Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-10-11T22:51:16Z No. of bitstreams: 1 LilianGraceDaSilvaSolon_TESE.pdf: 7051337 bytes, checksum: 79a5b10c1ce003624bdd49bff3af8afd (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-10-18T00:03:19Z (GMT) No. of bitstreams: 1 LilianGraceDaSilvaSolon_TESE.pdf: 7051337 bytes, checksum: 79a5b10c1ce003624bdd49bff3af8afd (MD5) / Made available in DSpace on 2016-10-18T00:03:19Z (GMT). No. of bitstreams: 1 LilianGraceDaSilvaSolon_TESE.pdf: 7051337 bytes, checksum: 79a5b10c1ce003624bdd49bff3af8afd (MD5) Previous issue date: 2016-02-04 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / A ind?stria farmac?utica e laborat?rios anal?ticos de todo o mundo tem focado na qualidade, seguran?a e efic?cia de seus produtos. Processos utilizados para minimizar os riscos, como o Quality by Design (QbD), recentemente tem sido atribu?do ao desenvolvimento de m?todos anal?ticos, principalmente os m?todos cromatogr?ficos. O Analytical Quality by Design ou Qualidade Anal?tica Baseada no Projeto (aQbD), utiliza ferramentas de planejamento de experimentos, an?lise de risco e monitoramento cont?nuo. Para isso, faz-se uso de softwares simuladores, ferramentas estat?sticas e quimiom?tricas. Sabe-se que os m?todos cromatogr?ficos de an?lise s?o bastante consolidados e exigidos pelas ag?ncias regulat?rias, aplicando-se em diversas determina??es dentro do campo farmac?utico, como identifica??o e quantifica??o de f?rmacos, metab?litos, impurezas e produtos de degrada??o. O presente estudo teve como objetivo, utilizar ferramentas aQbD para o desenvolvimento de m?todos em cromatografia l?quida de ultra efici?ncia. Foram desenvolvidos quatro m?todos, a saber: quantifica??o simult?nea de dexametasona acetato e clotrimazol em formas farmac?uticas semiss?lidas, atrav?s de transfer?ncia de m?todo de CLAE para CLUE (cap?tulo 1); determina??o simult?nea de corticosteroides e conservantes em coluna de n?cleo s?lido com tamanho de part?cula 1.3 ?m utilizando software simulador (cap?tulo 2); quantifica??o de betametasona valerato em amostras de creme, gel, lo??o e pomada ap?s desenvolvimento de m?todo por planejamento fatorial completo 33 (cap?tulo 3); e determina??o simult?nea de corticosteroides ap?s desenvolvimento de modelo de previs?o de fator de reten??o por QSRR (cap?tulo 4). Os resultados mostraram que apesar da necessidade de otimiza??o pelo analista, o uso de ferramentas aQbD, como o planejamento estat?stico ou uso de softwares, s?o promissoras no desenvolvimento de m?todos cromatogr?ficos de ultra efici?ncia, uma vez que foram capazes de promover economia de tempo, diminuir os gastos e riscos. Os ensaios apresentaram resultados satisfat?rios em termos de velocidade anal?tica e diminui??o no consumo de solventes. / The pharmaceutical industry and analytical laboratories around the world have focused on quality, safety and efficacy of their products. Processes used to minimize risks, such as Quality by Design (QbD), which recently has been attributed to the development of analytical methods, especially chromatographic methods. The Analytical Quality by Design (aQbD) uses planning tools experiments, risk analysis and continuous monitoring. For this, it makes use of simulation software, statistical tools and chemometrics. It is known that chromatographic methods are well consolidated and required by the regulatory agencies. It has been applied in various determinations in the pharmaceutical field, such as identification and quantification of drugs, metabolites, degradation products and impurities. The aim of this study was to use aQbD tools for the development of methods for ultra high performance liquid chromatography (UHPLC). Four methods were developed, namely: simultaneous quantification of dexamethasone acetate and clotrimazole in semisolid dosage forms, via HPLC to UHPLC method transfer (Chapter 1); simultaneous determination of corticosteroids and preservatives in solid core column with particle size of 1.3 ?m by using simulation software (Chapter 2); betamethasone valerate quantification in samples of cream, gel, lotion and ointment after method development by full factorial design 33 (Chapter 3); and simultaneous determination of corticosteroids after retention factor prediction model by QSRR (Chapter 4). The results showed that despite the need for optimization by the analyst, the use of aQbD tools such as statistical design or use of software, the aQbD is promising in the development of chromatographic methods of ultra efficiency, since they were able to promote time savings, lower costs and risks. The tests showed satisfactory results in terms of analysis speed and decrease of solvent consumption.

