Lack of concordance in parapneumonic effusion management in children in central Europe.

Treatment of parapneumonic effusion in children remains controversial in the literature and in clinical practice. The aim of this study was to determine whether mutual consensus exists in the diagnosis and treatment of parapneumonic effusion in Central European countries. A questionnaire was sent to all directors of pediatric respiratory units in four adjacent Central European countries (Austria, France, Germany, Switzerland). The response rate was 61.8%. Responses reflected acceptable agreement regarding initial diagnostic procedures, as most centers performed chest X-ray and biological exams, followed by ultrasound, thoracocentesis, or computed tomography. However, antibiotic regimens were very heterogeneous, and the survey revealed complete lack of agreement on the indications and effusion volume threshold for invasive procedures, such as fibrinolytic instillation and thoracoscopy. In conclusion, apart from initial diagnostic procedures, this study showed a lack of mutual consensus among the four countries regarding the management of pediatric parapneumonic effusion. Multicenter prospective trials are clearly needed to acquire more evidence on the management of childhood parapneumonic effusion, enabling the development of evidence-based algorithms that could help to avoid unnecessary examinations with potential long-term side effects, such as radiation exposure at a young age.

[Pediatric emergencies -- the essential, briefly, for general practitioners]. / Pädiatrische Notfälle - das Wichtigste in Kürze für den Allgemeinmediziner.

For general practitioners, emergency assessment of a critically ill or injured child can be difficult, as history is usually given by caregivers, physical examination may be challenging due to lack of cooperation and vital signs are potentially difficult to interpret because of age-related variations. The Pediatric Assessment Triangle (PAT) is a rapid and simple observational tool to standardize the initial assessment of children regardless of complaint or underlying diagnosis. It only uses visual and auditory clues, requires no equipment, and takes only seconds to perform. It allows clinicians to assess whether an urgent intervention is necessary or whether a more detailed history and physical examination may be done. Respiratory distress, gastro-enteritis with dehydration, febrile convulsions and traumatic brain injury constitute four common pediatric complaints that are encountered in a general practitioners consultation and will be discussed in some detail.

A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection.

RATIONALE: Cystic fibrosis (CF) is characterized by progressive pulmonary inflammation that is infection-triggered. Pseudomonas aeruginosa represents a risk factor for deterioration of lung function and reduced life expectancy. OBJECTIVES: To assess T-cell cytokine/chemokine production in clinically stable children with CF and evaluate the association between T-cell subtypes and susceptibility for infection with P. aeruginosa. METHODS: T-cell cytokine/chemokine profiles were measured in bronchoalveolar lavage fluid (BALF) from children with CF (n = 57; 6.1 ± 5.9 yr) and non-CF control subjects (n = 18; 5.9 ± 4.3 yr). Memory responses to Aspergillus fumigatus and P. aeruginosa were monitored. High-resolution computed tomography-based Helbich score was assessed. In a prospective observational trial the association between BALF cytokine/chemokine profiles and subsequent infection with P. aeruginosa was studied. MEASUREMENTS AND MAIN RESULTS: Th1- (INF-γ), Th2- (IL-5, IL-13), Th17- (IL-17A), and Th17-related cytokines (IL-1ß, IL-6) were significantly up-regulated in airways of patients with CF. IL-17A, IL-13, and IL-5 were significantly higher in BALF of symptomatic as compared with clinically asymptomatic patients with CF. IL-17A and IL-5 correlated with the percentage of neutrophils in BALF (r = 0.41, P < 0.05 and r = 0.46, P < 0.05, respectively). Th17- (IL-17A, IL-6, IL-1ß, IL-8) and Th2-associated cytokines and chemokines (IL-5, IL-13, TARC/CCL17), but not IFN-γ levels, significantly correlated with high-resolution computed tomography changes (Helbich score; P < 0.05). P. aeruginosa- and A. fumigatus-specific T cells from patients with CF displayed significantly higher IL-5 and IL-17A mRNA expression. IL-17A and TARC/CCL17 were significantly augmented in patients that developed P. aeruginosa infection within 24 months. CONCLUSIONS: We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa.

Spirometry reference equations for central European populations from school age to old age.

