In vivo hydroquinone exposure causes tracheal hyperresponsiveness due to TNF secretion by epithelial cells

Hydroquinone (HQ) is the main oxidative substance in cigarette smoke and a toxic product of benzene biotransformation. Although the respiratory tract is an inlet pathway of HQ exposure, its effect on airway muscle responsiveness has not been assessed. We thus investigated the effects of low dose in vivo HQ-exposure on tracheal responsiveness to a muscarinic receptor agonist. Male Swiss mice were exposed to aerosolised 5% ethanol/saline solution (HQ vehicle; control) or 0.04 ppm HQ (1 h/day for 5 days) and tracheal rings were collected 1 h after the last exposure. HQ exposure caused tracheal hyper-responsiveness to methacholine (MCh), which was abolished by mechanical removal of the epithelium. This hyperresponsiveness was not dependent on neutrophil infiltration, but on tumour necrosis factor (TNF) secretion by epithelial cells. This conclusion was based on the following data: (1) trachea from HQ-exposed mice presented a higher amount of TNF, which was abrogated following removal of the epithelium; (2) the trachea hyperresponsiveness and TNF levels were attenuated by in vivo chlorpromazine (CPZ) treatment, an inhibitor of TNF synthesis. The involvement of HQ-induced TNF secretion in trachea mast cell degranulation was also demonstrated by the partial reversion of tracheal hyperresponsiveness in sodium cromoglicate-treated animals, and the in vivo HQ-exposure-induced degranulation of trachea connective tissue and mucosal mast cells, which was reversed by CPZ treatment. Our data show that in vivo HQ exposure indirectly exacerbates the parasympathetic-induced contraction of airway smooth muscle cells, mediated by TNF secreted by tracheal epithelial cells, clearly showing the link between environmental HQ exposure and the reactivity of airways. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Foreign Body Ingestion During Dental Implant Procedures

Two cases of swallowing of foreign material related to dental implants during dental practice are described. A conservative approach by clinical-radiographic follow-up was performed in both cases; however, one of the patients required colonoscopy under general anesthesia for the removal of the impacted foreign body from the intestinal region. These complications not only have associated economic cost but also carry the risk of malpractice litigation against the professional; thus, the surgeon was responsible for all the costs of hospital and surgery management of this case. Details of the clinical signs, radiographic examinations, type of treatment, and follow-up are presented.

Exercise Inhibits Allergic Lung Inflammation

Aerobic conditioning (AC) performed either during or after sensitization reduces allergic inflammation in mice; however, the effects of AC performed before and during allergic sensitization on airway inflammation are unknown. Mice were divided into Control, AC, OVA, and AC + OVA groups. Mice were trained in a treadmill followed by either ovalbumin (OVA) sensitization or saline administration. Peribronchial inflammation, OVA-specific IgE and IgG1 titers, the expression of Th1 and Th2 cytokines, and airway remodeling were evaluated, as well as the expression of Eotaxin, RANTES, ICAM-1, VCAM-1, TGF-beta and VEGF. Aerobic conditioning performed before and during allergic sensitization displayed an inhibitory effect on the OVA-induced migration of eosinophils and lymphocytes to the airways, a reduction of IgE and IgG1 titers and an inhibition of the expression of Th2 cytokines. The AC + OVA group also demonstrated reduced expression of ICAM-1, VCAM-1, RANTES, TGF-beta and VEGF, as well as decreased airway remodeling (p < 0.05). The effects of AC before and during the sensitization process inhibit allergic airway inflammation and reduce the production of Th2 cytokines and allergen-specific IgE and IgG1.

