Hidrocefalia por meningitis tuberculosa con líquido cefalorraquídeo ventricular normal / Tuberculous meningitis hydrocephalus with normal ventricular cerebrospinal fluid

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Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes.

BACKGROUND: Leukotriene B(4) (LTB(4)) and cysteinyl leukotrienes (cysLTs) are important immune mediators, often found concomitantly at sites of inflammation. Although some of the leukotriene-mediated actions are distinctive (e.g., bronchial constriction for cysLTs), many activities such as leukocyte recruitment to tissues and amplification of inflammatory responses are shared by both classes of leukotrienes. OBJECTIVE: We used human monocytes to characterize leukotriene-specific signaling, gene expression signatures, and functions and to identify interactions between LTB(4)- and cysLTs-induced pathways. METHODS: Responsiveness to leukotrienes was assessed using oligonucleotide microarrays, real-time PCR, calcium mobilization, kinase activation, and chemotaxis assays. RESULTS: Human monocytes were found to express mRNA for high- and low-affinity LTB(4) receptors, BLT(1) and BLT(2), but signal predominantly through BLT(1) in response to LTB(4) stimulation as shown using selective agonists, inhibitors, and gene knock down experiments. LTB(4) acting through BLT(1) coupled to G-protein α inhibitory subunit activated calcium signaling, p44/42 mitogen-activated protein kinase, gene expression, and chemotaxis. Twenty-seven genes, including immediate early genes (IEG), transcription factors, cytokines, and membrane receptors were significantly up-regulated by LTB(4). LTB(4) and LTD(4) had similar effects on signaling, gene expression, and chemotaxis indicating redundant cell activation pathways but costimulation with both lipid mediators was additive for many monocyte functions. CONCLUSION: Leukotriene B(4) and LTD(4) display both redundant and cooperative effects on intracellular signaling, gene expression, and chemotaxis in human monocytes. These findings suggest that therapies targeting either leukotriene alone may be less effective than approaches directed at both.

Montelukast reduces eosinophilic inflammation by inhibiting both epithelial cell cytokine secretion (GM-CSF, IL-6, IL-8) and eosinophil survival.

Leukotriene receptor antagonists, such as montelukast (MK), are currently used to treat rhinitis and asthma, but their anti-inflammatory role in eosinophil inflammation is not well understood. The aim of this study is to investigate the effect of MK on an in vitro model of upper-airway eosinophil inflammation by reducing pro-inflammatory cytokines from both nasal mucosa (NM) and polyp (NP) epithelial cells and reducing eosinophil survival primed by epithelial cell secretions. Epithelial cells were stimulated with fetal bovine serum (FBS) with or without MK for 24 hours, and cytokine concentrations in epithelial secretions were measured by ELISA. After incubating peripheral blood eosinophils with epithelial cell-conditioned media (ECM) with or without MK up to 3 days, eosinophil survival was assessed by Trypan blue dye exclusion. Results are expressed as mean±SEM of cytokine concentration (percent of control) or eosinophil survival (percent). Epithelial cell stimulation increased GM-CSF, IL-6, IL-8, and sICAM-1 secretion in both NM and NP. MK had a significant inhibitory effect on FBS-induced GM-CSF, IL-6, and IL-8 secretion, but not sICAM-1, in both NM and NP. MK also showed an inhibitory effect (p<0.05) on ECM-induced eosinophil survival from both NM (from 10(-5)M to 10(-7)M, n=7) and NP (at 10(-5)M, n=7), after 3 days of incubation. These anti-inflammatory effects on epithelial cell cytokine secretion and on eosinophil survival suggest that montelukast may contribute to the reduction of eosinophilic inflammation in upper-airway inflammatory diseases such as rhinitis and nasal polyposis.

Parálisis diafragmática en el postoperatorio de cirugía cardiaca infantil / Diaphragmatic paralysis after pediatric cardiac surgery

