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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. PMID:26267078

  2. 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

  3. [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

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

    PubMed

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

    2011-01-01

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

  5. 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

  6. [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

  7. COST OF FEBRILE NEUTROPENIA TREATMENT IN BOSNIA AND HERZEGOVINA

    PubMed Central

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

    2016-01-01

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

  8. COST OF FEBRILE NEUTROPENIA TREATMENT IN BOSNIA AND HERZEGOVINA.

    PubMed

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

    2016-04-01

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

  9. 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. PMID:26378158

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. [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

  13. 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. PMID:27162322

  14. Parental perspectives on inpatient versus outpatient management of pediatric febrile neutropenia.

    PubMed

    Diorio, Caroline; Martino, Julia; Boydell, Katherine Mary; Ethier, Marie-Chantal; Mayo, Chris; Wing, Richard; Teuffel, Oliver; Sung, Lillian; Tomlinson, Deborah

    2011-01-01

    To describe parent preference for treatment of febrile neutropenia and the key drivers of parental decision making, structured face-to-face interviews were used to elicit parent preferences for inpatient versus outpatient management of pediatric febrile neutropenia. Parents were presented with 4 different scenarios and asked to indicate which treatment option they preferred and to describe reasons for this preference during the face-to-face interview. Comments were recorded in writing by research assistants. A consensus approach to thematic analysis was used to identify themes from the written comments of the research assistants. A total of 155 parents participated in the study. Of these, 80 (51.6%) parents identified hospital-based intravenous treatment as the most preferred treatment scenario for febrile neutropenia. The major themes identified included convenience/disruptiveness, physical health, emotional well-being, and modifiers of parental decision making. Most parents preferred hospital-based treatment for febrile neutropenia. An understanding of issues that influence parental decision making may assist health care workers in planning program implementation and further support families in their decision-making process. PMID:22194148

  15. 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

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

    PubMed

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

    2006-09-01

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

  17. [A Case of Nasopharyngeal Cancer with Febrile Neutropenia Followed by Death during Adjuvant Chemotherapy].

    PubMed

    Nakahara, Susumu; Kitamura, Koji; Honma, Keiichiro; Yamamoto, Yoshifumi; Takenaka, Yukinori; Yasui, Toshimichi; Hanamoto, Atsushi; Morii, Eiichi; Inohara, Hidenori

    2015-06-01

    Chemotherapy-related death can occur, but is rarely experienced in the case of head and neck cancer. In this report, we present the case of a 55-year-old male who died of a severe febrile neutropenia during adjuvant chemotherapy. He was initially diagnosed as having nasopharyngeal carcinoma (cT2N0M0), and concurrent chemoradiotherapy was used as a primary treatment. He did not show any critical side effects during that therapy. After residual disease was proven by biopsy, docetaxel, cisplatin and 5-fluorouracil (TPF) therapy was introduced as adjuvant chemotherapy. The patient developed a high fever with a decreased neutrophil count on day 8, and went into a state of shock on day 9. He underwent immediate systemic management, but methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and enteritis were uncontrolled, resulting in death on day 43. The autopsy findings suggested that the main cause of death was acute respiratory distress syndrome (ARDS), but cytomegalovirus (CMV) infection was also noted in multiple organs. . Since it is assumed from literature that the mortality rate in TPF therapy is about 2-4%, it was considered that prior sufficient explanations and informed consent should be required before this therapy. PMID:26336750

  18. Efficacy of intravenous ciprofloxacin in patients with febrile neutropenia refractory to initial therapy.

    PubMed

    Matsuoka, Hitoshi; Tsukamoto, Atsuko; Shirahashi, Akihiko; Koga, Shin; Suzushima, Hitoshi; Shibata, Keisuke; Uozumi, Kimiharu; Yamashita, Kiyoshi; Okamura, Seiichi; Kawano, Fumio; Tamura, Kazuo

    2006-08-01

    We previously reported that monotherapy with carbapenem or cefepime exhibited efficacy equivalent to cefepime plus an aminoglycoside as initial therapy for febrile neutropenia (FN), achieving an adequate response in two-thirds of the patients. However, only one-third of the remaining poor responders to monotherapy became afebrile after an aminoglycoside was added to the initial carbapenem or cefepime. The present study was designed to evaluate the benefit of intravenous ciprofloxacin for neutropenic patients with fever who were refractory to initial therapy given for the first 3 days. Patients with FN--as defined by an axillary temperature >or=37.5 degrees C and a neutrophil count <1,000/microL-who had no response to initial therapy with carbapenem or cefepime for 72 hours were to receive additional ciprofloxacin 600 mg/day. They were otherwise managed according to the Japanese guidelines for FN. An adequate response was defined as a decline of temperature to <37.5 degrees C within 7 days after initiation of ciprofloxacin treatment. Thirty-one patients with FN (seventeen male and fourteen female; mean age 53.1 +/- 14.8 years) were entered in the study. The initial antibiotics were cefepime (2 - 4 g/day) in twenty and carbapenem (1 - 2 g/day) in eleven. Three patients were excluded from analysis, leaving 28 patients for evaluation of efficacy. The response rate was 16/31 patients (51.6%),with four patients judged non-assessable due to adverse effects, protocol violation or early change to other agents. Adverse events occurred in seventeen patients, but all were mild and reversible. Only three patients had adverse events (skin rash, hepatic dysfunction and elevation of alkaline phosphatase in one patient, respectively) considered related to ciprofloxacin. These findings indicate that addition of intravenous ciprofloxacin is effective against FN refractory to initial antibiotic therapy and has acceptable toxicity. PMID:16966275

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

    PubMed

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

    2016-06-01

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

  20. 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

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

    PubMed

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

    2016-04-01

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

  2. 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

  3. 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

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

    PubMed Central

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

    2014-01-01

    Background Predictive models for febrile neutropenia (FN) would be informative for physicians in clinical decision making. This study aims to validate a predictive model (Jenkin’s model) that comprises pretreatment hematological parameters in early-stage breast cancer patients. Patients and Methods A total of 428 breast cancer patients who received neoadjuvant/adjuvant chemotherapy without any prophylactic use of colony-stimulating factor were included. Pretreatment absolute neutrophil counts (ANC) and absolute lymphocyte counts (ALC) were used by the Jenkin’s model to assess the risk of FN. In addition, we modified the threshold of Jenkin’s model and generated Model-A and B. We also developed Model-C by incorporating the absolute monocyte count (AMC) as a predictor into Model-A. The rates of FN in the 1st chemotherapy cycle were calculated. A valid model should be able to significantly identify high-risk subgroup of patients with FN rate >20%. Results Jenkin’s model (Predicted as high-risk when ANC≦3.1*10∧9/L;ALC≦1.5*10∧9/L) did not identify any subgroups with significantly high risk (>20%) of FN in our population, even if we used different thresholds in Model-A(ANC≦4.4*10∧9/L;ALC≦2.1*10∧9/L) or B(ANC≦3.8*10∧9/L;ALC≦1.8*10∧9/L). However, with AMC added as an additional predictor, Model-C(ANC≦4.4*10∧9/L;ALC≦2.1*10∧9/L; AMC≦0.28*10∧9/L) identified a subgroup of patients with a significantly high risk of FN (23.1%). Conclusions In our population, Jenkin’s model, cannot accurately identify patients with a significant risk of FN. The threshold should be changed and the AMC should be incorporated as a predictor, to have excellent predictive ability. PMID:24945817

  5. Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy.

    PubMed

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

    2013-04-01

    Chemotherapy-induced febrile neutropenia (FN) is associated with increased patient mortality and health care costs. Comorbid conditions such as liver and renal dysfunction have been linked to increased risk of FN. However, the effects of other chronic comorbid conditions on risk of FN have not been well studied. To examine the association between chronic comorbid conditions and FN in breast cancer patients, we identified incident breast cancer patients from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. Patients who received primary prophylactic granulocyte colony-stimulating factor (G-CSF) were excluded. We assessed history of comorbid conditions prior to cancer diagnosis using ICD-9 codes and disease registries. FN events were identified in the first chemotherapy cycle using a combination of ICD-9 codes and hospital discharge diagnoses. For each comorbid condition, propensity scores that included patient characteristics and other predisposing comorbid conditions were calculated and adjusted for in Cox models to determine associations between that comorbid condition and FN. We also evaluated secondary models that additionally adjusted for cancer stage, baseline absolute neutrophil count (ANC), chemotherapy regimen, and dose reductions. A total of 7,127 breast cancer patients were included; median age was 55 years, and the majority had localized (47 %) or regional (49 %) disease at diagnosis. In the first chemotherapy cycle, 335 (4.7 %) patients developed FN. Congestive heart failure (HR = 3.0; 95 % CI: 1.3-5.9), osteoarthritis (HR = 2.0; 95 % CI: 1.4-2.8), previous cancer (HR = 3.4; 95 % CI: 1.2-7.5), and thyroid disorder (HR = 1.6; 95 % CI: 1.1-2.3) were associated with increased risk of FN. These estimates were similar to those from secondary models that also adjusted for additional cancer and treatment-related covariates. Our findings suggest that several chronic comorbid

  6. Febrile neutropenia in French emergency departments: results of a prospective multicentre survey

    PubMed Central

    2010-01-01

    Introduction Febrile neutropenia (FN) is common in cancer patients receiving myelotoxic therapy. The procedures to treat FN are well established in oncology, but it is unclear whether management is adequate in the emergency department (ED). Methods This prospective, multicentre, observational study was carried out in 47 French EDs for 6 months. Patients were adults presenting at the ED with FN after myelotoxic treatment for cancer. Severity of infection was defined according to Bone criteria for severe sepsis and septic shock (SS/SSh) and risk was determined according to Multinational Association of Supportive Care in Cancer (MASCC) criteria. The end point was the implementation of guidelines. Management of patients with SS/SSh required: (i) adequate intravenous (IV) antimicrobial therapy for the first 90 min (broad-spectrum beta-lactam with or without an aminoglycoside); (ii) fluid challenge (500 mL); (iii) lactate measurement; (iv) at least one blood culture; and (v) hospitalization. Management of patients without SS/SSh required: (1) no initiation of granulocyte - cell stimulating factor (G-CSF); (2) adequate IV antimicrobial therapy (broad-spectrum beta-lactam) and hospitalization if the patient was high-risk according to MASCC criteria; (3) adequate oral antimicrobial therapy (quinolone or amoxicillin/clavulanate or cephalosporin) and hospital discharge if the patient was low-risk. Results 198 patients were enrolled; 89 patients had SS/SSh, of whom 19 received adequate antimicrobial therapy within 90 min and 42 received appropriate fluid challenge. Blood cultures were obtained from 87 and lactate concentration was measured in 29. Overall, only 6 (7%) patients with SS/SSh received adequate management. Among 108 patients without SS/SSh, 38 (35%) were high-risk and 70 (65%) low-risk. In the high-risk group, adequate antimicrobial therapy was given to 31 patients, G-CSF was initiated in 4 and 35 were hospitalized. In the low-risk group, 4 patients received

  7. A de-escalation protocol for febrile neutropenia cases and its impact on carbapenem resistance: A retrospective, quasi-experimental single-center study.

    PubMed

    Alshukairi, Abeer; Alserehi, Haleema; El-Saed, Aiman; Kelta, Mouhammed; Rehman, Jalil U; Khan, Farrukh A; Alsalmi, Hanadi; Alattas, Majda; Aslam, Muhammad

    2016-01-01

    Our objective was to evaluate the impact of using an imipenem de-escalation protocol for empiric febrile neutropenia on the development of carbapenem resistance. A pre-post intervention design was used. The intervention was adopting the imipenem de-escalation approach, which began on January 1, 2012. A retrospective chart review of cases of febrile neutropenia bacteremia was performed one year before and one year after the intervention. We compared the development of carbapenem resistance between the two study periods. Seventy-five episodes of febrile neutropenia bacteremia were included in the study. They had similar demographics, clinical features and outcomes. There were 78 and 12 pathogens in the primary and follow-up blood cultures, respectively. Approximately 61% and 66% of the primary and follow-up blood cultures, respectively, were gram-negative bacteria with similar carbapenem resistance profiles in the two study periods. In our study population, 57% of the gram-negative bacteria were ESBL pathogens. The resistance of the gram-negative bacteria to piperacillin/tazobactam (72% versus 53%, p=0.161), imipenem (16% versus 11%, p=0.684), and meropenem (8% versus 16%, p=0.638) did not significantly change after our policy change. In conclusion, the use of the carbapenem de-escalation approach for febrile neutropenia in our institution was not associated with an increase in carbepenem resistance. Future prospective multi-center studies are recommended to further confirm the current findings. PMID:26688375

  8. 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

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

    PubMed

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

    2016-05-01

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

  10. 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

  11. 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

  12. 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. PMID:27057782

  13. 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

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

    PubMed

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

    2011-02-01

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

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

    PubMed Central

    Rosa, Regis G.

    2014-01-01

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

  16. The Role of Multidetector Computed Tomography in the Early Diagnosis of Invasive Pulmonary Aspergillosis in Patients with Febrile Neutropenia Undergoing Hematopoietic Stem Cell Transplantation

    PubMed Central

    Çiledağ, Nazan; Arda, Kemal; Arıbaş, Bilgin Kadri; Tekgündüz, Ali Irfan Emre; Altuntaş, Fevzi

    2012-01-01

    Objective: To evaluate vessel involvement and the role of multidetector computed tomography (MDCT) in the earlydiagnosis of invasive pulmonary aspergillosis (IPA) in patients with febrile neutropenia and antibiotic-resistant feverundergoing autologous bone morrow transplantation. Material and Methods: In all, 74 pulmonary MDCT examinations in 37 consecutive hematopoietic stem celltransplantation patients with febrile neutropenia and clinically suspected IPA were retrospectively evaluated. Results: Diagnosis of IPA was based on Fungal Infections Cooperative Group, and National Institute of Allergy andInfectious Diseases Mycoses Study Consensus Group criteria. In all, 0, 14, and 11 patients were diagnosed as proven,probable, and possible IPA, respectively. Among the 25 patients accepted as probable and possible IPA, all had pulmonaryMDCT findings consistent with IPA. The remaining 12 patients were accepted as having fever of unknown origin (FUO)and had patent vessels based on MDCT findings.In the patients with probable and possible IPA, 72 focal pulmonary lesions were observed; in 41 of the 72 (57%) lesionsvascular occlusion was noted and the CT halo sign was observed in 25 of these 41 (61%) lesions. Resolution of feveroccurred following antifungal therapy in 19 (76%) of the 25 patients with probable and possible IPA. In all, 6 (25%)of the patients diagnosed as IPA died during follow-up. Transplant-related mortality 100 d post transplant in patientswith IPA and FUO was 24% and 0%, respectively. Conclusion: In conclusion, MDCT has a potential role in the early diagnosis of IPA via detection of vessel occlusion. PMID:24744620

  17. 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

  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. 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

  20. 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

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

    PubMed Central

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

    2015-01-01

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

  2. 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

  3. 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

  4. 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

  5. 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 ...

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2012-06-01

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

  8. Prediction of outcome in cancer patients with febrile neutropenia: comparison of the Multinational Association of Supportive Care in Cancer risk-index score with procalcitonin, C-reactive protein, serum amyloid A, and interleukins-1beta, -6, -8 and -10.

    PubMed

    Uys, A; Rapoport, B L; Fickl, H; Meyer, P W A; Anderson, R

    2007-11-01

    The primary objective of the study was to compare the predictive potential of procalcitonin (PCT), C-reactive protein (CRP), serum amyloid A (SAA), and interleukin (IL)-1beta, IL-6, IL-8, and IL-10, with that of the Multinational Association of Supportive Care in Cancer (MASCC) risk-index score in cancer patients on presentation with chemotherapy-induced febrile neutropenia (FN). Seventy-eight consecutive FN episodes in 63 patients were included, and MASCC scores, as well as concentrations of CRP, SAA, PCT, and IL-1beta, IL-6, IL-8 and IL-10, and haematological parameters were determined on presentation, 72 h later and at outcome. Multivariate analysis of data revealed the MASCC score, but none of the laboratory parameters, to be an accurate, independent variable (P < 0.0001) for prediction of resolution with or without complications and death. Of the various laboratory parameters, PCT had the strongest association with the MASCC score (r = -0.51; P < 0.0001). In cancer patients who present with FN, the MASCC risk-index score is a useful predictor of outcome, while measurement of PCT, CRP, SAA, or IL-1beta, IL-6, IL-8 and IL-10, is of limited value. PMID:17944761

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

    PubMed Central

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

    2016-01-01

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

  10. 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 ...

  11. Febrile seizures

    MedlinePlus

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

  12. 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 ...

  13. Febrile seizures

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000980.htm Febrile seizures To use the sharing features on this page, please enable JavaScript. A febrile seizure is a convulsion in a child triggered by ...

  14. Febrile seizures

    PubMed Central

    2014-01-01

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

  15. 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

  16. 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 ...

  17. Febrile convulsion--an overview.

    PubMed

    Mukherjee, Arabinda; Mukherjee, Asha

    2002-05-01

    Febrile convulsion is the most frequently occurring epilepsy syndrome, experienced in infants/children between 6 months and 5 years of age associated with fever >38 degrees C. Children having first or second degree relative with history of febrile convulsion, neonatal nursery stay of more than 30 days, developmental delay or attendance at day care centre are at increased risk of developing febrile convulsion. Single febrile convulsion does not increase the risk of epilepsy and there is no causal relationship between febrile convulsion and subsequent epilepsy. It has been recognised that there is significant genetic component for susceptibility to febrile seizures. To make the diagnosis of febrile convulsion, meningitis, encephalitis, serious electrolyte imbalance and other acute neurologic illnesses are to be excluded. While managing acute attack the steps to be taken are--airway management, a semi-prone position to avoid aspiration, monitoring vital signs and other supportive care. Diazepam or lorazepam is the drug to be used. There is no reason to expect phenobarbitone administered at the time of fever to be effective in prevention of febrile convulsion. The parents should be counselled about the benign nature of the convulsion. Although the febrile convulsion a frightening event, still it is a benign condition. PMID:12418634

  18. [Fluoroquinolones to prevent bacterial infection in children with chemotherapy induced neutropenia: is it reasonable?].

    PubMed

    Dubos, F; Delebarre, M; Lagrée, M

    2013-11-01

    Chemotherapy-induced febrile neutropenia is a frequent event in children with cancer, with a high morbidity. Antibiotic prophylaxis has been proposed for many years to prevent infectious diseases in patients with neutropenia. Fluoroquinolone prophylaxis induced a significant reduction of mortality and infectious morbidities in these situations. Less data are available in children with neutropenia. The emergence of antimicrobial resistance involving not only quinolones, but also cephalosporins, aminoglycosides and penems, is the main long term risk. This article summarise the usefulness of the prophylactic antibiotic treatment and its perspective in children with cancer. PMID:24360309

  19. Retrospective study of late febrile seizures.

    PubMed

    Webb, D W; Jones, R R; Manzur, A Y; Farrell, K

    1999-04-01

    This retrospective study documents the clinical features, electroencephalographic data, and outcome of 50 children with a history of seizures with fever that occurred after 5 years of age. Children with afebrile seizures before the onset of febrile seizures were excluded. Outcome was based on a cross-sectional survey and the follow-up period was 1-13 years. Of the 50 children, 40 had two or fewer febrile seizures after 5 years of age, and febrile seizures did not occur after 10 years of age. Twenty had complex febrile seizures, and 16 had a first-degree relative with febrile seizures. Five developed afebrile seizures, and 18 had educational difficulties. Epileptiform electroencephalographic abnormalities were observed in 22 but were not predictive of later afebrile seizures. Febrile seizures that occur after 5 years of age recur infrequently and cease by 10 years of age. The risk of developing afebrile seizures in this group is small. PMID:10328275

  20. 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

  1. Drug-induced immune neutropenia/agranulocytosis.

    PubMed

    Curtis, Brian R

    2014-01-01

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

  2. Psychotropic drug-induced neutropenia.

    PubMed

    Duggal, Harpreet S; Singh, Ira

    2005-08-01

    Psychotropic medications have been known to cause blood dyscrasias, including neutropenia, and since the advent of clozapine, this side effect is now increasingly being recognized. Almost all the major classes of psychotropic medications have been associated with neutropenia. Operational definitions for blood dyscrasias have allowed us to create an epidemiological database on this rare side effect of psychotropic medications. With increased awareness of drug-induced neutropenia among physicians, methods of early detection and treatment of this side effect have also been the focus of recent literature. Another area of active research has been identifying the risk factors and mechanism of drug-induced neutropenia. This article attempts to synthesize our current understanding of psychotropic drug-induced neutropenia and also provide insights into future research in this realm. PMID:16234875

  3. Evaluation and Management of Patients with Isolated Neutropenia

    PubMed Central

    Newburger, Peter E.; Dale, David C.

    2013-01-01

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

  4. [Fortuitously discovered neutropenia in children: diagnosis and follow-up].

    PubMed

    Gaudichon, J; Cornet, E; Minckes, O; Bodet, D

    2015-08-01

    Neutropenia seems to be quite frequent in current pediatric practice and can confuse the clinician since it may result from a severe cause. The aim of this study was to provide a prospective description of episodes of neutropenia in children to assess its clinical relevance in a general pediatric cohort consulting and/or hospitalized in a French university hospital. In this prospective observational and monocentric study conducted from April 2012 to April 2013, we included all the patients under 18 years of age who presented neutropenia (defined as an absolute neutrophil count [ANC] below 1×10(9)/L before 1 year of age and below 1.5×10(9)/L beyond) on a whole blood count (WBC) performed in our hospital. Patients treated with chemotherapy were not included. Medical records were regularly checked for at least 1 year after inclusion, and clinical and biological data were collected prospectively to compare transient episodes of neutropenia (<3 months) with persistent episodes of neutropenia (>3months). Of 55,018 consultations and 13,967 hospitalizations (chemotherapy excluded), 8966 blood counts were performed and 250 episodes of neutropenia were found in 238 patients. Data concerning clinical progression were available in 195 cases of which 136 had at least one subsequent WBC. Two hundred thirty-one episodes corresponded to new episodes, while neutropenia preexisted before inclusion in the others. The median follow-up was 12.8 months. Most episodes of neutropenia occurred in children <2 years of age (52%), with a median age of 22.2 months. Mean ANC was 0.943×10(9)/L (±0.340) and a few episodes of neutropenia were below 0.5×10(9)/L (9.2%). Neutropenia persisted more than 3 months in only 13.2% of cases. When neutropenia was below 0.5×10(9)/L, it significantly persisted (RR=3.08; 95% CI [1.31-7.22]). Other factors associated with persistent neutropenia were thrombocytopenia, monocytopenia, a CRP more than 70mg/L, significant abnormality on the clinical exam, and

  5. High dose intravenous ciprofloxacin in febrile neutropenic patients.

    PubMed

    Johnson, P R; Yin, J A; Tooth, J A

    1990-12-01

    We have evaluated the use of high-dose intravenous ciprofloxacin as monotherapy in the empirical therapy of febrile episodes in neutropenic patients during the course of a randomized trial comparing ciprofloxacin with a standard combination regimen. Sixty-four episodes of fever were studied in a high risk population of 42 patients mostly undergoing intensive chemotherapy for leukaemia. Ciprofloxacin achieved clinical responses as follows: completely successful in 39%, partially successful in 20%, and unsuccessful in 41%. Infections were microbiologically documented in 37 (58%), with Gram-positive bacteria (of which 37% were coagulase negative staphylococci and 34% were streptococci) accounting for 81% of all organisms cultured. Responses in documented infections were as follows; completely successful in 32%, partially successful in 27%, and unsuccessful in 41%. One infection-related death occurred 30 h after starting ciprofloxacin, and a further three patients died before the resolution of neutropenia. The early death was caused by fulminant infection with a ciprofloxacin-resistant Pseudomonas aeruginosa. No other ciprofloxacin resistance was seen amongst eight Gram-negative isolates. There was no evidence of emerging ciprofloxacin resistance during the course of the study. Ciprofloxacin was associated with a low incidence of adverse events with skin rash (five cases) and nausea (one case) being reported as possibly or probably related to ciprofloxacin. We conclude that high-dose intravenous ciprofloxacin may be safely employed as monotherapy in the empirical treatment of febrile episodes in neutropenic patients. It has the additional advantages of twice daily administration, the availability of intravenous and oral presentations, and absence of cross-allergy in beta-lactam antibiotic hypersensitive patients. PMID:2292537

  6. Molecular genetics of febrile seizures.

    PubMed

    Iwasaki, Nobuaki; Nakayama, Junko; Hamano, Kenzo; Matsui, Akira; Arinami, Tadao

    2002-01-01

    Febrile seizures are the most common form of convulsion, occurring in 2-5% of infants in Europe and North America and in 6-9% in Japan. In large families, the febrile seizure (FS) susceptibility trait is inherited by the autosomal dominant pattern with reduced penetrance. Two putative FS loci, FEB1 (chromosome 8q13-q21) and FEB2 (chromosome 19p13.3) have been mapped. A clinical subset of FS, termed generalized epilepsy with febrile seizures plus (GEFS+), was reported. In GEFS+ families, a mutation in the voltage-gated sodium channel beta1 subunit gene (SCN1B) at chromosome 19q13.1 and two mutations of the same alpha1 subunit gene (SCN1A) at chromosome 2q24 were identified. These loci are linked to febrile convulsions in large families. We conducted a genome-wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families using nonparametric allele-sharing methods, and found a new FS susceptibility locus, FEB4 (chromosome 5q14-q15). In contrast to the FEB1, FEB2, and GEFS+ genetic loci, linkage to FEB4 was suggested in nuclear FS families, indicating that FEB4 may be the most common linkage locus in FS families. PMID:12383277

  7. 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

  8. 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

  9. 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

  10. 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

  11. [Complicated febrile convulsion vs herpes-encephalitis].

    PubMed

    Millner, M

    1993-01-01

    Since Acyclovir is available a sufficient treatment of herpes simplex virus (HSV) encephalitis exists. Febrile convulsions may occur as the initial manifestation of an encephalitis, particularly of an HSV encephalitis. Within 25 months out of 151 children with febrile convulsions five children with complicated febrile convulsions were admitted at the pediatric department of Graz. In all children HSV antibodies in serum and cerebrospinal fluid (CSF) were negative and the diagnosis of an HSV encephalitis was made by positive CSF HSV polymerase chain reaction (PCR). Therefore, in any suspected case, i.e. in any case of a complicated febrile convulsion, CSF should be investigated including a HSV PCR to rapidly confirm or exclude HSV encephalitis. PMID:8386831

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

    PubMed Central

    Kullar, Ravina; Maziarz, Richard T.

