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1.
Clin Microbiol Infect ; 25(9): 1096-1113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158517

RESUMO

SCOPE: Presenting symptoms, distributions and patterns of diseases and vulnerability to invasive aspergillosis (IA) are similar between children and adults. However, differences exist in the epidemiology and underlying conditions, the usefulness of newer diagnostic tools, the pharmacology of antifungal agents and in the evidence from interventional phase 3 clinical trials. Therefore, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) have developed a paediatric-specific guideline for the diagnosis and management of IA in neonates and children. METHODS: Review and discussion of the scientific literature and grading of the available quality of evidence was performed by the paediatric subgroup of the ESCMID-ECMM-European Respiratory Society (ERS) Aspergillus disease guideline working group, which was assigned the mandate for the development of neonatal- and paediatric-specific recommendations. QUESTIONS: Questions addressed by the guideline included the epidemiology of IA in neonates and children; which paediatric patients may benefit from antifungal prophylaxis; how to diagnose IA in neonates and children; which antifungal agents are available for use in neonates and children; which antifungal agents are suitable for prophylaxis and treatment of IA in neonates and children; what is the role of therapeutic drug monitoring of azole antifungals; and which management strategies are suitable to be used in paediatric patients. This guideline provides recommendations for the diagnosis, prevention and treatment of IA in the paediatric population, including neonates. The aim of this guideline is to facilitate optimal management of neonates and children at risk for or diagnosed with IA.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/normas , Aspergillus/efeitos dos fármacos , Criança , Gerenciamento Clínico , Monitoramento de Medicamentos , Humanos , Recém-Nascido
2.
Clin Microbiol Infect ; 24 Suppl 1: e1-e38, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544767

RESUMO

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Gerenciamento Clínico , Anticorpos Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/complicações , Aspergilose/imunologia , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Biópsia/métodos , Lavagem Broncoalveolar , Diagnóstico Precoce , Flucitosina/farmacologia , Flucitosina/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Imagem por Ressonância Magnética , Mananas/análise , Testes de Sensibilidade Microbiana , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico
4.
PLoS One ; 10(7): e0131927, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26162090

RESUMO

BACKGROUND: Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. METHODS: In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. RESULTS: Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. CONCLUSION: By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.


Assuntos
Fator Estimulador de Colônias de Granulócitos/sangue , Infecções por Vírus Respiratório Sincicial/sangue , Biomarcadores/sangue , Feminino , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/genética , Hospitalização , Humanos , Lactente , Masculino , Estudos Prospectivos , Respiração Artificial , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/terapia , Índice de Gravidade de Doença
5.
Emerg Infect Dis ; 21(6): 1041-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25988348

RESUMO

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.


Assuntos
Antifúngicos/farmacologia , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus fumigatus/efeitos dos fármacos , Azóis/farmacologia , Farmacorresistência Fúngica , Vigilância da População , Aspergillus fumigatus/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Prevalência , Estudos Prospectivos
6.
Antimicrob Agents Chemother ; 59(2): 782-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25403672

RESUMO

The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n=355) and amphotericin B deoxycholate (n=195). The most common indications for antifungal administration in children were medical prophylaxis (n=325), empirical treatment of febrile neutropenia (n=122), and treatment of confirmed or suspected IFI (n=100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n=103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n=371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children.


Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Ácido Desoxicólico/administração & dosagem , Adolescente , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Hospitais , Humanos , Lactente , Recém-Nascido
7.
Trop Med Int Health ; 18(3): 286-95, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23320622

RESUMO

OBJECTIVES: To estimate the prevalence of nasopharyngeal bacterial colonisation (NPBC) patterns in young Tanzanian HIV-exposed infants and to analyse the influence of maternal NPBC and of the infant's HIV status on the NPBC pattern. METHODS: Longitudinal cohort study of neonates born to HIV-infected mothers visiting Kilimanjaro Christian Medical Centre, Tanzania, between 2005 and 2009. Demographic and clinical data and nasopharyngeal bacterial cultures were obtained at the age of 6 weeks, 3 and 6 months, and at one time point, a paired mother-infant nasopharyngeal swab was taken. RESULTS: Four hundred and twenty-two swabs were taken from 338 eligible infants. At 6 weeks of age, colonisation rates were 66% for Staphylococcus aureus, 56% for Streptococcus pneumoniae, 50% for Moraxella catarrhalis and 14% for Haemophilus influenzae. Colonisation with S. aureus diminished over time and was more common in HIV-infected infants. S. pneumoniae and H. influenzae colonisation rose over time and was more prevalent in HIV-uninfected children. Co-colonisation of S. pneumoniae with H. influenzae or M. catarrhalis was mostly noticed in HIV-infected infants. S. pneumoniae and M.catarrhalis colonisation of the mother was a risk factor for colonisation in HIV-uninfected infants, while maternal S. aureus colonisation was a risk factor for colonisation in HIV-infected infants. Among the 104 S. pneumoniae isolates, 19F was most prevalent, and 57 (55%) displayed capsular serotypes represented in the 13-valent pneumococcal conjugate vaccine. CONCLUSIONS: NPBC was common in Tanzanian HIV-exposed infants. The significant prevalence of pneumococcal vaccine serotypes colonising this paediatric population justifies the use of the 13-valent pneumococcal vaccine to reduce the burden of pneumococcal invasive disease.


