Dissertations / Theses on the topic 'Functional gastrointestinal disorders'

Despite the fact that functional gastrointestinal disorders (FGID), such as irritable bowel syndrome, are common, our understanding of them is limited. The Joint Hypermobility Syndrome (JHS) is a common non-inflammatory connective tissue disorder which is thought to be associated with FGID although this has never been proven. Thus, further understanding of the link between JHS and GI symptoms is warranted. Our aim was to fully characterise the gastrointestinal (GI) manifestations of JHS, to determine if there is a true association between GI symptoms in JHS and FGID, and to determine the factors that are involved in this association. Using a cross-sectional design I demonstrate in the first study that patients with a known diagnosis of JHS who are referred from rheumatologists to gastroenterologists have significantly increased gastro-oesophageal symptoms, alternating bowel habit, bloating and abdominal pain compared to other patients referred to the GI clinics. Autonomic factors, and to a lesser extent, somatic hypersensitivity factors appear to mediate the association between JHS and gastro-oesophageal symptoms. In the second study, I demonstrate that healthy university students with JHS are more likely to experience postprandial dyspeptic symptoms compared to those without JHS. Although autonomic and somatic symptoms are increased in JHS their presence does not seem to confound the association with GI symptoms in this group of healthy individuals. In a case-control study of patients attending secondary care GI clinics, I demonstrate that JHS is overrepresented in patients with FGID and reflux disease but not in those with organic disease. Furthermore, the association with FGID is specifically with postprandial distress syndrome and this association is dependent on autonomic factors. In the final chapter, I confirm that abnormalities in GI physiology are common in JHS patients with GI symptoms attending a physiology unit. 60% of JHS patients with reflux symptoms have non-erosive pathological acid reflux, 56% with dysphagia have oesophageal hypomotility, and 87% with dyspeptic symptoms have gastroparesis. My studies suggest that there is overlap between JHS, gastro-oeosphageal symptoms, FGID and GI dysmotility. Understanding the mechanisms underlying GI involvement in JHS may further our understanding of FGID.

Thesis (Ph. D.)-- University of Sydney, 1999.
Title from title screen (viewed Apr. 21, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Depts. of Psychological Medicine and Medicine. Includes tables. Includes bibliography. Also available in print form.

Although a vast literature attests to the belief that psychosocial disturbance is an important component of functional gastrointestinal disorders (FGID), the relation of life stress, psychological distress and personality to the development of these disorders is poorly understood. The broad objective of this thesis is to provide data on relations between psychosocial factors and FGID, especially irritable bowel syndrome (IBS) and functional dyspepsia (FD), in representative outpatient samples. Issues not previously addressed are examined in a series of studies. The first two studies are concerned with relations between psychosocial factors, extraintestinal (somatic) symptoms and the number and type of FGID syndromes present at consultation and, in IBS patients, the prospective relation of psychosocial factors to changes in symptom intensity over 16 months. The last three studies relate psychosocial factors to gastrointestinal (GI) transit, motor, and sensory function in FGID, abnormalities in these parameters representing the putative origin of symptoms in FGID. In total, 350 patients participated, representing a 95% participation rate. Important features of the methodology include the use of a recently standardised symptom-based classification system for FGID, an objective and reliable interview-based life stress instrument (The Life Events and Difficulties Schedule), and sophisticated and sensitive technologies to assess GI transit, motor and sensory function. Novel measures, which conceptually take into account the chronic, fluctuating and recurrent course of IBS and FD syndromes, and the tendency of these syndromes to coexist, are also included. Thus, measures of symptom outcome assess the number of syndromes present, while the symptom intensity variable reflects the severity and frequency of both FD and IBS symptoms, if both are present. Similarly, with respect to altered transit, and motor and sensory function, physiological outcome variables reflect not only the presence of an abnormality but the number of regions affected, and the type and number of abnormalities present. Cross-sectional findings showed for the first time that psychosocial disturbance is associated with FGID symptomatology in a quantitative manner, that chronic life stress threat is central to this process and this stress-related process is a prominent feature of a particular group of syndromes (ie IBS/FD) defined primarily by the presence of pain and discomfort. A combination of psychological, social and biological factors combined to predict the number of FGID syndromes present at entry into the study. Prominent among them was an angry, reactive and anxious (neurotic) personality, chronic life stress threat, increased coping, poor emotional support and increased age. In addition to a greater number of FD/IBS syndromes, individuals with an anger-reactive response style had experienced more intense pain and discomfort, and displayed more complete sensorimotor disturbance. Longitudinal data demonstrated (also for the first time) the strength, consistency and unequivocal direction of the relation of chronic threat to symptom intensity over time. Almost all of the within subject variance in symptom intensity levels (assessed on 3 occasions over a 16 month period) was explained by the severity of chronic threat during the previous 6 months or more. For 76% of IBS patients, the presence vs the absence of one or more highly threatening chronic stressors predicted with considerable precision, the long-term clinical outcome. Thus, no patient exposed to even one such stressor improved clinically (ie by at least 50%) over the follow-up period, while in contrast, all patients who improved clinically did so in the absence of such a stressor. For 24% of patients, however, failure to improve clinically could not be explained by any psychological, social (including life stress) or demographic factor included in this study. Key risk indicators of a poor outcome at 16 months were identified - chronic life stress threat, the severity of baseline GI symptomatology, and female gender. Life stress is important because it alone determined the magnitude and direction of change in symptom intensity over time, while the severity of baseline GI symptomatology revealed the extent of improvement required to achieve a recovery, and female gender predicted the presence of a larger number of FD/IBS syndromes in women long-term. Widespread hypomotility, which was almost exclusive to women in this study, represents one factor that may inhibit improvement (or rate of improvement) for women over time. Finally, these findings have identified a psychophysiological subgroup, with underlying psychosocial, motor (and perhaps also sensory) dysfunctions that are more specific for women than men, and which does not seem to be distinctive of any particular FGID subgroup.

Purpose: While there are diagnostic criteria for functional gastrointestinal disorders (FGIDs), their evaluation is challenging. This is because criteria are based on symptoms, and the underlying pathophysiology is not clear; as such, there are no gold standard tests. Diagnosis is further challenged by considerable clinical overlap between different FGIDs as well as other organic diseases, while many people with FGIDs have more anxiety and depression than healthy individuals. I hypothesised that assessment of separate components of FGIDs that also indicate their effect on the patient could improve diagnosis. My aim was to investigate the evolution of opinions from experts involved in the development of FGID diagnostic criteria on the proposal for the development of multiaxial assessment criteria (MAC) for FGIDs. Methods: I conducted a web-based Delphi study using a group of purposively sampled experts identified from committees of the Rome Foundation and the International Foundation for Gastrointestinal Disorders. From a systematic search of relevant articles, I generated132 items that were sent to experts as a first round survey. The items assessed risk and contributing factors, the therapeutic relationship, areas of evaluation and the advantages and disadvantages of multiaxial assessment. Consensus on an item was reached when 75% of experts indicated that they agreed or strongly agreed with the statement. Key results: 36 of 68 eligible participants (52%) responded to the first round. Consensus was reached on 96 items. Using participant feedback, thematic analysis was used to generate 33 additional items for round two. Thirty-one of 36 participants (86%) replied to rounds two and three. In round two, 19 items gained consensus, and in round three, nine items gained consensus. Participants agreed that multiaxial assessment was needed, using a systematic approach to establish the physiological and psychosocial components of FGIDs. Participants were unable to agree on the importance of physical risk factors such as previous surgery and genetic association. Overall, 124 of the 167 items achieved consensus. Conclusion and inferences: The key finding from my study shows that experts agree that multiaxial assessment of FGIDs is needed. I also identified expert agreement on the consideration of psychological risk factors and the importance of the impact of FGID symptoms on daily life. Findings also show that experts disagreed on the impact of physical risk factors, socioeconomic status and spirituality on people with FGIDs. While experts could not agree on genetic and gender-based risk factors, they considered that these areas are important and require further research.

