of rickettsial infections unique to Southeast Asia are discussed, and data on emerging resistance to antimicrobial drugs and treatment/prevention options are also reviewed. PMID:24957537

Aung, Ar Kar; Spelman, Denis W; Murray, Ronan J; Graves, Stephen

2014-09-01

243

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

SciTech Connect

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

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

1986-04-01

244

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. PMID:24353713

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

2013-01-01

245

Emergency Management of Febrile Status Epilepticus: Results of the FEBSTAT study  

PubMed Central

Objective Treatment of seizures varies by region with no standard emergency treatment protocol. Febrile status epilepticus (FSE) is often a child’s first seizure; therefore, families are rarely educated about emergency treatment. Methods From 2002 to 2010, 199 subjects, age 1 month to 6 years, were recruited as part of a prospective, multicenter study of consequences of FSE. FSE was defined as a febrile seizure or series of seizures lasting >30 minutes. The patients’ charts were reviewed. No standardized treatment protocol was implemented for this observational study. Results 179 received at least one antiepileptic drug (AED) to terminate FSE and more than one AED was required in 140 patients (70%). Median time from the seizure onset to first AED by EMS or ED was 30 minutes. Mean seizure duration was 81 minutes for subjects given medication prior to ED and 95 minutes for those who did not (p=0.1). Median time from the first dose of AED to end of seizure was 38 minutes. Initial dose of lorazepam or diazepam was suboptimal in 32 of 166 patients (19%). Ninety-five (48%) subjects received respiratory support by EMS or ED. Median seizure duration for respiratory support group was 83 minutes; for non-respiratory support group was 58 minutes (p-value < 0.001). Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration. Significance FSE rarely stops spontaneously, is fairly resistant to medications and even with treatment persists for a significant period of time. The total seizure duration is composed of two separate factors; the time from seizure onset to AED initiation, and the time from first AED to seizure termination. Earlier onset of treatment results in shorter total seizure duration. A standard pre-hospital treatment protocol should be used nationwide and education of EMS responders is necessary. PMID:24502379

Seinfeld, Syndi; Shinnar, Shlomo; Sun, Shumei; Hesdorffer, Dale C; Deng, Xiaoyan; Shinnar, Ruth C; O’Hara, Kathryn; Nordli, Douglas R; Frank, L Matthew; Gallentine, William; Moshé, Solomon L; Pellock, John M

2014-01-01

246

DMSA study performed during febrile urinary tract infection: a predictor of patient outcome?  

PubMed

Technetium-99m dimercaptosuccinic acid (DMSA) study has been advocated as a method for the assessment of renal sequelae after acute febrile urinary tract infection (UTI). However, it is not known whether DMSA scintigraphy performed during acute UTI has any prognostic value for outcome assessment. The objective of this study was to evaluate the usefulness of DMSA scintigraphy performed during UTI as a predictor of patient outcome, to identify children at risk of events [vesico-ureteral reflux (VUR) or recurrent UTI] that may lead to the development of progressive renal damage. One hundred and fifty-two children (including 78 girls) with a mean age of 20 months (range 1 month to 12 years) with first febrile UTI were evaluated by DMSA scintigraphy during acute UTI. After acute UTI, children were explored by voiding cysto-urethrography. Children who presented an abnormal DMSA study, or a normal DMSA study but VUR or recurrent UTI, underwent a DMSA control study 6 months after UTI. Children with VUR were followed up by direct radionuclide cystography. DMSA scintigraphy performed during acute UTI was normal in 112 children (74%). In 95 of these children, follow-up DMSA scintigraphy was not performed owing to a good clinical outcome. In the remaining 17 children, follow-up scintigraphy was normal. Forty children (26%) presented abnormal DMSA study during acute UTI. Twenty-five of them presented a normal follow-up DMSA, and 15 presented cortical lesions. Children with abnormal DMSA had a higher frequency of VUR than children with normal DMSA (48% vs 12%). It is concluded that children with normal DMSA during acute UTI have a low risk of renal damage. Children with normal follow-up DMSA and low-grade VUR have more frequent spontaneous resolution of VUR. PMID:14758509

Camacho, V; Estorch, M; Fraga, G; Mena, E; Fuertes, J; Hernández, M A; Flotats, A; Carrió, I

2004-06-01

247

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

PubMed Central

Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA) molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-?, tumor necrosis factor-?, and transforming growth factor-?1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients. PMID:22956967

Mavroudi, Irene; Papadaki, Helen A.

2012-01-01

248

Stochastic Hypothesis of Transition from Inborn Neutropenia to AML: Interactions of Cell Population Dynamics and Population Genetics  

PubMed Central

We present a stochastic model of driver mutations in the transition from severe congenital neutropenia to myelodysplastic syndrome to acute myeloid leukemia (AML). The model has the form of a multitype branching process. We derive equations for the distributions of the times to consecutive driver mutations and set up simulations involving a range of hypotheses regarding acceleration of the mutation rates in successive mutant clones. Our model reproduces the clinical distribution of times at diagnosis of secondary AML. Surprisingly, within the framework of our assumptions, stochasticity of the mutation process is incapable of explaining the spread of times at diagnosis of AML in this case; it is necessary to additionally assume a wide spread of proliferative parameters among disease cases. This finding is unexpected but generally consistent with the wide heterogeneity of characteristics of human cancers. PMID:23641360

Kimmel, Marek; Corey, Seth

2013-01-01

249

Granulocyte colony-stimulating factor for hepatitis C therapy-associated neutropenia: systematic review and economic evaluation.  

PubMed

Hepatitis C virus (HCV) treatment requires maximal adherence to pegylated interferon (Peg-IFN) and ribavirin to achieve a sustained virologic response (SVR). Neutropenia is the most common cause for Peg-IFN dose reduction. Our objectives were to evaluate the effectiveness, safety and cost-effectiveness of granulocyte colony-stimulating factor (G-CSF) versus Peg-IFN dose reduction for HCV therapy-associated neutropenia in treatment naïve adults. We conducted a systematic review to identify controlled trials and observational studies. Study selection, quality assessment and data extraction were completed independently by two investigators. Cost-effectiveness and cost-utility analyses compared G-CSF with dose reduction. Nineteen studies were included. In one trial, the SVR for those receiving G-CSF was 54.5% (95% CI: 34.7-73.1) compared with 26.3% (95% CI: 11.8-48.8) for dose reduction. The remaining studies were case series or retrospective cohorts and provided weak evidence for the relationship between SVR and G-CSF. The risk of adverse events, including infection, associated with G-CSF was low (13.1%; 95% CI: 8.0-20.8) and clinically insignificant. G-CSF had an incremental cost-effectiveness ratio of $41,701 per SVR achieved in genotype 1, and $16,115 per SVR achieved in genotype 2 or 3. Estimates were robust under a variety of resource and intervention scenarios. While administration of G-CSF may enable patients to remain on or resume optimal HCV therapy, there was weak evidence that this improves the likelihood of SVR compared with dose reduction. Adverse effects of G-CSF are mild. The economic evaluation was inconclusive. PMID:21692951

Tandon, P; Doucette, K; Fassbender, K; Vandermeer, B; Durec, T; Dryden, D M

2011-07-01

250

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

PubMed Central

Of 13 135 children followed up from birth to the age of 5 years, 303 (2.3%) had febrile convulsions. Prior neurological abnormality had been noted in 13. Of the 290 remaining children, 57 (20%) presented with a complex convulsion, and 103 children (35%) went on to have further febrile convulsions. The risk of further febrile convulsions varied with the age at first convulsion and the presence of a history of convulsive disorders in relatives. There were no significant differences between the sexes. PMID:3922469

Verity, C M; Butler, N R; Golding, J

1985-01-01

251

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. PMID:23355934

Obasa, Temitope O.; Sowunmi, Funmilola Olusola

2012-01-01

252

Bacterial Lipopolysaccharide Augments Febrile-Range Hyperthermia-Induced Heat Shock Protein 70 Expression and Extracellular Release in Human THP1 Cells.  

PubMed

Sepsis, a devastating and often lethal complication of severe infection, is characterized by fever and dysregulated inflammation. While infections activate the inflammatory response in part through Toll-like receptors (TLRs), fever can partially activate the heat shock response with generation of heat shock proteins (HSPs). Since extracellular HSPs, especially HSP70 (eHSP70), are proinflammatory TLR agonists, we investigated how exposure to the TLR4 agonist, bacterial lipopolysaccharide (LPS) and febrile range hyperthermia (FRH; 39.5°C) modify HSP70 expression and extracellular release. Using differentiated THP1 cells, we found that concurrent exposure to FRH and LPS as well as TLR2 and TLR3 agonists synergized to activate expression of inducible HSP72 (HSPA1A) mRNA and protein via a p38 MAP kinase-requiring mechanism. Treatment with LPS for 6 h stimulated eHSP70 release; levels of eHSP70 released at 39.5°C were higher than at 37°C roughly paralleling the increase in intracellular HSP72 in the 39.5°C cells. By contrast, 6 h exposure to FRH in the absence of LPS failed to promote eHSP70 release. Release of eHSP70 by LPS-treated THP1 cells was inhibited by glibenclamide, but not brefeldin, indicating that eHSP70 secretion occurred via a non-classical protein secretory mechanism. Analysis of eHSP70 levels in exosomes and exosome-depleted culture supernatants from LPS-treated THP1 cells using ELISA demonstrated similar eHSP70 levels in unfractionated and exosome-depleted culture supernatants, indicating that LPS-stimulated eHSP70 release did not occur via the exosome pathway. Immunoblot analysis of the exosome fraction of culture supernatants from these cells showed constitutive HSC70 (HSPA8) to be the predominant HSP70 family member present in exosomes. In summary, we have shown that LPS stimulates macrophages to secrete inducible HSP72 via a non-classical non-exosomal pathway while synergizing with FRH exposure to increase both intracellular and secreted levels of inducible HSP72. The impact of increased macrophage intracellular HSP70 levels and augmented secretion of proinflammatory eHSP70 in the febrile, infected patient remains to be elucidated. PMID:25659128

Tulapurkar, Mohan E; Ramarathnam, Aparna; Hasday, Jeffrey D; Singh, Ishwar S

2015-01-01

253

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

254

Does Lupus Occur in Men?  

MedlinePLUS

... Understanding lupus Understanding lupus Does lupus occur in men? As a man with lupus, the first thing you may discover ... know that having lupus doesn’t diminish a man’s levels of testosterone, ability to perform sexually, or ...

255

Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients  

PubMed Central

Purpose To determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR. Methods Pre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA. Results Of 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV–V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7–10.6, AUC = 0.759). Conclusions Focal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV–V VUR and 76% with recurrent UTI had normal DMSA. PMID:23465483

Snodgrass, Warren T.; Shah, Anjana; Yang, Mary; Kwon, Jeannie; Villanueva, Carlos; Traylor, Janelle; Pritzker, Karen; Nakonezny, Paul A.; Haley, Robert W.; Bush, Nicol Corbin

2013-01-01

256

Are Clinical, Laboratory, and Imaging Markers Suitable Predictors of Vesicoureteral Reflux in Children With Their First Febrile Urinary Tract Infection?  

PubMed Central

Purpose This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. Materials and Methods One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Results Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38?, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2? and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. Conclusions This study revealed fever>38.2? and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux. PMID:25132949

Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

2014-01-01

257

Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS  

Microsoft Academic Search

Environmental hyperthermia and exercise produce extensive changes in gene expression in human blood cells, but it is unknown\\u000a whether this also happens during febrile-range hyperthermia. We tested the hypothesis that heat shock protein (HSP) and immunomodulatory\\u000a stress gene expression correlate with fever in intensive care unit patients. Whole blood messenger RNA was obtained over consecutive\\u000a days from 100 hospitalized patients

Larry A. Sonna; Lauren Hawkins; Matthew E. Lissauer; Pam Maldeis; Michael Towns; Steven B. Johnson; Richard Moore; Ishwar S. Singh; Mark J. Cowan; Jeffrey D. Hasday

2010-01-01

258

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

259

Comparison of Serum Zinc Levels among Children with Simple Febrile Seizure and Control Group: A Systematic Review  

PubMed Central

Objective Several factors are involved in the etiology of febrile seizure (FS), among them is zinc (Zn), which has been discussed in various studies. The present systematic review compares Zn levels in children with FS and a control group. Materials & Methods We searched keywords of febrile seizure, febrile convulsion, children, childhood, fever, trace elements, risk factor, predisposing, zinc, Zn, and epilepsy in the following databases: SCOPUS, PubMed, and Google Scholar. The quality of research papers was assessed using a checklist. Data was extracted from primary studies based on demographic variables and amounts of Zn in case and control groups. Results Twenty primary studies were entered in the present study. Of which, eighteen studies, reported that Zn serum levels were significantly lower in the case group (patients with FS) than the control group. Conclusion The present systematic review indicated that Zn is one factor for predicting FS. A low level of this element among children can be regarded as a contributing factor for FS, a conclusion with a high consensus among different studies carried out in different parts of the world. PMID:25798166

NASEHI, Mohammad Mehdi; SAKHAEI, Roya; MOOSAZADEH, Mahmood; ALIRAMZANY, Maryam

2015-01-01

260

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. PMID:24083276

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

2013-01-01

261

Delta neutrophil index as a marker for differential diagnosis between flare and infection in febrile systemic lupus erythematosus patients.  

PubMed

Fever is a common symptom of systemic lupus erythematosus (SLE), and because of this it is difficult to discriminate between SLE flare and infection. The delta neutrophil index (DNI), automatically determined by the ADVIA 2120 electronic cell analyzer, has been reported to reflect the fraction of circulating immature granulocytes and to be associated with the presence of infection. In this study, we investigated the utility of DNI in discriminating infections from SLE flares in febrile SLE patients. In total, 111 episodes in 92 febrile SLE patients were reviewed. The infection group showed significantly higher white blood cell counts, neutrophil counts, C-reactive protein and procalcitonin than the SLE flare group. Complement (C)3 and C4 levels were decreased significantly in the SLE flare group. Patients in the SLE flare group had significantly lower DNI than those in both infection groups, with or without bacteremia. In a multivariate logistic regression analysis, only DNI was a significant independent factor for the presence of infection (odds ratio (OR): 18.9). When we selected a DNI value of 2.8% as the cutoff for infection, SLE patients with DNI?? 2.8% were found to be at higher risk for infection than those with DNI?<2.8% (relative risk 8.48-fold). Our data suggest that DNI may be a marker to differentiate infections from SLE flares in febrile SLE patients. PMID:23934401

Pyo, J Y; Park, J S; Park, Y-B; Lee, S-K; Ha, Y-J; Lee, S-W

2013-10-01

262

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

263

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

264

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. PMID:25058149

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

265

Health-related quality of life anticipated with different management strategies for paediatric febrile neutropaenia  

PubMed Central

Background: To describe (1) anticipated health-related quality of life during different strategies for febrile neutropaenia (FN) management and (2) attributes of those preferring inpatient management. Methods: Respondents were parents of children 0–18 years and children 12–18 years receiving cancer treatment. Anticipated health-related quality of life was elicited for four different FN management strategies: entire inpatient, early discharge, outpatient oral and outpatient intravenous (i.v.) therapy. Tools used to measure health-related quality of life were visual analogue scale (VAS), willingness to pay and time trade off. Results: A total of 155 parents and 43 children participated. For parents, median VAS scores were highest for early discharge (5.9, interquartile range 4.4–7.2) and outpatient i.v. (5.9, interquartile range 4.4–7.3). For children, median scores were highest for early discharge (6.1, interquartile range 4.6–7.2). In contrast, the most commonly preferred strategy for parents and children was inpatient in 55.0% and 37.2%, respectively. Higher current child health-related quality of life was associated with a stronger preference for outpatient management. Conclusion: Early discharge and outpatient i.v. management are associated with higher anticipated health-related quality of life, although the most commonly preferred strategy was inpatient care. This data may help with determining more cost-effective strategies for paediatric FN. PMID:21694729

Cheng, S; Teuffel, O; Ethier, M C; Diorio, C; Martino, J; Mayo, C; Regier, D; Wing, R; Alibhai, S M H; Sung, L

2011-01-01

266

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

267

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.

