Introdução: Citomegalovírus (CMV) é um DNA vírus de alta prevalência, e tem uma capacidade peculiar de infectar e permanecer integrado ao DNA das células do hospedeiro, mantendo-se na forma de infecção latente. O vírus também pode ocasionar doença, o que normalmente ocorre em pacientes imunocomprometidos, promovendo o aumento da morbidade e mortalidade nestes pacientes. As doenças inflamatórias intestinais (DII), doença de Crohn (DC) e retocolite ulcerativa (RCU), são enfermidades crônicas que afetam o trato gastrointestinal. A fisiopatologia e o tratamento destas doenças, muitas vezes, pode induzir um estado de imunossupressão. Isso incitou a ideia de que os pacientes com DII são mais susceptíveis à infecção e doença por CMV. Ainda há dúvidas e controvérsias sobre a relação entre a doença inflamatória intestinal e o CMV. Objetivos: Avaliar a frequência de infecção por CMV em pacientes com doença inflamatória intestinal, e se existe associação entre replicação viral do CMV com a atividade da DII, mediante índices clínicos e laboratoriais. Metodologia: Pacientes com DII previamente diagnosticada foram submetidos à entrevista, revisão de registros e coleta de amostras de sangue e fezes. Foram realizados os seguintes exames: pesquisa de citomegalovírus por IgG e IgM no sangue, pela técnica de reação em cadeia por polimerase (PCR) em tempo real no sangue e pela técnica de PCR qualitativa nas fezes. Estes resultados foram correlacionados com os valores de hemoglobina, proteína C-reativa, velocidade de hemossedimentação, calprotectina fecal e índices clínicos. Resultados: Quatrocentos pacientes foram elegíveis, sendo 249 com DC e 151 com RCU. No grupo de pacientes com DC, 67 apresentavam doença moderada ou grave pelo índice clínico, porém 126 se mostravam com doença ativa mediante a avaliação da calprotectina fecal. No grupo de pacientes com RCU, 21 exibiam doença moderada pelo índice clínico, mas 76 se encontravam com doença ativa, mediante a avaliação da calprotectina fecal. Drogas imunossupressoras foram amplamente utilizadas pelos pacientes, 143 pacientes com DC faziam uso de azatioprina e, destes, 48 usavam terapia combinada (anti TNF-alfa + azatioprina). Na RCU, a azatioprina foi usada por 41 pacientes e, destes, sete faziam uso de terapia combinada. Avaliando os dois grupos, 90,9% dos pacientes apresentaram anticorpos IgM contra o CMV no sangue e dez pacientes também exibiram IgG. A detecção do DNA CMV PCR em tempo real no sangue apresentou valores abaixo do limite inferior (150 cópias/mL) em todos os 400 pacientes. Enquanto isso, o DNA CMV PCR qualitativo, realizado na amostra fecal, indicou nove pacientes expressando valores positivos. Com efeito, nos 400 pacientes, identificaram-se 332 infectados sem replicação viral, 19 pacientes com replicação viral e 24 não infectados. Os pacientes com DII em uso de terapia combinada apresentaram uma chance maior de replicação viral 3,63 vezes em comparação aos pacientes que não fizeram uso deste tratamento. Conclusão: A infecção latente pelo CMV foi bastante prevalente, mas a infecção ativa foi rara. A utilização de terapia combinada, entretanto, em doentes com DII, tem associação com a replicação viral do CMV, mas sem indicar relação com a atividade inflamatória da DII / Background: Cytomegalovirus (CMV) is a highly prevalent DNA virus that has a peculiar ability to infect the host and remains integrated to his DNA as a latent infection. The virus can also appear in the form of disease, which most commonly occurs in immunocompromised patients, increasing their morbidity and mortality. Inflammatory bowel diseases (IBD), Crohn\'s disease (CD) and ulcerative colitis (UC) are chronic diseases that affect the gastrointestinal tract. The pathophysiology and treatment of these diseases often induce a state of immunosuppression, hence the assumption that patients with inflammatory bowel disease may be at greater risk for cytomegalovirus disease. However, there are still doubts and controversies about the relationship between IBD and CMV. Aim: Evaluate the frequency of CMV infection in patients with IBD correlating it with clinical and laboratorial activity indices of IBD. Methods: Patients with a previous diagnosis of IBD underwent interviews, a medical record review and collection of blood and fecal samples. The search of CMV was performed by IgG and IgM blood serology, real-time PCR in blood and qualitative PCR in feces. These results were correlated with red blood cell levels, Creactive protein, erythrocyte sedimentation rate and fecal calprotectin. Patients with CD were evaluated by Crohn\'s disease activity index and UC patients, by Truelove & Witts index. Results: Four hundred patients were eligible: 249 patients with CD and 151 with UC. In the CD group, using clinical index, 67 patients had moderate or severe disease, but 126 patients presented with active disease by evaluating fecal calprotectin. In patients with UC, 21 exhibited moderate disease by clinical index, but 76 patients presented with active