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Sample records for febrile neutropenia occurred

  1. Chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy.

    PubMed

    Hashiguchi, Yasunori; Kasai, Mari; Fukuda, Takeshi; Ichimura, Tomoyuki; Yasui, Tomoyo; Sumi, Toshiyuki

    2015-11-01

    Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24-84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1-12 days) and 3.4 days (range 1-9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (P<0.0001), less than five previous chemotherapy cycles (P=0.02), disseminated disease (P=0.03), platinum-based regimens (P<0.0001), taxane-containing regimens (P<0.0001), and combined therapy (P<0.0001). Febrile neutropenia was associated with poor performance status (P<0.0001), no previous chemotherapy (P<0.05), disseminated disease (P<0.0001), and distant metastatic disease (P=0.03). Neither chemotherapy-induced neutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy-induced neutropenia may be possible in patients with gynecologic malignancy.

  2. Neutropenia and febrile neutropenia in patients with Hodgkin's lymphoma treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy.

    PubMed

    Chand, Vikram K; Link, Brian K; Ritchie, Justine M; Shannon, Mary; Wooldridge, James E

    2006-04-01

    When uncomplicated neutropenia during doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy for the treatment of Hodgkin's lymphoma is encountered, it is unclear whether or not treatment should be modified. In the present study, we determined the incidence of neutropenia, febrile neutropenia, and the relationship of febrile neutropenia to grade III/IV neutropenia and dose modification, in a large university patient population. We reviewed the charts of patients diagnosed with Hodgkin's lymphoma between 1 January 1990 and 31 December 2002 who were treated with ABVD chemotherapy, and seen at the University of Iowa with complete diagnosis, staging, and treatment dosing records. Adequate data was available on 894 treatments in 81 patients with Hodgkin's lymphoma treated with ABVD chemotherapy. Grade III/IV neutropenia was present on the scheduled day of treatment in 187 (20.9%) treatments in 64 (79%) patients. Grade III/IV neutropenia was most common at cycle 1 day 15. Febrile neutropenia developed nine times in eight patients, and eight episodes of febrile neutropenia developed when the treatment-day absolute neutrophil count (ANC) > or =1000. Dose delay of >4 days and/or dose reduction to <80% of original doxorubicin dose following grade III/IV neutropenia occurred in 29 of 187 treatments, with no episodes of febrile neutropenia. With grade III/IV neutropenia on the day of therapy, 158 treatments were administered without dose reduction or dose delay with one subsequent episode of febrile neutropenia. Neutropenia during ABVD is common, and dose modification for uncomplicated neutropenia on the day of treatment may not reduce the risk of febrile neutropenia. It may be possible to maintain dose intensity in the face of uncomplicated neutropenia during ABVD therapy.

  3. Febrile neutropenia in children with acute lymphoblastic leukemia: single center experience

    PubMed Central

    Özdemir, Nihal; Tüysüz, Gülen; Çelik, Nigar; Yantri, Leman; Erginöz, Ethem; Apak, Hilmi; Özkan, Alp; Yıldız, İnci; Celkan, Tiraje

    2016-01-01

    Aim: An important life-threatening complication of intensive chemotherapy administered in children with leukemia is febrile neutropenia. The objective of this study was to evaluate the clinical features and consequences of febrile neutropenia attacks in children who were treated for acute lymphoblastic leukemia. Material and Methods: Nighty-six children who received chemotherapy for acute lymphoblastic leukemia in our center between January 1995 and December 2010 were included in the study. The data related to demographic characteristics, treatment features, relapse and febrile neutropenia incidences, risk factors, culture results and prognosis were retrospectively evaluated from the patients’ files. Results: A total of two hundred-ninety nine febrile neutropenia attacks observed in the patients during initial treatment and relapse treatment were evaluated. When the incidence of febrile neutropenia was evaluated by years, it was observed that the patients treated after year 2000 had statistically significantly more febrile neutopenia attacks compared to the patients treated before year 2000. When the incidences of febrile neutropenia during initial treatment and during relapse treatment were compared, it was observed that more febrile neutropenia attacks occured during relapse treatment. Fifty-nine percent of all febrile neutropenia attacks were fever of unknown origin. Eighty microorganisms grew in cultures during febrile neutropenia throughout treatment in 75 patients; 86% were bacterial infections (50% gram positive and 50% gram negative), 8% were viral infections and 6% were fungal infections. Coagulase negative staphylococcus (n=17) was the most frequent gram positive pathogen; E. Coli (n=17) was the most commonly grown gram negative pathogen. Conclusions: In this study, it was found that an increase in the incidence of febrile neutropenia occured in years. Increments in treatment intensities increase the incidence of febrile neutropenia while improving

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2014-10-01

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

  6. Serum Endocan Levels in Children with Febrile Neutropenia.

    PubMed

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

    2016-03-17

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

  7. Serum Endocan Levels in Children with Febrile Neutropenia

    PubMed Central

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

    2016-01-01

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

  8. [Prevention and treatment of febrile neutropenia].

    PubMed

    Montemurro, F; Gallicchio, M; Aglietta, M

    1997-01-01

    Many chemotherapy regimens are associated with variable periods of myelosuppression. In cancer patients, neutropenia (less than 500 neutrophils/microL) is the most important risk factor for infections. The incidence and severity of infectious complications are related to depth and duration of neutropenia, with the highest risk if neutrophils are less than 100/microL for more than a week. The period required for neutrophil recovery is usually short with standard regimens, but prolonged after high dose chemotherapy followed by autologous bone marrow transplant (-ABMT) or peripheral blood stem cell (PBSC) infusion. Under these conditions, the administration of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) accelerates neutrophil recovery and shortens the duration of hospitalization. In standard chemotherapy settings, prophylactic use of CSF's is a matter of debate. Several studies have reached contrasting conclusion, but, combining effectiveness and costs, it results that this use of CSF'S is not to be recommended unless the risk of infections (elderly patients, reduced marrow reserve) is high. The administration of G-CSF or GM-CSF to a febrile neutropenic patient (cfr CSF's therapy) shortens the duration of neutropenia, although no great clinical benefits are evident. Nevertheless the identification of subsets of patients with additional risk factors (i.e. absolute neutrophil count < 100/microL at the onset of fever or delayed neutrophil recovery) should be helpful in establishing the role of CSF's therapy. When prolonged periods of severe neutropenia (less than 500 neutrophils/microL) are expected, antibiotics should be prophylactically administered. Fluoroquinolones seem to be the optimal choice in heavily myelosuppressed patients (ie. bone marrow transplant recipients). Fluoroquinolones are effective in reducing the frequency of gram-negative bacteremia, but, because of incomplete coverage, gram

  9. Febrile neutropenia in children treated for malignancy.

    PubMed

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

    2015-06-01

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

  10. Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle.

    PubMed

    Li, Xiaoyan; Luthra, Rakesh; Morrow, Phuong K; Fisher, Maxine D; Reiner, Maureen; Barron, Richard L; Langeberg, Wendy J

    2016-10-01

    Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle. This case-control study used administrative claims from adult patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who received chemotherapy between 2007 and 2012. Each patient who developed febrile neutropenia (case) was matched with up to four patients without febrile neutropenia (controls) by cancer type, metastasis, chemotherapy regimen, age group, and sex. For each comorbidity (identified in the year before chemotherapy began), the adjusted odds ratio (aOR) for febrile neutropenia by cancer type was evaluated using conditional logistic regression models adjusted for potential confounding factors. Of 31,331 eligible patients, 672 developed febrile neutropenia in the first chemotherapy cycle. A total of 3312 febrile neutropenia cases and matched controls were analyzed. Across tumor types, comorbidity prevalence was higher in patients who developed febrile neutropenia than in those without febrile neutropenia. Among patients with breast cancer, osteoarthritis was more prevalent in patients with febrile neutropenia (aOR, 1.85; 95% CI, 1.07 to 3.18). Among patients with non-Hodgkin lymphoma, renal disease was more prevalent in patients with febrile neutropenia (aOR, 2.25; 95% CI, 1.23 to 4.11). Patients who developed febrile neutropenia in the first chemotherapy cycle presented with comorbidities more often than otherwise similar patients who did not develop febrile neutropenia. These findings warrant further investigation and support the inclusion of comorbidities into febrile neutropenia risk models.

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

    PubMed Central

    Chmielowska, Ewa; Filipczyk-Cisarż, Emilia; Krzemieniecki, Krzysztof; Leśniewski-Kmak, Krzysztof; Litwiniuk, Maria M.; Wieruszewska-Kowalczyk, Karolina; Kosno-Kruszewska, Elżbieta

    2014-01-01

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

  12. Management of Breast Cancer Patients with Chemotherapy-Induced Neutropenia or Febrile Neutropenia

    PubMed Central

    Fontanella, Caterina; Bolzonello, Silvia; Lederer, Bianca; Aprile, Giuseppe

    2014-01-01

    Summary Chemotherapy-induced neutropenia (CIN) is a common toxicity caused by the administration of anticancer drugs. This side effect is associated with life-threatening infections and may alter the chemotherapy schedule, thus impacting on early and long-term outcomes. Elderly breast cancer patients with impaired health status or advanced disease as well as patients undergoing dose-dense anthracycline/taxane- or docetaxel-based regimens have the highest risk of CIN. A careful assessment of the baseline risk for CIN allows the selection of patients who need primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) and/or antimicrobial agents. Neutropenic cancer patients may develop febrile neutropenia and CIN-related severe medical complications. Specific risk assessment scores, along with comprehensive clinical evaluation, are able to define a group of febrile patients with low risk for complications who can be safely treated as outpatients. Conversely, patients with higher risk of severe complications should be hospitalized and should receive intravenous antibiotic therapy with or without G-CSF. PMID:25404882

  13. Intensified prophylaxis of febrile neutropenia with ofloxacin plus rifampin during severe short-duration neutropenia in patients with lymphoma.

    PubMed

    Muñoz, L; Martino, R; Subirà, M; Brunet, S; Sureda, A; Sierra, J

    1999-08-01

    To analyse the impact of intensified prophylaxis with ofloxacin plus rifampin (O+R) in neutropenic patients we used this combination in 40 consecutive cycles of ifosfamide, cytarabine, prednisolone and etoposide (IAPVP-16). This salvage chemotherapy regimen for lymphoma usually produces four to six days of severe neutropenia without significant extrahematologic toxicities. We compared the infectious morbidity during neutropenia under O+R with 58 consecutives cycles using either norfloxacin or no prophylaxis (control group). Fifty-three percent of control group patients and 20% of the O+R group developed febrile neutropenia that required hospital admission (p<0.001, 95% CI for the difference between both proportions of 16% to 51%). Bacteremia was documented in two patients in the O+R group and six in the control group (p=0.08). Gram-positive cocci (GPC) accounted for all six bacteremias in the control group, while both cases in O+R group were due to a quinolone-resistant gram-negative bacteria (GNB) (p<0.01 for GPC). Five patients (13%) who received O+R and 23 (40%) in control group developed fever of unknown origin, p<0.001, while the total duration of hospitalization due to febril neutropenia was 42 days and 158 days, respectively (p<0.001). In conclusion, intensified prophylaxis with O+R appears to reduce the rate of febrile neutropenia and GPC bacteremia in patients with short and severe neutropenia, which translates into a reduction in the need for hospitalization.

  14. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study.

    PubMed

    Ishikawa, Takashi; Sakamaki, Kentaro; Narui, Kazutaka; Kaise, Hiroshi; Tsugawa, Koichiro; Ichikawa, Yasushi; Mukai, Hirofumi

    2016-07-01

    With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests.

  15. [Efficacy of Levofloxacin Hydrate in Febrile Neutropenia for Outpatient Chemotherapy].

    PubMed

    Inagaki, Manato; Sato, Junya; Nihei, Satoru; Kashiwaba, Masahiro; Kudo, Kenzo

    2016-05-01

    Management of febrile neutropenia (FN) is important for the safety of patients undergoing outpatient chemotherapy. Oral antimicrobials are usually prescribed as the initial treatment for FN, and outpatients are instructed to begin medication prior to chemotherapy. However, the effectiveness and safety of the use of these oral antibiotics have not yet been established. In this study, we investigated the effectiveness and safety of levofloxacin hydrate (LVFX) for breast cancer patients with FN, and the factors associated with the onset of FN in 134 breast cancer patients who underwent chemotherapy including the anticancer drug anthracycline (total, 513 courses), in an outpatient chemotherapy department. The effectiveness and safety of LVFX were defined respectively as defervescence within 5 days, and the appearance of side effects such as diarrhea and rashes. Fever was observed in 89 (66%) of the 134 patients, and during 164 (32%) of 513 courses. Defervescence was observed with the LVFX medication in 149 (93%) of 160 courses. The primary side effect was the development of rashes, and only 2 (1%) of the 160 courses were discontinued. Onset of stomatitis during chemotherapy was observed as a factor of FN (odds ratio: 1.36, p<0.05). Our results suggest that the use of LVFX according to the patients' discretion might be an effective and safe option for the management of FN during outpatient chemotherapy.

  16. [Efficacy of Levofloxacin Hydrate in Febrile Neutropenia for Outpatient Chemotherapy].

    PubMed

    Inagaki, Manato; Sato, Junya; Nihei, Satoru; Kashiwaba, Masahiro; Kudo, Kenzo

    2016-05-01

    Management of febrile neutropenia (FN) is important for the safety of patients undergoing outpatient chemotherapy. Oral antimicrobials are usually prescribed as the initial treatment for FN, and outpatients are instructed to begin medication prior to chemotherapy. However, the effectiveness and safety of the use of these oral antibiotics have not yet been established. In this study, we investigated the effectiveness and safety of levofloxacin hydrate (LVFX) for breast cancer patients with FN, and the factors associated with the onset of FN in 134 breast cancer patients who underwent chemotherapy including the anticancer drug anthracycline (total, 513 courses), in an outpatient chemotherapy department. The effectiveness and safety of LVFX were defined respectively as defervescence within 5 days, and the appearance of side effects such as diarrhea and rashes. Fever was observed in 89 (66%) of the 134 patients, and during 164 (32%) of 513 courses. Defervescence was observed with the LVFX medication in 149 (93%) of 160 courses. The primary side effect was the development of rashes, and only 2 (1%) of the 160 courses were discontinued. Onset of stomatitis during chemotherapy was observed as a factor of FN (odds ratio: 1.36, p<0.05). Our results suggest that the use of LVFX according to the patients' discretion might be an effective and safe option for the management of FN during outpatient chemotherapy. PMID:27210089

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

    PubMed

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

    2014-04-01

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

  18. Which Variables Are Useful for Predicting Severe Infection in Children With Febrile Neutropenia?

    PubMed

    Delebarre, Mathilde; Garnier, Nathalie; Macher, Emilie; Thebaud, Estelle; Mazingue, Françoise; Leblond, Pierre; Duhamel, Alain; Martinot, Alain; Dubos, François

    2015-11-01

    To distinguish children with chemotherapy-induced febrile neutropenia (FN) at low risk of severe infection, the variables that are significant risk factors must be identified. Our objective was to identify them by applying evidence-based standards. This retrospective 2-center cohort study included all episodes of chemotherapy-induced FN in children in 2005 and 2006. The medical history, clinical, and laboratory data available at admission were collected. Severe infection was defined by bacteremia, a positive culture of a normally sterile body fluid, invasive fungal infection, or localized infection at high risk of extension. Univariate analysis identified potential predictive variables. A generalized mixed model was used to determine the adjusted variables that predict severe infection. We analyzed 372 FN episodes. Severe infections occurred in 16.1% of them. Variables predictive of severe infection at admission were: disease with high risk of prolonged neutropenia (adjusted odds ratio [aOR]=2.5), blood cancer (aOR=1.9), fever ≥38.5°C (aOR=3.7), and C-reactive protein level ≥90 mg/L (aOR=4.5). Now that we have identified these variables significantly associated with the risk of severe infection, they must be validated prospectively before combining the best predictive variables in a decision rule that can be used to distinguish children at low risk.

  19. Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

    PubMed

    Contreras, Valeria; Sepúlveda, Sebastián; Heredia, Ana

    2016-02-24

    It is still controversial if the combined use of beta-lactam antibiotics and aminoglycosides has advantages over broad-spectrum beta-lactam monotherapy for the empirical treatment of cancer patients with febrile neutropenia. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including 14 pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the combination of beta-lactam antibiotics and aminoglycosides probably does not lead to a reduced mortality in febrile neutropenic cancer patients and it might increase nephrotoxicity.

  20. Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

    PubMed

    Contreras, Valeria; Sepúlveda, Sebastián; Heredia, Ana

    2016-01-01

    It is still controversial if the combined use of beta-lactam antibiotics and aminoglycosides has advantages over broad-spectrum beta-lactam monotherapy for the empirical treatment of cancer patients with febrile neutropenia. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including 14 pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the combination of beta-lactam antibiotics and aminoglycosides probably does not lead to a reduced mortality in febrile neutropenic cancer patients and it might increase nephrotoxicity. PMID:26938974

  1. Is preemptive antifungal therapy a good alternative to empirical treatment in prolonged febrile neutropenia?

    PubMed

    Koch, Erica; Rada, Gabriel

    2016-06-09

    Patients with prolonged febrile neutropenia are at high risk of invasive fungal infection, so it has been standard practice to initiate empirical antifungal therapy in these cases. However, this strategy is associated with important toxicity, so diagnostic test-guided preemptive antifungal therapy has been proposed as an alternative. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including twelve studies overall. Four randomized controlled trials addressed the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether preemptive strategy affects mortality because the certainty of the evidence is very low, but it might slightly decrease the use of antifungal agents in patients with prolonged febrile neutropenia.

  2. Is preemptive antifungal therapy a good alternative to empirical treatment in prolonged febrile neutropenia?

    PubMed

    Koch, Erica; Rada, Gabriel

    2016-01-01

    Patients with prolonged febrile neutropenia are at high risk of invasive fungal infection, so it has been standard practice to initiate empirical antifungal therapy in these cases. However, this strategy is associated with important toxicity, so diagnostic test-guided preemptive antifungal therapy has been proposed as an alternative. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including twelve studies overall. Four randomized controlled trials addressed the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether preemptive strategy affects mortality because the certainty of the evidence is very low, but it might slightly decrease the use of antifungal agents in patients with prolonged febrile neutropenia. PMID:27280389

  3. Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.

    PubMed

    Demirkaya, Metin; Tugcu, Deniz; Akcay, Arzu; Aydogan, Gönül; Akıcı, Ferhan; Salcioglu, Zafer; Ekmekci, Hakan; Sevinir, Betül; Balci Ekmekci, Ozlem

    2015-01-01

    In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

  4. Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study

    PubMed Central

    Söderman, Martina; Rhedin, Samuel; Tolfvenstam, Thomas; Rotzén-Östlund, Maria; Albert, Jan; Broliden, Kristina; Lindblom, Anna

    2016-01-01

    Objective Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. Study design Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. Results At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. Conclusion The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts. PMID:27309354

  5. Outpatient management of febrile neutropenia: time to revise the present treatment strategy.

    PubMed

    Carstensen, Mads; Sørensen, Jens Benn

    2008-01-01

    We reviewed medical literature on the efficacy and safety of outpatient versus hospital-based therapy of low-risk febrile neutropenia in adult cancer patients. A PubMed search for all studies evaluating the outpatient treatment of adults diagnosed with solid tumors who suffered from low-risk febrile neutropenia was completed; reference lists from identified articles also were used. In all, 10 trials were included in the analysis, which showed no significant difference in clinical failure rates and mortality for ambulatory regimens and standard hospital-based therapy. Subgroup analysis according to the type of fever episode showed no significant differences in clinical failure rates for fever of unknown origin and fever due to documented infections. Subgroup analyses in two independent trials identified an absolute neutrophil count < 100 cells/ mm3 as being predictive of outpatient treatment failure (P < 0.04). These findings need to be confirmed by further trials. Thus, outpatient management of adult cancer patients with low-risk febrile neutropenia is safe, effective, and comparable to standard hospital-based therapy. Patients at low risk are outpatients and are hemodynamically stable; they have no organ failure, they are able to take oral medications, and they do not suffer from acute leukemia. Low-risk prediction also may be based on the Multinational Association for Supportive Care in Cancer risk index.

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. Fluoroquinolone prophylaxis against febrile neutropenia in areas with high fluoroquinolone resistance--an Asian perspective.

    PubMed

    Ng, Esther Shu-Ting; Liew, Yixin; Koh, Liang Piu; Hsu, Li Yang

    2010-09-01

    Febrile neutropenia remains a major cause of morbidity and mortality in patients receiving chemotherapy. Major prophylactic strategies include granulocyte colony-stimulating factor and antibiotics, the most widely used of which are fluoroquinolones. While fluoroquinolone prophylaxis has been shown to be effective in areas where fluoroquinolone resistance is low, this same efficacy has not been proven in areas where resistance is high, such as in Asia. Given the increase in antimicrobial resistance with the use of prophylaxis, the risks and benefits of this strategy need to be carefully considered. This review presents the evidence for and against fluoroquinolone prophylaxis in areas of high fluoroquinolone resistance.

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

    PubMed

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

    2009-08-01

    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).

  11. Efficacy and safety of tazobactam/piperacillin as an empirical treatment for the patients of adult and child with febrile neutropenia in Japan.

    PubMed

    Tamura, Kazuo; Akiyama, Nobu; Kanda, Yoshinobu; Saito, Masahiro

    2015-09-01

    Tazobactam/piperacillin (4.5 g for adults and 90 mg/kg body weight for children, every 6 h) was administered to Japanese patients with febrile neutropenia to evaluate its defervescence and clinical efficacy and safety. The pharmacokinetics in children were also examined. Defervescence efficacy at day 4 of the treatment was achieved in 50.0% of 94 adult and 62.5% of 8 pediatric patients, respectively. The defervescence efficacy rate in relation to the neutrophil count in adults was 37.5% for the patients with a neutrophil count of less than 100/μL and 62.5% for that between 100 and 500/μL. The clinical efficacy rate at day 7 and at the end or discontinuation of the treatment was 79.6% and 59.1% in adult patients, respectively, and 57.1% and 75.0% in pediatric patients, respectively. Fifteen strains of causative bacteria were isolated in 13 adult patients at baseline. All strains were eradicated within 4 days of the treatment. The side effects that occurred in adult and pediatric patients during the treatment were all known and not specific to febrile neutropenia patients. The pharmacokinetics profiles of tazobactam/piperacillin in children with febrile neutropenia are unlikely to be different from those in children with a common bacterial infection and without any immunosuppressive conditions. The study results in Japanese patients with febrile neutropenia demonstrate that tazobactam/piperacillin treatment is efficacious and safe in adults. As for pediatric patients, given the limited number of cases studied, further investigation is needed (Clinical trial number: Japic CTI-121728).

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2015-05-01

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

  14. Patterns of neutropenia and risk factors for febrile neutropenia of diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

    PubMed

    Choi, Yong Won; Jeong, Seong Hyun; Ahn, Mi Sun; Lee, Hyun Woo; Kang, Seok Yun; Choi, Jin-Hyuk; Jin, U Ram; Park, Joon Seong

    2014-11-01

    Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age ≥65 yr, comorbidities, bone marrow involvement, and baseline serum albumin ≤3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.

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

    PubMed

    Nakagawa, Yasunori; Suzuki, Kenshi; Masaoka, Toru

    2009-06-01

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

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

    PubMed

    Nakagawa, Yasunori; Suzuki, Kenshi; Masaoka, Toru

    2009-06-01

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

  17. Impact of multiplex PCR on antimicrobial treatment in febrile neutropenia: a randomized controlled study.

    PubMed

    Idelevich, Evgeny A; Silling, Gerda; Niederbracht, Yvonne; Penner, Hanna; Sauerland, Maria Cristina; Tafelski, Sascha; Nachtigall, Irit; Berdel, Wolfgang E; Peters, Georg; Becker, Karsten

    2015-10-01

    Multiplex PCR (mPCR) directly from blood has been suggested as a promising method for rapid identification of pathogens causing sepsis. This study aimed to investigate whether mPCR has any impact on antimicrobial treatment. Hematological patients with febrile neutropenia were randomized into two groups. In the study group, mPCR was performed as an addition to standard diagnostics, and PCR finding was immediately communicated to the clinicians, thus being available for decision making. In the control group, clinicians were not aware of PCR result. PCR samples were collected simultaneously with clinically indicated blood culture specimens from peripheral vein and/or central venous catheter at fever onset and once again if fever persisted up to 72 h. Overall, 74 patients of the study group and 76 patients of the control group were enrolled and 253 samples collected. Therapy was changed to targeted antimicrobial therapy (AMT) in 12 patients (16.2%) in the study group and in 12 patients (15.8%) in the control group. For patients with changes, the median time to change to the targeted AMT was 21.4 h in the study group and 47.5 h in the control group (p = 0.018). In the study group, 57.1% (8/14) of changes to targeted AMT was due to PCR finding. PCR led to AMT change in 9.5% (7/74) of study group patients, i.e., in 33.3% (7/21) of patients who had positive PCR finding. There were no significant differences in patient outcomes (secondary endpoints). In conclusion, PCR method accelerates change to the targeted AMT in febrile neutropenic patients.

  18. Dose-Dependent Effect of Granulocyte Transfusions in Hematological Patients with Febrile Neutropenia.

    PubMed

    Teofili, Luciana; Valentini, Caterina Giovanna; Di Blasi, Roberta; Orlando, Nicoletta; Fianchi, Luana; Zini, Gina; Sica, Simona; De Stefano, Valerio; Pagano, Livio

    2016-01-01

    It is still under debate whether granulocyte transfusions (GTs) substantially increase survival in patients with febrile neutropenia. We retrospectively examined data relative to 96 patients with hematological malignancies receiving 491 GTs during 114 infectious episodes (IE). Patients were grouped according to the median doses of granulocytes transfused during the infectious episode (low-dose group: <1.5-x108 cells/Kg; standard-dose group: 1.5-3.0x108 cells/Kg and high-dose group: >3.0x108 cells/Kg). The impact of clinical, microbiological and GT-related variables on the infection-related mortality (IRM) was investigated. The IRM was not influenced by the number of GTs or by the total amount of granulocytes received, whereas a dose-related effect of the median dose received for IE was detected at univariate analysis (IRM of 18.4% in the standard-dose group, 44.4% in the low-dose group and 48.4% in the high-dose group, p = 0.040) and confirmed at multivariate analysis (OR 3.7, IC 95% 1.5-8.9; 0.004 for patients not receiving standard doses of GTs). Moreover, patients receiving GTs at doses lower or greater than standard had increased risk for subsequent ICU admission and reduced overall survival. The dose-related effect of GTs was confirmed in bacterial but not in fungal infections. Preliminary findings obtained from a subgroup of patients candidate to GTs revealed that levels of inflammatory response mediators increase in a dose-related manner after GTs, providing a possible explanation for the detrimental effect exerted by high-dose transfusions. GTs can constitute a valuable tool to improve the outcome of infections in neutropenic patients, provided that adequate recipient-tailored doses are supplied. Further investigations of the immunomodulatory effects of GTs are recommended. PMID:27487075

  19. Dose-Dependent Effect of Granulocyte Transfusions in Hematological Patients with Febrile Neutropenia

    PubMed Central

    Di Blasi, Roberta; Orlando, Nicoletta; Fianchi, Luana; Zini, Gina; Sica, Simona; De Stefano, Valerio; Pagano, Livio

    2016-01-01

    It is still under debate whether granulocyte transfusions (GTs) substantially increase survival in patients with febrile neutropenia. We retrospectively examined data relative to 96 patients with hematological malignancies receiving 491 GTs during 114 infectious episodes (IE). Patients were grouped according to the median doses of granulocytes transfused during the infectious episode (low-dose group: <1.5-x108 cells/Kg; standard-dose group: 1.5–3.0x108 cells/Kg and high-dose group: >3.0x108 cells/Kg). The impact of clinical, microbiological and GT-related variables on the infection-related mortality (IRM) was investigated. The IRM was not influenced by the number of GTs or by the total amount of granulocytes received, whereas a dose-related effect of the median dose received for IE was detected at univariate analysis (IRM of 18.4% in the standard-dose group, 44.4% in the low-dose group and 48.4% in the high-dose group, p = 0.040) and confirmed at multivariate analysis (OR 3.7, IC 95% 1.5–8.9; 0.004 for patients not receiving standard doses of GTs). Moreover, patients receiving GTs at doses lower or greater than standard had increased risk for subsequent ICU admission and reduced overall survival. The dose-related effect of GTs was confirmed in bacterial but not in fungal infections. Preliminary findings obtained from a subgroup of patients candidate to GTs revealed that levels of inflammatory response mediators increase in a dose-related manner after GTs, providing a possible explanation for the detrimental effect exerted by high-dose transfusions. GTs can constitute a valuable tool to improve the outcome of infections in neutropenic patients, provided that adequate recipient-tailored doses are supplied. Further investigations of the immunomodulatory effects of GTs are recommended. PMID:27487075

  20. Rapid lung MRI - paradigm shift in evaluation of febrile neutropenia in children with leukemia: a pilot study.

    PubMed

    Sodhi, Kushaljit Singh; Khandelwal, Niranjan; Saxena, Akshay Kumar; Bhatia, Anmol; Bansal, Deepak; Trehan, Amita; Singh, Meenu; Agarwal, Ritesh

    2016-01-01

    Immunocompromised children with hematological malignancies are at increased risk of developing potentially fatal pulmonary infections. Early detection and prompt treatment is critical to combat morbidity and mortality in these children. Twenty-six children with leukemia (age range: 5-13years) presenting with fever and neutropenia were included in this prospective study, which was approved by the institutional ethics committee. All patients underwent HRCT and MRI of the chest on the same day. The findings of HRCT and MRI were compared, with HRCT as the standard of reference. There was perfect agreement between MRI and CT examinations findings by kappa test (κ = 1). No significant difference was observed between the two modalities by the McNemar test (p > 0.05). Rapid lung MRI is technically feasible; has a high correlation, sensitivity and specificity to CT scan; and can emerge as the first line modality for the detection of pulmonary nodules in children with leukemia and persistent febrile neutropenia.

  1. The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febrile neutropenia resulted from methotrexate toxicity.

    PubMed

    Ozkol, Hatice Uce; Toptas, Tayfur; Calka, Omer; Akdeniz, Necmettin

    2015-01-01

    Methotrexate (MTX) remains one of the most frequently used anti-metabolite agents in dermatology. MTX is an analog of folate that competitively and irreversibly inhibits dihydrofolate reductase. Oral mucositis is a common side effect of chemotherapy drugs and is characterized by erythema, pain, poor oral intake, pseudomembranous destruction, open ulceration and hemorrhage of the oral mucosa. In this paper, we report a 32-year-old female with a case of mucositis due to MTX intoxication that resulted from an overdose for rheumatoid arthritis. The patient had abdominal pain, vomiting, and nausea. During follow-up, the patient's white blood cell count was found to be 0.9 × 10(9)/L (4-10 × 10(9)/L). The patient developed fever exceeding 40 °C. The patient was consulted to the hematology service. They suggested using granulocyte colony-stimulating factor for febrile neutropenia. On the fifth day of treatment, the white blood cell count reached 5.3 × 10(9)/L and the patient's fever and mucositis started to resolve. Here, we presented a case of hemorrhagic mucositis and febrile neutropenia resulted from high-dose MTX that responded very well to granulocyte colony-stimulating factor treatment and we reviewed the literature.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2010-04-01

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

  4. Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

    PubMed

    Lima, Stella Sala Soares; Nobre, Vandack; de Castro Romanelli, Roberta Maia; Clemente, Wanessa Trindade; da Silva Bittencourt, Henrique Neves; Melo, Ana Catarina Mourão; Salomão, Luciana Caetano Botelho; Serufo, José Carlos

    2016-06-01

    Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting. PMID:27118539

  5. Assessing patients' risk of febrile neutropenia: is there a correlation between physician-assessed risk and model-predicted risk?

    PubMed

    Lyman, Gary H; Dale, David C; Legg, Jason C; Abella, Esteban; Morrow, Phuong Khanh; Whittaker, Sadie; Crawford, Jeffrey

    2015-08-01

    This study evaluated the correlation between the risk of febrile neutropenia (FN) estimated by physicians and the risk of severe neutropenia or FN predicted by a validated multivariate model in patients with nonmyeloid malignancies receiving chemotherapy. Before patient enrollment, physician and site characteristics were recorded, and physicians self-reported the FN risk at which they would typically consider granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (FN risk intervention threshold). For each patient, physicians electronically recorded their estimated FN risk, orders for G-CSF primary prophylaxis (yes/no), and patient characteristics for model predictions. Correlations between physician-assessed FN risk and model-predicted risk (primary endpoints) and between physician-assessed FN risk and G-CSF orders were calculated. Overall, 124 community-based oncologists registered; 944 patients initiating chemotherapy with intermediate FN risk enrolled. Median physician-assessed FN risk over all chemotherapy cycles was 20.0%, and median model-predicted risk was 17.9%; the correlation was 0.249 (95% CI, 0.179-0.316). The correlation between physician-assessed FN risk and subsequent orders for G-CSF primary prophylaxis (n = 634) was 0.313 (95% CI, 0.135-0.472). Among patients with a physician-assessed FN risk ≥ 20%, 14% did not receive G-CSF orders. G-CSF was not ordered for 16% of patients at or above their physician's self-reported FN risk intervention threshold (median, 20.0%) and was ordered for 21% below the threshold. Physician-assessed FN risk and model-predicted risk correlated weakly; however, there was moderate correlation between physician-assessed FN risk and orders for G-CSF primary prophylaxis. Further research and education on FN risk factors and appropriate G-CSF use are needed.

  6. The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia.

    PubMed

    Sirinoglu, Melis; Soysal, Ahmet; Karaaslan, Ayşe; Kepenekli Kadayifci, Eda; Cinel, Ismail; Koç, Ahmet; Tokuç, Gülnur; Yaman, Ali; Haklar, Goncagül; Şirikçi, Önder; Turan, Serap; Altınkanat Gelmez, Gülşen; Söyletir, Güner; Bakır, Mustafa

    2016-04-01

    The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

  7. Prevalence of Resistant Gram-Negative Bacilli in Bloodstream Infection in Febrile Neutropenia Patients Undergoing Hematopoietic Stem Cell Transplantation

    PubMed Central

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

    2015-01-01

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

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

    ClinicalTrials.gov

    2013-07-10

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

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

    PubMed Central

    Gil-Navarro, M. Victoria; Aguilar-Guisado, Manuela; Espigado, Ildefonso; de Pipaón, Maite Ruiz Pérez; Falantes, José; Pachón, Jerónimo

    2013-01-01

    New approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more cost-effective than the EAT approach in the management of PFN in hematological patients. PMID:23856767

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-03-01

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

  12. [Imipenem combined with teicoplanin or vancomycin in the initial empirical treatment of febrile neutropenia. Analysis of the primary response and of a global sequential strategy in 126 episodes].

    PubMed

    Figuera, A; Tomás, J F; Hernández, L; Jiménez, M L; Peñarrubia, M J; del Rey, M C; Arranz, R; Cámara, R; López-Lorenzo, J L; Fernández-Rañada, J M

    1996-08-01

    The results of empiric antibiotic therapy in 126 episodes of febrile neutropenia in patients with hematologic neoplasms postchemotherapy and bone marrow transplantation are presented. The main objective of this work was the study of the initial control of infection comparing two glycopeptidic antibiotics: vancomycin and teicoplanin combined with imipenem in first line of empiric therapy. The secondary objective was to analyze the overall control of infection during the complete episode of neutropenia using a sequential empiric antibiotic therapy course which included the addition of amikacin followed by intravenous amphotericin B when fever persisted or recurred without microbiological documentation. Both initial courses (no guidelines), imipenem + vancomycin (arm A) and imipenem + teicoplanin (arm B) resulted in a similar percentage of response at 72 hours, both in episodes of fever of unknown origin (FUO) (55% and 68%, respectively; p = NS) and in those microbiologically documented (54% and 34.5%, p = NS); 58% and 79% of these episodes, respectively, were caused by gram-positive organisms. About 60% of patients in both arm ultimately required the empiric addition of amikacin, with or without amphotericin B, because of persistence or recurrence of fever; the percentage of overall responses in both arm did not differ significantly, both in FUO (70% and 86%, p = NS) and in microbiologically documented episodes (71% and 45%, p = NS). The overall infectious mortality for the whole group was 1.58%. In conclusion, no significant differences were observed in the clinical response or in toxicity between the combination of imipenem with any of the two glycopeptides: vancomycin or teicoplanin, for the initial empiric therapy of febrile neutropenia. The sequential empiric use of amikacin followed by amphotericin B assured an adequate overall control of infection in a group of patients with prolonged severe neutropenia.

  13. High-throughput pharmacogenetics identifies SLCO1A2 polymorphisms as candidates to elucidate the risk of febrile neutropenia in the breast cancer RAPP-01 trial.

    PubMed

    Callens, Céline; Debled, Marc; Delord, Marc; Turbiez-Stalain, Isabelle; Veyret, Corinne; Bièche, Ivan; Brain, Etienne

    2015-09-01

    The RAPP-01 clinical trial compared two adjuvant chemotherapies, doxorubicin plus docetaxel (arm A) versus doxorubicin plus cyclophosphamide (arm B), in 627 women with breast cancer. It stopped prematurely when three severe adverse events occurred among patients with febrile neutropenia (FN), all in the arm A. FN occurred in 40.8% (126/311) in arm A versus 7.1% (22/316) in arm B. We investigated Single Nucleotide Polymorphisms (SNPs) in drug transporter and metabolism genes potentially incriminated in this excess of FN. Using a dedicated DNA chip, we tested association of SNPs belonging to 97 transporter and 68 metabolizing genes with FN occurrence in 155 patients enrolled in the RAPP-01 trial, 85 in arm A and 70 in arm B. Association study in the 85 patients receiving docetaxel identified two SNPs, rs4762699 and rs2857468, both located in the SLCO1A2 gene. Haplotype T-T was associated with a high risk of FN: 83.3% of patients with at least one copy of T-T versus 32.8% in patients with other haplotypes (odds ratio = 10.25, P = 1.4e-4). In a multivariate logistic model adjusted for treatment arm, effect of haplotype T-T remained significant (odds ratio = 6.84, P = 1.15e-4). FN in patients receiving docetaxel in the RAPP-01 trial is significantly associated with the haplotype T-T in rs4762699 and rs2857468 in the SLCO1A2 transporter gene. This result should be validated in an independent cohort.

  14. Predictive modeling of the outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (MONITOR-GCSF study)

    PubMed Central

    Aapro, M.; Ludwig, H.; Bokemeyer, C.; Gascón, P.; Boccadoro, M.; Denhaerynck, K.; Krendyukov, A.; Gorray, M.; MacDonald, K.; Abraham, I.

    2016-01-01

    Background Risk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle. Design We applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at the patient (‘ever’ during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being ‘nested’ under patients was managed using generalized estimation equations. Predictive performance of each model was evaluated using bootstrapped c concordance statistics. Results Static patient-level risk models of ‘ever’ experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history, risk factors, and prophylaxis initiation and intensity. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics. Conclusion(s) These ‘real-world evidence’ models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically

  15. The role of ¹⁸F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia.

    PubMed

    Gafter-Gvili, Anat; Paul, Mical; Bernstine, Hanna; Vidal, Liat; Ram, Ron; Raanani, Pia; Yeshurun, Moshe; Tadmor, Boaz; Leibovici, Leonard; Shpilberg, Ofer; Groshar, David

    2013-09-01

    We assessed the performance of PET/CT for diagnosis and management of infections in high-risk hematological cancer patients with persistent febrile neutropenia in a prospective study. (18)F-FDG PET/CT with contrast-enhanced CT was performed on day 5-7 of persistent fever. Between 2008 and 2011, 91 PET/CT examinations were performed for different episodes in 79 patients, resulting in 117 diagnoses. The sensitivity of the PET/CT was 79.8% (71/89) compared to 51.7% (46/89) with chest/sinus CT alone. Specificities were 32.14% (9/28) vs. 42.85% (12/28), respectively. PET/CT resulted in a change from the pre-test diagnosis in 63/91 (69%) of episodes and in modification of patients' management in 46/91 (55%). PET/CT was beneficial in diagnosing abdominal infections. PET/CT has a potential role in the diagnostic evaluation of patients with persistent febrile neutropenia.

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

    PubMed

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

    2015-03-01

    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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    2013-01-01

    Introduction Endothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN. Methods This was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome. Results A total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality. Conclusions A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia. PMID:23915833

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2015-09-01

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

  2. High pentraxin 3 level predicts septic shock and bacteremia at the onset of febrile neutropenia after intensive chemotherapy of hematologic patients

    PubMed Central

    Vänskä, Matti; Koivula, Irma; Hämäläinen, Sari; Pulkki, Kari; Nousiainen, Tapio; Jantunen, Esa; Juutilainen, Auni

    2011-01-01

    We evaluated pentraxin 3 as a marker for complications of neutropenic fever in 100 hematologic patients receiving intensive chemotherapy. Pentraxin 3 and C-reactive protein were measured at fever onset and then daily to day 3. Bacteremia was observed in 19 patients and septic shock in 5 patients (three deaths). In comparison to C-reactive protein, pentraxin 3 achieved its maximum more rapidly. Pentraxin 3 correlated not only with the same day C-reactive protein but also with the next day C-reactive protein. High pentraxin 3 on day 0 was associated with the development of septic shock (P=0.009) and bacteremia (P=0.046). The non-survivors had constantly high pentraxin 3 levels. To conclude, pentraxin 3 is an early predictor of complications in hematologic patients with neutropenic fever. High level of pentraxin 3 predicts septic shock and bacteremia already at the onset of febrile neutropenia. (ClinicalTrials.gov Identifier: NCT00781040.) PMID:21880642

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-06-27

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

  5. Potential of polymerase chain reaction and galactomannan for the diagnosis of invasive aspergillosis in patients with febrile neutropenia.

