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A B S T R A C T Background and objectives: The aim of this study is to analyze the presence of circadian rhythm in the time of onset of symptoms of acute myocardial infarction treated by a prehospital emergency system and the influence of modifiable cardiovascular risk factors and non-modifiable as modulators of that circadian rhythm. Patients and methods: Retrospective analysis of 709 patients clinically diagnosed with acute myocardial infarction on-site in the prehospital setting. The variables were time to onset of symptoms, age, sex, previous ischemic heart disease, hypertension, diabetes mellitus, hyperlipidemia and smoking. We analyzed the rhythm with cosinor multiple sinusoid method, with 3 harmonics (24, 12 and 8 h) for the

Objetivos: Analizar las características cronobiológicas y las variaciones temporales del paro cardiaco extrahospitalario (PCEH). Diseño: Estudio descriptivo retrospectivo. Pacientes: Todos los casos de PCEH de origen cardíaco registrados en la base de datos del servicio de emergencias médicas (SEM) de la Comunidad Autónoma de Castilla y León (España) durante 18 meses. Variables de interés principales: Edad, sexo, recuperación de la circulación espontánea, primer ritmo monitorizado (desfibrilable /no desfibrilable), lugar de alerta [(hogar, lugar público, centro atención primaria (AP)], testigo (familiar, transeúnte, fuerzas de seguridad, personal AP), hora de alerta (0-8; 8-16; 16-24), hora de activación del equipo de emergencias, hora de atención y día de la semana. Análisis univariante mediante Chi², varianza y tests no paramétricos. Análisis cronobiológico mediante transformada rápida de Fourier y test Cosinor. Resultados: Se estudiaron 1.286 casos registrados entre enero 2007 y junio 2008. Se observaron diferencias estadísticas significativas en menor edad (p

To cite this article: Matias V, San Feliciano L, Fernandez JE, Lapena S, Garrido E, Ardura J, Soga MJ, Aragon MP, Remesal A, Benito F, Andres J, Centeno F, Marugan V, Bachiller R, Bermejo-Martin JF. Host and environmental factors influencing respiratory secretion of pro-wheezing biomarkers in preterm children. Pediatric Allergy Immunology 2012: 23: 441–447. Abstract Cytokines are actively secreted by the respiratory mucosa of preterm children and participate in the pathogenesis of wheezing. This study aimed to identify the factors that could potentially influence respiratory secretion of cytokines in these children. A nasopharyngeal aspirate (NPA) was collected from 77 preterm children 1 yr after birth. NPAs from 14 healthy, 1-yr-old term children were collected in parallel. 27 cytokines were measured in the NPAs using a multiplex assay. Multivariate stepwise regression analysis with Bonferroni correction evidenced that the variable [daycare attendance] was associated with higher levels of [monocyte chemoattractant protein-1 (MCP-1), IL-6, vascular endothelial growth factor (VEGF), IL-1β, IL-10, tumor necrosis factor (TNF)-α]; [male sex] with higher levels of (MCP-1, VEGF, and IL-1β); [smokers at home] was associated with higher levels of MCP-1 (p

Human respiratory syncytial virus (RSV) is the leading viral cause of severe respiratory illness in infants and young children worldwide. RSV isolates can be divided into 2 subgroups, type A and type B. Here, we compare for the first time the nasal profiles of 27 immune mediators in response to both viral subtypes in 14 children infected with RSV/A, 8 children infected with RSV/B, 11 children coinfected with RSV/A plus other respiratory viruses, and finally, 27 control children, all

Background and aim: Several seasonal variations have been found in birth rates in different countries at different periods. The characteristics of the rhythmic patterns vary according to geographical location and chronological changes. This study presents data on spanish birth seasonality over six decades. Methods: A time series composed of 33 421 731 births in Spain in the period 1941–2000 was analysed. The series comes from the National Institute of Statistics and was processed according to the following norms: (1) normalisation of the duration of months and years; (2) clinical analysis of temporal series (isolation of seasonal component); (3) Fourier’s spectral analysis; and (4) cosinor analysis (adjustment to the cosine curve of two harmonics). Results: Significant seasonal rhythm was found in the set of births, both for a 12-month period and a 6-month period. The rhythm shows bimodal morphology, with a pronounced birth peak in April and a smaller one in September. These peaks correspond to July and December conceptions, respectively. The major birth peak shifted to March–May between the 1940s and the 1980s. Birth rhythm changed after the 1960s, with a decrease in amplitude and later loss of seasonality in the 1990s. Conclusions: In Spain, seasonal birth rhythm shows a decline from 1970, and, finally, lack of birth seasonality in 1991–2000. This trend is similar to other European countries, although Spain shows a more intense loss of seasonality.