Impact of urban atmospheric environment on hospital admissions in the elderly

OBJECTIVE: To analyze the impact of intra-urban atmospheric conditions on circulatory and respiratory diseases in elder adults. METHODS: Cross-sectional study based on data from 33,212 hospital admissions in adults over 60 years in the city of Sao Paulo, southeastern Brazil, from 2003 to 2007. The association between atmospheric variables from Congonhas airport and bioclimatic index, Physiological Equivalent Temperature, was analyzed according to the district's socioenvironmental profile. Descriptive statistical analysis and regression models were used. RESULTS: There was an increase in hospital admissions due to circulatory diseases as average and lowest temperatures decreased. The likelihood of being admitted to the hospital increased by 12% with 1 degrees C decrease in the bioclimatic index and with 1 degrees C increase in the highest temperatures in the group with lower socioenvironmental conditions. The risk of admission due to respiratory diseases increased with inadequate air quality in districts with higher socioenvironmental conditions. CONCLUSIONS: The associations between morbidity and climate variables and the comfort index varied in different groups and diseases. Lower and higher temperatures increased the risk of hospital admission in the elderly. Districts with lower socioenvironmental conditions showed greater adverse health impacts.

Levothyroxine Absorption in Morbidly Obese Patients Before and After Roux-En-Y Gastric Bypass (RYGB) Surgery

Roux-en-Y gastric bypass (RYGB) modifies the anatomical structure of the upper intestine tract, reduces gastric acid secretion, and may impair LT4 absorption. The aim of this study was to evaluate the LT4 absorption in morbidly obese patients before and after RYGB. Thirty morbidly obese patients were divided in two groups: The NS group included 15 patients before RYGB surgery (BMI = 43.1 +/- 4 kg/m(2)), and the S group included 15 patients after surgery (BMI = 37.3 +/- 4 kg/m(2)). Two baseline samples were collected, and 600 mu g of oral LT4 tablets were administered. Blood samples were collected at 30, 60, 120, 180, 240, 300, and 1440 min. Serum-free T4 (FT4), total T4 (TT4), and TSH were measured at each time point. The increase in TT4, FT4, and TSH (Delta TT4, Delta FT4, and Delta TSH) was calculated, subtracting from the baseline mean value. The pharmacokinetics parameters regarding LT4 absorption, maximum Delta TT4, and area under the curve(AUC) of both Delta TT4 and Delta FT4 were significantly higher in the S group compared with the NS group (p < 0.05). It was observed, however, that there was a significant delay in the absorption of LT4 in the S group. Basal serum TSH and leptin levels were higher in the NS group (p = 0.016 and 0.026, respectively), whereas basal serum TT4, FT4, Delta TSH, and the AUC of Delta TSH were similar between groups. In this study, we have demonstrated that Roux-en-Y bypass surgery does not diminish LT4 absorption. A small but significant delayed absorption of LT4, however, was observed in patients after surgery.

Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4-the AdAPT Method

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).

The Differential Clinical Impact of Human Coronavirus Species in Children With Cystic Fibrosis

We investigated the clinical impact of human coronaviruses (HCoV) OC43, 229E, HKU1 and NL63 in pediatric patients with cystic fibrosis (CF) during routine and exacerbation visits. A total of 408 nasopharyngeal aspirate samples were obtained from 103 patients over a 1-year period. Samples positive for HCoV were submitted for nucleotide sequencing to determine the species. Nineteen samples (4.65%) were positive for HCoV, of which 8 were positive for NL63, 6 for OC43, 4 for HKU1, and 1 for 229E. Identification of HCoV was not associated with an increased rate of respiratory exacerbations, but NL63-positive patients had higher exacerbation rates than patients who were positive for other HCoV species.

Association between particulate matter air pollution and monthly inhalation and nebulization procedures in Ribeirao Preto, Sao Paulo State, Brazil

The study was designed to investigate the impact of air pollution on monthly inhalation/nebulization procedures in Ribeirao Preto, Sao Paulo State, Brazil, from 2004 to 2010. To assess the relationship between the procedures and particulate matter (PM10) a Bayesian Poisson regression model was used, including a random factor that captured extra-Poisson variability between counts. Particulate matter was associated with the monthly number of inhalation/nebulization procedures, but the inclusion of covariates (temperature, precipitation, and season of the year) suggests a possible confounding effect. Although other studies have linked particulate matter to an increasing number of visits due to respiratory morbidity, the results of this study suggest that such associations should be interpreted with caution.

