Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity.

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures. This article is protected by copyright. All rights reserved.

Retraction

Vareille M, Kieninger E, Alves MP, et al. Impaired type I and type III interferon induction and rhinovirus control in human cystic fibrosis airway epithelial cells. Thorax 2012;67:517-25. This article has been retracted. In our article recently published in Thorax, we described a novel mechanism explaining the increased susceptibility of patients with cystic fibrosis (CF) to rhinovirus infections, namely defective interferon type I and III production by CF airway epithelial cells. In experiments performed after publication of the article we were unable to consistently replicate our findings of deficient interferon type I and III production by CF airway epithelial cells upon rhinovirus infection. In the light of these results, we carried out detailed investigations of the data reported in the above manuscript and regrettably found evidence of deliberate manipulation of experimental data by the first author Dr M. Vareille. This manipulation was accompanied in some instances by absence of original data files. The manipulation/original data absence involved data presented in most, if not all of the figures, thus we wish to fully retract the paper and apologise to the readers of Thorax and to the scientific community for the inconvenience this has caused. We also checked data published by our group in manuscripts on which Dr Vareille was a co-author and found that data published in these manuscripts had not been manipulated. These two manuscripts, whose data and conclusions we stand by are: Edwards MR, Regamey N, Vareille M, et al. Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. Mucosal Immunol 2013;6:797–806. doi: 10.1038/mi.2012.118. and Kieninger E, Vareille M, Kopf BS, et al. Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis. Eur Respir J 2012;39:297–304. doi: 10.1183/09031936.00054511. Dr. Vareille has received a letter from the Secretary General of the University of Bern condemning her scientific misconduct as a severe offence against the rules of scientific integrity. Her current employers have also been informed. All co-authors of the publication including Dr. Vareille concur with the retraction statement.

Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study.

BACKGROUND Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephone interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS 27% of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months (OR=1.71, p=0.01, 95% CI 1.13-2.61), outdoor temperatures between 5-10 °C (OR=2.33, p=0.001, 95% CI 1.41-3.86), older siblings (OR=2.60, p=0.001, 95% CI 1.50-4.51) and childcare attendance (OR=1.53, p=0.07, 95% CI 0.96-2.44). 51% of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first three months of life (OR=0.34, p=0.003, 95% CI 0.17-0.69) and in infants with atopic mothers (OR=0.44, p=0.008, 95% CI 0.24-0.80). Increased tidal volume (OR=1.67, p=0.03, 95% CI 1.04-2.68) and outdoor temperatures between 2-5 °C (OR=2.79, p=0.02, 95% CI 1.17-6.61) were associated with more symptoms. CONCLUSIONS RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy, or premorbid lung function.

Reacciones titulares liquenoides

Fil: Rivarola, Emilce. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas

Manifestaciones cutáneas no infecciosas en pacientes con VIH

El complejo VIH-SIDA puede desarrollar clínicamente una gran variedad de manifestaciones dermatológicas, 90% de los pacientes presentan alguna manifestación en piel, mucosas o anexos. Las mismas han sido clasificadas en infecciosas y no infecciosas para su mayor comprensión. Se puede observar patología exclusiva asociada a la enfermedad y/o entidades dermatológicas comunes, como la dermatitis seborreica, las verrugas genitales o el herpes zoster pero con presentaciones atípicas, extensas y resistentes al tratamiento. Se comunica una serie de pacientes que presentaron manifestaciones dermatológicas no infecciosas en el contexto de infección por VIH.

Wheat allergy in celiac children

Gluten is the main structural protein complex of wheat with equivalent toxic proteins found in other cereals (rye, barley, and oats) which are responsible for different immunologic responses with different clinical expressions of disease. The spectrum of gluten-related disorders has been classified according to pathogenic, clinical, and epidemiological differences in three main forms: (i) wheat allergy (WA), an IgE-mediated disease; (ii) autoimmune disease, including celiac disease (CD), dermatitis herpetiformis, and gluten ataxia; and (iii) possibly immune-mediated, gluten sensitivity [1]. WA is an immunologic Th2 response with typical manifestations which can vary from dermatological, respiratory, and/or intestinal to anaphylactic reactions. In contrast, CD is an autoimmune disorder, a gliadin-specific T-cell response which is enhanced by the action of intestinal tissue transglutaminase (tTG), with a wide clinical spectrum including symptomatic cases with either intestinal (e.g., chronic diarrhea, weight loss) or extraintestinal features (e.g., anemia, osteoporosis, neurologic disturbances) and silent forms that are occasionally discovered as a result of serological screening [1]. We studied wheat allergy in two children with early diagnosis of CD, who developed immediate allergic symptoms after eating small amounts of wheat flour.

NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response

A wealth of evidence supports increased NO (NO⋅) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO⋅ and NO⋅ chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} was the only NO⋅ derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{2}^{-}}}\end{equation*}\end{document} was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO⋅ dynamics derived from the current findings predicts that NO⋅ may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO⋅ derivatives.