Assuntos
Infecções Bacterianas/epidemiologia , Portador Sadio/epidemiologia , Infecções por HIV/epidemiologia , Nasofaringe/microbiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/transmissão , Portador Sadio/microbiologia , Portador Sadio/prevenção & controle , Portador Sadio/transmissão , Comorbidade , Feminino , Haemophilus influenzae , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Modelos Logísticos , Estudos Longitudinais , Mães , Análise Multivariada , Vacinas Pneumocócicas , Prevalência , Fatores de Risco , Staphylococcus aureus , Streptococcus pneumoniae/classificação , Tanzânia/epidemiologia
8.
Trop Med Int Health ; 17(12): 1449-56, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23094704

RESUMO

OBJECTIVES: The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dose recommendations for children, with dose increases proposed for each drug. No pharmacokinetic data are available from South American children. We examined the need for implementation of these revised guidelines in Venezuela. METHODS: Plasma isoniazid, rifampicin, pyrazinamide and ethambutol concentrations were assessed prior to and at 2, 4 and 8 h after intake of TB drugs by 30 TB patients aged 1-15 years. The effects of dose in mg/kg, age, sex, body weight, malnutrition and acetylator phenotype on maximum plasma drug concentrations (Cmax) and exposure (AUC0-24) were determined. RESULTS: 25 patients (83%) had an isoniazid Cmax below 3 mg/l and 23 patients (77%) had a rifampicin Cmax below 8 mg/l. One patient (3%) had a pyrazinamide Cmax below 20 mg/l. The low number of patients on ethambutol (n = 5) precluded firm conclusions. Cmax and AUC0-24 of all four drugs were significantly and positively correlated with age and body weight. Patients aged 1-4 years had significantly lower Cmax and AUC0-24 values for isoniazid and rifampicin and a trend to lower values for pyrazinamide compared to those aged 5-15 years. The geometric mean AUC0-24 for isoniazid was much lower in fast acetylators than in slow acetylators (5.2 vs. 12.0, P < 0.01). CONCLUSION: We provide supportive evidence for the implementation of the revised WHO pediatric TB drug dose recommendations in Venezuela. Follow-up studies are needed to describe the corresponding plasma levels that are achieved by the recommended increased doses of TB drugs.


Assuntos
Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Guias de Prática Clínica como Assunto , Tuberculose/tratamento farmacológico , Acetiltransferases/genética , Adolescente , Fatores Etários , Área Sob a Curva , Disponibilidade Biológica , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Etambutol/administração & dosagem , Etambutol/farmacocinética , Feminino , Humanos , Lactente , Isoniazida/administração & dosagem , Isoniazida/farmacocinética , Análise dos Mínimos Quadrados , Masculino , Desnutrição/metabolismo , Polimorfismo Genético , Pirazinamida/administração & dosagem , Pirazinamida/farmacocinética , Rifampina/administração & dosagem , Rifampina/farmacocinética , Tuberculose/etnologia , Venezuela , Organização Mundial da Saúde
9.
Tuberculosis (Edinb) ; 92(6): 505-12, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22877977

RESUMO

The immune regulatory mechanisms involved in the acquisition of Mycobacterium tuberculosis infection in children are largely unknown. We investigated the influence of parasitic infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity in Warao Amerindians in Venezuela. Pediatric household contacts of sputum smear-positive tuberculosis (TB) cases were enrolled for TST, chest radiograph, plasma cytokine analyses, QuantiFERON-TB Gold In-Tube (QFT-GIT) testing and stool examinations. Factors associated with TST positivity were studied using generalized estimation equations logistic regression models. Of the 141 asymptomatic contacts, 39% was TST-positive. After adjusting for age, gender and nutritional status, TST positivity was associated with Trichuris trichiura infections (OR 3.5, 95% CI 1.1-11.6) and low circulating levels of T helper 1 (Th1) cytokines (OR 0.51, 95% CI 0.33-0.79). Ascaris lumbricoides infections in interaction with Th2- and interleukin (IL)-10-dominated cytokine profiles were positively associated with TST positivity (OR 3.1, 95% CI 1.1-8.9 and OR 2.4, 95% CI 1.04-5.7, respectively). A negative correlation of QFT-GIT mitogen responses with Th1 and Th2 levels and a positive correlation with age were observed (all p < 0.01). We conclude that helminth infections and low Th1 cytokine plasma levels are significantly associated with TST positivity in indigenous Venezuelan pediatric TB contacts.