disease by evaluating fecal calprotectin. Immunosuppressive drugs were widely used by patients. On CD, 143 patients of them were using azathioprine, and of these, 48 were using combo therapy (anti TNFalpha + azathioprine). On the UC, azathioprine was used in 41 patients, and seven of these were taking combo therapy. The great majority of patients (90,9%) had positive CMV IgG, ten patients had positive CMV IgM, nine patients had positive qualitative detection of CMV DNA by PCR in faeces, and in all 400 patients quantitative detection of CMV DNA by real-time PCR in blood was negative. In the 400 patients, we identified 332 CMV infected without viral replication, 19 patients CMV infected with viral replication (active infection) and 24 non-infected CMV patients. Analyzing the 19 patients with active infection, we only found an association with the use of combo therapy (anti TNF-alpha + azathioprine), and patients on combo therapy have a viral replication chance 3.63 times compared to patients who do not use this treatment. Conclusion: Latent cytomegalovirus infection is extremely frequent in the inflammatory bowel disease population, but the active cytomegalovirus infection is rare; and the use of combination therapy in patients with IBD is associated with viral replication of CMV, but without presenting relation to inflammatory activity of IBD

Introdução: O envolvimento gastroduodenal pode ocorrer na doença de Crohn (DC). Seu diagnóstico histológico definitivo é habitualmente realizado através da demonstração do granuloma não caseoso. O achado de gastrite focal H. pylori negativa em biopsias gástricas de pacientes com DC ileal e/ou colônica, apesar de não ser específico, também sugere o envolvimento da doença neste segmento. Objetivos: avaliar a frequência da gastrite focal em pacientes com DC comparada à de pacientes com retocolite ulcerativa (RCU) e controles, assim como as frequências da infecção pelo H. pylori nessas populações e correlacioná-las com a presença de gastrite focal; avaliar a capacidade da imunohistoquímica em diferenciar a gastrite focal nos três grupos; avaliar as associações entre dados demográficos, aspectos clínicos, laboratoriais, uso de medicamentos, presença de sintomas do trato gastrintestinal (TGI) superior e achados endoscópicos com presença de gastrite focal em pacientes com doença inflamatória intestinal (DII); e avaliar a associação entre uso de medicamentos nesses pacientes e infecção pelo H. pylori. Métodos: Foram estudados 62 pacientes com DC, 35 pacientes com RCU e 40 pacientes controles. Todos foram submetidos à endoscopia digestiva alta (EDA) com biopsias para o teste da urease, exame histológico e imunohistoquímico. Resultados: Dos 137 pacientes estudados foram excluídos dois pacientes com DC e um com RCU. Não houve diferença estatisticamente significante entre os grupos com relação à idade (p=0,921) e sexo (p=0,192). A maioria dos pacientes com DC estava em remissão clínica (75%). Cerca de 80% dos pacientes com DC faziam uso de azatioprina. H. pylori foi positivo em 18/60 (30%) pacientes com DC, 12/34 (35%) na RCU e 20/40 (50%) no grupo controle sem diferença estatisticamente significante entre os grupos (p=0,131). Não foram observadas associações estatisticamente significantes entre uso de medicamentos e infecção pelo H. pylori nos pacientes com DII. A gastrite focal H. pylori negativa foi diagnosticada em 7/42 (16,7%) na DC, 3/22 (13,6%) na RCU e 2/20 (10%) no grupo controle, sem diferença estatisticamente significante entre eles (p=0,919). A gastrite focal H. pylori positiva foi diagnosticada em 2/18 (11%) na DC, 3/12 (25%) na RCU e 7/20 (35%) no grupo controle, sem diferença estatisticamente significante (p=0,213). Não foram observadas associações estatisticamente significantes entre características clínicas, laboratoriais, uso de medicamentos, sintomas do TGI superior, achados endoscópicos e gastrite focal. No entanto, foi observado que o uso de azatioprina nos pacientes com DC H. pylori negativos apresentou uma tendência a reduzir a gastrite focal. A imunohistoquímica da gastrite focal dos pacientes com DC e RCU H. pylori negativos foi semelhante e diferiu do grupo controle por este apresentar um maior acúmulo de linfócitos B (CD20). Já a imunohistoquímica da gastrite focal dos pacientes com DC, RCU e controles H. pylori positivos foi indistinguível. Conclusões: Pacientes com DII tendem a ser menos infectados pela bactéria H. pylori. A frequência de gastrite focal H. pylori negativa diagnosticada em nosso estudo foi menor do que a descrita na literatura. O uso de imunossupressor (azatioprina) pode estar relacionado com tal achado / Introduction: Gastroduodenal involvement may occur in Crohns disease (CD). Definitive histological diagnosis of CD in the upper gastrointestinal (GI) tract normally relies on the demonstration of epitheloid granuloma which is considered the histological hallmark of gastric CD. If granulomas are absent, the description of focally enhanced gastritis (FEG) or focal active