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Febrile neutropenia.  


This review summarizes the current status and diagnostic-therapeutic challenges in febrile neutropenia. Patients with neutropenia-associated infections have a poor prognosis. A large meta-analysis of trials assessing prophylactic antibiotics has shown significant survival benefits; clinical significance of resistance is unclear. Administering broad-spectrum antibiotics to established febrile neutropenic patients has become selective, vancomycin is withheld unless absolutely necessary, and low-risk patients are identified with biological markers. Such patients are now managed with oral antibiotics at home or even without antibiotics. Protracted prolonged neutropenia is the setting par excellence for invasive fungal infections. Conventional amphotericin B administered to such risk patients reduces the incidence of fungal infections. New antifungal drugs have heightened efficacy and lowered toxicity. Novel antifungal diagnostic tests include imaging, particularly the CT "halo" sign (aspergillosis), and serology (glucan, galactomannan), and provide earlier diagnosis and treatment and better outcomes. Negative tests may indicate withholding antifungal therapy. High intermittent dosing of liposomal amphotericin B seems as safe and as effective as standard dosing regimens, but at half the drug acquisition cost. The use of nonantibiotic agents has offered alternative management strategies. Recombinant interleukin-11 reduces bacteremia, through a cytoprotective mechanism on the gut. rhIL-11 releases C-reactive protein and causes shedding of soluble TNF receptor-1, modulating the immunological milieu and the systemic inflammatory response. Other candidate molecules include RANTES and long-pentraxin 3. Recombinant growth factors reduce febrile episodes, permitting completion of chemotherapy, increase overall survival, and minimize infection mortality. PMID:18837909

Ellis, Michael



Febrile neutropenia: outline of management.  


Febrile neutropenia is a common emergency encountered in children receiving chemotherapy for a malignancy. Left untreated, it can lead to serious morbidity and mortality. Febrile neutropenia is suspected in any patient on chemotherapy who presents with fever. Prompt evaluation and management by the primary contact pediatrician is essential for a successful outcome. A detailed history and physical examination is warranted to identify source of infection, although two thirds of them may not have localizing symptoms or signs. Risk stratification is valuable in categorizing the severity and guiding therapy. Initial stabilization, prompt initiation of appropriate antibiotics and adequate supportive care are the cornerstone of treatment. Knowledge of the locally prevailing bacteriological profile and antimicrobial susceptibility data is crucial for each hospital/unit to frame and periodically modify guidelines for the choice of antimicrobials. Delay in initiating antimicrobials significantly worsens the outcome. Education of the family as well as the members of the treating unit is important in this regard. Pro-active steps must be taken to reduce incidence of hospital acquired sepsis. Diagnosis and management in relevance to the emergency room is reviewed and institutional practice is shared. PMID:23180404

Oberoi, Sapna; Suthar, Renu; Bansal, Deepak; Marwaha, R K



Microbial Etiology of Febrile Neutropenia  

PubMed Central

Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case–control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E. coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns.

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



Brucella melitensis: a rare cause of febrile neutropenia.  


Although brucellosis is endemic in Middle Eastern and Mediterranean countries, febrile neutropenia caused by Brucella species has rarely been reported in childhood. In this report the authors described an unusual case of febrile neutropenia due to Brucella melitensis. PMID:20863159

Citak, Elvan Caglar; Arman, Dilek



Controversies in Empiric Therapy of Febrile Neutropenia  

Microsoft Academic Search

\\u000a Antineoplastic chemotherapy regimens induced myelosuppression was quickly recognized as a major limitation to the full utility\\u000a of cytotoxic drug regimens targeting cancer. Measures taken to mitigate harm from myelosuppression have led to a number of\\u000a controversies over the years. The first controversy faced by clinicians was whether or not empiric antibiotic therapy for\\u000a febrile neutropenia is appropriate. The concerns was

John R. Wingard


Acute Myelogenous Leukemia and Febrile Neutropenia  

Microsoft Academic Search

\\u000a Aggressive chemotherapy has a deleterious effect on all components of the defense system of the human body. The resulting\\u000a neutropenia as well as injury to the pulmonary and gastrointestinal mucosa allow pathogenic micro-organisms easy access to\\u000a the body. The symptoms of an incipient infection are usually subtle and limited to unexplained fever due to the absence of\\u000a granulocytes. This is

Alexandra Herbers; Ben E. de Pauw


Antimicrobial treatment of febrile neutropenia: pharmacokinetic-pharmacodynamic considerations.  


Patients with cancer or hematologic diseases are particularly at risk of infection leading to high morbidity, mortality and costs. Extensive data show that optimization of the administration of antimicrobials according to their pharmacokinetic and pharmacodynamic parameters improves clinical outcome. Evidence is growing that when pharmacokinetic and pharmacodynamic parameters are used to target not only clinical cure but also eradication, the selection resistance is also contained. This is of particular importance in patients with neutropenia in whom increasing rates of drug-resistant Gram-negative bacteria have been reported, particularly Pseudomonas aeruginosa. Based on experimental and clinical studies, pharmacokinetic and pharmacodynamic parameters are discussed in this review for each antibiotic used in febrile neutropenia in order to help physicians improve dosing and optimization of antimicrobial agents. PMID:23807657

Goulenok, Tiphaine; Fantin, Bruno



Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials  

Microsoft Academic Search

Objectives: Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several b-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen b-lactam. Methods: Systematic review and meta-analysis of randomized controlled trials comparing anti- pseudomonal b-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library,

Mical Paul; Dafna Yahav; Abigail Fraser; Leonard Leibovici



[Clinical evaluation of biapenem for febrile neutropenia in patients with hematological disorders].  


We examined the clinical evaluation of biapenem (BIPM) for febrile neutropenia in patients with hematological disorders. BIPM was administrated by drip infusion when fever developed over 37.5 degrees C with a neutrophil counts lower than 1000/microl. The underlying diseases were acute myelogenous leukemia in 16 cases, acute lymphocytic leukemia in 1, malignant lymphoma in 14, myelodysplastic syndrome in 1, aplastic anemia in 1. Microbiologically documented infections were found in 3 cases (9.1%) before treatment. Clinical effect was excellent in 9 cases, good in 11, fair in 6, poor in 7. Factors associated with efficacy rate were concomitant use of granulocytecolony stimulating factor, duration of neutropenia and neutrophil counts at day 3 of day after start of the therapy. No serious adverse events were observed in all cases, although one case developed exanthema. In conclusion, these results confirmed the efficacy and safety of BIPM for febrile neutropenia in patients with hematological disorders. PMID:17612259

Sakai, Hirotaka; Sanada, Masashi; Shimamoto, Kenji; Azuma, Remi; Harada, Hiroshi; Mori, Hiraku; Niikura, Haruo; Omine, Mitsuhiro



Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases  

PubMed Central

Background Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Methods Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive “gold standard” (ANC <1.0×109/L, and body temperature ?38.3°C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. Results Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24–45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78–95) and sensitivity was 57% (46–68). For the definition including neutropenia in any position (n=71), PPV was 77% (68–87) and sensitivity was 67% (56–77). Conclusions Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.



Cefepime monotherapy as an empirical initial treatment of patients with febrile neutropenia  

Microsoft Academic Search

Currently, monotherapy is considered a valid alternative to the combination antibiotic treatments used for initial, empirical\\u000a management of febrile neutropenia. The advent of new cephalosporins warrants assessment. The aim of this study was to prospectively\\u000a evaluate the effectiveness of cefepime monotherapy in the treatment of cancer patients with febrile granulocytopenia (< 1000\\u000a leukocytes\\/µL and\\/or<500 neutrophils\\/µL).\\u000a \\u000a A prospective, multicenter, nonrandomized trial

J. Montalar; A. Segura; C. Bosch; A. Galan; O. Juan; C. Molins; V. Giner; J. Aparicio



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


We reviewed medical literature on the efficacy and safety of outpatient versus hospital-based therapy of low-risk febrile neutropenia in adult cancer patients. A PubMed search for all studies evaluating the outpatient treatment of adults diagnosed with solid tumors who suffered from low-risk febrile neutropenia was completed; reference lists from identified articles also were used. In all, 10 trials were included in the analysis, which showed no significant difference in clinical failure rates and mortality for ambulatory regimens and standard hospital-based therapy. Subgroup analysis according to the type of fever episode showed no significant differences in clinical failure rates for fever of unknown origin and fever due to documented infections. Subgroup analyses in two independent trials identified an absolute neutrophil count < 100 cells/ mm3 as being predictive of outpatient treatment failure (P < 0.04). These findings need to be confirmed by further trials. Thus, outpatient management of adult cancer patients with low-risk febrile neutropenia is safe, effective, and comparable to standard hospital-based therapy. Patients at low risk are outpatients and are hemodynamically stable; they have no organ failure, they are able to take oral medications, and they do not suffer from acute leukemia. Low-risk prediction also may be based on the Multinational Association for Supportive Care in Cancer risk index. PMID:18551855

Carstensen, Mads; Sørensen, Jens Benn


Role of HRCT in detection and characterization of pulmonary abnormalities in patients with febrile neutropenia  

PubMed Central

Background: Fever is of grave concern in the management of patients with neutropenia with early detection of a focus of infection being the major goal. As lungs are the most common focus, chest imaging is of vital importance. This Institute Review Board approved prospective study was undertaken to assess the usefulness of high resolution computed tomography (HRCT) in early detection and characterization of pulmonary abnormalities in febrile neutropenia. Materials and Methods: A total of 104 consecutive patients (M:F:75:29, age range 11–66 years) with fever of 38.2°C or more with an absolute neutrophil count <500/?l underwent HRCT chest. HRCT diagnosis was compared with final diagnosis based on ancillary investigations. Results: HRCT could detect pulmonary abnormalities in 93 patients (89.4%) with air space consolidation being the predominant finding (n = 57), followed by ground-glass opacities (Ground glass opacity (GGO), n = 49) and nodules (n = 39). HRCT could correctly characterize the infective lesions in 76 patients (81.7%). Presence of random or pleural-based nodules >10 mm with or without surrounding GGO or cavitations was sensitive (95.23%) and specific (96.7%) for fungal infection, while small (1–4 mm) random or centrilobular nodules with tree-in-bud appearance was sensitive (90%) and highly specific (97.02%) for tuberculosis. Diagnosis of pyogenic infection based on presence of air-space consolidation, pleural effusion, GGO or centrilobular nodules showed a sensitivity of 84.78% and specificity of 93.84%, whereas patchy or diffuse GGO, interstitial thickening and/or air-space consolidation showed high sensitivity (86.7%) and specificity (96.8%) for Pneumocystis jiroveci pneumonia. Conclusion: HRCT chest is an excellent modality in the diagnostic work-up of patients with febrile neutropenia allowing early detection and characterization of pulmonary abnormalities.

Kang, Mandeep; Deoghuria, Debasis; Varma, Subash; Gupta, Dheeraj; Bhatia, Anmol; Khandelwal, Niranjan



Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropenia in patients with hematological malignancies.  


Recent studies have shown the prophylactic efficacy of fluoroquinolones against infections in patients with chemotherapy-induced neutropenia. However, little is known about the differences between fluoroquinolones, and there are some concerns about the emergence of resistant bacteria. In this retrospective study, we compared the prophylactic efficacy of moxifloxacin (MFLX) and tosufloxacin (TFLX) for chemotherapy-induced febrile neutropenia. The cumulative incidences of febrile neutropenia were 74.7% (59 of 79) in the MFLX group and 81.1% (219 of 270) in the TFLX group (log-rank test p = 0.044). Subgroup analysis revealed a more prominent prophylactic advantage of MFLX in patients with acute myeloid leukemia (AML) or long duration of neutropenia (p = 0.013 and 0.008, respectively). There were no significant differences in the incidences of adverse events and fluoroquinolone resistant bacteria in both groups. This study indicates that prophylaxis with MFLX is more beneficial to reduce febrile neutropenia episodes than TFLX, especially in patients with high-risk disease. PMID:22978686

Shinohara, Akihito; Yoshiki, Yumiko; Masamoto, Yosuke; Hangaishi, Akira; Nannya, Yasuhito; Kurokawa, Mineo



[A general description of the clinical guideline for the management of febrile neutropenia].  


The most serious adverse event in cancer patients who receive anti-neoplastic agents is febrile neutropenia(FN). The clinical guideline for the use of antimicrobial agents in managing patients with FN was published by the Infectious Diseases Society of America. However, the dosage and administration of antimicrobial agents are not completely adapted for Japanese insurance coverage. The Japanese Society of Medical Oncology therefore decided to develop a clinical guideline for the management of FN in Japanese patients. In this study, we provide a general description of the guideline. According to the guideline, fever is defined as a single axillary temperature of B37. 5°C(or an oral temperature of B38°C)and neutropenia is defined as a neutrophil count of <500/mL or <1, 000/mL if the count is expected to decrease to <500/mL within the next 48 h. In patients who develop FN, empirical anti-pseudomonal b-lactam agent monotherapy should be administered promptly at the onset of fever. Antibiotic therapy should continue until patients become afebrile and their neutrophil counts recover to B500/mL. If fever persists for 4-7 days under antibiotic therapy in high-risk patients, empirical antifungal therapy should be considered. Granulocyte colony-stimulating factor prophylaxis should be considered for high-risk patients with an anticipated risk of FN of B20%. PMID:23863646

Takamatsu, Yasushi



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

PubMed Central

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

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



Empirical therapy with ceftazidime combined with levofloxacin or once-daily amikacin for febrile neutropenia in patients with neoplasia: a prospective comparative study.  


Combination antimicrobial therapy represents common practice in the treatment of febrile neutropenia aiming to broaden the antimicrobial spectrum against Gram-negative pathogens. We did a prospective, non-randomized, comparative study to evaluate ceftazidime plus either levofloxacin or once-daily amikacin as empirical regimens for febrile neutropenia in patients with solid tumor or hematopoietic neoplasm in a region of high baseline resistance prevalence. We included 285 febrile neutropenic episodes in 235 individual patients. One hundred forty-eight cases received levofloxacin and 137 received amikacin, both in combination with ceftazidime. More cases in the levofloxacin than the amikacin group had underlying hematological malignancy; most other characteristics of the two groups were well balanced. Nephrotoxicity requiring treatment discontinuation occurred in one case in the amikacin group. No difference in clinical success (79.7% vs. 80.3%, p>0.99) or all-cause mortality (12.8% vs. 11.7%, p=0.86) was noted between the levofloxacin and the amikacin groups, even after adjustment for the independent predictor variables for each endpoint. Sepsis at presentation, presence of localizing symptoms/signs of infection, and isolation of a non-susceptible Gram-negative pathogen independently predicted both clinical success and all-cause mortality. Additionally, underlying solid tumor independently predicted clinical success, while poor prognosis of the underlying neoplasia and skin/soft tissue infection independently predicted mortality. Ceftazidime plus levofloxacin had similar effectiveness to ceftazidime plus amikacin as empirical regimens for febrile neutropenia. Nephrotoxicity with once-daily amikacin was minimal. Inappropriate empirical therapy was associated with worse prognosis. PMID:22037822

Samonis, G; Koutsounaki, E; Karageorgopoulos, D E; Mitsikostas, P; Kalpadaki, C; Bozionelou, V; Bompolaki, I; Sgouros, J; Taktikou, V; Falagas, M E



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

Microsoft Academic Search

A multi-institutional study was conducted to assess efficacy and safety of biapenem (BIPM), a carbapenem antibiotic, as an\\u000a initial-stage therapeutic agent for febrile neutropenia (FN) in patients with hematopoietic diseases. A total of 216 patients\\u000a from 25 medical institutions were enrolled in this study; of these, 204 were included in the safety analysis and 178 in the\\u000a efficacy analysis. The

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



Professional oral health care reduces oral mucositis and febrile neutropenia in patients treated with allogeneic bone marrow transplantation  

Microsoft Academic Search

Goal of work  Little is known about the effects of professional oral health care (POHC) on the outcome of hematopoietic stem cell transplantation\\u000a (HSCT). We evaluated the effects of POHC given by dentists and dental hygienists on the development of oral mucositis and\\u000a febrile neutropenia (FN) after allogeneic bone marrow transplantation (BMT).\\u000a \\u000a \\u000a \\u000a \\u000a Patients and methods  We retrospectively studied 140 adult patients who

Haruhiko Kashiwazaki; Takae Matsushita; Junichi Sugita; Akio Shigematsu; Kumiko Kasashi; Yutaka Yamazaki; Takashi Kanehira; Satoshi Yamamoto; Takeshi Kondo; Tomoyuki Endo; Junji Tanaka; Satoshi Hashino; Mitsufumi Nishio; Masahiro Imamura; Yoshimasa Kitagawa; Nobuo Inoue


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

Microsoft Academic Search

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

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



Evaluation of caspofungin or micafungin as empiric antifungal therapy in adult patients with persistent febrile neutropenia: A retrospective, observational, sequential cohort analysis  

Microsoft Academic Search

Background: Caspofungin is approved in the United States for empiric antifungal therapy for persistent febrile neutropenia (FN). There are limited data about the use of other echinocandins in this setting.Objective: After a formulary change, we retrospectively evaluated the safety and effectiveness of caspofungin and micafungin as empiric antifungal therapy for FN at Brigham and Women's Hospital (Boston, Massachusetts).Methods: This was

David W. Kubiak; Julie M. Bryar; Anne M. McDonnell; Jorge O. Delgado-Flores; Emily Mui; Lindsey R. Baden



[Tips on the use of granulocyte colony-stimulating factors in cancer patients predisposed to chemotherapy - induced febrile neutropenia].  


Chemotherapy-induced febrile neutropenia(FN)is a major risk factor for severe infections, with a dose-limiting toxicity that necessitates dose reductions and/or delays in scheduled chemotherapy sessions. Therefore, the use of granulocyte colony- stimulating factors(G-CSF)is recommended in cancer patients at a risk of chemotherapy-induced FN. Three types of GCSF, filgrastim, lenograstim, and nartograstim, have been available thus far. The differences in potency and efficacy among these G-CSF needs to be thoroughly understood. Prophylactic G-CSF is recommended in patients receiving a chemotherapy regimen associated with a high risk(>20%)of FN. A chemotherapy regimen associated with intermediate risk(10-20%)of FN, requires particular attention to the neutrophil count and observation of symptoms of infection after chemotherapy. Prophylactic G-CSF could be included in subsequent chemotherapy regimens, if needed. PMID:23863645

Murakawa, Yasuko



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

PubMed Central

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.

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



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

PubMed Central

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

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



External validation of a risk model of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma.  


Abstract Febrile neutropenia (FN) is a common and serious complication of chemotherapy treatment. Clinical risk models may help to identify patients at high risk of FN but must undergo external validation before implementation in medical practice. Therefore, this study externally validated previously published clinical models of FN occurrence during chemotherapy in 240 patients with non-Hodgkin lymphoma by using an independent observational dataset (n = 1829). The models demonstrated predictive ability, and validation criteria for predicting any cycle of FN were partially met but a larger than expected decrease in performance was noted (area under the receiver operating characteristic curve was 0.71 in the validation dataset and 0.83 in the training dataset). Age, weight, baseline white blood cell count and planned chemotherapy parameters were confirmed to predict FN risk. Chemotherapy dose reductions, dose delays and colony-stimulating factor use were confirmed as risk modifiers during treatment. Further work is needed to improve the predictive ability of FN risk models. PMID:23452152

Schwenkglenks, Matthias; Bendall, Kate Louise; Pfeil, Alena M; Szabo, Zsolt; Pettengell, Ruth



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


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

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



A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma.  


The purpose of this study was to develop a model for predicting the occurrence of life-threatening neutropenia (LN, ANC < or = 0.5 x 10(9)/l) and febrile neutropenia (FN, an ANC < 0.5x10(9)/l in association with a body temperature of > or = 38.3 degrees C) after the first cycle of CHOP therapy in patients newly diagnosed with aggressive NHL. One hundred and forty-five patients, aged > or = 15 years, with newly diagnosed diffuse mixed, diffuse large-cell or large-cell immunoblastic lymphoma (IWF categories, F, G, H), who had been treated with CHOP at King Chulalongkorn Memorial Hospital between June 1994 and December 1998, were entered into the study. The criteria for eligibility included complete work-up for baseline evaluation, treatment with standard CHOP chemotherapy, at least one complete blood count performed during days 8-14 post-treatment or if at any time the patients experienced a BT of > or = 38.3 degrees C and were not treated with any colony-stimulating factors (CSFs). The median age of the patients was 47 years (range, 17-78). Forty-eight percent of the patients were in stage III/IV, 36% had ECOG performance status (PS) II-IV, 30% had > or = 2 extranodal diseases, 59% had serum LDH > 1 x normal and 23% had bone marrow involvement. The frequencies of patients in the low-, low-intermediate, high-intermediate and high risk groups according to the international index were 29%, 28%, 17% and 26%, respectively. Thirty-nine percent of the patients had LN at nadir and 33% developed FN after the first course of CHOP. By using stepwise logistic regression analysis, the pretreatment variables independently predictive of the LN at nadir and the FN were serum albumin concentration of < or = 3.5 g/dl, serum LDH > 1 x normal and whether there was bone marrow involvement of lymphoma at presentation. The model, based on the incorporation of these three factors, identified three risk groups of patients with a predicted probability of developing LN at nadir of 81.5% (95% CI, 68.5-90.7) (high risk), 23.9% (95% CI, 12.6-38.8) (intermediate risk) and 4.4% (95% CI, 0.5-15.1) (low risk). The predicted rate of FN in the three groups were 72.2% (95% CI, 58.4-83.5), 17.4% (95% CI, 7.8-31.4) and 2.2% (95% CI, 0.05-11.8), respectively. In conclusion, our model could be used as a means to identify patients with newly diagnosed aggressive NHL, treated with CHOP, who are at high risk (> or = 50% probability) of developing post-first course LN and FN, in whom CSF and/or antibiotic prophylaxis might be indicated. PMID:10752986

Intragumtornchai, T; Sutheesophon, J; Sutcharitchan, P; Swasdikul, D



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


The bactericidal activity of ?-lactams is determined by the time that concentrations in tissue and serum are above the minimum inhibitory concentration (T>MIC) for the pathogen. The aim of this study was to compare the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for meropenem between administration by bolus injection and a 3-h infusion. The study was a randomised, three-way, cross-over design in eight febrile neutropenic patients with bacteraemia. Each subject received meropenem in three regimens consecutively: (i) a bolus injection of 1g every 8 h (q8h) for 24 h; (ii) a 3-h infusion of 1 g q8h for 24 h; and (iii) a 3-h infusion of 2 g q8h for 24h. For pathogens with an MIC of 4 ?g/mL, the PTA of achieving 40% T>MIC following administration of meropenem by a bolus injection of 1g q8h, a 3-h infusion of 1 g q8h and a 3-h infusion of 2g q8h was 75.7%, 99.24% and 99.96%, respectively. Only the 3-h infusion of 2 g q8h achieved a PTA >99% for 40% T>MIC for a MIC of 8?g/mL. By referral to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC distributions, the three regimens of meropenem were predicted to achieve a CFR?90% against Escherichia coli and Klebsiella spp. In conclusion, a 3-h infusion of 2 g of meropenem q8h resulted in the highest PTA rates. The three regimens of meropenem had high probabilities of achieving optimal impact against E. coli and Klebsiella spp. PMID:21726984

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



2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours  

Microsoft Academic Search

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3\\/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and\\/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival.In Europe,

M. S. Aapro; J. Bohlius; D. A. Cameron; Lissandra Dal Lago; J. Peter Donnelly; N. Kearney; G. H. Lyman; R. Pettengell; V. C. Tjan-Heijnen; J. Walewski; Damien C. Weber; C. Zielinski



Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies  

PubMed Central

Background During febrile neutropenia in only 30 to 60 percent an infectious agent is identified. This diagnostic gap could hypothetically be reduced with the broad implementation of molecular detection techniques like PCR, which has revolutionized the detection of infectious diseases during the last two decades. Findings We performed a longitudinal prospective study (N = 81) of neutropenic patients to assess the role of respiratory viruses in neutropenic fever and to determine the clinical relevance of blind screening for these viruses. Respiratory viruses were recovered in 14% of the patients prior to neutropenia. In 13% of neutropenic patients without fever and in 19% of those with fever, a respiratory virus was detected. Comparing different sample types; nasal swabs performed significantly better (16/117 = 43%), than throat swabs (6/106 = 6%). Throat gurgles did not show significant differences from the latter sample types. Conclusions Blind diagnostic screening for respiratory viruses before or during neutropenia is not useful. Nasal swabs are sensitive and practical option for screening on respiratory viruses.



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

PubMed Central

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.

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



[Application value of procalcitonin and immune inflammatory factors for prediction of bacteriemia in patients with hematologic malignancy combined with febrile neutropenia].  


This study was purposed to evaluate the diagnositic value of procalcitonin(PCT), C-reactive protein, interleukin-6(IL-6), serum amyloid A(SAA) for bacteremia in patients with hematologic malignancy combined with febrile neutropania. The total of 297 patients with hematologic malignancy combined with febrile neutropania were analyzed retrospectively from 1253 patients admitted to West China hospital of Sichuan University from March 2011 to Octerber 2012. They were divided into sepsis group(n = 95) and non-sepsis group(n = 202) according to blood culture. The results showed that the levels of PCT, CRP, IL-6 and SAA in sepsis group were higher than those in non-sepsis group, and there was statistically significant difference between these two groups (P < 0.05). The PCT had an AUC value of 0.974 (P < 0.05), and obviously higher than that of CRP (AUC = 0.681, P < 0.05), IL-6 (AUC = 0.661, P < 0.05) and SAA (AUC = 0.605, P < 0.05). When PCT had cut-off value of 1.06 ng/ml, sensitivity of 95.8%, specificity of 92.1%, and the Youden indicator of 0.879, the negative and positive predictive values were 97.8% and 85.0% respectively, the negative and positive likelihood ratios were 0.05 and 12.5 respectively, and all significanlly higher than that of CRP, IL-6 and SAA. It is concluded that for patients with hematologic malignancy combined with febrile neutropenia and bacterial infection, the diagnostic value of serum PCT is superior to that of immune inflammatory factors(CRP, IL-6 and SAA), the PCT can predict the bacterium infection, provide laboratory evidence for rational antimicrobial drug usage and mortality reduction. PMID:24156453

Fu, Yang; Jiang, Hong; Li, Li-Xin; Chen, Jie; Zhang, Jun-Long; Wang, Lan-Lan



Clinical practice patterns of managing low-risk adult febrile neutropenia during cancer chemotherapy in the USA  

Microsoft Academic Search

Purpose  The purpose of the study was to determine oncologists’ current practice patterns for antibiotic management of low-risk fever\\u000a and neutropenia (FN) after chemotherapy.\\u000a \\u000a \\u000a \\u000a Materials and methods  A self-administered survey was developed to query management practices for low-risk FN patients and sent to 3,600 randomly\\u000a selected American Society of Clinical Oncology physician members; hypothetical case scenarios were included to assess factors\\u000a influencing

Alison Freifeld; Jayashri Sankaranarayanan; Fred Ullrich; Junfeng Sun



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

PubMed Central

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



Impact of fluorine-18 fluorodeoxyglucose positron emission tomography on diagnosis and antimicrobial utilization in patients with high-risk febrile neutropenia.  


Early and targeted antimicrobial therapy improves outcomes in patients with febrile neutropenia (FN). We evaluated the impact of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) on antimicrobial utilization in the management of FN. A cohort of patients with FN and hematological malignancy was identified. Cases (in whom FDG-PET was performed, n =?37) were compared with controls (in whom conventional investigations excluding FDG-PET were performed, n =?76). An underlying cause for FN was determined in 94.6% of cases, compared to 69.7% of controls. FDG-PET had a significant impact on antimicrobial utilization compared to conventional imaging (35.1% vs. 11.8%; p =?0.003), and was associated with shorter duration of liposomal amphotericin-B therapy for systemic fungal infection (median 4.0 days cases vs. 10.0 days controls; p =?0.001). Cases had a longer length of hospitalization (p =?0.016). In the management of patients with high-risk FN, FDG-PET improves diagnostic yield and allows rationalization of antifungal therapy. The impact upon healthcare costs associated with antimicrobial therapy for FN requires further evaluation. PMID:22448920

Koh, Kwee Choy; Slavin, Monica A; Thursky, Karin A; Lau, Eddie; Hicks, Rodney J; Drummond, Elizabeth; Wong, Peng Shyan; Worth, Leon J



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


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

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



Febrile seizures.  


Febrile seizures are the most common form of childhood seizures, occurring in 2 to 5% of children in the United States. Most febrile seizures are considered simple, although those with focal onset, prolonged duration, or that occur more than once within the same febrile illness are considered complex. Risk factors for a first febrile seizure, recurrence of febrile seizures, and development of future epilepsy are identifiable and varied. Children with febrile seizures encounter little risk of mortality and morbidity and have no association with any detectable brain damage. Recurrence is possible, but only a small minority will go on to develop epilepsy. Although antiepileptic drugs can prevent recurrent febrile seizures, they do not alter the risk of subsequent epilepsy. This has led to a changing view of how we approach the treatment of these common and largely benign seizures. This chapter will review the current understanding of the prognosis and management of febrile seizures. PMID:11918463

Shinnar, Shlomo; Glauser, Tracy A



Empiric Ther. of FEbrile Neutropenia  

Center for Drug Evaluation (CDER)

Text Version... For organisms that might represent a contaminant (eg, Staphylococcus epidermidis or Bacillus species), at least two positive cultures, with all ... More results from


Transient hypoxaemia during neutrophil recovery in febrile patients  

Microsoft Academic Search

In previous anecdotal reports, treatment with granulocyte colony-stimulating factor has been associated with pulmonary toxicity. In 35 consecutive admissions for chemotherapy-induced febrile neutropenia, transient hypoxia occurred in 12. 10 of the 12 followed treatment with filgrastim to induce neutrophil recovery. There was no consistent association with cytotoxic regimen.

K. White; J. Cebon



Clinical efficacy and safety of cefepime in febrile neutropenic patients with lung cancer  

Microsoft Academic Search

Fever often occurs along with chemotherapy-induced neutropenia. This condition is referred to as febrile neutropenia (FN).\\u000a Excellent guidelines for FN treatment have recently been published; however, there has so far been insufficient research concerning\\u000a FN associated with solid tumors, especially in Japan. A multi-institution prospective study of cefepime for the treatment\\u000a of FN in lung cancer patients was conducted. The

Masaki FujitaHiroshi; Hiroshi Ouchi; Yuichi Inoue; Ichiro Inoshima; Tsukasa Ohshima; Chikara Yoshimura; Hiroshi Wataya; Masayuki Kawasaki; Shoji Tokunaga; Yoichi Nakanishi



A case of endogenous endophthalmitis complicated by neutropenia following bacteremia with Streptococcus mitis resistant to beta-lactam antibiotics.  


This report is focused on a case of endogenous endophthalmitis following Streptococcus mitis bacteremia that occurred during chemotherapy for acute myeloid leukemia, despite broad-spectrum beta-lactam antibiotics and vancomycin. The patient partially recovered visual acuity. In conclusion, Streptococcus mitis bacteremia complicated by febrile neutropenia may cause endogenous endophthalmitis within a very short timeframe. PMID:22830590

Ono, Yuichiro



Febrile Seizures  


NINDS Febrile Seizures Information Page Condensed from Febrile Seizures Fact Sheet Table of Contents (click to jump to sections) What are ... being done? Clinical Trials Organizations What are Febrile Seizures? Febrile seizures are convulsions brought on by a ...


Cyclic and chronic neutropenia.  


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

Dale, David C; Welte, Karl



[Persistent neutropenia].  


We report the case of a 72-old patient with persistent neutropenia diagnosed during investigation of sialadenitis. Further examination led to the diagnosis of immune neutropenia and systemic lupus erythematosus. Anamnesis and the clinical course made initial diagnosis of drug-induced lupus erythematosus implausible. Steroid trial was done, followed by maintenance therapy, with good control of symptoms. PMID:20700874

Bürki, S; Oestmann, Andreas; Vogel, D; Oertle, S



Clinical characteristics and antimicrobial susceptibilities of viridans streptococcal bacteremia during febrile neutropenia in patients with hematologic malignancies: a comparison between adults and children  

PubMed Central

Background This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies. Methods The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB. Results A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome. Conclusions There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary.



Febrile Seizures  


... can I get more information? What are febrile seizures? Febrile seizures are convulsions brought on by a ... not triggered by fever. How common are febrile seizures? Approximately one in every 25 children will have ...


Febrile seizures  


... minutes. The child had more than one febrile seizure in 24 hours. The child has abnormal findings when examined . ... Meningitis causes less than 0.1% of febrile seizures. It should always be considered, especially in children less than 1 year old, or those who ...


Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis  

PubMed Central

Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV.

Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.



