Beta-lactam allergy in adults with cystic fibrosis

Background: Allergic reactions to one or more beta-lactam antibiotic can pose a management problem in patients with cystic fibrosis (CF), and may limit antibiotic choice. Method: The aim of this study was to assess the prevalence of allergy to anti-pseudomonal beta-lactam antibiotics in an adult CF centre and to assess variables, which may contribute to the development of allergic reactions. A questionnaire-based interview and a review of medical records were performed. Results: Of the 150 patients, 54 (36%) had allergic reactions to one or more beta-lactam antibiotics and 20 (19%) had allergic reactions to multiple beta-lactam antibiotics. The proportion of patients allergic to specific beta-lactam antibiotics varied from 10% to 26%. Rates of reactions were highest for penicillins and cephalosporins, intermediate for carbepenems and lowest for aztreonam. Of all reactions, 40% occurred within 24 h of the commencement of an individual antibiotic course. Patients with one or more beta-lactam allergic reactions had received greater cumulative exposure (p < 0.0001), were older (p=0.016) and had lower lung function (p=0.037) than patients without a history of beta-lactam allergy. Cystic Fibrosis transmembrane regulator (CFTR) status, gender, peripheral blood eosinophil count and total IgE concentrations were not different in patients with allergic reactions. Conclusions: This study demonstrates that the prevalence of allergic reactions to beta-lactam antibiotics is high in adults with CF. Increasing age; cumulative exposure and decreasing FEV1 were associated with the development of allergy. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Safety and use of sputum induction in children with cystic fibrosis

We assessed the safety and use of induced sputum (IS) in children with cystic fibrosis (CF). Forty-eight children (19 males) with CF, mean age 12.6 (range, 7.3-17.0) years and median forced expired volume in 1 sec (FEV1) 48% (range, 14-77%) predicted were recruited. Patients spontaneously expectorated sputum and then performed sputum induction by inhalation of nebulized 7% hypertonic saline. Samples were sent for bacteriological culture, and for measurement of the following inflammatory mediators: interleukin-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase activity. FEV1 was performed before and after inhalation of hypertonic saline. There was no increase in mediator levels in IS compared to expectorated sputum (ES) samples. Only 3 patients demonstrated significant bronchoconstriction following inhalation of hypertonic saline, by the method used. From the ES samples, Pseudomonas aeruginosa was isolated in 13 patients, Staphylococcus aureus in 7 patients, Stenotrophomonas maltophilia in 1 patient, and both Pseudomonas aeruginosa and Staphylococcus aureus in 5 patients. All these organisms were found in the IS samples. However, in 2 patients whose ES grew no organisms, one patient's IS grew Pseudomonas aeruginosa, and the other patient's IS grew Staphylococcus aureus. In our study, sputum induction was safe, with no proinflammatory effect.

Effects of recombinant human DNase and hypertonic saline on airway inflammation in children with cystic fibrosis

Recombinant human DNase (rhDNase) is an established treatment in cystic fibrosis (CF), but it may liberate cationic mediators bound to DNA in the airways. An alternative mucolytic therapy is hypertonic saline (HS); however, HS may potentiate neutrophilic inflammation. We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum. In a randomized, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase, alternate-day 2.5 mg rhDNase, and twice-daily 7% HS. Sputum levels of total interleukin-8 (IL-8), free IL-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase (NE) activity were measured before and after each treatment. The change in mediator levels from baseline with daily rhDNase and HS was not significant; however, with alternate-day rhDNase, there was an increase in free IL-8. When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS, no significant differences were detected. Only changes in NE activity were associated with changes in lung function. In summary, we were unable to show that rhDNase or HS promote airway inflammation in CF.

Is Aphtous Oral Ulceration Biopsy always Useless?

Objective: To report a case of Behçet’s disease whose diagnosis was only confirmed thanks to an oral aphthous lesion biopsy. Materials and methods: Conventional histopathological analysis of a biopsy of an aphthous oral lesion that had appeared two days previously. Results: A small vein vasculitis with eosinophil and neutrophil granulocytes was evidenced. Conclusion: The presence of a small vein vasculitis was here strongly in favour of Behçet's disease, whereas such a diagnosis was not confirmed according to the International Study Group’s criteria.

Effect of vitamin D supplementation on bone status, glucose homeostasis and immune function in children with vitamin D deficiency