    PubMed

    Aslan, Muge; Oz, Yasemin; Aksit, Filiz; Akay, Olga M

    2015-06-01

    The incidence of invasive aspergillosis (IA) has increased over the last years, especially in immuncompromised patients with high mortality rates. Because of difficulties about the diagnosis; serological methods [galactomannan (GM) antigen test] and polymerase chain reaction (PCR) developed in recent years. MycAssay Aspergillus PCR performance in the diagnosis of IA was evaluated and compared with the GM and in-house PCR. This study was conducted with 358 serum samples obtained from 99 patient with febrile neutropenic episodes who were followed in haematology and bone marrow transplantation units. Patients were classified by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 18 of them is proven and probable IA. GM antigen test and two different real-time PCR; one of them is fist commercial PCR for IA; Mycassay Aspergillus and the other one is in-house real-time PCR performed. Sensitivity values were Mycassay Aspergillus PCR, in-house PCR, and GM 65.38%, 11.53% and 23.07%, respectively. The high sensitivity obtained from Mycassay Aspergillus PCR and sensitivity is increased by using a combination of diagnostic methods. GM antigen test and real-time PCR could be beneficial for early diagnosis and treatment of IA. For routine usage of PCR as diagnostic assay more studies needed in future.

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

    PubMed Central

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

    2016-01-01

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

  7. Clinical Outcomes and Cost-effectiveness of Primary Prophylaxis of Febrile Neutropenia During Adjuvant Docetaxel and Cyclophosphamide Chemotherapy for Breast Cancer.

    PubMed

    Yu, Joanne L; Chan, Kelvin; Kurin, Michael; Pasetka, Mark; Kiss, Alex; Sridhar, Srikala S; Warner, Ellen

    2015-01-01

    Docetaxel and cyclophosphamide (TC) is a widely used breast cancer adjuvant regimen. We sought to compare the rates of febrile neutropenia (FN) between patients receiving no primary prophylaxis (PP) and those receiving PP with either granulocyte-colony stimulating factor (G-CSF) or antibiotics. We also analyzed cost-effectiveness of TC with and without either G-CSF or antibiotics. Charts were reviewed of all 340 patients who received adjuvant TC between January 2008 and December 2012 at two major cancer centers. Rates of FN in the three groups - no PP, PP with G-CSF and PP with antibiotics were compared. A Markov model was constructed comparing cost-effectiveness of PP with G-CSF, PP with antibiotics, and secondary prophylaxis (SP) with G-CSF after an episode of FN in a previous cycle. Costs were based on actual resource utilization and supplemented by the published literature, adjusted to 2012 Canadian dollars. Of the 73 (21%) patients who did not receive any PP, 23 (32%) of patients developed FN. Of the 192 (57%) patients receiving PP with G-CSF alone, only two (1%; p < 0.0001) developed FN; and of the 53 (16%) receiving PP with antibiotics alone, six (11%; p < 0.01) developed FN. From a cost-standpoint, PP with G-CSF was less cost-effective than PP with antibiotics. The rate of FN with TC chemotherapy exceeds 30%, and American Society of Clinical Oncology guidelines recommend PP with G-CSF in this situation. PP with antibiotics is more cost-effective, and is a reasonable option in resource-limited settings or for patients who decline or do not tolerate G-CSF.

  8. Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

    PubMed

    Younis, T; Rayson, D; Jovanovic, S; Skedgel, C

    2016-10-01

    The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold. PMID:27572552

  9. Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

    PubMed

    Younis, T; Rayson, D; Jovanovic, S; Skedgel, C

    2016-10-01

    The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold.

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

    PubMed Central

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

    2015-01-01

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

  11. Estimating resource use and cost of prophylactic management of neutropenia with filgrastim.

    PubMed

    Annemans, L; Van Overbeke, N; Standaert, B; Van Belle, S

    2005-05-01

    The study objective is to develop a methodology for the measurement of time, resource use and cost of the prophylactic management of neutropenia with filgrastim in different settings where the drug is routinely used: in-hospital care, outpatient care and home care. The activity-based costing method is used to analyse the cost of managing prophylactically neutropenia and comprises four steps. First, department heads in each of the chosen settings were selected and interviewed to obtain key elements in the workflow that involves the management of neutropenia, followed by the second step involving in-depth, structured interviews of key personnel. The third step was the measurement of the time required for frequently occurring activities in monitoring neutropenia and the administration of filgrastim by a study nurse. Finally, information on resource unit costs and personnel salaries were collected from the administration units to calculate an average cost. Sensitivity analyses were undertaken on estimated variables in the study. A list of eight to 14 consecutive activities linked to the prophylactic management of neutropenia was observed. The number and type of activities do not differ between an in-hospital oncology ward and an outpatient setting except for blood samplings. The difference is more pronounced between hospital and home care settings, as in the latter the patient performs many of the activities him/herself. The cost estimate per setting for prophylactic drug use is 6.30 Euros for in-hospital care, 3.67 Euros for outpatient care and 5.49 Euros for home care. Taking the two most frequently occurring scenarios per chemotherapy cycle (i.e. with or without febrile neutropenia), the following cost estimates are obtained: 60.41 Euros for a patient with febrile neutropenia and 56.77 Euros for a patient without febrile neutropenia, excluding drug costs. With the activity-based costing method it is possible to accurately demonstrate cost savings in the management

  12. The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis.

    PubMed

    Do, Tran; Medhekar, Rohan; Bhat, Raksha; Chen, Hua; Niravath, Polly; Trivedi, Meghana V

    2015-10-01

    The febrile neutropenia (FN) rates reported with the docetaxel 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) (TC) regimen given every 3 weeks vary from 4 to 69 % in early-stage breast cancer (ESBC) patients. This creates uncertainty as to whether patients receiving the TC regimen should also receive granulocyte colony-stimulating factor primary prophylaxis (G-CSFpp), which is recommended when chemotherapy regimens have ≥20 % FN rate. We conducted a meta-analysis of published studies to determine FN rate with the TC regimen, its dependence on patients' age, and the efficacy of G-CSFpp in reducing it in ESBC patients. We systematically searched the literature via PUBMED using the following terms: 'docetaxel', 'cyclophosphamide', 'febrile neutropenia', and 'breast cancer'. Inclusion criteria were full text peer-reviewed clinical studies in English reporting FN rates with TC regimen in relationship to G-CSFpp. Comprehensive meta-analysis software was used for all statistical analyses. Eight studies (N = 1542 patients) were included in our meta-analysis. The pooled mean FN rate was 23.2 % (95 % confidence interval (CI) 6.9-55.2 %; Q = 218.17, I (2) = 97.7). The FN risk in <65 years old patients was lower by 67.7 % compared to that in patients ≥65 years old (pooled odds ratio (OR) 0.323; 95 % CI 0.127-0.820; P = 0.017). The FN risk was reduced by 92.3 % with G-CSFpp (pooled OR 0.077; 95 % CI 0.013-0.460; P = 0.005). Our meta-analysis demonstrated that TC regimen was associated with ≥20 % FN risk, which was significantly higher in patients ≥65 years old and improved with G-CSFpp. G-CSFpp should be considered for all ESBC patients receiving TC regimen, especially those ≥65 years old.

  13. Neutropenia - infants

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007230.htm Neutropenia - infants To use the sharing features on this page, please enable JavaScript. Neutropenia is an abnormally low number of white blood ...

  14. Febrile Seizures

    MedlinePlus

    ... febrile seizure does not mean a child has epilepsy, since that disorder is characterized by reoccurring seizures ... outcome but carry an increased risk of developing epilepsy. How common are febrile seizures? Febrile seizures are ...

  15. Fever and neutropenia in children with malignant disease.

    PubMed

    Roguin, A; Kasis, I; Ben-Arush, M W; Sharon, R; Berant, M

    1996-01-01

    Treatment of episodes of fever and neutropenia in pediatric hematology-oncology patients includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic. The present analysis characterizes retrospectively febrile episodes in neutropenic pediatric hematology-oncology patients with regard to frequency of documented infections, organisms associated with these infections, efficacy of a standardized antibiotic regimen, and safety of early antibiotic discontinuation under defined conditions. A total of 149 pediatric febrile neutropenic episodes were identified during a 4-year period between 1990 and 1994. These occurred in 47 male and 19 female patients, of a mean age of 7.6 years (range 0.5-15). The most frequent diagnoses were leukemia (41% of patients), lymphoma (21%), rhabdomyosarcoma (7%), soft tissue sarcoma (5%), Ewing's sarcoma (5%), and osteosarcoma (4%). Infection was certain in 36% of febrile episodes, probable in 14%, and not determined in 50%. Patients with severe neutropenia (absolute neutrophil count < 100) had a slightly, although not significantly higher incidence of documented and probable infection (57%). Patients with solid tumor had documented infection in 40% of their febrile episodes, and the detection rate in the children with leukemia was 31% (P < .20) Blood cultures were positive in 21 (14%) of 149 episodes. Staphylococci (both coagulase-negative and coagulase-positive strains) and Pseudomonas were the organisms most frequently isolated (six episodes each). Mouth and throat (11), lungs (10), and skin (10) were the next most frequent sites of localized infection. Initial treatment consisted of piperacillin and amikacin or of vancomycin and amikacin when the source of fever was thought to be an infected central line catheter, with addition of amphotericin B by the seventh day of treatment when fever with neutropenia persisted or upon clinical suspicion of underlying fungal infection

  16. A clinical and epidemiological study of an epidemic of febrile illness with haemorrhagic manifestations which occurred at Kanpur, India, in 1968.

    PubMed

    Chaturvedi, U C; Kapoor, A K; Mathur, A; Chandra, D; Khan, A M; Mehrotra, R M

    1970-01-01

    An epidemic of febrile illness associated with haemorrhagic manifestations and shock occurred at Kanpur, India, during 1968. The epidemic was widespread in the city, involving about one-tenth of the population; cases were more frequent in thickly populated localities with poor sanitary conditions. Those affected were mainly adolescents and adults of both sexes and multiple cases occurred in families. The disease was characterized by the sudden onset of fever, associated with severe headache and low backache. A number of patients had bradycardia, vomiting and diarrhoea and macular skin rashes associated with itching. A small percentage of the patients had haemorrhagic manifestations in the form of haematemesis, haemoptysis, melaena, haematuria and bleeding per vaginum. The mortality was very low. Dengue type 4 virus has been implicated in the epidemic.

  17. Febrile Seizures

    MedlinePlus

    ... or prolonged seizures are a risk factor for epilepsy but most children who experience febrile seizures do ... develop the reoccurring seizures that re characteristic of epilepsy. Certain children who have febrile seizures face an ...

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

    PubMed Central

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

    2014-01-01

    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

  19. Evidence-based guidelines for the management of neutropenia following outpatient hematopoietic stem cell transplantation.

    PubMed

    West, Fran; Mitchell, Sandra A

    2004-12-01

    Hematopoietic stem cell transplantation (HSCT) involves the transfer of stem cells to establish hematopoiesis in patients who have received myeloablative chemotherapy with or without whole body irradiation. Following high-dose therapy and HSCT, all patients experience a period of neutropenia. Outpatient care delivery models place expanded responsibilities on patients and their families for the management of this treatment side effect. Proactive management of neutropenia is critical to decrease the depth and duration of neutropenia following HSCT, limit exposure to opportunistic and nosocomial pathogens, and ensure prompt intervention should febrile neutropenia or infection develop. Patient and family education, psychosocial support, and coordination of care are key nursing responsibilities.

  20. Febrile and other occasional seizures.

    PubMed

    Bast, T; Carmant, L

    2013-01-01

    Seizures with fever that result from encephalitis or meningitis usually occur late in the course of febrile illness, and are focal and prolonged. Febrile seizures are by far the most common affecting 5% of the population, followed by posttraumatic seizures and those observed in the setting of a toxic, infectious, or metabolic encephalopathy. This chapter reviews the clinical presentation of the three most common forms, due to fever, trauma, and intoxication. Febrile seizures carry no cognitive or mortality risk. Recurrence risk is increased by young age, namely before 1 year of age. Febrile seizures that persist after the age of 6 years are usually part of the syndrome of Generalized epilepsy febrile seizures plus. These febrile seizures have a strong link with epilepsy since non-febrile seizures may occur later in the same patient and in other members of the same family with an autosomal dominant transmission. Complex febrile seizures, i.e., with focal or prolonged manifestations or followed by focal defect, are related to later mesial temporal epilepsy with hippocampal sclerosis; risk factors are seizure duration and brain malformation. Prophylactic treatment is usually not required in febrile seizures. Early onset of complex seizures is the main indication for AED prophylaxis. Early posttraumatic seizures, i.e., within the first week, are often focal and indicate brain trauma: contusion, hematoma, 24 hours amnesia, and depressed skull fracture are major factors of posttraumatic epilepsy. Prophylaxis with antiepileptic drugs is not effective. Various psychotropic drugs, including antiepileptics, may cause seizures.

  1. Febrile seizures

    MedlinePlus

    ... does not have a history of seizure disorders (epilepsy). A tonic-clonic seizure involves the entire body. ... no evidence that they cause death, brain damage, epilepsy, or learning problems. Most children outgrow febrile seizures ...

  2. Neutropenia in primary immunodeficiency

    PubMed Central

    Sokolic, Robert

    2016-01-01

    Purpose of review Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs). Because of the diverse pathophysiologies of the PIDDs and the rarity of each disorder, data are often lacking, leading to the necessity of empiric treatment. Recent developments in the understanding of neutropenia in several of the PIDDs make a review of the data timely. Recent findings The category of severe congenital neutropenia continues to expand. Mutations in G6PC3 have been identified as the cause of neutropenia in a minority of previously molecularly undefined cases. Recent advances have broadened our understanding of the pathophysiology and the clinical expression of this disorder. A possible function of the C16orf57 gene has been hypothesized that may explain the clinical overlap between Clerucuzio-type poikiloderma with neutropenia and other marrow diseases. Plerixafor has been shown to be a potentially useful treatment in the warts, hypogammaglobulinemia, infection, and myelokathexis syndrome. Investigations of patients with adenosine deaminase deficient severe combined immunodeficiency have identified neutropenia, and particularly susceptibility to myelotoxins, as a feature of this disorder. Granulocyte-colony stimulating factor is the treatment of choice for neutropenia in PIDD, whereas hematopoietic cell transplantation is the only curative option. Summary The number of PIDDs associated with neutropenia has increased, as has our understanding of the range of phenotypes. Additional data and hypotheses have been generated helping to explain the diversity of presentations of neutropenia in PIDDs. PMID:23196894

  3. Genetics Home Reference: cyclic neutropenia

    MedlinePlus

    ... Understand Genetics Home Health Conditions cyclic neutropenia cyclic neutropenia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Cyclic neutropenia is a disorder that causes frequent infections and ...

  4. Drug-induced immune neutropenia/agranulocytosis.

    PubMed

    Curtis, Brian R

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study.

    PubMed

    Jeong, Seong Hyun; Kim, Dae Young; Jang, Jun Ho; Mun, Yeung-Chul; Choi, Chul Won; Kim, Sung-Hyun; Kim, Jin Seok; Park, Joon Seong

    2016-01-01

    Micafungin, a clinically important echinocandin antifungal drug, needs to be investigated as empirical therapy in febrile neutropenia in comparison with azole compounds. A prospective randomized study was conducted to compare clinical outcomes between micafungin and intravenous itraconazole as an empirical therapy for febrile neutropenia in hematological malignancies. The antifungal drug (micafungin 100 mg or itraconazole 200 mg IV once daily) was given for high fever that was sustained despite the administration of appropriate antibiotics. Treatment success was determined by composite end points based on breakthrough invasive fungal infection (IFI), survival, premature discontinuation, defervescence, and treatment of baseline fungal infection. Duration of fever, hospital stay, and overall survival (OS) were studied. A total of 153 patients were randomized to receive micafungin or itraconazole. The overall success rate was 7.1 % point higher in the micafungin group (64.4 vs. 57.3 %, p = 0.404), satisfying the statistical criteria for the non-inferiority of micafungin. The duration of fever and hospital stay were significantly shorter in the micafungin group (6 vs. 7 days, p = 0.014; 22 vs. 27 days, p = 0.033, respectively). Grade 3 adverse events including hyperbilirubinemia (2 vs. 7), elevation of transaminase levels (2 vs. 4), electrolyte imbalance (1 vs. 2), atrial fibrillation (1 vs. 0), and anaphylaxis (1 vs. 0) occurred in 7 and 13 patients in the micafungin (10.4 %) and itraconazole (18.8 %) groups, respectively. Micafungin, when compared with itraconazole, had favorably comparable success rate and toxicity profiles on febrile neutropenia in patients with hematological malignancies. In addition, it showed superior effect on shortening the hospital stay.

  7. Colony-stimulating factors for the management of neutropenia in cancer patients.

    PubMed

    Dale, David C

    2002-01-01

    Neutropenia and its subsequent infectious complications represent the most common dose-limiting toxicity of cancer chemotherapy. Febrile neutropenia (FN) occurs with common chemotherapy regimens in 25 to 40% of treatment-naive patients, and its severity depends on the dose intensity of the chemotherapy regimen, the patient's prior history of either radiation therapy or use of cytotoxic treatment, and comorbidities. The occurrence of FN often causes subsequent chemotherapy delays or dose reductions. It may also lengthen hospital stay, increase monitoring, diagnostic and treatment costs, and reduce patient quality of life. A decade after their introduction, colony-stimulating factors (CSFs) such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are now an integral part of the prevention of potentially life-threatening FN; however, only G-CSF has US Food and Drug Administration approval for use in chemotherapy-induced neutropenia. These adjunctive agents accelerate formation of neutrophils from committed progenitors, thereby reducing the duration and severity of neutropenia. Important uses of CSFs in oncology are prevention of FN after chemotherapy, treatment of febrile neutropenic episodes and support following bone marrow transplantation, and collection of CSF-mobilised peripheral blood progenitor cells. G-CSF is used more frequently than GM-CSF for all of these indications because of fewer associated adverse effects. Clinical trials to date have not demonstrated a significant effect on overall survival or disease-free survival, which is most likely to be due to small sample size and lack of power to prove effect. However, they have demonstrated clinical utility in allowing the delivery of planned chemotherapy dose on schedule, an important clinical goal especially in curative tumour settings. The high cost of these agents limits their widespread use. Current American Society of Clinical Oncology

  8. Severe neutropenia in dengue patients: prevalence and significance.

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  11. New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim.

    PubMed

    Ghidini, Michele; Hahne, Jens Claus; Trevisani, Francesco; Panni, Stefano; Ratti, Margherita; Toppo, Laura; Tomasello, Gianluca

    2016-01-01

    Neutropenia and febrile neutropenia are two major complications of chemotherapy. Dose reductions, delays in treatment administration, and the use of granulocyte colony-stimulating factors are equally recommended options to preserve absolute neutrophil count in case of chemotherapy regimens bringing a risk of febrile neutropenia of 20% or higher. Recombinant granulocyte colony-stimulating factors, such as filgrastim and lenograstim, have a short elimination half-life (t1/2) and need to be used daily, while others, like pegfilgrastim and lipegfilgrastim, are characterized by a long t1/2 requiring only a single administration per cycle. Balugrastim is a novel long-acting recombinant granulocyte colony-stimulating factor obtained by means of a genetic fusion between recombinant human serum albumin and granulocyte colony-stimulating factor. Albumin binding increases the molecular weight and determines a high plasmatic stability leading to a t1/2 of ~19 days. Balugrastim's efficacy, safety, and tolerability have been assessed in four different clinical trials involving breast cancer patients treated with doxorubicin and docetaxel. Pegfilgrastim was chosen as a comparator. Balugrastim was noninferior to pegfilgrastim with regard to the reduction of mean duration of severe neutropenia during cycle 1. Moreover, both treatments were comparable in terms of efficacy and safety profile. Balugrastim was well tolerated, with the only related adverse event being mild to moderate bone pain. The aim of this review is to summarize the currently available literature data on balugrastim. PMID:27445479

  12. New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim

    PubMed Central

    Ghidini, Michele; Hahne, Jens Claus; Trevisani, Francesco; Panni, Stefano; Ratti, Margherita; Toppo, Laura; Tomasello, Gianluca

    2016-01-01

    Neutropenia and febrile neutropenia are two major complications of chemotherapy. Dose reductions, delays in treatment administration, and the use of granulocyte colony-stimulating factors are equally recommended options to preserve absolute neutrophil count in case of chemotherapy regimens bringing a risk of febrile neutropenia of 20% or higher. Recombinant granulocyte colony-stimulating factors, such as filgrastim and lenograstim, have a short elimination half-life (t1/2) and need to be used daily, while others, like pegfilgrastim and lipegfilgrastim, are characterized by a long t1/2 requiring only a single administration per cycle. Balugrastim is a novel long-acting recombinant granulocyte colony-stimulating factor obtained by means of a genetic fusion between recombinant human serum albumin and granulocyte colony-stimulating factor. Albumin binding increases the molecular weight and determines a high plasmatic stability leading to a t1/2 of ~19 days. Balugrastim’s efficacy, safety, and tolerability have been assessed in four different clinical trials involving breast cancer patients treated with doxorubicin and docetaxel. Pegfilgrastim was chosen as a comparator. Balugrastim was noninferior to pegfilgrastim with regard to the reduction of mean duration of severe neutropenia during cycle 1. Moreover, both treatments were comparable in terms of efficacy and safety profile. Balugrastim was well tolerated, with the only related adverse event being mild to moderate bone pain. The aim of this review is to summarize the currently available literature data on balugrastim. PMID:27445479

  13. The Risk of Serious Bacterial Infection in Neutropenic Immunocompetent Febrile Children.

    PubMed

    Barg, Assaf A; Kozer, Eran; Mordish, Yair; Lazarovitch, Tsilia; Kventsel, Iris; Goldman, Michael

    2015-08-01

    Only few reports have looked into the risk of invasive bacterial infection in children with neutropenia that is not malignancy related. The objective of the current study was to determine the clinical significance of neutropenia as a predictor of serious bacterial infection (SBI) in immunocompetent children. We conducted a retrospective case-control study including children 3 months to 18 years of age with fever ≥ 38°C hospitalized or presenting to the emergency department. Patients who had neutropenia ≤ 1000 ANC/μL and had a blood culture taken were matched for age with the consecutive febrile patients for whom a blood culture was taken. The main outcome was the rate of SBI. SBIs were more prevalent among the control group than in the group of children with neutropenia, 19/71 and 6/71, respectively (P = 0.0005). More children were treated with antibiotics among the control group than in the group of children with neutropenia, 39/71 and 20/71, respectively (P < 0.0001). Acute-phase reactants including CRP and platelets were higher in the control group. We concluded that immunocompetent patients with fever and moderate neutropenia do not carry a higher risk for SBIs compared with patients with fever who do not have neutropenia.

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

    PubMed

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

    2014-11-01

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

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

    PubMed

    Whiskey, Eromona; Taylor, David

    2007-01-01

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

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

    PubMed

    Whiskey, Eromona; Taylor, David

    2007-01-01

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

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

    PubMed Central

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

    2008-01-01

    Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined. PMID:18317581

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

    PubMed

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

    2004-11-01

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

  19. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    PubMed Central

    Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

    2016-01-01

    OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

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

    PubMed

    2010-04-01

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

  1. Febrile convulsions in selected large families: a single-major-locus mode of inheritance?

    PubMed

    Maher, J; McLachlan, R S

    1997-02-01

    As part of a genetic linkage study of febrile convulsions, families with at least four members with the disorder were identified. By applying known principles of human inheritance, possible modes of transmission of febrile convulsions and factors which might impede progress in understanding their inheritance were analyzed. In eight families, 75 of 333 members had febrile convulsions. Inheritance of the disorder occurred in 43, 51, and 46% of children, siblings and all first-degree relatives of probands respectively. Vertical transmission occurred through three to four generations, including from male to male. In these families with multiple affected members, the findings support an autosomal dominant mode of inheritance of febrile convulsions.

  2. Two USA Ehrlichia spp. cause febrile illness in goats.

    PubMed

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

    2008-08-25

    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

  3. Two USA Ehrlichia spp. cause febrile illness in goats.

    PubMed

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

    2008-08-25

    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.

  4. Food-borne bacteremic illnesses in febrile neutropenic children

    PubMed Central

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

    2011-01-01

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

  5. Food-borne bacteremic illnesses in febrile neutropenic children.

    PubMed

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

    2011-08-31

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

  6. Food-borne bacteremic illnesses in febrile neutropenic children.

    PubMed

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

    2011-08-31

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

  7. Chemotherapy-induced neutropenia among pediatric cancer patients in Egypt: Risks and consequences

    PubMed Central

    Badr, Mohamed; Hassan, Tamer; Sakr, Hanan; Karam, Nehad; Rahman, Doaa Abdel; Shahbah, Doaa; Zakaria, Marwa; Fehr, Sahbaa

    2016-01-01

    Chemotherapy-induced neutropenia (CIN) is the major dose-limiting toxicity of systemic chemotherapy and it is associated with significant morbidity, mortality and treatment cost. The aim of the present study was to identify the risk factors that may predispose pediatric cancer patients who receive myelosuppressive chemotherapy to CIN and associated sequelae. A total of 113 neutropenia episodes were analyzed and the risk factors for CIN were classified as patient-specific, disease-specific and regimen-specific, while the consequences of CIN were divided into infectious and dose-modifying sequelae. The risks and consequences were analyzed to target high-risk patients with appropriate preventive strategies. Among our patients, 28% presented with a single neutropenia attack, while 72% experienced recurrent attacks during their treatment cycles. The mean absolute neutrophil count was 225.5±128.5 ×109/l (range, 10–497 ×109/l), starting 14.2±16.3 days (range, 2–100 days) after the onset of chemotherapy and resolving within 11.2±7.3 days, either with (45.1%) or without (54.9%) granulocyte colony-stimulating factor (G-CSF). No significant association was observed between any patient characteristics or disease stage and the risk for CIN. However, certain malignancies, such as acute lymphocytic leukemia (ALL), neuroblastoma and Burkitt's lymphoma, and certain regimens, such as induction block for ALL and acute myelocytic leukemia, exerted the most potent myelotoxic effect, with severe and prolonged episodes of neutropenia. G-CSF significantly shortened the duration of the episodes and enhanced bone marrow recovery. Febrile neutropenia was the leading complication among our cases (73.5%) and was associated with several documented infections, particularly mucositis (54.9%), respiratory (45.1%), gastrointestinal tract (38.9%) and skin (23.9%) infections. A total of 6% of our patients succumbed to infection-related complications. Neutropenia was responsible for treatment

  8. Clozapine Rechallenge After Neutropenia or Leucopenia.

    PubMed

    Prokopez, Cintia R; Armesto, Arnaldo R; Gil Aguer, María F; Balda, María V; Papale, Rosa M; Bignone, Inés M; Daray, Federico M

    2016-08-01

    To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia. PMID:27232877

  9. Neutropenia in the Elderly: A Rheumatology Perspective.

    PubMed

    Yeoh, Su-Ann; Fox, Christine; Hull, Richard

    2016-08-01

    The majority of rheumatic diseases are chronic and require long-term use of disease-modifying agents to confer the best chance of controlling the disease. A significant proportion of these drugs have a risk, albeit small, of potentially serious side effects, such as neutropenia; therefore, there has been an understandable concern over the use of potentially toxic rheumatic drugs in the elderly. Factors that may contribute to this concern include age, pre-existing co-morbidities, polypharmacy, difficulty in monitoring side effects, and patient perception. The risk of using such medication needs to be balanced with their benefits in controlling chronic disease. This review discusses how rheumatic disease and anti-rheumatic medication are associated with neutropenia in an older age group. Of the rheumatic diseases, we give special focus to rheumatoid arthritis and the use of methotrexate, as well as touching on management considerations in neutropenia. PMID:27402172

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

    SciTech Connect

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

    1990-01-01

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

  11. Refractory Thrombocytopenia and Neutropenia: a Diagnostic Challenge

    PubMed Central

    Gyan, Emmanuel; Dreyfus, François; Fenaux, Pierre

    2015-01-01

    The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors. Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS). Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS), and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification) as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008) are quite rare. These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates. PMID:25745545

  12. Genetics Home Reference: severe congenital neutropenia

    MedlinePlus

    ... Alter BP, Link DC, Stein S, Rodger E, Bolyard AA, Aprikyan AA, Bonilla MA, Dror Y, Kannourakis G, Newburger PE, ... PubMed or Free article on PubMed Central Schäffer AA, Klein C. Genetic heterogeneity in severe congenital neutropenia: ...

  13. Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer

    PubMed Central

    2016-01-01

    Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction. PMID:27366009

  14. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

    PubMed Central

    Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

    2016-01-01

    Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

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

    PubMed Central

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

    2015-01-01

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

  16. Meropenem-Induced Neutropenia in a Neonate

    PubMed Central

    Jones, Aubrey N.; Johnson, Peter N.

    2016-01-01

    Postmarketing surveillance has associated meropenem with the development of hematologic abnormalities, including agranulocytosis, neutropenia, and leukopenia, but the exact incidence in children is unknown. The case describes a full-term, 26-day-old neonate admitted for a sepsis workup. She was found to have a blood culture positive for Enterobacter cloacae and suspected meningitis and was initiated on meropenem 40 mg/kg/dose intravenously every 8 hours. On day 14 of antibiotic treatment, the patient developed an isolated neutropenia with an absolute neutrophil count of 288 cells/mm3. Meropenem was discontinued on hospital day 20, and a follow-up complete blood cell count 2 months later confirmed resolution of the hematologic abnormality. Clinicians should monitor complete blood cell counts diligently in children who receive large doses and prolonged courses of meropenem. PMID:27713676

  17. Ipilimumab-Induced Neutropenia in Melanoma

    PubMed Central

    Ban-Hoefen, Makiko; Burack, Richard; Sievert, Lynn; Sahasrabudhe, Deepak

    2016-01-01

    Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the overall survival of advanced melanoma. The most common adverse events associated with ipilimumab are immune-related. Severe hematological toxicity is rare. We report a case of severe neutropenia following ipilimumab therapy that fully resolved after the administration of prednisone, cyclosporine, and anti-thymocyte globulin therapies. PMID:27570779

  18. Ipilimumab-Induced Neutropenia in Melanoma.

    PubMed

    Ban-Hoefen, Makiko; Burack, Richard; Sievert, Lynn; Sahasrabudhe, Deepak

    2016-01-01

    Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the overall survival of advanced melanoma. The most common adverse events associated with ipilimumab are immune-related. Severe hematological toxicity is rare. We report a case of severe neutropenia following ipilimumab therapy that fully resolved after the administration of prednisone, cyclosporine, and anti-thymocyte globulin therapies. PMID:27570779

  19. Pedigree analysis in families with febrile seizures

    SciTech Connect

    Johnson, W.G.; Kugler, S.L.; Stenroos, E.S.; Meulener, M.C.

    1996-02-02

    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.

  20. Prevalence of recent immunisation in children with febrile convulsions

    PubMed Central

    Motala, Leya; Eslick, Guy D

    2016-01-01

    AIM To determine the prevalence of recent immunisation amongst children under 7 years of age presenting for febrile convulsions. METHODS This is a retrospective study of all children under the age of seven presenting with febrile convulsions to a tertiary referral hospital in Sydney. A total of 78 cases occurred in the period January 2011 to July 2012 and were included in the study. Data was extracted from medical records to provide a retrospective review of the convulsions. RESULTS Of the 78 total cases, there were five medical records which contained information on whether or not immunisation had been administered in the preceding 48 h to presentation to the emergency department. Of these five patients only one patient (1.28% of the study population) was confirmed to have received a vaccination with Infanrix, Prevnar and Rotavirus. The majority of cases reported a current infection as a likely precipitant to the febrile convulsion. CONCLUSION This study found a very low prevalence of recent immunisation amongst children with febrile convulsions presenting to an emergency department at a tertiary referral hospital in Sydney. This finding, however, may have been distorted by underreporting of vaccination history.

  1. Prevalence of recent immunisation in children with febrile convulsions

    PubMed Central

    Motala, Leya; Eslick, Guy D

    2016-01-01

    AIM To determine the prevalence of recent immunisation amongst children under 7 years of age presenting for febrile convulsions. METHODS This is a retrospective study of all children under the age of seven presenting with febrile convulsions to a tertiary referral hospital in Sydney. A total of 78 cases occurred in the period January 2011 to July 2012 and were included in the study. Data was extracted from medical records to provide a retrospective review of the convulsions. RESULTS Of the 78 total cases, there were five medical records which contained information on whether or not immunisation had been administered in the preceding 48 h to presentation to the emergency department. Of these five patients only one patient (1.28% of the study population) was confirmed to have received a vaccination with Infanrix, Prevnar and Rotavirus. The majority of cases reported a current infection as a likely precipitant to the febrile convulsion. CONCLUSION This study found a very low prevalence of recent immunisation amongst children with febrile convulsions presenting to an emergency department at a tertiary referral hospital in Sydney. This finding, however, may have been distorted by underreporting of vaccination history. PMID:27610346

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

    PubMed Central

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

    2003-01-01

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

  3. [Analysis of the risk factors for severe neutropenia in advanced non-small cell lung cancer after the first course of chemotherapy with third-generation agents].

    PubMed

    Shibuya, Midori; Kogo, Mari; Kurihara, Tatsuya; Shikama, Yusuke; Nakajima, Hiroaki; Yoneyama, Keiichiro; Kiuchi, Yuji

    2013-01-01

      We retrospectively evaluated clinical data before therapy to determine the risk factors for severe neutropenia in advanced non-small-cell lung cancer (NSCLC) patients treated with third-generation agents. We analyzed 100 patients who received such agents (paclitaxel, docetaxel, gemcitabine, irinotecan, or vinorelbine) for advanced NSCLC. The endpoint of the survey was the occurrence of severe neutropenia (grade 4). Risk factors significantly related to severe neutropenia were identified using logistic regression analysis. Of the 100 patients studied, the median age was 62.0 (32-81 years), and 77 (77.0%) were male. CEA 6.6 (0-2220) ng/dL and cytokeratin 19 fragment 21-1 (CYFRA) 4.8 (0.2-173.8) ng/dL before chemotherapy were higher than normal range. Severe neutropenia occurred in 36.0%, the incidence being highest in the first cycle (61.1%). In the univariate analysis, variables associated with severe neutropenia were sex, chest pain, absolute neutrophil count (ANC), Cr, CRP, and CYFRA. In the multivariate analysis, low CYFRA level was identified as a significant risk factor that contributed independently to chemotherapy-induced severe neutropenia (p<0.05). Our analysis suggests that low CYFRA level is the most important risk factor for severe neutropenia in advanced NSCLC patients after the first course of chemotherapy with third-generation agents. PMID:23728094

  4. [A child with neonatal allo-immune neutropenia].

    PubMed

    Markhorst, D G; Hack, W W; de Waal, F C; Kuypers, R

    1990-10-01

    A newborn child with neonatal neutropenia as a result of the presence of maternal IgG isoantibodies against neutrophil granulocyte blood group antigens is reported. Mechanism, diagnostics and therapy of the disease are discussed. The diagnosis not only has consequences for the child, but also for the mother and following pregnancies. A review of the most important causes of neonatal neutropenia is given.

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

    PubMed

    Henry, Meret; Sung, Lillian

    2015-02-01

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

  6. Simple febrile convulsions: evidence for best practice.

    PubMed

    Hawksworth, D L

    2000-01-01

    Febrile convulsions are common in early childhood and may be the first sign of an illness. Witnessing the convulsion and experiencing the subsequent admission is extremely stressful for parents. Children's nurses need to identify the evidence for best practice in the management of febrile convulsions. Parent education is an essential component of the management of care. PMID:11855470

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

    PubMed Central

    2011-01-01

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

  8. Febrile Illness with Skin Rashes

    PubMed Central

    2015-01-01

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

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

    PubMed Central

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

    1982-01-01

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

  10. [Consensus: Rational approach towards the patient with cancer, fever and neutropenia].

    PubMed

    Santolaya, María Elena; Rabagliati, Ricardo; Bidart, Teresa; Payá, Ernesto; Guzmán, Ana M; Morales, Ricardo; Braun, Stephanie; Bronfman, Lucía; Ferrés, Marcela; Flores, Claudio; García, Patricia; Letelier, Luz M; Puga, Bárbara; Salgado, Carmen; Thompson, Luis; Tordecilla, Juan; Zubieta, Marcela

    2005-01-01

    The severity and duration of post chemotherapy neutropenia were recognized during the 1960s as main predisposing factors for infections in cancer patients. At the beginning of the 70's a standard management approach for all febrile neutropenia (FN) episodes was proposed, based on hospitalization and intravenous empirical broad spectrum antibiotic therapy. Widespread use of this approach resulted in a significant reduction in mortality attributable to bacterial infections. During the last 10 to 15 years, reappraisal of this standard approach has been done by several research groups who question the benefit of treating all FN patients similarly without taking in to consideration differences in severity of the FN episodes. This reappraisal has led during the 1990s to the development of the concept of high and low risk FN episodes that has been the base for the adoption of selective therapies based on the risk categorization of the individual patient. The Chilean Infectious Diseases Society called upon two government National Programs responsible for the appropriate distribution of chemotherapeutic drugs to all pediatric and adults cancer patients within the public health system, and upon the Chilean Hematology Society for the development of a Consensus on Diagnosis, Treatment and Prevention of Infections during FN Episodes in Cancer patients. The need for this Consensus is based on two main aspects: the new approaches proposed during the past year for management of these episodes, and the increasing population of cancer patients receiving improved chemotherapeutic agents that has increased there survival possibilities as well as there possibility to suffer a FN episode. The topics discussed in this document are based on an updated systematic and analytic review of the medical literature including epidemiology, laboratory diagnostics, risk categorization, treatment and prophylaxis. National data was included when available in order to provide the healthcare personnel

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2013-01-01

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

  14. Effect of therapy on the neutropenia of hyperthyroidism

    SciTech Connect

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

    1983-03-01

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

  15. Neutropenia Associated with Long-Term Ceftaroline Use

    PubMed Central

    Anderson, Scott W.; Rice, Todd W.; Saavedra, Tatiana C.; O'Neal, Catherine S.

    2015-01-01

    Ceftaroline is a fifth-generation cephalosporin with potent antimicrobial activity against Gram-positive and Gram-negative pathogens. Neutropenia is a rare serious adverse event for the class of cephalosporins; however, we observed several cases of severe neutropenia in our outpatient infectious disease practice believed to be associated with ceftaroline use. The aim of this study was to determine the incidence of neutropenia among patients receiving ceftaroline therapy for more than 7 days. We conducted a retrospective cohort analysis of patients admitted to an 800-bed regional medical center between June 2012 and December 2014 who received ceftaroline for more than 7 days to assess the incidence of developing clinically significant neutropenia. Demographic and patient care data points as well as underlying admitting and chronic diagnoses were retrospectively collected from the medical record. Clinically significant neutropenia was defined as an absolute neutrophil count (ANC) less than 1,500 cells/mm3. Analysis was performed to determine the incidence, severity, and outcome of neutropenia following ceftaroline administration. A total of 39 patients were included in the cohort. The median duration of therapy was 27 days. Seven patients (18%) developed neutropenia while on ceftaroline therapy. Four (10%) of the neutropenic patients had an ANC of <500 cells/mm3. The median first neutropenic day was day 17, with the median ANC nadir of 432 cells/mm3 on day 24. We determined that extended ceftaroline infusion is associated with the development of neutropenia. We recommend obtaining a complete blood count (CBC) with differential at the onset of therapy and weekly thereafter. Should the ANC fall below 2,500 cells/mm3, then twice-weekly CBCs should be monitored for the duration of ceftaroline therapy, and therapy should be discontinued if the ANC falls to 1,500 cells/mm3 or less. PMID:26503657

  16. Primary immune-mediated neutropenia in a cat

    PubMed Central

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

    2014-01-01

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

  17. Antifungal prophylaxis with posaconazole vs. fluconazole or itraconazole in pediatric patients with neutropenia.

    PubMed

    Döring, M; Eikemeier, M; Cabanillas Stanchi, K M; Hartmann, U; Ebinger, M; Schwarze, C-P; Schulz, A; Handgretinger, R; Müller, I

    2015-06-01

    Pediatric patients with hemato-oncological malignancies and neutropenia resulting from chemotherapy have a high risk of acquiring invasive fungal infections. Oral antifungal prophylaxis with azoles, such as fluconazole or itraconazole, is preferentially used in pediatric patients after chemotherapy. During this retrospective analysis, posaconazole was administered based on favorable results from studies in adult patients with neutropenia and after allogeneic hematopoietic stem cell transplantation. Retrospectively, safety, feasibility, and initial data on the efficacy of posaconazole were compared to fluconazole and itraconazole in pediatric and adolescent patients during neutropenia. Ninety-three pediatric patients with hemato-oncological malignancies with a median age of 12 years (range 9 months to 17.7 years) that had prolonged neutropenia (>5 days) after chemotherapy or due to their underlying disease, and who received fluconazole, itraconazole, or posaconazole as antifungal prophylaxis, were analyzed in this retrospective single-center survey. The incidence of invasive fungal infections in pediatric patients was low under each of the azoles. One case of proven aspergillosis occurred in each group. In addition, there were a few cases of possible invasive fungal infection under fluconazole (n = 1) and itraconazole (n = 2). However, no such cases were observed under posaconazole. The rates of potentially clinical drug-related adverse events were higher in the fluconazole (n = 4) and itraconazole (n = 5) groups compared to patients receiving posaconazole (n = 3). Posaconazole, fluconazole, and itraconazole are comparably effective in preventing invasive fungal infections in pediatric patients. Defining dose recommendations in these patients requires larger studies.

