Assessment and management of asthma exacerbations in an emergency department unit.

BACKGROUND: The Pediatric Respiratory Assessment Measure (PRAM) score is a useful tool for the assessment of asthma exacerbations in children. This study aimed to estimate the risk of hospitalization in children, assessed with the PRAM score and having mild-moderate asthma exacerbation, who were treated with salbutamol delivered via a metered-dose inhaler and spacer (MDI/S). METHODS: The study population consisted of children aged 3-16 years with mild-moderate asthma exacerbations. All children received 1mg/kg prednisolone p.o. (max 40 mg) and 4-6 puffs of salbutamol via MDI/S. RESULTS: Fifty patients participated in the study. Admission was associated positively with the initial PRAM score (OR: 18.91, CI: 2.42-123.12, P = 0.005) and negatively with the improvement in PRAM score (OR: 0.52, CI: 0.01-0.78, P = 0.032). CONCLUSION: PRAM is a reliable tool that can be used effectively to estimate the asthma exacerbation severity.

Assessment and management of asthma exacerbations in an emergency department unit

Background: The Pediatric Respiratory Assessment Measure (PRAM) score is a useful tool for the assessment of asthma exacerbations in children. This study aimed to estimate the risk of hospitalization in children, assessed with the PRAM score and having mild–moderate asthma exacerbation, who were treated with salbutamol delivered via a metered-dose inhaler and spacer (MDI/S). Methods: The study population consisted of children aged 3–16 years with mild–moderate asthma exacerbations. All children received 1mg/kg prednisolone p.o. (max 40 mg) and 4–6 puffs of salbutamol via MDI/S. Results: Fifty patients participated in the study. Admission was associated positively with the initial PRAM score (OR: 18.91, CI: 2.42–123.12, P = 0.005) and negatively with the improvement in PRAM score (OR: 0.52, CI: 0.01–0.78, P = 0.032). Conclusion: PRAM is a reliable tool that can be used effectively to estimate the asthma exacerbation severity (AU)

Physicians' ability to recognize adventitious lung sounds.

BACKGROUND: Lung auscultation is an important tool for diagnosing respiratory diseases. However, the ability of observers to recognize respiratory sounds varies considerably and depends on the sound. The present study aimed to assess the auscultatory skills of healthcare professionals and medical students. METHODS: A total of 295 physicians (185 pediatricians, 69 pulmonologists, and 41 physicians of general/internal medicine and subspecialties), 55 residents, and 50 medical students participated in the survey. They listened to five audio-recorded respiratory sounds and described them in free-form answers. RESULTS: The rates of correct answers were 55.2% for fine crackles, 74.5% for coarse crackles, 72.2% for wheezes, 18.75% for squawks, and 11.25% for pleural friction rub. The medical specialty was correlated with the correct answers and both pediatricians and physicians of general/internal medicine and subspecialties recognized fewer sounds compared with respiratory physicians (odds ratio [OR]: 0.37; confidence interval [CI]: 0.22-0.62; p < 0.001 and, OR: 0.47; CI: 0.22-0.99, p = 0.048, respectively). Years of experience were negatively correlated with the number of correct answers (OR: 0.73; CI:0.62-0.84; p = 0.001). CONCLUSIONS: Gaps remain in both terminology and recognition of lung sounds among a wide population of Greek physicians. Less experienced physicians perform better on lung auscultation, indicating that continuing education with critical feedback should be offered.

Clinical Course of Children with Chronic Suppurative Lung Disease or Bronchiectasis Infected with Pseudomonas aeruginosa.

