EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from “mucogenic” strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease.

Two Cases of Arnold-Chiari Malformation with Respiratory Failure

Arnold–Chiari malformation is defined as downward displacement of the brainstem and cerebellum through the foramen magnum. It has different clinical presentations and four subtypes. It is known that downward migration of posterior fossa components through the foramen magnum and associated lower cranial nerve palsy and brainstem compression can cause respiratory failure. Acute respiratory failure could mark the onset of the disease. Posterior fossa decompression performed to treat primary disease can improve the central sleep abnormalities. As respiratory failure is rarely seen, this paper presents two cases of Arnold–Chiari malformation with respiratory failure.

Infección por virus sincitial respiratorio y su relación con valores de IGG en niños críticos

Antecedente: La infección por el virus sincitial respiratorio (VSR) representa una elevada morbimortalidad, y en algunos casos necesidad de manejo en unidades de cuidado intensivo pediátrico (UCIP). La respuesta inmunológica influye de manera directa en la expresión de la severidad y pronóstico de los pacientes con infección respiratoria. Metodología: Estudio de una cohorte retrospectiva de pacientes con infección respiratoria grave secundaria a VSR, sin historia de inmunodeficiencia, atendidos en la UCIP del Hospital Universitario Clínica San Rafael. Se realizó análisis descriptivoglobaly de acuerdo a la categorización de las prueba de IgG. Resultados: De 188 pacientes que ingresaron a la UCIP, 13% presentaron infección por VSR (24), con una edad promedio de 7,3 (DE=3,6) meses. Pertenecían al sexo masculino79,83%. Se encontró que 12,5% tenían un valor de IgGbajo para su edad, 58,33% tenían valores en límite inferior y el 29,17% dentro de rangos normales para su edad. En los pacientes con IgG baja, fue mayor la presentación de choque séptico que no responde a líquidos (100 vs 92 vs 86%), la mediana de días de ventilación mecánica fue mayor (8 vs 6 vs 5 respectivamente), así como la mortalidad (67 vs 7,1 vs 0%). Conclusión: Nuestra serie encontró que aquellos pacientes con niveles bajos o valores en el límite inferior de IgG sérica tuvieron mayor compromiso sistémico, mayor duración de ventilación mecánica y mayor mortalidad. Se necesitan estudios prospectivos que relaciones niveles bajos de IgG con severidad y pronostico en estos pacientes con infección grave por VSR.

Nat2, Xrcc1 And Hogg1 Polymorphisms, Cigarette Smoking, Alcohol Consumption And Risk Of Upper Aerodigestive Tract Cancer.

To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer. A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048). Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

Impact on human health of particulate matter emitted from burnings in the Brazilian Amazon region

OBJECTIVE: To analyze the impact on human health of exposure to particulate matter emitted from burnings in the Brazilian Amazon region. METHODS: This was an ecological study using an environmental exposure indicator presented as the percentage of annual hours (AH%) of PM2.5 above 80 μg/m3. The outcome variables were the rates of hospitalization due to respiratory disease among children, the elderly and the intermediate age group, and due to childbirth. Data were obtained from the National Space Research Institute and the Ministry of Health for all of the microregions of the Brazilian Amazon region, for the years 2004 and 2005. Multiple regression models for the outcome variables in relation to the predictive variable AH% of PM2.5 above 80 μg/m3 were analyzed. The Human Development Index (HDI) and mean number of complete blood counts per 100 inhabitants in the Brazilian Amazon region were the control variables in the regression analyses. RESULTS: The association of the exposure indicator (AH%) was higher for the elderly than for other age groups (β = 0.10). For each 1% increase in the exposure indicator there was an increase of 8% in child hospitalization, 10% in hospitalization of the elderly, and 5% for the intermediate age group, even after controlling for HDI and mean number of complete blood counts. No association was found between the AH% and hospitalization due to childbirth. CONCLUSIONS: The indicator of atmospheric pollution showed an association with occurrences of respiratory diseases in the Brazilian Amazon region, especially in the more vulnerable age groups. This indicator may be used to assess the effects of forest burning on human health.