Made available in DSpace on 2015-07-22T20:50:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Objetivo: Comparar efetividade e tolerância, a médio prazo, entre lavagem articular associada à infiltração intra-articular (IIA) com hexacetonide de triancinolona (HT) versus a IIA isolada de HT em pacientes com osteoartrite (OA) primária de joelhos. Material e Métodos: Foi realizado um estudo controlado, randomizado, duplo-cego com 60 pacientes que apresentavam OA primária de joelhos com dor em pelo menos um dos joelhos e índice de Kellgren Lawrence (KL) II e III divididos em dois grupos de intervenção: Grupo LA/HT: submetidos à LA com SF 0,9% (1000ml), finalizada pela introdução de HT 60 mg; Grupo HT: submetidos apenas à simulação de LA finalizada pela IIA de HT 60 mg. Os pacientes foram avaliados durante 12 semanas em cinco tempos de avaliação (T0, T1, T4, T8 e T12 semanas) por um avaliador “cego” através dos seguintes instrumentos de avaliação: escala visual analógica (EVA) para dor em repouso e ao movimento, goniometria, índice de WOMAC, questionário funcional de Lequesne, tempo de caminhada de 50 pés, porcentagem subjetiva de melhora, escala visual analógica de melhora (EVAM), segundo o paciente e segundo o avaliador, necessidade de anti-inflamatórios e analgésicos, número e tipo de efeitos colaterais locais. Foi realizada subanálise estatística na amostra segundo a classificação radiológica (KL II e KL III). Foi considerada uma significância estatística de 5%. Resultados: A média de idade foi de 63,7 (±8,59) anos, média de tempo de doença de 5,69 (±5,01) anos, proporção KL II/III de 33/27, sendo 88,3% de mulheres e 48,3.% de brancos. Apesar de ambos os grupos melhorarem estatisticamente na avaliação intragrupo, exceto para consumo de anti-inflamatório e EVAM, segundo o paciente, não houve diferença estatística na avaliação intergrupo para todas as variáveis estudadas no período de 12 semanas. De acordo com a subanálise realizada, observou-se, nos pacientes KL II, diferença estatística significante a favor do grupo HT para a variável flexão articular (p=0,03) no T4. Para os pacientes KL III, observou-se diferença estatística significante a favor do grupo LA/HT para as variáveis Lequesne (p=0,021) e WOMAC dor (p=0,01), assim como para a variável EVAM, segundo paciente (p=0,028) e avaliador (p=0,034) no T8. Conclusão: A combinação de LA à IIA com HT se mostrou mais efetiva a médio prazo que a IIA isolada com HT para o tratamento da OA primária de joelhos em pacientes KL III. Não houve diferença estatística quanto a tolerância destas duas intervenções. / Objective: Compare the medium-term effectiveness and tolerance intraarticular injection (IAI) with triamcinolone hexacetonide (TH) associated to joint lavage versus IAI with TH alone in patients with primary osteoarthritis (OA) of the knee. Methods: A randomized, double-blind, controlled study was carried out on 60 patients with primary OA of the knee, with pain in at least one of the knees and Grades II and III on the Kellgren-Lawrence index (KL II and III). Patients were randomized into two intervention groups: JL/TH Group – patients submitted to joint lavage with 0.9% saline solution (1000 ml) followed by a 60-mg injection of TH (3 ml); and TH Group – patients submitted to simulated joint lavage (sham) followed by a 60-mg injection of TH (3 ml). Patients were followed up for 12 weeks by a blinded observer using: visual analogue scale (VAS) for pain at rest and on movement; range of movement; Womac index; Lequesne’s questionnaire; timed 50-foot walk; subjective perception of improvement; Likert scale (0-5) for improvement assessment; the need for non-hormonal anti-inflammatory medication and analgesics; the local side effects. Results: Average age was 63.7 (± 8.59) years; mean duration of disease was 5.69 (± 5.01) years; the KL II/III proportion was 33/27; 88.3% were women and 48.3% were Caucasian. Although both groups demonstrated statistically significant improvement in the intra-group evaluation (except for Likert improvement scale according to the patient and the use of anti-inflammatory drugs), there were no statistically significant differences in the inter-group analysis for any of the variables studied over the 12-week period. In the KL II and III sub-analysis, there was a statistically significant difference regarding joint flexion among patients classified as KL II, favoring the TH group (p=0.03). For the KL III patients there were statistically significant differences favoring the JL/TH group regarding Lequesne score (p=0.021), WOMAC-pain score (p=0.01) and Likert improvement scale according to the patient (p=0.028) and the physician (p=0.034) at eight weeks. Conclusion: The combination of joint lavage and IAI with TH was more effective than IAI with TH alone in the treatment of primary OA of the knee in KL 3 patients. / TEDE / BV UNIFESP: Teses e dissertações

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-11T17:13:30Z No. of bitstreams: 1 MaraLuanaBatistaSevero_DISSERT.pdf: 1279812 bytes, checksum: d55a74719b46a51718b7399d61a2a556 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-07-15T18:45:17Z (GMT) No. of bitstreams: 1 MaraLuanaBatistaSevero_DISSERT.pdf: 1279812 bytes, checksum: d55a74719b46a51718b7399d61a2a556 (MD5) / Made available in DSpace on 2016-07-15T18:45:17Z (GMT). No. of bitstreams: 1 MaraLuanaBatistaSevero_DISSERT.pdf: 1279812 bytes, checksum: d55a74719b46a51718b7399d61a2a556 (MD5) Previous issue date: 2016-02-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Objetivo desse estudo foi analisar a imunoexpress?o de receptores de calcitonina (CTRs) e glicocorticoides (GCRs) em les?es centrais de c?lulas gigantes (LCCGs) agressivas e n?o agressivas. Trata-se de um estudo imuno-histoqu?mico (t?cnica da imunoperoxidase), quantitativo e descritivo de 52 casos de LCCGs dos ossos maxilares, nos quais 13 pacientes portadores de LCCG foram tratados com triancinolona intralesional ou calcitonina spray intranasal. A m?dia de imunomarca??o foi comparada entre os tipos celulares e subtipo cl?nico da les?o. O teste de Mann-Whitney foi realizado para essas compara??es. Dos 52 casos de LCCGs, 53.8% eram do g?nero feminino, com uma m?dia de idade de 25.69 anos. A mand?bula foi o s?tio anat?mico mais acometido. Trinta casos (57.7%) foram de LCCGs agressivas e 22 (42.3%) de n?o agressivas. A cirurgia foi o tratamento de escolha em 75% das LCCGs estudadas. Em 56.7% das LCCGs agressivas foi realizada cirurgia, enquanto 43.4% foram submetidas ao tratamento conservador. Dos submetidos ao tratamento conservador, a maioria (n = 8; 61.5%) respondeu bem ao tratamento. A express?o de CTR foi evidenciada em 67.3% da amostra e para o GCR em 96.15% dos casos. N?o houve diferen?a estatisticamente significante entre a express?o de CTRs e GCRs em c?lulas mononucleares e multinucleadas das LCCGs em rela??o ? agressividade, em rela??o ao tratamento realizado para os casos de les?es agressivas e em rela??o ? resposta ao tratamento conservador realizado nos casos de LCCGs agressivas (p>0.05). Os resultados da nossa pesquisa sugerem que a imunoexpress?o dos CTRs e GCRs n?o influenciou na resposta ao tratamento cl?nico com calcitonina ou triancinolona na amostra estudada e exibiu uma express?o variada independente da agressividade da les?o. / The aim of this study was to analyze the immunoexpression of calcitonin (CTR) and glucorticoid (GCR) receptors in aggressive and non-aggressive central giant cell lesions (CGCL). This is an immunohistochemistry study (immunoperoxidase technique) of 52 cases of CGCL of the jaws, in which 12 patients were treated with intralesional triamcinolone injections and one with calcitonin nasal spray. The mean of immunostaining was compared between the cell types and clinical subtype of the lesion. The correlations among means were analyzed by Mann-Whitney test. Of the 52 cases studied, 53.8% were females, with a mean of 25.69 years. Most lesions were located in the mandible. Thirty patients (57.7%) had aggressive lesions and 22 (42.3%) of the cases consisted of non-aggressive lesions. Surgery was the treatment of choice in 75% of the cases. In 56.7% of the aggressive CGCL surgery was performed, while 43.4% of patients were submitted to conservative treatment. Among cases submitted to conservative treatment, the majority (n = 8; 61.5%) responded well to treatment. CTR expression was observed in 67.3% and GCR in 96.15% of cases. There was no significant statistical difference between the expression of CTRs and GCRs in mononuclear and multinucleated CGCLscells, regarding aggressiveness, treatment performed for aggressive lesions and the response to conservative treatment (p>0.05). The results of our research suggest that the immunoreactivity of CTRs and GCRs did not influence the response to clinical treatment with calcitonin or triamcinolone in the sample studied and it exhibited a varied expression regardless of the aggressiveness of the lesion.

Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-22T13:04:16Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_JeanPierreParaboniIlha.pdf: 1681676 bytes, checksum: ef5dd7b09cf888688e12cc6e025e3cd4 (MD5) / Made available in DSpace on 2018-08-22T13:04:16Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_JeanPierreParaboniIlha.pdf: 1681676 bytes, checksum: ef5dd7b09cf888688e12cc6e025e3cd4 (MD5) Previous issue date: 2017-05-12 / High mortality rates are related to pediatric sepsis. Literature is limited on corticosteroid use context in pediatric septic shock, as in article numbers as in methodological quality of studies. The non-padronization for the beginning of this drug use is indicated as the main reason of discrepancy of studies results, and it can be one of the associated factors in mortality in this clinical situation. Based on this problem question, the present study had as general objective to systematize the corticosteroid utilization in cathecolamine resistant pediatric septic shock in a pediatric unity care of an education hospital. As specific objectives, this study considered: to make a bibliographic review on pediatric sepsis aiming the recent management of pediatric septic shock, and to capacitate the local medical staff for the application of corticosteroid utilization protocol in pediatric septic shock, monitoring its application on indicated children. In order to attending the first specific objective, it was made a bibliographic state-of-art review in children sepsis, with resources in internation data base Pubmed and Lilacs. The resulting date from the first specific objective resulted in a book chapter where it was inserted this knowledge, and also as theorical basis for protocol construction for corticosteroid use in the indicated moment in pediatric septic shock. It was concluded that this review, for punctuating the right moment of this drug utilization, aims to contribute to the management of the referred disease, With the purpose of systematizing the conducts and qualifying the professionals' performance, in this process. The second specific objective was about an action-research, involving the protocol construction process of corticosteroid utilization in cathecolamine resistant pediatric septic shock, matching to a specific part of the time sensitive algorithm for management of pediatric septic shock, internationally validated, and the capacitation of the medical staff from the referred unity for its utilization, in the period of june, 2016. From the result data of the second specific objective, and codificated on content analysis, three thematic categories were resulted: previous learning of protocol for treatment of the referred shock, positive actions associated to assistential protocols using in intensive care unities and continued education in these places. After effective medical capacitation there was utilization of this drug from systematic manner in 100% of the patients under this clinical condition, in a six-month period after capacitation, showing that the final product of this work had a good internal validity. With this optimization there is possibility of local future studies of clinical ending. / Altas taxas de mortalidade são relacionadas à sepse na população pediátrica. A literatura é limitada no contexto do uso de corticosteroides no choque séptico pediátrico, tanto em número de artigos quanto na qualidade metodológica dos estudos. A não padronização para o momento de início do uso desse fármaco é indicada como principal motivo da discrepância de resultados dos estudos e pode ser um dos fatores associados a mortalidade nessa situação clínica. Com base nessa questão-problema, o presente estudo teve como objetivo geral sistematizar a utilização de corticosteroide no choque séptico pediátrico resistente a catecolaminas em nível de Unidade de Terapia Intensiva Pediátrica de um hospital de ensino. Como objetivos específicos, este estudo considerou: fazer uma revisão bibliográfica sobre sepse em pediatria, com vistas ao manejo atual do choque séptico pediátrico e capacitar a equipe médica local para a aplicação de protocolo de utilização do corticosteroide no choque séptico pediátrico, monitorando sua aplicação nas crianças indicadas. Para atender ao primeiro objetivo específico foi realizada uma revisão de literatura acerca do estado da arte na sepse infantil, com pesquisas em bases de dados internacionais Pubmed e Lilacs. O dado resultante do primeiro objetivo específico emergiu em um capítulo de livro, onde se inseriu esse conhecimento e, também, como base teórica para a construção de protocolo para uso do corticosteroide no momento indicado, no choque séptico pediátrico. Concluiu-se que essa revisão, em termos de pontuar o momento correto de utilização desse fármaco, permite contribuir para a melhoria no manejo da referida doença, com o propósito de sistematizar as condutas e qualificar a atuação dos profissionais, neste processo. O segundo objetivo específico envolveu uma pesquisa-ação, abrangendo o processo de construção do protocolo do uso de corticoide no choque séptico pediátrico resistente a catecolaminas, correspondendo a uma parte específica do algoritmo tempo-sensível, internacionalmente validado para manejo do referido choque, e à capacitação da equipe médica da unidade citada para a utilização do mesmo, no período de julho de 2016. Dos dados resultantes do segundo objetivo específico, codificados pela análise de conteúdo, resultaram três categorias temáticas: conhecimento prévio de protocolo de manejo do referido choque, ações positivas quanto ao uso de protocolos assistenciais em unidades de terapias intensivas e educação continuada nesses locais. A partir da capacitação efetiva da equipe médica, houve utilização desse fármaco de maneira sistemática em 100% dos pacientes sob tal condição clínica, no período de seis meses decorridos da capacitação, evidenciando-se que o produto final desse trabalho obteve uma boa validade interna. Com essa rotinização, existe possiblidade de futuros estudos locais de desfecho clínico.