Objetivo: Describir la frecuencia, morbimortalidad y tratamiento de la disfunción diafragmática (DD) en el postoperatorio de la cirugía cardiaca infantil. Pacientes y métodos: Serie de casos de DD identificados entre la población de niños intervenidos de cirugía cardiaca en el hospital «12 de Octubre» de Madrid, entre 1997 y 2006. Se obtuvieron retrospectivamente datos demográficos, de la cirugía y del postoperatorio, así como de la estancia hospitalaria yde la morbimortalidad. Resultados: Cirugía cardiaca en 1.063 niños, diagnosticándose 23 casos de DD. Se excluyó un caso secundario a neuropatía generalizada. La frecuencia global fue del 2,1%. La mediana de edad fue de 14 días (1 día-16 meses), siendo 20 de los casos menores de 1 año. Se realizó plicatura en 13 pacientes (62%). Las indicaciones de plicatura fueron: fracaso de extubación (n= 11) y dificultad respiratoria persistente (n= 2).Fue preciso realizar plicatura quirúrgica en 9 de los 13 neonatos. El tiempo de ventilación mecánica invasiva, estancia en unidad de cuidados intensivos pediátricos (UCIP) y estancia hospitalaria en los casos con paresia fue de 8, 12 y 20 días(mediana), respectivamente. Las parálisis precisaron mayor tiempo de ventilación invasiva y de ingreso (19, 34 y 47,5 días). Conclusiones: A todo neonato intervenido de una cardiopatía compleja debería realizársele una ecografía diafragmática en respiración espontánea previa a su extubación, para así establecer el diagnóstico de manera precoz, con el objetivo de reducir el tiempo de ventilación mecánica y la morbilidad asociada (AU)

The objective of this study is to describe the frequency, morbimortality and treatment of diaphragmatic dysfunction (DD) after pediatric cardiac surgery. Patients and methods: Series of DD cases identified among the population of children who underwent cardiac surgery at the hospital 12 de Octubre of Madrid from the years 1997-2006. Demographic, surgical and postsurgical data have been obtained retrospectively, as well as data on hospital stay and the morbimortality. Results: A total of 1,063 children underwent cardiac surgery, diagnosing 23 DD cases. A secondary case was excluded due to generalized neuropathy. The global frequency was of 2.1%,the mean age was 14 days (1 d-16 m), being 20 of the cases under 1 year of age. Reefing was performed in 13 patients (62%). The indications for reefing were due to extubation failure (n= 11) and persistent respiratory difficulties (n= 2).Surgical reefing had to be performed in 9 from the 13 newborns. In the cases of paresis the length of the invasive mechanical ventilation, stay at the PICU and hospital stay was 8,12 and 20 days (mean) respectively. The paralysis required alonger time of invasive ventilation and hospitalization (19, 34 and 47,5 days).Conclusions: A diaphragm echography in spontaneous breathing should be performed on any newborn that underwent a complex cardiopathy surgery previous to the extubation in order to determine an early diagnosis and to reduce the length of mechanical ventilation and associated morbidity (AU)

Glucocorticoid therapy increases COX-2 gene expression in nasal polyps in vivo.

The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal polyps. In total, 65 patients with nasal polyps were randomly (3:1) treated with (n = 51; 33 with asthma) or without (n = 14) oral prednisone and intranasal budesonide for 2 weeks plus intranasal budesonide for 10 additional weeks. Biopsies were obtained at baseline and after 2 and 12 weeks of treatment. All samples were analysed for cyclooxygenase-1 and cyclooxygenase-2 mRNA. Attempts were made to detect cyclooxygenase-2 protein. At baseline, cyclooxygenase-1 and cyclooxygenase-2 expression did not differ between polyps from nonasthmatic and asthmatic patients. Cyclooxygenase-1 mRNA was unchanged by glucocorticoid treatment, while cyclooxygenase-2 mRNA increased in glucocorticoid-treated patients at week 2 compared with baseline and then decreased at week 12. Within subgroups, increased cyclooxygenase-2 mRNA was found at week 2 in polyps from nonasthmatic and asthmatic patients compared with baseline. At week 12, cyclooxygenase-2 expression remained high in nonasthmatics while it decreased in asthmatics. Cyclooxygenase-2 protein was not detected under any circumstances. Glucocorticoid therapy enhances cyclooxygenase-2 expression in vivo in nasal polyps, a finding that does not follow the generally accepted assumption that cyclooxygenase-2 expression is suppressed by glucocorticoids.

Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids.

BACKGROUND: Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) alpha and beta or to downregulation of GRalpha. We aimed to evaluate the in vivo regulation of GR isoforms in GC-treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels. METHODS: Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (10(2) cDNA copies/mug total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa (n = 11) was also investigated. Data are presented as median and 25-75th percentile. RESULTS: At w0, nasal polyps expressed less GRalpha mRNA (1343;683-2263; P < 0.05) and GR protein (41;29-54; P < 0.05) than nasal mucosa (2474;1346-2933; 60;51-72, respectively). GRbeta immunoreactivity was higher in nasal polyps (11;4-19; P < 0.05) than in nasal mucosa (5;2-5). At w2, increased GRalpha mRNA (2010;1037-2732; P < 0.01) and GR protein (56;27-71; P = 0.056) were found compared with w0 (1177;759-2058; 37;29-55, respectively). At w12, GRalpha mRNA and GR protein were similar to w0. GRbeta expression was unaltered by treatment. Neither GRalpha nor GRbeta correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = -0.478; P < 0.001). CONCLUSIONS: GRalpha is downregulated in nasal polyps and upregulated by GC treatment. Neither GRalpha nor GRbeta appear to determine the sensitivity to GCs in nasal polyposis.

