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Cancer treatments including chemotherapy and radiotherapy treat cancer by targeting rapidly dividing cells. Although these forms of treatment damage rapidly dividing cancer cells, they are also toxic to the cells of the gastrointestinal tract, leading to inflammation of the mucosal layer (mucositis) and causing nausea, vomiting, diarrhea, and abdominal pain. Improvement in symptoms may allow patients to have better performance status permitting ongoing treatment and possibly a better prognosis. This article describes the pathophysiology of chemotherapy-induced mucositis and includes 3 case reports of treatment of mucositis with serum bovine immunoglobulin.

博士(心理学) / Doctor of Philosophy in Psychology / 同志社大学 / Doshisha University

<p>Stress is known to play an important role in the natural history of gastrointestinal diseases, and functional disorders in particular. In health, activation of the stress response serves to maintain homeostasis in response to harmful stimuli. However, prolonged activation of the stress response can become maladaptive and contribute to the initiation and maintenance of symptoms in disorders such as irritable bowel syndrome (IBS). The mechanisms underlying this detrimental effect are unclear. This thesis investigates this relationship by examining the influence of 10 days of water avoidance stress on a murine model of acute bacterial gastroenteritis; a known trigger in a subset of IBS patients. Results indicate that stress can increase the level of the stress hormone norepinephrine in the gut. However, the overall influence of host stress during infection proves to be beneficial in this model, with decreased colonic inflammation and earlier clearance of the pathogen. Next, we utilized the olfactory bulbectomy (OBx) model of depression comorbid anxiety, which shows a heightened stress response, to examine mechanism underlying stress-mediated susceptibility in a more chronic setting. OBx resulted in increased neural activity and motility in the gut, and a change in composition of gut microbiota. These responses were not accompanied by changes in gut permeability or immune activation. Thus stress alters the habitat of commensal bacteria via a neurally mediated change in colonic motility. These results have bearing on the ability of stress to alter the microbiota: a feature of functional GI disorders.</p> / Doctor of Philosophy (Medical Science)

Background: IBS is the most common functional gastrointestinal disorders and affects approximately 10-20 % of the general population and is widespread in all societies and socio-economic groups. Although the disorder does not have a life-threatening course, it still seriously affects the patients in their everyday life. Aim: The general aims of this thesis were to estimate the occurrence of irritable bowel syndrome in the general population and to achieve a better understanding of present treatment of this disorder and impact on every-day life in those suffering from IBS. Material and methods: The LIPS study comprises two parts. Part I was a retrospective register study where the data collection was based on computerised medical records at three selected Primary Health Care centres in a defined region. Part II was a population based case-control study. The identified IBS cases from part I constitute the cases, while their control groups were randomly selected from the population census register in the same area as the cases. Data in part II were collected by means of a postal questionnaire to cases and controls. The study was conducted in Linköping, a city located in the south-east of Sweden with 135 000 inhabitants. Results: The female IBS patients reported lower influence on planning their work and working hours as well as fewer opportunities to learn new things at their work compared to their controls, even after adjustments in multiple logistic regressions for potential confounders like; mood, sleeping problems and perceived health. The female IBS patients had considerably lower HRQOL in all dimensions compared to their controls, even when compared to male patients. Younger female IBS cases (18-44 years) reported lower mental health on the SF-36 scale than the older IBS female cases (p=0.015). In the multivariate analysis these variables, lack of influence on planning the work, family history of IBS, anxiety and sleeping disturbance displayed an association with being diagnosed with IBS in women. In men, lack of influence on working pace, family history of IBS was associated with an IBS diagnosis.The consultation incidence of IBS in part I was 3.4 (95% CI 3.20-3.70) per 1000 person-years for all IBS cases, among females; the incidence rate was 4.6 per 1000 person-years (95% CI 4.16-4.97) and males; 2.3 per 1000 person-years (95% CI 2.01-2.59). The dominating pharmacological treatment prescribed for abdominal complaints were fibre and bulking laxatives agents as well as acid suppressive drugs. These variables had an independent impact on the probability of a follow-up consultation; diagnosed co-morbidity besides the IBS diagnosis, rectoscopy ordered and laboratory tests ordered. Conclusions: IBS patients identified in primary care are significantly affected in their working-life compared to individuals in the general population. Especially female IBS-patients report lower decision latitude at work and they also appear to have a particularly impaired psychosocial functioning in their every day life and impaired HRQOL. Factors associated with IBS diagnosis among females are anxiety as well as family history of IBS and lack of co-determination at work. The incidence rate of IBS was 3.4 per 1000 person-years which increased with age and with an overrepresentation of females. IBS patients did not appear to be heavy utilisers of primary care and those who attended were treated by their GP without further consultation. The strongest predictors for having a follow-up consultation were diagnosed co-morbidity, rectoscopy and laboratory tests ordered / Figure on page 8 reprinted from Lancet 360(9332), Nicholas, J Talley and Robin Spiller, "Irritable bowel syndrome: a little understood organic bowel disease?", pp. 555-564, Copyright 2006 with permission from Elsevier. On the day of the public defence of the doctoral thesis, the status of articles III and IV was Submitted.