A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.

Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and the development of scales and crusts. The histopathology revealed hyperplasia of the epidermis, subcorneal microabscesses, orthohyperkeratosis, parakeratosis, and lymphocyte exocytosis, which are features in common with human psoriasis and other hyperproliferative inflammatory skin disorders. Repetitive cultures failed to demonstrate bacterial or fungal organisms potentially involved in the pathogenesis of this disease, and the dermatitis resolved rapidly after subcutaneous administration of dexamethasone. Homozygous mutant mice on a (PL/J x C57BL/6J)F1 background did not develop the disease and backcross experiments suggest that a small number of genes (perhaps as few as one), in addition to CD18, determine susceptibility to the disorder. This phenotype provides a model for inflammatory skin disorders, may have general relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the beta2 integrins in inflammatory processes.

Aspectos comparativos entre el cáncer mamario humano y canino con especial referencia al cáncer mamario inflamatorio:grado histológico de malignidad, mecanismos endocrinos e interleucinas

El cáncer mamario humano (CMH) es un gran problema de salud puesto que es el cáncer que más frecuentemente se diagnostica en la mujer y es la segunda causa de muerte por cáncer. El cáncer mamario inflamatorio (CI) humano y canino (CIH y CIC, respectivamente) es un tipo de cáncer mamario especialmente agresivo de baja prevalencia. El CIC se ha propuesto como modelo para el estudio de la enfermedad humana. El CI se define como una entidad clínicopatológica caracterizada clínicamente por edema difuso, eritema y dolor de la mama, ocupando la mayor parte de la misma y, frecuentemente, sin presentar nódulo mamario, lo que complica el diagnóstico al poder confundirse con una dermatitis o una mastitis. Por otro lado, los tumores mamarios caninos (TMC) se presentan como el primer grupo de tumores en la perra, suponiendo un 52% de todas las neoplasias y el segundo tras los tumores cutáneos teniendo en cuenta ambos sexos. En la especie canina el CI representa el 7,6% de todos los tumores mamarios caninos y el 17% de todas las neoplasias mamarias malignas. Una gran parte del conocimiento sobre el cáncer mamario humano (CMH) se basa en las investigaciones realizadas in vitro o in vivo. En numerosas ocasiones se han propuesto los TMC espontáneos como modelo para el estudio del CMH. Como previamente se ha indicado, se ha demostrado que la perra es un buen modelo animal para el estudio del CIH, ya que tienen características epidemiológicas, clínicas e histológicas similares. Sin embargo, la mayoría de los aspectos comparables en los cánceres de mama de ambas especies, incluyendo el perfil hormonal o la presencia de ciertas citocinas, no han sido todavía evaluados...

Polissensibilização alimentar : um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Modelos de regressão para identificação de marcadores preditivos de asma na descendência de mulheres com atopia

Trabalho de projecto de mestrado, Bioestatística, Universidade de Lisboa, Faculdade de Ciências, 2016

Physical Health Problems and Environmental Challenges Influence Balancing Behaviour in Laying Hens

With rising public concern for animal welfare, many major food chains and restaurants are changing their policies, strictly buying their eggs from non-cage producers. However, with the additional space in these cage-free systems to perform natural behaviours and movements comes the risk of injury. We evaluated the ability to maintain balance in adult laying hens with health problems (footpad dermatitis, keel damage, poor wing feather cover; n = 15) using a series of environmental challenges and compared such abilities with those of healthy birds (n = 5). Environmental challenges consisted of visual and spatial constraints, created using a head mask, perch obstacles, and static and swaying perch states. We hypothesized that perch movement, environmental challenges, and diminished physical health would negatively impact perching performance demonstrated as balance (as measured by time spent on perch and by number of falls of the perch) and would require more exaggerated correctional movements.We measured perching stability whereby each bird underwent eight 30-second trials on a static and swaying perch: with and without disrupted vision (head mask), with and without space limitations (obstacles) and combinations thereof. Video recordings (600 Hz) and a three-axis accelerometer/gyroscope (100 Hz) were used to measure the number of jumps/falls, latencies to leave the perch, as well as magnitude and direction of both linear and rotational balance-correcting movements. Laying hens with and without physical health problems, in both challenged and unchallenged environments, managed to perch and remain off the ground. We attribute this capacity to our training of the birds. Environmental challenges and physical state had an effect on the use of accelerations and rotations to stabilize themselves on a perch. Birds with physical health problems performed a higher frequency of rotational corrections to keep the body centered over the perch, whereas, for both health categories, environmental challenges required more intense and variable movement corrections. Collectively, these results provide novel empirical support for the effectiveness of training, and highlight that overcrowding, visual constraints, and poor physical health all reduce perching performance.

Assessment of foot health and animal welfare: clinical findings in 229 dairy Mediterranean Buffaloes (Bubalus bubalis) affected by foot disorders.