Children with chronic wet cough and without cystic fibrosis (non-CF) may suffer from chronic suppurative lung disease (CSLD) or bronchiectasis. Pseudomonas aeruginosa (Pa) can be one of the offending microbes in these children. The present study aimed to describe the clinical course of children with the above two conditions who were infected with Pa. Data of 54 children with CSLD/bronchiectasis who were diagnosed and attended in our department were retrospectively analysed through a Cox proportional hazard model, with age, presence of bronchiectasis, use of inhaled colistin, azithromycin, inhaled hypertonic saline as the covariates. In 42 of the 54 patients, there was no identifiable cause or underlying chronic disorder. Microbiological clearance was defined as the absence of daily wet cough for four months along with four negative cultures taken during the last four consecutive follow-up visits. Multivariate analysis was performed with a Cox proportional hazard model with time to microbiological clearance as the outcome. Results are described as Hazard Ratios (HR) with 95% Confidence Intervals (95%CI). Nebulised antibiotics and the presence of bronchiectasis were statistically significant predictors of remission (HR: 3.99; 95%CI: 1.12-14.14; p = 0.032, and HR: 0.24; 95%CI: 0.08-0.71; p = 0.010). In conclusion, the rate of microbiological clearance increases with the use of inhaled colistin and decreases when there is established bronchiectasis.

Asthma-Like Features and Anti-Asthmatic Drug Prescription in Children with Non-CF Bronchiectasis.

Bronchiectasis and asthma may share some characteristics and some patients may have both conditions. The present study aimed to examine the rationale of prophylactic inhaled corticosteroids (ICS) prescription in children with bronchiectasis. Data of children with radiologically established bronchiectasis were retrospectively reviewed. Episodes of dyspnea and wheezing, spirometric indices, total serum IgE, blood eosinophil counts, sensitization to aeroallergens, and air-trapping on expiratory CT scans, were recorded. The study included 65 children 1.5-16 years old, with non-CF bronchiectasis. Episodes of dyspnea or wheezing were reported by 22 (33.8%) and 23 (35.4%), respectively. Skin prick tests to aeroallergens (SPTs) were positive in 15 (23.0%) patients. Mosaic pattern on CT scans was observed in 37 (56.9%) patients. Dyspnea, presence of mosaic pattern, positive reversibility test, and positive SPTs were significantly correlated with the prescription of ICS. The prescription of ICS in children with bronchiectasis is more likely when there are certain asthma-like characteristics. The difficulty to set the diagnosis of real asthma in cases of bronchiectasis may justify the decision of clinicians to start an empirical trial with ICS in certain cases.

In Vitro and In Vivo Preclinical Effects of Type I IFNs on Gliomas.

The interferons (IFNs) are a family of cytokines with diverse cellular actions such as control of cell proliferation and regulation of immune responses; therefore, they have been extensively studied as antitumor agents for a variety of malignancies, including gliomas. Type I IFNs exert their antitumor effects either directly, by targeting the tumor cells or the tumor stem cells, or indirectly, by regulating the anticancer activities of the immune system. More specifically, IFN-beta and IFN-alpha exhibit antiproliferative effects by p53 induction, CD8+ T-lymphocyte and macrophage activation, chemokine secretion, and miR-21 downregulation. In vitro and in vivo studies provide evidence that immunotherapy could have a role in glioma treatment, especially when first-line therapeutic interventions fail to produce durable responses. These effects are more obvious when combining IFN-beta with classical antitumor therapies such as temozolamide, an oral chemotherapeutic, for both newly diagnosed and recurrent gliomas. However, further clinical studies are needed to determine whether IFNs will have a definite place in the management of gliomas.

Prognostic markers of pediatric meningococcal sepsis.

Having available tools to determine the prognosis of pediatric meningococcal sepsis at admission to the Intensive Care Unit or during the course of the disease constitutes a clinical necessity. Recently, new readily measurable circulating biomarkers have been described as an additional tool for severity classification and prediction of mortality in meningococcal disease. These biomarkers have been associated with increased risk of mortality scores and a number of organ failures in heterogeneous samples of critically ill children. In future, genetic markers may be used for identification of high-risk patients by creating prediction rules for clinical course and sequelae, and potentially provide more insight in the complex immune response in meningococcal sepsis. We briefly summarize the data pointing at the emerging genome-wide expression profiling studies and review the prognostic value of the main markers investigated in pediatric meningococcal sepsis putting them in the current frame of sepsis in general.

