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1

[An unusual cause of febrile neutropenia: brucellosis].  

PubMed

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

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

2014-10-01

2

Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia.  

PubMed

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

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

2015-02-01

3

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

4

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

PubMed

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

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

2013-12-01

5

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

6

Febrile neutropenia: Median door-to-needle time - Results of an initial audit.  

PubMed

Background Recently, due to inadequacies during immediate management of patients with febrile neutropenia, a new gold standard 'door-to-needle' time of 1 hour for the administration of intravenous antibiotics was introduced. Objective The aim of this audit was to identify whether that target was being met in our emergency department (ED). This is phase 1 of the study which will be followed by identification of barriers to the achievement of the target and recommendations for improvement. Materials and methods Data were collected from January 2013 to April 2013 of consecutive patients (adult and pediatric age group) who presented to the ED with febrile neutropenia for various underlying causes. Fever was defined as single oral temperature of >38.3°C (101°F) or a temperature of >38.0°C (100.4°F) sustained for more than 1 hour. Neutropenia was defined as absolute neutrophil count <0.5 × 10(9)/l, or expected to fall below that number. Variables analyzed included age, gender, antibiotics administered, underlying diagnosis, day of presentation, and door-to-needle time. Results During the study period, there were n = 81 patients who presented with febrile neutropenia. There were n = 49 were males and n = 32 were females. There were n = 37 patients in the pediatric age group while rest were adults. Patients most commonly had an underlying hematological malignancy (n = 49). A combination of piperacillin/tazobactam (4.5 g × Q8hrly) and amikacin (750 mg × once daily) was most frequently administered (n = 57) to these patients. The median door-to-needle time was 45 minutes (range ± SD: 10 minutes to 6 hours ± 1 hour 10 minutes). Long delays of over 4 hours occurred in n = 4 patients (all were adults). There were minimal delays observed in pediatric patients due to 'red alert' policy implementation. Long delays occurred on weekdays and weekends, equally. Conclusion The overall median door-to-needle time was 45 minutes, which was in the accepted range. However, delays that occurred demand improvements like introducing 'red alert' policy for adult patients, counseling of staff and residents, identifying potential barriers in achieving the target time along with solutions, and developing hospital-based guidelines on managing patients with neutropenic sepsis. PMID:24724830

Ali, Natasha; Baqir, Muhammad; Hamid, Aasma; Khurshid, Mohammad

2015-01-01

7

Transient neutropenia in children with febrile illness and associated infectious agents: 2 years' follow-up.  

PubMed

The aim of the study was to identify the relationship of acquired neutropenia with childhood infections and to assess its clinical course, complications, and outcome. Children admitted to two pediatric wards over a 4-year period with febrile neutropenia were prospectively investigated for underlying infections with inflammatory markers, cultures of body fluids, and serological tests. The study included 161 previously healthy children with febrile neutropenia/leukopenia aged (mean?±?SD) 3.02?±?3.86 years (range, 0.1-14). One hundred and thirty-six out of 161 patients (84.5 %) had transient neutropenia (TN), while in 25 patients, neutropenia was chronic (CN) and persisted for ?180 days. An infectious agent was isolated in 98/161 (60.9 %) cases, in 68.4 % patients with TN, and in 20 % of those with CN (p?=?0.001). Among the patients with CN, seven had positive antineutrophil antibodies (autoimmune neutropenia) and four were eventually diagnosed with hematological malignancy. In all age groups, TN was of short duration (<1 month), of mild to moderate severity, and was predominantly associated with viral infections. Two years after diagnosis, 143/161 children (88.8 %) were available for follow-up. One hundred and thirty-seven of 143 (95.8 %) had recovered completely, while the rest remained neutropenic. The latter patients had a benign course despite severe neutropenia. In conclusion, febrile neutropenia during childhood is usually transient, often following viral and common bacterial infections, without serious complications and in the majority of cases it resolves spontaneously. However, in a considerable percentage of patients, neutropenia is discovered incidentally during the course of an infection on the ground of an underlying hematological disease. PMID:23408310

Alexandropoulou, Ourania; Kossiva, Lydia; Haliotis, Fotis; Giannaki, Maria; Tsolia, Maria; Panagiotou, I P; Karavanaki, Kyriaki

2013-06-01

8

Evaluating the Total Costs of Chemotherapy-Induced Febrile Neutropenia: Results from a Pilot Study with Community Oncology Cancer Patients  

Microsoft Academic Search

Purpose. While cancer chemotherapy-related febrile neutropenia affects patients' activities and medical ex- penditures, few studies have reported on the total costs of this condition. Here, we evaluate the feasibility of ob- taining detailed and comprehensive cost information on patientswhoexperiencefebrileneutropeniaduringcan- cer chemotherapy treatment. Methods. Community oncology cancer patients who experienced chemotherapy-associated febrile neutrope- nia recorded information about use of medical care,

CHARLES L. BENNETT; ELIZABETH A. CALHOUNb; Robert H. Lurie

9

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

10

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

11

Utility of a Commercially Available Multiplex Real-Time PCR Assay To Detect Bacterial and Fungal Pathogens in Febrile Neutropenia ?  

PubMed Central

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

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

2009-01-01

12

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

13

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

PubMed Central

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

2011-01-01

14

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

15

Prophylaxis of febrile neutropenia in adults receiving chemotherapy needs to be adapted to the risk.  

PubMed

A major advance in the management of febrile neutropenia (FN) has been the stratification of the population of adult patients with FN for the risk of complications and death. Using validated reliable predictive instruments, such as the Multinational Association for Supportive Care in Cancer score, it is possible to identify a population of 'low-risk' patients, who can benefit from simplified and less expensive therapeutic approaches (e.g., orally administered antimicrobial therapy and early home return). Prevention of FN by the use of granulopoietic colony-stimulating factor (G-CSF) has been successfully applied to patients at 'high risk' of developing FN. In addition to the aggressiveness of chemotherapy, which usually defines the 'high-risk' status, the role of a series of factors that increase both the risk of FN and the complications rate has been recognized and should probably be taken into consideration when selecting patients for G-CSF prophylaxis. The cost of the G-CSF is the major limiting factor for their broad use; further efforts should be made to match the cost issue with the need of protecting from the development of FN most patients treated with chemotherapy for cancer. PMID:25431921

Georgala, Aspasia; Klastersky, Jean A

2015-02-01

16

Comparing the Efficacy of Ceftazidime and Meropenem in Treatment of Febrile Neutropenia in Pediatric Patients with Cancer  

PubMed Central

Background In cancer patients, various infections were developed due to severe neutropenia resulted from chemotherapy. Ceftazidime is commonly used as monotherapy of cancer patients with fever and neutropenia. Meropenem is a new carbapenem with more extended antibacterial spectrum including anaerobes. It provides better coverage against gram positives. This trial compared the efficacy and safety of meropenem with ceftazidime as empirical monotherapy for febrile neutropenia in pediatric patients with cancer. Materials and Methods A prospective, double-blind, randomized clinical trial was conducted at Departments of Pediatric Haematology/Oncology, University Hospitals, Yazd, Iran, during the years 2012 to 2013. A total of 48 cancer patients participated in the trial. Result In this study, 26 patients (54.16%) were treated by ceftazidime and 22 patients (45.84%) by meropenem. Mean duration of fever in those who responded to treatment in ceftazidime group was 19.43+/-31.04 hours, and in meropenem group was 16.53+/-28.77 hours (P-value = 0.965). Conclusion Finding of this study indicate that ceftazidime and meropenem have similar efficacy in treatment of fever and sever neutropenia. Due to more availability and lower cost of ceftazidime than meropenem, ceftazidime is suggested as a first line treatment in fever and neutropenia. PMID:24575280

Ferdosian, F; Ghiliyan, R; Hashemi, A; Akhondzadeh, B; Gholampoor, E

2013-01-01

17

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

PubMed Central

Objective: The aim of this study was to investigate the epidemiology and antibiotic susceptibility profiles of isolated bacterial organisms in relation to empiric treatment of neutropenic fever over a 15-year period. Methods: All patients with or at risk for febrile neutropenia and treated in the hematology ward of the Antwerp University Hospital during 1994–2008 were prospectively included. Skin, blood, and urine cultures were taken. Oral quinolone prophylaxis was started in patients with neutropenia without fever. Empiric starting therapy consisted of amikacin in combination with cefepime. Results: A total of 3624 bacteria were isolated. The most common pathogens were coagulase-negative Staphylococci (46%), followed by Escherichia coli (25%), Enterobacteriaceae (15.6%), Staphylococcus aureus (7.2%), and Pseudomonas aeruginosa (3.8%). The balance between Gram-positive and Gram-negative bacteria remained stable, with a majority of Gram-positive bacteria. A shift from oxacillin-sensitive to oxacillin-resistant coagulase-negative Staphylococci was observed. Regarding susceptibility patterns, no vancomycin resistance was detected in coagulase-negative Staphylococci or in S. aureus. The E. coli susceptibility rates remained stable. However, 66% of bloodstream infections were ciprofloxacin-resistant. A reduced susceptibility of P. aeruginosa strains to meropenem was noticed. Conclusions: Improvement in antibiotic susceptibility of inducible Enterobacteriaceae following a switch of empiric antibiotic therapy was maintained 15 years after starting the latter treatment. Further improvement in antibiotic susceptibility of these bacteria to ceftazidime was observed, but continuous vigilance is warranted. PMID:21694894

Mebis, J; Jansens, H; Minalu, G; Molenberghs, G; Schroyens, WA; Gadisseur, AP; van de Velde, A; Vrelust, I; Goossens, H; Berneman, ZN

2010-01-01

18

Etiology and Clinical Course of Febrile Neutropenia in Children with Cancer  

PubMed Central

Background The etiology, clinical course and outcome of fever and neutropenia (FN) in children with cancer using the current FN guidelines and diagnostic resources in the United States have not been well described. Patients and Methods Medical records of one randomly selected FN episode per patient during 2004–2005 at a pediatric oncology center were reviewed. Patients were managed as per institutional FN guidelines and blood cultures collected in continuously-read BACTEC™ bottles. Results Of 337 FN episodes, infection was proven in 86 (25%) and probable in 75 (22%). 177 episodes (53%) were judged fever of unknown origin (FUO). Bacteremia accounted for most (41) of the proven bacterial episodes, with viridans streptococci (13), Pseudomonas spp (6) and E. coli (6) the most frequently isolated organisms. The median time to positivity of blood cultures was 12 hrs (range 5.4 – 143.7) with 93% positive within 24 hours of incubation. Viral pathogens were identified in 29 (34%) episodes. Compared to other patients, those with FUO had shorter median duration of fever (0.5 vs. 2.0 days; p<0.0001) and hospitalization (3 vs. 6 days; p<0.0001), longer median duration since last chemotherapy (6.0 vs. 4.0 days; p=0.01) and were less likely to have a diagnosis of acute myelogenous leukemia (AML) (11% vs 22%; p=0.009) or develop a clinical complication (5.1% vs 24.4%; p<0.0001). Conclusion Despite currently available diagnostic resources, the majority of patients with FN have FUO marked by a low rate of clinical complications and no infection-related mortality. Emergence of viridans streptococci as the most common blood isolate has affected FN treatment recommendations. Study findings will help further development of strategies for risk stratified management of fever with neutropenia in pediatric patients. PMID:19644403

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

2009-01-01

19

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

20

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

21

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

22

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

PubMed

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

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

2014-01-01

23

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

PubMed

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

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

2014-06-27

24

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

PubMed Central

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

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

2008-01-01

25

Bacterial spectrum and antimicrobial susceptibility pattern of bloodstream infections in children with febrile neutropenia: experience of single center in southeast of Turkey.  

PubMed

Empirical antimicrobial therapy is usually started in febrile neutropenic patients without having culture results. The aim of this study was to help determine the policies of empirical antibiotic usage in febrile neutropenic children by detecting the antimicrobial susceptibility profile in this group of patients. In this study 811 blood cultures taken from neutropenic children hospitalized at the Department of Oncology of Gaziantep Children Hospital November 2007 and February 2010 were retrospectively evaluated. Blood cultures were routinely collected in aerobic and anaerobic media and incubated using the BACTEC system. Identification and antimicrobial susceptibility testing of the isolates to antimicrobial agents was performed using the Vitek2(®) system according to the recommendations of the Clinical and Laboratory Standards Institute. Of 811 isolates analyzed, 128 (56.4%) were gram positive cocci, 43 (18.9%) were gram negative bacilli and fungi accounted for 56 (24.7%). The main isolated Gram-positive bacteria from blood were coagulase-negative staphylococcus (56.7%), followed by methicillin-resistant Staphylococcus aureus (14.1%). S. aureus and Streptococcus spp. were all susceptible to linezolid, vancomycin and teicoplanin. S aureus was still susceptible to few other antimicrobial agents such as tetracycline (82.4%), chloramphenicol (55.6%). Seven E. faecium, 7 E. fecalis and 1 E. hirae was isolated from blood cultures. Vancomycin resistance was detected in 6 out of 15 (40%) Enterococcus spp. isolates. Among gram-negative bacteria E. coli (30.2%) was followed by Klebsiella pneumoniae (20.9%) and Proteus spp. (18.6%). Imipenem (89.2%), meropenem (86.6%), chloramphenicol (88.9%), amicasin (82.4%) and fosfomycin (81.3%) showed highest susceptibility in vitro activity against all Gram-negative isolates. To know the antimicrobial susceptibility profile of the pathogens frequently isolated from febrile neutropenic children and to consider this profile before starting an empirical antibiotic therapy would help the clinics which have any role in the treatment of these patients to determine the empirical antibiotic usage policies. PMID:23729883

Aslan, Selda; Citak, Elvan Caglar; Yis, Reyhan; Degirmenci, Suleyman; Arman, Dilek

2012-06-01

26

Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia.  

PubMed

Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Like most other bone marrow failure syndromes, it is associated with a marked propensity to transform into a myelodysplastic syndrome (MDS) or acute leukemia, with a cumulative rate of transformation to MDS/leukemia that exceeds 20%. The genetic (and/or epigenetic) changes that contribute to malignant transformation in SCN are largely unknown. In this study, we performed mutational profiling of 14 genes previously implicated in leukemogenesis using 14 MDS/leukemia samples from patients with SCN. We used high-throughput exon-based resequencing of whole-genome-amplified genomic DNA with a semiautomated method to detect mutations. The sensitivity and specificity of the sequencing pipeline was validated by determining the frequency of mutations in these 14 genes using 188 de novo AML samples. As expected, mutations of tyrosine kinase genes (FLT3, KIT, and JAK2) were common in de novo AML, with a cumulative frequency of 30%. In contrast, no mutations in these genes were detected in the SCN samples; instead, mutations of CSF3R, encoding the G-CSF receptor, were common. These data support the hypothesis that mutations of CSF3R may provide the "activated tyrosine kinase signal" that is thought to be important for leukemogenesis. PMID:17494858

Link, Daniel C; Kunter, Ghada; Kasai, Yumi; Zhao, Yu; Miner, Tracie; McLellan, Michael D; Ries, Rhonda E; Kapur, Deepak; Nagarajan, Rakesh; Dale, David C; Bolyard, Audrey Anna; Boxer, Laurence A; Welte, Karl; Zeidler, Cornelia; Donadieu, Jean; Bellanné-Chantelot, Christine; Vardiman, James W; Caligiuri, Michael A; Bloomfield, Clara D; DiPersio, John F; Tomasson, Michael H; Graubert, Timothy A; Westervelt, Peter; Watson, Mark; Shannon, William; Baty, Jack; Mardis, Elaine R; Wilson, Richard K; Ley, Timothy J

2007-09-01

27

Febrile Seizures  

MedlinePLUS

... impact that febrile seizures might have on intelligence, behavior, school achievement, and the development of epilepsy. For example, scientists conducting studies in animals are assessing the effects of febrile seizures, and ...

28

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

29

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

30

Neutropenia in the Newborn  

PubMed Central

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

Maheshwari, Akhil

2013-01-01

31

Diurnal variation in febrile convulsions.  

PubMed

This study sought to determine diurnal variations in febrile convulsions, and to investigate whether such variations influenced the severity of febrile convulsions. The study involved 326 children, between ages 6 months and 6 years, with simple febrile convulsions. Data were collected systematically by interviewing witnesses within the week after febrile convulsions occurred. The frequency of febrile convulsions was approximately 5 times greater in the evening than in early morning. An adaptation curve revealed that the maximum occurrence of febrile convulsions was at 4:00 pm (4:00-4:59 pm), and the minimum, at 4:00 am (4:00-4:59 am), similar to the pattern of human body temperature. Temperature and seizure duration did not differ significantly between high-frequency and low-frequency zones (2:00-7:00 pm and 2:00-7:00 am, respectively) (high-frequency zone vs low-frequency zone, 39.20 degrees C (S.D., 0.68 degrees C) vs 39.22 degrees C (S.D., 0.64 degrees C) and 3.82 minutes (S.D., 5.27 minutes) vs 3.14 minutes (S.D., 3.19 minutes)). These results suggest that the circadian rhythm does not change seizure propensity, but its hourly occurrence is attributable to an elevation in the temperature set point in the 24-hour period. The prevention of recurrent febrile convulsions by rectal administration of anticonvulsants in high-frequency zones would be clinically helpful. PMID:20472192

Ogihara, Masaaki; Shirakawa, Shuuichirou; Miyajima, Tasuku; Takekuma, Kouji; Hoshika, Akinori

2010-06-01

32

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

33

Cognitive Dysfunction after Experimental Febrile Seizures  

PubMed Central

While the majority of children with febrile seizures have an excellent prognosis, a small percentage are latter discovered to have cognitive impairment. Whether the febrile seizures produce the cognitive deficits or the febrile seizures are a marker or the result of underlying brain pathology is not clear from the clinical literature. We evaluated hippocampal and prefrontal cortex function in adult rats with a prior history of experimental febrile seizures as rat pups. All of the rat pups had MRI brain scans following the seizures. Rats subjected to experimental febrile seizures were found to have moderate deficits in working and reference memory and strategy shifting in the Morris water maze test. A possible basis for these hippocampal deficits involved abnormal firing rate and poor stability of hippocampal CA1 place cells, neurons involved in encoding and retrieval of spatial information. Additional derangements of interneuron firing in the CA1 hippocampal circuit suggested a complex network dysfunction in the rats. MRI T2 values in the hippocampus were significantly elevated in 50% of seizure-experiencing rats. Learning and memory functions of these T2-positive rats were significantly worse than those of T2-negative cohorts and of controls. We conclude that cognitive dysfunction involving the hippocampus and prefrontal cortex networks occur following experimental febrile seizures and that the MRI provides a potential biomarker for hippocampal deficits in a model of prolonged human febrile seizures. PMID:19000675

Dube, Celine M; Zhou, Jun-Li; Hamamura, Mark; Zhao, Qian; Ring, Alex; Abrahams, Jennifer; McIntyre, Katherine; Nalcioglu, Orhan; Shatskih, Tatiana; Baram, Tallie Z.; Holmes, Gregory L.

2009-01-01

34

Evaluation and management of patients with isolated neutropenia.  

PubMed

Neutropenia, defined as an absolute neutrophil count (ANC) <1.5 × 10(9)/L, encompasses a wide range of diagnoses, from normal variants to life-threatening acquired and congenital disorders. This review addresses the diagnosis and management of isolated neutropenia, not multiple cytopenias due to splenomegaly, bone marrow replacement, or myelosuppression by chemotherapy or radiation. Laboratory evaluation generally includes repeat complete blood cell counts (CBCs) with differentials and bone marrow examination with cytogenetics. Neutrophil antibody testing may be useful but only in the context of clinical and bone marrow findings. The discovery of genes responsible for congenital neutropenias now permits genetic diagnosis in many cases. Management of severe chronic neutropenia includes commonsense precautions to avoid infection, aggressive treatment of bacterial or fungal infections, and administration of granulocyte colony-stimulating factor (G-CSF). Patients with severe chronic neutropenia, particularly those who respond poorly to G-CSF, have a risk of eventually developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and require monitoring for this complication, which also can occur without G-CSF therapy. Patients with cyclic, idiopathic, and autoimmune neutropenia have virtually no risk of evolving to MDS or AML. Hematopoietic stem cell transplantation is a curative therapy for congenital neutropenia with MDS/AML or with cytogenetic abnormalities indicating impending conversion. PMID:23953336

Newburger, Peter E; Dale, David C

2013-07-01

35

Evaluation and Management of Patients with Isolated Neutropenia  

PubMed Central

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

Newburger, Peter E.; Dale, David C.

2013-01-01

36

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

37

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

38

Genetics Home Reference: Cyclic neutropenia  

MedlinePLUS

... and proteins to help fight the infection. ELANE gene mutations that cause cyclic neutropenia lead to an abnormal neutrophil elastase ... pattern, which means one copy of the altered gene in each cell is sufficient to ... inherits the mutation from one affected parent. Other cases result from ...

39

[Recurrent infections, severe neutropenia and neutrophil chemotaxis defect in paroxysmal nocturnal hemoglobinuria].  

PubMed

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease, whose origin seems to lie in a acquired defect in the membrane of the pluri-potential hematopoietic cell. Chronic or intermittent acute hemolytic syndrome is the most frequent clinical manifestation, although in the literature there are also some references to the leukocytic and immunologic disorders of this disease. In this paper, we present the case of a 63-year-old patient with NPH who developed severe neutropenia and sustained febrile syndrome. In the past four years, she had suffered frequent episodes of fever and leukopenia, which apparently disappeared spontaneously. In the physical exploration, we observed hepatosplenomegaly. The hemogram showed mild iron deficiency anemia (hemoglobin 10.8 g/dl), severe neutropenia (neutrophil 0.3 x 10(9)/l) and significant reticulocytosis (610 x 10(9)/l). Iron deposits were greatly reduced in the marrow. Simultaneously to a new febrile episode and isolation of Escherichia coli in the urine, there was a severe anemization (hemoglobin 5 g/dl) and a significant thrombopenia (platelets 30 x 10(9)) resulting in a positive hemosiderinuria and sucrose test. The study of the leukocytic function showed a defect in the neutrophil chemotaxis, although a normal phagocytic capacity and microbicidal activity. In the following nine months, the patient had several severe infections, with intense but transitory pancytopenia, which always improved when treating the infection with antibiotics. The patient died due to a septic shock twelve months after the diagnosis. Recurrent febrile episodes and severe neutropenia are very rare in the PNH (less than 4% of the cases). The cause of these disorders is still unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7865656

González Moraleja, J; Rubio Pérez, P; Cabello Carro, J; García-Casasola, G; Alvarez-Sala, J L

1994-10-01

40

Development of hippocampal sclerosis after a complex febrile seizure.  

PubMed

The role of prolonged febrile seizures in the genesis of hippocampal sclerosis is controversial; statistical analysis and data from epilepsy surgery suggest a causal relationship. A three-year-old boy had an initial febrile seizure with a transient postictal flaccid hemiparesis. Magnetic resonance imaging (MRI) showed no abnormality of the hippocampal areas of both sides. At the age of four a prolonged febrile seizure occurred. An MRI was done immediately and gave abnormal results in the right hippocampal area where T2-weighted and dark fluid sequences showed increased signal intensity; in diffusion-weighted sequences this region appeared hyperintense, which is in agreement with acute neuronal damage. Six weeks later the right hippocampal region still gave hyperintense signals in MRI (T2-weighted), while the diffusion coefficient was unremarkable. A final MRI scan was done 16 months following the second febrile seizure where the right hippocampal region still gave hyperintense signals and was reduced in size as is typical for hippocampal sclerosis. This case illustrates the development of a hippocampal lesion following a prolonged focal febrile seizure without any preexisting hippocampal lesion or positive family history. This suggests that prolonged febrile seizures alone can be a causative factor of hippocampal sclerosis. PMID:18633642

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

2009-04-01

41

Two USA Ehrlichia spp. cause febrile illness in goats.  

PubMed

Ehrlichia spp. are not currently recognized as a cause of illness in goats in the USA, but three Ehrlichia are enzootic in lone star ticks (Amblyomma americanum) in the eastern USA, and related bacteria in other countries cause illness in goats. We exposed naïve goats to Ehrlichia-infected Amblyomma and demonstrated that infection and clinical illness can be caused by two USA species, E. ewingii and the recently discovered Panola Mountain Ehrlichia sp. Clinical features in all five goats are described; ehrlichioses were associated with pyrexia, serous nasal discharge, inappetance, lethargy, decreased alkaline phosphatase, and, in most cases, neutropenia. Goats remained chronically infected for several months following exposure to ehrlichiae and transmitted the pathogens to uninfected ticks. In the eastern USA, undifferentiated febrile illness in goats might be caused by previously unrecognized ehrlichial infections, and pastures housing-infected goats could become infested with a large number of infected ticks. PMID:18328644

Loftis, Amanda D; Levin, Michael L; Spurlock, J Paul

2008-08-25

42

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

PubMed

Single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) immediately induced a decrease in the number of circulating neutrophils in rats. This neutropenia occurred 10 minutes after the injection but disappeared 40 minutes after injection. This transient neutropenia was dose-dependently induced by rhG-CSF and also induced by repeated injections. We studied the kinetics of circulating neutrophils in transient neutropenia. rhG-CSF markedly decreased the number of 3H-diisopropylfluorophosphate (3H-DFP) labeled neutrophils in the circulation 10 minutes after injection but the labeled neutrophils recovered to near the control level 40 minutes after the injection. These results indicate that the neutrophil margination accounts for the neutropenia and the marginated neutrophils return to the circulation. PMID:1700253

Okada, Y; Kawagishi, M; Kusaka, M

1990-01-01

43

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

Microsoft Academic Search

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

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

1996-01-01

44

Pedigree analysis in families with febrile seizures  

SciTech Connect

Febrile seizures are the most common form of seizures, occurring in an estimated 2-5% of North American children. We carried out a systematic pedigree study of febrile seizure probands. Forty of 52 probands (77%) in a referral population selected for increased severity had more than one case per family: one family had 10 cases, one family had 7, 3 families had 6, 2 had 5, 3 had 4, 13 had 3, and 17 had 2 cases. Mode of inheritance in the multicase families best fit the hypothesis of autosomal dominance with reduced penetrance. Polygenic inheritance could not be excluded for some of the smaller families. There was no support for X-linked or mitochondrial inheritance. Penetrance was calculated to be 0.64. Because the cases were selected for increased severity, this represents a useful estimate of the upper limit of penetrance and is in agreement with twin studies. Simulated lod scores showed adequate power for a linkage study in the absence of heterogeneity. Individual families had simulated average lod scores as high as 2.1. However, with potential heterogeneity, assuming only 70% of families share the same disease locus, average lod scores were marginal, and a high density map of marker loci and additional families would be required to document linkage. 41 refs., 3 figs., 2 tabs.

Johnson, W.G.; Kugler, S.L.; Stenroos, E.S.; Meulener, M.C. [Robert Wood Johnson Medical School, Piscataway, NJ (United States)] [and others] [Robert Wood Johnson Medical School, Piscataway, NJ (United States); and others

1996-02-02

45

Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia  

Microsoft Academic Search

The bactericidal activity of ?-lactams is determined by the time that concentrations in tissue and serum are above the minimum inhibitory concentration (T>MIC) for the pathogen. The aim of this study was to compare the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for meropenem between administration by bolus injection and a 3-h infusion. The study

Sutep Jaruratanasirikul; Thanya Limapichat; Monchana Jullangkoon; Nanchanit Aeinlang; Natnicha Ingviya; Wibul Wongpoowarak

2011-01-01

46

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

47

Hyponatraemia in children with febrile convulsions  

Microsoft Academic Search

In a study of 23 children admitted to hospital with a febrile convulsion, mild hyponatraemia was found on 8 occasions. In 6 of these cases there was evidence of inappropriate secretion of antidiuretic hormone. The hyponatraemia is unlikely to be the cause of the convulsion, but probably predisposes the child to a subsequent convulsion during the same febrile illness.

N Rutter; M J OCallaghan

1978-01-01

48

Febrile Urinary Tract Infection After Prostate Biopsy and Quinolone Resistance  

PubMed Central

Purpose Complications after prostate biopsy have increased and various causes have been reported. Growing evidence of increasing quinolone resistance is of particular concern. In the current retrospective study, we evaluated the incidence of infectious complications after prostate biopsy and identified the risk factors. Materials and Methods The study population included 1,195 patients who underwent a prostate biopsy between January 2007 and December 2012 at Chung-Ang University Hospital. Cases of febrile UTI that occurred within 7 days were investigated. Clinical information included age, prostate-specific antigen, prostate volume, hypertension, diabetes, body mass index, and biopsy done in the quinolone-resistance era. Patients received quinolone (250 mg intravenously) before and after the procedure, and quinolone (250 mg) was orally administered twice daily for 3 days. We used univariate and multivariate analysis to investigate the predictive factors for febrile UTI. Results Febrile UTI developed in 39 cases (3.1%). Core numbers increased from 2007 (8 cores) to 2012 (12 cores) and quinolone-resistant bacteria began to appear in 2010 (quinolone-resistance era). In the univariate analysis, core number?12 (p=0.024), body mass index (BMI)>25 kg/m2 (p=0.004), and biopsy done in the quinolone-resistance era (p=0.014) were significant factors. However, in the multivariate analysis adjusted for core number, the results were not significant, with the exception of BMI>25 kg/m2 (p=0.011) and biopsy during the quinolone-resistance era (p=0.035), which were significantly associated with febrile UTI. Conclusions Quinolone resistance is the main cause of postbiopsy infections in our center. We suggest that further evaluation is required to validate similar trends. Novel strategies to find alternative prophylactic agents are also necessary. PMID:25324949

Choi, Joong Won; Chang, In Ho; Kim, Kyung Do; Moon, Young Tae; Myung, Soon Chul; Kim, Jin Wook; Kim, Min Su; Kwon, Jong Kyou

2014-01-01

49

Clindamycin-induced neutropenia following major head and neck surgery.  

PubMed

A 64-year-old man undergoing major head and neck surgery received clindamycin for perioperative antimicrobial prophylaxis. On the third postoperative day, he became acutely neutropenic. The neutropenia resolved 3 days later, after the administration of filgrastim. After ruling out other causes of acute neutropenia, we determined that the neutropenia was secondary to clindamycin toxicity. While clindamycin-induced neutropenia has been reported elsewhere, to our knowledge this is the first report of its occurrence following head and neck surgery. Otolaryngologists should be aware of this potentially serious reaction. PMID:22996716

Schmidt, Robert S; Reiter, Evan R

2012-09-01

50

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

51

Clostridium tertium septicemia in patients with neutropenia.  

PubMed

Eighteen adult patients with hematologic malignancy developed bacteremia due to Clostridium tertium while neutropenic. Fifteen had accompanying abdominal pain, colonic bleeding, or diarrhea, and three had perianal cellulitis. Fourteen recovered with antibiotic therapy alone; no patient was treated by surgery. C. tertium is an unusual Clostridium because it is resistant to many beta-lactam antibiotics and to metronidazole but is susceptible to vancomycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. It is possible that use of third-generation cephalosporins (cefotaxime, ceftizoxime, ceftazidime) for treating febrile episodes in the absence of any selective intestinal decontamination with trimethoprim-sulfamethoxazole or ciprofloxacin may have resulted in selection for C. tertium in our patients. PMID:3198941

Speirs, G; Warren, R E; Rampling, A

1988-12-01

52

Neutropenia in Patients with Primary Antibody Deficiency Disorders  

Microsoft Academic Search

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's

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

2004-01-01

53

Renal Function in Children with Febrile Convulsions  

PubMed Central

Objective Febrile convulsions (FC) are the most frequent seizure disorder in children. Some studies have detected serum electrolyte disturbances in patients with FC. This study determines serum electrolytes, renal function tests, and frequency of urinary tract infection in hospitalized children with FC. Materials & Methods In this descriptive, cross sectional study, we evaluated 291 children with FC admitted to the Neurology ward of Ali-Asghar Children’s Hospital from 2008– 2013. Data was recorded on age, sex, type (simple, complex), and recurrence of seizures, family history of FC and epilepsy, serum electrolytes, renal function tests, and urinary tract infections. Results A total of 291 patients with diagnosis of FC were admitted to our center. Of these 291 patients, 181 (62.2%) were male. The mean age was 24.4 ± 14.6 months. There were simple, complex, and recurrent FCs in 215 (73.9%), 76 (26.1%) and 61 (21%) of patients, respectively. Urinary tract infections (UTI) were found in 13 (4.5%) patients, more present in females (p-value = 0.03) and under 12 months of age (p-value = 0.003). Hyponatremia, hypocalcemia, and hypokalemia was detected in 32 (11%), 16 (5.5%), and 4 (1.4%) of cases, respectively. Twentyfour (8.2%) patients had a glomerular filtration rate less than 60 ml/min/1.73m2. There were no abnormalities in serum magnesium, BUN, and creatinine levels. Conclusion During FCs, mild changes may occur in renal function but a serum electrolyte evaluation is not necessary unless patients are dehydrated. In children with FC, urinary tract infections should be ruled out.

AFSHARKHAS, Ladan; TAVASOLI, Azita

2014-01-01

54

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

55

Neutropenia in rheumatoid arthritis: studies on possible contributing factors.  

PubMed Central

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

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

1982-01-01

56

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

57

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

58

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

59

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

60

Immune complexes and the pathogenesis of neutropenia in Felty's syndrome.  

