This thesis presents studies relating to effects of different macronutrients, predominantly fat and carbohydrate, on gastrointestinal motility, hormone release/suppression, appetite and energy intake in healthy subjects, and on symptom generation in patients with functional dyspepsia. The three broad areas that have been investigated in these studies are: (i) the effect of load, and duration, of small intestinal nutrient exposure on gastric motility, gastrointestinal hormone release/suppression, appetite and energy intake in healthy subjects, (ii) the dietary factors that may contribute to symptom generation in patients with functional dyspepsia, through analysis of diet diaries and acute nutrient challenges, and (iii) the effects of the herbal medication, Iberogast®, on gastric motility in healthy subjects. The ingestion of nutrients, triggers a number of gastrointestinal responses, including the modulation of antropyloroduodenal motility, gastrointestinal hormone release/suppression, and the suppression of appetite and energy intake, resulting in a slowing of gastric emptying to an average rate of 1 - 3 kcal/min, which is required for efficient nutrient digestion and absorption. Additionally, the rate at which glucose enters the small intestine influences postprandial glycaemia and incretin responses. These responses have been demonstrated in animals to be dependent on the length, and region, of the small intestine exposed to fat and glucose, however, this has not been directly investigated in humans. Functional dyspepsia is a clinical condition, characterised by chronic upper abdominal symptoms, such as nausea, bloating and early fullness, without a known cause, which affects approximately 11 - 29 % of the population. Many studies have reported that disturbed gastric motor activity may be the cause of these symptoms, but patients frequently experience symptoms following ingestion of food, and some patients report to eat smaller meals more frequently and avoid fatty and spicy foods. In addition, laboratory-based studies have indicated that functional dyspepsia patients may be hypersensitive to fat, but not carbohydrate. To date, the treatments used to reduce symptoms are frequently directed at the normalisation of gastroduodenal motility, using prokinetics. However, the beneficial effect of these drugs is relatively small and variable, and their adverse effects can be substantial. Herbal drug preparations have recently received considerable interest as an alternative treatment option in functional dyspepsia. A commercially available herbal preparation, Iberogast® which contains nine plant extracts, has been reported to improve upper abdominal symptoms in functional dyspepsia and to decrease fundic tone, increase antral contractility and decrease afferent nerve sensitivity in experimental animals. The effects of Iberogast® in the human gastrointestinal tract have not been investigated. The first three studies presented in this thesis have focused on the effects of delivering fat and glucose into the small intestine at different loads (Chapter 5, 6 and 7), lower, comparable to, and higher than gastric emptying normally occurs, and at different durations of infusion (but still at similar caloric loads - Chapter 5, fat only), on gastrointestinal motility, plasma hormone release/suppression, glycaemia, and energy intake in healthy male subjects. The study in Chapter 5 demonstrated that antral pressure waves and pressure wave sequences were suppressed, and basal pyloric pressure, isolated pyloric pressure waves, and plasma cholecystokinin and peptide YY stimulated, during both the low (1.33 kcal/min for 50 min: 67 kcal/min), and high (4 kcal/min for 50 min: 200 kcal), loads of lipid. The effect of the 4 kcal/min load was sustained so that the suppression of antral pressure waves and pressure wave sequences and increase in peptide YY remained evident after cessation of the infusion. The prolonged lipid infusion (1.33 kcal/min for 150 min: 200 kcal) suppressed antral pressure waves, stimulated cholecystokinin and peptide YY and basal pyloric pressure and tended to stimulate isolated pyloric pressure waves when compared with saline throughout the entire infusion period. These results indicate that both the load, and duration, of small intestinal lipid have an influence on antropyloroduodenal motility and patterns of cholecystokinin and peptide YY release. Chapter 6 demonstrated that lipid loads lower than gastric emptying normally occurs (0.25 kcal/min for 50 min: 12.5 kcal) transiently stimulated isolated pyloric pressure waves and cholecystokinin release and suppressed pressure wave sequences and hunger scores. Loads comparable to (1.5 kcal/min for 50 min: 75 kcal) and higher (4 kcal/min for 50 min: 200 kcal), than the normal rate of gastric emptying, were required to stimulate basal pyloric tone and peptide YY release and suppress antral and duodenal pressure waves. Only the 4 kcal/min load suppressed energy intake. The effects of lipid on all parameters, with the exception of hunger, were load-dependent. In addition, there were relationships between antropyloroduodenal motility and cholecystokinin and peptide YY concentrations with energy/food intake. The study in Chapter 7 demonstrated that loads of glucose lower than (1 kcal/min for 120 min: 120 kcal), comparable to (2 kcal/min for 120 min: 240 kcal) and higher than (4 kcal/min for 120 min: 480 kcal) the rate gastric emptying normally occurs, stimulated blood glucose, plasma insulin, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and cholecystokinin concentrations and suppressed the number of antral pressure waves, 2 and 4 kcal/min loads were required for the suppression of duodenal pressure waves and pressure wave sequences and the stimulation of basal pyloric pressure and suppression of energy intake only after the 4 kcal/min loads. There were also relationships between glucagon-like peptide-1 and glucose-dependent insulinotropic peptide with basal pyloric tone, and food/energy intake with pyloric pressures. The studies presented in the subsequent three chapters investigated the contribution of dietary factors on the generation of symptoms in patients with functional dyspepsia when compared with healthy subjects (Chapter 8 and 9) and the effect of Iberogast® on motility in the healthy gastrointestinal tract (Chapter 10). The effects of equi-caloric high-carbohydrate vs. high-fat yoghurt preloads on symptom generation, plasma hormone concentrations, antral area and energy intake were compared between functional dyspepsia