Within this thesis the role of cognitive processes in irritable bowel syndrome (IBS) will be examined. A systematic review and meta-analysis of the rate of psychiatric comorbidity in IBS participants, relative to controls, was performed. Evidence supported heightened rates of psychiatric disorder. A novel hypothesis regarding overlapping cognitive vulnerability to IBS and psychiatric disorders was found to fit well with the pattern of comorbidity. Competing hypotheses and the potential moderators were examined. Overall, no single model of psychiatric morbidity in IBS could fully account for the results of the meta-analysis. The implications of this meta-analysis for a cognitive approach to IBS are discussed. Cognitive processes were directly investigated in two experiments. First, in a modified exogenous cueing task, which assessed attention to pain words, there was faster orienting towards, and engagement with pain words in IBS participants relative to controls. Next, participants completed a primed lexical decision task, which indexed interpretation biases by measuring response times to targets after ambiguous illness primes. Relative to controls, IBS participants’ responses were slower to target words presented after ambiguous illness primes, and demonstrated priming for targets related to the neutral meaning of the illness prime. In the second study, different IBS and healthy control participants completed an internet-based survey of autobiographical memory. Participants described and rated painful and emotional autobiographical events. IBS participants reported pain memories from a more observer perspective relative to controls, suggesting a possible coping strategy for pain content. Finally, three cognitive styles, alexithymia, rumination and self-blame, were evaluated using existing and novel self-report measures. Overall, when compared with healthy participants, IBS participants reported: less difficulty identifying feelings as indexed by the alexithymia measure; increased pain-focused rumination; and a general, negative self-blame. These results may imply a vigilance-avoidance model of cognitive processing in IBS.

Les bénéfices attribués aux probiotiques sont nombreux : effets bénéfiques sur le microbiote intestinal, confort digestif, modulation du système immunitaire et prévention des infections intestinales. Ces effets divers et variés sont souches-spécifiques. Actuellement, de nombreuses études visent à mieux caractériser ces effets probiotiques.Ces travaux avaient pour objectif de déterminer et d’analyser les effets probiotiques de trois souches de la collection Danone : la souche de Lactobacillus paracasei CNCM I-3689, la souche de L. rhamnosus CNCM I-3690 ainsi que la souche de Bifidobacterium animalis subps. lactis CNCM I-2494. Dans un premier temps, leurs effets ont été caractérisés dans des modèles in vitro pour des propriétés anti-pathogènes, des propriétés d’immuno-modulation ainsi que pour des propriétés de protection de la barrière épithéliale intestinale. Dans un second temps, leurs effets de la protection de la barrière ont été confirmés dans un modèle murin de faible inflammation.Une analyse des mécanismes sous-jacents à ces effets à la fois chez la souche probiotique et chez l’hôte a été initiée par la construction et l’analyse fonctionnelle de banques génomiques bactériennes ainsi que par l’étude de la modulation des gènes impliqués dans le maintien de la barrière intestinale chez l’hôte. / Health benefits of probiotic bacteria are numerous: beneficial effects on the intestinal microbiota, digestive comfort, modulation of the immune system and prevention of winter infection. These diverse and various effects are strain-specific. Nowadays, numerous studies aim at better characterizing those probiotics effects.This project aimed at identifying and analyzing the probiotic effects of three strains from Danone collection: Lactobacillus paracasei CNCM I-3689, L. rhamnosus CNCM I-3690 and Bifidobacterium animalis subsp. lactis CNCM I-2494. First, their effects were assessed in in vitro models for immunomodulation properties, antipathogens activity and intestinal barrier protection. Secondly, their beneficial effects were confirmed in low-grade inflammation murine model.The analysis of the underlying mechanisms has been initiated both in the bacterial strains by the construction and the functional analysis of genomic libraries and in the host by measuring the modulation of the genes involved in the intestinal barrier maintain.