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-14T11:38:20Z No. of bitstreams: 1 lilianaandradechebli.pdf: 509558 bytes, checksum: 46eb6aa1950b8cf02f40073b054ed6c3 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-07-19T14:23:32Z (GMT) No. of bitstreams: 1 lilianaandradechebli.pdf: 509558 bytes, checksum: 46eb6aa1950b8cf02f40073b054ed6c3 (MD5) / Made available in DSpace on 2016-07-19T14:23:32Z (GMT). No. of bitstreams: 1 lilianaandradechebli.pdf: 509558 bytes, checksum: 46eb6aa1950b8cf02f40073b054ed6c3 (MD5) Previous issue date: 2011-10-17 / Colite ulcerativa é uma doença inflamatória intestinal idiopática da mucosa colônica caracterizada clinicamente por episódios intermitentes de exacerbações alternados com períodos de remissão. Os corticosteroides permanecem como uma das drogas mais efetivas no tratamento das exacerbações moderadas a graves da colite ulcerativa. Entretanto, eles não são adequados para terapia de manutenção devido à falta de eficácia na prevenção de recorrências. Além disso, seu uso associa-se frequentemente com vários efeitos adversos e, aproximadamente, 25% dos pacientes que respondem aos corticosteroides serão incapazes de tolerar sua retirada sem que apresentem recorrências sintomáticas. Consequentemente, ―dependência de esteróides‖ em pacientes com colite ulcerativa é um problema de grande relevância na prática e manutenção da remissão sem esteróides é meta importante a ser alcançada. Diversas modalidades terapêuticas podem ser empregadas em pacientes com colite ulcerativa córtico-dependente (CUCD). Tradicionalmente, a escolha é entre a cirurgia ou o escalonamento do tratamento clínico, que geralmente envolve o uso de imunossupressores. O tratamento com azatioprina (AZA) tem tido amplo uso neste cenário. Entretanto, estudos no longo prazo avaliando a eficácia da AZA na CUCD são inexistentes. Os objetivos deste estudo foram avaliar em pacientes com CUCD, a eficácia da AZA no longo prazo para manutenção da remissão clínica sem esteróides, bem como a segurança desta droga neste contexto. Neste estudo de coorte prospectivo observacional, pacientes adultos com CUCD foram recrutados para tratamento com AZA durante o período de 36 meses. AZA foi ajustada para a dose alvo de 2-3 mg/Kg/dia. A redução da dose de esteróides durante o estudo seguiu um esquema previamente padronizado. A avaliação primária de eficácia foi a taxa anual de pacientes que alcançaram resposta sustentada a AZA sem esteróides. Resposta sustentada foi definida como a retirada completa dos corticosteroides e manutenção da remissão clínica sem a necessidade de se reintroduzir esteróides durante pelo menos seis meses adicionais. As principais avaliações de eficácia secundária foram: dose cumulativa anual de esteróides, número anual de recorrências da colite após introdução da AZA e efeitos adversos. Em base intenção de tratar, a proporção de pacientes permanecendo em remissão sem esteróides em 12, 24, e 36 meses foi 0.55, 0.52, e 0.45, respectivamente. Significante diminuição na taxa de recidivas clínicas assim como no requerimento para esteróides foram observados durante três anos de tratamento com AZA comparado com o ano prévio (P=0.000 para ambos). Pacientes com e sem resposta sustentada foram similares de acordo com demografia, extensão da doença, dose de AZA, uso de esteróides e 5-ASA. Apenas a duração menor da doença (<36 meses) associou-se à remissão sem esteróides (P=0.02, OR 3.12 95% IC 1.89-7.64). AZA foi bem tolerada e o perfil risco-benefício favorável. Neste estudo, AZA mostrou eficácia sustentada para manutenção da remissão clínica sem esteróides e para poupar esteróides durante três anos de terapia em pacientes com CUCD. Pacientes com colite ulcerativa de início mais recente são aqueles que mais provavelmente alcançarão remissão sustentada sem esteróides no final de 12 meses enquanto em uso de AZA. Isto parece se manter por até 36 meses. / Ulcerative colitis (UC) is a lifelong, immune-mediated inflammatory condition of the colonic mucosa, which is characterized by a relapsing and remitting course. Corticosteroids remain one of the most effective therapies for inducing remission in patients with moderate-to-severe UC. Nonetheless, corticosteroids are not used in maintenance therapy, mainly because undesirable side effects outweigh the possible benefits. Furthermore, approximately 25% of the patients is unable to support its withdrawal without relapsing, suggesting that the need to start steroid therapy in UC is associated with a dismal long-term prognosis. Thus, corticosteroid dependence in patients with UC is a pivotal clinical problem and maintenance of steroid-free remission is an important current evolving treatment goal. Patients with steroid dependent UC are usually given a choice between colectomy or stepped-up medical treatment, which traditionally involves prescription of an immunosuppressive drug. Azathioprine (AZA) therapy has found widespread use for this setting in clinical practice. However, studies assessing the efficacy of azathioprine in steroid-dependent ulcerative colitis (SD-UC) are scarce. The purpose of this trial was to explore the efficacy and safety of AZA in maintaining long-term steroid-free remission in SD-UC patients and the factors associated to sustained response. In this observational cohort study 42 subjects with SD-UC were recruited for AZA therapy during a 3-year period. AZA was adjusted for a target dose of 2-3 mg/Kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the annual rate of steroid-free response to AZA. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment. On an intention-to-treat basis, the proportion of patients remaining in steroid-free remission at 12, 24, and 36 months was 0.55, 0.52, and 0.45, respectively. A significant decrease in the flare-ups rate and in requirement for steroids were observed during 3 years on AZA compared with the previous year (P=0.000 for both). Patients with and without sustained response were comparable according to demographics, extent of disease, dose of AZA, steroids and 5-ASA use. Only disease duration <36 months was associated to off-steroids remission (P=0.02, OR 3.12 95% CI 1.89-7.64). The AZA benefit-risk profile was favorable. In this open-label observational trial AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 3 years of therapy in SD-UC. Patients with earlier UC are those who most probably will have sustained steroid-free remission at the end of 12 months while on AZA. This appears to sustain until 36 months.