patients and healthy subjects (Chapter 8). Nausea and pain were greater in patients after the high-fat, when compared with high-carbohydrate and control, preloads and with healthy subjects. Discomfort was greater after all preloads in patients when compared with healthy subjects. Fasting cholecystokinin and stimulation of cholecystokinin by the high-fat preload were greater in patients, while fasting and postprandial peptide YY were lower in patients than in healthy subjects, with no differences in fasting, or postprandial, plasma ghrelin between patients and healthy subjects. Fasting antral area was greater in patients, with no differences postprandially between patients and healthy subjects. There were no differences in energy intake between the two groups. The relationship between the effect of dietary intake and eating behaviour over a 7-day period on the occurrence and severity of abdominal symptoms was compared between patients and healthy subjects (Chapter 9). The symptoms experienced by the patients included nausea, fullness discomfort, bloating and upper abdominal, and epigastric, pain, of a modest severity, which occurred within 30 min of eating. The number of “meals” ingested was significantly less in functional dyspepsia patients and there was a trend for total energy and fat intake to be less. The occurrence of these symptoms was also statistically related to the ingestion of fat and energy intake. The results of these studies indicate that diet, particularly the ingestion of fat, influences the development of symptoms in a subgroup of patients with functional dyspepsia. The study in Chapter 10 evaluated the effect of the herbal drug Iberogast® on gastric motility in the gastrointestinal tract. Iberogast® increased proximal gastric volume, increased antral pressure waves without affecting pyloric or duodenal pressures, and slightly increased the retention of liquid in the total stomach, but had no effect on gastric emptying of solids or intragastric distribution. These results demonstrate that Iberogast® affects gastric motility in humans, and the stimulation of gastric relaxation and antral motility may contribute to the reported therapeutic efficacy of Iberogast® in functional dyspepsia. The studies reported in this thesis provide new information about the regulation of gastric motility, hormone release/suppression, appetite and energy intake, by varying the loads of lipid and glucose infused into the small intestine in healthy subjects, which may have implications in patients with altered gastric motor functions, such as obese, type-2 diabetes and functional dyspepsia patients. In addition, studies in functional dyspepsia patients revealed that diet, in particular the ingestion of fat, contribute to the cause of their symptoms, and these findings may have important implications for the development of diet-based therapies for the treatment of functional dyspepsia. Furthermore, functional dyspepsia patients with impaired gastric relaxation and antral dysmotility may benefit from the effects of Iberogast® as demonstrated in the healthy gastrointestinal tract. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1331606 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2008

Bakgrund: Irritable Bowel Syndrome (IBS) och Funktionell Dyspepsi (FD) är två syndrom som många personer lider av och som det inte finns någon botande behandling för. Då syndromen bara går att symptomlindra tar många av personerna som lider av dessa till egenvårdsmetoder som ofta är kostrelaterade. Att stötta och vägleda patienter i sin egenvård är en uppgift som sjuksköterskor i allmänhet har, och i synnerhet för dessa patienter eftersom ingen botande behandling finns. Syfte: Syftet med föreliggande litteraturstudie var att beskriva kostrelaterade egenvårdsmetoder för patienter med Irritable Bowel Syndrome och/eller Funktionell Dyspepsi där upplevda och/eller observerade effekter beskrivits. Syftet var även att beskriva de valda studiernas datainsamlingsmetoder. Metod: En litteraturstudie med beskrivande design. Datainsamlingen har skett från databaserna PubMed och CINAHL. Huvudresultat: Tretton studier har inkluderats. Utifrån dessa har det framkommit att patienter som lider av IBS och/eller FD kan ta till en mängd olika kostrelaterade egenvårdsmetoder. Effekter av dessa har visat sig förebygga och/eller lindra fysiska symptom från mag-tarmkanalen samt i och med detta ge förbättrad livskvalitet. De datainsamlingsmetoder som beskrivits har visat sig variera mellan frågeformulär och skattningsskalor, dagböcker, kroppsliga markörer samt gruppintervjuer. Slutsats: Patienter med IBS och/eller FD kan använda sig av ett flertal olika kostrelaterade egenvårdsmetoder i syfte att förebygga och/eller lindra sina symptom från mag-tarmkanalen. En mängd olika datainsamlingsmetoder kan användas för att identifiera olika kostrelaterade egenvårdsmetoder och dess påverkan på symptom från IBS och/eller FD. / Background: Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD) are two syndromes that many people suffers from and that has no curing treatment. Since the syndromes only has a symptomatic treatment many people that suffers from it uses self-care methodes that often includes diet. Support and guidance in patiens self-care are a main task for nurses in general and especially for these patients since no curing treatment is available. Aim: The aim of the present study was to describe dietary self-care practices for patients with Irritable Bowel Syndrome and/or Functional Dyspepsia where the perceived and/or observed effects was described. The aim was also to describe the selected studies data collection methods. Method: A literature review with descriptive design. Data has been collected from the databases PubMed and CINAHL. Main Results: Thirteen studies were included. From these, it has been found that patients suffering from IBS and/or FD may use a variety of dietary self-care methods. Effects of these have been shown to prevent and/or alleviate physical symptoms from the gastrointestinal tract and therefore provide better quality of life. The data collection methods described have been found to vary between questionnaires and rating scales, diaries, physical markers and group interviews. Conclusion: Patients with IBS and/or FD can make use of many diet related self-care methods to prevent and/or relieve their symptoms from the gastrointestinal tract. Many different data collection methods can be used to identify diet related self-care practices and its effect on the symptoms of IBS and/or FD.