  18. The current spectrum of infection in cancer patients with chemotherapy related neutropenia.

    PubMed

    Nesher, Lior; Rolston, Kenneth V I

    2014-02-01

    Despite advancements in the treatment and supportive care of patients with malignant disorders, neutropenia remains the major side effect of most antineoplastic regimens. Infections occur frequently in neutropenic patients and are associated with considerable morbidity and mortality. The spectrum of infection continues to change, and is influenced by various factors including local epidemiology, the use of chemoprophylaxis, and the use of central venous catheters and other medical devices. Bacterial infections are common in the early stages of neutropenia, with fungal infections emerging if neutropenia persists beyond 7-10 days. Gram-positive organisms cause most bacteremic infections (although this trend appears to be changing), whereas infections at other sites are often caused by Gram-negative bacilli or are polymicrobial, especially if deep tissue infection is present. Candida spp., and Aspergillus spp., remain the most common fungal pathogens, although several opportunistic fungi have emerged. Resistance to antimicrobial and antifungal agents commonly used for the prevention and treatment of infections in neutropenic patients has become a significant problem. The prompt administration of appropriate, empiric, antimicrobial therapy, prior to the availability of microbiological culture results, is the standard of care. Up to date knowledge of the spectrum of infection and local susceptibility/resistance patterns, is critical. In this report, we describe the current spectrum of infection in patients with malignancies and neutropenia, and emphasize the fact that local and geographic differences are not infrequent. We recommend that individual institutions conduct periodic epidemiological surveys in order to have the latest data available for the optimal management of their patients. PMID:23975584

  19. Febrile Seizures and Epilepsy: Possible Outcomes

    MedlinePlus

    ... whether they could increase the risk of developing epilepsy later. Febrile seizures are defined as seizures that ... brains of patients who underwent surgery for severe epilepsy. 3 The children with FSE were com- pared ...

  20. Outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer

    PubMed Central

    Kimura, Kosei; Tanaka, Satoru; Iwamoto, Mitsuhiko; Fujioka, Hiroya; Sato, Nayuko; Terasawa, Risa; Kawaguchi, Kanako; Matsuda, Junna; Umezaki, Nodoka; Uchiyama, Kazuhisa

    2016-01-01

    The purpose of this study was to retrospectively analyze the feasibility of outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer. A total of 131 consecutive patients with breast cancer treated with adjuvant or neoadjuvant chemotherapy from 2011 to 2013 at Osaka Medical College Hospital (Osaka, Japan) were retrospectively reviewed. In the case of developing a fever (body temperature, ≥38°C), the outpatients had been instructed to take previously prescribed oral antibiotics for 3 days without any initial assessment, and if no improvement had occurred by then, they were required to visit the hospital for examination and to undergo treatment based on the results of a risk assessment for complications. The primary aim of the present study was to assess the outcome of febrile episodes, while the secondary aim was to assess the incidence of febrile episodes, hospitalizations, and the type of chemotherapy. The 131 patients received 840 chemotherapy administrations. Fifty-five patients (42.0%) had a total of 75 febrile episodes after 840 chemotherapy administrations (8.9%). Treatment failure occurred in 12 of the 75 episodes (16.0%) in 11 of the 55 patients (20.0%). Only four episodes required hospitalization. Treatment success was achieved in 63 episodes (84.0%). In conclusion, the feasibility of outpatient management without initial assessment was evaluated in the present study for febrile patients undergoing adjuvant chemotherapy for breast cancer, and the outpatient strategy regimen may be safe and convenient for these patients. PMID:27699031

  1. Outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer

    PubMed Central

    Kimura, Kosei; Tanaka, Satoru; Iwamoto, Mitsuhiko; Fujioka, Hiroya; Sato, Nayuko; Terasawa, Risa; Kawaguchi, Kanako; Matsuda, Junna; Umezaki, Nodoka; Uchiyama, Kazuhisa

    2016-01-01

    The purpose of this study was to retrospectively analyze the feasibility of outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer. A total of 131 consecutive patients with breast cancer treated with adjuvant or neoadjuvant chemotherapy from 2011 to 2013 at Osaka Medical College Hospital (Osaka, Japan) were retrospectively reviewed. In the case of developing a fever (body temperature, ≥38°C), the outpatients had been instructed to take previously prescribed oral antibiotics for 3 days without any initial assessment, and if no improvement had occurred by then, they were required to visit the hospital for examination and to undergo treatment based on the results of a risk assessment for complications. The primary aim of the present study was to assess the outcome of febrile episodes, while the secondary aim was to assess the incidence of febrile episodes, hospitalizations, and the type of chemotherapy. The 131 patients received 840 chemotherapy administrations. Fifty-five patients (42.0%) had a total of 75 febrile episodes after 840 chemotherapy administrations (8.9%). Treatment failure occurred in 12 of the 75 episodes (16.0%) in 11 of the 55 patients (20.0%). Only four episodes required hospitalization. Treatment success was achieved in 63 episodes (84.0%). In conclusion, the feasibility of outpatient management without initial assessment was evaluated in the present study for febrile patients undergoing adjuvant chemotherapy for breast cancer, and the outpatient strategy regimen may be safe and convenient for these patients.

  2. Periodontal disease in three siblings with familial neutropenia.

    PubMed

    Kirstilä, V; Sewón, L; Laine, J

    1993-06-01

    The periodontal status and treatment of three teenagers in a Finnish family with familial neutropenia is described. The mother was also diagnosed with neutropenia. At initial examination, the 15-year-old male and the 10-year-old female had severe periodontitis, whereas the 13-year-old male had oral ulcerations but no significant periodontal disease. The two siblings with periodontitis were treated and followed approximately 5 years. It was concluded that periodontal therapy including scaling, surgery, and use of antimicrobial agents can be successful in patients with familial neutropenia, and that such patients are not necessarily candidates for full mouth extraction. The role of granulocyte colony-stimulating factor in which was used in the treatment of these patients remains to be established.

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

    PubMed

    Khair, Abdulhafeez M; Elmagrabi, Dalal

    2015-01-01

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

  4. Febrile seizures in Kaduna, north western Nigeria

    PubMed Central

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

    2012-01-01

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

  5. A clinical study of febrile myoclonus in children.

    PubMed

    Onoe, Sachiko; Nishigaki, Toshinori

    2004-08-01

    Fever is sometimes associated with chill, myoclonus, delirium and convulsion. We previously reported EEG findings of febrile delirium, when we found that 18% of patients showed febrile myoclonus simultaneously with febrile delirium. The purpose of this study is to clarify the clinical features of febrile myoclonus and to investigate the relation to febrile convulsion. Myoclonic episodes were studied in 11 patients, aged 8 months to 11 years. EEG was recorded in eight patients. In the past history, febrile convulsion was noted in two patients and one of them also had febrile delirium. The age range of patients with febrile myoclonus was similar to those developing febrile convulsion except for one case. The duration of febrile myoclonus was usually from several to 30 min, but was longer than 2 h in four patients. Seventy-three percent of patients showed fear, surprise and shouting. EEG was abnormal in four patients and spike components were found in two patients. Myoclonic jerks were seen during the EEG recording in two patients and EEG findings were not concordant with epileptic myoclonic attack. Ten patients were followed for 1-2 years, and none had afebrile seizures. Febrile myoclonus is a benign symptom associated with fever. Mood change, fear or surprise and shouting with myoclonic jerks may suggest action of cytokine on the hypothalamus induced by infection. Febrile myoclonus, delirium and convulsion were seen in one patient in his first 3 years of life. These three symptoms seem to appear in children depending on their predisposition. PMID:15165673

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

    PubMed

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

    2015-10-01

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

  7. Anti-TNF-α therapy may cause neonatal neutropenia.

    PubMed

    Guiddir, Tamazoust; Frémond, Marie-Louise; Triki, Tewfik Bibi; Candon, Sophie; Croisille, Laure; Leblanc, Thierry; de Pontual, Loïc

    2014-10-01

    Although anti-tumor necrosis factor (anti-TNF) antibodies are associated with a clear risk of agranulocytosis in adults and are known to cross the placenta, monitoring of the absolute neutrophil count (ANC) in neonates born to mothers receiving these biological agents is not currently recommended. Here, we report on the first case series of 4 newborn patients with severe neutropenia born to mothers treated for ulcerative colitis with infliximab during pregnancy (including the third trimester). The newborns presented with severe neutropenia at birth, which was subsequently complicated by skin infections. The newborns' ANCs returned to the normal range within 8 to 14 weeks, at which time infliximab could not be detected in the blood. Anti-TNF agents probably exert a direct, toxic effect on the bone marrow. Furthermore, the detection of a CD16 autoantibody in 1 mother-newborn pair suggests that infliximab can induce autoimmune neutropenia. Abnormally high levels of the CD16 autoantibody in newborn serum or immaturity of the fetal bone marrow might explain why neutropenia was observed in the child but not in the mother. We recommend the systematic measurement of ANC on cord blood at birth and (in the event of an infection) in the weeks thereafter. PMID:25266439

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

    PubMed

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

    2011-07-15

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

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

    PubMed

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

    2012-04-01

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

  10. A hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia.

    PubMed

    Ordoñez-Rueda, Diana; Jönsson, Friederike; Mancardi, David A; Zhao, Weidong; Malzac, Aurélie; Liang, Yinming; Bertosio, Elodie; Grenot, Pierre; Blanquet, Véronique; Sabrautzki, Sybille; de Angelis, Martin Hrabě; Méresse, Stéphane; Duprez, Estelle; Bruhns, Pierre; Malissen, Bernard; Malissen, Marie

    2012-09-01

    Using N-ethyl-N-nitrosourea-induced mutagenesis, we established a mouse model with a novel form of neutropenia resulting from a point mutation in the transcriptional repressor Growth Factor Independence 1 (Gfi1). These mice, called Genista, had normal viability and no weight loss, in contrast to mice expressing null alleles of the Gfi1 gene. Furthermore, the Genista mutation had a very limited impact on lymphopoiesis or on T- and B-cell function. Within the bone marrow (BM), the Genista mutation resulted in a slight increase of monopoiesis and in a block of terminal granulopoiesis. This block occurred just after the metamyelocytic stage and resulted in the generation of small numbers of atypical CD11b(+) Ly-6G(int) neutrophils, the nuclear morphology of which resembled that of mature WT neutrophils. Unexpectedly, once released from the BM, these atypical neutrophils contributed to induce mild forms of autoantibody-induced arthritis and of immune complex-mediated lung alveolitis. They additionally failed to provide resistance to acute bacterial infection. Our study demonstrates that a hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia characterized by a split pattern of functional responses, reflecting the distinct thresholds required for eliciting neutrophil-mediated inflammatory and anti-infectious responses.

  11. Genetic Heterogeneity in Severe Congenital Neutropenia: How Many Aberrant Pathways Can Kill a Neutrophil?

    PubMed Central

    Schäffer, Alejandro A.; Klein, Christoph

    2008-01-01

    Purpose of review Severe congenital neutropenia (SCN) is a primary immunodeficiency in which lack of neutrophils causes inadequate innate immune host response to bacterial infections. SCN occurs with sporadic, autosomal dominant (AD), autosomal recessive (AR), and X-linked recessive (XLR) inheritance, as well as in a variety of multi-system syndromes. A principal stimulus for this review is the identification of novel genetic defects and pathophysiological insights into the role of neutrophil apoptosis. Recent findings Identification of mutations in HAX1 in autosomal recessive SCN (Kostmann disease), large epidemiological study estimating the risk of progression from SCN to leukemia, better understanding of how heterozygous mutations in neutrophil elastase (ELA2) cause SCN, molecular characterization of a novel syndromic form of SCN called p14 deficiency, and new animal models for several syndromic forms of SCN. Summary We consider the numerous genes mutated in SCN, many attempts to make animal models of SCN, and results from both human and mouse studies investigating the molecular mechanisms of neutrophil apoptosis. Investigations of how SCN genes and apoptosis pathways are connected should lead to better understanding of the pathogenesis of neutropenia and apoptosis pathways relevant to many cell types. PMID:17989524

  12. [Epidemiological surveillance of febrile rash illness].

    PubMed

    Pérez-Pérez, Gabriela Fidela; Rojas-Mendoza, Teresita; Cabrera-Gaytán, David Alejandro; Grajales-Muñiz, Concepción; Maldonado-Burgos, Martha Alejandra

    2015-01-01

    Introducción: en 2011 se detectaron tres casos importados de sarampión, por lo que se intensificó la vigilancia epidemiológica con emisión de alertas epidemiológicas. El objetivo de este estudio es describir el fenómeno de la intensificación de la vigilancia epidemiológica de enfermedad febril exantemática ante la importación de casos confirmados de sarampión en el territorio nacional en el Instituto Mexicano del Seguro Social. Métodos: se obtuvieron los casos del sistema especial de vigilancia epidemiológica de 2011, se compararon con el año previo. Se determinó t de Student para diferencia de medias, prueba de Wilson para proporciones; ambas con un valor alfa del 0.05. Resultados: en 2011 se notificaron 2786 casos de enfermedad febril exantemática, 51.2 % más casos que el año anterior; el número de casos reportados con relación a los esperados aumentó en 29 de las 35 Delegaciones del IMSS con un incremento en el promedio de casos notificados a partir de la semana 26. El 67.4 % de los casos notificados se concentró en los menores de 5 años de edad. Conclusiones: se apreció un incremento importante de casos notificados de enfermedad febril exantemática en comparación con el año previo. El Instituto cuenta con un sistema de vigilancia epidemiológica de enfermedad febril exantemática robusto y flexible, que ha permitido identificar riesgos a la población.

  13. Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco.

    PubMed

    Mostefai, Rahima; Morice-Picard, Fanny; Boralevi, Franck; Sautarel, Michel; Lacombe, Didier; Stasia, Marie José; McGrath, John; Taïeb, Alain

    2008-11-01

    Three siblings from Morocco consanguineous family presented with cutaneous poikiloderma following postnatal ichthyosiform lesions, associated with papillomatous lesions, palmoplantar keratoderma, pachyonychia of toenails, fragile carious teeth, and lachrymal duct obstruction. Photosensitivity and blistering improved with age. Atrophic scars were prominent on the limbs. Neutropenia developed in the first year secondary to dysmyelopoiesis affecting the granulocyte lineage, associated with a polyclonal hypergammaglobulinemia. Several broncho-pulmonary infectious episodes complicated the evolution, and cystic fibrosis was first considered on the basis of repeated abnormal sweat chloride tests but not confirmed by molecular analyses. This autosomal recessive disorder matches that described originally as poikiloderma with neutropenia-Clericuzio type in Navajo Indians (OMIM 604173). It is discussed within the group of the major hereditary poikiloderma disorders, that is, Rothmund-Thomson syndrome, dyskeratosis congenita, and Kindler syndrome. PMID:18925663

  14. Severe febrile respiratory illnesses as a cause of mass critical care.

    PubMed

    Sandrock, Christian E

    2008-01-01

    Febrile respiratory illnesses with respiratory failure are one of the most common reasons for admission to the intensive care unit. Most causes of febrile respiratory illness are bacterial and viral agents of community-acquired pneumonia. However, a small number of rare and highly contagious agents can initially present as febrile respiratory illnesses, which can lead to an epidemic that can greatly impact the health care system. This impact includes sustained mass critical care, with potential scarcity of critical resources (eg, positive-pressure ventilators), spread of disease to health care workers, sustained spread within the community, and extensive morbidity and mortality. The main agents of febrile respiratory illness that would lead to an epidemic include influenza, the coronavirus that causes severe acute respiratory syndrome, smallpox, viral hemorrhagic fever, plague, tularemia, and anthrax. Recognition of these agents occurs largely based on epidemiological clues, and management consists of antibiotics, antivirals, supportive care, and positive-pressure ventilation. Acute respiratory failure and acute respiratory distress syndrome occur with these agents, so a lung-protective (low tidal volume) ventilation strategy is indicated. Additional respiratory care measures, such as nebulized medications, bronchoscopy, humidified oxygen, and airway suctioning, potentiate aerosolization of the virus or bacteria and increase the risk of transmission to health care workers and patients. Thus, appropriate personal protective equipment, including an N95 mask or powered air-purifying respirator, is indicated. A basic understanding of the epidemiology, clinical findings, diagnosis, and treatment of these agents will provide a foundation for early isolation, evaluation, infection control, and public health involvement and response in cases of a febrile respiratory illness that causes respiratory failure. PMID:18173859

  15. Chronic idiopathic and secondary neutropenia: clinical and serological investigations.

    PubMed

    van der Veen, J P; Hack, C E; Engelfriet, C P; Pegels, J G; von dem Borne, A E

    1986-05-01

    Clinical data on 49 patients with chronic idiopathic neutropenia (CIN) and 42 patients with neutropenia secondary to a well-defined immunological disorder (SN) were collected and related to serological parameters. In 47% of the patients with CIN and 53% of those with SN, a positive direct immunofluorescence test was obtained with granulocytes from the patients. In the sera from the patients in the two groups, antibodies against donor granulocytes were detected by the indirect immunofluorescence test, the leucoagglutination test and/or the granulocytotoxicity test in 15%, 19% and 15%, respectively. The results of the above tests could not be correlated with any clinical or haematological parameter. Immune complexes in the serum were detected by the 125I-Clq-binding test in 29% of patients with CIN and in 58% of those with SN. The presence of serum immune complexes correlated well with the existence of a low neutrophil count, but not with the presence of recurrent infections, with bone-marrow abnormalities, or with positive reactions in other serological tests. The sera of eight out of 14 patients with CIN and seven out of 12 patients with SN had inhibitory activity for myeloid colony formation in vitro (CFU-GM). This CFU-GM inhibitory activity was correlated with the presence of recurrent infections and with hypoplasia of the myeloid compartment of the bone marrow, but not with positive reactions in other tests. We conclude that the 125I-Clq-binding test probably detects circulating immune complexes that induce a shift neutropenia, whereas serum activity inhibitory for CFU-GM possibly relates to clinically more serious forms of neutropenia. The significance of neutrophil-bound Ig and granulocyte-reactive antibodies in the serum is not clear.

  16. Susceptibility to febrile seizures: more than just a faulty thermostat!

    PubMed

    Prasad, Asuri N; Seshia, Shashi S

    2009-05-01

    Febrile seizures, always a hot topic, continue to fire up the interest of a wide spectrum of clinical and basic neuroscientists. Several clinical investigators, amongst them the Halifax group (spearheaded by the Camfields to whom we owe a great debt of gratitude for their contributions in this field), have provided us with a sound foundation for clinical management. We now need to explore febrile seizures in new ways to clarify factors and identify mechanisms that contribute to the intriguing age-dependent susceptibility. The complex processes involved in thermoregulation and the febrile response are important pieces of the puzzle. The contributory factors are likely different for isolated simple febrile, recurrent febrile and complex febrile seizures. A 'systems biology approach' is needed to investigate the intricate genome-proteome-metabolome interaction in determining susceptibility. Population studies that incorporate current clinical, experimental, infectious and molecular genetic knowledge in their concept and design will help to 'conquer' the final frontiers of febrile seizures. In 2006, Engel suggested that febrile seizures could 'encompass many different entities', an increasingly plausible opinion. A higher profile for febrile seizures and related syndromes in the ILAE classification scheme will further catalyze progress in the field. The resultant knowledge can only improve management. PMID:19534326

  17. Use of a bovine model to study the role of adhesion molecule CD11/CD18 in hemodialysis-induced neutropenia.

    PubMed

    Rabb, Hamid; Chandran, Prem K G; Arnaout, M Amin; Kehrli, Marcus E

    2002-03-01

    The early neutropenia that occurs with cellulose-based dialysis membranes is believed to result from a cascade of immune events: complement activation, engagement of leukocyte adhesion molecules, cytokine release, and leukocyte sequestration. The beta2 integrin CR3 (CD11b/CD18) is upregulated during hemodialysis, binds complement factor iC3b, and mediates leukocyte adhesion to endothelium and leukoaggregation. Despite being invoked in dialysis-induced neutropenia, there is no direct evidence of a role for CD11b/CD18 in the neutropenia. A unique animal model of beta2-integrin deficiency was discovered in calves experiencing recurrent infections and a paucity of leukocytes in infected tissue. We hypothesized that beta2 integrins mediate the neutropenia of dialysis and directly tested this hypothesis using beta2-integrin-deficient calves. Two 3-month old beta2-integrin-deficient and two age-matched Holstein calves were dialyzed using cuprophane dialyzers. Beta2-integrin-deficient calves had less than 2% of normal neutrophil CD18 expression by flow cytometry. Normal calves had a marked decrease in circulating neutrophils (P < 0.05) to 15% of normal 15 minutes into dialysis (total, four treatments), as well as a decrease in monocytes to 39% (P < 0.05) and lymphocytes to 58% (P < 0.05). CD18-deficient calves had an attenuated decrease in neutrophils (65%; P = not significant), monocytes (78%; P = not significant), and lymphocytes (105%; P = not significant) at 15 minutes. These data, although obtained in a small sample, show that a bovine model can be used to study the early neutropenia of dialysis. These data also suggest that a direct role of beta2 integrins may be occurring in this process. PMID:11877578

  18. Rituximab-induced neutropenia in a patient with inflammatory myopathy and systemic sclerosis overlap disease

    PubMed Central

    Roberts, Mark; Oddis, Chester; Herrick, Arianne; Chinoy, Hector

    2016-01-01

    Rituximab (RTX) is a monoclonal chimeric antibody directed against the CD20 antigen of B lymphocytes. Late onset neutropenia (LON) is a recognised complication of rituximab usually occurring 4 weeks after the last dose and is reported in both haematological and rheumatological conditions. However, it has never been described in a patient with myositis and systemic sclerosis overlap disease. We describe a case of LON in a 54-year-old man who was diagnosed with myositis and then systemic sclerosis overlap disease. It resolved within 7 days, and the patient did not suffer neutropenic sepsis or any other complications. We propose similar mechanisms for LON as described in other conditions and routine blood monitoring in such patients. PMID:27407275

  19. [Febrile ulceronecrotic Mucha-Habermann disease].

    PubMed

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

    2016-01-01

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

  20. Undifferentiated febrile illnesses in military personnel.

    PubMed

    Burns, Daniel S; Bailey, Mark S

    2013-09-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    PubMed Central

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

    2008-01-01

    vancomycin was noted. Conclusion This rising trend of highly resistant organisms stresses the increasing importance of continuous surveillance system and stewardship of antibiotics as strategies in the overall management of patients with febrile neutropenia. PMID:18541017

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

    PubMed

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

    2016-04-01

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

  4. Generation of poikiloderma with neutropenia (PN) induced pluripotent stem cells (iPSCs).

    PubMed

    Mills, Jason A; Hudock, Kristin M; Sullivan, Spencer K; Herrera, Pamela; Sullivan, Lisa M; Gadue, Paul; French, Deborah L

    2015-11-01

    Poikiloderma with neutropenia (PN, Clericuzio-type poikiloderma with neutropenia) is a rare autosomal recessive disorder caused by biallelic mutations in the USB1 gene (Alias C16orf57 and MPN1). To date, there have been only 37 reported cases worldwide of this disorder that presents with neutropenia, early onset poikiloderma, respiratory infections, palmo-plantar hyperkeratosis, and skeletal defects. Here we described the generation of human induced pluripotent stem cell lines (PN1 and PN2) from the peripheral blood of a 1-year-old patient using the dox-inducible STEMCCA vector. This patient presented with bacteremia, pneumonia, and neutropenia. Analysis of bone marrow demonstrated normal cellularity with trilineage hematopoiesis and neutropenia.

  5. Interleukin 1 administration in mice produces hypoferremia despite neutropenia.

    PubMed Central

    Gordeuk, V R; Prithviraj, P; Dolinar, T; Brittenham, G M

    1988-01-01

    To determine whether the hypoferremic response to inflammation requires neutrophils, we administered human recombinant IL-1 to mice made neutropenic with cyclophosphamide. With single intraperitoneal injections of IL-1 the plasma iron concentrations decreased significantly in mice with either normal neutrophil counts or neutropenia. After single injections transferrin concentrations were not significantly changed, but the decrease in serum iron lowered mean transferrin saturations from a baseline of 45 to 24-30% in nonneutropenic mice, and from 99 to 70-77% in neutropenic mice. Similar changes were observed after intraperitoneal injections of Escherichia coli. 4-d continuous infusions of IL-1 also led to reductions in serum iron concentrations, but transferrin concentrations doubled. The combination of a decrease in serum iron and an increase in transferrin concentration after chronic infusion in neutropenic mice led to a greater decline in mean transferrin saturations, from a baseline of 110 to 25%. In mice not given cyclophosphamide, chronic IL-1 infusion was associated with a reduction in mean hemoglobin concentrations from 14.7 to 13.5 g/dl, consistent with restricted availability of iron for erythropoiesis associated with low saturation of transferrin. We conclude that IL-1 can decrease the serum iron despite profound peripheral neutropenia and that transferrin in a positive acute phase reactant in the mouse. PMID:3264289

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Undifferentiated febrile illnesses in military personnel.

    PubMed

    Burns, Daniel S; Bailey, Mark S

    2013-09-01

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

  9. Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions.

    PubMed

    Kanagasegar, Sivalingam; Cimaz, Rolando; Kurien, Biji T; Brucato, Antonio; Scofield, R Hal

    2002-01-01

    Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.

  10. Pediatric febrile seizures and childhood headaches in primary care.

    PubMed

    Reinhold, J; Bentti, A L

    2000-03-01

    Febrile seizures and migraine headaches in children are two of the most common neurological diagnoses seen by primary care practitioners. It is essential that a knowledge base be developed to better care for this population. This article reviews pediatric febrile seizures, including management and treatment recommendations and childhood headaches, with an emphasis on migraine headaches. Diagnosis, management, and referral criteria are also reviewed. PMID:10673570

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

    PubMed Central

    Dufour, Carlo

    2015-01-01

    Autoimmune neutropenia of infancy (AIN), also called primary autoimmune neutropenia, is a disease in which antibodies recognize membrane antigens of neutrophils, mostly located on immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb 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

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

    PubMed

    Farruggia, Piero; Dufour, Carlo

    2015-02-01

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

  13. Copper deficiency as a cause of neutropenia in a case of coeliac disease.

    PubMed

    Khera, Daisy; Sharma, Baldev; Singh, Kuldeep

    2016-01-01

    We report a 17 year-old male patient, who presented with chronic diarrhoea, progressive pallor, short stature, anaemia (haemoglobin of 4.9 g/dL) and neutropenia and was diagnosed as coeliac disease. His neutropenia did not respond to 8 months of gluten-free diet, iron, folic acid and vitamin B12 therapy. So we suspected copper deficiency and his serum copper levels were tested, which was low. His neutrophil counts normalised after 2 months of copper supplementation. Hence we concluded that the cause of neutropenia in our case was copper deficiency. PMID:27635061

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. Severe neutropenia due to naproxen therapy in rheumatoid arthritis: a case report and review of literature.

    PubMed

    Kalksma, R; Jansen, T L Th A; Bruyn, G A W

    2002-08-01

    Rheumatoid arthritis is a chronic inflammatory disease that primarily affects the joints and is often treated with non-steroidal anti-inflammatory drugs (NSAIDs) on demand and disease-modifying antirheumatic drugs (DMARDs), with a relatively low risk of side effects. Although an infrequent side effect, neutropenia has been described as a sequel of NSAIDs. We report a case of neutropenia proven (by rechallenge) to be due to naproxen therapy. The literature on neutropenia during treatment with NSAIDs and DMARDs is briefly reviewed.

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

    PubMed Central

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

    2015-01-01

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

  18. Risk factors for neutropenia with lenalidomide plus dexamethasone therapy for multiple myeloma.

    PubMed

    Mitani, Y; Usami, E; Kimura, M; Nakao, T; Okada, K; Matsuoka, T; Kokuryou, T; Yoshimura, T; Yamakawa, M

    2016-06-01

    Neutropenia may develop as an adverse event in patients with multiple myeloma receiving lenalidomide (LEN) plus dexamethasone (DEX) therapy. In the present study, we examined the risk factors associated with grade 3/4 neutropenia during the first cycle of LEN plus DEX therapy. We observed that hemoglobin level (≤ 8.5 g/dl) was a significant risk factor for grade 3/4 neutropenia during the first cycle of therapy (odds ratio: 19.40; 95% confidence interval: 2.68-141.00; p < 0.01). thus, our findings suggest that determining the hemoglobin level could be useful in the risk management for neutropenia in patients receiving LEN plus DEX therapy. PMID:27455556

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

    ClinicalTrials.gov

    2012-09-20

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

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

    PubMed

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

    2013-02-01

    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

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

    PubMed Central

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

    2014-01-01

    Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 × 109/L) due to these diseases were enrolled in this multi-center phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 μg/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of ≥ 1.5 × 109/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently: adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. PMID:8490166

  2. Febrile seizures associated with influenza A.

    PubMed

    Hara, Keita; Tanabe, Takuya; Aomatsu, Tomoki; Inoue, Nao; Tamaki, Hirohumi; Okamoto, Nami; Okasora, Keisuke; Morimoto, Takahiro; Tamai, Hiroshi

    2007-01-01

    To clarify the clinical impact of influenza A on the development of febrile seizures (FS), consecutive FS patients brought to our hospital between October 2003 and September 2004 were prospectively surveyed. Patients infected with influenza A (influenza A patients) and those uninfected with influenza (non-influenza patients) were compared with regard to clinical characteristics of FS. Influenza infection was determined by rapid antigen test and/or serologically. Associations of influenza A with atypical findings of FS, including partial seizures, prolonged seizures, multiple seizures during the same illness, and 30-min or longer prolonged postictal impairment of consciousness (PPIC), were analyzed by multiple logistic regression. A total of 215 patients (47 influenza A and 168 non-influenza patients) were enrolled in the study. Age was significantly higher in the influenza A group (39.85+/-22.16 months vs. 27.51+/-17.14 months, P<0.001). Of 42 patients aged 48 months or older, which corresponded to the 80th percentile for age, 15 (35.7%) were influenza A patients, with a significantly higher incidence of such patients than in the subgroup of patients aged 47 months or younger (32/173, 18.5%) (P=0.015). On multiple logistic regression analysis, influenza A was independently associated with PPIC (odds ratio: 4.44, 95% confidence interval: 1.52-12.95, P=0.006), but not with other atypical findings. The positive association of influenza A with PPIC suggests that influenza may affect state of consciousness at the same time that it induces seizures with fever.

  3. Febrile illness experience among Nigerian nomads

    PubMed Central

    2012-01-01

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

  4. Lymphocytes subsets in children with febrile convulsions.

    PubMed

    Tuncer, Oğuz; Karaman, Sait; Caksen, Hüseyin; Oner, Ahmet Faik; Odabas, Dursun; Yilmaz, Cahide; Atas, Bülent

    2007-07-01

    In this study, lymphocytes subsets including blood CD3, CD4, CD8, CD16, CD19, and CD56 values were analyzed in children with febrile convulsion (FC) to determine whether there was the association of lymphocytes subsets in the pathogenesis of FC. The study includes 48 children with FC, and 55 healthy age matched control subjects, followed in Yüzüncü Yil University, Faculty of Medicine, Department of Pediatrics between October 2003 and June 2004. Blood CD3, CD4, CD8, CD16, CD19, and CD56 values were examined in the study and control groups. The analyses were performed in the Hematology Laboratory, Yüzüncü Yil University Faculty of Medicine, with flow cytometer device (Coulter Epics XL2, Flow Cytometer). A total of 48 children [17 girls (35.5%) and 31 boys (64.5%)], aged 6 months to 60 months (mean 22.20 +/- 13.75 months) with FC and 55 healthy children [28 girls (51%) and 27 boys (49%)], aged 6 months to 60 months (mean 28.87 +/- 17.04 months) were included in the study. When compared with the control group, the study found significantly decreased blood CD3 and CD4 values in the study group (p <.05). However, there was not significant difference in CD8, CD16, CD19, and CD56 values between the control and study groups (p >.05). When comparing the children with and without positive family history for FC, the study did not find any difference for all CD values between the groups (p >.05). Similarly, there was not significant difference in CD values between the children with simple and complex FC (p >.05). The findings suggested that decreased blood CD3 and CD4 values might be responsible for the infections connected with FC or that they might be related to the pathogenesis of FC in some children.

  5. Inherited biallelic CSF3R mutations in severe congenital neutropenia

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    1994-01-01

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

  7. Cerebral Abscess Presenting as a Complex Febrile Seizure.

    PubMed

    Anand, Anjoli; Salas, Alicia; Mahl, Evan; Levine, Marla C

    2015-07-01

    Currently, there is no standardized approach to the management of complex febrile seizures in children and there are no published practice guidelines for the procurement of neuroimaging. Presented is a 2-year-old female patient who experienced a 3- to 5-minute episode of staring and unilateral mouth twitching associated with high fever. On initial presentation, the patient appeared well and had a normal neurological examination. No focus of infection was identified, and she was diagnosed with complex febrile seizure. The patient was discharged home with close neurology and primary care follow-up but returned the following day with altered mental status, toxic appearance, and right lower extremity weakness. Magnetic resonance imaging of the brain revealed left-sided cranial empyema and the patient was managed with antibiotics and surgical drainage. A literature review to answer the question "Do children with complex febrile seizures require emergent neuroimaging?" yielded a small number of retrospective reviews describing the utility of computed tomography, magnetic resonance imaging and lumbar puncture in the work-up of febrile seizures. Current evidence indicates that neuroimaging is not indicated in an otherwise healthy child who presents with complex febrile seizure if the patient is well appearing and has no evidence of focal neurological deficit on examination. As this case demonstrates, however, serious conditions such as meningitis and brain abscess (though rare) should be considered in the differential diagnosis of complex febrile seizure and physicians should remain aware that the need for neuroimaging and/or lumbar puncture may arise in the appropriate clinical setting.

  8. Cerebral Abscess Presenting as a Complex Febrile Seizure.

    PubMed

    Anand, Anjoli; Salas, Alicia; Mahl, Evan; Levine, Marla C

    2015-07-01

    Currently, there is no standardized approach to the management of complex febrile seizures in children and there are no published practice guidelines for the procurement of neuroimaging. Presented is a 2-year-old female patient who experienced a 3- to 5-minute episode of staring and unilateral mouth twitching associated with high fever. On initial presentation, the patient appeared well and had a normal neurological examination. No focus of infection was identified, and she was diagnosed with complex febrile seizure. The patient was discharged home with close neurology and primary care follow-up but returned the following day with altered mental status, toxic appearance, and right lower extremity weakness. Magnetic resonance imaging of the brain revealed left-sided cranial empyema and the patient was managed with antibiotics and surgical drainage. A literature review to answer the question "Do children with complex febrile seizures require emergent neuroimaging?" yielded a small number of retrospective reviews describing the utility of computed tomography, magnetic resonance imaging and lumbar puncture in the work-up of febrile seizures. Current evidence indicates that neuroimaging is not indicated in an otherwise healthy child who presents with complex febrile seizure if the patient is well appearing and has no evidence of focal neurological deficit on examination. As this case demonstrates, however, serious conditions such as meningitis and brain abscess (though rare) should be considered in the differential diagnosis of complex febrile seizure and physicians should remain aware that the need for neuroimaging and/or lumbar puncture may arise in the appropriate clinical setting. PMID:26151351

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

    PubMed

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

    2014-08-01

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

  10. Postnatal overfeeding leads to obesity and exacerbated febrile responses to lipopolysaccharide throughout life.

    PubMed

    Clarke, M A; Stefanidis, A; Spencer, S J

    2012-03-01

    The perinatal environment can be crucial for programming long-term physiology, including the mechanisms regulating body weight, and postnatal overfeeding can lead to obesity throughout life. Inflammation-related complications are of particular concern in the obese. However, little is known about how postnatal overfeeding contributes to changes in the ability to respond to inflammation. In the present study, we investigate changes in the febrile and neurochemical response to immune challenge with lipopolysaccharide (LPS), in juvenile and adult, male and female Wistar rats made obese by overfeeding during the postnatal period. We demonstrate that febrile responses to LPS are exacerbated in these rats, with peak core temperatures being up to 0.5 °C higher compared to those in controls, and this is associated with an enhanced pro-inflammatory cytokine profile and enhanced hypothalamic-pituitary-adrenal (HPA) axis activation. Plasma pro-inflammatory cytokines concentrations were approximately three-fold greater in neonatally overfed rats after LPS and there were approximately twice as many neurones activated in the paraventricular nucleus of the hypothalamus as in controls, with a prolonged corticosterone response. We also observed elevated expression of toll-like receptors (TLR) 2 and 4 in adipose tissue and greater inhibitory factor κB phosphorylation in these obese animals. Despite similar changes in expression of adipose TLR3, there was no corresponding alteration in the response to a viral mimetic that acts at this receptor. We suggest that an elevated febrile response to LPS therefore occurs in cases of obesity and this is associated with altered HPA axis function and enhanced TLR2/4 expression in adipose tissue and an up-regulated downstream pro-inflammatory cascade.

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

    PubMed

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

    2012-01-01

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

  12. [Serum lactate as a biomarker of severe sepsis in children with cancer, neutropenia and fever].

    PubMed

    Pacheco-Rosas, Daniel Octavio; Huelgas-Plaza, Ana Celia; Miranda-Novales, María Guadalupe

    2014-01-01

    INTRODUCCIÓN: la neutropenia es una complicación frecuente secundaria a la quimioterapia en los pacientes con cáncer, en quienes la prevalencia de sepsis es de 12.9 a 17.4 % y la letalidad es de 16 %. El objetivo de este estudio fue determinar la utilidad del lactato como biomarcador de sepsis grave en niños con cáncer, fiebre y neutropenia. MÉTODOS: se realizó un estudio de prueba diagnóstica fase II. Se midieron los niveles del lactato al ingreso. Los episodios de neutropenia se clasificaron en tres grupos: I, con sepsis II, sin sepsis; III, pacientes neutropénicos sin fiebre (controles). Se calculó sensibilidad, especificidad, valores predictivos positivo y negativo e índices de verosimilitud. El estándar de oro fue el diagnóstico clínico de sepsis grave.

  13. Coexistence of sickle cell disease and severe congenital neutropenia: first impressions can be deceiving.

    PubMed

    Wali, Yasser; Beshlawi, Ismail; Fawaz, Naglaa; Alkhayat, Aisha; Zalabany, Mahmoud; Elshinawy, Mohamed; Al-Kindi, Salam; Al-Rawas, Abdul Hakim A; Klein, Christoph

    2012-09-01

    We report an Omani family in whom the propositus had a rare coexistence of sickle cell disease and severe congenital neutropenia associated with a mutation in ELANE. In contrast to his siblings with sickle cell disease, the severity of HbSS-associated complications such as painful crises and acute chest syndrome was significantly reduced. His course of the disease had markedly worsened after initiating G-CSF therapy. These clinical observations suggest that neutropenia may ameliorate inflammatory responses and thus display a modulating factor with respect to the clinical course of sickle cell disease.

