Deuterium Metabolic Imaging Differentiates Glioblastoma Metabolic Subtypes and Detects Early Response to Chemoradiotherapy.

Metabolic subtypes of glioblastoma (GBM) have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. In this study, we used 2H magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging (MRSI) measurements of [6,6'-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived GBM xenografts in vivo. The metabolism of patient-derived cells was first characterized in vitro by measuring the oxygen consumption rate, a marker of mitochondrial tricarboxylic acid cycle activity, as well as the extracellular acidification rate and 2H-labeled lactate production from [6,6'-2H2]glucose, which are markers of glycolytic activity. Two cell lines representative of a glycolytic subtype and two representative of a mitochondrial subtype were identified. 2H magnetic resonance spectroscopy and MRSI measurements showed similar concentrations of 2H-labeled glucose from [6,6'-2H2]glucose in all four tumor models when implanted orthotopically in mice. The glycolytic subtypes showed higher concentrations of 2H-labeled lactate than the mitochondrial subtypes and normal-appearing brain tissue, whereas the mitochondrial subtypes showed more glutamate/glutamine labeling, a surrogate for tricarboxylic acid cycle activity, than the glycolytic subtypes and normal-appearing brain tissue. The response of the tumors to chemoradiation could be detected within 24 hours of treatment completion, with the mitochondrial subtypes showing a decrease in both 2H-labeled glutamate/glutamine and lactate concentrations and glycolytic tumors showing a decrease in 2H-labeled lactate concentration. This technique has the potential to be used clinically for treatment selection and early detection of treatment response. SIGNIFICANCE: Deuterium magnetic resonance spectroscopic imaging of glucose metabolism has the potential to differentiate between glycolytic and mitochondrial metabolic subtypes in glioblastoma and to evaluate early treatment responses, which could guide patient treatment.

Baked milk tolerant patient: Is there any special feature?

BACKGROUND: Determining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. OBJECTIVES: The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. MATERIALS AND METHODS: A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. RESULTS: Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin (p=0.01) and casein (p=0.004) and the serum specific IgE for casein (p=0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p=0.037). CONCLUSIONS: Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance.

Early versus late readmission of subarachnoid haemorrhage patients into neurocritical care.

INTRODUCTION: Subarachnoid haemorrhage (SAH) patients will typically require monitoring in a specialised Neurocritical Care Unit (NCCU) regardless of the primary treatment modality. Once discharged from NCCU, readmission within 48 h is regarded as a "failed" discharge. The aims of this study are to (1) Evaluate the readmission rate of SAH patients into NCCU, (2) Identify the indications for readmission, (3) Analyse clinical parameters on discharge between patients readmitted early and late. MATERIALS AND METHODS: Retrospective observational study of the Intensive Care National Audit and Research Centre (ICNARC) database of patients from our unit diagnosed with SAH from January 2009-December 2014, who were readmitted into NCCU. Demographic data, World Federation of Neurosurgical Societies (WFNS) grade, Fisher grade, length of initial and subsequent NCCU stay, time of readmission, indication for readmission, and mortality rate data were collected. Patients were categorised by early (<48 h) and late (>48 h) readmission, and their clinical parameters on NCCU discharge were statistically analysed. RESULTS: Five hundred and seventy-five SAH patients were admitted into NCCU, of which 49 patients (9%) were readmitted after discharge to ward-level care. The mean age of readmitted patients was 64.1 ± 11.6 years old. The most common indications were delayed cerebral ischaemia (DCI) (50%) and infection (19%). Readmitted SAH patients were typically WFNS grade I-II (n = 22) and Fisher grade III-IV (n = 44). 17 (35%) patients were readmitted early, and were older (p = 0.0049) with a lower GCS (p = 0.0077) compared to patients readmitted later. White cell count and C-reactive protein were higher in patients readmitted early, but did not reach statistical significance (p = 0.09, p = 0.07). CONCLUSION: DCI and infection were the most common indications for NCCU readmission in SAH patients. "Failed" discharged patients from NCCU are typically older with a lower GCS than patients readmitted after 48 h, and therefore clinicians should be more cautious in discharging these patients prematurely.

Revealing Hearing Loss: A Survey of How People Verbally Disclose Their Hearing Loss.