Darbo tikslas - įvertinti sergančiųjų funkcine dispepsija skrandžio gleivinės morfologinius pakitimus bei jų pokyčius gydant skirtingomis augalinės kilmės antioksidanto astaksantino dozėmis. Tikslui pasiekti buvo nustatyti ir išspręsti šie uždaviniai: įvertinti infekuotumą Helicobacter pylori mikroorganizmais bei skrandžio gleivinės histomorfologinius pakitimus pagal Sidnėjaus ir OLGA klasifikacijas sergantiesiems funkcine dispepsija; ištirti funkcine dispepsija sergančių ligonių uždegimo žymenų IL-4, IL-6, IL-8, IL-10, IFN-γ bei lastelių žymenų CD4, CD8, CD14, CD19, CD25, CD30 raišką skrandžio gleivinėje; palyginti funkcine dispepsija sergančių ligonių, gydytų augalinės kilmės antioksidanto astaksantino skirtingomis dozėmis ir placebu, skrandžio gleivinės morfologinius pokyčius; palyginti funkcine dispepsija sergančių ligonių, gydytų augalinės kilmės antioksidantu astaksantinu ir placebu, uždegimo žymenų IL-4, IL-6, IL-8, IL-10, IFN-γ bei lastelių žymenų CD4, CD8, CD14, CD19, CD25, CD30 raišką skrandžio gleivinėje. / The aim of the study was to evaluate histomorphological changes of the gastric mucosa in functional dyspepsia patients and their dynamics after treatment with the natural antioxidant astaxanthin. The following objectives were established and reached: to determine the presence of Helicobacter pylori infection and evaluate the histomorphological changes of gastric mucosa in functional dyspepsia patients; to evaluate interleukins IL-4, IL-6, IL-8, IL-10 and interferon-γ as well as the cell markers CD4, CD8, CD14, CD19, CD25 and CD30 in functional dyspepsia patients; to evaluate histomorphological changes of the gastric mucosa in functional dyspepsia patients after treatment with the natural antioxidant astaxanthin; to evaluate interleukins IL-4, IL-6, IL-8, IL-10 and interferon-γ as well as the cell markers CD4, CD8, CD14, CD19, CD25 and CD30 in functional dyspepsia patients and their dynamics after treatment with the natural antioxidant astaxanthin.

Introdução: Define-se dispepsia funcional (DF) por dor ou desconforto centrado no abdômen superior, na ausência de lesões estruturais que expliquem os sintomas. Apesar de muito prevalente, a DF permanece sendo uma entidade de difícil estudo, pela falta de ferramentas adequadas para mensuração de desfechos significativos. Isto acontece porque a DF não possui um substrato anatômico ou fisiopatológico mensurável, e, portanto, torna-se obrigatória a valorização de aspectos subjetivos para se quantificar benefícios de intervenções terapêuticas. Objetivo: Validar o Questionário Diagnóstico de Roma III para Dispepsia Funcional na língua portuguesa. Métodos: O questionário foi traduzido seguindo as recomendações do Grupo de Roma. O grupo de casos foi formado por 109 pacientes consecutivos com DF, que responderam o questionário em 4 momentos diferentes. Já o grupo de controles, foi composto por 100 doadores de sangue consecutivos, sem relato de sintomas digestivos. As seguintes propriedades clinimétricas foram avaliadas: consistência interna (através do alfa de Cronbach), reprodutibilidade, responsividade (através do X² de McNemar), validade discriminante (através do X² de Pearson), validade de conteúdo. Resultados: O Coeficiente alfa de Cronbach foi de 0,92. O questionário mostrou-se reprodutível, indicando que os pacientes responderam de maneira parecida nos dois momentos em que o questionário foi aplicado, a discordância entre as respostas não foi significativa (p=1,00). O questionário foi capaz de identificar alterações quando elas ocorreram, de maneira significativa (p<0,01). Os dois gastroenterologistas “cegos” concordaram que o questionário avalia DF. Quando comparamos as respostas dos casos com os controles (pareados por sexo e idade) o questionário indicou que 5,3% dos controles tinha DF, contra 91,2% dos pacientes, uma diferença significativa (p<0,01). Conclusão: O Questionário Diagnóstico de Roma III para Dispepsia Funcional está pronto para ser utilizado em estudos na língua portuguesa, tendo sido validado com sucesso. / Background: Validated questionnaires are essential tools to be utilized in epidemiological research. At the moment there are no Rome III diagnostic questionnaires translated to Portuguese. Aim: To validate the Portuguese version of the Rome III Diagnostic Questionnaire for Functional Dyspepsia (FD). Methods: The questionnaire has been translated following the Rome III recommendations. A hundred and nine consecutive patients with FD answered the questionnaire. The control group comprised 100 healthy consecutive blood donors, without digestive symptoms. Internal consistency, reproducibility, responsiveness, discriminant validity and content analysis were evaluated. Results: Cronbach‟s α coefficient was 0.92. The questionnaire showed reliability: the patients answered it in a similar way on two distinct occasions and their responses were substantially very similar (p=1.00). The questionnaire was able to demonstrate changes when they occur (p<0,01). Two “blinded” gastroenterologists agreed that the questionnaire adequately evaluated FD. When we compared the answers between patients and controls, the questionnaire showed that 5,3% of controls had FD symptoms compared with 91,2% of the patients (p<0,01). Conclusion: The Rome III Diagnostic Questionnaire for FD is ready to be used in clinical researches in Portuguese, as it has been successfully validated in Portuguese.