PubMed Central

The effect of the injection of serum from patients with rheumatoid arthritis (RA) and Felty's syndrome (FS) into mice on the number of circulating polymorphonuclear cells (PMN) was studied. The number of circulating PMN dropped to 61% (range 34-98%) of the initial counts after the injection of FS serum. This phenomenon was observed less frequently after injection of RA serum. In contrast, injection of serum from healthy controls always resulted in an immediate increase in the number of circulating PMN. No decrease in PMN counts was found after injection of FS sera pretreated with polyethylene glycol to precipitate immune complexes (IC). Gel filtration of FS sera on Sepharose 4B showed that the effect on the PMN counts in mice did not coincide with the 7S peak but occurred only in fractions containing larger material. Serum fractions from FS patients that contained IC were more active in producing neutropenia than the corresponding fractions from patients with RA. Microscopic and immunohistochemical examination of the organs from mice injected with FS serum showed sequestration of PMN and deposition of human IgG, IgA, and IgM in the vascular bed of the lungs. These results indicate that the interaction between PMN and IC of patients with FS leads to sequestration of PMN in mice and suggests that this interaction in humans may have a role in the pathogenesis of FS. PMID:3740999

Breedveld, F C; Lafeber, G J; de Vries, E; van Krieken, J H; Cats, A

1986-01-01

61

Iron deficiency as a risk factor for first febrile seizure  

Microsoft Academic Search

We conducted this study to determine the role of iron deficiency as a risk factor for first febrile seizure in children. Fifty\\u000a children between 6 months to 6 years with first febrile seizure (Cases) and 50 children with febrile illness but without convulsions\\u000a (Controls) were enrolled from the pediatric ward of a tertiary care hospital. Iron deficiency was determined by

Rajwanti K. Vaswani; Praveen G. Dharaskar; Swati Kulkarni; K. Ghosh

2010-01-01

62

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

63

Neutropenia after penicillins: toxic or immune-mediated?  

PubMed

Eight patients treated with a total of 220-550 million U penicillin-G developed neutropenia. These cases have been compared with eight patients receiving a similar dose of pencillin-G with no adverse reactions and with eight untreated subjects. All penicillin-treated patients showed raised levels of anti-IgG antibodies and lymphocyte culture stimulation indices. These values were highest in the neutropenia group. Both of the two tests significantly discriminated the three groups. Antineutrophil antibodies could be detected in four of seven neutropenic patients with a staphylococcal-slide-assay while indirect immunofluorescence and microcytotoxicity tests failed to reveal these antibodies. The literature dealing with neutropenias induced by penicillin-G and its congeners is reviewed. We conclude that (1) penicillin-G in doses exceeding a total of 200 million U frequently induces neutropenia, (2) an immune-mediated pathogenesis a highly probable, (3) neutropenia after penicillins is different from two hither-to accepted types of this side effect, (4) sufficiently high amounts of penicillin-G intravenously always induce sensitization against this drug. PMID:7278079

Neftel, K A; Wälti, M; Spengler, H; von Felten, A; Weitzman, S A; Bürgi, H; de Weck, A L

1981-08-17

64

Alloimmune neonatal neutropenia and neonatal isoerythrolysis in a Thoroughbred colt.  

PubMed

A 3-day-old Thoroughbred colt was originally presented for treatment of neonatal isoerythrolysis, which was treated with a blood transfusion. However, persistent neutropenia was observed despite the absence of detectable infection. Subsequently, a granulocyte agglutination test was performed by incubating the colt's neutrophils with the mare's serum; results were positive, leading to a clinical diagnosis of alloimmune neonatal neutropenia. The diagnosis was further supported via flow cytometric analysis. The colt was hospitalized and treated prophylactically with antimicrobials and 4 separate doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 1.4-3.5 µg/kg, subcutaneously) in attempts to maintain the neutrophil count within reference intervals over a 4-week period. The colt's neutrophil count increased after administration of rhG-CSF and eventually stabilized within reference intervals by day 20. The colt maintained normal neutrophil counts after discharge and was reportedly healthy at 6 months of age. Alloimmune neonatal neutropenia should be considered in foals with persistent neutropenia in the absence of infection. Alloimmune neonatal neutropenia can be treated with prophylactic antimicrobials combined with rhG-CSF with a favorable outcome. PMID:22362958

Wong, David M; Alcott, Cody J; Clark, Sandra K; Jones, Douglas E; Fisher, Phyllis G; Sponseller, Brett A

2012-01-01

65

A case of systemic amyloidosis associated with cyclic neutropenia.  

PubMed

Reactive AA amyloidosis is caused by the accumulation of the acute phase reactant, serum amyloid A (SAA), as a complication of chronic inflammatory conditions. Cyclic neutropenia is a rare hereditary disorder characterized by repeated episodes of neutropenia at regular intervals, with or without concurrent infection, and is known to be a rare cause of AA amyloidosis. Here, we report a case of a patient who developed systemic AA amyloidosis following a prolonged course of undiagnosed cyclic neutropenia. The patient had a history of recurrent infections since infancy and developed goiter, proteinuria, and azotemia at age 14 years. Her SAA level was markedly increased (601.8 ?g/mL, normal range <8 ?g/mL), and a thyroid and kidney biopsy revealed typical lesions of AA amyloidosis. Amyloid deposits were also detected in the myocardium, colon, and gallbladder. She had repeated episodes of neutropenia regularly at 3-week intervals and a pathogenic mutation in the ELA2 gene. After 10 months of treatment with recombinant human granulocyte colony-stimulating factor, her SAA level normalized (<2.5 ?g/mL), but her renal function did not recover. This case clearly shows that cyclic neutropenia can be complicated by AA amyloidosis unless it is detected early and treated adequately. PMID:21161286

Lee, HyunKyung; Han, Kyoung Hee; Jung, Yun Hye; Kang, Hee Gyung; Moon, Kyung Chul; Ha, Il Soo; Choi, Yong; Cheong, Hae Il

2011-04-01

66

Studies of neutrophil production and turnover in grey collie dogs with cyclic neutropenia  

PubMed Central

12 grey collie dogs had cyclic neutropenia with the neutropenia recurring at 11.8±0.1-day intervals. The recovery from neutropenia was accompanied by a single wave of myeloid proliferation, an increase in marrow myeloid-labeling indices, and an increase in serum muramidase levels. After recovery from neutropenia during the period when blood neutrophils (PMN) were normal or increased, marrow myeloid precursors became scarce. The decline in marrow precursors and marrow PMN reserves heralded the recurrence of neutropenia. Neither diisopropyl fluorophosphate (DF32P) leukokinetic studies nor the rate of development of neutropenia suggested shortened PMN survival as a mechanism for the neutropenia. These studies indicate that the cyclic neutropenia is due to a regularly recurring failure in PMN production. Images PMID:5054471

Dale, D. C.; Ward, S. B.; Kimball, H. R.; Wolff, S. M.

1972-01-01

67

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

68

Cyclic neutropenia in mammals Jorge M. Pacheco,1  

E-print Network

Cyclic neutropenia in mammals Jorge M. Pacheco,1 Arne Traulsen,2 Tibor Antal,3 and David Dingli4 of hematopoiesis is invariant across mammals, we use allometric scaling techniques to correctly pre- dict the period of cycling in the gray collie and extend it to other mammals from mice to elephants. This work

Traulsen, Arne

69

Neutropenia, inflammation, and the kinetics of transfused neutrophils in rabbits.  

PubMed

A rabbit model was used to study the effects of neutropenia and inflammation on the intravascular distribution, survival, and tissue accumulation of transfused neutrophils. Donor blood labeled with [(3)H]thymidine was infused into normal or neutropenic (vinblastine treated) animals. Inflammation was created by subcutaneous implantation of polyvinyl sponges, some with added endotoxin. Initial circulating neutrophil pool recovery, survival, and inflammatory site accumulation of labeled neutrophils were measured. Neutropenia was associated with a relative increase in the marginal pool size, manifested by a diminished initial circulating pool (CNP) recovery of transfused cells. The CNP recovery was directly proportional to recipient neutrophil count. Neutropenia had no effect on the intravascular survival of transfused cells and was accompanied by only a modest decrease in the inflammatory site recovery of the transfused neutrophils (10.4+/-5.4 vs. 14.4+/-4.0% in normals). Inflammation in the form of subcutaneous polyvinyl sponges was accompanied by an increase in margination with initial CNP recoveries of 24.3+/-4.7 and 27.6+/-8.8% at zero and 4 h after implantation respectively (normal, 38.2+/-9.9%). Transit through the CNP was hastened by inflammation with a t((1/2)) of 2.02+/-0.72 h (normal, 3.2+/-1.0 h). Addition of endotoxin to the sponges further perturbed cell kinetics. CNP recoveries were considerably lower and half-lifes were initially shorter and subsequently uninterpretable in studies done after endotoxin sponge insertion. Inflammatory site accumulation was markedly diminished to 7.4+/-1.9% of injected neutrophil label in the endotoxin sponge animals, suggesting that many of the transfused cells were functionally unavailable rather than marginated. These studies demonstrate that neutropenia and inflammation with or without endotoxin markedly alter the kinetics of transfused neutrophils and that CNP recovery of transfused cells is not necessarily predictive of their inflammatory site accumulation. PMID:457870

Rosenshein, M S; Price, T H; Dale, D C

1979-08-01

70

Neutropenia, Inflammation, and the Kinetics of Transfused Neutrophils in Rabbits  

PubMed Central

A rabbit model was used to study the effects of neutropenia and inflammation on the intravascular distribution, survival, and tissue accumulation of transfused neutrophils. Donor blood labeled with [3H]thymidine was infused into normal or neutropenic (vinblastine treated) animals. Inflammation was created by subcutaneous implantation of polyvinyl sponges, some with added endotoxin. Initial circulating neutrophil pool recovery, survival, and inflammatory site accumulation of labeled neutrophils were measured. Neutropenia was associated with a relative increase in the marginal pool size, manifested by a diminished initial circulating pool (CNP) recovery of transfused cells. The CNP recovery was directly proportional to recipient neutrophil count. Neutropenia had no effect on the intravascular survival of transfused cells and was accompanied by only a modest decrease in the inflammatory site recovery of the transfused neutrophils (10.4±5.4 vs. 14.4±4.0% in normals). Inflammation in the form of subcutaneous polyvinyl sponges was accompanied by an increase in margination with initial CNP recoveries of 24.3±4.7 and 27.6±8.8% at zero and 4 h after implantation respectively (normal, 38.2±9.9%). Transit through the CNP was hastened by inflammation with a t½ of 2.02±0.72 h (normal, 3.2±1.0 h). Addition of endotoxin to the sponges further perturbed cell kinetics. CNP recoveries were considerably lower and half-lifes were initially shorter and subsequently uninterpretable in studies done after endotoxin sponge insertion. Inflammatory site accumulation was markedly diminished to 7.4±1.9% of injected neutrophil label in the endotoxin sponge animals, suggesting that many of the transfused cells were functionally unavailable rather than marginated. These studies demonstrate that neutropenia and inflammation with or without endotoxin markedly alter the kinetics of transfused neutrophils and that CNP recovery of transfused cells is not necessarily predictive of their inflammatory site accumulation. PMID:457870

Rosenshein, Marc S.; Price, Thomas H.; Dale, David C.

1979-01-01

71

Grade 3 trastuzumab-induced neutropenia in breast cancer patient.  

PubMed

Trastuzumab, a humanized monoclonal antibody, is widely considered the most important development in the treatment of breast cancer since tamoxifen. Previous studies have found trastuzumab reduces the risk of relapse in breast cancer patients significantly when given in the adjuvant setting. As a targeted therapy, it has lesser side effects in comparison with conventional chemotherapy. However, the administration of this agent can cause serious side effects. We report on a 45-year-old woman with breast cancer, positive for human epidermal growth factor receptor 2 by immunohistochemistry score 3+, who was treated in an adjuvant setting with trastuzumab and developed severe neutropenia. Twenty seven weeks after initiation of trastuzumab, the patient developed fever, neutropenia (grade 3), and oral stomatitis (grade 4). The maintenance therapy was stopped for approximately 8 weeks. After recovery of the neutrophils, trastuzumab was restarted. Two weeks later, the patient developed the same pattern of toxicity. The situation necessitated the discontinuation of trastuzumab. Thereafter, the neutrophils normalized and the patient's condition improved. To our knowledge, this is the first case in the literature describing severe neutropenia directly related to trastuzumab during the adjuvant maintenance therapy. Clinicians should be aware of this rare side effect of trastuzumab, as stopping this agent can prevent severe complications. PMID:23804626

Ghani, Ehab A; Kerr, Ian; Dada, Reyad

2014-04-01

72

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

Microsoft Academic Search

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

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

2000-01-01

73

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

74

Febrile illness experience among Nigerian nomads  

PubMed Central

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

2012-01-01

75

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

PubMed Central

Abstract Objective The purpose of this study was to retrospectively analyze rates of neutropenia and risk factors for neutropenia in hospitalized children and adolescents treated with clozapine. Methods A retrospective chart review was conducted for all patients who received clozapine at any time during a hospitalization at the National Institute of Mental Health (NIMH) between 1990 and 2011. All patients satisfied screening criteria for the NIMH childhood-onset schizophrenia study, including onset of psychosis before the age of 13 years. Absolute neutrophil count (ANC) values recorded during inpatient hospitalization were extracted for 87 eligible patients with a mean age of 13.35±2.46 years at hospitalization and a mean length of stay of 117±43 days. Results Mild neutropenia only (lowest ANC<2000/mm3 but>1500/mm3) was observed in 27 (31%) patients and moderate neutropenia (any ANC<1500/mm3) was observed in 17 (20%) patients. There were no cases of agranulocytosis or severe infection. Significant risk factors for mild neutropenia compared with no hematologic adverse effects (HAEs) were male gender (p=0.012) and younger age (p<0.001). Male gender was also a significant risk factor for moderate neutropenia compared with no HAEs (p=0.003). If a child of African American ethnicity developed neutropenia during hospitalization at all that child was significantly more likely to develop moderate neutropenia than mild neutropenia only (p=0.017). African American boys had the highest rate of moderate neutropenia at 47%. Sixteen of the 17 patients exhibiting moderate neutropenia were successfully treated with clozapine by the time of discharge; 8 of these 16 required adjunctive lithium carbonate administration to maintain ANC>2000/mm3. Conclusions Our study shows that the rates of neutropenia in clozapine-treated children and adolescents are considerably higher than in the adult population. Younger age, African American ethnicity, and male gender were significant risk factors. These are also risk factors for benign neutropenia in healthy children and adolescents. Despite these high rates of neutropenia, all but one of the patients with neutropenia during hospitalization were successfully discharged on clozapine. PMID:23510445

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

2013-01-01

76

Recognition memory is impaired in children after prolonged febrile seizures  

PubMed Central

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

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

2012-01-01

77

Hematopoietic Stem Cell Transplantation for Severe Congenital Neutropenia  

PubMed Central

Purpose of review Hematopoietic stem cell transplant (HCT) is the only curative option for patients with severe congenital neutropenia (SCN). Transplant success is dependent on identifying at risk patients and proceeding to transplant before the development of severe infections or malignant transformation. This review focuses on recent advancements in risk stratification of SCN patients, indications for HCT, and review of published transplant studies. Recent findings Patients with poor neutrophil response despite high doses of granulocyte colony-stimulating factor (G-CSF) are at greatest risk for malignant transformation. Other studies demonstrate elevated risk with mutations in the G-CSF receptor gene and a specific mutation in the ELANE gene. These patients are at high-risk of sepsis or leukemia development and should proceed to transplant with best available donor. As recent published studies demonstrate, HCT is highly successful in patients without leukemia and therefore may be considered in selected low-risk patients given the life-long risk of malignancy and infection. Summary The decision whether to proceed to HCT in healthy patients maintained on G-CSF is difficult. As transplant related mortality continues to decrease, the role of transplant in severe congenital neutropenia is likely to expand to more patients. PMID:22080845

Connelly, James A.; Choi, Sung W.; Levine, John E.

2012-01-01

78

Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers  

PubMed Central

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

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

2010-01-01

79

Recurrent febrile syndromes—what a rheumatologist needs to know  

Microsoft Academic Search

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

Anna Simon; Hal M. Hoffman

2009-01-01

80

[Pharmacokinetics and pharmacodynamics of huangqin tang in febrile rats].  

PubMed

The pharmacodynamic (PD) and pharmacokinetic (PK) properties of Huangqin Tang (HQT) were investigated in yeast-induced febrile rats. Blood sample and rectal temperature data of the rats were collected at different times after single oral administration of HQT at 20 g x kg(-1). The plasma concentrations of paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid were quantified by a sensitive liquid chromatography-tandem mass spectrometric (LC-MS) method. The blood concentrations of PGE2, 1L-1? and TNF-? were detected by radioimmunoassay (RIA). All pharmacokinetic parameters were processed by non-compartmental analysis using WinNonlin software. The potential relationship between the mean concentration of eight constituents and the antifebrile efficacy was investigated by calculating Pearson correlation coefficients. It was found that HQT had significant antifebrile efficacy in yeast-induced febrile rats, but had no effect to normal rats. The antifebrile effect of HQT can be attributed to the inhibition of PGE2, 1L-1? and TNF-?. The constituents (baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic acid and glycyrrhetinic acid) in febrile rats had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC than those in normal rats. Febrile condition could affect the pharmacokinetic behaviour of HQT in vivo; the flavonoids with the same backbone showed the similar fate in the body; baicalein and wogonin had a strong positive correlation (R > 0.66, P ? 0.02) with the antifebrile efficacy determined. Together, these constituents demonstrated different pharmacokinetic properties in the febrile body. PMID:25577872

Li, Tao; Wang, Yi-Wei; Wang, Yan-Li; Zhang, Dong; Zhang, Hui-Hui; Chen, Li; Zhuang, Shuai-Xing; Zhou, Zhong-Ming; Yang, Wei-Peng

2014-10-01

81

Ulcerative dermatitis, thrombocytopenia, and neutropenia in neonatal foals.  

PubMed

This report describes transient ulcerative dermatitis, severe thrombocytopenia, and mild neutropenia in 6 foals from 4 mares from geographically diverse regions of the United States. The foals presented at <4 days of age with oral and lingual ulcers, and crusting and erythema around the eyes, muzzle, and perineal, inguinal, axillary, trunk, and neck regions. There was a severe thrombocytopenia (0-30,000 platelets/microL), leukopenia (1900-3200 white blood cells/microL), and mild neutropenia (500-1800 neutrophils/microL). Four of the 6 foals had petechiae and ecchymotic hemorrhages and 3 had bleeding tendencies. Results of examination of a bone marrow biopsy from 1 foal were normal and results of a platelet surface immunoglobulin test in another were negative. Histopathology of the skin in all foals showed subepidermal clefting with subjacent vascular dilation, dermal hemorrhage, and superficial papillary necrosis. The foals were treated supportively with broad-spectrum antibiotics (5/6), corticosteroids (3/6), gastric ulcer prophylaxis (6/6), whole-blood transfusion (4/6), and platelet-rich plasma (1/6). The skin lesions and thrombocytopenia (>50,000 platelets/microL) improved in 2 weeks (4/6). Two foals had a decline in their platelet counts when the steroids were decreased and needed protracted treatment. All foals survived and were healthy as yearlings. Two mares that had 2 affected foals each, upon subsequent pregnancies to different stallions, had healthy foals when an alternate source of colostrum was given. The findings in the cases in this report suggest a possible relationship between colostral antibodies or some other factor in the colostrum and the thrombocytopenia and skin lesions, although further investigation is warranted to confirm or refute this hypothesis. PMID:15822566

Perkins, G A; Miller, W H; Divers, T J; Clark, C K; Belgrave, R L; Sellon, D C

2005-01-01

82

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

83

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

PubMed Central

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

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

2013-01-01

84

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

PubMed

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

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

2012-04-01

85

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

86

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

PubMed

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

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

2013-03-01

87

Epileptogenesis after prolonged febrile seizures: mechanisms, biomarkers and therapeutic opportunities  

PubMed Central

Epidemiological and recent prospective analyses of long febrile seizures (FS) and febrile status epilepticus (FSE) support the idea that in some children, such seizures can provoke temporal lobe epilepsy (TLE). Because of the high prevalence of these seizures, if epilepsy was to arise as their direct consequence, this would constitute a significant clinical problem. Here we discuss these issues, and describe the use of animal models of prolonged FS and of FSE to address the following questions: Are long FS epileptogenic? What governs this epileptogenesis? What are the mechanisms? Are there any predictive biomarkers of the epileptogenic process, and can these be utilized, together with information about the mechanisms of epileptogenesis, for eventual prevention of the TLE that results from long FS and FSE. PMID:21356275

McClelland, Shawn; Dubé, Céline M.; Yang, Jaqueline; Baram, Tallie Z.

2011-01-01

88

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

89

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

90

An unusual cause of severe persistent neutropenia in a child with nephrotic syndrome  

PubMed Central

A 5-year-old boy presented with neutropenia 9?weeks following the administration of rituximab for management of his steroid-dependent nephrotic syndrome. Extensive investigations failed to identify any underlying cause. In keeping with adult reports, rituximab was thought to be the likely cause for this ‘late-onset’ neutropenia (LOP). He was treated successfully with granulocyte-colony-stimulating factor. Patients treated with rituximab need to be carefully monitored for LOP. PMID:23365164

Kshirsagar, Archana A; Reid, Christopher J D; Alamelu, Jayanthi; Sinha, Manish D

2013-01-01

91

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

Microsoft Academic Search

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

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

2000-01-01

92

Risk Factors for Severe Neutropenia following Intra-Arterial Chemotherapy for Intra-Ocular Retinoblastoma  

PubMed Central

Purpose Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (?grade 3) neutropenia. Methods Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1) blood count results were available in the 7 to 14 days post-treatment interval and (2) concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0. Results 54 cycles (29%) were associated with grade 3 (n?=?43) or grade 4 (n?=?11) neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg) was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33–12.73, p?=?0.01), but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis. Conclusions Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted. PMID:25303673

Dunkel, Ira J.; Shi, Weiji; Salvaggio, Kim; Marr, Brian P.; Brodie, Scott E.; Gobin, Y. Pierre; Abramson, David H.

2014-01-01

93

Pathogenesis and prognosis of neutropenia in infants and children admitted in a university children hospital in Egypt.  

PubMed

This study aimed to assess the prevalence, severity, and etiology of neutropenia in infants and children admitted to a children's hospital in Egypt. A total of 200 patients with neutropenia were recruited from April 1, 2010 to September 30, 2010. Patients with a known hematological or immunological disease were excluded. Patients were followed till recovery or an underlying cause was uncovered. Viral serological analysis was done for patients with moderate/severe neutropenia, including cytomegalovirus (CMV); Epstein-Barr virus (EBV); hepatitis A, B, and C viruses; and HIV. Antineutrophil cytoplasmic antibody (ANCA) tested by enzyme immunoassay and bone marrow aspirate were done for prolonged neutropenia. The results revealed that neutropenia was mild in 90 (45%), moderate in 56 (28%), and severe in 54 (27%). Clinical diagnosis at admission was bronchopneumonia (38%), pyrexia of undetermined etiology (17%), bronchiolitis (13%), urinary tract infection (9%), acute gastroenteritis (8%), hepatitis (6.5%), and septicemia (5%). Patients with mild neutropenia recovered within 1 week. Among 110 patients with moderate/severe neutropenia, 80 (73%) recovered in <3 weeks. Predictors of prolonged neutropenia were age younger than 18 months (P < .01), absolute neutrophils count (ANC) < 500/mm(3) (P < .05), hemoglobin < 10 gm/dL (P < .05), and positive CMV serology (P < .01). CMV and EBV serology were positive in 34.5% and 7.3% of patients, respectively. ANCA was positive in 42.8% of patients with prolonged severe neutropenia. In conclusion, neutropenia is a frequent finding in Egyptian infants and children, usually mild and transient, and mainly associated with infection. CMV and EBV are associated with prolonged neutropenia. Immune neutropenia is a common cause of moderate/severe neutropenia in the first two years of life. PMID:23190007

Tantawy, Azza Abdel Gawad; Sallam, Tarif Hamza; Ibrahim, Dalia Mohamed; Sallam, Mohamed Tarif; Ragab, Iman Ahmed

2013-02-01

94

Neonatal neutropenia: what diagnostic evaluation is needed and when is treatment recommended?  

PubMed

Neutropenia is a relatively frequent finding in the neonatal intensive care unit, particularly in very low birth weight neonates during the first week of life. Healthy term and preterm neonates have blood neutrophil counts within the same basic range as adults, but their neutrophil function, and their neutrophil kinetics during infection, differ considerably from those of adults. Neutrophil function of neonates, particularly preterm neonates, is less robust than that of adults and might also contribute to the increase in propensity to infection. In premature infants, early-onset neutropenia is correlated with sepsis, maternal hypertension, intrauterine growth restriction, severe asphyxia, and periventricular haemorrhage, and might be associated with an increase in the incidence of early-onset sepsis, nosocomial infection, and Candida colonisation. Some varieties of neutropenia in the NICU are very common and others are extremely rare. The most common causes of neutropenia in the NICU have an underlying cause that is often evident, and require little diagnostic evaluation. Unlike, persistent neutropenia should prompt evaluation even if it is of moderate severity. The laboratory tests to consider are those that provide a specific diagnosis. The first tests that should be ordered are a blood film, a complete blood count on the mother, and, if her blood neutrophil concentration is normal, maternal neutrophil antigen typing and an anti-neutrophil antibody screen. A bone marrow biopsy can be useful in cases with prolonged, unusual, or refractory neutropenia. Various treatments have been proposed as means of enhancing neutrophil production and function in preterm infants. Both recombinant granulocyte stimulating factor and recombinant granulocyte macrophage-colony-stimulating factor have been tried with variable success. Intravenous immunoglobulin, corticosteroids, granulocyte transfusions, and gamma interferon did not show a clear adequate beneficial role for the therapy of neonatal neutropenia. PMID:22633505

Del Vecchio, A; Christensen, R D

2012-05-01

95

Comprehensive Pharmacogenetic Analysis of Irinotecan Neutropenia and Pharmacokinetics  

PubMed Central

Purpose We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients. Patients and Methods Pharmacokinetic, genetic, and clinical data were obtained from 85 advanced cancer patients treated with single-agent CPT-11 every 3 weeks at doses of 300 mg/m2 (n = 20) and 350 mg/m2 (n = 65). Forty-two common variants were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies. Univariate and multivariate models of absolute neutrophil count (ANC) nadir and pharmacokinetic parameters were evaluated. Results Almost 50% of the variation in ANC nadir is explained by UGT1A1*93, ABCC1 IVS11 –48C>T, SLCO1B1*1b, ANC baseline levels, sex, and race (P < .0001). More than 40% of the variation in CPT-11 area under the curve (AUC) is explained by ABCC2 –24C>T, SLCO1B1*5, HNF1A 79A>C, age, and CPT-11 dose (P < .0001). Almost 30% of the variability in SN-38 (the active metabolite of CPT-11) AUC is explained by ABCC1 1684T>C, ABCB1 IVS9 –44A>G, and UGT1A1*93 (P = .004). Other models explained 17%, 23%, and 27% of the variation in APC (a metabolite of CPT-11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AUCs, respectively. When tested in univariate models, pretreatment total bilirubin was able to modify the existing associations between genotypes and phenotypes. Conclusion On the basis of this exploratory analysis, common polymorphisms in genes encoding for ABC and SLC transporters may have a significant impact on the pharmacokinetics and pharmacodynamics of CPT-11. Confirmatory studies are required. PMID:19349540

Innocenti, Federico; Kroetz, Deanna L.; Schuetz, Erin; Dolan, M. Eileen; Ramírez, Jacqueline; Relling, Mary; Chen, Peixian; Das, Soma; Rosner, Gary L.; Ratain, Mark J.

2009-01-01

96

Acute febrile encephalopathy in adults from Northwest India  

PubMed Central

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

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

2010-01-01

97

Febrile infants less than eight weeks old. Predictors of infection.  

PubMed

Febrile infants less than eight weeks old frequently are admitted and receive parenteral antibiotics for treatment of possible sepsis. The authors assess 52 infants less than eight weeks old with a rectal temperature of 38.1 degrees C or higher as having either a readily identifiable focus of infection by physical examination, appearing "toxic" without a focus, or appearing well. The authors screened patients by using white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and chest radiographs in addition to blood, cerebrospinal fluid and urine cultures. The authors found a 9.6% incidence of bacteria in the 52 infants evaluated, with a 4.3% incidence in those febrile infants who appeared well. Five patients had positive blood cultures with Group B B Hemolytic streptococcus (four patients), and Viridans streptococcus (one patient). A clinical assessment of toxicity and a total band count greater than or equal to 0.5 x 10(3) cells/uL together were sensitive indicators of bacteremia, as were toxicity and a positive CRP. A "toxic" appearance, a WBC count greater than or equal to 15 x 10(3) cells/uL and an ESR greater than 30 were specific indicators of bacteria. Based on these data, identification of bacteremia in febrile infants may be possible with clinical assessment and screening laboratory tests. Because of the relatively small sampling size of this study, the authors feel that evaluation of a larger number of patients is warranted to evaluate these sensitivities in a more diffuse patient population. PMID:2208902

Broner, C W; Polk, S A; Sherman, J M

1990-08-01

98

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

PubMed Central

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

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

2009-01-01

99

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

100

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

ERIC Educational Resources Information Center

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

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

2012-01-01

101

Case of Fatal Blastoschizomyces capitatus Infection Occurring in a Patient Receiving Empiric Micafungin Therapy?  

PubMed Central

We report the first case, to our knowledge, of Blastoschizomyces capitatus infection occurring in a patient receiving empirical echinocandin therapy for neutropenic fevers. Clinicians should consider B. capitatus infection in those neutropenic patients who remain febrile despite echinocandin therapy or who develop yeast bloodstream infections while receiving an echinocandin. PMID:19738005

Chittick, Paul; Palavecino, Elizabeth L.; Delashmitt, Brian; Evans, James; Peacock, James E.

2009-01-01

102

Prolonged febrile seizures cause reversible reductions in white matter integrity.  

PubMed

Prolonged febrile seizures (PFS) are the commonest cause of childhood status epilepticus and are believed to carry a risk of neuronal damage, in particular to the mesial temporal lobe. This study was designed to determine: i) the effect of prolonged febrile seizures on white matter and ii) the temporal evolution of any changes seen. 33 children were recruited 1 month following PFS and underwent diffusion tensor imaging (DTI) with repeat imaging at 6 and 12 months after the original episode of PFS. 18 age-matched healthy control subjects underwent similar investigations at a single time point. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) between patients and controls on a voxel-wise basis within the white matter skeleton. Widespread reductions in FA along multiple white matter tracts were found at 1 and 6 months post-PFS, but these had resolved at 12 months. At one month post-PFS the main changes seen were reductions in AD but at 6 months these had predominantly changed to increases in RD. These widespread white matter changes have not previously been noted following PFS. There are many possible explanations, but one plausible hypothesis is that this represents a temporary halting of normal white matter development caused by the seizure, that then resumes and normalises in the majority of children. PMID:24273734

Yoong, M; Seunarine, K; Martinos, M; Chin, R F; Clark, C A; Scott, R C

2013-01-01

103

Prolonged febrile seizures cause reversible reductions in white matter integrity?  

PubMed Central

Prolonged febrile seizures (PFS) are the commonest cause of childhood status epilepticus and are believed to carry a risk of neuronal damage, in particular to the mesial temporal lobe. This study was designed to determine: i) the effect of prolonged febrile seizures on white matter and ii) the temporal evolution of any changes seen. 33 children were recruited 1 month following PFS and underwent diffusion tensor imaging (DTI) with repeat imaging at 6 and 12 months after the original episode of PFS. 18 age-matched healthy control subjects underwent similar investigations at a single time point. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) between patients and controls on a voxel-wise basis within the white matter skeleton. Widespread reductions in FA along multiple white matter tracts were found at 1 and 6 months post-PFS, but these had resolved at 12 months. At one month post-PFS the main changes seen were reductions in AD but at 6 months these had predominantly changed to increases in RD. These widespread white matter changes have not previously been noted following PFS. There are many possible explanations, but one plausible hypothesis is that this represents a temporary halting of normal white matter development caused by the seizure, that then resumes and normalises in the majority of children. PMID:24273734

Yoong, M.; Seunarine, K.; Martinos, M.; Chin, R.F.; Clark, C.A.; Scott, R.C.

2013-01-01

104

Acute EEG findings in children with febrile status epilepticus  

PubMed Central

ABSTRACT Objective: The FEBSTAT (Consequences of Prolonged Febrile Seizures) study is prospectively addressing the relationships among serial EEG, MRI, and clinical follow-up in a cohort of children followed from the time of presentation with febrile status epilepticus (FSE). Methods: We recruited 199 children with FSE within 72 hours of presentation. Children underwent a detailed history, physical examination, MRI, and EEG within 72 hours. All EEGs were read by 2 teams and then conferenced. Associations with abnormal EEG were determined using logistic regression. Interrater reliability was assessed using the ? statistic. Results: Of the 199 EEGs, 90 (45.2%) were abnormal with the most common abnormality being focal slowing (n = 47) or attenuation (n = 25); these were maximal over the temporal areas in almost all cases. Epileptiform abnormalities were present in 13 EEGs (6.5%). In adjusted analysis, the odds of focal slowing were significantly increased by focal FSE (odds ratio [OR] = 5.08) and hippocampal T2 signal abnormality (OR = 3.50) and significantly decreased with high peak temperature (OR = 0.18). Focal EEG attenuation was also associated with hippocampal T2 signal abnormality (OR = 3.3). Conclusions: Focal EEG slowing or attenuation are present in EEGs obtained within 72 hours of FSE in a substantial proportion of children and are highly associated with MRI evidence of acute hippocampal injury. These findings may be a sensitive and readily obtainable marker of acute injury associated with FSE. PMID:23136262

Moshé, Solomon L.; Shinnar, Shlomo; Hesdorffer, Dale C.; Sogawa, Yoshimi; Pellock, John M.; Lewis, Darrell V.; Frank, L. Matthew; Shinnar, Ruth C.; Sun, Shumei

2012-01-01

105

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

106

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

107

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

108

[SFGM-TC recommendation on indications for allogeneic stem cell transplantation in children with congenital neutropenia].  

PubMed

In this report, we address the issue of allogeneic stem cell transplantation in children with congenital neutropenia. Constitutional disorders with neutropenia are exceptional. Treatment and prevention of severe infections are a major concern in the management of chronic neutropenia. These disorders, especially Kostmann's disease and Shwachman-Bodian-Diamond syndrome, are associated with an increased risk of leukemia. The role of allogeneic stem cell transplantation in these patients is still unclear. In an effort to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. PMID:24973857

Dalle, J-H; Donadieu, J; Paillard, C; Rialland, F; Schneider, P; Sicre De Fontbrune, F; Hichri, Y; Neven, B; Yakoub-Agha, I

2014-08-01

109

LTB4-induced transient neutropenia in the rat: a model for evaluating efficacy and bioavailability of LTB4 receptor antagonists.  