2012-12-06

268

Neutropenia Enhances Lung Dendritic Cell Recruitment in Response to Aspergillus via a Cytokine-to-Chemokine Amplification Loop  

PubMed Central

Current understanding of specific defense mechanisms in the context of neutropenic infections is limited. It has previously been reported that invasive aspergillosis, a prototypic opportunistic infection in neutropenic hosts, is associated with marked accumulation of inflammatory dendritic cells (DCs) in the lungs. Given recent data indicating that neutrophils can modulate immune responses independent of their direct microbial killing, we hypothesized that neutropenia impacts the host response to Aspergillus by determining the migration and phenotype of lung DCs. Inflammatory DCs, but not other DC subsets, were found to accumulate in the lungs of neutropenic hosts challenged with killed or live-attenuated Aspergillus as compared to non-neutropenic hosts, indicating that the accumulation was independent of neutrophil microbicidal activity. The mechanism of this accumulation in neutropenic hosts was found to be augmented influx of DCs, or their precursors, from the blood to the lungs. This effect was attributable to greatly elevated lung TNF expression in neutropenic as compared to non-neutropenic animals. This resulted in greater lung expression of the chemokine ligands CCL2 and CCL20 which, in turn, mediated enhanced recruitment of TNF-producing inflammatory DCs resulting in a positive-feedback cycle. Finally, in the context of neutropenic invasive aspergillosis, depletion of DCs resulted in impaired fungal clearance, indicating that this mechanism is protective for the host. These observations identify a novel defense mechanism in invasive aspergillosis that is the result of alterations in DC traffic and phenotype and is specific to neutropenic hosts. PMID:20926800

Park, Stacy J; Burdick, Marie D; Brix, William K; Stoler, Mark H; Askew, David S; Strieter, Robert M; Mehrad, Borna

2011-01-01

269

The Effect of Granulocyte Colony Stimulating Factor Administration on Preterm Infant with Neutropenia and Clinical Sepsis: A Randomized Clinical Trial  

PubMed Central

Background This study was conducted to evaluate the clinical effect of Granulocyte Colony Stimulating Factor (GCSF) on prognosis of neonatal sepsis. Materials and Methods Present study is a double- blinded randomized clinical trial, conducted on 46 preterm infants with neutropenia (Absolute Neutrophil Count (ANC) ? 5000 / ?L) and clinical sepsis. Infants were randomly allocated into two groups. In the first group (treatment group), infants were treated with GCSF for up to 5 consecutive days with 10 ?g/ kg in addition to standard treatment protocols, and in other group, infants received normal saline as the placebo. Each infant was monitored for 14 days. Primary outcome was mortality during 14 days after entering the study, and secondary outcome was the incidence of positive blood culture, weight gain on the fourteenth day, the duration of hospitalization and medication side effects. Results In the treated group, only one death was observed (P-value=1.00). However, no positive results for cultures were reported. Only one case in the treatment group and 3 patients in the control group showed feeding intolerance and needed respiratory support (P-value= 0.608). Length of hospitalization was 25 ± 6 days for the treatment group and 30 ± 7 days for the control group which was statistically significant (P-value=0.042). Conclusion The results of this study demonstrated that GCSF could reduce the hospital stay, but no significant effect was observed on mortality rate, respiratory or feeding status. PMID:24575272

Borjianyazdi, L; Froomandi, M; Noori Shadkam, M; Hashemi, A; Fallah, R

2013-01-01

270

Neutropenia enhances lung dendritic cell recruitment in response to Aspergillus via a cytokine-to-chemokine amplification loop.  

PubMed

Current understanding of specific defense mechanisms in the context of neutropenic infections is limited. It has previously been reported that invasive aspergillosis, a prototypic opportunistic infection in neutropenic hosts, is associated with marked accumulation of inflammatory dendritic cells (DCs) in the lungs. Given recent data indicating that neutrophils can modulate immune responses independent of their direct microbial killing, we hypothesized that neutropenia impacts the host response to Aspergillus by determining the migration and phenotype of lung DCs. Inflammatory DCs, but not other DC subsets, were found to accumulate in the lungs of neutropenic hosts challenged with killed or live-attenuated Aspergillus as compared with nonneutropenic hosts, indicating that the accumulation was independent of neutrophil microbicidal activity. The mechanism of this accumulation in neutropenic hosts was found to be augmented influx of DCs, or their precursors, from the blood to the lungs. This effect was attributable to greatly elevated lung TNF expression in neutropenic as compared with nonneutropenic animals. This resulted in greater lung expression of the chemokine ligands CCL2 and CCL20, which, in turn, mediated enhanced recruitment of TNF-producing inflammatory DCs, resulting in a positive feedback cycle. Finally, in the context of neutropenic invasive aspergillosis, depletion of DCs resulted in impaired fungal clearance, indicating that this mechanism is protective for the host. These observations identify what we believe is a novel defense mechanism in invasive aspergillosis that is the result of alterations in DC traffic and phenotype and is specific to neutropenic hosts. PMID:20926800

Park, Stacy J; Burdick, Marie D; Brix, William K; Stoler, Mark H; Askew, David S; Strieter, Robert M; Mehrad, Borna

2010-11-15

271

Foliicolous microfungi occurring on Encephalartos.  

PubMed

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

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

2008-12-01

272

Risk of febrile seizures after first dose of measles–mumps–rubella–varicella vaccine: a population-based cohort study  

PubMed Central

Background: The combination measles–mumps–rubella–varicella (MMRV) vaccine currently used in Canada (Priorix-Tetra) may increase the risk of febrile seizures relative to the separate vaccines (MMR and varicella) previously administered. We determined the risk of febrile seizure after the first dose of MMRV, as well as any additional risk for children at high risk for seizures because of pre-existing medical conditions. Methods: In this retrospective, population-based cohort study, we compared the risk of seizures after the first dose of MMRV with the risk after same-day administration of separate MMR and varicella vaccines (MMR+V) in children 12 to 23 months of age in the province of Alberta. We deterministically linked vaccination data to health service utilization data for seizures. We used Poisson regression, with adjustment for age and calendar year, to determine the risk for the full cohort and for high-risk children. Results: The risk of seizures 7 to 10 days after vaccination was twice as high with MMRV as with MMR+V (relative risk [RR] 1.99, 95% confidence interval [CI] 1.30–3.05). The excess absolute risk of seizures was 3.52 seizures per 10 000 doses of MMRV relative to MMR+V. In high-risk children, the risk was not differentially higher for MMRV (RR 1.30, 95% CI 0.60–2.79). Interpretation: Despite an increased risk of febrile seizures following MMRV (compared with MMR+V), the absolute level of risk was small. Policy-makers need to balance these findings with the potential benefits of administering the combination vaccine or determine whether the choice of vaccine rests with clinicians and/or parents. PMID:24914115

MacDonald, Shannon E.; Dover, Douglas C.; Simmonds, Kimberley A.; Svenson, Lawrence W.

2014-01-01

273

Rapid Diagnostic Tests for Dengue Virus Infection in Febrile Cambodian Children: Diagnostic Accuracy and Incorporation into Diagnostic Algorithms  

PubMed Central

Background Dengue virus (DENV) infection is prevalent across tropical regions and may cause severe disease. Early diagnosis may improve supportive care. We prospectively assessed the Standard Diagnostics (Korea) BIOLINE Dengue Duo DENV rapid diagnostic test (RDT) to NS1 antigen and anti-DENV IgM (NS1 and IgM) in children in Cambodia, with the aim of improving the diagnosis of DENV infection. Methodology and principal findings We enrolled children admitted to hospital with non-localised febrile illnesses during the 5-month DENV transmission season. Clinical and laboratory variables, and DENV RDT results were recorded at admission. Children had blood culture and serological and molecular tests for common local pathogens, including reference laboratory DENV NS1 antigen and IgM assays. 337 children were admitted with non-localised febrile illness over 5 months. 71 (21%) had DENV infection (reference assay positive). Sensitivity was 58%, and specificity 85% for RDT NS1 and IgM combined. Conditional inference framework analysis showed the additional value of platelet and white cell counts for diagnosis of DENV infection. Variables associated with diagnosis of DENV infection were not associated with critical care admission (70 children, 21%) or mortality (19 children, 6%). Known causes of mortality were melioidosis (4), other sepsis (5), and malignancy (1). 22 (27%) children with a positive DENV RDT had a treatable other infection. Conclusions The DENV RDT had low sensitivity for the diagnosis of DENV infection. The high co-prevalence of infections in our cohort indicates the need for a broad microbiological assessment of non-localised febrile illness in these children. PMID:25710684

Carter, Michael J.; Emary, Kate R.; Moore, Catherine E.; Parry, Christopher M.; Sona, Soeng; Putchhat, Hor; Reaksmey, Sin; Chanpheaktra, Ngoun; Stoesser, Nicole; Dobson, Andrew D. M.; Day, Nicholas P. J.; Kumar, Varun; Blacksell, Stuart D.

2015-01-01

274

Febrile seizures in one-five aged infants in tropical practice: Frequency, etiology and outcome of hospitalization  

PubMed Central

Background: Convulsive seizures are the common neurological emergencies in developing regions. Objectives: The aim was to determine the prevalence, causes and outcome of seizures in childhood. Patients and Methods: Participants were children aged 1–5 years old, admitted consecutively with a history of febrile convulsions or were presented seizures with fever during hospitalization, in two pediatric university hospitals. The prospective study covered a period from January to December 2013. At admission, emergency care and resuscitation procedures were provided according to the national guidelines. The history included the number and a parental description of seizures. Children with epilepsy, any central nervous system infections and other disease were excluded. Results: We have recorded 3647 children. Among them, 308 (8.4%) infants had presented with febrile seizures including 174 males and 134 females admitted to both pediatric hospitals (Tokoin University Teaching Hospitals: 206/3070, Campus University Teaching Hospitals: 102/577). Infants from 1 to 3 years age were the most common affected and constituted 65.9% of all patients. The months of September, December and January had recorded the high frequency of admission due to seizures. Regarding the seizures type, generalized tonic-clonic seizures were predominant (46.4%) followed by tonic seizures (17.2%) and status epilepticus in 9%. The etiologies were marked by falciparum malaria (52.3%), and other infections in 47.7%. At discharge, we have noted 11% (34/308) with neurodevelopmental disabilities, 6.7% of epilepsy and 9.7% (30/308) of death. Conclusion: The febrile seizure in child younger 5 years is an indicator of severe malaria in tropical nations. The campaign for “roll back malaria” must continue in developing countries to avoid long-term gross neurological deficits.

Assogba, Komi; Balaka, Bahoura; Touglo, Fidato A.; Apetsè, Kossivi M.; Kombaté, Damelan

2015-01-01

275

Death receptors mediate the adverse effects of febrile-range hyperthermia on the outcome of lipopolysaccharide-induced lung injury  

PubMed Central

We have shown that febrile-range hyperthermia enhances lung injury and mortality in mice exposed to inhaled LPS and is associated with increased TNF-? receptor activity, suppression of NF-?B activity in vitro, and increased apoptosis of alveolar epithelial cells in vivo. We hypothesized that hyperthermia enhances lung injury and mortality in vivo by a mechanism dependent on TNF receptor signaling. To test this, we exposed mice lacking the TNF-receptor family members TNFR1/R2 or Fas (TNFR1/R2?/? and lpr) to inhaled LPS with or without febrile-range hyperthermia. For comparison, we studied mice lacking IL-1 receptor activity (IL-1R?/?) to determine the role of inflammation on the effect of hyperthermia in vivo. TNFR1/R2?/? and lpr mice were protected from augmented alveolar permeability and mortality associated with hyperthermia, whereas IL-1R?/? mice were susceptible to augmented alveolar permeability but protected from mortality associated with hyperthermia. Hyperthermia decreased pulmonary concentrations of TNF-? and keratinocyte-derived chemokine after LPS in C57BL/6 mice and did not affect pulmonary inflammation but enhanced circulating markers of oxidative injury and nitric oxide metabolites. The data suggest that hyperthermia enhances lung injury by a mechanism that requires death receptor activity and is not directly associated with changes in inflammation mediated by hyperthermia. In addition, hyperthermia appears to enhance mortality by generating a systemic inflammatory response and not by a mechanism directly associated with respiratory failure. Finally, we observed that exposure to febrile-range hyperthermia converts a modest, survivable model of lung injury into a fatal syndrome associated with oxidative and nitrosative stress, similar to the systemic inflammatory response syndrome. PMID:21515659

Matute-Bello, Gustavo; Herrero, Raquel; Wong, Venus A.; Mongovin, Stephen M.; Martin, Thomas R.