Background Transthyretin amyloid (ATTR) amyloidosis is a systemic disorder caused by amyloid deposits formed by misfolded transthyretin (TTR) monomers. Two main forms exist – wild-type and hereditary ATTR amyloidosis, the latter associated with TTR gene mutations. Wild-type ATTR amyloidosis has a late onset and primarily cardiac manifestations, whereas hereditary ATTR amyloidosis is a rare autosomal dominant condition with a considerable phenotypic diversity. Both disorders are present all over the world, but endemic areas of the hereditary form are found in Sweden, Portugal, Brazil and Japan. Gastrointestinal (GI) complications are common in hereditary ATTR amyloidosis and play an important role in the patients’ morbidity and mortality. Malfunction of the autonomic and enteric nervous systems has been proposed to contribute to the GI disturbances, but the underlying mechanisms have not been fully elucidated. The aims of this thesis were to assess the prevalence of GI disturbances for different subtypes of ATTR amyloidosis, to further explore the mechanisms behind these disturbances, and to evaluate the outcome of the patients’ GI function after liver transplantation, which currently is the standard treatment for hereditary ATTR amyloidosis. Methods The Transthyretin Amyloidosis Outcomes Survey (THAOS) is the first global, multicenter, longitudinal, observational survey that collects data on patients with ATTR amyloidosis. THAOS enrollment data were used to assess the prevalence of GI symptoms and to evaluate their impact on nutritional status (mBMI) and health-related quality of life (EQ-5D Index Score). Data from routine investigations of heart-rate variability and cardio-vascular response to tilt tests were utilized to evaluate the impact of autonomic neuropathy on the scintigraphically measured gastric emptying half-times in Swedish patients with hereditary ATTR amyloidosis. Gastric wall autopsy specimens from Japanese patients with hereditary ATTR amyloidosis and Japanese non-amyloidosis controls were analyzed with immunohistochemistry and computerized image analysis to assess the densities of interstitial cells of Cajal (ICC) and nervous tissue. Data from gastric emptying scintigraphies and validated questionnaires were used to evaluate the outcome of Swedish patients’ GI function after liver transplantation for hereditary ATTR amyloidosis. Results Sixty-three percent of the patients with TTR mutations and 15 % of those with wild-type ATTR amyloidosis reported GI symptoms at enrollment into THAOS. Subsequent analyses focused on patients with TTR mutations and, among them, unintentional weight loss was the most frequent symptom (32 %) followed by early satiety (26 %). Early-onset patients (<50 years of age) reported GI symptoms more frequently than late-onset cases (70 % vs. 50 %, p <0.01), and GI symptoms were more common in patients with the V30M mutation than in those with non-V30M mutations (69 % vs. 56 %, p <0.01). Both upper and lower GI symptoms were significant negative predictors of nutritional status and health-related quality of life (p <0.01 for both). Weak but significant correlations were found between gastric emptying half-times and the function of both the sympathetic (rs = -0.4, p <0.01) and parasympathetic (rs = -0.3, p <0.01) nervous systems. The densities of c-Kit-immunoreactive ICC were significantly lower in the circular (median density 0.0 vs. 2.6, p <0.01) and longitudinal (median density 0.0 vs. 1.8, p <0.01) muscle layers of the gastric wall in patients compared to controls. Yet, no significant differences in protein gene product 9.5-immunoreactive nervous cells were found between patients and controls either in the circular (median density 3.0 vs. 6.8, p = 0.17) or longitudinal (median density 1.4 vs. 2.5, p = 0.10) muscle layers. Lastly, the patients’ GI symptoms scores had increased slightly from before liver transplantation to the follow-ups performed in median two and nine years after transplantation (median score 7 vs. 10 vs. 13, p <0.01). However, their gastric emptying half-times (median half-time 137 vs. 132 vs. 125 min, p = 0.52) and nutritional statuses (median mBMI 975 vs. 991 vs. 973, p = 0.75) were maintained at follow-ups in median two and five years after transplantation. Conclusion GI disturbances are common in hereditary ATTR amyloidosis and have a negative impact on the patients’ nutritional status and health-related quality of life. Fortunately, a liver transplantation appears to halt the progressive GI involvement of the disease, although the patients’ GI symptoms tend to increase after transplantation. An autonomic neuropathy and a depletion of gastrointestinal ICC seem to contribute to the GI disturbances, but additional factors must be involved.

