Evaluation of biochemical markers and quality of life in different pulmonary rehabilitation exercises for COPD patients: Avaliação de marcadores bioquímicos e qualidade de vida em diferentes treinos na reabilitação pulmonar nos portadores de DPOC

Background: Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide, causing gradual muscle dysfunction deterioration. Muscle impairment may be controlled after a specific and individualized pulmonary rehabilitation training program, which is essential for the management of COPD. This study aimed to assess indirect biochemical parameters related to muscle behavior and quality of life in patients with COPD in different pulmonary rehabilitation training programs. Methods: Thirty patients (GOLD stages II-IV) were prospectively included in a 12-week multidisciplinary pulmonary rehabilitation program. Patients who performed high-intensity training (n=15) were assigned to Group A and those performing low-intensity training (n=15) were placed in Group B. Besides clinical evaluation, serum creatine kinase, lactate, fibrinogen, and vitamin D levels, cardiopulmonary test and 6-minute walk test results, and quality of life were assessed before and after intervention. Results: There was a significant reduction in fibrinogen (458 vs. 284 mg/dl) (p<0.001) associated with an improvement in quality of life (27.9 vs. 19.3 points) (p=0.024) in group A. Conclusions: Pulmonary rehabilitation with a structured program that included high-intensity training was well tolerated by the patients and was more efficient in reducing fibrinogen as an inflammatory marker, improving quality of life

Hereditary Angioedema-Associated Acute Pancreatitis in C1-Inhibitor Deficient and Normal C1-Inhibitor Patients: Case Reports and Literature Review

Abdominal pain due to intestinal swellings is one of the most common manifestations in hereditary angioedema (HAE). Bowel swellings can cause severe abdominal pain, nausea, vomiting, and diarrhea, which may lead to misdiagnosis of gastrointestinal disorders. In rare cases, HAE abdominal attacks can be accompanied by acute pancreatitis. Here, we report 3 patients with HAE and acute pancreatitis and present a literature review of similar cases. Patients with confirmed diagnosis of HAE secondary to C1-inhibitor (C1-INH) deficiency (n = 2) and HAE with normal C1-INH and F12 mutation (F12-HAE) (n = 1) were included. Pancreatitis was diagnosed based on clinical symptoms and high lipase and amylase levels. Three HAE patients were diagnosed with acute pancreatitis based on increased amylase levels during severe abdominal swelling episodes. Two were previously diagnosed with HAE type I and one with F12-HAE. Pancreatitis was efficiently treated in two patients using Icatibant, with pain relief within hours. When conservatively treated, pancreatitis pain took longer time to resolve. Eighteen pancreatitis cases in HAE with C1-INH deficiency were previously reported and none in F12-HAE. Most patients (12/18) underwent invasive procedures and/or diagnostic methods. Although rare, severe abdominal HAE attacks could cause pancreatitis; HAE-specific treatments may be efficient for HAE-associated pancreatitis. HAE should be considered as a differential diagnosis of acute idiopathic pancreatitis. To our knowledge, this is the first report of HAE-associated pancreatitis in a F12-HAE patient treated with Icatibant

The use of reverse transcription-PCR for the diagnosis of X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by a defective oxidative burst of phagocytes and subsequent impairment of their microbicidal activity. Mutations in one of the NADPH-oxidase components affect gene expression or function of this system, leading to the phenotype of CGD. Defects in gp91-phox lead to X-linked CGD, responsible for approximately 70% of CGD cases. Investigation of the highly heterogeneous genotype of CGD patients includes mutation analysis, Northern blot or Western blot assays according to the particular case. The aim of the present study was to use reverse transcription (RT)-PCR for the analysis of molecular defects responsible for X-linked CGD in eight Brazilian patients and to assess its potential for broader application to molecular screening in CGD. Total RNA was prepared from Epstein B virus-transformed B-lymphocytes and reverse transcribed using random hexamers. The resulting cDNA was PCR-amplified by specific and overlapping pairs of primers designed to amplify three regions of the gp91-phox gene: exons 1-5, 3-9, and 7-13. This strategy detected defective gp91-phox expression in seven patients. The RT-PCR results matched clinical history, biochemical data (nitroblue tetrazolium or superoxide release assay) and available mutation analysis in four cases. In three additional cases, RT-PCR results matched clinical history and biochemical data. In another case, RT-PCR was normal despite a clinical history compatible with CGD and defective respiratory burst. We conclude that this new application of RT-PCR analysis - a simple, economical and rapid method - was appropriate for screening molecular defects in 7 of 8 X-linked CGD patients.Universidade Estadual de Campinas Faculdade de Ciências Médicas Centro de Investigação em Pediatria e Departamentos de Pediatria e FarmacologiaUniversidade de São Paulo Instituto de Ciências Biomédicas Departamento de ImunologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUniversidade de São Paulo Faculdade de Medicina Departamento de DermatologiaUNIFESP, EPM, Depto. de PediatriaSciEL