  14. Intestinal Infections Among Febrile Hospitalized Patients in the Republic of Armenia: A Retrospective Chart Review.

    PubMed

    Zardaryan, Eduard; Paronyan, Lusine; Bakunts, Vahe; Gevorgyan, Zaruhi; Asoyan, Vigen; Apresyan, Hripsime; Hovhannisyan, Alvard; Palayan, Karo; Kuchuloria, Tinatin; Rivard, Robert G; Bautista, Christian T

    2016-10-01

    In the past, several enteric outbreaks in 1996, 1998, 1999, and 2003 caused by Salmonella typhi, a Gram-negative bacterium, have occurred in Armenia. This study describes the demographic, epidemiological, and clinical characteristics of febrile hospitalized patients with intestinal infections in Armenia. Using a chart review study design, medical data from adult patients who were hospitalized at the Nork hospital during 2010-2012 were reviewed. A total of 600 medical charts were reviewed. Of these, 51 % were diagnosed with intestinal infections. Among these patients, 59 % had an intestinal infection of known etiology, with three main pathogens identified: Salmonella sp. (32 %), Shigella sp. (32 %), and Staphylococcus aureus (18 %). After controlling for the calendar year, age in years, and gender, patients detected with Salmonella sp. were more likely to reported the presence of a family member with similar signs or symptoms [odds ratio (OR) 9.0; 95 % CI 2.4-33.7] and the lack of a water tap at home (OR 3.9; 95 % CI 1.7-9.5). Evidence indicates that Salmonella sp., Shigella sp., and S. aureus as the most common etiologies reported among febrile hospitalized patients. A high percentage of patients had intestinal infections of unknown etiology; thus, improvement in laboratory capacity (enabling more advanced tests, such as polymerase chain reaction) would increase the identification of the enteropathogens causing disease in Armenia. PMID:26992893

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

    PubMed

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

    2003-05-01

    Background. Dengue occurs in many tourist destinations, and is increasingly imported by returning travellers. We review the epidemiology and clinical features of confirmed dengue in returning travellers presenting to a UK regional infectious diseases unit. Methods. A retrospective, case-record review of febrile returning travellers, admitted to Leicester Royal Infirmary during 2000-2002. The presenting clinical features of patients with positive dengue serology were compared to those who had negative serological tests. Results. Dengue, including two cases of dengue haemorrhagic fever (DHF) and 1 shock syndrome, was diagnosed in 16 of approximately 250 (6.4%) hospitalised returning travellers. 10/16 (62.5%) patients returned from Asia. There was no difference in symptoms between those with or without serological evidence of dengue. Dengue was associated with thrombocytopenia (p=0.001), leucopenia (p=0.03) and elevated alanine transminase (p=0.01). Following multivariate analysis, dengue was associated with first time travel to an endemic area (odds ratio 10.9, 95% CI 1.21-99.9), early onset of symptoms after return (OR 1.91, 95% CI 1.07-3.43), duration of time overseas (OR 1.08, 95% CI 1.01-1.15) and thrombocytopenia (OR 29.4, 95% CI 1.8-494). Conclusions. Dengue is an important cause of illness in hospitalised febrile returning travellers. It should be considered in first-time travellers, with thrombocytopenia and negative malaria films who present with symptoms soon after return.

  16. Severe chronic primary neutropenia in adults: report on a series of 108 patients.

    PubMed

    Sicre de Fontbrune, Flore; Moignet, Aline; Beaupain, Blandine; Suarez, Felipe; Galicier, Lionel; Socié, Gérard; Varet, Bruno; Coppo, Paul; Michel, Marc; Pautas, Cécile; Oksenhendler, Eric; Lengline, Etienne; Terriou, Louis; Moreau, Philippe; Chantepie, Sylvain; Casadevall, Nicole; Michot, Jean Marie; Gardembas, Martine; Michallet, Mauricette; Croisille, Laure; Audrain, Marie; Bellanné-Chantelot, Christine; Donadieu, Jean; Lamy, Thierry

    2015-10-01

    Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 10(9)/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 10(9)/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 10(9)/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients. PMID:26261239

  17. Severe congenital neutropenia or hyper-IgM syndrome? A novel mutation of CD40 ligand in a patient with severe neutropenia.

    PubMed

    Rezaei, Nima; Aghamohammadi, Asghar; Ramyar, Asghar; Pan-Hammarstrom, Qiang; Hammarstrom, Lennart

    2008-01-01

    Severe congenital neutropenia (SCN) and CD40 ligand deficiency (CD40LD) are two primary immunodeficiency diseases caused by different underlying genetic defects. In this report, we present a case who clinically presented as a SCN patient, but subsequent mutation analysis of this patient was compatible with CD40LD. The patient is a 3-year-old boy, who was referred to our center because of pneumonia, oral and anal ulcers, and periodontitis. As severe consistent neutropenia and maturation arrest in the myeloid series were observed in the bone marrow, a diagnosis of SCN was made. However, no mutations were found in the ELA2 and HAX1 genes. As functional T cell defects were observed, we suspected CD40LD. DNA sequencing showed a 17-base pair deletion in the CD40L gene. Although the patient did not have a decreased serum level of IgA, and his serum IgM level was within the normal range, the diagnosis of CD40LD was confirmed, suggesting that CD40LD should be suspected in any male patient with recurrent infections and neutropenia. PMID:18594157

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

    PubMed Central

    Yang, T. J.

    1978-01-01

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

  19. [Complex febrile crises: should we change the way we act?].

    PubMed

    Martinez-Cayuelas, E; Herraiz-Martinez, M; Villacieros-Hernandez, L; Cean-Cabrera, L; Martinez-Salcedo, E; Alarcon-Martinez, H; Domingo-Jimenez, R; Perez-Fernandez, V

    2014-11-16

    Introduccion. Las convulsiones febriles son una de las causas mas frecuentes de consulta. Hasta ahora, los pacientes con convulsiones febriles complejas (CFC) deben ingresar, dado el mayor porcentaje de epilepsia y complicaciones agudas descrito clasicamente. En la actualidad hay estudios que apoyan ser menos invasivos en el abordaje de estos pacientes. Objetivo. Describir las caracteristicas de los pacientes ingresados por CFC y proponer un nuevo protocolo de actuacion. Pacientes y metodos. Analisis retrospectivo de historias clinicas de ingresados por CFC (enero de 2010-diciembre de 2013). Se ofrecen datos epidemiologicos, clinicos, pruebas complementarias y evolucion. Resultados. Las CFC suponian un 4,2% de los ingresos de neuropediatria (n = 67). Edad media al evento: 25 meses. El 47% tenia antecedentes familiares patologicos, y el 31%, antecedentes personales de convulsion febril previa. En el 54% de los pacientes, la CFC duro menos de cinco minutos; hubo recurrencia, la mayoria con un total de dos crisis y durante el primer dia (las CFC por recurrencia son las mas frecuentes). De las pruebas complementarias realizadas, ninguna de ellas sirvio como apoyo diagnostico en el momento agudo. Durante su seguimiento, cinco pacientes presentaron complicaciones. Los pacientes con antecedentes familiares de convulsiones febriles presentan mayor riesgo de epilepsia o recurrencia (p = 0,02), sin diferencias significativas respecto a la edad, numero de crisis, intervalo de fiebre, estado epileptico o tipo de CFC. Conclusiones. Las CFC no asocian mayores complicaciones agudas; las exploraciones complementarias no permiten discriminar precozmente a los pacientes de riesgo. Su ingreso podria evitarse en ausencia de otros signos clinicos y limitarse a casos seleccionados.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. No association between ApoE polymorphism and febrile seizures.

    PubMed

    Lavenex, Pierre; Lavenex, Pamela Banta; Cachat, François; Gehri, Mario; Juvet, Typhaine

    2016-01-01

    Seizures associated with fever are a common pediatric problem, affecting about 2-7 % of children between 3 months and 5 years of age. Differentiation of febrile seizures from acute symptomatic seizures secondary to central nervous system infections or seizures associated with fever in children with epilepsy is essential to provide appropriate treatment and follow-up care. Here, we tested the hypothesis that children who exhibit simple febrile seizures during early childhood, but do not develop epileptic seizures later in life, might preferentially carry the ApoE2 allele of the gene coding for the apolipoprotein E. We did not find any differences in the distribution of ApoE alleles or genotypes between individuals who exhibited simple febrile seizures (n = 93) and age-matched, typically developing subjects (n = 80). We found that the observed allele and genotype frequencies did not deviate from Hardy-Weinberg equilibrium, which suggests that the frequencies of ApoE alleles and genotypes are stable in the Swiss population from which our samples were derived. Across both groups of subjects (n = 173), we found an ApoE2 allele frequency of 0.064, an ApoE3 frequency of 0.829 and an ApoE4 frequency of 0.107. Our findings are consistent with previous reports of the distribution of ApoE polymorphism for European subjects free of any neurological disorders, and show that the different alleles of the gene coding for the apolipoprotein E are not associated with the occurrence of simple febrile seizures. PMID:26233231

  3. Clonal predominance of CD8+ T cells in patients with unexplained neutropenia

    PubMed Central

    Wlodarski, Marcin Wojciech; Nearman, Zachary; Jiang, Ying; Lichtin, Alan; Maciejewski, Jaroslaw Pawel

    2008-01-01

    Objective T-cell-mediated autoimmunity may be involved in some cases of idiopathic neutropenia. We hypothesized that a precise T-cell receptor repertoire analysis may uncover cytotoxic T-cell (CTL) expansions that are less pronounced than those seen in T large granular lymphocyte leukemia (T-LGL), but are pathophysiologically analogous and thus can serve as markers of a T-cell-mediated process. Materials and Methods Using rational algorithms for T-cell receptor analysis and in vivo tracking of CTL responses previously established in our laboratory, we studied patients with unexplained chronic neutropenia (n = 20), T-LGL (n = 15), and healthy controls (n = 12). We further investigated the involvement of soluble inhibitory factors by coculture assays. To determine the level of immune activation, we studied interferon-g expression in CD8+cells using Taqman polymerase chain reaction. Results Fifteen expanded (immunodominant) CTL clones were detected in 12 of 20 patients. In comparison to LGL leukemia, these clones were less immunodominant, but clearly discernible from subclinical lymphoproliferations in controls. As a surrogate of cytotoxic activity, we found markedly increased production of interferon-γ in most of the neutropenia patients, irrespective of the presence of immunodominant CTL clones. Conclusions These results suggest that, while immunodominant CTL clones are detectable in a proportion of patients only, CTL-mediated pathophysiology may be a general mechanism operating in idiopathic neutropenia. Oligogoclonal CTL expansions in chronic neutropenia may indicate an ongoing autoimmune process, while highly polarized monoclonalities in a subset of neutropenic LGL patients may represent the “extreme” end of the clonal continuum. PMID:18279717

  4. Use of Granulocyte Colony–Stimulating Factor During Pregnancy in Women With Chronic Neutropenia

    PubMed Central

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

    2014-01-01

    Objective To report outcomes associated with the administration of granulocyte colony–stimulating factor (G-CSF) to women with chronic neutropenia during pregnancy. Methods We conducted an observational study of women of child-bearing potential with congenital, cyclic, idiopathic, or autoimmune neutropenia enrolled in the Severe Chronic Neutropenia International Registry to determine outcomes of pregnancies, without and with chronic G-CSF therapy, 1999–2014. Treatment decisions were made by the patients’ personal physicians. A research nurse conducted telephone interviews of all enrolled U.S. women of child-bearing potential using a standard questionnaire. Comparisons utilized Fisher’s exact test analysis and Student’s t-test. Results One-hundred seven women reported 224 pregnancies, 124 without G-CSF therapy and 100 on chronic G-CSF therapy (median dose: 1.0 mcg/kg/day, range 0.02–8.6 mcg/kg/day). There were no significant differences in adverse events between the groups considering all pregnancies or individual mothers, e.g., spontaneous terminations (all pregnancies: no G-CSF 27/124, G-CSF 13/100; P=0.11, Fisher’s exact test,), preterm labors (all pregnancies, no G-CSF 9/124, G-CSF 2/100, P=0.12,). A study with at least 300 per group would be needed to detect a difference in these events with 80% statistical power (alpha=0.05). Four newborns of mothers with idiopathic or autoimmune neutropenia not on G-CSF (4/101) had life-threatening infections, whereas there were no similar events (0/90) in the treated group, but this difference was also not statistically significant. (p=0.124). Adverse events in the neonates were similar for the two groups. Conclusions This observational study showed no significant adverse effects of administration of G-CSF to women with severe chronic neutropenia during pregnancy. PMID:25560125

  5. Zinc supplementation prolongs the latency of hyperthermia-induced febrile seizures in rats.

    PubMed

    Aydın, L; Erdem, S R; Yazıcı, C

    2016-03-01

    Some studies have shown a relationship between febrile seizures and zinc levels. The lowest dose zinc supplementation in pentylenetetrazole seizure model has a protective effect. But, zinc pretreatment has no effect in maximal electroshock model. However, it is unclear how zinc supplementation affects hyperthermia-induced febrile seizures. The aim of the present study was to investigate the effects of zinc supplementation on febrile seizures in male Sprague-Dawley rats. The rats were randomly assigned to four groups. Zinc supplementation was commenced 5 days prior to febrile seizure induction by placing the animals in a water bath at 45°C. We measured the rectal temperature and determined the febrile seizure latency, duration, and stage. In the zinc-supplemented group, both the seizure latency and the rectal temperature triggering seizure initiation were significantly higher than in the other groups. We suggest that zinc supplementation can positively modulate febrile seizure pathogenesis in rats.

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

    PubMed

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

    2011-09-01

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

  7. Evaluation of Risk Factors Associated with First Episode Febrile Seizure

    PubMed Central

    Sharawat, Indar Kumar; Singh, Jitender; Singh, Amitabh

    2016-01-01

    Introduction Febrile seizure (FS) is the single most common type of seizure seen in children between 6 months to 5 years of age. The purpose of our study was to identify the risk factors associated with the first episode of febrile seizures, which would help in the better management and preventive measures in children at risk for FS episodes. Aim To evaluate the risk factors associated with the first episode of febrile seizures in Indian children. Materials and Methods This was a hospital based, case control study. The purpose of this study was to identify the risk factors associated with the first FS episode in children. Seventy (70) children between age 6 months to 5 years with their first episode of FS were compared with 70 children with fever but without seizures based on various risk factors. Results The mean age was 24.90±16.11 months in cases and 26.34±16.93 months in controls. Male: female ratio was 2:1. A positive family history was found in 31.4% of first degree and 11.4% in second degree relatives. Mean maximum temperature was 102.06±1.1°F and URI (upper respiratory infection) was most common cause of fever. Antenatal complication was significantly higher in the case group. RBC (Red Blood Cells) indices like lower mean haemoglobin, MCV (Mean Corpuscular Volume), MCH (Mean Corpuscular Haemoglobin concentration) and higher RDW (Red Cell Distribution Width) values were seen in patients. Serum sodium, Serum calcium and random blood sugar values of the cases were significantly lower than those of controls (p<0.05). Conclusion Our study shows that male gender, family history of febrile seizures, peak body temperature, underlying cause of fever, antenatal complications, low serum calcium, sodium, blood sugar and microcytic hypochromic anaemia are the risk factors associated with the occurrence of first episode of febrile seizure and, thus, preventive measures in removing these risk factors could lead to a decrease in incidence of FS. PMID:27437319

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-02-01

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

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

    PubMed Central

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

    2013-01-01

    Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m2 of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P = 0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients. PMID:23188068

  11. Co-Occurring Disorders

    MedlinePlus

    ... Care of You Top Ten Freshman Year Issues Alcohol, Substance Abuse and Depression Winter Break Survival Tips for College Students Implementing ... supporters and consumers in the mental health field. Alcohol and Drug Abuse, Addiction and Co-occurring Disorders: Co-occurring ... In Crisis? Call ...

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

    PubMed

    Chantorn, Rattanavalai; Shwayder, Tor

    2012-01-01

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

  13. Acute febrile encephalopathy in adults from Northwest India

    PubMed Central

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

    2010-01-01

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

  14. Osteoporosis in severe congenital neutropenia treated with granulocyte colony-stimulating factor.

    PubMed

    Bishop, N J; Williams, D M; Compston, J C; Stirling, D M; Prentice, A

    1995-04-01

    Recombinant human granulocyte colony-stimulating factor (G-CSF) has substantially improved life expectancy for children with severe congenital neutropenia (SCN). Severe osteoporosis, reported in this population, may relate to the disease process, or be a therapeutic side-effect. This report details bone loss, quantitated absorptiometrically and histomorphometrically, in a child with SCN and vertebral collapse, and the positive response to anabolic steroid and bisphosphonate therapy.

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

    PubMed Central

    Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry

    2011-01-01

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

  16. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder.

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Deonna, Thierry

    2012-01-01

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

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

    PubMed

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

    2014-12-01

    Febrile seizures represent a serious adverse event following measles, mumps and rubella (MMR) vaccination. We conducted a series of genome-wide association scans comparing children with MMR-related febrile seizures, children with febrile seizures unrelated to vaccination and controls with no history of febrile seizures. Two loci were distinctly associated with MMR-related febrile seizures, harboring the interferon-stimulated gene IFI44L (rs273259: P = 5.9 × 10(-12) versus controls, P = 1.2 × 10(-9) versus MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653: P = 9.6 × 10(-11) versus controls, P = 1.6 × 10(-9) versus MMR-unrelated febrile seizures). Furthermore, four loci were associated with febrile seizures in general, implicating the sodium channel genes SCN1A (rs6432860: P = 2.2 × 10(-16)) and SCN2A (rs3769955: P = 3.1 × 10(-10)), a TMEM16 family gene (ANO3; rs114444506: P = 3.7 × 10(-20)) and a region associated with magnesium levels (12q21.33; rs11105468: P = 3.4 × 10(-11)). Finally, we show the functional relevance of ANO3 (TMEM16C) with electrophysiological experiments in wild-type and knockout rats.

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    PubMed

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

    2013-06-24

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

  2. [Initial evaluation of febrile neutropenic patients: risk quantification].

    PubMed

    Vázquez, Lourdes; García, José Elías

    2005-12-01

    Infection in immunocompromised hosts represents a serious clinical situation due the high morbidity and mortality it produces and is one of the most frequent complications in patients with cancer. In patients treated with chemotherapy the risk of infection mainly depends on the duration and intensity of neutropenia. It is essential to evaluate which pathogens are involved so that the most appropriate treatment can be selected a priori, as well as to determine the patient's general clinical status so that more or less aggressive treatment can be provided from the beginning, bearing in mind that "low risk" patients can be managed in the home. These questions can be determined by evaluating the patient's clinical history, physical examination, laboratory investigations, and radiological tests. Prompt initiation of broad-spectrum antibiotic therapy adapted to the the patient's risk is crucial.

  3. Brucellosis among Hospitalized Febrile Patients in Northern Tanzania

    PubMed Central

    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

    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

  4. Brucellosis among hospitalized febrile patients in northern Tanzania.

    PubMed

    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

    2012-12-01

    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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. "Naturally occurring asbestos

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2010-07-01

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

  10. [Exanthema as a main symptom in the febrile child].

    PubMed

    Aebi, C

    2005-08-01

    Distinguishing in febrile children between harmless rashes and those, which require specific action, is a common problem in pediatric primary care. Major exanthematous diseases necessitating emergency hospitalization include invasive meningococcal disease and rarely gram-negative septicaemia caused by other pathogens, staphylococcal and streptococcal toxic shock syndrome, endocarditis, fever and rash in travellers returning from tropical countries and drug hypersensitivity syndrome. Therapeutic intervention is also necessary in patients with scarlet fever, rheumatic fever, varicella in postpuberal and immunocompromised individuals, in Kawasaki's disease, in Still's disease and in other non-infectious, inflammatory diseases (e.g., familial mediterranean fever). Finally, various specific measures need to be taken in reportable diseases, erythema infectiosum (parvovirus B19), primary HIV infection and in Henoch-Schölein purpura.

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

    PubMed Central

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

    2015-01-01

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

  12. Naturally occurring insecticides.

    PubMed Central

    Soloway, S B

    1976-01-01

    Naturally occurring insecticides are abundant and varied in their effects, though but a few are articles of commerce. Even for these, pyrethrum, nicotine, rotenone, hellebore, ryania, and sabadilla, there is a paucity of information on mammalian toxicology and environmental effects. In general, these materials are characterized favorably by low acute toxicity and ready dissipation in nature. Unfavorable aspects of natural insecticides are the contained mixture of active and inactive components and the low active ingredient content on a crop yield basis pointing to a high unit cost. Natural insecticides can serve additionally as leads to unnatural mimics, of which the commercially successful synthetic pyrethroids are prime examples. The chemical nature, relationship of insecticidal activity to chemical structure, occurrence, production, and utilization, registered uses, metabolism, and insect and mammalian toxicity are reviewed. PMID:789058

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

    PubMed

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

    2011-09-01

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

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

    PubMed Central

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

    2005-01-01

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

  15. Naturally Occurring Food Toxins

    PubMed Central

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

    2010-01-01

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

  16. Ceftriaxone and amikacin versus ceftazidime and amikacin in febrile granulocytopenia.

    PubMed

    Schmid, L; Jeschko, M; Wilder-Smith, C; Schafroth, U; Thürlimann, B; Pedrazzini, A; Senn, H

    1991-01-01

    The efficacy and safety of the two antibiotic combinations, ceftazidime plus amikacin and ceftriaxone plus amikacin were compared in an open randomized trial. 100 episodes of neutropenia caused by malignant diseases and/or cytostatic drugs were evaluated in 66 males and 34 females with a mean age of 49.4 years. The types of infections treated were: septicemia 38, fever of undetermined origin 26, pneumonia 13, ear, nose and throat infections 11 and others 12. 17 episodes were not evaluable (6 protocol violations, 6 doubtful infections and 5 non-bacterial infections). The overall results were comparable, with a 74% success rate for ceftazidime and a 70% rate for ceftriaxone (criteria of the European Organization for Research and Treatment of Cancer). In the patients with septicemia, the success rate was 64% in the ceftriaxone and 57% in the ceftazidime group. Eight patients died during the treatment, in 5 cases due to infectious complications. There were no differences between the two groups in respect of efficacy or toxicity.

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

    PubMed

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

    2016-04-01

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

  18. Bloodstream infections in febrile neutropenic patients at a tertiary cancer institute in South India: A timeline of clinical and microbial trends through the years

    PubMed Central

    Babu, K Govind; Lokanatha, D.; Lakshmaiah, K. C.; Suresh Babu, M. C.; Jacob, Linu A.; Bhat, Gita R.; Vardhana, Harsha; Sinha, Mahua; Vijaykumar, B. R.; Sumati, B. G.; Jayshree, R. S.

    2016-01-01

    Introduction: Febrile neutropenia (FN) is an oncological emergency. The choice of empiric therapy depends on the locally prevalent pathogens and their sensitivities, the sites of infection, and cost. The Infectious Diseases Society of America guidelines are being followed for the management of FN in India. Methods: This is a prospective observational study conducted at a tertiary care cancer centre from September 2012 to September 2014. Objectives: The objectives of this study were as follows: (1) To review the pattern of microbial flora, susceptibility pattern, and important clinical variables among bloodstream infections in febrile neutropenic patients with solid tumors and hematological malignancies. (2) As per the institutional protocol to periodically review the antibiotic policy and susceptibility pattern, and compare the findings with an earlier study done in our institute in 2010. This was a prospective study conducted from September 2012 to September 2014. Results: About 379 episodes of FN were documented among 300 patients. About 887 blood cultures were drawn. Of these, 137 (15%) isolates were cultured. Isolates having identical antibiograms obtained from a single patient during the same hospitalization were considered as one. Hence, 128 isolates were analyzed. About 74 (58%) cultures yielded Gram-negative bacilli, 51 (40%) were positive for Gram-positive cocci, and 3 (2%) grew fungi. Among Gram-negative organisms, Escherichia coli followed by Acinetobacter baumannii and Klebsiella pneumoniae accounted for 78% of the isolates. Among Gram-positive cocci, Staphylococcus species accounted for 84% of the isolates. We have noted a changing trend in the antibiotic sensitivity pattern over the years. Following the switch in empirical antibiotics, based on the results of the study done in 2010 (when the empirical antibiotics were ceftazidime + amikacin), the sensitivity to cefoperazone-sulbactam has plunged from about 80% to 60%%. Similar reduction in

  19. Methotrexate Treatment in Children with Febrile Ulceronecrotic Mucha-Habermann Disease: Case Report and Literature Review

    PubMed Central

    Bulur, Isil; Kaya Erdoğan, Hilal; Nurhan Saracoglu, Zeynep; Arık, Deniz

    2015-01-01

    Febrile Ulceronecrotic Mucha-Habermann disease is a rare and potentially fatal variant of pityriasis lichenoides et varioliformis acuta and is characterized by high fever, constitutional symptoms, and acute oncet of ulceronecrotic lesions. We present an 11-year-old male with Febrile Ulceronecrotic Mucha-Habermann disease who was cured with methotrexate and review the use of methotrexate for this disorder in the pediatric age group with the relevant literature. PMID:26413356

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

    PubMed Central

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

    2016-01-01

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

  1. Bilateral reductions in hippocampal volume in adults with epilepsy and a history of febrile seizures

    PubMed Central

    Barr, W.; Ashtari, M.; Schaul, N.

    1997-01-01

    OBJECTIVES—To examine the degree and frequency of reductions in hippocampal volume in patients with temporal lobe epilepsy with and without a history of febrile seizures.
METHODS—In vivo measures of hippocampal volume were computed from three dimensional gradient echo (FLASH) images in 44 patients undergoing comprehensive evaluations for epilepsy surgery. Twenty one patients (48%) reported a history of febrile seizures. The volumes from these patients were compared with those from 23 patients without a history of febrile seizures and 34 healthy controls.
RESULTS—The febrile seizure group had significant reductions in volume, both ipsilateral (30% decrease) and contralateral (15% decrease), to the EEG seizure focus. Twelve of 18 patients with febrile seizures exhibited clinically significant ipsilateral volume reductions, defined as volumes falling 2 SD below the mean obtained from the control sample. Only four of 19 patients without febrile seizures exhibited this degree of reduction. No significant correlations were found between seizure variables (for example, duration of epilepsy, seizure frequency) and ipsilateral reductions in volume. However, a significant inverse correlation (r=−0.45, P<0.05) between seizure frequency and the volume of the hippocampus contralateral to the seizure focus was found in the febrile seizure group.
CONCLUSION—These results suggest that a history of febrile seizures is associated with the finding of a smaller hippocampus on the side ipsilateral to the subsequent temporal lobe focus whereas chronic factors seem to be be related to pathology contralateral to the seizure focus.

 PMID:9343124

  2. Role of nitric oxide and lipid peroxidation in mechanisms of febrile convulsions in Wistar rat pups.

    PubMed

    Klyueva, Y A; Bashkatova, V G; Vitskova, G Y; Narkevich, V B; Mikoyan, V D; Vanin, A F; Chepurnov, S A; Chepurnova, N E

    2001-01-01

    Generation of nitric oxide and the content of lipid peroxidation products in the brain are increased in rat pups during febrile convulsions. NO-synthase inhibitor N-nitro-L-arginine in a dose of 250 mg/kg prevented hyperthermia-induced accumulation of nitric oxide, increased the latency febrile convulsions, and had no effect on the content of lipid peroxidation products. PMID:11329081

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-06-24

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. Characterization of antineutrophil antibodies in patients with neutropenia associated with nutritional copper deficiency.

    PubMed

    Higuchi, S; Hirashima, M; Nunoi, H; Higashi, A; Naoe, H; Matsuda, I

    1995-01-01

    Six antineutrophil antibody (ANA)-positive patients with copper deficiency were classified into two groups; those with (group A, n = 3) and those without (group B, n = 3) neutropenia. The percent binding of ANA for normal peripheral neutrophils was similar in both groups (83.5 +/- 7.2 vs. 79.1 +/- 10.5%). The percent binding of sera to cultured promyelocytic leukemia cells (HL-60) was increased in group A (from 3.7 +/- 3.2 to 12.2 +/- 2.3%) but not in group B (from 65.3 +/- 21.7 to 40.7 +/- 6.3%) after stimulation of HL-60 with DMSO. The stimulated HL-60 cells expressed CD 16 and CD 11b antigens. In the presence of monoclonal antibody for CD 16, the titer of ANA was nil in group A and unchanged in group B. Thus, ANA of patients with neutropenia may recognize mainly the CD 16 antigen, the Fc gamma receptor III of neutrophils.

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

    PubMed Central

    Crona, DJ; Ramirez, J; Qiao, W; de Graan, A-J; Ratain, MJ; van Schaik, RHN; Mathijssen, RHJ; Rosner, GL; Innocenti, F

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

  10. Clinical profile and treatment outcome of febrile infection-related epilepsy syndrome in South Indian children

    PubMed Central

    Patil, Sandeep B.; Roy, Arun Grace; Vinayan, Kollencheri Puthenveettil

    2016-01-01

    Purpose: To describe the clinical features and outcome of febrile infection-related epilepsy syndrome (FIRES), a catastrophic epileptic encephalopathy, in a cohort of South Indian children. Materials and Methods: We performed a retrospective chart review of a cohort of children with previously normal development who presented with status epilepticus or encephalopathy with recurrent seizures following a nonspecific febrile illness during the period between January 2007 and January 2012. They were divided into two groups super refractory status epilepticus (SRSE) and refractory status epilepticus (RSE) depending on the duration and severity of the seizures. Key Findings: Fifteen children who met the inclusion criteria were included for the final analysis. The age of the children at presentation ranged 3-15 years (median 6.3 years). All the children presented with prolonged or recurrent seizures occurring 1-12 days (median 4 days) after the onset of fever. Eight children had SRSE while seven children had refractory seizures with encephalopathy. Cerebrospinal fluid (CSF) analysis was done in all the children in the acute phase, and the cell count ranged 0-12 cells/μL (median 2 cells/μL) with normal sugar and protein levels. Initial neuroimaging done in all children (MRI in 10 and CT in 5), and it was normal in 13 children. Treatment modalities included multiple antiepileptic drugs (AEDs) (4-9 drugs) (median 5 drugs). Midazolam (MDZ) infusion was administered in seven patients. Eight patients required barbiturate coma to suppress the seizure activity. The duration of the barbiturate coma ranged 2-90 days (median 3 days). Steroids were used in 14 children and intravenous immunoglobulin (2 g/kg) in 7 children. Three children died in the acute phase. All children were maintained on multiple AEDs till the last follow-up, the number of AEDs ranged 1-6 (median 5 AEDs). The patients with super refractory status in the acute phase were found to be more severely disabled at

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

    PubMed

    Bergmann, O J; Andersen, P L

    1990-01-01

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

  12. Febrile-range hyperthermia augments pulmonary neutrophil recruitment and amplifies pulmonary oxygen toxicity.

    PubMed

    Hasday, Jeffrey D; Garrison, Allen; Singh, Ishwar S; Standiford, Theodore; Ellis, Garrettson S; Rao, Srinivas; He, Ju-Ren; Rice, Penny; Frank, Mariah; Goldblum, Simeon E; Viscardi, Rose M

    2003-06-01

    Febrile-range hyperthermia (FRH) improves survival in experimental infections by accelerating pathogen clearance, but may also increase collateral tissue injury. We hypothesized that FRH would worsen the outcome of inflammation stimulated by a non-replicating agonist and tested this hypothesis in a murine model of pulmonary oxygen toxicity. Using a conscious, temperature-controlled mouse model, we showed that maintaining a core temperature at FRH (39 degrees C to 40 degrees C) rather than at euthermic levels (36.5 degrees C to 37 degrees C) during hyperoxia exposure accelerated lethal pulmonary vascular endothelial injury, reduced the inspired oxygen threshold for lethality, induced expression of granulocyte-colony stimulating factor, and expanded the circulating neutrophil pool. In these same mice, FRH augmented pulmonary expression of the ELR(+) CXC chemokines, KC and LPS-induced CXC chemokine, enhanced recruitment of neutrophils, and changed the histological pattern of lung injury to a neutrophilic interstitial pneumonitis. Immunoblockade of CXC receptor-2 abrogated neutrophil recruitment, reduced pulmonary vascular injury, and delayed death. These combined data demonstrate that FRH may enlist distinct mediators and effector cells to profoundly shift the host response to a defined injurious stimulus, in part by augmenting delivery of neutrophils to sites of inflammation, such as may occur in infections. In certain conditions, such as in the hyperoxic lung, this process may be deleterious.

  13. Experimental febrile seizures impair interastrocytic gap junction coupling in juvenile mice.

    PubMed

    Khan, Dilaware; Dupper, Alexander; Deshpande, Tushar; Graan, Pierre N E De; Steinhäuser, Christian; Bedner, Peter

    2016-09-01

    Prolonged and focal febrile seizures (FSs) have been associated with the development of temporal lobe epilepsy (TLE), although the underlying mechanism and the contribution of predisposing risk factors are still poorly understood. Using a kainate model of TLE, we previously provided strong evidence that interruption of astrocyte gap junction-mediated intercellular communication represents a crucial event in epileptogenesis. To elucidate this aspect further, we induced seizures in immature mice by hyperthermia (HT) to study the consequences of FSs on the hippocampal astrocytic network. Changes in interastrocytic coupling were assessed by tracer diffusion studies in acute slices from mice 5 days after experimental FS induction. The results reveal that HT-induced FSs cause a pronounced reduction of astrocyte gap junctional coupling in the hippocampus by more than 50%. Western blot analysis indicated that reduced connexin43 protein expression and/or changes in the phosphorylation status account for this astrocyte dysfunction. Remarkably, uncoupling occurred in the absence of neuronal death and reactive gliosis. These data provide a mechanistic link between FSs and the subsequent development of TLE and further strengthen the emerging view that astrocytes have a central role in the pathogenesis of this disorder. © 2016 Wiley Periodicals, Inc. PMID:26931373

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

    The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R = 0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R = 0.405) (P < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency, and in conditions in which bone marrow myelopoiesis is negatively affected. PMID:26119962

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. Acute febrile illness surveillance in a tertiary hospital emergency department: comparison of influenza and dengue virus infections.

    PubMed

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

    2013-03-01

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

  20. Acute febrile illness surveillance in a tertiary hospital emergency department: comparison of influenza and dengue virus infections.

    PubMed

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

    2013-03-01

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

  1. Kidney imaging in management of delayed febrile urinary tract infection.

    PubMed

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

    2011-11-01

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

  2. Predictors of malaria in febrile children in Sokoto, Nigeria

    PubMed Central

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

    2014-01-01

    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. PMID:25538366

  3. Novel GABRG2 mutations cause familial febrile seizures

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2011-01-01

    Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Methods Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Results Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. Conclusions A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls. PMID:22145762

  5. Paternal Somatic Mosaicism of a Novel Frameshift Mutation in ELANE Causing Severe Congenital Neutropenia.

    PubMed

    Kim, Hee-Jung; Song, Min-Jung; Lee, Ki-O; Kim, Sun-Hee; Kim, Hee-Jin

    2015-12-01

    Severe congenital neutropenia (SCN) is a bone marrow failure disease with an autosomal dominant inheritance from mutations in ELANE. Here, we report a 7-week-old Korean male with SCN. His elder sister died from pneumonia at 2 years. Direct sequencing of ELANE in the proband identified a heterozygous novel frameshift mutation: c.658delC (p.Arg220Glyfs20*). Family study involving his asymptomatic parents with normal cell counts revealed that his father had the same mutation, but at a lower burden than expected in a typical heterozygous state. Further molecular investigation demonstrated somatic mosaicism with ~18% mutant alleles. We concluded the proband inherited the mutation from his somatic mosaic father.

  6. Effect of prostacyclin (PGI2) on immune-complex-induced neutropenia.

    PubMed Central

    Camussi, G; Bussolino, F; Tetta, C; Caligaris Cappio, F; Coda, R; Macchiorlatti, E; Alberton, M; Roffinello, C; Segoloni, G

    1983-01-01

    This study reports the results of in vitro and in vivo investigations on the effect of prostacyclin (PGI2) on polymorphonuclear neutrophils (PMN) challenged with immune complexes (IC). In vitro, PGI2 does not affect the interaction of IC with PMN membrane receptors, but prevents the ensuing PMN aggregation and secretion of platelet-activating factor, a lipid mediator responsible for immune-induced PMN aggregation. In vivo, the infusion of PGI2 in New Zealand white rabbits injected with IC prevents IC-induced neutropenia and thrombocytopenia as well as the embolization of PMN into the pulmonary peripheral capillary network. These results suggest a physiological role for PGI2 in modulating the interaction between IC and PMN. Images Figure 1 Figure 3 PMID:6339375

  7. Imaging inflammation with 99Tcm-labeled chemotactic peptides: analogues with reduced neutropenia.

    PubMed

    Pollak, A; Goodbody, A E; Ballinger, J R; Duncan, G S; Tran, L L; Dunn-Dufault, R; Meghji, K; Lau, F; Andrey, T W; Boxen, I; Sumner-Smith, M

    1996-02-01

    Two 99Tcm-labelled analogues of the chemotactic peptide ForMLF were evaluated as potential agents for imaging inflammation and infection, in the hope that they would be simple to use and would give diagnostically useful images shortly after injection. The peptides differed in the chelation site for 99Tcm and the presence of a hydrophilic spacer. The sequences of RP050 and RP056 were ForNleLFNleYK(G)G-C(Acm)-GPic and ForNleLFNleYKK(DG)GC(Acm)SPic respectively, where Pic is picolinic acid. In in vitro tests of binding to the ForMLF receptor on polymorphonuclear neutrophils and potency for release of myeloperoxidase, RP056 was similar in potency to ForMLF, whereas RP050 was 10 times more potent. When administered in 5-nmol doses to rats, RP050 produced less extensive neutropenia than ForMLF, whereas RP056 produced very little neutropenia. Following labelling by ligand exchange from tartrate or glucoheptonate at 100 degrees C and purification using a C-18 solid-phase extraction cartridge, 4-MBq doses were administered to rats bearing infectious (Escherichia coli) or sterile (zymosan) inflammation sites in the thigh. The inflammation-to-normal muscle ratios at 30 min after injection were 3.9 +/- 0.4 for RP050 and 4.7 +/- 0.3 for RP056 (mean +/- S.E.M., n = 4), and the ratios were maintained for up to 3 h. These peptides are promising agents for imaging inflammation and infection.

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

    PubMed

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

    2011-02-01

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

  9. Efficacy of Adenine in the Treatment of Leukopenia and Neutropenia Associated with an Overdose of Antipsychotics or Discontinuation of Lithium Carbonate Administration: Three Case Studies

    PubMed Central

    Tomita, Takashi; Goto, Hidekazu; Sumiya, Kenji; Yoshida, Tadashi; Tanaka, Katsuya; Kohda, Yukinao

    2016-01-01

    Because adenine is effective for managing cases of radiation-induced and drug-induced leukopenia, it may be effective in cases of antipsychotic-induced leukopenia and neutropenia. Here, we report our experience with patients with leukopenia and neutropenia caused by an antipsychotic overdose or discontinuation of lithium carbonate, in whom adenine administration ameliorated the white blood cell and neutrophil counts. The progress of patients suggests that adenine is effective in cases of leukopenia and neutropenia associated with lithium carbonate discontinuation and an antipsychotic overdose. PMID:27776394

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

    PubMed Central

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

    2011-01-01

    Objective It is propounded that febrile neonates with low risk criteria (LRC) can be carefully observed without parenteral antimicrobial therapy; but yet, reliability of LRC to exclude serious bacterial infection (SBI) is uncertain. Methods The records of all febrile term neonates, seen in the emergency room and admitted in neonatal ward of 17 Shahrivar children's hospital of Rasht, Iran from January 2004 to January 2009 were reviewed. All of them underwent full sepsis workup. The prevalence of SBI in total population and LRC positive and negative neonates were calculated Findings A total of 202 records of previously healthy febrile neonates were evaluated. SBI was shown in 38 (18.8%). The most common type of SBI was urinary tract infection (UTI). Sixty-two (31%) neonates had LRC, and only one (1.6%) had SBI (UTI with E. coli). SBI was significantly more common in neonates without LRC (26.6% versus 1.6%, P<0.001). The negative predictive value (NPV) of LRC to exclude SBI was 98.4% (95%confidence interval: 96.7% to 100%). Conclusion These findings suggest that LRC may be relied upon to exclude SBI in febrile neonates. We propose that all febrile neonates be admitted, ill or LRC negative neonates should undergo a full sepsis work up and be administered systemic antibiotics immediately. LRC positive neonates should be under close observation. PMID:23056828

  11. Effects of hydration on febrile temperature patterns in rabbits.

    PubMed

    Richmond, C A

    2001-04-01

    Patients with fever have a predisposition to experience dehydration, which may alter their thermoregulatory responses to elevated body temperature. In view of the recent discovery of the antipyretic activity of arginine vasopressin (AVP), it is possible that dehydration has a beneficial role during fever. Dehydration may enhance endogenous antipyresis by stimulating AVP release, making aggressive fluid replacement, which may inhibit AVP release, undesirable during fever. This study addressed the effects of manipulation of hydration status on temperature and cardiovascular responses in endotoxin-injected rabbits. Eight unanesthetized chronically instrumented rabbits were exposed to lipopolysaccharide (LPS) while in euhydrated state, after furosemide (5 mg/kg) and 24 hours of water deprivation (dehydrated), after infusion of saline (30 mL/kg) while in euhydrated state (hyperhydrated), and after saline (mL/per overnight body weight loss in grams) while in dehydrated state (rehydrated). Dehydrated rabbits display higher fevers that are biphasic in nature and are accompanied by increased vasoconstriction and duration of mean arterial pressure increases, indicating that activation of antipyretic mechanisms in dehydrated rabbits was not sufficient to reduce body core temperature. In addition, fluid supplementation in euhydrated rabbits did not alter the febrile response; however, a marked decrease in heart rate was noted. Furthermore, fluid supplementation in dehydrated rabbits significantly attenuates the rectal temperature and heart rate response to LPS injection, indicating the possibility that activation of antipyretic mechanisms of AVP in rehydrated rabbits was sufficient to reduce body core temperature. The results suggest that fluid supplementation has a beneficial role in keeping body temperature lower .