BACKGROUND Lameness represents the third most important health-related cause of economic loss in the dairy industry after fertility and mastitis. Although, dairy Mediterranean Buffaloes (MB) and dairy cows share similar breeding systems predisposing to similar herd problems, published studies exploring its relevance and role in these ruminants are still rare and incomplete. The aims of this study were to describe the clinical findings of foot disorders (FDs) in dairy MB and their influence on animal welfare, determined by assessment of locomotion score (LS), body condition score (BCS) and cleanliness score (CS). RESULTS Of 1297 multiparous MB submitted to routine trimming procedures, 229 buffaloes showed at least one FD. The prevalence of buffaloes affected by FDs was 17.7 %, while motility and lameness indexes were 84.1 % (1091/1297) and 15.9 % (206/1297), respectively. Overgrowth was present in 17.0 % (220/1297), corkscrew claw in 15.8 % (205/1297), interdigital phlegmon in 0.9 % (12/1297), white line abscess in 0.8 % (11/1297), digital dermatitis in 0.1 % (1/1297) and interdigital hyperplasia in 0.1 % (1/1297). Simultaneous presence of FDs was recorded in 17.0 % of MB (221/1297): overgrowth and corkscrew claw occurred together in 15.8 % of cases (205/1297), overgrowth and interdigital phlegmon in 0.3 % (4/1297), overgrowth and white line abscess in 0.8 % (11/1297), digital dermatitis and interdigital hyperplasia in 0.1 % (1/1297). The presence of FDs was always associated with lameness (LS > 2), except from 23 MB with simultaneous overgrowth and interdigital phlegmon occurrence. The majority of MB within the under-conditioned group (95.5 %, 43/45) and all those with CS > 2 (122/122) had a locomotion score above the threshold of normality (LS > 2). Furthermore, foot diseases such as interdigital hyperplasia, white line abscess and digital dermatitis or interdigital hyperplasia seemed to occur more frequently associated with decreased BCS and increased CS scores. CONCLUSIONS This study describes for the first time the involvement of white line disease, interdigital phlegmona, digital dermatitis and interdigital hyperplasia in foot disorders of dairy Mediterranean buffalo and shows their association with an impairment of animal welfare.

Major quantitative trait locus for eosinophil count is located on chromosome 2q

Background: Eosinophils are granulocytic white blood cells implicated in asthma and atopic disease. The degree of eosinophilia in the blood of patients with asthma correlates with the severity of asthmatic symptoms. Quantitative trait loci (QTL) linkage analysis of eosinophil count may be a more powerful strategy of mapping genes involved in asthma than linkage analysis using affected relative pairs. 1 Objective: To identify QTLs responsible for variation in eosinophil count in adolescent twins. Methods: We measured eosinophil count longitudinally in 738 pairs of twins at 12, 14, and 16 years of age. We typed 757 highly polymorphic microsatellite markers at an average spacing of similar to5 centimorgans across the genome. We then used multipoint variance components linkage analysis to test for linkage between marker loci and eosinophil concentrations at each age across the genome. Results: We found highly significant linkage on chromosome 2q33 in 12-year-old twins (logarithm of the odds = 4.6; P = .000002) and suggestive evidence of linkage in the same region in 14-year-olds (logarithm of the odds = 1.0; P = .016). We also found suggestive evidence of linkage at other areas of the genome, including regions on chromosomes 2, 3, 4, 8, 9, 11, 12, 17, 20, and 22. Conclusion: A QTL for eosinophil count is present on chromosome 2q33. This QTL might represent a gene involved in asthma pathophysiology.

Atmospheric Poaceae pollen frequencies and associations with meteorological parameters in Brisbane, Australia: a 5-year record, 1994-1999

Grass pollen is an important risk factor for allergic rhinitis and asthma in Australia and is the most prevalent pollen component of the aerospora of Brisbane, accounting for 71.6% of the annual airborne pollen load. A 5-year (June 1994-May 1999) monitoring program shows the grass pollen season to occur during the summer and autumn months (December-April), however the timing of onset and intensity of the season vary from year to year. During the pollen season, Poaceae counts exceeding 30 grains m(-3) were recorded on 244 days and coincided with maximum temperatures of 28.1 +/- 2.0degreesC. In this study, statistical associations between atmospheric grass pollen loads and several weather parameters, including maximum temperature, minimum temperature and precipitation, were investigated. Spearman's correlation analysis demonstrated that daily grass pollen counts were positively associated (P < 0.0001) with maximum and minimum temperature during each sampling year. Precipitation, although considered a less important daily factor (P < 0.05), was observed to remove pollen grains from the atmosphere during significant periods of rainfall. This study provides the first insight into the influence of meteorological variables, in particular temperature, on atmospheric Poaceae pollen counts in Brisbane. An awareness of these associations is critical for the prevention and management of allergy and asthma for atopic individuals within this region.