Assuntos
Citocinas/imunologia , Helmintíase/imunologia , Desnutrição/imunologia , Mycobacterium tuberculosis/imunologia , Grupos Populacionais , Teste Tuberculínico , Tuberculose/imunologia , Animais , Ascaris lumbricoides/isolamento & purificação , Criança , Pré-Escolar , Estudos Transversais , Características da Família , Feminino , Helmintíase/diagnóstico , Helmintíase/epidemiologia , Humanos , Modelos Logísticos , Masculino , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Prevalência , Kit de Reagentes para Diagnóstico , Fatores de Risco , Trichuris/isolamento & purificação , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Venezuela/epidemiologia
10.
Genes Immun ; 12(6): 434-44, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21390052

RESUMO

Artemis deficiency is known to result in classical T-B- severe combined immunodeficiency (SCID) in case of Artemis null mutations, or Omenn's syndrome in case of hypomorphic mutations in the Artemis gene. We describe two unrelated patients with a relatively mild clinical T-B- SCID phenotype, caused by different homozygous Artemis splice-site mutations. The splice-site mutations concern either dysfunction of a 5' splice-site or an intronic point mutation creating a novel 3' splice-site, resulting in mutated Artemis protein with residual activity or low levels of wild type (WT) Artemis transcripts. During the first 10 years of life, the patients suffered from recurrent infections necessitating antibiotic prophylaxis and intravenous immunoglobulins. Both mutations resulted in increased ionizing radiation sensitivity and insufficient variable, diversity and joining (V(D)J) recombination, causing B-lymphopenia and exhaustion of the naive T-cell compartment. The patient with the novel 3' splice-site had progressive granulomatous skin lesions, which disappeared after stem cell transplantation (SCT). We showed that an alternative approach to SCT can, in principle, be used in this case; an antisense oligonucleotide (AON) covering the intronic mutation restored WT Artemis transcript levels and non-homologous end-joining pathway activity in the patient fibroblasts.


Assuntos
Proteínas Nucleares/genética , Oligorribonucleotídeos Antissenso/genética , Sítios de Splice de RNA/genética , Imunodeficiência Combinada Severa/genética , Linfócitos B/imunologia , Linfócitos B/patologia , Sequência de Bases , Células Cultivadas , Criança , Proteínas de Ligação a DNA , Endonucleases , Feminino , Humanos , Mutação , Proteínas Nucleares/deficiência , Tolerância a Radiação/genética , Radiação Ionizante , Análise de Sequência de DNA , Imunodeficiência Combinada Severa/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
11.
Case Rep Med ; 2010: 241791, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20671981

RESUMO

Cardiac zygomycosis can be a critical condition with sudden onset of severe congestive heart failure followed by severe hemodynamic deterioration. We report a fatal course of disseminated fungal infection with a massive intra-atrial thrombosis caused by a zygomycete, in a five year old boy treated for acute lymphoblastic leukaemia. In addition, we discuss the literature concerning infections caused by zygomycetes involving the heart. Prognosis is poor. A high index of suspicion and an aggressive diagnostic and therapeutic approach with the prompt start of preemptive antifungal therapy are key factors to improve outcome.

12.
J Hosp Infect ; 76(1): 56-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20542590

RESUMO

Published data implicate hospital water as a potential source of opportunistic fungi that may cause life-threatening infections in immunocompromised patients. Point-of-care filters are known to retain bacteria, but little is known about their efficacy in reducing exposure to moulds. We investigated the effect of point-of-use filters (Pall-Aquasafe) on the level of contamination of Aspergillus fumigatus and other filamentous fungi. The point-of-use filters were applied to several outlets (taps and showers) on the paediatric bone marrow transplantation (BMT) unit of the National Hospital in Oslo, Norway. In addition the efficacy was investigated using a test rig. The laboratory experiments showed that the filters were highly effective in reducing the number of colony-forming units for a period of at least 15 days. In the BMT unit the filters eliminated the fungi from the water on day 1 but due to particles present in the water the filters occluded, which prevented further evaluations. Our results show that point-of-use filtration might be an effective preventive measure to eliminate filamentous fungi at individual points of water use, thereby reducing patients' exposure.