2011-01-01

276

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

PubMed Central

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

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

2015-01-01

277

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. PMID:25020130

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

2014-01-01

278

Clinical observation of the therapeutic effects of pegylated recombinant human granulocyte colony-stimulating factor in patients with concurrent chemoradiotherapy-induced grade IV neutropenia  

PubMed Central

The aim of the present study was to investigate the efficacy and side-effects of preventive treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on concurrent chemoradiotherapy-induced grade IV neutropenia and to provide a rational basis for its clinical application. A total of 114 patients with concurrent chemoradiotherapy-induced grade IV neutropenia were enrolled. A randomized approach was used to divide the patients into an experimental group and a control group. The experimental group included three subgroups, namely a P-50 group, P-100 group and P + R group. The P-50 group had 42 cases, which were given a single 50-?g/kg subcutaneous injection of PEG-rhG-CSF. The P-100 group had 30 cases, which received a single 100-?g/kg subcutaneous injection of PEG-rhG-CSF. The P + R group comprised 22 cases, which were given a single 50-?g/kg subcutaneous injection of PEG-rhG-CSF and rhG-CSF 5 ?g/kg/day; when the absolute neutrophil count (ANC) was ?2.0×109/l, the administration of rhG-CSF was stopped. The control group (RC group) comprised 20 patients, who received rhG-CSF 5 ?g/kg/day by subcutaneous injection until the ANC was ?2.0×109/l. Changes in the neutrophil proliferation rate and ANC values over time, the neutropenic symptom remission time and incidence of adverse drug reactions were analyzed statistically in each group of patients. In the experimental group, the neutrophil proliferation rate and ANC values were significantly higher than those in the control group; the clinical effects began 12–24 h after treatment in the experimental group, and indicated that the treatment improved neutropenia in ~48 h after treatment. There was no significant difference in the neutrophil proliferation rate and ANC values between the P-50 and P+R groups. In the experimental group, the remission time of neutropenia-induced fever and muscle pain after administration was significantly shorter than that in the control group, with a statistically significant difference (P<0.05). The adverse drug reaction rates showed no significant difference between the experimental group and the control group. PEG-rhG-CSF had good efficacy and safety in the treatment of concurrent chemotherapy-induced grade IV neutropenia. For the treatment of concurrent chemotherapy-induced grade IV neutropenia, a single subcutaneous injection of 50 ?g/kg PEG-rhG-CSF is the recommended dose. The effects begin at 12–24 h; if the ANC values are not significantly improved during this time, no supplementary administration of rhG-CSF is necessary. PMID:25667625

WU, FENG-PENG; WANG, JUN; WANG, HUI; LI, NA; GUO, YIN; CHENG, YUN-JIE; LIU, QING; YANG, XIANG-RAN

2015-01-01

279

Caffeine, a naturally occurring acaricide.  

PubMed

Since caffeine is a plant alkaloid that has been described as a naturally occurring insecticide, its acaricidal effect on Dermatophagoides pteronyssinus (Dp) was investigated. Twelve cultures were established by adding 30 Dp to 200 mg of Tetramin fish food and brewer's yeast (8:2 ratio); six cultures were treated with 20 mg of finely ground caffeine. All 12 cultures were incubated at 75% relative humidity, 25 degrees C, and observed during 8 weeks. Live mites were then counted under a stereoscope, cultures were extracted, and supernatants were analyzed for Der p I and Der f I allergen content with a two-site monoclonal RIA. Live mite counts in untreated cultures varied from 146 to 274 (215 +/- 47.1), and in caffeine-treated cultures from 0 to 3 (1 +/- 1.2; p less than or equal to 0.0001). Der p I concentrations in untreated cultures varied from 588 to 9000 ng/gm (3138.3 +/- 2990.8 ng/gm), and in caffeine-treated cultures from 52 to 117 ng/gm (78 +/- 23.8 ng/gm; p less than or equal to 0.01). Der p I was not detected in the food media or caffeine; Der f I was not detected in any of the cultures. Results demonstrate that caffeine inhibits mite growth and allergen production. PMID:1991914

Russell, D W; Fernández-Caldas, E; Swanson, M C; Seleznick, M J; Trudeau, W L; Lockey, R F

1991-01-01

280

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

281

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. PMID:23451170

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

282

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. PMID:23171239

2012-01-01

283

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. PMID:9154027

Gøtzsche, P. C.; Johansen, H. K.

1997-01-01

284

Effects of timing of vaccination (day 0 versus day 14 of a receiving period) with a modified-live respiratory viral vaccine on performance, feed intake, and febrile response of beef heifers  

Technology Transfer Automated Retrieval System (TEKTRAN)

The objective of this study was to evaluate the effects of timing of the administration of a modified-live respiratory viral vaccine on day 0 or on day 14 of a receiving period on performance, feed intake, and febrile response in beef heifers. Our hypothesis was vaccine timing will alter febrile res...

285

[Study of the incidence of malaria in febrile patients and among schoolchildren in the region of Trarza, Islamic Republic of Mauritania].  

PubMed

A study was performed to appreciate the importance of malaria in the low valley of the Senegal River North Bank in Mauritania. The malaria incidence was assessed among patients visiting the regional hospital of Rosso (Trarza region) for a "presumptive malaria", a diagnosis assigned by the clinicians based on fever and other suggestive symptoms of malaria. The malaria prevalence rate was also measured in schoolchildren. A total of 1431 febrile outpatients were sampled for thick and thin blood films, between December 2004 and March 2005, August and November 2005, and April and July 2006. The average malaria prevalence rate was 2.5% (36/1431). It varied from 0.7% (4/576) for the period from December 2004 to March 2005 to 3.8% (18/475) from August to November 2005 and 2.1% (8/380) from April to July 2006. Of the 1040 school children of 6 to 14 years of age, the average malaria parasite prevalence rate was 0.9% (9/1040). It was 0.4% (1/224), 1.7% (7/413) and 0.2% (1/402), Respectively, in February 2004 (cold and dry season), October 2005 (rainy season) and June 2006 (hot and dry season). These very low levels of malaria endemicity and incidence are comparable with those recorded in the same area on the (South) bank of the river in Senegal. In this context of unstable malaria, characterized by the absence or a low level of natural immunity of the population, an effective monitoring is essential for an early detection and a damming up of the malaria epidemic blazes that likely occur. PMID:21698482

Ouldabdallahi, M; Ouldbezeid, M; Dieye, M; Yacine, B; Faye, O

2011-10-01

286

The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI.  

PubMed

We assessed the role of therapeutic delay time (TDT) in acute renal cortical scintigraphic lesion (ASL) and ultimate scar formation (USF) in children with first febrile UTI and whether it is affected by the presence of vesico-ureteral reflux (VUR). 230 children, 90 girls and 140 boys with first febrile UTI were included. Radiologic (USG, DMSA, and VCUG), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (CBC with differential count, ANC (absolute neutrophil count), BUN, Creatinine, urine analysis, gram stain, culture, CRP and ESR) variables were analysed. DMSA was performed within 5 days and after six months. VCUG was performed after acute phase of UTI. The differences in TDT according to the presence of ASL, USF and VUR were assessed. And the correlation between ASL or USF with the duration of TDT was assessed. Of 230 patients enrolled, 142 patients had refluxing UTI and 88 patients had non-refluxing UTI. TDT was the risk factor associated with ASL and USF along with presence of VUR. TDT was longer in ASL positive group compared with the ASL negative group. Also USF group showed longer TDT compared with those without USF in both refluxing UTI and non refluxing UTI. The TDT was significantly shorter in USF group with the presence of VUR. Positive linear association was noted between prevalence of ASL and USF and duration of TDT. In conclusion, the impact of UTI on formation of USF may be enhanced by the presence of VUR with shorter duration of TDT. PMID:22048628

Oh, Mi Mi; Kim, Jin Wook; Park, Min Gu; Kim, Je Jong; Yoo, Kee Hwan; Moon, Du Geon

2012-03-01

287

Prevalence of Malaria among Acute Febrile Patients Clinically Suspected of Having Malaria in the Zeway Health Center, Ethiopia.  

PubMed

Malaria diagnosis is a common challenge in developing countries with limited diagnostic services. Common febrile illnesses were assessed in 280 malaria-suspected patients, and each case was subjected to clinical and laboratory examinations for malaria, relapsing fever, typhoid fever, typhus, and brucellosis. Data were entered and analyzed using Epi Info version 3.1 software. Malaria accounted for 17% (CI, 12.6-21.4%) of febrile illnesses. The remaining cases were associated with typhoid fever (18.5%; CI, 13.95-23.05%), typhus (17.8%; CI, 13.32-22.28%), brucellosis (1%; CI, -0.17-2.17%), relapsing fever (2%; CI, 0.36-3.64%), and unknown causes (44%). Approximately 7% of patients had coinfections, and 2% of patients treated as monoinfections. Approximately 1.4% of the nonmalarial patients received antimalarial treatment. The sensitivity and specificity of the CareStart Pf/pan rapid diagnostic tests in comparison with those of microscopy were 100% and 91%, respectively, with positive- and negative-predictive values of 94% and 100%, respectively. Compared with microscopy, the positive-predictive value of each malaria symptom was much lower than that of the symptoms combined: fever, 17%; sweating, 30%; headache, 18%; general body ache, 22%; loss of appetite, 21%. The study findings revealed a high proportion of nonmalarial illnesses were clinically categorized as malaria. Parasite-based diagnosis is recommended for the management of malarial and nonmalarial cases. PMID:25420658

Feleke, Sendeaw M; Animut, Abebe; Belay, Mulugeta

2015-01-26

288

Antibiotics in 30 minutes or less for febrile neutropenic patients: a quality control measure in a new hospital.  

PubMed

Infections are the most common complication in patients receiving treatment for cancer with neutropenia being the primary risk factor for the development of an infection. In the neutropenic patient, bacteremia remains a significant cause of mortality. Although the literature reports that prompt empiric antibiotic therapy to prevent death caused by virulent organisms is the standard of care, the literature fails to identify what prompt antibiotic administration means. Door/fever-to-patient antibiotic delivery was evaluated as a quality control measure in a new children's hospital. Initially, door/fever-to-patient time was significantly delayed. Collaboration between pharmacy, hospital bed control, medical, and nursing staff resulted in many changes in practice by all groups. As a result, the goal for prompt antibiotic delivery of thirty minutes or less is now achievable. PMID:18539908

Corey, Amy L; Snyder, Stacy

2008-01-01

289

Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C.  

PubMed

Cytopenia during interferon-based (IFN-based) therapy for chronic hepatitis C (CHC) often necessitates reduction of doses of drugs and premature withdrawal from therapy resulting in poor response to treatment. To identify genetic variants associated with IFN-induced neutropenia, we conducted a genome-wide association study (GWAS) in 416 Japanese CHC patients receiving IFN-based therapy. Based on the results, we selected 192 candidate single nucleotide polymorphisms (SNPs) to carry out a replication analysis in an independent set of 404 subjects. The SNP rs2305482, located in the intron region of the PSMD3 gene on chromosome 17, showed a strong association when the results of GWAS and the replication stage were combined (OR = 2.18, P = 3.05 × 10(-7) in the allele frequency model). Logistic regression analysis showed that rs2305482 CC and neutrophil count at baseline were independent predictive factors for IFN-induced neutropenia (OR = 2.497, P = 0.0072 and OR = 0.998, P < 0.0001, respectively). Furthermore, rs2305482 genotype was associated with the doses of pegylated interferon (PEG-IFN) that could be tolerated in hepatitis C virus genotype 1-infected patients treated with PEG-IFN plus ribavirin, but not with treatment efficacy. Our results suggest that genetic testing for this variant might be useful for establishing personalized drug dosing in order to minimize drug-induced adverse events. PMID:25515861

Iio, Etsuko; Matsuura, Kentaro; Nishida, Nao; Maekawa, Shinya; Enomoto, Nobuyuki; Nakagawa, Mina; Sakamoto, Naoya; Yatsuhashi, Hiroshi; Kurosaki, Masayuki; Izumi, Namiki; Hiasa, Yoichi; Masaki, Naohiko; Ide, Tatsuya; Hino, Keisuke; Tamori, Akihiro; Honda, Masao; Kaneko, Shuichi; Mochida, Satoshi; Nomura, Hideyuki; Nishiguchi, Shuhei; Okuse, Chiaki; Itoh, Yoshito; Yoshiji, Hitoshi; Sakaida, Isao; Yamamoto, Kazuhide; Watanabe, Hisayoshi; Hige, Shuhei; Matsumoto, Akihiro; Tanaka, Eiji; Tokunaga, Katsushi; Tanaka, Yasuhito

2015-03-01

290

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

PubMed

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

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

2015-01-01

291

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

PubMed Central

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

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

2015-01-01

292

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. PMID:21677667

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

293

Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis  

PubMed Central

Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Mutations of the ELA2 gene encoding neutrophil elastase (NE) are responsible for most cases of SCN and cyclic neutropenia (CN), a related but milder disorder of granulopoiesis. However, the mechanisms by which these mutations disrupt granulopoiesis are unclear. We hypothesize that the ELA2 mutations result in the production of misfolded NE protein, activation of the unfolded protein response (UPR), and ultimately apoptosis of granulocytic precursors. Expression of mutant NE but not wild-type NE strongly induced BiP/GRP78 mRNA expression and XBP1 mRNA splicing, 2 classic markers of the UPR. The magnitude of UPR activation by a specific ELA2 mutation correlated with its associated clinical phenotype. Consistent with the UPR model, expression of mutant NE in primary human granulocytic precursors increased expression of CHOP (DDITS) and induced apoptosis in a protease-independent fashion. Most strikingly, UPR activation and decreased NE protein expression were detected in primary granulocytic precursors from SCN patients. Collectively, these data provide strong support for a UPR model of SCN disease pathogenesis and place SCN in a growing list of human diseases caused by misfolded proteins. PMID:17761833

Grenda, David S.; Murakami, Mark; Ghatak, Jhuma; Xia, Jun; Boxer, Laurence A.; Dale, David; Dinauer, Mary C.

2007-01-01

294

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

295

Fever Screening and Detection of Febrile Arrivals at an International Airport in Korea: Association among Self-reported Fever, Infrared Thermal Camera Scanning, and Tympanic Temperature  

PubMed Central

OBJECTIVES: The purpose of this research was to measure fever prevalence and the effectiveness of a fever screening procedure in detecting febrile arrivals at an international airport in Korea. METHODS: Data were retrieved from arrivals’ health declaration forms and questionnaires for febrile arrivals at an international airport collected by a national quarantine station during the year 2012. Self-reported health declaration forms were returned by 355,887 arrivals (61% of the total arrivals). Of these, 608 symptomatic arrivals (0.2%) including 6 febrile arrivals were analyzed. RESULTS: Fever prevalence at an international airport in Korea was 0.002%. Self-reported fever was significantly positively associated with tympanic temperature (p<0.001). The difference between the thermal camera temperature (36.83°C) and tympanic (or ear) temperature (38.14°C) was not statistically significant. CONCLUSIONS: The findings imply that a procedure for mass detection of fever such as self-reported questionnaires and thermal camera scanning may serve as an effective tool for detecting febrile arrivals at quarantine stations. Future research can benefit from looking at the sensitivity, specificity, positive predictive value, and negative predictive value of the entry screening system. PMID:25045577

Cho, Kyung Sook; Yoon, Jangho

2014-01-01

296

Association of antepartum and postpartum depression in Ghanaian and Ivorian women with febrile illness in their offspring: a prospective birth cohort study.  