gastritis in gastric biopsies of patients with known ileal and/or colonic CD, although not exclusive to CD, suggests the involvement of the disease at this site. Objectives: To access the prevalence of FEG in CD patients compared with a group of ulcerative colitis (UC) and CD/UC-free controls, as well as the frequencies of H. pylori infection in those population and correlate them to the presence of FEG; evaluate the capacity of immunohistochemistry in differentiating FEG in the three groups; evaluate the correlation with demographic and clinical characteristics, laboratory findings, current medical therapy as well as the presence of forgut symptoms and mucosal lesions at endoscopy with the presence or absence of FEG in patients with inflammatory bowel disease (IBD) and evaluate the association between medical therapy and H. pylori infection in IBD patients. Methods: We studied 62 patients with CD, 35 patients with UC and 40 patients from control group. All underwent upper GI endoscopy. Biopsy specimens taken from angulus, antrum and gastric body were evaluated by urease test, histology and immunohistochemistry. Results: Of the 137 patients studied we excluded 2 patients with CD and 1 with UC. There was no statistically significant difference among the groups in terms of age (p=0.921) and gender (p=0.192). The majority of CD patients were in clinical remission (75%). Around 80% of CD patients were taking azathioprine. H. pylori was positive in 18/60 (30%) CD patients, in 12/34 (35%) UC and in 20/40 (50%) controls with no statistically significance difference among the groups (p=0.131). No association was found between use of medications and H. pylori infection in IBD patients. In H. pylori negative patients, FEG was diagnosed in 16.7% cases (7/42) of CD, compared with 13.6% (3/22) of UC patients and 10% (2/20) of controls, with no statistically significance difference among them (p=0.919). In H.pylori positive patients, FEG was diagnosed in 11% cases (2/18) of DC, 25% (3/12) in UC and 35% (7/20) of controls with no significant difference among them (p=0.213). There was no statistical interrelationship between FEG and demographic and clinical characteristics, laboratory findings, use of medications, upper GI symptoms and endoscopic findings. However, it was observed that use of azathioprine in H. pylori negative CD patients presented a tendency to reduce FEG. In H. pylori negative patients, immunohistochemistry of FEG of CD and UC was similar and differed from controls as it presented a higher accumulation of B lymphocytes (CD20). On the other hand in H. pylori positive IBD patients, immunohistochemistry of FEG was indistinguishable from controls. Conclusions: IBD patients tend to be less infected by H. pylori. The frequency of H. pylori negative FEG diagnosed in our study was lower than described in literature. The use of immunossupressants (azathioprine) may be related to such findings

Introdução: O conhecimento da fisiopatogênese da Doença Inflamatória Intestinal (DII) tem evoluído nas últimas décadas. No entanto, apesar das terapias terem evoluído, 2/3 dos casos ainda necessitam de drogas alternativas e terapias de suporte. A busca constante de tratamentos alternativos e modalidades mais eficazes tem gerado algumas abordagens promissoras, tais como a utilização do oxigênio hiperbárico (HBO). O uso dessa terapia cresceu rapidamente nos anos 90 mostrando bons resultados e poucos efeitos colaterais sendo, posteriormente \"esquecida\" ante a eficácia apresentada pelo uso das terapias biológicas. Objetivos: Os objetivos deste trabalho foram avaliar os efeitos do tratamento com HBO em camundongos com colite induzida quimicamente pelo ácido 2,4,6 trinitro benzeno sulfônico 2,5% (TNBS), sobre a avaliação dos animais, a análise histológica, o perfil inflamatório através das citocinas IL-4, IL-10, IL-12, IL-13, IL-17, fator de necrose tumoral alfa (TNFalfa) e Interferon y e da atividade das enzimas antioxidantes superóxido dismutase (SOD), glutationa peroxidase (GPx) e glutationa redutase (GR) em intestino de camundongos. Metodologia: Camundongos machos foram divididos em 6 grupos. No grupo 1, a colite foi induzida por TNBS 2,5% + Etanol 35%, sendo chamado de grupo TNBS; o grupo 2 também recebeu TNBS 2,5% + Etanol 35% seguido do tratamento com o HBO, sendo chamado de grupo TNBS+HBO; o grupo 3 recebeu apenas o veículo etanólico a 35%, sendo chamado de grupo ÁLCOOL; o grupo 4 também recebeu o veículo etanólico a 35% associado ao HBO, sendo chamado de grupo ÁLCOOL+HBO; o grupo 5 recebeu apenas solução salina (NaCl 0,9%), sendo chamado de grupo SALINA; e o grupo 6 recebeu a solução salina associado ao HBO, sendo chamado de grupo SALINA+HBO. Durante o tratamento os animais foram avaliados diariamente. O tratamento com HBO foi realizado por 4 dias e, ao final, as amostras da porção final do intestino foram retiradas e armazenadas para análise histológica, enzimas antioxidantes e citocinas. Resultados: A avaliação mostrou que o HBO promoveu uma melhora significativa