Streptococcus pneumoniae: susceptibility to penicillin and moxifloxacin

Objective: To determine the minimum inhibitory concentrations (MICs) of parenteral penicillin and moxifloxacin against Streptococcus pneumoniae strains isolated at a hospital center. Methods: In-vitro, prospective study involving 100 S. pneumoniae isolates collected from patients who had been treated, between October of 2008 and July of 2010, at the Hospital das Clinicas complex of the University of Sao Paulo School of Medicine, located in the city of Sao Paulo, Brazil. The isolates were obtained from respiratory tract cultures or blood samples unrelated to meningeal infections, and they were tested for penicillin and moxifloxacin susceptibility by E-test. The MIC category interpretations were based on updated standards. Results: All isolates were fully susceptible to parenteral penicillin (MIC <= 2 mu g/mL), and, consequently, they were also susceptible to amoxicillin, ampicillin, third/fourth generation cephalosporins, and ertapenem. Of the S. pneumoniae strains, 99% were also susceptible to moxifloxacin, and only one strain showed an MIC = 1.5 mu g/mL (intermediate). Conclusions: Our results showed high susceptibility rates to parenteral penicillin and moxifloxacin among S. pneumoniae isolates unrelated to meningitis, which differs from international reports. Reports on penicillin resistance should be based on updated breakpoints for non-meningitis isolates in order to guide the selection of an antimicrobial therapy and to improve the prediction of the clinical outcomes.

Phylodynamics and Dispersal of HRSV Entails Its Permanence in the General Population in between Yearly Outbreaks in Children

Background: Human respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide. Methodology/Principal Findings: Here through a comprehensive analysis of the two major HRSV groups A and B (n = 1983) which comprise of several genotypes, we present a complex pattern of population dynamics of HRSV over a time period of 50 years (1956-2006). Circulation pattern of HRSV revealed a series of expansions and fluctuations of co-circulating lineages with a predominance of HRSVA. Positively selected amino acid substitutions of the G glycoprotein occurred upon population growth of GB3 with a 60-nucleotide insertion (GB3 Insert), while other genotypes acquired substitutions upon both population growth and decrease, thus possibly reflecting a role for immune selected epitopes in linkage to the traced substitution sites that may have important relevance for vaccine design. Analysis evidenced the co-circulation and predominance of distinct HRSV genotypes in Brazil and suggested a year-round presence of the virus. In Brazil, GA2 and GA5 were the main culprits of HRSV outbreaks until recently, when the GB3 Insert became highly prevalent. Using Bayesian methods, we determined the dispersal patterns of genotypes through several inferred migratory routes. Conclusions/Significance: Genotypes spread across continents and between neighboring areas. Crucially, genotypes also remained at any given region for extended periods, independent of seasonal outbreaks possibly maintained by re-infecting the general population.

Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma

Laryngeal squamous cell carcinoma is one of the most common malignant neoplasms of the head and neck. In Brazil, laryngeal tumors represent 2% of all cancers and are associated with approximately 3,000 deaths annually. Human papillomavirus (HPV) has been reported to play an important role in the etiology of laryngeal cancer. The aim of the present study was to evaluate the expression of p53, p27, and Mdm2 in laryngeal carcinomas. Sixty-three larynx biopsies were selected for the study, including 9 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastasis and 27 laryngeal carcinomas with metastasis. Twenty-seven cervical lymph nodes from patients with metastatic lesions were also evaluated. The expression levels of p53, p27, and Mdm2 were assessed by immunohistochemistry using a computer-assisted system. HPV detection and typing were performed using PCR, and the HPV types that were evaluated included HPV 6, 11, 16, 18, 31 and 33. Out of 63 patients, 53 (84.1%) were positive for beta-globin (internal control), and 10 (15.9%) were beta-globin negative and therefore excluded from the evaluation. Thus, 7 (13.2%) out of 53 patients were HPV positive, and 46 (86.8%) out of 53 patients were HPV negative. Statistically significant differences (p < 0.05) in Mdm2 expression levels were observed in the in situ laryngeal carcinoma samples compared with the laryngeal carcinoma samples with metastasis. No statistically significant differences (p > 0.05) in either p53 or p27 expression levels were detected. These findings suggest that Mdm2 may be associated with the invasiveness and aggressiveness of laryngeal carcinomas.