PubMed

In low-income countries, perinatal depression is common, but longitudinal data on its influence on child health are rare. We examined the association between maternal depression and febrile illness in children. There were 654 mother/child dyads in Ghana and Côte d'Ivoire that were enrolled in a prospective birth cohort in 2010-2011 and underwent 2-years of follow up. Mothers were examined for depression using the Patient Health Questionnaire depression module antepartum and 3 and 12 months postpartum. The hazard of febrile illness in children of depressed and nondepressed mothers was estimated using a recurrent event Cox proportional hazards model. The prevalences of antepartum depression in mothers from Côte d'Ivoire and Ghana were 28.3% and 26.3%, respectively. The prevalences of depression at 3 and 12 months postpartum were 11.8% and 16.1% (Côte d'Ivoire) and 8.9% and 7.2% (Ghana). The crude and adjusted (for country and socioeconomic status) hazard ratios of febrile illness in children of depressed mothers compared with those in children of nondepressed mothers were 1.57 (95% confidence interval: 1.20, 2.07) and 1.32 (95% confidence interval: 1.01, 1.74) respectively. Perinatal depression was frequent and associated with febrile illness in the offspring. Our results showed that a high prevalence of depression in sub-Saharan Africa may pose a serious public health threat to women and their offspring. PMID:24013202

Guo, Nan; Bindt, Carola; Te Bonle, Marguerite; Appiah-Poku, John; Hinz, Rebecca; Barthel, Dana; Koffi, Mathurin; Posdzich, Sarah; Deymann, Simon; Barkmann, Claus; Schlüter, Lisa; Jaeger, Anna; Blay Nguah, Samuel; Eberhardt, Kirsten A; N'Goran, Eliezer; Tagbor, Harry; Ehrhardt, Stephan

2013-11-01

297

A comparison of lipopolysacchardie-induced febrile responses across heat-tolerant and -sensitive Bos taurus cattle in different thermal environments  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

298

Febrile renal transplant recipient with discordant findings of 99mTc-Leukoscan (Sulesomab) and 67Ga-citrate scan in pyelonephritis  

PubMed Central

Nuclear medicine techniques like 99mTc-Leukoscan and 67Ga-citrate scan have been used in localizing infectious pathologies in renal transplant patients. We present an interesting case of febrile renal transplant with discordant findings of tracer uptake in the transplant kidney on 99mTc-Leukoscan and 67Ga-citrate scan. PMID:23559719

Sonavane, Sunita Tarsarya; Marwah, Atul; Jaiswar, Rajnath

2011-01-01

299

Radiographic evaluation of children with febrile urinary tract infection: bottom-up, top-down, or none of the above?  

PubMed

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. PMID:21860620

Prasad, Michaella M; Cheng, Earl Y

2012-01-01

300

Evidence of a major reservoir of non-malarial febrile diseases in malaria-endemic regions of Bangladesh.  

PubMed

In malaria-endemic regions any febrile case is likely to be classified as malaria based on presumptive diagnosis largely caused by a lack of diagnostic resources. A district-wide prevalence study assessing etiologies of fever in 659 patients recruited in rural and semi-urban areas of Bandarban district in southeastern Bangladesh revealed high proportions of seropositivity for selected infectious diseases (leptospirosis, typhoid fever) potentially being misdiagnosed as malaria because of similarities in the clinical presentation. In an area with point prevalences of more than 40% for malaria among fever cases, even higher seroprevalence rates of leptospirosis and typhoid fever provide evidence of a major persistent reservoir of these pathogens. PMID:24420774

Swoboda, Paul; Fuehrer, Hans-Peter; Ley, Benedikt; Starzengruber, Peter; Ley-Thriemer, Kamala; Jung, Mariella; Matt, Julia; Fally, Markus A; Mueller, Milena K S; Reismann, Johannes A B; Haque, Rashidul; Khan, Wasif A; Noedl, Harald

2014-02-01

301

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. PMID:24885820

2014-01-01

302

Utility of adding Pneumocystis jirovecii DNA detection in nasopharyngeal aspirates in immunocompromised adult patients with febrile pneumonia.  

PubMed

Detection of viral and bacterial DNA in nasopharyngeal aspirates (NPAs) is now a routine practice in emergency cases of febrile pneumonia. We investigated whether Pneumocystis jirovecii DNA could also be detected in these cases by conducting retrospective screening of 324 consecutive NPAs from 324 adult patients (198 or 61% were immunocompromised) admitted with suspected pulmonary infections during the 2012 influenza epidemic season, using a real-time quantitative polymerase chain reaction (PCR) assay (PjqPCR), which targets the P. jirovecii mitochondrial large subunit ribosomal RNA gene. These NPAs had already been tested for 22 respiratory pathogens (18 viruses and 4 bacteria), but we found that 16 NPAs (4.9%) were PjqPCR-positive, making P. jirovecii the fourth most prevalent of the 23 microorganisms in the screen. Eleven of the 16 PjqPCR-positive patients were immunocompromised, and five had underlying pulmonary conditions. Nine NPAs were also positive for another respiratory pathogen. Six had PjqPCR-positive induced sputa less than 3 days after the NPA procedure, and five were diagnosed with pneumocystis pneumonia (four with chronic lymphoproliferative disorders and one AIDS patient). In all six available pairs quantification of P. jirovecii DNA showed fewer copies in NPA than in induced sputum and three PjqPCR-negative NPAs corresponded to PjqPCR-positive bronchoalveolar lavage fluids, underscoring the fact that a negative PjqPCR screen does not exclude a diagnosis of pneumocystosis. Including P. jirovecii DNA detection to the panel of microorganisms included in screening tests used for febrile pneumonia may encourage additional investigations or support use of anti-pneumocystis pneumonia prophylaxis in immunocompromised patients. PMID:25550391

Guigue, Nicolas; Alanio, Alexandre; Menotti, Jean; Castro, Nathalie De; Hamane, Samia; Peyrony, Olivier; LeGoff, Jérôme; Bretagne, Stéphane

2015-04-01

303

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. PMID:23394216

2013-01-01

304

A rare case of variable immune deficiency with type II dysgammaglobulinaemia, light chain defect, gut associated IgA deficiency and progressive neutropenia.  

PubMed

This report describes in detail an unusual variant of a common variable immunodeficiency disease in a seven-year-old boy. The unique features were progressive neutropenia due to defective myelopoiesis, serum IgG and IgA deficiencies, defective immunoglobulin light-chain synthesis, absence of secretory IgA and IgM gammopathy. He had been born healthy, but following a thermal injury at the age of 1 1/2 years, he suffered recurrent attacks of sinopulmonary and urinary tract infections, enteritis due to enteropathogenic E. coli, Giardia lamblia and E. histolytica, developed pulmonary tuberculosis and died of deep mycotic infection of the oral cavity and obstruction of the bronchial tree. The cause of the defective myelopoiesis could not be determined, but it might have been due to prolonged sulphomamide therapy administered for controlling his persistent urinary tract infection due to paraphymosis. PMID:3935129

Saha, K; Chopra, K; Dutta, B R

1985-12-01

305

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

PubMed Central

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

2013-01-01

306

Co-infection of Long-Term Carriers of Plasmodium falciparum with Schistosoma haematobium Enhances Protection from Febrile Malaria: A Prospective Cohort Study in Mali  

PubMed Central

Background Malaria and schistosomiasis often overlap in tropical and subtropical countries and impose tremendous disease burdens; however, the extent to which schistosomiasis modifies the risk of febrile malaria remains unclear. Methods We evaluated the effect of baseline S. haematobium mono-infection, baseline P. falciparum mono-infection, and co-infection with both parasites on the risk of febrile malaria in a prospective cohort study of 616 children and adults living in Kalifabougou, Mali. Individuals with S. haematobium were treated with praziquantel within 6 weeks of enrollment. Malaria episodes were detected by weekly physical examination and self-referral for 7 months. The primary outcome was time to first or only malaria episode defined as fever (?37.5°C) and parasitemia (?2500 asexual parasites/µl). Secondary definitions of malaria using different parasite densities were also explored. Results After adjusting for age, anemia status, sickle cell trait, distance from home to river, residence within a cluster of high S. haematobium transmission, and housing type, baseline P. falciparum mono-infection (n?=?254) and co-infection (n?=?39) were significantly associated with protection from febrile malaria by Cox regression (hazard ratios 0.71 and 0.44; P?=?0.01 and 0.02; reference group: uninfected at baseline). Baseline S. haematobium mono-infection (n?=?23) did not associate with malaria protection in the adjusted analysis, but this may be due to lack of statistical power. Anemia significantly interacted with co-infection (P?=?0.009), and the malaria-protective effect of co-infection was strongest in non-anemic individuals. Co-infection was an independent negative predictor of lower parasite density at the first febrile malaria episode. Conclusions Co-infection with S. haematobium and P. falciparum is significantly associated with reduced risk of febrile malaria in long-term asymptomatic carriers of P. falciparum. Future studies are needed to determine whether co-infection induces immunomodulatory mechanisms that protect against febrile malaria or whether genetic, behavioral, or environmental factors not accounted for here explain these findings. PMID:25210876

Sangala, Jules; Li, Shanping; Doumtabe, Didier; Kone, Younoussou; Traoré, Abdrahamane; Bathily, Aboudramane; Sogoba, Nafomon; Coulibaly, Michel E.; Huang, Chiung-Yu; Ongoiba, Aissata; Kayentao, Kassoum; Diallo, Mouctar; Dramane, Zongo; Nutman, Thomas B.; Crompton, Peter D.; Doumbo, Ogobara; Traore, Boubacar

2014-01-01

307

HEDS Discussion Paper 09/08 Disclaimer  

E-print Network

-stimulating factors, G-CSFs, febrile neutropenia, mixed treatment comparison, methodology Running title: The benefits of MTC: A case study #12;3 Abstract Objectives This study aims to highlight the benefits of Bayesian, filgrastim and lenograstim) for the prevention of febrile neutropenia (FN) following chemotherapy. Methods

Oakley, Jeremy

308

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. PMID:23351502

2012-01-01

309

The efficacy of ultrasound and dimercaptosuccinic acid scan in predicting vesicoureteral reflux in children below the age of 2 years with their first febrile urinary tract infection  

Microsoft Academic Search

We evaluated the efficacy of dimercaptosuccinic acid (DMSA) scan and ultrasound (US) in comparison with voiding cystourethrography\\u000a (VCUG) in predicting vesicoureteral reflux (VUR) in children below the age of 2 years. Medical records and radiologic studies\\u000a of children (<2 years) suffering their first febrile urinary tract infection (UTI) between January 2001 and May 2007 were\\u000a retrospectively reviewed. We evaluated the sensitivity, specificity,

Hye-young Lee; Byung Hyun Soh; Chang Hee Hong; Myung Joon Kim; Sang Won Han

2009-01-01

310

Repeated febrile convulsions impair hippocampal neurons and cause synaptic damage in immature rats: neuroprotective effect of fructose-1,6-diphosphate  

PubMed Central

Fructose-1,6-diphosphate is a metabolic intermediate that promotes cell metabolism. We hypothesize that fructose-1,6-diphosphate can protect against neuronal damage induced by febrile convulsions. Hot-water bathing was used to establish a repetitive febrile convulsion model in rats aged 21 days, equivalent to 3–5 years in humans. Ninety minutes before each seizure induction, rats received an intraperitoneal injection of low- or high-dose fructose-1,6-diphosphate (500 or 1,000 mg/kg, respectively). Low- and high-dose fructose-1,6-diphosphate prolonged the latency and shortened the duration of seizures. Furthermore, high-dose fructose-1,6-diphosphate effectively reduced seizure severity. Transmission electron microscopy revealed that 24 hours after the last seizure, high-dose fructose-1,6-diphosphate reduced mitochondrial swelling, rough endoplasmic reticulum degranulation, Golgi dilation and synaptic cleft size, and increased synaptic active zone length, postsynaptic density thickness, and synaptic interface curvature in the hippocampal CA1 area. The present findings suggest that fructose-1,6-diphosphate is a neuroprotectant against hippocampal neuron and synapse damage induced by repeated febrile convulsion in immature rats. PMID:25206915

Zhou, Jianping; Wang, Fan; Zhang, Jun; Gao, Hui; Yang, Yufeng; Fu, Rongguo

2014-01-01

311

Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation  

PubMed Central

Heat shock response is characterized by the induction of heat shock proteins (HSPs), which facilitate protein folding, and non-HSP proteins with diverse functions, including protein degradation, and is regulated by heat shock factors (HSFs). HSF1 is a master regulator of HSP expression during heat shock in mammals, as is HSF3 in avians. HSF2 plays roles in development of the brain and reproductive organs. However, the fundamental roles of HSF2 in vertebrate cells have not been identified. Here we find that vertebrate HSF2 is activated during heat shock in the physiological range. HSF2 deficiency reduces threshold for chicken HSF3 or mouse HSF1 activation, resulting in increased HSP expression during mild heat shock. HSF2-null cells are more sensitive to sustained mild heat shock than wild-type cells, associated with the accumulation of ubiquitylated misfolded proteins. Furthermore, loss of HSF2 function increases the accumulation of aggregated polyglutamine protein and shortens the lifespan of R6/2 Huntington's disease mice, partly through ?B-crystallin expression. These results identify HSF2 as a major regulator of proteostasis capacity against febrile-range thermal stress and suggest that HSF2 could be a promising therapeutic target for protein-misfolding diseases. PMID:21813737

Shinkawa, Toyohide; Tan, Ke; Fujimoto, Mitsuaki; Hayashida, Naoki; Yamamoto, Kaoru; Takaki, Eiichi; Takii, Ryosuke; Prakasam, Ramachandran; Inouye, Sachiye; Mezger, Valerie; Nakai, Akira

2011-01-01

312

Hypothalamus metabolomic profiling to elucidate the tissue-targeted biochemical basis of febrile response in yeast-induced pyrexia rats.  

PubMed

In the previous reports regarding thermoregulation, the hypothalamus is thought to be the primary centre in the central nervous system for controlling the body temperature. However, to date, there has not been sufficient evidence to reveal its thermoregulatory mechanism. In the current study, we utilised a tissue-targeted metabolomics strategy to elucidate the underlying biochemical mechanisms of thermoregulation in the fever process by analysing the global metabolic profile of the hypothalamus in yeast-induced pyrexia rats. Data acquisition was completed using the HPLC-LTQ-Orbitrap/MS in both positive and negative ion mode. Principal component analysis was used to observe the cluster characteristics between the control group and the pyrexia group. Potential biomarkers were screened using orthogonal partial least-squares-discriminant analysis. Seventeen potential biomarkers were identified in the hypothalamus samples to discriminate the control and pyrexia groups, including amino acids, nucleic acids, vitamins, carbohydrates, and phospholipids. As a result, purine metabolism was enhanced pronouncedly, and perturbation of lipid metabolism was also observed. Meanwhile, amino acid metabolism and energy metabolism were also activated significantly. In conclusion, the study indicated that hypothalamus-targeted metabolomics could provide a powerful tool to further understand the pathogenesis of febrile response. PMID:25746356

Liu, Haiyu; Zhang, Li; Zhao, Baosheng; Zhang, Zhixin; Qin, Lingling; Zhang, Qingqing; Wang, Qing; Lu, Zhiwei; Gao, Xiaoyan

2015-04-25

313

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

PubMed Central

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

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

2013-01-01

314

An outbreak of acute febrile illness caused by Sandfly Fever Sicilian Virus in the Afar region of Ethiopia, 2011.  