no quadro clínico desses animais. A aplicação do ácido 2,4,6 trinitro benzeno sulfônico nos animais do grupo TNBS resultou na perda de 12,71% do peso corpóreo dos animais após 24 horas e, ao final do período experimental uma perda de peso total de 14,63%. Por outro lado, os animais que também receberam 2,4,6 trinitro benzeno sulfônico associado ao tratamento com o HBO (TNBS+HBO) tiveram uma perda de apenas 7,52% nas primeiras 24 horas, apresentando uma recuperação de 5,58% de seu peso no final do período experimental. A avaliação do quadro histológico mostrou uma melhora significativa entre o grupo TNBS+HBO quando comparado com o grupo TNBS. O tratamento com HBO aumentou a atividade das enzimas antioxidantes SOD e GPx em todos os grupos, sendo somente significativo entre os grupos TNBS vs TNBS+HBO, não sendo observado diferença da GR entre os grupos. Com relação ao perfil inflamatório foi observado que o tratamento com o HBO promoveu a diminuição das citocinas pró-inflamatórias INFy, IL-12, IL-17 e TNF? e o aumento das citocinas anti-inflamatórias IL-4 e IL-10, e não houve alteração da IL-13. Em modelo experimental, esses dados representam, o potencial efeito anti-inflamatório e o do aumento das defesas antioxidantes enzimáticas promovido pelo HBO / Introduction: The Knowledge about the physiopathogenesis of inflammatory bowel disease (IBD) has evolved over the last decades. However, although therapies have improved, 2/3 of the cases still need alternative drugs and support therapy. The constant search for alternative treatments and more effective modalities has brought to light some promising strategies, as the use of hyperbaric oxygen (HBO). The use of such therapy surged rapidly in the 90´s showing good results and few side effects being, later on, \"forgotten\" due to the efficacy shown by the use of biological therapies. Objective: This study aimed to evaluate the effects of HBO treatment in mice with chemically induced colitis, using 2,4,6 trinitrobenzene sulfonic acid 2,5% (TNBS) over the evaluation of the animals, histological analysis, inflammatory profile through cytokines IL-4, IL-10, IL-12, IL-13, IL-17, TNF- alfa and interferon y, and also the activity of the antioxidant enzymes superoxide dismutase (SOD), gluthatione peroxidase (GPx) and gluthatione reductase (GR) in intestine of mice. Methodology: Male mice were divided into 6 groups, in group 1, colitis was induced by TNBS 2,5%+ Ethanol 35%, named as TNBS, group 2 also received TNBS 2,5%+ Ethanol 35% + HBO, named as TNBS+HBO, group 3 received only Ethanol 35%, named as ALCOHOL, group 4 received Ethanol 35% associated with HBO, named as ALCOHOL+HBO, group 5 received Saline (NaCl 0,9%), named as SALINE and group 6 received Saline combined with HBO, named as SALINE+HBO. During the treatment the animals were evaluated daily. The treatment with HBO was performed for 4 days and at the end, the samples of the final portion of the bowel were removed and stored for histological, antioxidant enzymes and cytokines analysis. Results: This study has shown that the HBO promoted a significant improve on these animals clinical status. The group which received TNBS showed a 12,71% body weight loss after 24 hours, and by the end of the experimental period the average weight loss was 14,63%. On the other hand, the animals treated with HBO showed only 7,52% weight loss during the first 24 hours, having recovered the weight lost in 5,58% by the end of the experimental period. The histological evaluation of the TNBS+HBO group presented a significant improvement when compared with TNBS group. The treatment with HBO increased the activity of the antioxidant enzymes SOD and GPx in all groups, being only significant among the groups TNBS vs TNBS+HBO, difference in the activity of GR was not observed among the groups. Regarding the inflammatory profile, it was observed that the treatment with HBO promoted the decrease of pro-inflammatory cytokines INFy, IL-12, IL-17 and TNFalfa, as well as the increase of anti-inflammatory cytokines IL-4 and IL-10, while IL-13 was not affected. These data represents, in experimental model, the potential anti-inflammatory effect and the increase of the enzymatic antioxidant defenses promoted by the HBO

As doenças inflamatórias intestinais (DII) - doença de Crohn e retocolite ulcerativa, são condições crônicas que, na maioria dos casos, exigem controle com terapia medicamentosa. A atenção farmacêutica (AF), definida como a provisão responsável do tratamento farmacológico, com o propósito de alcançar resultados concretos que melhorem a qualidade de vida do paciente, constitui nova forma de cuidado ao paciente, que necessita ser mais extensivamente avaliada. Este estudo teve o objetivo de avaliar a contribuição da atenção farmacêutica ao tratamento clínico de pacientes com DII em acompanhamento ambulatorial em hospital terciário. Ao longo de um ano, foi avaliado um grupo que recebeu a atenção farmacêutica (GAF; N=18) e um grupo controle (GC; N=17) não submetido aos