OBJECTIVE: Hearing loss is the most common sensory deficit and congenital anomaly, yet the decision-making processes involved in disclosing hearing loss have been little studied. To address this issue, we have explored the phrases that adults with hearing loss use to disclose their hearing loss. DESIGN: Since self-disclosure research has not focused on hearing loss-specific issues, we created a 15-question survey about verbally disclosing hearing loss. English speaking adults (>18 years old) with hearing loss of any etiology were recruited from otology clinics in a major referral hospital. Three hundred and thirty-seven participants completed the survey instrument. Participants' phrase(s) used to tell people they have hearing loss were compared across objective characteristics (age; sex; type, degree, and laterality of hearing loss; word recognition scores) and self-reported characteristics (degree of hearing loss; age of onset and years lived with hearing loss; use of technology; hearing handicap score). RESULTS: Participants' responses revealed three strategies to address hearing loss: Multipurpose disclosure (phrases that disclose hearing loss and provide information to facilitate communication), Basic disclosure (phrases that disclose hearing loss through the term, a label, or details about the condition), or nondisclosure (phrases that do not disclose hearing loss). Variables were compared between patients who used and who did not use each disclosure strategy using χ or Wilcoxon rank sum tests. Multipurpose disclosers were mostly female (p = 0.002); had experienced reactions of help, support, and accommodation after disclosing (p = 0.008); and had experienced reactions of being overly helpful after disclosing (p=0.039). Basic disclosers were predominantly male (p = 0.004); reported feeling somewhat more comfortable disclosing their hearing loss over time (p = 0.009); had not experienced reactions of being treated unfairly or discriminated against (p = 0.021); and were diagnosed with mixed hearing loss (p = 0.004). Nondisclosers tended not to disclose in a group setting (p = 0.002) and were diagnosed with bilateral hearing loss (p = 0.005). In addition, all of the variables were examined to build logistic regression models to predict the use of each disclosure strategy. CONCLUSIONS: Our results reveal three simple strategies for verbally addressing hearing loss that can be used in a variety of contexts. We recommend educating people with hearing loss about these strategies-this could improve the experience of disclosing hearing loss, and could educate society at large about how to interact with those who have a hearing loss.

Quantitative polarized light microscopy of human cochlear sections.

Dysfunction of the inner ear is the most common cause of sensorineural hearing loss, which is the most common sensory deficit worldwide. Conventional imaging modalities are unable to depict the microanatomy of the human inner ear, hence the need to explore novel imaging modalities. We provide the first characterization of the polarization dependent optical properties of human cochlear sections using quantitative polarized light microscopy (qPLM). Eight pediatric cadaveric cochlear sections, aged 0 (term) to 24 months, were selected from the US National Temporal Bone Registry, imaged with qPLM and analyzed using Image J. Retardance of the bony otic capsule and basilar membrane were substantially higher than that of the stria vascularis, spiral ganglion neurons, organ of Corti and spiral ligament across the half turns of the spiraling cochlea. qPLM provides quantitative information about the human inner ear, and awaits future exploration in vivo.

Establishing a cut-off for the serum levels of specific IgE to milk and its components for cow's milk allergy: results from a specific population.

BACKGROUND: Cow's milk allergy diagnosis many times requires double-blind placebo-controlled food challenge (DBPCFC), which presents high accuracy but involves risks, specifically in infants and anaphylactic patients. The identification of the cut-off values for specific IgE to milk or its components would contribute to cow's milk allergy (CMA) diagnosis. The aim of this study was to compare discriminating concentration of a cow's milk specific IgE and its fractions (α-lactoalbumin, ß-lactoglobulin, casein) in children for the CMA diagnosis. METHODS: this study included 123 patients (M:F=1.3:1) median age at diagnosis=1.91 years, (3.5m to 13.21y) with CMA diagnosis via DBPCFC (n=26), proven anaphylaxis due to cow's milk (n=46) or a suggestive clinical history associated with a positive skin prick test (n=51) and open oral food challenge. The control group included 61 patients (1 male:1.1 female) ages ranging from 0.66 to 16.7 years (median=6.83 years). Receiver operator characteristics (ROC) curves were constructed to determine the best cut-offs that guarantees high specificity (>95%) for cow's milk and its components. RESULTS: considering 98% specificity, cut-off points were: 3.06 kU/L for cow's milk, 2.06 kU/L for α-lactalbumin, 1.85 kU/L for ß-lactoglobulin and 1.47kU/L for casein. The best ROC curve (area under the curve=0.929) was obtained evaluating cow's milk. CONCLUSION: this study showed that the cut-off point detected for whole cow's milk revealed a better discriminatory capacity for CMA diagnosis without the necessity of the milk components testing.

Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma.