PubMed

In malaria-endemic regions, many medical facilities have limited capacity to diagnose non-malarial etiologies of acute febrile illness (AFI). As a result, the etiology of AFI is seldom determined, although AFI remains a major cause of morbidity in developing countries. An outbreak of AFI was reported in the Afar region of Ethiopia in August of 2011. Retrospectively, 12,816 suspected AFI cases were identified by review of medical records. Symptoms were mild and self-limiting within 3 days after the date of onset; no fatalities were identified. All initial test results of AFI patient specimens were negative for selected pathogens using standard microbiological and molecular techniques. High-throughput sequencing of nucleic acid extracts of serum specimens from 29 AFI cases identified 17 (59%) of 29 samples as positive for Sandfly Fever Sicilian Virus (SFSV). These results were further confirmed by specific reverse transcription polymerase chain reaction. This is the first study implicating SFSV as an etiological agent for AFI in Ethiopia. PMID:25266349

Woyessa, Abyot Bekele; Omballa, Victor; Wang, David; Lambert, Amy; Waiboci, Lilian; Ayele, Workenesh; Ahmed, Abdi; Abera, Negga Asamene; Cao, Song; Ochieng, Melvin; Montgomery, Joel M; Jima, Daddi; Fields, Barry

2014-12-01

315

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

PubMed Central

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

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

2015-01-01

316

Febrile-range hyperthermia augments neutrophil accumulation and enhances lung injury in experimental gram-negative bacterial pneumonia.  

PubMed

We previously demonstrated that exposure to febrile-range hyperthermia (FRH) accelerates pathogen clearance and increases survival in murine experimental Klebsiella pneumoniae peritonitis. However, FRH accelerates lethal lung injury in a mouse model of pulmonary oxygen toxicity, suggesting that the lung may be particularly susceptible to injurious effects of FRH. In the present study, we tested the hypothesis that, in contrast with the salutary effect of FRH in Gram-negative peritonitis, FRH would be detrimental in multilobar Gram-negative pneumonia. Using a conscious, temperature-clamped mouse model and intratracheal inoculation with K. pneumoniae Caroli strain, we showed that FRH tended to reduce survival despite reducing the 3 day-postinoculation pulmonary pathogen burden by 400-fold. We showed that antibiotic treatment rescued the euthermic mice, but did not reduce lethality in the FRH mice. Using an intratracheal bacterial endotoxin LPS challenge model, we found that the reduced survival in FRH-treated mice was accompanied by increased pulmonary vascular endothelial injury, enhanced pulmonary accumulation of neutrophils, increased levels of IL-1beta, MIP-2/CXCL213, GM-CSF, and KC/CXCL1 in the bronchoalveolar lavage fluid, and bronchiolar epithelial necrosis. These results suggest that FRH enhances innate host defense against infection, in part, by augmenting polymorphonuclear cell delivery to the site of infection. The ultimate effect of FRH is determined by the balance between accelerated pathogen clearance and collateral tissue injury, which is determined, in part, by the site of infection. PMID:15749906

Rice, Penelope; Martin, Erica; He, Ju-Ren; Frank, Mariah; DeTolla, Louis; Hester, Lisa; O'Neill, Timothy; Manka, Cheu; Benjamin, Ivor; Nagarsekar, Ashish; Singh, Ishwar; Hasday, Jeffrey D

2005-03-15

317

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  

Microsoft Academic Search

end of the neutropenic period (>0.5 3 10 9 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

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

2000-01-01

318

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

PubMed Central

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

2012-01-01

319

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

PubMed Central

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

2012-01-01

320

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

PubMed Central

The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics due to increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased viscosity by up-regulating force applied to chromosomes and increased the density of microtubules at kinetochores. Mitotic abnormalities were due to overload of the aurora signalling pathway as subcritical inhibition of Aurora in CA-WASp cells caused increased cytokinesis failure, while overexpression reduced defects. These findings demonstrate that changes in cell mechanics can cause significant mitotic abnormalities leading to genomic instability, and highlights the importance of mechanical sensors such as Aurora B in maintaining the fidelity of haematopoietic cell division. PMID:22972986

Moulding, D.A.; Moeendarbary, E.; Valon, L.; Record, J.; Charras, G.T.; Thrasher, A.J.

2015-01-01

321

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

PubMed

The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics because of increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased viscosity by up-regulating force applied to chromosomes and increased the density of microtubules at kinetochores. Mitotic abnormalities were because of overload of the aurora signaling pathway as subcritical inhibition of Aurora in CA-WASp cells caused increased cytokinesis failure, while overexpression reduced defects. These findings demonstrate that changes in cell mechanics can cause significant mitotic abnormalities leading to genomic instability, and highlight the importance of mechanical sensors such as Aurora B in maintaining the fidelity of hematopoietic cell division. PMID:22972986

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

2012-11-01

322

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

PubMed Central

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

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

2000-01-01

323

Urinary Proteins, Vitamin D and Genetic Polymorphisms as Risk Factors for Febrile Urinary Tract Infection and Relation with Bacteremia: A Case Control Study  

PubMed Central

Objective/Purpose Febrile urinary tract infection (UTI) is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia. Methods A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787) included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, ?-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF. Results IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher ?-defensin 2 production. Conclusion Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype. PMID:25807366

van der Starre, Willize E.; van Nieuwkoop, Cees; Thomson, Uginia; Zijderveld-Voshart, Marleen S. M.; Koopman, Jan Pieter R.; van der Reijden, Tanny J. K.; van Dissel, Jaap T.; van de Vosse, Esther

2015-01-01

324

Reappraisal of the effectiveness of ??mTc-dimercaptosuccinic acid scans for selective voiding cystourethrography in children with a first febrile urinary tract infection.  

PubMed

Recent studies have yielded conflicting results regarding the ability of technetium-99m dimercaptosuccinic acid ((99m)Tc-DMSA) renal scans for identifying high-grade vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). This study aimed to reevaluate the effectiveness of (99m)Tc-DMSA renal scans for selective voiding cystourethrography (VCUG) in children with a first febrile UTI. The medical records of children aged ? 5 years who were admitted with a first febrile UTI were retrospectively reviewed. Ultrasonography (US) and DMSA renal scans were performed within 3-5 days after admission, and VCUG was performed 7-10 days after antibiotics treatment. A total of 653 children were enrolled for analysis, including 579 patients aged < 2 years (Group A) and 74 patients aged 2-5 years (Group B). In Group A, DMSA scans were abnormal for 346 patients (59.8%), and normal for 233 patients (40.2%). High-grade VUR was present in 99 of 346 patients (28.9%) with abnormal DMSA scans, but present in only 16 of 233 patients (6.9%) with normal DMSA scans (p < 0.001). Regarding the prediction of high-grade VUR, the sensitivity and negative predictive value (NPV) for the DMSA scans were 86.1% and 93.1%, respectively. In Group B, DMSA scans were abnormal for 36 patients (48.6%), and normal for 38 patients (51.4%). High-grade VUR was present in 12 of 36 patients (33.3%) with abnormal DMSA scans, whereas none of the 38 patients with normal DMSA scans had high-grade VUR (p < 0.001). The sensitivity and NPV of the DMSA scans were both 100%. Using the selective VCUG strategy, approximately 40% of Group A patients and 50% of Group B patients could be spared an unnecessary VCUG, respectively. Our study results suggest that (99m)Tc-DMSA renal scans are effective in identifying children with a first febrile UTI for selective VCUG. PMID:25476098

Shih, Bing-Fu; Tsai, Jeng-Daw; Tsao, Chin-Ho; Huang, Fu-Yuan

2014-12-01

325

Each summer, fish kills occur in freshwater and saltwater environments. They occur in natural  

E-print Network

. This process, known as photosynthesis occurs during daylight hours. Photosynthesis is conducted by submerged. Oxygen enters water from the atmosphere and through photosynthesis by aquatic plants and algae. Diffusion photosynthesis occurs only during daylight hours and respiration (or use of oxygen) occurs day and night

Jawitz, James W.

326

Phonetic Recalibration Only Occurs in Speech Mode  

ERIC Educational Resources Information Center

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

Vroomen, Jean; Baart, Martijn

2009-01-01

327

Naturally occurring genetic variation in Arabidopsis thaliana  

Microsoft Academic Search

Currently, genetic variation is probably the most important basic resource for plant biology. In addition to the variation artificially generated by mutants in model plants, naturally occurring genetic variation is extensively found for most species, including Arabidopsis. In many cases, natural variation present among accessions is multigenic, which has historically hampered its analysis. However, the exploitation of this resource down

Maarten Koornneef; Carlos Alonso-Blanco; Dick Vreugdenhil

2004-01-01

328

Young Children's Reports of when Learning Occurred  

ERIC Educational Resources Information Center

This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about…

Tang, Connie M.; Bartsch, Karen; Nunez, Narina

2007-01-01

329

Haemolytic glaucoma occurring in phakic eyes  

Microsoft Academic Search

The occurrence of haemolytic glaucoma in phakic eyes due to ghost cells has not previously been reported. Three cases of haemolytic glaucoma occurring over two years after massive vitreous haemorrhage in patients with an intact lens iris diaphragm are described. In one case there was histological confirmation of the presence of ghost cells in the anterior chamber. The mechanism proposed

A M Brooks; W E Gillies

1986-01-01

330

Deletions occur simultaneously at several hindlimb joints  

E-print Network

Deletions occur simultaneously at several hindlimb joints Hip and ankle Hip, andknee ankle 3 1000 in extensors4 500 ms Ankle extensors Hip and ankle extensors coSmab iLg iTa 1000 ms iPl coSmab iSmab iLg Ta MN innervating muscles at hip, knee and ankl

Manitoba, University of

331

POLLINATOR EFFECTIVENESS ON CO-OCCURRING MILKWEEDS  

E-print Network

POLLINATOR EFFECTIVENESS ON CO-OCCURRING MILKWEEDS (ASCLEPIAS; APOCYNACEAE, ASCLEPIADOIDEAE)1 assemblage of pollinators on three co-flowering species: Asclepias syriaca L., A. incarnata L., and A. verticillata L. Hymenopterans exceeded other insects in their prevalence as major pollinators, but most did

332

The problem of “naturally”occurring drought  

Microsoft Academic Search

Naturally-occurring drought is defined here to be drought arising from the nonlinear interactions which are an inherent part of the dynamics of the climatic system. As such it has no specific excitation mechanism, in contrast to forced drought where sea surface temperature anomalies are frequently cited as an important precursor. The essential difference between these two types of drought is

B G Hunt; H B Gordon

1988-01-01

333

Introduction to naturally occurring radioactive material  

Microsoft Academic Search

Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels

Egidi

1997-01-01

334

Addiction and Co-Occurring Mental Disorders  

Microsoft Academic Search

As many as 6 in 10 substance abusers also have at least one other mental disorder. Research increasingly supports the benefit of studying and treating co-occurring disorders together, with both medication and behavioral therapies. Tobacco smoking patterns highlight the striking relationship between addiction and mental illness. Mentally ill individuals are about twice as likely to smoke as others; although they

David Anderson; Johanna Weekley; Simon Weavers; Carl Sherman; Debra P. Davis; Maggie Bray; Jessica Campbell Chambers

335

Retrospective analysis of demographic and clinical factors associated with etiology of febrile respiratory illness among US military basic trainees.  

PubMed

BackgroundBasic trainees in the US military have historically been vulnerable to respiratory infections. Adenovirus and influenza are the most common etiological agents responsible for febrile respiratory illness (FRI) among trainees and present with similar clinical signs and symptoms. Identifying demographic and clinical factors associated with the primary viral pathogens causing FRI epidemics among trainees will help improve differential diagnosis and allow for appropriate distribution of antiviral medications. The objective of this study was to determine what demographic and clinical factors are associated with influenza and adenovirus among military trainees.MethodsSpecimens were systematically collected from military trainees meeting FRI case definition (fever ¿38.0 °C with either cough or sore throat; or provider-diagnosed pneumonia) at eight basic training centers in the USA. PCR and/or cell culture testing for respiratory pathogens were performed on specimens. Interviewer-administered questionnaires collected information on patient demographic and clinical factors. Polychotomous logistic regression was employed to assess the association between these factors and FRI outcome categories: laboratory-confirmed adenovirus, influenza, or other FRI. Sensitivity, specificity, positive and negative predictive value were calculated for individual predictors and clinical combinations of predictors.ResultsAmong 21,570 FRI cases sampled between 2004 and 2009, 63.6% were laboratory-confirmed adenovirus cases and 6.6% were laboratory-confirmed influenza cases. Subjects were predominantly young men (86.8% men; mean age 20.8¿±¿3.8 years) from Fort Jackson (18.8%), Great Lakes (17.1%), Fort Leonard Wood (16.3%), Marine Corps Recruit Depot (MCRD) San Diego (19.0%), Fort Benning (13.3%), Lackland (7.5%), MCRD Parris Island (8.7%), and Cape May (3.2%). The best multivariate predictors of adenovirus were the combination of sore throat (odds ratio [OR], 2.94; 95% confidence interval [CI], 2.66¿3.25), cough (OR, 2.33; 95% CI, 2.11¿2.57), and fever (OR, 2.07; 95% CI, 1.90¿2.26) with a PPV of 77% (p¿¿¿.05). A combination of cough, fever, training week 0¿2 and acute onset were most predictive of influenza (PPV =38%; p¿¿¿.05).ConclusionsSpecific demographic and clinical factors were associated with laboratory-confirmed influenza and adenovirus among military trainees. Findings from this study can guide clinicians in the diagnosis and treatment of military trainees presenting with FRI. PMID:25475044

Padin, Damaris S; Faix, Dennis; Brodine, Stephanie; Lemus, Hector; Hawksworth, Anthony; Putnam, Shannon; Blair, Patrick

2014-12-01

336

Changes in joint laxity occurring during pregnancy.  

PubMed

We have studied changes in peripheral joint laxity occurring during pregnancy in 68 females using both the finger hyperextensometer to quantify laxity at the metacarpophalangeal joint of the index finger and Beighton et al.'s modification of the Carter and Wilkinson scoring system. Although the latter system recorded no change, the more sensitive hyperextensometer demonstrated a significant increase in joint laxity during the last trimester of pregnancy (0.02 greater than p greater than 0.01) over the readings from the same individuals after parturition. When primigravidae and multigravidae were compared, a highly significant increase in laxity was found in women having their second baby over those having their first (0.01 greater than p greater than 0.001), though no further increase in laxity occurred in subsequent pregnancies. PMID:7073339

Calguneri, M; Bird, H A; Wright, V

1982-04-01

337

Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dose Escalation Study  

PubMed Central

Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (n = 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (n = 12). The mean ± standard deviation plasma isavuconazole areas under the concentration-time curves for the dosing period on day 7 were 60.1 ± 22.3 ?g · h/ml and 113.1 ± 19.6 ?g · h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (n = 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. (This study is registered at ClinicalTrials.gov under registration number NCT00413439.) PMID:25624327

Cornely, Oliver A.; Böhme, Angelika; Schmitt-Hoffmann, Anne

2015-01-01

338

Electronic nose technology for detection of invasive pulmonary aspergillosis in prolonged chemotherapy-induced neutropenia: a proof-of-principle study.  