procedimentos da AF. Os resultados da contribuição da AF foram avaliados pela comparação de diferentes variáveis entre os grupos, que foram obtidas na primeira entrevista - T(0), aos seis - T(6) e 12 - T(12) meses do estudo. Quanto aos aspectos clínicos, houve redução significativa dos índices de atividade clínica de T(6) para T(12) no GAF (mediana; variação: 2,20; 0,99 3,77 versus 1,90; 0,99 3,77; p=0,02), o que não ocorreu no GC (1,69; 0,99 3,77 versus 1,69; 0,99 3,48). No GAF, houve aumento significativo do percentual de pacientes mais aderentes ao tratamento medicamentoso (27,8% versus 72,2%; p<0,05), quando da avaliação por meio do teste de Morisky, mas não foram observadas diferenças (72,2% versus 88,9%) na adesão avaliada pelo cotejo entre medicamentos utilizados e prescrições registradas. Em ambas as formas de avaliação da adesão, tanto pelo teste de Morisky (41,2% versus 41,2%), quanto pelo confronto das medicações utilizadas e prescrições registradas (88,2% versus 82,4%), não foram observadas alterações no GC. Houve aumento significativo dos índices de conhecimento do paciente sobre o tratamento no GAF entre T(0) e T(12) (mediana; variação: 80%; 40% 100% versus 100%; 100% 100%; p0,0001), o que não ocorreu no GC (80%; 0 100% versus 80%; 60% 100%). No que se refere à qualidade de vida, avaliada pelo instrumento SF36, houve diferenças estatisticamente significativas nos dois grupos apenas no domínio de saúde mental. No GAF, houve elevação dos escores deste domínio entre T(0) e T(12) (54,0 versus 66,0; p=0,04), o que, também ocorreu no GC (60,0 versus 68,0; p=0,01). Porém, no GAF, esta mudança ocorreu mais precocemente, de T(0) para T(6) (54,0 versus 66,0; p<0,01). A AF possibilitou a identificação, em média, de 3,8 problemas relacionados ao medicamento por paciente, que em sua maioria foram resolvidos, com intervenções predominantemente focadas em orientações aos pacientes. Os pacientes do GAF, ao término do estudo, apresentaram alto grau de satisfação com a AF. Os resultados obtidos permitem concluir que a introdução de um programa de atenção farmacêutica a pacientes ambulatoriais com DII seguidos em hospital terciário trouxe contribuição positiva, proporcionando benefícios mensuráveis aos pacientes. / Inflammatory bowel diseases (IBD) Crohns disease and ulcerative colitis are chronic conditions which are usually controlled with drug therapy. Pharmaceutical care (PC), defined as the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve patients quality of life, is a new patient care modality, which needs to be more extensively evaluated. This study aimed at assessing the contribution of pharmaceutical care to the clinical treatment of outpatients with IBD assisted at a reference hospital. During one year, a group receiving pharmaceutical care (PCG; N=18) and a control group (CG; N=17), which did not undergo PC procedures, were evaluated. Results of PC contribution were assessed by comparing the two groups regarding different variables obtained in the first interview at - T(0), at six - T(6) and 12 - T(12) months of study. Regarding the clinical aspects, there was a significant decrease of clinical activity indexes from T(6) to T(12) in the PCG (median; range: 2.20; 0.99 3.77 versus 1.90; 0.99 3.77; p=0.22), but not in the CG (1.69; 0.99 3.77 versus 1.69; 0.99 3.48). In the PCG, there was a significant increase in the percentage of patients who were more compliant to drug treatment (27.8 % versus 72.2 %; p<0.05) as assessed using the Morisky scale; however, no differences in compliance rates were observed (72.2 % versus 88.9 %) by comparing drugs taken with registered prescriptions. In the CG, no differences were observed in none of the compliance assessment methods, neither by the Morisky scale (41.2% versus 41.2%), nor by comparing drugs taken with registered prescriptions (88.2% versus 81.2%). There was a significant increase in the values of an index for patients knowledge about the treatment in the PCG between T(0) and T(12) (median; range: 80%; 40 100 versus 100%; 100 100; p0,0001), but not in the CG (80%; 0 100 versus 80%; 60 100). With respect to quality of life, assessed by the SF36 scale, there were statistically significant differences in both groups only in the mental health domain. There was an increase in scores for this domain between T(0) and T(12) in both PCG (54.0 versus 66.0; p=0,04), and CG (60.0 versus 68.0; p=0,01). However, PCG had this increasing scores earlier, between T(0) and T(12) (54.0 versus 74.0; p<0,01). PC enabled the identification of a number of drug-related problems per patient (mean = 3.8), which were mostly solved by interventions predominantly focused on patient orientation. At the end of the study, patients in the PC group showed a high degree of satisfaction with the intervention. The achieved results allow concluding that the implementation of a pharmaceutical care program to outpatients with IBD followed at a tertiary hospital gave a positive contribution, providing measurable benefits to patients.