Androgen insensitivity syndrome: clinical features and molecular defects.

The end-organ resistance to androgens has been designated as androgen insensitivity syndrome (AIS), an X-linked disorder caused by mutations in the androgen receptor (AR) gene. It is generally accepted that defects in the AR gene prevent the normal development of both internal and external genital structures in 46,XY individuals, causing a variety of phenotypes ranging from male infertility to completely normal female external genitalia. Precise diagnosis requires clinical, hormonal and molecular investigation and is of great importance for appropriate gender assignment and management in general. The complexity of phenotypic presentation of AIS with genotype-phenotype variability of identical mutations complicates both the diagnostic procedure and genetic counseling of the affected families. More than 400 different AR gene mutations have thus far been reported but the receptor structure-function relationship and its phenotypic outcome is not yet fully understood. This review focuses on the clinical features and molecular pathophysiology of AIS and explores the relationship of the molecular defects in the AR gene to their clinical expression.

Sex-reversed phenotype in association with two novel mutations c.2494delA and c.T3004C in the ligand-binding domain of the androgen receptor gene.

OBJECTIVE: To establish the diagnosis of complete androgen insensitivity syndrome (CAIS) in two patients with characteristic clinical and hormonal findings, relative family history in one of them, and unusual Müllerian remnants in the other. DESIGN: Case report. SETTING: Research laboratory in the Department of Medical Genetics at a university children's hospital. PATIENT(S): Two patients with 46,XY sex reversal and two maternal aunts of the first patient with the same clinical condition were tested. INTERVENTION(S): Bilateral gonadectomy was performed on both patients. MAIN OUTCOME MEASURE(S): Genetic counseling, cancer prophylaxis, hormone substitution therapy. RESULT(S): Molecular analysis revealed two novel mutations, a frameshift familial (c.2494delA) in patient 1 and a missense sporadic (c.T3004C) in patient 2. The c.2494delA mutation was also detected in two of the three affected maternal aunts of patient 1. Patient 2 presents an unusual persistence of Müllerian structures. CONCLUSION(S): Genetic counseling of potential women carriers of androgen receptor (AR) mutations is crucial for the early diagnosis of the affected offspring. The presence of Müllerian remnants, although rare, should not exclude the diagnosis of CAIS. Both identified mutations are novel and provide further evidence for the correlation between specific AR mutations and phenotype.

The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major.

Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.

Binuclear copper(II) complexes of tolfenamic: synthesis, crystal structure, spectroscopy and superoxide dismutase activity.

The synthesis and characterization of copper(II) complexes with a potent non-steroidal anti-inflammatory drug, tolfenamic acid, Htolf, with formula [Cu(tolf)(2)L](2) (where L is H(2)O or DMF, N,N-dimethylformamide) were investigated. The crystal and molecular structure of [Cu(tolf)(2)(DMF)](2) was reported. Crystallographic data are as follows: monoclinic system, space group P2(1)/n with cell constants a=9.068(2) A, b=14.514(3) A, c=22.826(4) A, V=2948.9(10) A(3) and Z=2. The crystal structure consists of binuclear, quadruply bridged neutral molecule with a Cu-Cu bond length of 2.6075(19) A. The complex is self-assembled via C-H-pi intermolecular stacking interactions. Spectroscopic and electrochemical studies were reported. The superoxide dismutase activity is measured and compared with those of superoxide dismutase enzyme, SOD, the free ligand and related copper complexes with non-steroidal anti-inflammatory drugs, NSAIDs. IC(50) value was measured by the Fridovich test (1.97+/-0.17 microM), which showed that [Cu(tolf)(2)L](2) is a good superoxide scavenger.