PubMed

Although the high mortality rate of pulmonary invasive aspergillosis (IA) in patients with prolonged chemotherapy-induced neutropenia (PCIN) can be reduced by timely diagnosis, a diagnostic test that reliably detects IA at an early stage is lacking. We hypothesized that an electronic nose (eNose) could fulfill this need. An eNose can discriminate various lung diseases through the analysis of exhaled volatile organic compounds (VOCs). An eNose is cheap and noninvasive and yields results within minutes. In a single-center prospective cohort study, we included patients who were treated with chemotherapy expected to result in PCIN. Based on standardized indications, a full diagnostic workup was performed to confirm invasive aspergillosis or to rule it out. Patients with no aspergillosis were considered controls, and patients with probable or proven aspergillosis were considered index cases. Exhaled breath was examined with a Cyranose 320 (Smith Detections, Pasadena, CA). The resulting data were analyzed using principal component reduction. The primary endpoint was cross-validated diagnostic accuracy, defined as the percentage of patients correctly classified using the leave-one-out method. Accuracy was validated by 100,000 random classifications. We included 46 subjects who underwent 16 diagnostic workups, resulting in 6 cases and 5 controls. The cross-validated accuracy of the eNose in diagnosing IA was 90.9% (P = 0.022; sensitivity, 100%; specificity, 83.3%). Receiver operating characteristic analysis showed an area under the curve of 0.93. These preliminary data indicate that PCIN patients with IA have a distinct exhaled VOC profile that can be detected with eNose technology. The diagnostic accuracy of the eNose for invasive aspergillosis warrants validation. PMID:23467602

de Heer, Koen; van der Schee, Marc P; Zwinderman, Koos; van den Berk, Inge A H; Visser, Caroline Elisabeth; van Oers, Rien; Sterk, Peter J

2013-05-01

339

Electronic Nose Technology for Detection of Invasive Pulmonary Aspergillosis in Prolonged Chemotherapy-Induced Neutropenia: a Proof-of-Principle Study  

PubMed Central

Although the high mortality rate of pulmonary invasive aspergillosis (IA) in patients with prolonged chemotherapy-induced neutropenia (PCIN) can be reduced by timely diagnosis, a diagnostic test that reliably detects IA at an early stage is lacking. We hypothesized that an electronic nose (eNose) could fulfill this need. An eNose can discriminate various lung diseases through the analysis of exhaled volatile organic compounds (VOCs). An eNose is cheap and noninvasive and yields results within minutes. In a single-center prospective cohort study, we included patients who were treated with chemotherapy expected to result in PCIN. Based on standardized indications, a full diagnostic workup was performed to confirm invasive aspergillosis or to rule it out. Patients with no aspergillosis were considered controls, and patients with probable or proven aspergillosis were considered index cases. Exhaled breath was examined with a Cyranose 320 (Smith Detections, Pasadena, CA). The resulting data were analyzed using principal component reduction. The primary endpoint was cross-validated diagnostic accuracy, defined as the percentage of patients correctly classified using the leave-one-out method. Accuracy was validated by 100,000 random classifications. We included 46 subjects who underwent 16 diagnostic workups, resulting in 6 cases and 5 controls. The cross-validated accuracy of the eNose in diagnosing IA was 90.9% (P = 0.022; sensitivity, 100%; specificity, 83.3%). Receiver operating characteristic analysis showed an area under the curve of 0.93. These preliminary data indicate that PCIN patients with IA have a distinct exhaled VOC profile that can be detected with eNose technology. The diagnostic accuracy of the eNose for invasive aspergillosis warrants validation. PMID:23467602

van der Schee, Marc P.; Zwinderman, Koos; van den Berk, Inge A. H.; Visser, Caroline Elisabeth; van Oers, Rien; Sterk, Peter J.

2013-01-01

340

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

PubMed Central

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

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

2001-01-01

341

Safety and pharmacokinetics of isavuconazole as antifungal prophylaxis in acute myeloid leukemia patients with neutropenia: results of a phase 2, dose escalation study.  

PubMed

Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort (n = 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort (n = 12). The mean ± standard deviation plasma isavuconazole areas under the concentration-time curves for the dosing period on day 7 were 60.1 ± 22.3 ?g · h/ml and 113.1 ± 19.6 ?g · h/ml for the patients in the low-dose and high-dose cohorts, respectively. The adverse events in five patients in the low-dose cohort and in eight patients in the high-dose cohort were considered to be drug related. Most were mild to moderate in severity, and the most common adverse events were headache and rash (n = 3 each). One patient in the high-dose cohort experienced a serious adverse event (unrelated to isavuconazole treatment), and two patients each in the low-dose and high-dose cohorts discontinued the study due to adverse events. Of the 20 patients who completed the study, 18 were classified as a treatment success. In summary, the results of this analysis support the safety and tolerability of isavuconazole administered at 200 mg and 400 mg once-daily as prophylaxis in immunosuppressed patients at high risk of fungal infections. (This study is registered at ClinicalTrials.gov under registration number NCT00413439.). PMID:25624327

Cornely, Oliver A; Böhme, Angelika; Schmitt-Hoffmann, Anne; Ullmann, Andrew J

2015-04-01

342

Persulfate activation by naturally occurring trace minerals.  

PubMed

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

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

2011-11-30

343

Thermodynamic characterization of naturally occurring RNA tetraloops  

PubMed Central

Although tetraloops are one of the most frequently occurring secondary structure motifs in RNA, less than one-third of the 30 most frequently occurring RNA tetraloops have been thermodynamically characterized. Therefore, 24 stem–loop sequences containing common tetraloops were optically melted, and the thermodynamic parameters ?H°, ?S°, ?G°37, and TM for each stem–loop were determined. These new experimental values, on average, are 0.7 kcal/mol different from the values predicted for these tetraloops using the model proposed by Vecenie CJ, Morrow CV, Zyra A, Serra MJ. 2006. Biochemistry 45: 1400–1407. The data for the 24 tetraloops reported here were then combined with the data for 28 tetraloops that were published previously. A new model, independent of terminal mismatch data, was derived to predict the free energy contribution of previously unmeasured tetraloops. The average absolute difference between the measured values and the values predicted using this proposed model is 0.4 kcal/mol. This new experimental data and updated predictive model allow for more accurate calculations of the free energy of RNA stem–loops containing tetraloops and, furthermore, should allow for improved prediction of secondary structure from sequence. It was also shown that tetraloops within the sequence 5?-GCCNNNNGGC-3? are, on average, 0.6 kcal/mol more stable than the same tetraloop within the sequence 5?-GGCNNNNGCC-3?. More systemic studies are required to determine the full extent of non-nearest-neighbor effects on tetraloop stability. PMID:20047989

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

2010-01-01

344

Co-occurring psychiatric disorders and alcoholism.  

PubMed

Alcohol use disorder (AUD), a term that comprises both alcohol abuse and alcohol dependence, is a highly prevalent psychiatric disorder. Over 50% of treated AUD patients also suffer from other psychiatric disorder(s). Detailed study has revealed disorders across multiple psychiatric domains with rates of co-occurrence far greater than chance, suggesting a synergistic relationship. The basis of this synergy is explored along with its multiple forms, including behavioral and neurobiologic. Specific topics include the predisposition to both AUD and co-occurring psychopathology, the vulnerability to environmental risk factors that exacerbate these predispositions, and the nature of reinforcement in acute intoxication. Co-occurrence can also modify and exacerbate the neuroadaptations underpinning chronic dependence and relapse, the manifestations of acute and protracted withdrawal, emergence of medical and psychiatric complications, and ultimately the potential for relapse. The outcomes of co-occurrence as well as the unique impact it has on proper treatment are also discussed. Throughout, the significance of recognizing co-occurrence is emphasized since, both neurobiologically and clinically, the synergies between co-occurring disorders yield a result far more complex than a mere sum of the component disorders. PMID:25307597

Stephen Rich, J; Martin, Peter R

2014-01-01

345

Adverse drug events occurring following hospital discharge  

Microsoft Academic Search

OBJECTIVE: To describe the incidence of adverse drug events (ADEs), preventable ADEs, and ameliorable ADEs occurring after hospital\\u000a discharge and their associated risk factors.\\u000a \\u000a \\u000a DESIGN: Prospective cohort study.\\u000a \\u000a \\u000a \\u000a \\u000a SETTING: Urban academic health sciences center.\\u000a \\u000a \\u000a \\u000a \\u000a PATIENTS: Consecutive patients discharged home from the general medical service.\\u000a \\u000a \\u000a \\u000a \\u000a INTERVENTIONS: We determined posthospital outcomes approximately 24 days following discharge by performing a chart review and

Alan J. Forster; Harvey J. Murff; Josh F. Peterson; Tejal K. Gandhi; David W. Bates

2005-01-01

346

Does DNA repair occur during somatic hypermutation?  

PubMed Central

Activation-induced deaminase (AID) initiates a flood of DNA damage in the immunoglobulin loci, leading to abasic sites, single-strand breaks and mismatches. It is compelling that some proteins in the canonical base excision and mismatch repair pathways have been hijacked to increase mutagenesis during somatic hypermutation. Thus, the AID-induced mutagenic pathways involve a mix of DNA repair proteins and low fidelity DNA polymerases to create antibody diversity. In this review, we analyze the roles of base excision repair, mismatch repair, and mutagenesis during somatic hypermutation of rearranged variable genes. The emerging view is that faithful base excision repair occurs simultaneously with mutagenesis, whereas faithful mismatch repair is mostly absent. PMID:22728014

Saribasak, Huseyin; Gearhart, Patricia J.

2012-01-01

347

Naturally occurring antinociceptive substances from plants.  

PubMed

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

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

2000-09-01

348

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

PubMed Central

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

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

2015-01-01

349

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

PubMed Central

Background Poikiloderma with Neutropenia (PN) is a rare autosomal recessive genodermatosis caused by C16orf57 mutations. To date 17 mutations have been identified in 31 PN patients. Results We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel C16orf57 mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain. Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase. According to bioinformatic prediction, all known C16orf57 mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding. Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect. Conclusions In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of C16orf57 gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance. The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the main cutaneous and haematological clinical signs of PN patients. PMID:22269211

2012-01-01

350

Introduction to naturally occurring radioactive material  

SciTech Connect

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

Egidi, P.

1997-08-01

351

How Does Evaporation Occur From Sphagnum Mosses?  

NASA Astrophysics Data System (ADS)

How does evaporation occur from Sphagnum mosses? What are the contributions of liquid and vapour flux within the moss architecture to the flux from it? What is the evaporating surface? The poor understanding of these processes limits our ability to predict evaporation from, or the moisture distribution within, moss communities. To address this we measured evaporation (average 1.9 mm/d) from laboratory columns of "undisturbed" Sphagnum moss samples having a constant water table 20 cm below the surface being supplied with water from a common (isotopic) source. We then assessed the nature and magnitude of water fluxes by analyzing depth profiles of volumetric water content (VMC), relative humidity (RH) of pore gas, isotopic composition of pore water and related soil properties. VMC in the upper 15 cm was quite uniform averaging 13.6%, increasing to 25.9% at 20-25 cm, then saturation below. RH was 94% at 2.5 cm depth, progressively approaching 100% at 15 cm depth. Relative to oxygen-18 and deuteium of source water (-13.1 and -86.7 permil, respectively) enrichment was greatest in the 0-5 cm layer (average -6.57 and -61.10 permil, respectively), and decreased with depth. Corresponding oxygen- 18 and deuterium values clustered tightly along a common evaporation line having a slope of 3.76, as predicted for free water evaporation under the same experimental conditions. Given the vapour pressure deficit (RH<100%) in pore gases, and the resulting isotopic fractionation, it is apparent that latent heat exchange (vaporization) occurs 5 to 10 cm below the upper surface. However, the diffusive vapor flux based on Fick's law was estimated to be only 0.02-0.04 mm/d, or about 2% of the total evaporative flux from the community surface. Modeling of the isotope enrichment profiles assuming negligible net vapor-phase transport also yielded remarkably close agreement with measured mass flux from the columns, confirming that liquid flow within the profile is the dominant form of water transport. These results suggest that incorporation of water- isotope sampling into field studies may allow improved quantification of evaporation from natural moss communities, including the possibility of partitioning evaporative and transpirative fluxes in Sphagnum dominated peatlands colonized also by vascular plants.

Price, J. S.; Whittington, P. N.; Yi, Y.; Edwards, T. W.

2006-12-01

352

Naturally occurring contamination in the Mancos Shale.  