Assuntos
Filtração/métodos , Fungos/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , Microbiologia da Água , Purificação da Água/métodos , Contagem de Colônia Microbiana , Hospitais , Humanos , Noruega
13.
Eur Respir J ; 35(2): 247-65, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19840958

RESUMO

This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect. Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the beta-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.


Assuntos
Pediatria/métodos , Pneumologia/métodos , Transtornos Respiratórios/tratamento farmacológico , Corticosteroides/farmacologia , Antibacterianos/farmacologia , Pesquisa Biomédica/tendências , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Tratamento Farmacológico/métodos , Medicina Baseada em Evidências , Humanos , Imunossupressores/farmacologia , Lactente , Recém-Nascido , Triagem Neonatal , Uso Off-Label , Padrões de Prática Médica
14.
Arch Dis Child ; 94(6): 448-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19224889

RESUMO

Ataxia-telangiectasia (A-T) is characterised by progressive neurological abnormalities, oculocutaneous telangiectasias and immunodeficiency (decreased serum IgG subclass and/or IgA levels and lymphopenia). However, 10% of A-T patients present with decreased serum IgG and IgA with normal or raised IgM levels. As cerebellar ataxia and oculocutaneous telangiectasias are not present at very young age, these patients are often erroneously diagnosed as hyper IgM syndrome (HIGM). Eight patients with A-T, showing serum Ig levels suggestive of HIGM on first presentation, are described. All had decreased numbers of T lymphocytes, unusual in HIGM. The diagnosis A-T was confirmed by raised alpha-fetoprotein levels in all patients. To prevent mistaking A-T patients for HIGM it is proposed to add DNA repair disorders as a possible cause of HIGM.


Assuntos
Ataxia Telangiectasia/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/diagnóstico , Imunoglobulina G/análise , Criança , Pré-Escolar , Reparo do DNA , Feminino , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/imunologia , Lactente , Contagem de Linfócitos , Masculino , Linfócitos T/imunologia
17.
Ned Tijdschr Geneeskd ; 151(47): 2597-602, 2007 Nov 24.
Artigo em Holandês | MEDLINE | ID: mdl-18161258

RESUMO

A 52-year-old man underwent haematopoietic stem-cell transplant for myelodysplastic syndrome; after treatment with voriconazole for invasive aspergillosis, he was diagnosed with invasive zygomycosis caused by Rhizopus microsporus. He died despite treatment with intravenous liposomal amphotericin B and posaconazole. A 5-year-old boy with acute lymphatic leukaemia was diagnosed with invasive zygomycosis at autopsy. In a third case, a 16-year-old boy with acute myeloid leukaemia received repeated courses of empiric antifungal therapy, although the presence of an invasive fungal infection was not demonstrated. The patient died, and disseminated invasive zygomycosis caused by Rhizomucor pusillus was found at autopsy. Invasive infections by Zygomycetes are difficult to diagnose and are associated with a high mortality rate. The incidence of invasive zygomycosis appears to be increasing. Therefore, awareness of this type of invasive fungal infection is warranted. Lipid formulations ofamphotericin B remain the first choice for therapy.


Assuntos
Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido , Mucormicose/mortalidade , Rhizopus/isolamento & purificação , Zigomicose/mortalidade , Adolescente , Anfotericina B/uso terapêutico , Pré-Escolar , Evolução Fatal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Transplante de Órgãos , Rhizopus/efeitos dos fármacos , Imunologia de Transplantes , Triazóis/uso terapêutico , Zigomicose/tratamento farmacológico , Zigomicose/epidemiologia
18.
Curr Opin Otolaryngol Head Neck Surg ; 15(4): 202-7, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17620891

RESUMO

PURPOSE OF REVIEW: To examine the recent literature concerning advances in tongue reconstruction after tumor resection. RECENT FINDINGS: Reconstruction following resection of malignant tongue tumors remains one of the most difficult problems in head and neck oncology. Recent trends in tongue reconstruction have focused on optimizing speech and swallowing function and maximizing quality of life. In the recent literature, several new reconstructive strategies including omohyoid musculocutaneous and myofascial flaps overlayed with radial forearm free flaps have been described. In addition, several older reconstructive options, such as trapezius and pectoralis rotational flaps, have been revisited. There has also been a trend toward restoring innervation to these flaps rather than leaving them insensate. SUMMARY: Tongue cancer resection and subsequent reconstruction pose interesting challenges to the surgeon to maximize postoperative function and quality of life. Attention to the principles of tongue reconstruction and knowledge of the range of available reconstructive options can result in more favorable functional outcomes.