A adesão ao tratamento medicamentoso é um importante fator determinante no sucesso terapêutico. A adesão do paciente pode ser influenciada por fatores diversos, ligados à doença, ao tratamento, ao paciente, às condições sociais e econômicas, como também, relacionada ao sistema de saúde que o atende. Ainda que existam inúmeros estudos sobre a adesão ao tratamento em portadores com doenças crônicas, são escassas as investigações sobre este tema nas doenças inflamatórias intestinais. O presente trabalho teve o objetivo de avaliar a adesão ao tratamento medicamentoso e os possíveis fatores que a influenciam, em pacientes portadores de doenças inflamatórias intestinais (DII): doença de Crohn (DC) e retocolite ulcerativa (RCU), do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP), da Universidade de São Paulo. Como controles, foram investigados pacientes portadores de pancreatite crônica e insuficiência pancreática (PC), com medicação fornecida pelo hospital, tal como os pacientes portadores de DII. Foram também investigados pacientes portadores de afecções digestivas variadas (ADV), grupo no qual a medicação prescrita não era fornecida pelo hospital. Por meio de estudo transversal e indireto, foi realizada entrevista estruturada para avaliar a adesão de 110 pacientes, que foram caracterizados como apresentando maior ou menor grau de adesão. Esta classificação foi baseada no cotejo entre os dados do prontuário e os informados pelo paciente em entrevista, considerando a afirmação do paciente que usava a medicação e que conhecia o nome da droga em uso. Utilizou-se, também, o teste de Morisky, que permite avaliar o padrão de comportamento do paciente em relação ao uso diário do medicamento. Este teste consiste de quatro perguntas padronizadas relacionadas ao esquecimento, descuido com o horário de tomada do medicamento, percepção de efeitos colaterais e ausência de sintomas. Na análise dos medicamentos utilizados pelo paciente, foram observadas as seguintes proporções de pacientes classificados como menos aderentes: 15,4% em pacientes portadores de DC, 13,3% na RCU, 8,4% na PC e 16,6% nos pacientes do grupo ADV. Porém, o teste de Morisky mostrou as seguintes proporções de menos aderentes: 50% de pacientes portadores de DC, 63,3% na RCU, 54,2% na PC e 63,4% na ADV. Não houve diferenças estatisticamente significativas, entre os grupos de pacientes, tanto na análise dos medicamentos utilizados pelo paciente como pelos resultados do teste de Morisky. Em análise univariada, nenhum dos fatores demográficos, sociais, clínicos ou referentes ao tratamento medicamentoso apresentou relação estatisticamente significativa, comum a todos os grupos, que indicasse influência sobre a adesão ao tratamento. Apesar do alto grau de adesão, de acordo com a análise dos medicamentos utilizados, detectou-se alto percentual de não-adesão ao tratamento medicamentoso ligado ao comportamento habitual e independente do diagnóstico, ou do acesso gratuito aos medicamentos. Isto pode indicar a existência de um padrão específico de comportamento dos usuários do serviço, o que sugere a necessidade de maior atenção dos profissionais de saúde para o problema, bem como medidas de educação do paciente quanto ao uso dos medicamentos. / Compliance to drug therapy is an important factor determining a successful treatment. Patient compliance may be influenced by various factors related to the disease, to treatment, to the patient himself, to his socioeconomic condition, as well as to the health system. Although many studies have assessed compliance to treatment in patients with chronic diseases, few investigations are available in inflammatory bowel diseases (IBD). The objective of the present study was to assess compliance to drug therapy in patients with IBD - Crohn’s disease (CD) and ulcerative colitis (UC), seen at the University Hospital, Faculty of Medicine of Ribeirão Preto (HCFMRP), University of São Paulo, Brazil. Patients with chronic pancreatitis (CP) and pancreatic insufficiency who received free medication supplied by the hospital, like the IBD patients, were used as controls. Patients with various digestive affections (VDA) whose prescribed medication was not supplied by the hospital were also investigated. In a transverse and indirect study, a structured interview was applied to assess the compliance of 110 patients, who were characterized as presenting a higher or lower degree of compliance. This classification was based on a comparison of data in the medical records to the information provided by the patient in the interview, considering the patient’s statements that he/she actually used the medication and was capable of produce correctly its name. The Morisky test was also used to assess the behavioral pattern of the patient regarding the daily use of the medication. This test consists of four standardized questions that evaluate forgetfulness, carelessness regarding the time when the medication should be taken, the perception of side effects, and the absence of symptoms. In the analysis of patient statements on medication in use, the proportions of patients regarded as less compliant were as follows: 15.4% of patients with CD, 13.3% of those with UC, 8.4% of those with CP, and 16.6% of those with VDA. However, the Morisky test revealed the following proportions of less compliant patients: 50% of patients with CD, 63.3% of those with UC, 54.2% of those with CP, and 63.4% of those with VDA. No statistically significant differences were observed between the four groups regarding evaluation according to either the analysis of patient statements or the results of the Morisky test. Univariate analysis revealed that none of the demographic, social, or clinical factors or the variables related to drug therapy showed statistically significant relationships, common to all groups, that would indicate their influence on compliance to treatment. Despite the high degree of compliance evaluated by patient statements on medication in use, a high degree of noncompliance to treatment linked to habitual behavior was detected. Those findings were independent on either disease type or free access to medication. This may indicate the existence of a specific behavioral pattern common to the local health system users, which suggests the need for better consideration of the problem on the part of the health professionals, as well as the need for measures of patient education regarding medication use.