A Psicossomática se constituiu como campo de saber tendo como uma de suas principais influências as contribuições de Freud a respeito da relação entre mente e corpo. Desde Alexander até os teóricos de orientação psicanalítica mais atuais, a questão da somatização, no sentido lato, vem sendo discutida e, apesar das divergências teóricas, o que sempre está em pauta nas somatizações é o comprometimento da capacidade de simbolização do sujeito frente às vicissitudes da vida. Essa mesma característica é central nas neuroses atuais, de forma que há possível associação entre a somatização e a neurose atual. Dessa forma, os objetivos principais são verificar se esse comprometimento na capacidade de simbolização está presente e como se apresenta em sujeitos com somatização e em sujeitos com neurose atual. Para se realizar o estudo, foram eleitos dois transtornos que são representantes das categorias acima citadas: nas somatizações, vamos pensar a partir dos transtornos somatoformes, utilizando a subcategoria dos transtornos neurovegetativos somatoformes, elegendo a Síndrome do Intestino Irritável; e nas Neuroses Atuais, o Transtorno de Pânico (Neurose de Angústia). Os resultados vão permitir uma comparação, a partir da capacidade de simbolização, entre essas duas categorias e a verificação de maiores relações entre ambas, assim como relação com alexitimia, pensamento operatório e personalidade tipo A, características geralmente associadas a esses tipos de pacientes. A pesquisa foi feita a partir de estudos bibliográficos e psicodiagnóstico dos sujeitos da pesquisa, com entrevista semi-dirigida, aplicação de pranchas do TAT, escalas de alexitimia (TAS e OAS) e entrevista para Personalidade tipo A. Foram utilizados três sujeitos com Síndrome do Intestino Irritável e dois com Transtorno de Pânico. Nos sujeitos da pesquisa, quando aparece comprometimento na capacidade de simbolização, as histórias no TAT são mais curtas, descritivas, concretas, com introdução de nenhum ou poucos elementos externos à prancha, dificuldade na resolução de conflito, personagens pouco integrados, ausência de referências afetivas ou afetividade negativa, prejuízo da integração do ego, com predomínio de pensamento do tipo operatório. Pensar o comprometimento da capacidade de simbolização em pacientes com somatização a partir do pensamento operatório faz sentido, visto que os sujeitos apresentaram tal forma de pensamento, embora apresentem variações significativas na intensidade e frequência de funcionamento metal do tipo operatório. Contudo, definir o paciente com somatização ou com neurose atual necessariamente como alexitímico é insuficiente, visto que nem todos apresentaram tal característica. Pela análise de dados dos sujeitos, há pacientes os quais o comprometimento na capacidade de simbolização funciona como defesa psíquica diante da angústia, de forma a prejudicar a integração do ego em razão de manter um funcionamento mental mais estável; e há os que esse comprometimento é característico do funcionamento mental. Compreendendo o funcionamento psicológico que há por trás das somatizações o comprometimento da capacidade de simbolização e as formas como se configura na dinâmica psíquica do sujeito como defesa psíquica ou como característica do funcionamento mental pode-se estabelecer métodos de abordagens e técnicas psicoterápicas mais eficientes e condizentes com pacientes com somatizações / The Psychosomatic constituted itself as a field of knowledge has as one of his major influences the contributions of Freud on the relationship between mind and body. From Alexander to the psychoanalytic theoristis more current, the issue of somatization in the broadest sense, has been discussed and, despite the theoretical differences, is always at hand in somatization the impaired ability of symbolization of the subject facing the vicissitudes of life. This same feature is central to the actual neurosis, so that there is a possible association between somatization and actual neurosis. Thus, the main objectives are to determine if that impairment in the ability of symbolization is present and how shown in subjects with somatization and in subjects with actual neurosis. To perform the study, two disorders that are elected representatives of the categories mentioned above: in somatization, we think from the somatoform disorders, using the subcategory