Febrile convulsions  

PubMed Central

One hundred and fifteen of 121 children consecutively admitted to hospital, each with his first febrile convulsion, were subsequently assessed on the Griffiths's mental development scales during a period of 24 months The effect of anticonvulsant medication on intellectual development was studied in 50 of the 73 children without recurrence of convulsions who had either continuous phenobarbitone, continuous sodium valproate, or no drugs during the 24-month period. The effect of further fits was studied in 42 of the 115 children who had recurrences. Children with further febrile convulsions showed a decrease in Griffiths's development quotient between the initial and 24-month assessment, whereas children with no subsequent fits showed a trend in the reverse direction. The increase in Griffiths's development quotient in children with no subsequent fits was found irrespective of whether the children were on anticonvulsant medication, but there was a non-significant tendency for this increase to be greatest in the group without drugs. The present study suggests that further fits after an initial febrile convulsion are likely to be more detrimental in terms of overall intellectual development than continuous medication with either phenobarbitone or sodium valproate. If the decision to treat is based on the risk of further fits, the present study supports continuous anticonvulsant medication if this risk is significantly increased, until the child is past the vulnerable period. In children at low risk of further febrile fits, intellectual development may be better if drugs are avoided.

Smith, J Aldridge; Wallace, Sheila J



Neutropenia and G-CSF in lymphoproliferative diseases  

PubMed Central

Background Chemotherapy-induced neutropenia is a major cause of morbidity and mortality. It frequently causes dose reductions or treatment delay, which can be prevented or treated by the administration of granulocyte-colony-stimulating factor (G-CSF). However, a better knowledge of the incidence, day of onset after therapy, and duration of neutropenia is essential to optimize the use of G-CSF. Design and methods Six hundred and ninety-four patients from a single institution, affected by lympho-proliferative diseases, were retrospectively reviewed for the occurrence of grade 4 neutropenia and febrile neutropenia (FN). Duration of neutropenia and time of neutrophil nadir were also retrieved. The diagnoses included non-Hodgkin's lymphoma, Hodgkin's lymphoma, and multiple myeloma. Chemotherapy regimens were obviously different according to the diagnosis, disease stage, and first or subsequent lines of therapy. Results No patient received G-CSF as primary prophylaxis. Median nadir did not significantly differ among patients treated with first or successive lines of therapy. The incidence of grade 4 neutropenia and FN ranged from 0 to 94%, depending on the chemotherapy regimen. Patients receiving a first-line chemotherapy regimen had a significantly lower incidence of febrile grade 4 neutropenia compared to patients treated with a second or subsequent line of therapy. The duration of grade 4 neutropenia was significantly longer in patients given second or subsequent lines. Conclusion The results of this study could be useful to define the nadir onset in the hematologic setting in order to correctly tailor timing and duration of G-CSF prophylaxis and to assess the lowest fully effective dose.

Ria, Roberto; Reale, Antonia; Moschetta, Michele; Dammacco, Franco; Vacca, Angelo



Treatment of patients with hematologic neoplasm, fever, and neutropenia.  


Choices of empirical antibiotic therapy for patients with febrile neutropenia must be made with very little information about the source and site of infection. The clinician is aided by recognition of the subtle signs and symptoms of infection in immunocompromised patients. National guidelines should be applied according to the microbiological patterns and trends in drug resistance at each institution. Case studies are provided to illustrate these challenges in daily practice. PMID:15768331

Sepkowitz, Kent A



Neutropenia with a probable hereditary basis in Border Collies  

Microsoft Academic Search

This paper documents a disease of Border Collies characterised by chronic neutropenia which probably resulted in recurrent bacterial infections manifesting as osteomyelitis and sometimes gastroenteritis. The neutropenia occurred despite hyperplasia of the myeloid cells in the bone marrow and a “shift to the right” in myeloid cell maturation. The underlying defect is currently unknown but may result from the inability

F. J. Allan; K. G. Thompson; B. R Jones; H. M. Burbidge; R. L. McKinley



A non-interventional study of biosimilar granulocyte colony-stimulating factor as prophylaxis for chemotherapy-induced neutropenia in a community oncology centre  

PubMed Central

Objectives: Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the severity of chemotherapy-induced neutropenia. Biosimilar G-CSF is now approved for use, based on comparable efficacy, safety and quality with the originator product. Methods: We conducted a retrospective review of patients’ charts following the switch from originator G-CSF (Neupogen®) to biosimilar G-CSF (Zarzio®/Filgrastim Hexal®) in a large community oncology practice. A total of 77 consecutive patients with cancer who received biosimilar G-CSF were reviewed, as were 25 patients who received originator G-CSF at the same centre. Results: The median age of patients in the biosimilar G-CSF cohort was 67 years (range 20?83). In this cohort 48% had chemotherapy with a febrile neutropenia risk of >20%. Biosimilar G-CSF was given as primary prophylaxis in 52% and as secondary prophylaxis in 48% of patients. Age and febrile neutropenia in medical history or in previous chemotherapy were factors that triggered the use of G-CSF in patients with a febrile neutropenia risk of <20%. One patient developed febrile neutropenia. Neutropenia led to chemotherapy dose reductions in five patients (6.5%) and discontinuation in two patients (2.5%). No unexpected safety findings were observed. Patient characteristics were generally similar in the originator G-CSF cohort. Only 24% of patients had a febrile neutropenia risk >20% and 36% received primary prophylactic G-CSF. One patient developed febrile neutropenia. Neutropenia led to chemotherapy dose reductions in two patients (8%) and discontinuation in two patients (8%). Conclusions: Biosimilar G-CSF was effective and prevented dose reductions/discontinuation in the majority of patients. Biosimilar G-CSF was considered clinically comparable to its reference product.

Verpoort, Karl



Canine Cyclic Neutropenia  

PubMed Central

Two normal collie dogs were given 1,200 R total body irradiation followed by successful marrow grafts from their grey collie littermates with cyclic hematopoiesis. During observation periods of 97 and 41 days after grafting, both previously normal recipients showed regular cyclic fluctuations of their granulocyte and reticulocyte counts similar to those observed in their donors. These findings suggest that canine cyclic neutropenia is due to a defect in the marrow stem cell.

Weiden, Paul L.; Robinett, Barbra; Graham, Theodore C.; Adamson, John; Storb, Rainer



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


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

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



Effectiveness of a Protective Environment implementation for cancer patients with chemotherapy-induced neutropenia on fever and mortality incidence.  


In a quasiexperimental study conducted to evaluate the impact of a Protective Environment implementation, febrile neutropenia (P = .009), overall mortality (P = .001), and 30-day adjusted mortality (P = .02) were reduced in cancer patients with chemotherapy-induced neutropenia. Our study highlights the potential success of a set of prevention measures mainly designed to reduce invasive environmental fungal infections in allogeneic hematopoietic stem cell transplant patients, in reducing fever and mortality among neutropenic cancer patients. PMID:23102987

Stoll, Paula; Silla, Lúcia Mariano da Rocha; Cola, Caroline Mioto Menegat; Splitt, Bruno Ismail; Moreira, Leila Beltrami



Cognitive dysfunction after experimental febrile seizures.  


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

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



Evaluation and management of patients with isolated neutropenia.  


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

Newburger, Peter E; Dale, David C



Parvovirus B19 causing leucopenia and neutropenia in a healthy adult  

Microsoft Academic Search

A 27-year-old healthy female presented with a prolonged and intermittent febrile illness. She was found to have leucopenia, neutropenia and thrombocytopenia, but a normal haemoglobin. The patient recovered spontaneously and convalescent serology 1 month later was positive for specific parvovirus B19 IgM and IgG. Parvovirus B19 infection was confirmed by detection of viral DNA by dot blot hybridization in a

G. D. Barlow; M. W. McKendrick



Predictors of Occult Pneumococcal Bacteremia in Young Febrile Children  

Microsoft Academic Search

Study objective: Occult pneumococcal bacteremia (OPB) occurs in 2.5% to 3% of highly febrile children 3 to 36 months of age, and 10% to 25% of untreated patients with OPB experience complications, including 3% to 6% in whom meningitis develops. The purpose of this study was to identify predictors of OPB among a large cohort of young, febrile children treated

Nathan Kuppermann; Gary R Fleisher; David M Jaffe



Technical Report: Treatment of the Child With Simple Febrile Seizures  

Microsoft Academic Search

Overview. Simple febrile seizures that occur in children ages 6 months to 5 years are common events with few adverse outcomes. Those who advocate therapy for this disorder have been concerned that such seizures lead to additional febrile seizures, to epilepsy, and perhaps even to brain injury. Moreover, they note the potential for such seizures to cause parental anxiety. We

Robert J. Baumann


A prospective, controlled, randomized, non-blind, comparative study of the efficacy and safety of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in empirical therapy for febrile neutropenic patients  

Microsoft Academic Search

BackgroundEmpirical antibiotic treatment for febrile neutropenia is well established. The best regimen is still controversial. The purpose of this study was to evaluate the efficacy, safety, and cost of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in neutropenic febrile patients.

Simeon Metallidis; Panagiotis Kollaras; Theodoros Giannakakis; Basilis Seitanidis; Theodoros Kordosis; John Nikolaidis; Apostolos Hatzitolios; Pavlos Nikolaidis



Cyclic neutropenia in a cleft lip and palate patient: a case report.  


Cleft lip and palate is the most common congenital anomaly. Its association with hematologic disorders is rarely reported. Cyclic neutropenia is a rare blood disorder that may occur spontaneously or has a genetic predisposition. Periodicity/recurrence of cyclic neutropenia has a cyclical pattern reoccurring in multiples of 7 days, usually at 21- or 28-day intervals between attacks, with the patient being fairly asymptomatic. There is no case in the literature that has reported the presence of cyclic neutropenia in cleft patients. We report a case of cleft patient associated with cyclic neutropenia. The clinical features, diagnosis, and course of management are described. PMID:21309694

Desai, Anil; Gopalkrishnan, K; Joshi, V K; Rao, C Bhasker



Incidencia de episodios febriles en pacientes con mieloma múltiple sometidos a trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE)  

Microsoft Academic Search

Background: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in wich infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections

N. Fernández-Mosteirín; C. Salvador-Osuna; J. J. Gimeno Lozano; M. L. Marco Lamata; M. Blasco Alberdi; D. Rubio Félix; M. Giralt Raichs



Fever, febrile seizures and epilepsy.  


Seizures induced by fever (febrile seizures) are the most common type of pathological brain activity in infants and children. These febrile seizures and their potential contribution to the mechanisms of limbic (temporal lobe) epilepsy have been a topic of major clinical and scientific interest. Key questions include the mechanisms by which fever generates seizures, the effects of long febrile seizures on neuronal function and the potential contribution of these seizures to epilepsy. This review builds on recent advances derived from animal models and summarizes our current knowledge of the mechanisms underlying febrile seizures and of changes in neuronal gene expression and function that facilitate the enduring effects of prolonged febrile seizures on neuronal and network excitability. The review also discusses the relevance of these findings to the general mechanisms of epileptogenesis during development and points out gaps in our knowledge, including the relationship of animal models to human febrile seizures and epilepsy. PMID:17897728

Dubé, Céline M; Brewster, Amy L; Richichi, Cristina; Zha, Qinqin; Baram, Tallie Z



Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL6 are more reliable than C-reactive protein  

Microsoft Academic Search

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these

M. von Lilienfeld-Toal; M. P. Dietrich; A. Glasmacher; L. Lehmann; P. Breig; C. Hahn; I. G. H. Schmidt-Wolf; G. Marklein; S. Schroeder; F. Stuber



Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients  

Microsoft Academic Search

Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses\\u000a the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of\\u000a the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one\\u000a patients with hematological malignancies (55%) or solid tumors (45%), neutropenia <500\\/?l,

G. Behre; H. Link; G. Maschmeyer; P. Meyer; U. Paaz; M. Wilhelm; W. Hiddemann



Ceftazidime and ciprofloxacin as empiric therapy in febrile neutropenic patients undergoing hematopoietic stem cell transplantation  

Microsoft Academic Search

This pilot study was done to assess the efficacy and toxicity of intravenous ceftazidime and ciprofloxacin in patients developing febrile neutropenia while undergoing high-dose myeloablative therapy and hematopoietic stem cell transplantation (HSCT). All patients undergoing high-dose chemoradiotherapy and HSCT for leukemias, lymphomas, multiple myeloma, and solid tumors received open-label ceftazidime 2 g intravenously every 8 hours and ciprofloxacin 400 mg

Hassan H. Ghazal; Connie D. Ghazal; Imad A. Tabbara



Managing neutropenia in older patients with cancer receiving chemotherapy in a community setting.  


Older patients with cancer who may be more susceptible than younger patients to the myelosuppressive effects of chemotherapy undergo dose delays and reductions that can compromise treatment outcomes. Incidence of neutropenic complications and suboptimal chemotherapy delivery can be reduced with prophylactic colony-stimulating factors; however, their use in older patients with cancer has not been well studied. A randomized, multicenter, community-based trial was designed to compare prophylactic pegfilgrastim use (all cycles of chemotherapy) versus its more common reactive use (at clinicians' discretion) in patients aged 65 years or older with various cancers. Pegfilgrastim use in all cycles reduced the incidence of febrile neutropenia by about 60% and hospitalizations caused by neutropenia and febrile neutropenia by about 50% versus reactive pegfilgrastim use in later cycles. The study showed that older patients with cancer can be treated safely with optimal doses of chemotherapy with appropriate supportive care. Nurses, key collaborators in providing supportive care, can take an active role in identifying older patients who may benefit from pegfilgrastim in all cycles of chemotherapy. PMID:20118030

Flores, Irene Q; Ershler, William



Restarting clozapine after neutropenia: evaluating the possibilities and practicalities.  


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 neutropenia and agranulocytosis, makes any attempt to restart clozapine a high-risk venture requiring the utmost caution. PMID:17190527

Whiskey, Eromona; Taylor, David



Management of indwelling central venous catheters in pediatric cancer patients with fever and neutropenia.  


This prospective study comprises 97 episodes of fever and neutropenia in children with cancer and central venous access. In 76% of episodes, patients had a Broviac-Hickman-like catheter, and in 24% a totally implanted venous access chamber system. The need for catheter removal during a febrile infection was 0.32/1000 catheter days, and the documented sepsis rate was 0.59/1000 catheter days. Our data indicate that 94% of episodes of fever and neutropenia in total, 78% of documented septicemias, and 97% of fevers of unknown origin were curable with broad-coverage antimicrobial therapy without removing the central venous line. Totally implanted chambers had a lower infection rate than catheters of Broviac-Hickman type. PMID:8362233

Riikonen, P; Saarinen, U M; Lähteenoja, K M; Jalanko, H



Thermoregulatory responses of febrile monkeys during microwave exposure.  


We have examined experimentally the question of increased vulnerability to the thermalizing effects of MW exposure during febrile illness. In a controlled ambient temperature of 26 degrees C, autonomic mechanisms of heat production and heat loss were measured in febrile squirrel monkeys during 30-min exposures to 450 or 2450 MHz CW MW fields at different phases of the fever cycle (induction, plateau, defervescence). We have shown that MW energy absorbed during a febrile episode spares endogenous energy production, but may augment the fever if deposited deep in the body, as is the case during exposure at the resonant frequency. The fever may also be exacerbated if the MW exposure occurs late in the febrile episode, a condition that may put an organism at some risk, especially if the field strength exceeds safety guidelines. PMID:9100927

Adair, E R; Adams, B W; Kelleher, S A; Streett, J W



Vaccines and febrile seizures.  


Vaccine administration is the second leading cause of febrile seizures (FS). FS occurrence in children is a serious concern because it leads to public apprehension of vaccinations. This review discusses the clinical implications of FS, its potential link to vaccinations and its impact on official recommendations for vaccinations in children. Vaccines such as the pertussis antigen-containing vaccine, the measles-containing vaccine and the influenza vaccine have been linked to FS. However, FS events are very rare and are not usually associated with downstream complications or severe neurologic diseases. Considering their significant health benefits, vaccinations have not been restricted in the pediatric population. Nevertheless, vaccine-induced FS could be a problem, particularly in genetically predisposed children. Therefore, post-marketing surveillance studies are required to accurately assess the incidence of FS and identify individuals who are particularly susceptible to FS after vaccination. PMID:23984960

Principi, Nicola; Esposito, Susanna



Febrile seizures — treatment and outcome  

Microsoft Academic Search

Assessment of treatment strategies in febrile seizures should be based on short- and long-term outcomes, with and without acute, intermittent, or chronic medical intervention, as well as short- and long-term side effects. Febrile seizures are a benign condition with a normal neurological, motor, intellectual, and cognitive long-term outcome and have a low risk of later epilepsy in most cases. Even

Finn Ursin Knudsen



Febrile Seizures and Epilepsy: Possible Outcomes  


... 79;e80-e82 Neurology Jacqueline A. French Febrile seizures: Possible outcomes This information is current as of ... 79;e80-e82 Neurology Jacqueline A. French Febrile seizures: Possible outcomes This information is current as of ...


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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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



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

PubMed Central

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

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



Pedigree analysis in families with febrile seizures  

SciTech Connect

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

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



Prevalence, phenotype and inheritance of benign neutropenia in Arabs  

Microsoft Academic Search

BACKGROUND: Benign neutropenia, i.e., neutropenia not associated with an increased risk of infection, may result in serious medical consequences when a 'standard' definition of neutropenia (absolute neutrophil count (ANC) 9cells\\/L) is universally applied to all races. The aims of this study were to determine the prevalence of benign neutropenia among healthy Arabs and evaluate its mode of inheritance. METHODS: ANCs

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



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

Microsoft Academic Search

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



Evidence on the use of paracetamol in febrile children.  

PubMed Central

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

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



Renal amyloidosis in a child with neutropenia.  


Amyloidosis represents a heterogeneous group of disorders of protein metabolism and is characterized by deposition of fibrillar proteins in the intra- and extracellular spaces. Here, a case of generalized amyloidosis associated with neutropenia is presented. She had a medical history of multiple bacterial infections. At the age of 14 years, she developed nephrotic syndrome. An increase of antigenic stimulation during the intermittent bouts of acute infections would have been the main factor responsible for the development of secondary amyloidosis in this case. To the best of our knowledge, coexistence between neutropenic disorders and renal amyloidosis in children has not been reported till date. The purpose of this report is to present a case of secondary amyloidosis associated with neutropenia in pediatric age group, probably for the first time. PMID:21912038

Otukesh, Hasan; Hoseini, Rozita; Behzadi, Ashkan Heshmatzade; Fereshtehnejad, Seyed-Mohammad; Mehrazma, Mitra; Parvin, Mahmoud; Mojtahedzadeh, Mona; Razizadeh, Nazli; Pourfakharan, Mohammad



Childhood Febrile Seizures: Overview and Implications  

PubMed Central

This article provides an overview of the latest knowledge and understanding of childhood febrile seizures. This review also discusses childhood febrile seizure occurrence, health services utilization and treatment costs. Parental reactions associated with its occurrence and how healthcare providers can assist parents with dealing effectively with this potentially frightening and anxiety-producing event are also discussed.

Jones, Tonia; Jacobsen, Steven J.



Molecular basis and therapy of disorders associated with chronic neutropenia  

Microsoft Academic Search

There have been many recent advances in our understanding of the molecular basis of neutropenia disorders, primarily through\\u000a advances in genetic analysis of inherited disorders. Molecular and cellular studies now suggest that accelerated apoptosis\\u000a of neutrophil precursors in the bone marrow is the common pathophysiologic mechanism. Severe congenital neutropenia and cyclic\\u000a neutropenia, both usually inherited as autosomal-dominant disorders, are caused

Steven M. Stein; David C. Dale



Clindamycin-induced neutropenia following major head and neck surgery.  


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

Schmidt, Robert S; Reiter, Evan R



Febrile seizures: mechanisms and relationship to epilepsy.  


Studies of febrile seizures have been driven by two major enigmas: first, how these most common of human seizures are generated by fever has not been known. Second, epidemiological studies have linked prolonged febrile seizures with the development of temporal lobe epilepsy, yet whether long or recurrent febrile seizures cause temporal lobe epilepsy has remained unresolved. To investigate these questions, a model of prolonged (complex) febrile seizures was developed in immature rats and mice, permitting mechanistic examination of the potential causal relationships of fever and seizures, and of febrile seizures and limbic epilepsy. Although the model relied on hyperthermia, it was discovered that the hyperthermia-induced secretion of endogenous fever mediators including interleukin-1beta, which contributed to the generation of these 'febrile' seizures. In addition, prolonged experimental febrile seizures provoked epilepsy in a third of the animals. Investigations of the mechanisms of this epileptogenesis demonstrated that expression of specific ion (HCN) channels and of endocannabinoid signaling, may be involved. These may provide novel drug targets for intervention in the epileptogenic process. PMID:19232478

Dubé, Céline M; Brewster, Amy L; Baram, Tallie Z



Pegfilgrastim and daily granulocyte colony-stimulating factor: patterns of use and neutropenia-related outcomes in cancer patients in Spain - results of the LEARN Study  

PubMed Central

Daily granulocyte colony-stimulating factors [(G-CSFs); e.g. filgrastim, lenograstim] are frequently used to reduce the duration of chemotherapy-induced neutropenia (CIN) and the incidence of febrile neutropenia (FN) in cancer patients. A pegylated formulation of filgrastim, pegfilgrastim, which is administered once per cycle, was introduced in Spain in 2003. LEARN was a multi-centre, retrospective, observational study in Spain comparing patterns of use of daily G-CSF and pegfilgrastim, and CIN-related outcomes in adults with non-myeloid malignancies receiving myelosuppressive chemotherapy. Outcome measures were the percentage of patients receiving G-CSF for primary prophylaxis versus secondary prophylaxis/treatment, duration of treatment with G-CSF and incidence of CIN-related complications. Medical records from consecutive patients with documented pegfilgrastim (n = 75) or daily G-CSF (n = 111) use during 2003 were included. The proportion of patients receiving primary or secondary prophylaxis was comparable between the pegfilgrastim (39 and 48% respectively) and daily G-CSF (40 and 48% respectively) groups. However, there was a trend towards less frequent use to treat a neutropenic event such as FN or neutropenia in the pegfilgrastim group (17 versus 30% with daily G-CSF). Chemotherapy-induced neutropenia-related complications were less frequent in patients receiving pegfilgrastim (e.g. FN 11 versus 24% with daily G-CSF). This is the first study to show the potential benefits of pegfilgrastim over daily G-CSF in Spanish clinical practice.




Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program.  

PubMed Central

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Menichetti, F; Martino, P; Bucaneve, G; Gentile, G; D'Antonio, D; Liso, V; Ricci, P; Nosari, A M; Buelli, M; Carotenuto, M



Characteristics of fever, etiologic factors, antibiotic use and prognosis in febrile dermatology inpatients.  


Background? Generally, fever is observed in >30% of hospitalized patients. However, little is known about fever in dermatology inpatients. Objectives? The aim of this study was to investigate and document the incidence, characteristics, and etiologic factors of fever in febrile dermatology inpatients and to describe the practice of antibiotic use and prognosis in the same group. Methods? The medical records for 928 inpatients were retrospectively analyzed. Results? The incidence of fever was found to be 16.2%. Mean length of hospital stay was found to be longer in febrile patients. Of the 176 febrile episodes, 79 (44.9%) occurred in patients without infections, 43 (24.4%) in patients with community-acquired infections, 25 (14.2%) in patients with healthcare-associated infections, 18 (10.2%) in patients classified with fever of non-infectious/infectious causes, and 11 (6.3%) in a group for whom the etiologic factors of fever were undetermined. Antibiotic treatment was started in 36.2% of febrile inpatients. The overall mortality rate was 0.6%. Conclusions? This is the first study to investigate febrile episodes in dermatology inpatients. Fever is a frequently encountered symptom in dermatology inpatients. Febrile episodes resulted from mostly non-infectious entities, mainly consisting of inflammatory dermatologic disorders. Antibiotics were ordered in a higher percentage of patients in the febrile group. Dermatologists started prophylactic or empiric antibiotic therapy in febrile patients with non-infectious or inflammatory diagnoses on the assumption that these patients had an increased risk for infection as a result of impaired skin integrity and use of immunosuppressive drug therapy. The overall mortality rate was very low in the study group of dermatology inpatients. PMID:23432609

Göktay, Fatih; Ceran, Nurgül; Ayd?ngöz, Ikbal Esen; Mansur, Ay?e Tülin



Survey on the Management of Febrile Seizures.  

National Technical Information Service (NTIS)

A survey regarding the management of the child with febrile seizures was mailed to 10,000 child neurologists, pediatricians, family and general practitioners. The response rate varied by specialty, and overall slightly more than half the physicians respon...

D. G. Hirtz Y. J. Lee J. H. Ellenberg K. B. Nelson



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

PubMed Central

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

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



Febrile myoclonus: a missed clinical diagnosis.  


Myoclonic jerks presenting with fever have only rarely been reported and have often been misdiagnosed as febrile seizures. The presentation may be dramatic enough to provoke unnecessary investigation and treatment. Considering the benign nature of this condition, it is important that the condition is recognized by the physician so that hospitalisation and diagnostic procedures such as lumbar puncture and electroencephalogram are prevented. The authors report three cases of febrile myoclonus and review the subject. PMID:23340986

Chauhan, Urmila; Shanbag, Preeti; Mallad, Veerabhadra



Assessment of febrile seizures in children  

Microsoft Academic Search

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

Arne Fetveit



Assessment of febrile seizures in children  

Microsoft Academic Search

Febrile seizures are the most common form of childhoodseizures,affecting2-5%of allchildrenandusually appearing between 3 months and 5 years of age. Despite its predominantly benign nature, a febrile seizure (FS) is a terrifying experience for most parents. The condition is perhaps one of the most prevalent causes of admittance to pediatric emergency wards worldwide. FS, defined as either simple or complex, may

Arne Fetveit



Severe Neutropenia in Japanese Patients with X-Linked Agammaglobulinemia  

Microsoft Academic Search

X-linked agammaglobulinemia (XLA) is clinically characterized by recurrent bacterial infections during early infancy. Although it is not a phagocytic disorder, XLA is sometimes associated with neutropenia. We conducted a nation-wide survey to determine the frequency of neutropenia among Japanese XLA patients. Responses were received from 87 (86%) of 101 patients in which BTK mutations were previously identified, and of these,

Hirokazu Kanegane; Hiromichi Taneichi; Keiko Nomura; Takeshi Futatani; Toshio Miyawaki



Fever and neutropenia in pediatric hematopoietic stem cell transplant patients.  


The objective of this study was to identify patterns of fever and neutropenia in pediatric patients undergoing initial hospitalization for hematopoietic stem cell transplantation. A retrospective review of 75 HSCTs over a 4-year period at a single institution was performed, of which 68% were allogeneic and 32% were autologous. Stem cell sources included bone marrow (29%), PBSC (52%) and umbilical cord blood (16%). Fever occurred in 74 (98%) of the episodes. Unexplained fever (FUO) occurred in 43%. Bacteremia without an anatomic focus occurred in 29%, while CVC associated infections occurred in 17%. In 49% of transplants at least one blood culture was positive. The incidence of bacteremia was higher in allogeneic HSCTs (58%) than in autologous transplants (29%). Gram-positive bacteria accounted for 71% of the isolates. Lower rates of bacteremia were observed in patients receiving oral fluoroquinolone prophylaxis. The median duration of fever was 12.5 days and time to engraftment 14 days. Regression analysis demonstrated that duration of fever was strongly associated with time to engraftment, and that time to engraftment was associated with source of cells and number of CD34+ cells/kg administered. Recipients of autologous PBSC had the shortest durations of fever and time to engraftment, while recipients of allogeneic umbilical cord blood had the longest. Bone Marrow Transplantation (2000) 25, 59-65. PMID:10654016

Mullen, C A; Nair, J; Sandesh, S; Chan, K W



Congenital neutropenia: diagnosis, molecular bases and patient management  

PubMed Central

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



Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma  

PubMed Central

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

Vakkalanka, Bhanu; Link, Brian K.



[Simple febrile seizure, complex seizure, generalized epilepsy with febrile seizure plus, FIRES and new syndromes].  


Febrile seizures are the most common seizures in childhood. They have been observed in 2-5% of children before the age of 5, but in some populations this figure may increase to 15%. It is a common cause of pediatric hospital admissions and cause of anxiety for parents. Febrile seizures could be the first manifestation of epilepsy. About 13% of epileptic patients have a history of febrile seizure, and 30% have had recurrent febrile seizures. Their phenotypic characteristics allow, in the majority of cases, a classification of the seizure, an elaboration of a prognosis and to assume a specific therapeutic attitude. It is possible to describe a spectrum according to their severity, from the benign simple seizure to the more complex, febrile seizure plus, Dravet'syndrome, and FIRES. During the past decade, molecular genetic studies have contributed to the identification of genetic factors involved in febrile seizure and related disorders, making the necessity of a careful follow up of these patients in order to detect risk factors earlier. We have reviewed the medical literature to update current knowledge of febrile seizures, their prognosis and their relation to new epileptic syndromes. PMID:24072053

Moreno de Flagge, Noris



Febrile illnesses of different etiology among outpatients in four health centers in Northwestern Ethiopia.  


Fever of different etiology is common in tropical and subtropical countries of the world. Etiological agents of febrile illnesses were assessed in 653 acute febrile patients aged 3 to 17 years who attended the outpatient departments of Dembecha Health Center, Jiga Health Center, Quarit Health Center, and Finoteselam Hospital in western Gojjam zone, northwestern Ethiopia. Malaria was the most prevalent illness, infecting 62% of all cases. Its prevalence varied significantly from 52% (Dembecha) to 72.7% (Quarit) (chi(2)=15.02, P=0.000). Plasmodium falciparum was the first cause of malaria (47.3%) followed by P. vivax (23%). Mixed infection of both P. falciparum and P. vivax was found in 7.2% of the cases. The other febrile infections were pneumonia (7%), typhoid (5.8%), typhus (5.1%), and brucellosis (2.6%). The availability of diagnostic facilities and the awareness of the community regarding the prevalence of non-malaria febrile illnesses are very low, and these illnesses are diagnosed clinically. As these illnesses are nonspecific, especially during the early stages of onset, misdiagnosis and mistreatment can occur. Therefore, it is recommended that the necessary diagnostic materials and awareness should be in place for prompt treatment of febrile cases in these districts. PMID:19305049

Animut, Abebe; Mekonnen, Yalemtsehay; Shimelis, Damte; Ephraim, Eden



A case report of a family with overlapping features of autosomal dominant febrile seizures and GEFS+.  


Familial febrile seizures occur in both generalized epilepsy with febrile seizures plus (GEFS+) and autosomal dominant febrile seizures (ADFS). The literature largely separates families with GEFS+ from those with ADFS. However, there is clinical overlap, and families with ADFS also include individuals with afebrile seizures. The phenotypic spectrum of GEFS+ is broader now than when first described, resulting in unclear boundaries between these two familial syndromes. The purpose of this report is to highlight the phenotypic similarities of GEFS+ and ADFS. A multigenerational family with febrile and afebrile seizures is described and the clinical features are compared to those of previously reported GEFS+ and ADFS families. This family meets the requirements for both ADFS and the broader definition of GEFS+. Linkage analysis has shown no clear linkage to known febrile seizure or GEFS+ loci. Despite locus heterogeneity, identified mutations in reported GEFS+ have so far all been in sodium channel or gamma-aminobutyric acid (GABA)-receptor genes, with other modifier genes postulated to affect individual phenotypes. The two mutations identified in families with ADFS are in genes implicated in GEFS+, SCN1A, and GABRG2. We conclude that it is inappropriate to separate GEFS+ and ADFS at present given the clinical and genotypic overlap. PMID:19054398

Hindocha, Neeti; Nabbout, Rima; Elmslie, Frances; Makoff, Andrew; Al-Chalabi, Ammar; Nashef, Lina



Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery  

PubMed Central

Background In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients. Study design Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events. Results Chemotherapy delivery was suboptimal (with a relative dose intensity ? 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis. Conclusions In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.



Splenic abscesses in therapy-resistant acute myeloblastic leukemia presenting as recurrent febrile neutropenia and unresolved splenomegaly.  


A 14 7/12-year-old boy with acute myeloblastic leukemia M3v was admitted with disseminated intravascular coagulation, otitis media, lobar pneumonia, and splenomegaly. After induction therapy, M2 bone marrow was attained but splenomegaly persisted. Abdominal ultrasonography, which revealed diffuse splenomegaly at admission, showed splenic nodular lesions at the end of the induction therapy. The lesions persisted after M1 bone marrow was attained. He developed acute appendicitis and was operated. Ultrasonography-guided aspiration biopsy revealed nonspecific purulent abscess. Gram's stain and aerobic culture revealed no microorganism or fungi. Splenectomy was performed. The pathologic examination confirmed the diagnosis. He did not have an appropriate bone marrow donor, and developed bone marrow relapse and died. PMID:17990589

Olcay, Lale; Dingil, Gürbüz; Yildirim, Emin; Dilek, Gülay; Dirim, Ece


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


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

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



Pegfilgrastim: a review of the pharmacoeconomics for chemotherapy-induced neutropenia.  