    2013-01-01

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

  13. Chronic Neutropenia in Childhood: Experience From a Single Center.

    PubMed

    Karapinar, Tuba H; Oymak, Yeşim; Ay, Yilmaz; Köker, Sultan A; Töret, Ersin; Hazan, Filiz; Vergin, Canan

    2016-01-01

    Chronic neutropenia (CN) is defined as neutropenia that persists for >3 months; it is caused by a heterogeneous group of diseases in children. The aim of the present study was to evaluate the significance and clinical manifestations of CN in children at a single children's hospital. Between October 2004 and April 2014, CN patient data were evaluated retrospectively. Thirty-one patients were assessed in this study. Thirteen of them (41.9%) were younger than 12 months of age at initial diagnosis. There was no difference in the absolute number of neutrophils at diagnosis between the children aged younger than 12 months and those aged 12 months and older at CN onset. Twenty-two of the patients (70.9%) were diagnosed during treatment for acute infections. A total of 11 patients (35.5%) were hospitalized because of recurrent infections. Most of the recurrent infections occurred in the lungs (81.8%). Congenital neutropenia (CoN) was identified in 14 patients (45.1%). Eight of 14 patients (57.1%) required granulocyte-colony stimulating factor treatment, and none of them experienced adverse effects from this treatment. Fifteen patients (48.3%) were diagnosed with idiopathic neutropenia. Comparison between the idiopathic and CoN groups revealed no differences in age, the absolute number of neutrophils, or the presence of infection at diagnosis; however, differences were detected in sex and the rate of spontaneous recovery from neutropenia. Ten of the patients (32.2%) experienced spontaneous recovery from neutropenia during a follow-up period of 7 to 52 months. In current study, we found a higher CoN ratio in the CN patients compared with previous reports, which may be due to the high rate of consanguineous marriages in our country. However, the finding of CN requires several laboratory investigations, prolonged follow-up, and advanced molecular analysis, and its etiology can remain idiopathic. PMID:26479986

  14. 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

  15. Seizure recurrence after a first febrile convulsion.

    PubMed

    Laditan, A A

    1994-01-01

    In this study, 140 children aged from 6 months to 6 years who presented with a first febrile convulsion at the King Fahad Hofuf Hospital, Al-Hassa, Saudi Arabia were retrospectively identified. Information about these children was obtained from their medical records covering a follow-up period of 3 years from July 1989 to June 1992. Recurrent febrile convulsions occurred in 60 of them (43%). Relevant risk factors that were observed to be significantly associated with seizure recurrence included an age of less than 18 months (odds ratio [OR] = 3.82; 95% confidence interval [CI] = 9.26, 1.58), an initial febrile convulsion that was complex (OR = 4.41; CI = 9.50, 2.05) and a positive family history of febrile convulsions (OR = 4.12; CI = 10.74; 1.58), while a decreased risk of recurrence occurred with a temperature of over 39 degrees C (OR = 4.60; CI = 9.44; 2.24). There was no association between seizure recurrence and the duration of the initial febrile convulsion (OR = 0.93; CI = 2.33; -2.04) or family history of epilepsy (OR = 0.88; CI = 4.22, -3.27). An important observation in the present study is the close association (ORM-H = 2.36; X2M-H = 9.65) between the development of an afebrile convulsion and seizure recurrence among the group of children with CFC. Anticonvulsant prophylaxis should therefore be considered for children whose initial febrile convulsions are complex in nature. PMID:7880092

  16. Molecular genetics of febrile seizures.

    PubMed

    Nakayama, Junko; Arinami, Tadao

    2006-08-01

    Febrile seizures (FSs) represent the most common form of childhood seizures, occurring in 2-5% of infants in Europe and North America and in 6-9% in Japan. It has been recognized that there is a significant genetic component for susceptibility to this type of seizure. Six susceptibility FS loci have been identified on chromosomes 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15 (FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6). Furthermore, mutations in the voltage-gated sodium channel alpha-1, alpha-2 and beta-1 subunit genes (SCN1A, SCN2A and SCN1B) and the GABA(A) receptor gamma-2 subunit gene (GABRG2) have been identified in families with a clinical subset of seizures termed "generalized epilepsy with febrile seizure plus (GEFS+)". However, the causative genes have not been identified in most patients with FSs or GEFS+. Common forms of FSs are genetically complex disorders believed to be influenced by variations in several susceptibility genes. Recently, several association studies in FSs have been reported, but the results vary among different groups and no consistent or convincing FS susceptibility genes have emerged. To find a true association, larger sample size and newer methodologic refinements are recommended. PMID:16887333

  17. Digenic mutations in severe congenital neutropenia

    PubMed Central

    Germeshausen, Manuela; Zeidler, Cornelia; Stuhrmann, Manfred; Lanciotti, Marina; Ballmaier, Matthias; Welte, Karl

    2010-01-01

    Severe congenital neutropenia a clinically and genetically heterogeneous disorder. Mutations in different genes have been described as causative for severe neutropenia, e.g. ELANE, HAX1 and G6PC3. Although congenital neutropenia is considered to be a group of monogenic disorders, the phenotypic heterogeneity even within the yet defined genetic subtypes points to additional genetic and/or epigenetic influences on the disease phenotype. We describe congenital neutropenia patients with mutations in two candidate genes each, including 6 novel mutations. Two of them had a heterozygous ELANE mutation combined with a homozygous mutation in G6PC3 or HAX1, respectively. The other 2 patients combined homozygous or compound heterozygous mutations in G6PC3 or HAX1 with a heterozygous mutation in the respective other gene. Our results suggest that digenicity may underlie this disorder of myelopoiesis at least in some congenital neutropenia patients. PMID:20220065

  18. Febrile seizures - what to ask your doctor

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000223.htm Febrile seizures - what to ask your doctor To use the ... please enable JavaScript. Your child has had a febrile seizure. A simple febrile seizure stops by itself within ...

  19. Clinical update: febrile convulsion in childhood.

    PubMed

    Paul, Siba Prosad; Blaikley, Sarah; Chinthapalli, Ravindranath

    2012-07-01

    Febrile convulsion is common in young children and occurs in 3-4% of children aged under six years of age. This is the most common seizure disorder and it is not epilepsy. It occurs generally with high temperatures and recurs in one third of children during a subsequent febrile illness. These episodes can be extremely frightening for parents and lot of reassurance needs to be provided by health professionals after an episode. Most often the episodes are short lived and self-terminating and long-term anticonvulsant medicines are not required. The prognosis is generally good and affected children do not suffer any long-term health problems. Community practitioners can provide education, support and counselling to help families return to normality after an event. PMID:22866531

  20. 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

  1. 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

  2. Early-onset neutropenia induced by rituximab in a patient with lupus nephritis and hemolytic anemia.

    PubMed

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

    2015-01-01

    Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 10(9)/L) after the second weekly rituximab infusion (375 mg/m(2) weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections. PMID:25767732

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

    PubMed Central

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

    2015-01-01

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

  4. Ticagrelor as an alternative in clopidogrel-associated neutropenia.

    PubMed

    Shah, Rahman; Keough, Leigh Anne; Belalcazar-Portacio, Astrid; Ramanathan, Kodangudi B

    2015-01-01

    Aspirin in combination with platelet P2Y12 receptor blocker has become the mainstay antiplatelet treatment strategy for the prevention of stent thrombosis. Ticlopidine was the first widely used P2Y12 receptor blockers, but clopidogrel has mostly replaced the use of ticlopidine due to its more favorable adverse event profile on bone marrow. However, when clopidogrel induced bone marrow toxicity occurs, little is known about the efficacy and safety of alternative treatments, and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced severe neutropenia in a patient treated with coronary stent and safety of alternative treatment with ticagrelor. PMID:24433137

  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. PMID:22184532

  6. 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

  7. 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

  8. 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: ...

  9. Febrile Illness in the Athlete

    PubMed Central

    Dick, Natalie A.; Diehl, Jason J.

    2014-01-01

    Context: Acute febrile illnesses are common in athletes over the course of training and competition seasons. Complete recovery and rapid yet safe return to participation are critical for competitive athletes. Alterations in thermoregulation, metabolism, fluid homeostasis, muscle strength, and endurance, as well as potential complications for the athlete and others, must be considered. Evidence Acquisition: The PubMed database was searched (1970-2013) for all English-language articles related to febrile illness in sport, using the keywords fever, febrile, body temperature, thermoregulation, infection, illness, disease, exercise, athlete, sport, performance, return to play, metabolism, hydration, and dehydration. Study Design: Clinical review. Level of Evidence: Level 4. Results: Limited data confirm that febrile illness is correlated with alterations in the body’s thermoregulatory system, with increases in metabolic rate, and with effects in fluid homeostasis. Human and animal studies demonstrate a decrease in muscle strength and endurance secondary to muscle catabolism in febrile illness. However, indirect evidence suggests that regular exercise enhances the immune response. No strong clinical research has been published on return to play during or following acute febrile illness, excluding mononucleosis and myocarditis. Conclusion: Fever is correlated with an increase in insensible fluid losses, dehydration, metabolic demands, and dysregulation of body temperature. Fever can have detrimental effects on the musculoskeletal system, including decreasing strength and endurance, generalized muscle catabolism, and increase in perceived fatigue. Participating in strenuous exercise during febrile illness can worsen the illness and has demonstrated increased lethality in animal models. No consensus recommendations support return to activity before resolution of fever, and training should be resumed gradually once fever and dehydration have resolved. PMID:24790692

  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. 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

  12. Febrile/cold agglutinins

    MedlinePlus

    ... diagnose certain infections and find the cause of hemolytic anemia (a type of anemia that occurs when red ... or cold agglutinins can help explain why the hemolytic anemia is occurring and direct treatment.

  13. 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

  14. 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

  15. An international, multicenter, prospective, observational study of neutropenia in patients being treated with lenalidomide + dexamethasone for relapsed or relapsed/refractory multiple myeloma (RR-MM).

    PubMed

    Leleu, Xavier; Terpos, Evangelos; Sanz, Ramón García; Cooney, Julian; O'Gorman, Peter; Minarik, Jiri; Greil, Richard; Williams, Catherine; Gray, Diep; Szabo, Zsolt

    2016-08-01

    Neutropenia is a well-known dose-limiting toxicity associated with lenalidomide plus dexamethasone treatment in patients with multiple myeloma; however, little is known about its management and associated outcomes in the real world setting. The present prospective, multicenter, observational study evaluated the incidence, management, and outcomes of grade 3/4 neutropenia in patients with relapsed or relapsed/refractory multiple myeloma who initiated treatment with lenalidomide plus dexamethasone. Of 198 patients, 62 (31%, 95% CI: 25, 38) experienced grade 3/4 neutropenia, and half of these patients experienced 3 or more events during the 12-month observational period. Grade 3/4 neutropenia occurred throughout lenalidomide treatment, with a median time to first event of 8.8 weeks (Q1, Q3: 5.9, 17.3). In a multivariate analysis, diagnosis of relapsed and refractory disease was associated with grade 3/4 neutropenia. Lenalidomide exposure reduction, use of G-CSF, unplanned hospitalization, and outpatient clinic visits were more common in patients who experienced grade 3/4 neutropenia than in those who did not. In conclusion, grade 3/4 neutropenia is a common toxicity and patients are at continued risk throughout treatment with lenalidomide and dexamethasone. Further efforts should be made to improve the recommendations for neutropenia management in this population. Am. J. Hematol. 91:806-811, 2016. © 2016 Wiley Periodicals, Inc. PMID:27169523

  16. 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

  17. Recent Research on Febrile Seizures: A Review

    PubMed Central

    Syndi Seinfeld, DO; Pellock, John M.

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  19. Lower degree of fever at the initial febrile convulsion is associated with increased risk of subsequent convulsions.

    PubMed

    El-Radhi, A S

    1998-01-01

    We studied 132 children admitted consecutively with their first febrile convulsion to assess whether the degree of fever at the onset of the convulsion can predict the risk of subsequent convulsions. The children studied were reviewed at least 2 years after the initial febrile convulsion to determine the number of children who had recurrences of febrile convulsions and/or afebrile convulsions. Children with body temperatures below 39 degrees C at the onset of their initial febrile convulsion (Group 1) were two and half times more likely to experience multiple convulsions within the same illness than those with body temperatures above 39 degrees C (Group 2). This occurred when the body temperature rose above that which had triggered the initial febrile convulsion. Children in Group 1 were also over three times more likely to experience recurrent febrile convulsion in subsequent illnesses than those in Group 2. As for subsequent development of afebrile convulsion or epilepsy, although the risk was low, it only occurred in Group 1. It is suggested that the known association between multiple convulsions, recurrent febrile convulsions and epilepsy may be due to the single predisposing factor of a low degree of fever at the onset of febrile convulsion. Each child with febrile convulsion may have his own threshold for eliciting a convulsion with fever; the lower this threshold is, the more likely are subsequent convulsions. PMID:10724102

  20. Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies.

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2003-01-01

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

  3. 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

  4. Evaluation of interleukin 1β in febrile convulsion.

    PubMed

    Behmanesh, Fatemeh; Ashrafzadeh, Farah; Varasteh, Abdoreza; Shakeri, Abdoreza; Shahsavand, Shabnam

    2012-12-01

    Febrile convulsion (FC) is the most common type of seizure in childhood that occurs in 2-5 % of the children younger than 6 years. Interleukin 1β (IL-1β) is a cytokine that contributes to febrile inflammatory responses. There are conflicting results on increasing this cytokine in serum during FC. Thus we measured IL-1ß in febrile children with or without seizure. 60 febrile children (6 months to 5 years old) were divided in two groups, one group consisted of 30 children with FC, the other group consisting of 30 children without seizure which served as control. Blood samples were collected from members of both groups and serum samples were prepared. Interleukin 1β concentrations were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. We found that there was a difference in serum levels of interleukin 1β between FC and control group but it was not significant. This result may be due to the low number of samples or the result of interleukin 1β binding to some large proteins such as α2-macroglobolin, complement and soluble type 2 Interleukin 1 receptor, that affected the free interleukin 1β concentration.We could not find a significant relationship between serum interleukin 1β concentration and FC. PMID:23264411

  5. Neutropenia in antibody-deficient patients under IVIG replacement therapy.

    PubMed

    Lemos, Sonia; Jacob, Cristina M A; Pastorino, Antonio C; Castro, Ana Paula B M; Fomin, Angela B F; Carneiro-Sampaio, Magda M S

    2009-02-01

    Patients with antibody deficiencies are more prone to develop acute neutropenic episodes even during immunoglobulin replacement. The aims of this study were to evaluate the presence of acute neutropenia in 42 patients with primary antibody immunodeficiencies, currently receiving intravenous immunoglobulin (IVIG), and to describe the clinical and laboratory findings during neutropenic episodes. Of all patients, 10 (23.8%) presented acute neutropenia (absolute neutrophil count <1500 cells/mm3) during follow up (mean of 6.4 yr). The absolute neutrophil count ranged from 71 to 1488 cells/mm3. Neutropenia was not clearly associated with antibiotic prophylactic therapy or immunoglobulin levels, while infections were associated with neutropenia in the majority of episodes. Most acute neutropenia episodes were mild or moderate, except in CVID patients who present more severe neutropenia. Although IVIG may have contributed to reducing the severity of neutropenia, it does not prevent its occurrence in all patients. In conclusion, primary immunodeficient patients, even submitted to IVIG replacement therapy, must be regularly evaluated for neutropenia in order to minimize the risk of infections and its appropriate approach. PMID:18373514

  6. Approach to the patient with neutropenia in childhood

    PubMed Central

    Celkan, Tiraje; Koç, Begüm Şirin

    2015-01-01

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

  7. Role of apolipoprotein E in febrile convulsion.

    PubMed

    Giray, Ozlem; Ulgenalp, Ayfer; Bora, Elçin; Uran, Nedret; Yilmaz, Ebru; Unalp, Aycan; Erçal, Derya

    2008-10-01

    Apolipoprotein E is consistently associated with the progression of some common human neurodegenerative diseases, e.g., epilepsy. We hypothesized that genetic variations in the apolipoprotein E gene have implications for susceptibility to, and prognoses in, febrile convulsion, which plays an apparent role in the development of epilepsy. We used the polymerase chain reaction and restriction enzyme digestion to characterize variations of the apolipoprotein E gene. Sixty-nine patients with febrile convulsion (simple/complex) and a corresponding cohort of healthy patients (n = 75) were used. There was no significant difference in genotypic distribution and allelic frequencies of the apolipoprotein E gene between the febrile convulsion and control groups. Comparing subpopulations of the febrile convulsion group (patients with simple and complex febrile convulsion), we noted that no patients with the epsilon3/epsilon4 genotype had complex febrile convulsions. The apolipoprotein E epsilon3/epsilon4 genotype was more frequently seen in the simple febrile than in the complicated febrile convulsion group (9 versus 0 patients, respectively). The data indicate an association with the epsilon3/epsilon4 genotype of the apolipoprotein E gene with a milder phenotype. Although apolipoprotein E4 is not a vulnerability factor regarding febrile convulsions, it seems effective in regard to prognoses. PMID:18805361

  8. [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

  9. Factors predisposing to a complicated initial febrile convulsion.

    PubMed Central

    Wallace, S J

    1975-01-01

    131 consecutive admissions to hospital for a first febrile convulsion were studied to find which factors predisposed to a complicated fit--defined as one lasting more than 30 minutes, unilateral, or repeated within the same illness. A significant excess of complicated attacks occurred where the age of onset was less than 16 months, where both family history of convulsive disorder and perinatal abnormality were present, and, in females only, where it was suspected that neurological disorder preceded the first fit. PMID:1220608

  10. 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

  11. 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

  12. Suppressor cell-mediated neutropenia in Felty's syndrome.

    PubMed Central

    Abdou, N I; NaPombejara, C; Balentine, L; Abdou, N L

    1978-01-01

    The mechanism of neutropenia in Felty's Syndrome (FS) was tested. The suppressor capacity of mononuclear cells from patients with FS on normal bone marrow granulopoiesis was tested by the in vitro colony forming unit in culture assay. Peripheral blood, bone marrow, and spleen cells from FS patients with marked neutropenia (less than 1,000 neutrophils/mm3) suppressed the colony forming unit in culture of normal bone marrow. Cells from rheumatoid arthritis patients without neutropenia, cells from patients with drug-induced neutropenia without rheumatoid arthritis, or plasma from FS patients failed to suppress the colony forming unit in culture. Though suppressor cells were predominantly thymus-derived (T) cells, monocytes were also effective in suppression. The suppressor efficiency of cells from the various compartments were spleen greater than bone marrow greater than peripheral blood. Splenectomy in FS transiently corrected the neutropenia and eliminated suppressor cell activity. Hyperactive suppressor cells may be responsible for the neutropenia in some patients with FS. Correction of neutropenia in these patients should be directed at modulating the suppressor cell subpopulation. PMID:305925

  13. Management of febrile convulsion in children.

    PubMed

    Paul, Siba Prosad; Rogers, Eleanor; Wilkinson, Rachel; Paul, Biswajit

    2015-05-01

    The causes of febrile convulsions are usually benign. Such convulsions are common in children and their long-term consequences are rare. However, other causes of seizures, such as intracranial infections, must be excluded before diagnosis, especially in infants and younger children. Diagnosis is based mainly on history taking, and further investigations into the condition are not generally needed in fully immunised children presenting with simple febrile convulsions. Treatment involves symptom control and treating the cause of the fever. Nevertheless, febrile convulsions in children can be distressing for parents, who should be supported and kept informed by experienced emergency department (ED) nurses. This article discusses the aetiology, clinical presentation, diagnosis and management of children with febrile convulsion, and best practice for care in EDs. It also includes a reflective case study to highlight the challenges faced by healthcare professionals who manage children who present with febrile convulsion. PMID:25952398

  14. 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

  15. Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma

    PubMed Central

    Vakkalanka, Bhanu; Link, Brian K.

    2011-01-01

    A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma. PMID:21687649

  16. Does a SCN1A gene mutation confer earlier age of onset of febrile seizures in GEFS+?

    PubMed

    Sijben, Angelique E J; Sithinamsuwan, Pasiri; Radhakrishnan, Ashalata; Badawy, Radwa A B; Dibbens, Leanne; Mazarib, Aziz; Lev, Dorit; Lerman-Sagie, Tally; Straussberg, Rachel; Berkovic, Samuel F; Scheffer, Ingrid E

    2009-04-01

    SCN1A is the most clinically relevant epilepsy gene and is associated with generalized epilepsy and febrile seizure plus (GEFS+) and Dravet syndrome. We postulated that earlier onset of febrile seizures in the febrile seizure (FS) and febrile seizure plus (FS+) phenotypes may occur in the presence of a SCN1A mutation. This was because of the age-related onset of Dravet syndrome, which typically begins in the first year of life. We found that patients with FS and FS+ with SCN1A mutations had earlier median onset of febrile seizures compared to the population median. Patients with GABRG2 mutations had a similar early onset in contrast to patients with SCN1B mutations where onset was later. This study is the first to demonstrate that a specific genetic abnormality directly influences the FS and FS+ phenotype in terms of age of onset. PMID:19292758

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. [Severe inflammation during recovery from neutropenia: the immune reconstitution inflammatory syndrome following chemotherapy].

    PubMed

    van Lier, Dirk P T; Janssen, Nico A F; Snoeren, Miranda M; Verweij, Paul E; Blijlevens, Nicole M A; van der Velden, Walter J F M

    2015-01-01

    Immune reconstitution inflammatory syndrome (IRIS) occurs when a patient is recovering from a transient immunodeficiency and results in an uncontrolled inflammatory response to infectious agents and tissue damage. Symptoms such as fever and radiological signs seem to paradoxically appear or worsen, unmasking a previously unrecognized infection. The patient's clinical condition may then deteriorate as a result of increasing tissue damage and this may even lead to death. IRIS was initially described in patients suffering from a HIV infection who experienced immune recovery following the initiation of antiretroviral therapy. Increasingly, however, the syndrome is being reported in patients who are recovering from an episode of neutropenia following chemotherapy, hypomethylating agent use or a stem cell transplantation for the treatment of a solid tumour or haematological cancers. We describe two cases of IRIS following an episode of neutropenia in patients with a haematological malignancy and elaborate on the pathogenesis, diagnosis and treatment of IRIS in cancer patients. PMID:26246060

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

    PubMed Central

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

    2016-01-01

    Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An on-line 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 two 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 0.048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL. 40% preferred discharge on oral antibiotics when the ANC<500/μL. Triaging for febrile pediatric patients with cancer is significantly influenced by the providers’ perceptions of local EDs. Future investigation of local hospitals’ ability to provide urgent evaluation, combined with parental perspectives could lead to improvements in timely and effective management. PMID:26086779

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

    PubMed

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

    2015-01-01

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

  2. 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

  3. Neutropenia Associated with Long-Term Ceftaroline Use.

    PubMed

    LaVie, Katherine W; Anderson, Scott W; O'Neal, Hollis R; Rice, Todd W; Saavedra, Tatiana C; O'Neal, Catherine S

    2016-01-01

    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/mm(3). 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/mm(3). The median first neutropenic day was day 17, with the median ANC nadir of 432 cells/mm(3) 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/mm(3), 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/mm(3) or less. PMID:26503657

  4. 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

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

    PubMed Central

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

    2013-01-01

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

  6. 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 ...

  7. Seasonal variation of febrile convulsion in Japan.

    PubMed

    Tsuboi, T; Okada, S

    1984-05-01

    The 6-year incidence rates of febrile convulsions in all 3-year-old children in Fuchu (covering 95% of children, number examined 17,044) was 8.2%. The incidence was higher in boys than in girls (9.0%: 7.5%, P less than 0.001). The incidence rates varied with the month and year of birth, but the variations observed were slight. Two peak appearances of seasonal variation of the first febrile convulsion were found in November-January and in June-August. The former could be interpreted as a tendency to winter virus infection of the upper respiratory tract in children. The other peak in summer could be explained as a tendency to gastrointestinal infection. Liability to febrile convulsion was influenced by the age of children and by the seasonal variations of febrile illness, but not by the season of birth. PMID:6464667

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Hypozincemia during fever may trigger febrile convulsion.

    PubMed

    Izumi, Y; Ishii, K; Akiba, K; Hayashi, T

    1990-05-01

    Febrile convulsions are generally thought to be induced by metabolic changes during the rise-phase of body temperature. The mechanism by which convulsions are induced, however, is not fully elucidated. In this article, we propose a new hypothesis about the induction mechanism of febrile convulsions that takes into account the hypozincemia during fever. This hypozincemia activates the NMDA receptor, one of the glutamate family of receptors, which may play an important role in the induction of epileptic discharge. PMID:2190072

  11. Serum trace element levels in febrile convulsion.

    PubMed

    Amiri, Mojtaba; Farzin, Leila; Moassesi, Mohammad Esmail; Sajadi, Fattaneh

    2010-06-01

    Febrile convulsion is the most common disorder in childhood with good prognosis. There are different hypotheses about neurotransmitters and trace element changes in biological fluids which can have a role in pathogenesis of febrile convulsion. In this study, serum selenium, zinc, and copper were measured by atomic absorption spectrometry in the children with febrile convulsion (n = 30) and in the control group (n = 30). The age and sex of the subjects were registered. Selenium and zinc were found to be significantly lower in febrile convulsion cases than in the control group (p < 0.0001 and p < 0.0001, respectively). There was no significant difference in the value of copper between the two groups (p = 0.16). While selenium and zinc levels were 44.92 +/- 10.93 microg/l and 66.13 +/- 18.97 microg/dl in febrile convulsion, they were found to be 62.98 +/- 9.80 microg/l and 107.87 +/- 28.79 microg/dl in healthy children. Meanwhile, copper levels were 146.40 +/- 23.51 microg/dl in the patients and 137.63 +/- 24.19 microg/dl in the control group, respectively. This study shows that selenium and zinc play an important role in the pathogenesis of febrile convulsion. PMID:19669113

  12. Development and validation of a prediction model for diagnosing blood stream infections in febrile, non-neutropenic children with cancer

    PubMed Central

    Esbenshade, Adam J.; Di Pentima, M. Cecilia; Zhao, Zhiguo; Shintani, Ayumi; Esbenshade, Jennifer C.; Simpson, Monique E.; Montgomery, Kathleen C.; Lindell, Robert B.; Lee, Haerin; Wallace, Ato; Garcia, Kelly L.; Moons, Karel G.M.; Debra L., Friedman

    2014-01-01

    Background Pediatric oncology patients are at increased risk for blood stream infections (BSI). Risk in the absence of severe neutropenia (absolute neutrophil count (ANC) ≥500/µl) is not well defined. Procedure In a retrospective cohort of febrile (temperature ≥38.0° for > 1 hour or ≥38.3°) pediatric oncology patients with ANC≥500/µl , a diagnostic prediction model for BSI was constructed using logistic regression modeling and the following candidate predictors: age, ANC, absolute monocyte count, body temperature, inpatient/outpatient presentation, sex, central venous catheter type, hypotension, chills, cancer diagnosis, stem cell transplant, upper respiratory symptoms, and exposure to cytarabine, anti-thymocyte globulin, or anti-GD2 antibody. The model was internally validated with bootstrapping methods. Results Among 932 febrile episodes in 463 patients, we identified 91 cases of BSI. Independently significant predictors for BSI were higher body temperature (Odds ratio (OR) 2.36 p<0.001), tunneled external catheter (OR 13.79 p<0.001), peripherally inserted central catheter (PICC) (OR 3.95 p=0.005), elevated ANC (OR 1.19 p=0.024), chills (OR 2.09 p=0.031) and hypotension (OR 3.08 p=0.004). Acute lymphoblastic leukemia diagnosis (OR 0.34 p=0.026), increased age (OR 0.70 p=0.049) and drug exposure (OR 0.08 p<0.001) were associated with decreased risk for BSI. The risk prediction model had a C-index of 0.898; after bootstrapping adjustment for optimism, corrected C-index 0.885. Conclusions We developed a diagnostic prediction model for BSI in febrile pediatric oncology patients without severe neutropenia. External validation is warranted before use in clinical practice. PMID:25327666

  13. Oral health comparison between children with neutropenia and healthy controls.

    PubMed

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

    2014-01-01

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

  14. Multiplex PCR assay underreports true bloodstream infections with coagulase-negative staphylococci in hematological patients with febrile neutropenia.

    PubMed

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

    2016-08-01

    SeptiFast multiplex PCR assay was evaluated for detecting true bloodstream infections (BSIs) with coagulase-negative staphylococci (CoNS) in neutropenic hematological patients. Sensitivity for samples representing true CoNS-BSIs was 23.3% with an integrated cutoff and increased to 83.3% if the cutoff was neglected. Hence, the cutoff may prohibit timely targeted antimicrobial therapy. PMID:27220608

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

    Khair, Abdulhafeez M.; Elmagrabi, Dalal

    2015-01-01

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

  17. 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

  18. Renal Function in Children with Febrile Convulsions

    PubMed Central

    AFSHARKHAS, Ladan; TAVASOLI, Azita

    2014-01-01

    Objective Febrile convulsions (FC) are the most frequent seizure disorder in children. Some studies have detected serum electrolyte disturbances in patients with FC. This study determines serum electrolytes, renal function tests, and frequency of urinary tract infection in hospitalized children with FC. Materials & Methods In this descriptive, cross sectional study, we evaluated 291 children with FC admitted to the Neurology ward of Ali-Asghar Children’s Hospital from 2008– 2013. Data was recorded on age, sex, type (simple, complex), and recurrence of seizures, family history of FC and epilepsy, serum electrolytes, renal function tests, and urinary tract infections. Results A total of 291 patients with diagnosis of FC were admitted to our center. Of these 291 patients, 181 (62.2%) were male. The mean age was 24.4 ± 14.6 months. There were simple, complex, and recurrent FCs in 215 (73.9%), 76 (26.1%) and 61 (21%) of patients, respectively. Urinary tract infections (UTI) were found in 13 (4.5%) patients, more present in females (p-value = 0.03) and under 12 months of age (p-value = 0.003). Hyponatremia, hypocalcemia, and hypokalemia was detected in 32 (11%), 16 (5.5%), and 4 (1.4%) of cases, respectively. Twentyfour (8.2%) patients had a glomerular filtration rate less than 60 ml/min/1.73m2. There were no abnormalities in serum magnesium, BUN, and creatinine levels. Conclusion During FCs, mild changes may occur in renal function but a serum electrolyte evaluation is not necessary unless patients are dehydrated. In children with FC, urinary tract infections should be ruled out. PMID:25657771

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

    ERIC Educational Resources Information Center

    Wallace, S.J.