PubMed

An animal model of leukotriene B4- (LTB4) induced neutropenia has been developed to evaluate LTB4 receptor antagonists in vivo. LTB4, a potent chemotactic inflammatory mediator, when administered intravenously, induces a profound, rapid, and transient redistribution of blood neutrophils from the circulating pool to the marginated pool. This phenomenon is applied in the neutropenia model whereby circulating blood neutrophil counts prior to and after intravenous infusion of LTB4 are compared. Kinetics of LTB4-induced neutrophil responses are determined through the use of a Technicon H*1 automated blood cell analyzer. LTB4 receptor antagonists are identified by inhibition of LTB4-induced neutropenia. Standard antiinflammatory compounds including BW-755C, Abbott A-64077 (zileuton), dexamethasone-21-acetate, indomethacin, and naproxen did not affect LTB4-induced neutropenia. A potent LTB4 receptor antagonist, designated "RPR," inhibited LTB4-induced neutropenia following oral administration in a dose-dependent fashion. PMID:8305713

Pellas, T C; Colombo, C; Fryer, L R; Pastor, G; Haston, W; Raychaudhuri, A; Kotyuk, B; Greenspan, P D; Healy, C; DiPasquale, G

1993-11-01

110

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

111

Recurrent febrile respiratory distress in infant: which diagnosis?  

PubMed

Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare congenital anomaly. CCAM diagnosis can be made by prenatal ultrasound or in postnatal cases with regard to respiratory distress or recurrent respiratory infections. We present, for diagnostic purposes, a case of a patient, aged 4 months who had suffered since birth from recurrent bronchopulmonary infections. He was hospitalised several times for febrile respiratory distress. Chest x-rays previously performed were interpreted as normal. A final radiograph indicated the diagnosis and it was confirmed by CT. Surgical resection was performed with a positive result. CCAM responds to the prenatal diagnosis and requires frequent ultrasound checks during pregnancy and allowing for optimal management. The radiological assessment leads to the diagnosis and addresses the treatment which is based on a surgical cure. PMID:23008370

Lahlou, Zineb; Salimi, Soundousse; Slaoui, Bouchra; Dehbi, Fatima

2012-01-01

112

Cancrum oris (noma) in a patient with acute lymphoblastic leukaemia. A complication of chemotherapy induced neutropenia.  

PubMed

Cancrum oris (noma) has been most commonly described in malnourished debilitated children with poor oral hygiene following systemic childhood infections such as measles, pertussis or scarlet fever. We describe a patient who developed this condition during a period of profound neutropenia following cytotoxic chemotherapy for acute lymphoblastic leukaemia. PMID:9619095

Brady-West, D C; Richards, L; Thame, J; Moosdeen, F; Nicholson, A

1998-03-01

113

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

PubMed Central

Objectives to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer. Methods observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant. Results 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia. Conclusion neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care.

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

2014-01-01

114

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.

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

2015-01-01

115

Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia  

PubMed Central

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

2009-01-01

116

Continuation of deferiprone therapy in patients with mild neutropenia may not lead to a more severe drop in neutrophil count.  

PubMed

Approximately 6% of patients with thalassemia receiving deferiprone develop neutropenia. Present practice is to monitor absolute neutrophil count (ANC) weekly and to interrupt treatment at the first sign of neutropenia, lest continuation lead to progressive neutrophil reduction. In a 6-month study evaluating the safety and efficacy of a liquid form of deferiprone in 100 children, ANC was initially checked weekly for all patients. For individuals experiencing mild neutropenia, deferiprone was continued but monitoring was increased to daily until resolution. Therapy was to be suspended only if the episode was prolonged or if it worsened. Four patients experienced single episodes of mild neutropenia, and two others each experienced two episodes. All eight episodes resolved within 4-7 d despite continued therapy. (One patient later developed agranulocytosis and had treatment terminated.) This study showed that not all cases of mild neutropenia during deferiprone therapy develop into agranulocytosis, and suggests that many may not be caused by deferiprone. Transient declines in ANC to levels defined as neutropenic are common even in healthy individuals, particularly children; and it could be that the frequent monitoring of ANC mandated during deferiprone therapy may reveal cases of transient neutropenia that would otherwise have gone undetected and resolved on their own without clinical consequences. In patients with thalassemia, several factors increase the probability of a transient fall in ANC. These findings raise the question of whether deferiprone should be routinely stopped in cases of mild neutropenia, provided that such patients have their ANC monitored more frequently during the neutropenic episode. PMID:24330079

El-Beshlawy, Amal M; El-Alfy, Mohsen S; Sari, Teny T; Chan, Lee L; Tricta, Fernando

2014-04-01

117

Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes  

E-print Network

; environ- mental stress MALARIA affects 400 million people and causes 1­3 million deaths annually. A cardinal symptom of human malaria is the occurrence of febrile episodes resulting in body temperatures

Suresh, Subra

118

The importance of regular dental treatment in patients with cyclic neutropenia. Follow-up of 2 cases.  

PubMed

Data on two patients with cyclic neutropenia are presented. They demonstrate that regular tooth care and professional dental treatment can prevent progressive periodontal breakdown but that neglecting oral hygiene soon leads to periodontal pathology. Regular, monthly professional removal of dental plaque and calculus, and rinsing with 0.2% chlorhexidine gluconate during neutropenia help maintain periodontal attachment level. The caries susceptibility and the apical periodontitis in the intact anterior tooth of the female patient indicate the possibility of cyclic neutropenia playing a role in caries and pulpal pathology. PMID:8708974

Pernu, H E; Pajari, U H; Lanning, M

1996-04-01

119

Long-Term Plasticity of Endocannabinoid Signaling Induced by Developmental Febrile Seizures  

Microsoft Academic Search

Febrile (fever-induced) seizures are the most common form of childhood seizures, affecting 3%–5% of infants and young children. Here we show that the activity-dependent, retrograde inhibition of GABA release by endogenous cannabinoids is persistently enhanced in the rat hippocampus following a single episode of experimental prolonged febrile seizures during early postnatal development. The potentiation of endocannabinoid signaling results from an

Kang Chen; Anna Ratzliff; Lutz Hilgenberg; Attila Gulyás; Tamás F Freund; Martin Smith; Thien P Dinh; Daniele Piomelli; Ken Mackie; Ivan Soltesz

2003-01-01

120

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

121

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

122

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

123

Predictors of malaria in febrile children in Sokoto, Nigeria  

PubMed Central

Background: Presumptive diagnosis of malaria is widespread, even where microscopy is available. As fever is very nonspecific, this often leads to over diagnosis, drug wastage and loss of opportunity to consider alternative causes of fever, hence the need to improve on the clinical diagnosis of malaria. Materials and Methods: In a prospective cross-sectional comparative study, we examined 45 potential predictors of uncomplicated malaria in 800 febrile children (0-12 years) in Sokoto, Nigeria. We developed a clinical algorithm for malaria diagnosis and compared it with a validated algorithm, Olaleye's model. Results: Malaria was confirmed in 445 (56%). In univariate analysis, 13 clinical variables were associated with malaria. In multivariate analysis, vomiting (odds ratio, OR 2.6), temperature ? 38.5°C (OR 2.2), myalgia (OR 1.8), weakness (OR 1.9), throat pain (OR 1.8) and absence of lung crepitations (OR 5.6) were independently associated with malaria. In children over age 3 years, any 3 predictors had a sensitivity of 82% and specificity of 47% for malaria. An Olaleye score ? 5 had a sensitivity of 62% and a specificity of 51%. Conclusion: In hyperendemic areas, the sensitivity of our algorithm may permit presumptive diagnosis of malaria in children. Algorithm positive cases can be presumptively treated, and negative cases can undergo parasitological testing to determine need for treatment.

Singh, Sanjay; Madaki, Aboi J.K.; Jiya, Nma M.; Singh, Rupashree; Thacher, Tom D.

2014-01-01

124

Vancomycin-induced neutropenia in a patient positive for an antineutrophil antibody.  

PubMed

A 48-year-old man, hospitalized after experiencing subarachnoid hemorrhage secondary to a basilar aneurysm, received vancomycin for methicillin-resistant Staphylococcus aureus sepsis. He developed neutropenia 16 days after the start of vancomycin therapy, and his white blood cell count decreased to a nadir of 1200 cells/mm3. Vancomycin was discontinued, and granulocyte-colony stimulating factor (G-CSF) therapy was begun. The patient was rechallenged with a single dose of vancomycin 1 g in preparation for intraarterial aneurysm coiling. His white blood cell count dropped to 600 cells/mm3 but returned to normal with continued G-CSF therapy. A diagnosis of vancomycin-induced neutropenia was considered. Subsequent testing by granulocyte agglutination and granulocyte immunofluorescence assays revealed that his serum was positive for an antigranulocyte antibody. A test for HLA antibody reactivity was negative. Monoclonal antibody immobilization of granulocyte antigens assay failed to determine the antigen specificity of his granulocyte antibody. PMID:12066971

Schwartz, Michael D

2002-06-01

125

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

PubMed Central

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

Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry

2011-01-01

126

Exercise induced mobilisation of the marginated granulocyte pool in the investigation of ethnic neutropenia  

PubMed Central

This study was designed to determine whether ethnic neutropenia is caused by an increased proportion of neutrophils being present in the marginated granulocyte pool. Thirty two healthy volunteers, half of whom were African or Afro-Caribbean and half of whom were white, exercised vigorously for 10 minutes on a step machine to mobilise granulocytes from the marginated granulocyte pool into the circulating granulocyte pool. The amount of work performed and the pulse rate response of the two ethnic groups were compared to determine whether the exercise carried out was comparable. A full blood count and an automated differential count were performed before and after the exercise. The haemoglobin concentration, platelet count, and absolute counts of total leucocytes and leucocyte subsets before and after exercise were compared in each individual and the values in the two ethnic groups both before and after exercise were compared. The absolute increase in neutrophils in the two ethnic groups was compared. The African/Afro-Caribbean group was found to have a reduced rather than enhanced ability to mobilise neutrophils from the marginated granulocyte pool. Therefore, increased margination of neutrophils is unlikely to be the cause of ethnic neutropenia. Key Words: ethnic neutropenia • circulating and marginated granulocyte pool • exercise PMID:10911809

Phillips, D.; Rezvani, K.; Bain, B.

2000-01-01

127

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

128

Distribution Of Febrile Seizure Duration And Associations With Development  

PubMed Central

Objectives In prior studies of febrile seizures (FS), prolonged FS are defined, absent empirical evidence, as lasting 10 or 15 minutes or more. We assessed the distribution of FS duration in a cohort with first FS, and the association between FS duration and baseline characteristics of the children. Methods We calculated the observed cumulative probability, S(t), that a FS would last at least t minutes, S(t) = exp(?t/ ?) . Data were also fit using a model obtained as the sum of two exponential distributions [S(t) = ?exp(?t/?1)+(1-?)exp(?t/?2)]. After assessing the best fit, the cut off defining long FS was determined. Logisitic regression was used to examine associations between long FS and baseline characteristics, behavior and development. Results In 158 children with a first FS, median duration was 4.0 minutes. Duration of FS was best fit by a two-component mixture exponential model. Using this model we identified one population that accounts for 82.3% of FS and has a mean duration of 3.8 minutes (short FS) and a second population that accounts for 17.7% of FS and has a mean duration of 39.8 minutes (long FS). Long FS were significantly associated with developmental delay (p=0.010) and delays and younger age at first FS (p=0.048). Interpretation Like the distribution of afebrile seizure duration in children, the distribution of first FS duration is best modeled by assuming two populations. Developmental delay and younger age are associated with prolonged FS. Our data lend further support to defining 10 minutes as the upper limit for a simple FS. PMID:21437934

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

2011-01-01

129

MRI abnormalities following febrile status epilepticus in children  

PubMed Central

Objective: The FEBSTAT study is a prospective study that seeks to determine the acute and long-term consequences of febrile status epilepticus (FSE) in childhood. Methods: From 2003 to 2010, 199 children age 1 month to 5 years presenting with FSE (>30 minutes) were enrolled in FEBSTAT within 72 hours of the FSE episode. Of these, 191 had imaging with emphasis on the hippocampus. All MRIs were reviewed by 2 neuroradiologists blinded to clinical details. A group of 96 children with first simple FS who were imaged using a similar protocol served as controls. Results: A total of 22 (11.5%) children had definitely abnormal (n = 17) or equivocal (n = 5) increased T2 signal in the hippocampus following FSE compared with none in the control group (p < 0.0001). Developmental abnormalities of the hippocampus were more common in the FSE group (n = 20, 10.5%) than in controls (n = 2, 2.1%) (p = 0.0097) with hippocampal malrotation being the most common (15 cases and 2 controls). Extrahippocampal imaging abnormalities were present in 15.7% of the FSE group and 15.6% of the controls. However, extrahippocampal imaging abnormalities of the temporal lobe were more common in the FSE group (7.9%) than in controls (1.0%) (p = 0.015). Conclusions: This prospective study demonstrates that children with FSE are at risk for acute hippocampal injury and that a substantial number also have abnormalities in hippocampal development. Follow-up studies are in progress to determine the long-term outcomes in these children. PMID:22843278

Bello, Jacqueline A.; Chan, Stephen; Hesdorffer, Dale C.; Lewis, Darrell V.; MacFall, James; Pellock, John M.; Nordli, Douglas R.; Frank, L. Matthew; Moshe, Solomon L.; Gomes, William; Shinnar, Ruth C.; Sun, Shumei

2012-01-01

130

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

131

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

132

Diagnostic Workup of Febrile Children Under 24 Months of Age: A Clinical Review  

PubMed Central

One of the most challenging situations encountered by primary care physicians is the diagnostic workup of a febrile child. Several studies have shown the surprisingly high incidence of clinically unsuspected, potentially major illness in febrile children. Bacteremia, pneumonia and urinary tract infection are particularly likely to present in an occult manner, while meningitis is more likely to be clinically suspected. An examination of the literature regarding febrile children under two years of age is necessary in order to synthesize the relevant information. Although there are large gaps in our knowledge, it is possible to make specific recommendations for a treatment plan, keeping in mind that areas of controversy and other reasonable approaches exist. PMID:6753341

Soman, Michael

1982-01-01

133

Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis  

PubMed Central

Experimental prolonged febrile seizures (FS) lead to structural and molecular changes that promote hippocampal hyperexcitability and reduce seizure threshold to further convulsants. However, whether these seizures provoke later-onset epilepsy, as has been suspected in humans, has remained unclear. Previously, intermittent EEGs with behavioural observations for motor seizures failed to demonstrate spontaneous seizures in adult rats subjected to experimental prolonged FS during infancy. Because limbic seizures may be behaviourally subtle, here we determined the presence of spontaneous limbic seizures using chronic video monitoring with concurrent hippocampal and cortical EEGs, in adult rats (starting around 3 months of age) that had sustained experimental FS on postnatal day 10. These subjects were compared with groups that had undergone hyperthermia but in whom seizures had been prevented (hyperthermic controls), as well as with normothermic controls. Only events that fulfilled both EEG and behavioural criteria, i.e. electro-clinical events, were considered spontaneous seizures. EEGs (over 400 recorded hours) were normal in all normothermic and hyperthermic control rats, and none of these animals developed spontaneous seizures. In contrast, prolonged early-life FS evoked spontaneous electro-clinical seizures in 6 out of 17 experimental rats (35.2%). These seizures consisted of sudden freezing (altered consciousness) and typical limbic automatisms that were coupled with polyspike/sharp-wave trains with increasing amplitude and slowing frequency on EEG. In addition, interictal epileptiform discharges were recorded in 15 (88.2%) of the experimental FS group and in none of the controls. The large majority of hippocampally-recorded seizures were heralded by diminished amplitude of cortical EEG, that commenced half a minute prior to the hippocampal ictus and persisted after seizure termination. This suggests a substantial perturbation of normal cortical neuronal activity by these limbic spontaneous seizures. In summary, prolonged experimental FS lead to later-onset limbic (temporal lobe) epilepsy in a significant proportion of rats, and to interictal epileptifom EEG abnormalities in most others, and thus represent a model that may be useful to study the relationship between FS and human temporal lobe epilepsy. PMID:16446281

Dubé, Céline; Richichi, Cristina; Bender, Roland A.; Chung, Grace; Litt, Brian; Baram, Tallie Z.

2011-01-01

134

Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery  

PubMed Central

Introduction Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice. Methods Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined. Results Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-?, interleukin (IL)-1?, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-? and c-KIT in imatinib or nilotinib group were significantly lower than LPS group. Conclusions Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery. PMID:23787115

2013-01-01

135

Leukokinetic studies. XIV. Blood neutrophil kinetics in chronic, steady-state neutropenia.  

PubMed

The kinetics of blood neutrophils was investigated by means of the in vitro radioactive diisopropyl fluorophosphate method in 35 patients with a chronic, steady-state neutropenia. There were 17 patients in whom the half disappearance time of neutrophils was normal. In 10 of these patients, the production of neutrophils was low and in 7, production was normal. In 18 patients the half disappearance time of neutrophilic granulocytes was shorter than normal. The production of neutrophilic granulocytes was low in five of these patients, normal in eight patients, and increased in five. An attempt was made to correlate other laboratory measurements with the kinetic picture, but no relationship was found; the marrow neutrophil reserve as measured by endotoxin or cortisol injection; marrow cellularity on aspiration or biopsy; in vitro-labeling index with (3)HTdR; or serum lysozyme concentration proved of no value in identifying the various kinetic groups. The only finding that seemed to correlate with the kinetic picture was the presence or absence of splenomegaly. In 12 of the 18 patients with a short half disappearance time, splenomegaly was present whereas in 15 of 17 patients with a normal half disappearance time, there was no splenomegaly. Of 20 patients with greater than 1000 neutrophils per mm(3), 17 were found to have a normal total-blood neutrophil pool. Thus these patients, with many of their cells marginated, agree to have a "shift neutropenia."Myelocyte to blood transit time and myelocyte generation time, as measured in seven patients by in vivo labeling with diisopropy fluorophosphate, proved to be essentially normal. Thus, it appears that in chronic neutropenia, increased or decreased production of neutrophils is accomplished by increasing or decreasing early precursor input into the system. PMID:5097574

Bishop, C R; Rothstein, G; Ashenbrucker, H E; Athens, J W

1971-08-01

136

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

PubMed

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

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

2011-07-01

137

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

138

Co-Occurring Disorders  

MedlinePLUS

... supporters and consumers in the mental health field. Alcohol and Drug Abuse, Addiction and Co-occurring Disorders: ... to MHA Mental Health Information Anxiety Bipolar Depression Post Traumatic Stress Disorder All Other Topics A-Z Policy & Advocacy Legislative ...

139

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

PubMed

The etiological relation of prolonged febrile seizures with hippocampal sclerosis and cerebral hemiatrophy is controversial. Causal relationship is mainly adopted from retrospective statistical analysis and data from epilepsy surgery. We report a 17-month-old boy who had a prolonged febrile seizure with a transient postictal flaccid hemiparesis and anisocoria. Family history was unremarkable. Magnetic resonance imaging (MRI) revealed abnormal results in the right hippocampal area where diffusion-weighted sequences showed increased signal intensity consistent with acute neuronal edema. Repeat MRI 5 months later demonstrated sclerosis and atrophy of the right hippocampus in association with an increased T2-weighted signal and atrophy of the right frontal, temporal, and parietal lobe. In addition, 18-fluorodeoxyglucose positron emission tomography and 99mTc-ECD single-photon emission computed tomography revealed glucose hypometabolism and decreased perfusion in the right hemisphere, respectively. A final MRI, 12 months following the seizure, was widely unchanged. Interestingly, during a follow-up of 42 weeks, only minor motor deficits were observed. This case uniquely presents the acute onset of hippocampal sclerosis and, consecutively, cerebral hemiatrophy after a single febrile seizure. This suggests that a single prolonged febrile seizure may cause global morphological changes of the brain, not only affecting hippocampal formation. PMID:21416226

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

2011-06-01

140

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

141

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

Microsoft Academic Search

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

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

1999-01-01

142

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

ERIC Educational Resources Information Center

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

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

2009-01-01

143

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

Microsoft Academic Search

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

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

144

Febrile Infants Less than Eight Weeks OldPredictors of Infection  

Microsoft Academic Search

Febrile infants less than eight weeks old frequently are admitted and receive parenteral antibiotics for treatment of possible sepsis. The authors assess 52 infants less than eight weeks old with a rectal temperature of 38.1 °C or higher as having either a readily identifiable focus of infection by physical examination, appearing \\

Cynthia W. Broner; Sara A. Polk; James M. Sherman

1990-01-01

145

Exercise induced mobilisation of the marginated granulocyte pool in the investigation of ethnic neutropenia.  

PubMed

This study was designed to determine whether ethnic neutropenia is caused by an increased proportion of neutrophils being present in the marginated granulocyte pool. Thirty two healthy volunteers, half of whom were African or Afro-Caribbean and half of whom were white, exercised vigorously for 10 minutes on a step machine to mobilise granulocytes from the marginated granulocyte pool into the circulating granulocyte pool. The amount of work performed and the pulse rate response of the two ethnic groups were compared to determine whether the exercise carried out was comparable. A full blood count and an automated differential count were performed before and after the exercise. The haemoglobin concentration, platelet count, and absolute counts of total leucocytes and leucocyte subsets before and after exercise were compared in each individual and the values in the two ethnic groups both before and after exercise were compared. The absolute increase in neutrophils in the two ethnic groups was compared. The African/Afro-Caribbean group was found to have a reduced rather than enhanced ability to mobilise neutrophils from the marginated granulocyte pool. Therefore, increased margination of neutrophils is unlikely to be the cause of ethnic neutropenia. PMID:10911809

Phillips, D; Rezvani, K; Bain, B J

2000-06-01

146

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

PubMed

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

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

2012-01-01

147

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

148

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean  

PubMed Central

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0·0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0·0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry. PMID:18710383

Grann, Victor R; Ziv, Elad; Joseph, Cecil K; Neugut, Alfred I; Wei, Ying; Jacobson, Judith S; Horwitz, Marshall S; Bowman, Natalie; Beckmann, Kenneth; Hershman, Dawn L

2008-01-01

149

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

PubMed

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

Cohen, Philip R

2007-01-01

150

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

PubMed Central

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

Cohen, Philip R

2007-01-01

151

Matrix-metalloproteinases and proinflammatory cytokines in children with febrile convulsions and epilepsy--cause or consequence?  

PubMed

This is the first investigation of MMPs in children with febrile seizures. In a prospective, cross sectional study, serum levels of matrix metalloproteinases (MMP8/9), tissue inhibitor of metalloproteinases (TIMP1/2), of children with FS (n=13), children with febrile infection (FI, n=13) and children with unprovoked generalized seizures (US, n=11) were compared. Neither provoked nor unprovoked seizures in FS and US seem to elevate levels of MMPs or TIMPs, whereas in case of febrile infection blood level of MMP8 was significant elevated. Seizures in general might have no influence on this distinctive inflammatory process or even might have suppressive impact. PMID:23313321

Haberlandt, Edda; Rauchenzauner, Markus; Morass, Maike; Wondrak, Petra; Scholl-Bürgi, Sabine; Rostásy, Kevin; Karall, Daniela

2013-07-01

152

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

153

Do double-beta-lactam combinations prolong neutropenia in patients undergoing chemotherapy or bone marrow transplantation for hematological disease?  

PubMed Central

The total period of neutropenia was assessed in 174 episodes after chemotherapy or bone marrow transplantation in which patients received antibiotics for fever in a randomized prospective trial. Log rank analysis demonstrated no significant difference in the total duration of neutropenia between patients receiving netilmicin plus either piperacillin or azlocillin and those given ceftazidime plus either piperacillin or azlocillin. Of 86 patients in the single-beta-lactam group, 27 had a persistent neutrophil count of 0.1 x 10(9) per liter during treatment compared with 27 of 88 patients in the double-beta-lactam group, and 29 of 68 patients treated with the single-beta-lactam combination had a total period of neutropenia greater than 30 days versus 36 of 75 in the double-beta-lactam group. The use of two beta-lactam antibiotics rather than one does not appear to prolong neutropenia in patients undergoing treatment of hematological malignancy. However, in order to determine the effect of a single-beta-lactam combination, a similar carefully controlled prospective randomized study in which such treatment is compared with a non-beta-lactam-containing regimen is required. PMID:2658793

Kibbler, C C; Prentice, H G; Sage, R J; Hoffbrand, A V; Brenner, M K; Noone, P

1989-01-01

154

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

Microsoft Academic Search

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

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

2004-01-01

155

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

156

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

PubMed Central

Opportunistic infections (OI) and the human immunodeficiency virus (HIV) cause significant morbidity and mortality in developing countries. Immune cell and cytokine profiles may be related to the type and course of OI and to the OI-HIV interaction. Examining cell-specific cytokine production ex vivo has only recently become feasible. In Thailand, 53 febrile, hospitalized adults were enrolled in a study of the immune correlates of bloodstream infections (BSI). On site, blood cells were stimulated ex vivo. Cell-surface antigens and eight intracellular cytokines were subsequently analyzed using flow cytometry to determine associations with mortality and the organism causing the BSI. By logistic regression analysis, the percentage of CD3+ CD16/56+ cells making tumor necrosis factor alpha (TNF-?) (P = 0.033) and the percentage of CD3? CD16/56+ cells (NK) (P = 0.032) were related to HIV positivity. Lymph node enlargement with HIV infection and the percentage of CD3+ CD16/56+ making TNF-? were predictive of death. A lower percentage of CD3+ CD8+ lymphocytes making interleukin-8 (IL-8) (P = 0.005), fewer monocytes expressing CD14 (P = 0.009), and the percentage of CD3+ CD8+ cells producing gamma interferon (P = 0.011) were associated with blood culture positivity and the causative organism. For every one point decrease in the percentage of CD3+ CD8+ cells making IL-8, the likelihood of a positive culture increased 23%; for every one point decrease in the percentage of monocytes expressing CD14, the likelihood of a positive culture increased by 5%. Only a few immune cell types and three of their related cytokines were significantly associated with HIV disease outcome or the BSI organism. These cell types did not include CD3+ CD8? cells (a surrogate for CD4+ cells), nor did they involve cytokines associated with a type I to type II cytokine shift, which might occur with advancing HIV infection. These associations support the premise that CD8+ and CD16/56+ lymphocytes play significant roles in HIV and type I infections. PMID:9874667

Jason, Janine; Archibald, Lennox; McDonald, L. Clifford; Hart, W. Michael; Rheanppumikankit, Sunthorn; Tansuphwaswadikul, Somsit; Byrd, Martha G.; Larned, Joshua; Han, Alison; Green, Timothy A.; Jarvis, William R.

1999-01-01

157

Nonchemotherapy drug-induced neutropenia and agranulocytosis: could medications be the culprit?  

PubMed

Drug-induced agranulocytosis is a severe complication that has been implicated with most classes of medications. Medications such as clozapine, trimethoprim-sulfamethoxazole and methimazole have been more commonly associated with agranulocytosis than other agents. Although the pathogenesis isn't fully elucidated, it appears to be two-fold with a direct toxicity to the myeloid cell line and immune-mediated destruction. Patients may be asymptomatic at the time neutropenia is discovered or may present with more severe complications such as sepsis. In approximately 5% of cases drug-induced agranulocytosis may be fatal. Management of drug-induced agranulocytosis includes the immediate discontinuation of the offending medication, initiation of broad-spectrum antibiotics and consideration of the use of granulocyte colony-stimulating factors in high-risk patients. PMID:25124379

Pick, Amy M; Nystrom, Kelly K

2014-10-01

158

Splenic tuberculosis presenting as fever of unknown origin with severe neutropenia  

PubMed Central

Fever of undetermined origin always poses a challenging problem to the physician. Tuberculosis is an important health problem in developing countries. It is mostly seen in immune-compromised patients. And it is one of the common causes of fever of unknown origin. I am reporting a case of a splenic tuberculosis in 48 years old male who is not known of any immune deficiency state, he was presented with 3 weeks history of fever and found to have severe neutropenia and with negative work up for all hematological, rheumatological and malignant causes. A computerized tomography scan of the abdomen confirmed splenic enlargement with multiples hypo dense lesions consist with either splenic infection or splenic lymphoma so exploratory splenectomy was performed. Histological examination revealed granulomatouse inflammation with numerous acid fast bacilli consist with tuberculosis. He was started on four anti-tuberculouse drugs. in less than one week his fever subside with normalization of his neutrophilic count PMID:23777575

2013-01-01

159

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

160

Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures.  

PubMed

Febrile (fever-induced) seizures are the most common form of childhood seizures, affecting 3%-5% of infants and young children. Here we show that the activity-dependent, retrograde inhibition of GABA release by endogenous cannabinoids is persistently enhanced in the rat hippocampus following a single episode of experimental prolonged febrile seizures during early postnatal development. The potentiation of endocannabinoid signaling results from an increase in the number of presynaptic cannabinoid type 1 receptors associated with cholecystokinin-containing perisomatic inhibitory inputs, without an effect on the endocannabinoid-mediated inhibition of glutamate release. These results demonstrate a selective, long-term increase in the gain of endocannabinoid-mediated retrograde signaling at GABAergic synapses in a model of a human neurological disease. PMID:12925275

Chen, Kang; Ratzliff, Anna; Hilgenberg, Lutz; Gulyás, Attila; Freund, Tamás F; Smith, Martin; Dinh, Thien P; Piomelli, Daniele; Mackie, Ken; Soltesz, Ivan

2003-08-14

161

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

PubMed

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

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

162

Maternal responses to childhood febrile illnesses in an area of seasonal malaria transmission in rural Ethiopia.  

PubMed

Although malaria is the leading cause of illness and death among children less than 5 years of age, there is limited information on mother's response and experience about diagnosis and treatment of the disease in children in rural areas of Ethiopia. The objective of this study was to assess maternal responses and treatment seeking behaviour for children reported to have malaria. A community-based cross-sectional study was conducted between October and November 2003 in Adami Tulu District, south-central Ethiopia. Mothers/caretakers of children less than 5 years of age were interviewed about history of febrile illness suspected to be malaria for all under-five children and the actions taken in the 2 weeks prior to the survey. Of 3872 children identified in 2372 households, 817 (21.1%) had febrile illness reported to be malaria according to the mothers/caretakers. The main symptoms included fever (99%), shivering/chills (92.2%), vomiting (55.1%), sleeplessness/restlessness (12.9%) and refusal to feed (21.3%). Of the total febrile children, 27.3% sought the first care from a public health facility, 27% visited community health workers (CHWs), 25.7% taken to private clinics, 6.4% received home treatment, and 13.3% did not get any care. Among 710 children who reported to receive any type of anti-malarial treatment, 78.8% got it from one source, 19.4% visited two sources and 1.8% sought three sources. Only 28% of the children received any form of treatment within 24h of the onset of illness. Public facilities, private clinics and CHWs were the main sources of care sought by febrile children. Strengthening peripheral health services and community-based interventions using CHWs at village levels would improve the early diagnosis and treatment of malaria among children. PMID:17395142

Deressa, Wakgari; Ali, Ahmed; Berhane, Yemane

2007-04-01

163

Pentoxifylline and cyclosporine in the treatment of febrile ulceronecrotic Mucha-Habermann disease.  

PubMed

We describe two pediatric cases of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) with response to pentoxifylline and cyclosporine therapies. Based on our review of the literature, we are presenting the first case of FUMHD treated with pentoxifylline and the third case of FUMHD successfully treated with cyclosporine. These agents may be of therapeutic benefit in the treatment of FUMHD, in part by suppressing tumor necrosis factor-alpha, which we believe may mediate the disease process. PMID:23005254

Uzoma, Miranda A; Wilkerson, Michael G; Carr, Vicki L; Westhoven, Gail S; Raimer, Sharon A S

2014-01-01

164

Chest radiography for predicting etiology of febrile illness among inpatients in Moshi, Tanzania  

PubMed Central

AIM To describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting. MATERIALS AND METHODS Febrile patients were enrolled in Moshi, Tanzania, and chest radiographs were evaluated by radiologists in Tanzania and the United States. Radiologists were blinded to the results of extensive laboratory evaluations to determine the cause of disease. RESULTS Of 870 febrile patients, 515 (59.2%) had a chest radiograph available; including 268 (66.5%) of the adults and adolescents, the remainder were children and infants. One hundred and nineteen (44.4%) adults and 51 (20.6%) children were human immunodeficiency virus (HIV)-infected. Among adults, radiographic abnormalities were present in 139 (51.9%), including 77 (28.7%) with homogeneous and heterogeneous lung opacities, 26 (9.7%) with lung nodules, 25 (9.3%) with pleural effusion, 23 (8.6%) with cardiomegaly, and 13 (4.9%) with lymphadenopathy. Among children, radiographic abnormalities were present in 87 (35.2%), including 76 (30.8%) with homogeneous and heterogeneous lung opacities and six (2.4%) with lymphadenopathy. Among adults and adolescents, the presence of opacities was predictive of Streptococcus pneumoniae and Coxiella burnetii, whereas the presence of pulmonary nodules was predictive of Histoplasma capsulatum and Cryptococcus neoformans. CONCLUSIONS Chest radiograph abnormalities among febrile inpatients are common in northern Tanzania. Chest radiography is a useful adjunct for establishing a causal diagnosis of febrile illness and may provide useful information for patient management, in particular for pneumococcal disease, Q fever, and fungal infections. PMID:23809268

Fiorillo, Suzanne P.; Diefenthal, Helmut C.; Goodman, Philip C.; Ramadhani, Habib O.; Njau, Boniface N.; Morrissey, Anne B.; Maro, Venance P.; Saganda, Wilbrod; Kinabo, Grace D.; Mwako, Mtumwa S.; Bartlett, John A.; Crump, John A.