Se reporta el caso de un varón de 62 años quien presentó tos y dolor abdominal por dos semanas, con hallazgos tomográficos pulmonares compatibles con probable infección por SARS-CoV-2, que recibió tempranamente corticoterapia a dosis altas y de manera ambulatoria. El paciente presentó evolución tórpida, fue hospitalizado y falleció en el posoperatorio inmediato por un cuadro de abdomen agudo quirúrgico. El estudio anatomopatológico mostró estructuras parasitarias con características compatibles con amebas, como causa de una colitis aguda fulminante complicada, con perforación múltiple y peritonitis aguda. La colitis aguda fulminante por amebiasis intestinal en el contexto de un paciente con probable COVID-19 no había sido reportada en el Perú. Resulta importante resaltar la presentación fulminante con desenlace fatal de esta infección parasitaria prevalente en nuestro medio, en el contexto del uso de corticoides ante una probable infección pulmonar por COVID-19. / We report the case of a 62-year-old male with cough and abdominal pain for two weeks, associated with pulmonary tomographic findings compatible with probable infection by SARS-CoV-2, and who received high doses of early corticotherapy as an outpatient. The patient showed clinical deterioration, was hospitalized and died in the immediate postoperative period due to acute surgical abdomen. The anatomopathological study showed parasitic structures with characteristics compatible with amebae, which was pointed to as the cause of a complicated acute fulminant colitis, with multiple perforations and acute peritonitis. Acute fulminant colitis due to intestinal amebiasis in the context of a patient with probable COVID-19 had not been previously reported in Peru. It is important to highlight the fulminant presentation with fatal outcome of this prevalent parasitic infection, in the context of corticosteroids use in a probable SARS-CoV-2 pulmonary infection.

Introdução: Os corticosteroides intra-articulares (IA) são amplamente utilizados no tratamento da osteoartrite (OA) de joelho, porém é desconhecido qual dentre estes agentes é o mais eficaz. Objetivo: O objetivo do presente estudo foi comparar a eficácia das infiltrações IA de triancinolona hexacetonida (TH) e de acetato de metilprednisolona (AM) na OA de joelho. Pacientes e Métodos: Pacientes com OA sintomática de joelho, graus II ou III de Kellgren-Lawrence, foram randomizados para receber uma única infiltração IA com 40mg de TH ou AM. As avaliações clínicas foram realizadas nas semanas 4, 12 e 24. O desfecho primário do estudo foi a melhora da dor do joelho pelo paciente por escala visual analógica (EVA) da visita basal à semana 4. Os desfechos secundários incluíram a avaliação global da doença pelo paciente e pelo médico, o questionário de osteoartrite Western Ontario and McMaster Universities (WOMAC), o índice de Lequesne e o critério de resposta Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI). Na análise estatística, foram empregadas equações de estimativa generalizada, com estatística de Wald para contrastes do tipo 3 e ajustes de Tukey-Kramer para comparações múltiplas. Resultados: Cem pacientes foram incluídos na população com intenção de tratar, 50 em cada braço do estudo. Uma melhora significativa na dor pela EVA foi observada na semana 4 para ambos os grupos (P < 0,0001), não havendo diferença entre eles (P=0,352). Esta melhora foi sustentada até a semana 24. Uma melhora significativa em relação à avaliação basal foi observada na avaliação global da doença pelo paciente e pelo médico, no questionário WOMAC e no índice de Lequesne, não havendo diferença entre os grupos. A melhora nos desfechos secundários de avaliação foi sustentada durante o estudo, exceto para a avaliação global da doença pelo paciente. O critério de resposta OMERACT-OARSI foi alcançado por 74% e 72% dos pacientes dos grupos TH e AM, respectivamente. Conclusão: TH e AM são igualmente eficazes na OA de joelho, e a melhora na dor e na função física pode ser sustentada por até 24 semanas / Introduction: Intra-articular (IA) corticosteroid injections are broadly used in the treatment of knee osteoarthritis (OA), but it is unknown which of these agents is the most effective. Objective: The aim of the present study was to compare the efficacy of triamcinolone hexacetonide (TH) and methylprednisolone acetate (MA) IA injections in knee OA. Patients and Methods: Patients with symptomatic knee OA, Kellgren-Lawrence grades II or III, were randomized to receive a single IA injection with 40mg of TH or MA. Evaluations were performed at 4, 12 and 24 weeks. The primary outcome of the study was to evaluate the improvement in the patient\'s knee pain by visual analogue scale (VAS) from baseline to week 4. Secondary outcomes included the global assessment of the disease by the patient and the physician, the Western Ontario and McMaster Universities osteoarthritis questionnaire (WOMAC), the Lequesne index and the Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of response. Generalized estimating equations with Wald statistics for type 3 contrasts and Tukey-Kramer multiple comparison adjustment were employed in statistical analysis. Results: The intention-to-treat population included one hundred patients; 50 in each study arm. A significant improvement in pain by VAS was observed at week 4 for both groups (P<0.0001), with no difference between them (P=0.352). This improvement was sustained up to week 24. A significant improvement from the baseline was observed for the patients\' and the physicians\' global assessments, WOMAC questionnaire, and Lequesne index, with no differences between the groups. Improvements in the secondary outcomes were sustained during the study, except for the patients\' global assessment of disease. OMERACT-OARSI criteria of response was achieved by 74% and 72% of patients in the TH and the MA groups, respectively. Conclusion: TH and MA are equally effective in knee OA and improvement in pain and physical function can be sustained for up to 24 week