    1984-01-01

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

  20. 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

  1. Fatal bacteremic melioidosis in patients with prolonged neutropenia.

    PubMed

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

    2016-03-01

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

  2. Antibodies to myeloid precursor cells in autoimmune neutropenia.

    PubMed

    Hartman, K R; LaRussa, V F; Rothwell, S W; Atolagbe, T O; Ward, F T; Klipple, G

    1994-07-15

    Antibodies to mature blood neutrophils and to bone marrow myeloid cells have been described in the sera of some patients with apparent autoimmune neutropenia. To further explore the prevalence and specificities of antibodies to myeloid precursor cells, we evaluated sera from 148 patients with suspected autoimmune neutropenia for the presence of antibodies to neutrophils, to cultured myeloid cell lines, and to highly purified bone marrow myeloid progenitor cells. Using an immunofluorescence flow cytometric assay, we identified IgG antibodies in 42 (28%) of these sera that bound specifically to K562 cells, a multilineage cell line originally derived from a patient with chronic myelogenous leukemia. Twenty-two (15%) of the sera also contained IgG antibodies that bound specifically to the primitive myelomonocytic leukemia cell line KG1a. Twenty-five (17%) of the sera had IgG antibodies to myeloid cell lines in the absence of antibodies to mature neutrophils. There was a trend toward more severe neutropenia in patients with antibodies to K562 cells, without antineutrophil antibodies. In further studies, antibodies from 12 sera bound to mononuclear CD34+ cells that had been purified from normal human bone marrow by an immunomagnetic separation procedure. Moreover, two of these sera suppressed the growth of granulocyte-macrophage colony-forming units (CFU-GM) in methylcellulose cultures. The presence of antibodies to primitive hematopoietic cells in the sera of some patients with suspected immune neutropenia suggests that these antibodies may have a role in the pathogenesis of the neutropenia observed. PMID:7517722

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

    PubMed

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

    2010-02-01

    Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion abnormalities predispose to septic shock and increased mortality in neutropenic setting. We aimed at determining predictors of severe sepsis in neutropenic patients. Between 1 October and 31 December 2007, 41 patients (21 with acute myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem cell transplantation for a mantle cell lymphoma) with chemotherapy-induced neutropenia (<0.5 x 10(9)/l) lasting for more than 7 days were included in this study. The median age was 28 years (range: 3-58 years). All patients were on oral antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B) prophylaxis. The first neutropenic febrile episode was treated with piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h from the start of this first line of treatment, amphotericin B i.v. is added. Imipenem was introduced in the case of non-response and finally glycopeptides were introduced according to the IDSA criteria. Severe sepsis and septic shock are defined according to the criteria of the consensus conference of the ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic. Ninety-four febrile episodes were observed: 27 microbiologically documented (28.7%), six clinically documented (6.3%) and 61 fever of unknown origin (65%). Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram-positive organisms and three combined (Gram+ and -). Clinically documented infections were pneumonia (two), neutropenic enterocolitis (one), sinuses infection (one) and cutaneous infection (two). Severe sepsis accounted for 22 febrile episodes. Factors associated with the occurrence of severe sepsis were: hypophosphatemia (<0.8 mmol/l; p=0.05, OR=3.9, 95% CI: 1.3-45.7), hypoproteinemia (<62 g/l; p=0.006, OR=4.1, 95% CI: 1.4-11.4) and non-adapted antibiotherapy at the onset of severe sepsis (p=0.019, OR=2.7, 95% CI: 1

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

    PubMed

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

    2005-01-01

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

  5. 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

  6. Ecthyma gangrenosum and neutropenia in a previously healthy child.

    PubMed

    Pacha, Omar; Hebert, Adelaide A

    2013-01-01

    Ecthyma gangrenosum is the cutaneous manifestation of pseudomonas infection in patients with sepsis. A previously healthy 7-month-old girl who developed ecthyma gangrenosum without apparent inciting factors became neutropenic secondary to autoimmune neutropenia 2 months after initial presentation. She was treated with appropriate surgical and medical intervention and was discharged in stable condition only to die suddenly 2 days after discharge. PMID:22471737

  7. Recognition and management of febrile convulsion in children.

    PubMed

    Paul, Siba Prosad; Kirkham, Emily Natasha; Shirt, Bethany

    2015-08-26

    Febrile convulsion is characterised by convulsion associated with fever in an infant or child aged between six months and six years. The febrile illness causing the convulsion should not be secondary to an intracranial infection (meningitis or encephalitis) or acute electrolyte imbalance. Most cases of febrile convulsion are short lived and self-terminating. However, a few cases of prolonged febrile convulsion may need anticonvulsant medication to stop the seizure. Management is mainly symptomatic, although anticonvulsants may have a role in a small number of children with complex or recurrent febrile convulsion. Referral to paediatric neurologists may be necessary in cases of complex or recurrent febrile convulsion, or in those where a pre-existing neurological disorder exists. One third of children will develop a further febrile convulsion during subsequent febrile illness. Nurses have a vital role in managing children with febrile convulsion, educating parents about the condition and dispelling myths. This article outlines the presentation, management, investigations and prognosis for febrile convulsion, indicating how nurses working in different clinical areas can help to manage this common childhood condition. PMID:26307316

  8. Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis.

    PubMed Central

    Shoup, M; Weisenberger, J M; Wang, J L; Pyle, J M; Gamelli, R L; Shankar, R

    1998-01-01

    OBJECTIVE: To determine the mechanisms that lead to the decrease in bone marrow production of neutrophils during burn sepsis. SUMMARY BACKGROUND DATA: Impaired bone marrow granulopoiesis during burn sepsis often results in neutropenia despite elevated circulating levels of granulocyte colony-stimulating factor (G-CSF). To date, neither the specific stages of neutrophil maturation involved in the bone marrow suppression nor the mechanisms for the impairment have been determined. METHODS: Peripheral blood absolute neutrophil count and G-CSF levels were determined in mice 3 days after randomization to control, burn alone, or burn plus a topical inoculation of Pseudomonas aeruginosa (1000 colony-forming units). Bone marrow aspirates were analyzed for their neutrophil differentiation patterns by Gr-1 antigen expression and their G-CSF receptor status. Histologic analysis of liver, lung, spleen, and wound site was performed. RESULTS: In burn sepsis, absolute neutrophil count was reduced whereas plasma G-CSF levels were elevated, and myeloid differentiation was significantly shifted toward the immature mitotic myeloid cells. Bone marrow G-CSF receptor mRNA levels and G-CSF-stimulated proliferation were substantially decreased in burn sepsis. Histologic analysis revealed no significant neutrophil infiltration into the tissues. CONCLUSIONS: In thermal injury with superimposed sepsis, neutropenia and myeloid maturation arrest, despite the elevated levels of G-CSF, correlate with the reduction in bone marrow G-CSF receptor expression. These observations may provide a potential mechanism for neutropenia in sepsis. Images Figure 5. Figure 6. Figure 8. Figure 9. PMID:9671075

  9. Urinary tract infection in febrile convulsions.

    PubMed Central

    Lee, P; Verrier Jones, K

    1991-01-01

    A retrospective review of the casenotes of 403 children admitted to hospital with febrile convulsions was performed to estimate the frequency of symptomatic urinary tract infection and examine medical practice in making this diagnosis. A total of 228 (56%) children had urine cultured: 150 bag specimens, 76 clean voided samples, and two suprapubic aspirates. There were 13 'probable' and six 'possible' infected urine samples together representing 5% of the whole study population (n = 403), 8% of those having urine cultured (n = 228), and 12% of those providing uncontaminated urine samples (n = 155). Those with first febrile convulsions and those aged under 18 months were more likely to have urine examined. Practices varied significantly between different hospitals. These results suggest that there has indeed been a need for practice guidelines, and that further audit of practice is required to assess their impact. PMID:1755639

  10. Lumbar puncture refusal in febrile convulsion.

    PubMed

    Ling, S G; Boey, C C

    2000-10-01

    A descriptive study was carried out on patients admitted for febrile convulsion over a two-year period to determine rate of lumbar puncture (LP) refusal, factors associated with LP refusal and outcome of such patients. From 77 patients indicated and requested for LP, 19 (25%) patients refused the procedure. Refusal of LP was significantly more common among the Malay ethnic group (p = 0.01) but not significantly associated with age,gender or whether the patient was admitted for a first or recurrent febrile convulsion. Half of the patients who refused LP had to be started empirically on antibiotics for meningitis. Patients who refused LP were also 8.5 times more likely to discharge themselves "at own risk" (AOR), compared to other patients with febrile convulsion (p = 0.004). In conclusion, LP refusal is a common problem in the local setting and is a hindrance to the proper management of patients with fever and seizure. Appropriate measures must be carried out to educate the public, particularly those from the Malay ethnic group on the safety and usefulness of the procedure. Reasons for patients discharging AOR following LP refusal also need to be addressed and problems rectified. PMID:11281439

  11. 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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

    Popovic, V; Schaffer, R; Popovic, P

    1976-09-01

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

  14. 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

  15. [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

  16. [Febrile convulsion. A clinical study of 303 patients].

    PubMed

    Calderón-González, R; Vallejo-Moreno, D; Carrera-Sandoval, J P; Sevilla-Castillo, R; de la Peña-Saucedo, F

    1990-01-01

    The clinical characteristics of 303 patients who had episodes of feverish convulsions (FC) were retrospectively reviewed. No preference was seen for either sex (1.3/1). In 75.3% of the cases, the convulsions occurred in children under two. There was some predominance of tonic-clonic crisis and generalized clonic-tonic convulsions (85.5%) with 21.8% of complex partial crisis. In 44.8% of the cases a perinatal history of high risk was noted. A comparative investigation was carried out in a subgroup of 244 children in who FC vs non-febrile convulsions (NFC) were during two years. In 35.2% of the patients neurological abnormalities were found associated, among them were language difficulties (27.4%) and psychomotor retardation (11.9%). In 36.4% of the cases, the EEG was found to be abnormal, and paroxysmal in 27%. The predominating perinatal pathological complications were perinatal hypoxia-anoxia and prematurity. In 84% of the patients, anti-convulsive medication was administered. Of the 244 patients, 62 (25.4) of them had NFC which were directly related to the number of risk factors and their characteristics. Among those risk factors were partial convulsions, neurological deficit, abnormal EEG, convulsions lasting over 10 minutes and a previous family history of epilepsy. It is noteworthy that 15.7% of the patients had no risk factors related to epilepsy. In those patients who suffered from convulsions from an early age, who had convulsions of a partial--complex type, which lasted over 20 minutes and repeated frequently--were seen to be the most likely to develop epilepsy. The medications prescribed prevented the occurrence of the FC but did not significantly diminish the development of epilepsy. Febrile convulsions; epilepsy; perinatal. PMID:1692466

  17. 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…

  18. Use of tunnelled catheters in haematological malignancy patients with neutropenia.

    PubMed

    Sariosmanoglu, N; Uğurlu, B; Turgut, N H; Demirkan, F; Ozsan, H; Ergor, G; Gulay, Z; Hazan, E; Oto, O

    2008-01-01

    This prospective study analysed 83 patients (age 45 +/- 17 years) with haematological neoplasms, implanted with 93 tunnelled catheters, who were neutropenic or developed neutropenia during treatment. Catheters were implanted in the right (n = 82) or left (n = 11) jugular vein by the same surgical team using the same technique. They remained in place for 124 +/- 88 days: 29% were removed due to infection; 18% due to treatment termination and 2% due to mechanical problems. Seventeen patients died with catheters in place. At 30, 60, 90, 120 and 200 days mean catheter duration rates were 82%, 75%, 65%, 60% and 35%, respectively, and freedom from catheter removal due to infection was 92%, 88%, 80%, 77% and 67%, respectively. Patient diagnosis and history of previous catheter infection did not increase catheter infection risk, but patients undergoing stem cell transplantation had an increased infection risk. Tunnelled catheters can be used in high-risk patients with neutropenia. Systemic infections can be managed in most patients without catheter removal. PMID:18831907

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

    PubMed

    Caselli, Désirée; Cesaro, Simone; Aricò, Maurizio

    2016-01-01

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

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

    PubMed Central

    Caselli, Désirée; Cesaro, Simone; Aricò, Maurizio

    2016-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  2. 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

  3. Urinary tract infection in febrile children with sickle cell anaemia in Ibadan, Nigeria.

    PubMed

    Asinobi, A O; Fatunde, O J; Brown, B J; Osinusi, K; Fasina, N A

    2003-06-01

    A prospective study to determine the prevalence of bacteriuria and bacterial isolates in the urine of febrile children with sickle cell anaemia (SCA) was carried out at University College Hospital, Ibadan. Altogether, 171 febrile children (aged 1-15 years) with SCA and 171 age- and sex-matched controls were studied. After obtaining a history of the illness from the parents or guardians, each child was physically examined and a mid-stream urine specimen collected and subjected to microscopy and culture. The prevalence of bacteriuria in children with SCA was 21.6% compared with 15.8% in the controls. Escherichia coli and Klebsiella species were the predominant isolates from the urine, accounting for 64.9% and 18.9%, respectively, of the isolates from the SCA group and 63% and 22.2%, respectively, in the controls. In the SCA group, significant bacteriuria also occurred with other conditions such as pneumonia and osteomyelitis. Urinary tract infection (UTI) is common in children with SCA. Routine screening for it is therefore recommended during febrile illnesses. Children with fever from other overt causes, however, should not be exempted from the urine screening procedure in case there might be concomitant UTI. PMID:12803742

  4. 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

  5. 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

  6. 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

  7. 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

  8. Frequency of neutropenia among Turkish and Syrian pediatric thalassemia patients under deferiprone monotherapy.

    PubMed

    Belen, Burcu Fatma; Polat, Meltem; Özsevik, Sevinç Nursev; Soylu, Esma

    2016-02-01

    Weekly monitoring of absolute neutrophil count (ANC) under deferiprone therapy in thalassemia patients is recommended to avoid agranulocytosis adverse event. Actually, this recommendation may not be applicable in clinical setting. Our study aimed to establish incidence of neutropenia under deferiprone (DFP) monotherapy when it was monitored bimonthly due to socioeconomic conditions effecting local and refugee thalassemic patients including Syrian origin (SYR; n = 26) and Turkish origin (TR; n = 26) groups. Patients on DFP were followed up for 12 months. Fifteen neutropenic episodes were seen in 5 patients. All 5 patients (4 from SYR group and 1 from TR group) had splenomegaly and hypersplenism, and neutropenia ceased in 4 patients after splenectomy despite continuation of deferiprone. In the TR group, the frequency of patients who have neutropenia (absolute neutrophil count [ANC] <1500/mm(3)) was 3.8% (n = 1) in the 1st month, no patients in TR group had neutropenia until 10th month when again there was 1 patient with mild neutropenia. In SYR group, the frequency of patients who have neutropenia was 3.8% (n = 1), 7.7% (n = 2), and 11.5% (n = 3) in the 1st, 2nd, and 3rd months, respectively, and was found to be 3.8% (n = 1) between 6 and 12 months. Whether or not DFP therapy should be interrupted in case of mild neutropenia and the frequency of monitoring ANC in real-life conditions should be documented with further studies. Other causes of neutropenia in DFP-treated patients should also be kept in mind. PMID:26918459

  9. Undifferentiated febrile illness in Kathmandu, Nepal.

    PubMed

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

    2015-04-01

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

  10. Lack of association between TNF-α gene polymorphisms at position -308 A, -850T and risk of simple febrile convulsion in pediatric patients

    PubMed Central

    Khoshdel, Abolfazl; Kheiri, Soleman; Habibian, Roya; Nozari, Ahora; Baradaran, Azar

    2012-01-01

    Background: Febrile convulsions (FCs), occurring between 6 months and 6 years of age is the most common seizure disorder during childhood. The febrile response is thought to be mediated by the release of pyrogenic cytokines, such as tumor necrosis factor and interleukin-1 (IL-1). There is a significant relationship between genetic components for susceptibility of FCs and different report mutation. We investigated association between two polymorphisms in the tumor necrosis factor (TNF)-α promoter region (G-308A, C-850T) and FCs in the southwest area of Iran. Materials and Methods: In this matched case–control study, 100 patients with febrile convulsion as case group and 130 healthy children as control group were enrolled in the study. Peripheral blood samples were collected and DNA was extracted by standard phenol–chloroform method. The genotype and allele frequencies of TNF- α polymorphisms in case and control groups were determined by using PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) method. Statistical analysis was done using Chi-square test. Results: The average age of case and control groups were 3.4 ± 1.4 and 3.4 ± 1.2 years, respectively. There was no significant difference between age and sex in both the groups (P > 0.05). A family history of febrile convulsion was detected in 44% of patients. Moreover, the simple febrile convulsion was detected in 85% of the case group. Conclusion: RFLP analysis of TNF- α promoter region polymorphisms, considering P = 0.146 and P = 0.084 for G-308A and C-850T, respectively, showed no correlation between TNF- α polymorphisms and predisposition to simple febrile, based on the kind of convulsion (atypical and simple febrile convulsion). We found a significant relation between genotype distribution of G-308A and atypical febrile convulsion in case group (P = 0.04). A significant correlation between genotype distribution of G-308A and atypical febrile convulsion in the case group was

  11. Effect of Adenine on Clozapine-induced Neutropenia in Patients with Schizophrenia: A Preliminary Study

    PubMed Central

    Takeuchi, Ippei; Kishi, Taro; Hanya, Manako; Uno, Junji; Fujita, Kiyoshi; Kamei, Hiroyuki

    2015-01-01

    Objective This study examined the utility of adenine for preventing clozapine-induced neutropenia. Methods This retrospective study examined the effect of adenine on clozapine-induced neutropenia in patients with treatment-resistant schizophrenia and was conducted at Okehazama Hospital in Japan from July 2010 to June 2013. Adenine was available for use from June 2011 onwards. Twenty-one patients started receiving clozapine treatment from July 2010 to April 2011 (the pre-adenine adoption group), and 47 patients started receiving it from May 2011 to June 2013 (the post-adenine adoption group). The effects of adenine were assessed based on changes in the patients’ leukocyte counts and the frequency of treatment discontinuation due to clozapine-induced neutropenia. Results Sixty-eight patients were treated with clozapine from July 2010 to June 2013. Of the 21 patients in the pre-adenine adoption group, 4 discontinued treatment due to clozapine-induced neutropenia, whereas only 2 of the 47 patients in the post-adenine adoption group discontinued treatment. The frequency of treatment discontinuation due to clozapine-induced neutropenia was significantly lower in post-adenine adoption group than in the pre-adenine adoption group (p=0.047). Conclusion Adenine decreased the frequency of treatment discontinuation due to clozapine-induced neutropenia. Our data suggest that combined treatment with clozapine and adenine is a safe and effective strategy against treatment-resistant schizophrenia. PMID:26243842

  12. Characterization of the bone marrow immunofluorescence test in childhood autoimmune neutropenia.

    PubMed

    Lane, S W; Hassell, P; Kennedy, G A; Fung, Y L; Williams, B A

    2009-10-01

    The bone marrow immunofluorescenece test (BMIFT) demonstrates autoantibodies to granulocytes and their precursors on fresh-frozen bone marrow slides. It may be used to differentiate childhood autoimmune neutropenia (AIN) from other causes of childhood neutropenia, even when circulating neutrophil counts are low. We sought to characterize the diagnostic utility of the BMIFT in childhood AIN. All BMIFT requests for investigation of children with neutropenia between January 1998 and May 2007 were reviewed. Patients were classified as AIN or nonautoimmune causes. Baseline demographic data, results of BMIFT, granulocyte immunofluorescence testing and bone marrow findings were collected from clinical records and the institutional laboratory database. Seventy-six children had BMIFT performed for investigation of neutropenia. There were 45 patients diagnosed with AIN, 28 with nonimmune neutropenia and three failed tests. The median age of children with AIN was 1.2 years (range 0.3-15.3), compared with 3.6 years (range 0.1-15.7) in the nonautoimmune group. The median neutrophil count in AIN was 0.3 x 10(9)/l (0.9 x 10(9)/l in nonautoimmune). BMIFT was positive in 24 of 45 patients with AIN and 0 of 28 with nonautoimmune neutropenia (sensitivity 53%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value 57%). Ten patients had other autoimmune diatheses at diagnosis. The BMIFT is a simple, highly specific test with excellent PPV and thus is a clinically useful test to confirm AIN in children. PMID:18637806

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

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. Increased frequency of monoclonal gammopathy of undetermined significance in patients with nonimmune chronic idiopathic neutropenia syndrome.

    PubMed

    Papadaki, H A; Eliopoulos, D G; Ponticoglou, C; Eliopoulos, G D

    2001-04-01

    This study describes the frequency of monoclonal gammopathy of undetermined significance (MGUS) and the changes in some inflammation-related serum proteins in 157 patients with nonimmune chronic idiopathic neutropenia syndrome (NI-CINS). Of these patients, 42 had pronounced neutropenia with neutrophil counts < 1500/microL, and 115 had mild neutropenia with neutrophil counts ranging from 1500 to 2499/microL. Sixty-six volunteers served as healthy control subjects and 157 age- and sex-matched patients hospitalized for nonmalignant diseases served as patient control subjects. We found that 28.6% of patients with pronounced neutropenia and 14.8% of patients with mild neutropenia had increased serum gamma globulins (above the 95% confidence limit of values of the control subjects). In the group of patients with pronounced neutropenia, 30.9% had increased immunoglobulin (Ig)G values and 23.8% had increased IgA values. In the group of patients with mild neutropenia, 17.4% had increased IgG values and 21.7% had increased IgA values. IgG and IgA values strongly correlated with the neutrophil count. No changes in serum IgM were found. Three of 42 patients with pronounced neutropenia (7.14%) and 3 of 115 patients with mild neutropenia (2.61%) had serum immunofixation tests which showed a small monoclonal spike--4 were IgG-kappa type, 1 was IgG-lambda type, and 1 was IgA-kappa type. None of the healthy or patient control subjects had any evidence of MGUS. No significant changes in the amount of monoclonal spikes were documented during an 18- to 143-month follow-up (median, 58 months). Except for significantly increased alpha1-antitrypsin levels, there were no significant differences in the levels of acute-phase proteins studied between the study patients and the control subjects. These findings are consistent with our previous report suggesting the possible existence of an unrecognized low-grade chronic inflammation in patients with NI-CINS, which may be involved in the

  16. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    PubMed

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

    2010-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Human Herpes Virus Type 6 and Febrile Convulsion

    PubMed Central

    HOUSHMANDI, Mohammad Mehdi; MOAYEDI, Alireza; RAHMATI, Mohammad Bagher; NAZEMI, Abdulmajid; FAKHRAI, Darioush; ZARE, Shahram

    2015-01-01

    Objective Febrile Convulsion (FC) is occurred in 6 months to 5 yr old children. The aim of this study was to investigate the prevalence of HHV-6 infection in FC admitted patients of Bandar Abbas Children Hospital, southern Iran. Materials & Methods In a cross-sectional study, 118 children aged 6-60 months who had FC were selected by a simple random method in 2010-11. Demographic data, clinical manifestation and two blood samples gathered to assess the human herpes virus type 6 (HHV6). Blood sample obtained at the time of admission and 10 days after the first examination. ELISA was used to detect HHV-6 IgG. The subjects were studied in two groups with and without infection of HHV-6. Two groups were compared by t-test and X2. Results Fifty-three subjects completed the study, including 30 boys (56.6 %) and 23 girls (43.4%). The HHV-6 infection was detected in 23 patients out of 53 studied subjects. The mean of age for the groups with and without HHV-6 infection was 19.7±9.7 and 20.4±10.2 months old, respectively. The most common clinical presentation in both groups was rhinorrhea, diarrhea, vomiting and lethargy without any significant difference between two groups. Five patients (21.7%) in HHV-6 group and 1 patient (3.3%) in HHV-6 negative group had postictal phase more than 15 minutes (P<0.05). Convulsion within 1 hour from beginning of fever was more frequent in HHV-6 infection group than the other group (P<0.01). Conclusion There was not any difference in terms of age group, gender and clinical manifestation of infected and non-infected children with FC. Postictal phase and seizure during 1 hour after the fever were significantly different between two groups. PMID:26664436

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

    PubMed

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

    2006-05-01

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

  20. Selenium and leptin levels in febrile seizure: a case-control study in children

    PubMed Central

    Khoshdel, Abolfazl; Abbasi, Maedeh

    2013-01-01

    Purpose Febrile seizures (FS) are seizures that occur between the age of 6 and 60 months, but its pathophysiology still is not fully understood. There is limited information about the correlation between levels of selenium and leptin with FS. This study aimed to determine the relationship between serum levels of selenium and leptin in children with FS. Methods This case-control study was conducted in a University Hospital in Shahrekord, Iran, in 2011. The serum levels of selenium and leptin of 25 children with simple febrile seizure (case group) were compared with 25 febrile children without seizure (control group) in acute phase and after three months. The levels of serum selenium and leptin were measured by flame atomic absorption spectrophotometer and enzyme-linked immunosorbent assay method, respectively. Results In acute phase, the mean serum level of selenium in case and control groups were 95.88±42.55 and 113.25±54.43 µg/dL, respectively, and difference was not significant (P=0.415), but after three months, this level had a significant increase in both groups (P<0.001). In acute phase, the mean serum leptin level in case and control groups were 0.94±0.5 and 0.98±0.84 ng/mL, respectively, but difference was not significant (P=0.405). After three months, serum leptin level had no significant change in both groups (P=0.882). Conclusion These observations suggest that serum levels of selenium and leptin have not specific relation with FS but overllay is lower, however, further study is recommended. Also selenium level in stress and acute phase was significantly lower than recovery phase. PMID:23482826

  1. Imipenem-Cilastatin versus Sulbactam-Cefoperazone plus Amikacin in the Initial Treatment of Febrile Neutropenic Cancer Patients

    PubMed Central

    ÖZYILKAN, Özgür; YALÇINTAŞ, ÜlKü; BAŞKAN, Sezgin

    1999-01-01

    The treatment of infectious complications in cancer patients has evolved as a consequence of the developments in the chemotherapy of cancer patients. In this prospective, randomized study, we compared imipenem-cilastatin and sulbactam-cefoperazone with amikacin in the empiric therapy of febrile neutropenic (<1000/mm3) patients with liquids and solid tumours. Of 30 evaluable episodes, 15 were treated with imipenem-cilastatin and 15 were treated with sulbactam-cefoperazone plus amikacin. 73% of episodes were culture-positive; gram-positive pathogens accounted for 62% of the isolates. Bacteremia was the most frequent site of infection. The initial clinical response rate for both regimens was 60% (p>0.05). No major adverse effects occurred. This study demonstrated that imipenem-cilastatin monotherapy and combination therapy of sulbactam-cefoperazone plus amikacin were equally effective empiric therapy for febrile granulocytopenic cancer patients. PMID:10461420

  2. Population pharmacokinetic–pharmacodynamic analysis for eribulin mesilate-associated neutropenia

    PubMed Central

    van Hasselt, J G Coen; Gupta, Anubha; Hussein, Ziad; Beijnen, Jos H; Schellens, Jan H M; Huitema, Alwin D R

    2013-01-01

    Aims Eribulin mesilate is an inhibitor of microtubule dynamics that is approved for the treatment of late-stage metastatic breast cancer. Neutropenia is one of the major dose-limiting adverse effects of eribulin. The objective of this analysis was to develop a population pharmacokinetic–pharmacodynamic model for eribulin-associated neutropenia. Methods A combined data set of 12 phase I, II and III studies for eribulin mesilate was analysed. The population pharmacokinetics of eribulin was described using a previously developed model. The relationship between eribulin pharmacokinetic and neutropenia was described using a semi-physiological lifespan model for haematological toxicity. Patient characteristics predictive of increased sensitivity to develop neutropenia were evaluated using a simulation framework. Results Absolute neutrophil counts were available from 1579 patients. In the final covariate model, the baseline neutrophil count (ANC0) was estimated to be 4.03 × 109 neutrophils l−1 [relative standard error (RSE) 1.2%], with interindividual variability (IIV, 37.3 coefficient of variation % [CV%]). The mean transition time was estimated to be 109 h (RSE 1.8%, IIV 13.9CV%), the feedback constant (γ) was estimated to be 0.216 (RSE 1.4%, IIV 12.2CV%), and the linear drug effect coefficient (SLOPE) was estimated to be 0.0451 μg l−1 (RSE 3.2%, IIV 54CV%). Albumin, aspartate transaminase and receival of granulocyte colony-stimulating factor (G-CSF) were identified as significant covariates on SLOPE, and albumin, bilirubin, G-CSF, alkaline phosphatase and lactate dehydrogenase were identified as significant covariates on mean transition time. Conclusions The developed model can be applied to investigate optimal treatment strategies quantitatively across different patient groups with respect to neutropenia. Albumin was identified as the most clinically important covariate predictive of interindividual variability in the neutropenia time course. PMID:23601153

  3. Febrile convulsion--a clinical survey and a review of its current concept of management.

    PubMed

    Saw, A H; Ho, L; Lim, K W; Cheng, H K

    1989-01-01

    Between February 1986 to November 1986, 335 cases of febrile convulsion were admitted to the paediatric ward, Tan Tock Seng Hospital. The study revealed 87 cases (26%) were complex febrile convulsion and 73 cases (21.8%) were recurrent febrile convulsion. 51 patients with complex febrile convulsion and 32 patients with recurrent febrile seizures were put on long term phenobarbitone. The number of patients with recurrent and complex convulsion was big. The role of anticonvulsant prophylaxis is reviewed and its efficacy discussed. PMID:2638720

  4. Concurrent bacteraemia and malaria in febrile Nigerian infants.

    PubMed

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

    2005-01-01

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

  5. Phenotypes and genotypes in epilepsy with febrile seizures plus.

    PubMed

    Ito, M; Yamakawa, K; Sugawara, T; Hirose, S; Fukuma, G; Kaneko, S

    2006-08-01

    In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some febrile seizures related epilepsies. In 19 unrelated Japanese families whose probands had febrile seizures plus or epilepsy following febrile seizures plus, we identified 2 missense mutations of SCN1A to be responsible for the seizure phenotypes in two FS+ families and another mutation of SCN2A in one family. The combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in SCN2A, showed digenic inheritance, and another modifier gene was thought to take part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and most of EFS+ display a complex pattern of inheritance, even when it appears to be an autosomal-dominant inheritance. There is a possibility of simultaneous involvement of multiple genes for seizure phenotypes. PMID:16884893

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

    PubMed Central

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

    2014-01-01

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

  7. EEG longitudinal studies in febrile convulsions. Genetic aspects.

    PubMed

    Doose, H; Ritter, K; Völzke, E

    1983-05-01

    It was the purpose of the study to obtain viewpoints on the genetics of febrile convulsions and their relationship to epilepsy by EEG long term follow up. 89 children with febrile convulsions could be followed up to the age of 11 to 13 years (in total 1046 EEG records). The study was concentrated on genetically determined EEG patterns: bilaterally synchronous spikes and waves, photosensitivity and 4-7 cps rhythms. The statistical evaluation was based on standards derived from known strict age dependence of the different patterns. Theta rhythms were found in 54%, spikes and waves of the resting record in 49% and photosensitivity in 42%. In total, genetically determined EEG patterns were found in 81% of the cases which were sufficiently investigated according to given standards. Spikes and waves are strongly age dependent with a maximum at the age of 5-6 years and appear very inconstantly. Theta rhythms and spikes and waves are closely correlated. Spikes and waves are a heterogeneous phenomenon. The type described here must be interpreted as a facultative symptom of the same functional anomaly which forms the basis of 4-7 cps rhythms. The possible pathophysiological basis of the pattern is discussed.--Photosensitivity is interpreted as the symptom of a genetically independent pathogenetic mechanism, which can lead to additive effects by interaction with other genetic abnormalities as well as exogenous factors.--The pathogenesis of febrile convulsions is multifactorial in the strict sense. While the exogenous pathogenetic factors are rather uniform, the genetic predisposition apparently is not. It is based on different genetic anomalies. Each of them is polygenically determined. In the individual case one or different factors can be involved. The genetic predisposition to febrile convulsions is definitely not only polygenic, but of heterogeneous nature. Finally the genetic relationship between febrile convulsions and epilepsy is discussed. PMID:6877532

  8. Cyclic Neutropenia and Severe Congenital Neutropenia in Patients with a Shared ELANE Mutation and Paternal Haplotype: Evidence for Phenotype Determination by Modifying Genes

    PubMed Central

    Newburger, Peter E.; Pindyck, Talia N.; Zhu, Zhiqing; Bolyard, Audrey Anna; Aprikyan, Andrew A. G.; Dale, David C.; Smith, Gary D.; Boxer, Laurence A.