Icatibant, An Inhibitor Of Bradykinin Receptor 2, For Hereditary Angioedema Attacks: Prospective Experimental Single-cohort Study.

Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.132261-

Genetic Variation of Kallikrein-Kinin System and Related Genes in Patients With Hereditary Angioedema

Hereditary angioedema (HAE) is an autosomal dominant disease caused by C1-INH deficiency due to mutations in SERPING1 (C1-INH-HAE) in most of the cases, or by specific mutations in factor XII gene, F12 (F12-HAE). Identification of polymorphisms in the genes encoding proteins from key pathways driving HAE can help to understand how genetic diversity contributes to its phenotypic variability. Here, 15 genes related to the Kallikrein-Kinin System (KKS) were analyzed by next generation sequencing in 59 patients with C1-INH-HAE or F12-HAE from Brazil, Denmark and Spain, and 19 healthy relatives in a total of 31 families. We identified 211 variants, from which 23 occurred only in Danish subjects and 79 were found only in Brazilian individuals, resulting in 109/211 variations in common between European and Brazilian population in the HAE families analyzed. BDKRB2 and CPM presented a large number of variants in untranslated regions, 46/49 and 19/24, respectively; whereas ACE (n = 26), SERPING1 (n = 26), CPM (n = 24), and NOS3 (n = 16) genes presented the higher number of variants directly affecting amino acid sequence. Despite the large amount of variants identified, the lack of association between genotype and phenotype indicates that the modulation of HAE symptom requires a more complex regulation, probably involving pathways beyond the KKS, epigenetics and environmental factors. Considering the new HAE types recently described, molecules involved in the regulation of vasculature and in plasminogen activation become promising targets for future genetic studies

Diagnosing congenital toxoplasmosis: where are we? A systematic review

Purpose: Compile information on laboratory methods for diagnosis of congenital toxoplasmosis, considering the tests conducted since the gestational stage until the child period. Methods:A systematic review of 01.01.2006 to 31.12.2013 was held by VHL (Virtual Health Library). The search was performed with the descriptors ''toxoplasmosis†and “diagnosis. The selected articles were indexed in MEDLINE. The information pertinent to the study was selected, categorized and analyzed. Of the 186 articles found, 41 met the eligibility criteria. Results: Laboratory tests are based on the presence of antibodies IgM and IgG anti-Toxoplasma gondii, in this sense it is important to correctly interpret serology, because the detection of specific antibodies is often delayed by the presence of maternal IgG or late production of specific antibodies in newborns. Molecular techniques (PCR) have emerged as alternative due to its higher sensitivity and specificity in diagnosing instruments, given the ability to detect parasite DNA and non-dependence of the immune response of the patient, such as serological tests.Conclusions: The need for early treatment of congenital toxoplasmosis in order to avoid sequelae justifies the search for more sensitive and specific laboratory tests in early detection of the parasite. Theintegration among the different levels of care in the public health system is essential for obtaining effective control of toxoplasmosis in pregnant women.Â