Submitted by GABRIELA NASCIMENTO HERCOS (ghercos@hotmail.com) on 2018-07-30T13:42:48Z No. of bitstreams: 1 WLT DISSERTAÇÃO FINAL PARA REPOSITÓRIO.pdf: 2479083 bytes, checksum: cd2c2572fc69fad4a63148cf6359bebc (MD5) / Approved for entry into archive by Sulamita Selma C Colnago null (sulamita@btu.unesp.br) on 2018-07-31T12:42:04Z (GMT) No. of bitstreams: 1 hercos_gn_me_bot.pdf: 2479083 bytes, checksum: cd2c2572fc69fad4a63148cf6359bebc (MD5) / Made available in DSpace on 2018-07-31T12:42:04Z (GMT). No. of bitstreams: 1 hercos_gn_me_bot.pdf: 2479083 bytes, checksum: cd2c2572fc69fad4a63148cf6359bebc (MD5) Previous issue date: 2018-07-25 / Hercos GN. Aplicabilidade clínica do teste de sobrecarga de água em crianças com dor abdominal crônica e dispepsia. [Dissertação]. Botucatu: Hospital das Clínicas da Faculdade de Medicina de Botucatu:- Universidade Estadual Paulista UNESP, 2018. Introdução. A ingestão está associada a mudanças no controle motor gástrico, como o armazenamento inicial da refeição, através do reflexo da acomodação gástrica, seguido de esvaziamento a uma taxa que corresponde à capacidade de absorção do intestino delgado. Alteração nos receptores sensoriais ou na função da via neural pode resultar em maior sensibilidade visceral, podendo resultar em dor. O Teste de Sobrecarga de Água é proposto para avaliar a acomodação e a sensibilidade visceral. O objetivo do estudo foi: determinar a aplicabilidade do teste de sobrecarga de água como um instrumento na investigação de crianças com Dor Abdominal Crônica, avaliando se seria discriminatório para crianças com dor de origem orgânica ou funcional e com e sem dispepsia. Métodos. Estudo prospectivo, transversal de pacientes com Dor Abdominal Crônica. Critérios de Inclusão: idade de 7 a 15 anos; Dor Abdominal Crônica conforme critérios de Apley; diagnóstico de Dor Abdominal Crônica Funcional segundo Critérios de Roma IV; diagnóstico Dor Abdominal Crônica de etiologia orgânica realizado de acordo com os métodos e critérios padrões utilizados na pratica clínica. Critérios de exclusão foram: doença crônica genética, neurológica, metabólica, renal, hepática, infecciosa, hematológica, cardiovascular, ou doença pulmonar, história de hemorragia gastrintestinal prévia ou cirurgia abdominal. Procedimentos: durante a primeira consulta foram coletados dados clínicos, antropométricos. Na segunda consulta foi realizado o Teste de Sobrecarga de Água e a aplicação de um Escore Clínico de Sintomas Dispépticos durante e após o teste. Todos os dados foram compilados utilizando-se o programa estatístico GraphPad Prism versão 7.00. Os testes estatísticos foram bicaudais e o nível de significância considerado em p <0,05. Resultados: Foram avaliadas 83 crianças com DAC, sendo 55 com DAC Funcional e 28 com DAC Orgânica (44 do subgrupo Dispepsia, dos quais 18 com Dispepsia Funcional e 26 com Dispepsia Orgânica). Não houve diferença estatisticamente significativa quanto as variáveis antropométricas entre os subgrupos de DAC. O Escore Clínico de Sintomas Dispépticos foi significativamente maior no subgrupo DAC Orgânica e no subgrupo Dispepsia. Não houve diferença no Volume Máximo Tolerado entre os diferentes subgrupos de DAC. Crianças maiores de 10 anos e do sexo masculino toleraram volume maior de água. Houve correlação positiva entre Volume Máximo Tolerado e Escore Clínico de Sintomas Dispépticos no subgrupo Não Dispepsia 30 minutos após o teste. Observou- se correlação positiva entre Volume Máximo Tolerado e o peso, estatura e IMC para os diferentes subgrupos. Discussão e conclusão: o teste de Sobrecarga de Água não mostrou poder discriminatório entre os diferentes subtipos de DAC. Provavelmente a não inibição do esvaziamento gástrico com refeição teste com água tenha impedido a retenção adequada para desencadear um defeito na acomodação gástrica. Palavras chave: Teste de Sobrecarga de Água; Dor Abdominal Crônica; Dispepsia; Criança / Introduction. Ingestion is associated with changes in gastric motor control, such as primary storage of the meal through the reflex of gastric accommodation, followed by emptying at a rate that corresponds to the absorption capacity of the small intestine. Alteration in sensory receptors or neural pathway function may result in increased visceral sensitivity and may result in pain. The Water Load Test (WLT) is proposed to assess gastric accommodation and visceral sensitivity. Objective: to determine the applicability of the WLT as an instrument for the investigation children with Chronic Abdominal Pain (CAP), evaluating whether it would be discriminatory for children with the pain of organic or functional origin and with and without dyspepsia. Methods. Prospective, cross-sectional study of patients with CAP. Inclusion Criteria: age between 7-15 years; CAP according to Apley criteria; diagnosis of Functional Abdominal Pain according to Rome IV Criteria; diagnosis of organic CAP performed according to the standard methods and approaches used in clinical practice. Exclusion criteria: chronic genetic, neurological, metabolic, renal, hepatic, infectious, hematological, cardiovascular or pulmonary disease, history of previous gastrointestinal bleeding or abdominal surgery. Procedures: During the first visit, clinical and anthropometric data were collected. During the second visit, the WLT and the Clinical Dyspepsia Symptoms Score were performed during and after the test. All data were compiled using the statistical program GraphPad Prism version 7.00. The statistical tests were two-tailed and the level of significance considered at p <0.05. Results: 83 children with CAP were evaluated, 55 with functional CAP and 28 with organic CAP (44 dyspepsia, of which 18 with functional and 26 with organic dyspepsia). There was no statistical difference in the anthropometric variables between the subgroups of CAP. The Clinical Dyspepsia Symptoms Score was significantly higher in the CAP Organic and Dyspepsia subgroup. There was no difference in Maximum Tolerated Volume (MTV) between the different subgroups of CAP. Children older than ten years and males had more MTV. There was a positive correlation between MTV and Clinical Dyspepsia Symptoms Score in the No Dyspepsia subgroup 30 minutes after the test. There was a positive correlation between MTV and weight, height and BMI for the different subgroups. Discussion and conclusion: WLT did not show discriminatory power between the different subtypes of CAP. Probably not inhibiting gastric emptying with a test meal with water has prevented adequate retention to trigger a defect in gastric accommodation. Keywords: Water Load test; Chronic abdominal pain; Dyspepsia; Children.