  12. THE BICARBONATE RESERVE AND THE DISSOCIATION CURVE OF OXYHEMOGLOBIN IN FEBRILE CONDITIONS.

    PubMed

    White, A C

    1925-02-28

    From Fig. 1 it may be seen that the effect of elevated temperature during the pyrexial period upon 1/K and therefore on the dissociation curve of oxyhemoglobin was, on the average, greater than would have been expected from experiments on normal blood in vitro, and greater than would be expected in view of the alkalosis occurring See PDF for Structure during fever. Temperature rise, and excess hydroxyl ion acting in vitro in the opposite directions, seemed to indicate a more stable state of affairs than was found. Apparently other factors have come into play, as, for example, alterations in the proportions and concentrations of the various electrolytes. In pneumonia, for instance, there is a retention of chloride during the febrile period with excessive loss of phosphates. The variations were not due to variations in the hemoglobin molecule itself since from the work of Adair, Barcroft, and Bock (18) hemoglobin must apparently be reckoned as having identical properties in normal individuals of the same species. If Barcroft's (19) hypothesis be right, namely that the C(H) within the corpuscle is higher than that of the plasma, the observed variations of 1/K may not be so surprising. In view of the fact that the hemoglobin inside the corpuscle is enclosed within a semipermeable membrane, the possibility arises of the setting up of membrane equilibria which will protect the respiratory pigment from excessive changes of reaction that may occur in the plasma, and thus the optimum conditions for the carriage of oxygen to the tissues may be maintained. Krogh and Leitch (10) in 1919 also drew attention to the protected situation of hemoglobin inside the corpuscle. In Case 6 it seems as if the alkalosis consequent on the febrile state had gained the upper hand and had extinguished the normal temperature reaction. This is rather confirmed by the fact that clinically the case showed one of the earlier signs of an alkalosis; namely, twitching of the facial muscles. Case 10

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

    PubMed Central

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

    2012-01-01

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

  14. Prenatal stress and risk of febrile seizures in children: a nationwide longitudinal study in Denmark.

    PubMed

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

    2009-07-01

    We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost a close relative during pregnancy or within 1 year before the pregnancy and they were included in the exposed group. The exposed children had a risk of febrile seizures similar to that of the unexposed children (hazard ratio (HR) 1.00, 95% CI 0.94-1.06). The HRs did not differ according to the nature or timing of bereavement. Our data do not suggest any causal link between exposure to prenatal stress and febrile seizures in childhood.

  15. Identification of Bartonella infections in febrile human patients from Thailand and their potential animal reservoirs.

    PubMed

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

    2010-06-01

    To determine the role of Bartonella species as causes of acute febrile illness in humans from Thailand, we used a novel strategy of co-cultivation of blood with eukaryotic cells and subsequent phylogenetic analysis of Bartonella-specific DNA products. Bartonella species were identified in 14 blood clots from febrile patients. Sequence analysis showed that more than one-half of the genotypes identified in human patients were similar or identical to homologous sequences identified in rodents from Asia and were closely related to B. elizabethae, B. rattimassiliensis, and B. tribocorum. The remaining genotypes belonged to B. henselae, B. vinsonii, and B. tamiae. Among the positive febrile patients, animal exposure was common: 36% reported owning either dogs or cats and 71% reported rat exposure during the 2 weeks before illness onset. The findings suggest that rodents are likely reservoirs for a substantial portion of cases of human Bartonella infections in Thailand. PMID:20519614

  16. Infectious etiologies of acute febrile illness among patients seeking health care in south-central Cambodia.

    PubMed

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

    2012-02-01

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

  17. Hospital-based prevalence of malaria and dengue in febrile patients in Bangladesh.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  20. Pathologic features of naturally occurring juvenile polyarteritis in beagle dogs.

    PubMed

    Snyder, P W; Kazacos, E A; Scott-Moncrieff, J C; HogenEsch, H; Carlton, W W; Glickman, L T; Felsburg, P J

    1995-07-01

    Eighteen young Beagle dogs (eight males and 10 females), ages 6-40 months, with canine juvenile polyarteritis syndrome (CJPS), a naturally occurring vasculitis and perivasculitis of unknown etiology, were necropsied, and their tissues were examined by histopathologic and histochemical methods. The condition is characterized by recurring episodes of an acute onset of fever (> 40 C) and neck pain that persist for 3-7 days. The major histopathologic alterations were a systemic vasculitis and perivasculitis. During the febrile, painful period of CJPS, the vascular lesions ranged from a histiocytic-lymphocytic periarterial infiltration to transmural arterial inflammation with concomitant fibrinoid necrosis and vascular thrombosis. Massive periarterial accumulations of inflammatory cells were common and often extended into adjacent tissues. The small- to medium-sized muscular arteries of the heart, cranial mediastinum, and cervical spinal meninges were consistently involved. Vasculitis occasionally occurred in other organ systems. The vascular lesions in dogs examined during clinically normal periods consisted of intimal and medial fibrosis, ruptured elastic laminae, and mild perivasculitis; these lesions were probably related to previous episodes of vasculitis. Eight dogs that had experienced repeated acute episodes also developed splenic, hepatic, and renal amyloidosis. The clinical signs, laboratory abnormalities, and the vascular lesions suggest that the condition may be immune-system mediated. CJPS may serve as a naturally occurring animal model of human immune-system-mediated vasculitides such as polyarteritis nodosa, infantile polyarteritis, and Kawasaki disease.

  1. Study of Aetiology and Outcome in Acute Febrile Illness Patients with Multiple Organ Dysfunction Syndrome

    PubMed Central

    Muthaiah, Bhanukumar; Kondareddy, Srinivas; Chikkegowda, Prathima

    2016-01-01

    Introduction Acute febrile illness with Multi Organ Dysfunction Syndrome (MODS) carries significant morbidity and mortality despite standard therapy in intensive care settings. Infections are the most common cause of MODS followed by polytrauma. Present study was undertaken in medical intensive care units of a tertiary hospital to study the aetiology and outcome among patients with acute febrile illness developing MODS. Aim 1) To study the aetiology of acute febrile illness in patients developing MODS. 2) To study the final outcome among these patients. Materials and Methods The present study was conducted at a tertiary care hospital in Mysuru, Karnataka, India, over a period of 6 months from July 2013 to December 2013. The Institutional Ethics Committee Approval (IEC) was obtained before the commencement of the study. A total of 213 cases admitted in intensive care unit with acute febrile illness with two or more organ dysfunction were screened for the inclusion and exclusion criterias. Results A total of 213 cases of acute febrile illness with one or more organ dysfunction were screened. Of the screened patients 75 patients were finally included in the study out of which 46 (61.3%) patients were males and 29 (38.7%) patients were females. Aetiology for acute febrile illness with MODS could be established in 49 (65.3%) patients and it was obscure in 26 (34.7%) patients despite repeated investigations. Dengue infection (29.3%) was the commonest cause of febrile illness with MODS followed by leptospirosis (22.7%). Majority of these patients had haematological derangements (78.7%) and liver function test abnormalities (68%). Out of these 75 cases, 54 (72%) patients recovered completely and 21 (28%) patients died. Among males (N=46), 35 (76.1%) patients recovered and 11 (23.9%) patients died where as among females (N=29), 19 (65.5%) patients recovered and 10 (34.5%) patients died. Mortality was proportionate with the number of organ dysfunction, especially Central

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

    PubMed Central

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

    2015-01-01

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

  3. G-CSF, but not corticosterone, mediates circulating neutrophilia induced by febrile-range hyperthermia.

    PubMed

    Ellis, Garrettson S; Carlson, Drew E; Hester, Lisa; He, Ju-Ren; Bagby, Gregory J; Singh, Ishwar S; Hasday, Jeffery D

    2005-05-01

    We previously showed that sustained exposure to febrile-range hyperthermia (FRH) for 24 h caused an increase in circulating granulocyte colony-stimulating factor (G-CSF) levels and a peripheral neutrophilia in mice (Hasday J, Garrison A, Singh I, Standiford T, Ellis G, Rao S, He JR, Rice P, Frank M, Goldblum S, and Viscardi R. Am J Pathol 162: 2005-2017, 2003). In this study, we utilized a conscious temperature-clamped mouse model to analyze the kinetics of G-CSF expression and peripheral neutrophil expansion and the contributions of FRH-induced G-CSF expression, glucocorticoid generation, and catecholamine-induced neutrophil demargination. In conscious mice housed at an ambient temperature of 34.5 degrees C, core temperature rapidly equilibrated at 39.5-40 degrees C. Peripheral neutrophil counts increased 2-fold after 24-h exposure to hyperthermia, peaked at 3.6-fold baseline levels after 36-h exposure to FRH, and returned to baseline levels after 42 h of sustained hyperthermia. Plasma G-CSF levels were increased by 6.8-fold after 24 h and peaked at 40-fold baseline levels after 36 h in the hyperthermic mice. Plasma corticosterone levels peaked at 3.3-fold baseline levels after 30-h sustained hyperthermia and returned to baseline by 42 h. Immunoneutralization of G-CSF blocked FRH-induced peripheral neutrophilia, but blockade of the glucocorticoid receptor with mifepristone failed to modify FRH-induced neutrophilia. Epinephrine induced similar increases in peripheral blood absolute neutrophil counts in euthermic mice (2.2-fold increase) and mice exposed to FRH for 36 h (1.8-fold increase). Collectively, these data suggest that FRH-induced expression of G-CSF drives the sustained peripheral neutrophilia that occurs during sustained (36 h) hyperthermia, whereas glucocorticoid generation and catecholamine-induced demargination play little role in this response.

  4. Giant Cell Arteritis which Developed after the Administration of Granulocyte-colony Stimulating Factor for Cyclic Neutropenia.

    PubMed

    Umeda, Masataka; Ikenaga, Jin; Koga, Tomohiro; Michitsuji, Toru; Shimizu, Toshimasa; Fukui, Shoichi; Nishino, Ayako; Nakasima, Yoshikazu; Kawashiri, Sin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Kawakami, Atsushi

    2016-01-01

    A 78-year-old woman diagnosed with cyclic neutropenia 5 years previously had been treated with recombinant granulocyte-colony stimulating factor (G-CSF). She developed fever, tenderness and distension of temporal arteries after the treatment with G-CSF. Magnetic resonance imaging and ultrasonography revealed wall thickening of the temporal arteries. She was therefore diagnosed with giant cell arteritis (GCA). Small vessel vasculitis has been reported as a complication of G-CSF. However, the development of large vessel vasculitis after G-CSF treatment is quite rare. To our knowledge, the present case is the first report of GCA suspected to be associated with coexisting cyclic neutropenia and G-CSF treatment. PMID:27523011

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

    PubMed Central

    Craike, Melinda; Slavin, Monica

    2012-01-01

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

  6. Successful non-myeloablative allogenic bone marrow transplantation in a child with severe congenital neutropenia complicated by chronic pulmonary infection.

    PubMed

    Nino, Nanako; Kozaki, Aiko; Hasegawa, Daiichiro; Ueda, Go; Takahashi, Hironobu; Miyata, Kenji; Ochi, Satoshi; Yamashita, Tatsuya; Takafuji, Satoru; Uemura, Suguru; Yokoi, Takehito; Saito, Atsuro; Ishida, Toshiaki; Kawasaki, Keiichiro; Nakamura, Kazuhiro; Kobayashi, Masao; Kosaka, Yoshiyuki

    2016-06-01

    We herein describe a 2-year-old boy with severe congenital neutropenia (SCN) who was successfully treated with reduced-intensity bone marrow transplantation (HSCT). He had suffered recurrent episodes of bacterial pneumonia from 12 months of age, and was found to have severe neutropenia with white blood cell counts below 100/μl. The patient harbored a heterozygous missense mutation in ELANE exon 4 (p.Gln134Pro, NM_001972.2: c.401A>C). This was a novel mutation. Due to intractable pneumonia and severe persistent neutropenia, reduced-intensity HSCT was performed from an HLA-matched sibling donor. The preparative regimen consisted of melphalan, fludarabine, and 4 Gy of total body irradiation. Hematopoietic engraftment was rapidly obtained, i.e., by day +14, and complete donor chimerism was subsequently achieved. The lung complications observed pre-transplantation markedly improved after neutrophil recovery, i.e., by day +60. We concluded that HSCT is a useful treatment for SCN patients, especially for those at high risk of leukemic transformation. Fludarabine-based reduced-intensity HSCT may represent a safe and effective therapeutic option for patients with SCN who need HSCT even if they have intractable infectious complications. PMID:27384854

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-08-01

    Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation

  9. Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction

    PubMed Central

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

    2016-01-01

    Background Despite modern antimicrobials and supportive therapy bacterial and fungal infections are still major complications in people with prolonged disease-related or treatment-related neutropenia. Transfusions of granulocytes have a long history of usage in clinical practice to support and treat severe infection in high-risk groups of patients with neutropenia or neutrophil dysfunction. However, there is considerable current variability in therapeutic granulocyte transfusion practice, and uncertainty about the beneficial effect of transfusions given as an adjunct to antibiotics on mortality. This is an update of a Cochrane review first published in 2005. Objectives To determine the effectiveness and safety of granulocyte transfusions compared to no granulocyte transfusions as adjuncts to antimicrobials for treating infections in people with neutropenia or disorders of neutrophil function aimed at reducing mortality and other adverse outcomes related to infection. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 2). MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 11 February 2016. Selection criteria RCTs comparing people with neutropenia or disorders of neutrophil dysfunction receiving granulocyte transfusions to treat infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, language or publication status. Data collection and analysis We used standard methodological procedures expected by the Cochrane Collaboration. Main results We identified 10 trials that met the inclusion criteria with a total of 587 participants. We also identified another ongoing trial. These trials were conducted between 1975 and 2015. None of

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Rituximab associated late-onset neutropenia-a rheumatology case series and review of the literature.

    PubMed

    Monaco, William E; Jones, Jonathan D; Rigby, William F C

    2016-10-01

    Recently in the rheumatology literature, Rituximab (RTX) has been associated with late-onset neutropenia (LON), defined as an absolute neutrophil count (ANC) <1.5 × 10(9)/L at least 4 weeks after the last infusion. We determined the incidence of LON in patients with rheumatic disease at a single tertiary medical center, ascertained patient characteristics including results of bone marrow biopsies performed on four neutropenic patients, and performed a literature review. The incidence at our institution was 6.5 %, similar to that reported in the literature. Bone marrow biopsies from four neutropenic patients had the predominant cell line as lymphocytes, comprising an average of 41 % (range 24-50 %) of the cellular aspirate suggesting that there is a selective reduction in granulopoiesis and maturation arrest at the promyelocyte stage. Sixty percent of patients presented without serious infections, and all survived without adverse sequelae. Treatment with granulocyte colony-stimulating factor shortened time to recover of ANC but did not change overall outcomes. Among 25 patients re-challenged with RTX after resolution of LON, only two developed recurrence of LON. Among patients at our institution and identified from a review of the literature, LON is not usually associated with serious infections that lead to significant adverse outcomes, G-CSF therapy does not appear to be necessary as it does not change outcomes, and RTX re-treatment after recovery from LON appears safe.

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2015-10-01

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

  15. Chikungunya Virus in Febrile Humans and Aedes aegypti Mosquitoes, Yucatan, Mexico

    PubMed Central

    Cigarroa-Toledo, Nohemi; Blitvich, Bradley J.; Cetina-Trejo, Rosa C.; Talavera-Aguilar, Lourdes G.; Baak-Baak, Carlos M.; Torres-Chablé, Oswaldo M.; Hamid, Md-Nafiz; Friedberg, Iddo; González-Martinez, Pedro; Alonzo-Salomon, Gabriela; Rosado-Paredes, Elsy P.; Rivero-Cárdenas, Nubia; Reyes-Solis, Guadalupe C.; Farfan-Ale, Jose A.; Garcia-Rejon, Julian E.

    2016-01-01

    Chikungunya virus (CHIKV) was isolated from 12 febrile humans in Yucatan, Mexico, in 2015. One patient was co-infected with dengue virus type 1. Two additional CHIKV isolates were obtained from Aedes aegypti mosquitoes collected in the homes of patients. Phylogenetic analysis showed that the CHIKV isolates belong to the Asian lineage. PMID:27347760

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

    PubMed

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

    2015-11-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Chikungunya Virus in Febrile Humans and Aedes aegypti Mosquitoes, Yucatan, Mexico.

    PubMed

    Cigarroa-Toledo, Nohemi; Blitvich, Bradley J; Cetina-Trejo, Rosa C; Talavera-Aguilar, Lourdes G; Baak-Baak, Carlos M; Torres-Chablé, Oswaldo M; Hamid, Md-Nafiz; Friedberg, Iddo; González-Martinez, Pedro; Alonzo-Salomon, Gabriela; Rosado-Paredes, Elsy P; Rivero-Cárdenas, Nubia; Reyes-Solis, Guadalupe C; Farfan-Ale, Jose A; Garcia-Rejon, Julian E; Machain-Williams, Carlos

    2016-10-01

    Chikungunya virus (CHIKV) was isolated from 12 febrile humans in Yucatan, Mexico, in 2015. One patient was co-infected with dengue virus type 1. Two additional CHIKV isolates were obtained from Aedes aegypti mosquitoes collected in the homes of patients. Phylogenetic analysis showed that the CHIKV isolates belong to the Asian lineage. PMID:27347760

  2. Molecular Detection of Fastidious and Common Bacteria as Well as Plasmodium spp. in Febrile and Afebrile Children in Franceville, Gabon.

    PubMed

    Mourembou, Gaël; Fenollar, Florence; Socolovschi, Cristina; Lemamy, Guy Joseph; Nzoughe, Hermann; Kouna, Lady Charlene; Toure-Ndouo, Fousseyni; Million, Matthieu; Mbiguino, Angelique Ndjoyi; Lekana-Douki, Jean Bernard; Raoult, Didier

    2015-05-01

    Malaria was considered as the main cause of fever in Africa. However, with the roll back malaria initiative, the causes of fever in Africa may change. This study aimed to evaluate the prevalence of bacteria and Plasmodium spp. in febrile and afebrile (controls) children from Franceville, Gabon. About 793 blood samples from febrile children and 100 from controls were analyzed using polymerase chain reaction (PCR) coupled with sequencing. Plasmodium spp. was the microorganism most detected in febrile (74.5%, 591/793) and controls (13%, 13/100), P < 0.0001. Its coinfection with bacteria was found only in febrile children (P = 0.0001). Staphylococcus aureus was the most prevalent bacterium in febrile children (2.8%, 22/793) and controls (3%, 3/100). Eight cases of Salmonella spp. (including two Salmonella enterica serovar Paratyphi) and two of Streptococcus pneumoniae were found only among febrile children. Borrelia spp. was found in 2 controls while Rickettsia felis was detected in 10 children (in 8 febriles and 2 afebriles). No DNA of other targeted microorganisms was detected. Plasmodium spp. remains prevalent while Salmonella spp., Staphylococcus aureus, and Streptococcus pneumoniae were common bacteria in Gabon. Two fastidious bacteria, Rickettsia felis and Borrelia spp., were found. Inclusion of controls should improve the understanding of the causes of fever in sub-Saharan Africa.

  3. Molecular Detection of Fastidious and Common Bacteria as well as Plasmodium spp. in Febrile and Afebrile Children in Franceville, Gabon

    PubMed Central

    Mourembou, Gaël; Fenollar, Florence; Socolovschi, Cristina; Lemamy, Guy Joseph; Nzoughe, Hermann; Kouna, Lady Charlene; Toure-Ndouo, Fousseyni; Million, Matthieu; Mbiguino, Angelique Ndjoyi; Lekana-Douki, Jean Bernard; Raoult, Didier

    2015-01-01

    Malaria was considered as the main cause of fever in Africa. However, with the roll back malaria initiative, the causes of fever in Africa may change. This study aimed to evaluate the prevalence of bacteria and Plasmodium spp. in febrile and afebrile (controls) children from Franceville, Gabon. About 793 blood samples from febrile children and 100 from controls were analyzed using polymerase chain reaction (PCR) coupled with sequencing. Plasmodium spp. was the microorganism most detected in febrile (74.5%, 591/793) and controls (13%, 13/100), P < 0.0001. Its coinfection with bacteria was found only in febrile children (P = 0.0001). Staphylococcus aureus was the most prevalent bacterium in febrile children (2.8%, 22/793) and controls (3%, 3/100). Eight cases of Salmonella spp. (including two Salmonella enterica serovar Paratyphi) and two of Streptococcus pneumoniae were found only among febrile children. Borrelia spp. was found in 2 controls while Rickettsia felis was detected in 10 children (in 8 febriles and 2 afebriles). No DNA of other targeted microorganisms was detected. Plasmodium spp. remains prevalent while Salmonella spp., Staphylococcus aureus, and Streptococcus pneumoniae were common bacteria in Gabon. Two fastidious bacteria, Rickettsia felis and Borrelia spp., were found. Inclusion of controls should improve the understanding of the causes of fever in sub-Saharan Africa. PMID:25802432

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

    Cohen, Philip R

    2007-01-01

    Sweet's syndrome (the eponym for acute febrile neutrophilic dermatosis) is characterized by a constellation of clinical symptoms, physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions (papules, nodules, and plaques), and a diffuse infiltrate consisting predominantly of mature neutrophils that are typically located in the upper dermis. Several hundreds cases of Sweet's syndrome have been published. Sweet's syndrome presents in three clinical settings: classical (or idiopathic), malignancy-associated, and drug-induced. Classical Sweet's syndrome (CSS) usually presents in women between the age of 30 to 50 years, it is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately one-third of patients with CSS experience recurrence of the dermatosis. The malignancy-associated Sweet's syndrome (MASS) can occur as a paraneoplastic syndrome in patients with an established cancer or individuals whose Sweet's syndrome-related hematologic dyscrasia or solid tumor was previously undiscovered; MASS is most commonly related to acute myelogenous leukemia. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer. Hence, MASS can be the cutaneous harbinger of either an undiagnosed visceral malignancy in a previously cancer-free individual or an unsuspected cancer recurrence in an oncology patient. Drug-induced Sweet's syndrome (DISS) most commonly occurs in patients who have been treated with granulocyte-colony stimulating factor, however, other medications may also be associated with DISS. The pathogenesis of Sweet's syndrome may be multifactorial and still remains to be definitively established. Clinical and laboratory evidence suggests that cytokines have an etiologic role. Systemic corticosteroids are the therapeutic gold standard for Sweet's syndrome. After initiation of treatment with systemic

  8. Systematic review of fever, febrile convulsions and serious adverse events following administration of inactivated trivalent influenza vaccines in children.

    PubMed

    Li-Kim-Moy, J; Yin, J K; Rashid, H; Khandaker, G; King, C; Wood, N; Macartney, K K; Jones, C; Booy, R

    2015-06-18

    In 2010, increased febrile convulsions (FC) occurred after administration of inactivated trivalent influenza vaccine (TIV) in Australia. We systematically reviewed the rates of fever, FC and serious adverse events (SAEs) after TIV, focussing on published and unpublished clinical trial data from 2005 to 2012, and performed meta-analysis of fever rates. From 4,372 records in electronic databases, 18 randomised controlled trials (RCTs), 14 non-randomised clinical trials, six observational studies and 12 registered trials (five RCTs and seven non-randomised) were identified. In published RCTs, fever ≥ 38 °C rates after first dose of non-adjuvanted TIV were 6.7% and 6.9% for children aged 6–35 months and ≥ 3 years, respectively. Analysis of RCTs by vaccine manufacturer showed pooled fever estimates up to 5.1% with Sanofi or GlaxoSmithKline vaccines; bioCSL vaccines were used in two non-randomised clinical trials and one unpublished RCT and were associated with fever in 22.5–37.1% for children aged 6–35 months. In RCTs, FCs occurred at a rate of 1.1 per 1,000 vaccinated children. While most TIVs induced acceptably low fever rates, bioCSL influenza vaccines were associated with much higher rates of fever in young children. Future standardised study methodology and access to individual level data would be illuminating.

  9. Prognostic Value of Chemotherapy-Induced Neutropenia at the First Cycle in Invasive Breast Cancer

    PubMed Central

    Ma, Rui-Min; Chen, Chuan-Zhi; Zhang, Wei; You, Jie; Huang, Du-Ping; Guo, Gui-Long

    2016-01-01

    Abstract Chemotherapy-induced neutropenia (CIN) was the most apparent side effects of bone marrow suppression with adjuvant chemotherapy. Recently, several studies revealed that CIN may predict better outcomes. However, the researches upon breast cancer were still indefinite. We reviewed the female patients with pathologically diagnosed invasive breast cancer at the First Affiliated Hospital of Wenzhou Medical University, between Jan 2008 and Dec 2010. The lowest neutrophil counts in the second week after the first cycle of chemotherapy were collected. Clinicopathological characteristics and survival rates were compared and analyzed between the CIN group and non-CIN group. The median follow-up time was 62 months. The differences of over-all survival and local recurrence-free survival between the 2 groups were nonsense (P = 0.938, P = 0.695, respectively). But the disease-free survival and distant metastasis-free survival of the CIN group were statically significantly better (HR = 0.391, P = 0.009, and HR = 0.315, P = 0.005, respectively). The bone metastasis-free survival may be responsible for the differences (HR = 0.469, P = 0.005). Subgroup analyses showed the CIN may predict lower bone metastases rates with ER positive status, premenopause or younger age (≤ 40) (P = 0.002, P = 0.004, and P = 0.0001, respectively). Cox analysis showed younger ages, N staging, and the presence of CIN were associated with bone metastasis-free survival independently adjusting to peritumoral vascular invasion (P < 0.05). CIN may predict a decreased recurrence risk of breast cancer, especially bone metastases. PMID:27043697

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    2015-11-21

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

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

    PubMed Central

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

    2014-01-01

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

  13. Beliefs about the prevention of dengue and other febrile illnesses in Mérida, Mexico.

    PubMed

    Winch, P; Lloyd, L; Godas, M D; Kendall, C

    1991-12-01

    A series of open interviews and a survey were conducted in several neighbourhoods in the city of Mérida, Mexico to find out whether poor response to government dengue control programmes might be related to the explanatory models about dengue and its prevention held by community members. Dengue was grouped by informants with other mild febrile illnesses, all of which were thought to be inevitable and capable of converting into more serious illnesses. Although vector control personnel think of prevention in terms of eliminating the larval habitats of mosquito vectors, the form of prevention most commonly described involved looking after oneself once sick, so that mild fevers do not evolve into serious fevers. Due to the prevalence of this different model of prevention, it is argued that simple messages about dengue may be misinterpreted. Vector control programmes need to take into account local models of febrile illnesses and their prevention in order to be effective.

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

    PubMed Central

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

    2015-01-01

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

  15. Transient reduced diffusion in the cortex in a child with prolonged febrile seizures.

    PubMed

    Kato, Toru; Okumura, Akihisa; Hayakawa, Fumio; Tsuji, Takeshi; Natsume, Jun

    2012-10-01

    We report on a 4-year-old boy with transient reduced diffusion in the cortex, thalamus, and hippocampus on diffusion-weighted imaging (DWI) performed after prolonged febrile seizures (PFS). He had experienced intermittent right hemiconvulsions lasting about 90 min during the febrile illness, but his neurological symptom resolved completely after several hours. DWI performed immediately after the PFS showed abnormally high signal intensities in the left extended cortex and pulvinar of the ipsilateral thalamus. Two days later, these DWI lesions resolved completely, but abnormally high signal intensities were observed in the left hippocampus. Three months later, the DWI was normal, and no atrophy or gliosis was seen. This patient had unique lesions on DWI after PFS, but it is nevertheless important to attend to such lesions on the DWI of patients with PFS.

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

    PubMed

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

    2015-05-01

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

  17. Coxsackievirus-positive cervices in women with febrile illnesses during the third trimester in pregnancy.

    PubMed

    Reyes, M P; Zalenski, D; Smith, F; Wilson, F M; Lerner, A M

    1986-07-01

    Coxsackievirus B5 infection was demonstrated in five of seven third-trimester pregnant women with undifferentiated febrile illnesses or aseptic meningitis. Coxsackievirus B5 was recovered from the cervix and throat in four women and from the rectum in three. No obvious illnesses were evident in the babies. These findings suggest that previously unrecognized cervical enterovirus carriage or infection is common in infected pregnant women in the last trimester and that subsequent neonatal infection at delivery may result. PMID:3014880

  18. [Effects of eserine and ouabain on the febrile reaction induced by lipopolysaccharide].

    PubMed

    Ogawa, Y; Kano, S

    1976-07-01

    We investigated the effects of eserine and ouabain on the permeability of the blood-brain barrier (B.B.B.) as related to the febrile response induced with LPS in rabbit. Results are as follows; The febrile response induced by LPS (0.02 and 1.0 mug/kg) i.v. was suppressed by administration of ouabain (0.06 mg/kg, i.v.). Contrary to the febrile response of LPS given i.c. (10(-4) and 10(-3) mug/kg), the febrile response was not suppressed with the same dose of ouabain. The pyrogenicity of cerebrospinal fluid (CSF) withdrawn at two hours after rabbits had been injected with LPS (25 mug/kg) was suppressed by ouabain (0.06 mg/kg, i.v.). Pyrogenic response was enhanced by pretreatment with eserine (0.5 mg/kg, s.c.) given one hr before LPS (1 mug/kg, i.v.). The pyrogenicity of CSF was also potentiated to a greater extent by pretreatment of eserine than with LPS alone. In the eserinized rabbit (0.5 mg/kg, s.c.), the pyrogenicity of CSF was potentiated to a greater extent by ACh (10 mug/kg, i.v.) than by LPS (1 mug/kg, i.v.) alone. From these data, it is concluded that the inhibition of Na, K-ATPase by ouabain decreases the pyrogenicity of LPS, while the inhibition of cholinesterase by eserine enhances the pyrogenicity. PMID:1033114

  19. Colonization with Escherichia coli Strains among Female Sex Partners of Men with Febrile Urinary Tract Infection

    PubMed Central

    Sandberg, Torsten; Scheutz, Flemming; Clabots, Connie; Johnston, Brian D.; Thuras, Paul; Johnson, James R.

    2015-01-01

    Of 23 unique Escherichia coli strains from 10 men with febrile urinary tract infections (UTIs) and their female sex partners, 6 strains (all UTI causing) were shared between partners. Molecularly, the 6 shared strains appeared more virulent than the 17 nonshared strains, being associated with phylogenetic group B2, sequence types ST73 and ST127, and multiple specific virulence genes. This indicates that UTIs are sometimes sexually transmitted. PMID:25832302

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

    Yagoubi, Nawel; Jomni, Yosra; Sakly, Mohsen

    2015-01-01

    The aim of this study was to characterize a novel animal model hyperthermia-induced febrile seizure and to investigate the impacts of repetitive febrile seizures on spatial learning and memory performances in immature rats. Methods. Rats were subjected to hyperthermia exposure one, two, or three times in 10-day intervals during 30 min in a water bath warmed at 45–50°C and their behaviour was monitored. Morris water maze spatial learning and memory were examined for control and treated groups. Results showed that rats subjected to 30-minute hyperthermia hot water developed rapidly myoclonic jerks and then generalized seizures. After a single hyperthermia exposure, the time for generalised tonic-clonic seizures appearance was 16.08 ± 0.60 min and it decreased gradually with repetitive exposure to reach 12.46 ± 0.39 min by the third exposure. Febrile seizures altered the spatial learning and memory abilities in Morris water maze and increased the time spent to attain the platform after one or two exposures, while after a third exposure rats exhibited the same latency compared to controls. Similar results were obtained in probe test where rats, subjected to hyperthermia for one or two episodes, spent less time in the target quadrant compared to corresponding controls. Further, when platform was moved from northwest to southwest quadrant, memory transfer test indicated that after one or two hyperthermia exposures cognitive performances were slightly altered, while after a third exposure the latency to escape increased significantly compared to untreated group. It was concluded that 30 min of hyperthermia hot water was sufficient to induce febrile seizures in immature rats and an increase of susceptibility was observed with repetitive hyperthermia exposure. Hyperthermia treatment impaired cognitive performances but the effects were mostly transient and moderate. PMID:26063965

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

    PubMed

    Kolahi, Ali-Asghar; Tahmooreszadeh, Shahrokh

    2009-02-01

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

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

    PubMed

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

    2015-02-01

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

  4. Incidence and severity of infections according to the development of neutropenia during combined therapy with pegylated interferon-alpha2a plus ribavirin in chronic hepatitis C infection.

    PubMed

    Juarez-Navarro, A; Vera-de-León, L; Navarro, J M; Chirino-Sprung, R; Díaz-Hernandez, M; Casillas-Davila, L; Dehesa-Violante, M

    2005-06-01

    The evolution of treatment of chronic hepatitis C virus infection has led to improved therapeutic efficacy. However, a major problem is the presence of side effects that require modification or withdrawal of drug therapy in 15-20% of cases. This could potentially influence the lack of sustained viral response in 50% of the cases. Side effects are common, even with pegylated interferon. This study aimed to assess the incidence and severity of infections based on the development of neutropenia associated with combined therapy with pegylated interferon-alpha2a plus ribavirin in 209 patients with chronic hepatitis C infection. All patients were administered pegylated interferon-alpha2a (180 microg/week) plus ribavirin (800 mg/day for 24 weeks in cases of nongenotype 1, or 1000-1200 mg/day for 48 weeks for genotype 1, according to whether patients weighed more or less than 75 kg). Patients with preexisting neutropenia of any cause or cirrhosis were excluded. Neutropenia was defined as a neutrophil count (NC) of <1500 cells/microl. Neutropenia was classified into three levels during treatment: 750neutropenia (mean 2100+/-804 cells/microl), while 95 had an NC<1500 cells/microl (mean 1100+/-250 cells/microl). It was found that patients who developed neutropenia during treatment of chronic hepatitis C virus infection with a combined therapy based on pegylated interferon-alpha2a plus ribavirin did not show a higher infection rate or increased severity of the disease. PMID:16082419

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

    PubMed

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

    2011-02-01

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

  6. A study of'febrile illnesses on the Thai-Myanmar border: predictive factors of rickettsioses.

    PubMed

    PicKard, Amy L; McDaniel, Philip; Miller, R Scott; Uthaimongkol, Nichapat; Buathong, Nillawan; Murray, Clinton K; Telford, Sam R; Parola, Philippe; Wongsrichanalai, Chansuda

    2004-09-01

    We have performed a case-control analysis to determine the significance of clinical, laboratory and epidemiological features as predictive factors of rickettsioses among patients in Sangkhla Buri, Thailand (Thai-Myanmar border). Fifteen serologically-confirmed rickettsiosis patients including Spotted Fever Group (SFG) rickettsioses, scrub typhus, and murine typhus were classified as 'cases'; one hundred and sixty-three acutely febrile patients presenting to the same hospital during the same time period, who had no serological evidence of acute rickettsiosis, were classified as 'controls'. Patients' report of rash/arthropod bite [Odds ratio (OR) 22.90, 95% CI (confidence interval) 6.23, 84.13] and history of jungle trips (OR 5.30, 95% CI 1.69-16.62) were significant risk factors. Elevated ALT (OR 3.04, 95% CI 1.04, 8.88) and depressed platelet count (OR 3.38, 95% CI 1.13, 10.10) were also useful differentiating markers of rickettsioses in this population. Definitive diagnosis of rickettsioses is difficult without specialized diagnostic capabilities that are rarely available in remote areas such as Sangkhla Buri, where other acute febrile illnesses with similar presentation are commonly found. The relative importance of predictive factors presented here may provide clinicians with some useful guidance in distinguishing rickettsioses from other acute febrile illnesses. Timely administration of empiric treatment in highly suspicious cases can deter potential morbidity from these arthropod-borne infections.

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

    PubMed Central

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

    1998-01-01

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

 PMID:9489540

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-04-01

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

  12. Naturally Occurring Radioactive Materials (NORM)

    SciTech Connect

    Gray, P.

    1997-02-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training).

  13. Foliicolous microfungi occurring on Encephalartos.

    PubMed

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

    2008-12-01

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

  14. A novel UGT1 marker associated with better tolerance against irinotecan-induced severe neutropenia in metastatic colorectal cancer patients.

    PubMed

    Chen, S; Laverdiere, I; Tourancheau, A; Jonker, D; Couture, F; Cecchin, E; Villeneuve, L; Harvey, M; Court, M H; Innocenti, F; Toffoli, G; Lévesque, E; Guillemette, C

    2015-12-01

    The risk of severe irinotecan-induced neutropenia has been shown to be related to the UGT1 variant UGT1A1*28, which increases exposure to the potent metabolite SN-38. Our goal was to identify a novel UGT1 marker(s) using 28 haplotype-tagged single nucleotide polymorphisms genotyped by mass spectrometry. By characterizing the UGT1 sequence from a cohort of 167 Canadian metastatic colorectal cancer (mCRC) patients and a validation cohort of 250 Italian mCRC patients, we found rs11563250G, located in the intergenic region downstream of UGT1, to be significantly associated with reduced risk of severe neutropenia (odds ratio (OR)=0.21; P=0.043 and OR=0.27; P=0.036, respectively, and OR=0.31 when combined; P=0.001), which remained significant upon correction for multiple testing in the combined cohort (P=0.041). For the two-marker haplotype rs11563250G and UGT1A1*1 (rs8175347 TA6), the OR was of 0.17 (P=0.0004). Genetic testing of this marker may identify patients who might benefit from increased irinotecan dosing. PMID:25778466

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

    Abstract Granulopoiesis abnormalities have been described in association with thyroid disorders (TD). However, data regarding systematic evaluation of adult neutropenia and concurrent or prior TD are scarce. To investigate the frequency of TD among patients presenting with neutropenia, and the immunophenotypic and immunologic profile of neutropenic patients with concomitant thyroidopathy. Two hundred eighteen consecutive neutropenic patients were prospectively evaluated in our outpatient Hematology Clinic, with a detailed laboratory screen, including thyroid function tests, antineutrophil antibodies, blood lymphocytes immunophenotyping, and detection of T-cell clonality by PCR. Among 218 patients with neutropenia, 95 (43.6%) had TD, 65 chronic immunologic neutropenia, 20 clonal proliferation of T-large granular lymphocytes (T-LGL), 5 autoimmune disorders, and 33 other diagnoses. TD-patients had an increased frequency of recurrent infections compared with other patients (P = 0.045). The following correlations were found: negative correlation between FT3 and absolute neutrophil count (ANC) (r2 = −0.274, P = 0.007), negative correlation between TPO-Abs/TG-Abs and C4 (r2 = −0.16, P = 0.045; r2 = −0.266, P = 0.001), and CD4+ counts were inversely correlated to T4 and positively to TSH (r2 = −0.274, P = 0.024; r2 = 0.16, P = 0.045). In addition, TD-patients had significantly higher percentages of CD4+ lymphocytes (P = 0.003). Among TD-patients, 23.4% had Hashimoto thyroiditis (HT), 4.1%, Graves disease (GD), 8.2% nontoxic multinodular goiter (NTMG), 5% subclinical hypothyroidism, and 2.8% had undergone total thyroidectomy associated with nodules (TTM). Thirteen TD-patients displayed T-LGL. Patients with autoimmune thyroidopathy had an increased frequency of concomitant autoimmune manifestations (P = 0.03). Significant differences between the different thyroidopathies included: HT-patients had higher percentages

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

    PubMed Central

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

    2015-01-01

    Background Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in people with prolonged disease-related or therapy-related neutropenia. Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in people who lack their own functional granulocytes. This is an update of a Cochrane review first published in 2009. Objectives To determine the effectiveness and safety of prophylactic granulocyte transfusions compared with a control population not receiving this intervention for preventing all-cause mortality, mortality due to infection, and evidence of infection due to infection or due to any other cause in people with neutropenia or disorders of neutrophil function. Search methods We searched for randomised controlled trials (RCTs) and quasi-RCTs in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to April 20 2015. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs comparing people receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results Twelve trials met the inclusion criteria. One trial is still ongoing, leaving a total of 11 trials eligible involving 653 participants. These trials were conducted between 1978 and 2006 and enrolled participants from fairly comparable patient populations. None of the studies included people with

  18. Histiocytic sarcoma

    PubMed Central

    Machado, Eduardo Silva; de Miranda, Ana Carolina; Escopelli, Ticiane; Caron, Ruggero; Escopelli, Alessandra Cristhina

    2011-01-01

    A 59-year-old white woman, SC, after being treated for pneumonia, presented with an increase in the size of lymph nodes. The immunohistochemical examination diagnosed histiocytic sarcoma. Relapse occurred 12 months after starting chemotherapy. The patient evolved with febrile neutropenia, septic shock and death. PMID:23284265

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

    PubMed

    Whiskey, Eromona; Olofinjana, Olubanke; Taylor, David

    2011-06-01

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

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

    PubMed

    Whiskey, Eromona; Olofinjana, Olubanke; Taylor, David

    2011-06-01

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

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

    PubMed Central

    2012-01-01

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

  2. Caffeine, a naturally occurring acaricide.

    PubMed

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

    1991-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  5. Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan

    PubMed Central

    Hoskins, Janelle M; Rosner, Gary L; Ratain, Mark J; McLeod, Howard L; Innocenti, Federico

    2009-01-01

    Aims A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan. Materials & methods DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Associations between genotypes and haplotypes and log(absolute neutrophil count nadirs) were assessed by linear regression. Results No associations were observed. Conclusion Our findings suggest that the genes we tested do not influence toxicity of irinotecan when adminstered at 300-350 mg/m2. PMID:19604089

  6. Non-genetic leuko-neutropenia is related to dietary cholesterol: an experimental model with the rat.

    PubMed

    Ogunranti, J O

    1994-01-01

    A dietary factor is thought to be responsible for constant non-genetic neutropenia in Africans. The identify of this factor is unknown. The effect of diet on the differential white cell count in rat is studied. Twenty rats were divided into four dietary groups: (1) control rats on pellets, (2) millet, (3) peanut and (4) a special diet containing high cholesterol and saturated fatty acids from coconut, egg yolk, milk and Danish butter. After 3 months, group 4 rats had significantly higher total white cell counts and percentages of neutrophils in addition to higher serum cholesterol levels and higher weights. In the second experiment, pure cholesterol was injected intraperitoneally to rats while control rats received saline. Neutrophil counts increased 6 h after injection and peaked only in the test rats. It is concluded that low-cholesterol diet decreases neutrophil count. PMID:7817705

  7. Typhoid fever vs. malaria in a febrile returning traveler: typhomalaria revisited--an Oslerian perspective.

    PubMed

    Cunha, Burke A; Gran, Arthur; Munoz-Gomez, Sigridh

    2013-01-01

    Diagnostic efforts are usually centered on malaria in febrile travelers returning from the tropics. However, by focusing on malaria other important diagnostic considerations are easily overlooked. Patients returning from malarial areas are also exposed to other tropical diseases which have features in common with malaria, e.g., typhoid fever, dengue fever, chikungunya fever. However, there are a few key findings that clinically differentiate these infections from malaria. We present a case of a traveler with fever returning from India without localizing signs with persistent monocytosis initially thought to have malaria. PMID:23084022

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

    PubMed

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

    2015-01-01

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

  9. Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children

    PubMed Central

    2016-01-01

    Background The incidence of bacteremia caused by Gram-negative bacteria has increased recently in febrile neutropenic patients with the increase of antibiotic-resistant Gram-negative bacterial infections. This study aimed to identify the distribution of causative bacteria and the proportion of antibiotic-resistant bacteria in bacteremia diagnosed in febrile neutropenic children. Materials and Methods The medical records of febrile neutropenic children diagnosed with bacteremia between 2010 and 2014 were retrospectively reviewed. The causative bacteria and proportion of antibiotic-resistant bacteria were investigated and compared yearly during the study period. The clinical impact of antibiotic-resistant bacterial infections was also determined. Results A total of 336 bacteremia episodes were identified. During the entire study period, 181 (53.9%) and 155 (46.1%) episodes were caused by Gram-negative and Gram-positive bacteria, respectively. Viridans streptococci (25.9%), Klebsiella spp. (16.7%), and Escherichia coli (16.4%) were the most frequent causative bacteria. The overall distribution of causative bacteria was not significantly different annually. Antibiotic-resistant bacteria were identified in 85 (25.3%) episodes, and the proportion of antibiotic-resistant bacteria was not significantly different annually. Extended-spectrum β-lactamase-producing E. coli and Klebsiella spp. were most common among antibiotic-resistant Gram-negative bacteria, and they accounted for 30.6% (n = 34) of the identified E. coli and K. pneumoniae. Methicillin-resistant coagulase-negative staphylococci were most common among antibiotic-resistant Gram-positive bacteria, and it accounted for 88.5% (n = 23) of the identified coagulase-negative staphylococci. Antibiotic-resistant bacterial infections, especially antibiotic-resistant Gram-negative bacterial infections, caused significantly higher mortality due to bacteremia compared with non-antibiotic-resistant bacterial infections (P <0

  10. Febrile Ulceronecrotic Mucha-Habermann Disease: Two Cases with Excellent Response to Methotrexate.

    PubMed

    Griffith-Bauer, Kelly; Leitenberger, Sabra L; Krol, Alfons

    2015-01-01

    Febrile ulceronecrotic Mucha-Habermann disease (FUMHD), a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA), featuring large, ulcerative, necrotic skin plaques, high fever, and other systemic symptoms, is a rare disorder of unknown etiology. No randomized controlled trials have established treatment guidelines and multiple modalities are often employed, making it difficult to assess the efficacy of any single agent. We report two cases of this condition in which treatment with methotrexate plus antibiotic treatment for superinfection led to rapid improvement. PMID:26584702

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

    PubMed Central

    Bitar, Roger A

    2015-01-01

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

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

    PubMed

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

    2013-06-01

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

  13. Ciprofloxacin versus colistin prophylaxis during neutropenia in acute myeloid leukemia: two parallel patient cohorts treated in a single center

    PubMed Central

    Pohlen, Michele; Marx, Julia; Mellmann, Alexander; Becker, Karsten; Mesters, Rolf M.; Mikesch, Jan-Henrik; Schliemann, Christoph; Lenz, Georg; Müller-Tidow, Carsten; Büchner, Thomas; Krug, Utz; Stelljes, Matthias; Karch, Helge; Peters, Georg; Gerth, Hans U.; Görlich, Dennis; Berdel, Wolfgang E.