Assuntos
Procedimentos Cirúrgicos Reconstrutivos/métodos , Língua/cirurgia , Deglutição/fisiologia , Humanos , Retalhos Cirúrgicos , Neoplasias da Língua/cirurgia
19.
Ned Tijdschr Geneeskd ; 150(13): 741-6, 2006 Apr 01.
Artigo em Holandês | MEDLINE | ID: mdl-16623349

RESUMO

A newborn male was diagnosed with congenital rubella syndrome. His 31-year-old mother had had erythematous exanthema during a period of amenorrhea lasting 7 weeks; she was not vaccinated and had never had a rubella infection. The infection was confirmed serologically. The mother gave birth to an icteric, microcephalic, dysmature neonate with hepatosplenomegaly and exanthema with multiple, small purple-red spots. Ultrasound cardiography revealed a persistently open arterial duct and a small defect of the ventricular septum. Radiological evaluation of the long bones showed the characteristic longitudinal lucent strands ('celery stalk appearance'). Ultrasound of the cerebrum showed diffuse widespread calcifications in the white matter and basal ganglia, striatal vasculopathy and diffuse parenchymal disorders. Psychomotor development was impaired. The patient was completely deaf in the left ear and had severely poor hearing in the right ear. After the introduction of the rubella vaccine in the Netherlands in 1974 a substantial decrease was seen in the incidence of rubella infections as well as congenital rubella syndrome. An epidemic of rubella infections has been present within the non-vaccinated population since September 2004. Recognition of the clinical symptoms and confirmation of the clinical suspicion with proper viral diagnostic methods are needed to control the current epidemic and to prevent secundary spread. Infants born with congenital rubella syndrome remain infectious to non-vaccinated individuals for a prolonged period of time; the virus is excreted in the urine and faeces. Long-term medical follow-up is necessary because the congenital rubella infection can cause abnormalities after the neonatal period.


Assuntos
Complicações Infecciosas na Gravidez/epidemiologia , Síndrome da Rubéola Congênita/diagnóstico , Rubéola (Sarampo Alemão)/epidemiologia , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Países Baixos/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Rubéola (Sarampo Alemão)/diagnóstico , Vacina contra Rubéola/administração & dosagem
20.
Scand J Immunol ; 62(2): 148-54, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16101821

RESUMO

Disseminated fungal infections are increasing. However, the interactions between the body's largest population of tissue macrophages, the Kupffer cells and the fungal pathogens are scarcely understood. The aim of this study was to examine the involvement of Toll-like receptor 4 (TLR4) signalling in cytokine production, using primary cultures of rat and murine Kupffer cells exposed to Aspergillus fumigatus and Candida albicans hyphae and conidia. All fungal components induced the release of tumour necrosis factor-alpha (TNF-alpha), but with delayed kinetics compared with lipopolysaccharide (LPS). Candida albicans was the most potent inducer of TNF-alpha protein and mRNA and the only inducer of interleukin-10 (IL-10) in rat Kupffer cells. All fungal components induced enhanced mRNA levels of macrophage inhibitory protein-2 (MIP-2) in the cells, similar to LPS. Inhibitors of Src tyrosine kinases added to cells prior to stimulation led to attenuation in the release of both TNF-alpha (60%, P < 0.05) and IL-10 (70%, P < 0.05) induced by C. albicans conidia but did not influence the LPS-mediated cytokine release. Murine Kupffer cells (C57BL/10J) also released TNF-alpha as well as the chemokines keratinocyte-derived chemokine (KC) and MIP-2 in response to fungal component. Surprisingly, Kupffer cells from TLR4-deficient C57BL/ScCr mice exhibited significantly enhanced production of KC and MIP-2 upon stimulation by fungal components compared with control littermates (P < 0.05). Our study demonstrates that Aspergillus and Candida components induce cytokine production in rat Kupffer cells and that the response to C. albicans conidia involves Src tyrosine kinases. The experiments with TLR4-deficient Kupffer cells suggest that the cytokine response in these cells to fungal component is not mediated by TLR4.


Assuntos
Aspergilose/imunologia , Aspergillus fumigatus/imunologia , Candida albicans/imunologia , Candidíase/imunologia , Citocinas/imunologia , Macrófagos do Fígado/imunologia , Proteínas Tirosina Quinases/imunologia , Animais , Aspergilose/microbiologia , Candidíase/microbiologia , Quimiocina CXCL2 , Quimiocinas CXC/imunologia , Citocinas/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Macrófagos do Fígado/enzimologia , Macrófagos do Fígado/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/química , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos SHR , Receptores Imunológicos/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/imunologia
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