Objetivo: Uma série de casos sugerindo uma possível associação de pancreatite aguda (PA) e síndrome de ativação macrofágica (SAM) em lúpus eritematoso sistêmico pediátrico (LESP) foi reportada em dez crianças no nosso serviço, no entanto, não existem dados relativos à comparação entre PA e SAM em grandes populações de LESP e LES adulto (LESA). Métodos: Este estudo incluiu 362 pacientes LESP e 1.830 pacientes LESA. SAM foi diagnosticada de acordo com os critérios diagnósticos preliminares e PA de acordo com a presença de dor abdominal e/ou vômitos associados a um aumento de enzimas pancreáticas e/ou alterações radiológicas pancreáticas nos exames de ultrassonografia e/ou tomografia abdominal. Dados demográficos, características clínicas, SLEDAI-2K, SLICC/ACR-DI e tratamento foram avaliados. Resultados: A frequência de PA foi significantemente aumentada no LESP em comparação ao LESA [12/362 (3,3%) vs. 20/1830 (1,1%), p=0,003], com similar duração da PA nos dois grupos [22 (6-60) vs. 15 (4-90), dias, p=0,534]. As frequências de SAM (85% vs 30%, p=0,003) e óbito (31% vs. 0%; p=0,017) foram significantemente elevadas em crianças com PA comparadas com adultos com PA. Na análise dos pacientes com PA e SAM em comparação com os com somente PA sem SAM demonstrou que a idade dos pacientes com PA e SAM foi significantemente menor em comparação com aqueles sem SAM [15 (8,8- 55) vs. 33,5 (10,2-45,7) anos, p=0,007]. As frequências de febre (94% vs. 37%, p=0,001), leucopenia (82% vs. 19%, p=0,0001), trombocitopenia (65% vs. 19%, p=0,013), hipertrigliceridemia (87% vs. 42%, p=0,037) e hiperferritinemia (93% vs. 37%, p=0,011) foram significantemente aumentadas nos pacientes com PA e SAM comparados aos pacientes com somente PA. A concomitância de febre e hiperferritinemia foi significantemente mais freqüente no primeiro grupo (86% vs. 12%, p=0,0015). Conclusões: Este estudo forneceu novos dados que evidenciaram que SAM ocorreu na maioria dos LESP com PA com uma maior mortalidade em comparação com LESA. Além disso, foram identificados em pacientes com PA e SAM, um conjunto de parâmetros clínicos e laboratoriais associado com as duas complicações / Objective: We previously reported a case series of acute pancreatitis (AP) and macrophage activation syndrome (MAS) in childhood (cSLE) patients, however there are no data regarding the comparison of AP and MAS in large populations of cSLE and adult SLE (aSLE). Methods: This study included 362 cSLE and 1,830 aSLE patients. MAS was diagnosed according to preliminary diagnostic guidelines and AP according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Demographic data, clinical features, SLEDAI-2K, SLICC/ACR-DI and treatment were assessed. Results: Higher and significant frequency of AP in cSLE compared to aSLE patients [12/362(3.3%) vs. 20/1830(1.1%), p=0.003], with similar AP duration [22(6- 60) vs. 15(4-90) days, p=0.534]. MAS (85% vs. 30%, p=0.003) and death by MAS complication (31% vs. 0%, p=0.017) were significantly higher in children with AP compared with aSLE with AP. Further analysis of patients with AP and MAS compared with AP without MAS demonstrated that age in MAS patients was significantly lower compared with those without this complication [15(8.8-55) vs. 33.5(10.2-45.7) years, p=0.007]. The frequencies of fever (94% vs. 37%,p=0.001), leucopenia (82% vs. 19%,p=0.0001), thrombocytopenia (65% vs. 19%,p=0.013), hypertriglyceridemia (87% vs. 42%,p=0.037) and hyperferritinemia (93% vs. 37%,p=0.011) were also more frequently observed in AP patients with MAS compared in AP patients without MAS. Fever and hyperferritinemia concomitantly were more frequent in the former group (86% vs. 12%, p=0.0015). Conclusions: This study provides novel data demonstrating that MAS occur in the majority of cSLE with AP with a higher mortality compared to aSLE. In addition, we identified in AP patients, a cluster of MAS clinical and laboratorial parameters more associated with this complication

Introdução: Os corticosteroides intra-articulares (IA) são amplamente utilizados no tratamento da osteoartrite (OA) de joelho, porém é desconhecido qual dentre estes agentes é o mais eficaz. Objetivo: O objetivo do presente estudo foi comparar a eficácia das infiltrações IA de triancinolona hexacetonida (TH) e de acetato de metilprednisolona (AM) na OA de joelho. Pacientes e Métodos: Pacientes com OA sintomática de joelho, graus II ou III de Kellgren-Lawrence, foram randomizados para receber uma única infiltração IA com 40mg de TH ou AM. As avaliações clínicas foram realizadas nas semanas 4, 12 e 24. O desfecho primário do estudo foi a melhora da dor do joelho pelo paciente por escala visual analógica (EVA) da visita basal à semana 4. Os desfechos secundários incluíram a avaliação global da doença pelo paciente e pelo médico, o questionário de osteoartrite Western Ontario and McMaster Universities (WOMAC), o índice de Lequesne e o critério de resposta Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI). Na análise estatística, foram empregadas equações de estimativa generalizada, com estatística de Wald para contrastes do tipo 3 e ajustes de Tukey-Kramer para comparações múltiplas. Resultados: Cem pacientes foram incluídos na população com intenção de tratar, 50 em cada braço do estudo. Uma melhora significativa na dor pela EVA foi observada na semana 4 para ambos os grupos (P < 0,0001), não havendo diferença entre eles (P=0,352). Esta melhora foi sustentada até a semana 24. Uma melhora significativa em relação à avaliação basal foi observada na avaliação global da doença pelo paciente e pelo médico, no questionário WOMAC e no índice de Lequesne, não havendo diferença entre os grupos. A melhora nos desfechos secundários de avaliação foi sustentada durante o estudo, exceto para a avaliação global da doença pelo paciente. O critério de resposta OMERACT-OARSI foi alcançado por 74% e 72% dos pacientes dos grupos TH e AM, respectivamente. Conclusão: TH e AM são igualmente eficazes na OA de joelho, e a melhora na dor e na função física pode ser sustentada por até 24 semanas / Introduction: Intra-articular (IA) corticosteroid injections are broadly used in the treatment of knee osteoarthritis (OA), but it is unknown which of these agents is the most effective. Objective: The aim of the present study was to compare the efficacy of triamcinolone hexacetonide (TH) and methylprednisolone acetate (MA) IA injections in knee OA. Patients and Methods: Patients with symptomatic knee OA, Kellgren-Lawrence grades II or III, were randomized to receive a single IA injection with 40mg of TH or MA. Evaluations were performed at 4, 12 and 24 weeks. The primary outcome of the study was to evaluate the improvement in the patient\'s knee pain by visual analogue scale (VAS) from baseline to week 4. Secondary outcomes included the global assessment of the disease by the patient and the physician, the Western Ontario and McMaster Universities osteoarthritis questionnaire (WOMAC), the Lequesne index and the Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of response. Generalized estimating equations with Wald statistics for type 3 contrasts and Tukey-Kramer multiple comparison adjustment were employed in statistical analysis. Results: The intention-to-treat population included one hundred patients; 50 in each study arm. A significant improvement in pain by VAS was observed at week 4 for both groups (P<0.0001), with no difference between them (P=0.352). This improvement was sustained up to week 24. A significant improvement from the baseline was observed for the patients\' and the physicians\' global assessments, WOMAC questionnaire, and Lequesne index, with no differences between the groups. Improvements in the secondary outcomes were sustained during the study, except for the patients\' global assessment of disease. OMERACT-OARSI criteria of response was achieved by 74% and 72% of patients in the TH and the MA groups, respectively. Conclusion: TH and MA are equally effective in knee OA and improvement in pain and physical function can be sustained for up to 24 week