of somatoform autonomic dysfunction, electing the Irritable Bowel Syndrome, and in Actual Neurosis, the Panic Disorder (Anxiety Neurosis). The results will allow a comparison, from the capacity for symbolization, between these two categories and the verification of relations between the two, as well as compared with alexithymia, operational thinking and type A personality, characteristics associated with these types of patients. The survey was conducted from bibliographic studies and psychodiagnostic research subjects, with semi-directed interview, application of TAT cards scales of alexithymia (TAS and OAS) and interview for Type A Personality. We used three subjects with Irritable Bowel Syndrome and two with Panic Disorder. In the research subjects, when it appears impairment in the ability of symbolization, the TAT stories are shorter, descriptive, concrete, with few or no introduction of foreign elements to the board, difficulty in conflict resolution, low integrated characters, no references affective or negative affectivity, impaired ego integration, with a predominance of thought like operatory. Thinking the impaired ability of symbolization in patients with somatization from operational thinking makes sense, because the subjects had this way of thinking, although they have shown significant variations in intensity and frequency of operation of the metal type operatory. However, defining the patient with somatization or actual neurosis necessarily as alexithymic is insufficient, since not everyone had such a feature. For the data analysis of the subjects, there are patients who compromise the ability to symbolizing as psychic defense in the face of anguish, in order to undermine the integration of the ego to maintain a more stable mental functioning, and there are that this commitment is characteristic of mental functioning. Understanding the psychological functioning that is behind the somatization - the impaired ability of symbolization - and the ways to configure the psychic dynamics of the subject - such as defense or as a psychological characteristic of mental functioning - can establish methods of psychotherapeutic approaches and techniques more efficient and consistent with patients with somatization

Na Psicossomática, dentro do modelo biopsicossocial, entende-se que respostas psicológicas a condições de vida podem interagir com fatores somáticos existentes, alterando a susceptibilidade e manifestação da doença, o que se mostra evidente nas somatizações, como na Síndrome do Intestino Irritável (SII), onde há alteração da motilidade intestinal e no formato das fezes, acompanhada de dores abdominais. O funcionamento mental associado às somatizações, no qual a pessoa apresenta dificuldade em relacionar o adoecimento com seu universo psicológico, é que a capacidade de simbolização, ou seja, a construção de representações mentais para o alívio do estado emocional, é afetada, cronificando as alterações fisiológicas correspondentes. O objetivo da pesquisa foi verificar se o atendimento clínico psicológico, baseado na técnica da Psicoterapia Breve Operacionalizada (PBO), com ênfase na promoção da capacidade de simbolização em relação a determinadas questões significativas, pode contribuir para a melhora dos sintomas no quadro clínico de pacientes com SII. O método utilizado na pesquisa foi o clínico-qualitativo, a partir do estudo de caso de duas pacientes adultas, com o diagnóstico principal de transtorno neurovegetativo somatoforme, portadoras de SII. A intervenção psicológica foi estruturada em três fases: 1) psicodiagnóstico, composto por entrevista semi-dirigida, Sistema Diagnóstico Adaptativo Operacionalizado (SISDAO) e Teste de Apercepção Temática (TAT), questionário de avaliação clínica da SII; 2) psicoterapia breve, em doze sessões; 3) reavaliação após seis meses. A capacidade de simbolização da primeira participante era comprometida fundamentalmente relacionada à sua dificuldade em lidar com a perda da mãe quando criança, num luto não elaborado. Apresentava dores abdominais forte, a cada dois ou três dias, evacuando uma vez ao dia e quando em crise, duas ou três vezes por dia. A segunda participante apresentou uma capacidade de simbolização que passava a ser comprometida quando o conflito entre o desejo de ser aceita por sua família, em especial sua mãe, e o de rompimento tornava-se