BACKGROUND: Spirometry reference values are important for the interpretation of spirometry results. Reference values should be updated regularly, derived from a population as similar to the population for which they are to be used and span across all ages. Such spirometry reference equations are currently lacking for central European populations. OBJECTIVE: To develop spirometry reference equations for central European populations between 8 and 90 years of age. MATERIALS: We used data collected between January 1993 and December 2010 from a central European population. The data was modelled using "Generalized Additive Models for Location, Scale and Shape" (GAMLSS). RESULTS: The spirometry reference equations were derived from 118'891 individuals consisting of 60'624 (51%) females and 58'267 (49%) males. Altogether, there were 18'211 (15.3%) children under the age of 18 years. CONCLUSION: We developed spirometry reference equations for a central European population between 8 and 90 years of age that can be implemented in a wide range of clinical settings.

Allergic rhinitis as a predictor for wheezing onset in school-aged children.

BACKGROUND: Rhinitis in older children and adults has been shown to be a predictor for adolescent- and adult-onset asthma. These findings suggest an interaction between the upper and lower airways. Whether rhinitis is a predictor for childhood-onset asthma is unknown. OBJECTIVE: We sought to investigate whether rhinitis in early childhood is an independent predictor for wheezing between the ages of 5 and 13 years in the German Multicentre Allergy Study birth cohort. METHODS: The German Multicentre Allergy Study cohort initially included 1314 healthy children. They were followed from birth to the age of 13 years with regular questionnaires and interviews. Specific IgE levels were measured at yearly intervals. Airway hyperresponsiveness was assessed at 7 years. RESULTS: Allergic rhinitis until the age of 5 years was found to be a predictor for developing wheezing between the ages of 5 and 13 years, with an adjusted relative risk of 3.82 (P < .001). This association was not attributable to the type of sensitization, the severity of sensitization, or atopic dermatitis during the first 2 years of life. In this group of children, 41.5% of all new cases of wheezing occurred among children with preceding allergic rhinitis. CONCLUSIONS: The first manifestation of allergic rhinitis occurs in preschool children in whom it is a predictor for subsequent wheezing onset. Preschool children with rhinitis might thus benefit from early assessment of allergic sensitization to identify the children at high risk of wheezing.

Disagreement between symptom-reflux association analysis parameters in pediatric gastroesophageal reflux disease investigation.

AIM: To assess the agreement within 3 commonly used symptom-reflux association analysis (SAA) parameters investigating gastroesophageal reflux disease (GERD) in infants. METHODS: Twenty three infants with suspected GERD were included in this study. Symptom index (SI), Symptom sensitivity index (SSI) and symptom association probability (SAP) related to cough and irritability were calculated after 24 h combined pH/multiple intraluminal impedance (MII) monitoring. Through defined cut-off values, SI, SSI and SAP values are differentiated in normal and abnormal, whereas abnormal values point towards gastroesophageal reflux (GER) as the origin of symptoms. We analyzed the correlation and the concordance of the diagnostic classification of these 3 SAA parameters. RESULTS: Evaluating the GER-irritability association, SI, SSI and SAP showed non-identical classification of normal and abnormal cases in 39.2% of the infants. When irritability was taken as a symptom, there was only a poor inter-parameter association between SI and SSI, and between SI and SAP (Kendall's tau b = 0.37, P < 0.05; Kendall's tau b = 0.36, P < 0.05, respectively). Evaluating the GER-cough association, SI, SSI and SAP showed non-identical classification of normal and abnormal cases in 52.2% of the patients. When cough was taken as a symptom, only SI and SSI showed a poor inter-parameter association (Kendall's tau b = 0.33, P < 0.05). CONCLUSION: In infants investigated for suspected GERD with pH/MII-monitoring, SI, SSI and SAP showed a poor inter-parameter association and important disagreements in diagnostic classification. These limitations must be taken into consideration when interpreting the results of SAA in infants.

Association between peer relationship problems and childhood overweight/obesity.

AIMS: To assess the association between peer relationship problems and childhood overweight and obesity. METHODS: Data on 4718 preschool children were obtained at the obligatory school entry health examination in Bavaria. Parentally reported peer relationship problems ('normal', 'borderline' or 'abnormal') were assessed from the Strengths and Difficulties Questionnaire. Overweight and obesity were defined according to age- and gender-specific BMI cut-off points. Multivariate logistic regression analysis was performed to control potential confounders. RESULTS: The prevalence of overweight and obesity was higher among children with 'borderline' or 'abnormal' peer relationship problems compared to 'normal' children. The association of 'abnormal' peer relationship problems was still significant in the final logistic regression model for girls [odds ratio (OR) for overweight 2.0; 95% confidence interval (CI): 1.4-3.0; OR for obesity 2.6; 95% CI: 1.3-5.0]. Among boys the adjusted odds ratio were lower and no longer significant. CONCLUSION: The significantly increased prevalence of overweight and obesity among preschool children with peer relationship problems could not be explained by confounding. It seems evident that there is a relevant co-morbidity of peer relationship problems and obesity in pre-school children pointing to the need of interventions focusing on both physical as well as psychosocial health.