2013-01-01

165

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

PubMed Central

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

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

2010-01-01

166

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

PubMed Central

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 show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2–0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the Ih current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes. PMID:16819552

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

2006-01-01

167

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

168

A novel syndrome with congenital neutropenia caused by mutations in G6PC3  

PubMed Central

Background Severe congenital neutropenia (SCN) is characterized by early onset of severe bacterial infections due to a paucity of mature neutrophils. There is also an increased risk of leukemia. The genetic causes of SCN are unknown in many patients. Methods Genome-wide genotyping and linkage analysis were performed on two consanguineous pedigrees with a total of five children affected with SCN. Candidate genes from the linkage interval were sequenced. Functional assays and reconstitution experiments were carried out. Results All index patients had susceptibility to bacterial infections and myeloid maturation arrest in the bone marrow; some had structural heart defects and venous angiectasia on the trunk and extremities. Linkage analysis of the two index families yielded a combined multipoint LOD score of 5.74 on a linkage interval on chromosome 17q21. Sequencing of the candidate gene glucose-6-phosphatase catalytic subunit 3 (G6PC3) revealed a homozygous missense mutation in exon 6 in all affected children in the two families, abrogating enzymatic activity of Glucose-6-phosphatase. Neutrophils and fibroblasts of patients had increased susceptibility to apoptosis. Myeloid cells showed evidence of increased endoplasmic reticulum stress and increased activity of GSK3?. We identified seven additional, unrelated SCN patients with syndromic features and distinct biallelic mutations in G6PC3. Conclusions Defective function of G6PC3 defines a novel SCN syndrome associated with cardiac and urogenital malformations. PMID:19118303

Boztug, Kaan; Appaswamy, Giridharan; Ashikov, Angel; Schäffer, Alejandro A.; Salzer, Ulrich; Diestelhorst, Jana; Germeshausen, Manuela; Brandes, Gudrun; Lee-Gossler, Jacqueline; Noyan, Fatih; Gatzke, Anna-Katherina; Minkov, Milen; Greil, Johann; Kratz, Christian; Petropoulou, Theoni; Pellier, Isabelle; Bellanné-Chantelot, Christine; Rezaei, Nima; Mönkemöller, Kirsten; Irani-Hakimeh, Noha; Bakker, Hans; Gerardy-Schahn, Rita; Zeidler, Cornelia; Grimbacher, Bodo; Welte, Karl; Klein, Christoph

2009-01-01

169

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

2014-12-01

170

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

PubMed

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

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

1990-07-01

171

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

PubMed

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

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

2015-01-01

172

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

173

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

174

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

175

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

176

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

177

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

178

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

179

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

PubMed Central

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

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

2014-01-01

180

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

Microsoft Academic Search

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

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

2011-01-01

181

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

182

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

183

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

PubMed Central

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

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

2014-01-01

184

PREVALENCE OF MALARIA AMONG CLINICALLY MALARIA SUSPECTED ACUTE FEBRILE PATIENTS IN ZEWAY HEALTH CENTER, ETHIOPIA.  

PubMed

Malaria diagnosis is a common challenge in developing countries with limited diagnostic services. The common febrile illnesses were assessed from 280 malaria suspected patients and each case was subjected to clinical and laboratory examination of malaria, relapsing fever, typhoid fever, typhus and brucellosis. Data was entered and analyzed using Epi-info version 3.1 software. Malaria accounted for 17 % (CI: 12.6% to 21.4%) of febrile illnesses. The remaining was associated with typhoid fever (18.5%; CI: 13.95% to 23.05%), typhus (17.8%; CI: 13.32% to 22.28%), brucellosis (1%; CI:-0.17% to 2.17%); relapsing fever (2%; CI: 0.36% to 3.64%) and unknown fever cause (44%). About 7% Coinfections were recorded, of which 2% treated as monoinfection. About 1.4 % non malarial patients received antimalarial treatment. Sensitivity and specificity of Carestart Pf/pan RDTs compared to microscopy were 100% and 91%, respectively with positive and negative predictive values of 94% and 100%, respectively. The PPV of each malaria symptoms compared to microscopy were very low than the combined symptoms: fever 17%, sweating 30%, headache 18%, general body ache 22% and loss of appetite 21%. The study findings revealed high proportion of non malarial illness clinically categorized as malaria cases. Relying on parasite based diagnosis is recommended to manage malarial and non malarial cases. PMID:25420658

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

2014-11-25

185

A Prospective Multicenter Study of Microbiologically Defined Infections in Pediatric Cancer Patients With Fever and Neutropenia  

PubMed Central

Background: Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. Methods: Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multicenter study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. Results: MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared with patients without MDI, fever [median, 5 (interquartile range: 3–8) vs. 2 (interquartile range: 1–3) days, P < 0.001] and hospitalization [10 (6–14) vs. 5 (3–8) days, P < 0.001] lasted longer, transfer to the intensive care unit was more likely [13 of 95 (14%) vs. 7 of 346 (2.0%), P < 0.001], and antibiotics were given longer [10 (7–14) vs. 5 (4–7) days, P < 0.001]. Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but also the purposeful omission of coverage for coagulase-negative staphylococci and enterococci was taken into account [81% (95% confidence interval: 68–90) vs. 96.6% (95% confidence interval: 87–99.4), P = 0.004]. Conclusions: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia. PMID:24618935

Kontny, Udo; Nadal, David; Leibundgut, Kurt; Niggli, Felix; Simon, Arne; Kronenberg, Andreas; Frei, Reno; Escobar, Hugo; Kühne, Thomas; Beck-Popovic, Maja; Bodmer, Nicole; Ammann, Roland A.

2014-01-01

186

Febrile seizures  

MedlinePLUS

... seizures. Pediatrics . 2008;121:1281-1286. Mick NW. Pediatric fever. In: Marx JA, Hockberger RS, Walls RM, et al., eds. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, Pa: ...

187

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

PubMed Central

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

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

2003-01-01

188

Procalcitonin as a potent marker of bacterial infection in febrile Afro-Caribbean patients at the emergency department.  

PubMed

Procalcitonin (PCT) has been shown to be of additional value in the work-up of a febrile patient. This study is the first to investigate the additional value of PCT in an Afro-Caribbean febrile population at the emergency department (ED) of a general hospital. Febrile patients were included at the ED. Prospective, blinded PCT measurements were performed in patients with a microbiologically or serologically confirmed diagnosis or a strongly suspected diagnosis on clinical grounds. PCT analysis was performed in 93 patients. PCT levels differentiated well between confirmed bacterial and confirmed viral infection (area under the curve [AUC] of 0.82, sensitivity 85%, specificity 69%, cut-off 0.24 ng/mL), between confirmed bacterial infection and non-infectious fever (AUC of 0.84, sensitivity 90%, specificity 71%, cut-off 0.21 ng/mL) and between all bacterial infections (confirmed and suspected) and non-infectious fever (AUC of 0.80, sensitivity 85%, specificity 71%, cut-off 0.21 ng/mL). C-reactive protein (CRP) levels were shown to be less accurate when comparing the same groups. This is the first study showing that, in a non-Caucasian febrile population at the ED, PCT is a more valuable marker of bacterial infection than CRP. These results may improve diagnostics and eventually decrease antibiotic prescriptions in resource-limited settings. PMID:21594556

Limper, M; de Kruif, M D; Ajubi, N E; van Zanten, A P; Brandjes, D P M; Duits, A J; van Gorp, E C M

2011-07-01

189

Detection of “Candidatus Neoehrlichia mikurensis” in Two Patients with Severe Febrile Illnesses: Evidence for a European Sequence Variant?  

PubMed Central

Recently, a new genus of Anaplasmataceae termed “Candidatus Neoehrlichia” was discovered in ticks and rodents. Here, we report on two patients who suffered from febrile bacteremia due to “Candidatus Neoehrlichia mikurensis” associated with thrombotic or hemorrhagic events. 16S rRNA and groEL gene sequencing provided evidence of three groups of sequence variants. PMID:20519481

von Loewenich, Friederike D.; Geißdörfer, Walter; Disqué, Claudia; Matten, Jens; Schett, Georg; Sakka, Samir G.; Bogdan, Christian

2010-01-01

190

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

PubMed Central

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

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

2013-01-01

191

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

192

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

193

Bacillus cereus pneumonia in a patient with acute lymphoblastic leukemia  

Microsoft Academic Search

Reported here is a case of Bacillus cereus pneumonia that occurred in a patient with acute lymphoblastic leukemia. The presentation was severe, essentially marked by respiratory distress and pleuritic chest pain. Classic empirical treatment initiated for febrile neutropenia did not cover this rare pathogen and appropriate therapy was therefore delayed. B. cereus is most often a culture contaminant, but it

J. Frankard; R. Li; F. Taccone; M. J. Struelens; F. Jacobs; A. Kentos

2004-01-01

194

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

195

Concurrent protracted febrile myalgia syndrome in a child with diabetic ketoacidosis.  

PubMed

Familial Mediterranean Fever (FMF), characterized by recurrent attacks of inflammation in predominantly serosal and synovial membranes, is caused by MEFV gene mutations resulting in abnormal pyrin. Protracted febrile myalgia syndrome (PFMS), a kind of vasculitis requiring corticosteroid treatment, is associated with M694V mutation of MEFV gene. Here, we report a case where the patient developed PFMS leading to the diagnosis of FMF concurrently at the time of treatment for diabetic ketoacidosis (DKA) of new-onset type 1 diabetes mellitus and discuss the possible mechanisms of simultaneous DKA and FMF-associated PFMS. DKA-associated cytokine release may be a predisposing factor or trigger for FMF-associated PFMS. PMID:22487161

Demir, Korcan; Carman, Kür?at B; Kasap, Belde

2012-09-01

196

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

PubMed

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

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

2014-08-01

197

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

198

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

PubMed Central

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

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

2013-01-01

199

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

PubMed Central

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

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

2014-01-01

200

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

PubMed Central

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

201

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

202

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

PubMed

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

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

2014-11-14

203

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

204

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

205

A possible role for endogenous peripheral corticotrophin-releasing factor-41 in the febrile response of conscious rabbits.  

PubMed

1. The actions of peripheral corticotrophin-releasing factor-41 (CRF-41) on the febrile responses of conscious rabbits induced by peripherally administered polyinosinic.polycytidylic acid (poly(I).poly(C)) have been studied using a CRF-41 receptor antagonist (alpha-helical CRF(9-41) and anti-CRF-41 monoclonal antibodies. 2. Temperature responses were monitored continuously using rectal thermistor probes. Test substances were administered intravenously (i.v.), or for central CRF-41 antagonism experiments, via an indwelling third ventricle cannula (I.C.V.). Blood samples were taken at time intervals from a marginal ear vein and plasma cortisol 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. 4. The febrile response to poly(I).poly(C) (2.5 micrograms/kg I.V.) was antagonized by blockade of peripheral CRF-41 actions using either monoclonal anti-CRF-41 antibodies (2.5 mg/kg i.v.) or the CRF-41 receptor antagonist (alpha-helical CRF(9-41); 25 micrograms/kg i.v.) administered 5 min prior to the pyrogen. 5. Centrally administered CRF-41 receptor antagonist (2.5 micrograms/kg I.C.V.) failed to affect the febrile response to poly(I).poly(C) (2.5 micrograms/kg i.v.). 6. CRF-41 immunoneutralization after the onset of temperature rises caused an immediate and significant defervescence. 7. In conclusion, these results suggest a modulatory pro-pyretic role for endogenous peripheral CRF-41 in the febrile responses to poly(I).poly(C). PMID:8229843

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

1993-06-01

206

Association between use of air-conditioning or fan and survival of elderly febrile patients: a prospective study.  

PubMed

Elderly individuals are more susceptible to excess summer heat. We sought to examine whether the use of cooling systems (air-conditioning or fan) affected the clinical outcomes of elderly febrile patients. We prospectively followed elderly (? 75 years old) febrile patients requesting the medical services of the SOS Doctors (a network of physicians performing house-call visits) from July 10 to August 20, 2011. Patients who used cooling systems ("users") were compared with those who did not ("non-users") regarding mortality, clinical outcome of primary illness (improvement or deterioration), and emergency hospitalization. Prospectively collected data were available for 339 individual elderly febrile patients. "Users" had lower mortality (10 % vs. 19 %, p?febrile patients living in a large city. Large prospective studies are warranted in order to provide further insight into potential individual and public health initiatives aiming to alleviate the impact of excess summer heat on the health of elderly patients. PMID:23532568

Theocharis, G; Tansarli, G S; Mavros, M N; Spiropoulos, T; Barbas, S G; Falagas, M E

2013-09-01

207

Texture analysis of high resolution MRI allows discrimination between febrile and afebrile initial precipitating injury in mesial temporal sclerosis.  

PubMed

A computational pipeline combining texture analysis and pattern classification algorithms was developed for investigating associations between high-resolution MRI features and histological data. This methodology was tested in the study of dentate gyrus images of sclerotic hippocampi resected from refractory epilepsy patients. Images were acquired using a simple surface coil in a 3.0T MRI scanner. All specimens were subsequently submitted to histological semiquantitative evaluation. The computational pipeline was applied for classifying pixels according to: a) dentate gyrus histological parameters and b) patients' febrile or afebrile initial precipitating insult history. The pipeline results for febrile and afebrile patients achieved 70% classification accuracy, with 78% sensitivity and 80% specificity [area under the reader observer characteristics (ROC) curve: 0.89]. The analysis of the histological data alone was not sufficient to achieve significant power to separate febrile and afebrile groups. Interesting enough, the results from our approach did not show significant correlation with histological parameters (which per se were not enough to classify patient groups). These results showed the potential of adding computational texture analysis together with classification methods for detecting subtle MRI signal differences, a method sufficient to provide good clinical classification. A wide range of applications of this pipeline can also be used in other areas of medical imaging. PMID:22287318

de Carvalho Alegro, Maryana; Valotta Silva, Alexandre; Yumi Bando, Silvia; de Deus Lopes, Roseli; Martins de Castro, Luiz Henrique; Hungtsu, Wen; Moreira-Filho, Carlos Alberto; Amaro, Edson

2012-11-01

208

Factors associated with mortality in febrile patients in a government referral hospital in the kenema district of sierra leone.  

PubMed

There is a paucity of data on the etiologies and outcomes of febrile illness in rural Sierra Leone, especially in the Lassa-endemic district of Kenema. We conducted a retrospective study of patients with subjective or documented fever (T ? 38.0°C) who were admitted to a rural tertiary care hospital in Kenema between November 1, 2011 and October 31, 2012. Of 854 patients admitted during the study period, 429 (50.2%) patients had fever on admission. The most common diagnoses were malaria (27.3%), pneumonia (5.1%), and Lassa fever (4.9%). However, 53.4% of febrile patients had no diagnosis at discharge. The in-hospital mortality rate was 18.9% and associated with documented temperature ? 38.0°C (adjusted odds ratio [AOR] = 2.89, P = 0.001) and lack of diagnosis at discharge (AOR = 2.04, P = 0.03). Failure to diagnose the majority of febrile adults and its association with increased mortality highlight the need for improved diagnostic capacity to improve patient outcomes. PMID:25404077

Roth, Prerana J; Grant, Donald S; Ngegbai, Amara S; Schieffelin, John; McClelland, R Scott; Jarrett, Olamide D

2015-01-01

209

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

PubMed

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

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

2014-06-01

210

Repetition Blindness Occurs in Nonwords  

ERIC Educational Resources Information Center

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

Harris, Catherine L.; Morris, Alison L.

2004-01-01

211

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.

212

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

PubMed

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

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

2012-03-01

213

Etiology of acute undifferentiated febrile illness in the Amazon basin of Ecuador.  

PubMed

We conducted a longitudinal observational study of 533 patients presenting to two hospitals in the Ecuadorean Amazon basin with acute undifferentiated febrile illness (AUFI) from 2001 through 2004. Viral isolation, reverse transcription-polymerase chain reaction (RT-PCR), IgM seroconversion, and malaria smears identified pathogens responsible for fever in 122 (40.1%) of 304 patients who provided both acute and convalescent blood samples. Leptospirosis was found in 40 (13.2%), malaria in 38 (12.5%), rickettsioses in 18 (5.9%), dengue fever in 16 (5.3%), Q fever in 15 (4.9%), brucellosis in 4 (1.3%), Ilhéus infection in 3 (1.0%), and Venezuelan equine encephalitis (VEE), Oropouche, and St. Louis encephalitis virus infections in less than 1% of these patients. Viral isolation and RT-PCR on another 229 participants who provided only acute samples identified 3 cases of dengue fever, 2 of VEE, and 1 of Ilhéus. None of these pathogens, except for malaria, had previously been detected in the study area. PMID:19556580

Manock, Stephen R; Jacobsen, Kathryn H; de Bravo, Narcisa Brito; Russell, Kevin L; Negrete, Monica; Olson, James G; Sanchez, José L; Blair, Patrick J; Smalligan, Roger D; Quist, Brad K; Espín, Juan Freire; Espinoza, Willan R; MacCormick, Fiona; Fleming, Lila C; Kochel, Tadeusz

2009-07-01

214

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

PubMed Central

In October 2009, two–3 months after an outbreak of a febrile disease with joint pain on the eastern coast of Madagascar, we assessed serologic markers for chikungunya virus (CHIKV), dengue virus (DENV), and Rift Valley fever virus (RVFV) in 1,244 pregnant women at 6 locations. In 2 eastern coast towns, IgG seroprevalence against CHIKV was 45% and 23%; IgM seroprevalence was 28% and 5%. IgG seroprevalence against DENV was 17% and 11%. No anti-DENV IgM was detected. At 4 locations, 450–1,300 m high, IgG seroprevalence against CHIKV was 0%–3%, suggesting CHIKV had not spread to higher inland-altitudes. Four women had IgG against RVFV, probably antibodies from a 2008 epidemic. Most (78%) women from coastal locations with CHIKV-specific IgG reported joint pain and stiffness; 21% reported no symptoms. CHIKV infection was significantly associated with high bodyweight. The outbreak was an isolated CHIKV epidemic without relevant DENV co-transmission. PMID:23092548

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

2012-01-01

215

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

216

Febrile-Range Hyperthermia Modifies Endothelial and Neutrophilic Functions to Promote Extravasation  

PubMed Central

Acute respiratory distress syndrome (ARDS) is a neutrophil (polymorphonuclear leukocyte; PMN)–driven lung injury that is associated with fever and heat-stroke, and involves approximately 40% mortality. In murine models of acute lung injury (ALI), febrile-range hyperthermia (FRH) enhanced PMN accumulation, vascular permeability, and epithelial injury, in part by augmenting pulmonary cysteine-x-cysteine (CXC) chemokine expression. To determine whether FRH increases chemokine responsiveness within the lung, we used in vivo and in vitro models that bypass the endogenous generation of chemokines. We measured PMN transalveolar migration (TAM) in mice after intratracheal instillations of the human CXC chemokine IL-8 in vivo, and of IL-8–directed PMN transendothelial migration (TEM) through human lung microvascular endothelial cell (HMVEC-L) monolayers in vitro. Pre-exposure to FRH increased in vivo IL-8–directed PMN TAM by 23.5-fold and in vitro TEM by 7-fold. Adoptive PMN transfer demonstrated that enhanced PMN TAM required both PMN donors and recipients to be exposed to FRH, suggesting interdependent effects on PMNs and endothelium. FRH exposure caused the activation of extracellular signal–regulated kinase (ERK) and p38 mitogen–activated protein kinase in lung homogenates and circulating PMNs, with an associated increase in HSP27 phosphorylation and stress-fiber formation. The inhibition of these signaling pathways with U0126 and SB203580 blocked the effects of FRH on PMN extravasation in vivo and in vitro. Collectively, these results (1) demonstrate that FRH augments chemokine-directed PMN extravasation through direct effects on endothelium and PMNs, (2) identify ERK and p38 signaling pathways in the effect, and (3) underscore the complex effects of physiologic temperature change on innate immune function and its potential consequences for lung injury. PMID:22281986

Tulapurkar, Mohan E.; Almutairy, Eid A.; Shah, Nirav G.; He, Ju-ren; Puche, Adam C.; Shapiro, Paul; Singh, Ishwar S.

2012-01-01

217

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

PubMed Central

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

Potts, James A.; Rothman, Alan L.

2009-01-01

218

Temperature-Sensitive Cav1.2 Calcium Channels Support Intrinsic Firing of Pyramidal Neurons and Provide a Target for the Treatment of Febrile Seizures  

PubMed Central

Febrile seizures are associated with increased brain temperature and are often resistant to treatments with antiepileptic drugs, such as carbamazepine and phenytoin, which are sodium channel blockers. Although they are clearly correlated with the hyperthermic condition, the precise cellular mechanisms of febrile seizures remain unclear. We performed patch-clamp recordings from pyramidal cells in acute rat brain slices at temperatures up to 40°C and found that, at ?37°C, L-type calcium channels are active at unexpectedly hyperpolarized potentials and drive intrinsic firing, which is also supported by a temperature-dependent, gadolinium-sensitive sodium conductance. Pharmacological data, RT-PCR, and the current persistence in Cav1.3 knock-out mice suggested a critical contribution of Cav1.2 subunits to the temperature-dependent intrinsic firing, which was blocked by nimodipine. Because intrinsic firing may play a critical role in febrile seizures, we tested the effect of nimodipine in an in vivo model of febrile seizures and found that this drug dramatically reduces both the incidence and duration of febrile seizures in rat pups, suggesting new possibilities of intervention for this important pathological condition. PMID:23761887

Radzicki, Daniel; Yau, Hau-Jie; Pollema-Mays, Sarah L.; Mlsna, Lauren; Cho, Kangho; Koh, Sookyong

2013-01-01

219

An Analysis of Hematological Parameters as a Diagnostic test for Malaria in Patients with Acute Febrile Illness: An Institutional Experience  

PubMed Central

Objectives Hematological changes are among the most common complications encountered in malaria. This study analyzes and statistically evaluates the hematological changes as a diagnostic test for malaria in patients with acute febrile illness and whether these could guide the physician to institute specific antimalarial treatment. Methods The present study was an observational study, conducted from January to December 2012. A total of 723 patients presenting with acute febrile illness at our hospital were evaluated. A complete blood count and malarial parasite microscopy were performed for each patient. Results The findings showed that 172 out of 723 patients (24%) were diagnosed to have malaria by positive smear report. There were 121 males and 51 females with a male to female ratio of 2.3:1. Maximum number of cases were seen in the 20-30 years age group. There was a statistically significant reduction in hemoglobin (p<0.005), platelet count (p<0.001) and total leukocyte count (p<0.001) levels in patients with malaria compared to those without the disease. Likelihood ratios for a positive result of platelets (6.2) and total leukocyte count (3.4) was relevant as compared to hemoglobin (1.61) and Red cell distribution width (1.79). The negative predictive values for hemoglobin (79%), total leukocyte count (86%), platelets (94%) and Red cell distribution width (93%) were significant. Red cell distribution width values were found to be higher in patients with malaria than in patients without malaria (p<0.001). Conclusion This study revealed that routinely used laboratory findings such as hemoglobin, leukocytes, platelet counts and even red cell distribution width values can provide a diagnostic clue in a patient with acute febrile illness in endemic areas, thus increasing the probability of malaria and enhancing prompt initiation of treatment. PMID:24498476

Jairajpuri, Zeeba Shamim; Rana, Safia; Hassan, Mohd Jaseem; Nabi, Farhat; Jetley, Sujata

2014-01-01

220

Population Pharmacokinetic Study of Amikacin Administered Once or Twice Daily to Febrile, Severely Neutropenic Adults  

PubMed Central

Once-daily (o.d.) administration of 20 mg of amikacin per kg of body weight to neutropenic patients has been validated by clinical studies, but amikacin pharmacokinetics have been documented only for the 7.5-mg/kg twice-daily (b.i.d.) regimen in this population. In order to determine in neutropenic patients (i) the influence of the dosing regimen on the kinetics of amikacin, (ii) the linearity of kinetics of amikacin in the range of 7.5 to 20 mg/kg, and (iii) the influence of patient characteristics on the disposition of amikacin and (iv) to provide a rationale for dosing recommendations, we evaluated the population pharmacokinetics of amikacin administered to 57 febrile neutropenic adults (neutrophil count, <500/mm3) being treated for a hematological disorder and receiving amikacin at 7.5 mg/kg b.i.d. (n = 29) or 20 mg/kg o.d. (n = 28) and administered intravenously over 0.5 h. A total of 278 blood samples were obtained (1 to 14 samples per patient) during one or several administration intervals (1 to 47). Serum amikacin levels were measured by the enzyme-multiplied immunoassay technique. A mixed-effect modeling approach was used to fit a bicompartmental model to the data (NONMEM software). The influences of the dosing regimen and the demographic and biological indices on the pharmacokinetic parameters of amikacin were evaluated by the maximum-likelihood ratio test on the population model. The dosing regimen had no influence on amikacin pharmacokinetic parameters, i.e., the kinetics of amikacin were linear over the range of 7.5 to 20 mg/kg. Amikacin elimination clearance (CL) was only correlated with creatinine clearance or its covariates, namely, sex, age, body weight, and serum creatinine level. The interindividual variability of CL was 21%, while those of the central volume of distribution, the distribution clearance, and the tissue volume of distribution were 15, 30, and 25%, respectively. On the basis of the expected distribution of amikacin concentrations in this population, dosing recommendations as a function of creatinine clearance (CLCR) are proposed: for patients with normal renal function (CLCR of 80 to 130 ml/min), 20 mg/kg o.d. is recommended, whereas for patients with severe renal impairment (CLCR, 10 to 20 ml/min), a dosage of 17 mg/kg every 48 h is recommended. PMID:9559795

Tod, Michel; Lortholary, Olivier; Seytre, Delphine; Semaoun, Rémi; Uzzan, Bernard; Guillevin, Loïc; Casassus, Philippe; Petitjean, Olivier

1998-01-01

221

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...

222

Scrub typhus in patients reporting with acute febrile illness at a tertiary health care institution in Goa  

PubMed Central

Background & objectives: Scrub typhus is one of the differential diagnoses of haemorrhagic fevers especially if associated with jaundice and/or renal failure. Goa State in the western region of India has been witnessing increased incidence of such fevers, therefore, the present study was undertaken to identify whether scrub typhus is the aetiological agent. Methods: Adult patients presenting with undiagnosed febrile illness between June 2009 to October 2010, were evaluated. Testing was done using a commercial ELISA kit for specific IgM antibodies against Orientia tsutsugamushi. Results: Of the 44 patients included in the study, 15 (34%) were found to be positive for IGM antibodies against O. tsutsugamushi. The cases were seen mainly in the months between July to November. The common symptoms noted were fever, myalgias, gastrointestinal complaints, followed by breathlessness, rash and jaundice. The pathognomonic features such as eschar and lymphadenopathy were seen only in two patients. Nearly two third of the patients had leukocytosis (67%) and low serum albumin (60%). The most common complication noticed was hepatitis (80%) followed by acute respiratory distress syndrome (ARDS) (60%), thrombocytopenia (40%) and acute renal failure (33%). Five patients died in the course of illness. Interpretation & conclusions: Our results showed that scrub typhus should be considered in the differential diagnosis of acute febrile illness associated with gastrointestinal symptoms, rash, myalgia, including those with organ dysfunctions such as hepatorenal syndrome, coagulopathy or ARDS. Empirical treatment with doxycycline or macrolides may be given in cases with strong suspicion of scrub typhus. PMID:23391799

Narvencar, Kedareshwar P.S.; Rodrigues, Savio; Nevrekar, Ramnath P.; Dias, Lydia; Dias, Amit; Vaz, Marina; Gomes, E.

2012-01-01

223

Mucormycosis and chromoblastomycosis occurring in a patient with leprosy type 2 reaction under prolonged corticosteroid and thalidomide therapy.  

PubMed

Mucormycosis is an uncommon fungal infection caused by Mucorales. It frequently occurs in patients with neutropenia, diabetes, malignancy and on corticoid therapy. However, it is rare in patients with AIDS. Clinical disease can be manifested in several forms. The case reported illustrates the rare occurrence of chromoblastomycosis and mucormycosis in an immunosuppressed patient with multibacillary leprosy, under prolonged corticosteroid and thalidomide therapy to control leprosy type 2 reaction. Neutrophil dysfunction, thalidomide therapy and work activities are some of the risk factors in this case. Chromoblastomycosis was treated by surgical excision and mucormycosis with amphotericin B. Although the prognosis of mucormycosis is generally poor, in the reported case the patient recovered successfully. This case should alert dermatologists to possible opportunistic infections in immunosuppressed patients. PMID:23044573

Basílio, Flávia Machado Alves; Hammerschmidt, Mariana; Mukai, Maira Mitsue; Werner, Betina; Pinheiro, Rosângela Lameira; Moritz, Sandra

2012-01-01

224

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

225

Acupuncture for Chemotherapy-Induced Neutropenia in Patients with Gynecologic Malignancies: A Pilot Randomized, Sham-Controlled Clinical Trial  

PubMed Central

Abstract Objectives The objective of this study was to investigate the effect of acupuncture administered during myelosuppressive chemotherapy on white blood cell (WBC) count and absolute neutrophil count (ANC) in patients with ovarian cancer. Design This study is a pilot, randomized, sham-controlled clinical trial. Patients received active acupuncture versus sham acupuncture while undergoing chemotherapy. A standardized acupuncture protocol was employed with manual and electrostimulation. The frequency of treatment was 2–3 times per week for a total of 10 sessions, starting 1 week before the second cycle of chemotherapy. Setting The setting was two outpatient academic centers for patients with cancer. Subjects Twenty-one (21) newly diagnosed and recurrent ovarian cancer patients were the subjects. Outcome measures WBC count, ANC, and plasma granulocyte colony-stimulating factor (G-CSF) were assessed weekly. Results The median leukocyte value in the acupuncture arm at the first day of the third cycle of chemotherapy was significantly higher than in the control arm after adjusting for baseline value (8600 cells/?L, range: 4800–12,000 versus 4400 cell/?L, range: 2300–10,000) (p = 0.046). The incidence of grade 2–4 leukopenia was less in the acupuncture arm than in the sham arm (30% versus 90%; p = 0.02). However, the median leukocyte nadir, neutrophil nadir, and recovering ANC were all higher but not statistically significantly different (p = 0.116–0.16), after adjusting for baseline differences. There were no statistically significant differences in plasma G-CSF between the two groups. Conclusions We observed clinically relevant trends of higher WBC values during one cycle of chemotherapy in patients with ovarian cancer, which suggests a potential myeloprotective effect of acupuncture. A larger trial is warranted to more definitively determine the efficacy of acupuncture on clinically important outcomes of chemotherapy-induced neutropenia. PMID:19552597

Lu, Weidong; Matulonis, Ursula A.; Doherty-Gilman, Anne; Lee, Hang; Dean-Clower, Elizabeth; Rosulek, Andrew; Gibson, Carolyn; Goodman, Annekathryn; Davis, Roger B.; Buring, Julie E.; Wayne, Peter M.; Rosenthal, David S.; Penson, Richard T.

2009-01-01

226

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

227

Bortezomib inhibits STAT5-dependent degradation of LEF-1, inducing granulocytic differentiation in congenital neutropenia CD34(+) cells.  

PubMed

The transcription factor lymphoid enhancer-binding factor 1 (LEF-1), which plays a definitive role in granulocyte colony-stimulating factor (G-CSF) receptor-triggered granulopoiesis, is downregulated in granulocytic progenitors of severe congenital neutropenia (CN) patients. However, the exact mechanism of LEF-1 downregulation is unclear. CN patients are responsive to therapeutically high doses of G-CSF and are at increased risk of developing acute myeloid leukemia. The normal expression of LEF-1 in monocytes and lymphocytes, whose differentiation is unaffected in CN, suggests the presence of a granulopoiesis-specific mechanism downstream of G-CSF receptor signaling that leads to LEF-1 downregulation. Signal transducer and activator of transcription 5 (STAT5) is activated by G-CSF and is hyperactivated in acute myeloid leukemia. Here, we investigated the effects of activated STAT5 on LEF-1 expression and functions in hematopoietic progenitor cells. We demonstrated that constitutively active STAT5a (caSTAT5a) inhibited LEF-1-dependent autoregulation of the LEF-1 gene promoter by binding to the LEF-1 protein, recruiting Nemo-like kinase and the E3 ubiquitin-ligase NARF to LEF-1, leading to LEF-1 ubiquitination and a reduction in LEF-1 protein levels. The proteasome inhibitor bortezomib reversed the defective G-CSF-triggered granulocytic differentiation of CD34(+) cells from CN patients in vitro, an effect that was accompanied by restoration of LEF-1 protein levels and LEF-1 messenger RNA autoregulation. Taken together, our data define a novel mechanism of LEF-1 downregulation in CN patients via enhanced ubiquitination and degradation of LEF-1 protein by hyperactivated STAT5. PMID:24394665

Gupta, Kshama; Kuznetsova, Inna; Klimenkova, Olga; Klimiankou, Maksim; Meyer, Johann; Moore, Malcolm A S; Zeidler, Cornelia; Welte, Karl; Skokowa, Julia

2014-04-17

228

78 FR 48175 - Retrospective Review of Draft Guidance Documents Issued Before 2010; Withdrawal of Guidances  

Federal Register 2010, 2011, 2012, 2013

...bloodstream infections, febrile neutropenia, gonorrhea, Lyme disease, streptococcal pharyngitis and tonsillitis, uncomplicated...Drugs for Treatment''--issued July 1998. 7. ``Lyme Disease--Developing Antimicrobial Drugs for...

2013-08-07

229

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...

230

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...

