Modulação Eletrofisiológica das Aurículas e Veias Pulmonares: Interação da Estimulação Simpática e Parassimpática na Inducibilidade de Fibrilhação Aguda Auricular num Modelo Experimental In Vivo

A influência do sistema nervoso autónomo (SNA) na génese da fibrilhac¸ão auricular (FA) envolve múltiplos mecanismos complexos com impacto nas propriedades eletrofisiológicas cardíacas. A importância dos efeitos da estimulac¸ão autonómica no substrato elétrico auricular e das veias pulmonares (VP) e na vulnerabilidade para FA requer melhor compreensão. Objetivo: Avaliar os efeitos da estimulac¸ão vagal (estim vag) e simpática (estim simp) aguda na condução e refratariedade das aurículas e VP e na indutibilidade de FA no coração de coelho in vivo com inervação autonómica preservada. Métodos: Estudámos 17 coelhos New Zealand de ambos os sexos. Para abordagem de «toráxaberto» procedeu-se a anestesia, entubação e ventilação após bloqueio neuro-muscular. O ECG foi obtido a partir de 3 derivações dos membros. Os eletrogramas foram registados com 4 elétrodos monopolares colocados na superfície epicárdica, distribuídos ao longo das aurículas e com um elétrodo circular adaptado à porção proximal das VP. Estimulou-se o nervo vago cervical direito e o tronco simpático torácico com elétrodos bipolares de platina. Estudámos os períodos refratários efetivos (PRE) e a condução elétrica auricular, entre a aurícula direita lateral-alta (AD) e a aurícula esquerda lateral-alta (AE), e entre AD e VP, em condições basais e durante estim vag, estim simp e estimulação autonómica combinada (dual estim). Para indução de FA, procedeu-se a pacing rápido (50 Hz, 10 s, isolado ou com estim vag, estim simp ou dual estim) com elétrodo bipolar no apêndice auricular direito (AAD), apêndice auricular esquerdo (AAE) e VP. Resultados: Em condições basais: os PRE eram maiores no AAE e registou-se um atraso na ativação da AD para as VP, comparando com a condução interauricular. Durante estim vag ou dual estim: os PRE encurtaram significativamente em todos os locais, o intervalo de condução interauricular variou de 20 ± 4 ms para 30 ± 10 ms (p < 0,05) e 31 ± 11 ms (p < 0,05),respetivamente. Com estim simp obteve-se uma redução significativa dos PRE no AAE e do tempo de condução interauricular para 16 ± 11 ms (p < 0,05). Induziu-se FA em 35 a 53% dos animais com 50 Hz, 65 a 76% com estim vagal ou estim simp, e 75 a 100% com dual estim (p < 0,05). A duração da FA aumentou significativamente durante estim vagal e/ou estim simp. Em 2/3 dos animais com indução de FA com duração >10 s a arritmia terminou imediatamente após interrupção da estim vagal. Conclusões: No coração de coelho inervado in vivo, a estimulação autonómica aguda encurta a refratariedade auricular e das VP, e modifica a velocidade de condução auricular, potenciando a indução e duração de FA. Os resultados sugerem que as variações agudas e a interação da atividade autonómica podem desempenhar um papel importante na fisiopatologia da FA.

Fexofenadine is Efficacious and Safe in Children (Aged 6-11 Years) with Seasonal Allergic Rhinitis

Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup,double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point.

Epidemiology of Asthma and Allergic Diseases in Portuguese Speaking Regions

The application of the same epidemiological methods in different countries allows important comparisons between different races and cultures. During the last decade, two large multi-centres epidemiological studies, the Portuguese Study of Allergic Diseases in Childhood (PAC study) and the International Study of Asthma and Allergies in Childhood (ISAAC study), were implemented in Portuguese speaking regions. The main objectives were to assess and compare allergic diseases prevalence. The authors stress out the significant differences observed in schoolchildren from the three continents, with different genetic and environmental background. It was found an increase trend in the prevalence of all allergic diseases, mainly rhinitis, in last decade. Rhinitis has been identified as an independent risk factor for asthma in Caucasian population.

Development Process and Cognitive Testing of CARATkids - Control of Allergic Rhinitis and Asthma Test for Children

Background: Allergic rhinitis and asthma (ARA) are chronic inflammatory diseases of the airways that often coexist in children. The only tool to assess the ARA control, the Control of Allergic Rhinitis and Asthma Test (CARAT) is to be used by adults. We aimed to develop the Pediatric version of Control of Allergic Rhinitis and Asthma Test (CARATkids) and to test its comprehensibility in children with 4 to 12 years of age. Methods: The questionnaire development included a literature review of pediatric questionnaires on asthma and/or rhinitis control and two consensus meetings of a multidisciplinary group. Cognitive testing was carried out in a cross-sectional qualitative study using cognitive interviews. Results: Four questionnaires to assess asthma and none to assess rhinitis control in children were identified. The multidisciplinary group produced a questionnaire version for children with 17 questions with illustrations and dichotomous (yes/no) response format. The version for caregivers had 4-points and dichotomous scales. Twenty-nine children, 4 to 12 years old, and their caregivers were interviewed. Only children over 6 years old could adequately answer the questionnaire. A few words/expressions were not fully understood by children of 6 to 8 years old. The drawings illustrating the questions were considered helpful by children and caregivers. Caregivers considered the questionnaire complete and clear and preferred dichotomous over the 4-points scales. The proportion of agreement between children and their caregivers was 61%. The words/expressions that were difficult to understand were amended. Conclusion: CARATkids, the first questionnaire to assess a child’s asthma and rhinitis control was developed and its content validity was assured. Cognitive testing showed that CARATKids is well-understood by children 6 to 12 years old. The questionnaire’s measurement properties can now be assessed in a validation study.