Functional constipation (FC) is a major gastrointestional (GI) disorder which affects about 14% population worldwide. However, due to efficacy and safety concerns, more than 50% FC patients are not completely satisfied with current conventional therapies, thus alternative therapies are needed. A substantial part of FC patients have symptom of slow colonic motility, while therapy targeting a single pathway cannot benefit all of them. In this thesis, we searched for novel FC therapeutics from two distinct sources, both of which can improve colonic motility significantly: (1) MaZiRenWan (MZRW), an herb formula from Traditional Chinese Medicine (TCM); and (2) Spexin (SPX), a newly identified neuropeptide that is deregulated in FC. On the basis of efficacy validation for MZRW by randomized, placebo-controlled clinical studies, we investigated the bioactive compounds and pharmacological actions of MZRW. Firstly, a machine-learning based method, namely MOST, was developed to relate bioactive compounds with their mechanism-of-action targets. MOST demonstrated good performance in 7-fold cross-validation (over 87% accuracy) and temporal validation (over 76% accuracy). In the case laxative effect, MOST predicted that acetylcholinesterase (ACHE) was the mechanism-of-action target of aloe-emodin; in vivo studies validated this prediction. Secondly, we analyzed the bioactive compounds and mechanism-of-actions of MZRW with combination of UPLC-QTOF-MS/MS, clustering analysis, organ bath, and MOST approaches. 97 compounds were identified in MZRW extract, and 35 of them can be found in plasma and feces samples of rats with oral administration of MZRW. Chemical space analysis suggested that these compounds can be classified into component groups, while the corresponding pharmacology can be studied with representative compounds. Emodin, amygdalin, albiflorin, honokiol, and naringin were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro. Biological targets in ACh-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and component groups. Pharmacological actions of MZRW are mixture of five classic paradigms. Thirdly, the latest results of three-armed, randomized and controlled clinical study showed that MZRW demonstrated comparable efficacy with the first line drug Senna, the first line drug for constipation in HK, during treatment period, both were better than placebo; and the efficacy was more sustainable in follow-up period when comparing that of Senna and placebo. These data suggested the unique pharmacological profile of MZRW for FC. With pharmacometabolomic analysis, we found that change of oleamide is negatively correlated (pearson r = -0.59, p<0.001) with improvement of Complete Spontaneous Bowel Movement (CSBM) in MZRW group, but not in Senna or placebo group. Oleamide is up-regulated in FC patients compared with healthy controls, and MZRW can significantly reduce oleamide in FC patients (n=30), healthy human volunteers (n=23), and in normal mice (n=12) serum, ileum, and colon. The regulation of oleamide by MZRW is possibly via augmenting FAAH-mediated degradation. Lastly, we investigated the possibility to use SPX, the newly identified, FC-associated neuropeptide to change GI motility. The deregulation of SPX has been found in several disorders including FC, however, the metabolic instability of SPX prevent it to be directly used in clinical practices. Our investigation through combination of molecular dynamics (MD) simulations and NMR analysis suggested a β-turn-helix-β-turn (βαβ) conformation for human spexin (hSPX) adopts in solution. Consistent with this conformation, cyclic analogues of hSPX with a disulfide bond between residue 1 and 13, LH101 (CWTPQAMLYLKGCQ-NH2), activated both GalR2 (EC50=1.19 μM) and GalR3 (EC50=1.56 μM) with potency comparable to wild type, and that the acetylation at the N-terminal, LH101(Ac) raises the potency EC50=0.38 μM on GalR2 and EC50=0.39 μM on GalR3. The serum half lives of LH101 (t1/2=355.7 min) and LH101(Ac) (t1/2=1973.7 min) were significantly longer than the wild type (t1/2=66.5 min), and LH101(Ac) induces the contractions of mice intestinal segment in vitro and attenuates the oleamide-induced slow GI motility in vivo. Collectively, our studies in MZRW suggested that estrogen and oleamide signaling pathways are potential new targets to develop novel therapeutics for FC, while lead compounds targeting these pathways could be found from MZRW. The final study suggested CSAs have potential to be developed as new FC therapy by targeting the galanin receptor associated pathway.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-05-20T12:20:13Z No. of bitstreams: 1 flaviaaltafdarochalima.pdf: 1162345 bytes, checksum: 18a62c489991ceea8aa434e2b2a63f89 (MD5)
Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-02T11:21:12Z (GMT) No. of bitstreams: 1 flaviaaltafdarochalima.pdf: 1162345 bytes, checksum: 18a62c489991ceea8aa434e2b2a63f89 (MD5)
Made available in DSpace on 2016-07-02T11:21:12Z (GMT). No. of bitstreams: 1 flaviaaltafdarochalima.pdf: 1162345 bytes, checksum: 18a62c489991ceea8aa434e2b2a63f89 (MD5) Previous issue date: 2012-08-14
FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
Introdução: A dispepsia funcional (DF) representa um transtorno gastrointestinal frequente na prática clínica. Por apresentar mecanismos etiopatogênicos diversos, a terapia medicamentosa não se mostra totalmente eficaz, razão pela qual a busca por terapias complementares como a acupuntura é fundamental. Objetivo: avaliar a eficácia da acupuntura como terapia complementar ao tratamento medicamentoso convencional em pacientes com DF. Método: ensaio clínico randomizado, com portadores de dispepsia funcional, segundo os critérios de Roma III. Dois grupos foram formados: Grupo I (terapia medicamentosa e acupuntura específica) e Grupo II (terapia medicamentosa e acupuntura não específica). Foram avaliados o índice de sintomas gastrointestinais (Gastrointestinal Scale Related Symptoms – GSRS), a presença de transtornos psíquicos (Escala Hospitalar de Ansiedade e Depressão) e a qualidade de vida (Short-form Health Survey – SF 36) no início, no fim e três meses após o tratamento. Resultados: após 4 semanas de tratamento houve melhora dos sintomas gastrointestinais no Grupo I (55 ± 12 vs. 29 ± 8,8; p = 0,001) e Grupo II (50,3 ± 10,2 vs. 46 ± 10,5; p = 0,001). A qualidade de vida foi significativamente melhor no Grupo I (93,4 ± 7,3 vs. 102,4 ± 5,1; p = 0,001). Transtornos de ansiedade (93,3% vs. 0%; p = 0,001) e depressão (46,7% vs. 0%; p = 0,004) foram significativamente menores no Grupo I. Na comparação intergrupos os sintomas gastrointestinais (29 ± 8,8 vs. 46 ± 10,5; p < 0,001) e a qualidade de vida (102,4 ± 5,1 vs. 96 ± 6,1; p = 0,021) foram significativamente melhores no Grupo I. Três meses após o tratamento, os sintomas gastrointestinais permaneceram melhores no Grupo I quando comparados aos valores pré-tratamento (38 ± 11,3 vs. 55 ± 12; p = 0,001). Conclusão: em portadores de dispepsia funcional o tratamento complementar com acupuntura foi superior ao tratamento convencional. A acupuntura pode ser uma terapia complementar eficaz no tratamento de pacientes com DF.
Introduction: Functional dyspepsia (FD) represents a frequent gastrointestinal disorder in clinical practice. By presenting various etiopathogenic mechanisms, often the drug therapy is not entirely effective. Therefore, the search for complementary therapies such as acupuncture is essential. Objective: Evaluate the effectiveness of acupuncture as a complement to conventional treatment in functional dyspepsia patients. Methods: randomized clinical trial with functional dyspepsia patients in according with ROME III criteria. Two groups were created: Group I (drug therapy and specific acupuncture) and Group II (drug therapy and non-specific acupuncture). The gastrointestinal symptoms (Gastrointestinal Scale Related Symptoms – GSRS), presence of psychiatric disorders (Hospital Anxiety and Depression Scale – HADS) and quality of life (Short-form Health Survey – SF 36) were evaluated, at the end and three months after treatment. Results: After 4 weeks of treatment there was significantly improvement of gastrointestinal symptoms in Group I (55 ± 12 vs. 29 ± 8,8; p = 0,001) and Group II (50 ± 10 vs. 46 ± 10,5; p = 0,001). Quality of life was significantly better in Group I (93,4 ± 7,3 vs. 102,4 ± 5,1; p = 0,001). Anxiety and depression disorders were significantly lower in Group I (93% vs. 0%; p = 0,001 and 46% vs. 0%; p = 0,004; respectively). Inter-group, gastrointestinal symptoms comparison and quality of life were significantly better in Group I (29 ± 8,8 vs. 46 ± 10,5; p < 0,001 and 102,4 ± 5,1 vs. 96,4 ± 6,1; p = 0,021; respectively). Three months after the treatment, gastrointestinal symptoms remained best in Group I, when compared to the pre-treatment values (38 ± 11,3 vs. 55 ± 12; p = 0,001). Conclusion: In patients with functional dyspepsia the complementary acupuncture treatment was superior to conventional treatment. Acupuncture as a complementary treatment can be effective in treating patients with FD.