Long-term follow-up of a 26-year-old male with duplication of 16p: clinical report and review.

We report on a 26-year-old male with profound psychomotor retardation and a pattern of dysmorphic features and malformations characteristic for duplication of the short arm of chromosome 16. He has an elongated face, sparse hair, upslanting palpebral fissures, anteverted nostrils, hypoplastic thumbs on both hands, and dislocation of several joints. His chromosome aberration was diagnosed at birth and was due to an unbalanced segregation of a maternal translocation t(2;16)(q36;p11). At 26 years of age he is, to the best of our knowledge, the oldest patient with duplication of 16p reported to date. We present a long-term observation of growth, psychomotor development, dysmorphic features and evolution of his skeletal and joint defects as well as a review of the literature.

Hypoxia causes down-regulation of 11 beta-hydroxysteroid dehydrogenase type 2 by induction of Egr-1.

Hypoxia causes several renal tubular dysfunctions, including abnormal handling of potassium and sodium and increased blood pressure. Therefore, we investigated the impact of hypoxia on 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) enzyme, a crucial prereceptor gatekeeper for renal glucocorticosteroid-mediated mineralocorticoid action. The effect of hypoxia was assessed in vitro by incubating LLC-PK1 cells with antimycin A, an inhibitor of mitochondrial oxidative phosphorylation. Antimycin A induced a dose- and time-dependent reduction of 11beta-HSD2 activity. The early growth response gene, Egr-1, a gene known to be stimulated by hypoxia was investigated because of a potential Egr-1 binding site in the promoter region of 11beta-HSD2. Antimycin A induced Egr-1 protein and Egr-1-regulated luciferase gene expression. This induction was prevented with the MAPKK inhibitor PD 98059. Overexpression of Egr-1 reduced endogenous 11beta-HSD2 activity in LLC-PK1 cells, indicating that MAPK ERK is involved in the regulation of 11beta-HSD2 in vitro. In vivo experiments in rats revealed that Egr-1 protein increases, whereas 11beta-HSD2 mRNA decreases, in kidney tissue after unilateral renal ischemia and in humans the renal activity of 11beta-HSD2 as assessed by the urinary ratio of (tetrahydrocortisol+5alpha-tetrahydrocortisol)/tetrahydrocortisone declined when volunteers were exposed to hypoxemia at high altitude up to 7000 m. Thus, hypoxia decreases 11beta-HSD2 transcription and activity by inducing Egr-1 in vivo and in vitro. This mechanism might account for enhanced renal sodium retention and hypertension associated with hypoxic conditions.

Chenodeoxycholic acid and deoxycholic acid inhibit 11 beta-hydroxysteroid dehydrogenase type 2 and cause cortisol-induced transcriptional activation of the mineralocorticoid receptor.

Inappropriate activation of the mineralocorticoid receptor (MR) results in renal sodium retention and potassium loss in patients with liver cirrhosis. Recent evidence suggested that this MR activation is, at least in part, a result of bile acid-dependent reduction in 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) activity, an enzyme preventing cortisol-dependent activation of MR by converting cortisol to cortisone. Here, we investigated the molecular mechanisms underlying bile acid-mediated MR activation. Analysis of urinary bile acids from 12 patients with biliary obstruction revealed highly elevated concentrations of chenodeoxycholic acid (CDCA), cholic acid (CA), and deoxycholic acid (DCA), with average concentrations of 50-80 microm. Although CDCA and DCA both mediated nuclear translocation of MR in the absence of 11 beta HSD2 and steroids in transiently expressing HEK-293 cells, the transcriptional activity of MR was not stimulated. In contrast, CDCA and DCA both inhibited 11 beta HSD2 with IC(50) values of 22 and 38 microm, respectively and caused cortisol-dependent nuclear translocation and increased transcriptional activity of MR. LCA, the bile acid that most efficiently inhibited 11 beta HSD2, was present at very low concentrations in cholestatic patients, whereas the weak inhibitor CA did not cause MR activation. In conclusion, these findings indicate that CDCA, and to a lesser extent DCA, by inhibiting 11 beta HSD2, mediate cortisol-dependent nuclear translocation and transcriptional activation of MR and are responsible at least for a part of the sodium retention and potassium excretion observed in patients with biliary obstruction.