For oncology patients, febrile neutropenia (FN) can be a serious and costly toxicity of chemotherapy, often forcing a reduction in chemotherapy dose intensity and/or duration. Several therapeutic agents are used to reduce the occurrence of neutropenic episodes: granulocyte colony-stimulating factors (G-CSFs) and granulocyte-macrophage colony-stimulating factors. Appropriate administration of colony-stimulating factors reduces the risk of FN episodes and the costs associated with FN treatment. In the USA, the two most commonly used G-CSFs are filgrastim and the longer-acting pegfilgrastim. This pharmacoeconomic review of pegfilgrastim briefly considers some of the early research of G-CSFs, then focuses on the most recent comparative studies of pegfilgrastim against the backdrop of forthcoming US patent expiration for both products. The authors conclude with commentary on the market for pegfilgrastim in light of the growing debate surrounding the optimal selection of patients, treatment costs and future alternatives for the use of these agents in chemotherapy. PMID:23252353

Rofail, Pierre; Tadros, Mariam; Ywakim, Riham; Tadrous, Mina; Krug, Allison; Cosler, Leon E



Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.  


Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy. PMID:11450887

Agaoglu, L; Devecioglu, O; Anak, S; Karakas, Z; Yalman, N; Biner, B; Eryilmaz, E; Goksan, B; Unuvar, A; Agirbasli, H; Can, M; Bilgen, H; Gedikoglu, G



Urinary tract infection in febrile convulsions.  

PubMed Central

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.

Lee, P; Verrier Jones, K



After-hours management of febrile children.  


During a nine-month period approximately 15 percent of the children less than ten years of age in a university family practice had an after-hours medical contact for a febrile illness. Children less than two years of age accounted for 55 percent of the encounters. The most frequent diagnoses were upper respiratory tract infection, acute otitis media, and undifferentiated fever. Slightly less than one half of the children were seen by the on-call resident, and age and level of fever did not correlate with the likelihood of being seen. Very few of the children had a white blood cell count obtained, and none had a blood culture or lumbar puncture. In this practice, after-hours management of the febrile infant differed substantially from guidelines in the literature based on experiences in university emergency rooms and walk-in clinics. PMID:7276872

Blake, R L; Spencer, D; Daugird, A



Intermittent clobazam therapy in febrile seizures  

Microsoft Academic Search

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

Winsley Rose; Chellam Kirubakaran; Julius Xavier Scott



Cyclic neutropenia—Unusual cause of acute abdomen  

Microsoft Academic Search

Cyclic neutropenia, a rare blood disorder, may be complicated by spontaneous necrosis of the cecum and ascending colon. We describe one such case, where a staged surgical approach achieved a successful outcome. The importance of recognition of this disorder is stressed, since this allows both performance of appropriate surgery and consultation with hematologic colleagues.

T. O'Hanrahan; P. Dark; M. H. Irving



Mucosal Damage and Neutropenia Are Required for Candida albicans Dissemination  

Microsoft Academic Search

Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for

Andrew Y Koh; Julia R Köhler; Kathleen T Coggshall; Nico Van Rooijen; Gerald B Pier



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

Microsoft Academic Search

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

Ronit Elhasid; Jacob M. Rowe



"Simple febrile seizures plus (SFS+)": more than one febrile seizure within 24 hours is usually okay.  


This study aimed to investigate whether children with recurrent febrile seizures within a 24-hour period need to be worked up differently from children with simple febrile seizures. Inclusion criteria included the following: (i) children with first seizure cluster between 4 months and 3 years of age, (ii) children who had more than one febrile seizure within 24 hours, and (iii) children who returned to baseline between and after each event. Thirty-two patients met the inclusion criteria over a 3-year period. All patients underwent brain CT and/or MRI and EEG. All head CTs were normal. Two children had abnormal MRI findings - both benign: one is thought to represent postictal changes, and the other one is an incidental arachnoid cyst. Of the 4 abnormal EEGs, one showed epileptiform discharges, while the others showed generalized ictal or postictal features. We propose the term "simple febrile seizures plus (SFS+)" to describe children who have more than one seizure within 24 hours but who are otherwise not different in presentation from children with SFS. PMID:23624109

Grill, Marie F; Ng, Yu-Tze



A study of childhood febrile convulsions with particular reference to HHV-6 infection: pathogenic considerations  

Microsoft Academic Search

Most febrile convulsions (FC) in infants occur during a viral infection, particularly in children of less than 3 years of age; human herpesvirus 6 (HHV-6) has an important pathogenic role. To evaluate the link between this and other viruses and FC, a group of 65 children (mean age 18.46 months, SD±9.19) with a first episode of simple FC (G1) was

Maria Francesca Bertolani; Marinella Portolani; Francesca Marotti; Anna Maria Sabbattini; Claudio Chiossi; Maria Rosa Bandieri; Giovanni Battista Cavazzuti



Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection.  


Sterile cerebrospinal fluid pleocytosis occurs in febrile infants with urinary tract infection. Coinfection with enterovirus is a possible cause. We evaluated 57 infants with urinary tract infection and cerebrospinal fluid pleocytosis. All had enterovirus testing by polymerase chain reaction. An explanation for pleocytosis was determined for 24 infants (42%). Enterovirus infection was detected in 4 and is an uncommon cause of cerebrospinal fluid pleocytosis in infants with urinary tract infection. PMID:23584580

Doby, Elizabeth H; Stockmann, Chris; Korgenski, E Kent; Blaschke, Anne J; Byington, Carrie L



Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures  

ERIC Educational Resources Information Center

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

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



Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures  

ERIC Educational Resources Information Center

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

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




Microsoft Academic Search

-1 body weight intravenously to a group of eight healthy rabbits and compared these results to values in same eight rabbits with EEIF. Pharmacokinetic parameters of ofloxacin in normal and febrile rabbits were determined by using two compartment open kinetic model. Peak plasma level (Cmax) and area under the plasma concentration-time curve (AUC0-?) in normal and febrile rabbits did not




Dengue and other Febrile Illnesses among Children in the Philippines  

Microsoft Academic Search

In view of the increasing trend of DHF in the Philippines, a prospective study was undertaken to define the clinical and haematological differences between DF\\/DHF and other febrile illnesses (OFI) between 1999 and 2001. A total of 503 paediatric patients, who had acute febrile illness without an apparent focus of infection and who were admitted to St. Luke's Medical Center

Kazunori Oishia; Cynthia A. Mapuae; Celia C. Carlosd; Maria T. D. D. Cinco-Abanesd; Mariko Saitob; Shingo Inouec; Kouichi Moritac; Filipinas F. Natividade


Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis.  

PubMed Central

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.

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



Undifferentiated febrile illnesses in military personnel.  


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

Burns, Daniel S; Bailey, Mark S



Molecular Factors and Biochemical Pathways Induced by Febrile Temperature in Intraerythrocytic Plasmodium falciparum Parasites? †  

PubMed Central

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

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



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

PubMed Central

Background This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant Enterococcus species. Methods A descriptive study was performed by reviewing the blood culture reports from febrile neutropenic patients during the two study periods i.e., 1999–00 and 2001–06. Blood cultures were performed using BACTEC 9240 automated system. Isolates were identified and antibiotic sensitivities were done using standard microbiological procedures. Results Seven twenty six febrile neutropenic patients were admitted during the study period. A total of 5840 blood cultures were received, off these 1048 (18%) were culture positive. Amongst these, 557 (53%) grew Gram positive bacteria, 442 (42%) grew Gram negative bacteria, 43 (4%) fungi and 6 (1%) anaerobes. Sixty (5.7%) out of 1048 positive blood cultures were polymicrobial. In the Gram negative bacteria, Enterobacteriaceae was the predominant group; E. coli was the most frequently isolated organism in both study periods. Amongst non- Enterobacteriaceae group, Pseudomonas aeruginosa was the commonest organism isolated during first study period followed by Acinetobacter spp. However, during the second period Acinetobacter species was the most frequent pathogen. Enterobacteriaceae group showed higher statistically significant resistance in the second study period against ceftriaxone, quinolone and piperacillin/tazobactam, whilst no resistance observed against imipenem/meropenem. The susceptibility pattern of Acinetobacter species shifted from sensitive to highly resistant one with significant p values against ceftriaxone, quinolone, piperacillin/tazobactam and imipenem/meropenem. Amongst Gram positive bacteria, MRSA isolation rate remained static, vancomycin resistant Enterococcus species emerged in second study period while no Staphylococcus species resistant to vancomycin was noted. Conclusion This rising trend of highly resistant organisms stresses the increasing importance of continuous surveillance system and stewardship of antibiotics as strategies in the overall management of patients with febrile neutropenia.

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



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

Microsoft Academic Search

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

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



Cost Effective Screening for UTI in Febrile Children.  

National Technical Information Service (NTIS)

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

K. Shaw



High Cefepime Plasma Concentrations and Neurological Toxicity in Febrile Neutropenic Patients with Mild Impairment of Renal Function?  

PubMed Central

High-dose cefepime therapy is recommended for febrile neutropenia. Safety issues have been raised in a recent meta-analysis reporting an increased risk of mortality during cefepime therapy. Cefepime-related neurological toxicity has been associated with overdosing due to severe renal dysfunction. This study aimed to investigate the association between cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients. Cefepime trough concentrations (by high-performance liquid chromatography) were retrospectively analyzed for 30 adult febrile neutropenic patients receiving the recommended high-dose regimen (6 g/day for a glomerular filtration rate [GFR] of >50 ml/min). The dose adjustment to renal function was evaluated by the ratio of the cefepime daily dose per 100 ml/min of glomerular filtration. The association between cefepime plasma concentrations and neurological toxicity was assessed on the basis of consistent neurological symptoms and/or signs (by NCI criteria). The median cefepime concentration was 8.7 mg/liter (range, 2.1 to 38 mg/liter) at a median of 4 days (range, 2 to 15 days) after the start of therapy. Neurological toxicity (altered mental status, hallucinations, or myoclonia) was attributed to cefepime in 6/30 (20%) patients (median GFR, 45 ml/min; range, 41 to 65 ml/min) receiving a median dose of 13.2 g/day per 100 ml/min GFR (range, 9.2 to 14.3 g/day per 100 ml/min GFR). Cefepime discontinuation resulted in complete neurological recovery for five patients and improvement for one patient. A multivariate logistic regression model confirmed high cefepime concentrations as an independent predictor of neurological toxicity, with a 50% probability threshold at ?22 mg/liter (P = 0.05). High cefepime plasma concentrations are associated with neurological toxicity in febrile neutropenic patients with mild renal dysfunction. Careful adherence to normalized dosing per 100 ml/min GFR is crucial. Monitoring of plasma concentrations may contribute to preventing neurological toxicity of high-dose therapy for this life-threatening condition.

Lamoth, F.; Buclin, T.; Pascual, A.; Vora, S.; Bolay, S.; Decosterd, L. A.; Calandra, T.; Marchetti, O.



Febrile urinary tract infection: Escherichia coli susceptibility to oral antimicrobials  

Microsoft Academic Search

Empirical treatment is indicated for young children with febrile urinary tract infection (UTI). In this clinical setting,\\u000a oral antibiotics are as safe and effective as intravenous therapy. The aim of this study was to investigate in children with\\u000a febrile UTI whether there were longitudinal changes in the prevalence of bacteria and in the pattern of Escherichia coli susceptibility to oral

Noemia P. Goldraich; Angélica Manfroi



Cefazolin-induced neutropenia and thrombocytopenia following trauma: a case report.  


Cefazolin, a first generation cephalosporin, is a rare cause of cyclical fevers, neutropenia, and thrombocytopenia following surgical prophylaxis. We present the case of an otherwise healthy 21-year-old male who sustained a 50-cm laceration to his chest and abdomen. He received emergency department prophylaxis with cefazolin and surgical repair. Subsequently, he developed cyclical fevers, neutropenia, and thrombocytopenia, all of which resolved after antibiotic discontinuation. This is the first case report in which the perioperative administration of cefazolin following trauma resulted in significant neutropenia and thrombocytopenia. Also discussed in this report are the etiology, workup, and treatment of cefazolin-induced neutropenia. PMID:22479926

Walker, Avery S; Causey, Marlin W; Sebesta, James A



Endogenous neuropeptide Y prevents recurrence of experimental febrile seizures by increasing seizure threshold.  


Febrile seizures (FSs) typically occur at the onset of fever and do not recur within the same febrile episode despite enduring or increased hyperthermia. Recurrent seizures during the same febrile episode are considered "complex," with potentially altered prognosis. A characterized immature rat model of FS was used to test the hypotheses that (1) a first FS influences the threshold temperature for subsequent ones, and (2) the underlying mechanisms involve the release and actions of the endogenous inhibitory hippocampal neuropeptide Y (NPY). Experimental FSs were induced two or three times, at 3- to 4-h intervals, and threshold temperatures measured. To determine the potential effects of seizure-induced endogenous NPY on thresholds for subsequent seizures, an antagonist of the major hippocampal NPY receptor (type 2) was infused prior to induction of the second seizure. As an indicator of NPY release, NPY expression was determined 4 and 24 h later. Threshold core and brain temperatures for hyperthermic seizures were consistent with those observed during human fever. Threshold temperatures for a second and third seizure were significantly and progressively higher than those required for the first. This "protective" effect involved induction of endogenous NPY because it was abolished by the NPY antagonist. In addition, NPY mRNA expression was increased in dentate gyrus, CA3 and CA1, after an experimental FS, consistent with peptide release. Collectively these data indicate that the absence of repetitive seizures during a febrile episode involves the inhibitory actions of endogenous NPY, suggesting that the signaling cascade triggered by this peptide might provide targets for therapeutic intervention. PMID:15800380

Dubé, Céline; Brunson, Kristen L; Eghbal-Ahmadi, Mariam; Gonzalez-Vega, Rebeca; Baram, Tallie Z



Laboratory predictors of dengue shock syndrome during the febrile stage.  


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

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



Clinical characteristics of febrile convulsions during primary HHV-6 infection  

PubMed Central

OBJECTIVE—To clarify clinical characteristics of children with febrile convulsions during primary human herpesvirus 6 (HHV-6) infection.?SUBJECTS AND METHODS—The clinical characteristics of first febrile convulsion were compared between those with and without primary HHV-6 infection in 105 children. HHV-6 infection was verified by culture or acute/convalescent anti-HHV-6 antibody titres.?RESULTS—Primary infection with HHV-6 was seen in 21 of 105 patients with febrile convulsions (3 upper respiratory infection, 1 lower respiratory infection, and 17 exanthem subitum). 13 of 23 patients < 1 year, 19 of 79 patients with first febrile convulsion, and 2 of 15 with second convulsion were infected with HHV-6. The median age of patients with first febrile convulsion and HHV-6 was significantly lower than those without infection. The frequency of clustering seizures, long lasting seizures, partial seizures, and postictal paralysis was significantly higher among those with primary HHV-6 infection than among those without. The frequency of atypical seizures in 19 patients with first febrile convulsion associated with primary infection was significantly higher than in 60 patients without primary infection. The frequency in infants younger than 1 year of age was also significantly higher than that in 10 age matched infants without primary infection.?CONCLUSIONS—These findings suggest that primary infection with HHV-6 is frequently associated with febrile convulsions in infants and young children and that it often results in the development of a more severe form of convulsions, such as partial seizures, prolonged seizures, and repeated seizures, and might be a risk factor for subsequent development of epilepsy.??

Suga, S.; Suzuki, K.; Ihira, M.; Yoshikawa, T.; Kajita, Y.; Ozaki, T.; Iida, K.; Saito, Y.; Asano, Y.



Febrile illness experience among Nigerian nomads  

PubMed Central

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



S100B proteins in febrile seizures.  


S100B protein concentrations correlate with the severity and outcome of brain damage after brain injuries, and have been shown to be markers of blood-brain barrier damage. In children elevated S100B values are seen as a marker of damage to astrocytes even after mild head injuries. S100B proteins may also give an indication of an ongoing pathological process in the brain with respect to febrile seizures (FS) and the likelihood of their recurrence. To evaluate this, we measured S100B protein concentrations in serum and cerebrospinal fluid from 103 children after their first FS. 33 children with acute infection without FS served as controls for the serum concentrations. In the FS patients the mean S100B concentration in the cerebrospinal fluid samples was 0.21 ?g/L and that in the serum samples 0.12 ?g/L. The mean serum concentration in the controls was 0.11 ?g/L (difference 0.01 ?g/L, 95% confidence interval -0.02 to 0.04 ?g/L, P = 0.46). There was a correlation between age and serum S100B concentration (r = -0.28, P = 0.008) in children under four years, but S100B concentrations did not predict the clinical severity of the FS nor their recurrence. There was no correlation between time of arrival at the hospital after FS and S100B concentration in serum (r = -0.130, P = 0.28) or in cerebrospinal fluid samples (r=-0.091, P = 0.52). Our findings indicate that FS does not cause significant blood-brain barrier openings, and increase the evidence that these seizures are relatively harmless for the developing brain. PMID:22130006

Mikkonen, Kirsi; Pekkala, Niina; Pokka, Tytti; Romner, Bertil; Uhari, Matti; Rantala, Heikki



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

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/?l 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.

Troger, Wilfried; Jezdic, Svetlana; Zdrale, Zdravko; Tisma, Nevena; Hamre, Harald J.; Matijasevic, Miodrag



Recognition memory is impaired in children after prolonged febrile seizures  

PubMed Central

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

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



Late febrile convulsions: a clinical follow-up.  


A joint study was performed on patients from the Pediatric Clinics of Catania and Modena. Two hundred and twenty-two children who presented with febrile convulsions (FC) after the age of six years (LFC) were followed up in order to evaluate the risk of recurrence and type of convulsions. The overall results showed that 94 patients out of 222 (42.3%) had subsequent fits, both febrile and afebrile. The present study suggests that the risk of subsequent afebrile crises in LFC is higher (15.8%) than observed after "simple" FC (2-3%) and similar to that reported after "complex" FC (13-17%). PMID:2751066

Pavone, L; Cavazzuti, G B; Incorpora, G; Galli, V; Parano, E; Benatti, A; Rizzo, R; Ciccarone, V



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

Microsoft Academic Search

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

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



Mosaic tetraploidy and transient GFI1 mutation in a patient with severe chronic neutropenia.  


This report presents the case of a 15-year-old male with severe chronic neutropenia, leukopenia, and persistent tetraploid mosaicism in the bone marrow and peripheral blood. His father had mild neutropenia and bone marrow tetraploidy. Flow cytometric analysis of DNA content peripheral blood showed tetraploidy in 20% of granulocytes and 15% of monocytes. Sequence analysis of the ELA2 gene was normal, but the GFI1 gene exhibited transient appearance of single base changes the coding region and promoter. We speculate that an underlying genetic defect, inherited in an autosomal dominant pattern, leads to both disordered mitosis and neutropenia in this kindred. PMID:17096407

Hochberg, Jessica C; Miron, Patricia M; Hay, Beverly N; Woda, Bruce A; Wang, Sa A; Richert-Przygonska, Monika; Aprikyan, Andrew A G; Newburger, Peter E



Current management of febrile seizures in Japan: An overview  

Microsoft Academic Search

Febrile seizures (FS) require both acute and chronic management. Acute management includes the treatment and differential diagnosis of FS and depend on the presence of seizures and a patient’s level of consciousness upon arrival at hospital: a patient may be discharged after physical examination if there are no seizures and no alteration of consciousness; close observation and laboratory examinations may

Kenji Sugai



Hippocampal abnormalities after prolonged febrile convulsion: a longitudinal MRI study  

Microsoft Academic Search

Summary Mesial temporal sclerosis (MTS) is the most common lesion in patients who require epilepsy surgery, and ~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, includ- ing PFC, can cause MTS. Our recently published data on children investigated within 5 days of a

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



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

Microsoft Academic Search

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

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



Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis  

Microsoft Academic Search

Experimental prolonged febrile seizures (FS) lead to structural and molecular changes that promote hippocampal hyperexcitability and reduce seizure threshold to further convulsants. However, whether these seizures provoke later-onset epilepsy, as has been suspected in humans, has remained unclear. Pre- viously, intermittent EEGs with behavioural observations for motor seizures failed to demonstrate sponta- neous seizures in adult rats subjected to experimental

Celine Dube; Cristina Richichi; Roland A. Bender; Grace Chung; Brian Litt; Tallie Z. Baram



Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers.  


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

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



Febrile and afebrile convulsions: a clinical follow-up  

Microsoft Academic Search

A joint study was performed on 204 children who suffered separate febrile (FS) and afebrile seizures (aFS) within a short space of time to evaluate the risk of subsequent convulsive crises. The data obtained revealed frequent recurrence of seizures and high risk of subsequent convulsive afebrile crises in these children.

Lorenzo Pavone; Vanna Galli; Renata Rizzo; Vanna Ciccarone; Mariadonatella Cocuzza; Giovan Battista Cavazzuti; Felicia Di Gregorio



Febrile and afebrile convulsions: a clinical follow-up.  


A joint study was performed on 204 children who suffered separate febrile (FS) and afebrile seizures (aFS) within a short space of time to evaluate the risk of subsequent convulsive crises. The data obtained revealed frequent recurrence of seizures and high risk of subsequent convulsive afebrile crises in these children. PMID:8374919

Pavone, L; Galli, V; Rizzo, R; Ciccarone, V; Cocuzza, M; Cavazzuti, G B; Di Gregorio, F



Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers  

PubMed Central

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

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



Venezuelan equine encephalitis febrile cases among humans in the Peruvian Amazon River region.  


A survey was conducted from October 1, 1993 to June 30, 1995 to determine the arboviral etiologies of febrile illnesses in the city of Iquitos in the Amazon River Basin of Peru. The study subjects were patients who were enrolled at medical care clinics or in their homes by Peruvian Ministry of Health (MOH) workers as part of the passive and active disease surveillance program of the MOH. The clinical criterion for enrollment was the diagnosis of a suspected viral-associated, acute, undifferentiated febrile illness of < or = 5 days duration. A total of 598 patients were enrolled in the study. Demographic information, medical history, clinical data, and blood samples were obtained from each patient. The more common clinical features were fever, headache, myalgia, arthralgia, retro-ocular pain, and chills. Sera were tested for virus by the newborn mouse and cell culture assays. Viral isolates were identified initially by immunofluorescence using polyclonal antibody. An ELISA using viral-specific monoclonal antibodies and nucleotide sequence analysis were used to determine the specific variety of the viruses. In addition, thin and thick blood smears were observed for malaria parasites. Venezuelan equine encephalitis (VEE) virus subtype I, variety ID virus was isolated from 10 cases, including three cases in October, November, and December 1993, five cases in January and February 1994, and two cases in June 1995. The ELISA for IgM and IgG antibody indicated that VEE virus was the cause of an additional four confirmed and four presumptive cases, including five from January through March 1994 and three in August 1994. Sixteen cases were positive for malaria. The 18 cases of VEE occurred among military recruits (n = 7), agriculture workers (n = 3), students (n = 3), and general laborers (n = 5). These data indicated that an enzootic strain of VEE virus was the cause of at least 3% (18 of 598) of the cases of febrile illnesses studied in the city of Iquitos in the Amazon Basin region of Peru. PMID:9452289

Watts, D M; Callahan, J; Rossi, C; Oberste, M S; Roehrig, J T; Wooster, M T; Smith, J F; Cropp, C B; Gentrau, E M; Karabatsos, N; Gübler, D; Hayes, C G



Neutropenia associated with osteomyelitis due to Hepatozoon canis infection in a dog.  


A 4-year-old, intact male Shiba dog was referred to Yamaguchi University Animal Medical Center, Yamaguchi, Japan, for the following complaints: anorexia, lethargy, intermittent fever, gingival bleeding and abdominal purpura. The dog presented with persistent neutropenia. Histopathological examination of a bone marrow sample revealed round to oval structures that resembled Hepatozoon micromerozoites and formed a "wheel-spoke" pattern. Furthermore, mature neutrophils were observed around these structures. PCR and sequencing using bone marrow aspirate confirmed Hepatozoon canis (H. canis) infection. These findings suggest that the neutropenia observed in this case was associated with osteomyelitis due to H. canis infection. This is the first report of neutropenia associated with H. canis infection. H. canis infection can be included in the differential diagnosis in canine cases of neutropenia in areas where the disease is endemic. PMID:21697643

Shimokawa Miyama, Takako; Umeki, Saori; Baba, Kenji; Sada, Kumiko; Hiraoka, Hiroko; Endo, Yasuyuki; Inokuma, Hisashi; Hisasue, Masaharu; Okuda, Masaru; Mizuno, Takuya



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

Microsoft Academic Search

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

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



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


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

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



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

PubMed Central

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

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



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

PubMed Central

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

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



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


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

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



Approach to the febrile patient in the ICU.  


Fever is a normal adaptive brain response to infectious and noninfectious causes involving a cytokine-mediated response, the generation of acute phase reactants, and the activation of numerous physiologic, endocrinologic and immunologic systems. Ninety percent of patients with severe sepsis in the intensive care unit (ICU) will experience fever during their hospitalization, while the half of the new detected febrile episodes are of noninfectious origin. In the ICU, fever should be treated in cardiorespiratory and neurosurgical patients and in those in whom temperature exceeds 40 degrees C (104 degrees F). Antipyretic therapy must be justified regardless of the metabolic cost (if fever exceeds its physiologic benefit), the result (if the symptomatic relief adversely affects the course of the febrile illness) and the side effects. PMID:19665078

Dimopoulos, George; Falagas, Matthew E



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


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

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



Ultrasonography after the first febrile urinary tract infection in children.  


The importance of ultrasonography after the first febrile urinary tract infection has been recently challenged. The aim of this study was to evaluate the role of ultrasonography in detection of significant non-reflux abnormalities in the kidneys and the urinary tract, and to determine whether these findings influence treatment in these children. The clinical data and ultrasonography results of 155 children admitted to a university hospital with the first febrile urinary tract infection were analysed retrospectively. Renal ultrasonography was abnormal in 23 patients (14.8%). The major portion of these patients (81%) were younger than 2 years of age. Management of nine of these patients was changed based primarily on ultrasonography findings. Four of these patients were treated operatively. Conclusion: Our findings indicate that ultrasonography performed after the first urinary tract infection may offer clinically important information about non-reflux abnormalities in the kidneys and urinary tract that can affect the management of children with these complications. PMID:16565830

Jahnukainen, Timo; Honkinen, Olli; Ruuskanen, Olli; Mertsola, Jussi



C-reactive protein velocity to distinguish febrile bacterial infections from non-bacterial febrile illnesses in the emergency department  

PubMed Central

Introduction C-reactive protein (CRP) is a real-time and low-cost biomarker to distinguish febrile bacterial infections from non-bacterial febrile illnesses. We hypothesised that measuring the velocity of the biomarker instead of its absolute serum concentration could enhance its ability to differentiate between these two conditions. Methods We prospectively recruited adult patients (age ? 18 years) who presented to the emergency department with fever. We recorded their data regarding the onset of fever and accompanying symptoms. CRP measurements were obtained upon admission. CRP velocity (CRPv) was defined as the ratio between CRP on admission and the number of hours since the onset of fever. Patients were diagnosed by clinical symptoms, blood cultures and imaging studies, and the diagnoses were confirmed by an infectious disease specialist. The efficacy of CRPv as a diagnostic marker was evaluated by using receiver operator curves (ROC). Excluded were patients who did not know the time fever started with certainty, patients with malignancy, patients with HIV infection and patients who had been using antibiotics upon presentation. Results Of 178 eligible patients, 108 (60.7%) had febrile bacterial infections (mean CRP: 63.77 mg/L, mean CRPv: 3.61 mg/L/hour) and 70 (39.3%) had non-bacterial febrile illnesses (mean CRP: 23.2 mg/L, mean CRPv: 0.41 mg/L/hour). The area under the curve for CRP and CRPv were 0.783 (95% confidence interval (CI) = 0.717 to 0.850) and 0.871 (95% CI = 0.817 to 0.924), respectively. In a 122-patient subgroup with a CRP level of less than 100 mg/L, the area under the curve increased from 0.689 (95% CI = 0.0595 to 0.782) to 0.842 (95% CI = 0.77 to 0.914) by using the CRPv measurements. Conclusions CRPv improved differentiation between febrile bacterial infections and non-bacterial febrile illnesses compared with CRP alone, and could identify individuals who need prompt therapeutic intervention.

Paran, Yael; Yablecovitch, Doron; Choshen, Guy; Zeitlin, Ina; Rogowski, Ori; Ben-Ami, Ronen; Katzir, Michal; Saranga, Hila; Rosenzweig, Tovit; Justo, Dan; Orbach, Yaffa; Halpern, Pinhas; Berliner, Shlomo



Register-based studies on febrile seizures in Denmark  

Microsoft Academic Search

During a short period of brain development, one out of 25 children experience seizures when exposed to fever. The risk and consequences of these febrile seizures remain incompletely understood. We have conducted a number of studies within a population-based cohort of 1.6 million children born in Denmark (1977–2004). We constructed the cohort by linking registers on civil service, health, and

Mogens Vestergaard; Jakob Christensen



Histamine H1 antagonists and clinical characteristics of febrile seizures  

PubMed Central

Background The purpose of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures. Methods The current descriptive study was carried out from April 2009 to February 2011 in 250 infants and children who visited the Madinah Maternity and Children’s Hospital as a result of febrile convulsions. They were divided into two groups according to administration of antihistamines at the onset of fever. Results Detailed clinical manifestations were compared between patients with and without administration of antihistamines. The time from fever detection to seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than in the nonantihistamine group. No significant difference was found in time from fever detection to seizure onset or seizure duration between patients who received a first-generation antihistamine and those who received a second-generation antihistamine. Conclusion Due to their central nervous system effects, H1 antagonists should not be administered to patients with febrile seizures and epilepsy. Caution should be exercised regarding the use of histamine H1 antagonists in young infants, because these drugs could potentially disturb the anticonvulsive central histaminergic system.

Zolaly, Mohammed A



Human Febrile Illness Caused by Encephalomyocarditis Virus Infection, Peru  

PubMed Central

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

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



Human febrile illness caused by encephalomyocarditis virus infection, Peru.  


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

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



Late-onset neutropenia following primary treatment of diffuse large B-cell lymphoma with rituximab-containing therapy.  


Late-onset neutropenia (LON) following rituximab therapy is a recently recognized adverse effect occurring in various clinical settings. However, the true incidence and pathogenesis of this adverse effect are not fully understood. We retrospectively reviewed the medical records of 160 patients with diffuse large B-cell lymphoma (DLBCL) in complete remission (CR) following first-line treatment with rituximab-containing therapy. The incidence of LON was 26.9% (grade 1, 2, 3 and 4) and the incidence of severe LON (grade 3 and 4) was 7.5%. The risk factors for the occurrence of LON were not identified, and overall survival did not differ between patients who developed LON and those who did not. This study suggests that LON is a quite common complication to rituximab therapy. However, more studies are needed in order to elucidate the true mechanism behind and risk factors for LON. PMID:22563814

Rozman, Samo; Sonc, Monika; Novakovic, Barbara Jezersek



Molecular Confirmation of Co-Infection by Pathogenic Leptospira spp. and Orientia tsutsugamushi in Patients with Acute Febrile Illness in Thailand.  


Abstract. Leptospirosis and scrub typhus are major causes of acute febrile illness in rural Asia, where co-infection is reported to occur based on serologic evidence. We re-examined whether co-infection occurs by using a molecular approach. A duplex real-time polymerase chain reaction was developed that targeted a specific 16S ribosomal RNA gene of pathogenic Leptospira spp. and Orientia tsutsugamushi. Of 82 patients with an acute febrile illness who had dual infection on the basis of serologic tests, 5 (6%) had polymerase chain reaction results positive for both pathogens. We conclude that dual infection occurs, but that serologic tests may overestimate the frequency of co-infections. PMID:24002486

Sonthayanon, Piengchan; Chierakul, Wirongrong; Wuthiekanun, Vanaporn; Limmathurotsakul, Direk; Amornchai, Premjit; Smythe, Lee D; Day, Nicholas P; Peacock, Sharon J




PubMed Central

Background: Fever is the most common sign of childhood illnesses and febrile children constitute a substantial proportion of the practice of pediatrics and family medicine. Objectives: To highlight the pattern of febrile illnesses in children attending pediatric ambulatory health-care settings. Methods: A one-year prospective study was conducted on febrile children who were consecutively seen and managed at two walk-in primary-care clinics in Sulaimania Children's Hospital, Riyadh. Data collection and analysis were structured around the principal study objectives. Results: Among the 16,173 children seen, 4086 (25.3%) were identified as having a fever and evaluated to determine the aetiology of their febrile illness. Boys outnumbered girls and a significant increase in the frequency of febrile illnesses was noted in children 4 to 24 months of age. Upper respiratory tract infections were the commonest cause of fever (75%) and most of these infections were viral rhinopharyngitis. Viral gastroenteritis and pneumonia were prominent diagnoses, each accounting for 5% of febrile illnesses. Notably of low frequency were serious bacterial infections, such as meningitis (0.5%), cellulitis and bone or joint infection (1.8%) and urinary tract infection (0.7%). Only 9% of the febrile children required hospitalization. The ambulatory management of the other febrile children included the prescription of oral antibiotics to 64% of them. Conclusion: The proper clinical assessment of these febrile children and the prudent use of laboratory tests and antimicrobials remain the most important management strategies in primary health-care practice.