Le chat est la seule espèce animale qui développe spontanément une entité clinique similaire à bien des égards à lasthme allergique humain. Communément appelée « asthme félin » par homologie à la maladie humaine, cette entité pathologique est le résultat dune inflammation persistante des voies respiratoires, associée à des phases aiguës de bronchospasme, une hyperréactivité bronchique à des stimuli divers et dans les stades avancés à des remaniements tissulaires de la paroi bronchique (e.g., érosions épithéliales, hypertrophie de la musculature lisse, hyperplasie glandulaire). Des modèles dasthme félin, obtenus par sensibilisation expérimentale à un allergène, reproduisent la majorité des caractéristiques cliniques, fonctionnelles et lésionnelles de la maladie naturelle et sont au premier plan de la découverte de nouvelles stratégies thérapeutiques (i.e., cyclosporine A, corticostéroïdes oraux et inhalés, immunothérapie spécifique). De la pathogénie de lasthme, ressort toute limportance de dominer lobstruction récurrente des voies respiratoires. Même si les bronchodilatateurs inhalés sont recommandés dans la prise en charge des crises dasthme chez le chat, leur efficacité clinique reste incertaine et peu étayée. Ainsi, les principes actifs, les posologies et les protocoles thérapeutiques actuellement préconisés sont dans une large mesure empiriques et/ou extrapolés de la médecine humaine, et nécessitent dêtre validés dans des conditions expérimentales contrôlées. Nos travaux sinscrivent donc dans cette optique et visent à définir une approche thérapeutique tant préventive que symptomatique des crises de bronchospasme chez le chat, ainsi quune utilisation rationnelle des bronchodilatateurs à longue durée daction pour un contrôle optimal de linflammation asthmatique. Lors dune première étude, nous avons investigué lactivité in vitro, vis-à-vis du muscle lisse bronchique félin, de différentes agents bronchodilatateurs parmi lesquels des agonistes β2-adrénergiques (isoprotérénol, salbutamol [SAL], fénotérol, formotérol, salmétérol [SLM]), un anticholinergique (ipratropium bromide [IB]) et une méthylxanthine (théophylline). Tous ont produit une relaxation dose-dépendante de la musculature lisse bronchique, avec des spécificités propres en termes de puissance, defficacité ou dactivité intrinsèque. Sur une base comparative, le formotérol est le ß2-mimétique le plus puissant, et lisoprotérénol le plus efficace avec le fénotérol. Le fénotérol et le formotérol sont des agonistes complets des récepteurs ß2-adrénergiques, le SAL et le SLM des agonistes partiels. Tenant compte des résultats des essais in vitro et de la disponibilité de formulations administrables par aérosols dans lespèce féline, les effets bronchoprotecteurs (intensité, durée daction) de six médications inhalées ont été caractérisés chez le chat sain, en préambule à leur utilisation dans des conditions pathologiques. Un modèle de bronchoconstriction induite par le carbachol a été retenu dans le cadre de cette deuxième étude. Il ressort de cette étude que le SLM en aérosol-doseur (25µg) présente un effet bronchoprotecteur soutenu persistant 24 heures mais est aussi la médication la moins efficace. Le SAL et lIB (nébulisation ou aérosol-doseur) sont des bronchodilatateurs à courte durée daction (48 heures) dont lutilisation combinée en aérosol-doseur (SAL IB : 100µg/20µg) met en exergue une synergie daction. Les conditions naturelles étant souvent incompatibles avec une approche anticipative de la crise dasthme, les traitements instaurés sont davantage à visée curative que prophylactique. Dans une troisième étude, nous avons exploré les effets bronchorelaxants du SAL (100µg) et de lIB (20µg), administrés seuls ou en traitement combiné, sur une bronchoconstriction induite par un aéroallergène (Ascaris suum) chez des chats rendus expérimentalement asthmatiques. La technique dinhalation par aérosol-doseur a été privilégiée vu les effets synergiques de la combinaison « SAL IB » et lintérêt de cette voie dadministration dans la gestion à domicile des crises dasthme. Aux doses testées, les bronchodilatateurs inhalés nont exercé aucun effet notable, naffectant en rien la résolution du bronchospasme induit. Chez lhomme, les crises et les épisodes dexacerbation de lasthme sont fréquents dans le cours évolutif de la maladie. Aucune étude chez le chat asthmatique en crise aiguë (induite ou spontanée) natteste de lefficacité des corticostéroïdes inhalés ni ne mentionne dans ce contexte lintérêt scientifique dune association aux ß2-mimétiques à longue durée daction. Nous avons donc comparé les effets de la prednisolone orale (1mg/kg q12h) à ceux dune dose élevée de fluticasone inhalée, seule (500µg q12h aérosol-doseur) ou en traitement combiné avec du SLM (500µg/50µg q12h aérosol-doseur), sur la fonction et linflammation pulmonaires dans un modèle félin dasthme aigu. Cette quatrième étude a montré quune courte cure orale de prednisolone diminue significativement linflammation bronchique à éosinophiles. De fortes doses de fluticasone inhalée se sont avérées bénéfiques dans le contrôle de lhyperréactivité bronchique non spécifique, sans toutefois exercer des effets marqués sur linflammation bronchique sous-jacente. Combiner cette corticothérapie inhalée au SLM a permis dobtenir des effets anti-éosinophiliques accrus et comparables à ceux de la prednisolone orale. Aucune des médications testées na modifié significativement la réponse clinique et fonctionnelle consécutive à linhalation de lallergène. Létude précédente permet de supposer que le SLM potentialise lactivité anti-inflammatoire des corticostéroïdes inhalés et/ou est doté de propriétés anti-inflammatoires intrinsèques. Dans une cinquième étude, nous avons donc investigué les effets du SLM en monothérapie (50µg q12h aérosol-doseur) sur la