Background: Between 1961-1971 vitamin D deficiency was recognized as a public health issue in the UK, because of the lack of effective sunlight and the population mix [1, 2]. In recent years, health care professionals have cited evidence suggesting a re-emergence of the vitamin D deficiency linked to a number of health consequences as a concern [3-6]. Evidence from observational studies has linked low vitamin D status with impairment in glucose homeostasis and immune dysfunction [7-9]. However, interventional studies, particularly those focused on paediatric populations, have been limited and inconsistent. There is a need for detailed studies, to clarify the therapeutic benefits of vitamin D in these important clinical areas. Objective: The aims of this PhD thesis were two-fold. Firstly, to perform preliminary work assessing the association between vitamin D deficiency and bone status, glucose homeostasis and immune function, and to explore any changes in these parameters following short term vitamin D3 replacement therapy. Secondly, to assess the effectiveness of an electronic surveillance system (ScotPSU) as a tool to determine the current incidence of hospital-based presentation of childhood vitamin D deficiency in Scotland. Methods: Active surveillance was performed for a period of two years as a part of an electronic web-based surveillance programme performed by the Scottish Paediatric Surveillance Unit (ScotPSU). The validity of the system was assessed by identifying cases with profound vitamin D deficiency (in Glasgow and Edinburgh) from the regional laboratory. All clinical details were checked against those identified using the surveillance system. Thirty-seven children aged 3 months to 10 years, who had been diagnosed with vitamin D deficiency, were recruited for the bone, glucose and immunity studies over a period of 24 months. Twenty-five samples were analysed for the glucose and bone studies; of these, 18 samples were further analysed for immune study. Treatment consisted of six weeks taking 5000 IU units cholecalciferol orally once a day. At baseline and after completion of treatment, 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), alkaline phosphatase (ALP), collagen type 1 cross-linked C-telopeptide (CTX), osteocalcin (OCN), calcium, phosphate, insulin, glucose, homeostasis model assessment index, estimated insulin resistance (HOMA IR), glycated hemoglobin (HbA1c), sex hormone binding globulin (SHBG), lipids profiles, T helper 1 (Th1) cytokines (interleukin-2 ( IL-2), tumor necrosis factors-alpha (TNF-α), interferon-gamma (INF-γ)), T helper 2 (Th2) cytokines (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6)), T helper 17 (Th17) cytokine (interleukin-17 (IL-17)), Regulatory T (Treg) cytokine (interleukin-10 (IL-10)) and chemokines/cytokines, linked with Th1/Th2 subset balance and/or differentiation (interleukin-8 (IL-8), interleukin-12 (IL-12), eosinophil chemotactic protein ( EOTAXIN), macrophage inflammatory proteins-1beta (MIP-1β), interferon-gamma-induced protein-10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1(MCP-1)) were measured. Leukoocyte subset analysis was performed for T cells, B cells and T regulatory cells and a luminex assay was used to measure the cytokiens. Results: Between September 2009 and August 2011, 163 cases of vitamin D deficiency were brought to the attention of the ScotPSU, and the majority of cases (n = 82) were reported in Glasgow. The cross-validation checking in Glasgow and Edinburgh over a one-year period revealed only 3 (11%) cases of clearly symptomatic vitamin D deficiency, which had been missed by the ScotPSU survey in Glasgow. While 16 (67%) symptomatic cases had failed to be reported through the ScotPSU survey in Edinburgh. For the 23 children who are included in bone and glucose studies, 22 (96%) children had basal serum 25(OH)D in the deficiency range (< 50 nmol/l) and one (4%) child had serum 25(OH)D in the insufficiency range (51-75 nmol/l). Following vitamin D3 treatment, 2 (9%) children had final serum 25(OH)D lower than 50 nmol/l, 6 (26%) children had final serum 25(OH)D between >50-75 nmol/l, 12 (52%) children reached a final serum 25(OH)D >75-150 nmol/l and finally 3 (13%) exceeded the normal reference range with a final 25(OH)D >150 nmol/l. Markers for remodelling ALP and PTH had significantly decreased (p = 0.001 and <0.0001 for ALP and PTH respectively). In 17 patients for whom insulin and HOMA IR data were available and enrolled in glucose study, significant improvements in insulin resistance (p = 0.04) with a trend toward a reduction in serum insulin (p = 0.05) was observed. Of those 14 children who had their cytokines profile data analysed and enrolled in the immunity study, insulin and HOMA IR data were missed in one child. A significant increase in the main Th2 secreted cytokine IL-4 (p = 0.001) and a tendency for significant increases in other Th2 secreted cytokines IL-5 (p = 0.05) and IL-6 (p = 0.05) was observed following vitamin D3 supplementation. Conclusion: An electronic surveillance system can provide data for studying the epidemiology of vitamin D deficiency. However, it may underestimate the number of positive cases. Improving vitamin D status in vitamin D deficient otherwise healthy children significantly improved their vitamin D deficient status, and was associated with an improvement in bone profile, improvements in insulin resistance and an alteration in main Th2 secreting cytokines.

Changes in Hematological Parameters and Erythrocyte Osmotic Fragility in Lame and Aged Horses Administered with Resveratrol Supplement

The study was aimed at evaluating the changes in haematological parameters and erythrocyte osmotic fragility in lame and aged horses administered with resveratrol supplement (Equithrive joint®). A total of 16 horses of both sexes, aged 18 ± 0.65 and showing lameness grade 3 were used for the study. The horses weighed 350-450 kg and comprised 8 horses which were administered with resveratrol supplement for 4 weeks and 8 others, which served as controls and given only Saccharomyces cerevisiae yeast strain used as carrier in the supplement. Blood samples were collected from each horse before supplementation and at weekly intervals for 4 weeks of the experiment. Haematological parameters and erythrocyte osmotic fragility were determined by standard methods. Equithrive joint® increased significantly (P ˂ 0.05) packed cell volume, haemoglobin concentration and erythrocyte counts in the treated horses while total leucocyte, neutrophil and eosinophil counts decreased significantly (P ˂ 0.05) in the treated horses compared with the untreated horses. Erythrocyte osmotic fragility test showed decreased haemolysis in the treated horses. The result indicated that equithrive joint® a potent antioxidant and anti-inflammatory agent maintained the membrane integrity of red blood cells and may be of value in aiding horses move with ease during ageing.

Parâmetros morfológicos de ativação dos eosinófilos do sangue periférico : uma nova ferramenta para triagem de pacientes portadores de esofagite eosinofílica

Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Patologia Molecular, 2015.

Desvendando a resposta dos eosinófilos, dos neutrófilos e dos monócitos nas parasitoses intestinais, na asma e na associação de ambas em crianças

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Pós-graduação em Medicina Tropical, 2015.