Al-Eissa, Youssef A; Ghazal, Sameeh S.; Al-Zamil, Fahad A.; Al-Salloum, Abdullah A.; Al-Omair, Abdullah O.; Al-Nasser, Mohammed N.



Continuing clozapine with granulocyte colony-stimulating factor in patients with neutropenia  

PubMed Central

Background: The current guidelines dictate that clozapine should be stopped following the emergence of neutropenia. Various alternative approaches have been tried in the past, among them one rarely used alternative being to continue treatment with clozapine with coprescription of granulocyte colony-stimulating factor (G-CSF). Aim and method: In this case series we aim to describe the treatment and progress of a number of patients in a secure psychiatric hospital in the UK. These patients were restarted on clozapine in combination with G-CSF, in spite of previous neutropenia associated with clozapine treatment. Discussion and conclusion: We hope that this case series will raise the profile of a potentially effective alternative to discontinuing clozapine after neutropenia.

Harvey, Jake; Sengupta, Samrat



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


We report an Omani family in whom the propositus had a rare coexistence of sickle cell disease and severe congenital neutropenia associated with a mutation in ELANE. In contrast to his siblings with sickle cell disease, the severity of HbSS-associated complications such as painful crises and acute chest syndrome was significantly reduced. His course of the disease had markedly worsened after initiating G-CSF therapy. These clinical observations suggest that neutropenia may ameliorate inflammatory responses and thus display a modulating factor with respect to the clinical course of sickle cell disease. PMID:22758217

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



Acute febrile encephalopathy in adults from Northwest India  

PubMed Central

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

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



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


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

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



In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.  

PubMed Central

Equine infectious anemia virus (EIAV) is a good model for studying mechanisms generating escaped retrovirus variants. We previously sequenced the entire gp90-encoding region of 22 cDNA clones obtained from five antigenically distinct isolates (F1V to F5V) recovered during febrile episodes in horse 493 experimentally infected with the Japanese virulent EIAV strain V70. The results showed that the mutations occurred in the principal neutralizing domain (PND) by insertions/duplications. In this study, we further characterized the PND of virus isolates sequentially recovered during 22 febrile episodes in seven horses newly infected with V70 or one of the V70-derived variants. Sequencing of 70 cDNA clones derived from the 22 episodes confirmed the generation of various new viral quasispecies with insertions/duplications in the PND. Although the insertion/duplication sequences in a total of 92 cDNA clones were extensively heterogeneous, we hypothesized that all the insertions/duplications occurred during reverse transcription from viral genomic RNA to minus strand DNA. The insertion/duplication regions were derived from a part of the PND sequence, which consisted of five small units. These small units, some with various substitutions and/or deletions, were also generated, especially in regions with insertions/duplications. Of particular note was that all these virus variants, except for two cDNA variants, were generated by essentially four different duplication pathways. Thus, these results extend the significance of insertions/duplications in the PND to the novel generation of EIAV in vivo during febrile episodes.

Zheng, Y H; Sentsui, H; Nakaya, T; Kono, Y; Ikuta, K



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

Microsoft Academic Search

OBJECTIVESTo examine the degree and frequency of reductions in hippocampal volume in patients with temporal lobe epilepsy with and without a history of febrile seizures.METHODSIn vivo measures of hippocampal volume were computed from three dimensional gradient echo (FLASH) images in 44 patients undergoing comprehensive evaluations for epilepsy surgery. Twenty one patients (48%) reported a history of febrile seizures. The volumes

William B Barr; Manzar Ashtari; Neil Schaul



Molecular Factors and Biochemical Pathways Induced by Febrile Temperature in Intraerythrocytic Plasmodium falciparum Parasites  

Microsoft Academic Search

Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in

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



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

Microsoft Academic Search

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

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



Age and Sex-Related Differences in Febrile Response to Peripheral Pyrogens in the Rabbit  

Microsoft Academic Search

A reduced febrile response with aging has been reported in mice, rats, rabbits, squirrel monkeys and man. Young adult male and female rats and rabbits respond differently to pyrogens, but little is known about relative febrile responses in old male and female animals. To further describe the effects of age and sex on fever, we gave intravenous injections of Salmonella

L. B. Deeter; L. W. Martin; J. M. Lipton



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

ERIC Educational Resources Information Center

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

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



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

ERIC Educational Resources Information Center

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

Deonna, Thierry



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

ERIC Educational Resources Information Center

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

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



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

Microsoft Academic Search

In a prospective randomised study, 289 children admitted consecutively to hospital with their first febrile seizure were allocated, by date of admission, to short term diazepam prophylaxis (n = 152) or to no prophylaxis (n = 137) and followed for 18 months. In untreated children, five major risk factors for recurrent febrile convulsions were identified: age 15 months or less

F U Knudsen




Microsoft Academic Search

Introduction: Identifying clinical features that differentiate acute febrile thrombocytopaenia from acute febrile illness without thrombocytopaenia can help primary care physician to decide whether to order a full blood count (FBC). This is important because thrombocytopaenia in viral fever may signify more serious underlying aetiology like dengue infection. Objective: The aim of this study was to compare the clinical features of

Tong Seng Fah; Noorazah Abdul Aziz; Chin Gek Liew; Khairani Omar


Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study  

Microsoft Academic Search

Objective To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. Design Prospective randomised study. Setting Paediatric emergency department in a general hospital. Subjects 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. Interventions Intranasal

Eli Lahat; Michael Goldman; Joseph Barr; Tzvi Bistritzer; Matithyahu Berkovitch; Assaf Harofeh



Leptospirosis among Hospitalized Febrile Patients in Northern Tanzania  

PubMed Central

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

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



Prostanoid inhibition and group B hemolytic streptococci (GBS) induced neutropenia in newborn piglets.  


GBS (Group B Hemolytic Streptococci) cause pulmonary hypertension with associated neutropenia. We investigated whether there is a correlation between the neutropenia of sepsis and GBS-induced pulmonary vasoconstriction, through study of the effects of inhibiting pulmonary vasoconstriction on the neutropenia of GBS in newborn piglets. Fifteen piglets were infused with GBS. After one hour, animals were given either a thromboxane inhibitor (DAZ), a combined cyclooxygenase/lipoxygenase inhibitor, BW755C, or placebo. With GBS infusion, WBC and PMN counts dropped steadily, from similar baselines, to 2250 +/- 570, 3300 +/- 500 and 5400 +/- 1100 cells/mm3 respectively (p less than 0.05; DAZ and BW vs. placebo). PMN's dropped similarly to 710 +/- 320, 2390 + 1240 and 3130 +/- 1050 cells/mm3 respectively (p less than 0.05; DAZ vs. BW and placebo). The drop in WBC's predominantly resulted from proportional decreases in PMN's (DAZ: r = 0.98; BW: r = 0.88; placebo r = 0.93). Compared to GBS alone, DAZ reduced pulmonary vasoconstriction, but exacerbated the granulocytopenia. BW755C similarly reduced pulmonary hypertension: however, it ameliorated the exacerbation of GBS induced neutropenia described above. These data imply that there is no direct correlation between GBS induced granulocytopenia and pulmonary hypertension. PMID:2125731

Hammerman, C; Aramburo, M J; Choi, J H



Impact of neutropenia duration on short-term mortality in neutropenic critically ill cancer patients  

Microsoft Academic Search

Objective. To identify predictors of 30-day mortality and to assess the impact of neutropenia recovery (NR) on 30-day mortality in critically ill cancer patients (CICPs). Design and setting. Retrospective review of the medical records of the 102 neutropenic CICPs admitted to a medical intensive care unit (ICU) over a 10-year period. Intervention. None. Measurements and results. Malignancies consisted of acute

Michael Darmon; Elie Azoulay; Corinne Alberti; Fabienne Fieux; Delphine Moreau; Jean-Roger Le Gall; Benoît Schlemmer



Early tooth loss due to cyclic neutropenia: long-term follow-up of one patient.  


In young patients with abnormal loosening of teeth and periodontal breakdown, dental professionals should consider a wide range of etiological factors/diseases, analyze differential diagnoses, and make appropriate referrals. The long-term oral and dental follow-up of a female patient diagnosed in early infancy with cyclic neutropenia is reviewed, and recommendations for care are discussed. PMID:11203896

da Fonseca, M A; Fontes, F


Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia  

Microsoft Academic Search

BACKGROUND: Five cases of severe neutropenia (neutrophil counts 9 cells\\/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the

Lewinda Knowles; Jane A Buxton; Nataliya Skuridina; Ifeoma Achebe; Donald LeGatt; Shihe Fan; Nancy Yan Zhu; James Talbot



Effect of Neutropenia and Treatment Delay on the Response to Antifungal Agents in Experimental Disseminated Candidiasis  

Microsoft Academic Search

Disseminated candidiasis is associated with a high rate of morbidity and mortality. The presence of neutrophils and the timely administration of antifungal agents are likely to be critical factors for a favorable therapeutic outcome of this syndrome. The effect of neutropenia on the temporal profile of the burden of Candida albicans in untreated mice and those treated with amphotericin B

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



Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia  

PubMed Central

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



Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability  

Microsoft Academic Search

Febrile seizures are the most common type of developmental seizures, affecting up to 5% of children. Experimental complex febrile seizures involving the immature rat hippocampus led to a persistent lowering of seizure threshold despite an upregulation of inhibition. Here we provide a mechanistic resolution to this paradox by showing that, in the hippocampus of rats that had febrile seizures, the

Kang Chen; Ildiko Aradi; Niklas Thon; Mariam Eghbal-Ahmadi; Tallie Z. Baram; Ivan Soltesz



Effect of early postnatal neutropenia in very low birth weight infants born to mothers with pregnancy-induced hypertension  

PubMed Central

Purpose In this study, we aimed to investigate the perinatal clinical conditions of very low birth weight (VLBW) infants born to mothers with pregnancy-induced hypertension (PIH) focusing on the effects of early postnatal neutropenia. Methods We reviewed the medical records of 191 VLBW infants who were born at Konyang University Hospital, between March 2003 and May 2011. We retrospectively analyzed the clinical characteristics of the infants and their mothers and compared the incidence of perinatal diseases and mortality of the infants according to the presence or absence of maternal PIH and neutropenia on the first postnatal day. Results Infants born to mothers with PIH showed an increased incidence of neutropenia on the first postnatal day (47.4%), cesarean delivery, and intrauterine growth restriction. When the infants born to mothers with PIH showed neutropenia on the first postnatal day, their incidence of respiratory distress syndrome (RDS) was increased (P=0.031); however, the difference was not found to be significant through logistic regression analysis. In all the VLBW infants, neutropenia on the first postnatal day was correlated with the development of RDS. The incidence of the other perinatal diseases involving sepsis and mortality did not significantly differ according to the presence or absence of neutropenia in infants born to mothers with PIH. Conclusion In VLBW infants born to mothers with PIH, the incidence of neutropenia on the first postnatal day was increased and it was not significantly correlated with the development of perinatal diseases involving RDS, sepsis, and mortality.

Park, Yang Hee; Lee, Gyung Min; Yoon, Jung Min; Cheon, Enn Jung; Ko, Kyung Ok; Lee, Yung Hyuk



Recurrent febrile respiratory distress in infant: which diagnosis?  


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

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



Dengue in the early febrile phase: viremia and antibody responses.  


A multicenter effort was begun in 1994 to characterize the pathophysiology of dengue using a study design that minimized patient selection bias by offering enrollment to all children with undifferentiated fever for <72 h. In the first year, 189 children were enrolled (age range, 8 months to 14 years). Thirty-two percent of these children had dengue infections (60 volunteers). The percentage of children with a secondary dengue infection was 93%, with only 4 (7%) having a primary dengue infection. The virus isolation rate from the plasma of children with dengue was 98%. Viremia correlated highly with temperature. All four dengue virus serotypes were isolated at both study sites. This study demonstrates that all four serotypes of dengue virus can cause dengue hemorrhagic fever, that all dengue patients as defined by serology experience viremia during the febrile phase, and that as fever subsides, so does viremia. PMID:9237696

Vaughn, D W; Green, S; Kalayanarooj, S; Innis, B L; Nimmannitya, S; Suntayakorn, S; Rothman, A L; Ennis, F A; Nisalak, A



Protracted febrile myalgia syndrome in familial Mediterranean fever.  


Familial Mediterranean fever (FMF) is an autosomal, recessively inherited multisystem disease that affects various groups of people originating from the Mediterranean Sea region, most specifically those of Jewish, Turkish, Armenian, and Arabic ethnicity. Recurrent attacks of fever and sterile polyserositis of the peritoneum, synovial membranes, and pleura are the main clinical features, although the clinical features of FMF have been expanded in recent years to also include severe myalgia, scrotal swelling, cardiac involvement, and protracted febrile myalgia syndrome (PFMS). PFMS is seen in only a small percentage of FMF patients and is characterized by severe debilitating myalgia of the upper and lower extremities and high fever, occasionally accompanied by abdominal pain, diarrhea, arthritis/arthralgia, and transient vasculitic purpura mimicking Henoch-Schönlein purpura (HSP). Here, we report on a patient with FMF who also presents with PFMS, which is an uncommon and severe manifestation of the disease. PMID:20352466

Senel, Kazim; Melikoglu, Meltem Alkan; Baykal, Tuba; Melikoglu, Mehmet; Erdal, Akin; Ugur, Mahir



Leptospirosis in febrile men ingesting Agouti paca in South America.  


To explore the relationship between the ingestion of Agouti paca (AP) and human leptospirosis in Guyana, 19 febrile men who said they had hunted and eaten A. paca were screened for malaria, using bloodsmears, and for leptospirosis, using an enzyme immuno-assay that detects Leptospira -specific IgM. Those found positive for anti-Leptospira IgM were then evaluated further, with a microscopical agglutination test based on a limited panel of serovars from three pathogenic species of Leptospira. Although six of the 18 patients who provided suitable samples for the serology were found seropositive for acute leptospirosis, only three of the 19 patients were found smear-positive for malaria. A clinical-decision model, based on medical histories, the results of physical examinations, and the use of routine urine dipsticks, and enabling prediction of the serological results, was developed. This model, which had 83% sensitivity and 100% specificity for leptospirosis, indicated that, in the absence of serology, most febrile patients reporting AP ingestion could be correctly treated if each was checked for malaria using traditional bloodsmears. The smear-positives should be treated with antimalarial drugs whereas the smear-negatives should be treated for leptospirosis if they had any of the following: a skin rash; lymphadenopathy; abnormal urine sediment (proteinuria or haematuria); and/or no previous history of malaria. In the present study, the relative risk of leptospirosis among the patients who were smear-negative for malaria and fulfilled at least one of these four criteria was 13 (P = 0.0007). In Guyana at least, leptospirosis appears to be common among men who hunt, prepare and ingest AP. Vaccines may be the best, practical form of protection among such men. PMID:15667717

Silverman, M S; Aronson, L; Eccles, M; Eisenstat, J; Gottesman, M; Rowsell, R; Ferron, M; Scolnik, D



Febrile illness at the emergency department of Cayenne Hospital, French Guiana.  


Febrile illness is a common cause of attendance at emergency departments. The purpose of this study was to describe infectious aetiologies of fever in a tropical setting. We prospectively included 1443 febrile patients, all French Guiana residents, who presented at Cayenne Hospital emergency department. This report will propose an overview of aetiologies of febrile illness in French Guiana, and tropical diseases such as malaria and arbovirus infections are discussed. Almost 30% of fevers remained unexplained. Further prospective multicentre studies are warranted to improve the diagnosis of overlooked pathogens in French Guiana. Such studies would lead to conclusions of specific interest in the travel medicine field. PMID:18640694

de Lavaissiere, Marc; D'Ortenzio, Eric; Dussart, Philippe; Fontanella, Jean Michel; Djossou, Felix; Carme, Bernard; Marchou, Bruno



Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and necklace fibers due to a DNM2 mutation.  


Dynamin 2 gene (DNM2) mutations result in an autosomal dominant centronuclear myopathy (CNM) and a Charcot-Marie-Tooth (CMT) neuropathy. DNM2-CMT but not DNM2-CNM patients were noted to have neutropenia. We here report a man with paravertebral muscles hypertrophy and mild neutropenia. His muscle biopsy was typical for CNM with additional "necklace" fibers. Sequencing of DNM2 revealed a known heterozygous c.1269C>T (p.Arg369Trp) mutation. Necklace fibers were considered as a pathological hallmark of late onset X-linked CNM due to mutations in MTM1 but have not been observed in DNM2-CNM. The findings broaden the features of DNM2-myopathy. PMID:20817456

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



Managing the hematologic side effects of antiviral therapy for chronic hepatitis C: anemia, neutropenia, and thrombocytopenia.  


Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common cause of dose reduction or discontinuation. Bone marrow suppression also contributes to the anemia and is the predominant mechanism for interferon-induced neutropenia and thrombocytopenia. Although dose reduction or discontinuation of combination therapy can reverse these abnormalities, they may reduce virologic response. Hematopoietic growth factors may provide a useful alternative for managing these hematologic side effects without reducing the optimal dose of the combination antiviral regimen. Treatment of anemia also may improve patients' health-related quality of life and their adherence to combination antiviral therapy. The impact of growth factors on sustained virologic response and their cost-effectiveness in patients with chronic hepatitis C need further assessment. PMID:15468613

Ong, Janus P; Younossi, Zobair M



[Non-fortuitous dynamin II mutation-related association: neutropenia and Charcot-Marie-Tooth disease].  


Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is a genetically and clinically heterogeneous group of disorders of the peripheral nervous system. Mutations in multiple genes are currently known. We report an original case of CMT associated with chronic neutropenia in a patient with a K562del mutation in the dynamin 2 (DNM2) gene in a patient presenting with alterated cognitive function. Associated manifestations may guide molecular study. PMID:22385972

Saint-Lézer, A; Solé, G; Ribeiro, E; Latour, P; Mercié, P; Longy-Boursier, M



A novel phenotype variant of severe congenital neutropenia caused by G6PC3 deficiency.  


Severe congenital neutropenia type 4 (SCN4) is associated with mutations in the G6PC3 gene. To date, all patients bearing the p.Gly260Arg variant of the G6PC3 gene show heart defects. Here, we present a case of the p.Gly260Arg variant in a patient who did not have structural or functional heart anomalies. Treatment with granulocyte colony-stimulating factor recovered the absolute neutrophil count and neutrophil functional competence. PMID:23441086

Estévez, Orlando A; Ortega, Consuelo; Tejero, Ángeles; Fernández, Silvia; Aguado, Rocío; Aróstegui, Juan I; González-Roca, Eva; Peña, José; Santamaría, Manuel





From Fig. 1 it may be seen that the effect of elevated temperature during the pyrexial period upon 1/K and therefore on the dissociation curve of oxyhemoglobin was, on the average, greater than would have been expected from experiments on normal blood in vitro, and greater than would be expected in view of the alkalosis occurring See PDF for Structure during fever. Temperature rise, and excess hydroxyl ion acting in vitro in the opposite directions, seemed to indicate a more stable state of affairs than was found. Apparently other factors have come into play, as, for example, alterations in the proportions and concentrations of the various electrolytes. In pneumonia, for instance, there is a retention of chloride during the febrile period with excessive loss of phosphates. The variations were not due to variations in the hemoglobin molecule itself since from the work of Adair, Barcroft, and Bock (18) hemoglobin must apparently be reckoned as having identical properties in normal individuals of the same species. If Barcroft's (19) hypothesis be right, namely that the C(H) within the corpuscle is higher than that of the plasma, the observed variations of 1/K may not be so surprising. In view of the fact that the hemoglobin inside the corpuscle is enclosed within a semipermeable membrane, the possibility arises of the setting up of membrane equilibria which will protect the respiratory pigment from excessive changes of reaction that may occur in the plasma, and thus the optimum conditions for the carriage of oxygen to the tissues may be maintained. Krogh and Leitch (10) in 1919 also drew attention to the protected situation of hemoglobin inside the corpuscle. In Case 6 it seems as if the alkalosis consequent on the febrile state had gained the upper hand and had extinguished the normal temperature reaction. This is rather confirmed by the fact that clinically the case showed one of the earlier signs of an alkalosis; namely, twitching of the facial muscles. Case 10, who had been on salicylate, also showed an analogous effect, when 6 days after the first observation the temperature shift was practically nil. The relationship between pH, 1/K, and the febrile temperature still awaits investigation. The extent of the shift of the dissociation curve was not by any means uniform; in neither Fig. 1 nor Fig. 2 is the highest value of 1/K at the highest temperature recorded. Fig. 2 shows the effect of temperature rise upon 1/K after cessation of the pyrexia; the effect is not so marked. Some cases, however, showed a variation in excess of the normal as if there was not yet complete return to normal. See PDF for Structure Biologically these changes are of importance in that this shifting of the dissociation curve to the right in fever means that there is more oxygen available for the tissues than normally, more especially at higher pressures. The tension of unloading is raised. This, in addition to the accelerated circulation and the probable increased velocity o[ reaction, means that even in a localized area of inflammation, if there is increased temperature, the tissues are placed in a better position for resisting infection as a result of their better oxygenation. That there is increased metabolism during fever has been conclusively shown by Du Bois (20) and others using large bed calorimeters. Du Bois has shown that the increase in metabolism obeys van't Hoff's law, increasing 13 per cent for each 1 degrees C. rise. This shifting of the curve then falls into line with these observations as an adaptive response to the febrile condition, and the febrile temperature, if not too great, would seem to be a purposive attempt to aid the combating of infection. This shifting of the curve probably explains Uyeno's (21) observation on the effect of increased temperature on the circulation in the cat; namely, increased coefficient of utilization, and increased fall in the saturation of the mixed venous blood. Turning now to Table II, we find that, if the CO(2) dissociation curve of Haldane (12) is accepted as normal, the bicarbonate reserve o

White, A C



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

Microsoft Academic Search

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

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



Etiology of Acute Undifferentiated Febrile Illness in the Amazon Basin of Ecuador.  

National Technical Information Service (NTIS)

We conducted a longitudinal observational study of 533 patients presenting to two hospitals in the Ecuadorean Amazon basin with acute undifferentiated febrile illness (AUFI) from 2001 through 2004. Viral isolation, reverse transcription-polymerase chain r...

K. H. Jacobsen K. L. Russell M. Negrete N. Brito de Bravo S. R. Manock



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

National Technical Information Service (NTIS)

Background: Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public he...

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



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

PubMed Central

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

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



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

PubMed Central

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

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



Sudden death, febrile seizures, and hippocampal and temporal lobe maldevelopment in toddlers: a new entity.  


Recently, we reported hippocampal and temporal lobe abnormalities in 5 toddlers with sudden unexplained death in childhood (SUDC). The association of these anomalies with a high incidence (40%) of individual/family histories of simple febrile seizures in the cases raised concern that febrile seizures can be associated with death. In a series of 64 toddlers with sudden death, we tested the hypothesis that an SUDC subset is characterized by hippocampal and temporal lobe maldevelopment and an individual and/or family history of simple familial seizures. Cases of sudden and unexplained death in children aged 1.0 to 5.9 years (median 1.7 years) were divided into groups based upon a history of febrile or nonfebrile seizures, familial febrile seizures, and autopsy classification of cause of death. Forty-nine of the 64 cases (77%) were classified as SUDC, of which 40% had an individual/family history of febrile seizures. Of the 26 SUDC cases with available hippocampal sections, 62% (16/26) had hippocampal and temporal lobe anomalies, including 82% (9/11) of cases with an individual/family history of febrile seizures. Cases with these anomalies were all found dead during a sleep period, typically in the prone (87%) position. We conclude that a potential new entity may account for the majority of SUDC in toddlers, defined by sleep-related death in the prone position, individual/family history of febrile seizures, and hippocampal and temporal lobe anomalies. The mechanism of death appears analogous to sudden death in (temporal lobe) epilepsy, with a putative unwitnessed seizure during sleep leading to airway occlusion and death. This study mandates further research into the potential link between simple febrile seizures and death. PMID:19606910

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


First febrile convulsions: inquiry about the knowledge, attitudes and concerns of the patients’ mothers  

Microsoft Academic Search

In comparison with other diseases, febrile convulsion, despite its excellent prognosis, is a cause of high anxiety among mothers.\\u000a The objective of our study was to evaluate the knowledge, concerns, attitudes and practices of the mothers of children with\\u000a first febrile convulsion. A prospective questionnaire-based study was carried out at the Mofid Children’s Hospital. One hundred\\u000a and twenty-six mothers of

Ali-Asghar Kolahi; Shahrokh Tahmooreszadeh



Permanent renal parenchymal defects after febrile UTI are closely associated with vesicoureteric reflux  

Microsoft Academic Search

The finding of scintigraphic renal defects in children with febrile urinary tract infection (UTI) even in the absence of vesicoureteric\\u000a reflux (VUR) has led to the conclusion that VUR is a weak predictor of renal defects in these patients. We used isotopic cystography\\u000a (IC) for diagnosis of VUR in children with febrile UTI. Dimercaptosuccinic acid renal scintigraphy was performed 6

Cesare Polito; Pier Francesco Rambaldi; Giuseppe Signoriello; Luigi Mansi; Angela La Manna



Medical drug utilization patterns for febrile patients in rural areas of Mexico  

Microsoft Academic Search

The objective of this study was to evaluate the medication pattern of febrile patients and determine what proportion of these drugs were included in the Mexican Essential Drugs List. A cross-sectional study was conducted in 32 rural communities located in malarial endemic areas near the Mexico-Guatemala border. Of 817 febrile patients interviewed, 55% self-medicated, while 16% consulted a physician. The

René Leyva-F; Joaquina Erviti-E; Janine M. Ramsey; Nadine Gasman



Possible contribution of interferon-alpha to febrile seizures in influenza.  


The systemic symptoms associated with influenza infection are mainly attributable to cytokines. To elucidate whether the high incidence of creatine kinase elevation and febrile seizures in influenza infection could be related to cytokines, we examined the serum levels of creatine kinase and cytokines (interferon-alpha, interleukin-6, and tumor necrosis factor-alpha) in patients with influenza and other febrile illness. Among those in the influenza group, 12 of 43 patients demonstrated elevated levels of creatine kinase (more than 200 IU/L), whereas in the control group two of 14 patients demonstrated elevated creatine kinase levels. When age was limited to under 7 years, seven of 32 patients (21.9%) in the influenza group had febrile seizures, whereas one of seven patients (14.3%) had a seizure in the control group. The influenza group demonstrated significantly high levels of interferon-alpha and interleukin-6. There was no correlation between cytokine levels and duration of fever or serum creatine kinase levels. The number of patients with high levels of interferon-alpha (>400 pg/mL) was significantly larger in the febrile seizure group than in the control group (six of seven patients in the febrile seizure group, 16 of 36 in the control group; P < 0.05). The present findings suggest the possible contribution of interferon-alpha in the pathogenesis of febrile seizures. PMID:12435568

Masuyama, Tatsuo; Matsuo, Muneaki; Ichimaru, Tomohiro; Ishii, Kiyohisa; Tsuchiya, Katsunori; Hamasaki, Yuhei



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


In September 2008, the Austrian Agency for Health and Food Safety (AGES) learned of an outbreak of diarrheal illness that included a 71-year-old patient hospitalized for gastroenteritis with a blood culture positive for Listeria monocytogenes. Three stool specimens provided by seven of 19 persons attending a day trip to a foreign city, including a final break at an Austrian tavern, yielded L. monocytogenes. All isolates were of serovar 4b and had fingerprints indistinguishable from each other. A cohort study revealed that the outbreak of gastroenteritis occurred among 16 persons who had eaten dinner at the wine tavern on September 6. Of the 15 persons who ate from platters of mixed cold-cuts, 12 (80%) developed symptoms of febrile gastroenteritis within 24-48 h. The median age of those who became ill was 62 years. A 72-year-old patient recovered from gastroenteritis but was hospitalized with bacterial meningitis on day 19 after the dinner. The epidemiological investigation identified the consumption of mixed cold-cuts (including jellied pork) at the wine tavern as the most likely vehicle of the foodborne outbreak (P = 0.0015). This hypothesis was confirmed by microbiological investigation of jellied pork produced by the tavern owner on September 3. L. monocytogenes was isolated from leftover food in numbers of 3 x 10(3)-3 x 10(4) colony forming units/g and was indistinguishable from the clinical outbreak isolates. Symptoms reported by the 12 patients included unspecified fever (12x), diarrhea (9x), headache (5x), vomiting (4x), body aches (2x) and sore throat (1x). Active case finding identified one case of rhombencephalitis (female, age 48) among another group of four guests, among whom only the patient and her asymptomatic husband had eaten jellied pork on September 6. This is the first outbreak of L. monocytogenes-associated gastroenteritis reported in Austria. The occurrence of a secondary case of meningitis (diagnosed on day 19 after consumption of jellied pork) indicates a significant risk of systemic listeriosis among elderly patients with febrile gastroenteritis caused by L. monocytogenes; antibiotic therapy should therefore be considered in such cases of documented listerial gastroenteritis. PMID:19280142

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



A study of childhood febrile convulsions with particular reference to HHV-6 infection: pathogenic considerations.  


Most febrile convulsions (FC) in infants occur during a viral infection, particularly in children of less than 3 years of age; human herpesvirus 6 (HHV-6) has an important pathogenic role. To evaluate the link between this and other viruses and FC, a group of 65 children (mean age 18.46 months, SD +/- 9.19) with a first episode of simple FC (G1) was compared with 24 children (mean age 19.29 months, SD +/- 13.17) with a febrile syndrome but without FC (G2). Virological study showed the following infections: HHV-6 in 23/65 of G1 and in 12/24 of G2, adenoviruses (ADV) in 9/65 of G1 and in 0/24 of G2, syncytial respiratory virus (SRV) in 3/28 of G1 and in 0/2 of G2, HSV-1 in 6/65 of G1 and in 1/24 of G2, cytomegalovirus (CMV) in 2/65 of G1 and in 0/24 of G2 and HHV-7 in 1/42 of G1 and in 1/13 of G2. Children in G1, statistically compared with G2, were significantly more likely to have a family history of FC and circulating granulocytes, while IgM and alpha 2-globulin were less probable. Some cytokines (IL 1 beta, TNF beta and GM-CSF) were found in 24 children in G1 and 12 in G2; no differences were found between the two groups. In the light of our data and of the recent literature, the possibility that the cytokines may act on the nervous system cannot be excluded. Among the HHV-6-infected children, those suffering from convulsions were statistically more likely to have a family history of FC and IgM, while IgA were less likely. In G1, 57 cases were followed up over 2 years: 9 of them had a second episode of FC. Virological diagnosis at the first episode of FC revealed HHV-6 infection in 3 cases, 2 of these being due to viral reactivation. We underline the important role of HHV-6 infection in FC and postulate a relationship between family history and the immunity of the patient; this is confirmed by the loss of statistical significance in the reduction of IgM in G1 compared with G2 with no family history of FC. The reactivation of FC by HHV-6 is a possibility to be borne in mind; an increased number of cases would be needed to confirm this hypothesis. PMID:8906369

Bertolani, M F; Portolani, M; Marotti, F; Sabbattini, A M; Chiossi, C; Bandieri, M R; Cavazzuti, G B



Naturally Occurring Anthracyclines  

NASA Astrophysics Data System (ADS)

The present article gives an overview of the natural occurring anthracyclines and anthracyclinones reported from microorganisms. A general description, discussion of their physicochemical properties, including NMR increments, and their structural classification are reported. In addition to a compilation of their sugar moieties, an exhaustive list of naturally occurring anthracyclines and anthracyclinones has been added.

Laatsch, Hartmut; Fotso, Serge


Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures  

Microsoft Academic Search

See commentary, “Prevention of recurrent febrile seizures”Acetaminophen and low doses of diazepam were evaluated for the prevention of recurrences of febrile seizures in a placebo-controlled, double-blind trial. Children after their first febrile seizure were assigned to receive either one dose of rectally administered diazepam, and then, after 6 hours, oral doses of 0.2 mg\\/kg three times a day for the

M. Uhari; H. Rantala; L. Vainionpää; R. Kurttila



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

Microsoft Academic Search

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.