PubMed

Some uranium mill tailings disposal cells were constructed on dark-gray shale of the Upper Cretaceous Mancos Shale. Shale of this formation contains contaminants similar to those in mill tailings. To establish the contributions derived from the Mancos, we sampled 51 locations in Colorado, New Mexico, and Utah. Many of the groundwater samples were saline with nitrate, selenium, and uranium concentrations commonly exceeding 250,?000, 1000, and 200 ?g/L, respectively. Higher concentrations were limited to groundwater associated with shale beds, but were not correlated with geographic area, stratigraphic position, or source of water. The elevated concentrations suggest that naturally occurring contamination should be considered when evaluating groundwater cleanup levels. At several locations, seep water was yellow or red, caused in part by dissolved organic carbon concentrations up to 280 mg/L. Most seeps had (234)U to (238)U activity ratios greater than 2, indicating preferential leaching of (234)U. Seeps were slightly enriched in (18)O relative to the meteoric water line, indicating limited evaporation. Conceptually, major ion chemical reactions are dominated by calcite dissolution following proton release from pyrite oxidation and subsequent exchange by calcium for sodium residing on clay mineral exchange sites. Contaminants are likely released from organic matter and mineral surfaces during weathering. PMID:22225529

Morrison, Stan J; Goodknight, Craig S; Tigar, Aaron D; Bush, Richard P; Gil, April

2012-02-01

353

Epigenetic Mechanisms in Commonly Occurring Cancers  

PubMed Central

Cancer is a collection of very complex diseases that share many traits while differing in many ways as well. This makes a universal cure difficult to attain, and it highlights the importance of understanding each type of cancer at a molecular level. Although many strides have been made in identifying the genetic causes for some cancers, we now understand that simple changes in the primary DNA sequence cannot explain the many steps that are necessary to turn a normal cell into a rouge cancer cell. In recent years, some research has shifted to focusing on detailing epigenetic contributions to the development and progression of cancer. These changes occur apart from primary genomic sequences and include DNA methylation, histone modifications, and miRNA expression. Since these epigenetic modifications are reversible, drugs targeting epigenetic changes are becoming more common in clinical settings. Daily discoveries elucidating these complex epigenetic processes are leading to advances in the field of cancer research. These advances, however, come at a rapid and often overwhelming pace. This review specifically summarizes the main epigenetic mechanisms currently documented in solid tumors common in the United States and Europe. PMID:22519822

2012-01-01

354

Attenuation of Naturally Occurring Arsenic at  

E-print Network

(USEPA) lowered the maximum contaminant level (MCL) for dissolved arsenic in groundwater from 0.050 mg/L to 0.010 mg/L due to long-term chronic health effects of low concentrations of arsenic in drinking water. This has heightened public and regulatory awareness of dissolved arsenic in groundwater. Arsenic occurrence at petroleum-impacted sites can be summarized by five basic principles that govern the fate and transport of arsenic in shallow aquifers impacted by petroleum hydrocarbons. These are: 1. If arsenic is not present in the site mineralogy, or if arsenic has not been emplaced due to human activity, petroleum impacts will not cause arsenic impacts to groundwater. Arsenic is not a major contaminant in petroleum hydrocarbons; 2. For sites that have naturally occurring arsenic-bearing minerals, sorbed arsenic phases, or aged anthropogenic arsenic sources, there is a stable arsenic geochemistry present that determines the ambient (background) level of dissolved arsenic in groundwater. If the background level of arsenic naturally exceeds the new MCL, then the MCL is unachievable as an attenuation or remediation goal;

Petroleum Hydrocarbon–impacted Sites; Richard A. Brown; Katrina E. Patterson

355

Cellular internalization of exosomes occurs through phagocytosis.  

PubMed

Exosomes play important roles in many physiological and pathological processes. However, the exosome-cell interaction mode and the intracellular trafficking pathway of exosomes in their recipient cells remain unclear. Here, we report that exosomes derived from K562 or MT4 cells are internalized more efficiently by phagocytes than by non-phagocytic cells. Most exosomes were observed attached to the plasma membrane of non-phagocytic cells, while in phagocytic cells these exosomes were found to enter via phagocytosis. Specifically, they moved to phagosomes together with phagocytic polystyrene carboxylate-modified latex beads (biospheres) and were further sorted into phagolysosomes. Moreover, exosome internalization was dependent on the actin cytoskeleton and phosphatidylinositol 3-kinase, and could be inhibited by the knockdown of dynamin2 or overexpression of a dominant-negative form of dynamin2. Further, antibody pretreatment assays demonstrated that tim4 but not tim1 was involved in exosomes uptake. We also found that exosomes did not enter the internalization pathway involving caveolae, macropinocytosis and clathrin-coated vesicles. Our observation that the cellular uptake of exosomes occurs through phagocytosis has important implications for exosome-cell interactions and the exosome intracellular trafficking pathway. PMID:20136776

Feng, Du; Zhao, Wen-Long; Ye, Yun-Ying; Bai, Xiao-Chen; Liu, Rui-Qin; Chang, Lei-Fu; Zhou, Qiang; Sui, Sen-Fang

2010-05-01

356

Differential dormancy of co-occurring copepods  

NASA Astrophysics Data System (ADS)

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

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

1998-08-01

357

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

PubMed Central

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

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

2010-01-01

358

Prevalence of patients with acute febrile illnesses and positive dengue NS1 tests in a tertiary hospital in Papua New Guinea.  

PubMed

Because the prevalence of dengue fever in urban settings in Papua New Guinea is unknown, we investigated the presence of dengue using the NS1 antigen test in an outpatient-based prospective observational study at Port Moresby General Hospital. Of 140 patients with acute febrile illnesses, dengue fever was diagnosed in 14.9% (20 of 134; 95% confidence interval [95% CI] = 9.6-22.4). Malaria (2 of 137; 1.5%; 95% CI = 0.3-5.7), chikungunya (3 of 140; 2.1%; 95% CI = 0.6-6.6), and bacterial bloodstream infections (0 of 80; 0%; 95% CI = 0-5.7) were uncommon. Dengue fever should no longer be considered rare in Papua New Guinea. PMID:25331803

Asigau, Viola; Lavu, Evelyn K; McBride, William J H; Biloh, Eric; Naroi, Francis; Koana, Egi; Ferguson, John K; Laman, Moses

2015-01-01

359

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

PubMed Central

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

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

2012-01-01

360

Information Needs While A Disaster Is Occurring  

NASA Astrophysics Data System (ADS)

Evidence from recent earthquakes, wildfires, and debris flows in southern California indicates that many people - local officials as well as residents and visitors - lack important understanding during the time that a disaster is unfolding, a time of uncertainty and confusion. While some of the uncertainty is inherent, some could be alleviated. Physical scientists and engineers know what to expect as the event unfolds. Social scientists know how humans will react during a disaster, and how to effectively communicate the warnings or evacuation orders that may precede it. Such knowledge can improve public safety. As just a few of many examples: - Based on questions posed at numerous public talks, many individuals who practice "Drop Cover and Hold" during earthquake drills do not understand what they are protecting themselves against, and thus cannot determine what to do when an earthquake strikes and they have no cover available. Similarly, they do not know how to act during the aftershocks that follow. - The 2009 Station Fire in the San Gabriel Mountains put foothills communities at risk, first from the wildfire and then from debris flows. Some neighborhoods received multiple evacuation notices during a few days or months. Local officials have expressed frustration and concern about an evacuation compliance rate that is steadily dropping and is now below 50%. The debris flow danger will persist over the next 2-4 winters yet evacuation compliance may drop lower still. - On February 6, 2010, a significant rainstorm brought the threat of imminent debris flows to areas burned by the Station Fire. In one neighborhood, residents loaded their cars with important belongings then waited for indications that they should evacuate. Powerful debris flows suddenly appeared, sweeping the cars downhill and destroying both cars and belongings. Some residents did understand that rainfall intensity would control the generation of debris flows in that storm. But they didn't understand that rainfall intensity at their homes might be less than the intensity up in the mountains where the debris flows would start. Nor did they know that debris flows travel too quickly to be outrun. These and many other examples indicate need for social and natural scientists to increase awareness of what to expect when the disaster strikes. This information must be solidly understood before the event occurs - while a disaster is unfolding there are no teachable moments. Case studies indicate that even those who come into a disaster well educated about the phenomenon can struggle to apply what they know when the real situation is at hand. In addition, psychological studies confirm diminished ability to comprehend information at times of stress.

Perry, S. C.

2010-12-01

361

Antigenotoxic activity of naturally occurring furanocoumarins.  

PubMed

This study was designed to investigate the antigenotoxic effects of a series of naturally occurring furanocoumarins (NOFs) including isoimperatorin, imperatorin, (+)-oxypeucedanin, (+)-byakangelicol, and (+)-byakangelicine on antigenotoxic activities against genotoxicity induced by carcinogens [furylfuramide and N-methyl-N'-nitro-N-nitrosoguanidine], and procarcinogens 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4) and 2-amino-3,4-dimethyl-3H-imidazo-[4,5-f] quinoline (MeIQ)] to genotoxic metabolites catalyzed by rat S9 or rat and human recombinant cytochrome P450 (CYP) 1As by using the umu test based on SOS response. Five different NOFs, which were found in the human diets, strongly inhibited the umuC induction by procarcinogens, but did not be affected by carcinogens. Notably, isoimperatorin and (+)-byakangelicol were found to be potent inhibitors on the metabolic activation of PBTA-4 and MeIQ to genotoxic metabolites catalyzed by rat and human CYP1A1, or rat and human CYP1A2, respectively. In addition, to elucidate the mechanism of their antigenotoxic effects against procarcinogens, the effects of NOFs on rat and human CYP1A1- or rat and human CYP1A2-related enzyme activities of 7-ethoxyresorufin-O-deethylase (EROD) were also investigated. Reduction of the EROD activities by some of the NOFs with IC(50) values of 0.23-20.64 ?M was found to be due to strong inhibition of CYP1A1 and CYP1A2 dependent monooxygenases. Furthermore, the mechanism of inhibitions by NOFs on human CYP1A1 and CYP1A2 was analyzed by means of Dixon plots plus Cornish-Bowden plots. The kinetic studies of inhibition types revealed that these compounds inhibited the human CYP1A1 and CYP1A2 a variety of modes rather than by a uniform one. Moreover, experiments with a two-stage incubation indicated that NOFs, except for imperatorin, inhibited human CYP1A1 in a mechanism-based manner, but directly inhibited human CYP1A2. This data suggest that certain NOFs, to which humans are exposed in the diet, may be capable of affecting the metabolic activation of procarcinogens due to inhibitions of CYP1A1 and CYP1A2 enzymes. PMID:21786339

Marumoto, Shinsuke; Oda, Yoshimitsu; Miyazawa, Mitsuo

2011-10-01

362

33 CFR 330.3 - Activities occurring before certain dates.  

Code of Federal Regulations, 2010 CFR

...occurring before certain dates. 330.3 Section 330.3 Navigation and Navigable Waters...NATIONWIDE PERMIT PROGRAM § 330.3 Activities occurring before certain...United States that occurred before the phase-in dates which extended...

2010-07-01

363

Antimicrobial therapy of febrile complications after high-dose chemo-\\/radiotherapy and autologous hematopoietic stem cell transplantation  

Microsoft Academic Search

Infectious complications occur in 60–100% of patients following high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT), and are commonly caused by Gram-negative aerobic bacteria (such as Pseudomonas aeruginosa and enterobacteriacea e) and Gram-positive cocci (such as enterococci, streptococci and staphylococci), which should be covered by empiric first-line antibiotic therapy. Less frequently, infections are caused by fungi and anaerobic

Hartmut Bertz; Holger W. Auner; Florian Weissinger; Hans-Jürgen Salwender; Hermann Einsele; Gerlinde Egerer; Michael Sandherr; Silke Schüttrumpf; Thomas Südhoff; Georg Maschmeyer

2003-01-01

364

A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer ? ? Access the “Journal Club” discussion of this paper at http:\\/\\/www.elsevier.com\\/locate\\/ajmselect  

Microsoft Academic Search

purpose: To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer.patients and methods: A total of 317 neutropenic patients (<500 cells\\/mm3) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were randomly assigned to receive either fluconazole (400 mg intravenously once daily) or amphotericin B

Drew J Winston; James W Hathorn; Mindy G Schuster; Gary J Schiller; Mary C Territo

2000-01-01

365

A LONGITUDINAL INVESTIGATION OF IgG AND IgM ANTIBODY RESPONSES TO THE MEROZOITE SURFACE PROTEIN1 19-KILODALTON DOMAIN OF PLASMODIUM FALCIPARUMIN PREGNANT WOMEN AND INFANTS: ASSOCIATIONS WITH FEBRILE ILLNESS, PARASITEMIA, AND ANEMIA  

Microsoft Academic Search

This study was aimed at delineating characteristics of naturally acquired immunity against the merozoite surface antigen-1 (MSP-1) of Plasmodium falciparum,a candidate malaria vaccine antigen. A case\\/control study was performed on 75 case\\/control pairs of infants with febrile illness at the time of the first detected infection indicating a clinical case. The presence and level of antibodies at one month prior

ORALEE H. BRANCH; VENKATACHALAM UDHAYAKUMAR; ALLEN W. HIGHTOWER; AGGREY J. OLOO; WILLIAM A. HAWLEY; BERNARD L. NAHLEN; PETER B. BLOLAND; DAVID C. KASLOW; ALTAF A. LAL

366

A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS+) mutation.  

PubMed

Mutations in the voltage-gated sodium channel SCN1A are responsible for a number of seizure disorders including Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). To determine the effects of SCN1A mutations on channel function in vivo, we generated a bacterial artificial chromosome (BAC) transgenic mouse model that expresses the human SCN1A GEFS+ mutation, R1648H. Mice with the R1648H mutation exhibit a more severe response to the proconvulsant kainic acid compared with mice expressing a control Scn1a transgene. Electrophysiological analysis of dissociated neurons from mice with the R1648H mutation reveal delayed recovery from inactivation and increased use-dependent inactivation only in inhibitory bipolar neurons, as well as a hyperpolarizing shift in the voltage dependence of inactivation only in excitatory pyramidal neurons. These results demonstrate that the effects of SCN1A mutations are cell type-dependent and that the R1648H mutation specifically leads to a reduction in interneuron excitability. PMID:19409490

Tang, Bin; Dutt, Karoni; Papale, Ligia; Rusconi, Raffaella; Shankar, Anupama; Hunter, Jessica; Tufik, Sergio; Yu, Frank H; Catterall, William A; Mantegazza, Massimo; Goldin, Alan L; Escayg, Andrew

2009-07-01

367

An enhanced home cage modulates hypothalamic CRH-ir Labeling in juvenile rats, with and without sub-threshold febrile convulsions.  

PubMed

Pre and postnatal environments can have a profound impact on offspring development. This is especially true when considering the origin of neurological diseases, including epilepsy, a relatively common and chronic neurological condition, affecting 1-2% of the population. Previously, we have used maternal stress and an enhanced home cage (EHC) in an effort to identify potential factors in the early environment that may increase the risk for experiencing seizures. First, pregnant Long-Evans rats were exposed to a predator stress (PS). Then, at birth, litters were divided into standard cage (SC) and EHC groups until postnatal Day 14 (PD14) when a model of febrile convulsions was used to determine convulsion susceptibility of the various groups. Twenty-four hours later, pup brains were processed for immunohistochemical detection of corticotrophic releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus. Analysis of CRH immunoreactive (-ir) patterns revealed a buffering of CRH-ir in EHC reared offspring. Further, experiencing convulsions led to decreased CRH-ir. Our results support the concept that postnatal environmental influences affect neonatal programming and neurodevelopment of processes that could underlie seizure susceptibility, and that these effects can be modulated by EHC conditions. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 57: 374-381, 2015. PMID:25783951

Korgan, Austin C; Vonkeman, Janeske; Esser, Michael J; Perrot, Tara S

2015-04-01

368

32 CFR 716.6 - Death occurring after active service.  

Code of Federal Regulations, 2014 CFR

...2014-07-01 2014-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

2014-07-01

369

32 CFR 716.6 - Death occurring after active service.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

2013-07-01

370

32 CFR 716.6 - Death occurring after active service.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

2010-07-01

371

32 CFR 716.6 - Death occurring after active service.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

2012-07-01

372

32 CFR 716.6 - Death occurring after active service.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Death occurring after active service. 716... DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after active service....