Não existem instrumentos validados para o português do Brasil que avaliem a qualidade de vida relacionada à saúde (QVRS) em dispepsia funcional (DF). Esse tipo de avaliação tem se tornado cada vez mais importante para análise do desfecho de ensaios clínicos e para o desenvolvimento de pesquisas transculturais em pacientes dispépticos funcionais. Objetivo: traduzir e validar o questionário doença-específico de QVRS “Patient Assessment of Upper Gastrointestinal Disorders – Quality of Life (PAGI-QOL)” em DF. Metodologia: estudo transversal para validação. Após adequado processo de tradução, 5 testes psicométricos foram realizados. Para cada teste um número variável de pessoas foi avaliado, considerando cálculo amostral: consistência interna (n=150 casos e 150 controles), reprodutibilidade (n=44 casos), a validade de conteúdo contou com a participação de 3 gastroenterologistas experientes em distúrbios funcionais “cegos” para o estudo; validade de critério (n=113 casos) e validade discriminante (n=86 casos e 86 controles). Grupo de casos: pacientes dispépticos funcionais diagnosticados segundo Critério de Roma III. Grupo controle: doadores de sangue que não apresentavam sintomas gastrointestinais e outras co-morbidades clinicamente relevantes. Amostras foram coletadas por conveniência e consecutivamente e completaram os questionários PAGI-QOL e SF-36 versão 2. O estudo foi aprovado pelo Comitê de Ética em Pesquisa. Consentimento informado foi assinado por todos os indivíduos. Resultados: consistência interna: 0,976 (α de Cronbach); reprodutibilidade dos escores totais: 0,841 (coeficiente de correlação intra-classe); e valor p = 0,331 para diferença entre as duas observações; validade de critério entre o escore total do PAGI-QOL e os escores dos componentes físicos e mentais do SF-36 versão 2: rs = -0,289 (p = 0,002) e rs = -0,437 (p <0,001), respectivamente; validade discriminante para todos os domínios: p<0,0001 (Mann-Whitney). Validade de conteúdo foi adequada. Conclusão: O PAGI-QOL em português do Brasil é um questionário válido e confiável para avaliar a QVRS em DF. / There are no validated instruments to Brazilian Portuguese to assess health related quality of life (HRQoL) in functional dyspepsia (FD). This type of assessment has become increasingly important with the objective of evaluating outcomes in clinical trials and development of cross-cultural research in FD patients. Objective: To translate and validate the HRQOL disease-specific questionnaire "Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QoL)" in FD. Methodology: cross sectional study for validation. After an adequate the translation process, 5 psychometric tests were performed. For each of them a variable number of individuals were assessed, considering sample size calculation: internal consistency (n = 150 patients and 150 controls), reproducibility (n = 44 patients), content validity with the participation of 3 gastroenterologists experienced in functional gastrointestinal disorders, blinded to the study; concurrent validity = n = 113 patients and discriminant validity = 86 patients and 86 controls. FD patients: diagnosed according to Rome III criteria. Control group: blood donors who had no gastrointestinal symptoms and no other clinically relevant co-morbidities. Both samples were collected by convenience and consecutively, and completed questionnaires PAGI-QoL and SF-36 version 2. The study was approved by the Institutional Research Ethics Committee. Informed consent form was signed by all individuals. Results: Internal consistency: 0.976 (Cronbach's α), reproducibility of total scores: 0.841 (correlation coefficient of intra-class) and p value = 0.331 for differences between the two observations; concurrent validity between the total score of the PAGI-QOL and the scores of physical and mental components of SF-36 version 2: rs = -0,289 (p = 0.002) and rs = -0,437 (p <0.001), respectively; discriminant validity for all domains: p <0.0001 (Mann-Whitney). Content validity was adequate. Conclusion: The PAGI-QoL in Brazilian Portuguese language is a valid and reliable questionnaire to assess HRQoL in FD.