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



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


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

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



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

PubMed Central

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



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


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

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



Distribution Of Febrile Seizure Duration And Associations With Development  

PubMed Central

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

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



Febrile seizures and mechanisms of epileptogenesis: insights from an animal model.  


Temporal lobe epilepsy (TLE) is the most prevalent type of human epilepsy, yet the causes for its development, and the processes involved, are not known. Most individuals with TLE do not have a family history, suggesting that this limbic epilepsy is a consequence of acquired rather than genetic causes. Among suspected etiologies, febrile seizures have frequently been cited. This is due to the fact that retrospective analyses of adults with TLE have demonstrated a high prevalence (20-->60%) of a history of prolonged febrile seizures during early childhood, suggesting an etiological role for these seizures in the development of TLE. Specifically, neuronal damage induced by febrile seizures has been suggested as a mechanism for the development of mesial temporal sclerosis, the pathological hallmark of TLE. However, the statistical correlation between febrile seizures and TLE does not necessarily indicate a causal relationship. For example, preexisting (genetic or acquired) 'causes' that result independently in febrile seizures and in TLE would also result in tight statistical correlation. For obvious reasons, complex febrile seizures cannot be induced in the human, and studies of their mechanisms and of their consequences on brain molecules and circuits are severely limited. Therefore, an animal model was designed to study these seizures. The model reproduces the fundamental key elements of the human condition: the age specificity, the physiological temperatures seen in fevers of children, the length of the seizures and their lack of immediate morbidity. Neuroanatomical, molecular and functional methods have been used in this model to determine the consequences of prolonged febrile seizures on the survival and integrity of neurons, and on hyperexcitability in the hippocampal-limbic network. Experimental prolonged febrile seizures did not lead to death of any of the seizure-vulnerable populations in hippocampus, and the rate of neurogenesis was also unchanged. Neuronal function was altered sufficiently to promote synaptic reorganization of granule cells, and transient and long-term alterations in the expression of specific genes were observed. The contribution of these consequences of febrile seizures to the epileptogenic process is discussed. PMID:15250596

Bender, Roland A; Dubé, Celine; Baram, Tallie Z



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


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

Kasperaviciute, Dalia; Catarino, Claudia B; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Bárbara; Hessel, Ellen V S; Hallmann, Kerstin; Hildebrand, Michael S; Dahl, Hans-Henrik M; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J; Zumsteg, Dominik; Duncan, Susan; Kälviäinen, Reetta K; Eriksson, Kai J; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M; Stogmann, Elisabeth; Zimprich, Fritz; Théâtre, Emilie; Smith, Colin; O'Brien, Terence J; Meng Tan, K; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R; Buono, Russell J; Hakonarson, Hakon; Chaves, João; Costa, Paulo P; Silva, Berta M; da Silva, António M; de Graan, Pierre N E; Koeleman, Bobby P C; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo M; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E; Berkovic, Samuel F; Weale, Michael E; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L; Kunz, Wolfram S; Sisodiya, Sanjay M



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

PubMed Central

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

Kasperaviciute, Dalia; Catarino, Claudia B.; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Barbara; Hessel, Ellen V. S.; Hallmann, Kerstin; Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P.; Dorn, Thomas; Hansen, Jorg; Kramer, Gunter; Steinhoff, Bernhard J.; Zumsteg, Dominik; Duncan, Susan; Kalviainen, Reetta K.; Eriksson, Kai J.; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M.; Stogmann, Elisabeth; Zimprich, Fritz; Theatre, Emilie; Smith, Colin; O'Brien, Terence J.; Meng Tan, K.; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R.; Buono, Russell J.; Hakonarson, Hakon; Chaves, Joao; Costa, Paulo P.; Silva, Berta M.; da Silva, Antonio M.; de Graan, Pierre N. E.; Koeleman, Bobby P. C.; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S.; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rossler, Karl; Buchfelder, Michael; Hamer, Hajo M.; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E.; Berkovic, Samuel F.; Weale, Michael E.; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L.; Kunz, Wolfram S.



Anticonvulsive Effect of Paeoniflorin on Experimental Febrile Seizures in Immature Rats: Possible Application for Febrile Seizures in Children  

PubMed Central

Febrile seizures (FS) is the most common convulsive disorder in children, but there have been no clinical and experimental studies of the possible treatment of FS with herbal medicines, which are widely used in Asian countries. Paeoniflorin (PF) is a major bioactive component of Radix Paeoniae alba, and PF-containing herbal medicines have been used for neuromuscular, neuropsychiatric, and neurodegenerative disorders. In this study, we analyzed the anticonvulsive effect of PF and Keishikashakuyaku-to (KS; a PF-containing herbal medicine) for hyperthermia-induced seizures in immature rats as a model of human FS. When immature (P5) male rats were administered PF or KS for 10 days, hyperthermia-induced seizures were significantly suppressed compared to control rats. In cultured hippocampal neurons, PF suppressed glutamate-induced elevation of intracellular Ca2+ ([Ca2+]i), glutamate receptor-mediated membrane depolarization, and glutamate-induced neuronal death. In addition, PF partially suppressed the elevation in [Ca2+]i induced by activation of the metabotropic glutamate receptor 5 (mGluR5), but not that mediated by ?-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors. However, PF did not affect production or release of ?-aminobutyric acid (GABA) in hippocampal neurons. These results suggest that PF or PF-containing herbal medicines exert anticonvulsive effects at least in part by preventing mGluR5-dependent [Ca2+]i elevations. Thus, it could be a possible candidate for the treatment of FS in children.

Hino, Hitomi; Takahashi, Hisaaki; Suzuki, Yuka; Tanaka, Junya; Ishii, Eiichi; Fukuda, Mitsumasa



Efficacy and safety of doripenem for sepsis with neutropenia in Japanese patients with hematologic diseases.  


Doripenem (DRPM) is one of the carbapenems which has a broad-spectrum and strong activity against Pseudomonas aeruginosa. This observational study was conducted between April 2006 and March 2007 in Japan to evaluate the efficacy and safety of DRPM 0.5 g three times a day for sepsis with neutropenia in patients with hematologic diseases. One hundred-nineteen patients were enrolled from 34 medical institutes, comprising 117 patients for safety evaluation and 104 for efficacy evaluation. Monotherapy of DRPM 0.5 g three times a day (DRPM monotherapy) was evaluated in 73 patients. The response rates of DRPM monotherapy at 72 hours and at Day 7 were 31.5% (23/73) and 67.1% (49/73), respectively. The incidence of adverse reactions including abnormal changes in laboratory values was 23.1%, and hepatic toxicity was most common. All of these adverse events were judged by the investigators as non-serious and tolerable. These results suggest that DRPM is useful for sepsis with neutropenia, though further study may be warranted. PMID:23259255

Akiyama, Nobu; Kanamaru, Akihisa; Tamura, Kazuo; Tanimoto, Mitsune; Ohyashiki, Kazuma; Nakagawa, Yasunori; Urabe, Akio; Masaoka, Toru



The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia.  


Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN). We screened CN (n = 395) or CyN (n = 92) patients for ELANE mutations and investigated the impact of mutations on mRNA expression, protein expression, and activity. We found 116 different mutations in 162 (41%) CN patients and 26 in 51 (55%) CyN patients, 69 of them were novel. CyN-associated mutations were predicted to be more benign than CN-associated mutations, but the mutation severity largely overlapped. The frequency of acquired CSF3R mutations, malignant transformation, and the need for hematopoietic stem cell transplantation was significantly higher in CN patients with ELANE mutation than in ELANE mutation negative patients. Cellular elastase activity was reduced in neutrophils from CN/CyN patients, irrespective of the mutation status. In CN, enzymatic activity was significantly lower in patients with ELANE mutations compared with those with wild-type ELANE. Despite differences in the spectrum of mutations in CN or CyN, type or localization of mutation only partially determine the clinical phenotype. Specific ELANE mutations have limited predictive value for leukemogenesis; the risk for leukemia was correlated with disease severity rather than with occurrence of an ELANE mutation. PMID:23463630

Germeshausen, Manuela; Deerberg, Sabine; Peter, Yvonne; Reimer, Christina; Kratz, Christian P; Ballmaier, Matthias



Neutropenia and neoplasia: an overview of the pharmacoeconomics of sargramostim in cancer therapy.  


Sargramostim is a myeloid growth factor that is widely used as adjunctive support in patients with neutropenia. Sargramostim enhances neutrophil recovery and myeloid engraftment, reduces infectious complications, and shortens the duration of hospitalization in selected patients. The high cost of sargramostim and other myeloid growth factors and their ability to reduce infections and days of hospitalization have generated interest in their pharmacoeconomic impact. Cost minimization studies in patients receiving chemotherapy for acute myelogenous leukemia and in recipients of autologous bone marrow transplantation (BMT) show estimated cost savings with sargramostim of 1996 US$12,513 and 1994 US$14,500, respectively. These data are consistent with cost savings of 1989 US$16,000 using molgramostim in autologous BMT recipients. Although no pharmacoeconomic data have been published in patients with other conditions, clinical outcomes research demonstrates a clear benefit for sargramostim administration in recipients of peripheral blood progenitor cell and allogeneic BMT and in patients who experience graft delay or failure. Because of reductions in the duration of hospitalization and infectious complications, economic outcomes of these conditions would probably also support sargramostim use. More data regarding the use of sargramostim for chemotherapy-induced neutropenia are required to properly assess the pharmacoeconomic impact in these patients. PMID:9377627

Desch, C E; Ozer, H


A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia.  


Mutations in ELA2, encoding the human serine protease neutrophil elastase, cause cyclic and severe congenital neutropenia, and recent evidence indicates that the mutations alter the membrane trafficking of neutrophil elastase. These disorders feature impaired bone marrow production of neutrophils along with excess monocytes-terminally differentiated lineages corresponding to the two alternative fates of myeloid progenitor cells. We utilized a modified yeast two-hybrid system and identified a new, widely expressed gene, N2N, whose product is homologous to Notch2, that interacts with neutrophil elastase. N2N is a 36-kDa protein distributed throughout the cell and secreted. Its amino-terminal sequence consists of several EGF repeats identical to those of the extracellular region of Notch2, and its carboxyl terminus contains a unique 24-residue domain required for interaction with neutrophil elastase. Neutrophil elastase cleaves N2N within EGF repeats in vitro and in living cells, but the C-terminal domain retards proteolysis. In vitro, N2N represses transcriptional activities of Notch proteins. Disease-causing mutations of neutrophil elastase disrupt the interaction with N2N, impair proteolysis of N2N and Notch2, and interfere with Notch2 signaling, suggesting defective proteolysis of an inhibitory form of Notch as an explanation for the alternate switching of cell fates characteristic of hereditary neutropenia. PMID:14673143

Duan, Zhijun; Li, Feng-Qian; Wechsler, Jeremy; Meade-White, Kimberly; Williams, Kayleen; Benson, Kathleen F; Horwitz, Marshall



Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of trabectedin (ET-743, Yondelis) induced neutropenia.  


Myelosuppression was found to be one of the main toxicities of trabectedin (ET-743, Yondelis) during phase I/II studies. Our objective was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model that describes the time course of the absolute neutrophil counts (ANCs) in cancer patients receiving trabectedin. Data from 699 patients who received intravenous trabectedin as monotherapy (dose range: 0.006-1.8 mg/m2) as a 1-, 3-, or 24-h infusion every 21 days; 1- or 3-h infusion on days 1, 8, and 15 every 28 days; or a 1-h infusion daily for 5 consecutive days every 21 days were used to develop (N=405; ANCs=7,291) and validate (N=294; ANCs=5,029) the model. The PK/PD model comprised a trabectedin-sensitive progenitor cell compartment, linked to the peripheral blood compartment, through three transition compartments representing the maturation chain in the bone marrow. To capture the rebound effect due to endogenous growth factors, the model included a feedback mechanism. The model estimated three system-related parameters: ANC at baseline (Circ0), mean transit time in bone marrow (MTT), and a feedback parameter (gamma). A first-order process quantified by the rate constant k(e0) described the trabectedin concentrations at the effect compartment (C(e)), which were assumed to reduce the proliferation rate and/or to increase the killing rate of the progenitor cells according to the function alphaC(e)beta. The model was qualified and simulations were undertaken to evaluate the neutropenia schedule dependency and the effects of selected covariates. NONMEM software was used to perform the modeling and simulation analyses. For a typical man of 70 kg, the mean values (between-subject variability; %) of the Circ0, MTT, gamma, k(e0), alpha, and beta were estimated to be 4.46 x 10(9)/l (37.9%), 4.0 days (37.5%), 0.218 (41.8%), 2.09 h(-1) (77.9%), 2.00 l/microg (85.1%), and 1.26, respectively. Although in women, k(e0) was reduced by 29% and a 25% increase in body weight resulted in a 12.6% reduction in the beta parameter, the clinical relevance of these effects is limited. The model evaluation procedure indicated accurate prediction of the observed incidence of neutropenia grades 3 and 4 across the dosing regimens evaluated. Simulations indicated that trabectedin dose and interdose interval, but not infusion duration, are the main determinants of the neutropenia severity. The model-predicted time course of the ANC and its variability confirmed that neutropenia is reversible, of short duration, and non-cumulative. The extent and time course of neutropenia following six different dosing regimens of trabectedin were well predicted by the semiphysiological PK/PD model. PMID:17597713

Hing, J; Perez-Ruixo, J J; Stuyckens, K; Soto-Matos, A; Lopez-Lazaro, L; Zannikos, P




Microsoft Academic Search

The objective of this study is to determine the effect of permethrin insecticide-treated bed net (PITN) use on the incidence of febrile episodes and on household malaria expenses in Benin. Over the course of one year, 208 randomly selected PITN user and non-user households were visited weekly to determine expenditures on febrile morbidity and its treatment, and to monitor spending



"Naturally occurring asbestos  

NASA Astrophysics Data System (ADS)

The term asbestos refers to six silicate minerals from amphibole and serpentine groups. By definition, it consists in bundles of thin and flexible long fibers, with high-tensile strength, and chemical and heat resistance. In contrast to asbestos found within commercial products and mining, the specific term ''naturally occurring asbestos'' (NOA) refers to asbestiform minerals occurring within rocks or soils that can be released by human activities or weathering processes. The fact that the exposure to asbestos is related to lung pathologies is now widely demonstrated (e.g. asbestosis, mesothelioma and lung cancer). However, if health risks associated with exposure to NOA exist, they are not yet well documented. The crystallization of natural asbestos occurs in specific Mg-rich lithologies associated with peculiar structural and metamorphic conditions. By recognizing and combining such specific geologic criteria, the presence or the absence of asbestos in bedrock terrains can be reasonably predicted and maps of NOA hazard can be drawn. We present here new results of geological mapping and petrological study concerning the evaluation of the NOA hazard in the Alps and Corsica, in France. The three folds approach consists in (1) a determination of lithologies with potential NOA from a bibliographic compilation and extraction of target zones from a geological geodatabase (2) a geological mapping of the target zones followed by a petrological characterization of sampled asbestiform minerals in the laboratory (optical microscopy, TEM, SEM, and Raman spectroscopy technics), and (3) the drawing of the final map of NOA hazard, at regional-scale. Occurrence criteria can be retained as follows: 1. NOA are abundant in the internal zones of the Alps and Corsica, especially within ophiolitic complexes. Natural asbestos are mostly concentrated within ultramafic rocks but can also occur within basic lithologies such as Mg-metagabbros, metabasalts and meta-pillow-lavas, 2. Asbestos is commonly located within fractures, shear-bands or shear-planes, developed during late retrograde metamorphic history, 3. Tremolite-actinolite-type asbestos is abundant both in ultramafic and mafic rocks, 4. Natural asbestos occur in few places within the external zones of the Alps, especially within hercynian ophiolitic massifs or concentrated in late Alpine fractures affecting leptyno-amphibolic lithologies.

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



Therapeutic hypothermia for febrile infection-related epilepsy syndrome in two patients.  


Despite advances in critical care, febrile infection-related epilepsy syndrome remains the most important cause of mortality and neurologic deficits during childhood. Only a few therapeutic agents were reported to shorten the acute phase and improve outcomes. Therapeutic hypothermia was reported effective in stabilizing immune activation, brain edema, and seizure activity, to protect the brain from ongoing functional, apoptotic neural, and glial damage and the systemic expansion of the cytokine storm. We present two pediatric cases of febrile infection-related epilepsy syndrome, refractory to conventional medical therapy. Moderate therapeutic hypothermia at 33°C resulted in fast, sustained control of refractory status epilepticus. After 3 months, both patients recovered with a Glasgow Outcome Scale score of 4. Therapeutic hypothermia may play an important role in children with febrile infection-related epilepsy syndrome. PMID:23127267

Lin, Jainn-Jim; Lin, Kuang-Lin; Hsia, Shao-Hsuan; Wang, Huei-Shyong



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

PubMed Central

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

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



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


We conducted a nationwide study at six tertiary hospitals from December 2008 through November 2009 to investigate etiologies of febrile illnesses in Bangladesh. Febrile patients meeting a clinical case definition were enrolled from inpatient and outpatient medicine and pediatric units. We assessed 720 febrile patients over 12 months; 69 (9.6%) were positive for IgM antibodies against dengue virus by enzyme-linked immunosorbent assay, and four malaria patients (0.56%) were confirmed with immuno-chromatography and microscopic slide tests. We identified dengue cases throughout the year from rural (49%) and urban areas (51%). We followed-up 55 accessible dengue-infected patients two months after their initial enrollment: 45 (82%) patients had fully recovered, 9 (16%) reported ongoing jaundice, fever and/or joint pain, and one died. Dengue infection is widespread across Bangladesh, but malaria is sufficiently uncommon that it should not be assumed as the cause of fever without laboratory confirmation. PMID:22232452

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



Estimating the Incidence of Typhoid Fever and Other Febrile Illnesses in Developing Countries  

PubMed Central

To measure the incidence of typhoid fever and other febrile illnesses in Bilbeis District, Egypt, we conducted a household survey to determine patterns of health seeking among persons with fever. Then we established surveillance for 4 months among a representative sample of health providers who saw febrile patients. Health providers collected epidemiologic information and blood (for culture and serologic testing) from eligible patients. After adjusting for the provider sampling scheme, test sensitivity, and seasonality, we estimated that the incidence of typhoid fever was 13/100,000 persons per year and the incidence of brucellosis was 18/100,000 persons per year in the district. This surveillance tool could have wide applications for surveillance for febrile illness in developing countries.

Youssef, Fouad G.; Luby, Stephen P.; Wasfy, Momtaz O.; Rangel, Josefa M.; Taalat, Maha; Oun, Said A.; Mahoney, Frank J.



Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis.  


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

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



Mutations in the ELANE Gene are Associated with Development of Periodontitis in Patients with Severe Congenital Neutropenia  

Microsoft Academic Search

Background  Patients with severe congenital neutropenia (SCN) often develop periodontitis despite standard medical and dental care. In\\u000a light of previous findings that mutations in the neutrophil elastase gene, ELANE, are associated with more severe neutropenic phenotypes, we hypothesized an association between the genotype of SCN and development\\u000a of periodontitis.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Fourteen Swedish patients with SCN or cyclic neutropenia harboring different genetic backgrounds

Ying Ye; Göran Carlsson; Biniyam Wondimu; Annika Fahlén; Jenny Karlsson-Sjöberg; Mats Andersson; Lars Engstrand; Tülay Yucel-Lindberg; Thomas Modéer; Katrin Pütsep


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

National Technical Information Service (NTIS)

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



Diagnosis and antimicrobial therapy of pulmonary infiltrates in febrile neutropenic patients  

Microsoft Academic Search

Patients with severe neutropenia lasting for more than 10 days, who develop fever and pulmonary infiltrates, are at high risk of treatment failure and infection-related death, under conventional broad-spectrum antibiotics. Early supplementation by a systemic antifungal therapy active against Aspergillus spp. has been shown to markedly improve their clinical outcome. Prognosis is significantly influenced by early identification of lung infiltrates

Georg Maschmeyer; Thomas Beinert; Dieter Buchheidt; Hermann Einsele; Claus Peter Heussel; Michael Kiehl; Joachim Lorenz



Procalcitonin—a sensitive inflammation marker of febrile episodes in neutropenic children with cancer  

Microsoft Academic Search

Objective  Sensitive parameters of inflammations, are rare or of limited validity in neutropenic patients. Procalcitonin (PCT) proven\\u000a to be a sensitive inflammatory marker in nonneutropenic patients was evaluated for its diagnostic relevance in febrile episodes\\u000a of neutropenic patients with cancer\\u000a \\u000a \\u000a \\u000a Methods  Plasma levels of PCT were determined by an immunoluminometric assay in children with febrile neutropenic episodes (n=376)\\u000a starting at the date

G. Fleischhack; D. Cipic; J. Juettner; C. Hasan; U. Bode



Ceftibuten versus trimethoprim-sulfamethoxazole for oral treatment of febrile urinary tract infection in children  

Microsoft Academic Search

A randomized, open, coordinated multi-center trial compared the bacteriological and clinical efficacy and safety of orally\\u000a administered ceftibuten and trimethoprim-sulfamethoxazole (TMP-SMX) in children with febrile urinary tract infection (UTI).\\u000a Children aged 1 month to 12 years presenting with presumptive first-time febrile UTI were eligible for enrolment. A 2:1 assignment\\u000a to treatment with ceftibuten 9 mg\\/kg once daily (n?=?368) or TMP-SMX (3 mg + 15 mg)\\/kg

Staffan Mårild; Ulf Jodal; Torsten Sandberg



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

Microsoft Academic Search

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

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


Early-onset neutropenia is a risk factor for Candida colonization in very low-birth-weight neonates  

Microsoft Academic Search

Neutropenia is a major risk factor for bacterial colonization and sepsis in preterm neonates in the neonatal intensive care unit (NICU), but little is known about its relationships with candidal colonization (CC) in these settings. We performed a case-control study on neonates with birth weight of <1500 g admitted to our NICU during a 7-year period (1996–2003, N = 585).

Paolo Manzoni; Daniele Farina; Cesare Monetti; Claudio Priolo; MariaLisa Leonessa; Chiara Giovannozzi; Giovanna Gomirato



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

PubMed Central

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

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



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

Microsoft Academic Search

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

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



Naturally occurring cardiac glycosides.  


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

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



Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients.  

PubMed Central

In a prospective randomized study, 120 febrile, granulocytopenic patients received as initial therapy ceftazidime with or without teicoplanin. At the onset of fever, patients had no obvious infectious focus. For 103 assessable episodes, initial bacteremias were detected in 18 of 51 patients (35%) given ceftazidime and 20 of 52 patients (38%) given the combination; 13 and 17 bacteremias caused by gram-positive bacteria occurred in these groups, respectively. There was no difference in terms of the final response (25 of 51 patients [49%] treated with ceftazidime alone versus 33 of 52 patients [63%] given the combination), and the morbidity was comparable for both treatment groups. The duration of fever and of total antibiotic therapy were similar in both groups. Initial therapy was modified in 26 patients (51%) treated with ceftazidime, with 20 surviving the infection, and in 19 patients (37%) treated with the combination, with 15 surviving. Persistent fever was the main reason for changing treatment, and no patient died of a gram-positive infection. Subsequent infective events occurred in 16 patients (31%) given ceftazidime and in 25 patients (48%) given the combination. Lung infiltrates developed in 12 and 13 patients, respectively, but more new infections occurred in the combination group. Allergic skin reactions were also more frequent in this group. Thus, while teicoplanin provides simple, reliable, and safe treatment of patients with presumed gram-positive infections, it is not useful when given empirically to this patient population, and treatment may result in more infective complications and adverse events.

Novakova, I; Donnelly, J P; De Pauw, B



Rituximab associated neutropenia: Description of three cases and an insight into the underlying pathogenesis  

PubMed Central

Summary Background To describe Rituximab associated neutropenia (RAN), and to explore its underlying mechanism. Case Report We describe three patients with RAN. The effect of patient’s plasma on colony forming unit, Granulocyte-Monocyte (CFU-GM) was measured by the addition of plasma to the culture of a healthy bone-marrow. Repeated tests were performed after recovery of white count. In the leukopenic period the patient’s plasma inhibited CFU growth completely. Control plasma did not have such an effect. Addition of patient’s cell supernatant to bone marrow cells did not change the number of CFU. The same effect was demonstrated in normal control. After recovery the patient’s plasma did not inhibit colony formation, similar to control. Conclusions RAN is a clinically significant side effect. It may take place during treatment or several months afterwards. Circulating antibodies in the plasma may be responsible for this unique BM toxicity.

Weissmann-Brenner, Alina; Brenner, Baruch; Belyaeva, Inessa; Lahav, Meir; Rabizadeh, Esther



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

PubMed Central

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

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



Electrocardiographic pattern of Brugada syndrome disclosed by a febrile illness: clinical and therapeutic implications  

Microsoft Academic Search

Background Recent studies have identified a direct link between the ionic mechanisms responsible for the electro- cardiographic (ECG) pattern of the Brugada syndrome (BS) and the in vitro experimental temperature, pointing to the possibility that some BS patients may display the ECG phenotype only during a febrile state, being in this setting at risk of lethal arrhythmias. Case report A

N. Patruno; D. Pontillo; A. Achilli; G. Ruggeri; G. Critelli


Rickettsia felis infection in febrile patients, western Kenya, 2007-2010.  


To determine previous exposure and incidence of rickettsial infections in western Kenya during 2007-2010, we conducted hospital-based surveillance. Antibodies against rickettsiae were detected in 57.4% of previously collected serum samples. In a 2008-2010 prospective study, Rickettsia felis DNA was 2.2× more likely to be detected in febrile than in afebrile persons. PMID:22304807

Maina, Alice N; Knobel, Darryn L; Jiang, Ju; Halliday, Jo; Feikin, Daniel R; Cleaveland, Sarah; Ng'ang'a, Zipporah; Junghae, Muthoni; Breiman, Robert F; Richards, Allen L; Njenga, M Kariuki



Rickettsia felis Infection in Febrile Patients, Western Kenya, 2007-2010  

PubMed Central

To determine previous exposure and incidence of rickettsial infections in western Kenya during 2007–2010, we conducted hospital-based surveillance. Antibodies against rickettsiae were detected in 57.4% of previously collected serum samples. In a 2008–2010 prospective study, Rickettsia felis DNA was 2.2× more likely to be detected in febrile than in afebrile persons.

Maina, Alice N.; Knobel, Darryn L.; Jiang, Ju; Halliday, Jo; Feikin, Daniel R.; Cleaveland, Sarah; Ng'ang'a, Zipporah; Junghae, Muthoni; Breiman, Robert F.; Richards, Allen L.




Microsoft Academic Search

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



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

Microsoft Academic Search

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

Tallie Z. Baram; Angelika Gerth; Linda Schultz



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

Microsoft Academic Search

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.

Philip R Cohen



First Case of Human "Candidatus Neoehrlichia mikurensis" Infection in a Febrile Patient with Chronic Lymphocytic Leukemia ?  

PubMed Central

An immunocompromised patient presented with febrile episodes, an erysipelas-like rash, and thromboembolic complications. Amplification of 16S rRNA gene sequences from blood and sequence analysis revealed “Candidatus Neoehrlichia mikurensis.” We report the first case of human disease caused by “Ca. Neoehrlichia mikurensis.”

Welinder-Olsson, Christina; Kjellin, Eva; Vaht, Krista; Jacobsson, Stefan; Wenneras, Christine



Association of the nicotinic receptor beta 2 subunit and febrile seizures.  


The nicotinic acetylcholine receptors are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. Mutations in neuronal nicotinic acetylcholine receptor beta 2 subunit have been associated with autosomal dominant nocturnal frontal lobe epilepsies. A major challenge is to establish whether the monogenic epilepsy gene also contributes to the common epilepsies. Because febrile seizures represent the majority of childhood seizures, and a genetic predisposition, we investigated the possibility that the nicotinic acetylcholine receptor beta 2 subunit might be involved in the etiology of febrile seizures. Children were divided into two groups: those with febrile seizures (group 1; n = 104) and control patients (group 2; n = 83). Polymerase chain reaction was used to identify the G/C and T/C polymorphisms of the nicotinic acetylcholine receptor beta 2 subunit gene, which is mapped on chromosome 1. Genotypes and allelic frequencies for nicotinic acetylcholine receptor beta 2 subunit gene polymorphisms in both groups were compared. The results indicated that genotypes and allelic frequencies in both groups were not significantly different. These data suggest that nicotinic acetylcholine receptor beta 2 subunit polymorphisms are not a useful marker for prediction of the susceptibility to febrile seizures. PMID:15033200

Peng, Ching-Tien; Chou, I-Ching; Li, Chia-Ing; Hsu, Yu-An; Tsai, Chang-Hai; Tsai, Fuu-Jen



Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction  

PubMed Central

Accepted 16 April 1997? Primary human herpesvirus 6 (HHV-6) and 7 (HHV-7) infections were identified in febrile children by qualitative and quantitative polymerase chain reaction (PCR) assays. Diagnosis was based on the differential detection of viral DNA in peripheral blood mononuclear cells (PBMC), but not in saliva. Six of 41 febrile infants, but none of seven non-febrile controls, were identified with primary infections (three HHV-6, three HHV-7). These children had significantly higher viral loads in PBMC (HHV-6, median 24 213 genomes/106 PBMC; HHV-7, median 6 040 000 genomes/106 PBMC) than DNA-aemic, saliva PCR positive children (HHV-6, median 1606 genomes/106 PBMC, p < 0.01; HHV-7, median 7089 genomes/106 PBMC, p < 0.05). Viral DNA was detected in serum by PCR in only 50% of primary infections. All three children with primary HHV-7 infection had febrile convulsions. Thus PCR, including quantitative assays, may identify primary HHV-6 and HHV-7 infections when an appropriate combination of clinical specimens is used.??

Clark, D.; Kidd, I; Collingham, K.; Tarlow, M.; Ayeni, T.; Riordan, A.; Griffiths, P.; Emery, V.; Pillay, D.



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

Richard Bachur; Marvin B. Harper



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

ERIC Educational Resources Information Center

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

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



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

Microsoft Academic Search

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

Ingrid E. Scheffer; Samuel F. Berkovic



Building-associated risk of febrile acute respiratory diseases in Army trainees  

Microsoft Academic Search

Airborne transmission of infectious agents and associations of indoor air pollutants with respiratory illnesses are well documented. We hypothesized that energy conservation measures that tighten buildings also increase risks of respiratory infection among building occupants. At four Army training centers during a 47-month period, incidence rates of febrile acute respiratory disease were compared between basic trainees in modern (energy-efficient design

J. F. Brundage; R. M. Scott; W. M. Lednar; D. W. Smith; R. N. Miller



The Clinical Characteristics and Infectious Outcomes of Febrile Infants Aged 8 to 12 Weeks  

Microsoft Academic Search

We reviewed 356 consecutive cases of febrile infants aged 8 to 12 weeks who received outpatient evaluation for sepsis over 4 years. Thirty-three infants (9.3%) had a serious bacterial infection (SBI), including bacterial meningitis, bacteremia, urinary tract infection (UTI), and Salmonella enteritis. The SBI rate, which was directly proportional to fever height, was significantly greater for infants with hyperpyrexia (35%)

William A. Bonadio; Douglas S. Smith; Svapna Sabnis



Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants  

PubMed Central

Background Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, ?0.69% (95% confidence interval [CI] ?2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI ?1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. Registration Numbers NCT01086878 (, NCT00197587 (, and NCT00270296 (

Dryden-Peterson, Scott; Jayeoba, Oluwemimo; Hughes, Michael D.; Jibril, Haruna; McIntosh, Kenneth; Modise, Taolo A.; Asmelash, Aida; Powis, Kathleen M.; Essex, Max; Shapiro, Roger L.; Lockman, Shahin



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


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

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



Investigation of an Outbreak of Acute Febrile Respiratory Illness Among Recruits at Lackland Air Force Base, TX.  

National Technical Information Service (NTIS)

A large sustained outbreak of febrile respiratory illness (FRI) began in the Fall of 1999 among basic trainees at Lackland Air Force Base, Texas. Adenovirus was quickly identified as the predominant etiologic pathogen; every isolate typed was found to be ...

M. R. Torok J. A. Benevento I. R. Heemink J. S. Neville K. M. Neuhauser



Domiciliary treatment of febrile episodes in cancer patients: a prospective randomized trial comparing oral versus parenteral empirical antibiotic treatment  

Microsoft Academic Search

Hospitalization and empirical broad-spectrum, intravenous antibiotics are the standard treatment for febrile cancer patients.\\u000a Recent evidence supports the suggestion that febrile episodes in a low-risk population can be managed successfully in an outpatient\\u000a setting, but the optimal drug regimen is unknown. In a prospective randomized clinical trial we compared ciprofloxacin 750\\u000a mg p.o. twice a day with ceftriaxone 2 g

V. Minotti; G. Gentile; G. Bucaneve; A. P. Iori; A. Micozzi; F. Cavicchi; G. Barbabietola; G. Landonio; F. Menichetti; P. Martino; A. Del Favero



Augmented currents of an HCN2 variant in patients with febrile seizure syndromes.  