[Initial signs and symptoms of brain tumors in children]. / Síntomas y signos iniciales de los tumores cerebrales pediátricos.

INTRODUCTION: This is a study of the presenting features of brain tumors in children, their localization and histology which is aimed at describing the most frequent symptoms at the beginning and at the moment of diagnosis and minimize the time needed to reach a diagnosis. METHODS: Retrospective and descriptive study. Data were collected from the medical records of the patients (aged: 0-16) operated on for a brain tumor in our Department from 1999 to 2004. All analyses were conducted with the SPSS 11.0. RESULTS: In our study, the prevalence of brain tumors was higher in males (58%) older than five years. Of these, 52% were supratentorial and the most frequent one was astrocytome. Median time to diagnosis was 30 days. A total of 75% were diagnosed during the first 60 days of the onset of the symptoms. We found a statistically significant relationship between age and mean time to d i a gnosis. The most frequent initial symptom was increased head circumference and nausea/vomiting in children younger than 2 years, vomiting and headache in children aged 2-5, and headache in older than 5 years. In all groups, 83% of headache was accompanied by vomiting. CONCLUSIONS: Mean time to diagnosis in our study is similar to other series. Presenting features vary based on age and they are not pathognomonic of the brain tumors. This hinders early diagnosis. In order to make an early diagnosis, it is important to pay attention to the associated symptoms and chronology.

Corticosteroid therapy increases membrane-tethered while decreases secreted mucin expression in nasal polyps.

BACKGROUND: Mucus hypersecretion is a hallmark of nasal polyposis (NP). Corticosteroids (CS) are first-line treatment for NP, decreasing their size and inflammatory component. However, their effect on mucin production is not well-understood. The aim of this (pilot) study was to investigate CS effect on mucin expression in NP. METHODS: Patients were randomized in control (n = 9) and treatment (oral prednisone for 2 weeks and intranasal budesonide for 12 weeks; n = 23) groups. Nasal polyposis from nonasthmatic (NP; n = 13), aspirin-tolerant (NP-ATA; n = 11) and aspirin-intolerant (NP-AIA; n = 8) asthmatics were studied. Nasal polyposis biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of CS treatment. Secreted (MUC5AC, MUC5B and MUC8) and membrane-tethered (MUC1, MUC4) mucins (immunohistochemistry) and goblet cells (Alcian blue-periodic acid Schiff) were quantified in both epithelium and glands. Rhinorrea and nasal obstruction were also assessed. RESULTS: At w2, steroids increased MUC1 (from 70 to 97.5) and MUC4 (from 80 to 100) in NP-ATA patients' epithelium compared with baseline (w0). At w12, steroids decreased MUC5AC (from 40 to 5) and MUC5B (from 45 to 2.5) in NP-ATA patients' epithelium and glands, respectively, compared with baseline. No mucin presented significant changes in NP-AIA patients. MUC5AC and MUC5B expression correlated with goblet and mucous cell numbers, respectively, and MUC5AC also with rhinorrea score. CONCLUSIONS: These results suggest: (i) CS up-regulate membrane (MUC1, MUC4) while down-regulate secreted (MUC5AC, MUC5B) mucins; (ii) there exists a link between secreted mucin expression and goblet cell hyperplasia; and (iii) NP from AIA may develop resistance to CS treatment.

Síntomas y signos iniciales de los tumores cerebrales pediátricos / Initial signs and symptoms of brain tumors in children

tumores cerebrales en niños, sus características histológicasy su localización con el fin de conocer los síntomasmás habituales al inicio y en el momento del diagnóstico eintentar disminuir el tiempo hasta éste.Métodos. Estudio retrospectivo, descriptivo. Informaciónrecogida de las historias clínicas de 50 pacientes pediátricosintervenidos en nuestro centro de tumor cerebral primarioentre 1999 y 2004 analizada con SPSS 11.0.Resultados. En nuestra serie los tumores cerebralesfueron más prevalentes en niños (58%) mayores de 5 años,un 52% era supratentorial y el astrocitoma fue el más frecuente.La mediana de tiempo al diagnóstico fue de 30 díasy el 75% se diagnosticaron en los 60 días siguientes a la primeraconsulta. Encontramos una relación estadísticamentesignificativa entre el tiempo transcurrido hasta el diagnósticoy la edad. La clínica más frecuente en el diagnóstico eraaumento del perímetro craneal y náuseas/vómitos en losmenores de 2 años, náuseas/vómitos y cefalea en los niñosde 2 a 5 años y cefalea en los mayores de 5 años. En todoslos grupos el 83% de las cefaleas se acompañaban de náuseas/vómitos.Conclusiones. El tiempo medio hasta el diagnóstico ennuestra serie es aceptable comparado con otras. La clínicavaría en función de la edad y no es patognomónica de lostumores cerebrales, lo que dificulta el diagnóstico precoz.Para un diagnóstico precoz es importante fijarse en la asociaciónde síntomas y en la cronología (AU)

