Intrauterine exposure to lead may enhance sensitization to common inhalant allergens in early childhood: a prospective prebirth cohort study

Background

Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines.

Objectives

The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood.

Material and methods

The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child’s gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts.

Results and conclusion

In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21−4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood.     

p53 and MDM2 expression in odontogenic cysts and tumours

OBJECTIVE: The aim of this report was to assess p53 and MDM2 expression in odontogenic cysts and tumours, as they are known to play important roles in cell proliferation and tumorigenesis. MATERIALS AND METHODS: The expression of p53 and MDM2 proteins was determined immunohistochemically in 51 formalin-fixed, paraffin embedded specimens of odontogenic cysts and tumours.RESULTS: No positivity to p53 was found in the cases studied. MDM2 expression in ameloblastoma was higher than in radicular cysts, but lower than that observed in odontogenic keratocysts. No difference was observed between MDM2 expression in radicular cyst and adenomatoid odontogenic tumour. The clear-cell odontogenic ameloblastoma presented strong immunoreaction to this antigen.CONCLUSIONS: The results suggest that MDM2 overexpression may be involved in the pathogenesis of some odontogenic lesions.     

Immune responses to Aspergillus antigen in IL‐4‐/‐ mice and the effect of eosinophil ablation

BACKGROUND: Exposure to Aspergillus fumigatus allergens results in enhanced total serum IgE and peripheral blood eosinophils in mice. The associated pulmonary inflammation and immunologic responses are comparable to those detected in human allergic bronchopulmonary aspergillosis. Allergen-induced cytokines are thought to regulate the inflammatory and immune responses in these animals. METHODS: In the present study, we exposed C57BL/6 and BALB/c mice to A. fumigatus antigen. Both wild-type and IL-4 knockout phenotypes of animals of both strains were used. Some animals were also treated with anti-IL-5 or anti-IFN-gamma. Total serum IgE, Aspergillus species IgG subclass, peripheral blood eosinophils, and lung histology were studied. RESULTS: The results demonstrate similar lung inflammation in all wild-type and IL-4-/- animals exposed to A. fumigatus antigen. Similarly, in spite of the diverse immune response produced by the anticytokine treatment, no major differences were detected among any of the animal groups studied. CONCLUSIONS: It can be concluded that A. fumigatus exposure in an immunologically unaltered host is predominantly of a Th2 type, and that depletion of the Th2 cytokine leads to a similar lung inflammation but with a characteristic Th1 response, suggesting that the pathogenesis of allergic aspergillosis is the result of multiple induction pathways.     

Influencing clinical practice regarding the use of antiepileptic medications during pregnancy: Modeling the potential impact on the prevalences of spina bifida and cleft palate in the United States

Selected antiepileptic drugs (AEDs) increase the risk of birth defects. To assess the impact of influencing AED prescribing practices on spina bifida and cleft palate we searched the literature for estimates of the association between valproic acid or carbamazepine use during pregnancy and these defects and summarized the associations using meta-analyses. We estimated distributions of the prevalence of valproic acid and carbamazepine use among women of childbearing age based on analyses of four data sets. We estimated the attributable fractions and the number of children born with each defect that could be prevented annually in the United States if valproic acid and carbamazepine were not used during pregnancy. The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0–21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3–9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3–7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1–4.5) in the United States. Approximately 40 infants (95% UI: 10–100) with spina bifida and 35 infants (95% UI: 10–70) with cleft palate could be born without these defects each year if valproic acid were not used during pregnancy; 5 infants (95% UI: 0–15) with spina bifida and 5 infants (95% UI: 0–15) with cleft palate could be born without these defects each year if carbamazepine were not used during pregnancy. This modeling approach could be extended to other medications to estimate the impact of translating pharmacoepidemiologic data to evidence-based prenatal care practice. Published 2011 Wiley-Liss, Inc.     

Early wheeze as reported by mothers and lung function in 4‐year‐olds. Prospective cohort study in Krakow

The purpose of the study was to check the hypothesis that early wheezing as reported by mothers would be associated with reduced lung function in 4‐year olds. Study participants were recruited prenatally, as part of a prospective cohort study on the respiratory health of young children exposed to various ambient air pollutants. After delivery, infants were followed over 4 years and the interviewers visited participants at their home to record respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months in the 3rd and 4th years. In the 4th year of follow‐up, children were invited for standard lung function testing by spirometry quantified by forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV₁), and forced expiratory volume in 0.5 sec (FEV_0.5) levels. Out of 258 children attending spirometry testing 139 performed at least two acceptable exhalation efforts. Cohort children with acceptable spirometric measurements did not differ with respect to wheezing experience and exposure characteristics from those without. The study shows that episodic wheeze was reported in 28.1% of 4‐year olds, 6.5% had transient wheeze, and 4.3% had recurrent wheeze. There was an increased frequency of wheezing symptoms and their duration in transient and recurrent wheezers. Adjusted multivariable regression models for gender and height showed that children who reported more than two episodes of wheezing at any point over the follow‐up had FVC values lower by 120.5 ml (P = 0.016) and FEV₁ values lower by 98.3 ml (P = 0.034) compared to those who did not report any wheezing; children experiencing more than 10 wheezing days by age 4 showed FVC deficit of 87.4 ml (P = 0.034) and FEV₁ values of 65.7 ml (P = 0.066). The ratios of FEV₁/FVC%, and FEV_0.5/FVC% were neither associated with wheezing episodes nor wheezing days. In recurrent wheezers, lung function decrement amounted to 207 ml of FVC, 175 ml of FEV₁, and 104 ml of FEV_0.5. In conclusion, our findings show that wheezing experience during early postnatal life may be associated with lung function deficit of restrictive character in preschool children and detailed history of wheeze in early postnatal life, even though not physician‐confirmed, may help define the high risk group of children for poor lung function testing. Pediatr. Pulmonol. 2010; 45:919–926. © 2010 Wiley‐Liss, Inc.     