The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were approximately 35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy. PMID:20437590

Dibbens, Leanne M; Reid, Christopher A; Hodgson, Bree; Thomas, Evan A; Phillips, Alison M; Gazina, Elena; Cromer, Brett A; Clarke, Alison L; Baram, Tallie Z; Scheffer, Ingrid E; Berkovic, Samuel F; Petrou, Steven



Major and minor bio-element status in children with febrile seizure.  


Febrile seizures (FS) are the most common cause of seizures in children. The exact etiopathogenesis is unknown but involves factors like genetic predisposition and alterations in the levels of neurotransmitters and some trace elements. The study includes 48 consecutive children with FS, and 55 healthy age matched control subjects. Calcium, magnesium and potassium concentrations in the febrile study group were lower than in the control group (p<0.05). Iron and Gallium levels in the study group were lower than in the control group (p<0.01). Serum Selenium (p<0.001), Zinc (p<0.001) and Strontium (p0.05). The aim of the present prospective analytical case-control study was to determine whether there was any change in element levels in children with FS (Ref. 33). PMID:22794517

Akbayram, S; Cemek, M; Büyükben, A; Aymelek, F; Karaman, S; Yilmaz, F; Dogan, M; Caksen, H



Acute febrile illness caused by hantavirus: serological and molecular evidence from India.  


Study of hantavirus infections in India is in its early stages. As early symptoms of hantavirus disease can be non-specific and the diagnosis confirmed only by laboratory testing, use of appropriate diagnostic tools is important. To improve the diagnosis of hantavirus infections in India, commercial ELISA systems followed by indirect immunofluorescence assays were used to detect anti-hantavirus IgM and IgG in samples from patients with acute febrile illness. Of 347 patients tested, 5.2% showed serological evidence of hantavirus infection. Sequences obtained from patients showing molecular evidence of hantavirus infection were related to Hantaan virus. In the absence of mu-capture ELISA, we recommend the use of combination testing systems in areas non-endemic for hantavirus infections. In India there is an increased risk of rodent-borne infections and the differential diagnosis of undifferentiated febrile illness should include hantavirus infection. PMID:19237179

Chandy, Sara; Yoshimatsu, Kumiko; Boorugu, Hari Kishan; Chrispal, Anugrah; Thomas, Kurien; Peedicayil, Abraham; Abraham, Priya; Arikawa, Jiro; Sridharan, Gopalan



Augmented Currents of an HCN2 Variant in Patients with Febrile Seizure Syndromes  

PubMed Central

The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were ~35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy.

Dibbens, Leanne M.; Reid, Christopher A.; Hodgson, Bree; Thomas, Evan A.; Phillips, Alison M.; Gazina, Elena; Cromer, Brett A.; Clarke, Alison L.; Baram, Tallie Z.; Scheffer, Ingrid E.; Berkovic, Samuel F.; Petrou, Steven



A novel syndrome with congenital neutropenia caused by mutations in G6PC3  

PubMed Central

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

Boztug, Kaan; Appaswamy, Giridharan; Ashikov, Angel; Schaffer, 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; Bellanne-Chantelot, Christine; Rezaei, Nima; Monkemoller, Kirsten; Irani-Hakimeh, Noha; Bakker, Hans; Gerardy-Schahn, Rita; Zeidler, Cornelia; Grimbacher, Bodo; Welte, Karl; Klein, Christoph



A novel HAX1 gene mutation in severe congenital neutropenia (SCN) associated with neurological manifestations.  


Autosomal recessive severe congenital neutropenia (SCN) results from a maturation arrest of granulopoiesis at the level of promyelocytes and apoptosis of myeloid cells. In SCN patients, mutations have been described in the HAX1 gene. Most of the SCN patients who carry nonsense mutations that are common to both transcript variants of the HAX1 gene also exhibit neurological deficits. This study describes an SCN patient with neurological manifestations including daily episodes of atonic seizures, learning disabilities, and developmental delay. Sequencing of the HAX1 gene of this SCN patient identified a novel nonsense c.463_464insC homozygous mutation in exon 3, which is common to both transcript variants of the gene. This mutation encodes for a p.Gln155ProfsX14 change and causes premature truncation of the HAX1 protein. Neutrophils isolated from the patient exhibited spontaneous apoptosis and loss of inner mitochondrial membrane potential, which were further enhanced upon treatment with hydrogen peroxide. This study adds to the spectrum of novel HAX1 gene mutations and disease manifestations in ethnically distinct SCN patients. Our report describes the only nonsense mutation in the HAX1 gene present in SCN patients of Arab origin. PMID:20182745

Faiyaz-Ul-Haque, Muhammad; Al-Jefri, Abdullah; Al-Dayel, Fouad; Bhuiyan, Jalaluddin A K M; Abalkhail, Hala A; Al-Nounou, Randa; Al-Abdullatif, Ahmed; Pulicat, Monogaran S; Gaafar, Ameera; Alaiya, Ayodele A; Peltekova, Iskra; Zaidi, Syed H E



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


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

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



NB1, a new neutrophil-specific antigen involved in the pathogenesis of neonatal neutropenia  

PubMed Central

A new human antigen is reported which is present only on blood neutrophils. A neutrophil-specific antigen, designated NA1, has previously been identified in two unrelated families, and was shown to be involved in fetomaternal incompatibility and the development of isoimmune neonatal neutropenia in five newborns. In the present paper, a second antigen, designated NB1, is identified in four families with seven affected children. Antibodies that react with this second antigen are shown to produce selective agglutination of neutrophils but not other blood cells. They are neither absorbed by cells prepared from solid tissues nor by non-neutrophilic blood cells. By family and population studies, NB is shown to be distinct from NA, representing an independent genetic locus. 68% of the New York population are homozygous for NB1, 29% heterozygous, and 3% negative. The NB locus is shown to be independent from those of HL-A and other known leukocyte antigens. No evidence for linkage between NA, NB, and red cell antigens was obtained.

Lalezari, Parviz; Murphy, Georgette B.; Allen, Fred H.



Hydrogen sulfide may improve the hippocampal damage induced by recurrent febrile seizures in rats  

Microsoft Academic Search

The aim of the present study was to investigate the possible role of hydrogen sulfide (H2S) in the pathogenesis of recurrent febrile seizures (FS) in rats. On a rat model of recurrent FS, the ultrastructure of hippocampal neurons, the plasma level of H2S, the expressions of cystathionine b-synthase (CBS) and c-fos, and the development of mossy fiber sprouting (MFS) in

Ying Han; Jiong Qin; Xingzhi Chang; Zhixian Yang; Xiuying Tang; Junbao Du



Electrocardiographic pattern of Brugada syndrome disclosed by a febrile illness: clinical and therapeutic implications  

Microsoft Academic Search

Background Recent studies have identified a direct link between the ionic mechanisms responsible for the electrocardiographic (ECG) pattern of the Brugada syndrome (BS) and the in vitro experimental temperature, pointing to the possibility that some BS patients may display the ECG phenotype only during a febrile state, being in this setting at risk of lethal arrhythmias.Case report A 53-year-old man

N. Patruno; D. Pontillo; A. Achilli; G. Ruggeri; G. Critelli



Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients?  

Microsoft Academic Search

Plasma concentrations of procalcitonin (PCT) have been shown to be elevated in bacterial and fungal infections. In contrast to C-reactive protein (CRP), PCT is not elevated in inflammations of noninfectious origin. Febrile inflammatory conditions are frequent in patients with hemato-oncological diseases. A reliable marker to discriminate infectious inflammations from drug-related and tumor-associated fever is still lacking. To evaluate the impact

S. Schüttrumpf; L. Binder; T. Hagemann; D. Berkovic; L. Trümper; C. Binder



Leukocyte and neutrophil counts in differential diagnosis of acute febrile conditions.  


Leukocyte and neutrophil counts are two of the commonest laboratory tests used in clinical medicine. The usefulness of the tests is still controversial. It has been found that the tests were useful to a limited extent. We performed leukocyte and neutrophil counts in patients manifesting acute febrile illness, to identify the best cut-off point in differential diagnosis of underlying disorders causing such conditions. Patients were enrolled randomly on the basis of acute febrile illness. Those who suffered from diseases affecting myeloproliferative system were excluded. Leukocyte and neutrophil counts were performed by the standard method. Diagnosis of target organ disorder was obtained from the house staff's final diagnosis. Both laboratory and clinical performance were assessed in double blind fashion. Patients were divided into 2 groups. Group 1 consisted of 47 patients with acute bacterial infections and group 2 consisted of 53 cases with acute febrile conditions caused by diverse, non-bacterial disease. Various cut off points ranging from 5,000-25,000/mm3 and 10-100 per cent were used for leukocyte and neutrophil counts. Sensitivity, specificity and Youden index for each cut off point were determined. Receiver operating characteristic (ROC) curves were constructed. It was found that sensitivity and specificity for each cut off point for both leukocyte and neutrophil counts displayed perfect trade-offs and the Youden indices were similar. The ROC curves for both counts were depicted as a 45-degree lines of non-discrimination. Leukocyte and neutrophil counts were proved to be non-discriminate of acute febrile conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1861131

Aswapokee, N; Rittimat, W



First febrile convulsions: inquiry about the knowledge, attitudes and concerns of the patients' mothers.  


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

Kolahi, Ali-Asghar; Tahmooreszadeh, Shahrokh



Empiric antimicrobial therapy of febrile neutropenic patients undergoing haematopoietic stem cell transplantation  

Microsoft Academic Search

This study was conducted to assess the efficacy and toxicity of intravenous (i.v.) ceftazidime and ciprofloxacin in neutropenic febrile patients undergoing high dose myeloablative therapy and hematopoietic stem cell transplantation (HSCT). All patients undergoing HSCT for leukaemia, lymphoma, multiple myeloma and solid tumours received open-label ceftazidime 2 g i.v. every 8 h and ciprofloxacin 400 mg i.v. every 12 h

Bassema A Antabli; Peter Bross; Robert S Siegel; Connie D Small; Imad A Tabbara



The Effect of Cold Stimulation to the Face on the Metabolic Rate of the Febrile Piglet  

Microsoft Academic Search

Sudden infant death syndrome has been associated with winter climates, infection, and overwrapping of babies. The hypothesis has been tested in this laboratory that two different causes of increased metabolic rate, high core temperature (via the van’t Hoff or ‘Q10’ effect) and face-cooling, might synergistically induce hyperthermia. This proved not to be the case. We now report on a ‘febrile

L. J. Voss; B. C. Galland; D. P. G. Bolton; B. J. Taylor



Infections in acute myeloid leukemia: an analysis of 382 febrile episodes  

Microsoft Academic Search

Neutropenic fever is an important cause of morbidity and mortality during therapy of acute myeloid leukemia (AML). We retrospectively\\u000a analyzed 382 febrile episodes encountered during induction and consolidation chemotherapy to determine the potential etiology,\\u000a microbiologic spectrum, response\\/resistance to antibiotics and outcome. Between May, 2001 and December, 2006, 95 patients\\u000a with de novo non-M3 AML received remission induction chemotherapy followed by

Ajay Gupta; Mansher Singh; Harkirat Singh; Lalit Kumar; Atul Sharma; Sameer Bakhshi; Vinod Raina; Sanjay Thulkar



Evaluating different imaging strategies in children after first febrile urinary tract infection  

Microsoft Academic Search

We conducted a retrospective multicenter review to estimate the prevalence of urological abnormalities in Chinese children\\u000a with first febrile urinary tract infection (UTI) and to evaluate the selective imaging strategy recommended by the NICE guideline\\u000a for detecting underlying abnormalities. Atypical UTI was defined as in the NICE UTI guideline. Overall, 576 boys and 244 girls\\u000a aged below 24 months were

Sik-Nin Wong; Niko Kei-Chiu Tse; Kwok-Piu Lee; So-Fun Yuen; Lettie Chuk-Kwan Leung; Benjamin Chee-Kit Pau; Winnie Kwai-Yu Chan; Kwok-Wai Lee; Hon-Ming Cheung; Stella Chim; Cynthia Mung-Sze Yip



Genes and loci involved in febrile seizures and related epilepsy syndromes  

Microsoft Academic Search

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 (GEFS1) is a familial epilepsy syndrome in which patients can have classic FS, FS that persist beyond the age of 5 years (i.e., FS1), and\\/or epilepsy. Both genetic and environmental

Dominique Audenaert; Christine Van Broeckhoven; Peter De Jonghe



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


Mutations in more than 15 genes are now known to cause severe congenital neutropenia (SCN); however, the pathologic mechanisms of most genetic defects are not fully defined. Deficiency of G6PC3, a glucose-6-phosphatase, causes a rare multisystem syndrome with SCN first described in 2009. We identified a family with 2 children with homozygous G6PC3 G260R mutations, a loss of enzymatic function, and typical syndrome features with the exception that their bone marrow biopsy pathology revealed abundant neutrophils consistent with myelokathexis. This pathologic finding is a hallmark of another type of SCN, WHIM syndrome, which is caused by gain-of-function mutations in CXCR4, a chemokine receptor and known neutrophil bone marrow retention factor. We found markedly increased CXCR4 expression on neutrophils from both our G6PC3-deficient patients and G6pc3(-/-) mice. In both patients, granulocyte colony-stimulating factor treatment normalized CXCR4 expression and neutrophil counts. In G6pc3(-/-) mice, the specific CXCR4 antagonist AMD3100 rapidly reversed neutropenia. Thus, myelokathexis associated with abnormally high neutrophil CXCR4 expression may contribute to neutropenia in G6PC3 deficiency and responds well to granulocyte colony-stimulating factor. PMID:20616219

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



Mutations in Growth Factor Independent-1 Associated with Human Neutropenia Block Murine Granulopoiesis through Colony Stimulating Factor-1  

PubMed Central

SUMMARY Severe congenital neutropenia (SCN) is characterized by a deficiency of mature neutrophils, leading to recurrent bacterial and fungal infections. Although mutations in Elastase-2, neutrophil (ELA2) predominate in human SCN, mutation of Ela2 in mice does not recapitulate SCN. The growth factor independent-1 (GFI1) transcription factor regulates ELA2. Mutations in GFI1 are associated with human SCN, and genetic deletion of Gfi1 results in murine neutropenia. We examined whether human SCN-associated GFI1N382S mutant proteins are causal in SCN and found that GFI1 functions as a rate-limiting granulopoietic molecular switch. The N382S mutation inhibited GFI1 DNA binding and resulted in a dominant-negative block to murine granulopoiesis. Moreover, Gfi1N382S selectively derepressed the monopoietic cytokine CSF1 and its receptor. Gfi1N382S–expressing Csf1?/? cells formed neutrophils. These results reveal a common transcriptional program that underlies both human and murine myelopoiesis, and that is central to the pathogenesis of SCN associated with mutations in GFI1. This shared transcriptional pathway may provide new avenues for understanding SCN caused by mutations in other genes and for clinical intervention into human neutropenias.

Zarebski, Adrian; Velu, Chinavenmeni S.; Baktula, Avinash M.; Bourdeau, Tristan; Horman, Shane R.; Basu, Sudeep; Bertolone, Salvatore J.; Horwitz, Marshal; Hildeman, David A.; Trent, John O.; Grimes, H. Leighton



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

Microsoft Academic Search

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

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



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

PubMed Central

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

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



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

PubMed Central

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

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



Emergency Department Crowding and Time to Antibiotic Administration in Febrile Infants  

PubMed Central

Introduction: Early antibiotic administration is recommended in newborns presenting with febrile illness to emergency departments (ED) to avert the sequelae of serious bacterial infection. Although ED crowding has been associated with delays in antibiotic administration in a dedicated pediatric ED, the majority of children that receive emergency medical care in the United States present to EDs that treat both adult and pediatric emergencies. The purpose of this study was to examine the relationship between time to antibiotic administration in febrile newborns and crowding in a general ED serving both an adult and pediatric population. Methods: We conducted a retrospective chart review of 159 newborns presenting to a general ED between 2005 and 2011 and analyzed the association between time to antibiotic administration and ED occupancy rate at the time of, prior to, and following infant presentation to the ED. Results: We observed delayed and variable time to antibiotic administration and found no association between time to antibiotic administration and occupancy rate prior to, at the time of, or following infant presentation (p>0.05). ED time to antibiotic administration was not associated with hospital length of stay, and there was no inpatient mortality. Conclusion: Delayed and highly variable time to antibiotic treatment in febrile newborns was common but unrelated to ED crowding in the general ED study site. Guidelines for time to antibiotic administration in this population may reduce variability in ED practice patterns.

Light, Jennifer K.; Hoelle, Robyn M.; Herndon, Jill Boylston; Hou, Wei; Elie, Marie-Carmelle; Jackman, Kelly; Tyndall, J. Adrian; Carden, Donna L.



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

PubMed Central

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

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



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


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

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



[Empirical antimicrobial therapy of infection and fever episodes in children and adolescents with neutropenia caused by cytotoxic chemotherapy].  


The experience with empirical antimicrobial therapy of septicemia and febrile episodes in pediatric neutropenic patients was analyzed retrospectively. Between January 1985 and March 1988 in 49 patients 77 episodes were observed. Bacteremia was found in 15 (20%), culture proven localized bacterial infection in 11 (14%) and clinically diagnosed bacterial infection was found in 7 (9%) of the febrile episodes. Thus, 33 (43%) documented bacterial infections were observed. For initial therapy a combination of aminoglycoside plus 2nd/3rd generation cephalosporin (60%) or aminoglycoside plus piperacillin (30%) was usually chosen. Both regimens were equally effective. 52% and 56%, respectively, were sufficiently treated with the initial regimen. 95% of all episodes resolved completely, the mortality rate was 5%. Central venous catheters remained in situ in 84% of the cases. The period of time necessary for recovery of granulopoiesis had an influence on the therapy success. PMID:2717190

Fink, F M; Frischhut-Schiffer, E M; Ausserer, B; Allerberger, F; Guggenbichler, J P



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

PubMed Central

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

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



Febrile seizures after 2010-2011 influenza vaccine in young children, United States: a vaccine safety signal from the vaccine adverse event reporting system.  


During the 2010-2011 influenza season, the Centers for Disease Control and Prevention and the Food and Drug Administration conducted enhanced vaccine safety monitoring for possible febrile seizures in all trivalent influenza vaccine (TIV) products in the United States using the Vaccine Adverse Event Reporting System (VAERS). We used Empirical Bayesian data mining techniques to assess disproportionate reporting after TIV and reviewed febrile seizure reports in children aged <5 years. On November 23, 2010, the combination of the coding term "febrile convulsion" and the Fluzone(®) TIV product exceeded a predetermined threshold in the VAERS database. By December 10, we confirmed 43 reports of febrile seizure following TIV in children aged 6-23 months. Clinical features of most reports were consistent with typical uncomplicated febrile seizures, and all children recovered. Further epidemiologic assessment of a possible association between TIV and febrile seizures was undertaken in a separate, population-based vaccine safety monitoring system. PMID:22361303

Leroy, Z; Broder, K; Menschik, D; Shimabukuro, T; Martin, D



Myasis occuring in a neonate  

PubMed Central

Myasis is the infestation of skin by larvae or maggots of a variety of flies. It is a condition that occurs more commonly in adults who are living and/or have visited tropical countries. It rarely occurs in neonates, and even when seen, only few larvae are extracted. This case report describes myasis occurring in an 11-day-old female who had 47 larvae in her skin.

Obasa, Temitope O.; Sowunmi, Funmilola Olusola



Sequence Analysis of the Human Virome in Febrile and Afebrile Children  

PubMed Central

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

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



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

PubMed Central

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

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



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

PubMed Central

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

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



Electrocardiographic findings compatible with Brugada syndrome in a patient with febrile respiratory infection.  


Brugada syndrome is an inherited autosomal dominant-type disease characterized by ST-segment abnormalities and increased fatal ventricular tachyarrhythmias. We hereby present a 57-years-old patient with no symptoms or history of cardiovascular disease, diagnosed with febrile respiratory infection (39?). Electrocardiographic (ECG) findings were typical of Brugada-like type I syndrome that gradually turned to Brugada type II and III, following fever remission, and finally became normal. Other clinical evaluation tests (echocardiographic evaluation, treadmill stress test, Holter ECG, procainamide provocation test) did not relate to Brugada syndrome. PMID:20981176

Tsarouhas, K; Papalexis, P; Kafantaris, I; Tsitsimpikou, Ch; Vavetsi, S; Rentoukas, E



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

Microsoft Academic Search

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

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



Chikungunya and Dengue Fever among Hospitalized Febrile Patients in Northern Tanzania  

PubMed Central

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

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.



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

SciTech Connect

Thirty-six patients with acquired immunodeficiency syndrome (AIDS), who were febrile but without localizing signs, underwent indium-111 leukocyte scintigraphy 24 hours after injection of labeled white blood cells (WBCs) and were restudied 48 hours after injection of gallium-67 citrate. Fifty-six abnormalities were identified as possible sources of the fever; 27 were confirmed with biopsy. Of these 27, 15 were identified only on In-111 WBC scans (including colitis, sinusitis, and focal bacterial pneumonia); six, only on Ga-67 scans (predominantly Pneumocystis carinii pneumonia and lymphadenopathy); and six, on both studies (predominantly pulmonary lesions). In-111 WBC scanning revealed 21 of 27 abnormalities (78%) and gallium scanning, 12 of 27 (44%). If only one scintigraphic study has been performed, particularly with Ga-67, a significant number of lesions would not have been detected. The authors believe radionuclide evaluation of the febrile AIDS patient without localizing signs should begin with In-111 WBC scintigraphy. Gallium scanning may be used depending on results of In-111 WBC scans or if there is a high index of suspicion for P carinii pneumonia.

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



Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes  

PubMed Central

Parasitic infection with Plasmodium falciparum is responsible for the most severe form of human malaria in which patients suffer from periodic fever. It is well established that during intra-erythrocytic maturation of the parasite in the red blood cell (RBC), the RBC becomes significantly more cytoadhesive and less deformable; these and other biochemical factors together with human host factors such as compromised immune status are important contributors to the disease pathology. There is currently substantial interest in understanding the loss of RBC deformability due to P. falciparum infection, but few results are available concerning effects of febrile conditions or parasitization on RBC membrane rheology. Here, for the first time, we report rheology of the single, isolated RBC with and without P. falciparum merozoite invasion, spanning a range from room temperature to febrile conditions (41°C), over all the stages of parasite maturation. As expected, stiffness increased with parasite maturation. Surprisingly, however, stiffness increased acutely with temperature on a scale of minutes, particularly in late trophozoite and schizont stages. This acute stiffening in late falciparum stages may contribute to fever-dependent pathological consequences in the microcirculation.

Marinkovic, Marina; Diez-Silva, Monica; Pantic, Ivan; Fredberg, Jeffrey J.; Suresh, Subra; Butler, James P.



Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes.  


Parasitic infection with Plasmodium falciparum is responsible for the most severe form of human malaria in which patients suffer from periodic fever. It is well established that during intra-erythrocytic maturation of the parasite in the red blood cell (RBC), the RBC becomes significantly more cytoadhesive and less deformable; these and other biochemical factors together with human host factors such as compromised immune status are important contributors to the disease pathology. There is currently substantial interest in understanding the loss of RBC deformability due to P. falciparum infection, but few results are available concerning effects of febrile conditions or parasitization on RBC membrane rheology. Here, for the first time, we report rheology of the single, isolated RBC with and without P. falciparum merozoite invasion, spanning a range from room temperature to febrile conditions (41 degrees C), over all the stages of parasite maturation. As expected, stiffness increased with parasite maturation. Surprisingly, however, stiffness increased acutely with temperature on a scale of minutes, particularly in late trophozoite and schizont stages. This acute stiffening in late falciparum stages may contribute to fever-dependent pathological consequences in the microcirculation. PMID:18596215

Marinkovic, Marina; Diez-Silva, Monica; Pantic, Ivan; Fredberg, Jeffrey J; Suresh, Subra; Butler, James P



Reversible Splenic Lesion in a Patient with Febrile Infection-Related Epilepsy Syndrome (FIRES).  


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

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



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

PubMed Central

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

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



A Case of Neonatal Alloimmune Neutropenia Associated with Anti-Human Neutrophil Antigen-1a (HNA-1a) Antibody  

PubMed Central

Neonatal alloimmune neutropenia (NAN) is an uncommon disease of the newborn provoked by the maternal production of neutrophil-specific alloantibodies, whereby neutrophil IgG antibodies cross the placenta and induce the destruction of fetal neutrophils. Affected newborns are usually identified by the occurrence of bacterial infections. The most frequent antigens involved in NAN are the human neutrophil antigen-1a (HNA-1a), HNA-1b, and HNA-2a. We report a neonate who was delivered at 36 weeks and had a severe neutropenia but who responded well to recombinant human granulocyte colony-stimulating factor (rhG-CSF). Anti-HNA-1a antibody was identified by mixed passive hemagglutination assay in both the sera of the baby and the mother. The baby had HNA-1a and HNA-1b but the mother had only HNA-1b on granulocytes. This is the first Korean report of NAN in which the specificity of the causative antibody was identified.

Han, Tae Hee; Chey, Myoung-Jae



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

PubMed Central

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 parasites compared to that of control group. After culture under high temperature with artesunate, the total parasite number of all strains including K1, 3D7 and PF91 was extremely decreased and the parasite was not found at the end. Additionally, the expression of pfHsp70s was found in all strains and conditions as shown in 120 kDa hybridized band. However, the proteome extracted from K1 grown under heat shock with chloroquine, anti-pfHsp70 interacted with additional three bands identified by MALDI-TOF as elongation factor-1? (83 kDa), pfHsp86 (60 kDa) and phosphoethanolamine N-methyltransferase (43 kDa). Conclusion In conclusion, febrile temperature was capable of markedly inhibiting the growth of field isolate P. falciparum while the development, reinfection rate and drug (chloroquine, mefloquine and quinine) resistant level of standard strain K1 was enhanced. However, the febrile temperature coped with chloroquine had no effect to the development, drug sensitivity and the parasite number of K1 strain. In the opposite way, heat shock and chloroquine showed extremely effect toward 3D7 and field isolate PF91 as shown by some died parasites. Heat shock protein 70 (pfHSP70) of strain K1 under heat shock with chloroquine might involved in many pathways in order to sustain the parasite.

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



Febrile reactions occurring with second cycle of high-dose melphalan and SCT in patients with AL amyloidosis: a ‘melphalan recall’ reaction  

Microsoft Academic Search

Aggressive treatment with high-dose i.v. melphalan followed by auto-SCT (HDM\\/SCT) is effective in inducing hematological and clinical remissions, and in extending survival in AL amyloidosis. Tandem cycles of HDM\\/SCT have been shown to increase hematologic complete response rates in patients with AL amyloidosis. Between April 1994 and July 2008, 57 patients with AL amyloidosis at the Boston University Medical Center

M Rosenzweig; D C Seldin; D G Remick; M Skinner; K Quillen; B Oran; K T Finn; V Sanchorawala



Cones of skin occur where hypertrophic scar occurs.  


Hypertrophic scarring is devastating for the patient, however the pathophysiology and treatment remain unknown after decades of research. The process follows deep dermal injury, occurs only on certain body parts, does not occur in the early fetus or in animals, and is a localized event. This suggests that an anatomic structure in human, deep dermis may be involved. The dermis is a matrix perforated by cones containing many structures including skin appendages and fat domes. We hypothesized that studying the cones might reveal a structure related to scarring. We examined tangential wounds from various body parts on human cadavers along with skin histology from various human body parts, the early fetus, partial thickness burns, hypertrophic scars, and two other species-rats and rabbits. We found that the cones may in fact be the structure. They exist where hypertrophic scar occurs-cheek, neck, chest, abdomen, back, buttock, arm, forearm, dorsal hand, thigh, leg, dorsal foot, helix and ear lobe. They do not exist where hypertrophic scar does not occur-scalp, forehead, concha, eyelid, palm, early fetus, and in rat, or rabbit. It also became apparent that the cones have been omitted from most considerations of skin histology. We suggest that the cones need to be studied in relation to hypertrophic scarring and restored to skin diagrams. PMID:11679135

Matsumura, H; Engrav, L H; Gibran, N S; Yang, T M; Grant, J H; Yunusov, M Y; Fang, P; Reichenbach, D D; Heimbach, D M; Isik, F F


Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia  

Microsoft Academic Search

BACKGROUND. In severe congenital neutropenia the maturation of myeloid\\u000a progenitor cells is arrested. The myelodysplastic syndrome and acute\\u000a myeloid leukemia develop in some patients with severe congenital\\u000a neutropenia. Abnormalities in the signal-transduction pathways for\\u000a granulocyte colony-stimulating factor (G-CSF) may play a part in the\\u000a progression to acute myeloid leukemia. METHODS. We isolated genomic DNA\\u000a and RNA from hematopoietic cells obtained

Fan Dong; Russell K. Brynes; Nicola Tidow; Karl Welte; Bob Löwenberg; Ivo P. Touw



Utilization of public or private health care providers by febrile children after user fee removal in Uganda  

Microsoft Academic Search

BACKGROUND: Despite investments in providing free government health services in Uganda, many caretakers still seek treatment from the drug shops\\/private clinics. The study aimed to assess determinants for use of government facilities or drug shops\\/private clinics for febrile illnesses in children under five. METHODS: Structured questionnaires were administered to caretakers in 1078 randomly selected households in the Iganga – Mayuge

Elizeus Rutebemberwa; George Pariyo; Stefan Peterson; Goran Tomson; Karin Kallander



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

Microsoft Academic Search

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

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



Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison  

Microsoft Academic Search

Goals: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are im- portant issues. Several strategies have been reported to be similarly effective: monotherapy with cefe- pime, ceftazidime or a carbapenem or duotherapy with an antipseudo- monal ?-lactam antibiotic or ceftri- axone in combination with an ami- noglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting

M. Gorschlüter; C. Hahn; A. Fixson; U. Mey; C. Ziske; E. Molitor; R. Horré; T. Sauerbruch; G. Marklein; I. G. H. Schmidt-Wolf; A. Glasmacher



Functional Variant in Complement C3 Gene Promoter and Genetic Susceptibility to Temporal Lobe Epilepsy and Febrile Seizures  

Microsoft Academic Search

BackgroundHuman mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make

Sarah Jamali; Annick Salzmann; Nader Perroud; Magali Ponsole-Lenfant; Jennifer Cillario; Patrice Roll; Nathalie Roeckel-Trevisiol; Ariel Crespel; Jorg Balzar; Kurt Schlachter; Ursula Gruber-Sedlmayr; Ekaterina Pataraia; Christoph Baumgartner; Alexander Zimprich; Fritz Zimprich; Alain Malafosse; Pierre Szepetowski; Francesc Palau



The Predictive and Diagnostic Values of Procalcitonin and C-Reactive Protein for Clinical Outcome in Febrile Neutropenic Patients  

Microsoft Academic Search

Background. Procalcitonin (PCT) represents a new marker of systemic inflamma- tory reactions to bacterial infections. The main aim in this study was to determine the diagnostic value of PCT in predicting the clinical severity of febril neutropenic at- tacks, compare it with that of C-reactive protein (CRP), and clarify its importance in culture-positive attacks. Methods. Between February 2001 and April

Nilgun Erten; Sema Genc; Sevgi K Besisik; Bulent Saka; M Akif Karan



Microsoft Academic Search

A computer program has been written to assist medical personnel in the diagnosis of eruptions with fever. Thirty-four criteria are utilized in the diagnosis of 33 clinical entities. Diagnosis is based on template analysis, Bayesian statistical analysis, or a combination of the two. Of 97 cases of febrile illnesses with eruption, 62 were documented diagnoses within the universe of the

Terrv P Hadiley; Daniel. E. Geer; S. B. Howard; L. Bleich; Irwin M. Freedberg



The relationship of transient hemiparesis following febrile convulsions in infancy to subsequent temporal lobectomy for intractable seizures.  

PubMed Central

Nine patients with transient hemiparesis following a febrile convulsion were part of a group of 71 patients undergoing temporal lobectomy with mesial temporal sclerosis or non-specific changes in the specimen. There was no gross evidence of additional brain damage in tests before surgery and their response to surgery was as good as the 62 patients without this history.

Darkins, A; Polkey, C E



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


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

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



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

PubMed Central

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

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



Interleukin-1beta contributes to the generation of experimental febrile seizures.  