Els trastorns funcionals digestius són els trastorns més freqüents en gastroenterologia. Es tracta d'un grup de trastorns de la interacció cervell-intestí, que es classifiquen d'acord amb els símptomes predominants, els més coneguts són la dispèpsia funcional, la síndrome d'intestí irritable, el restrenyiment i els trastorns de la defecació. Se sap que hi ha una relació entre la dieta, funció i els símptomes digestius. No obstant això, la fisiopatologia dels trastorns funcionals digestius no està d'el tot aclarida. En aquesta tesi doctoral plantegem la següent hipòtesi general: el contingut intestinal és un factor clau en el desencadenament de símptomes en pacients amb diferents tipus de síndromes digestius funcionals. L'objectiu principal va ser determinar si els factors de determinar el contingut intestinal, tant la dieta com l'hàbit deposicional, influeixen sobre els símptomes digestius funcionals. En primer lloc, vam realitzar un estudi randomitzat, doble cec, en pacients amb trastorns funcionals digestius, on es va comparar l'efecte d'un suplement (2.8 g / dia Bimuno que conté 1.37 g B GOS) més un placebo (dieta mediterrània típica) vs 1 suplement de placebo (2.8 g de xilosa) més una dieta baixa en FODMAPs. L'objectiu d'aquest estudi va ser determinar la influència específica de diferents tipus de residus fermentables de la dieta (prebiòtics i FODMAPs) sobre els símptomes relacionats amb el gas intestinal en pacient amb síndromes funcionals digestius. Els resultats van ser que tots dos tractaments van presentar millora en els scores de símptomes. Tanmateix, les dues estratègies van tenir conseqüències després de discontinuar el tractament. Tot i que la millora dels símptomes persistir 2 setmanes després de l'administració de l'prebiòtic, els símptomes van empitjorar després de discontinuar la dieta baixa en FODMAPs. A més, els tractaments indueixen efectes diferents en la microbiota, en relació a les Bifidobacteris (increment amb prebiòtics i disminució amb la dieta baixa en FODMAP). A continuació, vam realitzar un estudi randomitzat, paral·lel, en pacients amb dispèpsia funcional amb síndrome de distress postprandial i amb restrenyiment funcional amb disinergia defecatòria, on es va comparar la correcció de la disinergia defecatòria mitjançant biofeedback anorectal vs un suplement de fibra (3.5 g de plantago de ovata per dia) durant 4 setmanes. L'objectiu d'aquest estudi va ser determinar el paper fisiopatològic de l'estrenyiment en la dispèpsia funcional, és a dir si el restrenyiment associat influeix sobre els símptomes dispèptics. Els resultats van ser que la correcció de la disinergia defecatòria va estar associat amb una millora en els símptomes dispèptics i aquesta millora subjectiva va estar associada amb una reducció objectiva en el nombre d'evacuacions de gas anal, cap d'aquests efectes es va observar en el grup que va rebre suplements de fibra. Les conclusions d'aquesta tesi doctoral van ser que els factors que determinen el contingut intestinal, tant la dieta com l'hàbit deposicional, influeixen sobre els símptomes digestius funcionals i que els diferents síndromes funcionals digestius comparteixen una base fisiopatològica comú que involucra el contingut intestinal.
Los trastornos funcionales digestivos son los trastornos más frecuentes en gastroenterología. Se trata de un grupo de trastornos de la interacción cerebro-intestino, que se clasifican de acuerdo con los síntomas predominantes, los más conocidos son la dispepsia funcional, el síndrome de intestino irritable, el estreñimiento y los trastornos de la defecación. Se sabe que hay una relación entre la dieta, función y los síntomas digestivos. Sin embargo, la fisiopatología de los trastornos funcionales digestivos no está del todo aclarada. En esta tesis doctoral planteamos la siguiente hipótesis general: el contenido intestinal es un factor clave en el desencadenamiento de síntomas en pacientes con distintos tipos de síndromes digestivos funcionales. El objetivo principal fue determinar si los factores que determinar el contenido intestinal, tanto la dieta como el hábito deposicional, influyen sobre los síntomas digestivos funcionales. En primer lugar, realizamos un estudio randomizado, doble ciego, en pacientes con trastornos funcionales digestivos, donde se comparó el efecto de un suplemento (2.8 g/día Bimuno que contiene 1.37 g B-GOS) más un placebo (dieta mediterránea típica) vs un suplemento de placebo (2.8 g de xilosa) más una dieta baja en FODMAPs. El objetivo de este estudio fue determinar la influencia específica de distintos tipos de residuos fermentables de la dieta (prebióticos y FODMAPs) sobre los síntomas relacionados con el gas intestinal en paciente con síndromes funcionales digestivos. Los resultados fueron que ambos tratamientos presentaron mejoría en los scores de síntomas. Sin embargo, ambas estrategias tuvieron consecuencias después de descontinuar el tratamiento. Aunque la mejoría de los síntomas persistió 2 semanas después de la administración del prebiótico, los síntomas empeoraron después de descontinuar la dieta baja en FODMAPs. Además, los tratamientos inducen efectos diferentes en la microbiota, en relación a las Bifidobacterias (incremento con prebióticos y disminución con la dieta baja en FODMAP). A continuación, realizamos un estudio randomizado, paralelo, en pacientes con dispepsia funcional con síndrome de distress postprandial y con estreñimiento funcional con disinergia defecatoria, donde se comparó la corrección de la disinergia defecatoria mediante biofeedback anorectal vs un suplemento de fibra (3.5 g de plantago de ovata por día) durante 4 semanas. El objetivo de este estudio fue determinar el papel fisiopatológico del estreñimiento en la dispepsia funcional, es decir si el estreñimiento asociado influye sobre los síntomas dispépticos. Los resultados fueron que la corrección de la disinergia defecatoria estuvo asociado con una mejora en los síntomas dispépticos y esta mejoría subjetiva estuvo asociada con una reducción objetiva en el número de evacuaciones de gas anal, ninguno de estos efectos se observó en el grupo que recibió suplementos de fibra. Las conclusiones de esta tesis doctoral fueron que los factores que determinan el contenido intestinal, tanto la dieta como el hábito deposicional, influyen sobre los síntomas digestivos funcionales y que los distintos síndromes funcionales digestivos comparten una base fisiopatológica común que involucra el contenido intestinal.
Functional gastrointestinal disorders are the most common diagnoses in gastroenterology disorders. It is a group of disorders of the gut-brain interaction and are classified according to the predominant symptoms. The best known are functional dyspepsia, irritable bowel syndrome, constipation and defecation disorders. It is known that there is a relationship between diet, function and digestive symptoms. However, the pathophysiology of functional gastrointestinal disorders is not entirely clear. In this doctoral thesis we propose the following general hypothesis: intestinal content is a key factor in triggering symptoms in patients with different types of functional gastrointestinal syndromes. The main aim was to determine if the factors that determine the intestinal content, both the diet and depositional habit, influence functional gastrointestinal symptoms. Firstly, we performed a randomized, parallel and double-blind study of patients with functional gastrointestinal disorders, and compared the effect of a prebiotic supplement (2.8 g/d Bimuno containing 1.37 g B-GOS) plus a placebo (Mediterranean-type diet) versus a placebo supplement (2.8 g xylose) plus a diet low in FODMAP. The arm of this study was to determine the specific influence of different types of fermentable residues from the diet (prebiotics and FODMAP) on gas-related symptoms in patient, with functional gastrointestinal disorders. The results were that both treatments improved the symptoms to a similar extent. However, both strategies had different consequences after treatment discontinuation; while the improvement of symptoms persisted 2 weeks after prebiotic administration was discontinued, the symptoms relapsed after the termination of the low FODMAP diet. Also, both treatments induced different effects on microbiota, particularly in relation to the Bifidobacterium (increased with prebiotic and decreased with low FODMAP diet). Next, we performed a randomized, parallel study of patients with functional dyspepsia with postprandial distress syndrome and functional constipation with dyssynergic defecation and compared correction of dyssynergic defecation by biofeedback techniques vs fiber supplementation (3.5 g plantago ovata per day) for 4 weeks. The arm of this study was to determine the pathophysiologic role of constipation in functional dyspepsia, that is, if the associated constipation influences dyspeptic symptoms. The results were that the correction of dyssynergic defecation was associated with a significant improvement of dyspeptic symptoms and this subjective improvement was associated with an objective reduction in the number of anal gas evacuations. None of these effects were observed in the group that received fiber supplements. The conclusions of this doctoral thesis were that the factors that determine the intestinal content, both the diet and the depositional habit, influence the functional gastrointestinal symptoms and that the different functional gastrointestinal syndromes share a common pathophysiological basis that involves the intestinal content.