This thesis describes studies in patients with inflammatory bowel disease (IBD) and collagenous colitis (CC). We investigated mucosal eosinophil and neutrophil granulocytes and T-cells involved in the inflammatory processes and aimed at determining whether these processes are reflected in the faecal (F) contents of specific proteins secreted by cells in the intestinal mucosa. Thus, we measured eosinophil cationic protein (ECP) and eosinophil protein X (EPX) and the neutrophil derived myeloperoxidase (MPO) and calprotectin (C); and in addition, chromogranin A (CgA), Chromogranin B (CgB) and secretoneurin (SN), derived from EEC cells and cells in the enteric nervous system. We found that a normalised FC level can serve as a surrogate marker for successful treatment in patients with IBD, but persistently high FC levels need further evaluation (study I). Furthermore, FC and F-MPO appear to relate better than F-EPX to treatment outcome in IBD. We evaluated F-ECP, F-EPX, F-MPO and FC as markers of disease activity and treatment outcome in patients with CC (study III) and concluded that F-ECP was the best discriminator of detecting active CC. Normalised F-ECP and F-EPX could serve as markers of successful treatment. We showed that the inflammation in CC is characterised by activated eosinophils, but that there is no neutrophil activity (study II). T-cells have a lower grade of activity in active CC than in control subjects. During budesonide treatment the normal activation of eosinophils and T-cells is restored, with concomitant clinical remission. The findings in studies II and III indicate that the eosinophils have an essential role in the pathophysiology of CC. Markedly higher values of F-CgA, F-CgB and F-SN were found in patients with CC than in those with IBD and controls (study IV) indicating a crucial role for the intestinal neuro-endocrine system in the pathogenesis of collagenous colitis.

Hintergrund: Angaben zu Inzidenz und Prävalenz von chronisch entzündlichen Darmerkrankungen (CED) bei Kindern und Jugendlichen in Deutschland fehlen bisher, die Daten des im Jahr 2000 gegründeten Sächsischen CED-Registers für Kinder und Jugendliche wurden bisher nicht veröffentlicht. Bei internen Diskussionen der Registerdaten zeigte sich stets eine nicht erklärbare abfallende altersspezifische Inzidenz der CED ab dem 15. Lebensjahr. Es wurde vermutet, dass einige ältere Jugendliche ausschließlich von Erwachsenengastroenterologen betreut wurden und bei einigen Adoleszenten eine längere diagnostische Latenz zur Diagnosestellung nach dem 18. Lebensjahr führte. Patienten und Methoden: Zur Prüfung der Thesen wurden alle gastroenterologisch tätigen Internisten in Leipzig aufgesucht und Patienten eingeschlossen, bei denen bis zum 26. Lebensjahr in den Jahren 2005-2009 eine CED endoskopisch neu diagnostiziert wurde. Die Auswertung des Sächsischen CED-Registers erfolgte hinsichtlich Inzidenz, Prävalenz, Geschlechterverteilung und diagnostischer Latenz im Zehnjahreszeitraum 2000-2009. Ergebnisse: Es wurden tatsächlich einige Jugendliche vor dem 18. Lebensjahr ausschließlich von Internisten betreut und nicht an das Register gemeldet. Die korrigierte Inzidenz von CED bei Patienten bis zum 18. Lebensjahr in Leipzig lag um 37 % höher als im Register angegeben. Nach dem 15. Lebensjahr wurde – ebenfalls in Abweichung zu den Registerdaten – ein kontinuierlicher Anstieg der altersspezifischen Inzidenz bis zum 18. Lebensjahr registriert. Es zeigte sich eine Tendenz zur längeren diagnostischen Latenz bei Adoleszenten, die sich jedoch nicht statistisch sichern ließ. Bis zum 15. Lebensjahr wurden nahezu alle Patienten im CED-Register erfasst.