Aim: The objective of this study was to describe the rhythm of respiratory syncytial virus (RSV) bronchiolitis seasonal outbreaks in hospitalized children. Methods: Data was collected from 1324 patients, who were admitted to our hospital with bronchiolitis, over an 11-year period, from 1994 to 2004. The epidemic onset was established according to the epidemic index. Virological diagnosis was made with immunofluorescent assay from nasopharyngeal washings. Rhythm study was carried-out by spectral analysis with the fast-Fourier transformed and cosinor method. Results: Epidemics begin in September (45%) and October (55%); the highest peak was observed in January, the minimum in August and the end in February (73%), March (18%) and April (9%). When the epidemic outbreak begins sooner, the end is sooner as well. Epidemic onset varies but not its length and the onset was less variable than its conclusion. Spectral analysis showed a 12-months cyclic period along the study years and cosinor analysis demonstrated significant circannual rhythm. When data was segregated by long and short hospital stay, no significant differences were found between the rhythms. Comorbid association among bronchiolitis, otitis and gastroenteritis was very common. Conclusion: Bronchiolitis epidemics onset and conclusion varies along time years in hospitalized infants and showed circannual rhythmicity with a 12-months period.

The aim of this study was to determine the existence of the circadian rhythm (CR) in the onset of acute myocardial infarction (AMI) in different patient subgroups. Information was collected about 41,244 infarctions from the database of the ARIAM (Analysis of Delay in AMI) Spanish multicenter study. CR in AMI were explored in subgroups of cases categorized by age, gender, previous ischemic heart disease (PIHD), outcome in coronary care unit, infarction electrocardiograph (ECG) characteristics (Q wave or non-Q wave), and location of AMI. Cases were classified according to these variables in the different subgroups. To verify the presence of CR, a simple test of equality of time series based on the multiple-sinusoid (24, 12, and 8 h periods) cosinor analysis was developed. For the groups as a whole, the time of pain onset as an indicator of the AMI occurrence showed a CR (p0.0001), with a morning peak at 10:10 h. All the analyzed subgroups also showed CR. Comparison between subgroups showed significant differences in the PIHD (p0.01) and infarction ECG characteristics (p0.01) groups. The CR of the subgroup with Q-wave infarction differed from that of non-Q wave subgroup (p0.01) when the patients had PIHD (23% in Q wave infarction vs. 39.2% in non-Q wave). AMI onset followed a CR pattern, which is also observed in all analyzed subgroups. Differences in the CR according to the Q/non-Q wave infarction characteristics could be determined by PIHD. The cosinor model fit with three components (24, 12, and 8 h periods) showed a higher sensitivity than the single 24 h period analysis.

Objetivo Estudiar la presencia y caracteristicas del ritmo circadiano en la hora de inicio de los sintomas del infarto de miocardio (IAM) en un grupo de poblacion geriatrica espanola. Ambito Unidades Coronarias adscritas al proyecto ARIAM. Diseno Estudio de cohorte retrospectivo. Pacientes registrados en el proyecto multicentrico ARIAM. Se seleccionaron los pacientes con diagnostico de IAM al alta de la Unidad Coronaria (54.249 pacientes), registrados entre mayo de 1994 y octubre de 2003. Intervencion Ninguna. Variables de interes principales Se analiza la hora de inicio del IAM, caracteristicas generales de la poblacion y del IAM (sexo, edad, extension y localizacion del IAM y mortalidad dentro de la Unidad Coronaria). Se estratifica la poblacion por edad (menores de 65 anos, 65-74 anos, 75-84 anos y mayores de 85 anos) y se comparan entre si los subgrupos resultantes. Se aplica la prueba del χ 2 sobre el porcentaje de pacientes agrupados en periodos de 6 horas. Resultados La hora de inicio del dolor en el IAM muestra ritmo circadiano en todos los subgrupos de edad (p Conclusiones El IAM en la poblacion geriatrica, al igual que en la no geriatrica, muestra ritmo circadiano en la hora de presentacion de sus sintomas. El pico de maxima incidencia matinal se acentua con la edad. La incidencia minima es nocturna, salvo en los muy ancianos, que es vespertina.