Introducción: Es conocida la elevada psicopatología asociada a los diferentes subtipos de pacientes con trastornos gastrointestinales funcionales (TGF) y la dificultad para el gastroenterólogo para detectarla y manejarla, pudiendo generar diagnósticos digestivos tardíos y en ocasiones erróneos. Los trastornos de la motilidad gastrointestinal (TMG) han sido menos estudiados desde ésta perspectiva. Tener en cuenta la experiencia subjetiva del paciente en relación a su enfermedad en comparación con la evaluación del gastroenterólogo y el nivel de incongruencia entre los dos puede ser de utilidad en el abordaje de estos pacientes. Objetivos: Estudiar la psicopatología, la calidad de vida y los rasgos de personalidad en una muestra de pacientes ingresados para estudio de la motilidad digestiva en una unidad hospitalaria altamente especializada. Por otro lado, se investigó la incongruencia de la funcionalidad evaluada por clínicos y pacientes y su relación con la psicopatología. Metodología: La presente investigación se describe como un estudio observacional, transversal, de pacientes que ingresan en la unidad de hospitalización digestiva para estudio de la motilidad gastrointestinal. Durante dos años, se incluyeron en este estudio todos los pacientes hospitalizados para la evaluación de la función motora gastrointestinal en una unidad de patología digestiva altamente especializada, de un centro de referencia terciario. Se incluyeron un total de 103 pacientes y fueron evaluados por el psiquiatra en las primeras 72 horas posteriores a la admisión al hospital. Se llevó a cabo una entrevista clínica y se administraron las siguientes escalas autoaplicadas: HADS, SCL-90-R, TAS-20, SF-36 y NEO-FFI-R. A nivel digestivo se realizaron las pruebas de motilidad oportunas así como la administración del Karnofsky Performance Status Scale (KPS) para evaluar la funcionalidad. Se definió la variable incongruencia como la diferencia entre KPS y las subescalas de funcionamiento físico del SF-36 (ambos en rango 0-100). Resultados: No se detectaron diferencias destacables entre los dos grupos en relación a datos sociodemográficos, rasgos de personalidad ni psicopatología. Sin embargo, la correlación de la funcionalidad medida por el clínico con el funcionamiento físico subjetivo fue alta y estadísticamente significativa sólo en el caso de los pacientes diagnosticados de TMG. La incongruencia entre la evaluación clínica y subjetiva de la funcionalidad correlacionó con todas las subescalas del SCL-90R. Cuando estratificamos por grupo de diagnóstico digestivo, en el grupo de TGF todas las subescalas del SCL-90R correlacionaron con la incongruencia mientras que en el grupo de TMG sólo fue significativa la correlación con somatización. Los análisis de covarianza no mostraron diferencias estadísticamente significativas en los niveles de psicopatología entre los grupos de diagnóstico digestivo al controlar por la incongruencia. En cambio, ésta última, mostró covariación estadísticamente significativa en todos los casos, por lo que la incongruencia mostró mayor capacidad predictiva de psicopatología que el diagnostico gastrointestinal per se. Usando modelos lineales generales, se encontró que la incongruencia era la variable con mayor relación con las variables psicopatológicas, incluso controlando por diagnóstico. Se encontraron interacciones entre la incongruencia y el diagnóstico digestivo (TMG vs. TGF), que refleja que los pacientes con TGF cuya evaluación subjetiva del funcionamiento es incongruente con la del clínico, tienen niveles más altos de psicopatología en comparación con pacientes afectos de TMG, en casi todos los casos independientemente de la incongruencia en estos últimos. Conclusiones: La psicopatología parece estar relacionada con las diferentes percepciones de la enfermedad que tienen clínicos y pacientes. La incongruencia del paciente y del clínico puede utilizarse como una herramienta simple de cribaje de psicopatología o distrés psicológico, especialmente entre los pacientes con trastornos gastrointestinales funcionales, facilitando los procesos de interconsulta psiquiátrica.
Introduction: Psychopathology is highly associated with different subtypes of patients diagnosed of functional gastrointestinal disorders (FGDs). It is known by the gastroenterologist’ the difficulty to detect and manage psychopathology, generating late and sometimes erroneous digestive diagnoses. Gastrointestinal motility disorders (GMDs) have been less studied from this perspective. Taking into account the subjective experience of the patient in relation to their disease, compared to the evaluation of the gastroenterologist and the level of incongruence between the two may be useful in the approach of these patients. Objectives: To study psychopathology, quality of life and personality traits of patients admitted for specialized assessment in an inpatient tertiary Digestive Unit. On the other hand, the incongruence of the functionality evaluated by clinicians and patients and its relation with psychopathology was investigated. Methods: The present research is described as an observational, cross-sectional study. We included all patients hospitalized for evaluation of gastrointestinal motor function in a highly specialized Digestive Unit based at a tertiary referral center during two years. A total of 103 patients were included and evaluated by the psychiatrist within 72 hours of admission to the hospital. A clinical interview was conducted and the following self-administered scales were used: HAD, SCL-90-R, TAS-20, SF-36 and NEO-FFI-R. Digestive diagnostic tests were performed; to evaluate the functionality Karnofsky Performance Status Scale (KPS) was used. The incongruence variable was defined as the difference between KPS and the physical performance subscales of the SF-36 (both in the 0-100 range). Results: There were no remarkable differences between the two groups in relation to sociodemographic data, personality traits or psychopathology. However, the correlation of the functionality measured by the clinician with the subjective physical functioning was high and statistically significant only in the case of patients diagnosed with GMDs. Incongruence between the clinicians’ and patients’ evaluation of functionality correlated with all SCL-90-R subscales. When stratified by digestive diagnosis group, all SCL-90-R subscales correlated with incongruence in the FGDs group, whereas only the correlation with somatization was statistically significant among patients with GMDs. Covariance analyses did not show statistically significant differences in the levels of psychopathology among the digestive diagnosis groups when controlling for incongruence. In contraposition, this incongruence data showed statistically significant covariation in all cases, so the incongruence showed a greater predictive capacity for psychopathology than gastrointestinal diagnosis per se. Using general linear models, it was found that incongruence was the variable with stronger relationships with psychopathological variables, even when controlled by diagnosis. Interactions between incongruence and digestive diagnosis were found (GMDs vs. FGDs), demonstrating that patients with FGDs whose subjective performance evaluation is inconsistent with that of the clinician, have higher levels of psychopathology compared to patients with GMDs, in most cases regardless of incongruence in the latter. Conclusions: Psychopathology seems to be related to the different perceptions of the disease that the clinicians and the patients have. Patient and clinician incongruence can be used as a simple screening tool for psychopathology or psychological distress, especially among patients with functional gastrointestinal disorders, facilitating psychiatric liaison consultations.