    2016-01-01

    Patients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapy-related neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. We report a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of more than seven days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematologic services at our hospital, as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs. without prophylaxis; P=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs. 79.5% in the colistin group; P=0.07), as determined by univariate analysis. This result was confirmed through multivariate analysis (OR: 0.475, 95%CI: 0.236–0.958; P=0.041). The prophylactic agents did not differ with regard to the microbiological findings (P=0.6, not significant). Of note, the use of ciprofloxacin was significantly associated with an increased rate of infections with pathogens that are resistant to the antibiotic used for prophylaxis (79.5% vs. 9.5% in the colistin group; P<0.0001). The risk factors for higher infection rates were the presence of a central venous catheter (P<0.0001), mucositis grade III/IV (P=0.0039), and induction/relapse courses (vs. consolidation; P<0.0001). In conclusion, ciprofloxacin prophylaxis appears to be of particular benefit during induction and relapse chemotherapy for acute myeloid leukemia. To prevent and control drug resistance, it may be safely replaced by colistin during consolidation cycles of acute myeloid leukemia therapy. PMID:27470601

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

    PubMed

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

    2001-12-01

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

  15. Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES).

    PubMed

    Pardo, Carlos A; Nabbout, Rima; Galanopoulou, Aristea S

    2014-04-01

    The mechanisms of epileptogenesis in pediatric epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with age-specific epileptic syndromes, such as infantile spasms and West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as infections or fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric epileptic syndromes in which acute and rapidly progressive encephalopathies preceded by fever and/or infections, such as febrile infection-related epilepsy syndrome, or in chronic progressive encephalopathies, such as Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8(+) T lymphocytes and neuroglial responses has been demonstrated in Rasmussen encephalitis, although the triggering factor of these responses remains unknown. Although the beneficial response to steroids and adrenocorticotropic hormone of infantile spasms, or preceding fever or infection in FIRES, may support a potential role of neuroinflammation as pathogenic factor, no definite demonstration of such involvement has been achieved, and genetic or metabolic factors are suspected. A major challenge for the future is discovering pathogenic mechanisms and etiological factors that facilitate the introduction of novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments in these pediatric epileptic syndromes. PMID:24639375

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

    PubMed Central

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

    2015-01-01

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

  17. Prenatal stress and early life febrile convulsions compromise hippocampal genes MeCP2/REST function in mid-adolescent life of Sprague-Dawley rats.

    PubMed

    Cassim, Sadiyah; Qulu, Lihle; Mabandla, Musa V

    2015-11-01

    Early life neuronal insults exacerbate the development of febrile seizures and can result in epigenetic changes in the hippocampus. The MeCP2 and REST genes play a pivotal role in cognition as both contribute to neuronal function. In this study, cognitive function and expression of the MeCP2 and REST genes in the hippocampus were investigated in four groups of Sprague Dawley rats offspring viz. (1) Normally reared treated with saline (NSS). (2) Prenatally stressed treated with saline (SS). (3) Normally reared with febrile seizures (NSFS). (4) Prenatally stressed with febrile seizures (SFS). Pregnant dams were subjected to 1h of restraint stress for 7days starting on gestational day 14. Following birth, a once-off exposure to saline injections or febrile seizure induction was conducted on postnatal day (PND) 14. Behavioural tests were conducted using the Morris-Water maze on PND 21 and 30. Our results showed a febrile seizure effect on learning and memory in the non-stressed animals. However, febrile seizures did not exacerbate learning deficits in the prenatally stressed animals. Gene analysis found a down-regulation in MeCP2 gene expression and an up-regulation of the REST gene in prenatally stressed animals. Exposure to febrile seizure resulted in down-regulation of both MeCP2 and REST gene expression in the non-stressed animals, but febrile seizures did not exacerbate the stress effect on gene expression. This suggests that exposure to prenatal stress (SS) and febrile seizures (NSFS) may impair cognitive behavioural function. However, in the NSFS animals, there seems to be an attempt to counteract the effects of febrile seizures with time. PMID:26358644

  18. Cognitive performance and convulsion risk after experimentally-induced febrile-seizures in rat.

    PubMed

    Rajab, Ebrahim; Abdeen, Zahra; Hassan, Zuhair; Alsaffar, Yousif; Mandeel, Mohammad; Al Shawaaf, Fatima; Al-Ansari, Sali; Kamal, Amer

    2014-05-01

    Many reports indicated that small percentage of children with febrile seizures develop epilepsy and cognitive disorders later in adulthood. In addition, the neuronal network of the hippocampus was reported to be deranged in adult animals after being exposed to hyperthermia-induced seizures in their neonatal life. The aims of this study were to investigate (1) latency and probability of seizures, (2) spatial learning and memory, in adult rats after neonatal hyperthermia-induced febrile seizures (FS). Prolonged FS were elicited in 10-day old, male Sprague Dawleys (n=11/group) by exposure to heated air (48-52 °C) for 30 min; control rats were exposed to 30 °C air. After 1.5 months the animal's cognitive performance was assessed by 5 day trial in the Morris water maze. In another experiment the latency and probability of seizures were measured in response to pentylenetetrazole (PTZ) injections (increased doses ranged from 7 to 140 mg/kg; i.p.). In water maze, both groups showed improvements in escape latency and distance swam to reach the platform; effects were significantly greater in control versus hyperthermia-treated animals on days 3 and 4. Latency and probability of PTZ-induced seizures were shorter and higher respectively, in hyperthermia-treated animals compared to controls. We concluded that FS in neonatal rats leads to enhanced susceptibility for seizures, as well as cognitive deficits in adults.

  19. Unsuspected Dengue as a Cause of Acute Febrile Illness in Children and Adults in Western Nicaragua

    PubMed Central

    Reller, Megan E.; de Silva, Aravinda M.; Miles, Jeremy J.; Jadi, Ramesh S.; Broadwater, Anne; Walker, Katie; Woods, Christopher; Mayorga, Orlando; Matute, Armando

    2016-01-01

    Background Dengue is an emerging infectious disease of global significance. Suspected dengue, especially in children in Nicaragua’s heavily-urbanized capital of Managua, has been well documented, but unsuspected dengue among children and adults with undifferentitated fever has not. Methodology/Principal Findings To prospectively study dengue in semi-urban and rural western Nicaragua, we obtained epidemiologic and clinical data as well as acute and convalescent sera (2 to 4 weeks after onset of illness) from a convenience sample (enrollment Monday to Saturday daytime to early evening) of consecutively enrolled patients (n = 740) aged ≥ 1 years presenting with acute febrile illness. We tested paired sera for dengue IgG and IgM and serotyped dengue virus using reverse transcriptase-PCR. Among 740 febrile patients enrolled, 90% had paired sera. We found 470 (63.5%) were seropositive for dengue at enrollment. The dengue seroprevalance increased with age and reached >90% in people over the age of 20 years. We identified acute dengue (serotypes 1 and 2) in 38 (5.1%) patients. Only 8.1% (3/37) of confirmed cases were suspected clinically. Conclusions/Significance Dengue is an important and largely unrecognized cause of fever in rural western Nicaragua. Since Zika virus is transmitted by the same vector and has been associated with severe congenital infections, the population we studied is at particular risk for being devastated by the Zika epidemic that has now reached Central America. PMID:27792777

  20. Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria

    PubMed Central

    Tran, Tuan M.; Jones, Marcus B.; Ongoiba, Aissata; Bijker, Else M.; Schats, Remko; Venepally, Pratap; Skinner, Jeff; Doumbo, Safiatou; Quinten, Edwin; Visser, Leo G.; Whalen, Elizabeth; Presnell, Scott; O’Connell, Elise M.; Kayentao, Kassoum; Doumbo, Ogobara K.; Chaussabel, Damien; Lorenzi, Hernan; Nutman, Thomas B.; Ottenhoff, Tom H. M.; Haks, Mariëlle C.; Traore, Boubacar; Kirkness, Ewen F.; Sauerwein, Robert W.; Crompton, Peter D.

    2016-01-01

    Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naïve Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naïve Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria. PMID:27506615

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

    SciTech Connect

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

    1989-03-01

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

  2. General practitioners' patterns of treatment of febrile travellers in north Queensland: an exploratory study.

    PubMed

    Engström, Kajsa L; Mills, Jane; McBride, William J H; Johansson, Caroline M

    2012-01-01

    In north Queensland, recurring epidemics of dengue fever are a public health concern. Each epidemic is initiated by an index case: an infected person arriving from an endemic country or region with dengue activity who then transmits the disease to local mosquitoes. A timely diagnosis of dengue in an index case and notification to public health services is essential to prevent epidemics. This qualitative study explores north Queensland general practitioners' experiences and patterns of treatment of febrile travellers. Individual, semi-structured interviews with 50 general practitioners working in north Queensland were conducted. Analysis of the data resulted in four themes for discussion: characteristics of febrile travellers presenting to local general practitioners, the cost of pathology tests as a barrier to diagnosis, appropriate pathology testing, and notifying tropical public health services. Recommendations from this study point to a need for ongoing education and training for general practitioners in best practice with regards pathology testing for suspected dengue fever cases. As well, there is a need to provide clearer guidelines to general practitioners on when to notify tropical public health services of suspicious diagnoses of dengue.

  3. Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania.

    PubMed

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

    2012-01-01

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

  4. Enhanced Surveillance for Fatal Dengue-Like Acute Febrile Illness in Puerto Rico, 2010-2012

    PubMed Central

    Rivera, Aidsa; Torres-Velasquez, Brenda; Hunsperger, Elizabeth A.; Munoz-Jordan, Jorge L.; Sharp, Tyler M.; Rivera, Irma; Sanabria, Dario; Blau, Dianna M.; Galloway, Renee; Torres, Jose; Rodriguez, Rosa; Serrano, Javier; Chávez, Carlos; Dávila, Francisco; Perez-Padilla, Janice; Ellis, Esther M.; Caballero, Gladys; Wright, Laura; Zaki, Sherif R.; Deseda, Carmen; Rodriguez, Edda; Margolis, Harold S.

    2016-01-01

    Background Dengue is a leading cause of morbidity throughout the tropics; however, accurate population-based estimates of mortality rates are not available. Methods/Principal Findings We established the Enhanced Fatal Acute Febrile Illness Surveillance System (EFASS) to estimate dengue mortality rates in Puerto Rico. Healthcare professionals submitted serum and tissue specimens from patients who died from a dengue-like acute febrile illness, and death certificates were reviewed to identify additional cases. Specimens were tested for markers of dengue virus (DENV) infection by molecular, immunologic, and immunohistochemical methods, and were also tested for West Nile virus, Leptospira spp., and other pathogens based on histopathologic findings. Medical records were reviewed and clinical data abstracted. A total of 311 deaths were identified, of which 58 (19%) were DENV laboratory-positive. Dengue mortality rates were 1.05 per 100,000 population in 2010, 0.16 in 2011 and 0.36 in 2012. Dengue mortality was highest among adults 19–64 years and seniors ≥65 years (1.17 and 1.66 deaths per 100,000, respectively). Other pathogens identified included 34 Leptospira spp. cases and one case of Burkholderia pseudomallei and Neisseria meningitidis. Conclusions/Significance EFASS showed that dengue mortality rates among adults were higher than reported for influenza, and identified a leptospirosis outbreak and index cases of melioidosis and meningitis. PMID:27727271

  5. Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.

    PubMed

    Tran, Tuan M; Jones, Marcus B; Ongoiba, Aissata; Bijker, Else M; Schats, Remko; Venepally, Pratap; Skinner, Jeff; Doumbo, Safiatou; Quinten, Edwin; Visser, Leo G; Whalen, Elizabeth; Presnell, Scott; O'Connell, Elise M; Kayentao, Kassoum; Doumbo, Ogobara K; Chaussabel, Damien; Lorenzi, Hernan; Nutman, Thomas B; Ottenhoff, Tom H M; Haks, Mariëlle C; Traore, Boubacar; Kirkness, Ewen F; Sauerwein, Robert W; Crompton, Peter D

    2016-01-01

    Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naïve Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naïve Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria. PMID:27506615

  6. The incidence of human herpesvirus 6 infection in children with febrile convulsion admitted to the University Hospital, Kuala Lumpur.

    PubMed

    Chua, K B; Lam, S K; AbuBakar, S; Koh, M T; Lee, W S

    1997-12-01

    From October 1996 to March 1997, 31 children with febrile convulsions were admitted to the University Hospital, Kuala Lumpur. Human Herpesvirus 6 (HHV 6) was virologically and/or serologically confirmed to be the cause of the febrile episode in 5 of these children (16.1%). Age, sex and other associated clinical features (diarrhoea, cough, running nose and type of seizure) were not useful in differentiating cases of febrile convulsion due to HHV 6 from those of other aetiology. However, uvulo-palatoglossal junctional ulcers were noted in children in whom the cause of the seizure could be attributed to HHV 6 but not in the remaining cases in the study group. HHV 6 DNA was detected in peripheral blood mononuclear cells from all patients with febrile convulsions attributed to HHV6, and in patients shown serologically to have already been exposed to the virus by nested polymerase chain reaction amplification. Only genotype HHV 6B was detected from patients with seizure due to HHV 6 but both genotype 6A and 6B were detected in the remaining cases studied.

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

    SciTech Connect

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

    1987-05-01

    Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (/sup 3/H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.

  8. Clericuzio-type Poikiloderma with Neutropenia Syndrome in a Turkish Family: a Three Report of Siblings with Mutation in the C16orf57 gene.

    PubMed

    Patiroglu, Turkan; Akar, H Haluk

    2015-06-01

    Clericuzio-type poikiloderma with neutropenia (PN) is characterized by poikiloderma, non-cyclic neutropenia, recurrent sinopulmonary infections, pachyonychia, and palmo-plantar hyperkeratosis. Mutations in the C16orf57 gene, which is located on chromosome 16q13, have been identified as the cause of PN. PN was first described by Clericuzio in Navajo Indians. Herein, we reported the clinical presentations and laboratory investigations of PN in three siblings from Turkey. The older siblings presented with typical cutaneous poikiloderma, plantar keratoderma, pachyonychia of toenails, and recurrent upper respiratory infections. As the most affected patient, in addition to classic manifestations, the youngest sibling had recurrent pneumonia, hepatosplenomegaly, dental caries, failure to thrive, and hand malformation. Genetic study revealed a homozygous mutation (c.531delA) in the C16orf57 gene in siblings. With the presented study, we aimed to draw attention to PN which can be a predisposing factor to malignancies. PMID:26546903

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  12. A Clinical Study of Acute Kidney Injury in Tropical Acute Febrile Illness

    PubMed Central

    Bhat, Ajay; Prabhu, Mangalore Venkatraya

    2016-01-01

    Introduction Tropical Acute Febrile Illness (TAFI) is one of the most common causes of morbidity within the community. Acute Kidney Injury (AKI) due to infective and non infective causes is a major complication. Presence of AKI is a major cause of mortality among patients with TAFI. Aim To study the spectrum of tropical acute febrile illness; the proportion, spectrum and staging of acute kidney injury; Renal Replacement Therapy (RRT) initiation and in-hospital mortality. Materials and Methods A total of 600 TAFI patients were prospectively studied at a tertiary care centre in coastal Karnataka between September 2012 and September 2014 for the aetiology of TAFI; the development and staging of AKI based on Kidney disease: Improving global outcomes (KDIGO) guidelines; the initiation of RRT and in-hospital mortality. Statistical Analysis: Data analysis was done using SPSS version 17.0 with statistical significance calculated using chi-square and Fisher’s exact t-test for which p-value <0.05 was considered significant. Results The spectrum of TAFI, in decreasing order, was vivax malaria, leptospirosis, dengue fever, falciparum malaria, mixed malaria, enteric fever, scrub typhus and the most common aetiology was malaria. The proportion of AKI was 54%. The most common cause of AKI, its stages 2 and 3, RRT initiation and in-hospital mortality was leptospirosis; and AKI stage 1 was dengue fever. KDIGO AKI stage 1, 2 and 3 was seen in 46.9%, 31.2% and 21.9% of AKI patients, respectively. RRT initiation was required in 10.2% of AKI patients and in-hospital mortality was 3% among all patients. AKI, RRT initiationand in-hospital mortality were significantly associated with older age, fever duration and other presenting complaints, examination findings, renal function and other parameters, leptospirosis, dengue fever, falciparum malaria. Conclusion The aetiology in about half of TAFI patients in coastal Karnataka was malaria. More than 50% develop AKI with greater than one

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2010-12-01

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

  15. Utilization of public or private health care providers by febrile children after user fee removal in Uganda

    PubMed Central

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

    2009-01-01

    Background Despite investments in providing free government health services in Uganda, many caretakers still seek treatment from the drug shops/private clinics. The study aimed to assess determinants for use of government facilities or drug shops/private clinics for febrile illnesses in children under five. Methods Structured questionnaires were administered to caretakers in 1078 randomly selected households in the Iganga – Mayuge Demographic Surveillance site. Those with children who had had fever in the previous two weeks and who had sought care from outside the home were interviewed on presenting symptoms and why they chose the provider they went to. Symptoms children presented with and reasons for seeking care from government facilities were compared with those of drug shops/private clinics. Results Of those who sought care outside the home, 62.7% (286/456) had first gone to drug shops/private clinics and 33.1% (151/456) first went to government facilities. Predictors of having gone to government facilities with a febrile child were child presenting with vomiting (OR 2.07; 95% CI 1.10 – 3.89) and perceiving that the health providers were qualified (OR 10.32; 95% CI 5.84 – 18.26) or experienced (OR 1.93; 95% CI 1.07 – 3.48). Those who took the febrile child to drug shops/private clinics did so because they were going there to get first aid (OR 0.20; 95% CI 0.08 – 0.52). Conclusion Private providers offer 'first aid' to caretakers with febrile children. Government financial assistance to health care providers should not stop at government facilities. Multi-faceted interventions in the private sector and implementation of community case management of febrile children through community medicine distributors could increase the proportion of children who access quality care promptly. PMID:19284673

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

    PubMed

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

    2016-07-10

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

  17. A LARGE KINDRED WITH X-LINKED NEUTROPENIA WITH AN I294T MUTATION OF THE WISKOTT-ALDRICH SYNDROME GENE

    PubMed Central

    Beel, Karolien; Cotter, Melanie M.; Blatny, Jan; Bond, Jonathan; Lucas, Geoff; Greene, Frances; Vanduppen, Vik; Leung, Daisy W.; Rooney, Sean; Smith, Owen P.; Rosen, Michael K.; Vandenberghe, Peter

    2011-01-01

    X-linked neutropenia (XLN, OMIM #300299) is a rare form of severe congenital neutropenia. It was originally described in a three-generation family with 5 affected members and with an L270P mutation in the GTP-ase binding domain (GBD) of the Wiskott-Aldrich-syndrome protein (WASP) (Devriendt, et al 2001). Here, we report and describe a large three-generation family with XLN, with 10 affected males and 8 female carriers. A c.882T>C WAS gene mutation was identified, resulting in an I294T mutation. The infectious course is variable and mild in view of the deep neutropenia. In addition to the original description, low-normal IgA levels, low to low-normal platelet counts and reduced NK-cell counts also appear as consistent XLN features. However, inverted CD4/CD8 ratios were not found in this family, nor were cases identified with myelodysplastic syndrome or acute myeloid leukaemia. Female carriers exhibited a variable attenuated phenotype. Like L270P WASP, I294T WASP is constitutively active towards actin polymerisation In conclusion, this largest XLN kindred identified to date provides new independent genetic evidence that mutations disrupting the auto-inhibitory GBD of WASP are the cause of XLN. Reduced NK cells, low to low normal platelet counts and low to low-normal IgA levels are also features of XLN. PMID:19006568

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

    SciTech Connect

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

    1986-04-01

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

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

    PubMed

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

    2008-05-01

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

  20. Unsuspected Dengue and Acute Febrile Illness in Rural and Semi-Urban Southern Sri Lanka

    PubMed Central

    Bodinayake, Champika; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara-Arachichi, Wasantha; Strouse, John J.; Broadwater, Anne; Østbye, Truls; de Silva, Aravinda; Woods, Christopher W.

    2012-01-01

    Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults. PMID:22304972

  1. Rickettsial Infections in Southeast Asia: Implications for Local Populace and Febrile Returned Travelers

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  3. Febrile episode among a floating population of C.R.P.F. Jawans stationed at Calcutta.

    PubMed

    Bhattacharjee, N; De, P M; Chakravarti, S K; Chakraborty, M S; Neogi, D K; Mukherjee, K K

    1995-06-01

    A virological investigation was carried out to establish the etiologic agent of a febrile outbreak amongst a floating population of C.R.P.F. Jawans, stationed at Calcutta during May-July, 1993. The illness was associated with fever, severe headache, bodyache and arthralgia which lasted for 2-4 days in most of the cases. Fifty cases were examined clinically and blood samples (both acute and convalescent) were subjected to virological study. One mouse-pathogenic agent could be isolated in suckling mice and identified as DEN-3. Sero-investigation of 50 single sera by HI & CF method revealed evidence of presumptive dengue infection in 33, while sero-conversion could be noted in 10 out of 25 available paired sera tested. Results of MAC ELISA revealed evidence of primary dengue infection in 6 out of 12 acute phase sera examined. Thus, the study shows that the episode is strongly suggestive of primary dengue infection.

  4. Unsuspected dengue and acute febrile illness in rural and semi-urban southern Sri Lanka.

    PubMed

    Reller, Megan E; Bodinayake, Champika; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara-Arachichi, Wasantha; Strouse, John J; Broadwater, Anne; Østbye, Truls; de Silva, Aravinda; Woods, Christopher W

    2012-02-01

    Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults.

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

    PubMed

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

    2013-10-01

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

  6. Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes.

    PubMed

    Udomsangpetch, Rachanee; Pipitaporn, Busaba; Silamut, Kamolrat; Pinches, Robert; Kyes, Sue; Looareesuwan, Sornchai; Newbold, Christopher; White, Nicholas J

    2002-09-01

    In falciparum malaria, the malaria parasite induces changes at the infected red blood cell surface that lead to adherence to vascular endothelium and other red blood cells. As a result, the more mature stages of Plasmodium falciparum are sequestered in the microvasculature and cause vital organ dysfunction, whereas the ring stages circulate in the blood stream. Malaria is characterized by fever. We have studied the effect of febrile temperatures on the cytoadherence in vitro of P. falciparum-infected erythrocytes. Freshly obtained ring-stage-infected red blood cells from 10 patients with acute falciparum malaria did not adhere to the principle vascular adherence receptors CD36 or intercellular adhesion molecule-1 (ICAM-1). However, after a brief period of heating to 40 degrees C, all ring-infected red blood cells adhered to CD36, and some isolates adhered to ICAM-1, whereas controls incubated at 37 degrees C did not. Heating to 40 degrees C accelerated cytoadherence and doubled the maximum cytoadherence observed (P < 0.01). Erythrocytes infected by ring-stages of the ICAM-1 binding clone A4var also did not cytoadhere at 37 degrees C, but after heating to febrile temperatures bound to both CD36 and ICAM-1. Adherence of red blood cells infected with trophozoites was also increased considerably by brief heating. The factor responsible for heat induced adherence was shown to be the parasite derived variant surface protein PfEMP-1. RNA analysis showed that levels of var mRNA did not differ between heated and unheated ring-stage parasites. Thus fever-induced adherence appeared to involve increased trafficking of PfEMP-1 to the erythrocyte membrane. Fever induced cytoadherence is likely to have important pathological consequences and may explain both clinical deterioration with fever in severe malaria and the effects of antipyretics on parasite clearance. PMID:12177447

  7. Frequency of Epstein - Barr Virus in Patients Presenting with Acute Febrile Illness in Kenya

    PubMed Central

    Masakhwe, Clement; Ochanda, Horace; Nyakoe, Nancy; Ochiel, Daniel; Waitumbi, John

    2016-01-01

    Background Most acute febrile illnesses (AFI) are usually not associated with a specific diagnosis because of limitations of available diagnostics. This study reports on the frequency of EBV viremia and viral load in children and adults presenting with febrile illness in hospitals in Kenya. Methodology/Principal Findings A pathogen surveillance study was conducted on patients presenting with AFI (N = 796) at outpatient departments in 8 hospitals located in diverse regions of Kenya. Enrollment criterion to the study was fever without a readily diagnosable infection. All the patients had AFI not attributable to the common causes of fever in Kenyan hospitals, such as malaria or rickettsiae, leptospira, brucella and salmonella and they were hence categorized as having AFI of unknown etiology. EBV was detected in blood using quantitative TaqMan-based qPCR targeting a highly conserved BALF5 gene. The overall frequency of EBV viremia in this population was 29.2%, with significantly higher proportion in younger children of <5years (33.8%, p = 0.039) compared to patients aged ≥5 years (26.3% for 5–15 years or 18.8% for >15 years). With respect to geographical localities, the frequency of EBV viremia was higher in the Lake Victoria region (36.4%), compared to Kisii highland (24.6%), Coastal region (22.2%) and Semi-Arid region (25%). Furthermore, patients from the malaria endemic coastal region and the Lake Victoria region presented with significantly higher viremia than individuals from other regions of Kenya. Conclusions/Significance This study provides profiles of EBV in patients with AFI from diverse eco-regions of Kenya. Of significant interest is the high frequency of EBV viremia in younger children. The observed high frequencies of EBV viremia and elevated viral loads in residents of high malaria transmission areas are probably related to malaria induced immune activation and resultant expansion of EBV infected B-cells. PMID:27163791

  8. Increased excitability and molecular changes in adult rats after a febrile seizure.

    PubMed

    Reid, Aylin Y; Riazi, Kiarash; Campbell Teskey, G; Pittman, Quentin J

    2013-04-01

    Both early life inflammation and prolonged febrile seizures have been associated with increased excitation in the adult brain. We hypothesized this may be due in part to changes in the cation-chloride cotransporter system. Rat pups received saline or lipopolysaccharide/kainic acid (LPS/KA) resulting in inflammation, followed by a behavioral febrile seizure (FS) in approximately 50% of rats. Adult animals from the saline, inflammation, or inflammation + FS groups underwent the following: (1) in vitro electrophysiologic studies; (2) Western blotting or polymerase chain reaction; or (3) application of the Na-K-Cl cotransporter 1 (NKCC1) blocker bumetanide to determine its effect on reversing increased excitability in vitro. The inflammation and inflammation + FS groups demonstrated increased excitability in vitro and increased hippocampal protein expression of NR2B and GABAA α5 receptor subunits and mRNA expression of NKCC1. The inflammation + FS group also had decreased protein expression of GluR2 and GABAA α1 receptor subunits and mRNA and protein expression of KCC2. Bumetanide decreased in vitro 4-aminopyridine-induced inter-ictal activity in the inflammation and inflammation + FS groups. The results demonstrate early-life inflammation with or without a behavioral FS can lead to long-lasting molecular changes and increased excitability in the adult rat hippocampus, although some changes are more extensive when inflammation is accompanied by behavioral seizure activity. Bumetanide is effective in reversing increased excitability in vitro, providing evidence for a causal role for cation-chloride cotransporters and suggesting this drug may prove useful for treating epilepsy that develops after a FS. PMID:23293960

  9. Urinary Colorimetric Sensor Array and Algorithm to Distinguish Kawasaki Disease from Other Febrile Illnesses

    PubMed Central

    Jin, Bo; Deng, Xiaohong; Hu, Guang; Liu, Xiaodan; Zhang, Jie; Jin, Hua; Huang, Min; Kanegaye, John T.; Tremoulet, Adriana H.; Burns, Jane C.; Wu, Jianmin; Cohen, Harvey J.; Ling, Xuefeng B.

    2016-01-01

    Objectives Kawasaki disease (KD) is an acute pediatric vasculitis of infants and young children with unknown etiology and no specific laboratory-based test to identify. A specific molecular diagnostic test is urgently needed to support the clinical decision of proper medical intervention, preventing subsequent complications of coronary artery aneurysms. We used a simple and low-cost colorimetric sensor array to address the lack of a specific diagnostic test to differentiate KD from febrile control (FC) patients with similar rash/fever illnesses. Study Design Demographic and clinical data were prospectively collected for subjects with KD and FCs under standard protocol. After screening using a genetic algorithm, eleven compounds including metalloporphyrins, pH indicators, redox indicators and solvatochromic dye categories, were selected from our chromatic compound library (n = 190) to construct a colorimetric sensor array for diagnosing KD. Quantitative color difference analysis led to a decision-tree-based KD diagnostic algorithm. Results This KD sensing array allowed the identification of 94% of KD subjects (receiver operating characteristic [ROC] area under the curve [AUC] 0.981) in the training set (33 KD, 33 FC) and 94% of KD subjects (ROC AUC: 0.873) in the testing set (16 KD, 17 FC). Color difference maps reconstructed from the digital images of the sensing compounds demonstrated distinctive patterns differentiating KD from FC patients. Conclusions The colorimetric sensor array, composed of common used chemical compounds, is an easily accessible, low-cost method to realize the discrimination of subjects with KD from other febrile illness. PMID:26859297

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

    PubMed

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

    2013-03-01

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

  11. Bacterial lipopolysaccharide augments febrile-range hyperthermia-induced heat shock protein 70 expression and extracellular release in human THP1 cells.

    PubMed

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

    2015-01-01

    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

  12. Tricuspid Papillary Fibroelastoma Mimicking Tricuspid Vegetation in a Patient with Severe Neutropenia

    PubMed Central

    Choi, Kuk Bin; Kim, Hwan Wook; Kim, Do Yeon; Jo, Keon Hyon; Choi, Hang Jun; Hong, Seok Beom

    2016-01-01

    We report a 72-year-old male with known myelodysplastic syndrome who presented to the emergency department with a 7-day history of fever and dyspnea. Echocardiography revealed a round echogenic mass 13×16 mm in size attached to the atrial side of the tricuspid valve. Considering the high risk of infective endocarditis in the patient with a low absolute neutrophil count (130/mm3), emergency surgery was performed. Intraoperatively, a single gelatinous neoplasm was resected, and subsequent reconstruction of the involved leaflet was accomplished using autologous pericardium. The tumor was pathologically confirmed as papillary fibroelastoma with no evidence of infective endocarditis. Papillary fibroelastoma is a rare cardiac neoplasm that occurs in either the mitral or aortic valves. Interestingly, a few cases of tricuspid valve papillary fibroelastoma have been reported so far. Similar echocardiographic findings between vegetation and tricuspid valve neoplasm make it difficult to distinguish these two disease entities. PMID:27298798

  13. Simple Prognostic Criteria can Definitively Identify Patients who Develop Severe Versus Non-Severe Dengue Disease, or Have Other Febrile Illnesses

    PubMed Central

    Falconar, Andrew K.I.; Romero-Vivas, Claudia M.E.

    2012-01-01

    Background Severe dengue disease (SDD) (DHF/DSS: dengue hemorrhagic fever/dengue shock syndrome) results from either primary or secondary dengue virus (DENV) infections, which occur 4 - 6 days after the onset of fever. As yet, there are no definitive clinical or hematological criteria that can specifically identify SDD patients during the early acute febrile-phase of disease (day 0 - 3: < 72 hours). This study was performed during a SDD (DHF/DSS) epidemic to: 1) identify the DENV serotypes that caused SDD during primary or secondary DENV infections; 2) identify simple clinical and hematological criteria that could significantly discriminate between patients who subsequently developed SDD versus non-SDD (N-SDD), or had a non-DENV fever of unknown origin (FUO) during day 0 - 3 of fever; 3) assess whether DENV serotype co-infections resulted in SDD. Methods First serum samples, with clinical and hematological criteria, were collected from 100 patients during the early acute febrile-phase (day 0 - 3: < 72 hours), assessed for DENV or FUO infections by IgM- and IgG-capture ELISAs on paired serum samples and by DENV isolations, and subsequently graded as SDD, N-SDD or FUO patients. Results In this study: 1) Thirty-three patients had DENV infections, predominantly secondary DENV-2 infections, including each SDD (DHF/DSS) case; 2) Secondary DENV-2/-3 and DENV-2/-4 serotype co-infections however resulted in N-SDD; 3) Each patient who subsequently developed SDD, but none of the others, displayed three clinical criteria: abdominal pain, conjunctival injection and veni-puncture bleeding, therefore each of these criteria provided definitively significant prognostic (P < 0.001) values; 4) Petechia, positive tourniquet tests and hepatomegaly, and neutrophilia or leukopenia also significantly identified those who: a) subsequently developed SDD versus N-SDD, or had a FUO; b) subsequently developed SDD versus N-SDD; c) subsequently developed N-SDD versus FUOs, respectively

  14. Association of Serum Soluble Triggering Receptor Expressed on Myeloid Cells Levels in Malignant Febrile Neutropenic Patients with Bacteremia and Fungemia

    PubMed Central

    Arzanian, Mohammad-Taghi; Soltani, Babak; Fahimzad, Alireza; Shiva, Farideh; Shamshiri, Ahmad-Reza; Karimi, Abdollah

    2011-01-01

    Objective Infections are the major cause of morbidity and mortality in febrile neutropenic patients with malignancy. Rapid diagnostic tests are needed for prompt diagnosis and early treatment which is crucial for optimal management. We assessed the utility of soluble triggering receptor expressed on myeloid cells (sTREM-1) in the diagnosis of bacteremia and fungemia in febrile neutropenic patients. Methods Sixty-five febrile neutropenic children with malignancy hospitalized in Mofid Children's Hospital during a period of one year from January 2007 were recruited for this cross sectional study (mean age 66.2± 37 months; 35 females and 30 males). Thirty patients (46.2%) had acute lymphoblastic leukemia, 2 (3.1%) acute myeloid leukemia, one (1.5%) lymphoma and 32 (49.2%) were under treatment for solid tumors. Simultaneous blood samples were collected for measurement of serum sTREM-1 levels and for blood cultures which were grown in BACTEC media. Gold standard for the presence of infection was a positive BACTEC culture as a more sensitive method compared to current blood culture techniques. Findings Blood cultures with BACTEC system were positive in 13(20%) patients (12 bacterial and one fungal culture). The mean serum sTREM-1 level in BACTEC positive patients was 948.2±592.9 pg/ml but in BACTEC negative cases it was 76.3±118.8 pg/ml (P<0.001). The optimal cut-off point of sTREM-1 for detecting patients with positive result of BACTEC was 525 pg/ml with sensitivity and specificity of 84.6% and 100%, respectively. Conclusion Our study revealed a significant association between serum sTREM-1 level and bacteremia and fungemia in febrile neutropenic patients suffering malignancy with acceptable sensitivity and specificity. PMID:23056805

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

    PubMed

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

    2013-09-01

    Elderly individuals are more susceptible to excess summer heat. We sought to examine whether the use of cooling systems (air-conditioning or fan) affected the clinical outcomes of elderly febrile patients. We prospectively followed elderly (≥ 75 years old) febrile patients requesting the medical services of the SOS Doctors (a network of physicians performing house-call visits) from July 10 to August 20, 2011. Patients who used cooling systems ("users") were compared with those who did not ("non-users") regarding mortality, clinical outcome of primary illness (improvement or deterioration), and emergency hospitalization. Prospectively collected data were available for 339 individual elderly febrile patients. "Users" had lower mortality (10 % vs. 19 %, p < 0.05) than "non-users"; no difference was noted on clinical improvement (85 % vs. 76 %, p = 0.11) and emergency hospitalization rates (21 % vs. 30 %, p = 0.16). No difference was noted between users of air-conditioning and fan regarding mortality or clinical improvement, but fan use was associated with more hospitalizations (37 % vs. 19 %, p < 0.05). On multivariate analysis (assessing daily ambient temperature, use of cooling systems, patient age, and living conditions), the sole variable significantly associated with mortality was the non-use of cooling systems [odds ratio (OR): 2.18, 95 % confidence interval (CI): 1.06-4.50]. The use of air-conditioning or fan during hot summer periods appeared to be beneficial for elderly febrile patients living in a large city. Large prospective studies are warranted in order to provide further insight into potential individual and public health initiatives aiming to alleviate the impact of excess summer heat on the health of elderly patients.

  16. Comprehensive analysis of serum cytokines/chemokines in febrile children with primary human herpes virus-6B infection.