insuportável. Apresentava dores moderada, a cada cinco dias, evacuando quatro vezes ao dia e, quando em crise, seis vezes ao dia. A intervenção clinico psicológica em pacientes com SII, baseada na técnica da PBO, com elaboração da demanda psicológica e das questões significativas que comprometiam a capacidade de simbolização, possibilitou a elaboração psicológica dos estados emocionais que estariam influenciando os sintomas da SII, de forma que contribuiu para a melhora do quadro clínico das participantes. Após seis meses da psicoterapia, a primeira participante apresentou dores fracas a cada cinco dias, frequência única de evacuação por dia, não apresentou crises. A segunda participante estava evacuando uma a duas vezes por dia, dores fracas a cada cinco dias e crises ocorriam em menor frequência. O modelo de intervenção mostrou-se vantajoso para as participantes da pesquisa, de forma que seu uso no tratamento clinico psicológica para pacientes com SII, levando em consideração as especificidades do funcionamento mental associado às somatizações, apresenta-se promissor / In Psychosomatics, within the biopsychosocial model, it is understood that psychological responses to living conditions may interact with existing somatic factors, altering the susceptibility and manifestations of diseases, which is evidenced in somatizations, such as the case of Irritable Bowel Syndrome (IBS), where there is altered intestinal motility and stool format, accompanied by abdominal pain. The mental functioning associated with somatizations, in which a person presents difficulties in associating the illness to their psychological universe, that is, the capacity of symbolization, i.e. the construction of mental representations for the relief of the emotional state is affected, cronifying the physiological changes. The research objective was to determine whether psychological clinical care, based on the technique of Operationalized Brief Psychotherapy (OBP), with emphasises on promoting symbolization capacity regarding certain significant issues, can contribute to the improvement of symptoms in clinical condition of patients with IBS. The method used in the study was the clinical-qualitative, from the case study of two female adult patients with primary diagnosis of somatoform autonomic disorder, suffering from IBS. Psychological intervention was structured in three phases: 1) psychodiagnosis, composed of semi-directed interview, Operationalized Adaptive Diagnostic System (OADS) and Thematic Apperception Test (TAT), questionnaire of clinical evaluation of IBS; 2) brief psychotherapy split in twelve sessions; 3) re-evaluation after six months. The symbolization capacity of the first participant was compromised primarily because of her difficulty dealing with the loss of her mother when a child, in a non-elaborated mourning. The patient presented strong abdominal pains, every two or three days, evacuating once a day and when in crisis, two or three times a day. The second participant presented a symbolization capacity that began to be compromised when the conflict between the desire to be accepted by her family, especially her mother, and the disruption became unbearable. She felt moderate pain, every five days, evacuating four times a day, and when in crisis, six times a day. Psychological clinical intervention in patients with IBS, based on the technique of OADS, with development of psychological demand and significant issues that compromised the capacity of symbolization, allowed the psychological development of emotional states that would influence the symptoms of IBS, so it contributed to the improvement of the clinical condition of the participants. After six months of psychotherapy, the first participant presented weak pains every five days, single daily stool frequency, no crisis. The second participant was evacuating once or twice a day, felt weak pains every five days and crisis occurred less frequently. The intervention model was advantageous to the participants, so that its use in clinical psychological treatment for IBS patients presents promising, taking into account the specifics of mental functioning associated with somatization