Air pollution and hospital admissions for respiratory diseases in the subequatorial Amazon: a time series approach

The objective of the study is to evaluate the effect of the daily variation in concentrations of fine particulate matter (diameter less than 2.5µm - PM2.5) resulting from the burning of biomass on the daily number of hospitalizations of children and elderly people for respiratory diseases, in Alta Floresta and Tangará da Serra in the Brazilian Amazon in 2005. This is an ecological time series study that uses data on daily number of hospitalizations of children and the elderly for respiratory diseases, and estimated concentration of PM2.5. In Alta Floresta, the percentage increases in the relative risk (%RR) of hospitalization for respiratory diseases in children were significant for the whole year and for the dry season with 3-4 day lags. In the dry season these measurements reach 6% (95%CI: 1.4-10.8). The associations were sig-nificant for moving averages of 3-5 days. The %RR for the elderly was significant for the current day of the drought, with a 6.8% increase (95%CI: 0.5-13.5) for each additional 10µg/m3 of PM2.5. No as-sociations were verified for Tangara da Serra. The PM2.5 from the burning of biomass increased hospitalizations for respiratory diseases in children and the elderly.

Ventilação oscilatória de alta freqüência em pediatria e neonatologia

Este trabalho teve por objetivo rever a literatura e descrever a utilização da ventilação oscilatória de alta freqüência em crianças e recém-nascidos. Revisão bibliográfica e seleção de publicações mais relevantes sobre ventilação de alta freqüência utilizando as bases de dados MedLine e SciElo publicadas nos últimos 15 anos. As seguintes palavras-chave foram utilizadas: ventilação oscilatória de alta freqüência, ventilação mecânica, síndrome do desconforto respiratório agudo, crianças e recém-nascidos. Descreveu-se o emprego da ventilação oscilatória de alta freqüência em crianças com síndrome do desconforto respiratório agudo, síndrome de escape de ar e doença pulmonar obstrutiva. Avaliou em recém-nascidos, síndrome do desconforto respiratório, displasia broncopulmonar, hemorragia peri-intraventricular, leucoencefalomalácia e extravasamento de ar. Também, abordou a transição da ventilação mecânica convencional para a ventilação de alta freqüência e o manuseio específico da ventilação de alta freqüência quanto à oxigenação, eliminação de gás carbônico, realização de exame radiológico, realização de sucção traqueal e utilização de sedação e bloqueio neuromuscular. Foram abordados o desmame deste modo ventilatório e as complicações. Em crianças maiores a ventilação oscilatória de alta freqüência é uma opção terapêutica, principalmente na síndrome do desconforto respiratório agudo, devendo ser empregada precocemente. Também pode ser útil em casos de síndrome de escape de ar e doença pulmonar obstrutiva. Em recém-nascidos, não há evidências que demonstram superioridade da ventilação oscilatória de alta freqüência em relação à ventilação convencional, sendo a síndrome de escape de ar a única situação clínica em que há evidência de melhores resultados com este modo ventilatório.

Tendência da mortalidade relacionada à paracoccidioidomicose, Estado de São Paulo, Brasil, 1985 a 2005: estudou usando causas múltiplas de morte

Objetivo. Estudar a mortalidade relacionada à paracoccidioidomicose informada em qualquer linha ou parte do atestado médico da declaração de óbito. Métodos. Os dados provieram dos bancos de causas múltiplas de morte da Fundação Sistema Estadual de Análise de Dados (SEADE) de São Paulo entre 1985 e 2005. Foram calculados os coeficientes padronizados de mortalidade relacionada à paracoccidioidomicose como causa básica, como causa associada e pelo total de suas menções. Resultados. No período de 21 anos ocorreram 1 950 óbitos, sendo a paracoccidioidomicose a causa básica de morte em 1 164 (59,7%) e uma causa associada de morte em 786 (40,3%). Entre 1985 e 2005 observou-se um declínio do coeficiente de mortalidade pela causa básica de 59,8% e pela causa associada, de 53,0%. O maior número de óbitos ocorreu entre os homens, nas idades mais avançadas, entre lavradores, com tendência de aumento nos meses de inverno. As principais causas associadas da paracoccidioidomicose como causa básica foram a fibrose pulmonar, as doenças crônicas das vias aéreas inferiores e as pneumonias. As neoplasias malignas e a AIDS foram as principais causas básicas estando a paracoccidioidomicose como causa associada. Verificou-se a necessidade de adequar as tabelas de decisão para o processamento automático de causas de morte nos atestados de óbito com a menção de paracoccidioidomicose. Conclusões. A metodologia das causas múltiplas de morte, conjugada com a metodologia tradicional da causa básica, abre novas perspectivas para a pesquisa que visa a ampliar o conhecimento sobre a história natural da paracoccidioidomicose.