    2010-01-01

    Background Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other Procedure We performed ELANE genotyping on all individuals and paternal sperm in an SCN kindred with 8 SCN progeny of a sperm donor and 6 different mothers. Results One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype. The mutant allele was detected in the donor’s spermatozoa, representing 18% of the ELANE gene pool, but not in DNA from his lymphocytes, neutrophils, or buccal mucosa, indicating gonadal mosaicism. Conclusions The coexistence of CN and SCN phenotypes in this kindred with a shared paternal haplotype strongly suggests both a role for modifying genes in determination of congenital neutropenia disease phenotypes, and the classification of CN and SCN within a spectrum of phenotypes expressing varying degrees of the same disease process. PMID:20582973

  9. 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

  10. Impact of Selenium Supplementation in Neutropenia and Immunoglobulin Production in Childhood Cancer Patients.

    PubMed

    Rocha, Katya Cristina; Vieira, Maria Luiza Dos Santos; Beltrame, Registila Libania; Cartum, Jairo; Alves, Sarah Isabel P M do N; Azzalis, Ligia Ajaime; Junqueira, Virginia Berlanga Campos; Pereira, Edimar Cristiano; Fonseca, Fernando Luiz Affonso

    2016-06-01

    Essential to human health, selenium (Se) has enzymatic functions of fundamental importance to human biology due to its effects on DNA damage repair, its antioxidant properties, and cancer prevention. The best studied relationships between Se and the immune system is its role in the functions of neutrophils and of lymphocytes. Despite these observations, it is not yet clear by which mechanism Se is able to modify the immune status. This was a double-blind, crossover study: Group 1 received Se and Group 2 received placebo (30 days). After this, Group 1 received placebo and Group 2 received Se (30 days). Every 30 days, blood samples were collected for white blood cell count, red blood cell count, and Ig level measurement (IgA, IgG, IgE, IgM). Of the 36 patients, 17 were suffering from leukemia/lymphomas (LL) and 19 from solid tumors (ST). In the ST group's leukogram, a significant increase in neutrophils was observed after Se usage (P = .0192). During the analyzed period, Se minimized the triggering of neutropenia cases in both groups. IgA and IgG levels in ST patients were significantly higher than those identified in LL patients after Se usage (P = .0051 and P = .0055). For IgA, a significant increase in its production, after Se usage, was observed in the ST group when compared to the LL (P = .0011). The same did not occur to the IgM and IgE immunoglobulins. In our study, the supplementation with Se reduced the neutropenic cases (LL and ST patients) and reduced IgG and IgA levels in LL and increased in ST group. PMID:27266340

  11. Neutropenia as a prognostic factor and safety of second-line therapy with S-1 for advanced or recurrent pancreatic cancer

    PubMed Central

    Ikagawa, Makiko; Kimura, Michio; Iwai, Mina; Usami, Eiseki; Yoshimura, Tomoaki; Yasuda, Kimio

    2016-01-01

    The aim of this retrospective study was to investigate the safety of S-1 as second-line therapy and to evaluate the association between neutropenia occurring during first-line gemcitabine (GEM) therapy and survival for advanced or recurrent pancreatic cancer (APC). Between January, 2010 and December, 2014, 123 APC patients received chemotherapy at the Ogaki Municipal Hospital (Ogaki, Japan). Of those, 37 received GEM as first-line and S-1 as a second-line therapy (GEM→S-1 group). A further 60 patients received GEM as first-line therapy, but did not receive second-line therapy (GEM group). The median overall survival in the GEM→S-1 (n=37) and GEM (n=60) groups was 323 days [95% confidence interval (CI): 138–218.9 days] and 172 days (95% CI: 105–184.4 days), respectively (P=0.0004). The median overall survival in the mild (grade ≤2; n=63) and severe (grade ≥3; n=34) neutropenia groups was 178 days (95% CI: 182–275 days) and 330 days (95% CI: 297–514 days), respectively (log-rank test, P=0.0023). The severe non-haematological toxicities associated with S-1 as second-line therapy were nausea (2.7%) and hand-foot syndrome (2.7%). Second-line S-1 treatment was discontinued due to adverse events in 5.4% (2/37) of the cases. In conclusion, neutropenia occurring during GEM therapy administered as first-line treatment to APC patients was strongly associated with a better prognosis. S-1 therapy as second-line treatment was associated with a low incidence of severe adverse events and the patients were able to successfully continue treatment.

  12. 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

  13. 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

  14. Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia.

    PubMed

    Salipante, Stephen J; Benson, Kathleen F; Luty, Joanna; Hadavi, Valeh; Kariminejad, Roxana; Kariminejad, Mohamad H; Rezaei, Nima; Horwitz, Marshall S

    2007-09-01

    Heterozygous mutations of ELA2, encoding the protease neutrophil elastase (NE), cause either autosomal dominant cyclic neutropenia or severe congenital neutropenia (SCN). Three hypotheses have been proposed for how allelic mutations produce these different disorders: 1) disruption of proteolytic activity; 2) mislocalization of the protein; or 3) destabilization of the protein resulting in induction of the unfolded protein response. As with other dominant diseases with reduced reproductive fitness, sporadic cases can result from new mutations not inherited from either parent. Here we report an exceptional genetic phenomenon in which both a cyclic neutropenia patient and an SCN patient each possess two new ELA2 mutations. Because of the rarity of the phenomenon, we investigated the origins of the mutations and found that both arise nonmosaically and in cis from the paternally-inherited allele. Moreover, these cases offer a unique opportunity to investigate molecular pathways distinguishing these two forms of hereditary neutropenia. We have characterized the mutants separately and in combination, with respect to their effects on proteolysis, subcellular trafficking, and induction of the unfolded protein response. Each pair of mutations acts more or less additively to produce equivalent net effects on reducing proteolytic activity and induction of the unfolded protein response, yet each has different and somewhat opposing effects on disturbing subcellular localization, thus offering support for a role for protein mistrafficking as a disease mechanism. PMID:17436313

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

    PubMed Central

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

    2014-01-01

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

  16. A randomized trial of high-dose ciprofloxacin versus azlocillin and netilmicin in the empirical therapy of febrile neutropenic patients.

    PubMed

    Johnson, P R; Liu Yin, J A; Tooth, J A

    1992-08-01

    A prospective, randomized trial comparing monotherapy with high-dose ciprofloxacin versus a standard combination regimen of azlocillin and netilmicin in the empirical treatment of febrile episodes in neutropenic patients was performed. One hundred and forty-six patient episodes were randomized, but ten (seven ciprofloxacin and three azlocillin/netilmicin) were considered unevaluable for efficacy, and three episodes were withdrawn due to incorrect randomization or non-neutropenia. Of the remaining 133 episodes, infections resolved without modification of therapy in 25/66 (38%) versus 28/67 (42%) of ciprofloxacin and azlocillin/netilmicin treated groups respectively (P = 0.72). Considering all randomized episodes, therapy was modified in 46/73 (63%) episodes with ciprofloxacin and 39/70 (56%) with azlocillin/netilmicin (P = 0.40). Of 73 patient episodes randomized to ciprofloxacin, 25 (34%) received oral follow-on therapy after a median of three days of intravenous therapy. Infections were microbiologically documented in 31/73 (42%) ciprofloxacin and 32/70 (46%) azlocillin/netilmicin, of which 8/27 (30%) and 14/31 (45%) of evaluable episodes resolved without modification of therapy respectively (P = 0.28). Gram-positive organisms accounted for 78% of all organisms cultured with 36% coagulase-negative staphylococci. Bacteriological eradication was recorded in 18/24 (75%) and 26/29 (90%) evaluable patient episodes treated with ciprofloxacin and azlocillin/netilmicin respectively (P = 0.27). Superinfections were seen in 14% of episodes in both groups, and subsequent infections in 12% ciprofloxacin and 14% azlocillin/netilmicin treated patients. Two patients (one ciprofloxacin and one azlocillin/netilmicin) died within 48 h of randomization, and a further 13 patients (four ciprofloxacin and nine azlocillin/netilmicin) died before resolution of neutropenia. Adverse events were recorded in 9% and 15% of ciprofloxacin and azlocillin/netilmicin treated patients respectively

  17. 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

  18. 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

  19. 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

  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. PMID:26328000

  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. Vasopressin: its role in antipyresis and febrile convulsion.

    PubMed

    Veale, W L; Cooper, K E; Ruwe, W D

    1984-02-01

    When pyrogenic substances are injected intravenously into experimental animals, a sequence of events is set in motion which involves the hypothalamus and perhaps other portions of the diencephalon to produce a febrile response. We now present evidence that the brain produces its own endogenous antipyretic which may serve as a means of controlling the extent of the fever. When arginine vasopressin is perfused through the lateral septal area of the hypothalamus of the sheep, fever is suppressed. Vasopressin alone does not lower normal body temperature when perfused through this region of the brain. In addition, evidence is provided to indicate that vasopressin is released within the lateral septal area during the febrile response. It is concluded that, in fever, arginine vasopressin may be released in the lateral septal area of the brain and serve as an endogenous antipyretic. Results indicate that, following an initial application of vasopressin into the brain itself, a subsequent similar administration of vasopressin produces seizure-like activity. Therefore, it is suggested that this release of arginine vasopressin may contribute to the production of febrile convulsion. PMID:6722595

  3. Long term outcome of prophylaxis for febrile convulsions.

    PubMed Central

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

    1996-01-01

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

  4. Parental reactions to a child's first febrile convulsion. A follow-up investigation.

    PubMed

    Balslev, T

    1991-04-01

    The severe psychological reactions of most parents to the first febrile convulsions of their child contrast with the doctors' consideration of febrile convulsions as a simple and benign phenomenon. Fifty-two parents whose child had been admitted with febrile convulsions were interviewed about their immediate and long-term reactions. Most of the parents knew little about febrile convulsions before the fit. Parents with previous knowledge of febrile convulsions took more appropriate measures during the fit than parents without such knowledge. Sixty per cent of the parents slept restlessly for some time after the fit, 13% watched their child at night, and 29% had dyspeptic symptoms. Parents of young children should as a routine be offered general information by the family doctor about fever and febrile convulsions. Parents who have watched their child during a fit need specific information in order to avoid long-term reactions. PMID:2058397

  5. 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

  6. Diagnosis of autoimmune neutropenia by neutrophil-bound IgG and IgM antibodies.

    PubMed

    Ito, Taichi; Taniuchi, Shoichiro; Tsuji, Shoji; Iharada, Anna; Hasui, Masafumi; Kaneko, Kazunari

    2011-10-01

    Autoimmune neutropenia (AIN) in infancy is caused by antineutrophil (granulocyte-specific) autoantibodies. These antibodies are rarely found in circulation because their serum levels are extremely low. We hypothesized that a direct granulocyte immunofluorescence test (D-GIFT) that enables us to detect neutrophil-bound autoantibodies consisting of both immunoglobulin (Ig) G and IgM has better diagnostic value than the detection of circulating autoantibodies. Whole blood (100 μL) was obtained from 50 infants with AIN, 12 infants with transient neutropenia, and 37 control infants. D-GIFT was performed using both fluorescein isothiocyanate-conjugated antihuman IgG Fc portion monoclonal antibodies and fluorescein isothiocyanate antihuman IgM monoclonal antibodies. Results were assessed as relative fluorescence intensity (RFI). The RFIs of antineutrophil IgG-bound and antineutrophil IgM-bound cells in patients with AIN were significantly higher than those in patients with transient neutropenia and in controls. Positive results, as assessed by RFI scores of more than 1.81 in either antineutrophil IgG-bound or antineutrophil IgM-bound cells, showed the sensitivity and specificity of D-GIFT, and the areas under the receiver operating characteristic curve (0.98, 0.98, and 0.997, respectively) in the diagnosis of AIN. D-GIFT detecting both neutrophil-bound IgG autoantibodies and IgM autoantibodies has discriminatory power for identifying patients with AIN and, therefore, can be a useful diagnostic test. PMID:21941149

  7. 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

  8. Naturally occurring chemical carcinogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2002-09-01

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

  10. Subacute Sclerosing Panencephalitis in a Child with Recurrent Febrile Seizures

    PubMed Central

    Kartal, Ayşe; Çıtak Kurt, Ayşegül Neşe; Hirfanoğlu, Tuğba; Aydın, Kürşad; Serdaroğlu, Ayşe

    2015-01-01

    Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recurrent febrile seizures. The disease progressed with an appearance of myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis. PMID:25802788

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

    PubMed

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

    2015-02-01

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

  12. 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…

  13. 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…

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-10-15

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

  16. 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

  17. 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

  18. 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

  19. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?

    PubMed

    Scheffer, Ingrid E; Zhang, Yue-Hua; Jansen, Floor E; Dibbens, Leanne

    2009-05-01

    Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) can both arise due to mutations of SCN1A, the gene encoding the alpha 1 pore-forming subunit of the sodium channel. GEFS+ refers to a familial epilepsy syndrome where at least two family members have phenotypes that fit within the GEFS+ spectrum. The GEFS+ spectrum comprises a range of mild to severe phenotypes varying from classical febrile seizures to Dravet syndrome. Dravet syndrome is a severe infantile onset epilepsy syndrome with multiple seizure types, developmental slowing and poor outcome. More than 70% of patients with Dravet syndrome have mutations of SCN1A; these include both truncation and missense mutations. In contrast, only 10% of GEFS+ families have SCN1A mutations and these comprise missense mutations. GEFS+ has also been associated with mutations of genes encoding the sodium channel beta 1 subunit, SCN1B, and the GABA(A) receptor gamma 2 subunit, GABRG2. The phenotypic heterogeneity that is characteristic of GEFS+ families is likely to be due to modifier genes. Interpretation of the significance of a SCN1A missense mutation requires a thorough understanding of the phenotypes in the GEFS+ spectrum whereas a de novo truncation mutation is likely to be associated with a severe phenotype. Early recognition of Dravet syndrome is important as aggressive control of seizures may improve developmental outcome. PMID:19203856

  20. Progress in searching for the febrile seizure susceptibility genes.

    PubMed

    Nakayama, Junko

    2009-05-01

    Febrile seizures (FS) represent the most common form of childhood seizures. They affect 2-5% of infants in the Caucasian population and are even more common in the Japanese population, affecting 6-9% of infants. Some familial FS are associated with a wide variety of afebrile seizures. Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with a spectrum of phenotypes including FS, atypical FS (FS+) and afebrile seizures. A significant genetic component exists for susceptibility to FS and GEFS+: extensive genetic studies have shown that at least nine loci are responsible for FS. Furthermore, mutations in the voltage-gated sodium channel subunit genes (SCN1A, SCN2A and SCN1B) and the GABA(A) receptor subunit genes (GABRG2 and GABRD) have been identified in GEFS+. However, the causative genes have not been identified in most patients with FS or GEFS+. Common forms of FS are genetically complex disorders believed to be influenced by variations in several susceptibility genes. Recently, several association studies on FS have been reported, but the results vary among different groups and no consistent or convincing FS susceptibility gene has emerged. Herein, we review the genetic data reported in FS, including the linkage analysis, association studies, and genetic abnormalities found in the FS-related disorders such as GEFS+ and severe myoclonic epilepsy in infancy. PMID:19201561

  1. Assessments of blood lead levels in children with febrile convulsion

    PubMed Central

    Khosravi, Nastaran; Izadi, Anahita; Noorbakhsh, Samileh; Javadinia, Shima; Tabatabaei, Azardokht; Ashouri, Sarvenaz; Asgarian, Ramin

    2014-01-01

    Background: Lead elements have an adverse effect on human health. The most important complications of lead poisoning are disorders of nervous system particularly seizure .This study aimed to evaluate the blood lead levels and its association with convulsion in a group of hospitalized febrile children. Methods: In this analytic cross-sectional study, 60 hospitalized febrile children with 1- 60 month old participated in the study via non-probability convenience sampling method. All of the information included sex, age, weight, blood lead levels and history of convulsion gathered in the questionnaire. Finally all of data were statistically analyzed. Results: 66.7% of samples were male and 33.3% were female. The mean age was 32.57±38.27 months and the mean weight was 13.04±9.61kg. The Mean and Standard deviation of Blood lead level was 4.83±3.50μg/dL. 10% of samples had lead levels greater than 10μg/dL. 53.3% of patients have convulsion and other don’t have it. Blood lead levels was 4.91±3.65μg/dL in children with convulsion and 4.73± 3.38μg/dL in children without it; the difference was not significant (p= 0.8). Conclusion: Overall, no significant association was found between blood lead levels and convulsion. PMID:25664298

  2. Cerebrospinal fluid folate and cobalamin levels in febrile convulsion.

    PubMed

    Osifo, B O; Lukanmbi, F A; Familusi, J B

    1985-05-01

    Folate and cobalamin parameters were studied in the serum and cerebrospinal fluid of 40 febrile paediatric patients. Eighteen of these children were in a state of febrile convulsion while the remaining 22 were non-convulsing. The serum folate concentration of all the patients was higher than that of the control group but the highest value was found in the convulsing children. There was no significant difference in the CSF folate levels between the two groups of patients. The serum cobalamin levels of the patients were significantly lower than those of the control children and the lowest mean was observed in the convulsing state. On the other hand, there was no difference in the CSF cobalamin between the convulsing and non-convulsing children. These results confirm that there is an effective blood-brain barrier system for folate even when serum folate levels are higher than normal. There is also a definite decrease in serum cobalamin during pyrexia but this decrease is more apparent in the convulsing state. The role of cobalamin metabolism in convulsion is not clear. PMID:4009203

  3. 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 ...

  4. Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group.

    PubMed

    Sung, Lillian; Aplenc, Richard; Alonzo, Todd A; Gerbing, Robert B; Wang, Yi-Cheng; Meshinchi, Soheil; Gamis, Alan S

    2016-11-01

    Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five hundred and sixty-nine patients were included; 274 (48.2%) were favorable risk. The median cumulative time with neutropenia between Induction II to completion of Intensification II was 96 (range 54-204) days. Number of sterile site infections did not influence the risk of relapse or overall survival. However, longer duration of neutropenia was associated with a lower risk of relapse (hazard ratio 0.81 per 20 days neutropenia, p = 0.007). Longer duration of neutropenia was associated with a reduced risk of relapse for children with favorable and standard risk AML. Toxicity may be influenced by pharmacogenomics suggesting that individualized chemotherapy dosing may be an effective strategy. PMID:27312107

  5. Hippocampal abnormalities after prolonged febrile convulsion: a longitudinal MRI study.

    PubMed

    Scott, Rod C; King, Martin D; Gadian, David G; Neville, Brian G R; Connelly, Alan

    2003-11-01

    Mesial temporal sclerosis (MTS) is the most common lesion in patients who require epilepsy surgery, and approximately 50% of patients with MTS have a history of prolonged febrile convulsion (PFC) in childhood. The latter led to the hypothesis that convulsive status epilepticus, including PFC, can cause MTS. Our recently published data on children investigated within 5 days of a PFC showed that children investigated by MRI within 48 h of a PFC had large hippocampal volumes and prolongation of T2 relaxation time. Patients investigated >48 h from a PFC had large hippocampal volumes and normal T2 relaxation time. These data are strongly suggestive of hippocampal oedema that is resolving within 5 days of a PFC, but do not exclude the possibility of a pre-existing hippocampal lesion. Fourteen children from the original study had follow-up investigations carried out 4-8 months after the acute investigations. Of the 14 patients, four have had further seizures. Two had short febrile convulsions, one had PFC and one had non-febrile seizures. There was a significant reduction in hippocampal volume and T2 relaxation time between the first and second investigations, and there is now no difference in hippocampal volume or T2 relaxation time in patients compared with a control population. Moreover, there is a significant increase in hippocampal volume asymmetry in patients at follow-up when compared with initial data. Five out of 14 patients had asymmetry outside the 95th percentile for control subjects and, of these, three had one hippocampal volume outside the lower 95% prediction limit for control subjects. A reduction in hippocampal volume or T2 relaxation time, into or below the normal range between the first and second scans, indicates that the earlier findings are temporary and are strongly suggestive of hippocampal oedema as the abnormality in the initial investigations. The change in hippocampal symmetry in the patient group is consistent with injury and neuronal loss

  6. The Relationship between Iron Deficiency and Febrile Convulsion: A Case-Control Study

    PubMed Central

    Sharif, Mohammad Reza; Kheirkhah, Davood; Madani, Mahla; Kashani, Hamed Haddad

    2016-01-01

    Introduction: Febrile seizure is among the most common convulsion disorders in children, which strikes 2% to 5% of children between 3 to 60 months of age. Some studies have reported that iron deficiency could be a risk factor for febrile seizure. The present study was conducted to compare the rate of iron deficiency anemia in febrile children with and without seizure. Materials and Methods: This case-control study evaluated 200 children aged 6-60 month in two 100 person groups (febrile seizure and febrile without convulsion) in Kashan. The CBC diff, serum iron and TIBC were done for all of participants. Diagnosis of iron deficiency anemia based on mentioned tests. Results: No significant differences were found in two groups regarding to the age, gender, and the disease causing the fever. The presence of iron deficiency anemia was 45% in the convulsion group and 22% in the group with fever without convulsion. The Chi Square test indicated a significant difference between two groups. Conclusions: The findings suggest that a considerable percentage of children having febrile seizure suffer from iron-deficiency anemia and low serum iron. This means the low serum iron and presence of anemia can serve as a reinforcing factor for the febrile seizure in children. PMID:26383191

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

    PubMed Central

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

    2014-01-01

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

  8. PRRT2 Mutations Are Related to Febrile Seizures in Epileptic Patients

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2006-04-01

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

  12. Rodent-associated Bartonella Febrile Illness, Southwestern United States

    PubMed Central

    Iralu, Jonathan; Bai, Ying; Crook, Larry; Tempest, Bruce; Simpson, Gary; McKenzie, Taylor

    2006-01-01

    Serum specimens from 114 patients hospitalized with a febrile illness were tested with an indirect immunofluorescence assay (IFA) using Bartonella antigens prepared from 6 species of sigmodontine rodents and 3 known human Bartonella pathogens: B. henselae, B. quintana, and B. elizabethae. Acute- and convalescent-phase serum samples from 5 of these patients showed seroconversion with an IFA titer >512 to rodent-associated Bartonella antigens. The highest titer was against antigen derived from the white-throated woodrat (Neotoma albigula), although this rodent is not necessarily implicated as the source of infection. Three of the 5 who seroconverted showed no cross-reaction to the 3 Bartonella human pathogens. Common clinical characteristics were fever, chills, myalgias, leukopenia, thrombocytopenia, and transaminasemia. Although antibodies to Bartonella are cross-reactive, high-titer seroconversions to rodent-associated Bartonella antigens in adults with common clinical characteristics should stimulate the search for additional Bartonella human pathogens. PMID:16836824

  13. [Febrile urinary tract infection in infants: diagnostic strategy].

    PubMed

    Dubos, F; Raymond, J

    2012-11-01

    The diagnosis of febrile urinary tract infection in young children is difficult. Its prevalence is about 7.5 % but varies from 2 to 20 % according to the sex and age of the child. Except fever higher than 39°C for at least 48 h, no other anamnestic signs or from the clinical examination change significantly the probability of having a urinary tract infection or not. The most appropriate method of urine collection should be proposed to children clinically suspected of urinary tract infection, to avoid contamination and allow a proper diagnosis. Rapid tests (such as dipstick tests and microscopy) are useful to improve the likelihood of the diagnosis. This review focuses on the usefulness of anamnestic signs and clinical data, the way to collect urine and the performance of rapid diagnostic tests to increase or decrease the likelihood of acute urinary tract infection in children less than two years of age. PMID:23178130

  14. Autism in several members of a family with generalized epilepsy with febrile seizures plus.

    PubMed

    Dixon-Salazar, Tracy J; Keeler, Lesley C; Trauner, Doris A; Gleeson, Joseph G

    2004-08-01

    The neurobiologic basis for autism is not well understood. In contrast, there have been several recent discoveries into the genetics of generalized epilepsy with febrile seizures plus, a group of epilepsy syndromes characterized by multiple seizure phenotypes. Here we describe a family with generalized epilepsy with febrile seizures plus and variably expressed autism spectrum disorder that does not show linkage to any of the four known generalized epilepsy with febrile seizures plus loci. A relationship between these two disorders has not previously been described. PMID:15605469

  15. A case of L-2 hydroxyglutaric aciduria presenting as febrile seizure.

    PubMed

    Calik, M; Tuncer, F N; Sarikaya, S; Karakas, O; Cece, H; Iscan, A

    2014-01-01

    L-2 hydroxyglutaric aciduria (L2HGA) is a rare, infantile-onset, autosomal recessive organic aciduria affecting exclusively the central nervous system. A case is reported here of L2HGA presenting with macrocephaly and febrile seizure. Although there have been reports of epilepsy associated with L2HGA, to the best of our knowledge this is the second case in literature of febrile seizure in a patient with L2HGA. This report suggests that detailed neurological evaluation of macrocephalic children with febrile convulsion is important. Moreover, metabolic and genetic investigations may be necessary for these kinds of patients. PMID:25804013

  16. Delayed-onset grade 4 neutropenia associated with rituximab therapy in a patient with lymphoma: case report and literature review.