UNLABELLED: This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 µg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 µg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. ( CLINICAL TRIAL NUMBER: ISRCTN60408425).

Double-blind, placebo-controlled food challenges in Brazilian children: adaptation to clinical practice.

BACKGROUND: A double-blind, placebo-controlled food challenge (DBPCFC) is considered the gold standard for diagnosing food allergy, but because of methodological difficulties it is rarely conducted in clinical practice, especially in paediatric patients. The purpose of the study was to propose a DBPCFC protocol that is adapted to our conditions for the diagnosis of an IgE-mediated cow's milk allergy (CMA) in a Brazilian reference centre for paediatric allergies. METHODS: This study includes the experimental phase (choice of materials, adjustments made to protocols described in the literature) and the test execution phase. DBPCFCs were performed in 58 patients aged 1-15 years who were separated into two groups: Group 1 (n=39), sex 1.6 M:F, 5.3 years median age, suggestive history of IgE-mediated CMA; and Group 2 (n=19), sex 1.4 M:F, 8.3 years median age with symptoms not associated with milk ingestion and laboratory data not compatible with IgE-mediated CMA. RESULTS: The materials were standardised for testing: containers and disposable products, low-lactose cow's milk (CM) and vehicles, such as natural fruit juice, vegetable soup and soybean-based beverages. Each DBPCFC was performed in a single day with two blind, randomised phases with a 2-h interval between them. The milk doses were gradually increased and offered in regular intervals of 15-30 min. Following negative or inconclusive results, patients underwent an open oral challenge test with 200 mL of low-lactose CM. CONCLUSIONS: The proposed adaptation for the DBPCFC allowed to implement this important test for the diagnosis of IgE-mediated CMA in a reference centre for paediatric allergies. It was considered feasible and safe if performed in an appropriate setting with physician supervision.

Prediction of tolerance in children with IgE mediated cow's milk allergy by microarray profiling and chemometric approach.

The sera of a retrospective cohort (n=41) composed of children with well characterized cow's milk allergy collected from multiple visits were analyzed using a protein microarray system measuring four classes of immunoglobulins. The frequency of the visits, age and gender distribution reflected real situation faced by the clinicians at a pediatric reference center for food allergy in São Paulo, Brazil. The profiling array results have shown that total IgG and IgA share similar specificity whilst IgM and in particular IgE are distantly related. The correlation of specificity of IgE and IgA is variable amongst the patients and this relationship cannot be used to predict atopy or the onset of tolerance to milk. The array profiling technique has corroborated the clinical selection criteria for this cohort albeit it clearly suggested that 4 out of the 41 patients might have allergies other than milk origin. There was also a good correlation between the array data and ImmunoCAP results, casein in particular. By using qualitative and quantitative multivariate analysis routines it was possible to produce validated statistical models to predict with reasonable accuracy the onset of tolerance to milk proteins. If expanded to larger study groups, the array profiling in combination with the multivariate techniques show potential to improve the prognostic of milk allergic patients.

Common variable immunodeficiency associated with hepatosplenic T-cell lymphoma mimicking juvenile systemic lupus erythematosus.

Common variable immunodeficiency (CVID) is a heterogeneous disorder with susceptibility to infections, autoimmune manifestations, and cancer. To our knowledge, CIVD with T-cell lymphoma mimicking juvenile systemic lupus erythematosus (JSLE) was not described in the literature, and one case was reported herein. An 8-year-old female was admitted in our Pediatric Immunology Unit with a clinical history of hypogammaglobulinemia, recurrent upper respiratory infections, and pneumonias. She had a marked decrease of three serum immunoglobulin isotypes, and the diagnosis of CVID was established. At the age of 17 years, she presented with oral ulceration, nonerosive arthritis, nephritis, serositis, cytopenia, positive antiphospholipid antibodies, and positive antinuclear antibody fulfilling the American College of Rheumatology (ACR) criteria for SLE. She was treated with intravenous methylprednisolone for three consecutive days, and intravenous immunoglobulin, and maintenance therapy of chloroquine, azathioprine and prednisone 40 mg/day. Two months later, she died of septic shock secondary to acute pneumonia. The necropsy showed hepatosplenic T-cell lymphoma with diffuse involvement of bone marrow, spleen, liver, and lungs. The lymphoma cells were positive for CD3 immunostaining and negative for CD20 and lysozyme. In conclusion, the association of CVID and hepatosplenic T-cell lymphoma may simulate JSLE diagnosis.

Molecular characterization of patients with X-linked Hyper-IgM syndrome: description of two novel CD40L mutations.

Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X mutation which abolished CD40L expression. P2 had a previously described frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein expression. P3 demonstrated the previously known p.V126D change in exon 4, affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L mutation also located in the TNFH domain. In silico analysis of F229L predicted the change to be pathological, affecting the many hydrophobic interactions of this residue. Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible.

Sensitisation to aeroallergens in Brazilian adolescents living at the periphery of large subtropical urban centres.

OBJECTIVES: To evaluate the sensitization to aeroallergens determined by skin prick test (SPT) in Brazilian adolescents, and to correlate its positivity with the diagnosis of asthma and/or rhinitis based on the written questionnaire (WQ) of ISAAC phase III study. PATIENTS AND METHODS: A total of 996 adolescents (387 boys) were selected by systematic samples. A standard allergen extracts panel (positive/negative control, D pteronyssinus [Dpt], P americana [Pa], B germanica [Bg], dog, cat, fungal and grass mix) was used and its positivity compared with positive responses to asthma, rhinitis or both. RESULTS: Positive SPT to at least one allergen was observed in 466 adolescents (46.8 %), with sensitisation to Dpt in 79.1 %. Positivity to more than one allergen occurred in 232 students (49.8 %). The frequency of positive SPTs was significantly higher among adolescents with asthma (OR = 2.16), rhinitis (OR = 1.69), and asthma and rhinitis (OR = 2.03). Positive SPT to four or more allergens were higher among asthmatics (OR = 2.6) and among adolescents with asthma and rhinitis (OR = 3). CONCLUSIONS: A high sensitisation rate to aeroallergens was observed, significantly higher among those with asthma, rhinitis or a combination of both, especially in multiple sensitisations.

Prevalence of asthma, rhinitis and eczema in 6 - 7 years old students from the western districts of São Paulo City, using the standardized questionnaire of the "International Study of Asthma and Allergies in Childhood" (ISAAC)-phase IIIB.

UNLABELLED: The aims of the present work were the evaluation of allergic disease prevalence among 6 and 7 year-old students from the western districts of São Paulo city and the comparison of these data with those obtained in the International Study of Asthma and Allergies in Childhood (ISAAC) phase I, performed in the central-southern districts of São Paulo, using the ISAAC standardized written questionnaire. METHODS: 5,040 questionnaires were distributed and 3,312 were returned. Proportional differences were estimated by Chi square or Fisher exact tests. Odds Ratio and 95% confidence intervals between genders and allergic diseases were calculated. Values of p<0.05 were considered statistically significant. RESULTS: The corrected prevalences found were: asthma 24.4%, medical diagnosis of asthma 5.7%, rhinitis 25.7%, rhinoconjunctivitis 11.3%, medical diagnosis of rhinitis 20.0%, atopic eczema 9.2%. Significant associations between asthma and rhinitis (OR=3.3), asthma and eczema (OR=2.2), and rhinitis and eczema (OR=2.8) occurred. The male gender was prevalent regarding asthma and rhinitis. Compared to data from ISAAC phase I, higher asthma prevalence and severity, and lower values for rhinitis and eczema were observed in this study. CONCLUSIONS: The present study evidenced high prevalences for asthma and rhinitis compared to the children's medical diagnosis. The male gender predominated in all positive responses regarding asthma and rhinitis. The most frequent associations observed were between asthma and rhinitis and asthma and eczema. In the western districts of São Paulo, a higher prevalence of asthma symptoms and severity and lower prevalences for rhinitis and eczema occurred compared to the central-southern districts of the city.

Prevalence of symptoms of asthma, rhinitis, and atopic eczema in Brazilian adolescents related to exposure to gaseous air pollutants and socioeconomic status.