Introdução: A metaplasia intestinal (MI) do estômago é uma lesão onde ocorre a metaplasia das células epiteliais gástricas para um fenótipo intestinal. A MI gástrica é considerada uma lesão preneoplásica associada a um aumento do risco de desenvolvimento de carcinoma gástrico. Estudos epidemiológicos indicam uma relação entre hábitos alimentares e o risco de desenvolvimento de câncer de estômago: tanto podendo ter um efeito carcinogênico gástrico, como um fator protetor, sugerindo que os antioxidantes como as vitaminas A, C e E, diminuem o risco desse tipo de câncer Material e métodos: Trata-se de um estudo caso-controle, observacional, para o qual foram avaliados 320 pacientes portadores de dispepsia funcional, que separados em dois grupos, um grupo de casos I (indivíduos com metaplasia intestinal) tiveram seus hábitos alimentares comparado aos do grupo de casos controle (sem metaplasia intestinal), através de um questionário de frequência de consumo alimentar (QFCA). Resultados: Ao analisarmos o padrão alimentar dos pacientes dispépticos funcionais portadores de metaplasia intestinal e compará-lo com o padrão daqueles que não possuem MI constatou-se que os pacientes portadores de MI consomem mais alimentos como os enlatados e defumados, enquanto que os pacientes sem metaplasia intestinal apresentam um consumo expressivamente maior de frutas em geral e vegetais. Diferença no padrão de consumo de sal não foi identificada. Conclusões: Através dos resultados obtidos no presente estudo podemos supor que a modificação da dieta, por meio de uma diminuição na ingestão de alimentos como defumados e enlatados e um acréscimo na ingestão de frutas e vegetais, pode levar a uma diminuição de casos de metaplasia intestinal. / Introduction: Intestinal metaplasia (IM) of the stomach is a lesion in which metaplasia of gastric epithelial cells occurs for an intestinal phenotype. Gastric IM is considered a preneoplastic lesion associated with an increase in the risk of gastric carcinoma development. Epidemiologic studies indicate a relation between dietary habits and stomach cancer development, some habits increasing the risk for it, and others have a protective effect, suggesting that antioxidants, such as vitamins A, C, and E, decrease the risk of this type of cancer. Materials and methods: It is a case-control, observational study in which 320 patients with functional dyspepsia, divided in two groups, were assessed. The case I group (individuals with intestinal metaplasia) had their dietary pattern compared to that of the control group, constituted of individuals similar to those in the case group but without intestinal metaplasia, through a food frequency questionnaire (FFQ). Results: The analysis of the dietary pattern of functional dyspeptic patients with intestinal metaplasia, and its comparison with those without IM, showed a higher frequency of canned and smoked foods consumption in the first group, and, on the other hand, a higher consumption of fruits and vegetables in patients without IM. No effect of salt consumption was detected. Conclusions: The results obtained in this study suggest changes in the diet, with a decrease in the consumption of smoked and canned foods, and an increase in the consumption of fruits and vegetables, can lead to a diminution of intestinal metaplasia cases.

Introdução: Dispepsia funcional é uma doença que possui critérios diagnósticos definidos por reuniões de consenso, conhecidos por critérios de Roma. Apresenta alta prevalência mundial, grande impacto social e redução na qualidade de vida do indivíduo. Helicobacter pylori está envolvida na patogênese da dispepsia funcional, sendo indicada sua detecção e erradicação no tratamento dos pacientes dispépticos funcionais. H. pylori também tem sido sugerida como um importante agente na etiologia de níveis baixos de Vitamina B12 no soro. A hiperhomocisteinemia secundária à deficiência de Vitamina B12 e folato podem constituir um risco para as doenças cardiovasculares. Objetivo: investigar a relação entre os níveis séricos de Vitamina B12, folato e homocisteína e infecção pelo H. pylori em pacientes dispépticos funcionais. Métodos: Foram incluídos pacientes dispépticos funcionais, pelos critérios de Roma III do estudo HEROES (Helicobacter Eradication Relief of Dyspeptic Symptoms) - ClinicalTrials.gov número NCT00404534. Os pacientes dispépticos que apresentaram positividade para H. pylori foram randomizados para erradicação da bactéria com antibiticoterapia oral ou placebo. Após doze meses realizaram o segundo exame endoscópico com mesma metodologia. Da amostra total, 77 continuaram positivos para a infecação por H. pylori e 77 tiveram como resultado a erradicação da bactéria H. pylori, ou seja, negativaram. O material biológico foi previamente coletado e armazenado, além dos respectivos dados demográficos e clínicos. As amostras foram armazenadas a -80◦C em ependorf e realizadas medidas em soro dos níveis de vitamina B12 e folato e homocisteína. Resultados: Da amostra total, 77 pacientes eram H. pylori positivo (15 homens e 62 mulheres) e 77 eram H.pylori erradicados (21 homens e 56 mulheres). A média de idade foi de 47,8±11,5, em relação à idade e gênero não houve diferença significativa entre os grupos (p > 0,05). Quanto aos resultados reunidos em categorias (níveis de vitamina B12, folato e homocisteína), conforme os pontos de corte usados na literatura, não foi observada diferença estatisticamente significativa entre os dois grupos de pacientes (p > 0,6). Não houve correlação entre idade e níveis de vitamina B12 (p = 0,924). Houve diferença entre gêneros para homocisteína (p = 0,035), porém não houve significância para vitamina B12 (p = 0,584) e folato (p = 0,312). Não houve diferença entre níveis de homocisteína de pacientes H. pylori positivos e H. pylori erradicados para ambos os gêneros (p > 0,5). Conclusões: O presente estudo demonstrou que não houve relação significativa entre os níveis séricos de Vitamina B12, folato e homocisteína e infecção por H. pylori em relação aos H. pylori erradicados nos dispépticos funcionais. E quanto aos níveis de homocisteína comparados entre gêneros, os valores foram mais altos em homens. / Introduction: Functional dyspepsia a disease which has diagnosis criteria defined by consensus gatherings, known as the Rome criteria. It is highly prevalent worldwide, has great social impact, and reduces the quality of life of individuals. Helicobacter pylori is involved in the pathogenesis of functional dyspepsia, and its detection and eradication are indicated in the treatment of functional dyspepsia patients. H. pylori has also been suggested as an important agent in the etiology of low levels of vitamin B12 in serum. A hyperhomocysteinemia secondary to vitamin B12 and folate deficiencies could pose a risk for cardiovascular diseases. Objective: To investigate the relationship among the serum levels of Vitamin B12, folate and homocysteine, and the H. pylori infection in functional dyspeptic patients. Methodology: A group of patients with functional dyspepsia was included, following the Rome III criteria from the study HEROES (Helicobacter Eradication Relief of Dyspeptic Symptoms) – ClinicalTrials.gov number NCT00404534. The dyspeptic patients who were positive for H. pylori in tissue biopsy were randomized to eradication of the bacteria with oral antibiotic therapy or placebo. After twelve months, a second endoscopy was performed with the same methodology. Of the total sample, 77 patients remained positive for H. pylori and 77 patients had as a result the eradication of H. pylori bacteria, that is, they became negative. The biological material was previously collected and stored, besides its demographic and clinical data. The samples were stored at -80◦C in Eppendorf, they were measured in the serum of vitamin B12 folate and homocysteine levels. Results: Of the total sample, 77 patients were positive for H. pylori (15 men, 62 women) and 77 patients had the eradication of H. pylori (21 men, 56 women). The average age of the sample was about 47,8±11,5,regarding age and gender, it was not observed significant difference between the groups (p > 0,05). Concerning the results gathered into categories (the levels of vitamin B12, folate, and homocysteine), as the cut off points used in the literature, it was not observed statistically significant difference between the two groups of patients (p > 0,6). There was no correlation between age and vitamin B12 levels (p = 0,924). There was difference between genders for homocysteine (p = 0,035), but there was no significant difference for vitamin B12 (p = 0,584) and folate (p = 0,312). There was no difference between homocysteine levels of positive patients for H. pylori and H. pylori eradication in both genders (p > 0.5). Conclusions: The study showed no significant relationship between the serum levels of vitamin B12, folate, and homocysteine and the H. pylori infection in relation to H. pylori eradication in functional dyspeptic patients. Regarding homocysteine levels compared between genders, the values were higher in men.