Introdução: A má digestão de lactose detectada por testes respiratórios é bastante comum em pacientes com síndrome do intestino irritável (SII), e alguns pacientes com SII referem exacerbar seus sintomas após a ingestão de leite e produtos lácteos. A fim de uma melhor percepção sobre este tema, este trabalho investigou os efeitos da dieta isenta de lactose em pacientes com SII e teste respiratório de hidrogênio para avaliação da digestão de lactose normal ou anormal. Objetivo: Avaliar os efeitos de uma dieta isenta de lactose em pacientes de SII com ou sem teste positivo para má digestão de lactose (teste respiratório). Métodos: 80 pacientes atendidos no Ambulatório de Doenças Funcionais Intestinais do Serviço de Gastroenterologia Clínica do HCFMUSP foram recrutados para o estudo prospectivo. Os pacientes preencheram os critérios de Roma III para SII. Durante o ensaio do teste respiratório de hidrogênio todos os sintomas desencadeados pela ingestão de lactose foram anotados. Ambos os grupos de pacientes com e sem má digestão de lactose, foram submetidos a uma dieta isenta de lactose durante 4 semanas. A história prévia de intolerância ao leite e derivados também foi documentada. No final de cada semana, os pacientes foram solicitados a informar a respeito dos seus sintomas, e os resultados, foram devidamente marcados de acordo com a sua intensidade (Escore Global). Além disso, foi também obtida a Avaliação Global do Paciente no final do tratamento (AFG). Resultados: 33/80 (41,25%) pacientes com SII tiveram um teste respiratório anormal para a má digestão de lactose, e 47/80 dos pacientes (58,75%) com SII tiveram um teste respiratório normal (ns). Não houve diferença significativa na freqüência de queixas de intolerância prévia ao leite e derivados em ambos os grupos. No entanto, mais pacientes no grupo com má digestão de lactose referiram sintomas durante o teste respiratório com 25 g de lactose do que o grupo com digestão normal a lactose (p <0,001). Ambos os grupos igualmente melhoraram após uma dieta isenta de lactose, quando avaliados pelo escore geral e pelo AFG. Conclusões: Ambos os grupos de pacientes com SII, com e sem má digestão de lactose, melhoraram após 4 semanas de dieta isenta de lactose. Os nossos resultados sugerem que outros mecanismos, além da intolerância à lactose, devem ser levados em conta para explicar a melhora com uma dieta isenta de lactose em pacientes com SII / Introduction: Lactose intolerance detected by respiratory tests is rather common in patients with irritable bowel syndrome(IBS); also, some IBS patients refer their symptoms exacerbate after ingestion of milk and dairy products. In order to gain some insight into this topic we investigated the effects of a lactose-free diet in IBS patients with and without lactose intolerance diagnosed by means of the hydrogen respiratory test. Objective: To evaluate the effects of a lactose-free diet in IBS patients with and without lactose intolerance. Methodos: 80 patients who attended the outpatient clinic at the University of São Paulo School of Medicine Hospital, Brazil, were recruited for this prospective study. Patient met the Rome III criteria for IBS. During the hydrogen respiratory test all the symptoms triggered by lactose ingestion were taken down. Both groups of patients, with and without lactose intolerance, were submitted to a lactose-free diet for 4 weeks. Previous history of milk/dairy products intolerance was documented. At the end of each week, patients were asked to inform about their symptoms and the results were duly scored according to their intensity (Global Score). Also, the Patient Final Global Evaluation of the Treatment (PFGET) was obtained as well. Results: 33/80 (41.25%) IBS patients had an abnormal respiratory test for lactose intolerance; 47/80 (58.75%) IBS patients had a normal respiratory test (n.s.). There was no significant difference in the frequency of previous complaints after milk/dairy products ingestion in both groups. However, more patients in the lactose intolerant group referred symptoms during the respiratory test with 25 g of lactose than the lactose tolerant group (p<0,001). Both groups similarly improved after a lactose-free diet when evaluated by both the Global Score and the PFGET. Conclusions: Both groups of IBS patients, with and without lactose intolerance, improved after a 4-week lactose-free diet. Our results suggest that other mechanisms, in addition to lactose intolerance, should be taken into account to explain why IBS patients improve with a lactose-free diet