231

Use of drugs, perceived drug efficacy and preferred providers for febrile children: implications for home management of fever  

PubMed Central

Background Community distribution of anti-malarials and antibiotics has been recommended as a strategy to reduce the under-five mortality due to febrile illnesses in sub-Saharan Africa. However, drugs distributed in these interventions have been considered weak by some caretakers and utilization of community medicine distributors has been low. The aim of the study was to explore caretakers' use of drugs, perceptions of drug efficacy and preferred providers for febrile children in order to make suggestions for community management of pneumonia and malaria. Methods The study was conducted in eastern Uganda using four focus group discussions with fathers and mothers of children under five; and eight key informant interviews with health workers in government and non-governmental organization facilities, community medicine distributors, and attendants in drug shops and private clinics. Caretakers were asked the drugs they use for treatment of fever, why they considered them efficacious, and the providers they go to and why they go there. Health providers were interviewed on their opinions of caretakers' perceptions of drugs and providers. Analysis was done using content analysis. Results Drugs that have been phased out as first-line treatment for malaria, such as chloroquine and sulphadoxine/pyrimethamine, are still perceived as efficacious. Use of drugs depended on perception of the disease, cost and drug availability. There were divergent views about drug efficacy concerning drug combinations, side effects, packaging, or using drugs over time. Bitter taste and high cost signified high efficacy for anti-malarials. Government facilities were preferred for conducting diagnostic investigations and attending to serious illnesses, but often lacked drugs and did not treat people fast. Drug shops were preferred for having a variety of drugs, attending to clients promptly and offering treatment on credit. However, drug shops were considered disadvantageous since they lacked diagnostic capability and had unqualified providers. Conclusion Community views about drug efficacy are divergent and some may divert caretakers from obtaining efficacious drugs for febrile illness. Interventions should address these perceptions, equip community medicine distributors with capacity to do diagnostic investigations and provide a constant supply of drugs. Subsidized efficacious drugs could be made available in the private sector. PMID:19523220

Rutebemberwa, Elizeus; Nsabagasani, Xavier; Pariyo, George; Tomson, Goran; Peterson, Stefan; Kallander, Karin

2009-01-01

232

Scrub Typhus Is an Under-recognized Cause of Acute Febrile Illness with Acute Kidney Injury in India  

PubMed Central

Background Infection-related acute kidney injury (AKI) is an important preventable cause of morbidity and mortality in the tropical region. The prevalence and outcome of kidney involvement, especially AKI, in scrub typhus is not known. We investigated all patients with undiagnosed fever and multisystem involvement for scrub typhus and present the pattern of renal involvement seen. Methods From September 2011 to November 2012, blood samples of all the patients with unexplained acute febrile illness and/or varying organ involvement were evaluated for evidence of scrub typhus. A confirmed case of scrub typhus was defined as one with detectable Orientia tsutsugamushi deoxyribonucleic acid (DNA) in patient's blood sample by nested polymerase chain reaction (PCR) targeting the gene encoding 56-kDa antigen and without any alternative etiological diagnosis. Renal involvement was defined by demonstration of abnormal urinalysis and/or reduced glomerular filtration rate. AKI was defined as per Kidney Disease: Improving Global Outcomes (KDIGO) definition. Results Out of 201 patients tested during this period, 49 were positive by nested PCR for scrub typhus. Mean age of study population was 34.1±14.4 (range 11–65) years. Majority were males and a seasonal trend was evident with most cases following the rainy season. Overall, renal abnormalities were seen in 82% patients, 53% of patients had AKI (stage 1, 2 and 3 in 10%, 8% and 35%, respectively). The urinalysis was abnormal in 61%, with dipstick positive albuminuria (55%) and microscopic hematuria (16%) being most common. Acute respiratory distress syndrome (ARDS) and shock were seen in 57% and 16% of patients, respectively. Hyperbilirubinemia was associated with AKI (p?=?0.013). A total of 8 patients (including three with dialysis dependent AKI) expired whereas rest all made uneventful recovery. Jaundice, oliguria, ARDS and AKI were associated with mortality. However, after multivariate analysis, only oliguric AKI remained a significant predictor of mortality (p?=?0.002). Conclusions Scrub typhus was diagnosed in 24% of patients presenting with unexplained febrile illness according to a strict case definition not previously used in this region. Renal abnormalities were seen in almost 82% of all patients with evidence of AKI in 53%. Our finding is contrary to current perception that scrub typhus rarely causes renal dysfunction. We suggest that all patients with unexplained febrile illness be investigated for scrub typhus and AKI looked for in scrub typhus patients. PMID:24498445

Kumar, Vivek; Kumar, Vinod; Yadav, Ashok K.; Iyengar, Sreenivasa; Bhalla, Ashish; Sharma, Navneet; Aggarwal, Ritesh; Jain, Sanjay; Jha, Vivekanand

2014-01-01

233

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.

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

2015-01-01

234

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

235

Evidence of a Major Reservoir of Non-Malarial Febrile Diseases in Malaria-Endemic Regions of Bangladesh  

PubMed Central

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

2014-01-01

236

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

237

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

238

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

239

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

240

Health-related quality of life for pediatric emergency department febrile illnesses: an Evaluation of the Pediatric Quality of Life Inventory™ 4.0 generic core scales  

Microsoft Academic Search

OBJECTIVE: We sought to assess the validity and short-term responsiveness of the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL™) for febrile illnesses evaluated in the pediatric emergency department (ED). DESIGN: Prospective cohort study of children 2–18 years discharged after ED evaluation for fever (? 38°C). Self-administered, parent-report of health-related quality of life (HRQOL) was assessed using the

Rakesh D Mistry; Molly W Stevens; Marc H Gorelick

2009-01-01

241

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

242

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

243

Immunoblot studies to analyze antibody to the Rickettsia typhi group antigen in sera from patients with acute febrile cerebrovasculitis.  

PubMed Central

In 1986, an unusual syndrome of acute febrile cerebrovasculitis in the Piedmont Region of Virginia was reported. All patients had encephalopathy and prior exposure to both a sylvan environment and flea-infested animals. The initial serological studies suggested a rickettsial origin, corroborating clinical, epidemiological, and histopathological findings. Sera from four of five patients were subsequently studied by immunoblotting. Unabsorbed and absorbed sera were tested with electrophoresed and electroblotted Rickettsia typhi, Legionella bozemanii, and Proteus vulgaris OX19 antigens. The unabsorbed sera reacted with all three antigens. The P. vulgaris- and L. bozemanii-absorbed sera reacted with R. typhi only and without significantly less intensity. In contrast, the reactivity of R. typhi-absorbed sera was significantly lower with all three antigens. These results indicate that these patients had specific antibodies to a typhus group antigen. Although our findings suggest that a rickettsia of the typhus group may have caused this syndrome, no definitive diagnosis could be achieved because a rickettsial organism was not isolated. Images PMID:1723073

Hechemy, K E; Fox, J A; Gröschel, D H; Hayden, F G; Wenzel, R P

1991-01-01

244

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

PubMed

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

2011-10-01

245

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

246

A self-limited febrile illness produced in guinea pigs associated with oral administration of Legionella pneumophila.  

PubMed

The presumed route of human infection by Legionella pneumophila is inhalation. We investigated possible oral transmission of legionellosis in guinea pigs. Fifty-six guinea pigs (group 1) were given virulent L. pneumophila, serogroup 1, in drinking water. Fifty-nine guinea pigs (group 2) were inoculated with L. pneumophila via gastric intubation. Nineteen guinea pigs (group 3) were given heat-killed L. pneumophila in drinking water. Twenty-four guinea pigs (group 4, positive control) were inoculated intraperitoneally with L. pneumophila. Twenty-seven guinea pigs (group 5, negative control) were either intubated gastrically with phosphate-buffered saline or given drinking water without L. pneumophila. Sixty-six of 115 (57%) of the guinea pigs orally inoculated with viable L. pneumophila (groups 1 and 2) had a temperature greater than or equal to 103 degrees F and 8 of 115 (7%) had diarrhea, compared with 0 of 19 (0%) and 0 of 19 (0%), respectively, in group 3 and 1 of 27 (4%) and 0 of 27 (0%), respectively, in group 5. There were no fatalities in groups 1, 2, 3, and 5 compared with 15 of 24 (63%) in group 4. Groups 1, 2, and 4 consistently showed pneumonitis and splenitis. The pneumonitis of groups 1 and 2 was mild, predominantly interstitial, and mainly composed of macrophages; neither gross nor microscopic evidence of aspiration was seen. In group 1, 4 of 29 (14%) guinea pigs tested seroconverted to L. pneumophila compared with 0 of 7 (0%) in group 3 and 0 of 10 (0%) in group 5. In groups 1 and 2 combined, L. pneumophila was isolated from the lung of 5 of 57 (11%) guinea pigs and spleen of 5 of 47 (11%) guinea pigs compared with 0 of 14 guinea pigs in group 5. We conclude that viable L. pneumophila administered orally produces a self-limited febrile illness in guinea pigs. PMID:3181681

Katz, S M; Hammel, J M; Matus, J P; Poropatich, R; Katz, J

1988-12-01

247

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

248

Naturally occurring graphite cones John A. Jaszczaka,  

E-print Network

, and Yury Gogotsic a Department of Physics and the A. E. Seaman Mineral Museum, Michigan Technological and Sciences, and the A. E. Seaman Mineral Museum, Michigan Technological University, Houghton, Michigan, 49931.1 to 10 mm in diameter) [18] occur in calcite boudins up to 30 cm across from the Bancroft shear zone [19

Jaszczak, John A.

249

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

250

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

251

Bullous Emphysema Occurring in Pulmonary Sarcoidosis  

Microsoft Academic Search

We describe a rare case of bullous emphysema occurring in a young male with sarcoidosis. The patient had progressive pulmonary symptoms over 14 years. Chest radiology showed bilateral bullae predominantly of both upper and the left lower lobes and mild bronchiectasis. Pulmonary function tests revealed mild restrictive disease and a severe reduction in diffusion capacity. Loss of alveolar surface area

Heather J. Zar; Randolph P. Cole

1995-01-01

252

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

PubMed Central

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

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

2011-01-01

253

Evaluation of In-Hospital Management for Febrile Illness in Northern Tanzania before and after 2010 World Health Organization Guidelines for the Treatment of Malaria  

PubMed Central

Objective In 2010, the World Health Organization (WHO) published updated guidelines emphasizing and expanding recommendations for a parasitological confirmation of malaria before treating with antimalarials. This study aimed to assess differences in historic (2007–2008) (cohort 1) and recent (2011–2012) (cohort 2) hospital cohorts in the diagnosis and treatment of febrile illness in a low malaria prevalence area of northern Tanzania. Materials and Methods We analyzed data from two prospective cohort studies that enrolled febrile adolescents and adults aged ?13 years. All patients received quality-controlled aerobic blood cultures and malaria smears. We compared patients' discharge diagnoses, treatments, and outcomes to assess changes in the treatment of malaria and bacterial infections. Results In total, 595 febrile inpatients were enrolled from two referral hospitals in Moshi, Tanzania. Laboratory-confirmed malaria was detected in 13 (3.2%) of 402 patients in cohort 1 and 1 (0.5%) of 193 patients in cohort 2 (p?=?0.041). Antimalarials were prescribed to 201 (51.7%) of 389 smear-negative patients in cohort 1 and 97 (50.5%) of 192 smear-negative patients in cohort 2 (p?=?0.794). Bacteremia was diagnosed from standard blood culture in 58 (14.5%) of 401 patients in cohort 1 compared to 18 (9.5%) of 190 patients in cohort 2 (p?=?0.091). In cohort 1, 40 (69.0%) of 58 patients with a positive blood culture received antibacterials compared to 16 (88.9%) of 18 patients in cohort 2 (p?=?0.094). In cohort 1, 43 (10.8%) of the 399 patients with known outcomes died during hospitalization compared with 12 (6.2%) deaths among 193 patients in cohort 2 (p?=?0.073). Discussion In a setting of low malaria transmission, a high proportion of smear-negative patients were diagnosed with malaria and treated with antimalarials despite updated WHO guidelines on malaria treatment. Improved laboratory diagnostics for non-malaria febrile illness might help to curb this practice. PMID:24587056

Moon, Andrew M.; Biggs, Holly M.; Rubach, Matthew P.; Crump, John A.; Maro, Venace P.; Saganda, Wilbrod; Reddy, Elizabeth A.

2014-01-01

254

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

255

Will another damaging earthquake occur in Koyna?  

Microsoft Academic Search

AN earthquake of magnitude 5.1 (Richter scale) occurred on October 17, 1973, near the Koyna Dam (17°23'N, 73°45'E) which experienced a damaging earthquake1 on December 10, 1967. The former earthquake was preceded and followed by several foreshocks and aftershocks. Two of the foreshocks on the same day had magnitudes of the order of 4.0 and there was another significant earthquake

Harsh K. Gupta; B. K. Rastogi

1974-01-01

256

Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) guideline for prophylaxis with granulocyte colony-stimulating factors (G-CSF) in gynecologic malignancies, including breast cancer.  

PubMed

The current knowledge and recommendations on the clinical use of granulocyte colony-stimulating factors (G-CSF) in gynecologic cancers including breast cancer, along with the clinical experience of the members of the working group of the Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO), have been summarized. G-CSF is either administered as primary or secondary prophylaxis of febrile neutropenia. The term "primary prophylaxis" denotes the prophylactic use of G-CSF as early as during the first cycle of a new chemotherapeutic regimen. Secondary prophylaxis, on the other hand, defines the use of G-CSF after development of grade 4 neutropenia or febrile neutropenia in a preceding cycle of a particular chemotherapeutic regimen. When chemotherapy regimens are associated with a > 20 % risk of febrile neutropenia such as TAC (docetaxel-doxorubicin-cyclophosphamide), primary prophylaxis with G-CSF is indicated. When chemotherapy regimens are associated with a 10-20 % risk of febrile neutropenia, the decision for primary prophylaxis with G-CSF is based upon patient-related risk factors such as age > 65 years, previous cytotoxic treatment(s) and/or radiation therapy, preexisting tumor-related neutropenia or bone marrow involvement, preexisting neutropenia, infections/open sores, reduced Karnofsky performance status/WHO performance status and reduced nutritional status, advanced malignant disease, history of prior febrile neutropenia, impaired kidney function, and hepatic failure particularly with hyperbilirubinaemia. The patient's individual overall febrile neutropenia risk should be assessed prior to each chemotherapy cycle. PMID:22739650

Petru, Edgar; Zeimet, Alain Gustave; Sevelda, Paul; Seifert, Michael; Singer, Christian; Hubalek, Michael; Angleitner-Boubenizek, Lukas; Speiser, Paul; Benedicic, Christoph; Stummvoll, Wolfgang; Reinthaller, Alexander

2012-06-01

257

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

258

Alendronate reduces serum TNFa and IL1ß, increases neutrophil counts, and improves bone mineral density and bone metabolism indices in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia\\/osteoporosis  

Microsoft Academic Search

The current study was undertaken to investigate the effect of alendronate on bone mineral density (BMD), bone metabolism markers, and serum bone-resorbing cytokines in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia\\/osteoporosis. Sixteen randomly selected women, 7 with CIN-associated osteoporosis and 9 with CIN-associated osteopenia, and 14 age- and menopausal status-matched healthy volunteers, were enrolled in the study. Patients received 10?mg

Helen A. Papadaki; Christos Tsatsanis; Anna Christoforidou; Niki Malliaraki; Maria Psyllaki; Charis Pontikoglou; Maria Miliaki; Andrew N. Margioris; George D. Eliopoulos

2004-01-01

259

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

260

Nipah virus entry can occur by macropinocytosis  

SciTech Connect

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

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

2009-12-20

261

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

262

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

263

A randomized prospective study of ceftazidime versus ceftazidime plus flucloxacillin in the empiric treatment of febrile episodes in severely neutropenic patients.  

PubMed Central

In a prospective, randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime and flucloxacillin in 100 febrile neutropenic patients. Thirty-four bacteriologically documented infections, of which 26 were bacteremias, in 51 patients were treated with ceftazidime alone. Thirty-four bacteriologically proven infections, of which 29 were bacteremias, in 49 patients were treated with a combination of ceftazidime and flucloxacillin. The clinical response rate for ceftazidime monotherapy was 80%; the bacteriological cure rate was 90%. Efficacy against gram-negative pathogens appeared to be excellent, achieving a 100% cure rate. The clinical response and bacteriological cure rates for the combination were 76 and 86%, respectively. Three superinfections were registered in the ceftazidime group, and four, involving six pathogens, were registered in the combination group. Other side effects of ceftazidime were minimal. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients. It offers the opportunity to avoid the aminoglycosides in first-line treatment. It may be appropriate to combine ceftazidime with cephalothin or vancomycin or to modify therapy if resistant gram-positive strains are encountered. PMID:3909956

de Pauw, B; Williams, K; de Neeff, J; Bothof, T; de Witte, T; Holdrinet, R; Haanen, C

1985-01-01

264

A BFIS-like syndrome with late onset and febrile seizures: suggestive linkage to chromosome 16p11.2-16q12.1.  

PubMed

Benign familial infantile seizures (BFIS) is a dominant idiopathic epilepsy with partial and secondarily generalized seizures with age of onsetr between 3 and 12 months. Here we describe a four-generation family with some characteristic features of BFIS but with unusual clinical signs, in eight affected members with an unusual clinical phenotype. Onset was consistently between 14 and 20 months of age with clusters of complex-partial or generalized tonic-clonic seizures and a high rate of febrile seizures, which have not been described for BFIS previously. All affected members showed multifocal interictal epileptiform discharges in the EEG. The known loci for benign familial neonatal/infantile seizures (BFNS/BFNIS), generalized epilepsy with febrile seizures plus (GEFS+) and the BFIS locus on chromosome 19q were excluded. Further genetic analysis showed suggestive linkage to the major BFIS locus on chromosome 16 between markers D16S690 and D16S3136. This ;;BFIS-like'' syndrome may enlarge the phenotypic spectrum of diseases linked to the chromosome 16 region. PMID:18479394

Weber, Yvonne G; Jacob, Miriam; Weber, Gabriele; Lerche, Holger

2008-11-01

265

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

266

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

267

?,?-Dehydroamino acids in naturally occurring peptides.  

PubMed

?,?-Dehydroamino acids are naturally occurring non-coded amino acids, found primarily in peptides. The review focuses on the type of ?,?-dehydroamino acids, the structure of dehydropeptides, the source of their origin and bioactivity. Dehydropeptides are isolated primarily from bacteria and less often from fungi, marine invertebrates or even higher plants. They reveal mainly antibiotic, antifungal, antitumour, and phytotoxic activity. More than 60 different structures were classified, which often cover broad families of peptides. 37 different structural units containing the ?,?-dehydroamino acid residues were shown including various side chains, Z and E isomers, and main modifications: methylation of peptide bond as well as the introduction of ester group and heterocycle ring. The collected data show the relation between the structure and bioactivity. This allows the activity of compounds, which were not studied in this field, but which belong to a larger peptide family to be predicted. A few examples show that the type of the geometrical isomer of the ?,?-dehydroamino acid residue can be important or even crucial for biological activity. PMID:25323736

Siod?ak, Dawid

2015-01-01

268

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

269

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

270

Treatment duration of febrile urinary tract infection (FUTIRST trial): a randomized placebo-controlled multicenter trial comparing short (7 days) antibiotic treatment with conventional treatment (14 days)  

PubMed Central

Background Current guidelines on the management of urinary tract infection recommend treating febrile urinary tract infection or acute pyelonephritis with antimicrobials for at least 14 days. Few randomized trials showed the effectiveness of treatment durations of 5 to 7 days but this has only been studied in young previously healthy women. Methods/Design A randomized placebo-controlled double-blind multicenter non-inferiority trial in which 400 patients with community acquired febrile urinary tract infection will be randomly allocated to a short treatment arm (7 days of ciprofloxacin or 7 days of empirical ?-lactams ± gentamicin intravenously with early switch to oral ciprofloxacin followed by 7 days of blinded placebo) or standard treatment arm (7 days of ciprofloxacin or 7 days of empirical ?-lactams ± gentamicin intravenously with early switch to oral ciprofloxacin followed by 7 days of blinded ciprofloxacin). The study is performed in the Leiden region in which one university hospital, 6 general hospitals and 32 primary health care centers are clustered. Patients eligible for randomization are competent patients aged 18 years or above with a presumptive diagnosis of acute pyelonephritis as defined by the combination of fever, one or more symptoms of urinary tract infection and a positive urine nitrate test and/or the presence of leucocyturia. Exclusion criteria are known allergy to fluoroquinolones, female patients who are pregnant or lactating, polycystic kidney disease, permanent renal replacement therapy, kidney transplantation, isolation of ciprofloxacin-resistant causal uropathogen, renal abscess, underlying chronic bacterial prostatitis, metastatic infectious foci and inability to obtain follow-up. The primary endpoint is the clinical cure rate through the 10- to 18-day post-treatment visit. Secondary endpoints are the microbiological cure rate 10- to 18-day post-treatment, the 30- and 90-day overall mortality rate, the clinical cure rate 70- to 84-day post-treatment, relapse rate of UTI and adverse events or complications during 90 days of follow-up. Discussion This study aims to demonstrate that 7 days of antimicrobial treatment is non-inferior as compared with 14 days of treatment in patients with febrile urinary tract infection. In addition, it will generate insights into the side-effects of antimicrobial treatment in relation to its duration. The study population will also include men, the elderly and patients with significant co-morbidity. Reflecting daily practice of primary health care and emergency departments, the results of this study can be generalized to other locations. Trial registration (Trial registration at clinicaltrials.gov: NCT00809913 and trialregister.nl: NTR01583) PMID:19691829

2009-01-01

271

Accidental fall due to abnormal behavior after experiencing a Streptococcus pyogenes infection: febrile delirium or pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection?  

PubMed

An 11-year-old boy with a high fever (39.4 degrees C) presented at a local medical institution. His condition was diagnosed as hemolytic streptococcal infection, and he was prescribed an antibiotic. After returning home, he took a dose of his medication and rested; however, he suddenly began to run around while yelling incomprehensible words. He ran up to his room on the second floor and fell from the second floor window down to the ground. He lost consciousness and was transferred to our department. His history included being born as a twin with a low birth weight and pneumonia at 1 year of age. He regained consciousness on the seventh hospital day and was discharged without any neurological abnormality on the 14th day. His abnormal behavior might have resulted from febrile delirium or an unusual expression of pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection. PMID:19687712

Yanagawa, Youichi; Kaneko, Naoyuki; Higashidate, Seiki; Matsumoto, Hiroshi

2009-08-01

272

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

273

Approaches to describing inter-rater reliability of the overall clinical appearance of febrile infants and toddlers in the emergency department.  

PubMed

Objectives. To measure inter-rater agreement of overall clinical appearance of febrile children aged less than 24 months and to compare methods for doing so. Study Design and Setting. We performed an observational study of inter-rater reliability of the assessment of febrile children in a county hospital emergency department serving a mixed urban and rural population. Two emergency medicine healthcare providers independently evaluated the overall clinical appearance of children less than 24 months of age who had presented for fever. They recorded the initial 'gestalt' assessment of whether or not the child was ill appearing or if they were unsure. They then repeated this assessment after examining the child. Each rater was blinded to the other's assessment. Our primary analysis was graphical. We also calculated Cohen's ?, Gwet's agreement coefficient and other measures of agreement and weighted variants of these. We examined the effect of time between exams and patient and provider characteristics on inter-rater agreement. Results. We analyzed 159 of the 173 patients enrolled. Median age was 9.5 months (lower and upper quartiles 4.9-14.6), 99/159 (62%) were boys and 22/159 (14%) were admitted. Overall 118/159 (74%) and 119/159 (75%) were classified as well appearing on initial 'gestalt' impression by both examiners. Summary statistics varied from 0.223 for weighted ? to 0.635 for Gwet's AC2. Inter rater agreement was affected by the time interval between the evaluations and the age of the child but not by the experience levels of the rater pairs. Classifications of 'not ill appearing' were more reliable than others. Conclusion. The inter-rater reliability of emergency providers' assessment of overall clinical appearance was adequate when described graphically and by Gwet's AC. Different summary statistics yield different results for the same dataset. PMID:25401054

Walsh, Paul; Thornton, Justin; Asato, Julie; Walker, Nicholas; McCoy, Gary; Baal, Joe; Baal, Jed; Mendoza, Nanse; Banimahd, Faried

2014-01-01

274

Health-related quality of life for pediatric emergency department febrile illnesses: an Evaluation of the Pediatric Quality of Life Inventory™ 4.0 generic core scales  

PubMed Central

Objective We sought to assess the validity and short-term responsiveness of the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL™) for febrile illnesses evaluated in the pediatric emergency department (ED). Design Prospective cohort study of children 2–18 years discharged after ED evaluation for fever (? 38°C). Self-administered, parent-report of health-related quality of life (HRQOL) was assessed using the PedsQL™ Acute Version, a validated HRQOL instrument. HRQOL was measured on ED presentation and at 7–10 day follow-up. At follow-up, duration of fever, child functional impairment, missed daycare/school, and disrupted family unit functioning, were assessed. Results Of 160 subjects enrolled, 97 (61%) completed the study; mean follow-up was 8.7 days. Mean total HRQOL score on ED presentation was 76.4; mean follow-up score was 86.3. Compared to subjects that returned to baseline, statistically significant differences in HRQOL were noted for those with prolonged fever, child functional impairment, and relapse. Significant correlation was observed between HRQOL at follow-up and days of daycare/school missed (r = -0.35, p = .003) and days of family disruption (r = -0.43, p < .001). Mean change in HRQOL within subjects, from ED visit to follow-up, was +9.8 (95% CI: 5.6–14.6). Effect size was 0.53, indicating moderate responsiveness. Conclusion The PedsQL™ appears to be a valid and responsive indicator of HRQOL for short-term febrile illnesses evaluated in the ED. PMID:19178744

Mistry, Rakesh D; Stevens, Molly W; Gorelick, Marc H

2009-01-01

275

Approaches to describing inter-rater reliability of the overall clinical appearance of febrile infants and toddlers in the emergency department  

PubMed Central

Objectives. To measure inter-rater agreement of overall clinical appearance of febrile children aged less than 24 months and to compare methods for doing so. Study Design and Setting. We performed an observational study of inter-rater reliability of the assessment of febrile children in a county hospital emergency department serving a mixed urban and rural population. Two emergency medicine healthcare providers independently evaluated the overall clinical appearance of children less than 24 months of age who had presented for fever. They recorded the initial ‘gestalt’ assessment of whether or not the child was ill appearing or if they were unsure. They then repeated this assessment after examining the child. Each rater was blinded to the other’s assessment. Our primary analysis was graphical. We also calculated Cohen’s ?, Gwet’s agreement coefficient and other measures of agreement and weighted variants of these. We examined the effect of time between exams and patient and provider characteristics on inter-rater agreement. Results. We analyzed 159 of the 173 patients enrolled. Median age was 9.5 months (lower and upper quartiles 4.9–14.6), 99/159 (62%) were boys and 22/159 (14%) were admitted. Overall 118/159 (74%) and 119/159 (75%) were classified as well appearing on initial ‘gestalt’ impression by both examiners. Summary statistics varied from 0.223 for weighted ? to 0.635 for Gwet’s AC2. Inter rater agreement was affected by the time interval between the evaluations and the age of the child but not by the experience levels of the rater pairs. Classifications of ‘not ill appearing’ were more reliable than others. Conclusion. The inter-rater reliability of emergency providers’ assessment of overall clinical appearance was adequate when described graphically and by Gwet’s AC. Different summary statistics yield different results for the same dataset. PMID:25401054

Thornton, Justin; Asato, Julie; Walker, Nicholas; McCoy, Gary; Baal, Joe; Baal, Jed; Mendoza, Nanse; Banimahd, Faried

2014-01-01

276

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

277

Immediate fluid management of children with severe febrile illness and signs of impaired circulation in low-income settings: a contextualised systematic review  

PubMed Central

Objective To evaluate the effects of intravenous fluid bolus compared to maintenance intravenous fluids alone as part of immediate emergency care in children with severe febrile illness and signs of impaired circulation in low-income settings. Design Systematic review of randomised controlled trials (RCTs), and observational studies, including retrospective analyses, that compare fluid bolus regimens with maintenance fluids alone. The primary outcome measure was predischarge mortality. Data sources and synthesis We searched PubMed, The Cochrane Library (to January 2014), with complementary earlier searches on, Google Scholar and Clinical Trial Registries (to March 2013). As studies used different clinical signs to define impaired circulation we classified patients into those with signs of severely impaired circulation, or those with any signs of impaired circulation. The quality of evidence for each outcome was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings are presented as risk ratios (RRs) with 95% CIs. Results Six studies were included. Two were RCTs, one large trial (n=3141 children) from a low-income country and a smaller trial from a middle-income country. The remaining studies were from middle-income or high-income settings, observational, and with few participants (34–187 children). Severely impaired circulation The large RCT included a small subgroup with severely impaired circulation. There were more deaths in those receiving bolus fluids (20–40?mL/kg/h, saline or albumin) compared to maintenance fluids (2.5–4?mL/kg/h; RR 2.40, 95% CI 0.84 to 6.88, p=0.054, 65 participants, low quality evidence). Three additional observational studies, all at high risk of confounding, found mixed effects on mortality (very low quality evidence). Any signs of impaired circulation The large RCT included children with signs of both severely and non-severely impaired circulation. Overall, bolus fluids increased 48?h mortality compared to maintenance fluids with an additional 3 deaths per 100 children treated (RR 1.45, 95% CI 1.13 to 1.86, 3141 participants, high quality evidence). In a second small RCT from India, no difference in 72?h mortality was detected between children who received 20–40?mL/kg Ringers lactate over 15?min and those who received 20?mL over 20?min up to a maximum of 60?mL/kg over 1?h (147 participants, low quality evidence). In one additional observational study, resuscitation consistent with Advanced Paediatric Life Support (APLS) guidelines, including fluids, was not associated with reduced mortality in the small subgroup with septic shock (very low quality evidence). Signs of impaired circulation, but not severely impaired Only the large RCT allowed an analysis for children with some signs of impaired circulation who would not meet the criteria for severe impairment. Bolus fluids increased 48?h mortality compared to maintenance alone (RR 1.36, 95% CI 1.05 to 1.76, high quality evidence). Conclusions Prior to the publication of the large RCT, the global evidence base for bolus fluid therapy in children with severe febrile illness and signs of impaired circulation was of very low quality. This large study provides robust evidence that in low-income settings fluid boluses increase mortality in children with severe febrile illness and impaired circulation, and this increased risk is consistent across children with severe and less severe circulatory impairment. PMID:24785400

Opiyo, Newton; Molyneux, Elizabeth; Sinclair, David; Garner, Paul; English, Mike

2014-01-01

278

Challenges of Establishing the Correct Diagnosis of Outbreaks of Acute Febrile Illnesses in Africa: The Case of a Likely Brucella Outbreak among Nomadic Pastoralists, Northeast Kenya, March–July 2005  

PubMed Central

An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed. PMID:22049048

Ari, Mary D.; Guracha, Argata; Fadeel, Moustafa Abdel; Njuguna, Charles; Njenga, M. Kariuki; Kalani, Rosalia; Abdi, Hassan; Warfu, Osman; Omballa, Victor; Tetteh, Christopher; Breiman, Robert F.; Pimentel, Guillermo; Feikin, Daniel R.

2011-01-01

279

Lidocaine treatment in refractory status epilepticus resulting from febrile infection-related epilepsy syndrome: a case report and follow-up.  

PubMed

We report the management of refractory status epilepticus (SE) by using continuous intravenous infusions of lidocaine in a previously healthy 15-year-old girl with a "catastrophic encephalopathy" in whom a diagnosis of febrile infection-related epilepsy syndrome was supposed. One week after a banal pharyngitis and fever, the patient presented confusion and intractable clusters of seizures. Although she underwent multiple examinations investigating all possible etiologies (intracranial infection, autoimmune disease, or toxic and metabolic illness), all results were negative except a feeble positivity to Mycoplasma pneumoniae serum antibodies. SE was initially treated with benzodiazepine followed by administration of barbiturates and subsequent induction of coma because of refractory SE; different antiepileptic drugs (AEDs) were given at different times in a period of 6 weeks but clinical and electroencephalographic improvements were achieved only after continuous infusion of lidocaine. When she recovered from SE, the patient developed severe psychomotor and cognitive impairment associated with cerebral atrophy. Treatment with lidocaine or other alternative drugs in cases of prolonged SE should be taken into account as soon as it becomes clear that the clinical condition is refractory to common AEDs included in available guidelines for SE treatment, to improve the bad outcome of this severe condition, at least limiting the negative effects of prolonged high metabolic demand due to continuous epileptiform activity and/or the possible negative effects of prolonged burst-suppression coma. PMID:25343330

Capizzi, Giorgio; Vittorini, Roberta; Torta, Francesca; Davico, Chiara; Rainò, Elena; Conio, Alessandra; Longobardo, Annalisa; Briatore, Eleonora; Podestà, Barbara; Calzolari, Stefano

2015-02-01

280

Central mediators involved in the febrile response induced by polyinosinic-polycytidylic acid: Lack of involvement of endothelins and substance P.  