Fundamento y objetivo: Determinar la existencia de ritmo circadiano en la hora de inicio del infarto de miocardio (IM) segun su extension electrocardiografica Q/no Q. Pacientes y metodo: Estudio retrospectivo de una cohorte de pacientes del proyecto ARIAM que incluyo 54.249 IM. Se analizan variables generales del infarto (edad, sexo, cardiopatia isquemica previa, extension del infarto, localizacion, supervivencia al alta de la unidad de cuidados intensivos), factores de riesgo cardiovascular y tratamientos farmacologicos previos al episodio estudiado. Para verificar la presencia de ritmo circadiano se ha desarrollado un test simple de igualdad de series basado en el analisis cosinor de multiples sinusoides, utilizando 3 sinusoides de periodos de 24, 12 y 8 h. Resultados: La hora de inicio de los sintomas del infarto mostro ritmo circadiano (p < 0,0000) tanto en el IM Q como en el IM no Q. Los IM Q presentan un patron con un unico maximo de incidencia matinal y los no Q, un patron bimodal con doble pico de incidencia. La comparacion entre dichos patrones muestra diferencias significativas en su ajuste (p < 0,0000). Conclusiones: La hora de inicio del IM sigue un patron circadiano, que tambien se observa en los subgrupos analizados. Las diferencias entre los ritmos circadianos segun el tipo de IM (Q frente a no Q) podrian explicarse por el distinto mecanismo fisiopatologico de ambos subtipos de infarto. El modelo de analisis de cosinor ajustado con 3 componentes (periodos de 24, 12 y 8 h) muestra buena sensibilidad para la deteccion de ritmo circadiano.

Introduction and objectives. The aim of this study was to analyze the influence of modifiable cardiovascular risk factors on the circadian rhythm of acute myocardial infarction. Patiens and method. We analyzed a retrospective cohort of 54 249 patients from a multicenter study of acute myocardial infarction (the Spanish ARIAM study). The variables were time of onset of symptoms, age, sex, previous ischemic heart disease, coronary unit discharge status, previous stroke, familial antecedents of ischemic heart disease, hypertension, diabetes, dyslipidemia, smoking, and reinfarction. To verify the presence of circadian rhythm, we developed a simple test of equality of time series based on cosinor analysis of multiple sinusoid curves. Three sinusoids (24,12, and 8 hour periods) were used. Results. The time of onset of pain showed a circadian rhythm (P

Background: Increase in the gradient in congenital pulmonary valvular stenosis during follow-up is a subject of controversy and could determine the need for treatment in pediatric patients. Hypothesis: It is postulated that a gradient < 50 mmHg shows a stable or decreasing tendency at follow-up for congenital pulmonary valvular stenosis. Methods: Thirty-five patients with pulmonary stenosis, isolated and not treated, were followed for 7 years (interquartilic rank 5.7 years) at 1.5-year intervals. Clinical and complementary tests (electrocardiogram, x-ray, Doppler echocardiogram) were undertaken. The gradient was measured by Doppler and by using the clinical formula derived from the New England Study (Ellison). The changes observed from the initial to the final consultation were analyzed by means of the Student's t-test, paired Wilcoxon, and Pearson correlation coefficient. Results: No significant changes were noted on symptoms or physical examination. Signs of cardiac enlargement diminished on both ECG (R wave in V1, p < 0.0001) and x-ray (car-diothoracic ratio, p < 0.0007), with a decreasing gradient trend during the follow-up period (p < 0.026) as well. Conclusions: The gradient trend confirms the stable nature of mild pulmonary stenosis. In our study, we found that patients aged > 6 months, whose gradients were below 40 mmHg at the time of diagnosis, remained stable and required no treatment. Furthermore, the follow-up control and clinical management of these patients may then be performed at intervals of 2 years or more.

A circadian rhythm of heart rate and respiratory rate was seen at 1, 8, and 12 months of age in an infant born without ocular tissue, which supports the possibility that the time cues were nonphotic. No melatonin circadian rhythm was detected at any age up to 9 years of age, and this is most likely associated with the anophthalmia and lack of photic input to the suprachiasmatic nucleus. Usually circadian organization is present after the neonatal period and approaches adult levels with development.