OBJECTIVES: To evaluate the relationship between exposure to gaseous air pollutants (ozone [O3], carbon monoxide [CO], nitrogen dioxide [NO2], and sulfur dioxide [SO2]) socioeconomic status and the prevalence of symptoms of asthma, rhinitis and atopic eczema in adolescents. SUBJECTS AND METHODS: A sample of 16 209 adolescents from São Paulo West (SPW), São Paulo South (SPS), Santo André (SA), Curitiba (CR), and Porto Alegre (PoA) were enrolled. Data on air pollutants and socioeconomic status were compared to prevalence of symptoms with the Spearman correlation coefficient. RESULTS: Socioeconomic status was quite similar in all cities. The levels of O3 in SPW, SPS, and SA, and of CO in SA were higher than the acceptable ones. In relation to O3 and CO exposures, adolescents from SPW and SA had a significant risk of current wheezing, whereas living in SPW was associated with a high risk of rhinoconjunctivitis, eczema, and flexural eczema and living in CR to rhinitis. Exposure to NO2 was associated with a high risk of current wheezing in SPW and SA, and of severe asthma in SPW and PoA. Exposure to SO2 was associated with a high risk of current wheezing in SPW and SA, severe asthma in SPW and PoA, and nighttime cough, eczema, flexural eczema and severe eczema in SPW. Living in SPW, CR, or PoA was associated with a high risk of rhinitis, rhinoconjunctivitis, and severe rhinitis. CONCLUSIONS: Although we did not detect a characteristic pattern for all symptoms evaluated or a specific air pollutant, our data suggest a relationship between higher exposure to photochemical pollutants and high prevalence or risk of symptoms of asthma, rhinitis, and atopic eczema.

Prevalence of asthma, rhinitis and eczema in 6 - 7 years old students from the western districts of São Paulo City, using the standardized questionnaire of the "International Study of Asthma and Allergies in Childhood" (ISAAC)-phase IIIB

The aims of the present work were the evaluation of allergic disease prevalence among 6 and 7 year-old students from the western districts of São Paulo city and the comparison of these data with those obtained in the International Study of Asthma and Allergies in Childhood (ISAAC) phase I, performed in the central-southern districts of São Paulo, using the ISAAC standardized written questionnaire. METHODS: 5,040 questionnaires were distributed and 3,312 were returned. Proportional differences were estimated by Chi square or Fisher exact tests. Odds Ratio and 95 percent confidence intervals between genders and allergic diseases were calculated. Values of p<0.05 were considered statistically significant. RESULTS: The corrected prevalences found were: asthma 24.4 percent, medical diagnosis of asthma 5.7 percent, rhinitis 25.7 percent, rhinoconjunctivitis 11.3 percent, medical diagnosis of rhinitis 20.0 percent, atopic eczema 9.2 percent. Significant associations between asthma and rhinitis (OR=3.3), asthma and eczema (OR=2.2), and rhinitis and eczema (OR=2.8) occurred. The male gender was prevalent regarding asthma and rhinitis. Compared to data from ISAAC phase I, higher asthma prevalence and severity, and lower values for rhinitis and eczema were observed in this study. CONCLUSIONS: The present study evidenced high prevalences for asthma and rhinitis compared to the children's medical diagnosis. The male gender predominated in all positive responses regarding asthma and rhinitis. The most frequent associations observed were between asthma and rhinitis and asthma and eczema. In the western districts of São Paulo, a higher prevalence of asthma symptoms and severity and lower prevalences for rhinitis and eczema occurred compared to the central-southern districts of the city.

OBJETIVOS: Avaliar a prevalência das doenças alérgicas na região oeste de São Paulo entre escolares de 6 a 7 anos e comparar os dados obtidos com aqueles da fase I da região centro-sul, através do questionário padronizado do International Study of Asthma and Allergies in Childhood. MÉTODOS: Foram enviados 5040 questionários escritos com resposta de 3.312 alunos. As diferenças entre proporções foram avaliadas pelo Teste do Qui-quadrado ou Teste Exato de Fisher, se calculado a Razão das Chances, intervalo de confiança 95 por cento entre os sexos e doenças alérgicas. Os valores de p < 0,05 foram considerados como significantes. RESULTADOS: As prevalências corrigidas encontradas foram: asma 24,4 por cento, diagnóstico médico de asma 5,7 por cento, rinite 25,7 por cento, rinoconjuntivite 11,3 por cento, diagnóstico médico de rinite 20 por cento, eczema atópico 9,2 por cento. Houve associação significativa entre asma e rinite (OR=3,3), asma e eczema (OR=2,2) e rinite e eczema atópico (OR=2,8). O sexo masculino foi predominante para asma e rinite. Comparando-se os dados da fase I, observou-se prevalência mais elevada dos sintomas e gravidade de asma e valores menores para rinite e eczema. CONCLUSÕES: As prevalências de asma e rinite neste estudo mostraram valores elevados em comparação ao diagnóstico médico. Houve predomínio do sexo masculino para asma e rinite. As associações mais freqüentes foram entre asma e rinite e asma e eczema. Em relação à região centro-sul de São Paulo, observou-se que na região oeste houve maior prevalência dos sintomas e gravidade da asma e menor prevalência de rinite e eczema.

Salivary lysozyme levels in patients with primary immunodeficiencies.