Fever can provoke "febrile" seizures (FS). Because complex FS may promote development of temporal lobe epilepsy, understanding their mechanisms is clinically important. Using an immature rodent model and transgenic technology, we examined the role of interleukin-1beta, (IL-1beta), a pyrogenic, proinflammatory cytokine, in FS. IL-1beta receptor-deficient mice were resistant to experimental FS. This resistance appeared independent of genetic background and was attributed to lack of IL-1beta signaling, because exogenous cytokine reduced seizure threshold in wild-type but not receptor-deficient mice independent of strain. In addition, high IL-1beta doses induced seizures only in IL-1beta receptor-expressing mice. These data indicate that IL-1beta signaling contributes critically to fever-induced hyperexcitability underlying FS, constituting a potential target for their prevention. PMID:15622539

Dubé, Celine; Vezzani, Annamaria; Behrens, Marga; Bartfai, Tamas; Baram, Tallie Z



Isolated febrile seizures are not associated with structural abnormalities of the limbic system.  


The nature of the relationship between childhood febrile seizures (CFSs) and temporal lobe epilepsy (TLE) remains unknown. The purpose of this study was to perform a comprehensive analysis of measures of structural changes of the hippocampus and limbic white matter to determine whether structural abnormalities previously demonstrated in TLE were present in adults with isolated CFS. Twenty-three adults with past CFS but no history of nonfebrile seizures and 21 controls underwent research MRI for measurement of volume, T2 and mean diffusivity of the hippocampus and fractional anisotropy of the fornix and cingulum. No significant group differences were found in any of the measured parameters. These findings suggest that structural abnormalities of the hippocampus and limbic white matter that have been demonstrated in TLE are not associated with isolated CFS. PMID:23021381

Gong, Gaolang; Alexander, Ryan P D; Shi, Feng; Beaulieu, Christian; Gross, Donald W



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


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

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



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


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

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



Different imaging strategies in febrile urinary tract infection in childhood. What, when, why?  


Urinary tract infections (UTIs) are a common problem in childhood. During the last decade, published papers led to a deep revision in the use and usefulness of imaging tools in children with febrile UTIs. This new body of knowledge was partially endorsed by the guidelines published in 2007 by the UK's National Institute for Clinical Excellence and in 2011 by the American Academy of Pediatrics. Nevertheless, new data continuously arise and the scientific debate always revives. Recommendations of published guidelines and strengths and weaknesses of the available biochemical and imaging tools are here critically analysed for giving to the reader a complete, up-to-date and flexible overview on this hot topic. PMID:23525769

De Palma, Diego; Manzoni, Gianantonio



Unsuspected dengue and acute febrile illness in rural and semi-urban southern Sri Lanka.  


Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults. PMID:22304972

Reller, Megan E; Bodinayake, Champika; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara-Arachichi, Wasantha; Strouse, John J; Broadwater, Anne; Østbye, Truls; de Silva, Aravinda; Woods, Christopher W



Neurogenic pulmonary edema and acute respiratory distress syndrome in a healthy child with febrile status epilepticus.  


Neurogenic pulmonary edema is a clinical syndrome that manifests as an acute onset of pulmonary edema in the setting of a central nervous system injury, without cardiac dysfunction. Neurogenic pulmonary edema is rare in children, and the mechanism is still not completely understood.  The clinical pathology overlaps with acute lung injury and acute respiratory distress syndrome. The authors report a case of a 14-month-old previously healthy child who presented with febrile status epilepticus, fulminant neurogenic pulmonary edema, and acute respiratory distress syndrome.  Neurogenic pulmonary edema should be considered in the differential diagnosis for the rapid progression of respiratory failure following an acute neurological injury such as status epilepticus in a child. Prompt respiratory support and treatment of the acute neurological insult can prevent further cerebral hypoxemic injury. PMID:22899797

Nguyen, Thanh T; Hussain, Elora; Grimason, Michele; Goldstein, Joshua; Wainwright, Mark S



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

PubMed Central

Background Uganda embraced the World Health Organization guidelines that recommend a universal 'test and treat' strategy for malaria, mainly by use of rapid diagnostic test (RDT) and microscopy. However, little is known how increased parasitological diagnosis for malaria influences antibiotic treatment among patients with febrile illness. Methods Data collection was carried out within a feasibility trial of presumptive diagnosis of malaria (control) and two diagnostic interventions (microscopy or RDT) in a district of low transmission intensity. Five primary level health centres (HCs) were randomized to each diagnostic arm (diagnostic method in a defined group of patients). All 52,116 outpatients (presumptive 16,971; microscopy 17,508; and RDT 17,638) aged 5 months to ninety five years presenting with fever (by statement or measured) were included. Information from outpatients and laboratory registers was extracted weekly from March 2010 to July 2011. The proportion of patients who were prescribed antibiotics was calculated among those not tested for malaria, those who tested positive and in those who tested negative. Results Seven thousand and forty (41.5%) patients in the presumptive arm were prescribed antibiotics. Of the patients not tested for malaria, 1,537 (23.9%) in microscopy arm and 810 (56.2%) in RDT arm were prescribed antibiotics. Among patients who tested positive for malaria, 845 (25.8%) were prescribed antibiotics in the RDT and 273(17.6%) in the microscopy arm. Among patients who tested negative for malaria, 7809 (61.4%) were prescribed antibiotics in the RDT and 3749 (39.3%) in the microscopy arm. Overall the prescription of antibiotics was more common for children less than five years of age 5,388 (63%) compared to those five years and above 16798 (38.6%). Conclusion Prescription of antibiotics in patients with febrile illness is high. Testing positive for malaria reduces antibiotic treatment but testing negative for malaria increases use of antibiotics. Trial Registration NCT00565071



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

PubMed Central

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

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



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


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

Whiskey, Eromona; Olofinjana, Olubanke; Taylor, David



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

Microsoft Academic Search

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

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



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

PubMed Central

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

Mavroudi, Irene; Papadaki, Helen A.



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


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

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



Intravascular catheter-related bloodstream infection caused by Abiotrophia defectiva in a neutropenic child.  


Bacteraemia and endocarditis are the most frequently reported clinical infections due to Abiotrophia defectiva species. This species has been rarely implicated in infections in neutropenic patients. We report a rare case of long-term venous catheter-related infection caused by A. defectiva that occurred in a febrile child who had neutropenia and Langerhans' cell histiocytosis. PMID:23378563

Phulpin-Weibel, A; Gaspar, N; Emirian, A; Chachaty, E; Valteau-Couanet, D; Gachot, B





A well defined group of rod-like and coccoid organisms arranged in pairs and chains has been encountered in sour milk. The group comprises at least three species; the largest number ferment dextrose, lactose, maltose, mannitol, and salicin, and fail to ferment saccharose, raffinose, and inulin. A smaller number ferment saccharose in addition to dextrose, lactose, maltose, mannitol, and salicin. A few fail to attack mannitol. All three types grow luxuriantly at room temperature, coagulate milk, reduce litmus, and produce large amounts of acid in fermented bouillon containing dextrose. Specific morphological and cultural differences exist between the lactic acid streptococci and those associated with mastitis and those occurring in the udder. The lactic acid organisms outgrow the udder streptococci in the milk-souring process. When both types are implanted in sterile milk the udder type soon disappears. PMID:19868477

Jones, F S



Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia  

Microsoft Academic Search

Heterozygous mutations in neutrophil elastase have been detected in many sporadic cases of congenital neutrope- nia. However, a convincing pathoge- netic mechanism has not been estab- lished, and it is unclear whether the effects of the mutant enzyme occur within the cell of production or are paracrine in nature. The healthy father of a patient was demonstrated to be mosaic

Phil J. Ancliff; Rosemary E. Gale; Michael J. Watts; Ri Liesner; Ian M. Hann; Stephan Strobel; David C. Linch


Hemodialysis-Associated Neutropenia and Hypoxemia: The Effect of Dialyzer Membrane Materials  

Microsoft Academic Search

The fall in white blood cells (WBC) and arterial oxygen pressure that occurs during hemodialysis was investigated as a function of different dialysis membranes and different sterilization methods. 8 chronic hemodialysis patients were studied and each was dialyzed with three different membranes: cellulosic hollow fiber, polyacrylonitrile flat sheet and polymethylmethacrylate hollow fiber. Each dialyzer was studied with a dry sterilization

Raymond M. Hakim; Edmund G. Lowrie



Caffeine, a naturally occurring acaricide.  


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

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



Serological evidence of arboviral infection and self-reported febrile illness among U.S. troops deployed to Al Asad, Iraq  

PubMed Central

SUMMARY Understanding the epidemiology of current health threats to deployed U.S. troops is important for medical assessment and planning. As part of a 2004 study among U.S. military personnel deployed to Al Asad Air Base, in the western Anbar Province of Iraq, over 500 subjects were enrolled, provided a blood specimen, and completed a questionnaire regarding history of febrile illness during this deployment (average ?4 months in country). This mid-deployment serum was compared to pre-deployment samples (collected ?3 months prior to deployment) and evaluated for seroconversion to a select panel of regional arboviral pathogens. At least one episode of febrile illness was reported in 84/504 (17%) of the troops surveyed. Seroconversion was documented in nine (2%) of deployed forces tested, with no association to febrile illness. Self-reported febrile illness was uncommon although often debilitating, and the risk of illness due to arbovirus infections was relatively low.




Modulating effect of hydrogen sulfide on gamma-aminobutyric acid B receptor in recurrent febrile seizures in rats  

Microsoft Academic Search

Hydrogen sulfide (H2S) is recognized as a new neuromodulator in regulating various brain functions. Some of our recent studies showed that H2S alleviates the hippocampal damage induced by recurrent febrile seizures (FS). In the present study, we used a rat model of recurrent FS and found that sodium sulfhydrate (NaHS, a donor of H2S) down-regulated the expression of c-fos and

Ying Han; Jiong Qin; Xingzhi Chang; Zhixian Yang; Dingfang Bu; Junbao Du



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

Microsoft Academic Search

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




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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

BACKGROUND: Community distribution of anti-malarials and antibiotics has been recommended as a strategy to reduce the under-five mortality due to febrile illnesses in sub-Saharan Africa. However, drugs distributed in these interventions have been considered weak by some caretakers and utilization of community medicine distributors has been low. The aim of the study was to explore caretakers' use of drugs, perceptions

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



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

Microsoft Academic Search

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

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


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


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

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



Simple Prognostic Criteria can Definitively Identify Patients who Develop Severe Versus Non-Severe Dengue Disease, or Have Other Febrile Illnesses  

PubMed Central

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. Conclusions This is the first report of simple definitively prognostic criteria for SDD patients, including the first assessment and confirmation of conjunctival injection. The three definitive clinical criteria used alone, or supported by the other four criteria, could be essential for specifically identifying those patients needing prompt hospital-based therapies to lessen or avert SDD, without unnecessary hospitalization of the other patients. Keywords Dengue virus; Severe dengue; Dengue fever; Diagnostic; Criteria; Hemorrhage; Shock

Falconar, Andrew K.I.; Romero-Vivas, Claudia M.E.



Scientific investigations into febrile reactions observed in the paediatric population following vaccination with a 2010 Southern Hemisphere Trivalent Influenza Vaccine.  


During the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in the number of febrile reactions reported in the paediatric population in Australia shortly after vaccination with the CSL 2010 trivalent influenza vaccine (TIV) compared to previous seasons. A series of scientific investigations were initiated to identify the root cause of these adverse events, including in vitro cytokine/chemokine assays following stimulation of adult and paediatric whole blood, as well as mammalian cell lines and primary cells, profiling of molecular signatures using microarrays, and in vivo studies in rabbits, ferrets, new born rats and rhesus non-human primates (NHPs). Various TIVs (approved commercial vaccines as well as re-engineered TIVs) and their individual monovalent pool harvest (MPH) components were examined in these assays and in animal models. Although the scientific investigations are ongoing, the current working hypothesis is that the increase in febrile adverse events reported in Australia after vaccination with the CSL 2010 SH TIV may be due to a combination of both the introduction of three entirely new strains in the CSL 2010 SH TIV, and differences in the manufacturing processes used to manufacture CSL TIVs compared to other licensed TIVs on the market. Identification of the causal component(s) may result in the identification of surrogate assays that can assist in the formulation of TIVs to minimise the future incidence of febrile reactions in the paediatric population. PMID:23063831

Maraskovsky, Eugene; Rockman, Steve; Dyson, Allison; Koernig, Sandra; Becher, Dorit; Morelli, Adriana Baz; Barnden, Megan; Camuglia, Sarina; Bodle, Jesse; Vandenberg, Kirsten; Wang, I-Ming; Cristescu, Razvan; Loboda, Andrey; Citron, Mike; Fontenot, Jane; Hung, Derchieh; Schoofs, Peter; Pearse, Martin



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

PubMed Central

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

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



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


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

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



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

PubMed Central

Background: Adenosine Deaminase (ADA) has been suggested to be an important enzyme which is associated with the cell mediated immunity, but its clinical significance in typhoid fever has not yet been characterized. The present study was taken up to evaluate the serum ADA activity in patients of typhoid fever. The levels of ADA were also measured in the patients who were suffering from other febrile illnesses. Material and Method: This was a case control study. The subjects who were included in this study were divided into 3 groups. Group A consisted of 50 normal healthy individuals who served as the controls. Group B consisted of 50 patients, both males and females of all age groups, who were suffering from culture positive typhoid fever. Group C consisted of 50 patients who were suffering from febrile illnesses other than typhoid fever like viral fever, gastro enteritis, malaria, tonsillitis, upper respiratory tract infections, etc. The serum levels of ADA were estimated in all the subjects who were under study. Results: The serum ADA level was found to be increased in the patients of typhoid fever as compared to that in those with other febrile illnesses and in the controls. Conclusion: From the present study, it can be concluded that there was a statistically significant increase in the serum ADA levels in the patients with typhoid.

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



A study on the serum adenosine deaminase activity in patients with typhoid Fever and other febrile illnesses.  


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

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



Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing  

PubMed Central

Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ?40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.

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



Seroprevalence of antibodies against Chikungunya, Dengue, and Rift Valley fever viruses after febrile illness outbreak, Madagascar.  


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

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



A comprehensive analysis of 174 febrile patients admitted to okayama university hospital.  


Primary care physicians often encounter patients with fever of unknown origin and without apparent causes. Recent advances in laboratory medicine have facilitated diagnostic procedures;however, it is still difficult to determine the critical febrile factor at an early stage. We reviewed the medical records of 174 patients who were admitted due to a chief complaint of fever (?37.5?) to our hospital during the period from 2004 to 2010. The patients were categorized into patients with infection, inflammation, neoplasm and drug-induced fever. Based on the analysis done by category, it was revealed that the patient's age, body temperature and duration of fever were closely related to the final diagnosis. Serum CRP levels were significantly low in the nonbacterial infection group, while serum levels of sIL-2R were high in neoplasm and drug-induced cases. CRP level on admission was weakly but significantly correlated with body temperature, while duration of fever was inversely related to body temperature. The effectiveness of PET-CT and tissue biopsy for diagnosis was considerably high, particularly in the categories of neoplasm and nonspecific inflammation, respectively, though the effectiveness of bacterial culture was low. Thus, a careful review of physical and laboratory information including body temperature, CRP level, duration of fever, gender difference and history of medication is indispensable for diagnosis. Stepwise categorization and disease classification by comprehensive and systemic checkup are very helpful for determining the causes of fever. PMID:23970321

Ryuko, Hiromasa; Otsuka, Fumio



Serial MRI after experimental febrile seizures: altered T2 signal without neuronal death.  


Whereas most febrile seizures (FSs) carry a benign outcome, a subpopulation of individuals with prolonged FSs are at risk for later temporal lobe epilepsy. Signal changes on magnetic resonance imaging (MRI) may provide early markers for changes in neuronal integrity that may promote epileptogenesis in such individuals. Here, we used serial MRIs, obtained before and at several time points after experimental prolonged FSs, to determine the prevalence and distribution of signal changes on T2-weighted images and to investigate the pathological substrates leading to these changes. Seventy-five percent of immature rats with experimental prolonged FSs had abnormal T2 signal enhancement at 24 hours, and 87.5% at 8 days after the seizures. The altered T2 values involved the dorsal hippocampus (75%), the piriform cortex (87.5%), and the amygdala (25%). However, these changes were not accompanied by evidence of neuronal injury or death in these regions, as assessed using the Fluoro-Jade method. Thus, experimental prolonged FSs lead to relatively frequent abnormal MRI signal in "temporal lobe" structures. Although these changes do not signify cell death, they may denote pathological cellular processes that promote epileptogenesis. . PMID:15389889

Dubé, Céline; Yu, Hon; Nalcioglu, Orhan; Baram, Tallie Z



Serum hepcidin: indication of its role as an "acute phase" marker in febrile children  

PubMed Central

Background Hepcidin is classified as a type II acute phase protein; its production is a component of the innate immune response to infections. Objective To evaluate the alterations of serum hepcidin in children during and following an acute febrile infection. Materials and methods 22 children with fever of acute onset (< 6?hours) admitted to the 2nd Department of Pediatrics-University of Athens. Based on clinical and laboratory findings our sample formed two groups: the viral infection group (13 children) and the bacterial infection group (9 children). Hepcidin, ferritin and serum iron measurements were performed in all subjects. Results Serum hepcidin values did not differ notably between children with viral and bacterial infection, but a significant reduction of hepcidin was noted in both groups post-infection. Conclusion Our study provides clinical pediatric data on the role of hepcidin in the face of an acute infection. In our sample of children, hepcidin was found to rise during the acute infection and fall post-infection.



Dengue fever as an acute febrile disease after overseas travel: a report of two cases.  


Dengue fever (DF) is a relatively common infection in travelers, with about 100 cases being reported annually in Japan, and this number is increasing. We herein describe two patients who developed a fever after returning to Japan from Southeast Asia and who were serologically diagnosed with DF. Patient 1 was a 19-year-old man who spent 6 days in Thailand and developed diarrhea and a fever after returning to Japan. Virological studies showed dengue virus (DV) serotype 3 by reverse transcriptase PCR (RT-PCR), and anti-DV IgM and IgG antibodies were both positive by enzyme-linked immunosorbent assay (ELISA). Patient 2 was a 43-year-old man who spent time in various Asian countries and developed a fever and arthralgia after returning to Japan. Virological studies showed DV serotype 2 by RT-PCR, and anti-DV IgM and IgG antibodies were both positive by ELISA. DF and other febrile diseases, including Chikungunya fever, should be strongly suspected in patients who develop fever after returning to Japan from other Asian countries, irrespective of whether patients remember being bitten by mosquitoes. PMID:21519135

Tarumoto, Norihito; Abe, Yoshinobu; Yamaguchi, Toshiyuki; Takasaki, Tomohiko; Kurane, Ichiro; Maesaki, Shigefumi



[Imaging and follow-up of children with first febrile Urinary Tract Infection (UTI)].  


Urinary tract infection (UTI) in children might, in a minority of cases, cause renal scarring and permanent damage. Known risk factors for renal damage are: obstruction to urinary flow, vesicoureteric reflux and recurrent infections. The current recommendations for imaging and follow-up of children with first febrile UTI include renal ultrasound to rule out anatomic abnormalities, particularly obstruction, cystography for possible diagnosis of vesicoureteric reflux, and prophylactic antibiotic therapy to prevent recurrent infections in children with detected reflux. DMSA renal scanning for the detection of renal scars is recommended as part of the imaging protocol by some institutions. Recently, published data doubts the importance of the various imaging techniques, as well as the effectiveness of prophylactic antibiotic therapy. In the current review, the role of renal ultrasound is examined, especially with regards to familiar data from fetal ultrasound. The complex relationship between vesicoureteric reflux and renal scarring is presented, with the possible implications on the importance of performing routine cystography and DMSA scanning after UTI. Studies questioning the effectiveness of prophylactic antibiotic therapy emphasize the importance of rapid diagnosis and therapy of suspected recurrent UTI as the preferred approach to prevent renal damage. Imaging studies are only recommended for high risk groups and not as a routine following UTI. PMID:20073403

Grossman, Zachi; Miron, Dan



Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study.  


The adult patients who, between July 2001 and June 2002, presented at any of five hospitals in Thailand with acute febrile illness in the absence of an obvious focus of infection were prospectively investigated. Blood samples were taken from all of the patients and checked for aerobic bacteria and leptospires by culture. In addition, at least two samples of serum were collected at different times (on admission and 2-4 weeks post-discharge) from each patient and tested, in serological tests, for evidence of leptospirosis, rickettsioses, dengue and influenza. The 845 patients investigated, of whom 661 were male, had a median age of 38 years and a median duration of fever, on presentation, of 3.5 days. Most (76.5%) were agricultural workers and most (68.3%) had the cause of their fever identified, as leptospirosis (36.9%), scrub typhus (19.9%), dengue infection or influenza (10.7%), murine typhus (2.8%), Rickettsia helvetica infection (1.3%), Q fever (1%), or other bacterial infection (1.2%). The serological results indicated that 103 (12.2%) and nine (1%) of the patients may have had double and triple infections, respectively. Leptospirosis and rickettsioses, especially scrub typhus, were thus found to be major causes of acute, undifferentiated fever in Thai agricultural workers. PMID:16762116

Suttinont, C; Losuwanaluk, K; Niwatayakul, K; Hoontrakul, S; Intaranongpai, W; Silpasakorn, S; Suwancharoen, D; Panlar, P; Saisongkorh, W; Rolain, J M; Raoult, D; Suputtamongkol, Y



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


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

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



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

SciTech Connect

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (/sup 3/H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.

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



Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients  

Microsoft Academic Search

The duration of neutropenia (absolute neutrophil count (ANC) ?100\\/?l) identifies cancer patients at risk for infection. A test that precedes ANC?100\\/?l would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based

M L Grazziutti; L Dong; M H Miceli; M Cottler-Fox; S G Krishna; A Fassas; F van Rhee; B M Barlogie; E J Anaissie



Studies of human natural killer cells. III. Neutropenia associated with unusual characteristics of antibody-dependent and natural killer cell-mediated cytotoxicity  

Microsoft Academic Search

A 52-year-old Caucasian man with chronic neutropenia and recurrent infections was found to have an increased proportion of peripheral T lymphocytes having Fc receptors for IgG (T(?). Although levels of antibody-dependent cell-mediated cytotoxicity (ADCC) and “natural” killing (NK) by unfractionated lymphocytes were similar to those of a control donor, the frequency of NK cells was markedly increased. Removal of E

Hugh F. Pross; Joseph Pater; Isaac Dwosh; Alan Giles; Lucy A. Gallinger; Peter Rubin; William E. N. Corbett; Peter Galbraith; Malcolm G. Baines



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

Microsoft Academic Search

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 (³H-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

Kozo Yasui; Munehiro Yamazaki; Yukiaki Miyagawa; Atsushi Komiyama; Taro Akabane



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


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

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



Neutropenia is a risk factor for gram-negative bacillus bacteremia in human immunodeficiency virus-infected patients: results of a nested case-control study.  


A previous cohort study demonstrated a relation between neutropenia and bacteremia due to gram-negative bacilli among patients infected with human immunodeficiency virus (HIV). To explore further the relation between neutropenia and bacteremia due to Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa among HIV-infected patients, controlling for confounding factors, the authors conducted a nested case-control study with matching and risk-set sampling of controls. The cohort included 1,645 HIV-infected patients followed at the University of California, San Diego, Medical Center in San Diego, California, between 1991 and 1995. Absolute neutrophil count (ANC) was summarized as mean ANC during the 7-day interval preceding the index date of bacteremia. Covariates were ascertained by medical record review. The matching ratio was 6:1 (controls:cases). Odds ratios were estimated using conditional logistic regression. Forty-four incident cases of bacteremia were identified. After adjustment for covariates, the estimated odds ratio for the effect of neutropenia (ANC=500 vs. >500/microl) during the 7 days preceding the index date was 8.1 (95% confidence interval confidence interval 1.5-43.1). The rate of bacteremia due to E. coli, K. pneumoniae, or P. aeruginosa is increased eightfold if the average current-week ANC is less than or equal to 500/microl compared with more than 500/microl. PMID:9867263

Mathews, W C; Caperna, J; Toerner, J G; Barber, R E; Morgenstern, H



Mossy fiber plasticity and enhanced hippocampal excitability, without hippocampal cell loss or altered neurogenesis, in an animal model of prolonged febrile seizures.  


Seizures induced by fever (febrile seizures) are the most frequent seizures affecting infants and children; however, their impact on the developing hippocampal formation is not completely understood. Such understanding is highly important because of the potential relationship of prolonged febrile seizures to temporal lobe epilepsy. Using an immature rat model, we have previously demonstrated that prolonged experimental febrile seizures render the hippocampus hyperexcitable throughout life. Here we examined whether (1) neuronal loss, (2) altered neurogenesis, or (3) mossy fiber sprouting, all implicated in epileptogenesis in both animal models and humans, were involved in the generation of a pro-epileptic, hyperexcitable hippocampus by these seizures. The results demonstrated that prolonged experimental febrile seizures did not result in appreciable loss of any vulnerable hippocampal cell population, though causing strikingly enhanced sensitivity to hippocampal excitants later in life. In addition, experimental febrile seizures on postnatal day 10 did not enhance proliferation of granule cells, whereas seizures generated by kainic acid during the same developmental age increased neurogenesis in the immature hippocampus. However, prolonged febrile seizures resulted in long-term axonal reorganization in the immature hippocampal formation: Mossy fiber densities in granule cell- and molecular layers were significantly increased by 3 months (but not 10 days) after the seizures. Thus, the data indicate that prolonged febrile seizures influence connectivity of the immature hippocampus long-term, and this process requires neither significant neuronal loss nor altered neurogenesis. In addition, the temporal course of the augmented mossy fiber invasion of the granule cell and molecular layers suggests that it is a consequence, rather than the cause, of the hyperexcitable hippocampal network resulting from these seizures. PMID:12722980

Bender, Roland A; Dubé, Celine; Gonzalez-Vega, Rebeca; Mina, Erene W; Baram, Tallie Z



Interleukin-6 primarily produced by non-hematopoietic cells mediates the lipopolysaccharide-induced febrile response.  


Interleukin-6 (IL-6) is critical for the lipopolysaccharide (LPS)-induced febrile response. However, the exact source(s) of IL-6 involved in regulating the LPS-elicited fever is still to be identified. One known source of IL-6 is hematopoietic cells, such as monocytes. To clarify the contribution of hematopoietically derived IL-6 to fever, we created chimeric mice expressing IL-6 selectively either in cells of hematopoietic or, conversely, in cells of non-hematopoietic origin. This was performed by extinguishing hematopoietic cells in wild-type (WT) or IL-6 knockout (IL-6 KO) mice by whole-body irradiation and transplanting them with new stem cells. Mice on a WT background but lacking IL-6 in hematopoietic cells displayed normal fever to LPS and were found to have similar levels of IL-6 protein in the cerebrospinal fluid (CSF) and in plasma and of IL-6 mRNA in the brain as WT mice. In contrast, mice on an IL-6 KO background, but with intact IL-6 production in cells of hematopoietic origin, only showed a minor elevation of the body temperature after peripheral LPS injection. While they displayed significantly elevated levels of IL-6 both in plasma and CSF compared with control mice, the increase was modest compared with that seen in LPS injected mice on a WT background, the latter being approximately 20 times larger in magnitude. These results suggest that IL-6 of non-hematopoietic origin is the main source of IL-6 in LPS-induced fever, and that IL-6 produced by hematopoietic cells only plays a minor role. PMID:23827828

Hamzic, Namik; Tang, Yanjuan; Eskilsson, Anna; Kugelberg, Unn; Ruud, Johan; Jönsson, Jan-Ingvar; Blomqvist, Anders; Nilsberth, Camilla



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

PubMed Central

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

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



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


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

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


Hydrogen Sulfide and Carbon Monoxide Are in Synergy with Each Other in the Pathogenesis of Recurrent Febrile Seizures  

Microsoft Academic Search

Summary  \\u000a \\u000a \\u000a \\u000a 1. \\u000a The purpose of the present study was to investigate the interaction between hydrogen sulfide (H2S) and carbon monoxide (CO) during recurrent febrile seizures (FS)\\u000a \\u000a \\u000a \\u000a 2. \\u000a H2S and CO are important intra- and intercellular messengers, regulating various brain functions. Our recent studies showed\\u000a that both of them alleviate the hippocampal damage induced by recurrent FS. In the present study,

Ying Han; Jiong Qin; Xingzhi Chang; Zhixian Yang; Junbao Du



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


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

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



Molecular analysis of Anaplasma phagocytophilum isolated from patients with febrile diseases of unknown etiology in China.  


Although anaplasmosis cases have been nationally identified in China, no human isolates of A. phagocytophilum have been obtained, which limits the analysis of any molecular and genetic contributions to patients' severe clinical manifestations and the study of the bacteria's pathogeneses in China. Given this situation, a joint project was conducted in 2009-2010. A total of 421 febrile cases of unknown etiology were collected and the patients' blood samples were collected for laboratory diagnoses including serologic diagnosis based on the four-fold rise in the anti- A. phagocytophilum IgG titer by indirect micro-immunofluorescence assay (IFA), positive PCR assay and confirmation of A. phagocytophilum DNA and positive culture of A. phagocytophilum and confirmed by amplification and sequencing of the 16S rRNA and ank A genes of the A. phagocytophilum isolates. A total of 570 ticks were collected from the patients' domestic animals (456) and from wild fields (114) for culturing and amplifying and sequencing the 16S rRNA gene of A. phagocytophilum. Phylogenetic analyses were performed on the 16S rRNA and ank A gene sequences of the isolates and the ticks tested in the study. A total of 46 (10.9%) confirmed and 16 (3.8%) probable cases were diagnosed and severe clinical features and higher mortality rates were observed in these Chinese patients. Five isolates were obtained and the 16S rRNA genes of the 5 isolates were conserved but variety for ank A genes. Two human isolates and 1 tick isolate from Shandong Peninsula, where all patients exhibited severe clinical manifestations, were grouped as one clan based on the phylogenetic analyses, while 2 other human isolates were clustered in a second clan. 43.5% of H. longicornis were infected with A. phagocytophilum.The present study is the first to obtain clinical isolates of A. phagocytophilum in China. The diversity of the ank A genes of Chinese isolates will help us to further discern the relationship between the variations in the ank A genes and the severity of the disease's clinical manifestations in China. PMID:23451170

Zhang, Lijuan; Wang, Guiqiang; Liu, Qinghui; Chen, Chuangfu; Li, Jun; Long, Bo; Yu, Hong; Zhang, Zhilun; He, Jing; Qu, Zhangyi; Yu, Jiguang; Liu, Yuanni; Dong, Tuo; Yao, Na; Wang, Yong; Cheng, Xueqin; Xu, Jianguo



Application of a modified bioassay for monitoring serum teicoplanin and vancomycin in febrile neutropenic patients.  

PubMed Central

Teicoplanin is a glycopeptide antibiotic with a mode of action and spectrum of activity similar to those of vancomycin. Its efficacy and tolerability as empiric therapy and its pharmacokinetic properties in neutropenic patients are being studied in a double-blinded, randomized trial in comparison with those of vancomycin. We report here a modified agar diffusion bioassay which is suitable for monitoring levels of either teicoplanin or vancomycin in serum during combination therapy with beta-lactams, aminoglycosides, and amphotericin B. Serum samples spiked with either teicoplanin or vancomycin gave reproducible results (mean coefficient of variation, 8.8%) regardless of the presence of tobramycin, amikacin, piperacillin, ceftazidime, amphotericin B, or their combinations. Among 25 patients who received teicoplanin at a dosing schedule of 6 mg/kg every 24 h intravenously, steady state was reached after 14.2 +/- 4.0 days, and 1-h peak and trough concentrations of teicoplanin in serum at steady state were 40.8 +/- 15.0 and 12.5 +/- 3.2 mg/liter, respectively. In contrast, among 25 patients who received vancomycin at a dosing schedule of 15 mg/kg every 12 h intravenously, steady state was reached by 24 h, and the 1-h peak and trough concentrations in serum were 37.5 +/- 15.6 and 8.3 +/- 3.8 mg/liter, respectively. The elimination half-lives for teicoplanin estimated by two separate approaches agreed closely with each other: 80.5 +/- 21.5 h by an accumulation model (M. Gilbaldi and D. Perrier, Pharmacokinetics, 2nd ed., p. 121, 1982) and 87.3 +/- 19.3 h as predicted from the degree of renal function (M. Rowland, Clin. Pharmacokinetic 18:184-209, 1990). These values were 14- to 15-fold higher than that for vancomycin (5.6 +/- 1.8 h). Since considerable variability was noted in the pharmacokinetic parameters for both teicoplanin and vancomycin among the individual patients, our data further emphasized the need for frequent monitoring of these drugs during empiric therapy of the febrile neutropenic patient.

Kureishi, A; Jewesson, P J; Bartlett, K H; Cole, C D; Chow, A W



Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4) phenotype  

PubMed Central

Background Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4) is caused by autosomal recessive mutations in SLC45A2. Methods We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature. Results The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37?years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood. Conclusions This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.



Comparison between thermoregulatory effects mediated by alpha 1- and alpha 2-adrenoceptors in normothermic and febrile rabbits.  