Introduccion y objetivos El objetivo de este trabajo es analizar la influencia de los factores de riesgo cardiovascular modificables en el ritmo circadiano del infarto agudo de miocardio. Pacientes y metodo. Analisis retrospectivo de 54.249 pacientes incluidos en la base de datos del proyecto ARIAM con diagnostico de infarto agudo de miocardio. Se analizan las variables hora de inicio, edad, sexo, cardiopatia isquemica previa, estado en el momento del alta de la unidad coronaria, antecedentes familiares de cardiopatia isquemica, accidente cerebrovascular previo, hipertension arterial, dislipemia, diabetes, tabaquismo y reinfarto. El analisis de ritmo se ha efectuado utilizando un test simple de igualdad de series basado en el analisis cosinor de multiples sinusoides, eligiendo 3 armonicos (24,12 y 8 h) para su ajuste. Resultados La hora de inicio del infarto muestra ritmo circadiano (p Conclusiones El infarto agudo de miocardio presenta ritmo circadiano. La diabetes, el tabaquismo y el reinfarto pueden modificar el ritmo habitual de aparicion del infarto.

Objective: To assess the age at which the circadian rhythm of melatonin begins. Methods: 55 children, divided into groups from the neonatal period to 24 months of life, were studied. Urine samples were taken from 28 newborn babies to measure 6-sulfatoxymelatonin (aMT6s). Salivary samples were collected from infants (27 cases), to measure melatonin (aMT). aMT was measured by RIA and aMT6s by ELISA using commercial kits. Changes in the levels of aMT6s and aMT were evaluated using the Friedman test and Wilcoxon matched pair test. Results: The group aged 27–41 days showed statistically significant differences in daily aMT6s and aMT concentrations. The highest values were always found between 24.00 and 8.00 h. This day/night difference persisted from 2–3 to 13–24 months of age. Conclusion: The data indicate that the circadian melatonin rhythm appears at the end of the neonatal period and persists thereafter.

Patterns of circadian and ultradian rhythms in the heart rate (HR) are described in a full-term baby with birth asphyxia and convulsions. A 24h HR recording was carried out at the age of 1, 15, 56, 289, and 295 days; West syndrome diagnosis was made when the patient was 3 months old. The HR showed no circadian rhythm in the follow-up, whereas it is known that the circadian rhythm appears in healthy infants at the age of 1 month and remains thereafter. This observation may be an indirect indicator of the interference of West syndrome with centers of neurological maturity.

OBJECTIVE To study the circadian rhythm of melatonin in children with enuresis. PATIENTS AND METHODS Twenty-five children, divided into two groups (enuretic patients and controls) were assessed; salivary samples were collected to measure melatonin by radioimmunoassay using commercial kits. Friedman two-way anova and Wilcoxon tests were used to assess the circadian rhythm of melatonin, and anova with between-patient factors and Mann-Whitney tests to compare melatonin values and groups. RESULTS Both groups had statistically significant differences in melatonin concentration during the 24-h period (both P

Heart rate (HR) was recorded in healthy full-term newborns aged 1–90 days. The aim of this study was to study the existence of circadian and/or ultradian rhythms in HR to determine maturity. HR was recorded during 24 h, at 30-min intervals, at different postnatal ages. Six groups were investigated: day 1 (group 1); day 7 (group 7); day 15 (group 15); day 30 (group 30); day 60 (group 60), and day 90 (group 90). The chronograms for HR showed peaks and nadirs along the 24-hour periods, and the cosinor analysis proved the existence of 3-hour ultradian rhythm in groups 1, 7 and 30, and a 12-hour ultradian rhythm in group 90 (p < 0.01 in all cases). The same type of analysis confirmed the existence of a circadian rhythm in group 30. Similar results were obtained for groups 60 and 90 (p < 0.05). In conclusion: at birth, newborns have an endogenous ultradian period of 3 h. A circadian rhythm appears within 15–30 days of postnatal life.

The aims of this study were: (1) to investigate the evolution of the sleep pattern in preterm newborns during their first month of life; (2) to assess the influence of light–dark on the sleep pattern; and (3) to compare this pattern with that of full–term newborns. The population consisted of 60 healthy, preterm newborns and 63 full–term newborns, divided into four age groups, 1 week apart, throughout the first month of life. Preterm newborns were further divided into five groups according to conceptional (corrected) age. An observer took note every 30 min, for 24 h, of sleep or wakefulness in every case. The average sleeping time in preterm groups according to postnatal age remained unchanged during the first month of life: 17.57 honday 1 and 17.15h on day 28. When the preterm infants were re–grouped according to conceptional age, average daily sleep was 17.86 h at 32 weeks and 15.22 h at 37 weeks. The full–term newborns had an average daily sleep of 14.78 h on day 1 and 11.94 h on day 28, with a decrease throughout week 4 of life (p < 0.001). The decrease in daily sleeping time in the full–term groups, took place at the expense of the daylight span, where there was a decrease througout the first month of life (p < 0.01). There were no differences in preterm newborns during the light and dark phases. A progressive synchronization of sleep to the light–dark was seen in the control group. Therefore, the sleeping pattern could be taken as an indication of the degree of biological immaturity of preterm newborns.