    PubMed

    Nagasaka, Miwako; Morioka, Ichiro; Kawabata, Akiko; Yamagishi, Yoshiaki; Iwatani, Sota; Taniguchi-Ikeda, Mariko; Ishida, Akihito; Iijima, Kazumoto; Mori, Yasuko

    2016-09-01

    Cytokines and chemokines induced by primary human herpes virus (HHV)-6B infection may play a critical role in the clinical manifestations of infection. In this study, we analyzed 40 cytokines/chemokines in febrile children with primary HHV-6B infection. Blood samples from 233 febrile and 36 afebrile patients 0-3 years of age were used for this study. In febrile patients, primary HHV-6B infection was determined by detection of HHV-6B DNA without anti-HHV-6 immunoglobulin G in the blood (HHV-6B group). Infection by other pathogens was assumed when HHV-6B DNA was not detected in the blood (non-HHV-6B group). Of the 233 febrile patients, 30 patients (13%) were diagnosed with primary HHV-6B infection. To analyze serum cytokines/chemokines, patients were randomly chosen from the HHV-6B (n = 25) and non-HHV-6B groups (n = 8). Sera from 25 afebrile patients were used as a control. When comparing the levels of 40 cytokines/chemokines between the HHV-6B and control groups, we found that four chemokines (chemokine [C-X-C motif] ligand [CXCL] 11, CXCL10, CXCL16, and chemokine [C-C motif] ligand [CCL] 2) were significantly upregulated in the HHV-6B group compared with those in the control. Of these, only CXCL11 levels were significantly higher in the HHV-6B group than in the non-HHV-6B group. Because the induction of CCL2 was already reported in an early study, we found, for the first time, the induction of three new chemokines, i.e., CXCL11, CXCL10, and CXCL16 in patients with primary HHV-6B infection. Importantly, we demonstrated that serum CXCL11 levels increased specifically in patients with HHV-6B infection. PMID:27346377

  17. Molecular Detection of Streptococcus pneumoniae on Dried Blood Spots from Febrile Nigerian Children Compared to Culture

    PubMed Central

    Iroh Tam, Pui-Ying; Hernandez-Alvarado, Nelmary; Schleiss, Mark R.; Hassan-Hanga, Fatimah; Onuchukwu, Chuma; Umoru, Dominic; Obaro, Stephen K.

    2016-01-01

    Background Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture. Methods Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples. Results A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4–90.1%) and 62.5% (95% CI 24.5–91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture. Conclusions Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as

  18. Generalized epilepsy with febrile seizures plus (GEFS+) spectrum: clinical manifestations and SCN1A mutations in Indonesian patients.

    PubMed

    Herini, Elisabeth Siti; Gunadi; Harahap, Indra Sari Kusuma; Yusoff, Surini; Morikawa, Satoru; Patria, Suryono Yudha; Nishimura, Noriyuki; Sunartini; Sutaryo; Takada, Satoshi; Matsuo, Masafumi; Nishio, Hisahide

    2010-06-01

    Generalized epilepsy with febrile seizures plus (GEFS+) is a childhood genetic epilepsy syndrome. GEFS+ includes a wide spectrum of clinical manifestations, and SCN1A mutations have frequently been reported among the GEFS+-related gene abnormalities. In this study, to clarify the distributions of the clinical subtypes, we analyzed 34 families with GEFS+ in Indonesia using the hospital records of the patients and questionnaires for the family members. The number of patients with febrile seizures plus (FS+), FS+ and afebrile generalized/partial seizures, borderline severe myoclonic epilepsy in infancy (SMEB) and severe myoclonic epilepsy in infancy (SMEI) were 9, 11, 7, and 7, respectively. Most patients had a family history of febrile seizures. Next, we performed molecular analyses to clarify the contributions of SCN1A mutations to the development of the GEFS+ subtypes. Only 3 of 34 probands showed SCN1A mutations. These mutations were two missense mutations, p.V1612I and p.C1756G, in two patients with SMEI and SMEB, and one silent mutation, p.G1762G, in a patient with FS+ and afebrile partial seizures. In conclusion, the majority of GEFS+ patients in Indonesia were not associated with SCN1A mutations. To detect the GEFS+-causing mutations, we must search and analyze other genes in these patients.

  19. [Difficulties in the diagnosis of a febrile exanthema of different etiologies in a tuberculous patient in Madagascar].

    PubMed

    Rakotoarimanana, R; Rakotonirainy, O H; Razanamparany, O; Raonivelo, T; Ralandison, S

    2012-12-01

    This article illustrates the difficulties in the treatment of tuberculosis through the case of a patient with tuberculosis presenting with a haemophagocytic syndrome, severe drug hypersensitivity and a dissemination of the disease. A month after tuberculosis chemotherapy was started, Mrs. R.S, aged 45 years, presented with febrile exanthema, confusion, multiple lymph nodes enlargement/polyadenopathy, bi-cytopenia and a severe hepatic cytolysis. The haemophagocytic syndrome was confirmed by a myelogram and had shown a good response to the administration of methylprednisolone. Tuberculosis chemotherapy was stopped for a month and when resumed, there was a recurrence of the febrile exanthema without haematologic abnormalities but a moderate hepatic cytolysis. The association of haemophagocytic syndrome with tuberculosis is a rare occurrence. It was important to differentiate drug hypersensitivity and recurrence of haemophagocytic syndrome, as the sole treatment interruption was sufficient to heal the patient during the second febrile rash. Corticotherapy, discontinuation of tuberculostatic treatment and a very progressive reintroduction of antituberculosis drugs was successful though it caused the dissemination of the tuberculosis disease.

  20. Serum interleukin -8 is not a reliable marker for prediction of vesicoureteral reflux in children with febrile urinary tract infection

    PubMed Central

    Mahyar, Abolfazl; Ayazi, Parviz; Yarigarravesh, Mohammad Hadi; Khoeiniha, Mohammad Hossein; Oveisi, Sonia; Sahmani, Ahmad Ali; Esmaeily, Shiva

    2015-01-01

    ABSTRACT Objective: In view of the side effects of voiding cystourethrography (VCUG), identification of noninvasive markers predicting the presence of vesicoureteral reflux (VUR) is important. This study was conducted to determine the predictive value of serum interleukin-8 (IL-8) in diagnosis of VUR in children with first febrile urinary tract infection (UTI). Materials and Methods: Eighty children with first febrile UTI were divided into two groups, with and without VUR, based on the results of VCUG. The sensitivity, specificity, positive and negative predictive value positive and negative likelihood ratio, and accuracy of IL-8 for prediction of VUR were investigated. Results: Of the 80 children with febrile UTI, 30 (37.5%) had VUR. There was no significant difference between the children with and without VUR and also between low and high-grade VUR groups in terms of serum concentration of IL-8 (P>0.05). Based on ROC curve, the sensitivity, specificity, likelihood ratio positive, and accuracy of serum IL-8 was lower than those of erythrocyte sedimentation rate and C-reactive protein. Multivariate logistic regression analysis showed significant positive correlation only between erythrocyte sedimentation rate and VUR. Conclusions: This study showed no significant difference between the children with and without VUR in terms of the serum concentration of IL-8. Therefore, it seems that serum IL-8 is not a reliable marker for prediction of VUR. PMID:26742975

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

    PubMed

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

    2014-06-01

    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

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

    PubMed Central

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

    2013-01-01

    Background: Adenosine Deaminase (ADA) has been suggested to be an important enzyme which is associated with the cell mediated immunity, but its clinical significance in typhoid fever has not yet been characterized. The present study was taken up to evaluate the serum ADA activity in patients of typhoid fever. The levels of ADA were also measured in the patients who were suffering from other febrile illnesses. Material and Method: This was a case control study. The subjects who were included in this study were divided into 3 groups. Group A consisted of 50 normal healthy individuals who served as the controls. Group B consisted of 50 patients, both males and females of all age groups, who were suffering from culture positive typhoid fever. Group C consisted of 50 patients who were suffering from febrile illnesses other than typhoid fever like viral fever, gastro enteritis, malaria, tonsillitis, upper respiratory tract infections, etc. The serum levels of ADA were estimated in all the subjects who were under study. Results: The serum ADA level was found to be increased in the patients of typhoid fever as compared to that in those with other febrile illnesses and in the controls. Conclusion: From the present study, it can be concluded that there was a statistically significant increase in the serum ADA levels in the patients with typhoid. PMID:23730630

  3. 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

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

    2015-01-01

    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-μg/kg subcutaneous injection of PEG-rhG-CSF. The P-100 group had 30 cases, which received a single 100-μg/kg subcutaneous injection of PEG-rhG-CSF. The P + R group comprised 22 cases, which were given a single 50-μg/kg subcutaneous injection of PEG-rhG-CSF and rhG-CSF 5 μg/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 μg/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

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

    PubMed Central

    Gøtzsche, P. C.; Johansen, H. K.

    1997-01-01

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

  5. The role of biosimilar granulocyte colony stimulating factor (GCSF) Zarzio for progenitor cell mobilization and the treatment of therapy-induced neutropenia in adult hematopoietic stem cell transplantation.

    PubMed

    Severson, Cherie C

    2015-01-01

    Originator GCSF (Neupogen) has been used to mobilize progenitor stem cells and treat therapy-induced neutropenia in Canadian stem cell transplant settings for years. Although its benefit is not in question, viable alternatives are available. Biosimilar GCSF (Zarzio) is widely in use in Europe since 2009 and was recently approved in the U.S.for the same five indications as Neupogen. Zarzio is reported as safe, equally efficacious, more accessible and cost effective without negatively impacting patient outcomes. This paper summarizes the supporting evidence. PMID:26897866

  6. Two-Color Lateral Flow Assay for Multiplex Detection of Causative Agents Behind Acute Febrile Illnesses.

    PubMed

    Lee, Seoho; Mehta, Saurabh; Erickson, David

    2016-09-01

    Acute undifferentiated febrile illnesses (AFIs) represent a significant health burden worldwide. AFIs can be caused by infection with a number of different pathogens including dengue (DENV) and Chikungunya viruses (CHIKV), and their differential diagnosis is critical to the proper patient management. While rapid diagnostic tests (RDTs) for the detection of IgG/IgM against a single pathogen have played a significant role in enabling the rapid diagnosis in the point-of-care settings, the state-of-the-art assay scheme is incompatible with the multiplex detection of IgG/IgM to more than one pathogen. In this paper, we present a novel assay scheme that uses two-color latex labels for rapid multiplex detection of IgG/IgM. Adapting this assay scheme, we show that 4-plex detection of the IgG/IgM antibodies to DENV and CHIKV is possible in 10 min by using it to correctly identify 12 different diagnostic scenarios. We also show that blue, mixed, and red colorimetric signals corresponding to IgG, IgG/IgM, and IgM positive cases, respectively, can be associated with distinct ranges of hue intensities, which could be exploited by analyzer systems in the future for making accurate, automated diagnosis. This represents the first steps toward the development of a single RDT-based system for the differential diagnosis of numerous AFIs of interest. PMID:27490379

  7. Urinary tract infections in febrile infants younger than 8 weeks of age.

    PubMed

    Crain, E F; Gershel, J C

    1990-09-01

    In this prospective study of 442 infants younger than 8 weeks of age who attended a pediatric emergency department with temperature greater than or equal to 100.6 degrees F (38.1 degrees C), urinary tract infections (UTIs) were found in 33 patients (7.5%), 2 of whom were bacteremic. Clinical and laboratory data were not helpful for identifying UTIs. Of the 33 patients with UTIs, 32 had urinalyses recorded; 16 were suggestive of a UTI (more than five white blood cells per high-power field or any bacteria present). Of the 16 infants with apparently normal urinalysis results, three had an emergency department diagnosis suggesting an alternative bacterial focus of infection. If the physician had decided on the basis of apparently normal urinalysis results to forgo obtaining a urine culture, more than half of the UTIs would have been missed. Bag-collected specimens were significantly more likely to yield indeterminate urine culture results than either catheter or suprapubic specimens. In addition, uncircumcised males were significantly more likely to have a UTI than circumcised boys. These results suggest that a suprapubic or catheter-obtained urine specimen for culture is a necessary part of the evaluation of all febrile infants younger than 8 weeks of age, regardless of the urinalysis findings or another focus of presumed bacterial infection.

  8. Changing Epidemiology of Serious Bacterial Infections in Febrile Infants without Localizing Signs

    PubMed Central

    Watt, Kevin; Waddle, Erica; Jhaveri, Ravi

    2010-01-01

    Objective Historically, management of infants with fever without localizing signs (FWLS) has generated much controversy, with attempts to risk stratify based on several criteria. Advances in medical practice may have altered the epidemiology of serious bacterial infections (SBIs) in this population. We conducted this study to test the hypothesis that the rate of SBIs in this patient population has changed over time. Patients and Methods We performed a retrospective review of all infants meeting FWLS criteria at our institution from 1997–2006. We examined all clinical and outcome data and performed statistical analysis of SBI rates and ampicillin resistance rates. Results 668 infants met criteria for FWLS. The overall rate of SBIs was 10.8%, with a significant increase from 2002–2006 (52/361, 14.4%) compared to 1997–2001 (20/307, 6.5%) (p = 0.001). This increase was driven by an increase in E. coli urinary tract infections (UTI), particularly in older infants (31–90 days). Conclusions We observed a significant increase in E. coli UTI among FWLS infants with high rates of ampicillin resistance. The reasons are likely to be multifactorial, but the results themselves emphasize the need to examine urine in all febrile infants <90days and consider local resistance patterns when choosing empiric antibiotics. PMID:20805983

  9. Easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.

    PubMed

    Calvo, Eliana P; Sánchez-Quete, Fernando; Durán, Sandra; Sandoval, Isabel; Castellanos, Jaime E

    2016-11-01

    Dengue (DENV), chikungunya (CHIKV) and zika (ZIKV) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito Aedes aegypti. At initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. This paper reports the development of a rapid and specific nested-PCR for detection of DENV, CHIKV and ZIKV infection in the same sample. A set of six outer primers targeting the C-preM, E1, and E gene respectively was used in a multiplex one-step RT-PCR assay, followed by the second round of amplification with specific inner primers for each virus. The specificity of the present assay was validated with positive and negative serum samples for viruses and supernatants of infected cells. The assay was tested using clinical samples from febrile patients. In these samples, we detected mono and dual infections and a case of triple co-infection DENV-CHIKV-ZIKV. This assay might be a useful and an inexpensive tool for detection of these infections in regions where these arboviruses co-circulate.

  10. Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection

    PubMed Central

    Han, Song Yi; Lee, I Re; Park, Se Jin; Kim, Ji Hong

    2016-01-01

    Purpose Acute pyelonephritis (APN) is a serious bacterial infection that can cause renal scarring in children. Early identification of APN is critical to improve treatment outcomes. The neutrophil-lymphocyte ratio (NLR) is a prognostic marker of many diseases, but it has not yet been established in urinary tract infection (UTI). The aim of this study was to determine whether NLR is a useful marker to predict APN or vesicoureteral reflux (VUR). Methods We retrospectively evaluated 298 pediatric patients (age≤36 months) with febrile UTI from January 2010 to December 2014. Conventional infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and NLR were measured. Results WBC, CRP, ESR, and NLR were higher in APN than in lower UTI (P<0.001). Multiple logistic regression analyses showed that NLR was a predictive factor for positive dimercaptosuccinic acid (DMSA) defects (P<0.001). The area under the receiver operating characteristic (ROC) curve was high for NLR (P<0.001) as well as CRP (P<0.001) for prediction of DMSA defects. NLR showed the highest area under the ROC curve for diagnosis of VUR (P<0.001). Conclusion NLR can be used as a diagnostic marker of APN with DMSA defect, showing better results than those of conventional markers for VUR prediction. PMID:27186221

  11. The Optimal Management of Acute Febrile Encephalopathy in the Aged Patient: A Systematic Review

    PubMed Central

    Sheybani, Fereshte; Naderi, HamidReza; Sajjadi, Sareh

    2016-01-01

    The elderly comprise less than 13 percent of world population. Nonetheless, they represent nearly half of all hospitalized adults. Acute change in mental status from baseline is commonly seen among the elderly even when the main process does not involve the central nervous system. The term “geriatric syndrome” is used to capture those clinical conditions in older people that do not fit into discrete disease categories, including delirium, falls, frailty, dizziness, syncope, and urinary incontinence. Despite the growing number of elderly population, especially those who require hospitalization and the high burden of common infections accompanied by encephalopathy among them, there are several unresolved questions regarding the optimal management they deserve. The questions posed in this systematic review concern the need to rule out CNS infection in all elderly patients presented with fever and altered mental status in the routine management of febrile encephalopathy. In doing so, we sought to identify all potentially relevant articles using searches of web-based databases with no language restriction. Finally, we reviewed 93 research articles that were relevant to each part of our study. No prospective study was found to address how should AFE in the aged be optimally managed. PMID:26989409

  12. Unsuspected Leptospirosis Is a Cause of Acute Febrile Illness in Nicaragua

    PubMed Central

    Reller, Megan E.; Wunder, Elsio A.; Miles, Jeremy J.; Flom, Judith E.; Mayorga, Orlando; Woods, Christopher W.; Ko, Albert I.; Dumler, J. Stephen; Matute, Armando J.

    2014-01-01

    Background Epidemic severe leptospirosis was recognized in Nicaragua in 1995, but unrecognized epidemic and endemic disease remains unstudied. Methodology/Principal Findings To determine the burden of and risk factors associated with symptomatic leptospirosis in Nicaragua, we prospectively studied patients presenting with fever at a large teaching hospital. Epidemiologic and clinical features were systematically recorded, and paired sera tested by IgM-ELISA to identify patients with probable and possible acute leptospirosis. Microscopic Agglutination Test and PCR were used to confirm acute leptospirosis. Among 704 patients with paired sera tested by MAT, 44 had acute leptospirosis. Patients with acute leptospirosis were more likely to present during rainy months and to report rural residence and fresh water exposure. The sensitivity of clinical impression and acute-phase IgM detected by ELISA were poor. Conclusions/Significance Leptospirosis is a common (6.3%) but unrecognized cause of acute febrile illness in Nicaragua. Rapid point-of-care tests to support early diagnosis and treatment as well as tests to support population-based studies to delineate the epidemiology, incidence, and clinical spectrum of leptospirosis, both ideally pathogen-based, are needed. PMID:25058149

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

    PubMed

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

    2015-07-01

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

  14. The Optimal Management of Acute Febrile Encephalopathy in the Aged Patient: A Systematic Review.

    PubMed

    Sheybani, Fereshte; Naderi, Hamid Reza; Sajjadi, Sareh

    2016-01-01

    The elderly comprise less than 13 percent of world population. Nonetheless, they represent nearly half of all hospitalized adults. Acute change in mental status from baseline is commonly seen among the elderly even when the main process does not involve the central nervous system. The term "geriatric syndrome" is used to capture those clinical conditions in older people that do not fit into discrete disease categories, including delirium, falls, frailty, dizziness, syncope, and urinary incontinence. Despite the growing number of elderly population, especially those who require hospitalization and the high burden of common infections accompanied by encephalopathy among them, there are several unresolved questions regarding the optimal management they deserve. The questions posed in this systematic review concern the need to rule out CNS infection in all elderly patients presented with fever and altered mental status in the routine management of febrile encephalopathy. In doing so, we sought to identify all potentially relevant articles using searches of web-based databases with no language restriction. Finally, we reviewed 93 research articles that were relevant to each part of our study. No prospective study was found to address how should AFE in the aged be optimally managed. PMID:26989409

  15. Glucose-6-phosphate dehydrogenase deficiency A- variant in febrile patients in Haiti.

    PubMed

    Carter, Tamar E; Maloy, Halley; von Fricken, Michael; St Victor, Yves; Romain, Jean R; Okech, Bernard A; Mulligan, Connie J

    2014-08-01

    Haiti is one of two remaining malaria-endemic countries in the Caribbean. To decrease malaria transmission in Haiti, primaquine was recently added to the malaria treatment public health policy. One limitation of primaquine is that, at certain doses, primaquine can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd). In this study, we genotyped two mutations (A376G and G202A), which confer the most common G6PDd variant in West African populations, G6PDd A-. We estimated the frequency of G6PDd A- in a sample of febrile patients enrolled in an on-going malaria study who represent a potential target population for a primaquine mass drug administration. We found that 33 of 168 individuals carried the G6PDd A- allele (includes A- hemizygous males, A- homozygous or heterozygous females) and could experience toxicity if treated with primaquine. These data inform discussions on safe and effective primaquine dosing and future malaria elimination strategies for Haiti.

  16. Modified Glasgow Coma Scale to predict mortality in febrile unconscious children.

    PubMed

    Chaturvedi, P; Kishore, M

    2001-04-01

    A prospective hospital based study was conducted in the Department of Pediatrics of the Kasturba Hospital, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha to predict the mortality in children admitted with fever and unconsciousness using the Modified Glasgow Coma Scale (MGCS) score. Forty eight children were admitted with fever and unconsciousness; cases of febrile convulsions, epilepsy and cerebral palsy were excluded. MGCS scores were assessed on admission and repeated at 12 hours, 24 hours, 48 hours and 72 hours after admission in each case. Diagnosis in each case was confirmed by history, examinations and investigations. All the cases were regularly followed up till death/discharge. The overall mortality was 29.1% (14/48) out of which 85% (12/14) died within the first 24 hours. Mortality was highest in the toddler age group and in patients with pyogenic meningitis. There was a significant association between death and MGCS scores on admission with a post test probability for discharge being only 10% with a score of less than 5 and 99% with a score of more than 10 respectively. MGCS scores on admission can be used to predict mortality in patients hospitalized with fever and unconsciousness. The scale is simple, easy, can be applied at bed side and does not need any investigations. Its application in developing countries with limited investigative and intensive care facilities can help the treating physician decide regarding referral and counseling the parents regarding the probable clinical outcome.

  17. Virus identification in unknown tropical febrile illness cases using deep sequencing.

    PubMed

    Yozwiak, Nathan L; Skewes-Cox, Peter; Stenglein, Mark D; Balmaseda, Angel; Harris, Eva; DeRisi, Joseph L

    2012-01-01

    Dengue virus is an emerging infectious agent that infects an estimated 50-100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.

  18. Rapid diagnostic tests for non-malarial febrile illness in the tropics.

    PubMed

    Chappuis, F; Alirol, E; d'Acremont, V; Bottieau, E; Yansouni, C P

    2013-05-01

    The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.

  19. Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study.

    PubMed

    Suttinont, C; Losuwanaluk, K; Niwatayakul, K; Hoontrakul, S; Intaranongpai, W; Silpasakorn, S; Suwancharoen, D; Panlar, P; Saisongkorh, W; Rolain, J M; Raoult, D; Suputtamongkol, Y

    2006-06-01

    The adult patients who, between July 2001 and June 2002, presented at any of five hospitals in Thailand with acute febrile illness in the absence of an obvious focus of infection were prospectively investigated. Blood samples were taken from all of the patients and checked for aerobic bacteria and leptospires by culture. In addition, at least two samples of serum were collected at different times (on admission and 2-4 weeks post-discharge) from each patient and tested, in serological tests, for evidence of leptospirosis, rickettsioses, dengue and influenza. The 845 patients investigated, of whom 661 were male, had a median age of 38 years and a median duration of fever, on presentation, of 3.5 days. Most (76.5%) were agricultural workers and most (68.3%) had the cause of their fever identified, as leptospirosis (36.9%), scrub typhus (19.9%), dengue infection or influenza (10.7%), murine typhus (2.8%), Rickettsia helvetica infection (1.3%), Q fever (1%), or other bacterial infection (1.2%). The serological results indicated that 103 (12.2%) and nine (1%) of the patients may have had double and triple infections, respectively. Leptospirosis and rickettsioses, especially scrub typhus, were thus found to be major causes of acute, undifferentiated fever in Thai agricultural workers.

  20. Seroprevalence of antibodies against Chikungunya, Dengue, and Rift Valley fever viruses after febrile illness outbreak, Madagascar.

    PubMed

    Schwarz, Norbert G; 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

    2012-11-01

    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.

  1. Loss of synaptic Zn2+ transporter function increases risk of febrile seizures

    PubMed Central

    Hildebrand, Michael S.; Phillips, A. Marie; Mullen, Saul A.; Adlard, Paul A.; Hardies, Katia; Damiano, John A.; Wimmer, Verena; Bellows, Susannah T.; McMahon, Jacinta M.; Burgess, Rosemary; Hendrickx, Rik; Weckhuysen, Sarah; Suls, Arvid; De Jonghe, Peter; Scheffer, Ingrid E.; Petrou, Steven; Berkovic, Samuel F.; Reid, Christopher A.

    2015-01-01

    Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn2+) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn2+ homeostasis contributes to susceptibility is unknown. Synaptic Zn2+ is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn2+ into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn2+ increases the risk of FS and more broadly support the idea that impaired synaptic Zn2+ homeostasis can contribute to neuronal hyperexcitability. PMID:26647834

  2. Easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.

    PubMed

    Calvo, Eliana P; Sánchez-Quete, Fernando; Durán, Sandra; Sandoval, Isabel; Castellanos, Jaime E

    2016-11-01

    Dengue (DENV), chikungunya (CHIKV) and zika (ZIKV) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito Aedes aegypti. At initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. This paper reports the development of a rapid and specific nested-PCR for detection of DENV, CHIKV and ZIKV infection in the same sample. A set of six outer primers targeting the C-preM, E1, and E gene respectively was used in a multiplex one-step RT-PCR assay, followed by the second round of amplification with specific inner primers for each virus. The specificity of the present assay was validated with positive and negative serum samples for viruses and supernatants of infected cells. The assay was tested using clinical samples from febrile patients. In these samples, we detected mono and dual infections and a case of triple co-infection DENV-CHIKV-ZIKV. This assay might be a useful and an inexpensive tool for detection of these infections in regions where these arboviruses co-circulate. PMID:27477452

  3. Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer

    PubMed Central

    Di Lorenzo, Giuseppe; Bracarda, Sergio; Gasparro, Donatello; Gernone, Angela; Messina, Caterina; Zagonel, Vittorina; Puglia, Livio; Bosso, Davide; Dondi, Davide; Sonpavde, Guru; Lucarelli, Giuseppe; De Placido, Sabino; Buonerba, Carlo

    2016-01-01

    Abstract Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3–4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed “per cycle” incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel. The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis. “Per cycle” incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86–0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34–0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86–1; P = 0.07). Patients with a body surface area >2 m2 presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86–1; P = 0.07), but decreased odds of having G3 to 4 anemia. Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was

  4. Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles.

    PubMed

    Su, Fang-Yi; Chuang, Er-Yuan; Lin, Po-Yen; Chou, Yi-Chun; Chen, Chiung-Tong; Mi, Fwu-Long; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Lin, Kun-Ju; Sung, Hsing-Wen

    2014-04-01

    Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy.

  5. Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients.

    PubMed

    Atasilp, Chalirmporn; Chansriwong, Pichai; Sirachainan, Ekapob; Reungwetwattana, Thanyanan; Chamnanphon, Montri; Puangpetch, Apichaya; Wongwaisayawan, Sansanee; Sukasem, Chonlaphat

    2016-02-01

    UDP-glucuronosyltransferase1A1 (UGT1A1) polymorphisms have been related with irinotecan toxicity. The purpose of this study was to determine the associations between UGT1A1(*)28 and (*)6 polymorphisms and irinotecan toxicity in Thai patients with metastatic colorectal cancer. 44 metastatic colorectal cancer patients received irinotecan-based chemotherapy. Hematologic toxicities were determined in the first and second cycles of treatment. The genotypes of UGT1A1(*)28 and (*)6 were analyzed by pyrosequencing technique. The frequencies of genetic testing for UGT1A1(*)28 and (*)6 polymorphisms were 22.8% (TA6/TA7; 20.5%, TA7/TA7; 2.3%) and 15.9% (GA), respectively. No patients had the homozygous UGT1A1(*)6 (AA). Neither UGT1A1(*)28 nor UGT1A1(*)6 polymorphisms were significantly associated with severe hematologic toxicities. However, analysis of UGT1A1(*)28 and (*)6 in combination revealed an association with severe neutropenia in the first and second cycles (P = 0.044, P = 0.017, respectively). Both UGT1A1(*)28 and (*)6 polymorphisms may have an increased risk of irinotecan-induced neutropenia in Thai colorectal cancer patients. PMID:26830078

  6. Deficiency of the ribosome biogenesis gene Sbds in hematopoietic stem and progenitor cells causes neutropenia in mice by attenuating lineage progression in myelocytes.

    PubMed

    Zambetti, Noemi A; Bindels, Eric M J; Van Strien, Paulina M H; Valkhof, Marijke G; Adisty, Maria N; Hoogenboezem, Remco M; Sanders, Mathijs A; Rommens, Johanna M; Touw, Ivo P; Raaijmakers, Marc H G P

    2015-10-01

    Shwachman-Diamond syndrome is a congenital bone marrow failure disorder characterized by debilitating neutropenia. The disease is associated with loss-of-function mutations in the SBDS gene, implicated in ribosome biogenesis, but the cellular and molecular events driving cell specific phenotypes in ribosomopathies remain poorly defined. Here, we established what is to our knowledge the first mammalian model of neutropenia in Shwachman-Diamond syndrome through targeted downregulation of Sbds in hematopoietic stem and progenitor cells expressing the myeloid transcription factor CCAAT/enhancer binding protein α (Cebpa). Sbds deficiency in the myeloid lineage specifically affected myelocytes and their downstream progeny while, unexpectedly, it was well tolerated by rapidly cycling hematopoietic progenitor cells. Molecular insights provided by massive parallel sequencing supported cellular observations of impaired cell cycle exit and formation of secondary granules associated with the defect of myeloid lineage progression in myelocytes. Mechanistically, Sbds deficiency activated the p53 tumor suppressor pathway and induced apoptosis in these cells. Collectively, the data reveal a previously unanticipated, selective dependency of myelocytes and downstream progeny, but not rapidly cycling progenitors, on this ubiquitous ribosome biogenesis protein, thus providing a cellular basis for the understanding of myeloid lineage biased defects in Shwachman-Diamond syndrome. PMID:26185170

  7. Deficiency of the ribosome biogenesis gene Sbds in hematopoietic stem and progenitor cells causes neutropenia in mice by attenuating lineage progression in myelocytes

    PubMed Central

    Zambetti, Noemi A.; Bindels, Eric M. J.; Van Strien, Paulina M. H.; Valkhof, Marijke G.; Adisty, Maria N.; Hoogenboezem, Remco M.; Sanders, Mathijs A.; Rommens, Johanna M.; Touw, Ivo P.; Raaijmakers, Marc H. G. P.

    2015-01-01

    Shwachman-Diamond syndrome is a congenital bone marrow failure disorder characterized by debilitating neutropenia. The disease is associated with loss-of-function mutations in the SBDS gene, implicated in ribosome biogenesis, but the cellular and molecular events driving cell specific phenotypes in ribosomopathies remain poorly defined. Here, we established what is to our knowledge the first mammalian model of neutropenia in Shwachman-Diamond syndrome through targeted downregulation of Sbds in hematopoietic stem and progenitor cells expressing the myeloid transcription factor CCAAT/enhancer binding protein α (Cebpa). Sbds deficiency in the myeloid lineage specifically affected myelocytes and their downstream progeny while, unexpectedly, it was well tolerated by rapidly cycling hematopoietic progenitor cells. Molecular insights provided by massive parallel sequencing supported cellular observations of impaired cell cycle exit and formation of secondary granules associated with the defect of myeloid lineage progression in myelocytes. Mechanistically, Sbds deficiency activated the p53 tumor suppressor pathway and induced apoptosis in these cells. Collectively, the data reveal a previously unanticipated, selective dependency of myelocytes and downstream progeny, but not rapidly cycling progenitors, on this ubiquitous ribosome biogenesis protein, thus providing a cellular basis for the understanding of myeloid lineage biased defects in Shwachman-Diamond syndrome. PMID:26185170

  8. "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to Germany from Vacation in Southern Africa

    PubMed Central

    Wächtler, Martin; Margos, Gabriele; Ruske, Sabine; Jung, Jette; Löscher, Thomas; Wendtner, Clemens; Wieser, Andreas

    2016-01-01

    A 26 year-old female patient presented to the Tropical Medicine outpatient unit of the Ludwig Maximilians-University in Munich with febrile illness after returning from Southern Africa, where she contracted a bite by a large mite-like arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained blood smears and treatment was started with doxycycline for suspected tick-borne relapsing fever. The patient eventually recovered after developing a slight Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA-blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia duttonii, and B. parkeri. Further sequences obtained from the flagellin gene (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B. duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of 0.086 to B. hermsii in genetic analysis and only distant relations with classic Old World relapsing fever species. This revealed the presence of a novel species of tick-borne relapsing fever spirochetes that we propose to name “Candidatus Borrelia kalaharica”, as it was contracted from an arthropod bite in the Kalahari Desert belonging to both, Botswana and Namibia, a region where to our knowledge no relapsing fever has been described so far. Interestingly, the novel species shows more homology to New World relapsing fever Borrelia such as B. parkeri or B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. PMID:27031729

  9. Effects of peripheral cold application on core body temperature and haemodynamic parameters in febrile patients.

    PubMed

    Asgar Pour, Hossein; Yavuz, Meryem

    2014-04-01

    This study designed to assess the effects of peripheral cold application (PCA) on core body temperature and haemodynamic parameters in febrile patients. This study was an experimental, repeated-measures performed in the neurosurgical intensive-care unit. The research sample included all patients with fever in postoperative period. PCA was performed for 20 min. During fever, systolic blood pressure, mean arterial blood pressure and arterial oxygen saturation (O2 Sat) decreased by 5.07 ± 7.89 mm Hg, 0.191 ± 6.00 mm Hg and 0.742% ± 0.97%, respectively, whereas the pulse rate and diastolic blood pressure increased by 8.528 ± 4.42 beats/ min and 1.842 ± 6.9 mmHg, respectively. Immediately after PCA, core body temperature and pulse rate decreased by 0.3°C, 3.3 beats/min, respectively, whereas systolic, diastolic, mean arterial blood pressure and O2 Sat increased by, 1.40 mm Hg, 1.87 mm Hg, 0.98 mmHg and 0.27%, respectively. Thirty minutes after the end of PCA, core body temperature, diastolic, mean arterial blood pressure and pulse rate decreased by 0.57°C, 0.34 mm Hg, 0.60 mm Hg and 4.5 beats/min, respectively, whereas systolic blood pressure and O2 Sat increased by 0.98 mm Hg and 0.04%, respectively. The present results showed that PCA increases systolic, diastolic, mean arterial blood pressure and O2 Sat, and decreases core body temperature and pulse rate.

  10. Chikungunya Fever Among Patients with Acute Febrile Illness Attending a Tertiary Care Hospital in Mumbai

    PubMed Central

    Galate, Lata Baswanna; Agrawal, Sachee R; Shastri, Jayanthi S; Londhey, Vikram

    2016-01-01

    Background: Chikungunya fever (CHIK) is an arboviral disease. Dengue fever (DENG) and CHIK are indistinguishable clinically and need to be differentiated by laboratory investigations. Purpose: This study aimed at estimating the seroprevalence of CHIK mono-infection and CHIK and DENG dual infection in suspected patients. We also analyzed the age, sex distribution, joint involvement, and relation of joint movement restriction with visual analog scale (VAS). Materials and Methods: Two hundred patients clinically suspected with DENG and CHIK were enrolled from a Tertiary Care Hospital in Mumbai from April 2012 to October 2013. The detailed history and examination findings were recorded. Serum samples were subjected to DENG and CHIK immunoglobulin G (IgM) enzyme-linked immunosorbent assay (ELISA). Results: The seroprevalence of CHIK was 12.5%. Mono-infection of CHIK was 3%, and CHIK and DENG dual infection was 9.5%. Most affected age group in CHIK cases was 46–60 years wherein female preponderance was seen. All 6 patients with CHIK mono-infection had fever and joint involvement; knee and elbow were the most commonly affected joints. All CHIK patients had VAS score of 6–10 with restricted joint movement. Of the patients with dual infection, the majorities were from 31 to 45 years with male preponderance; all had fever and joint pain mainly affecting knee and elbow. Of patients who had VAS score 6–10 in patients with dual infection, only 5.26% had restricted joint movement. Conclusion: IgM ELISA for Chikungunya infection should be included in the routine laboratory tests for acute febrile illness. PMID:27365916

  11. Molecular viral epidemiology and clinical characterization of acute febrile respiratory infections in hospitalized children in Taiwan.

    PubMed

    Lee, Chun-Yi; Chang, Yu-Fen; Lee, Chia-Lin; Wu, Meng-Che; Ho, Chi-Lin; Chang, Yu-Chuan; Chan, Yu-Jiun

    2015-11-01

    Acute respiratory infection (ARI) is a leading cause of morbidity and hospitalization in children. To profile the viruses causing ARI in children admitted to a community-based hospital in central Taiwan, a cross-sectional study was conducted on children under 14 years of age that were hospitalized with febrile ARI. Viral etiology was determined using conventional cell culture and a commercial respiratory virus panel fast assay (xTAG RVP), capable of detecting 19 different respiratory viruses and subtype targets. Demographic, clinical, and laboratory data were recorded and analyzed. The RVP fast assay identified at least one respiratory virus in 130 of the 216 specimens examined (60.2%) and rose to 137 (63.4%) by combining the results of cell culture and RVP fast assay. In order of frequency, the etiological agents identified were, rhinovirus/enterovirus (24.6%), respiratory syncytial virus (13.8%), adenovirus (11.5%), parainfluenza virus (9.2%), influenza B (8.4%), influenza A (5.4%), human metapneumovirus (4.6%), human coronavirus (2%), and human bocavirus (2%). Co-infection did not result in an increase in clinical severity. The RVP assay detected more positive specimens, but failed to detect 6 viruses identified by culture. The viral detection rate for the RVP assay was affected by how many days after admission the samples were taken (P = 0.03). In conclusion, Rhinovirus/enterovirus, respiratory syncytial virus, and adenovirus were prevalent in this study by adopting RVP assay. The viral detection rate is influenced by sampling time, especially if the tests are performed during the first three days of hospitalization.

  12. Congenital Neutropenia Syndromes

    MedlinePlus

    ... Patients Procedure for Accessing Lab Services Data Package Requirements AIDS Therapies Resource Guide In Vitro Efficacy Evaluations ... Assurances to Users Application and Approval Process User Requirements Malaria Vaccine Production Services Data Sharing and Release ...

  13. Influence of pregnancy on the febrile response to ICV administration of PGE1 in rats studied in a thermocline.

    PubMed

    Eliason, H L; Fewell, J E

    1997-05-01

    Rats near term of pregnancy have an attenuated febrile response to intracerebroventricular (ICV) injection of prostaglandin E1 (PGE1) when they are studied at an ambient temperature below their thermoneutral zone. Given that nonshivering thermogenesis in brown adipose tissue is impaired in rodents near term of pregnancy, it is possible that the attenuated febrile response is forced by impairment of this component of the autonomic thermoregulatory response. If this were the case, then near-term pregnant rats should develop a "normal" fever after PGE1 administration if they were studied in a thermocline where they could utilize behavioral as well as autonomic thermoregulatory effectors to increase their body core temperature (Tbc). Experiments were, therefore, carried out on 13 nonpregnant and 14 pregnant chronically instrumented rats in a thermocline (temperature gradient 10-40 degrees C) to investigate their Tbc responses to ICV injection of PGE1. ICV injection of 0.2 microgram PGE1 produced significant increases in Tbc and fever index in both nonpregnant and pregnant animals (day 19 of gestation); the increases, however, were significantly attenuated in the pregnant compared with the nonpregnant rats. Behavioral (e.g., selected ambient temperature) and autonomic (e.g., oxygen consumption) thermoregulatory effectors were activated to increase Tbc after ICV PGE1 in both groups of animals, but the duration of activation was shortened in pregnant compared with nonpregnant rats. The abbreviated thermoregulatory effector responses and the resulting attenuated febrile response to PGE1 in the pregnant rats may have resulted from a pregnancy-related activation of an endogenous antipyretic system.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

  16. Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis

    PubMed Central

    Oguri, Masayoshi; Saito, Yoshiaki; Fukuda, Chisako; Kishi, Kazuko; Yokoyama, Atsushi; Lee, Sooyoung; Torisu, Hiroyuki; Toyoshima, Mitsuo; Sejima, Hitoshi; Kaji, Shunsaku; Hamano, Shin-ichiro; Okanishi, Toru; Tomita, Yutaka; Maegaki, Yoshihiro

    2016-01-01

    Background To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. Methods We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. Results Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. Conclusion Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD. PMID:27046946

  17. Adverse events occurring after smallpox vaccination.

    PubMed

    Lane, J Michael; Goldstein, Joel

    2003-07-01

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

  18. Stroke-Like Presentation Following Febrile Seizure in a Patient with 1q43q44 Deletion Syndrome

    PubMed Central

    Robinson, J. Elliott; Wolfe, Stephanie M.; Kaiser-Rogers, Kathleen; Greenwood, Robert S.

    2016-01-01

    Hemiconvulsion–hemiplegia–epilepsy syndrome (HHE) is a rare outcome of prolonged hemiconvulsion that is followed by diffuse unilateral hemispheric edema, hemiplegia, and ultimately hemiatrophy of the affected hemisphere and epilepsy. Here, we describe the case of a 3-year-old male with a 1;3 translocation leading to a terminal 1q43q44 deletion and a terminal 3p26.1p26.3 duplication that developed HHE after a prolonged febrile seizure and discuss the pathogenesis of HHE in the context of the patient’s complex genetic background. PMID:27199890

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

    PubMed

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

    2014-02-01

    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.