fonction et linflammation pulmonaires. Il ressort de cette étude, conduite sur un modèle félin dasthme aigu, que le SLM en monothérapie nexerce pas deffet protecteur sur la survenue dun bronchospasme allergique et est dépourvu de tout effet anti-inflammatoire propre. Les résultats obtenus, dans les conditions expérimentales de nos essais, conduisent aux conclusions suivantes : 1) les bronchodilatateurs inhalés (SAL, IB, SLM) sont dune efficacité thérapeutique limitée dans la prévention et le traitement symptomatique du bronchospasme allergique chez le chat sensibilisé à Ascaris suum 2) en revanche, recourir au SLM comme thérapie adjuvante aux corticostéroïdes inhalés ouvre de nouvelles perspectives thérapeutiques dans le contrôle de linflammation et de lhyperréactivité bronchiques chez le chat asthmatique./The cat is the only animal species that spontaneously develops a clinical entity closely similar to human allergic asthma and commonly referred to as feline asthma. Feline asthma is a chronic inflammatory disease of the lower airways characterised by intermittent respiratory distress due to bronchoconstriction, non-specific bronchial hyperresponsiveness and airway remodeling at latter stages (e.g., epithelial erosions, smooth muscle hypertrophy, glandular hyperplasia). Based on experimental sensitisation to allergens, models of feline asthma mimic many clinical, functional and lesional features of the naturally developing condition. Moreover, development and implementation of feline asthma models have greatly facilitated the search for novel therapies (i.e., cyclosporin A, oral and inhaled corticosteroids, specific immunotherapy). In considering the pathogenesis of asthma, it is of major importance to control recurrent airway obstruction. Although inhaled bronchodilators are recommended for the management of acute asthmatic exacerbations in cats, their clinical efficacy remains uncertain and poorly documented. Most currently recommended drugs, dosages and therapeutic schemes are largely empirical and extrapolated from human medicine, and need to be further validated under controlled experimental conditions. Hence, our work was aimed at determining the potential of inhaled bronchodilators for preventive and curative treatment of acute bronchospasms in asthmatic cats as well as at exploring the benefit of using long-acting bronchodilators to optimally control the airway inflammation. In the first study, we investigated in vitro effects on isolated feline bronchi of different bronchodilating agents including β2-adrenergic agonists (isoproterenol, salbutamol [SAL], fenoterol, formoterol, salmeterol [SLM]), an anticholinergic (ipratropium bromide [IB]) and a methylxanthin derivative (theophylline). All compounds caused a dose-related relaxation of bronchial smooth muscle, each exhibiting specificities in terms of potency, efficacy and intrinsic activity. On a comparative basis, isoproterenol and fenoterol are the most efficacious β2-mimetics while formoterol is the most potent one. Fenoterol and formoterol act as full agonists of β2-adrenoceptors, SAL and SLM as partial agonists. Taking into account results from in vitro testing procedures and availability of aerosol formulations suitable for lung delivery in cats, we compared the antispasmodic effects (magnitude, duration of action) of six inhaled medications against carbachol-induced bronchoconstriction in healthy cats. This second study showed that SLM by metered-dose inhaler (25µg) has a sustained activity for as long as 24 hours but is also the least efficacious medication. SAL and IB (nebulisation or metered-dose inhaler) are short-acting bronchodilators (4-8 hours) whose combination delivered with a metered-dose inhaler (SAL IB: 100µg/20µg) exhibits a synergistic antispasmodic effect. In the natural disease, asthmatic crisis are difficult to predict in terms of occurrence. Therefore, therapeutic interventions are more curative than preventive. In a third study, we explored the bronchodilating effects of SAL (100µg) and IB (20µg), delivered either alone or as a combined therapy, on allergen-induced bronchospasms in Ascaris suum-sensitised cats. The inhalation technique using a metered-dose inhaler was retained given the synergistic effects of the combination SAL IB with this method and its therapeutic interest for at-home management of asthmatic crisis. At the tested doses, these bronchodilators failed to reverse allergen-induced bronchospasms in cats with experimental asthma. In human beings, crisis and exacerbations of asthma are frequent events in the natural course of the disease. Efficacy of inhaled corticosteroids in cats with acute asthmatic exacerbations (induced or spontaneous) has not yet been determined, nor the potential benefit of adding long-acting β2-agonists in this context. Thus, the fourth study was aimed at comparing the effects of oral prednisolone (1mg/kg q12h) with those of inhaled fluticasone at high doses, alone (500µg q12h metered-dose inhaler) or combined with salmeterol (500µg/50µg q12h metered-dose inhaler), on lung function and airway inflammation in a feline model of acute asthma. This study showed that a short course of oral prednisolone significantly reduced allergen-induced bronchial eosinophilic inflammation. High doses of inhaled fluticasone proved to be efficient for decreasing non specific airway hyperresponsiveness but failed to markedly reduce the underlying airway inflammation. Adding salmeterol to inhaled fluticasone led to anti-eosinophilic effects of the same magnitude as those found for oral prednisolone. None of these treatments improved clinical and functional responses to allergen exposure. According to the previous study, it may be that SLM has an anti-inflammatory effect on its own and/or functions as a steroid-potentiating agent. In a fifth study, we investigated the effects of salmeterol as monotherapy (50 µg q12h metered-dose inhaler) on lung function and airway inflammation in our feline model of acute asthma. This inhaled medication did not prevent occurrence of allergic bronchospasm in Ascaris suum-sensitised and challenged cats, nor did it possess intrinsic anti-inflammatory activity. Under our experimental conditions, the main results achieved led to the following conclusions: 1) the inhaled bronchodilators (SAL, IB, SLM) are of limited efficacy for the prevention and symptomatic treatment of allergic bronchospasm in cats sensitised to Ascaris suum; 2) in contrast, using salmeterol as adjuvant therapy to inhaled corticosteroids opens up new perspectives for the treatment of bronchial inflammation and hyperresponsiveness in asthmatic cats.