Objetivos. Analizar las caracteristicas cronobiologicas y las variaciones temporales del paro cardiaco extrahospitalario (PCEH). Diseno. Estudio descriptivo retrospectivo. Pacientes. Todos los casos de PCEH de origen cardiaco registrados en la base de datos del servicio de emergencias medicas (SEM) de la Comunidad Autonoma de Castilla y Leon (Espana) durante 18 meses. Variables de interes principales. Edad, sexo, recuperacion de la circulacion espontanea, primer ritmo monitorizado (desfibrilable /no desfibrilable), lugar de alerta [(hogar, lugar publico, centro atencion primaria (AP)], testigo (familiar, transeunte, fuerzas de seguridad, personal AP), hora de alerta (0-8; 8-16; 16-24), hora de activacion del equipo de emergencias, hora de atencion y dia de la semana. Analisis univariante mediante Chi2, varianza y tests no parametricos. Analisis cronobiologico mediante transformada rapida de Fourier y test Cosinor. Resultados. Se estudiaron 1.286 casos registrados entre enero 2007 y junio 2008. Se observaron diferencias estadisticas significativas en menor edad (p

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children and adolescents; however, its etiology is still unknown, which hinders the existence of reliable, fast and inexpensive standard diagnostic methods. In this paper, we propose a novel methodology for automatic diagnosis of the combined type of ADHD based on nonlinear signal processing of 24h-long actigraphic registries. Since it relies on actigraphy measurements, it constitutes an inexpensive and non-invasive objective diagnostic method. Our results on real data reach 96.77% sensitivity and 84.38% specificity by means of multidimensional classifiers driven by combined features from different time intervals. Our analysis also reveals that, if features from a single time interval are used, the whole 24-h interval is the only one that yields classification figures with practical diagnostic capabilities. Overall, our figures overcome those obtained by actigraphy-based methods reported and are comparable with others based on more expensive (and not so convenient) adquisition methods.

The aim of this study is to analyze the presence of circadian rhythm in the time of onset of symptoms of acute myocardial infarction treated by a prehospital emergency system and the influence of modifiable cardiovascular risk factors and non-modifiable as modulators of that circadian rhythm.Retrospective analysis of 709 patients clinically diagnosed with acute myocardial infarction on-site in the prehospital setting. The variables were time to onset of symptoms, age, sex, previous ischemic heart disease, hypertension, diabetes mellitus, hyperlipidemia and smoking. We analyzed the rhythm with cosinor multiple sinusoid method, with 3 harmonics (24, 12 and 8h) for the adjustment.The time of onset of pain showed circadian rhythm (P,001), peaking at 10.39 and a valley at 4.28, showing a sinusoidal curve fitting bimodal aspect with a predominant morning peak and another evening one of lower amplitude. All subgroups categorized by the study variables showed circadian rhythm, with a cosine curve similar to the global infarction. Smokers had a predominantly evening peak.Acute myocardial infarction shows a circadian rhythm. Smoking and diabetes mellitus can modify the standard incidence rate of occurrence of myocardial infarction.

The diagnosis and therapy planning of high prevalence pathologies such as infantile colic can be substantially improved by statistical signal processing of activity/rest registries. Assuming that colic episodes are associated to activity episodes, diagnosis aid systems should be based on preprocessing techniques able to separate real activity from rest epochs, and feature extraction methods to identify meaningful indices with diagnostic capabilities. In this paper, we propose a two step diagnosis aid methodology for infantile colic in children below 3 months old. Identification of activity periods is performed by means of a wavelet based activity filter which does not depend on the acquisition device (as so far proposed methods do). In addition, symbolic dynamic analysis is used for extraction of discriminative indices from the activity time series. Results on real data yielded 100% sensitivity and 80% specificity in a study group composed of 46 cases and 10 control subjects.