Introdução: Recentemente, vários estudos têm investigado e até mesmo sugerindo a bactéria Helicobacter pylori como um importante componente no desenvolvimento de eventos restritos ou não ao trato gastrintestinal. A relação já bastante elucidada acerca da relação entre os fatores bacterianos de virulência e o risco aumentado para úlcera péptica e adenocarcinoma gástrico parece não estar muito definida em se tratando de alterações em marcadores de inflamação aguda, como a proteína C reativa (PCR), em indivíduos infectados pelas cepas mais virulentas do microrganismo. Neste trabalho, nós avaliamos a presença de H. pylori, virulência bacteriana e níveis séricos de PCR em pacientes dispépticos funcionais. Materiais e métodos: Estudo transversal que incluiu 489 indivíduos saudáveis com diagnóstico de dispepsia funcional firmado através de critérios do Consenso de Roma III. Após avaliação clínica e endoscópica, os pacientes foram incluídos por não apresentarem qualquer causa orgânica que pudesse estar relacionada aos sintomas de dispepsia. A presença da bactéria foi diagnosticada através de análise histológica e teste rápido da urease dos fragmentos biopsiados. Os níveis séricos de PCR foram obtidos por imunonefelometria e o status para o fator de virulência CagA foi determinado através de ensaio comercial imunoenzimático. Resultados: A prevalência de H. pylori foi de 66,3% e a presença de anticorpos anti-CagA foi detectada em aproximadamente 43% das amostras positivas. Houve uma associação estatisticamente significativa entre o consumo de chimarrão e a presença da bactéria. Observou-se um efeito importante da infecção por H. pylori na inflamação local, estimada através da atividade inflamatória e grau de inflamação do epitélio gástrico. Não foi constatada resposta inflamatória sistêmica ao patógeno através da dosagem de PCR, independente do status de virulência bacteriana. Conclusão: Na população de indivíduos disépticos funcionais avaliada, a bactéria parece não desencadear qualquer resposta inflamatória sistêmica, estando a virulência bacteriana associada a um maior grau e atividade inflamatória do epitélio gástrico. / Background: Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C reactive protein (CRP), with the pathogen. We evaluated the presence of H. pylori, bacterial virulence and CRP serum levels in individuals diagnosed with functional dyspepsia. Materials and Methods: Transversal study that evaluated 489 healthy individuals well characterized according to Rome III Consensus for the diagnosis of functional dyspepsia. The study population underwent to an endoscopic investigation and did not present any organic explanation for their symptoms. The bacterial infection was established by histology and urease rapid test. The levels of serum CRP were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined trough a commercial imunoenzimatic assay. Results: Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. We found a statistically significant relationship between yerba mate tea consumption and positive H. pylori status. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. No systemic response to the pathogen, measured through CRP levels, was observed, regardless of CagA status. Conclusion: In our study population, the presence of H. pylori seems not to be related with any important systemic inflammatory response. Bacterial virulence was related to a higher inflammation and inflammatory activity in gastric epithelium.