1. In order to better delineate the profile of thermoregulatory action of alpha 1-adrenoceptor antagonists; corynanthine (CRN) and BMY 20064 (BMY), and alpha 2-adrenoceptor agonist; medetomidine (MDT) and B-HT 920 (BHT), the effect of intravenous administration of two doses of these drugs on rectal (Tre) and ear skin (Te) temperatures, metabolic rate (M), respiratory evaporative heat loss (Eres) and respiratory rate (Rr) were examined in febrile and non-febrile rabbits. 2. Results indicate that alpha 1-adrenoceptor antagonists as well as alpha 2-adrenoceptor agonists markedly lowered body temperature exhibiting antipyretic and hypothermic actions. The hypothermic and antipyretic effect after the CRN or BMY, and BHT or MDT, treatment was associated with inhibition of metabolic rate and/or with body heat redistributed to peripheral tissues and an increase of the potential for heat loss to the environment. 3. BMY also abolished the thermogenic response to cold. However, BMY did not affect metabolic heat production on exposure to a cold ambient temperature. This unexpected phenomenon is difficult to explain at the present moment. Possible mechanisms responsible for the thermoregulatory activity of BMY are discussed. 4. These results indicate that alpha 1- and alpha 2-adrenoceptor drugs' thermoregulatory actions are similar in event and suggest that both subtypes of alpha-adrenoceptor might be implicated functionally in a variety of thermoregulatory processes. PMID:7901115

Szreder, Z



Prevalence of PCR detectable malaria infection among febrile patients with a negative Plasmodium falciparum specific rapid diagnostic test in Zanzibar.  


We screened for malaria in 594 blood samples from febrile patients who tested negative by a Plasmodium falciparum-specific histidine-rich protein-2-based rapid diagnostic test at 12 health facilities in Zanzibar districts North A and Micheweni, from May to August 2010. Screening was with microscopy, polymerase chain reaction (PCR) targeting the cytochrome b gene (cytbPCR) of the four major human malaria species, and quantitative PCR (qPCR). The prevalence of cytbPCR-detectable malaria infection was 2% (12 of 594), including 8 P. falciparum, 3 Plasmodium malariae, and 1 Plasmodium vivax infections. Microscopy identified 4 of 8 P. falciparum infections. Parasite density as estimated by microscopy or qPCR was > 4,000 parasites/?L in 5 of 8 cytbPCR-detectable P. falciparum infections. The infections that were missed by the rapid diagnostic test represent a particular challenge in malaria elimination settings and highlight the need for more sensitive point-of-care diagnostic tools to improve case detection of all human malaria species in febrile patients. PMID:23249688

Baltzell, Kimberly A; Shakely, Deler; Hsiang, Michelle; Kemere, Jordan; Ali, Abdullah Suleiman; Björkman, Anders; Mårtensson, Andreas; Omar, Rahila; Elfving, Kristina; Msellem, Mwinyi; Aydin-Schmidt, Berit; Rosenthal, Philip J; Greenhouse, Bryan



Local cytokine induction by LPS in the rat air pouch and its relationship to the febrile response.  


Peripheral induction of cytokines is a critical event in the induction of febrile responses. The sequence of induction and site of action of these cytokines, however, remain unclear. The objective of the present study was to investigate the kinetics of local and systemic production of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), with the aim of identifying the relationship between these cytokines and the febrile response induced by injection of lipopolysaccharide (LPS) into a subcutaneous air pouch in the rat. Intrapouch injection of LPS induced dose-dependent fevers and increases in the concentration of bioactive IL-6 in the plasma. Further studies using 100 microg/kg LPS demonstrated significant increases in local (air pouch) concentrations of bioactive IL-1, TNF and IL-6, and circulating IL-6. No significant increases in TNF or IL-1 were detected in the plasma of the same animals. Local TNF was induced rapidly and peaked 1 h after LPS injection. The kinetics of local IL-1 and IL-6 induction were similar and both peaked after 3 h. The rise in local IL-6 preceded that of plasma IL-6 and reached a peak concentration that was 25-fold higher than that observed in the plasma. The data indicate that IL-1 and TNF act locally at the site of inflammation and that locally induced IL-6 is the important systemic mediator of the response. PMID:9087647

Miller, A J; Luheshi, G N; Rothwell, N J; Hopkins, S J



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

PubMed Central

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

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



Effects of perineural capsaicin treatment of the abdominal vagus on endotoxin fever and on a non-febrile thermoregulatory event.  


Following perineural capsaicin pretreatment of the main trunks of the abdominal vagus of rats, the first and the second phases of the polyphasic febrile response to intravenous lipopolysaccharide were unaltered, while the third phase of fever course (peak at 5 h) was attenuated. In rats desensitized by intraperitoneal (i.p.) capsaicin (i.e. abdominal non-systemic desensitization), mainly the first but not the later fever phases were reduced. The postprandial hyperthermia to intragastric injection of BaSO4 suspension was attenuated by either i.p. or perineural capsaicin treatment. It is concluded that, in contrast to the accepted model of postprandial hyperthermia, which is mediated by capsaicin-sensitive fibers of the abdominal vagus, in the early phase of polyphasic fever the vagal afferent nerves appear to play no role. The influence of i.p. capsaicin-desensitization on this initiating fever phase is independent of the vagus, and a capsaicin-induced alteration of endotoxin action in the liver, prior to vagal nerve endings, is more likely. The late febrile phase is probably influenced by efferent vagal fibers, which might be damaged more easily by perineural than i.p. capsaicin treatment. PMID:16262998

Pétervári, Erika; Garami, András; Pákai, Eszter; Székely, Miklós



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

PubMed Central

Background For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM) to induce neutropenia. Although high doses (350–450 mg/kg) are still used and their effects on mouse leukocytes have been described, a lower dose (250 mg/kg) is widely preferred today, but the characteristics and applicability of this approach in outbred mice have not been determined. Methods Fifteen female ICR mice were injected intraperitoneally with 150 and 100 mg/kg of CPM on days 1 and 4, respectively. Blood samples (~160 ?L) were drawn from the retro-orbital sinus of each mouse on days 1, 4, 5, 6, 7 and 11. Leukocytes were counted manually and the number of granulocytes was based on microscopic examination of Wright-stained smears. The impact of neutropenia induced by this method was then determined with a variety of pathogens in three different murine models of human infections: pneumonia (Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus), meningoencephalitis (S. pneumoniae), and the thigh model (S. aureus, Escherichia coli, Bacteroides fragilis). Results The basal count of leukocytes was within the normal range for outbred mice. On day 4, there was an 84% reduction in total white blood cells, and by day 5 the leukopenia reached its nadir (370 ± 84 cells/mm3). Profound neutropenia (?10 neutrophils/mm3) was demonstrated at day 4 and persisted through days 5 and 6. Lymphocytes and monocytes had a 92% and 96% decline between days 1 and 5, respectively. Leukocytes recovered completely by day 11. Mice immunosupressed under this protocol displayed clinical and microbiological patterns of progressive and lethal infectious diseases after inoculation in different organs with diverse human pathogens. Conclusion A CPM total dose of 250 mg/kg is sufficient to induce profound and sustained neutropenia (<10 neutrophils/mm3) at least during 3 days in outbred mice, is simpler than previously described methods, and allows successful induction of infection in a variety of experimental models.

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



Allergies and Asthma: They Often Occur Together  


... may be reprinted for personal, noncommercial use only. Allergies and asthma: They often occur together By Mayo ... not share your e-mail address Sign up Allergies and asthma: They often occur together Allergies and ...


Inequalities in Care-seeking for Febrile Illness of Under-five Children in Urban Dhaka, Bangladesh  

PubMed Central

Fever is an easily-recognizable primary sign for many serious childhood infections. In Bangladesh, 31% of children aged less than five years (under-five children) die from serious infections, excluding confirmed acute respiratory infections or diarrhoea. Understanding healthcare-seeking behaviour for children with fever could provide insights on how to reduce this high rate of mortality. Data from a cross-sectional survey in the catchment areas of two tertiary-level paediatric hospitals in Dhaka, Bangladesh, were analyzed to identify the factors associated with the uptake of services from trained healthcare providers for under-five children with reported febrile illness. Health and demographic data were collected in a larger study of 7,865 children using structured questionnaires. Data were selected from 1,290 of these under-five children who were taken to any healthcare provider for febrile illness within two months preceding the date of visit by the study team. Certified doctors were categorized as ‘trained’, and other healthcare providers were categorized as ‘untrained’. Healthcare-seeking behaviours were analyzed in relation to these groups. A wealth index was constructed using principal component analysis to classify the households into socioeconomic groups. The odds ratios for factors associated with healthcare-seeking behaviours were estimated using logistic regression with adjustment for clustering. Forty-one percent of caregivers (n=529) did not seek healthcare from trained healthcare providers. Children from the highest wealth quintile were significantly more likely [odds ratio (OR)=5.6, 95% confidence interval (CI) 3.4-9.2] to be taken to trained healthcare providers compared to the poorest group. Young infants were more likely to be taken to trained healthcare providers compared to the age-group of 4-<5 years (OR=1.6, 95% CI 1.1-2.4). Male children were also more likely to be taken to trained healthcare providers (OR=1.5, 95% CI 1.2-1.9) as were children with decreased level of consciousness (OR=5.3, 95% CI 2.0-14.2). Disparities across socioeconomic groups and gender persisted in seeking quality healthcare for under-five children with febrile illness in urban Dhaka. Girls from poor families were less likely to access qualified medical care. To reduce child mortality in the short term, health education and behaviour-change communication interventions should target low-income caregivers to improve their recognition of danger-signs; reducing societal inequalities remains an important long-term goal.

Bennett, Catherine M.; Luby, Stephen P.



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


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


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

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



Dengue nonstructural protein 1 antigen in the urine as a rapid and convenient diagnostic test during the febrile stage in patients with dengue infection.  


A total of 136 matched serum and urine samples obtained from 55 patients with dengue infection and 30 other febrile illnesses were assayed for dengue nonstructural protein 1 (NS1) antigen. The urine NS1 ELISA was positive in patients with dengue fever (68.4%) and dengue hemorrhagic fever (63.9%), whereas the strip method showed a lower positive rate. PMID:21996098

Chuansumrit, Ampaiwan; Chaiyaratana, Wathanee; Tangnararatchakit, Kanchana; Yoksan, Sutee; Flamand, Marie; Sakuntabhai, Anavaj



The Role of Local Induction of Tumor Necrosis Factor by LPS within a Subcutaneous Air Pouch in the Development of a Febrile Response in Guinea Pigs  

Microsoft Academic Search

In rats, fever can be induced by injection of bacterial lipopolysaccharide (LPS) into a subcutaneous air pouch. This febrile response is in part dependent on the local action of interleukin-1? within the pouch. In the present study, we tried to find out if this model of fever induction can be applied in guinea pigs and if the local LPS-induced formation

Joachim Roth; Birgit Störr; Dave Martin; Karlheinz Voigt; Eugen Zeisberger



Using women advocacy groups to enhance knowledge and home management of febrile convulsion amongst mothers in a rural community of Sokoto State, Nigeria  

PubMed Central

Introduction Febrile convulsions (FC) are a common paediatric problem worldwide. Between 1 and 4% of children will have a febrile convulsion with about 4% of cases arising before the age of six months. Although FC is benign and does not cause death, brain damage or learning disorders, it is quite frightening to observers and parents who witness an episode of FC, would think the child is going to die. Methods This was a quasi-experimental study (a pre and post-test interventional, one group), aimed at assessing the impact of health education on knowledge and home management of febrile convulsion amongst mothers in a rural community in North Western Nigeria. A one in three samples of fifty mothers that met the eligibility criteria where selected using systematic random sampling. Structured interviewer administered questionnaire with close and open-ended questions was administered to obtain data at pre- and post intervention. Results The ages of the mothers ranged from 18-47 with a mean age of 33 ± 7.14years. The perceived causes of febrile convulsion included fever (28%), witch craft (80%) with majority (98%) of the mothers administering traditional medications. Proportion of study subjects with adequate knowledge of febrile convulsion at baseline and post intervention were 4% (mean knowledge score of 35.3± 9.48) and 96.0% (mean knowledge score of 77.69 ± 10.75) respectively (P < 0.0001). Conclusion Although inadequate knowledge and inappropriate home practices about FC were rampant in the study community, using community members to teach and sensitize the mothers on FC improved their knowledge base significantly. The use of effective educational intervention programmes and parental support groups will go a long way in reducing the incidence of FC among children in our communities.

Oche, Oche Mansur; Onankpa, Oloche Ben



Acetaminophen and Diphenhydramine Premedication for Allergic and Febrile Non-hemolytic Transfusion Reactions: Good Prophylaxis or Bad Practice?  

PubMed Central

Febrile non-hemolytic and allergic reactions are the most common transfusion reactions, but usually do not cause significant morbidity. In an attempt to prevent these reactions, US physicians prescribe acetaminophen or diphenhydramine premedication before more than 50% of blood component transfusions. Acetaminophen and diphenhydramine are effective therapies for fever and allergy respectively, so their use in transfusion has some biologic rationale. However, these medications also have potential toxicity, particularly in ill patients, and in the studies performed to date, they have failed to prevent transfusion reactions. Whether the benefits of routine prophylaxis with acetaminophen and diphenhydramine outweigh their risks and cost requires re-examination, particularly in light of the low reaction rates reported at many institutions even when pre-medication is not prescribed.

Geiger, Terrence L.; Howard, Scott C.



Radiographic Evaluation of Children with Febrile Urinary Tract Infection: Bottom-Up, Top-Down, or None of the Above?  

PubMed Central

The proper algorithm for the radiographic evaluation of children with febrile urinary tract infection (FUTI) is hotly debated. Three studies are commonly administered: renal-bladder ultrasound (RUS), voiding cystourethrogram (VCUG), and dimercapto-succinic acid (DMSA) scan. However, the order in which these tests are obtained depends on the methodology followed: bottom-up or top-down. Each strategy carries advantages and disadvantages, and some groups now advocate even less of a workup (none of the above) due to the current controversies about treatment when abnormalities are diagnosed. New technology is available and still under investigation, but it may help to clarify the interplay between vesicoureteral reflux, renal scarring, and dysfunctional elimination in the future.

Prasad, Michaella M.; Cheng, Earl Y.



[Place of malaria among febrile illnesses in two ethnic tribes living in sympatry in Mali from 1998 to 2008].  


In Africa, malaria is responsible for 25-40% of all outpatient visits and 20-50% of all hospitalizations. In malaria-endemic areas, individuals do not behave the same toward the outcome of clinical malaria. The aim of this study is to determine the prevalence of malaria in the locality among the different ethnic groups, evaluate the place of malaria among febrile illnesses, and assess the relationship between fever and parasite density of Plasmodium falciparum. Studies on susceptibility to malaria between the Fulani and Dogon groups in Mali were conducted in Mantéourou and the surrounding villages from 1998 to 2008. We carried out six cross-sectional studies during the malaria transmission and longitudinal surveys (July to December depending on the year) during the 10-year duration. In longitudinal studies, clinical data on malaria and other diseases frequently observed in the population were recorded. It appears from this work that malaria is the leading cause of febrile syndromes. We observed a significant reduction in malaria morbidity in the study population from 1998 to 2008. The pyrogenic threshold of parasitaemia was 1,000 parasites/mm(3) of blood in the Dogon and 5,000 parasites/mm(3) of blood in the Fulani.We have also found that high parasitical densities were not always associated with fever. Malaria morbidity was higher among the Dogon than in Fulani. The immunogenetic factors might account for this difference in susceptibility to malaria between Fulani and Dogon in the area under study. With regard to this study, it is important to take into account the ethnic origin of subjects when interpreting data of clinical and malarial vaccine trials. PMID:22932999

Dolo, A; Maïga, B; Dara, V; Tapily, A; Tolo, Y; Arama, C; Daou, M; Doumbo, O



Likely Health Outcomes for Untreated Acute Febrile Illness in the Tropics in Decision and Economic Models; A Delphi Survey  

PubMed Central

Background Modelling is widely used to inform decisions about management of malaria and acute febrile illnesses. Most models depend on estimates of the probability that untreated patients with malaria or bacterial illnesses will progress to severe disease or death. However, data on these key parameters are lacking and assumptions are frequently made based on expert opinion. Widely diverse opinions can lead to conflicting outcomes in models they inform. Methods and Findings A Delphi survey was conducted with malaria experts aiming to reach consensus on key parameters for public health and economic models, relating to the outcome of untreated febrile illnesses. Survey questions were stratified by malaria transmission intensity, patient age, and HIV prevalence. The impact of the variability in opinion on decision models is illustrated with a model previously used to assess the cost-effectiveness of malaria rapid diagnostic tests. Some consensus was reached around the probability that patients from higher transmission settings with untreated malaria would progress to severe disease (median 3%, inter-quartile range (IQR) 1–5%), and the probability that a non-malaria illness required antibiotics in areas of low HIV prevalence (median 20%). Children living in low transmission areas were considered to be at higher risk of progressing to severe malaria (median 30%, IQR 10–58%) than those from higher transmission areas (median 13%, IQR 7–30%). Estimates of the probability of dying from severe malaria were high in all settings (medians 60–73%). However, opinions varied widely for most parameters, and did not converge on resurveying. Conclusions This study highlights the uncertainty around potential consequences of untreated malaria and bacterial illnesses. The lack of consensus on most parameters, the wide range of estimates, and the impact of variability in estimates on model outputs, demonstrate the importance of sensitivity analysis for decision models employing expert opinion. Results of such models should be interpreted cautiously. The diversity of expert opinion should be recognised when policy options are debated.

Lubell, Yoel; Staedke, Sarah G.; Greenwood, Brian M.; Kamya, Moses R.; Molyneux, Malcolm; Newton, Paul N.; Reyburn, Hugh; Snow, Robert W.; D'Alessandro, Umberto; English, Mike; Day, Nick; Kremsner, Peter; Dondorp, Arjen; Mbacham, Wilfred; Dorsey, Grant; Owusu-Agyei, Seth; Maitland, Kathryn; Krishna, Sanjeev; Newton, Charles; Pasvol, Geoffrey; Taylor, Terrie; von Seidlein, Lorenz; White, Nicholas J.; Binka, Fred; Mills, Anne; Whitty, Christopher J. M.



Clinical and laboratory features that discriminate dengue from other febrile illnesses: a diagnostic accuracy study in Rio de Janeiro, Brazil  

PubMed Central

Background Dengue is an acute febrile illness caused by an arbovirus that is endemic in more than 100 countries. Early diagnosis and adequate management are critical to reduce mortality. This study aims to identify clinical and hematological features that could be useful to discriminate dengue from other febrile illnesses (OFI) up to the third day of disease. Methods We conducted a sectional diagnostic study with patients aged 12 years or older who reported fever lasting up to three days, without any evident focus of infection, attending an outpatient clinic in the city of Rio de Janeiro, Brazil, between the years 2005 and 2008. Logistic regression analysis was used to identify symptoms, physical signs, and hematological features valid for dengue diagnosis. Receiver-operating characteristic (ROC) curve analyses were used to define the best cut-off and to compare the accuracy of generated models with the World Health Organization (WHO) criteria for probable dengue. Results Based on serological tests and virus genome detection by polymerase chain reaction (PCR), 69 patients were classified as dengue and 73 as non-dengue. Among clinical features, conjunctival redness and history of rash were independent predictors of dengue infection. A model including clinical and laboratory features (conjunctival redness and leukocyte counts) achieved a sensitivity of 81% and specificity of 71% and showed greater accuracy than the WHO criteria for probable dengue. Conclusions We constructed a predictive model for early dengue diagnosis that was moderately accurate and performed better than the current WHO criteria for suspected dengue. Validation of this model in larger samples and in other sites should be attempted before it can be applied in endemic areas.



Naturally occurring, optically driven, cellular rotor  

NASA Astrophysics Data System (ADS)

We report the conversion of optical energy into mechanical energy by naturally occurring red blood cells (RBCs) placed in an optical trap. A trapped RBC undergoes folding due to the elastic nature of its cell membrane. On use of circularly polarized light in the trap, the folded RBCs rotate, indicating their birefringence. The cellular rotation speed depends on the size of the blood cells and on laser power. Rotating RBCs have implications for naturally occurring, optically driven, rotary micromachines.

Dharmadhikari, J. A.; Roy, S.; Dharmadhikari, A. K.; Sharma, S.; Mathur, D.



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

PubMed Central

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



Observation of Patients with Vesicoureteral Reflux Off Antibiotic Prophylaxis: Physician Bias on Patient Selection and Risk Factors for Recurrent Febrile Urinary Tract Infection  

PubMed Central

Purpose Observation off continuous antibiotic prophylaxis is an option for vesicoureteral reflux. We evaluated the characteristics of patients observed off continuous antibiotic prophylaxis and risk factors for febrile urinary tract infection. Materials and Methods We identified children 1 to 18 years old with primary vesicoureteral reflux between January 1, 2010 and December 31, 2010. We excluded patients with prior surgical correction from analysis. We recorded age, gender, race/ethnicity, primary language, insurance carrier, age at vesicoureteral reflux diagnosis, initial presentation and vesicoureteral reflux severity. We quantified bladder and bowel dysfunction with a validated questionnaire if toilet trained. We compared patients off vs on continuous antibiotic prophylaxis with the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. We used a univariate Cox proportional hazards model to assess predictors of febrile urinary tract infection during observation off continuous antibiotic prophylaxis. Results Of 529 eligible patients 224 were observed off continuous antibiotic prophylaxis. Patients off continuous antibiotic prophylaxis tended to be older (p < 0.001), to be older at diagnosis (p < 0.001), to have an initial presentation other than febrile urinary tract infection (p = 0.05), to have nondilating vesicoureteral reflux on most recent cystogram (p <0.001) and to have lower bladder/bowel dysfunction scores if toilet trained (p < 0.001). Of the patients off continuous antibiotic prophylaxis a febrile urinary tract infection developed in 19 (8.5%). Risk factors associated with febrile urinary tract infection included initial presentation of multiple febrile urinary tract infections (p = 0.03), older age at diagnosis (p = 0.03) and older age starting observation off continuous antibiotic prophylaxis (p = 0.0003). Conclusions Criteria to select patients with vesicoureteral reflux for observation off continuous antibiotic prophylaxis remain poorly defined in the literature. Observation will fail in a subset of patients with vesicoureteral reflux. Physician biases regarding patient selection for observation off continuous antibiotic prophylaxis should be considered when interpreting studies that evaluate treatment strategies.

Drzewiecki, Beth A.; Thomas, John C.; Pope, John C.; Adams, Mark C.; Brock, John W.; Tanaka, Stacy T.



Nosocomial Febrile Illness in the Elderly: Frequency, Causes, and Risk Factors  

Microsoft Academic Search

Objective: To determine the frequency, causes, and risk factors of NFI in elderly inpatients. Methods: This prospective study involved 608 pa- tients ($65 years of age) admitted in an acute geriatric unit. Investigators followed this cohort until 1 of the fol- lowing events occurred: development of NFI, discharge from the geriatric unit, or death. The cause of NFI was classified

Christophe Trivalle; Philippe Chassagne; Marc Bouaniche; Isabelle Landrin; Isabelle Marie; Nadir Kadri; Jean-Francois Menard; Jean-Francois Lemeland; Jean Doucet; Eric Bercoff



Why does vasodilatation occur during syncope?  


1. Syncopal or near syncopal episodes have been observed in five subjects who stood or were tilted and in whom blood samples were being taken. 2. In all subjects bradycardia and hypotension developed before the onset of symptoms. Increases in plasma adrenaline concentrations occurred in all subjects, beginning before the faint. Changes in plasma noradrenaline concentrations were variable: in three subjects there was a marked fall and in the other two subjects an increase. Plasma vasopressin increased in all subjects. 3. Increase in plasma adrenaline may be contributing to the vasodilatation and arterial hypotension which occur during syncope. PMID:3356108

Robinson, B J; Johnson, R H



Hidradenoma Papilliferum Occurring on the Nasal Skin  

PubMed Central

Hidradenoma papilliferum is a rare benign neoplasm that usually occurs in the female anogenital area. We present a 43-year-old female with a non-anogenital (ectopic) hidradenoma papilliferum on her nose. The patient had had a skin-colored subcutaneous nodule on her nose for 7 years. The histopathological findings showed variously shaped cystic spaces in the tumor. And the lumina were surrounded by a single or double layer of cell which showed decapitation secretion. In the English dermatological literature, only one case of ectopic hidradenoma papilliferum arising in nasal skin has been reported. Hence we suggest hidradenoma papilliferum occurring on the nasal skin is a peculiar and interesting event.

Lee, Hyun-Jae; Jung, So Young; Hong, Soon Kwon; Seo, Jong Keun; Sung, Ho Suck



Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene  

PubMed Central

In irinotecan (CPT-11)-based chemotherapy, neutropenia and diarrhea are often induced. In the present study, the clinical significance of the concentration ratios of 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronide (SN-38G) and SN-38 in the plasma in predicting CPT-11-induced neutropenia was examined. A total of 17 patients with colorectal cancer and wild-type UDP-glucuronosyltransferase (UGT)1A1 gene were enrolled and treated with CPT-11 as part of the FOLFIRI regimen [CPT-11 and fluorouracil (5-FU)]. Blood was taken exactly 15 min following a 2-h continuous infusion of CPT-11. Plasma concentrations of SN-38, SN-38G and CPT-11 were determined by a modified high-performance liquid chromatography (HPLC) method. The median, maximum and minimum values of plasma SN-38G/SN-38 ratios were 4.25, 7.09 and 1.03, respectively, indicating that UGT activities are variable among patients with the wild-type UGT1A1 gene. The plasma SN-38G/SN-38 ratios decreased with an increase in the trial numbers of chemotherapy (r=0.741, p=0.000669), suggesting that CPT-11 treatment suppresses UGT activity, and the low plasma SN-38G/SN-38 ratios resulted in the induction of greater neutropenia. However, in this analysis, 2 clearly separated regression lines were observed between plasma SN-38G/SN-38 ratios and neutropenia induction. In conclusion, UGT activity involved in SN-38 metabolism is variable among patients with the wild-type UGT1A1 gene, and each CPT-11 treatment suppresses UGT activity. One-point determination of the plasma SN-38G/SN-38 ratio may provide indications for the prediction of CPT-11-induced neutropenia and adjustment of the optimal dose, although further studies are required.




Young Children's Reports of when Learning Occurred  

ERIC Educational Resources Information Center

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

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



The photodegradation of some naturally occurring polymers  

Microsoft Academic Search

This review contains a discussion of how chemical and spectroscopic methods have been used to unravel the complex photodegradation processes that occur when wool and paper (made from high yield pulps) are exposed to light. Both materials yellow when exposed to UV light and are bleached by visible light. In addition, both materials are bleached when irradiated in solutions of

R. S. Davidson



Phonetic Recalibration Only Occurs in Speech Mode  

ERIC Educational Resources Information Center

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

Vroomen, Jean; Baart, Martijn



Naturally occurring genetic variation in Arabidopsis thaliana  

Microsoft Academic Search

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

Maarten Koornneef; Carlos Alonso-Blanco; Dick Vreugdenhil



Purifying food-grade, naturally occurring COâ  

Microsoft Academic Search

Technology to purify naturally occurring COâ into products suitable for enhanced oil recovery (EOR) and food grade COâ markets has been commercially demonstrated in a 20 MMscfd (1,100 ton\\/day) COâ processing facility owned and operated by Columbia Hydrocarbon Corp. The unit demonstrates that it is technically and economically feasible to process low grade natural gas to produce pipeline specification natural

J. E. Nobles; J. W. Stancik



Will Superflares Occur on Our Sun ?  

NASA Astrophysics Data System (ADS)

Supeflares are very big flares that release total energy much greater than that of the biggest solar flares ever observed (3 x 10^{32} erg). The famous Carrington flare in 1859 may correspond to the biggest solar flare. If such superflares will occur on our Sun, we would have extreme space weather events, which might lead to big hazards of terrestrial environments and our civilization. Astronomical observations revealed that young stars or fast rotating stars often show superflares (10^{34} - 10^{38} erg). Hence it has been thought that our Sun would have produced superflares when it was young and rotating faster (> 10 km/s). However it was not clear whether superflares would occur on the present Sun or not, since the present Sun is not young and is now slowly rotating (at 2 km/s). Recent observations of solar type stars with Kepler satellite (Maehara et al. 2012) have revealed existence of superflares (with energy of 10^{34}-10^{35} erg) on solar twins which are quite similar to our Sun on surface temperature (5600 K - 6000 K) and slow rotation (< 10 km/s). From the statistical analysis of these superflare observations, it is suggested that superflares with energy 10^{34} erg occur once in 500 years and superflares with 10^{35} erg occur once in 5000 years on solar twins and/or our present Sun. Finally, we will also give theoretical arguments whether superflares will occur on the present Sun or not on the basis of modern theories of flares and dynamo.

Shibata, Kazunari



Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania  

PubMed Central

Background In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania. Methods From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages. Results A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025) and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4% resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to meropenem, ciprofloxacin and ceftriaxone respectively. Conclusion Urinary tract infection caused by multi drug resistant Escherichia coli was the common cause of febrile illness in our setting. Improvement of malaria diagnosis and its differential diagnosis from other causes of febrile illnesses may provide effective management of febrile illnesses among children in Tanzania



Prescription patterns and drug use among pregnant women with febrile Illnesses in Uganda: a survey in out-patient clinics  

PubMed Central

Background Malaria is a public health problem in Uganda; affecting mainly women and children. Effective treatment has been hampered by over-diagnosis and over-treatment with anti-malarial drugs among patients presenting with fever. In order to understand the effect of drug pressure on sulfadoxine-pyrimethamine (SP) resistance in pregnancy, a sample of pregnant women presenting with fever in out–patient clinics was studied. The main objective was to assess prescription patterns and drug use in pregnancy especially SP; and draw implications on the efficacy of SP for intermittent preventive treatment of malaria in pregnancy (IPTp). Methods A total of 998 pregnant women with a history of fever were interviewed and blood samples taken for diagnosis of malaria and HIV infections. Data were captured on the drugs prescribed for the current febrile episode and previous use of drugs especially SP, anti-retroviral drugs (ARVs) and cotrimoxazole. Results Few pregnant women, 128 (12.8%) were parasitaemic for P.falciparum; and of these, 72 (56.3%) received first-line treatment with Artemether-lumefantrine (Coartem®) 14 (10.9%) SP and 33 (25.8%) quinine. Of the parasite negative patients (non-malarial fevers), 186 (21.4%) received Coartem, 423 (48.6%) SP and 19 (2.1%) cotrimoxazole. Overall, malaria was appropriately treated in 35.5% of cases. Almost all febrile pregnant women, 91.1%, were sleeping under a mosquito net. The majority of them, 911 (91.3%), accepted to have an HIV test done and 92 (9.2%) were HIV positive. Of the HIV positive women, 23 (25.0%) were on ARVs, 10 (10.9%) on cotrimoxazole and 30 (32.6%) on SP. A significant proportion of women, 40 (43.5%), were on both SP and cotrimoxazole. Age and occupation were associated with diagnosis and treatment of malaria and HIV infections. Conclusion There is inappropriate treatment of malaria and non-malarial fevers among pregnant women in these facilities. This is due to non-adherence to the guidelines. Over-prescription and use of anti-malarial drugs, especially SP may have implications on resistance against SP for malaria prevention in pregnancy. The policy implications of these findings are to evaluate SP efficacy as IPTp; and the need to enforce adherence to the current clinical treatment guidelines.



Comparative field performance and adherence to test results of four malaria rapid diagnostic tests among febrile patients more than five years of age in Blantyre, Malawi  

Microsoft Academic Search

BACKGROUND: Malaria rapid diagnostics tests (RDTs) can increase availability of laboratory-based diagnosis and improve the overall management of febrile patients in malaria endemic areas. In preparation to scale-up RDTs in health facilities in Malawi, an evaluation of four RDTs to help guide national-level decision-making was conducted. METHODS: A cross sectional study of four histidine rich-protein-type-2- (HRP2) based RDTs at four

Jobiba Chinkhumba; Jacek Skarbinski; Ben Chilima; Carl Campbell; Victoria Ewing; Miguel San Joaquin; John Sande; Doreen Ali; Don Mathanga



N-methyl-D-aspartate, hyperpolarization-activated cation current (Ih) and gamma-aminobutyric acid conductances govern the risk of epileptogenesis following febrile seizures in rat hippocampus.  


Febrile seizures are the most common types of seizure in children, and are generally considered to be benign. However, febrile seizures in children with dysgenesis have been associated with the development of temporal lobe epilepsy. We have previously shown in a rat model of dysgenesis (cortical freeze lesion) and hyperthermia-induced seizures that 86% of these animals developed recurrent seizures in adulthood. The cellular changes underlying the increased risk of epileptogenesis in this model are not known. Using whole cell patch-clamp recordings from CA1 hippocampal pyramidal cells, we found a more pronounced increase in excitability in r