Consenso em criptococose - 2008

Univ Sao Paulo, Fac Med, Div Clin Mol Infecciosas, Hosp Clin, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Med, Sao Paulo, BrazilUniv Estadual Campinas, Hosp Clin, Inst Infectol Emilio Ribas, Campinas, SP, BrazilFundacao Oswaldo Cruz, Dept Microbiol Immunol & Parasitol, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, BrazilUniv Fed Parana, Fac Med, Dept Saude Comunitaria, BR-80060000 Curitiba, Parana, BrazilUniv Fed Rio Grande do Sul, Fac Med, Dept Clin Med, Porto Alegre, RS, BrazilUniv Estadual Campinas, Fac Ciencias Med, Dept Clin Med, Sao Paulo, BrazilInst Doencas Trop Natan Portela, Teresina, PI, BrazilUniv Sao Paulo, Fac Med, Dept Mol Infecciosas & Parasitarias, Sao Paulo, BrazilUniv Estadual Campinas, Fac Ciencias Med, Dept Clin Med, Campinas, SP, BrazilUniv Fed Uberlandia, Fac Med, BR-38400 Uberlandia, MG, BrazilFac Med Triangulo Mineiro, Dept Clin Med, Uberaba, MG, BrazilInst Infectol Emilio Ribas, Sao Paulo, BrazilUniv Estadual Sao Paulo, Fac Med Botucatu, Dept Doencas Trop & Diagnost Imagem, Sao Paulo, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Med, Sao Paulo, BrazilWeb of Scienc

TRIAGEM NEONATAL DE IMUNODEFICIÊNCIAS GRAVES COMBINADAS POR MEIO DE TRECS E KRECS: SEGUNDO ESTUDO PILOTO NO BRASIL

RESUMO Objetivo: Validar a quantificação de T-cell receptor excision circles (TRECs) e kappa-deleting recombination circles (KRECs) por reação em cadeia de polimerase (polymerase chain reaction, PCR) em tempo real (qRT-PCR), para triagem neonatal de imunodeficiências primárias que cursam com defeitos nas células T e/ou B no Brasil. Métodos: Amostras de sangue de recém-nascidos (RN) e controles foram coletadas em papel-filtro. O DNA foi extraído e os TRECs e KRECs foram quantificados por reação duplex de qRT-PCR. O valor de corte foi determinado pela análise de Receiver Operating Characteristics Curve, utilizando-se o programa Statistical Package for the Social Sciences (SSPS) (IBM®, Armonk, NY, EUA). Resultados: 6.881 amostras de RN foram analisadas quanto à concentração de TRECs e KRECs. Os valores de TRECs variaram entre 1 e 1.006 TRECs/µL, com média e mediana de 160 e 139 TRECs/µL, respectivamente. Três amostras de pacientes diagnosticados com imunodeficiência grave combinada (severe combined immunodeficiency, SCID) apresentaram valores de TRECs abaixo de 4/µL e um paciente com Síndrome de DiGeorge apresentou TRECs indetectáveis. Os valores de KRECs encontraram-se entre 10 e 1.097 KRECs/µL, com média e mediana de 130 e 108 KRECs/µL, e quatro pacientes com diagnóstico de agamaglobulinemia tiveram resultados abaixo de 4 KRECs/µL. Os valores de corte encontrados foram 15 TRECs/µL e 14 KRECs/µL, e foram estabelecidos de acordo com a análise da Receiver Operating Characteristics Curve, com sensibilidade de 100% para detecção de SCID e agamaglobulinemia, respectivamente. Conclusões: A quantificação de TRECs e KRECs foi capaz de diagnosticar crianças com linfopenias T e/ou B em nosso estudo, validando a técnica e dando o primeiro passo para a implementação da triagem neonatal em grande escala no Brasil

Controlo químico de infestantes

Uma planta é considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada. As infestantes competem com as culturas para o espaço, a luz, água e nutrientes, podendo atrasar e prejudicar as operações de colheita, depreciar o produto final e assegurarem a reinfestação nas culturas seguintes. Dado o modo de propagação diferenciado das diversas espécies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propagação através de órgãos vegetativos (rizomas, bolbos, tubérculos, etc.), assim, também o seu controlo quer químico, quer mecânico terá que ser diferenciado, ou seja, para controlar infestantes anuais será suficiente destruir a sua parte aérea, enquanto para controlar infestantes perenes teremos que destruir os seus órgãos reprodutivos. O controlo de infestantes poderá ser químico, através da utilização de herbicidas, ou mecânico pela utilização de alfaias agrícolas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a técnica utilizada na instalação das culturas é a sementeira directa, o controlo das infestantes terá que ser obrigatoriamente químico, enquanto se o recurso à mobilização do solo for a técnica mais utilizada (sistema de mobilização tradicional ou sistema de mobilização reduzida), o controlo das infestantes tanto poderá ser químico como mecânico. Neste trabalho iremos abordar apenas, o controlo químico de infestantes