A study on melatonin rhythm in children with generalized idiopathic epilepsy and simple fever is presented in this article. A population of 40 children was divided into 4 groups, namely, epilepsy, febrile seizure, and 2 control groups. Salivary melatonin was measured by means of radioimmunoassay. Friedman 2-way analysis of variance (ANOVA) and Wilcoxon tests were employed to assess the existence of melatonin rhythm. Comparison across groups was performed by means of ANOVA and Mann-Whitney tests. Higher melatonin levels were found at night, with a peak at 04:00 h in all groups. Significant diurnal rhythm was also detected for these levels. No significant overall differences between case and control groups were found for melatonin levels, though patients showed lower peak melatonin values than controls at 04:00 h with a significant difference in the febrile seizure group (10.70 vs 19.5 pg/mL respectively; P

et al., Respiratory syncytial virus (RSV) infection is an important cause of recurrent wheezing in infants. Nevertheless, the link between RSV infection and wheezing has yet to be elucidated at the molecular level. Here, we present a preliminary study on the evolution of the immune response in the respiratory tract at long-term after RSV infection. Twenty-seven immune mediators were profiled in nasopharyngeal aspirates (NPAs) obtained from 20 children hospitalized due to a severe infection by RSV at discharge from hospital and again 1 yr later. The same mediators were profiled in parallel in NPAs from 12 healthy controls. In the year following discharge, 85% (17/20) of children of the RSV group suffered at least one episode of wheezing documented by the pediatrician. On the contrary, wheezing episodes were observed only in 25% (3/12) of children in the control group. While most of the mediators profiled returned to normal levels by 1 yr after discharge from hospital, RSV children showed a persistent nasal hyper-secretion of VEGF, G-CSF, IL-10, IL-6, IFN-γ, IL-7 and IL-13. In previous works VEGF, IL-10 and IFN-γ have been put in relation with the pathogenesis of post-virus induced asthma. G-CSF, IL-6, IL-7 and IL-13 are increased in respiratory and plasma samples of asthmatic patients. Here, we evidence for the first time a persistent elevation of these mediators as late as 1 yr after severe RSV disease resolution, reinforcing their possible implication in the pathogenesis of wheezing. © 2009 Blackwell Munksgaard., This work has been possible thanks to the financial support from “Fondo de Investigaciones Sanitarias, FIS, Programa para favorecer la incorporación de grupos de investigación en las Instituciones del Sistema Nacional de Salud, EMER07/050”.

Profiling of immune mediators in both nasal and plasma samples is a common approach to the study of pathogenesis in respiratory viral infections. Nevertheless, mucosal immunity functions essentially independently from peripheral immunity. In our study, 27 immune mediators were profiled in parallel, in nasopharyngeal aspirates (NPAs) and plasma from 222 year-old children with a severe respiratory syncytial virus infection involving the lower respiratory tract, using a multiplex assay. NPAs from 22 children with innocent heart murmurs were used as controls. Differences in mediator concentrations between NPAs from patients and controls were assessed using the Mann-Whitney test. Ratios of innate/adaptive-immunity mediators, Th2/Th1-cytokines and CXC/CC-chemokines were calculated for NPAs and plasmas and differences were assessed using the Wilcoxon test. Associations mediators, severity and leukocyte counts were studied using the Spearman-Karber test.increased levels of Th1 cytokines (IL-1beta, IL-2, IL-12p70, IFNgamma, TNFalpha), Th2 cytokines (IL-13, IL-4, IL-6, IL-10), chemokines (IP-10, IL-8, MIP1alpha, MIP-1beta), growth factors (FGFb, PDGFbb, GCSF) and IL-1RA, IL-17 were observed in patient NPAs in comparison to controls. In the relative comparisons between patient NPAs and plasmas, a predominance of innate immunity mediators, Th2 cytokines and CXC chemokines was found at the mucosal level. No association between the level of each mediator in NPAs and plasma was found. In plasma, PDGFbb, VEGF, MIP-1alpha, IL-8 correlated with severity; RANTES and IL-6 correlated with leukocyte counts.acute respiratory syncytial virus infection induces a relative predominance of innate-immunity mediators, Th2 cytokines and CXC chemokines in the mucosal compartment in infected children.