    PubMed

    Motl, Susannah E; Baskin, Reed C

    2005-08-01

    A 53-year-old man developed delayed-onset neutropenia 6 weeks after completing first-line therapy with rituximab, cyclophosphamide, mitoxantrone, vincristine, and prednisone for high-grade B-cell lymphoma. Bone marrow biopsy demonstrated hypercellular marrow with normal maturation. He also developed interstitial pneumonitis, an adverse event associated with rituximab use. Infiltrates of T cells were found in the patient's lungs. For the next 6 months, the patient required subcutaneous granulocyte colony-stimulating factor 300 mug twice/week to maintain a granulocyte count above 1000 cells/mm3. He also received oral antibiotics for mouth sores and thrush. Based on the existing evidence, monitoring blood counts for as long as 8 weeks after rituximab therapy may be advisable, although the literature reports that neutropenia can develop up to 1 year after treatment. The development of a registry and uniform testing may help uncover the cause of this delayed-onset neutropenia. PMID:16207108

  17. 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

  18. 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

  19. 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

  20. 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

  1. Systematic review and meta-analysis of the discriminatory performance of risk prediction rules in febrile neutropaenic episodes in children and young people

    PubMed Central

    Phillips, Bob; Wade, Ros; Stewart, Lesley A.; Sutton, Alex J.

    2010-01-01

    Introduction Febrile neutropaenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer, yet many children are aggressively over-treated. We aimed to undertake a systematic review and meta-analysis to summarise evidence on the discriminatory ability and predictive accuracy of clinical decision rules (CDR) of risk stratification in febrile neutropaenic episodes. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, using random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100453. Results We found 20 studies describing 16 different CDR assessed in 8388 episodes of FNP. No study compared different approaches and only one CDR had been subject to testing across multiple datasets. This review cannot conclude that any system is more effective or reliable than any other. Conclusion To maximise the value of the information already collected by these and other cohorts of children with febrile neutropaenia, an individual-patient-data (IPD) meta-analysis is required to develop and test new and existing CDR to improve stratification and optimise therapy. PMID:20621468

  2. "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

  3. 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

  4. Many parents think their child is dying when having a first febrile convulsion.

    PubMed

    Baumer, J H; David, T J; Valentine, S J; Roberts, J E; Hughes, B R

    1981-08-01

    Fifty parents of 36 consecutive children admitted to hospital with their first febrile convulsion were interviewed shortly after the event. Very few parents voluntarily said that they had thought their child was dying, but when asked specifically the majority said they had thought the child was dying or likely to die. This common fear should be kept in mind when discussing febrile convulsions with parents, who are unlikely to volunteer the information. PMID:7274593

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

    PubMed

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

    2009-01-01

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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia.

    PubMed

    Ward, Alister C; Gits, Judith; Majeed, Fidel; Aprikyan, Andrew A; Lewis, Rowena S; O'Sullivan, Lynda A; Freedman, Melvin; Shigdar, Sarah; Touw, Ivo P; Dale, David C; Dror, Yigal

    2008-08-01

    Most severe congenital neutropenia (SCN) cases possess constitutive neutrophil elastase mutations; a smaller cohort has acquired mutations truncating the granulocyte colony-stimulating factor receptor (G-CSF-R). We have described a case with constitutive extracellular G-CSF-R mutation hyporesponsive to ligand. Here we report two independent acquired G-CSF-R truncation mutations and a novel constitutive neutrophil elastase mutation in this patient. Co-expression of a truncated receptor chain restored STAT5 signalling responses of the extracellular G-CSF-R mutant, while constitutively-active STAT5 enhanced its proliferative capacity. These data add to our knowledge of SCN and further highlight the importance of STAT5 in mediating proliferative responses to G-CSF. PMID:18513286

  13. Naturally occurring cardiac glycosides.

    PubMed

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

    1986-05-12

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

  14. 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

  15. 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

  16. Fever and neutropenia hospital discharges in children with cancer: A 2012 update.

    PubMed

    Mueller, Emily L; Croop, James; Carroll, Aaron E

    2016-02-01

    Fever and neutropenia (FN) is a common precipitant for hospitalization among children with cancer, but hospital utilization trends are not well described. This study describes national trends for hospital discharges for FN among children with cancer for the year 2012, compared with the authors' previous analysis from 2009. Data were analyzed from the Kids' Inpatient Database (KID), an all-payer US hospital database, for 2012. Pediatric patients with cancer who had a discharge for FN were identified using age ≤19 years, urgent or emergent admit type, nontransferred, and a combination of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for fever and neutropenia. The authors evaluated factors associated with a "short length of stay" (SLOS). Sampling weights were used to permit national inferences. In 2012, children with cancer accounted for 1.8% of pediatric hospital discharges (n = 120,675), with 12.2% (n = 13,456) of cancer-related discharges meeting FN criteria. Two fifths of FN discharges had a SLOS, which accounted for $91 million (2015 US$) in hospital charges. The majority had no serious infections; most common infections were viral infection (9.6%) or upper respiratory infection (9.6%). Factors significantly associated with SLOS included having a diagnosis of ear infection (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.16-2.03), soft tissue sarcoma (OR = 1.47, CI: 1.10-1.95), and Hodgkin lymphoma (OR = 1.51, CI: 1.09-2.10), as compared with not having those diagnoses. SLOS admissions continue to be rarely associated with serious infections, but contribute substantially to the burden of hospitalization for pediatric FN. Implementation of risk stratification schemas to identify patients who meet low-risk criteria may decrease financial burden. PMID:26900730

  17. 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

  18. 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

  19. Lenograstim reduces the incidence of febrile episodes, when compared with filgrastim, in multiple myeloma patients undergoing stem cell mobilization.

    PubMed

    Orciuolo, Enrico; Buda, Gabriele; Marturano, Emerenziana; Mauro, Elisa; Milone, Giuseppe; Cangialosi, Clotilde; Di Renzo, Nicola; Pastore, Domenico; Specchia, Giorgina; De Paolis, Maria Rosaria; Mazza, Patrizio; Pietrantuono, Giuseppe; Petrini, Mario

    2011-07-01

    The aim of this study was to show a lower incidence of febrile episodes in multiple myeloma patients receiving lenograstim vs. filgrastim after high-dose cyclophosphamide for stem cell mobilization. Patients treated with cyclophosphamide were randomly assigned to receive filgrastim or lenograstim. Primary endpoint was the incidence of febrile episodes. 5.1% patients developed a febrile episode, 9.1% with filgrastim and 1.1% with lenograstim. Lenograstim group presented a significantly higher absolute CD34+ cell number compared with the filgrastim group but no differences were detected for collection efficacy. The study demonstrated a lower incidence of febrile episodes with lenograstim compared to filgrastim. PMID:21134693

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

    PubMed

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

    2016-06-01

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

  1. 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

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

    PubMed Central

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

    2014-01-01

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

  3. 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

  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 Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

    PubMed

    Uchiyama, Kimio; Yamada, Manabu; Tamate, Shusuke; Iwasaki, Konomi; Mitomo, Keisuke; Nakayama, Seiichi

    2015-09-01

    The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy). PMID:26469162

  6. Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B.

    PubMed

    Wallace, R H; Scheffer, I E; Parasivam, G; Barnett, S; Wallace, G B; Sutherland, G R; Berkovic, S F; Mulley, J C

    2002-05-14

    Generalized epilepsy with febrile seizures plus (GEFS(+)) is an important childhood genetic epilepsy syndrome with heterogeneous phenotypes, including febrile seizures (FS) and generalized epilepsies of variable severity. Forty unrelated GEFS(+) and FS patients were screened for mutations in the sodium channel beta-subunits SCN1B and SCN2B, and the second GEFS(+) family with an SCN1B mutation is described here. The family had 19 affected individuals: 16 with typical GEFS(+) phenotypes and three with other epilepsy phenotypes. Site-specific mutation within SCN1B remains a rare cause of GEFS(+), and the authors found no evidence to implicate SCN2B in this syndrome. PMID:12011299

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

    PubMed Central

    Rutter, N; Smales, O R

    1977-01-01

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

  8. 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

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

    PubMed Central

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

    2015-01-01

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

  10. 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

  11. [Autoimmune-alloimmune neonatal neutropenia. Serum reactive IgG and neutrophil-specific phenotype detected by flow cytometry].

    PubMed

    Riera, Norma E; Kantor, Gustavo L; Khoury, Marina; Nucci, Rodrigo Parias; Rapetti, Maria Cristina; Aixala, Monica; Goldsztein, Sofia; Flores, Gabriela; de Bracco, Maria M de E

    2006-01-01

    Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). They were evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established for serum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of different individuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensity of the patient's serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes were determined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Two maternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes were detected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility was detected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+. PMID:17137169

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

    PubMed Central

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

    2012-01-01

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

  13. Platelet satellitism, spurious neutropenia, and cutaneous vasculitis: casual or causal association?

    PubMed

    Lazo-Langner, Alejandro; Piedras, Josefa; Romero-Lagarza, Penélope; Lome-Maldonado, Carmen; Sánchez-Guerrero, Jorge; López-Karpovitch, Xavier

    2002-07-01

    About 90 cases of platelet satellitism (PS) have been published, most of them involving neutrophils, a few comprising monocytes, and one case involving basophils. The case of a 30-year-old female patient with cutaneous vasculitis who developed asymptomatic severe neutropenia is reported. All blood smears (BS) prepared from peripheral blood samples collected with either ethylenediaminetetraacetic acid, trisodium citrate, and heparin showed PS involving neutrophils, eosinophils, and monocytes. Immunohistochemistry analysis of her skin biopsy and BS, employing peroxidase stain for the detection of antibodies directed against IgG, IgA, IgM, and C3, revealed an intense positive reaction only for IgG in the endothelium and leukocyte clumps within the microvasculature, as well as in peripheral blood neutrophils displaying the PS phenomenon. Transfer of the PS phenomenon was demonstrated by incubating the patient's plasma with leukocytes from an ABO-compatible healthy donor. In our patient, PS did not disappear after incubation at 37 degrees C, suggesting that this might be a different or "atypical" PS phenomenon probably mediated by an autoimmune process involving an IgG-class antibody responsible for both conditions, PS, and cutaneous vasculitis. PMID:12111772

  14. 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

  15. 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

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

    PubMed

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

    2015-08-01

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

  17. Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia.

    PubMed

    Hilcenko, Christine; Simpson, Paul J; Finch, Andrew J; Bowler, Frank R; Churcher, Mark J; Jin, Li; Packman, Len C; Shlien, Adam; Campbell, Peter; Kirwan, Michael; Dokal, Inderjeet; Warren, Alan J

    2013-02-01

    The recessive disorder poikiloderma with neutropenia (PN) is caused by mutations in the C16orf57 gene that encodes the highly conserved USB1 protein. Here, we present the 1.1 Å resolution crystal structure of human USB1, defining it as a member of the LigT-like superfamily of 2H phosphoesterases. We show that human USB1 is a distributive 3'-5' exoribonuclease that posttranscriptionally removes uridine and adenosine nucleosides from the 3' end of spliceosomal U6 small nuclear RNA (snRNA), directly catalyzing terminal 2', 3' cyclic phosphate formation. USB1 measures the appropriate length of the U6 oligo(U) tail by reading the position of a key adenine nucleotide (A102) and pausing 5 uridine residues downstream.We show that the 3' ends of U6 snRNA in PN patient lymphoblasts are elongated and unexpectedly carry nontemplated 3' oligo(A) tails that are characteristic of nuclear RNA surveillance targets. Thus, our study reveals a novel quality control pathway in which posttranscriptional 3'-end processing by USB1 protects U6 snRNA from targeting and destruction by the nuclear exosome. Our data implicate aberrant oligoadenylation of U6 snRNA in the pathogenesis of the leukemia predisposition disorder PN. PMID:23190533

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

    PubMed Central

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

    2011-01-01

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

  19. A novel syndrome with congenital neutropenia caused by mutations in G6PC3

    PubMed Central

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

    2009-01-01

    Background Severe congenital neutropenia (SCN) is characterized by early onset of severe bacterial infections due to a paucity of mature neutrophils. There is also an increased risk of leukemia. The genetic causes of SCN are unknown in many patients. Methods Genome-wide genotyping and linkage analysis were performed on two consanguineous pedigrees with a total of five children affected with SCN. Candidate genes from the linkage interval were sequenced. Functional assays and reconstitution experiments were carried out. Results All index patients had susceptibility to bacterial infections and myeloid maturation arrest in the bone marrow; some had structural heart defects and venous angiectasia on the trunk and extremities. Linkage analysis of the two index families yielded a combined multipoint LOD score of 5.74 on a linkage interval on chromosome 17q21. Sequencing of the candidate gene glucose-6-phosphatase catalytic subunit 3 (G6PC3) revealed a homozygous missense mutation in exon 6 in all affected children in the two families, abrogating enzymatic activity of Glucose-6-phosphatase. Neutrophils and fibroblasts of patients had increased susceptibility to apoptosis. Myeloid cells showed evidence of increased endoplasmic reticulum stress and increased activity of GSK3β. We identified seven additional, unrelated SCN patients with syndromic features and distinct biallelic mutations in G6PC3. Conclusions Defective function of G6PC3 defines a novel SCN syndrome associated with cardiac and urogenital malformations. PMID:19118303

  20. 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

  1. 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

  2. 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

  3. 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

  4. A novel susceptibility locus at 2p24 for generalised epilepsy with febrile seizures plus.

    PubMed

    Audenaert, D; Claes, L; Claeys, K G; Deprez, L; Van Dyck, T; Goossens, D; Del-Favero, J; Van Paesschen, W; Van Broeckhoven, C; De Jonghe, P

    2005-12-01

    Generalised epilepsy with febrile seizures plus (GEFS+) is a clinically and genetically heterogeneous epilepsy syndrome. Using positional cloning strategies, mutations in SCN1B, SCN1A, and GABRG2 have been identified as genetic causes of GEFS+. In the present study, we describe a large four generation family with GEFS+ in which we performed a 10 cM density genome-wide scan. We obtained conclusive evidence for a novel GEFS+ locus on chromosome 2p24 with a maximum two point logarithm of the odds (LOD) score of 4.22 for marker D2S305 at zero recombination. Fine mapping and haplotype segregation analysis in this family delineated a candidate region of 3.24 cM, corresponding to a physical distance of 4.2 Mb. Linkage to 2p24 was confirmed (p = 0.007) in a collection of 50 nuclear and multiplex families with febrile seizures and epilepsy. Transmission disequilibrium testing and association studies provided further evidence (p < 0.05) that 2p24 is a susceptibility locus for febrile seizures and epilepsy. Furthermore, we could reduce the candidate region to a 2.14 cM interval, localised between D2S1360 and D2S2342, based upon an ancestral haplotype. Identification of the disease gene at this locus will contribute to a better understanding of the complex genetic aetiology of febrile seizures and epilepsy. PMID:15827091

  5. The role of vasopressin, somatostatin and GABA in febrile convulsion in rat pups.

    PubMed

    Nagaki, S; Nagaki, S; Minatogawa, Y; Sadamatsu, M; Kato, N; Osawa, M; Fukuyama, Y

    1996-01-01

    In order to further elucidate a possible role of neuropeptides and GABA in the pathogenesis of febrile convulsions, we studied changes of immunoreactive-arginine vasopressin (IR-AVP), IR-somatostatin (IR-SRIF) and gamma-aminobutyric acid (GABA) in the rat brain after febrile convulsions induced by ultra-red light (UR). Male Wistar rats at 16 days of age irradiated with UR developed generalized convulsions after 4.9 +/- 0.5 min irradiation. Six rats were killed by microwave irradiation 3 min after UR irradiation prior to convulsion development, and 29 rats were killed either 0 min, 2 h, 6 h, 24 h or 48 h after febrile convulsions. Non-irradiated rats served as controls. The rat brain was dissected into 4 regions; amygdala, hypothalamus, cortex and hippocampus, and subjected to radioimmunoassays. IR-AVP levels in hypothalamus were increased 3 min after UR and decreased at 2 h and 6 h after the convulsions. IR-SRIF levels were increased in cortex and hippocampus at 3 min after UR and 0 min after the convulsions. The GABA content increased in all regions tested at 2 h and 6 h after the convulsions. These results suggest that AVP, SRIF and GABA may be involved in the pathogenesis of febrile convulsions in different ways. PMID:8649210

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

    PubMed

    Cooper, A J; Egleston, C V

    1997-05-01

    The case is reported of a toddler who presented with an apparent febrile convulsion. The final diagnosis was that of accidental ingestion of Ecstasy. The child made an uneventful recovery. Ecstasy toxicity should be added to the list of differential diagnoses in a child presenting with fever and an unexplained seizure. PMID:9193992

  7. [The clinical study of the first febrile convulsion in children with brain-damage].

    PubMed

    Asoh, M

    1997-05-01

    Forty-nine patients with cerebral palsy, mental retardation, or other congenital neurological disorders who had experienced febrile convulsions and had no previous nonfebrile seizures were presented. They were followed for 1.6 years to 15 years (mean: 6.8 years) after the initial febrile convulsion. The incidence of subsequent epilepsy (two or more afebrile seizures) was 39%, and 80% of them developed epilepsy within 2 years after the first febrile convulsion. The paroxysmal discharges on EEG recorded prior to or after the first febrile convulsion did not predict the occurrence of later epilepsy. Also under 3 years of age, EEG findings led to the same result. There was no definite evidence that administration of anticonvulsive drugs prevented later epilepsy. Pre-existing neurological abnormality was identified as a risk factor for epilepsy, and was an indication of persistent medication. There is no clear prophylactic procedure against long-lasting attacks. Accordingly, medical therapy can be started when epilepsy has developed. Patients with very severe brain damage who could not move except lying comprised only 6% of all cases, and 69% of the epilepsy patients were well controlled. They showed a good prognosis as compared with children with brain-damage in general with epilepsy. PMID:9146028

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

    PubMed Central

    Cooper, A J; Egleston, C V

    1997-01-01

    The case is reported of a toddler who presented with an apparent febrile convulsion. The final diagnosis was that of accidental ingestion of Ecstasy. The child made an uneventful recovery. Ecstasy toxicity should be added to the list of differential diagnoses in a child presenting with fever and an unexplained seizure. PMID:9193992

  9. Expression of Hsp72 in lymphocytes in patients with febrile convulsion.

    PubMed

    Lin, Lung-Chang; Chen, Hsiang-Wen; Yang, Rei-Cheng

    2005-03-01

    The pathophysiology of febrile convulsion, the most common childhood neurologic disease, remains unclear. In this study, we investigated what role a heat shock protein plays in this disease. We enrolled eight boys and two girls with febrile convulsion and 10 age-matched healthy controls. We did a biosynthetic evaluation of both groups by separating lymphocytes and measuring the expression of heat shock protein 72 before and after heat shock treatment. Before the treatment, both groups were found to have small amounts of constitutive heat shock protein 72. Afterwards, its expression increased in both groups, and no statistical difference was found between the increases in the two groups. In addition, there was no obvious difference in the susceptibility to produce heat shock proteins. However, the febrile convulsion group was found to have a significant decrease in phosphorylation of heat shock protein 72. These results suggest the possible involvement of post-translational modification of heat shock proteins, most likely phosphorylation, in the pathogenesis of febrile convulsion. PMID:15875434

  10. 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. PMID:26488312

  11. 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…

  12. Febrile seizures: characterization of double-stranded RNA-induced gene expression.

    PubMed

    Sasaki, Kazuya; Matsuo, Muneaki; Maeda, Toshiyuki; Zaitsu, Masafumi; Hamasaki, Yuhei

    2009-08-01

    An association has long been suspected between febrile seizures and interleukin-1beta, the most potent endogenous pyrogen. Interleukin-1beta production increases after double-stranded RNA stimulation in leukocytes of febrile seizure patients. To elucidate the genetics of the immune response, the gene expression pattern after double-stranded RNA stimulation was investigated using DNA microarray. Compared with the control group, expression of the genes ACCN4 (sodium channel), KCNC3 (potassium channel), GABRE (gamma-aminobutyric acid receptor epsilon subunit), RIPK2 (receptor interacting protein kinase-2), TLR4 (toll-like receptor-4), IL26 (interleukin-26), and TNF (tumor necrosis factor), and CASP1 (caspase-1) was increased in the febrile seizure group (P < 0.01). Because RIPK2 and CASP1 are associated with interleukin-1beta production, increased expression might cause increased interleukin-1beta production in the febrile seizure patients. The induced expression of several ion channel genes by double-stranded RNA may affect neuronal excitability which leads to seizure susceptibility during infection. PMID:19589459

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

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. 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

  16. 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

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

    PubMed Central

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

    2012-01-01

    OBJECTIVE: Febrile infants in the first 90 days may have life-threatening serious bacterial infection (SBI). Well-appearing febrile infants with SBI cannot be distinguished from those without by examination alone. Variation in care resulting in both undertreatment and overtreatment is common. METHODS: We developed and implemented an evidence-based care process model (EB-CPM) for the management of well-appearing febrile infants in the Intermountain Healthcare System. We report an observational study describing changes in (1) care delivery, (2) outcomes of febrile infants, and (3) costs before and after implementation of the EB-CPM in a children’s hospital and in regional medical centers. RESULTS: From 2004 through 2009, 8044 infants had 8431 febrile episodes, resulting in medical evaluation. After implementation of the EB-CPM in 2008, infants in all facilities were more likely to receive evidence-based care including appropriate diagnostic testing, determination of risk for SBI, antibiotic selection, decreased antibiotic duration, and shorter hospital stays (P < .001 for all). In addition, more infants had a definitive diagnosis of urinary tract infection or viral illness (P < .001 for both). Infant outcomes improved with more admitted infants positive for SBI (P = .011), and infants at low risk for SBI were more often managed without antibiotics (P < .001). Although hospital admissions were shortened by 27%, there were no cases of missed SBI. Health Care costs were also reduced, with the mean cost per admitted infant decreasing from $7178 in 2007 to $5979 in 2009 (−17%, P < .001). CONCLUSIONS: The EB-CPM increased evidence-based care in all facilities. Infant outcomes improved and costs were reduced, substantially improving value. PMID:22732178

  18. 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

  19. Subgingival microflora and treatment in prepubertal periodontitis associated with chronic idiopathic neutropenia.

    PubMed

    Kamma, J J; Lygidakis, N A; Nakou, M

    1998-09-01

    Prepubertal periodontitis affects both primary and permanent dentition. The purpose of this study was to examine the composition of subgingival microflora of the permanent dentition in an 11-year-old Caucasian female, who had premature exfoliation of her deciduous teeth on her 5th year of age, and the response of this condition to the antibiotic therapy and supportive periodontal care. Gingival tissues were highly inflamed and alveolar bone loss was detected radiographically. The girl had experienced frequent upper respiratory tract infections, tonsilitis and recurrent otitis media. Her mother had history of early onset periodontitis associated with chronic idiopathic neutropenia. Blood chemistry tests and immunological examinations were also performed. Subgingival plaque samples were collected from the proximal sites of permanent molars, incisors, canines and maxillary premolars. 27 different microbial species were isolated from the subgingival microflora. Among the predominant species were Porphyromonas gingivalis (17.6%-7.3%), Prevotella intermedia (12.4%-4.7%), Capnocytophaga sputigena (14.4%-10.4%), Capnocytophaga ochracea (13.2%-6.9%) and Actinobacillus actinomycetemcomitans (9.3%-5.5%). Periodontal treatment consisted of scaling, root planing in conjunction with antibiotic administration of Augmentin 312.5 mg and Flagyl 200 mg, each t.i.d. for 10 days. 3 weeks after the antibiotic therapy, bacterial samples were collected from the same sites. All the periodontal pathogens were recovered in lower levels and A.actinomycetemcomitans was almost eliminated in the 3-week period. The evaluation of clinical indices at 3, 6 and 12 months showed that periodontal treatment in conjunction with antibiotics was effective and rapidly followed by marked clinical improvement. The microbiological monitoring at 3, 6 and 12 months after antibiotic treatment and each time prior to supportive periodontal care, revealed that the periodontal pathogens fluctuated in low levels even

  20. 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

  1. 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

  2. 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

  3. Clinical and genetic analysis of a new multigenerational pedigree with GEFS+ (Generalized Epilepsy with Febrile Seizures Plus).

    PubMed

    Gérard, Frédérique; Pereira, Sandrine; Robaglia-Schlupp, Andrée; Genton, Pierre; Szepetowski, Pierre

    2002-06-01

    Febrile seizures affect 2-5% of all children younger than 6 years. A small proportion of children with febrile seizures later develop epilepsy. The syndrome of generalized epilepsy with febrile seizures plus (GEFS+) is a heterogeneous disorder characterized by febrile seizures that may persist beyond age 6 years and nonfebrile seizures. Several genes have been localized for FS by linkage analysis, and three GEFS+ genes (SCN1A, SCN1B, GABRG2) have been identified. We identified a large multigenerational family with GEFS+ in France. All affected members had FSs. Among them, seven had other types of epileptic seizures including FSs after age 6 years, nonfebrile generalized seizures, or partial seizures later in life. Genetic linkage study excluded the candidate genes and loci for FS and GEFS+, thus proving the existence of a new GEFS+ genetic locus underlying the phenotype observed in this family. PMID:12060016

  4. 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

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

    PubMed

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

    2014-12-01

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

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

    PubMed

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

    2015-09-01

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

  7. [Progress in molecular genetics of generalized epilepsy with febrile seizures plus].

    PubMed

    Sun, Hui Hui; Zhang, Yue Hua

    2008-04-01

    Generalized epilepsy with febrile seizures plus (GEFS+) is a familial inherited epileptic syndrome characterized by phenotypic heterogeneity from the milder febrile seizures to the severest epileptic encephalopathy such as severe myoclonic epilepsy in infancy (SMEI). GEFS+ is a disorder with a genetic heterogeneity. Molecular genetics have revealed that four genes are associated with the pathogenesis of GEFS+. These include mutations in genes encoding subunits of neuronal voltage-gated sodium channels (SCN1A, SCN1B, SCN2A) and gamma(2) subunit of the gamma amino-butyric acid (GABA)(A) receptor (GABRG2). These genes have been confirmed as having a role in autosomal dominant GEFS+ families. In addition, the phenotypes of the affected members may depend on the types and locations of these gene mutations. This review states the molecular genetic progress of GEFS+ in brief. PMID:18458705

  8. A case of recurrent acute encephalopathy with febrile convulsive status epilepticus with carnitine palmitoyltransferase II variation.

    PubMed

    Sakai, Eiko; Yamanaka, Gaku; Kawashima, Hisashi; Morishima, Yasuyuki; Ishida, Yu; Oana, Shingo; Miyajima, Tasuku; Shinohara, Mayu; Saitoh, Makiko; Mizuguchi, Masashi

    2013-08-01

    Acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is the most common type of acute encephalopathy in childhood in Japan, which develops with prolonged febrile convulsion, followed by mild unconsciousness. It is generally sporadic and nonrecurrent. In this report, a 1-year-old girl showed signs of AEFCSE triggered by respiratory syncytial virus infection. Two years later, she presented with AEFCSE triggered by influenza virus infection, resulting in severe neurologic sequelae. The patient had a thermolabile genotype of carnitine palmitoyltransferase II (CPT II) variations consisting of three single nucleotide polymorphisms in exons 4 [1055T > G/F352C and 1102G > A/V368I] and 5 [1939A > G/M647V]. The polymorphism has been identified as a genetic predisposition for acute encephalopathy. This report presents the first case of recurrent encephalopathy with CPT II variations that may partially associate with pathogenesis of recurrent AEFCSE. PMID:23450341

  9. Arginine vasopressin in the pathogenesis of febrile convulsion and temporal lobe epilepsy.

    PubMed

    Gulec, Guldal; Noyan, Behzat

    2002-11-15

    We aimed to investigate the possible convulsant action of arginine vasopressin (AVP) in both a febrile convulsion model in rat pups and a temporal lobe epilepsy model in adult rats and to define the receptor type which mediates this effect. In rat pups, 125 ng V2 receptor antagonist significantly prevented hyperthermic seizures, but did not affect seizure latency. In adult rats, the only effective dose and agent was 125 ng V2 receptor antagonist, which prevented pilocarpine-induced status epilepticus, extended the status epilepticus latency and improved the 24 h survival rate. These data suggest that AVP has a convulsant activity in febrile convulsions and also in seizures independent of fever, and this effect is mediated by V2 receptors. PMID:12438923

  10. Recurrence rate of febrile convulsion related to the degree of pyrexia during the first attack.

    PubMed

    el-Radhi, A S; Withana, K; Banajeh, S

    1986-06-01

    Ninety-four children consecutively admitted to the hospital between January 1980 and December 1982 with their first febrile convulsion (FC) were studied to assess the influence of the degree of pyrexia on the recurrence rate of FC. Thirty-eight of sixty-three children between 6 and 18 months of age (the peak incidence of FC) with fever above 40 degrees C were almost seven times less likely to have subsequent convulsions with fever, than those whose initial febrile convulsion was associated with a lower degree of pyrexia. It is suggested that the degree of pyrexia is a factor that influences the recurrence of FC. This may explain why some children have a reduced frequency of subsequent FC compared with others who appear to be at comparable risk. PMID:3698455

  11. 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

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

    PubMed Central

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

    2015-01-01

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

  13. 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

  14. 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

  15. [Sweet syndrome (acute febrile neutrophilic dermatosis) and erythema nodosum in Crohn disease].