BACKGROUND: Lysozyme is a muramidase that acts on the peptideoglycan wall of Gram positive bacteria, causing cell death. It plays part in innate immunity and is present in blood, external fluid, as well in lysossomal granules of the phagocytes. Primary Immunodeficiencies are a diverse group of illnesses that, as a result of abnormalities of the immune system, increase susceptibility to infection. Among the examples of impaired natural immunity are defects in phagocytes and in the complement system. Innate immunity could be important in protecting mucosas against infections in patients with different forms of primary immunodeficiencies. The aim of this study was to investigate lysozyme concentrations in saliva from patients with primary immunodeficiencies. METHODS: Lysozyme levels in saliva samples from 34 patients with primary immunodeficiency (30 children and adolescents between the age of 3-13 years and 4 adults between the age of 20-33) and 60 age-matched healthy controls (49 children and adolescents between the ages of 3-15 and 11 adults between the ages of 22-42) were determined by the lysoplate method. RESULTS: There was no statistically significant difference between the lysozyme concentrations in the saliva of the immunodeficient subjects and those of the healthy controls. CONCLUSION: The results in the present work clearly show that salivary lysozyme levels in primary immunodeficient patients are equivalent to those found in healthy controls, suggesting that this enzyme still represents a remaining (but not a compensatory mechanism), contributing to the protection of there patients against infections.

Secondary hypogammaglobilinemia after use of carbamazepine: case report and review.

Immunologic disorders related to anticonvulsant therapy have been described in the last three decades, including cellular and humoral alterations that result in recurrent infections; however, the physiopathologic mechanisms are not completely understood. This report describes a patient with complex partial epilepsy and hypogammaglobulinemia while in treatment with carbamazepine, with significant improvement in clinical signs and laboratory tests after substitution to sodium valproate. The authors stress the importance of clinical and laboratory evaluation of patients in continuous anticonvulsant therapy, including immunoglobulins levels and peripheral blood evaluations.

[IgA deficiency: clinical and laboratory evaluation of 60 patients from the "Instituto da Criança"]. / Deficiência de IgA: avaliação clínico-laboratorial de 60 pacientes do Instituto da Criança.

OBJECTIVES: To evaluate the main clinical findings that suggest DIgA and describe the complications observed. PATIENTS AND METHOD: Sixty IgA deficient patients (IgA < 5mg/dl) were included, retrospectively. They were submitted to clinical evaluation and specific laboratorial tests. Their evolution was followed up to 15 years. RESULTS: The main complaints were: recurrent infections (50%), allergies (34%) or autoimmune diseases (10%). The respiratory system was the most affected by infections, and asthma and rhinitis were the most frequent allergic symptoms. No immunological impairment was detected, except for IgA deficiency. IgG and IgM levels were elevated in 50% of the patients. There was improvement of clinical symptoms and some of the patients became asymptomatic during the follow-up. CONCLUSION: IgA deficiency has a large clinical spectrum and early diagnosis would indicate prophylaxis for infections and allergy.

Deficiência de IgA: avaliaçäo clínico-laboratorial de 60 pacientes do Instituto da Criança / IgA deficiency: clinical and laboratorial evaluation of 60 patients from \"Instituto da Criança\"

Objetivos. Caracterizar os principais dados clínicos que orientem a pesquisa da DIgA e descrever sua evoluçao clínica e complicaçoes durante o seguimento ambulatorial. Material e Métodos. Foram avaliados, retrospectivamente, 60 pacientes portadores de DIgA (níveis séricos de IgA < 5 mg/dL) e submetidos à avaliaçao Clínica e provas laboratoriais específicas. Resultados. As queixas principais foram os processos infecciosos (50 por cento), quadros alérgicos (34 por cento) e doenças auto-imunes (10 por cento). Os processos infecciosos recorrentes acometeram preferencialmente o trato respiratório, sendo asma e rinite as manifestaçoes alérgicas mais frequentes. à avaliaçao laboratorial, além da deficiência de IgA, apenas os níveis de IgG e IgM encontravam-se elevados em 50 por cento dos pacientes. Durante a evoluçao, houve melhora da sintomatologia clínica e alguns pacientes tornaram-se assintomáticos durante a idade escolar e puberdade. Conclusao: A DIgA tem espectro clínico variado devendo ser sempre pesquisada em pacientes com infecçoes de repetiçao, processos alérgicos ou doenças auto-imunes para orientaçao de profilaxia precoce dos processos infecciosos e doenças alérgicas.