Inflammatory bowel disease (IBD), comprises Crohn’s disease (CD) and ulcerative colitis (UC), and is a chronic relapsing inflammation of gastrointestinal tract without any known cause or cure. Currently, it is accepted that IBD is a result of a dysfunctional immune response to commensal bacteria in a genetically susceptible host, and that environmental factors can trigger the onset or reactivation of the disease. This thesis considers the possibility of a specific pathogenic agent as well as an imbalance in the composition of the normal microflora in the pathogenesis of IBD. Gut biopsy tissues were taken from a population-based case-control tissue bank held at the University of Manitoba. Automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphisms (T-RFLP) were employed to assess the diversity of gut microbiota. The phylogenetic, virulence and biochemical characteristics of Escherichia coli isolated from IBD biopsies were examined using multi-locus sequence typing (MLST), DNA microarray technology and API 20E system. Utilizing ARISA and T-RFLP, a remarkable increase in the order of unclassified Clostridia was detected in inflamed tissues, particularly in CD patients (P < 0.05). Moreover, species richness and diversity were the highest in non-inflamed IBD biopsies. Culture-based quantification detected a significantly higher number of E. coli in IBD tissues (P < 0.05). Phylogenetic analysis revealed the tendency of E. coli isolated from IBD patients to be grouped into separate clonal clusters based on their allelic profiles (P = 0.02). A link was detected between uropathogenic E. coli (UPEC) CFT073 and strains isolated from IBD, with regards to gene distribution and virulence, using microarray technology. Amino acid substitutions N91S and S99N in FimH, the adhesive subunit of E. coli type I fimbria, were significantly associated to IBD (P < 0.05). This study demonstrated an increase in the microbial diversity of non-inflamed IBD tissues and suggested a recruitment phase of bacterial adherence and colonization, before the inflammation sets in. Furthermore, E. coli isolated from IBD tissues were distinct from commensal strains in both clonal and virulence characteristics and shared remarkable traits with extraintestinal pathogenic E. coli. Features involved in bacterial adhesion to epithelial cells may hold the key to E. coli pathogenesis in IBD.

Background: Inflammatory bowel disease (IBD) includes Crohn´s disease (CD) and ulcerative colitis (UK). The diseases are chronic and have a pattern of relapses interspersed with relatively symptom-free periods. Common symptoms during relapse are diarrhea, abdominal pain and weight loss. Since you have IBD for life it is important to find ways to relate to and cope with the disease. In that process a nurse can be of great help. Aim: The purpose of this literature review was to increase the understanding of how adult patients with inflammatory bowel disease experience their daily lives.   Method: The method used was a literature review. A literature search was performed in two separate databases which resulted in eleven examined and analyzed articles on the subject.  Results: After the analyze of the articles three different themes emerged: Limitations in daily life, Self-image and self-esteem and finally Self-care and strategies. Several individuals felt limited one way or the other in their daily life. They also described how their self-esteem was affected. Some positive changes due to the disease were also described. For example some changed their exercise and food habits for the better. Discussion: The results are discussed through the perspective of Antonovsky’s (1991/2005) salutogenic view and were connected to how the SOC (Sense of Coherence) was affected. The importance of relatives’ support and self-care was also discussed.

Inflammatory bowel disease (IBD), comprises Crohn’s disease (CD) and ulcerative colitis (UC), and is a chronic relapsing inflammation of gastrointestinal tract without any known cause or cure. Currently, it is accepted that IBD is a result of a dysfunctional immune response to commensal bacteria in a genetically susceptible host, and that environmental factors can trigger the onset or reactivation of the disease. This thesis considers the possibility of a specific pathogenic agent as well as an imbalance in the composition of the normal microflora in the pathogenesis of IBD. Gut biopsy tissues were taken from a population-based case-control tissue bank held at the University of Manitoba. Automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphisms (T-RFLP) were employed to assess the diversity of gut microbiota. The phylogenetic, virulence and biochemical characteristics of Escherichia coli isolated from IBD biopsies were examined using multi-locus sequence typing (MLST), DNA microarray technology and API 20E system. Utilizing ARISA and T-RFLP, a remarkable increase in the order of unclassified Clostridia was detected in inflamed tissues, particularly in CD patients (P < 0.05). Moreover, species richness and diversity were the highest in non-inflamed IBD biopsies. Culture-based quantification detected a significantly higher number of E. coli in IBD tissues (P < 0.05). Phylogenetic analysis revealed the tendency of E. coli isolated from IBD patients to be grouped into separate clonal clusters based on their allelic profiles (P = 0.02). A link was detected between uropathogenic E. coli (UPEC) CFT073 and strains isolated from IBD, with regards to gene distribution and virulence, using microarray technology. Amino acid substitutions N91S and S99N in FimH, the adhesive subunit of E. coli type I fimbria, were significantly associated to IBD (P < 0.05). This study demonstrated an increase in the microbial diversity of non-inflamed IBD tissues and suggested a recruitment phase of bacterial adherence and colonization, before the inflammation sets in. Furthermore, E. coli isolated from IBD tissues were distinct from commensal strains in both clonal and virulence characteristics and shared remarkable traits with extraintestinal pathogenic E. coli. Features involved in bacterial adhesion to epithelial cells may hold the key to E. coli pathogenesis in IBD.