  20. Prediction of Cortical Defect Using C-Reactive Protein and Urine Sodium to Potassium Ratio in Infants with Febrile Urinary Tract Infection

    PubMed Central

    Jung, Su Jin

    2016-01-01

    Purpose We investigated whether C-reactive protein (CRP) levels, urine protein-creatinine ratio (uProt/Cr), and urine electrolytes can be useful for discriminating acute pyelonephritis (APN) from other febrile illnesses or the presence of a cortical defect on 99mTc dimercaptosuccinic acid (DMSA) scanning (true APN) from its absence in infants with febrile urinary tract infection (UTI). Materials and Methods We examined 150 infants experiencing their first febrile UTI and 100 controls with other febrile illnesses consecutively admitted to our hospital from January 2010 to December 2012. Blood (CRP, electrolytes, Cr) and urine tests [uProt/Cr, electrolytes, and sodium-potassium ratio (uNa/K)] were performed upon admission. All infants with UTI underwent DMSA scans during admission. All data were compared between infants with UTI and controls and between infants with or without a cortical defect on DMSA scans. Using multiple logistic regression analysis, the ability of the parameters to predict true APN was analyzed. Results CRP levels and uProt/Cr were significantly higher in infants with true APN than in controls. uNa levels and uNa/K were significantly lower in infants with true APN than in controls. CRP levels and uNa/K were relevant factors for predicting true APN. The method using CRP levels, u-Prot/Cr, u-Na levels, and uNa/K had a sensitivity of 94%, specificity of 65%, positive predictive value of 60%, and negative predictive value of 95% for predicting true APN. Conclusion We conclude that these parameters are useful for discriminating APN from other febrile illnesses or discriminating true APN in infants with febrile UTI. PMID:26632389

  1. Co-circulation of Plasmodium and Bacterial DNAs in Blood of Febrile and Afebrile Children from Urban and Rural Areas in Gabon.

    PubMed

    Mourembou, Gaël; Nzondo, Sydney Maghendji; Ndjoyi-Mbiguino, Angélique; Lekana-Douki, Jean Bernard; Kouna, Lady Charlène; Matsiegui, Pierre Blaise; Manego, Rella Zoleko; Moukandja, Irene Pegha; Keïta, Alpha Kabinet; Tissot-Dupont, Hervé; Fenollar, Florence; Raoult, Didier

    2016-07-01

    Malaria is considered to be the most common etiology of fever in sub-Saharan Africa while bacteremias exist but are under assessed. This study aimed to assess bacteremias and malaria in children from urban and rural areas in Gabon. DNA extracts from blood samples of 410 febrile and 60 afebrile children were analyzed using quantitative polymerase chain reaction. Plasmodium spp. was the microorganism most frequently detected in febrile (78.8%, 323/410) and afebrile (13.3%, 8/60) children, (P < 0.001). DNA from one or several bacteria were detected in 15 febrile patients (3.7%) but not in the controls (P = 0.1). This DNA was more frequently detected as co-infections among febrile children tested positive for Plasmodium (4.6%, 15/323) than in those tested negative for Plasmodium (0%, 0/87; P = 0.04). The bacteria detected were Streptococcus pneumoniae 2.4% (10/410), Staphylococcus aureus 1.7% (7/410), Salmonella spp. 0.7% (3/410), Streptococcus pyogenes 0.2% (1/410) and Tropheryma whipplei 0.2% (1/410) only in febrile children. Coxiella burnetii, Borrelia spp., Bartonella spp., Leptospira spp., and Mycobacterium tuberculosis were not observed. This paper reports the first detection of bacteremia related to T. whipplei in Gabon and shows that malaria decreases in urban areas but not in rural areas. Co-infections in febrile patients are common, highlighting the need to improve fever management strategies in Gabon. PMID:27114297

  2. Young Children's Reports of when Learning Occurred

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  3. Naturally occurring iridoids. A review, part 1.

    PubMed

    Dinda, Biswanath; Debnath, Sudhan; Harigaya, Yoshihiro

    2007-02-01

    A compilation of new naturally occurring iridoid glycosides, iridoid aglycones, iridoid derivatives and bis-iridoids reported during 1994-2005 is provided with available physical and spectral data: mp, [alpha]D, UV, IR, 1H- and 13C-NMR as well as natural source with family and references. 418 compounds with 202 references are cited.

  4. Phonetic Recalibration Only Occurs in Speech Mode

    ERIC Educational Resources Information Center

    Vroomen, Jean; Baart, Martijn

    2009-01-01

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

  5. Preferential flow occurs in unsaturated conditions

    USGS Publications Warehouse

    Nimmo, John R.

    2012-01-01

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

  6. Cost of dengue and other febrile illnesses to households in rural Cambodia: a prospective community-based case-control study

    PubMed Central

    Huy, Rekol; Wichmann, Ole; Beatty, Mark; Ngan, Chantha; Duong, Socheat; Margolis, Harold S; Vong, Sirenda

    2009-01-01

    Background The average annual reported dengue incidence in Cambodia is 3.3/1,000 among children < 15 years of age (2002–2007). To estimate the economic burden of dengue, accurate cost-of-illness data are essential. We conducted a prospective, community-based, matched case-control study to assess the cost and impact of an episode of dengue fever and other febrile illness on households in rural Cambodia. Methods In 2006, active fever surveillance was conducted among a cohort of 6,694 children aged ≤ 15 years in 16 villages in Kampong Cham province, Cambodia. Subsequently, a case-control study was performed by individually assigning one non-dengue febrile control from the cohort to each laboratory-confirmed dengue case. Parents of cases and controls were interviewed using a standardized questionnaire to determine household-level, illness-related expenditures for medical and non-medical costs, and estimated income loss (see Additional file 1). The household socio-economic status was determined and its possible association with health seeking behaviour and the ability to pay for the costs of a febrile illness. Results Between September and November 2006, a total of 60 household heads were interviewed: 30 with dengue-positive and 30 with dengue-negative febrile children. Mean total dengue-related costs did not differ from those of other febrile illnesses (31.5 vs. 27.2 US$, p = 0.44). Hospitalization almost tripled the costs of dengue (from 14.3 to 40.1 US$) and doubled the costs of other febrile illnesses (from 17.0 to 36.2 US$). To finance the cost of a febrile illness, 67% of households incurred an average debt of 23.5 US$ and higher debt was associated with hospitalization compared to outpatient treatment (US$ 23.1 vs. US$ 4.5, p < 0.001). These costs compared to an average one-week expenditure on food of US$ 9.5 per household (range 2.5–21.3). In multivariate analysis, higher socio-economic status (odds ratio [OR] 4.4; 95% confidence interval [CI] 1.4–13

  7. Could a megaquake occur in the Himalayas?

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2011-12-01

    GPS measurements of crustal deformation are showing that a magnitude 9 earthquake could occur in the Himalayas. Roger Bilham of the University of Colorado at Boulder reported at the AGU Fall Meeting that the region, known to be seismically active, could produce a much larger earthquake than previously thought. Bilham and colleagues used GPS to monitor rates of crustal deformation in the Himalayas. They found that the potential rupture zone is larger than scientists had believed—the region where strain is building is twice as wide as expected. Previous estimates, which were based on the historical earthquake record, suggested that the largest earthquake that would occur in the region would have a magnitude in the low 8s. Such an earthquake could be devastating—the Kashmir valley region alone is home to 6 million people.

  8. Young children's reports of when learning occurred.

    PubMed

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

    2007-06-01

    This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about when the different learning events occurred. Responses of children who responded correctly to control questions about time supported the hypothesis that temporal distance questions would elicit more correct responses than would temporal location questions. Partial support was also found for the hypothesis that behavior learning would generate more correct reports than would fact learning. Implications for characterizations of children's developing understanding of knowledge and for applications of those characterizations in education and eyewitness testimony are discussed. PMID:17346740

  9. Synthesis of Naturally Occurring Tropones and Tropolones

    PubMed Central

    Liu, Na; Song, Wangze; Schienebeck, Casi M.; Zhang, Min; Tang, Weiping

    2014-01-01

    Tropones and tropolones are an important class of seven-membered non-benzenoid aromatic compounds. They can be prepared directly by oxidation of seven-membered rings. They can also be derived from cyclization or cycloaddition of appropriate precursors followed by elimination or rearrangement. This review discusses the types of naturally occurring tropones and tropolones and outlines important methods developed for the synthesis of tropone and tropolone natural products. PMID:25400298

  10. Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults

    PubMed Central

    Massaro, Karin SR; Costa, Silvia F; Leone, Claudio; Chamone, Dalton AF

    2007-01-01

    Background Procalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile. Methods 52 adult patients were enrolled in the study. Blood sample was collected in order to determine the serum concentrations of PCT, CRP and other hematological parameters at the onset of fever. The patients were divided into 2 groups, one with severe infection (n = 26) and the other in which the patients did not present such an infection (n = 26). Then PCT and CRP concentrations at the fever onset were compared between groups using non parametric statistical tests, ROC curve, sensitivity, specificity, likelihood ratio, and Spearman's correlation coefficient. Results The mean of PCT was significantly higher in the group with severe infection (6.7 ng/mL versus 0.6 ng/mL – p = 0.0075) comparing with CRP. Serum concentrations of 0.245 ng/mL of PCT displayed 100% de sensitivity and 69.2% specificity. PCT concentrations of 2,145 ng/mL presented a likelihood ratio of 13, which was not observed for any concentration of CRP. Conclusion PCT seems to be an useful marker for the diagnosis of systemic infection in febrile neutropenic patients, probably better than CRP. PMID:18034890

  11. Prevalence of malaria among acute febrile patients clinically suspected of having malaria in the Zeway Health Center, Ethiopia.

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2010-01-01

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

  13. spin pumping occurred under nonlinear spin precession

    NASA Astrophysics Data System (ADS)

    Zhou, Hengan; Fan, Xiaolong; Ma, Li; Zhou, Shiming; Xue, Desheng

    Spin pumping occurs when a pure-spin current is injected into a normal metal thin layer by an adjacent ferromagnetic metal layer undergoing ferromagnetic resonance, which can be understood as the inverse effect of spin torque, and gives access to the physics of magnetization dynamics and damping. An interesting question is that whether spin pumping occurring under nonlinear spin dynamics would differ from linear case. It is known that nonlinear spin dynamics differ distinctly from linear response, a variety of amplitude dependent nonlinear effect would present. It has been found that for spin precession angle above a few degrees, nonlinear damping term would present and dominated the dynamic energy/spin-moment dissipation. Since spin pumping are closely related to the damping process, it is interesting to ask whether the nonlinear damping term could be involved in spin pumping process. We studied the spin pumping effect occurring under nonlinear spin precession. A device which is a Pt/YIG microstrip coupled with coplanar waveguide was used. High power excitation resulted in spin precession entering in a nonlinear regime. Foldover resonance lineshape and nonlinear damping have been observed. Based on those nonlinear effects, we determined the values of the precession cone angles, and the maximum cone angle can reach a values as high as 21.5 degrees. We found that even in nonlinear regime, spin pumping is still linear, which means the nonlinear damping and foldover would not affect spin pumping process.

  14. Naturally occurring products in cancer therapy

    PubMed Central

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

    2015-01-01

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

  15. Naturally occurring antimicrobials for minimally processed foods.

    PubMed

    Davidson, P Michael; Critzer, Faith J; Taylor, T Matthew

    2013-01-01

    Natural antimicrobials are gaining increased interest from researchers and food manufacturers alike seeking to discover label-friendly alternatives to the widely implemented synthetic compounds. Naturally occurring antimicrobials can be applied directly to food to protect food quality, extend food shelf life by inhibiting or inactivating spoilage microorganisms, and improve food safety by inhibiting or inactivating food-borne pathogens. There are a great number of natural antimicrobials derived from animal, plant, and microbial sources. This manuscript reviews their efficacy against spoilage and pathogenic organisms, their methods of evaluation, and their application in various foods as well as the development of novel delivery systems and incorporation with other hurdles.

  16. Nipah virus entry can occur by macropinocytosis

    SciTech Connect

    Pernet, Olivier; Pohl, Christine; Ainouze, Michelle; Kweder, Hasan; Buckland, Robin

    2009-12-20

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

  17. Naturally occurring eastern equine encephalitis in a Hampshire wether.

    PubMed

    Bauer, Rudy W; Gill, Marjorie S; Poston, Rob P; Kim, Dae Young

    2005-05-01

    Eastern equine encephalitis (EEE) was diagnosed (postmortem) in a sheep with clinical signs attributable to a central nervous system disease. The sheep was febrile and initially had front limb incoordination, which progressed to paralysis of both front and hind limbs during a course of 2 days. The sheep maintained an alert attitude with the ability to eat up to the time of euthanasia. The only clinical pathologic abnormalities were neutrophilia and lymphopenia without appreciable leukocytosis, a moderate hyperglycemia, and an elevated creatine kinase. Treatment included hydrotherapy for lowering body temperature, intravenous fluids, thiamine hydrochloride, tetanus antitoxin, antibiotics, and corticosteroids. The only gross lesion at the time of necropsy was a wet glistening surface of the brain (leptomeninges). Microscopically, there was severe nonsuppurative meningoencephalitis, poliomyelitis, and polyradiculoneuritis with mild multifocal neutrophilic infiltration. The EEE virus was isolated from the brain, and subsequent fluorescent antibody testing for EEE was positive on cell culture.

  18. Serologic Surveillance for West Nile Virus and Other Flaviviruses in Febrile Patients, Encephalitic Patients, and Asymptomatic Blood Donors in Northern Mexico

    PubMed Central

    Rodríguez, María de Lourdes Garza; Rodríguez Rodriguez, Diana R.; Blitvich, Bradley J.; López, Miguel Á. Reyes; Fernández-Salas, Ildefonso; Jimenez, Javier Ramos; Farfán-Ale, José A.; Tamez, Rogelio Cazares; Longoria, César Martinez; Aguilar, Maria I. Tavitas

    2010-01-01

    Abstract A clinical and serological investigation was performed to determine the presence of West Nile virus (WNV) among febrile and encephalitic patients in northern Mexico. In addition, asymptomatic blood donors were serologically assayed for WNV to determine the seroprevalence of WNV in the general population. The study cohort consisted of 1432 individuals (588 febrile patients, 44 encephalitic patients, and 800 asymptomatic blood donors). All subjects were negative for WNV IgM. Sixty subjects were reactive for dengue virus (DENV) IgM (16 blood donors and 44 febrile patients). A subset (n = 425) of individuals was also screened by ELISA for flavivirus IgG. The prevalence of flavivirus IgG in febrile patients, encephalitic patients, and blood donors ranged from 40% to 59%. A subset (n = 147) of sera reactive for flavivirus IgG was further tested by plaque reduction neutralization test. Six individuals with no history of travel during the preceding 12 months were seropositive for WNV. Another 65 individuals were seropositive for DENV1 and 24 were seropositive for DENV2. The high prevalence of dengue antibodies in northern Mexico appears to limit the incidence of WNV infection in this region. Article Summary Line Antibodies to WNV, DENV-1, and DENV-2 were identified in humans in northern Mexico. PMID:19492946

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

    PubMed Central

    Cho, Kyung Sook; Yoon, Jangho

    2014-01-01

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

  20. Association of genetic polymorphism of pre-microRNA-146a rs2910164 and serum high-mobility group box 1 with febrile seizures in Egyptian children.

    PubMed

    Issac, Marianne Samir Makboul; Girgis, Marian; Haroun, Mervat; Shalaby, Amal

    2015-03-01

    Interaction between immune-inflammatory process and genetic factors might be implicated in the pathogenesis of febrile seizures. Pre-microRNA (miR)-146a rs2910164 polymorphism is postulated to modulate expression of miR-146a whose anti-inflammatory role involves regulation of high-mobility group box 1. Our aim is to examine whether rs2910164 polymorphism influences serum high-mobility group box 1 levels and whether an association exists between both and febrile seizures. The study included 136 children, divided into 4 groups. Real-time polymerase chain reaction was used for detection of rs2910164 polymorphism and high-mobility group box 1 was measured using enzyme-linked immunosorbent assay. High-mobility group box 1 levels were higher in febrile seizure patients compared to the other groups. Rs2910164 polymorphism was not associated with increased risk of febrile seizures. Rs2910164 polymorphism might be accompanied by an upregulation of the proinflammatory process as it might be associated with an increase in high-mobility group box 1 and leukocytic count.

  1. Evaluation of Magnesium Levels in Serum and Cerebrospinal Fluid of Patients with Febrile Convulsion Hospitalized in Bahrami Hospital in Tehran in 2010-2011.

    PubMed

    Khosroshahi, Nahid; Ghadirian, Laleh; Kamrani, Kamyar

    2015-12-01

    Evaluation of magnesium levels in serum and cerebrospinal fluid of patients with febrile convulsion (FC) hospitalized in Bahrami hospital in Tehran in 2010-2011. In the past, decreased levels of magnesium in serum and CSF of patients with FC were reported. The purpose of this study was to identify the possible role of magnesium in febrile seizures in children. Identifying this condition, we may control seizures and also prevent subsequent convulsion. In this cross-sectional study, inclusion criteria were the existence of convulsion due to fever and exclusion criteria were having a known neurological disease which could induce a seizure, and children younger than one month. In each group (cases include children with febrile convulsion and controls include febrile children without convulsion), Mg was measured in blood, and cerebrospinal fluid of 90 children and then they were compared. The data were analyzed by SPSS (α=0.05). The mean serum and CSF levels of Mg in case and control groups were equal (P<0.87 and P<0.22 respectively). There was no difference between two groups in terms of sex, but mean age was significantly different (P<0.003). There was not an association between serum and CSF levels of magnesium and the presence of FC. Therefore, it's not suggested to measure the level of magnesium in serum or CSF in children with fever routinely.

  2. Serologic surveillance for West Nile virus and other flaviviruses in febrile patients, encephalitic patients, and asymptomatic blood donors in northern Mexico.

    PubMed

    Rodríguez, María de Lourdes Garza; Rodriguez, Diana R Rodríguez; Blitvich, Bradley J; López, Miguel A Reyes; Fernández-Salas, Ildefonso; Jimenez, Javier Ramos; Farfán-Ale, José A; Tamez, Rogelio Cazares; Longoria, César Martinez; Aguilar, Maria I Tavitas; Rivas-Estilla, Ana Maria

    2010-03-01

    A clinical and serological investigation was performed to determine the presence of West Nile virus (WNV) among febrile and encephalitic patients in northern Mexico. In addition, asymptomatic blood donors were serologically assayed for WNV to determine the seroprevalence of WNV in the general population. The study cohort consisted of 1432 individuals (588 febrile patients, 44 encephalitic patients, and 800 asymptomatic blood donors). All subjects were negative for WNV IgM. Sixty subjects were reactive for dengue virus (DENV) IgM (16 blood donors and 44 febrile patients). A subset (n = 425) of individuals was also screened by ELISA for flavivirus IgG. The prevalence of flavivirus IgG in febrile patients, encephalitic patients, and blood donors ranged from 40% to 59%. A subset (n = 147) of sera reactive for flavivirus IgG was further tested by plaque reduction neutralization test. Six individuals with no history of travel during the preceding 12 months were seropositive for WNV. Another 65 individuals were seropositive for DENV1 and 24 were seropositive for DENV2. The high prevalence of dengue antibodies in northern Mexico appears to limit the incidence of WNV infection in this region. Article Summary Line: Antibodies to WNV, DENV-1, and DENV-2 were identified in humans in northern Mexico.

  3. Atypical Mycobacterium furunculosis occurring after pedicures.

    PubMed

    Redbord, Kelley Pagliai; Shearer, David A; Gloster, Hugh; Younger, Bruce; Connelly, Beverly L; Kindel, Susan E; Lucky, Anne W

    2006-03-01

    Mycobacterium fortuitum complex are rapidly-growing nontuberculous mycobacteria found ubiquitously in the environment including, water, soil, dust, and biofilms. M fortuitum has been reported to cause skin and soft-tissue infections in association with nail salon footbath use during pedicures. Four cases of M fortuitum complex furunculosis are reported that occurred after pedicures in the Cincinnati, Ohio/Northern Kentucky area. Dermatologists and clinicians should consider mycobacterial infections from the M fortuitum complex when patients present with nonhealing furuncles on the lower legs and should inquire about recent pedicures. Early recognition and institution of appropriate therapy are critical. Public health measures should be explored to protect against such infections, given the recent popularity of the nail care industry.

  4. Host Biomarkers for Distinguishing Bacterial from Non-Bacterial Causes of Acute Febrile Illness: A Comprehensive Review

    PubMed Central

    Kapasi, Anokhi J.; Dittrich, Sabine; González, Iveth J.; Rodwell, Timothy C.

    2016-01-01

    Background In resource limited settings acute febrile illnesses are often treated empirically due to a lack of reliable, rapid point-of-care diagnostics. This contributes to the indiscriminate use of antimicrobial drugs and poor treatment outcomes. The aim of this comprehensive review was to summarize the diagnostic performance of host biomarkers capable of differentiating bacterial from non-bacterial infections to guide the use of antibiotics. Methods Online databases of published literature were searched from January 2010 through April 2015. English language studies that evaluated the performance of one or more host biomarker in differentiating bacterial from non-bacterial infection in patients were included. Key information extracted included author information, study methods, population, pathogens, clinical information, and biomarker performance data. Study quality was assessed using a combination of validated criteria from the QUADAS and Lijmer checklists. Biomarkers were categorized as hematologic factors, inflammatory molecules, cytokines, cell surface or metabolic markers, other host biomarkers, host transcripts, clinical biometrics, and combinations of markers. Findings Of the 193 citations identified, 59 studies that evaluated over 112 host biomarkers were selected. Most studies involved patient populations from high-income countries, while 19% involved populations from low- and middle-income countries. The most frequently evaluated host biomarkers were C-reactive protein (61%), white blood cell count (44%) and procalcitonin (34%). Study quality scores ranged from 23.1% to 92.3%. There were 9 high performance host biomarkers or combinations, with sensitivity and specificity of ≥85% or either sensitivity or specificity was reported to be 100%. Five host biomarkers were considered weak markers as they lacked statistically significant performance in discriminating between bacterial and non-bacterial infections. Discussion This manuscript provides a summary

  5. Prevalence of malaria, prevention measures, and main clinical features in febrile children admitted to the Franceville Regional Hospital, Gabon

    PubMed Central

    Maghendji-Nzondo, Sydney; Nzoughe, Hermann; Lemamy, Guy Joseph; Kouna, Lady Charlene; Pegha-Moukandja, Irene; Lekoulou, Faustin; Mbatchi, Bertrand; Toure-Ndouo, Fousseyni; Lekana-Douki, Jean Bernard

    2016-01-01

    Recently, major progress has been made in controlling malaria in Africa. However, in Gabon, little information is available on the role of malaria in childhood febrile syndromes, the use and efficacy of preventive measures, and Plasmodium species distribution. Here, we characterized malaria in febrile children in Franceville, Gabon through a cross-sectional study at the pediatric unit of the Franceville Regional Hospital. We registered 940 febrile children. Their general condition was markedly altered in 11.7% of cases (n = 89/760); among them 19 (21.4%) had a severely altered condition. Malaria was the second most frequent etiology (22.0%; n = 162/738), after respiratory tract infections (37.3%; n = 275/738). Children with malaria (63 ± 39 months) were older than children without malaria (40 ± 37 months) (p = 0.0013). Hemoglobin, red blood cell, white blood cell, and platelet values were lower in children with malaria than in those without malaria (p < 0.0001). Anemia was the most common feature of severe malaria (70.6%; n = 12/17), followed by neurological involvement (23.5%; n = 4/17). The prevalence of malaria was significantly higher in children older than 60 months than in younger children (40% vs. 15.5%; p < 0.0001). Plasmodium falciparum accounted for 97.5% of cases (158/162), followed by Plasmodium malariae (2.5%; n = 4/162). Bed net use was high (74.4%; n = 697/936) and contributed to malaria prevention (p = 0.001). Good basic knowledge of malaria also had a preventive effect (p < 0.0001). The prevalence of malaria in children in Franceville did not decrease significantly from 2009 to 2012, remaining at about 20%, highlighting that preventive measures should be reinforced. PMID:27492564

  6. Prevalence of malaria, prevention measures, and main clinical features in febrile children admitted to the Franceville Regional Hospital, Gabon.

    PubMed

    Maghendji-Nzondo, Sydney; Nzoughe, Hermann; Lemamy, Guy Joseph; Kouna, Lady Charlene; Pegha-Moukandja, Irene; Lekoulou, Faustin; Mbatchi, Bertrand; Toure-Ndouo, Fousseyni; Lekana-Douki, Jean Bernard

    2016-01-01

    Recently, major progress has been made in controlling malaria in Africa. However, in Gabon, little information is available on the role of malaria in childhood febrile syndromes, the use and efficacy of preventive measures, and Plasmodium species distribution. Here, we characterized malaria in febrile children in Franceville, Gabon through a cross-sectional study at the pediatric unit of the Franceville Regional Hospital. We registered 940 febrile children. Their general condition was markedly altered in 11.7% of cases (n = 89/760); among them 19 (21.4%) had a severely altered condition. Malaria was the second most frequent etiology (22.0%; n = 162/738), after respiratory tract infections (37.3%; n = 275/738). Children with malaria (63 ± 39 months) were older than children without malaria (40 ± 37 months) (p = 0.0013). Hemoglobin, red blood cell, white blood cell, and platelet values were lower in children with malaria than in those without malaria (p < 0.0001). Anemia was the most common feature of severe malaria (70.6%; n = 12/17), followed by neurological involvement (23.5%; n = 4/17). The prevalence of malaria was significantly higher in children older than 60 months than in younger children (40% vs. 15.5%; p < 0.0001). Plasmodium falciparum accounted for 97.5% of cases (158/162), followed by Plasmodium malariae (2.5%; n = 4/162). Bed net use was high (74.4%; n = 697/936) and contributed to malaria prevention (p = 0.001). Good basic knowledge of malaria also had a preventive effect (p < 0.0001). The prevalence of malaria in children in Franceville did not decrease significantly from 2009 to 2012, remaining at about 20%, highlighting that preventive measures should be reinforced.

  7. Using women advocacy groups to enhance knowledge and home management of febrile convulsion amongst mothers in a rural community of Sokoto State, Nigeria

    PubMed Central

    Oche, Oche Mansur; Onankpa, Oloche Ben

    2013-01-01

    Introduction Febrile convulsions (FC) are a common paediatric problem worldwide. Between 1 and 4% of children will have a febrile convulsion with about 4% of cases arising before the age of six months. Although FC is benign and does not cause death, brain damage or learning disorders, it is quite frightening to observers and parents who witness an episode of FC, would think the child is going to die. Methods This was a quasi-experimental study (a pre and post-test interventional, one group), aimed at assessing the impact of health education on knowledge and home management of febrile convulsion amongst mothers in a rural community in North Western Nigeria. A one in three samples of fifty mothers that met the eligibility criteria where selected using systematic random sampling. Structured interviewer administered questionnaire with close and open-ended questions was administered to obtain data at pre- and post intervention. Results The ages of the mothers ranged from 18-47 with a mean age of 33 ± 7.14years. The perceived causes of febrile convulsion included fever (28%), witch craft (80%) with majority (98%) of the mothers administering traditional medications. Proportion of study subjects with adequate knowledge of febrile convulsion at baseline and post intervention were 4% (mean knowledge score of 35.3± 9.48) and 96.0% (mean knowledge score of 77.69 ± 10.75) respectively (P < 0.0001). Conclusion Although inadequate knowledge and inappropriate home practices about FC were rampant in the study community, using community members to teach and sensitize the mothers on FC improved their knowledge base significantly. The use of effective educational intervention programmes and parental support groups will go a long way in reducing the incidence of FC among children in our communities. PMID:23560132

  8. Introduction to naturally occurring radioactive material

    SciTech Connect

    Egidi, P.

    1997-08-01

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

  9. Epigenetic Mechanisms in Commonly Occurring Cancers

    PubMed Central

    2012-01-01

    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

  10. Naturally occurring contamination in the Mancos Shale.

    PubMed

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

    2012-02-01

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

  11. Febrile ulceronecrotic Mucha-Habermann disease following suspected hemorrhagic chickenpox infection in a 20-month-old boy.

    PubMed

    Lode, H N; Döring, P; Lauenstein, P; Hoeger, P; Dombrowski, F; Bruns, R

    2015-10-01

    We present the youngest pediatric patient so far with febrile ulcerative Mucha-Haberman disease (FUMHD) after an admitting clinical picture of hemorrhagic varicella infection. With a time to diagnosis of 25 days, the 20-month-old boy responded to low dose cyclosporine and prednisolone given for 3 months and is free of disease after 4 years of follow up. We describe a polyclonal CD8+ T cell response with elevated pro-inflammatory cytokines and a fivefold upregulation of the high-affinity Fc receptor type I (CD64) on granulocytes. Early consideration of FUMHD in the differential diagnosis of a systemic inflammatory disease combined with a generalized necrotizing rash is important for early and adequate management of children with this rare and challenging disease.

  12. Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar – Aetiologies, Antibiotic Treatment and Outcome

    PubMed Central

    Elfving, Kristina; Shakely, Deler; Andersson, Maria; Baltzell, Kimberly; Ali, Abdullah S.; Bachelard, Marc; Falk, Kerstin I.; Ljung, Annika; Msellem, Mwinyi I.; Omar, Rahila S.; Parola, Philippe; Xu, Weiping; Petzold, Max; Trollfors, Birger; Björkman, Anders; Lindh, Magnus; Mårtensson, Andreas

    2016-01-01

    Background Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. Methods We prospectively studied the aetiology of febrile illness in 677 children aged 2–59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. Findings NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection

  13. Update: outbreak of acute febrile illness among athletes participating in Eco-Challenge-Sabah 2000--Borneo, Malaysia, 2000.

    PubMed

    2001-01-19

    During September 7-11, 2000, CDC was notified by the Idaho Department of Health, the Los Angeles County Department of Health Services, and the GeoSentinel Global Surveillance Network of at least 20 cases of acute febrile illness in three countries; all ill patients had participated in the Eco-Challenge-Sabah 2000 multisport expedition race in Borneo, Malaysia, during August 21-September 3, 2000. Participants included athletes from 29 U.S. states and 26 countries. This report updates the ongoing investigation of this outbreak through December 2, which suggests that Leptospira were the cause of illness and that water from the Segama River was the primary source of infection. Participants in adventure sports and exotic tourism should be aware of potential exposure to unusual and emerging infectious agents. PMID:11215718

  14. Bacteriological profile and antimicrobial susceptibility patterns of blood culture isolates among febrile patients in Mekelle Hospital, Northern Ethiopia.

    PubMed

    Wasihun, Araya Gebreyesus; Wlekidan, Letemichael Negash; Gebremariam, Senay Aregawi; Dejene, Tsehaye Asmelash; Welderufael, Abadi Luel; Haile, Tadesse Dejenie; Muthupandian, Saravanan

    2015-01-01

    Bacterial bloodstream infections are a major public health problem, which leads to high morbidity and mortality of patients. On time diagnosis and appropriate medication will be the best way to save the lives of affected ones. The aim of the present study was to determine the bacterial profile of bloodstream infections and their antibiotic susceptibility pattern in Mekelle Hospital. Cross sectional study method was carried out in 514 (269 females and 245 males) febrile patients in Mekelle hospital from March to October 2014. Standard bacteriological methods were used for blood collection, bacterial isolation and antimicrobial susceptibility pattern. Out of the total 514 febrile patients, 144 (28%) culture positive were isolated. Staphylococcus aureus 54 (37.5%), Coagulase-negative staphylococci 44 (30.6%), Escherichia coli 16 (3.1%), Citrobacter spp. 9 (1.7%) and Salmonella typhi 8 (1.6%) were the most dominant isolates, collectively accounting for >90% of the isolates. Antimicrobial resistance pattern for gram positive and gram negative bacteria was 0-83.3% and 0-100%, respectively. High resistance was seen to Trimethoprim-sulphamethoxazole 101 (70.1%), Oxacillin 65 (62.5%), Ceftriaxone 79 (58.9%) and Doxycycline 71 (49.3%). Fifty-nine percent of the isolated bacteria in this study were multi drug resistant. Most bacterial isolates were sensitive to Gentamicin, Ciprofloxacin and Amoxicillin clavulanic acid. All gram positive isolates in this current study were sensitive to vancomycin. Prevalence of bacterial isolates in blood was high. It also reveals isolated bacteria species developed multi drug resistance to most of the antibiotics tested, which highlights for periodic surveillance of etiologic agent, antibiotic susceptibility to prevent further emergence and spread of resistant bacterial pathogens.

  15. Evaluation of a programme for ‘Rapid Assessment of Febrile Travelers’ (RAFT): a clinic-based quality improvement initiative

    PubMed Central

    Jazuli, Farah; Lynd, Terence; Mah, Jordan; Klowak, Michael; Jechel, Dale; Klowak, Stefanie; Ovens, Howard; Sabbah, Sam; Boggild, Andrea K

    2016-01-01

    Background Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting. Methods Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria include Plasmodium falciparum malaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence. Results From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16–78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0–4 days) postimplementation, compared to 5.4±1.8 days (range 0–26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%). Conclusions In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy. PMID:27473947

  16. Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children

    PubMed Central

    Vyas, Falgun Indravadan; Rana, Devang Ashwinkumar; Patel, Piyush M.; Patel, Varsha Jitendra; Bhavsar, Rekha H.

    2014-01-01

    Objective: Paracetamol and ibuprofen are widely used for fever in children as monotherapy and as combined therapy. None of the treatments is proven clearly superior to others. Hence, the study was planned to compare the efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Materials and Methods: This was an investigator blind, randomized, comparative, parallel clinical trial conducted in 99 febrile children, 6 months to 12 years of age, allocated to three groups. First group received paracetamol 15 mg/kg, second group received ibuprofen 10 mg/kg and third group received both paracetamol and ibuprofen, all as a single dose by the oral route. Patients were followed-up at intervals of 1, 2, 3 and 4 h post dose by tympanic thermometry. Results: Mean tympanic temperature after 4 h of drug administration was significantly lower in the combination group compared with paracetamol group (P < 0.05); however, the difference was not clinically significant (<1°C). The rate of fall of temperature was highest in the combination group. Number of afebrile children any time post dose until 4 h was highest in the combination group. Difference between combination and paracetamol was significant for the 1st h (P = 0.04). Highest fall of temperature was noted in the 1st h of drug administration in all the groups. No serious adverse events were observed in any of the groups. Conclusion: Paracetamol and ibuprofen combination caused quicker temperature reduction than either paracetamol or ibuprofen alone. If quicker reduction of body temperature is the desired goal of therapy, the use of combination of paracetamol + ibuprofen may be advocated. PMID:24551584

  17. Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors

    PubMed Central

    Oka, Takakazu; Oka, Kae; Kobayashi, Takuya; Sugimoto, Yukihiko; Ichikawa, Atsushi; Ushikubi, Fumitaka; Narumiya, Shuh; Saper, Clifford B

    2003-01-01

    Previous studies have disagreed about whether prostaglandin EP1 or EP3 receptors are critical for producing febrile responses. We therefore injected lipopolysaccharide (LPS) at a variety doses (1 μg kg−1−1 mg kg−1) intraperitoneally (I.P.) into wild-type (WT) mice and mice lacking the EP1 or the EP3 receptors and measured changes in core temperature (Tc) by using telemetry. In WT mice, I.P. injection of LPS at 10 μg kg−1 increased Tc about 1 °C, peaking 2 h after injection. At 100 μg kg−1, LPS increased Tc, peaking 5–8 h after injection. LPS at 1 mg kg−1 decreased Tc, reaching a nadir at 5–8 h after injection. In EP1 receptor knockout (KO) mice injected with 10 μg kg−1 LPS, only the initial (< 40 min) increase in Tc was lacking; with 100 μg kg−1 LPS the mice showed no febrile response. In EP3 receptor KO mice, LPS decreased Tc in a dose- and time-dependent manner. Furthermore, in EP3 receptor KO mice subcutaneous injection of turpentine did not induce fever. Both EP1 and EP3 receptor KO mice showed a normal circadian cycle of Tc and brief hyperthermia following psychological stress (cage-exchange stress and buddy-removal stress). The present study suggests that both the EP1 and the EP3 receptors play a role in fever induced by systemic inflammation but neither EP receptor is involved in the circadian rise in Tc or psychological stress-induced hyperthermia in mice. PMID:12837930

  18. Estimating the Burden of Leptospirosis among Febrile Subjects Aged below 20 Years in Kampong Cham Communities, Cambodia, 2007-2009

    PubMed Central

    Hem, Sopheak; Ly, Sowath; Votsi, Irene; Vogt, Florian; Asgari, Nima; Buchy, Philippe; Heng, Seiha; Picardeau, Mathieu; Sok, Touch; Ly, Sovann; Huy, Rekol; Guillard, Bertrand; Cauchemez, Simon; Tarantola, Arnaud

    2016-01-01

    Background Leptospirosis is an emerging but neglected public health challenge in the Asia/Pacific Region with an annual incidence estimated at 10–100 per 100,000 population. No accurate data, however, are available for at-risk rural Cambodian communities. Method We conducted anonymous, unlinked testing for IgM antibodies to Leptospira spp. on paired sera of Cambodian patients <20 years of age between 2007–2009 collected through active, community-based surveillance for febrile illnesses in a convenience sample of 27 rural and semi-rural villages in four districts of Kampong Cham province, Cambodia. Leptospirosis testing was done on paired serological samples negative for Dengue, Japanese encephalitis and Chikungunya viruses after random selection. Convalescent samples found positive while initial samples were negative were considered as proof of acute infection. We then applied a mathematical model to estimate the risk of fever caused by leptospirosis, dengue or other causes in rural Cambodia. Results A total of 630 samples are coming from a randomly selected subset of 2358 samples. IgM positive were found on the convalescent serum sample, among which 100 (15.8%) samples were IgM negative on an earlier sample. Seventeen of these 100 seroconversions were confirmed using a Microagglutination Test. We estimated the probability of having a fever due to leptospirosis at 1. 03% (95% Credible Interval CI: 0. 95%–1. 22%) per semester. In comparison, this probability was 2. 61% (95% CI: 2. 55%, 2. 83%) for dengue and 17. 65% (95% CI: 17. 49%, 18. 08%) for other causes. Conclusion Our data from febrile cases aged below 20 years suggest that the burden of leptospirosis is high in rural Cambodian communities. This is especially true during the rainy season, even in the absence of identified epidemics. PMID:27043016

  19. [Place of malaria among febrile illnesses in two ethnic tribes living in sympatry in Mali from 1998 to 2008].

    PubMed

    Dolo, A; Maïga, B; Dara, V; Tapily, A; Tolo, Y; Arama, C; Daou, M; Doumbo, O

    2012-12-01

    In Africa, malaria is responsible for 25-40% of all outpatient visits and 20-50% of all hospitalizations. In malaria-endemic areas, individuals do not behave the same toward the outcome of clinical malaria. The aim of this study is to determine the prevalence of malaria in the locality among the different ethnic groups, evaluate the place of malaria among febrile illnesses, and assess the relationship between fever and parasite density of Plasmodium falciparum. Studies on susceptibility to malaria between the Fulani and Dogon groups in Mali were conducted in Mantéourou and the surrounding villages from 1998 to 2008. We carried out six cross-sectional studies during the malaria transmission and longitudinal surveys (July to December depending on the year) during the 10-year duration. In longitudinal studies, clinical data on malaria and other diseases frequently observed in the population were recorded. It appears from this work that malaria is the leading cause of febrile syndromes. We observed a significant reduction in malaria morbidity in the study population from 1998 to 2008. The pyrogenic threshold of parasitaemia was 1,000 parasites/mm(3) of blood in the Dogon and 5,000 parasites/mm(3) of blood in the Fulani.We have also found that high parasitical densities were not always associated with fever. Malaria morbidity was higher among the Dogon than in Fulani. The immunogenetic factors might account for this difference in susceptibility to malaria between Fulani and Dogon in the area under study. With regard to this study, it is important to take into account the ethnic origin of subjects when interpreting data of clinical and malarial vaccine trials.

  20. Naturally occurring secoiridoids and bioactivity of naturally occurring iridoids and secoiridoids. A review, part 2.

    PubMed

    Dinda, Biswanath; Debnath, Sudhan; Harigaya, Yoshihiro

    2007-05-01

    Naturally occurring new secoiridoids published during 1994-2005 are reviewed with available physical and spectral data: mp, [alpha](D), UV, IR, (1)H- and (13)C-NMR and plant source. The works on biological and pharmacological activity of naturally occurring iridoids and secoiridoids reported during 1998-2005 are also reviewed. Bioactivities like antiallergic, antiarthritis, antibacterial, anticancer, anticoagulant, anticomplement, antifungal, antiinflammatory, antioxidative, antiprotozoal, antispasmodic, antiviral, immunomodulatory, neuroprotective, nerve growth factor potentiating and wound healing activities are highlighted.

  1. Differential dormancy of co-occurring copepods

    NASA Astrophysics Data System (ADS)

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

    1998-08-01

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

  2. Sundew adhesive: a naturally occurring hydrogel

    PubMed Central

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

    2015-01-01

    Bioadhesives have drawn increasing interest in recent years, owing to their eco-friendly, biocompatible and biodegradable nature. As a typical bioadhesive, sticky exudate observed on the stalked glands of sundew plants aids in the capture of insects and this viscoelastic adhesive has triggered extensive interests in revealing the implied adhesion mechanisms. Despite the significant progress that has been made, the structural traits of the sundew adhesive, especially the morphological characteristics in nanoscale, which may give