Počet obyvatel trpících různými infekčními, zánětlivými a alergickými nemocemi stejně jako výskyt laktózové nesnášenlivosti a vysoké hodnoty krevního cholesterolu, má narůstající tendenci. Některé z těchto zdravotních problémů jsou způsobeny nevyváženou střevní mikroflorou. Probiotika jsou pak chápána (nejen) jako potravní komponenty, které přispívají k ustanovení mikrobiální rovnováhy (Parker, 1974) mezi zdraví prospěšnými a škodlivými bakteriemi. Z tohoto důvodu, terapie založená na podávání probiotik pacientům přitáhla zájem ze strany vědců. Vhodný probiotický kmen se pak volí v závislosti na požadovaném zdravotním účinku (příp. zdravotním problému, který má být probiotickou terapií léčen). Lactobacillus plantarum 299v již prokázal své blahodárné účinky na lidech a zároveň byla i potvrzena jeho zdravotní bezpečnost, díky čemuž může tato bakterie být kategorizována jako probiotický kmen (Probi AB, Sweden). I díky tomu je Lactobacillus plantarum 299v ve značné oblibě přidáván do mnoha fukčních potravin a prodáván na trhu pod různými jmény, probiotický nápoj ProViva je jedním takovým příkladem. Cílem této práce bylo studovat fermentační proces na žitném, ječmenném a sojovém substrátu pomocí kmene Lactobacillus plantarum 299v, přičemž zvýšená pozornost byla věnována právě soji a ječmeni jako potenciálně novým substrátům pro výše uvedenou bakterii. Hlavními záměry bylo zkoumání růstu a metabolické aktivity bakterie Lactobacillus plantarum 299v v asociaci s různými cereálními substráty, a později bylo studováno totéž také ve směsi fermentované cereální komponenty s běžně dostupným ovocným džusem. K tomu, aby se dosáhlo optimálních podmínek fermentace, je třeba vzít v úvahu několik aspektů. Hlavní role při konceptování nového fermentovaného produktu patří především zpracování a taktéž kompozici surového materiálu, růstové kapacitě a produktivitě bakteriální kultury a stabilitě finálního produktu během skladování (De Vuyst, 2000). Tyto parametry jsou důležité hlavně ze strany výrobců. Krom toho jsou tu ale i zákazníci, pro něž je přijatelnost produktu založena z velké části na organoleptických vlastnostech finálního probiotického produktu, tj. aromatu a chuti. Přítomnost a dostupnost různých jednotlivých nutrientů, která byla obsažena ve fermentačním médiu výsledkem rozdílných použitých cereálních substrátů, pravděpodobně vyústila v odlišnosti metabolických drah, což pak později mohlo způsobit rozdíly v organoleptických vlastnostech finálního produktu.

Adolescents with type 1 diabetes (T1DM) are given nutritional education, but the knowledge about their adherence to the food recommendations and associations between dietary intake and metabolic control is poor. Gastrointestinal symptoms are more prevalent in adults with T1DM than in healthy controls, which may be due to disturbed gastrointestinal motility. The meal content affects the gastric emptying rate and the postprandial glycaemia in healthy adults and adults with type 2 diabetes. Meal ingestion also elicits several postprandial hormonal changes of importance for gastrointestinal motility and glycaemia. Eating disorders are more prevalent in young females with T1DM than in healthy females, and are associated with poor metabolic control. The prevalence of eating disorders in adolescent boys with T1DM is not known.  This thesis focuses on eating and gastrointestinal function in adolescents with T1DM. Three population-based, cross-sectional studies demonstrated that adolescents with T1DM consume healthy foods more often and have a more regular meal pattern than age- and sex-matched controls. Yet both boys and girls are heavier than controls. The intake of saturated fat is higher and the intake of fibre is lower than recommended in adolescents with T1DM. Patients with poor metabolic control consume more fat and less carbohydrates than patients with better metabolic control. Gastrointestinal symptoms are common in adolescents with T1DM, but the prevalence is not increased compared with controls. Gastrointestinal symptoms in patients are associated with female gender, daily cigarette smoking, long duration of diabetes, poor metabolic control during the past year, and an irregular meal pattern. Adolescent boys with T1DM are heavier and have higher drive for thinness than healthy boys, but do not differ from them in scales measuring psychopathology associated with eating disorders.   In a randomized, cross-over study, we found that a meal with a high fat and energy content reduces the initial (0–2 hours) postprandial glycaemic response and delays gastric emptying in adolescents with T1DM given a fixed prandial insulin dose compared with a low-fat meal. The glycaemic response is significantly associated with the gastric emptying rate. Both a high- and a low-fat meal increase the postprandial concentrations of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) and suppress the postprandial ghrelin levels in adolescents with T1DM. The postprandial changes of these hormones are more pronounced after the high-fat meal. Insulin-like growth factor binding-protein (IGFBP) –1 concentrations decrease after insulin administration irrespective of meal ingestion. The GLP-1 response is negatively associated with the gastric emptying rate. The fasting ghrelin levels are negatively associated with the postprandial glycaemic response, and the fasting IGFBP-1 levels are positively associated with the fasting glucose levels.  We conclude that nutritional education to adolescents with T1DM should focus more on energy intake and expenditure to prevent and treat weight gain. It should also focus on fat quality and fibre intake to reduce the risk of macrovascular complications and improve glycaemia. Gastrointestinal symptoms in adolescents with T1DM should be investigated and treated as in other people irrespective of having diabetes. However, adolescents with long duration of diabetes, poor metabolic control, and symptoms from the upper gut should have their gastric emptying rate examined during euglycaemia. There may be an increased risk for development of eating disorders in adolescent males with T1DM since they are heavier than healthy boys and have higher drive for thinness. This should be investigated in future, larger studies.  For the first time, we showed that a fat-rich meal delays gastric emptying and reduces the initial glycaemic response in patients with T1DM. The action profile of the prandial insulin dose to a fat-rich meal may need to be postponed and prolonged compared with the profile to a low-fat meal to reach postprandial normoglycaemia. Circulating insulin levels affect postprandial GIP, GLP-1, and ghrelin, but not IGFBP-1, responses less than the meal content. The pronounced GIP-response to a fat- and energy-rich meal may promote adiposity, since GIP stimulates lipogenesis. Such an effect would be disadvantageous for adolescents with T1DM since they already have increased body fat mass and higher weights compared with healthy adolescents. Adolescents with T1DM may have subnormal postprandial ghrelin suppression, which may be due to their increased insulin resistance or elevated growth hormone levels. This needs to be investigated in future, controlled studies.