2011-07-01

373

Infections in Hematogical Cancer Patients: The Contribution of Systematic Reviews and Meta-Analyses  

Microsoft Academic Search

Systematic reviews and meta-analyses have made a major contribution to the evidence-based management of infections in cancer patients. We review the contribution of systematic reviews with regard to antibiotic, antifungal, antiviral and Pneumocystis pneumonia prophylaxis; antibiotic and antifungal treatment of febrile neutropenia; use of intravenous immunoglobulins, and infection control strategies during neutropenia. We focus on limitations of randomized controlled trials

Mical Paul; Anat Gafter-Gvili; Elad Goldberg; Dafna Yahav

2011-01-01

374

Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore  

PubMed Central

Background Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools. Methods During the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ? 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model. Results By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit. Conclusions Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission. PMID:23206689

2012-01-01

375

Association between Iron Deficiency Anemia and Febrile Convulsion in 3- to 60-Month-Old Children: A Systematic Review and Meta-Analysis  

PubMed Central

Controversy exists regarding the association between Iron Deficiency Anemia (IDA), iron status, and Febrile Convulsion (FC) during childhood. In this article, a systematic review and meta-analysis is conducted in order to determine possible association and the degree of association between these statuses and FC. To identify all studies related to IDA and FC, various references such as MEDLINE (PubMed), Embase (OVID), Web of sciences (Thomson Reuters) and Google scholar were searched (up until 15 January 2013). Heterogeneity was assessed using the Q statistic, Tau2, and I2. Additionally, subgroup analyses were performed. The outcome of primary interest was the overall Odds Ratio (OR) of FC for IDA and standard mean differences (SMD) of ferritin level. In total, 21 articles were considered to assess the association between IDA and FC. Anemia was more prevalent among the FC patients compared with the controls and the overall OR was 1.52 (95% CI=1.03 to 2.25). In addition, the pooled OR for 17 studies performed in the populations with low and moderate prevalence of anemia was 2.04 (95% CI=1.46 to 2.85). Furthermore, 12 studies assessed the association between the ferritin level and FC. The overall SMD was -0.02 with a 95% CI of -0.09 to 0.06. Besides, the pooled SMD of ferritin was -0.57 (95% CI=-0.7 to -0.46) in 6 studies reporting no difference between the FC and the control group with respect to temperature. IDA was associated with a moderate increased risk of FC in children, particularly in the areas with low and moderate prevalence of anemia. PMID:25429171

Habibian, Narges; Alipour, Abbas; Rezaianzadeh, Abbas

2014-01-01

376

Association between Iron Deficiency Anemia and Febrile Convulsion in 3- to 60-Month-Old Children: A Systematic Review and Meta-Analysis.  

PubMed

Controversy exists regarding the association between Iron Deficiency Anemia (IDA), iron status, and Febrile Convulsion (FC) during childhood. In this article, a systematic review and meta-analysis is conducted in order to determine possible association and the degree of association between these statuses and FC. To identify all studies related to IDA and FC, various references such as MEDLINE (PubMed), Embase (OVID), Web of sciences (Thomson Reuters) and Google scholar were searched (up until 15 January 2013). Heterogeneity was assessed using the Q statistic, Tau(2), and I(2). Additionally, subgroup analyses were performed. The outcome of primary interest was the overall Odds Ratio (OR) of FC for IDA and standard mean differences (SMD) of ferritin level. In total, 21 articles were considered to assess the association between IDA and FC. Anemia was more prevalent among the FC patients compared with the controls and the overall OR was 1.52 (95% CI=1.03 to 2.25). In addition, the pooled OR for 17 studies performed in the populations with low and moderate prevalence of anemia was 2.04 (95% CI=1.46 to 2.85). Furthermore, 12 studies assessed the association between the ferritin level and FC. The overall SMD was -0.02 with a 95% CI of -0.09 to 0.06. Besides, the pooled SMD of ferritin was -0.57 (95% CI=-0.7 to -0.46) in 6 studies reporting no difference between the FC and the control group with respect to temperature. IDA was associated with a moderate increased risk of FC in children, particularly in the areas with low and moderate prevalence of anemia. PMID:25429171

Habibian, Narges; Alipour, Abbas; Rezaianzadeh, Abbas

2014-11-01

377

Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study  

PubMed Central

Background Initial management of chemotherapy-induced febrile neutropaenia (FN) comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there is sufficient evidence to indicate which antibiotic regimen should be administered initially. However, no randomized trial has evaluated whether adherence to an antimicrobial stewardship program (ASP) results in lower rates of mortality in this setting. The present study sought to assess the association between adherence to an ASP and mortality among hospitalised cancer patients with FN. Methods We conducted a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All adult patients who were admitted to the haematology ward with cancer and FN were followed up for 28 days. ASP adherence to the initial antimicrobial prescription was determined. The mortality rates of patients who were treated with antibiotics according to the ASP protocol were compared with those of patients treated with other antibiotic regimens. The multivariate Cox proportional hazards model and propensity score were used to estimate 28-day mortality risk. Results A total of 307 FN episodes in 169 subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox regression analysis, adjusted for propensity scores and other potential confounding factors, ASP adherence was independently associated with lower mortality (hazard ratio, 0.36; 95% confidence interval, 0.14–0.92). Conclusions Antimicrobial selection is important for the initial management of patients with FN, and adherence to the ASP, which calls for the rational use of antibiotics, was associated with lower mortality rates in this setting. PMID:24884397

2014-01-01

378

Clozapine treatment of patients with refractory schizophrenia, concurrent dengue infection and hematological abnormalities: three case reports  

PubMed Central

Background: Dengue is a febrile illness that is most common in tropical areas but is recognized worldwide as one of the most important arbovirus diseases of humans. This febrile illness generally has a course with mild alterations in white blood cell count, but there are also rare cases of severe neutropenia or agranulocytosis during dengue infection. Clozapine (CLZ) remains the most effective treatment for schizophrenia, but because of its poor side effect profile, in particular due to the increased risk of neutropenia and agranulocytosis, it is generally used for patients whose condition responds poorly to other antipsychotics. Methods: We report three cases of dengue infection in patients with refractory schizophrenia who were using CLZ, and we discuss the implications of this infection on the continuation of CLZ treatment in these patients. Results: Of these three cases with dengue infection and co-occurence of CLZ use, the first would be classified as severe neutropenia and the second as moderate leucopenia; the last case had a white blood cell (WBC) count inside the normal range, and had no need to change his antipsychotic. The first and the second patient presented a worsening in their schizophrenic psychopathologies, after CLZ withdrawal, evolving into catatonic states, that were reverted after the careful reintroduction of CLZ. Discussion: It is very likely that during dengue epidemics many patients with schizophrenia and using CLZ have their treatment permanently discontinued given WBC count concerns, causing relapse of symptoms of schizophrenia and impairment of quality of life of these patients.This is the first report of neutropenia cases among CLZ-treated patients during dengue infection that describes the withdrawal of CLZ and its successful readministration. PMID:24167679

Rezende, Tatiana M.N.; Morais, Silvio L.; Crippa, José A.S.; Dursun, Serdar M.; Baker, Glen B.; Hallak, Jaime E.C.

2013-01-01

379

5 CFR 847.505 - When transfer occurs.  

Code of Federal Regulations, 2010 CFR

...REGULATIONS (CONTINUED) ELECTIONS OF RETIREMENT COVERAGE BY CURRENT AND FORMER EMPLOYEES OF NONAPPROPRIATED FUND INSTRUMENTALITIES Transfers of Contributions Under the Retroactive Provisions § 847.505 When transfer occurs....

2010-01-01

380

Increased granulocyte colony-stimulating factor responsiveness but normal resting granulopoiesis in mice carrying a targeted granulocyte colony-stimulating factor receptor mutation derived from a patient with severe congenital neutropenia.  

PubMed Central

The role of mutations of the granulocyte colony-stimulating factor receptor (G-CSFR) in the pathogenesis of severe congenital neutropenia (SCN) and the subsequent development of acute myeloid leukemia (AML) is controversial. Mice carrying a targeted mutation of their G-CSFR that reproduces the mutation found in a patient with SCN and AML have been generated. The mutant G-CSFR allele is expressed in a myeloid-specific fashion at levels comparable to the wild-type allele. Mice heterozygous or homozygous for this mutation have normal levels of circulating neutrophils and no evidence for a block in myeloid maturation, indicating that resting granulopoiesis is normal. However, in response to G-CSF treatment, these mice demonstrate a significantly greater fold increase in the level of circulating neutrophils. This effect appears to be due to increased neutrophil production as the absolute number of G-CSF-responsive progenitors in the bone marrow and their proliferation in response to G-CSF is increased. Furthermore, the in vitro survival and G-CSF-dependent suppression of apoptosis of mutant neutrophils are normal. Despite this evidence for a hyperproliferative response to G-CSF, no cases of AML have been detected to date. These data demonstrate that the G-CSFR mutation found in patients with SCN is not sufficient to induce an SCN phenotype or AML in mice. PMID:9691084

McLemore, M L; Poursine-Laurent, J; Link, D C

1998-01-01

381

Internet Censorship in China: Where Does the Filtering Occur?  

Microsoft Academic Search

China filters Internet traffic in and out of the country. In order to circumvent the firewall, it is helpful to know where the filtering occurs. In this work, we explore the AS-level topology of China's network, and probe the firewall to find the locations of filtering devices. We find that even though most filtering occurs in border ASes, choke points

Xueyang Xu; Z. Morley Mao; J. Alex Halderman

2011-01-01

382

Original article Hydraulic conductance of two co-occuring neotropical  

E-print Network

Original article Hydraulic conductance of two co-occuring neotropical understory shrubs December 1999) Abstract ­ Whole plant hydraulic conductance was measured for two co-occuring neotropical hydraulic con- ductance and leaf specific conducance in the drought-avoiding species, P. trigonum, than

Paris-Sud XI, Université de

383

Factors affecting treatment-seeking for febrile illness in a malaria endemic block in Boudh district, Orissa, India: policy implications for malaria control  

PubMed Central

Background Orissa state in eastern India accounts for the highest malaria burden to the nation. However, evidences are limited on its treatment-seeking behaviour in the state. We assessed the treatment-seeking behaviour towards febrile illness in a malaria endemic district in Orissa. Methods A cross-sectional community-based survey was carried out during the high malaria transmission season of 2006 in Boudh district. Respondents (n = 300) who had fever with chills within two weeks prior to the day of data collection were selected through a multi-stage sampling and interviewed with a pre-tested and structured interview schedule. Malaria treatment providers (n = 23) were interviewed in the district to gather their insights on factors associated with prompt and effective treatment through a semi-structured and open-ended interview guideline. Results Majority of respondents (n = 281) sought some sort of treatment e.g. government health facility (35.7%), less qualified providers (31.3%), and community level health workers and volunteers (24.3%). The single most common reason (66.9%) for choosing a provider was proximity. Over a half (55.7%) sought treatment from appropriate providers within 48 hours of onset of symptoms. Respondents under five years (OR 2.00, 95% CI 0.84-4.80, P = 0.012), belonging to scheduled tribe community (OR 2.13, 95% CI 1.11-4.07, P = 0.022) and visiting a provider more than five kilometers (OR 2.04, 95% CI 1.09-3.83, P = 0.026) were more likely to have delayed or inappropriate treatment. Interviews with the providers indicated that patients' lack of trust in community volunteers providing treatment led to inappropriate treatment-seeking from the less qualified providers. The reasons for the lack of trust included drug side effects, suspicions about drug quality, stock-outs of drugs and inappropriate attitude of the provider. Conclusion Large-scale involvement of less qualified providers is suggested in the malaria control programme as volunteers after appropriate capacity development since the community has more trust in them. This should be supported by uninterrupted supply of drugs to the community volunteers, and involvement of the community-based organizations and volunteers in the planning, implementation, and monitoring of malaria control services. There is also a need for continuous and rigorous impact evaluations of the program to make necessary modifications, scale up and to prevent drug resistance. PMID:21192825

2010-01-01

384

INTRODUCTION Many crucial events in animal development occur by  

E-print Network

INTRODUCTION Many crucial events in animal development occur by movement and morphogenesis during branching morphogenesis (Bard, 1990). Some epithelia undergo an extreme structural transformation genetic system for analyzing epithelial morphogenesis (Manning and Krasnow, 1993; Samakovlis et al., 1996

Krasnow, Mark A.

385

INTRODUCTION Aggression and conflict occur ubiquitously throughout the animal  

E-print Network

, 2007), and are considered costly (Castro et al., 2006; Hack, 1997). As a result, they occur at frequencies inversely related to their cost (Hack, 1997), although game theory can be used to assess whether

Tattersall, Glenn

386

Internet Censorship in China: Where Does the Filtering Occur?  

Microsoft Academic Search

\\u000a China filters Internet traffic in and out of the country. In order to circumvent the firewall, it is helpful to know where\\u000a the filtering occurs. In this work, we explore the AS-level topology of China’s network, and probe the firewall to find the\\u000a locations of filtering devices. We find that even though most filtering occurs in border ASes, choke points

Xueyang Xu; Zhuoqing Morley Mao; J. Alex Halderman

2011-01-01

387

[Co-occuring mood and substance use disorders].  

PubMed

Mood and substance use disorders commonly co-occur, yet there is little evidence-based research to guide the pharmacologic management of these comorbid disorders. The authors review the existing empirical findings including current clinical pharmacotherapy practices for treating co-occurring mood and substance use disorders and call into question current clinical practices. The specific mood disorders reviewed are bipolar and major depressive disorders (either one co-occurring with a substance use disorder). The authors also highlight knowledge gaps that may serve as a basis for future research. Findings from the relatively small amount of available data indicate that pharmacotherapy for managing mood symptoms might be effective in patients with substance dependence, although results have not been consistent across all studies. In most studies, medications for managing mood symptoms did not appear to have an impact on the substance use disorder. Research has only begun to address optimal pharmacologic management of co-occurring disorders. In addition, current clinical treatment for drug dependence often exclude new pharmacotherapies approved by the French Haute Autorité de Santé for treating certain types of addiction. With new data becoming available, it appears that we need to revisit current practice in the pharmacological management of co-occurring mood and substance use disorders. PMID:25550243

Adida, M; Kaladjian, A; Fakra, E; Belzeaux, R; Azorin, J M

2014-12-01

388

MIBG superscan of metastatic paraganglioma occurring with neurofibromatosis type 1.  

PubMed

A Tc MDP bone superscan occurs when osseous activity is extremely intense and genitourinary and soft tissue activity is not identified. A similar phenomenon has been described with metaiodobenzylguanidine (MIBG) in metastatic pheochromocytoma and neuroblastoma. We present a case of metastatic paraganglioma resulting in an MIBG superscan. Neuroendocrine bone metastasis alters the biodistribution of MIBG such that the liver, heart, and urinary bladder are not well visualized. Our case occurred in association with neurofibromatosis type 1 and in the absence of an identified primary tumor. PMID:23455526

Harrison, Chester Earl; Barron, Bruce J

2013-06-01

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