Penicillin-resistant pneumococcus and risk of treatment failure in pneumonia

Objective: To determine whether the presence of in vitro penicillin-resistant Streptococcus pneumoniae increases the risk of clinical failure in children hospitalised with severe pneumonia and treated with penicillin/ampicillin. Design: Multicentre, prospective, observational study. Setting: 12 tertiary-care centres in three countries in Latin America. Patients: 240 children aged 3-59 months, hospitalised with severe pneumonia and known in vitro susceptibility of S pneumoniae. Intervention: Patients were treated with intravenous penicillin/ampicillin after collection of blood and, when possible, pleural fluid for culture. The minimal inhibitory concentration (MIC) test was used to determine penicillin susceptibility of the pneumococcal strains isolated. Children were continuously monitored until discharge. Main outcome measures: The primary outcome was treatment failure (using clinical criteria). Results: Overall treatment failure was 21%. After allowing for different potential confounders, there was no evidence of association between treatment failure and in vitro resistance of S pneumoniae to penicillin according to the Clinical Laboratory Standards Institute (CLSI)/National Committee for Clinical Laboratory Standards (NCCLS) interpretative standards ((adj)RR = 1.03; 95%Cl: 0.49-1.90 for resistant S pneumoniae). Conclusions: Intravenous penicillin/ampicillin remains the drug of choice for treating penicillin-resistant pneumococcal pneumonia in areas where the MIC does not exceed 2 mu g/ml.

Monitoring stress tolerance and occurrences of upper respiratory illness in basketball players by means of psychometric tools and salivary biomarkers

The aim of the study was to evaluate the possible relationships between stress tolerance, training load, banal infections and salivary parameters during 4 weeks of regular training in fifteen basketball players. The Daily Analysis of Life Demands for Athletes` questionnaire (sources and symptoms of stress) and the Wisconsin Upper Respiratory Symptom Survey were used on a weekly basis. Salivary cortisol and salivary immunoglobulin A (SIgA) were collected at the beginning (before) and after the study, and measured by enzyme-linked immunosorbent assay (ELISA). Ratings of perceived exertion (training load) were also obtained. The results from ANOVA with repeated measures showed greater training loads, number of upper respiratory tract infection episodes and negative sensation to both symptoms and sources of stress, at week 2 (p < 0.05). Significant increases in cortisol levels and decreases in SIgA secretion rate were noted (before to after). Negative sensations to symptoms of stress at week 4 were inversely and significantly correlated with SIgA secretion rate. A positive and significant relationship between sources and symptoms of stress at week 4 and cortisol levels were verified. In summary, an approach incorporating in conjunction psychometric tools and salivary biomarkers could be an efficient means of monitoring reaction to stress in sport. Copyright (C) 2010 John Wiley & Sons, Ltd.

Trypanosoma cruzi: The effects of zinc supplementation in the immune response during the course of experimental disease

Zinc is an essential nutritional component required for normal development and maintenance of immune functions. The possible effects of zinc in upregulating the host immune response during the acute and chronic phases of experimental Chagas` disease were evaluated. In young, infected and Zn-supplemented animals, higher concentrations of IFN-gamma and NO were observed. During the chronic phase, decreased concentrations of NO and IFN-gamma were found for older infected animals that received Zn supplementation. For young animals, hearts from Zn-supplemented groups displayed reduced inflammatory infiltrate, heart weight and number of amastigote burdens. For older, infected and Zn-supplemented animals amastigote nests were absent with reduced inflammatory cell infiltrate. This study identifies a potentially novel therapeutic approach that could control the parasite load during acute phase of disease, consequently preventing the deleterious, parasite-elicited responses observed during chronic phase. (C) 2008 Elsevier Inc. All rights reserved.