Detection of Antimicrobial Compounds by Bioautography of Different Extracts of Leaves of Selected South African Tree Species

The hexane, acetone, dichloromethane and methanol extracts of Combretum vendae A.E. van Wyk (Combretaceae), Commiphora harveyi (Engl.) Engl. (Burseraceae), Khaya anthotheca (Welm.) C.DC (Meliaceae), Kirkia wilmsii Engl. (Kirkiaceae), Loxostylis alata A. Spreng. ex Rchb. (Anacardiaceae), Ochna natalitia (Meisn.) Walp. (Ochnaceae) and Protorhus longifolia (Bernh. Ex C. Krauss) Engl. (Anacardiaceae) were screened for their antimicrobial activity. The test organisms included bacteria (Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus), and fungi (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Microsporum canis and Sporothrix schenckii). A simple bioautographic procedure, involving spraying suspensions of the bacteria or fungi on thin layer chromatography (TLC) plates developed in solvents of varying polarities was used to detect the number of antibacterial and antifungal compounds present in the extracts. All the extracts had antimicrobial activity against at least one of the test microorganisms. This activity was denoted by white spots against a red-purple background on the TLC plates after spraying with tetrazolium violet. Twenty seven TLC plates; 9 for each solvent system and 3 different solvent systems per organism were tested in the bioautographic procedure. Of the bacteria tested, S. aureus was inhibited by the most compounds separated on the TLC plates from all the tested plants. Similarly, growth of the fungus C. neoformans was also inhibited by many compounds present in the extracts. Loxostylis alata appeared to be the plant extract with the highest number of inhibition bands when compared with other plants tested against both bacteria and fungi. This species was selected for in depth further study.     

REVIEW ARTICLE: Paediatric nasopharyngeal rhabdomyosarcoma: A case series and literature review

Rhabdomyosarcoma (RMS) is the most common soft tissue tumour in children, with the head and neck region accounting for 35–40% of cases. Nasopharyngeal RMSs tend to grow rapidly and invade adjacent structures. Both the Intergroup Rhabdomyosarcoma Studies and the European Studies have established that the ideal management of this disease is multimodal, using a combination of surgery, chemotherapy and radiotherapy. This case series examines the role of radiotherapy in the management of paediatric nasopharyngeal RMSs, with particular reference to long-term morbidity and disease-free survival. The cases of five children with nasopharyngeal RMS were reviewed and a systematic review of the literature contained in the PubMed databases was conducted to establish 24 individually detailed cases. Management in all patients was multimodal, using a combination of chemotherapy, radiotherapy as well as surgery. External beam radiotherapy is an integral component of treatment for nasopharyngeal RMSs. With more patients surviving for longer periods, more long-term sequelae of radiotherapy have been reported. Complications include sensorineural deafness, endocrine manifestations following radiation of the pituitary gland, cranial nerve palsies, second malignancies within the radiation field, cataract formation, retinopathy and growth disturbance. Morbidity from radiotherapy may be considerable and depends on the field and dose of radiation. Current advances in radiotherapy are aimed at improving the rate of tumour control and reducing such complications. Recent improvements in imaging and conformal techniques have the potential to reduce the morbidity associated with radiotherapy in this cohort.     

Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non‐smoking mothers

Jedrychowski WA, Perera FP, Maugeri U, Mroz E, Klimaszewska‐Rembiasz M, Flak E, Edwards S, Spengler JD. Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non‐smoking mothers. Paediatric and Perinatal Epidemiology 2010. Impaired fetal development is associated with a number of adult chronic diseases and it is believed that these associations arise as a result of the phenomenon of prenatal programming, which involves persisting changes in structure and function of various body organs caused by ambient factors during critical and vulnerable periods of early development. The main goal of the study was to assess the association between lung function in early childhood and prenatal exposure to fine particulate matter (PM_2.5), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study, personal measurements of PM_2.5 were performed over 48 h in the second trimester of pregnancy. After delivery, infants were followed for 5 years; the interviewers visited participants in their homes to record children's respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months thereafter. In the fifth year of the follow‐up, children were invited for standard lung function testing of levels of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁) and forced expiratory volume in 0.5 s (FEV_0.5). There were 176 children of non‐smoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression showed a significant deficit of FVC at the highest quartile of PM_2.5 exposure (beta coefficient = ?91.9, P = 0.008), after adjustment for covariates (age, gender, birthweight, height and wheezing). Also FEV₁ level in children was inversely correlated with prenatal exposure to PM_2.5, and the average FEV₁ deficit amounted to 87.7 mL (P = 0.008) at the higher level of exposure. Although the effect of PM_2.5 exposure on FEV_0.5 was proportionally weaker (?72.7, P = 0.026), it was also statistically significant. The lung function level was inversely and significantly associated with the wheezing recorded over the follow‐up. The findings showed that significant lung function deficits in early childhood are associated with prenatal exposure to fine particulate matter, which may affect fetal lung growth.