PubMed

The present study evaluated the involvement of interleukin(IL)-1?, tumor necrosis factor-? (TNF-?), IL-6, interferon(IFN)-?, prostaglandins of the E2 series, endothelins, substance P and opioids within the central nervous system in polyinosinic:polycytidylic acid (Poly I:C)-induced fever in rats. Poly I:C injection induced a febrile response which was reduced by intracerebroventricular administration of the antibodies against TNF-?, IL-6, or IFN-?, or by IL-1 or ? receptor antagonists. Intraperitoneal injection of indomethacin or oral administration of celecoxib also reduced Poly I:C-induced fever. Poly I:C increased prostaglandin E2 levels in the cerebrospinal fluid of the animals which was also reduced by indomethacin. The intracerebroventricular injection of ETB or NK1 receptor antagonists did not alter Poly I:C-induced fever. These data suggest the involvement of IL-1?, TNF-?, IL-6, IFN-?, prostaglandin E2, and opioids but not endothelins and substance P on Poly I:C-induced fever. PMID:25595258

Bastos-Pereira, A L; Leite, M C G; Fraga, D; Zampronio, A R

2015-01-15

281

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

PubMed Central

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

2009-01-01

282

Application of Polymerase Chain Reaction to Detect Burkholderia Pseudomallei and Brucella Species in Buffy Coat from Patients with Febrile Illness Among Rural and Peri-Urban Population  

PubMed Central

Context: Melioidosis and Brucellosis are important endemic infections among people in India, especially in rural settings. Conventional detection techniques have several limitations. Only a few studies exist on the prevalence of Melioidosis and Brucellosis in rural area especially in India. Aim: We sought to evaluate detection of Burkholderia pseudomallei and Brucella spp. among patients presenting febrile illness. Material and Methods: Previously described polymerase chain reaction (PCR) assays for both pathogens were evaluated with Deoxyribonucleic acid extracts of buffy coat samples collected from 301 patients recruited prospectively. Data was not amenable to statistical analysis. Results: The PCR showed specific amplification and no non-specific amplification with heterologous Gram-negative bacilli. The lower limit of detection of the assay for B. pseudomallei was determined to be 1 colony-forming unit /mL and for Brucella it was 1.95 × 103 plasmids per microliter. Blood culture in automated blood culture system was negative for all the samples. This prospective study carried out in southern India for the first time. PCR for Brucella was positive in 1% of the patient samples whereas 0.3% was positive for B. pseudomallei. Conclusion: The finding of Brucella and Burkholderia infections in our populations leads us to suggest that tests for Brucella and B. pseudomallei should also form part of a diagnostic platform for patients with Pyrexia of unknown origin in tropical developing countries. PMID:22529625

Nandagopal, Balaji; Sankar, Sathish; Lingesan, Karthikeyan; Appu, KC; Sridharan, Gopalan; Gopinathan, Anilkumar

2012-01-01

283

A molecular survey of febrile cases in malaria-endemic areas along China-Myanmar border in Yunnan province, People’s Republic of China  

PubMed Central

Background: Imported malaria is a major threat to neighboring malaria-eliminating countries such as P.R. China and is difficult to monitor. A molecular survey of febrile patients with a history of traveling abroad along the Myanmar-China endemic border areas from January 2008 to August 2012 was carried out. The rates of infection with species of Plasmodium and compliance of microscopy diagnosis with nested PCR (Polymerase Chain Reaction) results were calculated. Results: Plasmodium genus-specific nested PCR confirmed that 384 cases were positive. Further species-specific nested PCR showed that the rate of Plasmodium vivax infection was 55% (213/384); that of Plasmodium falciparum was 21% (81/384) and 17% (67/384) of cases were co-infection cases of P. vivax and P. falciparum; the remaining 6% (23/384) of cases were caused by other species, such as Plasmodium ovale, P. malaria, P. knowlesi or mixed infections of Plasmodium. In total there was 13% (50/384) false microscopy diagnosis including 6% (22/384) error in species diagnosis and 7% (28/384) undiagnosed cases in co-infection or low parasitemia malaria cases. Conclusions: This study indicates that there are considerable numbers of malaria cases in the China-Myanmar endemic border areas that remain undiagnosed or misdiagnosed by microscopy, especially in low-level and/or complex co-infection cases. It is urgent to develop accurate rapid diagnostic tests and apply PCR confirmation for efficient surveillance. PMID:24954235

Zhou, Xia; Huang, Ji-Lei; Njuabe, Metoh Theresia; Li, Sheng-Guo; Chen, Jun-Hu; Zhou, Xiao-Nong

2014-01-01

284

Carbon monoxide offers neuroprotection from hippocampal cell damage induced by recurrent febrile seizures through the PERK-activated ER stress pathway.  

PubMed

Carbon monoxide (CO) is neuroprotective in various models of brain injury, but the precise mechanisms for this are yet to be established. In the present study, using a rat model of recurrent febrile seizures (FSs), we found an increase in plasma CO, evidence of neuronal damage and apoptosis, an increase in the expression of the endoplasmic reticulum stress (ERS) marker glucose-regulated protein 78 (GRP78) and C/EBP homologous binding protein (CHOP), and an increase in phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK)/eukaryotic translation initiation factor 2 alpha (p-eIF2?) in the hippocampus after 10 FSs. Administration of Hemin (a CO donor) in FS rats alleviated the neuronal damage, reduced neuronal apoptosis, upregulated GRP78 expression, decreased CHOP, and increased p-PERK and p-eIF2? expression in the hippocampus, compared to FS control rats. In contrast, treating FS rats with ZnPP-IX (a CO synthase inhibitor) aggravated the neuronal damage, enhanced neuronal apoptosis, downregulated GRP78 expression, increased CHOP, and decreased p-PERK and p-eIF2? expression, compared to FS control rats. These results suggest that endogenous CO limits the neuronal damage induced by recurrent FSs, through the PERK-activated ERS pathway. PMID:25434873

Han, Ying; Yi, Wenxia; Qin, Jiong; Zhao, Yang; Zhang, Jing; Chang, Xingzhi

2015-01-12

285

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

286

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

287

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

288

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

289

32 CFR 716.6 - Death occurring after active service.  

...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

290

Mechanism of Prion Propagation: Amyloid Growth Occurs by Monomer Addition  

E-print Network

Mechanism of Prion Propagation: Amyloid Growth Occurs by Monomer Addition Sean R. Collins, Adam yeast prion protein Sup35. Rapid polymerization occurs in the absence of observable intermediates of prion propagation: Amyloid growth occurs by monomer addition. PLoS Biol 2(10): e321. Introduction Many

Vale, Ronald D.

291

EXPERIMENTAL STUDIES ON YELLOW FEVER OCCURRING IN MERIDA, YUCATAN.  

PubMed

Injections into guinea pigs of the blood and the emulsions of liver and kidney obtained at autopsy from a fatal case of yellow fever in Merida induced in some of these animals, after a period of several days incubation, a rise of temperature which lasted 1, 2, or more days. When killed for examination at this febrile stage the animals invariably showed hemorrhagic areas of various size, sometimes few and sometimes numerous, in the lungs, and also, though less constantly, in the gastrointestinal mucosa, together with general hyperemia of the liver and kidneys. In a guinea pig (No. 6) inoculated with the liver emulsion of Case 1 there was a trace of jaundice on the 9th day. Injections of the blood or liver and kidney emulsions from such animals into normal guinea pigs reproduced the febrile reactions and the visceral lesions. The majority of the animals which were allowed to live and complete the course of the infection rapidly returned to normal (within several days). Examinations of these surviving guinea pigs after 2 weeks revealed the presence of rather old hemorrhagic foci in the lungs. In the course of further attempts to transfer the passage strain, a secondary infection by a bacillus of the paratyphoid group caused many deaths among the guinea pigs and resulted finally in the loss of the strain from Case 1. Most of the cultures made with the heart's blood taken at autopsy from Case 1 proved to be contaminated with a bacillus of the coli group. The contents of the apparently uncontaminated tubes were inoculated into guinea pigs, but the results were for the most part negative or vitiated by a secondary infection. Dark-field search for the leptospira with the autopsy materials was negative, although prolonged and thorough examination was not practicable at the time of these experiments. Our efforts were concentrated on obtaining positive animal transmission rather than on the time-consuming demonstration of the leptospira, which when unsuccessful does not necessarily exclude the presence of the organism in small numbers. Likewise, the dark-field work with the material from guinea pigs was confined to a brief examination and was omitted in many instances. Under these circumstances no leptospira was encountered in any of the material from Case 1. On the other hand, the results obtained with the specimens of blood from Case 2 were definitely positive, not only in the transmission of the disease directly, or indirectly by means of cultures, into guinea pigs, but also in the demonstration of the leptospira in the primary cultures and in the blood and organ emulsions of guinea pigs experimentally infected with such cultures. Definite positive direct transmissions were obtained with the specimens of blood drawn on the 2nd and 3rd days. No blood was taken on the 4th or 6th days. There were indications of abortive or mild leptospira infection in the guinea pigs inoculated with the blood taken on the 5th day. Regarding the inoculation of cultures from Case 2, it may be stated that only the cultures (leptospira +) made with the blood drawn on the 2nd day caused a definite fatal infection in guinea pigs. From this series a continuous passage in the guinea pig has been successfully accomplished. One of the guinea pigs (No. 48) inoculated with the culture 5 days old (leptospira +) made from the blood taken on the 3rd day presented typical symptoms, and a positive transfer from this to another animal (No. 98) was also made. Cultures of the blood drawn on the 5th and 7th days gave unsatisfactory results, owing to a secondary contamination. Leptospiras were detected in some of the culture tubes containing 2nd and 3rd day specimens of blood from Case 2; they were few in number and for the most part immotile, owing perhaps to some unfavorable cultural condition such as a fungus contamination. Charts 17, 18, and 19 give a summary of the experiments. See PDF for Structure. PMID:19868464

Noguchi, H; Kligler, I J

1920-10-31

292

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

293

A Case where a Paradox Like Braess's Occurs in the Nash Equilibrium but Does Not Occur in the Wardrop Equilibrium  

E-print Network

A Case where a Paradox Like Braess's Occurs in the Nash Equilibrium but Does Not Occur in the Wardrop Equilibrium ¯ A Situation of Load Balancing in Distributed Computer Systems ¯ Hisao Kameda \\Lambda of the other individuals. Another framework in which such a paradox may occur is that of the Nash equilibrium

294

Introducing the concept of a new pre-referral treatment for severely ill febrile children at community level: a sociological approach in Guinea-Bissau  

PubMed Central

Background Innovative strategies are needed to tackle childhood mortality in the rural tropics. Artesunate suppositories were developed to bring emergency treatment closer to severely ill children with malaria in rural areas where injectable treatment is not possible for several hours. Adding an antibacterial rectal drug would extend this strategy to treat non-malarial febrile illness as well. The objective of these studies was to assess acceptability of such a new pre-referral strategy by healthcare providers and likely uptake by the population. Methods Two qualitative studies were conducted between May and July 2009. Study 1 investigated the acceptability of introducing a combined antimalarial-antibacterial suppository by interviewing 27 representatives of the three administrative levels (central government, regional, local) of the health sector; Study 2 investigated treatment-seeking behaviour and acceptability of this intervention at community level by interviewing 74 mothers in 2 villages. Results and Conclusions Up to 92% of health representatives were in favour of introducing a new pre-referral strategy to tackle both malaria and non-malaria related severe illnesses in Guinea-Bissau, provided it was endorsed by international health authorities. The main obstacles to implementation were the very limited human and financial resources. In the two villages surveyed, 44% of the mothers associated severe illness with fever only, or fever plus one additional symptom. Mothers’ judgement of severity and ensuing decisions were not specific for serious illness, indicating that initial training to recognize signs of severe disease and treatment availability for non-severe, fever-associated symptoms will be required to prevent overuse of a new intervention designed as a pre-referral treatment for severely ill children. Level C health centres were the first resort in both villages (50% and 87% of respondents respectively). This information is encouraging for the implementation of a pre-referral treatment. PMID:24502695

2014-01-01

295

Febrile-range temperature modifies cytokine gene expression in LPS-stimulated macrophages by differentially modifying NF-?B recruitment to cytokine gene promoters  

PubMed Central

We previously showed that exposure to febrile-range temperatures (FRT, 39.5–40°C) reduces LPS-induced TNF-? expression, in part through the direct interaction of heat shock factor-1 (HSF1) with the TNF-? gene promoter. However, it is not known whether exposure to FRT also modifies more proximal LPS-induced signaling events. Using HSF1-null mice, we confirmed that HSF1 is required for FRT-induced repression of TNF-? in vitro by LPS-stimulated bone marrow-derived macrophages and in vivo in mice challenged intratracheally with LPS. Exposing LPS-stimulated RAW 264.7 mouse macrophages to FRT reduced TNF-? expression while increasing IL-1? expression despite the two genes sharing a common myeloid differentiation protein-88 (MyD88)-dependent pathway. Global activation of the three LPS-induced signaling intermediates that lead to cytokine gene expression, ERK and p38 MAPKs and NF-?B, was not affected by exposing RAW 264.7 cells to FRT as assessed by ERK and p38 phosphorylation and NF-?B in vitro DNA-binding activity and activation of a NF-?B-dependent synthetic promoter. However, chromatin immunoprecipitation (ChIP) analysis demonstrated that exposure to FRT reduced LPS-induced recruitment of NF-?B p65 to the TNF-? promoter while simultaneously increasing its recruitment to the IL-1? promoter. These data suggest that FRT exerts its effects on cytokine gene expression in a gene-specific manner through distal effects on promoter activation rather than proximal receptor activation and signal transduction. PMID:19846753

Cooper, Zachary A.; Ghosh, Arundhati; Gupta, Aditi; Maity, Tapan; Benjamin, Ivor J.; Vogel, Stefanie N.; Hasday, Jeffrey D.

2010-01-01

296

Obliquebanded leafroller The obliquebanded leafroller occurs throughout the  

E-print Network

Obliquebanded leafroller The obliquebanded leafroller occurs throughout the apple-growing areas the overwintering generation bore into opening buds. Later, when the leaves are available, they fold leaves

297

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

298

Internet Censorship in China: Where Does the Filtering Occur?  

E-print Network

Internet Censorship in China: Where Does the Filtering Occur? Xueyang Xu, Z. Morley Mao, and J Street, Ann Arbor, MI 48109 {xueyang,zmao,jhalderm}@umich.edu http://www.cse.umich.edu Abstract. China to know where the filtering occurs. In this work, we explore the AS-level topology of China's network

Mao, Zhuoqing Morley

299

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

300

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

301

Internet Censorship in China: Where Does the Filtering Occur?  

NASA Astrophysics Data System (ADS)

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 also exist in many provincial networks. The result suggests that two major ISPs in China have different approaches placing filtering devices.

Xu, Xueyang; Mao, Z. Morley; Halderman, J. Alex

302

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

303

Rapid diagnostic tests to improve treatment of malaria and other febrile illnesses: patient randomised effectiveness trial in primary care clinics in Afghanistan  

PubMed Central

Objective To assess the impact of rapid diagnostic tests on the diagnostic accuracy and treatment of malaria and non-severe fever in an Asian setting. Design Patient randomised trial in primary level clinics. Setting Two areas of Afghanistan where Plasmodium vivax and Plasmodium falciparum are endemic; one area with moderate transmission (eastern region) and one with low transmission (northern region). Participants 5794 patients of all ages with suspected malaria enrolled by 80 clinicians in 22 clinics. Interventions Malaria rapid diagnostic tests were compared with clinical diagnosis where no parasite diagnostic test was available, longer established field microscopy, and recently introduced microscopy. Main outcome measures Proportion of patients appropriately treated with an antimalarial, defined as patients with P vivax who received chloroquine, patients with P falciparum who received artemisinin based combination therapy, and patients with no malaria parasites who did not receive an antimalarial. Secondary outcomes included diagnostic test accuracy and the proportion of patients negative for malaria who received antibiotics and antimalarials. Results In the low transmission area, comparing rapid diagnostic tests with clinical diagnosis, 65% (212/325) versus 12% (40/321) of febrile patients were appropriately treated for malaria (adjusted odds ratio 92.7, 95% confidence interval 12.4 to 694.1, P<0.001). The proportion of patients who were negative for malaria and received an antibiotic was 57% (185/325) in the rapid diagnostic test arm compared with 14% (46/321) in the clinical diagnosis arm (16.9, 3.8 to 75.4, P<0.001). In the comparison of rapid diagnostic test with microscopy in the moderate transmission area, 83.6% (1696/2028) versus 76.3% (1512/1983) of patients were appropriately treated for malaria (1.70, 1.30 to 2.23, P<0.001). A higher proportion of P falciparum cases received appropriate treatment with artemisinin based combination therapy when malaria was diagnosed by rapid diagnostic test (82%, 58/71 v 32%, 24/76; 9.2, 3.88 to 21.66, P<0.001). Conclusions In South and central Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance. PMID:24948695

Mikhail, Amy; Mayan, Ismail; Cundill, Bonnie; Anwar, Mohammed; Bakhtash, Sayed Habib; Mohammed, Nader; Rahman, Habib; Zekria, Rohullah; Whitty, Christopher J M; Rowland, Mark

2014-01-01

304

A Fatal Spontaneous Gas Gangrene due to Clostridium perfringens during Neutropenia of Allogeneic Stem Cell Transplantation: Case Report and Literature Review  

PubMed Central

Most cases of gas gangrene caused by Clostridium species begin with trauma-related injuries but in rare cases, spontaneous gas gangrene (SGG) can occur when patients have conditions such as advanced malignancy, diabetes, or immunosuppression. Clostridium perfringens, a rare cause of SGG, exists as normal flora of skin and intestines of human. Adequate antibiotics with surgical debridement of infected tissue is the only curative therapeutic management. Mortality rate among adults is reported range of 67-100% and majority of deaths are occurred within 24 hours of onset. We experienced a case of SGG on the trunk, buttock and thigh in a neutropenic patient with acute lymphoblastic leukemia. His clinical course was rapid and fatal during pre-engraftment neutropenic period of allogeneic stem cell transplantation. PMID:25298910

Lee, Hae-Lim; Cho, Sung-Yeon; Ko, Yumi; Hyun, Ji In; Kim, Bo Kyoung; Seo, Jae Hyun; Lee, Jung Woo; Lee, Seok

2014-01-01

305

Arsenic poisoning in dairy cattle from naturally occurring arsenic pyrites.  

PubMed

An outbreak of arsenic poisoning occurred in which most of a 200 cow dairy herd were affected and six died. The source of the arsenic was naturally occurring arsenic pyrites from the Waiotapu Stream, near Rotorua. Arsenic levels in the nearby soil were as high as 6618 ppm. There was little evidence to suggest that treatment affected the course of the disease. Haematology was of little use in diagnosis, post-mortem signs were not always consistent and persistence of the element in the liver appeared short. Control of further outbreaks have been based on practical measures to minimise the intake of contaminated soil and free laying water by the stock. PMID:16031332

Hopkirk, R G

1987-10-01

306

POPULATION ECOLOGY Comparative Predation on Naturally Occurring Gypsy Moth  

E-print Network

POPULATION ECOLOGY Comparative Predation on Naturally Occurring Gypsy Moth (Lepidoptera(2): 293Ð296 (2006) ABSTRACT Predation is an important factor in the dynamics of gypsy moth (Lymantria. Here we compare predation rates on freeze-dried gypsy moth pupae af�xed with beeswax to pieces

Berkowitz, Alan R.

307

MAGNETIC TOPOLOGIES: WHERE WILL RECONNECTION OCCUR ? Pascal Demoulin  

E-print Network

1 MAGNETIC TOPOLOGIES: WHERE WILL RECONNECTION OCCUR ? Pascal D´emoulin Observatoire de Paris to power flares is thought to come from the coronal magnetic field. However, such energy release is efficient only at very small scales. Magnetic configurations with a complex topology, i.e. with sepa

Demoulin, Pascal

308

Merkel cell carcinoma occurring in renal transplant patients  

Microsoft Academic Search

Merkel cell carcinoma is a rare, highly aggressive tumor that usually affects the head and neck of elderly patients. We describe 3 cases of this high-grade, malignant tumor occurring in the setting of renal transplantation. (J Am Acad Dermatol 1999;41:289-91.)

Amy Urbatsch; W. Mitchell Sams; Marshall M. Urist; Rachel Sturdivant

1999-01-01

309

Integrative Priming Occurs Rapidly and Uncontrollably during Lexical Processing  

ERIC Educational Resources Information Center

Lexical priming, whereby a prime word facilitates recognition of a related target word (e.g., "nurse" [right arrrow] "doctor"), is typically attributed to association strength, semantic similarity, or compound familiarity. Here, the authors demonstrate a novel type of lexical priming that occurs among unassociated, dissimilar, and unfamiliar…

Estes, Zachary; Jones, Lara L.

2009-01-01

310

Predictive model of squeal noise occurring on a laboratory brake  

Microsoft Academic Search

This paper on brake squeal instability presents a reduced order model of a laboratory brake considered in a previous paper, and presents a description of the squeal mechanism occurring during experiments.The model uses the modal parameters of the laboratory brake components, the disc and the caliper, when they are not in contact between them. Successively, the caliper and the disc

Oliviero Giannini; Aldo Sestieri

2006-01-01

311

If a fire should occur... CLOSE the doors to  

E-print Network

If a fire should occur... · CLOSE the doors to stop the spread of the fire · SOUND the alarm, alert others to the danger · GET OUT of the building · NOTIFY the fire department DO NOT go back into the building or try to save your stuff. Clothes, books and papers can be replaced- YOU CAN'T! Living With Fire

Rose, Michael R.

312

On properties of certain classical operators occurring in Fourier analysis  

SciTech Connect

Properties of conjugate functions, Hilbert transforms, and certain maximal operators occurring in Fourier analysis in weighted Lebesgue spaces are established. For functions of several variables in Orlicz spaces the divergence in measure of the Cesaro and the Abel means of the conjugate trigonometric series, and the question of the existence of conjugate functions are investigated.

Zhizhiashvili, L V; Tkebuchava, G E [I. Javakhishvili Tbilisi State University, Tbilisi (Georgia)

2004-10-31

313

RUN OUTS OCCUR WHEN IRON HAS UNSEATED MOLDING SAND AND ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

RUN OUTS OCCUR WHEN IRON HAS UNSEATED MOLDING SAND AND RUN OUT OF THE MOLD UNDER POURING JACKETS AND SPILLS ONTO THE MOLDING PLATFORM. WORKERS GENERALLY WAIT SEVERAL MINUTES FOR THE IRON TO SOLIDIFY AND, WHILE IT IS STILL RED-HOT, REMOVE IT FROM THE PLATFORM AND SCRAP THE MOLD. - Southern Ductile Casting Company, Centerville Foundry, 101 Airport Road, Centreville, Bibb County, AL

314

If a fire should occur... CLOSE the doors to  

E-print Network

automatic fire sprinklers? Updated 10/01/01 What are sprinklers?...An automatic fire sprinkler system is oneIf a fire should occur... · CLOSE the doors to stop the spread of the fire · SOUND the alarm, alert · SimplexGrinnell · United States Fire Administration · University of Texas System Living With Fire

Rose, Michael R.

315

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study  

PubMed Central

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m?2on day 1 and gemcitabine 1125 mg m?2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaign PMID:10732750

van Putten, J W G; Eppinga, P; Erjavec, Z; de Leede, G; Nabers, J; Smeets, J B E; Sleijfer, D Th; Groen, H J M

2000-01-01

316

Issues related to regulatory control of naturally occurring radioactive materials  

SciTech Connect

Nearly 80% of human radiation exposure is from naturally occurring radioactive materials (NORM). While exposure from man-made sources of radiation has been well regulated, no consistent regulatory controls exist for NORM. Because elevated radiation levels have resulted from NORM enhancement activities such as occur in the petroleum, fertilizer, mining, and processing industries, some form of regulatory control is in order. In the US, regulation of NORM by federal agencies such as the Nuclear Regulatory Commission or the Environmental Protection Agency is not anticipated in the near future because there are no authorizing federal statutes. Important issues for addressing the control of NORM include source characterization and generation, radiation protection concerns, waste management and disposition, and the regulatory framework.

Chen, S.Y.

1997-04-01

317

Atrial tachycardias occurring late after open heart surgery.  

PubMed

Atrial tachycardias are common after open heart surgery. Most commonly these are macro-reentrant including cavotricuspid isthmus dependent atrial flutter, incisional right atrial flutter and left atrial flutter. Focal atrial tachycardias occur less frequently. The specific type of atrial tachycardia highly depends on the type of surgical incision. Catheter ablation can be very effective, however requires a thorough understanding of anatomy and surgical technique. PMID:25308810

Kohari, Maria; Pap, Robert

2015-01-01

318

Where and why do large shallow intraslab earthquakes occur?  

Microsoft Academic Search

We try to find how often, and in what regions large earthquakes (M?7.0) occur within the shallow portion (20–60km depth) of a subducting slab. Searching for events in published individual studies and the Harvard University centroid moment tensor catalogue, we find twenty such events in E. Hokkaido, Kyushu-SW, Japan, S. Mariana, Manila, Sumatra, Vanuatu, N. Chile, C. Peru, El Salvador,

Tetsuzo Seno; Masaki Yoshida

2004-01-01

319

Transmission of Streptococcus pneumoniae in adults may occur through saliva.  

PubMed

Of 742 army recruits tested for pneumococcal nasopharyngeal/oropharyngeal carriage, 6·6% were positive. Frequent sharing of a drinking glass/bottle was a common, strong and independent risk factor for pneumococcal carriage. Our findings strongly suggest, for the first time, that in young adults, transmission of pneumococci may occur via saliva and this should be considered when conducting an outbreak investigation and carriage studies. PMID:21676361

Levine, H; Zarka, S; Dagan, R; Sela, T; Rozhavski, V; Cohen, D I; Balicer, R D

2012-03-01

320

Naturally occurring auto-antibodies in homeostasis and disease  

Microsoft Academic Search

Antibodies with germline or close to germline configur- ation exist in vertebrates, and these so-called 'naturally occurring auto-antibodies' (NAb) are directed to self and altered self components. Such NAbs have been attract- ing increasing interest because several of them, in- cluding some in their recombinant forms, have therapeutic potential. Whereas a large number of IgM and IgG NAbs have tissue

Hans U. Lutz; Christoph J. Binder; Srini Kaveri

2008-01-01

321

Different forms of dizziness occurring after cochlear implant  

Microsoft Academic Search

Dizziness after cochlear implant (CI) was studied in a series of 94 consecutive adult patients receiving a cochlear implant,\\u000a 46 (49.0%) of whom experienced dizziness post-operatively. In 29 patients, post-operative dizziness occurred soon after surgery\\u000a and subsided within one month. Dizziness of the continuous type, lasting more than 6 months, was a complaint in only two patients.\\u000a In addition to

T. Kubo; Ko-ichi Yamamoto; Takako Iwaki; Katsumi Doi; Manabu Tamura

2001-01-01

322

Natural transformation of Campylobacter jejuni occurs beyond limits of growth.  

PubMed

Campylobacter jejuni is a human bacterial pathogen. While poultry is considered to be a major source of food borne campylobacteriosis, C. jejuni is frequently found in the external environment, and water is another well-known source of human infections. Natural transformation is considered to be one of the main mechanisms for mediating transfer of genetic material and evolution of the organism. Given the diverse habitats of C. jejuni we set out to examine how environmental conditions and physiological processes affect natural transformation of C. jejuni. We show that the efficiency of transformation is correlated to the growth conditions, but more importantly that transformation occurs at growth-restrictive conditions as well as in the late stationary phase; hence revealing that growth per se is not required for C. jejuni to be competent. Yet, natural transformation of C. jejuni is an energy dependent process, that occurs in the absence of transcription but requires an active translational machinery. Moreover, we show the ATP dependent ClpP protease to be important for transformation, which possibly could be associated with reduced protein glycosylation in the ClpP mutant. In contrast, competence of C. jejuni was neither found to be involved in DNA repair following DNA damage nor to provide a growth benefit. Kinetic studies revealed that several transformation events occur per cell cycle indicating that natural transformation of C. jejuni is a highly efficient process. Thus, our findings suggest that horizontal gene transfer by natural transformation takes place in various habitats occupied by C. jejuni. PMID:23049803

Vegge, Christina S; Brøndsted, Lone; Ligowska-Marz?ta, Ma?gorzata; Ingmer, Hanne

2012-01-01

323

Has the Solar Cycle 24 maximum already occurred?  

NASA Astrophysics Data System (ADS)

Infrared radiative cooling of the thermosphere by carbon dioxide and nitric oxide has been observed continuously since January 2002 by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics (TIMED) satellite. SABER has documented dramatic variability in the radiative cooling on timescales ranging from days to longer than the nominal 11-year solar cycle. SABER radiance measurements from emission by CO2 (at 15 ?m) and NO (at 5.3 ?m) are used to calculate global daily emitted thermosphere power. This unique dataset shows the direct effects of solar variability on the temperature (via CO2 emission) and composition (from NO emission) for nearly twelve years. The deep solar minimum between solar cycles 23 and 24 is evident in the low values of global mean radiative cooling that occur in the 2008-2009 period. Since then radiative cooling has been observed to increase in response to the transition into solar cycle 24. To more clearly identify extrema in the time series of radiative cooling, NO and CO2 cooling rates are deseasonalized to remove effects of the spacecraft yaw cycle. The deseasonalized data show a clear peak of radiative cooling in NO and CO2 occurring in December 2011. This peak in cooling corresponds to similar peaks in the ultraviolet flux emitted from the Sun measured by the SORCE and SEE instruments. These results show that a maximum in solar activity has clearly occurred. This may be a local maximum in time, depending on the future activity of the Sun in solar cycle 24. Reprocessing of version 2.0 of the SABER dataset is nearly complete and results from this new release will be presented. The SABER thermosphere power dataset will be continuously updated as new data are acquired to monitor the occurrence of solar maximum from the perspective of atmospheric cooling.

Hunt, L. A.; Mlynczak, M. G.; Marshall, B.; Russell, J. M.

2013-12-01

324

Frog Virus 3 DNA Replication Occurs in Two Stages  

PubMed Central

Viral DNA synthesis in frog virus 3 (FV3)-infected cells occurs both in the nucleus and in the cytoplasm (Goorha et al., Virology 84:32-51, 1978). Relationships between viral DNA molecules synthesized in these two compartments and their role in the virus replication were examined. The data presented here suggest that (i) FV3 DNA replicated in two stages and (ii) nucleus and cytoplasm were the sites of stages 1 and 2 of DNA replication, respectively. Stages 1 and 2 were further distinguished by their temporal appearance during infection and by the sizes of the replicating DNA as determined by sedimentation in neutral sucrose gradients. In stage 1, replicating molecules, between the size of unit and twice the unit length, were produced early in infection (2 h postinfection). In contrast, stage 2 of DNA replication occurred only after 3 h postinfection, and replicating molecules were large concatemers. Results of pulse-chase experiments showed that the concatemeric DNA served as the precursor for the production of mature FV3 DNA. Denaturation of concatemeric DNA with alkali or digestion with S1 nuclease reduced it to less than genome size molecules, indicating the presence of extensive single-stranded regions. Analysis of replicating DNA by equilibrium centrifugation in CsCl gradients after a pulse-chase suggested that these single-stranded regions were subsequently repaired. Based on these and previous data, a scheme of FV3 replication is presented. According to this scheme, FV3 utilizes the nucleus for early transcription and stage 1 of DNA replication. The viral DNA is then transported to the cytoplasm, where it participates in stage 2 DNA replication to form a concatemeric replication complex. The processing of concatemers to produce mature viral DNA and virus assembly also occurs in the cytoplasm. This mode of replication is strikingly different from any other known DNA virus. PMID:7109033

Goorha, R.

1982-01-01

325

Sensory-motor transformations for speech occur bilaterally  

PubMed Central

Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output1–4. A kind of ‘parity’ is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere5,6. While various theories have been proposed to unite perception and production2,7, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke’s area) and motor production processes occurred in the left inferior frontal gyrus (Broca’s area)8,9. Sensory activity was proposed to link to production activity via connecting fiber tracts, forming the left lateralized speech sensory-motor system10. While recent evidence indicates that speech perception occurs bilaterally11–13, prevailing models maintain that the speech sensory-motor system is left lateralized11,14–18 and facilitates the transformation from sensory-based auditory representations to motor-based production representations11,15,16. Evidence for the lateralized computation of sensory-motor speech transformations is, however, indirect and primarily comes from lesion patients with speech repetition deficits (conduction aphasia) and studies using covert speech and hemodynamic functional imaging16,19. Whether the speech sensory-motor system is lateralized like higher order language processes, or bilateral, like speech perception is controversial. Here, using direct neural recordings in subjects performing sensory-motor tasks involving overt speech production, we show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor, and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech perception- and production-based representations. These results establish a bilateral sublexical speech sensory-motor system. PMID:24429520

Cogan, Gregory B.; Thesen, Thomas; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Pesaran, Bijan

2014-01-01

326

Escape strategies in co-occurring calanoid copepods  

Microsoft Academic Search

Abstract We show,how,four co-occurring calanoid,copepod,species modulate,their responses,to two,contrasting hydrodynamic,stimuli. Species-specific patterns,in escape,behavior,included,quantitative,differences,in performance to each stimulus type. Using high-speed video, we compared escape reactions in Acartia hudsonica, Centropages hamatus, Tortanus discaudatus, and Temora longicornis. Responses to a flow field created by a suction tube involved,reorientation away,from,the source of suction followed,by a series of vigorous,power,strokes. Responses,to brief computer-controlled hydrodynamic,stimuli had,short latencies

Daniel S. Burdick; Daniel K. Hartline; Petra H. Lenz

327

An Update on Antitumor Activity of Naturally Occurring Chalcones  

PubMed Central

Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. PMID:23690855

Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

2013-01-01

328

Photoprotective substance occurs primarily in outer layers of fish skin  

USGS Publications Warehouse

Methanol extracts of dorsal skin layers, eyes, gills, and livers from ultraviolet-B (UVB) radiation-sensitive and UVB-tolerant species of freshwater fish were examined for a substance that appears to be photoprotective. Significantly larger amounts of this substance were found in extracts of outer dorsal skin layers from both UVB-sensitive and UVB-tolerant fish when compared with extracts of inner dorsal skin layers. This substance occurred in minor amounts or was not detected in eye, gill, and liver extracts. The apparent primary function of this substance in fish is to protect the cells in outer dorsal skin layers from harmful levels of UVB radiation.

Fabacher, D.L.; Little, E.E.

1998-01-01

329

Aggregatibacter actinomycetemcomitans leukotoxin cytotoxicity occurs through bilayer destabilization  

PubMed Central

Summary The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, is a common inhabitant of the human upper aerodigestive tract. The organism produces an RTX (Repeats in ToXin) toxin (LtxA) that kills human white blood cells. LtxA is believed to be a membrane-damaging toxin, but details of the cell surface interaction for this and several other RTX toxins have yet to be elucidated. Initial morphological studies suggested that LtxA was bending the target cell membrane. Because the ability of a membrane to bend is a function of its lipid composition, we assessed the proficiency of LtxA to release of a fluorescent dye from a panel of liposomes composed of various lipids. Liposomes composed of lipids that form nonlamellar phases were susceptible to LtxA-induced damage while liposomes composed of lipids that do not form non-bilayer structures were not. Differential scanning calorimetry demonstrated that the toxin decreased the temperature at which the lipid transitions from a bilayer to a nonlamellar phase, while 31P nuclear magnetic resonance studies showed that the LtxA-induced transition from a bilayer to an inverted hexagonal phase occurs through the formation of an isotropic intermediate phase. These results indicate that LtxA cytotoxicity occurs through a process of membrane destabilization. PMID:22309134

Brown, Angela C.; Boesze-Battaglia, Kathleen; Du, Yurong; Stefano, Frank P.; Kieba, Irene R.; Epand, Raquel F.; Kakalis, Lazaros; Yeagle, Philip L.; Epand, Richard M.; Lally, Edward T.