Background: Increase in the gradient in congenital pulmonary valvular stenosis during follow‐up is a subject of controversy and could determine the need for treatment in pediatric patients. Hypothesis: It is postulated that a gradient < 50 mmHg shows a stable or decreasing tendency at follow‐up for congenital pulmonary valvular stenosis. Methods: Thirty‐five patients with pulmonary stenosis, isolated and not treated, were followed for 7 years (interquartilic rank 5.7 years) at 1.5‐year intervals. Clinical and complementary tests (electrocardiogram, x‐ray, Doppler echocardiogram) were undertaken. The gradient was measured by Doppler and by using the clinical formula derived from the New England Study (Ellison). The changes observed from the initial to the final consultation were analyzed by means of the Student's t‐test, paired Wilcoxon, and Pearson correlation coefficient. Results: No significant changes were noted on symptoms or physical examination. Signs of cardiac enlargement diminished on both ECG (R wave in V1, p < 0.0001) and x‐ray (car‐diothoracic ratio, p < 0.0007), with a decreasing gradient trend during the follow‐up period (p < 0.026) as well. Conclusions: The gradient trend confirms the stable nature of mild pulmonary stenosis. In our study, we found that patients aged > 6 months, whose gradients were below 40 mmHg at the time of diagnosis, remained stable and required no treatment. Furthermore, the follow‐up control and clinical management of these patients may then be performed at intervals of 2 years or more.

An increased gradient in congenital valvular aortic stenosis (AS) during follow up remains the subject of controversy, and may determine a need for treatment in pediatric patients. It is hypothesized that a valvular gradient40 mmHg indicates a stable tendency at follow up for congenital valvular AS.Twenty-five cases with valvular AS, isolated but not treated, were followed for eight years (range: 0.14-18.8 years). Clinical and complementary tests (electrocardiography, X-radiography) were undertaken. The gradient anatomy and function were measured using M-mode, two-dimensional, and Doppler echocardiography.No significant changes were noted in symptoms or at physical examination. Signs of cardiac enlargement were decreased (p0.001), and the functional status and gradient remained stable during the follow up period (mean difference 2.38 mmHg; p = 0.74). The relationship between gradient and age showed a slowly increasing trend (r = 0.20).The trend in gradient confirmed the stable nature of mild AS. Patients in whom gradients were40 mmHg at the time of diagnosis remained stable and required no treatment. Subsequent follow up control and clinical management of these patients may be performed at intervals of two years, or more.

To determine the existence of circadian rhythm in the time of onset of acute myocardial infarction (AMI) according to their extension type (Q-wave vs. non-Q-wave).We studied a retrospective cohort of patients from a multicentre study of myocardial infarction (ARIAM study group). We collected information about 54,249 infarctions from the data base of the ARIAM (Analysis of Delay in AMI) Spanish multicentre study. The following variables were analysed: general variables --age, gender, previous ischemic heart disease, outcome at coronary care unit, infarction electrocardiograph type (Q wave or non-Q wave) and location of AMI--, cardiovascular risk factors, and previous drug treatment of the patients. To verify the presence of circadian rhythm we developed a simple test of equality of time series based on the multiple-sinusoid cosinor analysis. Three sinusoids (24-12-8 h periods) were used.The time of pain onset shows circadian rhythm (p0.0000), which also is observed in both infarction electrocardiograph characteristics subgroups (Q-wave infarction and non-Q-wave infarction) (p0.0000). Q-wave infarction shows sinusoid curve with one maximum morning peak and non-Q-wave shows bimodal curve, with two peaks. Comparison between their curves shows statistical significance (p0.0000).AMI onset follows a circadian rhythm pattern, which is also observed in analysed subgroups. Differences in the circadian rhythm according to the Q/non-Q wave infarction characteristics, could be determined by different physiopathologic mechanism. The cosinor model fit with three components (24, 12 and 8-hour-periods) show good sensitivity to determine circadian rhythm.

The aim of this study was to analyze the influence of modifiable cardiovascular risk factors on the circadian rhythm of acute myocardial infarction.We analyzed a retrospective cohort of 54,249 patients from a multicenter study of acute myocardial infarction (the Spanish ARIAM study). The variables were time of onset of symptoms, age, sex, previous ischemic heart disease, coronary unit discharge status, previous stroke, familial antecedents of ischemic heart disease, hypertension, diabetes, dyslipidemia, smoking, and reinfarction. To verify the presence of circadian rhythm, we developed a simple test of equality of time series based on cosinor analysis of multiple sinusoid curves. Three sinusoids (24, 12 and 8 hour periods) were used.The time of onset of pain showed a circadian rhythm (P.01), with a peak at 10:07 am and a trough at 4:46 am. All subgroups categorized according to the presence of the variables analyzed here showed a circadian rhythm, with a sinusoid curve after adjustment. In patients with diabetes or reinfarction or who were smokers, the sinusoid curve was bimodal.Time of onset of symptoms in patients with acute myocardial infarction follows a circadian rhythm. Diabetes, smoking and reinfarction can modify the standard circadian rhythm of onset of myocardial infarction.