The Oncological and Functional Risks of the Organ Preservation Experimental Treatment Approach

We increasingly face conservative surgery for rectal cancer and even the so called ‘wait and see’ approach, as far as 10–20% patients can reach a complete pathological response at the time of surgery. But what can we say to our patients about risks? Standard surgery with mesorectal excision gives a <2% local recurrence with a post operative death rate of 2–8% (may reach 30% at 6 months in those over 85), but low AR has some deterioration in bowel function and in low cancer a permanent stoma may be required. Also a long-term impact on urinary and sexual function is possible. Distant metastasis rate seem to be identical in the standard and conservative approach. It is difficult to evaluate conservative approach because a not clear standardization of surgery for low rectal cancer. Rullier et al tried to clarify, and they found identical results for recurrence (5–9%), disease free survival (70%) at 5y for coloanal anastomosis and intersphinteric resection. Other series have found local recurrence higher than with standard approach and functional results may be worse and, in some situations, salvage therapy is compromised or has more complications. In this context, functional outcomes are very important but most studies are incomplete in measuring bowel function in the context of conservative approach. In 2005 Temple et al made a survey of 122/184 patient after sphinter preserving surgery and found a 96.9% of incomplete evacuation, 94.4% clustering, 93.2% food affecting frequency, 91.8% gas incontinence and proposed a systematic evaluation with a specific questionnaire. In which concerns ‘Wait and see’ approach for complete clinical responders, it was first advocated by Habr Gama for tumors up to 7cm, with a low locoregional failure of 4.6%, 5y overall survival 96%, 72% for disease free survival; one fifth of patients failed in the first year; a Dutch trial had identical results but others had worse recurrence rates; in other series 25% of patients could not be salvaged even with APR; 30% have subsequent metastatic disease what seems equal for ‘wait and see’ and operated patients. In a recent review Glynne Jones considers that all the evaluated ‘wait and see’ studies are heterogeneous in staging, inclusion criteria, design and follow up after chemoradiation and that there is the suggestion that patients who progress while under observation fare worse than those resected. He proposes long-term observational studies with more uniform inclusion criteria. We are now facing a moment where we may be more aggressive in early cancer and neoadjuvant treatment to be more conservative in the subsequent treatment but we need a better stratification of patients, better evaluation of results and more clear prognostic markers.

The Management of the Allergic Child at School: EAACI/GA2LEN Task Force on the Allergic Child at School

Allergy affects at least one-quarter of European schoolchildren, it reduces quality of life and may impair school performance; there is a risk of severe reactions and, in rare cases, death. Allergy is a multi-system disorder, and children often have several co-existing diseases, i.e. allergic rhinitis, asthma, eczema and food allergy. Severe food allergy reactions may occur for the first time at school, and overall 20% of food allergy reactions occur in schools. Up to two-thirds of schools have at least one child at risk of anaphylaxis but many are poorly prepared. A cooperative partnership between doctors, community and school nurses, school staff, parents and the child is necessary to ensure allergic children are protected. Schools and doctors should adopt a comprehensive approach to allergy training, ensuring that all staff can prevent, recognize and initiate treatment of allergic reactions.

Quantitative Analysis of Immunoglobulin E Reactivity Profiles in Patients Allergic or Sensitized to Natural Rubber Latex (Hevea Brasiliensis)

Characterized native and recombinant Hevea brasiliensis (rHev b) natural rubber latex (NRL) allergens are available to assess patient allergen sensitization profiles. OBJECTIVE: Quantification of individual IgE responses to the spectrum of documented NRL allergens and evaluation of cross-reactive carbohydrate determinants (CCDs) for more definitive diagnosis. METHODS: Sera of 104 healthcare workers (HCW; 51 German, 21 Portuguese, 32 American), 31 spina bifida patients (SB; 11 German, 20 Portuguese) and 10 Portuguese with multiple surgeries (MS) were analysed for allergen-specific IgE antibody (sIgE) to NRL, single Hev b allergens and CCDs with ImmunoCAP technology. RESULTS: In all patient groups rHev b 5-sIgE concentrations were the most pronounced. Hev b 2, 5, 6.01 and 13 were identified as the major allergens in HCW and combined with Hev b 1 and Hev b 3 in SB. In MS Hev b 1 displayed an intermediate relevance. Different sIgE antibody levels to native Hevea brasiliensis (nHev b) 2 and rHev b 6.01 allowed discrimination of SB with clinical relevant latex allergy vs. those with latex sensitization. Sensitization profiles of German, Portuguese and American patients were equivalent. rHev b 5, 6.01 and nHev b 13 combined detected 100% of the latex-allergic HCW and 80.1% of the SB. Only 8.3% of the sera showed sIgE response to CCDs. CONCLUSIONS: Hev b 1, 2, 5, 6.01 and 13 were identified as the major Hev b allergens and they should be present in standardized latex extracts and in vitro allergosorbents. CCDs are only of minor relevance in patients with clinical relevant latex allergy. Component-resolved diagnostic analyses for latex allergy set the stage for an allergen-directed immunotherapy strategy