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) which can be defined as chronic, relapsing visceral pain with bloating associated with change in bowel habit. It affects up to 10-15% of the adult population in the UK and is more common in females. The cost of IBS in terms of health care utilisation is substantial, exceeding £45.6 million per year in the UK alone, yet its pathophysiology is incompletely understood. Visceral pain is the main and most difficult symptom to manage in IBS and many IBS female sufferers compare it to labour pain in its severity. Modulating visceral pain in healthy volunteers and IBS patients is therefore an important research area. Non-invasive magnetic stimulation may play a crucial role in this respect. Aim:The aim of this study is to ascertain whether non-invasive repetitive magnetic stimulation applied to the motor cortex and/or lumbosacrum can modulate gastrointestinal pain originating from the anorectum. Methods:Participants: 16 healthy volunteers and 10 IBS patients aged 18 and above were included in the study.Questionnaires: Healthy volunteers and IBS patients were asked to complete anxiety and depression questionnaire and IBS patients were requested to fill in an IBS severity questionnaire.Motor measurements in healthy subjects: Single-pulse lumbosacral magnetic stimulation (LSMS) was applied to the lumbosacral area for the anal sphincter where the largest motor evoked potential (MEP) amplitude response was detected. Single-pulse transcranial magnetic stimulation (TMS) was then performed at the pre-determined resting motor thresholds (RMT) for the anal sphincter and the hand.Sensory measurements in healthy subjects and IBS patients: Electrical stimulation was used to assess the changes in sensory and pain thresholds in the anorectal area. The subjects were asked to score the pain intensity using five-point categorical rating scales. In addition they were asked to describe the pain experienced using a shortened form of the McGill Pain Questionnaire. Intervention: Healthy volunteers received 6 paradigms of magnetic stimulation in a randomised order i.e. 3 repetitive LSMSs (1 Hz, 10 Hz and sham) and 3 repetitive TMSs (1 Hz, 10 Hz and sham) to investigate their modulatory effects on visceral sensitivity and to determine which of these interventions is most effective. The most effective active interventions (1 Hz rLSMS and 10 Hz rTMS) together with one sham were then trialled in a randomised fashion on IBS patients.Post intervention: Motor excitabilities were repeated at 30 min after each intervention. The assessment of sensory and pain thresholds at anal sphincter and rectum were done immediately, 30 and 60 min after each intervention. Results:Application of 1 Hz rLSMS led to alterations of anal sphincter motor excitabilities and resulted in a significant increase in the amplitude of lumbosacal-anal motor evoked potentials (MEPs) in healthy volunteers recorded at 30 min post intervention. In healthy volunteers, 1 Hz rLSMS and 10 Hz rTMS caused a significant increase in the rectal pain thresholds experienced immediately, 30 and 60 min after each intervention. 10 Hz rLSMS and 1 Hz rTMS only led to a significant rise in rectal pain thresholds immediately after their application. Furthermore, there was a significant increase in the rectal pain thresholds immediately, 30 and 60 min following 1 Hz rLSMS and 10 Hz rTMS in IBS patients. Conclusion:The application of magnetic stimulation to the cortical and lumbosacral areas to modulate visceral pain is a new concept, which reduced rectal sensitivity to painful stimuli and offers a much needed new approach in the management of abdominal pain in patients with IBS.

碩士
南華大學
自然生物科技學系自然療癒碩士班
104
Background and Purpose: Iridology is a science correlating iris morphology and the health condition of the human body. The iris is a microcosm of the human body. Through holographic principle, dynamic changes of the iris morphology can reflect pathological changes in the organ system. Functional gastrointestinal disorders(FGIDs) are chronic clinical conditions demonstrating a variety of symptoms. The purpose of the study was to correlate iris morphology with FGIDs. 　　Materials and Methods: From Sept. 2015 to Jan. 2016, 105 adult patients diagnosed with FGIDs using the Rome III Diagnostic Questionnaire Guidelines were prospectively included from a hospital in southern Taiwan. All of the subjects received iris detector measurements. The intestinal loop and gastric ring characteristics were quantitatively analyzed. The correlation between the patients demographic data, the Rome III classification questionnaire, and the iridology findings were analyzed with repeated measures Chi-square test. 　　Results: A total of 101 valid questionnaires were retrieved. The retrieval rate was 96.2%. Functional dyspepsia patients showed evidence of abnormalities in the right and left pupillary ruff. The left pupillary ruff abnormality is related to hiccough and multiple diseases, which indicates that the gastric mucosa was more vulnerable in these patients. The functional constipation patients showed gastric ring contraction on both sides, which means that the peristalsis function was not stable in these patients. The left first intestine ring representing the descending colon was dilated in functional dyspepsia and hiccough patients; The left 4th intestine ring representing transverse colon was dilated in functional abdominal bloating patients, signifying the loss of peristalsis power of the intestine. The iris morphology also showed significant correlation with age, sex, and many of the lifestyle factors, which were also correlated with FGIDs. 　　Conclusions: Functional gastroduodenal disorders and functional bowel disorders showed significant changes in iris morphology, these signs were also correlated with patient’s lifestyle habits. Our study showed that iridology examination is useful in early detection of FGIDs. In addition, adjustment of lifestyle and food choices could also be used to prevent or treat FGIDs.

碩士
國立陽明大學
醫務管理研究所
104
Background: The association between chronic obstructive pulmonary disease (COPD) and functional gastrointestinal disorders has rarely been examined in Asian populations. Methods: We investigated the hypothesis that COPD may increase the risk of functional gastrointestinal disorders in Taiwanese subjects using a nationwide population-based claims database. Our study cohort consisted of patients diagnosed with COPD between 2000 and 2005 (N = 9915). Three age- and gender-matched control patients for every patient in the study cohort were randomly selected from people without COPD for a comparison cohort (N = 29 745). All subjects were tracked for 5 years from the date of cohort entry to identify whether or not they had developed functional gastrointestinal disorders. Cox proportional-hazard regression models were used to evaluate the crude and adjusted hazard ratios (HRs) for functional gastrointestinal disorders for study and control patients. Results: The main finding of this study was that patients with COPD seemed to be at an increased risk of developing functional gastrointestinal disorders. A total of 3783 patients had functional gastrointestinal disorders during the 5-year follow-up period, this included 1567 COPD patients and 2216 control subjects. The adjusted HR for functional gastrointestinal disorders in patients with COPD was higher (HR: 2.02; 95% confidence interval (CI): 1.89-2.15; P < .001) than for the comparison patients. In our secondary analysis, functional gastrointestinal disorders were divided into gastroesophageal reflux disease, irritable bowel syndrome, and functional dyspepsia. Patients with COPD also had higher risks for all three subtypes of functional gastrointestinal disorders: irritable bowel syndrome (adjusted HR: 1.70; 95% CI: 1.51-1.91; P < .001), gastroesophageal reflux disease (adjusted HR: 2.31; 95% CI: 2.08-2.57; P < .001), and functional dyspepsia (adjusted HR: 2.04; 95% CI: 1.84-2.26; P < .001). Conclusions: In conclusion, during a 5-year follow-up period, patients with COPD seemed to be have a higher risk of developing functional gastrointestinal disorders compared with their non-COPD counterparts. Further similar investigations are still needed to confirm our association.