    PubMed

    Schlegel Gómez, R; Kiesewetter, F; von den Driesch, P; Hornstein, O P

    1990-07-01

    We report on 2 patients who developed an acute febrile neutrophilic dermatosis (Sweet's syndrome) and erythema nodosum in association with Crohn's disease. The first patient showed symmetrical painful erythemas on her cheeks after hemicolectomy. Additionally, red painful nodules appeared on her lower legs. The second patient disclosed typical Sweet's syndrome-like lesions with pustules and plaques on her face, scalp and extremities after activation of Crohn's disease. Simultaneously, erythema nodosum-like lesions appeared on her lower legs. PMID:2144848

  16. 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

  17. 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

  18. Immunological findings in epileptic and febrile convulsion patients before and under treatment.

    PubMed

    Tartara, A; Verri, A P; Nespoli, L; Moglia, A; Botta, M G

    1981-01-01

    Serum immunoglobulin levels of 86 epileptic patients have been evaluated in order to investigate the relationship between epilepsy, antiepileptic drugs and humoral immunity. The results confirm a high incidence of immunological disorders in the epileptic and febrile convulsion patients. These abnormalities were not related to clinical type of epilepsy nor to the therapy; the common feature seems the early onset of seizures and antiepileptic treatment. PMID:6791931

  19. [Evaluation of the protocol for management of the first uncomplicated febrile convulsion].

    PubMed

    Collet, J P; Gallet, S; Etokabeka, F; Hermier, M; Danzon, A; Descos, B; David, L; François, R; Floret, D

    1986-01-01

    A protocol of rationalized management of the first non complicated febrile seizure was used in 42 children and the results were compared with those observed in the past without the new protocol. The quality of medical data collected from the parents and those given to the family and their practitioner have been improved; the duration of the hospitalization was shorter, the examinations were fewer and the savings realised per child were 3,175 francs. PMID:3808844

  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. 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

  2. Streptococcus gallinaceus bacteraemia in an abattoir worker presenting with a febrile illness.

    PubMed

    Balm, Michelle N D; Truong, Han T; Choudhary, Anwar S; Robinson, Geoffrey M; Blackmore, Timothy K

    2006-07-01

    Streptococcus gallinaceus is a newly described species of viridans streptococci, previously only identified as causing disease in broiler chickens. This organism was recovered in pure culture from blood taken from a New Zealand abattoir worker presenting with a febrile illness. This first report of bacteraemia caused by S. gallinaceus in a human may help the understanding of the ecology of this recently described organism. PMID:16772426

  3. [T-cell granular lymphocyte-proliferative disorder without severe infection for 13 years despite severe neutropenia].

    PubMed

    Tanaka, Hiroaki; Hashimoto, Shinichiro; Sakai, Chikara; Abe, Daijiro; Sakai, Shio; Takagi, Toshiyuki

    2010-02-01

    A 68-year-old woman was referred to Oami Hospital for severe leukocytopenia. Laboratory data revealed severe leukocytopenia (0.8x10(9)/l), severe neutropenia (0.22x10(9)/l) and IgM-kappa monoclonal gammopathy. Granular lymphocytes accounted for more than 90% of leukocytes. Surface marker analysis revealed that these lymphocytes were CD3+, CD4-, CD8+ and CD16+, and monoclonal rearrangement of T-cell receptor genes was seen on Southern blot hybridization analysis. She was diagnosed with T-cell lineage granular lymphocyte proliferative disorder (T-GLPD). During 13-year follow-up without granulocyte-colony stimulating factor (G-CSF) administration, except for one hospitalization because of bacterial pneumonia, she has not experienced severe infection, despite severe neutropenia. T-GLPD should be kept in mind as a cause of leukocytopenia with or without monoclonal gammopathy, and surface marker or Southern blot hybridization analysis should be considered for determining the diagnosis. There are many reports about Caucasian patients with T-GLPD suffering from recurrent infections and dying of severe infection, but in Japanese T-GLPD patients, severe infection is very rare, as shown in the present case report. PMID:20379107

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

    PubMed

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

    2014-06-01

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

  5. 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

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

    PubMed

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

    2016-05-01

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

  7. Orofacial injuries associated with prehospital management of febrile convulsion in Nigerian children.

    PubMed

    Ndukwe, Kizito C; Folayan, Morenike O; Ugboko, Vincent I; Elusiyan, Jerome B E; Laja, Olajumoke O

    2007-04-01

    The aim of this prospective study was to determine in a population of pediatric patients with febrile convulsions the prevalence and pattern of orofacial and dental injuries caused by traditional remedies used in a suburban Nigerian community. Over the study period of 28 months, 75 cases of febrile convulsion presented to the Children's Emergency unit of our hospital. Of these, 27 children (36%) sustained orofacial injuries caused by forceful insertion of a spoon into the mouth (96.3%) or a bite (3.7%) during convulsive episodes. The ages of the patients ranged from 12 to 84 months with a mean 39.8 +/- 18.3 months. There were 15 males and 11 females with a male to female ratio of 1.4:1. The orofacial and dental injuries sustained from prehospital treatment at home were lacerations and bruising of soft tissues including lips, tongue, mucosa and commissures and tooth subluxation, displacement or avulsion. Other injuries sustained outside the mouth include second-degree burns to the feet, a chin laceration and facial bruises resulting from a fall. Many oral injuries were overlooked by pediatricians. Prompt recognition and appropriate management of febrile convulsion would be of great benefit to the pediatric patients. PMID:17367452

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

    PubMed

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

    1998-02-01

    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 without 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

  9. 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

  10. [Risk factors for the occurrence of recurrent convulsions following an initial febrile convulsion].

    PubMed

    Offringa, M; Derksen-Lubsen, G; Bossuyt, P M; Lubsen, J

    1992-03-14

    The results of a follow up study of 155 Dutch children who visited the emergency room of an urban paediatric hospital after experiencing their first febrile seizure are presented. Median follow up time was 38 months (range 27-60). Of these 155 initially untreated children 58 (37%) suffered at least one, 47 (30%) at least two and 27 (17%) at least three recurrent seizures. The recurrence hazard after any seizure was highest in the first six months, and dropped markedly after 6 months without seizures. The effect of the various postulated risk factors on the occurrence of any recurrent seizure and three or more recurrences was assessed. A first degree family history of febrile or nonfebrile seizures appears to be a predictor of multiple recurrences; an age of at least 30 months and a temperature of 40.0 degrees C or higher at the initial seizure are associated with a decreased risk. Several factors act together on the risk of recurrent seizures, sometimes in opposite directions. By considering the action of all relevant factors (age at onset, family history and features of the initial febrile seizure) subgroups of children with one year seizure recurrence rates as low as 15% and as high as 48% were identified. PMID:1552954

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

    PubMed

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

    2015-08-01

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

  12. 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

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

    PubMed

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

    2006-07-01

    Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes. PMID:16819552

  14. 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

  15. 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

  16. 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

  17. 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

  18. Pretreatment H2 receptor antagonists that differ in P450 modulation activity: comparative effects on paclitaxel clearance rates and neutropenia.

    PubMed

    Slichenmyer, W J; Donehower, R C; Chen, T L; Bowling, M K; McGuire, W P; Rowinsky, E K

    1995-01-01

    Histamine-2 receptor antagonists (H2RAs) are principal components of the premedication regimen used to prevent major hypersensitivity reactions in patients receiving paclitaxel. Several different H2RAs, including cimetidine, ranitidine and famotidine, have been used in clinical trials of paclitaxel, as well as by clinicians in different geographic regions and hospitals primarily because of differences in the availability of the various H2RAs. However, H2RAs have highly variable cytochrome P450-modulating capabilities, and the P450 system appears to play a major role in paclitaxel metabolism and disposition. Therefore, the use of different H2RAs may result in different pharmacologic, toxicologic and antitumor profiles due to differential effects on paclitaxel metabolism. This study evaluated whether cimetidine and famotidine, which possess disparate P450-modulating capabilities, differentially affect paclitaxel clearance rates and the agent's principal toxicity, neutropenia. Women with advanced, platinum-refractory ovarian carcinoma received two courses of treatment with 135 mg/m2 paclitaxel over 24 h while participating in the National Cancer Institute's Treatment Referral Center Protocol. A crossover design was employed in which consecutive patients received either 300 mg cimetidine i.v. or 20 mg famotidine i.v. before their first course of paclitaxel and the alternate H2RA before their second course. In order to evaluate the differential effects of cimetidine and famotidine on pertinent pharmacologic and toxicologic parameters in the same individual, paclitaxel concentrations at steady-state (Css), paclitaxel clearance rates, and absolute neutrophil counts (ANCs) were obtained during both courses. Paclitaxel Css values were not significantly different in individual patients when either cimetidine or famotidine preceded paclitaxel (p = 0.16). Mean paclitaxel clearance rates were 271 and 243 ml/min per m2 following cimetidine and famotidine, respectively. These

  19. 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

  20. Severe congenital neutropenia with neurological impairment due to a homozygous VPS45 p.E238K mutation: A case report suggesting a genotype-phenotype correlation.

    PubMed

    Meerschaut, Ilse; Bordon, Victoria; Dhooge, Catharina; Delbeke, Patricia; Vanlander, Arnaud V; Simon, Amos; Klein, Christoph; Kooy, R Frank; Somech, Raz; Callewaert, Bert

    2015-12-01

    VPS45 mutations cause severe congenital neutropenia (SCN). We report on a girl with SCN and neurological impairment harboring a homozygous p.E238K mutation in VPS45 (vacuolar sorting protein 45). She successfully underwent hematopoietic stem cell transplantation. Our findings delineate the phenotype and indicate a possible genotype-phenotype correlation for neurological involvement. PMID:26358756

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

    PubMed

    Whiskey, Eromona; Olofinjana, Olubanke; Taylor, David

    2011-06-01

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

  2. 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).

  3. Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28.

    PubMed Central

    Bolhuis, P A; Hensels, G W; Hulsebos, T J; Baas, F; Barth, P G

    1991-01-01

    X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria is clinically characterized by congenital dilated cardiomyopathy, skeletal myopathy, recurrent bacterial infections, and growth retardation. We analyzed linkage between the disease locus and X-chromosomal markers in a family with seven carriers, four patients, and eight unaffected sons of carriers. Highest lod scores obtained by two-point linkage analysis were 2.70 for St14.1 (DXS52, TaqI) at a recombination fraction of zero and 2.53 for cpX67 (DXS134) at a recombination fraction of zero. Multipoint linkage analysis resulted in a maximum lod score of 5.24 at the position of St35.691 (DXS305). The most distal recombination detected in this family was located between the markers II-10 (DXS466) and DX13 (DXS15). These data indicate the location of the mutated gene at Xq28. PMID:1998334

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

    PubMed Central

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

    2013-01-01

    Objective In a large population-based cohort in Denmark to examine if maternal use of antibiotics during pregnancy, as a marker of infection, increases the risk of febrile seizures in childhood in a large population-based cohort in Denmark. Methods All live-born singletons born in Denmark between January 1, 1996 and September 25, 2004 and who were alive on the 90th day of life were identified from the Danish National Birth Registry. Diagnoses of febrile seizures were obtained from the Danish National Hospital Register and maternal use of antibiotics was obtained from the National Register of Medicinal Product Statistics. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazard regression models. Results We followed 551,518 singletons for up to 5 years and identified a total of 21,779 children with a diagnosis of febrile seizures. Slightly increased hazard ratios were observed among most exposure groups when compared to the unexposed group, ex. HR 1.08 95% CI: 1.05–1.11 for use of any systemic antibiotic during pregnancy. Conclusion We found weak associations between the use of pharmacologically different antibiotics during pregnancy and febrile seizures in early childhood which may indicate that some infections, or causes or effects of infections, during pregnancy could affect the fetal brain and induce susceptibility to febrile seizures. PMID:23613800

  5. Analysis of the results of routine lumbar puncture after a first febrile convulsion in Hofuf, Al-Hassa, Saudi Arabia.

    PubMed

    Laditan, A A

    1995-06-01

    Cerebrospinal fluid (CSF) was analysed to determine a lumbar puncture (LP) yield for meningitis in 95 children who presented with their first febrile convulsions between July 1993 and June 1994. There were 52 males and 43 females aged six months to six years with a mean age of 21.9 +/- 13.0 months at presentation. 87(91.6%) had simple febrile convulsions (SFC) while the remaining 8(8.4%) had complex febrile convulsions (CFC). The majority of the subjects presented with a sudden onset of convulsions that were preceded by a day or two history of fever, coryza, cough and respiratory distress while others had their convulsions preceded by fever and passage of bloody stools. The LP yield for meningitis in this series was 6.3%. The CSF analysis revealed six cases of meningitis comprising an eight month old infant with Haemophilus influenzae type B (HIB) meningitis, two partially treated pyogenic meningitis and three aseptic meningitis. All of them had presented with febrile convulsions without signs of meningeal irritation. Excluding aseptic meningitis from this series, a 3.1% LP yield for pyogenic meningitis is significant enough to recommend continued performance of LP in children with first febrile convulsions, especially if under the age of eighteen months. PMID:7498008

  6. Timing of recombinant human granulocyte colony-stimulating factor administration on neutropenia induced by cyclophosphamide in normal mice.

    PubMed Central

    Misaki, M.; Ueyama, Y.; Tsukamoto, G.; Matsumura, T.

    1998-01-01

    The effects of altering the timing of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on neutropenia induced by cyclophosphamide (CPA) were studied experimentally in a mouse model. Experimental mice were divided into three groups: (a) treatment with rhG-CSF after CPA administration (post-treatment group); (b) treatment with rhG-CSF both before and after CPA administration (pre- and post-treatment group); and (c) treatment with saline after CPA administration (control group). The results were as follows. Mice receiving rhG-CSF on the 2 days preceding CPA treatment, in which progenitor cell counts outside the S-phase when CPA was administered were the lowest of all the groups, showed accelerated neutrophil recovery but decreased neutrophil nadirs compared with the control group despite rhG-CSF treatment. The pre- and post-treatment group, consisting of mice who received rhG-CSF treatment on days -4 and -3 before CPA treatment, and in which progenitor cell counts when CPA was administered were increased to greater levels than in the other groups, showed remarkably accelerated neutrophil recovery and the greatest increase in the neutrophil nadirs of all the groups. These results suggested that the kinetics of progenitor cell populations when chemotherapeutic agents were administered seemed to play an important role in neutropenia after chemotherapy, and that not only peripheral neutrophil cell and total progenitor cell counts but also progenitor cell kinetics should be taken into consideration when administering rhG-CSF treatment against the effects of chemotherapy. PMID:9528829

  7. Quick identification of febrile neonates with low risk for serious bacterial infection: an observational study

    PubMed Central

    Marom, R; Sakran, W; Antonelli, J; Horovitz, Y; Zarfin, Y; Koren, A; Miron, D

    2007-01-01

    Objective To examine the possible usefulness of simple and quick criteria for identifying febrile neonates with low risk for serious bacterial infection (SBI). Design All febrile neonates who were admitted between August 1998 and August 2003 to the Pediatric Emergency Department, HaEmek Medical Center, Afula, Israel, and to the Poriya Hospital, Tiberias, Israel, were included in the study. The recommended evaluation of each neonate included details of medical history and a complete physical examination, including blood culture, erythrocyte sedimentation rate (ESR), white cell count (WBC), and analysis and culture of urine and cerebrospinal fluid. Other tests were carried out as necessary. Patients who met all the following criteria were considered to have low risk for SBI: (1) unremarkable medical history; (2) good appearance; (3) no focal physical signs of infection; (4) ESR <30 mm at the end of the first hour; (5) WBC 5000–15 000/mm3; (6) a normal urine analysis by the dipstick method. Results Complete data were available for 386 neonates. SBI was documented in 108 (28%) neonates, of whom 14% had a urinary tract infection, 9.3% had acute otitis media, 2.3% had pneumonia, 1.3% had cellulitis, 0.5% had bacterial meningitis and 0.5% had bacterial gastroenteritis. The overall incidence of SBI was 1 in 166 (0.6%) neonates who fulfilled the criteria compared with 107 in 220 (48.6%) in the neonates who did not fulfil the criteria (p<0.001). The negative predictive value for SBI of the combination of the low‐risk criteria was 99.4% (95% confidence interval 99.35% to 99.45%). Conclusions Fulfilment of the criteria for low risk might be a reliable and useful tool for excluding SBI in febrile neonates. PMID:17185424

  8. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Guggenheim, J A; Williams, C

    2016-04-01

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

  11. Sub-microscopic gametocyte carriage in febrile children living in different areas of Gabon

    PubMed Central

    2013-01-01

    Background Considering malaria prevalence declines in parts of sub-Saharan Africa, such as Gabon, identification of the human infectious reservoir is important for successful malaria control. Microscopic and sub-microscopic parasites contribute to malaria transmission. The aim of the present study was to evaluate the proportion of microscopic and sub-microscopic gametocyte carriers among febrile patients in two different areas of Gabon. Methods Samples from febrile children aged less than 11 years old were collected from February 2008 to January 2009 at two health centres of Gabon. Patients were screened for the presence of asexual Plasmodium falciparum parasites. Gametocyte carriage was determined by microscopy and QT-NASBA. Results Gametocytes were detected in 5.3% (n = 16/304) of children by microscopy compared to 45.7% (n = 139/304) by QT-Nasba. Sub-microscopic gametocyte carriage (ie microscopy negative and QT-Nasba positive) was found in 89.2% (n = 124/139) of patients. Among patients with microscopically detected trophozoites, the proportion of sub-microscopic gametocyte (SMG) carriers was 58.4% (n = 118/202) and 6% in samples from children with negative slides (p < 0.01). In Oyem, where malaria prevalence is three-fold higher than in Owendo, SMG carriage was more frequent (49.0% vs 32.6% in Owendo; p < 0.01). Conclusion Sub-microscopic gametocytaemia is common among Gabonese febrile children. They might strongly contribute to maintain malaria transmission. However, further analysis of sub-microscopic parasite carriage among asymptomatic individuals will be helpful to better characterize malaria transmission. PMID:24168323

  12. Protracted febrile myalgia syndrome in a kidney transplant recipient with familial Mediterranean fever.

    PubMed

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

    2015-04-01

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

  13. 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

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

    PubMed Central

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

    2013-01-01

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

  15. A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy.

    PubMed

    Audenaert, D; Claes, L; Ceulemans, B; Löfgren, A; Van Broeckhoven, C; De Jonghe, P

    2003-09-23

    Generalized epilepsy with febrile seizures plus (GEFS+) is a clinically and genetically heterogeneous syndrome with childhood onset, characterized by febrile seizures (FS) and a variety of afebrile epileptic seizure types. The authors performed a mutational analysis of SCN1B on 74 unrelated probands with GEFS+, FS, or FS plus (FS+). In a family with FS+ and early-onset absence epilepsy, a mutation was identified that predicts a deletion of five amino acids in the extracellular immunoglobulin-like domain of SCN1B and potential loss of function. SCN1B mutations are associated with GEFS+ and may have a role in the elicitation of absence seizures. PMID:14504340

  16. 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

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

    PubMed

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

    2001-06-01

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

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

    PubMed

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

    2015-12-01

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

  19. Axon initial segment dysfunction in a mouse model of genetic epilepsy with febrile seizures plus

    PubMed Central

    Wimmer, Verena C.; Reid, Christopher A.; Mitchell, Suzanne; Richards, Kay L.; Scaf, Byron B.; Leaw, Bryan T.; Hill, Elisa L.; Royeck, Michel; Horstmann, Marie-Therese; Cromer, Brett A.; Davies, Philip J.; Xu, Ruwei; Lerche, Holger; Berkovic, Samuel F.; Beck, Heinz; Petrou, Steven

    2010-01-01

    Febrile seizures are a common childhood seizure disorder and a defining feature of genetic epilepsy with febrile seizures plus (GEFS+), a syndrome frequently associated with Na+ channel mutations. Here, we describe the creation of a knockin mouse heterozygous for the C121W mutation of the β1 Na+ channel accessory subunit seen in patients with GEFS+. Heterozygous mice with increased core temperature displayed behavioral arrest and were more susceptible to thermal challenge than wild-type mice. Wild-type β1 was most concentrated in the membrane of axon initial segments (AIS) of pyramidal neurons, while the β1(C121W) mutant subunit was excluded from AIS membranes. In addition, AIS function, an indicator of neuronal excitability, was substantially enhanced in hippocampal pyramidal neurons of the heterozygous mouse specifically at higher temperatures. Computational modeling predicted that this enhanced excitability was caused by hyperpolarized voltage activation of AIS Na+ channels. This heat-sensitive increased neuronal excitability presumably contributed to the heightened thermal seizure susceptibility and epileptiform discharges seen in patients and mice with β1(C121W) subunits. We therefore conclude that Na+ channel β1 subunits modulate AIS excitability and that epilepsy can arise if this modulation is impaired. PMID:20628201

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

    PubMed Central

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

    2012-01-01

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

  2. An investigation into febrile illnesses of unknown aetiology in Wipim, Papua New Guinea.

    PubMed

    Bande, Grace; Hetzel, Manuel W; Iga, Jonah; Barnadas, Celine; Mueller, Ivo; Siba, Peter M; Horwood, Paul F

    2014-01-01

    In Papua New Guinea the aetiology of febrile illnesses remains poorly characterized, mostly due to poor diagnostic facilities and the inaccessibility of much of the rural areas of the country. We investigated the aetiological agents of febrile illnesses for 136 people presenting to Wipim Health Centre in Western Province, Papua New Guinea. Arboviral and rickettsial real-time polymerase chain reaction (PCR) assays, malaria blood smears and a malaria PCR test were used to identify pathogens associated with a history of fever. In 13% (n = 18) of cases an aetiological agent was identified. Dengue virus type 1 was detected in 11% (n = 15) of the samples tested and malaria in 2% (n = 3). None of the other arboviral or rickettsial pathogens tested for were detected in any of the samples. Although dengue viruses have been identified in Papua New Guinea using serological methods, this study represents the first direct detection of dengue in the country. The detection of malaria, on the other hand, was surprisingly low considering the previous notion that this was a hyperendemic region of Papua New Guinea. PMID:26930888

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

    PubMed

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

    2011-01-01

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

  4. The first febrile convulsion: an analysis of 108 children in Saudi Arabia.

    PubMed

    Mahdi, A H; Taha, S A

    1982-09-01

    In 108 children admitted to the Maternity and Children's Hospital, Riyadh with their first febrile convulsion, clinical course, management and underlying causes were analysed. There was a preponderance of boys (69%) and a mean age of 18.6 months with a peak incidence (82%) between six months and three years. The commonest precipitating conditions were upper respiratory infection and gastroenteritis. Physical findings were confined to those of the primary disease. Routine investigations, including CSF analysis were not helpful. Convulsions were mainly of the simple type, single and symmetrical, and did not last for more than 30 minutes. Two thirds of the children reached hospital within two hours of the onset of their first convulsion, and the remainder up to ten hours after the convulsion had ceased. In only 18 patients did the parents take measures to lower the temperature or revive the child. Management of febrile convulsions is discussed. Since the condition is common and, if repeated, may have serious effects, methods of educating parents are suggested. PMID:6191623

  5. 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. PMID:24433986

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

    PubMed

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

    2006-01-01

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

  7. 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.

  8. Protective effect of the KCNQ activator flupirtine on a model of repetitive febrile seizures.

    PubMed

    Yu, Fang; Liu, Yanlan; Wang, Yuncui; Yin, Jun; Wang, Hui; Liu, Wanhong; Peng, Biwen; He, Xiaohua

    2011-11-01

    Activation of KCNQ-channels has been shown to decrease or reduce the propagation of neuronal excitation in the immature central nervous system, and KCNQ activators represent a new class of anticonvulsant compounds. Their effectiveness has been demonstrated in many seizure models but not in repetitive febrile seizures (RFS) models. This study aimed to test whether the KCNQ channel activator flupirtine is also effective for RFS in rats. RFS were induced in Sprague-Dawley (SD) rats at postnatal day 10 (P10) in a warm water bath for eight consecutive days with or without the pre-administration of flupirtine or phenobarbital. As results, both drugs significantly increased the latency and decreased the rate of febrile seizures. Furthermore, seizures in the flupirtine group had a significantly shorter duration and were less severe compared with the phenobarbital group. The flupirtine-treated group showed less impairment in learning and memory and less obvious pathological changes in the brain following RFS compared with the phenobarbital-treated group. In summary, flupirtine appears to be effective in RFS prophylaxis and may merit further study as a candidate for the treatment of RFS in infants and children. PMID:21831598

  9. Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome

    PubMed Central

    Calzavara-Silva, Carlos E.; Gomes, Ana L. V.; Brito, Carlos A. A.; Cordeiro, Marli T.; Silva, Ana M.; Magalhães, Cecilia; Andrade, Raoni; Gil, Laura H. V. G.; Marques, Ernesto T. A.

    2009-01-01

    Background We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2–3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. PMID:19936257

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

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. Detecting change as it occurs

    NASA Technical Reports Server (NTRS)

    Radok, Uwe; Brown, Timothy J.

    1992-01-01

    Traditionally climate changes have been detected from long series of observations and long after they have happened. Our 'inverse sequential' procedure, for detecting change as soon as it occurs, describes the existing or most recent data by their frequency distribution. Its parameter(s) are estimated both from the existing set of observations and from the same set augmented by 1,2,....j new observations. Individual-value probability products ('likelihoods') are used to form ratios which yield two probabilities for erroneously accepting the existing parameter(s) as valid for the augmented data set, and vice versa. A genuine parameter change is signaled when these probabilities (or a more stable compound probability) show a progressive decrease. New parameter values can then be estimated from the new observations alone using standard statistical techniques. The inverse sequential procedure will be illustrated for global annual mean temperatures (assumed normally distributed), and for annual numbers of North Atlantic hurricanes (assumed to represent Poisson distributions). The procedure was developed, but not yet tested, for linear or exponential trends, and for chi-squared means or degrees of freedom, a special measure of autocorrelation.

  13. 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

  14. The effect of mimicking febrile temperature and drug stress on malarial development

    PubMed Central

    Aunpad, Ratchaneewan; Somsri, Sangdao; Na-Bangchang, Kesara; Udomsangpetch, Rachanee; Mungthin, Mathirut; Adisakwattana, Poom; Chaijaroenkul, Wanna

    2009-01-01

    Background Malaria remains one of the most important tropical diseases of human with 1–2 million deaths annually especially caused by P. falciparum. During malarial life cycle, they exposed to many environmentally stresses including wide temperature fluctuation and pharmacological active molecules. These trigger malarial evolutionarily adaptive responses. The effect of febrile temperature on malarial growth, development and drug susceptibility by mimicking patient in treatment failure before and after drug uptake was examined. Methods Sensitivities of P. falciparum to antimalarial drug (chloroquine, mefloquine, quinine and artesunate) were investigated based on the incorporation of [3H] hypoxanthine into parasite nucleic acids or radioisotopic technique. The number of parasites was examined under microscope following Giemsa staining and the parasite development at the end of each phase was counted and comparison of parasite number was made. The proteome was separated, blotted and hybridized with anti-Hsp70s primary antibody. The hybridized proteins were separately digested with trypsin and identified by MALDI-TOF peptide mass fingerprint. Results The results show that febrile temperature is capable of markedly inhibiting the growth of field isolate P. falciparum but not to K1 and 3D7 standard strains. K1 and 3D7 grown under heat shock developed greater and the reinfection rate was increased up to 2-folds when compared to that of non-heat shock group. The IC50 value of K1 toward chloroquine, mefloquine and quinine under heat shock was higher than that of K1 under non-heat shock which is opposite to that of 3D7. Heat shock caused death in field isolated parasite. It was also found that the febrile temperature coped with chloroquine uptake had no effect to the development, drug sensitivity and the parasite number of K1 strain. In the opposite way, heat shock and chloroquine shows extremely effect toward 3D7 and field isolate PF91 as shown by higher number of dead

  15. 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

  16. 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.