2012-01-01

330

Leaching of technologically enhanced naturally occurring radioactive materials.  

PubMed

A form of waste associated with mining activities is related to the type of deposit being mined and to the procedure of exploitation and enrichment adopted. The wastes usually contain relatively large amounts of technologically enhanced naturally occurring radioactive materials (TENORM). The TENORM are often stored on the surface. Consequently, they can be leached as a result of interaction with aqueous solutions of different chemical composition. This further leads to pollution of water and soil in the vicinity of the stored wastes. The paper presents the results of laboratory investigation aimed at quantifying the leaching process of samples originating from uranium dumps and storage reservoirs associated with brine pumped from coal mines. The leaching process was investigated with respect to selected elements: uranium isotopes, radium isotopes, iron, barium and sodium. The samples were exposed to aqueous solutions of different chemical composition. The experiments revealed that TENORM in form of sulphate compounds are the most resistant against leaching. The leaching coefficient for radium isotopes varies from a few thousandth percent to a few hundredth percent. On the other hand, for TENORM occurring in sand or sludge, the leaching coefficient for uranium and radium isotopes ranged from a few hundredth percent to a few percent. PMID:17482828

Chau, Nguyen Dinh; Chru?ciel, Edward

2007-08-01

331

Naturally Occurring Radioactive Materials in Cargo at US Borders  

SciTech Connect

In the U.S. and other countries, large numbers of vehicles pass through border crossings each day. The illicit movement of radioactive sources is a concern that has resulted in the installation of radiation detection and identification instruments at border crossing points. This activity is judged to be necessary because of the possibility of an act of terrorism involving a radioactive source that may include any number of dangerous radionuclides. The problem of detecting, identifying, and interdicting illicit radioactive sources is complicated by the fact that many materials present in cargo are somewhat radioactive. Some cargo contains naturally occurring radioactive material or technologically-enhanced naturally occurring radioactive material that may trigger radiation portal monitor alarms. Man-made radioactive sources, especially medical isotopes, are also frequently observed and produce alarms. Such nuisance alarms can be an operational limiting factor for screening of cargo at border crossings. Information about the nature of the radioactive materials in cargo that can interfere with the detection of radionuclides of concern is necessary. This paper provides such information for North American cargo, but the information may also be of use to border control officials in other countries. (PIET-43741-TM-361)

Kouzes, Richard T.; Ely, James H.; Evans, John C.; Hensley, Walter K.; Lepel, Elwood A.; McDonald, Joseph C.; Schweppe, John E.; Siciliano, Edward R.; Strom, Daniel J.; Woodring, Mitchell L.

2006-01-01

332

Thermal resistance of naturally occurring airborne bacterial spores.  

PubMed Central

Simulation of a heat process used in the terminal dry-heat decontamination of the Viking spacecraft is reported. Naturally occurring airborne bacterial spores were collected on Teflon ribbons in selected spacecraft assembly areas and subsequently subjected to dry heat. Thermal inactivation experiments were conducted at 105, 111.7, 120, 125, 130, and 135 degrees C with a moisture level of 1.2 mg of water per liter. Heat survivors were recovered at temperatures of 135 degrees C when a 30-h heating cycle was employed. Survivors were recovered from all cycles studied and randomly selected for identification. The naturally occurring spore population was reduced an average of 2.2 to 4.4 log cycles from 105 to 135 degrees C. Heating cycles of 5 and 15 h at temperature were compared with the standard 30-h cycle at 111.7, 120, and 125 degrees C. No significant differences in inactivation (alpha = 0.05) were observed between 111.7 and 120 degrees C. The 30-h cycle differs from the 5-and 15-h cycles at 125 degrees C. Thus, the heating cycle can be reduced if a small fraction (about 10-3 to 10-4) of very resistant spores can be tolerated. PMID:727780

Puleo, J R; Bergstrom, S L; Peeler, J T; Oxborrow, G S

1978-01-01

333

Fenugreek: a naturally occurring edible spice as an anticancer agent.  

PubMed

In recent years, various dietary components that can potentially be used for the prevention and treatment of cancer have been identified. In this study, we demonstrate that extract (FE) from the seeds of the plant Trigonella foenum graecum, commonly called fenugreek, are cytotoxic in vitro to a panel of cancer but not normal cells. Treatment with 10-15 ug/mL of FE for 72 h was growth inhibitory to breast, pancreatic and prostate cancer cell lines (PCa). When tested at higher doses (15-20 ug/mL), FE continued to be growth inhibitory to PCa cell lines but not to either primary prostate or hTert-immortalized prostate cells. At least part of the growth inhibition is due to induction of cell death, as seen by incorporation of Ethidium Bromide III into cancer cells exposed to FE. Molecular changes induced in PCa cells are: in DU-145 cells: downregulation of mutant p53, and in PC-3 cells upregulation of p21 and inhibition of TGFbeta induced phosphorylation of Akt. The surprising finding of our studies is that death of cancer cells occurs despite growth stimulatory pathways being simultaneously upregulated (phosphorylated) by FE. Thus, these studies add another biologically active agent to our armamentarium of naturally occurring agents with therapeutic potential. PMID:19197146

Shabbeer, Shabana; Sobolewski, Michelle; Anchoori, Ravi Kumar; Kachhap, Sushant; Hidalgo, Manuel; Jimeno, Antonio; Davidson, Nancy; Carducci, Michael A; Khan, Saeed R

2009-02-01

334

Fenugreek: a naturally occurring edible spice as an anticancer agent  

PubMed Central

In recent years, various dietary components that can potentially be used for the prevention and treatment of cancer have been identified. In this study, we demonstrate that extract (FE) from the seeds of the plant Trigonella foenum graecum, commonly called fenugreek, are cytotoxic in vitro to a panel of cancer but not normal cells. Treatment with 10-15 ug/mL of FE for 72h was growth inhibitory to breast, pancreatic and prostate cancer cell lines (PCa). When tested at higher doses (15-20 ug/mL), FE continued to be growth inhibitory to PCa cell lines but not to either primary prostate or htert-immortalized prostate cells. At least part of the growth inhibition is due to induction of cell death, as seen by incorporation of Ethidium Bromide III into cancer cells exposed to FE. Molecular changes induced in PCa cells are: in DU-145 cells: down regulation of mutant p53, and in PC-3 cells up regulation of p21 and inhibition of TGF-? induced phosphorylation of Akt. The surprising finding of our studies is that death of cancer cells occurs despite growth stimulatory pathways being simultaneously up regulated (phosphorylated) by FE. Thus, these studies add another biologically active agent to our armamentarium of naturally occurring agents with therapeutic potential. PMID:19197146

Shabbeer, Shabana; Sobolewski, Michelle; Kachhap, Sushant; Davidson, Nancy; Carducci, Michael A.; Khan, Saeed

2011-01-01

335

Granulocyte antigen systems and antibodies and their clinical significance  

SciTech Connect

Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems. These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases. Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established. Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies. Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy.

McCullough, J.

1983-03-01

336

Implementing Residential Integrated Treatment for Co-occurring Disorders  

PubMed Central

Objective: Much is now known about effective treatment for co-occurring substance abuse and psychiatric difficulties and many evidence-based practice recommendations have been disseminated. Implementation of these recommended interventions in daily clinical practice has been more of a struggle. This article describes successful implementation of integrated treatment for co-occurring disorders in a small residential program. Methods: A traditional 28-day addiction service was transformed into a 3-month integrated treatment program and 155 individuals with co-occurring disorders agreed to participate in its evaluation. The transformation entailed a completely new manualized service, training in a number of clinical interventions for all program clinicians, ongoing clinical supervision, and formal measurement of clients’ backgrounds, substance abuse, quality of life, mental health symptoms, self-esteem, and satisfaction with the program. We also obtained collateral informants’ reports on participants’ symptoms, substance use, and quality of life. Fidelity to the treatment model was continuously assessed, as were participants’ knowledge and skill acquisition. In addition, impact of the implementation on the program clinicians’ morale and attitudes toward evidence-based practices was assessed, as was staff turnover and per diem costs. Results: Despite very problematic clinical and sociodemographic histories, the 86 participants who completed the program showed clinically significant mental health symptom improvement, acquisition of knowledge and skill, and high self-esteem and satisfaction with the program. Program fidelity, clinician morale, commitment to the program, and attitudes toward evidence-based practice were uniformly high. These successes were achieved while maintaining the lowest per–inpatient day cost of all hospital inpatient units. Conclusions: The findings support the contention that evidence-based integrated treatment can be implemented with fidelity in regular clinical practice to the benefit of participants, staff, and the hospital. Our experience was that having a scientist-practitioner working as a staff member on the program to lead the implementation was a key element. Future reports will focus on longer-term follow-up of substance use and quality of life outcomes. PMID:23976887

McKee, Shari A.; Harris, Grant T.; Cormier, Catherine A.

2013-01-01

337

Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection  

PubMed Central

Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8+ T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of “collateral damage” of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8+ T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology. PMID:16565492

Polakos, Noelle K.; Cornejo, Judith C.; Murray, Debbie A.; Wright, Kate O.; Treanor, John J.; Crispe, I. Nicholas; Topham, David J.; Pierce, Robert H.

2006-01-01

338

Cytotoxicity and superoxide anion generation by some naturally occurring quinones.  

PubMed

Four naturally occurring quinones, mansonone-D (MD), mansonone-H (MH), thespone (TP) and thespesone (TPE), extracted from the heartwood of Thespesia populnea have been tested for their cytotoxic action by aerobic incubation with human breast adenocarcinoma (MCF-7) cells. Toxicity of the quinones follows the order MD > TP > MH approximately TPE. EPR spectrometric and Clark electrode oximetric studies indicate that redox cycling of these quinones produce superoxide anion radical (O2*-) and H2O2 on aerobic incubation with NADH:cytochrome c reductase. Generation of superoxide radical during enzymatic reduction of quinones, was confirmed by EPR spin trapping experiment using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap. Cyclic voltammetric studies show reversible redox couples for MD and TP whereas TPE and MH show irreversible redox couple. The electrochemical results indicate that MH and TPE are more difficult to reduce than TP and MD. PMID:10381175

Johnson Inbaraj, J; Gandhidasan, R; Murugesan, R

1999-05-01

339

Naturally Occurring Animal Models of Human Hepatitis E Virus Infection  

PubMed Central

Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations. PMID:24936039

Yugo, Danielle M.; Cossaboom, Caitlin M.; Meng, Xiang-Jin

2014-01-01

340

Naturally occurring minichromosome platforms in chromosome engineering: an overview.  

PubMed

Artificially modified chromosome vectors are non-integrating gene delivery platforms that can shuttle very large DNA fragments in various recipient cells: theoretically, no size limit exists for the chromosome segments that an engineered minichromosome can accommodate. Therefore, genetically manipulated chromosomes might be potentially ideal vector systems, especially when the complexity of higher eukaryotic genes is concerned. This review focuses on those chromosome vectors generated using spontaneously occurring small markers as starting material. The definition and manipulation of the centromere domain is one of the main obstacles in chromosome engineering: naturally occurring minichromosomes, due to their inherent small size, were helpful in defining some aspects of centromere function. In addition, several distinctive features of small marker chromosomes, like their appearance as supernumerary elements in otherwise normal karyotypes, have been successfully exploited to use them as gene delivery vectors. The key technologies employed for minichromosome engineering are: size reduction, gene targeting, and vector delivery in various recipient cells. In spite of the significant advances that have been recently achieved in all these fields, several unsolved problems limit the potential of artificially modified chromosomes. Still, these vector systems have been exploited in a number of applications where the investigation of the controlled expression of large DNA segments is needed. A typical example is the analysis of genes whose expression strictly depends on the chromosomal environment in which they are positioned, where engineered chromosomes can be envisaged as epigenetically regulated expression systems. A novel and exciting advance concerns the use of engineered minichromosomes to study the organization and dynamics of local chromatin structures. PMID:21431718

Raimondi, Elena

2011-01-01

341

Forecasting Seizures in Dogs with Naturally Occurring Epilepsy  

PubMed Central

Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), low-gamma (30–70 Hz), and high-gamma (70–180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring. PMID:24416133

Stead, S. Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H.; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W. Douglas; Litt, Brian; Worrell, Gregory A.

2014-01-01

342

The dawn phenomenon does not occur in normal elderly subjects.  

PubMed

To determine whether the dawn phenomenon occurs in normal elderly subjects and thus contributes to the progressive mild fasting hyperglycemia of aging, we examined the effect of physiological insulin levels on glucose disposal and hepatic glucose production (HGO) between 0530 and 0800 h, and 0930 and 1200 h. Paired euglycemic insulin clamp studies (8 mU/m2 X min) were performed on healthy old subjects (n = 5), employing [3H]glucose methodology to measure glucose production and disposal rates. Basal plasma insulin, GH, glucagon, and cortisol levels, and HGO and glucose disposal rates were similar before each study. Steady state plasma insulin values were slightly, but not significantly, lower during the dawn study [dawn: 20.3 +/- 1.1 (SE); control: 23.5 +/- 2.1 microU/ml, P = 0.08]. Insulin clearance rates were higher during the dawn study (dawn: 523 +/- 16; control: 430 +/- 19 ml/m2 X min, P less than 0.01). Maximum glucose disposal rates (dawn: 3.10 +/- 0.24; control: 3.03 +/- 0.23 mg/kg X min) and minimum HGO levels (dawn: 0.83 +/- 0.09; control: 0.62 +/- 0.03 mg/kg X min) were not significantly different in each part of the study. There was a significant decrease in plasma GH during the dawn (P less than 0.01, analysis of variance) but not the control studies. There was no difference in cortisol levels during the euglycemic clamp between the dawn and control studies. The mean decrement in glucagon during the insulin infusion was similar in each part of the study. We conclude that the dawn phenomenon does not occur in healthy elderly subjects despite an increase in insulin clearance during the dawn period. PMID:3522617

Meneilly, G S; Elahi, D; Minaker, K L; Rowe, J W

1986-08-01

343

Phase I Results of Vinorelbine With Concurrent Radiotherapy in Elderly Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer: West Japan Thoracic Oncology Group (WJTOG3005-DI)  

SciTech Connect

Purpose: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m{sup 2} in Level 1 and 25 mg/m{sup 2} in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m{sup 2}) on Days 1 and 8 every 3 weeks for two cycles. Results: Four patients were enrolled at Level 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively. Conclusions: Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.

Harada, Hideyuki, E-mail: h.harada@scchr.jp [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Seto, Takashi [Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka (Japan); Igawa, Satoshi [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Tsuya, Asuka [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Wada, Mayuko [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Kaira, Kyoichi; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Hayakawa, Kazushige [Department of Radiology, Kitasato University School of Medicine, Kanagawa (Japan); Nishimura, Tetsuo [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Masuda, Noriyuki [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan)

2012-04-01

344

Naturally occurring mastitis disrupts developmental competence of bovine oocytes.  

PubMed

We examined the effects of naturally occurring mastitis on bovine oocyte developmental competence in vitro. Specifically, we investigated the effects of intramammary infection on the ovarian pool of oocytes (i.e., follicle-enclosed oocytes) and their ability to undergo in vitro maturation, fertilization, and further development to the blastocyst stage. Culled Holstein cows (n=50) from 9 commercial dairy farms in Israel were allotted to 3 groups according to somatic cell count (SCC) records of the last 3 monthly milk tests as well as of quarter samples collected before slaughter: (1) low SCC (n=7), (2) medium SCC (n=16), or (3) high SCC (n=27). Means of SCC values differed among low-, medium-, and high-SCC groups: 148,000, 311,000 and 1,813,000 cell/mL milk, respectively. Milk yield and days in milk did not differ among the 3 groups. Bacterial isolates included coagulase-negative staphylococci, Escherichia coli, Streptococcus dysgalactiae, or no bacteria found. Ovaries were collected at the abattoir and brought to the laboratory. Cumulus oocyte complexes were recovered separately from each cow and subjected individually to in vitro maturation and fertilization, followed by 8d in culture. The number of aspirated oocytes did not differ among groups, with a range of 17 to 21 oocytes per cow. The proportion of oocytes that cleaved into 2- to 4-cell-stage embryos (86.1 ± 3.4%) did not differ among groups. In contrast, mean percentages of embryos developed to the blastocyst stage on d 7 and 8 after fertilization were less in both medium- and-high SCC groups than in the low-SCC group (5.6 ± 2.3 and 4.1 ± 1.8 vs. 18.1 ± 4.6%, respectively). Additional analysis indicated that cleavage and blastocyst-formation rates did not differ among the bacterial types in the low-, medium-, and high-SCC groups. These are the first results to demonstrate that naturally occurring mastitis disrupts the developmental competence of the ovarian pool of oocytes, (i.e., oocytes at the germinal vesicle stage). The disruption was associated with elevation of SCC rather than bacterial type. The results may provide a partial explanation for the low fertility of cows that have contracted mastitic pathogens before insemination. PMID:23957998

Roth, Z; Dvir, A; Kalo, D; Lavon, Y; Krifucks, O; Wolfenson, D; Leitner, G

2013-10-01

345

Characteristics of deaths occurring in hospitalised children: changing trends  

PubMed Central

Background Despite a gradual shift in the focus of medical care among terminally ill patients to a palliative model, studies suggest that many children with life?limiting chronic illnesses continue to die in hospital after prolonged periods of inpatient admission and mechanical ventilation. Objectives To (1) examine the characteristics and location of death among hospitalised children, (2) investigate yearwise trends in these characteristics and (3) test the hypothesis that professional ethical guidance from the UK Royal College of Paediatrics and Child Health (1997) would lead to significant changes in the characteristics of death among hospitalised children. Methods Routine administrative data from one large tertiary?level UK children's hospital was examined over a 7?year period (1997–2004) for children aged 0–18?years. Demographic details, location of deaths, source of admission (within hospital vs external), length of stay and final diagnoses (International Classification of Diseases?10 codes) were studied. Statistical significance was tested by the Kruskal–Wallis analysis of ranks and median test (non?parametric variables), ?2 test (proportions) and Cochran–Armitage test (linear trends). Results Of the 1127 deaths occurring in hospital over the 7?year period, the majority (57.7%) were among infants. The main diagnoses at death included congenital malformations (22.2%), perinatal diseases (18.1%), cardiovascular disorders (14.9%) and neoplasms (12.4%). Most deaths occurred in an intensive care unit (ICU) environment (85.7%), with a significant increase over the years (80.1% in 1997 to 90.6% in 2004). There was a clear increase in the proportion of admissions from in?hospital among the ICU cohort (14.8% in 1998 to 24.8% in 2004). Infants with congenital malformations and perinatal conditions were more likely to die in an ICU (OR 2.42, 95% CI 1.65 to 3.55), and older children with malignancy outside the ICU (OR 6.5, 95% CI 4.4 to 9.6). Children stayed for a median of 13?days (interquartile range 4.0–23.25?days) on a hospital ward before being admitted to an ICU where they died. Conclusions A greater proportion of hospitalised children are dying in an ICU environment. Our experience indicates that professional ethical guidance by itself may be inadequate in reversing the trends observed in this study. PMID:17470499

Ramnarayan, Padmanabhan; Craig, Finella; Petros, Andy; Pierce, Christine

2007-01-01

346

Does immune suppression during stress occur to promote physical performance?  

PubMed

Two adaptationist hypotheses have been proposed to explain why stress, particularly elevation of stress hormones (i.e. glucocorticoids), tends to suppress immune functions. One is that immune suppression represents efforts to minimize autoimmune responses to self-antigens released as organisms cope with stressors (i.e. the autoimmune-avoidance hypothesis). The other is that immune suppression occurs to promote a shunting of resources to life processes more conducive to survival of the stressor (i.e. the re-allocation hypothesis). Here in wild-caught house sparrows (Passer domesticus), we tested the second hypothesis, asking whether sustained elevation of baseline glucocorticoids, due to captivity, caused a greater rate of decline in immune functions than flight performance. A greater decline in immune functions than flight performance would support the re-allocation hypothesis. As in previous studies, we found that captivity tended to alter baseline corticosterone, suggesting that house sparrows experience captivity as a stressor. Captivity also affected several constitutive and induced innate immune metrics: bacterial (Escherichia coli) killing activity of blood and oxidative burst of leukocytes both changed in a manner consistent with immune disregulation. In contrast, breast muscle size and vertical flight (hovering) duration improved over captivity. Collectively, these changes provide indirect support for the re-allocation hypothesis, although within individuals, changes in immune and physical performance were unrelated. PMID:22933612

Martin, Lynn B; Brace, Amber J; Urban, Alexandra; Coon, Courtney A C; Liebl, Andrea L

2012-12-01

347

Explanation for naturally occurring supernumerary limbs in amphibians.  

PubMed

The occasional occurrence of high frequencies of limb abnormalities, including extra limbs, in natural populations of amphibians has long been a puzzle. In this paper we report the discovery of a population in which such limb abnormalities appear to be caused by a parasitic flatworm (trematode) that uses amphibians as intermediate hosts. The cercarial larval stage of the trematode attacks amphibians, penetrating the skin to form cysts (metacercariae). The cysts are preferentially localized in the cloacal region, including the developing hind limb regions in larvae of both frogs (Hyla regilla) and salamanders (Ambystoma macrodactylum). A wide range of limb abnormalities are seen, including duplicated limb structures ranging from extra digits to several extra whole limbs. We hypothesize that these limb abnormalities result from localized regulatory responses of developing and regenerating limb tissues to mechanical disruption caused by the trematode cysts. We have tested this idea by implanting inert resin beads into developing limb buds of frogs and salamanders. Since this treatment can cause supernumerary limb structures, our hypothesis is sufficient to explain the naturally occurring extra limbs. PMID:2348164

Sessions, S K; Ruth, S B

1990-04-01

348

Oligodontia and curly hair occur with ectodysplasin-a mutations.  

PubMed

Oligodontia is the developmental absence of more than 5 permanent teeth except for the third molar. Familial oligodontia can occur as an isolated form or as part of a genetic syndrome. Mutations in the MSX1, PAX9, AXIN2, EDA, and WNT10A genes have been identified in familial non-syndromic oligodontia. Ectodermal dysplasia is a group of syndromes involving abnormalities of the ectodermal structures and is comprised of more than 150 different forms. Mutations in the ectodysplasin-A (EDA) gene have been associated with X-linked hypohidrotic ectodermal dysplasia, and partial disruption of the EDA signaling pathway has been shown to cause an isolated form of oligodontia. We identified 2 X-linked oligodontia families and performed mutational analysis of the EDA gene. The mutational analysis revealed 2 novel EDA mutations: c.866G>T, p.Arg289Leu and c.1135T>G, p.Phe379Val (reference sequence NM_001399.4). These mutations were perfectly segregated with oligodontia and curly hair within each family and were not found in the 150 control X-chromosomes with the same ethnic background and in the exome variant server. This study broadens the mutational spectrum of the EDA gene and the understanding of X-linked oligodontia with curly hair. PMID:24487376

Lee, K E; Ko, J; Shin, T J; Hyun, H K; Lee, S H; Kim, J W

2014-04-01

349

Scrap metal management issues associated with naturally occurring radioactive material  

SciTech Connect

Certain industrial processes sometimes generate waste by-products that contain naturally occurring radioactive material (NORM) at elevated concentrations. Some industries, including the water treatment, geothermal energy, and petroleum industries, generate scrap metal that may be contaminated with NORM wastes. Of these three industries, the petroleum industry probably generates the largest quantity of NORM-contaminated equipment, conservatively estimated at 170,000 tons per year. Equipment may become contaminated when NORM-containing scale or sludge accumulates inside water-handling equipment. The primary radionuclides of concern in these NORM wastes are radium-226 and radium-228. NORM-contaminated equipment generated by the petroleum industry currently is managed several ways. Some equipment is routinely decontaminated for reuse; other equipment becomes scrap metal and may be disposed of by burial at a licensed landfill, encapsulation inside the wellbore of an abandoned well, or shipment overseas for smelting. In view of the increased regulatory activities addressing NORM, the economic burden of managing NORM-contaminated wastes, including radioactive scrap metal, is likely to continue to grow. Efforts to develop a cost-effective strategy for managing radioactive scrap metal should focus on identifying the least expensive disposition options that provide adequate protection of human health and the environment. Specifically, efforts should focus on better characterizing the quantity of radioactive scrap available for recycle or reuse, the radioactivity concentration levels, and the potential risks associated with different disposal options.

Smith, K.P.; Blunt, D.L.

1995-08-01

350

Natural occurring epialleles determine vitamin E accumulation in tomato fruits.  

PubMed

Vitamin E (VTE) content is a low heritability nutritional trait for which the genetic determinants are poorly understood. Here, we focus on a previously detected major tomato VTE quantitative trait loci (QTL; mQTL(9-2-6)) and identify the causal gene as one encoding a 2-methyl-6-phytylquinol methyltransferase (namely VTE3(1)) that catalyses one of the final steps in the biosynthesis of ?- and ?-tocopherols, which are the main forms of VTE. By reverse genetic approaches, expression analyses, siRNA profiling and DNA methylation assays, we demonstrate that mQTL(9-2-6) is an expression QTL associated with differential methylation of a SINE retrotransposon located in the promoter region of VTE3(1). Promoter DNA methylation can be spontaneously reverted leading to different epialleles affecting VTE3(1) expression and VTE content in fruits. These findings indicate therefore that naturally occurring epialleles are responsible for regulation of a nutritionally important metabolic QTL and provide direct evidence of a role for epigenetics in the determination of agronomic traits. PMID:24967512

Quadrana, Leandro; Almeida, Juliana; Asís, Ramon; Duffy, Tomás; Dominguez, Pia Guadalupe; Bermúdez, Luisa; Conti, Gabriela; Corrêa da Silva, Junia V; Peralta, Iris E; Colot, Vincent; Asurmendi, Sebastian; Fernie, Alisdair R; Rossi, Magdalena; Carrari, Fernando

2014-01-01

351

Solution of naturally-occurring glasses in the geological environment  

SciTech Connect

As part of a study to investigate the feasibility of putting nuclear wastes in glass containers and burying them on land or dumping them in the ocean, we have made a study of the amount of solution experienced by naturally occurring glasses from two land sites and thirty-four deep-sea sites. The glasses used in this study are microtektites from three strewn fields (Australasian, Ivory Coast, and North American) and from the Zhamanshin impact crater in southern Siberia. The microtektites range in age from 0.7 to 35 m.y. and they have a wide range in composition. Although several criteria for determining the amount of solution were considered, most of the conclusions are based on two criteria: (1) width of cracks, and (2) elevation of silica-rich inclusions above the adjacent microtektite surface. The amount of solution was determined for about 170 microtektites; and measured amounts of solution range from 0.2 to at least 28 {mu}m, but most are less than 5 {mu}m. There appears to be no systematic relationship between age and amount of solution. 21 refs., 7 tabs.

Glass, B.P.

1982-12-01

352

Predictive model of squeal noise occurring on a laboratory brake  

NASA Astrophysics Data System (ADS)

This paper on brake squeal instability presents a reduced order model of a laboratory brake considered in a previous paper, and presents a description of the squeal mechanism occurring during experiments. The model uses the modal parameters of the laboratory brake components, the disc and the caliper, when they are not in contact between them. Successively, the caliper and the disc are put in contact through the pad that is modeled as a one degree of freedom system while the Coulomb law models the friction interaction between them. No stick slip motion of the pad is considered, because it was not observed in the experimental tests. As a result the model is linear and particularly suited for a parametric analysis. The stability of the model is studied by a complex eigenvalue analysis and the obtained results show a good agreement with the experimental data, provided that the key parameters of the model are consistent with the experimental set-up. The key role of the disc and the pad dynamics are discussed.

Giannini, Oliviero; Sestieri, Aldo

2006-09-01

353

Resolving the Diaporthe species occurring on soybean in Croatia.  

PubMed

Diaporthe (anamorph = Phomopsis) species are plant pathogens and endophytes on a wide range of hosts including economically important crops. At least four Diaporthe taxa occur on soybean and they are responsible for serious diseases and significant yield losses. Although several studies have extensively described the culture and morphological characters of these pathogens, their taxonomy has not been fully resolved. Diaporthe and Phomopsis isolates were obtained from soybean and other plant hosts throughout Croatia. Phylogenetic relationships were determined through analyses of partial translation elongation factor 1-alpha (EF1-?) gene and ITS nrDNA sequence data. By combining morphological and molecular data, four species could be distinguished on soybeans in Croatia. Diaporthe phaseolorum is described in this study and its synonyms are discussed. Diaporthe phaseolorum var. caulivora is raised to species status and the name Diaporthe caulivora is introduced to accommodate it. A species previously known as Phomopsis sp. 9 from earlier studies on sunflower, grapevine, rooibos and hydrangea is reported for the first time on soybean, and is formally described as Diaporthe novem. The well-known soybean pathogen Phomopsis longicolla was also collected in the present study and was transferred to Diaporthe longicolla comb. nov. The presence of these species on herbaceous hosts raises once more the relevance of weeds as reservoirs for pathogens of economically important plants. PMID:22403474

Santos, J M; Vrande?i?, K; Cosi?, J; Duvnjak, T; Phillips, A J L

2011-12-01

354

THE DISTRIBUTION OF THE IMMUNE BODIES OCCURRING IN ANTIPNEUMOCOCCUS SERUM  

PubMed Central

The immune bodies of antipneumococcus serum are completely precipitated by 38 to 42 per cent. saturation with ammonium sulphate. They are incompletely precipitated by (a) ammonium sulphate in less than 38 per cent. saturation, (b) saturation with sodium chloride, (c) dilution and saturation with carbon dioxide, (d) removal of crystalloids by dialysis. The immune bodies of antipneumococcus serum are, therefore, associated or combined with that fraction of the globulins precipitated by 38 to 42 per cent. saturation with ammonium sulphate. The immune body fraction does not correspond exactly with the ordinary euglobulin (one-third saturation with ammonium sulphate or complete saturation with sodium chloride) or with the insoluble globulins precipitated by carbon dioxide or dialysis. These fractions carry with them only a part of the immune bodies. Neither the albumin nor that fraction of the globulin not precipitated by 38 to 42 per cent. saturation of ammonium sulphate contain any of the demonstrable antibodies. The most promising method for the practical purification of the immune bodies occurring in antipneumococcus serum appears to be precipitation by 38 to 42 per cent. saturation with ammonium sulphate. PMID:19867856

Avery, Oswald T.

1915-01-01

355

Treatment of spontaneously occurring veterinary tumors with photodynamic therapy  

NASA Astrophysics Data System (ADS)

Chloroaluminum phthalocyanine tetrasulfonate was administered intravenously (1.0 mg/kg) to client owned cats and a dog with spontaneously occurring squamous cell carcinoma of head and neck. Light was delivered 48 hours post injection of the photosensitizer. An argon- pumped dye-laser was used to illuminate the lesions with 675 nm light delivered through a microlens fiber and/or a cylindrical diffuser. The light dose was 100 J/cm2 superficially or 300 J/cm interstitially. Eleven photodynamic therapy treatments in seven cats and one dog were performed. Two cats received a second treatment in approximately sixty days after the initial treatment. The superficial dose of light was increased to 200 J/cm2 for the second treatment. While the longest follow-up is twelve months, the responses are encouraging. The dog had a complete response. Among the cats, three showed complete response, three showed partial response and one showed no response. One cat expired two days post treatment. It is early to evaluate the response in two cats that received second treatments. Photodynamic therapy with chloroaluminum phthalocyanine tetrasulfonate was effective in treating squamous cell carcinoma in pet animals.

Panjehpour, Masoud; Legendre, Alfred; Sneed, Rick E.; Overholt, Bergein F.

1992-06-01

356

Naturally occurring phytochemicals for the prevention of Alzheimer's disease.  

PubMed

Alzheimer's disease (AD) is an age-related neurodegenerative disease increasingly recognized as one of the most important medical problems affecting the elderly. Although a number of drugs, including several cholinesterase inhibitors and an NMDA receptor antagonist, have been approved for use, they have been shown to produce diverse side effects and yield relatively modest benefits. To overcome these limitations of current therapeutics for AD, extensive research and development are underway to identify drugs that are effective and free of undesirable side effects. Certain naturally occurring dietary polyphenolic phytochemicals have received considerable recent attention as alternative candidates for AD therapy. In particular, curcumin, resveratrol, and green tea catechins have been suggested to have the potential to prevent AD because of their anti-amyloidogenic, anti-oxidative, and anti-inflammatory properties. These polyphenolic phytochemicals also activate adaptive cellular stress responses, called 'neurohormesis', and suppress disease processes. In this commentary, we describe the amyloid-beta-induced pathogenesis of AD, and summarize the intracellular and molecular targets of selected dietary phytochemicals that might slow the progression of AD. PMID:20050972

Kim, Jiyoung; Lee, Hyong Joo; Lee, Ki Won

2010-03-01

357

Visualizing Global Earthquakes â Where and Why do Earthquakes Occur?  

NSDL National Science Digital Library

This screenshot from this visualization shows a map of tectonic plate boundaries. The visualization transitions between global earthquake distribution to a map of plate boundaries, to clearly illustrate how they are related. This visualization also includes an overview of the distribution and magnitude of earthquakes at different types of plate boundaries. Click the image to enlarge or view the MP4 movie ( 31.1MB Jul27 11). The purpose of this activity is to introduce students to the distribution of earthquakes at and below the surface of earth and how their distribution is related to the geometry and type of plate boundaries. Because the depth of earthquakes can be difficult for students to visualize in 2D representations, this activity allows students to visualize the 3D distribution of earthquakes within Earth's surface, which is essential for understanding how different types of earthquakes occur in different tectonic settings. Talking points and questions are included to use this visualization as part of an interactive lecture. In addition to playing back the visualization, instructors can also download the visualization software and data set and explore it themselves.