Introduction. This is a study of the presenting featuresof brain tumors in children, their localization andhistology which is aimed at describing the most frequentsymptoms at the beginning and at the moment of diagnosisand minimize the time needed to reach a diagnosis.Methods. Retrospective and descriptive study. Datawere collected from the medical records of the patients(aged: 0-16) operated on for a brain tumor in our Departmentfrom 1999 to 2004. All analyses were conductedwith the SPSS 11.0.Results. In our study, the prevalence of brain tumorswas higher in males (58%) older than five years. Of these,52% were supratentorial and the most frequent onewas astrocytome. Median time to diagnosis was 30 days.A total of 75% were diagnosed during the first 60 daysof the onset of the symptoms. We found a statisticallysignificant relationship between age and mean time to diagnosis.The most frequent initial symptom was increasedhead circumference and nausea/vomiting in childrenyounger than 2 years, vomiting and headache in childrenaged 2-5, and headache in older than 5 years. In allgroups, 83% of headache was accompanied by vomiting.Conclusions. Mean time to diagnosis in our study issimilar to other series. Presenting features vary based onage and they are not pathognomonic of the brain tumors.This hinders early diagnosis. In order to make anearly diagnosis, it is important to pay attention to theassociated syntoms and chronology (AU)

Síndrome de «shock» tóxico: a propósito de dos casos / Toxic shock syndrome: a report of two cases

Los síndromes de shock tóxico y shock similar a tóxico son entidades causadas por superantígenos que ponen en marcha una respuesta sistémica que determina sus características clínicas. Exponemos dos casos detectados en nuestro hospital que cumplen los criterios diagnósticos de síndrome de shock tóxico al presentar una temperatura ³38,9 ºC, un exantema con posterior descamación, una hipotensión arterial y una afectación de 3 o más órganos. El primero evolucionó hacia un fallo multiorgánico con cultivos negativos, por lo que se diagnosticó de etiología probablemente estafilocócica. El paciente experimentó un deterioro progresivo, sin respuesta a las medidas de soporte, y falleció. El segundo caso se manifestó como una fascitis necrosante de la pared abdominal, que precisó un desbridamiento quirúrgico. El crecimiento de Streptococcus pyogenes se detectó en la faringe y en el exudado de la herida quirúrgica. Su evolución fue favorable, por lo que recibió el alta con una estenosis traqueal como única secuela. Los dos casos demuestran la importancia de la sospecha clínica en estos cuadros para pautar el tratamiento antibiótico e instaurar una terapia de soporte con rapidez

Toxic shock syndrome and toxic shock-like syndrome are diseases caused by superantigens that trigger a systemic inflammatory response, which is responsible for the clinical manifestations. We report two cases treated at our institution that meet the diagnostic criteria for toxic shock syndrome: body temperature ³38.9 ºC, rash with subsequent desquamation, hypotension and involvement of three or more organ systems. The first patient developed multisystem failure with negative cultures, suggesting a probable staphylococcal etiology. The patient experienced a progressive deterioration with no response to supportive care, and finally died. The second case presented as necrotising fasciitis of the abdominal wall, requiring surgical debridement. Streptococcus pyogenes was grown in the samples obtained from the pharynx and from the surgical wound. This patient had a favorable clinical course with tracheal stenosis as the only sequela at the discharge from hospital. High clinical suspicion is extremely important in this syndrome for the early initiation of antibiotic therapy and intensive care

Mucin genes have different expression patterns in healthy and diseased upper airway mucosa.