Doenças respiratórias e fatores associados: estudo de base populacional em São Paulo, 2008-2009

OBJETIVO: Estimar a prevalência de bronquite aguda, rinite e sinusite em crianças e adolescentes e identificar fatores associados. MÉTODOS: Estudo transversal, de base populacional. Foi realizado inquérito domiciliar com 1.185 crianças e adolescentes de São Paulo, SP, de 2008 a 2009. Os participantes foram selecionados a partir de amostragem probabilística, estratificada por sexo e idade e por conglomerados em dois estágios. Para análise ajustada foi realizada regressão múltipla de Poisson. RESULTADOS: Dos entrevistados, 7,3% referiram bronquite aguda, 22,6% rinite e 15,3% sinusite. Após análise ajustada, associaram-se à bronquite aguda auto-referida: idade de zero a quatro anos (RP = 17,86; IC95%: 3,65;90,91), cinco a nove anos (RP = 37,04; IC95%: 8,13;166,67), dez a 14 anos (RP = 20,83; IC95%: 4,93;90,91), referir ter alergia (RP = 3,12; IC95%: 1,70;5,73), cor da pele preta/parda (RP = 2,29; IC95%: 1,21;4,35) e morar em domicílio com um a três cômodos (RP = 1,85; IC95%: 1,17;2,94); à rinite auto-referida: idade dez a 14 anos (RP = 2,77; IC95%: 1,60;4,78), 15 a 19 anos (RP = 2,58; IC95%: 1,52;4,39), referir ter alergia (RP = 4,32; IC95%: 2,79;6,70), referir ter asma (RP = 2,30; IC95%: 1,30;4,10) e morar em apartamento (RP = 1,70; IC95%: 1,06;2,73); à sinusite auto-referida: idade cinco a nove anos (RP = 2,44; IC95%: 1,09;5,43), dez a 14 anos (RP = 2,99; IC95%: 1,36;6,58), 15 a 19 anos (RP = 3,62; IC95%: 1,68;7,81), referir ter alergia (RP = 2,23; IC95%: 1,41;3,52) e apresentar obesidade (RP = 4,42; IC95%: 1,56;12,50). CONCLUSÕES: As doenças respiratórias foram mais prevalentes em grupos populacionais com características definidas, como grupo etário, doenças auto-referidas, tipo de moradia e obesidade.

Impact of urban atmospheric environment on hospital admissions in the elderly

OBJECTIVE: To analyze the impact of intra-urban atmospheric conditions on circulatory and respiratory diseases in elder adults. METHODS: Cross-sectional study based on data from 33,212 hospital admissions in adults over 60 years in the city of São Paulo, southeastern Brazil, from 2003 to 2007. The association between atmospheric variables from Congonhas airport and bioclimatic index, Physiological Equivalent Temperature, was analyzed according to the district's socioenvironmental profile. Descriptive statistical analysis and regression models were used. RESULTS: There was an increase in hospital admissions due to circulatory diseases as average and lowest temperatures decreased. The likelihood of being admitted to the hospital increased by 12% with 1ºC decrease in the bioclimatic index and with 1ºC increase in the highest temperatures in the group with lower socioenvironmental conditions. The risk of admission due to respiratory diseases increased with inadequate air quality in districts with higher socioenvironmental conditions. CONCLUSIONS: The associations between morbidity and climate variables and the comfort index varied in different groups and diseases. Lower and higher temperatures increased the risk of hospital admission in the elderly. Districts with lower socioenvironmental conditions showed greater adverse health impacts.

Association between particulate matter air pollution and monthly inhalation and nebulization procedures in Ribeirão Preto, São Paulo State, Brazil

The study was designed to investigate the impact of air pollution on monthly inhalation/nebulization procedures in Ribeirão Preto, São Paulo State, Brazil, from 2004 to 2010. To assess the relationship between the procedures and particulate matter (PM10) a Bayesian Poisson regression model was used, including a random factor that captured extra-Poisson variability between counts. Particulate matter was associated with the monthly number of inhalation/nebulization procedures, but the inclusion of covariates (temperature, precipitation, and season of the year) suggests a possible confounding effect. Although other studies have linked particulate matter to an increasing number of visits due to respiratory morbidity, the results of this study suggest that such associations should be interpreted with caution.