Introdução e objetivos: Eosinofilia duodenal está associada com parasitoses intestinais e com alergias alimentares, e tem sido sugerida como possível fator etiológico da dispepsia funcional, pela capacidade de causar alterações na motilidade e na sensibilidade do aparelho digestivo. Sua relação com o Helicobacter pylori é pouco conhecida, tendo sido avaliada apenas como achado secundário em alguns estudos, com resultados controversos. Esse estudo tem como objetivos avaliar o papel da infecção gástrica pelo H. pylori no número de eosinófilos duodenais e avaliar a relação dos eosinófilos duodenais com os sintomas da dispepsia funcional. Métodos: foram avaliados 100 pacientes dispépticos funcionais, de acordo com os critérios de Roma III, dos quais 50 foram H. pylori positivos e 50 negativos. Os pacientes foram submetidos à endoscopia digestiva alta com biópsias gástricas e duodenais. A positividade do H. pylori foi avaliada pelo teste de urease e pelo exame histológico (Hematoxilina-eosina e Giemsa). As biópsias duodenais foram avaliadas com hematoxilina-eosina e a número de eosinófilos duodenais foi quantificada pela média de eosinófilos por 5 campos de grande aumento (CGA) aleatórios e não sobrepostos. Eosinofilia duodenal foi definida pela presença de >22 eosinófilos/CGA. As medianas das médias aritméticas dos eosinófilos duodenais por cinco CGA foram comparadas entre os pacientes H. pylori positivos e negativos. Também foi avaliada a relação do número de eosinófilos duodenais com a intensidade e tipo de sintomas dispépticos, determinados por questionário validado (PADYQ). Os eosinófilos duodenais foram avaliados para variáveis demográficas e endoscópicas. Resultados: Pacientes do sexo feminino representaram 88% da amostra e a idade média foi de 41,7 anos As características basais dos pacientes H. pylori positivos e H. pylori negativos foram semelhantes. Apenas um paciente, no grupo H. pylori positivo, apresentou eosinofilia duodenal. As medianas dos eosinófilos duodenais/CGA foram 4,6 [P25-75: 2,8-7,2] nos pacientes H. pylori negativos e 4,7 [P25-75: 3,4-8,4] nos H. pylori positivos (p= 0,403). O número de eosinófilos 8 duodenais foi significativamente maior em pacientes com sintomas mais intensos: pacientes com escore do PADYQ >22 (>50% da pontuação máxima) apresentaram mediana de eosinófilos duodenais/CGA de 5,4 [P25-75: 3,4–7,6] e pacientes com escore ≤22 de 3,4 [P25-75: 2,2–6,0] (p= 0,018). Os pacientes foram divididos em tercis, de acordo com a intensidade dos sintomas: grupo 1 com 31 pacientes (sintomas leves); grupo 2 com 30 pacientes (sintomas moderados); e grupo 3 com 31 pacientes (sintomas acentuados). A mediana dos eosinófilos duodenais/CGA no grupo 1 foi de 3,4 [P25-75: 2,2 -6,0]; no grupo 2 de 4,7 [P25-75: 3,2-6,4]; e o grupo 3 de 5,8 [P25-75: 3,6-8,2] (P=0,033). Houve diferença estatisticamente significativa no número de eosinófilos duodenais entre fumantes e não fumantes (p= 0,030) e entre pacientes com índice de massa corporal (IMC) <25 kg/m2 e IMC ≥ 25 kg/m2 (p= 0,035). Na análise multivariada por regressão linear, os fatores que tiveram influência sobre o número de eosinófilos duodenais foram o tabagismo (p= 0,026) e a intensidade dos sintomas dispépticos (p= 0,039). Conclusões: Esse estudo não mostrou associação entre a infecção pelo H. pylori e a contagem de eosinófilos duodenais, nessa população de pacientes dispépticos funcionais. Entretanto, foi demonstrada uma relação diretamente proporcional e estatisticamente significativa entre o número de eosinófilos duodenais e a intensidade dos sintomas dispépticos. / Background and Aims: Duodenal eosinophilia is associated with intestinal parasitosis and food allergies. It has also been implicated as a potential factor on the etiology of functional dyspepsia, probably by causing changes in digestive tract motility and sensitivity. The association with Helicobacter pylori is poorly understood, and has been only evaluated as a secondary finding in 9 previous studies, with conflicting results. This study aims to evaluate the potential role of gastric H. pylori infection in the duodenal eosinophil count, and the influence of duodenal eosinophils on symptoms in functional dyspeptic subjects. Methods: One hundred functional dyspeptic subjects, according to Rome III criteria, were evaluated, and 50 were H. pylori positive and 50 H. pylori negative. Patients were submitted to upper gastrointestinal endoscopy with gastric and duodenal biopsies. H. pylori positivity was evaluated by urease test and gastric histology (Hematoxylin-eosin and Giemsa). Duodenal biopsies were evaluated with Hematoxylin-Eosin staining, and the duodenal eosinophil count was determined by the mean of eosinophil by 5 random nonoverlapping high power fields (HPF). Duodenal eosinophilia was defined as >22 eosinophils/HPF. The median of the arithmetic means of the duodenal eosinophils counts per high power field were compared between H. pylori positive and H. pylori negative subjects. The relationship between the number of duodenal eosinophils and the intensity and type of dyspeptic symptoms was determined by validated questionnaire (PADYQ). Duodenal eosinophils counts were also evaluated by demographic variables and endoscopic findings. Results: 88% of the subjects were female and the mean age was 41.7 years. Baseline characteristics were similar between H. pylori positive and H. pylori negative subjects. Only one patient, in the H. pylori positive group, had duodenal eosinophilia. The median duodenal eosinophils/HPF were 4.6 [Percentiles 25-75(P25-75): 2.8-7.2] in H. pylori negative and 4.7 [P25-75: 3.4-8.4] in H. pylori positive subjects (p= 0.403). The duodenal eosinophil count was greater in subjects with higher symptoms severity: patients with PADYQ score more than 22 (>50% of the maximum score) had median duodenal eosinophil/HPF of 5.4 [P25-75: 3,4–7,6] and subjects with PADYQ score ≤22 of 3.4 [P25-75: 2.2–6.0] (p= 0.018). The patients were divided into terciles, according to symptoms severity: group 1 with 31 subjects (mild symptoms); group 2 with 30 subjects (moderate symptoms); and group 3 with 31 subjects (severe symptoms). 10 The median duodenal eosinophils/HPF was 3.4 [P25-75: 2.2-6.0] in group 1; 4.7 [P25-75: 3.2-6.4] in group 2; and 5.8 [P25-75: 3.6-8.2] in group 3 (p=0.033). There was a higher duodenal eosinophils count in smokers (current or former) (p=0.030), and subjects with BMI ≥ 25 kg/m2 (p=0.035). In the multivariate analysis by linear regression, the duodenal eosinophil count were influenced by smoking (p = 0.026) and dyspeptic symptoms severity (p= 0.039). Conclusion: This study did not show an association between H. pylori infection and the number of duodenal eosinophils, in this population of functional dyspeptic patients. However, a directly proportional and statistically significant relationship between the number of duodenal eosinophils and the intensity of dyspeptic symptoms has been demonstrated.