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

    PubMed

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

    2015-10-01

    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21-0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11-0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinib with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78-1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34-1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07-0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01-0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined

  18. 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. PMID:10968110

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. 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

  3. 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

  4. Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study [ISRCTN30487061

    PubMed Central

    Nabulsi, Mona M; Tamim, Hala; Mahfoud, Ziyad; Itani, Mohammad; Sabra, Ramzi; Chamseddine, Fadi; Mikati, Mohammad

    2006-01-01

    Background Alternating ibuprofen and acetaminophen for the treatment of febrile children is a prevalent practice among physicians and parents, despite the lack of evidence on effectiveness or safety. This randomized, double-blind and placebo-controlled clinical trial aims at comparing the antipyretic effectiveness and safety of a single administration of alternating ibuprofen and acetaminophen doses to that of ibuprofen mono-therapy in febrile children. Methods Seventy febrile children were randomly allocated to receive either a single oral dose of 10 mg/kg ibuprofen and 15 mg/kg oral acetaminophen after 4 hours, or a similar dose of ibuprofen and placebo at 4 hours. Rectal temperature was measured at baseline, 4, 5, 6, 7 and 8 hours later. Endpoints included proportions of afebrile children at 6, 7 and 8 hours, maximum decline in temperature, time to recurrence of fever, and change in temperature from baseline at each time point. Intent-to-treat analysis was planned with statistical significance set at P < 0.05. Results A higher proportion of subjects in the intervention group (83.3%) became afebrile at 6 hours than in the control group (57.6%); P = 0.018. This difference was accentuated at 7 and 8 hours (P < 0.001) with a significantly longer time to recurrence of fever in the intervention group (mean ± SD of 7.4 ± 1.3 versus 5.7 ± 2.2 hours), P < 0.001. Odds ratios (95%CI) for defervescence were 5.6 (1.3; 23.8), 19.5 (3.5; 108.9) and 15.3 (3.4; 68.3) at 6, 7 and 8 hours respectively. Two-way ANOVA with repeated measures over time revealed a significantly larger decline in temperature in the intervention group at times 7 (P = 0.026) and 8 (P = 0.002) hours. Conclusion A single dose of alternating ibuprofen and acetaminophen appears to be a superior antipyretic regimen than ibuprofen mono-therapy. Further studies are needed to confirm these findings. PMID:16515705

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

    PubMed Central

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

    2014-01-01

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

  6. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2010-12-01

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

  10. 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

  11. Cortical gray matter lesions in acute encephalopathy with febrile convulsive status epilepticus.

    PubMed

    Sato, Atsushi; Mizuguchi, Masashi; Mimaki, Masakazu; Takahashi, Kan; Jimi, Hanako; Oka, Akira; Igarashi, Takashi

    2009-09-01

    In acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), subcortical white matter lesions on diffusion-weighted images are sometimes encountered on magnetic resonance imaging (MRI), such as in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). We report here a severe case of AEFCSE following respiratory syncytial virus infection, with emphasis on the cranial MRI findings. MRI in this patient showed widespread T2-hyperintensity along the cerebral cortical gray matter from day 3 to day 22. Lesions with reduced diffusion were noted on day 3 in the deep zone of gray matter of the left occipito-temporo-parietal cortex, but on day 7 they shifted to the subcortical white matter of both the cerebral hemispheres. These MRI findings provide radiologic evidence for damage to the cortical gray matter in AEFCSE. The serial change of diffusion-weighted images suggests that the cortical gray matter may be injured prior to the involvement of the subcortical white matter. PMID:18848752

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

    PubMed

    Smyth, Dean; Selwyn, Jey

    2016-01-01

    We present a case of a 77-year-old man with a history of myeloproliferative disorder. He was admitted with a 2-week history of erythaema, swelling and significant pain of the right forearm following a mechanical fall at home, which had caused a skin laceration. During his admission, he developed ongoing intermittent fever and persistently elevated C reactive protein, and total white cell count. Initially, he was treated with antibiotics for suspected cellulitis. However, symptoms continued to progress, making a suitable management plan challenging. Wound swabs, blood cultures and viral PCR did not confirm infection. A punch biopsy of a skin lesion on the forearm was performed. The histology demonstrated a dense infiltrate of neutrophils and neutrophilic debris in keeping with acute febrile neutrophilic dermatosis (Sweet's syndrome). He was treated with oral steroids and after that he had a complete resolution of symptoms. However, he required a period of rehabilitation before returning home. PMID:27118753

  13. Genes and loci involved in febrile seizures and related epilepsy syndromes.

    PubMed

    Audenaert, Dominique; Van Broeckhoven, Christine; De Jonghe, Peter

    2006-05-01

    Epilepsy is a paroxysmal disorder with a cumulative incidence of about 3%. About 13% of patients with epilepsy have a history of febrile seizures (FS). Generalized epilepsy with FS plus (GEFS+) is a familial epilepsy syndrome in which patients can have classic FS, FS that persist beyond the age of 5 years (i.e., FS+), and/or epilepsy. Both genetic and environmental factors have been shown to contribute to the pathogenesis of FS and GEFS+. During the past 10 years, molecular genetic studies have contributed a great deal to the identification of genetic factors involved in FS and GEFS+. In this study we aimed to provide a comprehensive review of currently known genes for FS and GEFS+, and the methods and approaches used to identify them. We also discuss the knowledge we currently have and hypotheses regarding the effect of the mutations on their respective protein functions. PMID:16550559

  14. Emergency Department Evaluation and Management of Children With Simple Febrile Seizures.

    PubMed

    Carapetian, Stephanie; Hageman, Joseph; Lyons, Evelyn; Leonard, Daniel; Janies, Kathryn; Kelley, Kent; Fuchs, Susan

    2015-09-01

    Workup of simple febrile seizures (SFS) has changed as the American Academy of Pediatrics made revisions to practice guidelines. In 2011, revisions were made regarding need for lumbar puncture (LP) as part of the SFS workup. This study surveyed more than 100 emergency departments regarding workup of children with SFS and performed a medical record review of workup that was performed. The survey shows that laboratory workup is done routinely and LP is done infrequently. The majority documents a complete exam. The medical record review demonstrates documentation of the examination, frequent laboratory and infrequent LP evaluation. Consistent with the American Academy of Pediatrics' revisions, survey and record reviews demonstrate that LP testing is infrequent. Contrary to the guideline, laboratory studies are routinely performed. This study suggests there is an opportunity to improve management of SFS by directing efforts toward finding the source of the fever and away from laboratory workup. PMID:25667312

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

    PubMed Central

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

    2014-01-01

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

  16. 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.

  17. Value of Ultrasound in Detecting Urinary Tract Anomalies After First Febrile Urinary Tract Infection in Children.

    PubMed

    Ghobrial, Emad E; Abdelaziz, Doaa M; Sheba, Maha F; Abdel-Azeem, Yasser S

    2016-05-01

    Background Urinary tract infection (UTI) is an infection that affects part of the urinary tract. Ultrasound is a noninvasive test that can demonstrate the size and shape of kidneys, presence of dilatation of the ureters, and the existence of anatomic abnormalities. The aim of the study is to estimate the value of ultrasound in detecting urinary tract anomalies after first attack of UTI. Methods This study was conducted at the Nephrology Clinic, New Children's Hospital, Faculty of Medicine, Cairo University, from August 2012 to March 2013, and included 30 children who presented with first attack of acute febrile UTI. All patients were subjected to urine analysis, urine culture and sensitivity, serum creatinine, complete blood count, and imaging in the form of renal ultrasound, voiding cysto-urethrography, and renal scan. Results All the patients had fever with a mean of 38.96°C ± 0.44°C and the mean duration of illness was 6.23 ± 5.64 days. Nineteen patients (63.3%) had an ultrasound abnormality. The commonest abnormalities were kidney stones (15.8%). Only 2 patients who had abnormal ultrasound had also vesicoureteric reflux on cystourethrography. Sensitivity of ultrasound was 66.7%, specificity was 37.5%, positive predictive value was 21.1%, negative predictive value was 81.8%, and total accuracy was 43.33%. Conclusion We concluded that ultrasound alone was not of much value in diagnosing and putting a plan of first attack of febrile UTI. It is recommended that combined investigations are the best way to confirm diagnosis of urinary tract anomalies. PMID:26084536

  18. 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

  19. 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

  20. Translation of clinical prediction rules for febrile children to primary care practice: an observational cohort study

    PubMed Central

    van Ierland, Yvette; Elshout, Gijs; Berger, Marjolein Y; Vergouwe, Yvonne; de Wilde, Marcel; van der Lei, Johan; Mol, Henriëtte A; Oostenbrink, Rianne

    2015-01-01

    Background Clinical prediction rules (CPRs) to identify children with serious infections lack validation in low-prevalence populations, which hampers their implementation in primary care practice. Aim To evaluate the diagnostic value of published CPRs for febrile children in primary care. Design and setting Observational cohort study among febrile children (<16 years) who consulted five GP cooperatives (GPCs) in the Netherlands. Method Alarm signs of serious infection and clinical management were extracted from routine clinical practice data and manually recoded with a structured electronic data-entry program. Eight CPRs were selected from literature. CPR-variables were matched with alarm signs and CPRs were applied to the GPC-population. ‘Referral to emergency department (ED)’ was used as a proxy outcome measure for ‘serious infection’. CPR performance was assessed by calibration analyses, sensitivity, specificity, and area under the ROC-curve (ROC-area). Results A total of 9794 GPC-contacts were eligible, 54% male, median age 2.3 years (interquartile range 1.0–4.6 years) and 8.1% referred to ED. Frequencies of CPR-variables varied from 0.5% (cyanosis, drowsy) to 25% (temperature ≥40°C). Alarm signs frequently included in CPRs were ‘ill appearance’, ‘inconsolable’, and ‘abnormal circulatory or respiratory signs’. The height of the CPR’s predicted risks generally corresponded with being (or not being) referred to the ED in practice. However, calibration-slopes indicated that three CPRs underestimated the risk of serious infection in the GPC-population. Sensitivities ranged from 42% to 54%, specificities from 68% to 89%. ROC-areas ranged from 0.52 to 0.81, with best performance of CPRs for children aged <3 months. Conclusion Published CPRs performed moderately well in the primary out-of-hours care population. Advice is given on how to improve translation of CPRs to primary care practice. PMID:25824182

  1. 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

  2. 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

  3. Tricuspid Papillary Fibroelastoma Mimicking Tricuspid Vegetation in a Patient with Severe Neutropenia.

    PubMed

    Choi, Kuk Bin; Kim, Hwan Wook; Kim, Do Yeon; Jo, Keon Hyon; Choi, Hang Jun; Hong, Seok Beom

    2016-06-01

    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/mm(3)), 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

  4. 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

  5. Proton pump inhibitor-induced Sweet’s syndrome: report of acute febrile neutrophilic dermatosis in a woman with recurrent breast cancer

    PubMed Central

    Cohen, Philip R.

    2015-01-01

    Background: Sweet’s syndrome, also referred to as acute febrile neutrophilic dermatosis, can either occur as an idiopathic disorder or associated with another condition, including cancer, or induced by exposure to a drug. Proton pump inhibitors selectively inhibit gastric parietal cell H+-K+-adenosine triphosphatase and are most commonly used for the treatment of gastroesophageal reflux disease. Purpose: Proton pump inhibitor-associated Sweet’s syndrome is described in a woman with recurrent breast cancer. Methods: PubMed was used to search the following terms, separately and in combination: acute febrile neutrophilic dermatosis, breast cancer, malignancy, paraneoplastic, proton pump inhibitor, and Sweet’s syndrome. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Results: Proton pump inhibitors have previously been associated with cutaneous adverse reactions including maculopapular rash, subacute cutaneous lupus erythematosus and toxic epidermal necrolysis. However, drug-induced Sweet’s syndrome has not been observed in patients receiving proton pump inhibitors. The reported woman developed Sweet’s syndrome after initial exposure and subsequent repeat challenge to proton pump inhibitors; subsequent studies also observed recurrence of her breast cancer presenting as metastases to her stomach and bone. Conclusions: Drug-induced Sweet’s syndrome has most commonly been associated with granulocyte colony stimulating factor in oncology patients. Malignancy-associated Sweet’s syndrome has been observed in patients with solid tumors, including breast cancer. Confirmation of proton pump inhibitor-induced Sweet’s syndrome, by repeat challenge with another medication in the same class of drug, was observed in a woman with breast cancer; although the subsequent discovery of recurrent breast cancer presenting as gastric mucosa and vertebral metastases also raises the possibility of concurrent

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

    PubMed Central

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

    2014-01-01

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

  7. Expanding the role of the splicing USB1 gene from Poikiloderma with Neutropenia to acquired myeloid neoplasms.

    PubMed

    Negri, Gloria; Crescenzi, Barbara; Colombo, Elisa Adele; Fontana, Laura; Barba, Gianluca; Arcioni, Francesco; Gervasini, Cristina; Mecucci, Cristina; Larizza, Lidia

    2015-11-01

    Germline mutations of the U6 biogenesis 1 (USB1) gene underlie Poikiloderma with Neutropenia (PN), a rare autosomal recessive genodermatosis conferring an increased risk of myelodysplasia. Recent evidence highlights a key role of USB1 protein in the splicing process, but nothing is known about USB1 alterations in acquired myelodysplastic syndromes, even though mutations in the spliceosome machinery represent an ubiquitous pathway in leukaemogenesis. By molecular cytogenetics and direct sequencing, we searched for USB1 deletions/duplications and point mutations in 141 bone marrow DNA samples from patients with myelodysplastic syndromes (n = 126), myelodysplastic/myeloproliferative neoplasms (n = 12) and acute myeloid leukaemia (n = 3). Three unreported variants, two in USB1 5'UTR (c.-83G>T and c.-66A>G), one in IVS3 (c.450-68dupT) and one (<1%) in IVS4 (c.587+21A>G/rs200924980) were detected. The germline nature could be proved for the c.-66A>G, but remains undefined for c.-83G>T and c.450-68dupT. Matched controls analysis did not reveal either 5' UTR variants in 290 chromosomes and Real-time polymerase chain reaction showed a slight reduction in bone marrow RNA levels of the patient with c.-66A>G. No USB1 rearrangements were detected by interphase fluorescence in situ hybridization. This pilot investigation on USB1 expanded the variations repertoire of this gene, identifying three novel sequence variants, the role of which need further investigations in myeloid malignancies. PMID:26306619

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

    PubMed

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

    2014-04-17

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

  9. Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds.

    PubMed

    Smith, Bradley N; Ancliff, Phil J; Pizzey, Arnold; Khwaja, Asim; Linch, David C; Gale, Rosemary E

    2009-03-01

    Patients with autosomal dominant (AD), sporadic and X-linked severe congenital neutropenia (SCN) may have mutations in the elastase 2 (ELA2) or Wiskott-Aldrich syndrome (WAS) genes. Homozygous mutations in the HAX1 gene have recently been reported in autosomal recessive (AR) cases of primarily Middle-Eastern descent and the original Kostmann family. We screened 109 predominantly Caucasian SCN kindreds for mutations in these genes; 33 (30%) had 24 different ELA2 mutations, five of them novel, two kindreds (2%) had WAS mutations and four kindreds (4%) had three different HAX1 mutations, two of them novel. One HAX1 mutation (p.Ser43LeufsX11) was found in an AR Ashkenazi Jewish kindred, the other (p.Glu31LysfsX54) in two unrelated British patients with sporadic disease. Microsatellite analysis of the HAX1 locus revealed a common haplotype (maximum distance 4.1 Megabases) for the p.Glu31LysfsX54 patients, suggesting a possible ancestral founder. In functional assays, the level of spontaneous and staurosporine-induced apoptosis was increased in neutrophils from both p.Ser43LeufsX11 patients but not a p.Glu31LysfsX54 patient, suggesting the possible presence of modifying factors. The low incidence of HAX1 mutations in our study suggests that the frequency may vary between racial groups but suggests that irrespective of inheritance or racial origin, SCN patients should be screened for HAX1 mutations. PMID:19036076

  10. Long-term effects of febrile convulsion on seizure susceptibility in P77PMC rat--resistant to acoustic stimuli but susceptible to kainate-induced seizures.

    PubMed

    Zhao, D Y; Wu, X R; Pei, Y Q; Zuo, Q H

    1985-06-01

    A new audiogenic seizure (AGS)-susceptible strain of rats (P77PMC) was evaluated as a possible model of human febrile seizures. The long-term effects of experimental febrile seizures were observed. All 30-day-old rat pups exhibited clonic seizures during exposure to an ambient temperature of 45 +/- 0.5 degree C. The mean latency from the beginning of the hyperthermic stimulus to the onset of convulsion was 16.9 +/- 2.2 min. The rats survived this hyperthermic seizure, developed a resistance to acoustic stimulations, but were more susceptible at the age of 50 to 60 days to kainate-induced limbic seizures than controls. The results of this study imply that febrile seizures of developing P77PMC rats can change later seizure susceptibility, and there may be some correlation between febrile convulsion and temporal lobe epilepsy. PMID:3996515

  11. A family of generalized epilepsy with febrile seizures plus type 2-a new missense mutation of SCN1A found in the pedigree of several patients with complex febrile seizures.

    PubMed

    Nagao, Yoshiro; Mazaki-Miyazaki, Emi; Okamura, Nami; Takagi, Manabu; Igarashi, Takashi; Yamakawa, Kazuhiro

    2005-02-01

    We report a family with complex febrile seizures (FS). The proband is a 15-year-old boy with seizures that persisted beyond 6 years of age. His father, aunt, and cousin also have the histories of FS until 8, 9, and 8 years old, respectively. A base substitution 5569G-->T of voltage-gated sodium channel alpha-1 subunit gene was found in DNA derived from the affected members of this family. PMID:15715999

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

    PubMed Central

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

    2013-01-01

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

  13. Eosinophil-Rich Acute Febrile Neutrophilic Dermatosis in a Patient With Enteropathy-Associated T-cell Lymphoma, Type 1.

    PubMed

    Soon, Christopher W; Kirsch, Ilan R; Connolly, Andrew J; Kwong, Bernice Y; Kim, Jinah

    2016-09-01

    The presence of eosinophils within the neutrophilic infiltrates of acute febrile neutrophilic dermatosis (Sweet syndrome) is documented in the literature. Here, the authors describe a case of eosinophil-rich acute febrile neutrophilic dermatosis in the setting of new onset enteropathy-associated T-cell lymphoma (EATL), type 1. Histopathologic evaluation of the skin biopsies demonstrated a mixed superficial perivascular and inflammatory infiltrate composed of neutrophils, lymphocytes, and abundant eosinophils. EATL, type 1 is an aggressive although rare primary intestinal lymphoma that may be associated with celiac disease. This lymphoma is associated with a poor prognosis due to treatment resistance or bowel perforation. To the authors' knowledge, Sweet syndrome has not been reported in a patient with EATL. PMID:27097333

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

    PubMed Central

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

    2014-01-01

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

  15. 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

  16. 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

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

    PubMed

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

    2013-09-01

    Elderly individuals are more susceptible to excess summer heat. We sought to examine whether the use of cooling systems (air-conditioning or fan) affected the clinical outcomes of elderly febrile patients. We prospectively followed elderly (≥ 75 years old) febrile patients requesting the medical services of the SOS Doctors (a network of physicians performing house-call visits) from July 10 to August 20, 2011. Patients who used cooling systems ("users") were compared with those who did not ("non-users") regarding mortality, clinical outcome of primary illness (improvement or deterioration), and emergency hospitalization. Prospectively collected data were available for 339 individual elderly febrile patients. "Users" had lower mortality (10 % vs. 19 %, p < 0.05) than "non-users"; no difference was noted on clinical improvement (85 % vs. 76 %, p = 0.11) and emergency hospitalization rates (21 % vs. 30 %, p = 0.16). No difference was noted between users of air-conditioning and fan regarding mortality or clinical improvement, but fan use was associated with more hospitalizations (37 % vs. 19 %, p < 0.05). On multivariate analysis (assessing daily ambient temperature, use of cooling systems, patient age, and living conditions), the sole variable significantly associated with mortality was the non-use of cooling systems [odds ratio (OR): 2.18, 95 % confidence interval (CI): 1.06-4.50]. The use of air-conditioning or fan during hot summer periods appeared to be beneficial for elderly febrile patients living in a large city. Large prospective studies are warranted in order to provide further insight into potential individual and public health initiatives aiming to alleviate the impact of excess summer heat on the health of elderly patients. PMID:23532568

  18. 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

  19. Identification of a Premature Termination Mutation in the Proline-Rich Transmembrane Protein 2 Gene in a Chinese Family with Febrile Seizures.

    PubMed

    Zheng, Wen; Zhang, Jie; Deng, Xiong; Xiao, Jingjing; Yuan, Lamei; Yang, Yan; Guan, Liping; Song, Zhi; Yang, Zhijian; Deng, Hao

    2016-03-01

    Febrile seizures (FS), the most frequent type of seizures in children, occur in neurologically normal infants and children between the ages of 3 months and 5 years with genetic predisposition. The aim of this study was to identify the responsible gene in a four-generation Chinese Han pedigree with autosomal dominant FS. Seven family members (three affected and four unaffected) were enrolled in this study. Exome sequencing was conducted and a duplication mutation c.649dupC (p.R217Pfs*8) in the proline-rich transmembrane protein 2 gene (PRRT2) was identified. The mutation co-segregated with the disorder and was absent in normal controls. To our knowledge, this is the first report of a pedigree with complete penetrance of FS, which is caused by mutation in the PRRT2 gene. FS is a novel phenotype of the c.649dupC (p.R217Pfs*8) mutation. Our discovery broadens the spectrum of genetic causes of FS and the spectrum of phenotypes linked to mutation in the PRRT2 gene. PMID:25502464

  20. 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

  1. 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

  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. 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

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

    PubMed Central

    Schwarzinger, Michaël; Sagaon-Teyssier, Luis; Cabaret, Odile; Bretagne, Stéphane; Cordonnier, Catherine; Pautas, Cécile; Maury, Sébastien; Hicheri, Yosr; Botterel, Françoise; Foulet, Francoise; Vekhoff, Anne; Chaoui, Driss; Cornet, Muriel; Agnamey, Patrice; Farhat, Hassan; Castaigne, Sylvie; Eloy, Odile; Suarez, Felipe; Buzyn, Agnès; Delarue, Richard; Challier, Svetlana; Dhedin, Nathalie; Aljijakli, Ahmad; Delabesse, Emmanuelle; Datry, Annick; Isnard, Françoise; Fouillard, Loic; Poirot, Jean-Yves; Meliani, Leila; Adès, Lionel; Bouges-Michel, Claire; Deniau, Michèle; Kuhnowski, Frédérique; Dreyfus, François; Paugam, André; Baixench, Marie-Thérèse; Leclercq, Roland; Reman, Oumady; Duhamel, Chantal; Bourrhis, Jean-Henri; Chehata, Sami; Chachati, Isabelle; Foissaud, Vincent; Macnab, Christine; Tilly, Hervé; Leprêtre, Stéphane; Gray, Christian; Raffoux, Emmanuel; Lacroix, Claire; Goldhaber-Fiebert, Jeremy D; Bendavid, Eran; Farley, Brandon J

    2013-01-01

    Background The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking. Methods We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3)- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus. Results The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010), independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53). Conclusions The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a

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

    PubMed

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

    2013-06-01

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

  6. Hantavirus infection among children hospitalized for febrile illness suspected to be dengue in Barbados.

    PubMed

    Kumar, Alok; Krishnamurthy, Kandamaran; Nielsen, Anders L

    2016-01-01

    Emerging picture of hantavirus infection in the South America is characterized by greater proportion of childhood infection and wider spectrum of disease from mild asymptomatic to lethal cardiopulmonary disease. Barbados is endemic for dengue and leptospirosis, both of which share clinical features with hantavirus infection and in many cases neither of these diagnosis could be confirmed. We investigate whether some of the children hospitalized with suspected dengue could indeed have been hantavirus infections. In this prospective study children hospitalized with suspected dengue were tested for hantavirus infection using ELISA for the IgM antibodies. Thirty-eight children tested positive for hantavirus infection. They presented with fever, headache and mild respiratory and gastrointestinal symptoms and signs. None of them had features suggestive of hantavirus cardiopulmonary syndrome. Blood count values ranged from low to normal to high for their age. There were no deaths. Hantavirus infection is prevalent in this Caribbean country. It predominantly presents with milder disease and is responsible for some of the nonspecific febrile illnesses in children. PMID:26153080

  7. 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

  8. Rapid, Coordinate Inflammatory Responses after Experimental Febrile Status Epilepticus: Implications for Epileptogenesis

    PubMed Central

    Patterson, Katelin P.; Kinney-Lang, Eli; Dubé, Celine; Rashid, Faisal; Ly, Catherine; Obenaus, Andre

    2015-01-01

    Abstract Epilepsy is a common neurological disorder with many causes. For temporal lobe epilepsy, antecedent insults are typically found. These risk factors include trauma or history of long fever-associated seizures (febrile status epilepticus) in childhood. Whereas the mechanisms by which such insults promote temporal lobe epilepsy are unknown, an extensive body of work has implicated inflammation and inflammatory mediators in both human and animal models of the disorder. However, direct evidence for an epileptogenic role for inflammation is lacking. Here we capitalized on a model where only a subgroup of insult-experiencing rodents develops epilepsy. We reasoned that if inflammation was important for generating epilepsy, then early inflammation should be more prominent in individuals destined to become epileptic compared with those that will not become epileptic. In addition, the molecular and temporal profile of inflammatory mediators would provide insights into which inflammatory pathways might be involved in the disease process. We examined inflammatory profiles in hippocampus and amygdala of individual rats and correlated them with a concurrent noninvasive, amygdalar magnetic resonance imaging epilepsy-predictive marker. We found significant individual variability in the expression of several important inflammatory mediators, but not in others. Of interest, a higher expression of a subset of hippocampal and amygdalar inflammatory markers within the first few hours following an insult correlated with the epilepsy-predictive signal. These findings suggest that some components of the inflammatory gene network might contribute to the process by which insults promote the development of temporal lobe epilepsy. PMID:26730400

  9. 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

  10. 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

  11. 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

  12. Interaction between endogenous nitric oxide and carbon monoxide in the pathogenesis of recurrent febrile seizures.

    PubMed

    Yang, Zhi-Xian; Qin, Jiong

    2004-03-01

    The aim of the study was to investigate the interaction between nitric oxygenase (NOS)/nitric oxide (NO) and heme oxygenase (HO)/carbon monoxide (CO) system in the pathogenesis of recurrent febrile seizures (FS). On a rat model of recurrent FS, the ultrastructure of hippocampal neurons was observed under electron microscopy, and expression of neuronal NOS (nNOS) in hippocampus and NO formation in plasma were examined after treatment with ZnPP-IX, an HO-1 inhibitor. In the ultrastructure of hippocampal neurons, the expression of HO-1 in hippocampus and CO formation in plasma were examined after treatment with L-NAME, a NOS inhibitor. We found that hippocampal neurons were injured after recurrent FS. The gene and protein expression of nNOS and HO-1 increased markedly in hippocampus in FS rats, while CO formation in plasma increased markedly and the concentration of NO in plasma increased slightly. ZnPP-IX could worsen the neuronal damage of recurrent FS rats. However, it further increased the expression of nNOS and endogenous production of NO obviously. L-NAME alleviated the neuronal damage of recurrent FS rats, but decreased the expression of HO-1 and CO formation. The results of this study suggested that endogenous NOS/NO and HO/CO systems might interact with each other and therefore play an important regulating role in recurrent FS brain damage. PMID:14766214

  13. 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

  14. Differences in factors influencing the familial aggregation of febrile convulsion in population and hospital patients.

    PubMed

    Tsai, J J; Huang, M C; Lung, F W; Huang, C C; Change, Y C

    1996-11-01

    Socio-demographic data, initial clinical manifestations, outcome and family aggregation of febrile convulsion (FC) were compared between 85 population and 364 multicenter patients. More patients presented with clustering of seizures and had recurrence of FC in multicenter group than in population group. Multicenter patients had more fever episodes per year, more day-card attendance and a higher incidence of FC history in their parents. The odds ratio of FC in the siblings was 6:1 in population group and 12:1 in multicenter group. Lower socioeconomic status influenced the presence of FC in the sibling of population group. Instead, FC histories in the father and paternal cousins of probands had influence on the presence of FC in the siblings of multicenter group. We conclude that the population FC sample rather than the hospital sample is the more representative. And there are differences not only in the clinical manifestations but also in the effect of environmental and genetic influences on the family aggregation in population and hospital patients. PMID:8947282

  15. Long-term follow-up of a febrile convulsion cohort.

    PubMed

    Tsuboi, T; Endo, S; Iida, N

    1991-11-01

    Determining the clinical prognosis a 16-year follow-up study of a clinic-based FC cohort was made. The cohort comprises 528 FC children under 5 years of age at first clinic visit. Thirty-nine patients (7.4%) were found to have developing non-febrile seizures (FCC). Discrimination formula was applied; differences in actual cumulative FCC rates differed: a) whether the discriminant score was plus or minus (15%, 31/208 and 2.5% 8/320, respectively; p less than 0.001); b) whether the discriminant score was plus or minus in the group with no medication (47%, 22/47 and 3%, 6/229; p less than 0.001); and c) whether the treatment was applied or not in the group with plus value (6%, 9/161 and 47%, 22/47; p less than 0.001). No difference was detected whether the treatment was introduced or not in the group with a minus discriminant score (2%, 2/91 and 3%, 6/229, ns). The effective prediction and prevention for the FCC development were thus proved. Correlation between the number of predictive eight-risk factors and rates of FCC development are analyzed. PMID:1776383

  16. Treatment and outcome in patients with febrile convulsion associated with epileptiform discharges on electroencephalography.