BACKGROUND: Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper-secretion therapy. OBJECTIVE: The aim of this study was to evaluate and compare mucin gene expression at epithelial and glandular levels, and to identify potential mucin expression patterns for specific upper airways pathologies. METHODS: Immunohistochemistry for MUC1, MUC2, and MUC4-MUC8 mucins was performed on healthy nasal mucosa (NM; n=12), bilateral nasal polyps (NP; n=38), NP from CF patients (n=10), and antrochoanal (AC) polyps (n=11). MUC2, MUC4, MUC5AC, and MUC6 mRNA expression were also analysed by in situ hybridization. RESULTS: MUC1, MUC4, and MUC5AC mucins were highly expressed in the epithelium and their expression pattern was similar in all NP types, MUC1 and MUC4 being increased and MUC5AC decreased compared with NM. MUC8 was highly detected at both epithelial and glandular levels with marked variability between groups. MUC5B was mainly detected in glands and the expression in all polyp types was higher than in NM. Moreover, MUC5B expression was higher in NP epithelia from CF patients than in bilateral NP and healthy NM. Although MUC2 expression was low, especially in AC polyps, it was detected in most samples. In NM, MUC6 and MUC7 were scarcely detected and MUC7 expression was restricted to glands. CONCLUSIONS: These results suggest that NP have a different pattern of mucin expression than healthy NM and that CF polyps (increased MUC5B) and AC polyps (decreased MUC2) have a different mucin expression pattern than bilateral NP.

Habitos de consumo y preferencia de antitérmicos en pacientes de nuestro medio / Consumption habits and antipyretics preferences in patients in our setting

Objetivo: el objetivo del presente estudio es describir 105 hábitos de consumo y la preferencia de antitérmicos, asi como evaluar cómo tratan la fiebre 105 padres de nuestros pacientes. Pacientes y métodos: utilizando un modelo de encuesta, se recogieron 105 datos rellenadospor 105 padres de 107 pacientes de edad comprendida entre 6 meses y 10 años. Se realizó un análisis descriptivo de las variables objeto de la encuesta y se estimó la frecuencia de cada una de las respuestas. Resultados: el 92% de 105 padres ha dado alguna vez una determinada presentación de ibuprofeno oral (Dalsy) a sus hijos, y el 98% les ha dado alguna vez una determinada presentaciónde paracetamol oral (Apiretal). Entre 105 niños que alguna vez han consumido el preparado deibuprofeno citado, a un 65% le agrada su sabor y a un 23% no le gusta. Entre 105 que han consumidoel preparado de paracetamol mencionado, a un 61 % le gusta su sabor, ya un 22 % le desagrada. El 73% de 105 padres perciben que hay diferencia de eficacia entre 105 antitérmicos. De ellos, el 63 % opina que el más eficaz es el ibuprofeno, frente a un 27% que se inclina por el paracetamol. El 84% de 105 padres prefiere dar un antitérmico en concreto a su hijo; de ellos, el55% prefiere administrar el ibuprofeno frente a un 38% que prefiere darle el paracetamol. El 49% de 105 padres recurre a la alternancia de antitérmicos, y un 91 % emplea medidas fisicas. Conclusiones: ambos preparados de ibuprofeno y paracetamol, masivamente consumidospor nuestros niños, son fármacos de agradable sabor. Copan de forma casi exclusiva el mercado farmacéutico de la fiebre. Los padres centran su preferencia en el ibuprofeno citado. En casi la mitad de 105 casos recurren a la alternancia entre dos fármacos. En la mayor partede las situaciones febriles, acompañan el antitérmico de medidas físicas

Objedive: to describe the preferences and tendencies in the consume of antipyretics, as well as evaluate how the parents of our patients face up to treat fever. Patients and methods: data were colleded using a survey filled by the parents of 107 patients whose ages ranged from 6 months to 10 years. A descriptive analysis of the aimedvariables was made and frequency of each answer was estimated. Results: 92% of parents have sometime offered an ibuprofen (Dalsye) to their children,and 98% have given an acetaminophen (Apiretal). Among the children who had consumed ibuprofen, 65% liked its flavour and 23% disliked it. Those who had tried acetaminophen, 61 % liked his flavour and 22% disliked it 73% of parents noticed differences of efficacy ofantipyretics. 63% of them think ibuprofen is more effedive than acetaminophen, and 26% think acetaminophen is more effedive than ibuprofen. Most of parents (84%) prefer to give an specific antipyretic to their children. 55 % of them prefer ibuprofen and 38% prefer acetaminophen. 49 % alterna te two antipyretics and 91 % use physical measures. Conclusions: ibuprofen and acetaminophen, widely consumed by our children, are bothnice-flavoured. 80th drugs monopolise the current pharmaceutical market of fever in children.Parents lead their preferences to the ibuprofen mentioned. In almost half cases the parents alternate two antipyretics. In most of the feverish situations, they also use physical measures

Respuesta espectacular de una encefalomielitis aguda diseminada tras altas dosis de esteroides / Spectacular response of acute disseminated encephalomyelitis after high-dose steroid therapy

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