Children’s respiratory health and daily particulate levels in ten non-urban communities

We conducted a study to assess the association between the acute respiratory health of children and the levels of particulates in communities near and away from active opencast coal mines. The study enrolled children aged 1–11 years from the general population of five socioeconomically matched pairs of nonurban communities in northern England. Diaries of respiratory events were collected for 1405 children, and information was collected on the consultations of 2442 children with family/general practitioners over the 6-week study periods during 1996–1997, with concurrent monitoring of particulate levels. The associations found between daily PM10 levels and respiratory symptoms were frequently small and positive and sometimes varied between communities. The magnitude of these associations were in line with those from previous studies, even though daily particulate levels were low, and the children were drawn from the general population, rather than from the population with respiratory problems. The associations among asthma reliever use, consultations with general practitioners, and daily particulate levels were of a similar strength but estimated less precisely. The strength of association between all respiratory health measures and particulate levels was similar in communities near and away from opencast coal mining sites.

ASSOCIATION BETWEEN SADDLE NOSE DEFORMITY AND RETRO-ORBITAL MASS IN WEGENER`S GRANULOMATOSIS

Objectives: The relationship between saddle nose deformity (SND) in Wegener`s granulomatosis (WG) and other clinical features, including retro-orbital mass formation (ROM), has been poor described. Therefore, this relationship was analyzed retrospectively from 2000 to 2010. Patients and Methods: Eighteen consecutive WG patients with SND diagnosed by computed tomography were matched to 36 WG patients without SND (control group) for gender, age at WG diagnosis and disease duration. Results: No difference was found between the two groups in relation to WG type (limited and systemic forms), ethnicity, laboratory features, constitutional symptoms or clinical manifestations, including upper respiratory tract, and treatment, except for ROM (33.3 vs. 2.8% in SND(+) and SND(-) groups, respectively; p=0.004) and subglottic stenosis (22.2 vs. 2.8%; p=0.038). However, on multivariate analysis, only ROM (OR 17.15; 95% CI 1.11-265.52) was statistically associated to SND. In addition, in more than half of the cases, SND manifested prior to ROM. Conclusions: Results of this prospective analysis showed that SND was strongly associated to ROM in WG. Since early diagnosis and aggressive treatment of orbital involvement could lead to better prognosis, the presence of SND warrants additional vigilance.

Case Report: Severe, Symptomatic Hypomagnesemia in Acute Leptospirosis

We report a case severe hypomagnesemia in non-oliguric acute renal failure caused by leptospirosis that required large doses of magnesium replacement during the acute phase of disease. Biochemical studies confirmed kidney-related magnesium wasting and the mechanisms of this defect are discussed. Magnesium imbalance with its attendant clinical complications occurs in leptospirosis and should be monitored and treated aggressively in cases of leptospirosis-induced non-oliguric acute kidney injury.

The outer wall of small airways is a major site of remodeling in fatal asthma

Background: Structural and inflammatory changes in asthma involve both the large and small airways, with involvement of the distal lung being related to disease severity. We have previously shown that changes in the extracellular matrix (ECM) composition of the distal lung are associated with loss of alveolar attachments in patients with fatal asthma. However, major ECM elements, such as collagen I and fibronectin and their regulators, have not been addressed at the distal level. Objective: We sought to evaluate ECM remodeling in the distal lungs of asthmatic patients. Methods: Using immunohistochemistry and image analysis, we determined the content of collagen I and III, fibronectin, and matrix metalloproteinases; (MMPs) 1, 2, and 9 and tissue inhibitors of metalloproteinase (MMPs) 1 and 2 in the large and small airways and lung parenchyma of 24 patients with fatal asthma and compared the results with those of 11 nonasthmatic control subjects. Protein content was defined as the area of positive staining divided by basement membrane or septum length. Results: We observed increased collagen I and decreased collagen III content in the small airways of asthmatic patients compared with that seen in control subjects. Greater fibronectin and MMP-1, MMP-2, and MMP-9 content was observed at the outer area of the small airways in asthmatic patients. NIMP content was also increased in the peribronchiolar parenchyma in asthmatic patients. In contrast, TIMP expression was only increased in the large airways of asthmatic patients compared with that seen in control subjects. Conclusions: The outer area of the small airways is a major site of ECM remodeling in fatal asthma, potentially contributing to functional changes and the loss of airway-parenchyma interdependence observed in patients with fatal asthma. (J Allergy Clin Immunol 2009;123:1090-7.)