    PubMed

    Okumura, Akihisa; Ishiguro, Yoshiko; Sofue, Ayako; Suzuki, Yoshiko; Maruyama, Koichi; Kubota, Tetsuo; Negoro, Tamiko; Watanabe, Kazuyoshi

    2004-06-01

    The aim of this study is to determine the efficacy of prophylactic treatment for patients with febrile convulsions (FCs) in whom electroencephalograms (EEGs) revealed epileptiform discharges. We retrospectively investigated 43 patients who met the following criteria: (a) at least one FC during the study period; (b) epileptiform discharges were first recognized; (c) no unevoked seizures before epileptiform discharges were first seen; (d) normal psychomotor development and no neurological abnormality; and (e) follow-up >3 years. The clinical characteristics, treatment, and a later occurrence of FCs or unevoked seizures were studied. EEGs revealed focal epileptiform discharges in 25 patients and generalized ones in 18. There was no significant difference in the rate of recurrence of FC or occurrence of unevoked seizures between those with focal and generalized epileptiform discharges. No prophylaxis was performed in ten patients, 14 patients being treated with intermittent diazepam and 19 with a daily anticonvulsant. The rate of recurrence of FC was not significantly different between patients with and without prophylaxis. Unevoked seizures were only observed in two patients undergoing daily treatment. Intermittent or daily anticonvulsant therapy will not reduce the risk of recurrence of FCs or later development of unevoked seizures in patients with FC with epileptiform discharges. PMID:15130690

  17. 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

  18. What is your diagnosis? Subcutaneous mass fluid from a febrile dog.

    PubMed

    Bulla, Camilo; Thomas, Jennifer S

    2009-09-01

    A 10-month-old spayed female Doberman Pinscher was presented for lameness. On physical examination, the dog was lethargic and febrile and had a 2-cm raised subcutaneous mass at the base of the left ear. Fluid from the mass was drained. Direct smears of the fluid, stained with modified Wright's and new methylene blue, were highly cellular and contained large numbers of degenerate neutrophils with moderate numbers of macrophages. Large numbers of round yeast organisms, 8-20 mum in diameter, were observed extracellularly. The organisms had a thick blue wall and granular internal contents and broad-based budding was seen frequently. Branching hyphae or pseudohyphae, with parallel sides and 2-4 mum in diameter, appeared to extend from the surface of the yeast. The morphology of the yeast organisms was consistent with Blastomyces dermatitidis, with atypical hyphae formation. Culture results were not definitive because it was not possible to induce transition from the mycelial to the yeast form at 37 degrees C and because the morphology of the mycelial form of B. dermatitidis could not be differentiated from that of Emmonsia parvae. The organism was confirmed as Ajellomyces dermatitidis (the mycelial form of B. dermatitidis) using 18S ribosome RNA gene sequencing and comparison with an available databank. The mycelial form of B. dermatitidis is rarely found in the tissue of dogs, and may have been induced in this case by low environmental temperatures and the time delay between sample collection and slide preparation. PMID:19351342

  19. Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic Anemia

    PubMed Central

    Hashiba, Masamitsu; Tomino, Atsutoshi; Takenaka, Nobuyoshi; Hattori, Tomonori; Kano, Hideki; Tsuda, Masanobu; Takeyama, Naoshi

    2016-01-01

    Patient: Male, 82 Final Diagnosis: Clostridium perfringens infection Symptoms: Anemia • fever • shock Medication: — Clinical Procedure: Antimicrobial chemotherapy Specialty: Infectious Diseases Objective: Rare disease Background: Clostridium perfringens (C. perfringens) can cause various infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. Case Report: We present the case of a male patient with diabetes who developed a fatal liver abscess with massive intravascular hemolysis and septic shock caused by toxigenic C. perfringens. The peripheral blood smear showed loss of central pallor, with numerous spherocytes. Multiplex PCR only detected expression of the cpa gene, indicating that the pathogen was C. perfringens type A. Conclusions: C. perfringens infection should be considered in a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed blood sample, and negative Coombs test. The characteristic peripheral blood smear findings may facilitate rapid diagnosis. PMID:27049736

  20. Loss of synaptic Zn2+ transporter function increases risk of febrile seizures.

    PubMed

    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 (Zn(2+)) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn(2+) homeostasis contributes to susceptibility is unknown. Synaptic Zn(2+) is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn(2+) 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 Zn(2+) increases the risk of FS and more broadly support the idea that impaired synaptic Zn(2+) homeostasis can contribute to neuronal hyperexcitability. PMID:26647834

  1. 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

  2. Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

    PubMed

    Tao, K; Ichikawa, J; Matsuki, N; Ikegaya, Y; Koyama, R

    2016-03-24

    Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function. PMID:26794590

  3. Mutation screening of three Chinese families with genetic epilepsy with febrile seizures plus.

    PubMed

    Lin, Hua; Li, Jingyun; Wang, Mengyang; Wang, Zheng; Wang, Yuping; Wu, Liwen

    2011-08-15

    Genetic epilepsy with febrile seizures plus (GEFS+) is a familial autosomal dominant condition characterized by genetic heterogeneity. Five genes for GEFS+ identified in large families account for only a small proportion of families. Mutation in the majority of families with GEFS+ has not identified yet. The aim of our study is to search for the gene responsible for GEFS+ in three Chinese families by linkage analyses and a sequencing approach and to investigate the importance of coding and noncoding regions variations of four known GEFS+ genes (SCN1A, SCN1B, GABRG2 and SCN2A) in Chinese families. Results showed that a 6-cM candidate interval at 5q33-34 with a maximum LOD scores of 2.043 was identified in families B. Sequencing candidate gene GABRG2 and GABRA1 in this region did not identify a causative mutation. Moreover, no mutation was found in coding and noncoding regions of the four genes in three Chinese families. Besides excluding coding regions of four known GEFS+ genes, we also excluded the possibility of a mutation in the promoter, exon-intron boundaries, 5' untranslated regions (5' UTRs), and 3' UTRs of four known GEFS+ genes in three Chinese families. In conclusion, the present study demonstrates the heterogeneity of the etiologies of GEFS+. There are as yet undiscovered mechanisms underlying GEFS+. PMID:21704126

  4. 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 ...

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

    PubMed Central

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

    2015-01-01

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

  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. Nav1.1 Dysfunction in Genetic Epilepsy with Febrile Seizures Plus or Dravet Syndrome

    PubMed Central

    Volkers, Linda; Kahlig, Kristopher M.; Verbeek, Nienke E.; Das, Joost H.G.; van Kempen, Marjan J.A.; Stroink, Hans; Augustijn, Paul; van Nieuwenhuizen, Onno; Lindhout, Dick; George, Alfred L.; Koeleman, Bobby P.C.; Rook, Martin B.

    2011-01-01

    Relatively few SCN1A mutations associated with genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS) have been functionally characterized. In contrast to GEFS+, many mutations detected in DS patients are predicted to have complete loss-of-function. However, functional consequences are not immediately apparent for DS missense mutations. Therefore, we performed biophysical analysis of three SCN1A missense mutations (R865G, R946C, and R946H) we detected in six patients with DS. Furthermore, we compared the functionality of the R865G DS mutation with that of a R859H mutation detected in a GEFS+ patient; both mutations reside in the same voltage sensor domain of Nav1.1. The four mutations were co-expressed with β1 and β2-subunits in tsA201 cells and characterized using the whole-cell patch clamp technique. The two DS mutations, R946C and R946H, were non-functional. However, the novel voltage sensor mutants R859H (GEFS+) and R865G (DS) produced sodium current densities comparable to wild-type channels. Both mutants had negative shifts in the voltage dependence of activation, slower recovery from inactivation, and increased persistent current. Only the GEFS+ mutant exhibited a loss-of-function in voltage dependent channel availability. Our results suggest that the R859H mutation causes GEFS+ by a mixture of biophysical defects in Nav1.1 gating. Interestingly, while loss of Nav1.1 function is common in DS, the R865G mutation may cause DS by overall gain-of-function defects. PMID:21864321

  9. "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

  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. "Candidatus Borrelia kalaharica" Detected from a Febrile Traveller Returning to Germany from Vacation in Southern Africa.

    PubMed

    Fingerle, Volker; Pritsch, Michael; Wächtler, Martin; Margos, Gabriele; Ruske, Sabine; Jung, Jette; Löscher, Thomas; Wendtner, Clemens; Wieser, Andreas

    2016-03-01

    A 26 year-old female patient presented to the Tropical Medicine outpatient unit of the Ludwig Maximilians-University in Munich with febrile illness after returning from Southern Africa, where she contracted a bite by a large mite-like arthropod, most likely a soft-tick. Spirochetes were detected in Giemsa stained blood smears and treatment was started with doxycycline for suspected tick-borne relapsing fever. The patient eventually recovered after developing a slight Jarisch-Herxheimer reaction during therapy. PCR reactions performed from EDTA-blood revealed a 16S rRNA sequence with 99.4% similarity to both, Borrelia duttonii, and B. parkeri. Further sequences obtained from the flagellin gene (flaB) demonstrated genetic distances of 0.066 and 0.097 to B. parkeri and B. duttonii, respectively. Fragments of the uvrA gene revealed genetic distance of 0.086 to B. hermsii in genetic analysis and only distant relations with classic Old World relapsing fever species. This revealed the presence of a novel species of tick-borne relapsing fever spirochetes that we propose to name "Candidatus Borrelia kalaharica", as it was contracted from an arthropod bite in the Kalahari Desert belonging to both, Botswana and Namibia, a region where to our knowledge no relapsing fever has been described so far. Interestingly, the novel species shows more homology to New World relapsing fever Borrelia such as B. parkeri or B. hermsii than to known Old World species such as B. duttonii or B. crocidurae. PMID:27031729

  12. WHERE DOES WATERBORNE GIARDIASIS OCCUR, AND WHY

    EPA Science Inventory

    Over 60 outbreaks of waterborne giardiasis occurred in the United States between 1965 and 1982, mainly in the Northeast, the Rocky Mountain states, and the Pacific states. Outbreaks most often occurred as a result of inadequate or interrupted treatment. Disinfection problems and ...

  13. 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

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

    PubMed Central

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

    2015-01-01

    Background: Convulsive seizures are the common neurological emergencies in developing regions. Objectives: The aim was to determine the prevalence, causes and outcome of seizures in childhood. Patients and Methods: Participants were children aged 1–5 years old, admitted consecutively with a history of febrile convulsions or were presented seizures with fever during hospitalization, in two pediatric university hospitals. The prospective study covered a period from January to December 2013. At admission, emergency care and resuscitation procedures were provided according to the national guidelines. The history included the number and a parental description of seizures. Children with epilepsy, any central nervous system infections and other disease were excluded. Results: We have recorded 3647 children. Among them, 308 (8.4%) infants had presented with febrile seizures including 174 males and 134 females admitted to both pediatric hospitals (Tokoin University Teaching Hospitals: 206/3070, Campus University Teaching Hospitals: 102/577). Infants from 1 to 3 years age were the most common affected and constituted 65.9% of all patients. The months of September, December and January had recorded the high frequency of admission due to seizures. Regarding the seizures type, generalized tonic-clonic seizures were predominant (46.4%) followed by tonic seizures (17.2%) and status epilepticus in 9%. The etiologies were marked by falciparum malaria (52.3%), and other infections in 47.7%. At discharge, we have noted 11% (34/308) with neurodevelopmental disabilities, 6.7% of epilepsy and 9.7% (30/308) of death. Conclusion: The febrile seizure in child younger 5 years is an indicator of severe malaria in tropical nations. The campaign for “roll back malaria” must continue in developing countries to avoid long-term gross neurological deficits. PMID:25878734

  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. Investigating the presence of fungal agents in febrile neutropenic patients with hematological malignancies using different microbiological, serological, and molecular methods

    PubMed Central

    Sönmez, Ahu; Eksi, Fahriye; Pehlivan, Mustafa; Sahin, Handan Haydaroglu

    2015-01-01

    This study aimed to investigate fungal agents in febrile neutropenic patients with hematological malignancies. Direct microscopy and cultures were performed on clinical samples collected from febrile neutropenic episodes. The galactomannan (GM) antigen was tested using enzyme-linked immunosorbent assays, and Aspergillus fumigatus and Candida albicans deoxyribonucleic acid (DNA) assessed using real-time polymerase chain reaction (PCR) in consecutive serum samples. Of the 199 episodes investigated, 1.5% were classified as definite invasive aspergillosis (IA), 4.0% as IA with high probability, and 4.0% as IA with low probability. Additionally, candidaemia was detected in eight episodes (4.1%). The GM antigen was found negative for 86.4% of episodes, as one positive for 7.0% of episodes, as two or more consecutive positives for 5.5% of episodes, and as positive in any two serum samples in 1.0% of episodes. While no C. albicans DNA was detected in 98.5% of 199 ­episodes, one positive result was obtained in 1.0% of episodes, and two or more consecutive positives in 0.5% of episodes. A. fumigatus PCR results were found negative in 81.9% of episodes, as one positive in 16.1% of episodes, as positive in any two serum samples in 1.0% of episodes, and consecutively positive in 1.0% of episodes. GM antigen tests were found consecutively positive in all three patients diagnosed as having definite IA. These findings indicate that conventional, serological, and molecular methods should be used in combination to detect fungal agents in febrile neutropenic patients. PMID:26295293

  17. 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

  18. The risk of simple febrile seizures after immunisation with a new group B meningococcal vaccine, New Zealand.

    PubMed

    Stehr-Green, Paul; Radke, Sarah; Kieft, Charlotte; Galloway, Yvonne; McNicholas, Anne; Reid, Stewart

    2008-02-01

    As part of safety monitoring during a group B meningococcal disease vaccination campaign in New Zealand, we examined the possible excess risk of vaccine-associated simple febrile seizures (SFS). We conducted a cohort analysis using data from active hospital-based surveillance in the South Auckland area and a national immunisation register. Based on analysis of approximately 63,000 doses, we found no statistically significant increase in SFS incidence within 1, 2, 4, or 7 days after vaccination for any/all doses administered to children aged 6 months through 4 years. We concluded that the vaccine is unlikely to induce a heightened risk of SFS. PMID:18187240

  19. 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

  20. 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

  1. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial

    PubMed Central

    Donskih, Roman; Jones, C. Michael; Nixon, Allen; Vidal, Maria J.; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

    2016-01-01

    granulocyte colony-stimulating factor pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. Biosimilars are biologics with similar quality, safety, and efficacy to a reference product that may increase the affordability of treatment compared with their reference compounds. There are currently no approved biosimilars of pegfilgrastim in highly regulated markets. No previous phase III studies have been performed with LA-EP2006. PROTECT-2 was conducted to confirm the similarity of the proposed biosimilar LA-EP2006 to pegfilgrastim. Biosimilar pegfilgrastim (LA-EP2006) may benefit oncology patients by offering increased access to biological treatments that may improve clinical outcomes. This means that patients could potentially be treated prophylactically with biologics rather than only after complications have occurred. PMID:27091420

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. 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

  4. Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A.

    PubMed

    Ito, M; Nagafuji, H; Okazawa, H; Yamakawa, K; Sugawara, T; Mazaki-Miyazaki, E; Hirose, S; Fukuma, G; Mitsudome, A; Wada, K; Kaneko, S

    2002-01-01

    Evidence that febrile seizures have a strong genetic predisposition has been well documented. In families of probands with multiple febrile convulsions, an autosomal dominant inheritance with reduced penetrance is suspected. Four candidate loci for febrile seizures have been suggested to date; FEB1 on 8q13-q21, FEB2 on 19p, FEB3 on 2q23-q24, and FEB4 on 5q14-15. A missense mutation was identified in the voltage-gated sodium (Na(+))-channel beta 1 subunit gene, SCN1B at chromosome 19p13.1 in generalized epilepsy with the febrile seizures plus type 1 (GEFS+1) family. Several missense mutations of the (Na(+))-channel alpha 1 subunit (Nav1.1) gene, SCN1A were also identified in GEFS+2 families at chromosome 2q23-q24.3. The aim of this report is precisely to describe the phenotypes of Japanese patients with novel SCN1A mutations and to reevaluate the entity of GEFS+. Four family members over three generations and one isolated (phenotypically sporadic) case with SCN1A mutations were clinically investigated. The common seizure type in these patients was febrile and afebrile generalized tonic-clonic seizures (FS+). In addition to FS+, partial epilepsy phenotypes were suspected in all affected family members and electroencephalographically confirmed in three patients of two families. GEFS+ is genetically and clinically heterogeneous, and associated with generalized epilepsy and partial epilepsy as well. The spectrum of GEFS+ should be expanded to include partial epilepsies and better to be termed autosomal dominant epilepsy with febrile seizures plus (ADEFS+). PMID:11823106

  5. 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

  6. ST elevation occurring during stress testing

    PubMed Central

    Malouf, Diana; Mugmon, Marc

    2016-01-01

    A case is presented of significant reversible ST elevation occurring during treadmill testing, and the coronary anatomy and subsequent course are described, indicating that ischemia is a potential cause of this electrocardiographic finding. PMID:27124164

  7. Human external ophthalmomyiasis occurring in Barbados.

    PubMed

    Levett, P N; Brooker, L; Reifer, C; Prussia, P R; Eberhard, M L

    2004-06-01

    Human infection with the sheep nasal botfly Oestrus ovis occurs sporadically. In most cases, there is a history of a strike in the eye by the adult fly. Human O. ovis has been reported rarely from the Americas. We report the first case of O. ovis infection in the Caribbean region, which occurred in an urban area of Barbados. The patient responded to removal of the larvae from the conjunctiva and symptomatic treatment. PMID:15352754

  8. Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome

    PubMed Central

    Jun, Hyun Sik; Lee, Young Mok; Cheung, Yuk Yin; McDermott, David H.; Murphy, Philip M.; De Ravin, Suk See; Mansfield, Brian C.

    2010-01-01

    G6PC3 deficiency, characterized by neutropenia and neutrophil dysfunction, is caused by deficiencies in the endoplasmic reticulum (ER) enzyme glucose-6-phosphatase-β (G6Pase-β or G6PC3) that converts glucose-6-phosphate (G6P) into glucose, the primary energy source of neutrophils. Enhanced neutrophil ER stress and apoptosis underlie neutropenia in G6PC3 deficiency, but the exact functional role of G6Pase-β in neutrophils remains unknown. We hypothesized that the ER recycles G6Pase-β–generated glucose to the cytoplasm, thus regulating the amount of available cytoplasmic glucose/G6P in neutrophils. Accordingly, a G6Pase-β deficiency would impair glycolysis and hexose monophosphate shunt activities leading to reductions in lactate production, adenosine-5′-triphosphate (ATP) production, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Using annexin V–depleted neutrophils, we show that glucose transporter-1 translocation is impaired in neutrophils from G6pc3−/− mice and G6PC3-deficient patients along with impaired glucose uptake in G6pc3−/− neutrophils. Moreover, levels of G6P, lactate, and ATP are markedly lower in murine and human G6PC3-deficient neutrophils, compared with their respective controls. In parallel, the expression of NADPH oxidase subunits and membrane translocation of p47phox are down-regulated in murine and human G6PC3-deficient neutrophils. The results establish that in nonapoptotic neutrophils, G6Pase-β is essential for normal energy homeostasis. A G6Pase-β deficiency prevents recycling of ER glucose to the cytoplasm, leading to neutrophil dysfunction. PMID:20498302

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

    PubMed Central

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

    1998-01-01

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

  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. Hospital-Based Surveillance for Infectious Etiologies Among Patients with Acute Febrile Illness in Georgia, 2008-2011.

    PubMed

    Kuchuloria, Tinatin; Imnadze, Paata; Mamuchishvili, Nana; Chokheli, Maiko; Tsertsvadze, Tengiz; Endeladze, Marina; Mshvidobadze, Ketevan; Gatserelia, Lana; Makhviladze, Manana; Kanashvili, Marine; Mikautadze, Teona; Nanuashvili, Alexander; Kiknavelidze, Khatuni; Kokaia, Nora; Makharadze, Manana; Clark, Danielle V; Bautista, Christian T; Farrell, Margaret; Fadeel, Moustafa Abdel; Maksoud, Mohamed Abdel; Pimentel, Guillermo; House, Brent; Hepburn, Matthew J; Rivard, Robert G

    2016-01-01

    Information on the infectious causes of undifferentiated acute febrile illness (AFI) in Georgia is essential for effective treatment and prevention. In May 2008, a hospital-based AFI surveillance was initiated at six hospitals in Georgia. Patients aged ≥ 4 years with fever ≥ 38°C for ≥ 48 hours were eligible for surveillance. Blood culture and serologic testing were conducted for Leptospira spp., Brucella spp., West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus, Coxiella burnetii, tick-borne encephalitis virus (TBEV), hantavirus, Salmonella enterica serovar Typhi (S. Typhi), and Rickettsia typhi. Of 537 subjects enrolled, 70% were outpatients, 54% were males, and the mean age was 37 years. Patients reported having fatigue (89%), rigors (87%), sweating (83%), pain in joints (49%), and sleep disturbances (42%). Thirty-nine (7%) patients were seropositive for R. typhi, 37 (7%) for Brucella spp., 36 (7%) for TBEV, 12 (2%) for Leptospira spp., 10 (2%) for C. burnetii, and three (0.6%) for S. Typhi. None of the febrile patients tested positive for WNV antibodies. Of the patients, 73% were negative for all pathogens. Our results indicate that most of the targeted pathogens are present in Georgia, and highlight the importance of enhancing laboratory capacity for these infectious diseases. PMID:26438032

  12. Aetiologies of Acute Undifferentiated Febrile illness in Adult Patients – an Experience from a Tertiary Care Hospital in Northern India

    PubMed Central

    Ahmad, Sohaib; Agarwal, R K; Dhar, Minakshi; Mittal, Manish; Sharma, Shiwani

    2015-01-01

    Introduction Acute undifferentiated febrile illness (AUFI) is a common clinical entity in most of the hospitals. The fever can be potentially fatal if the aetiology is not recognized and appropriately treated early. Aim To describe the aetiology of fever among patients in a tertiary care hospital in Northern India. Materials and Methods A one-year retro-prospective, observational study was conducted in adults (age>18years) presenting with undifferentiated febrile illness (of duration 5-14 days). Diagnosis was confirmed by suitable laboratory tests after exhaustive clinical examination. Results A total of 2547 patients with AUFI were evaluated. Of these, 1663 (65.3%) were males and 884 (34.7%) were females. Dengue (37.54%); enteric fever (16.5%); scrub typhus (14.42%); bacterial sepsis (10.3%); malaria (6.8%); hepatitis A (1.9%); hepatitis E (1.4%); leptospirosis (0.14%); were the main infections while no specific diagnosis could be delineated in 11%. Mixed infections were noted in 48 (1.9%) patients. Conclusion A good clinical acumen supported by the basic investigations can help diagnose the cause of fever with reasonable certainty. PMID:26816892

  13. The first genome-wide scan in a tunisian family with generalized epilepsy with febrile seizure plus (GEFS+).

    PubMed

    Fendri-Kriaa, Nourhene; Louhichi, Nacim; Mkaouar-Rebai, Emna; Chabchoub, Ghazi; Kammoun, Fatma; Salem, Ikhlass Hadj; Rebai, Ahmed; Triki, Chahnez; Fakhfakh, Faiza

    2010-11-01

    Generalized epilepsy with febrile seizure plus (GEFS+) is an autosomal dominant disorder. In the literature, 5 responsible genes were identified and 2 novel susceptibility loci for GEFS+ at 2p24 and 8p23-p21 were reported, indicating the genetic heterogeneity of this disorder. The aim of this report is to identify the responsible loci in a large affected Tunisian family by performing a 10cM density genome-wide scan. The highest multipoint logarithm of odds (LOD) score (1.04) was found for D5S407 in the absence of recombination. Two other interesting regions were found around marker D19S210 (LOD=0.799) and D7S484 (LOD=0.61) markers. To fine map these loci, additional markers in 2 regions on 5q13.3 and 7p14.2 were analyzed and positive LOD scores for both loci were obtained. Sequencing of the Sodium channel subunit beta-1 gene (SCN1B) (19q13.1) showed the absence of any causal mutation. Our findings emphasized the genetic heterogeneity of febrile seizures. PMID:20382841

  14. 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

  15. Phase II dose-finding study of balugrastim in breast cancer patients receiving myelosuppressive chemotherapy.

    PubMed

    Gladkov, Oleg; Moiseyenko, Vladimir; Bondarenko, Igor N; Shparyk, Yaroslav; Barash, Steven; Adar, Liat; Bias, Peter; Avisar, Noa

    2015-06-01

    Balugrastim is a once-per-cycle, fixed-dose recombinant protein comprising human serum albumin and granulocyte colony-stimulating factor under development for prevention of severe neutropenia in cancer patients receiving myelosuppressive chemotherapy. This phase II, multicenter, active-controlled, dose-finding pilot study evaluated balugrastim safety and efficacy versus pegfilgrastim in breast cancer patients scheduled to receive myelosuppressive chemotherapy and investigated two doses with similar efficacy to pegfilgrastim for a subsequent phase III study. Patients received four cycles of doxorubicin/docetaxel chemotherapy and with each successive cycle were randomized sequentially to escalating doses of balugrastim [30 (n = 11), 40 (n = 21), or 50 mg (n = 20)] or a fixed dose of pegfilgrastim [6 mg (n = 26)] post-chemotherapy. Balugrastim doses were escalated as planned. The incidence of adverse events was similar among the balugrastim groups and between all balugrastim doses and pegfilgrastim. The most frequently reported adverse events were neutropenia, alopecia, and nausea. During cycle 1, severe neutropenia (absolute neutrophil count of <0.5 × 10(9)/L) occurred in 40, 67, and 50 % and febrile neutropenia occurred in 20.0, 9.5, and 10.0 % of patients receiving balugrastim 30, 40, and 50 mg, respectively; in patients receiving pegfilgrastim, 48 % experienced severe neutropenia and 8 % experienced febrile neutropenia. Duration of severe neutropenia (DSN) for each treatment group was 0.9, 1.6, 1.1, and 0.9 days, respectively. In the remaining three chemotherapy cycles, DSN was ≤1 day across all treatment groups. Balugrastim 50 mg was comparable to pegfilgrastim in terms of safety and overall efficacy in breast cancer patients receiving myelosuppressive chemotherapy. PMID:25966791

  16. 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…

  17. 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…

  18. 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. PMID:26749235

  19. The role of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the diagnosis of childhood febrile urinary tract infections

    PubMed Central

    İlarslan, Nisa Eda Çullas; Fitöz, Ömer Suat; Öztuna, Derya Gökmen; Küçük, Nuriye Özlem; Yalçınkaya, Fatma Fatoş

    2015-01-01

    Aim: This study assessed the ability of tissue harmonic imaging ultrasound combined with power Doppler ultrasound in the detection of childhood febrile urinary tract infections in comparison with the gold standard reference method: Tc-99m dimercaptosuccinicacid renal cortical scintigraphy. Material and Methods: This prospective study included 60 patients who were hospitalized with a first episode of febrile urinary tract infections. All children were examined with dimercaptosuccinicacid scan and tissue harmonic imaging ultrasound combined with power Doppler ultrasound within the first 3 days of admission. Results: Signs indicative of acute infection were observed in 29 patients according to the results of tissue harmonic imaging ultrasound combined with power Doppler ultrasound while dimercaptosuccinicacid scan revealed abnormal findings in 33 patients. The sensitivity, specificity, positive predictive value and negative predictive value of tissue harmonic imaging combined with power Doppler ultrasound using dimercaptosuccinicacid scintigraphy as the reference method in patients diagnosed with first episode febrile urinary tract infections were calculated as 57.58% (95% confidence interval: 40.81%–72.76%); 62.96% (95% confidence interval: 44.23%–78.47%); 65.52% (95% confidence interval: 52.04%–77%); 54.84% (95% confidence interval: 41.54%–67.52%); respectively. Conclusions: Although current results exhibit inadequate success of power Doppler ultrasound, this practical and radiation-free method may soon be comprise a part of the routine ultrasonographic evaluation of febrile urinary tract infections of childhood if patients are evaluated early and under appropriate sedation. PMID:26265892

  20. 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

  1. Changes in joint laxity occurring during pregnancy.

    PubMed Central

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

    1982-01-01

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

  2. 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

  3. Naturally Occuring Fish Poisons from Plants

    NASA Astrophysics Data System (ADS)

    Cannon, Jonathan G.; Burton, Robert A.; Wood, Steven G.; Owen, Noel L.

    2004-10-01

    Since prehistoric times, cultures throughout the world have used piscicidal (fish poisoning) plants for fishing. In recent times, scientists have identified many of the plant compounds responsible for killing the fish and have found that these compounds possess other important biological properties, such as insecticidal and anti-cancer activities. This article reviews some of the chemical research that has been performed on naturally occurring fish poisons, including plant sources, methods of use, toxicity, and mechanisms of action of piscicides.

  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