Some studies about the onset time of AMI revealed that the peak incidence of pain onset signaling the occurrence of AMI ranged from 08:00 to 11:00 h in presumably diurnally active persons [1,2]. A recent study published by our group showed a morning incidence peak as well [3]. Otherwise the use of beta blockers could be caused by an attenuation or complete removal of the peaks of incidence of myocardial ischemia andAMI [4,5].When cardio selective beta blocker agents were used, no peaks of incidence were found [6]. The objective of this study is to evaluate, by means of a new method of analysis [7], the presence of circadian variation in the time of onset of AMI in subgroups of patients receiving beta-adrenergic blockade agents. Patients with diagnosis of AMI at ICU discharge in 119 Spanish hospitals, according to WHO criteria, were collected from the ARIAM database. Among the whole group of 14,952 AMI, we selected a subgroup of 2055 patients who were taking beta-blocker agents. The selected study variable was the time of onset of symptoms. In order to carry out the rhythmometric analysis, we record and round AMI onset time to the nearest integer hour for every patient. With the purpose of verifying the presence of circadian rhythm, we used themultiple-sinusoid cosinor analysis.We identify the periods of these new sinusoids by means of nonlinear optimization techniques but it is also common to infer them using their clinical meaning. Following the latter approach, three sinusoids with periods of 24, 12 and 8 h were used [7]. We obtained the parameters of the model (MESOR and two additional parameters per sinusoid, namely, a function of the amplitude and the acrophase), as previously stated, by linear least squares fitting. A simple inspection of the cosinor fit and the original data showed that the fit was acceptable, and we did not consider further goodness-of-fit tests worth taking. The characteristics of the study population were: The mean age was 66.5±11.3 years old (64.8±11 for males and 71.3±9.2 for females). 46% were older than 70 years. Male/Female ratio was 72.9%/27.1%. 60.9% of AMI was Q-wave AMI. AMI location was anterior in 39.8%. 90.3% of AMI were alive at ICU discharge. In addition, previous cardiovascular risk factors were hypertension

Lighting, noise and temperature were monitored in two perinatal nurseries. Rhythms of several frequencies were found, including prominent 24-hour rhythms with acrophases around 13:00 (light intensity) and 16:00 (noise). For light and noise, the ratio formed by dividing the amplitude of a 1-week (circaseptan) or half-week (circasemiseptan) fitted cosine curve by the amplitude of a 24-hour fitted cosine curve is smaller than unity, since 24-hour rhythms are prominent for these variables. The amplitude ratios are larger than unity for temperature in the newborns' unit but not in the infants' unit. Earlier, the origin of the about-7-day rhythms of neonatal physiologic variables was demonstrated to have, in addition to a major endogenous, also a minor exogenous component. Hence, the possibility of optimizing maturation by manipulating environmental changes can be considered, using, as gauges of development, previously mapped chronomes (time structures of biologic multifrequency rhythms, trends and noise).

We report the results of treatment with amiodarone in nine children with dysrhythmias resistant to conventional drugs, namely, one with ventricular tachycardia, two with atrial tachycardia, one with junctional tachycardia, three with reciprocal rhythm tachycardia, and two with Wolff-Parkinson-White syndrome. The initial dose was 800 mg/1.73 m2, administered for two weeks, followed by half the dose for five days a week. The duration of the treatment varied from nine months to 19 months (mean duration, 13 months). Patients were followed up for a period ranging between nine and 33 months (mean period, 17 months). A complete remission was obtained in 56% of patients and partial success in 46%. The following side effects were detected: photosensitization in two; effect on weight, height, growth velocity, and thyroid hormones in three, six, five, and six, respectively; and acceleration in bone age in three. These effects were observed from two to nine months after the beginning of treatment. They persisted for 5–18 months after treatment had been suspended. The main side effect of amiodarone in children is presumably initial hypothyroidism, followed by a biological hyperthyroid reaction. For these reasons we suggest that amiodarone should be restricted as an alternative drug for resistant critical dysrhythmias and be used only for a limited period of two years.