Cara Harwood

358

Analysis of coal slag for naturally occurring radioactive material.  

PubMed

Samples of aerosolized coal slag were collected during an abrasive blasting operation to determine the concentration of naturally occurring radioactive materials (NORM) in the respirable and nonrespirable fractions. Each slag fraction was analyzed using alpha and gamma spectrometry. Since the slag is insoluble, it was necessary to dissolve samples completely by fusion with potassium fluoride and, after additional transposing and separation, mount the precipitate containing radium (Ra), the main radioactive component in NORM, on a membrane filter for alpha counting. The concentration of 226Ra in coal slag was independent of the particle size fraction and equal to 2.28 picocuries/gram (pCi/g) +/- 0.43 pCi/g, which is approximately twice the typical concentration of NORM in uncontaminated soil. Analysis of NORM by gamma spectrometry identified low concentrations of uranium, thorium, and potassium, all primordial radioactive materials that are commonly encountered in normal background soil. Integral exposure to workers from inhalation of NORM during abrasive blasting with coal slag is extremely low and could be essentially eliminated by use of appropriate respiratory protection. External radiation exposure to workers handling large quantities of NORM-contaminated coal slag during shipping or storage is also low, but would vary depending on the concentration of NORM in the slag. PMID:9697295

Spitz, H B; Rajaretnam, G

1998-07-01

359

Multisensor analysis of recent heavy precipitation events occurred over Italy  

NASA Astrophysics Data System (ADS)

Satellite-based microwave and infrared measurements, together with 3-D lightning data provided by LINET network, will be jointly used to describe and analyze the microphysical characteristics and the evolution of recent severe storms occurred over Italy. In addition, passive microwave precipitation retrieval algorithms (Sanò et al., 2013, Casella et al., 2013, Mugnai et al., 2013, Smith et al., 2013) will be applied to obtain instantaneous rain fields corresponding to LEO overpasses, while IR and lightning data will be also used to reproduce the time continuous evolution of precipitation (Dietrich et al., 2011, Di Paola et al., 2012). For two heavy precvipitation events observed during the HyMeX (Hydrological cycle in the Mediterranean eXperiment) SOP1.1 in the Central Italy target area in October 2012, the Polarimetric C-band radar (ISAC/CNR Polar 55C) located in Rome will provide also the ground reference for precipitation, microphysics structure, and volumetric distribution of precipitating clouds. Future perspectives of the utilization of the above techniques in supporting the operational activity of the Italian Civil Protection department will be discussed with the help of advanced graphical multisensor representation of real time remotely sensed quantities.

Dietrich, Stefano; Panegrossi, Giulia; Di Paola, Francesco; Sanò, Paolo; Casella, Daniele; Petracca, Marco; Baldini, Luca; Roberto, Nicoletta; Mugnai, Alberto

2013-04-01

360

Volatile analysis of ground almonds contaminated with naturally occurring fungi.  

PubMed

Aflatoxigenic aspergilli inflict major economic damage to the tree nut industry of California, with the highest negative impact to almonds. Aspergilli and fungi in general are known to emit volatiles in varying quantity and composition dependent upon their growth media. The goal of the study was to determine the volatile emission of whole and blanched almonds that had been picked out and labeled as inedible by processors. The aflatoxin content and number of colony forming units of each sample were also determined. A total of 23 compounds were consistently detected and identified. Several volatiles from the blanched almonds demonstrated significant increases when compared to the emissions of whole almonds. Several of these volatiles are considered fatty acid decomposition products and included hexanal, heptanal, octanal, nonanal, 3-octen-2-one, tetramethylpyrazine, and decanal. The almond samples investigated were characteristic of a typical postharvest environment and illustrative of potential contamination within a stockpile or transport container. Volatiles indicative of fatty acid decomposition were predominant in the samples that underwent some form of blanching. The emission amounts of hexanal, heptanal, octanal, and hexanoic acid increased 3-fold in samples contaminated with aflatoxin; however, due to variability between samples they could not be considered as indicator volatiles for aflatoxin content. The emission profile of volatiles from almond kernels contaminated with naturally occurring aspergilli and associated fungi is heretofore unreported. PMID:21528918

Beck, John J; Mahoney, Noreen E; Cook, Daniel; Gee, Wai S

2011-06-01

361

Pioneer round of translation occurs during serum starvation  

SciTech Connect

The pioneer round of translation plays a role in translation initiation of newly spliced and exon junction complex (EJC)-bound mRNAs. Nuclear cap-binding protein complex CBP80/20 binds to those mRNAs at the 5'-end, recruiting translation initiation complex. As a consequence of the pioneer round of translation, the bound EJCs are dissociated from mRNAs and CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E. Steady-state translation directed by eIF4E allows for an immediate and rapid response to changes in physiological conditions. Here, we show that nonsense-mediated mRNA decay (NMD), which restricts only to the pioneer round of translation but not to steady-state translation, efficiently occurs even during serum starvation, in which steady-state translation is drastically abolished. Accordingly, CBP80 remains in the nucleus and processing bodies are unaffected in their abundance and number in serum-starved conditions. These results suggest that mRNAs enter the pioneer round of translation during serum starvation and are targeted for NMD if they contain premature termination codons.

Oh, Nara; Kim, Kyoung Mi; Cho, Hana; Choe, Junho [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Yoon Ki [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)], E-mail: yk-kim@korea.ac.kr

2007-10-12

362

Covalent DNA-protein crosslinking occurs after hyperthermia and radiation  

SciTech Connect

Covalent DNA-protein crosslinks occur in exponentially growing mouse leukemia cells (L1210) after exposure to ionizing radiation. The amount of DNA-protein crosslinks as measured by a filter binding assay is dose dependent upon x irradiation. Although hyperthermia and radiation in combination are synergistic with respect to cell lethality, the combination does not result in an increase of DNA-protein crosslinks when assayed immediately following treatments. Hyperthermia (43/sup 0/C/15 min) given prior to radiation dose not alter the radiation dose dependency of the amount of initial crosslinking. In addition, the amount of DNA-protein crosslinking produced by heat plus radiation is independent of the length of heating the cells at 43/sup 0/C. The DNA-protein crosslinks produced y 50-Gy x ray alone are removed after 2 hr at 37/sup 0/C. However, if hyperthermia (43/sup 0/C/15 min) is given prior to 100-Gy x ray, the removal of DNA-protein crosslinks is delayed until 4.0 hr after radiation. Phospho-serine and phospho-threonine bonds are not produced with either radiation or the combination of hyperthermia plus radiation as judged by the resistance of the bonds to guanidine hydrochloride. However, hyperthermia plus radiation causes an increase in phosphate to nitrogen type bonding. These results show that radiation alone causes covalent DNA-protein crosslinks. Hyperthermia in combination with radiation does not increase the total amount of the crosslinks but delays the removal of the crosslinks and alters the distribution of the types of chemical bonding.

Cress, A.E.; Bowden, G.T.

1983-09-01

363

Covalent DNA-protein crosslinking occurs after hyperthermia and radiation  

SciTech Connect

Covalent DNA-protein crosslinks occur in exponentially growing mouse leukemia cells (L1210) after exposure to ionizing radiation. The amount of DNA-protein crosslinks as measured by a filter binding assay is dose dependent upon X irradiation. Although hyperthermia and radiation in combination are synergistic with respect to cell lethality, the combination does not result in an increase of DNA-protein crosslinks when assayed immediately following treatments. Hyperthermia (43 degrees C/15 min) given prior to radiation does not alter the radiation dose dependency of the amount of initial crosslinking. In addition, the amount of DNA-protein crosslinking produced by heat plus radiation is independent of the length of heating the cells at 43 degrees C. The DNA-protein crosslinks produced by 50-Gy X ray alone are removed after 2 hr at 37 degrees C. However, if hyperthermia (43 degrees C/15 min) is given prior to 100-Gy X ray, the removal of DNA-protein crosslinks is delayed until 4.0 hr after radiation. Phospho-serine and phospho-threonine bonds are not produced with either radiation or the combination of hyperthermia plus radiation as judged by the resistance of the bonds to guanidine hydrochloride. However, hyperthermia plus radiation causes an increase in phosphate to nitrogen type bonding. These results show that radiation alone causes covalent DNA-protein crosslinks. Hyperthermia in combination with radiation does not increase the total amount of the crosslinks but delays the removal of the crosslinks and alters the distribution of the types of chemical bonding. These data suggest that the synergistic action on hyperthermia with radiation is more related to the rate of removal and the type of chemical bonding involved in the covalent DNA-protein crosslinks rather than the amount of DNA-protein crosslinks.

Cress, A.E.; Bowden, G.T.

1983-09-01

364

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS NATURALLY OCCURRING PHASIC DOPAMINE SIGNALING  

PubMed Central

Methamphetamine (METH) is a highly addictive drug that is also neurotoxic to central dopamine (DA) systems. Although striatal DA depletions induced by METH are associated with behavioral and cognitive impairments, the link between these phenomena remains poorly understood. Previous work in both METH-pretreated animals and the 6-hydroxydopamine model of Parkinson’s disease suggests that a disruption of phasic DA signaling, which is important for learning and goal-directed behavior, may be such a link. However, prior studies used electrical stimulation to elicit phasic-like DA responses and were also performed under anesthesia, which alters DA neuron activity and presynaptic function. Here we investigated the consequences of METH-induced DA terminal loss on both electrically evoked phasic-like DA signals and so-called “spontaneous” phasic DA transients measured by voltammetry in awake rats. Not ostensibly attributable to discrete stimuli, these sub-second DA changes may play a role in enhancing reward-cue associations. METH-pretreatment reduced tissue DA content in the dorsomedial striatum and nucleus accumbens by ~55%. Analysis of phasic-like DA responses elicited by reinforcing stimulation revealed that METH pretreatment decreased their amplitude and underlying mechanisms for release and uptake to a similar degree as DA content in both striatal subregions. Most importantly, characteristics of DA transients were altered by METH-induced DA terminal loss, with amplitude and frequency decreased and duration increased. These results demonstrate for the first time that denervation of DA neurons alters naturally occurring DA transients and are consistent with diminished phasic DA signaling as a plausible mechanism linking METH-induced striatal DA depletions and cognitive deficits. PMID:23574406

Howard, Christopher D.; Daberkow, David P.; Ramsson, Eric S.; Keefe, Kristen A.; Garris, Paul A.

2013-01-01

365

Naturally occurring antioxidant nutrients reduce inflammatory response in mice.  

PubMed

The effects of mixed dietary coenzyme Q(9), alpha-tocopherol, and beta-carotene on immune cell activity and blood cytokine profile were studied in peritoneal macrophages, spleen lymphocytes, and blood plasma from mice with acute inflammation induced by lipopolysaccharide (LPS). The activity of each fat-soluble antioxidant was also investigated separately in several model systems, both in vivo and in vitro. NMRI male mice were fed a diet supplemented with fat-soluble antioxidants for 15 days prior to LPS injection. LPS-induced inflammation resulted in induction of cellular production of pro-inflammatory cytokines such as TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-6, IFN-gamma, and also IL-10, an anti-inflammatory cytokine, and subsequent accumulation of these cytokines in blood plasma. In animals fed the antioxidant-rich diet, the inflammatory response to LPS injection was significantly reduced. The production of anti-inflammatory cytokine IL-10 in response to toxic stress and its accumulation in plasma were not modified by the diet. In addition, the expression of the inducible form of heat-shock protein 70 in mice treated with endotoxin was reduced in the animals pretreated with the antioxidant-rich diet. We showed that the diet suppressed phosphorylation of NF-kappaB, I kappaB kinase and SAPK/JNK proteins, thereby preventing the activation of the NF-kappaB kinase and SAPK/JNK signaling pathways in LPS-treated mice. In this report we demonstrate the potential effectiveness of naturally occurring antioxidant nutrients in the reduction of the inflammatory response. Therefore, it may be possible to develop novel therapeutic combinations, containing coenzyme Q(9), alpha-tocopherol, and beta-carotene, which promote immune stimulation. PMID:19463810

Novoselova, Elena G; Lunin, Sergey M; Novoselova, Tatyana V; Khrenov, Maxim O; Glushkova, Olga V; Avkhacheva, Nadezhda V; Safronova, Valentina G; Fesenko, Evgeny E

2009-08-01

366

Death in pediatric Cushing syndrome is uncommon but still occurs.  

PubMed

Cushing syndrome (CS) in children is rare. Delayed diagnosis and treatment of CS may be associated with increased morbidity and, unfortunately, mortality. We performed a retrospective review of all patients with CS under the age of 18 years referred to the National Institutes of Health (NIH) from 1998 to 2013 in order to describe deceased patients among cases of pediatric CS referred to the National Institutes of Health (NIH). The deaths of four children (three females and one male), aged 7.5-15.5 years (mean age 11.2 years) with length of disease 2-4 years, were recorded among 160 (2.5 %) children seen at or referred to the NIH over the last 15 years. All died at different institutions, prior to coming to the NIH (two) or after leaving NIH (two). Presenting symptoms included increasing weight and decreasing height gain, facial plethora, dorsocervical fat pad (webbed neck), striae, headache, vision disturbances, and depression and other mood or behavior changes; there were no differences between how these patients presented and the others in our cohort. The causes of CS in the deceased patients were also not different, in fact, they spanned the entire spectrum of CS: pituitary disease (one), ectopic corticotropin production (one), and primary adrenal hyperplasia (one). In one patient, the cause of CS could not be verified. Three died of sepsis and one due to residual disease and complications of the primary tumor. Conclusions: Despite the advances in early diagnosis and treatment of pediatric CS, a 2.5 % mortality rate was identified in a large cohort of patients with this condition referred to an experienced, tertiary care referral center (although these deaths occurred elsewhere). Pediatricians need to recognize the possibility of death, primarily due to sepsis, in a patient with pediatric CS and treat accordingly. PMID:25241829

Gkourogianni, Alexandra; Lodish, Maya B; Zilbermint, Mihail; Lyssikatos, Charalampos; Belyavskaya, Elena; Keil, Margaret F; Stratakis, Constantine A

2014-09-23

367

Committed effective dose from naturally occuring radionuclides in shellfish  

NASA Astrophysics Data System (ADS)

Recognizing their importance in the average Malaysian daily diet, the radioactivity concentrations in mollusc- and crustacean-based food have been determined for key naturally occuring radionuclides. Fresh samples collected from various maritime locations around peninsular Malaysia have been processed using standard procedures; the radionuclide concentrations being determined using an HPGe ?-ray spectrometer. For molluscs, assuming secular equilibrium, the range of activities of 238U (226Ra), 232Th (228Ra) and 40K were found to be 3.28±0.35 to 5.34±0.52, 1.20±0.21 to 2.44±0.21 and 118±6 to 281±14 Bq kg-1 dry weight, respectively. The respective values for crustaceans were 3.02±0.57 to 4.70±0.52, 1.38±0.21 to 2.40±0.35 and 216±11 to 316±15 Bq kg-1. The estimated average daily intake of radioactivity from consumption of molluscs are 0.37 Bq kg-1 for 238U (226Ra), 0.16 Bq kg-1 for 232Th (228Ra) and 18 Bq kg-1 for 40K; the respective daily intake values from crustaceans are 0.36 Bq kg-1, 0.16 Bq kg-1 and 23 Bq kg-1. Associated annual committed effective doses from molluscs are estimated to be in the range 21.3 to 34.7 ?Sv for 226Ra, 19.3 to 39.1 ?Sv for 228Ra and 17.0 to 40.4 ?Sv for 40K. For crustaceans, the respective dose ranges are 19.6 to 30.5 ?Sv, 22.0 to 38.4 ?Sv and 31.1 to 45.5 ?Sv, being some several times world average values.

Khandaker, Mayeen Uddin; Wahib, Norfadira Binti; Amin, Yusoff Mohd.; Bradley, D. A.

2013-07-01

368

Manufactured Home Testing in Simulated and Naturally Occurring High Winds  

SciTech Connect

A typical double-wide manufactured home was tested in simulated and naturally occurring high winds to understand structural behavior and improve performance during severe windstorms. Seven (7) lateral load tests were conducted on a double-wide manufactured home at a remote field test site in Wyoming. An extensive instrumentation package monitored the overall behavior of the home and collected data vital to validating computational software for the manufactured housing industry. The tests were designed to approach the design load of the home without causing structural damage, thus allowing the behavior of the home to be accessed when the home was later exposed to high winds (to 80-mph). The data generally show near-linear initial system response with significant non-linear behavior as the applied loads increase. Load transfer across the marriage line is primarily compression. Racking, while present, is very small. Interface slip and shear displacement along the marriage line are nearly insignificant. Horizontal global displacements reached 0.6 inch. These tests were designed primarily to collect data necessary to calibrate a desktop analysis and design software tool, MHTool, under development at the Idaho National Laboratory specifically for manufactured housing. Currently available analysis tools are, for the most part, based on methods developed for “stick built” structures and are inappropriate for manufactured homes. The special materials utilized in manufactured homes, such as rigid adhesives used in the connection of the sheathing materials to the studs, significantly alter the behavior of manufactured homes under lateral loads. Previous full scale tests of laterally loaded manufactured homes confirm the contention that conventional analysis methods are not applicable. System behavior dominates the structural action of manufactured homes and its prediction requires a three dimensional analysis of the complete unit, including tiedowns. This project was sponsored by the US Department of Energy, US Department of Housing and Urban Development, and the Manufactured Housing Institute. The results of this research can lead to savings in annual losses of life and property by providing validated information to enable the advancement of code requirements and by developing engineering software that can predict and optimize wind resistance.

W. D. Richins; T. K. Larson

2006-08-01

369

May Diamondiferous Associations Occur In The Central Negev (israel)?  

NASA Astrophysics Data System (ADS)

Larson (1995) put forward a hypothesis on the extremely high development of diamond-bearing kimberlites in the Mid-Cretaceous period. In Israel, the Cretaceous magmatic activity is well known in the central Negev. The first microdiamond in Is- rael was found in the Negev (Flexer et al., 1988) in the Maastrichtian below the K/T boundary (the mentioned authors associated its origin with an extraterrestrial event). An integrated analysis of several geological and geophysical factors allowed to re- vealing for detailed investigations the Makhtesh Ramon area situated near the town of Mizpe-Ramon (central Negev). Within the area about 90 kg of samples for the subse- quent mineralogical-geochemical analyses have been selected. The following minerals of the anticipating diamondiferrous association in the selected samples were revealed: (first group) - chrome-diopside, orange garnet, bright-crimson pyrope, picroilmenite, black spinel, olivine, anatase and tourmaline. Chrome-diopside as an indicator mineral may be found only in the neighboring zone of basic pipe occurrence. Orange garnet, bright-crimson pyrope and tourmaline also are essential indicators of the presence of diamondiferrous association in the studied district. These minerals do not rolled that is additional evidence of the neighboring occurrence of the indigenous rocks. Data of electronic microscopy (Surkov et al., 2002) show that the grains of (1) picroilmenite and (2) pyrope contain, respectively: (1) cobalt, chrome, magnesium and nickel and (2) chrome, magnesium and aluminum. These data indicate that both picroilmenite and pyrope have the hyper-abyssal origin that also is an indicator of the possible occurring of diamondiferous pipes. Besides above mentioned minerals, list of determined min- erals in the samples (second group) includes: hexagonal quartz, feldspars, pyroxenes (black, green, dark-green, gray-green, brown-green), magnetite, hematite, ilmenite, galenite, pyrite, limonite, small magnetic spheres (quant. matter), mica, hydro-mica, chromite, leucoxene, zircon, rutile, secondary minerals of cuprum (green and blue), calcite, etc. These minerals (by their considering with the first group) are also indica- tors of the diamond-bearing of the studied area. It should be noted that the amount of 1 these minerals is extremely high: in 50 kg of investigated samples (selected from the loose deposits and conglomerate) till the present time (January 05, 2002) altogether al- most 1,800 grains (first group only) of the proposed diamondiferrous association have been detected. Thus, we could suggest that the Makhtesh Ramon area is perspective for discovering both basic diamondiferrous rocks (kimberlite and lamproite pipes) as well as diamond crystals in loose deposits. 2

Eppelbaum, L.; Vaksman, V.; Klepatch, C.; Kouznetsov, S.; Surkov, A.; Smirnov, S.; Bezlepkin, B.; Itkis, S.

370

Infrared monitoring of hydrothermal echanges occurring in a fracture  

NASA Astrophysics Data System (ADS)

We aim to characterize the heat exchange that occurs when water flows through a fracture at a different temperature from that of the surrounding rock. This happens during many man-made or natural processes. For instance, injection of water in the context of geothermal power plants or sudden mechanical movements (e.g. rockfalls, landslides, earthquakes) that transport water. It is presently challenging to estimate the heat transfer and temperature inside a fractured medium where water is flowing, despite various numerical models which have been proposed [Neuville et al, 2010, 2013; Kolditz et Clauser, 1998; Heuer, 1991]. The difficulties arise from the complexity of the fracture network, the fracture topography, as well as complex hydraulic flow (e.g. recirculation) and heat exchanges. As a consequence, various hypotheses were made in the models. More experimental data are required in order to calibrate these models, validate or refute the hypotheses. Our work aims to provide temperature data at the fracture scale, in an experiment where the pressure gradient an fracture topography are controlled, with slow hydraulic flow. This required to develop a setup from scratch. An infrared camera and thermistors are used to monitor the temperature in space and time. Water is injected through a partly natural rough fracture with impermeable walls. The bottom part of the fracture is a larvikite stone with a rough surface (presumably this surface was obtained from mode I fracturing), and the top part is a layer which is transparent in the infrared range. As a consequence the infrared camera is expected to measure the temperature at the interface between this transparent layer and the water. The topography of the surface of the rock was reconstituted using a photogrammetry software [MicMac, IGN], and compared to measurements made with a mechanical profiler. Using this geometry we carefully localize the temperature observations (infrared camera and thermistors) and correlate the temperature variations with the topography. Preliminary comparisons with simulations from a coupled lattice Boltzmann method that solves both the complete Navier-Stokes and advection-diffusion equations in three-dimensions are also presented. N. Heuer, T. Küpper and D. Windelberg, Mathematical model of a Hot Dry Rock system, Geophys. J. Int. 105, 659-664 (1991). O. Kolditz and C. Clauser, Numerical simulation of flow and heat transefer in fractured cristalline rocks: application to the hot dry rock site in Rosemanowes (U.K.), Geothermics, 27, 1, p 1-23, (1998). MicMac, IGN: sofware developed by the French Institut Géographique National (IGN) A. Neuville, R. Toussaint, and J. Schmittbuhl, Hydro-thermal flows in a self-affine rough fracture, Phys. Rev. E, 82, 036,317, (2010). A. Neuville, E.G. Flekkøy, R. Toussaint, Influence of asperities on fluid and thermal flow in a fracture: a coupled Lattice Boltzmann study. Journal of Geophysical Research, 118, 7, 3394-3407, (2013).

Neuville, Amélie; Flekkøy, Eirik; Galland, Olivier; Gundersen, Olav; Jørgen Måløy, Knut

2014-05-01

371

How much malaria occurs in urban Luanda, Angola? A health facility-based assessment.  

PubMed

We conducted a health facility-based survey of patients with fever during malaria transmission season to determine the proportion with laboratory-confirmed malaria in Luanda, Angola. We enrolled 864 patients at 30 facilities; each underwent a blood film for malaria and a questionnaire. Only 3.6% had a positive blood film. When stratified by distance of the facility to city center (< 15 km and > or = 15 km), the proportions were 1.5% (9/615) and 8.8% (22/249), respectively (P < 0.0001). Of patients traveling outside Luanda in the preceding 3 months, 6.8% (6/88) had malaria, compared with 3.2% (26/776) not traveling (P = 0.13). Children < 5 years of age were less likely to have malaria (2.4%; 12/510) than children ages 5-14 (8.7%; 9/104) and adults (4.0%; 10/250) (P = 0.03). The prevalence of laboratory-confirmed malaria in febrile patients in Luanda is very low, but increases with distance from the urban center. Prevention and treatment should be focused in surrounding rural areas. PMID:19270303

Thwing, Julie I; Mihigo, Jules; Fernandes, Alexandra Pataca; Saute, Francisco; Ferreira, Carolina; Fortes, Filomeno; de Oliveira, Alexandre Macedo; Newman, Robert D

2009-03-01

372

Antifungal prophylaxis during neutropenia and immunodeficiency.  

PubMed Central

Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

Lortholary, O; Dupont, B

1997-01-01

373

A Prospective Evaluation of Real-Time PCR Assays for the Detection of Orientia tsutsugamushi and Rickettsia spp. for Early Diagnosis of Rickettsial Infections during the Acute Phase of Undifferentiated Febrile Illness  

PubMed Central

One hundred and eighty febrile patients were analyzed in a prospective evaluation of Orientia tsutsugamushi and Rickettsia spp. real-time polymerase chain reaction (PCR) assays for early diagnosis of rickettsial infections. By paired serology, 3.9% (7 of 180) and 6.1% (11 of 180) of patients were confirmed to have acute scrub or murine typhus, respectively. The PCR assays for the detection of O. tsutsugamushi and Rickettsia spp. had high specificity (99.4% [95% confidence interval (CI): 96.8–100] and 100% [95% CI: 97.8–100], respectively). The PCR results were also compared with immunoglobulin M (IgM) immunofluorescence assay (IFA) on acute sera. For O. tsutsugamushi, PCR sensitivity was twice that of acute specimen IgM IFA (28.6% versus 14.3%; McNemar's P = 0.3). For Rickettsia spp., PCR was four times as sensitive as acute specimen IgM IFA (36.4% versus 9.1%; P = 0.08), although this was not statistically significant. Whole blood and buffy coat, but not serum, were acceptable specimens for these PCRs. Further evaluation of these assays in a larger prospective study is warranted. PMID:23732256

Watthanaworawit, Wanitda; Turner, Paul; Turner, Claudia; Tanganuchitcharnchai, Ampai; Richards, Allen L.; Bourzac, Kevin M.; Blacksell, Stuart D.; Nosten, François

2013-01-01

374

How Fetal Alcohol Spectrum Disorders Co-Occur with Mental Illness  

MedlinePLUS

... a diagnostic term used by clinicians. WHICH DISORDERS CO-OCCUR WITH FASD? Prenatal alcohol exposure can cause ... an individual’s treatment plan. HOW CAN WE RECOGNIZE CO-OCCURRING CONDITIONS? Co-occurring disorders among persons with ...

375

Two Adenovirus Serotype 3 Outbreaks Associated with Febrile Respiratory Disease and Pharyngoconjunctival Fever in Children under 15 Years of Age in Hangzhou, China, during 2011  

PubMed Central

Adenovirus serotype 3 and 7 outbreaks have occurred periodically in northern, eastern, and southern China since 1955, but there has been no report since the adenovirus serotype 7 outbreak first occurred in Hangzhou, China, in 1991. Here we explored the epidemiology and etiology of two adenovirus serotype 3 outbreaks in Hangzhou in 2011. One acute respiratory outbreak was found in Chun'an County, where a total of 371 cases were confirmed in 5 of 23 towns from 4 to 31 May 2011. The outbreak affected 18.57% (13/70) of schools and 14.49% (90/621) of classes. The incidence was 5.18% (371/7,163). The population was distributed among individuals ages 7 to 15 years. No parents or teachers were infected. Another pharyngoconjunctival fever outbreak was discovered in the Chenjinglun Swimming Center located in the Xihu District between 1 and 15 July 2011. A total of 134 cases were confirmed in 900 amateur swimmers, with an incidence of 14.89% (134/900). The ages ranged from 4 to 9 years. The two outbreaks had no severe complications or death. The viruses in 66.67% (10/15) of throat swabs from children with acute respiratory infections and 100% (10/10) of the swabs from children with pharyngoconjunctival fever were confirmed to be adenovirus serotype 3 with 100% homology by PCR. Of these samples, 60.0% (12/20) had a classical characteristic cytopathic effect, presented as grape-like clusters at 72 h after infection in HEp-2 cells. In conclusion, the acute respiratory infection and pharyngoconjunctival fever outbreak in Hangzhou were caused by the completely homologous type 3 adenovirus in subgenus B. Moreover, these outbreaks demonstrated rapid transmission rates, possibly due to close contact and droplet transmission. PMID:22442311

Xie, Li; Yu, Xin-Fen; Sun, Zhou; Yang, Xu-Hui; Huang, Ren-Jie; Wang, Jing; Yu, Apeng; Zheng, Lin; Yu, Man-Chu; Hu, Xiao-Wei; Wang, Ban-Ma; Chen, Jin; Pan, Jing-Cao

2012-01-01

376

Sarcocystis nesbitti Causes Acute, Relapsing Febrile Myositis with a High Attack Rate: Description of a Large Outbreak of Muscular Sarcocystosis in Pangkor Island, Malaysia, 2012  

PubMed Central

Background From the 17th to 19th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak. Methodology/Principal Findings All retreat participants were identified, and clinical and epidemiological information was obtained via clinical review and self-reported answers to a structured questionnaire. Laboratory, imaging and muscle biopsy results were evaluated and possible sources of exposure, in particular water supply, were investigated. At an average of 9–11 days upon return from the retreat, 89 (97%) of the participants became ill. A vast majority of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia was present in 91% of patients. Facial swelling from myositis of jaw muscles occurred in 9 (10%) patients. The median duration of symptoms was 17 days (IQR 7 to 30 days; range 3 to 112). Out of 4 muscle biopsies, sarcocysts were identified in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one biopsy without observed sarcocyst. Non-Malaysians had a median duration of symptoms longer than that of Malaysians (27.5 days vs. 14 days, p?=?0.001) and were more likely to experience moderate or severe myalgia compared to mild myalgia (83.3% vs. 40.0%, p?=?0.002). Conclusions/Significance The similarity of the symptoms and clustered time of onset suggests that all affected persons had muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever reported, with the specific Sarcocystis species identified. The largely non-specific clinical features of this illness suggest that S. nesbitti may be an under diagnosed infection in the tropics. PMID:24854350

Italiano, Claire M.; Wong, Kum Thong; AbuBakar, Sazaly; Lau, Yee Ling; Ramli, Norlisah; Syed Omar, Sharifah Faridah; Kahar Bador, Maria; Tan, Chong Tin

2014-01-01

377

electromagnetic wave does occur in the OLED sample. Hence, the superluminal effect may occur in the OLED sample as well. Next  

E-print Network

electromagnetic wave does occur in the OLED sample. Hence, the superluminal effect may occur in the OLED sample as well. Next we examine the result of the time-domain transformation, using a pulse the power-off OLED sample was separated into two parts, as shown by the short dashed line in Figure 3. One

Gürel, Levent

378

Fault tree analysis of commonly occurring medication errors and methods to reduce them  

E-print Network

Medication errors occur in health care settings and they continue to Pose significant challenges to hospital administrators, Physicians, Pharmacists and nurses. These medication errors may occur due to a lack of knowledge, substandard performance...

Cherian, Sandhya Mary

1994-01-01

379

29 CFR 4.188 - Ineligibility for further contracts when violations occur.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Ineligibility for further contracts when violations occur. 4.188 Section... LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Enforcement § 4.188 Ineligibility for further contracts when violations occur....

2012-07-01

380

29 CFR 4.188 - Ineligibility for further contracts when violations occur.  

...2013-07-01 true Ineligibility for further contracts when violations occur. 4.188 Section... LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Enforcement § 4.188 Ineligibility for further contracts when violations occur....

2014-07-01

381

29 CFR 4.188 - Ineligibility for further contracts when violations occur.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Ineligibility for further contracts when violations occur. 4.188 Section... LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Enforcement § 4.188 Ineligibility for further contracts when violations occur....

2013-07-01

382

Stress drop as a criterion to differentiate subduction zones where Mw 9 earthquakes can occur  

E-print Network

Stress drop as a criterion to differentiate subduction zones where Mw 9 earthquakes can occur segment in which at least one Mw 9 earthquake has occurred, and class 3: earthquakes in a sub- duction zone segment in which no Mw 9 earthquake has occurred. A total of 53 earthquakes are analyzed

Seno, Tetsuzo

383

Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia  

PubMed Central

Acute myeloid leukemia (AML) patients aged ?60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m2/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20–30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m2/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13–724 days). Grade 3–4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1–2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m2/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML. PMID:25132519

Sadashiv, Santhosh K; Hilton, Christie; Khan, Cyrus; Rossetti, James M; Benjamin, Heather L; Fazal, Salman; Sahovic, Entezam; Shadduck, Richard K; Lister, John

2014-01-01

384

Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone  

PubMed Central

Sierra Leone in West Africa is in a Lassa fever–hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ?500–700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%–40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%–70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus. PMID:24959946

Rossi, Cynthia A.; Khan, Sheik H.; Goba, Augustine; Fair, Joseph N.

2014-01-01

385

Undiagnosed acute viral febrile illnesses, Sierra Leone.  

PubMed

Sierra Leone in West Africa is in a Lassa fever-hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ?500-700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%-40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%-70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus. PMID:24959946

Schoepp, Randal J; Rossi, Cynthia A; Khan, Sheik H; Goba, Augustine; Fair, Joseph N

2014-07-01

386

Severe febrile systemic reaction to pneumococcal vaccine.  

PubMed Central

Polyvalent pneumococcal polysaccharide vaccine (Pneumovax, PPV) has been shown to substantially reduce the risk of Streptococcus pneumoniae infections in susceptible individuals. Side effects, such as mild local erythema, induration, pain and fever, have been reported with various frequencies. Rarely, systemic symptoms, including high fever, headache, nausea and photophobia, have been reported in the literature. This case report describes a 38-year-old male who developed severe and prolonged local and systemic symptoms necessitating hospitalization following a dose of pneumovax. PMID:15712794

Hasan, Syed; Yousef, Mahmoud; Shridharani, Sachin

2005-01-01

387

Bloodstream infections in patients with hematological malignancies: which is more fatal – cancer or resistant pathogens?  

PubMed Central

Background The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. Methods In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. Results During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in