碩士
元培醫事科技大學
醫務管理系碩士班
104
Background: Asthma is a potentially serious chronic disease and increasing incidence in the developing countries. Atopic dermatitis and allergic rhinitis are associated with asthma. However, the association of asthma and functional gastrointestinal disorder has rarely been studied. Aim: To investigate whether asthma may increase the risk of functional gastrointestinal disorders in Taiwan using a nationwide Taiwanese population-based claims database. Materials and methods: Our study cohort consisted of patients who received a diagnosis of asthma in 2003~2005 (n=11031). For a comparison cohort, four age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (n=55155). All subjects were tracked for five year from the date of cohort entry to identify whether or not they had developed functional gastrointestinal disorders. Cox proportional hazard regressions were performed to evaluate 5-year Functional gastrointestinal disorder-free survival rates. Results: Of the 55155 sampled patients, 11031 patients had asthma diagnosis during a mean follow-up period of 4.84 years. Patients with asthma have significantly higher incidences of hypertension (20.6% vs 17.0%, p <0.001), hyperlipidemia (15.4% vs 12.6%, p <0.001) and type 2 diabetes mellitus (11.2% vs 8.9%, p <0.001), depression (4.8% vs 3.0%, p <0.001) and obesity (1.6% vs 0.8%, p <0.001) compared with control patients (Table 1). After adjusting confounding variables by Cox proportion hazard regressions, patients with asthma experienced 1.68 fold (95% CI, 1.53-1.84; p <0.001) increase in incidence of development of functional gastrointestinal disorders during the 5-year follow-up period compared with control group. Patients with either different age or gender group all had significant higher incidence of development of functional gastrointestinal disorders. Kaplan-Meier analysis revealed a tendency of patients with asthma develop functional gastrointestinal disorders (log-rank test, p <0.001). Conclusion: The findings of our population-based study suggest that patients with asthma may have an increased risk of functional gastrointestinal disorders. These health associations should recognize this important finding and effectively treat asthma patients.

Functional gastrointestinal disorders (FGIDs) affect one in four people during their lifetime and are a growing public health concern. These disorders are characterised by distressing, chronic recurring symptoms that reduce quality of life, and negatively impact patients physically, psychologically, socially and economically. Although largely managed in primary care, referrals for specialist care represent up to 50% of ambulatory gastroenterology care. New developments in diagnostic criteria and effective management options are available but under-utilised. The aims of this study were to 1) determine current issues in the diagnosis and management of FGIDs in primary and tertiary care; 2) explore tested models of care for FGID; and 3) design and evaluate an algorithm-based approach to the diagnosis and management of FGIDs (ADAM-FGID). A cross sectional, mixed-methods study was undertaken based on referrals (July 2013-15) to one gastroenterology outpatient department triaged as ‘likely FGID’. Patient characteristics, concerns and satisfaction with care, and reasons for referral were explored. The clinical approach to FGID diagnosis and management in tertiary care was assessed via audits of specialist correspondence and endoscopic procedures. A systematic review of FGID models of care was performed and a novel algorithm-based approach to the diagnosis and management of FGIDs was developed and trialled. There was a clear paucity of research into models of care for FGID, with only 6 low-quality studies. Primary healthcare providers (PHCPs) referring to tertiary care lacked confidence in the diagnosis and management of FGIDs, and patients expressed dissatisfaction with the lack of provision of a diagnosis or effective management options. Within tertiary care, unclear diagnostic language was more prevalent in FGIDs than organic disorders (63% vs. 13%; p<.001), as were endoscopic investigations (79% vs. 63%; p<.05). Almost 80% of all patients diagnosed with FGID were found to have undergone upper gastrointestinal endoscopy (UGIE) or colonoscopy. Existing endoscopic appropriateness criteria were inadequate in their consideration of functional symptoms, and preliminary evidence showed locally developed alarm-based appropriateness criteria to have better negative predictive value. The ADAM-FGID was found to be both safe and effective. 39% of referrals required more urgent gastroenterological review than original triage category, with organic disease subsequently diagnosed in 31% of these. 82% of FGID diagnoses were stable during follow-up. Patient buy-in to the model was good, with 80% entering management and 61% reporting symptom improvement at 6 weeks. Moreover, 68% of patients, and all referring doctors found the approach to be at least moderately acceptable. Patients reported being reassured by the approach, and found the management options useful. Primary health care providers acknowledged the potential of this approach to reduce waiting times for endoscopic procedures and to provide reassurance to both patients and themselves. FGIDs are poorly handled in the public health system and little research into effective models of care has been conducted. This study identifies multiple issues and opportunities to improve patient care and strategies to achieve these improvements are presented. The clinical pathway for the diagnosis and management of FGIDs, which is not dependent upon specialist review, is safe, feasible and acceptable and has potential to capacity build by reducing specialist burden and expediting effective care.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 2017.

Research Doctorate - Doctor of Philosophy (PhD)
This thesis examines several aspects of two phenotypes of a common gastrointestinal disorder known as functional dyspepsia. Functional dyspepsia has a significant effect on the quality of life of sufferers, and the societal and economic impact of evaluating and managing this disorder is considerable. Many phenotypic expressions of functional dyspepsia have been recognized, and this thesis focuses on functional dyspepsia among patients with diabetes mellitus as well as patients with rumination syndrome. These two phenotypes share several clinical features and potentially also pathogenic mechanisms. In addition, therapeutic options for patients with diabetic dyspepsia and rumination syndrome are very limited, thus representing a significant unmet need. Research into these two specific phenotypes lags behind what has been achieved in functional dyspepsia alone. For these reasons, the projects in this thesis aimed to improve the understanding of pathogenesis in these two phenotypes, but also explore potential diagnostic and therapeutic avenues. Spread over two focuses, this work in the thesis encompasses a randomised controlled trial, a case-control study and two retrospective clinical studies. The work led to novel insights into the pathophysiology of diabetic dyspepsia; we now know that intestinal chemosensitivity is a contributor to this disease. Furthermore, the experiments and studies into rumination syndrome helped unravel the mechanics of how diaphragmatic breathing treats this disorder as well as exploring potential duodenal pathogenic mechanisms. Finally, this work in this thesis discovered that oesophageal baseline impedance, as measured during an oesophageal high resolution impedance manometry study is very abnormal among patients with rumination, and indistinguishable from patients with gastroesophageal reflux disease. Overall, this work contained with this thesis makes several steps forward in our understanding of several aspects of diabetic dyspepsia and rumination syndrome.

La présente étude en anthropologie médicale propose d’examiner la dimension socioculturelle des désordres fonctionnels gastro-intestinaux (DFGI) en considérant l’expérience de six familles québécoises francophones où un pré-adolescent souffre de symptômes associés à un DFGI. Le regard anthropologique qui nous a permis d’appréhender ces expériences de douleur s’appuie principalement sur les travaux issus de la psychiatrie transculturelle, de même que sur les influences de l’anthropologie du corps et de la phénoménologie. À travers ce regard, la somatisation est considérée comme une forme de communication de la douleur, modulée de manière importante par le contexte socioculturel et représentative d’une certaine souffrance sociale. Ce langage ponctué d’idiomes de détresse et de métaphores permet aux individus d’exprimer leur souffrance et de mobiliser un soutien social efficace pour la prendre en charge. Dès lors, le corps doit être perçu comme un corps vécu; comme un lieu de marquage du social, mais également comme un instrument de positionnement social et une frontière où des mouvements d’appartenance et de divergence sont exprimés. Par l’exploration, dans chacune de ces familles, des différentes manières de décrire les symptômes, de les interpréter et d’y réagir, nous avons procédé à la reconstruction d’histoires particulières pour voir comment ces symptômes venaient s’inscrire dans la biographie individuelle et familiale. À travers l’analyse de la construction du sens de la douleur et des pratiques adoptées pour la contrôler, la douleur abdominale nous est apparue comme intimement liée à l’expérience sociale et la médicalisation comme une base pour une meilleure appréhension de cette douleur. Par ses maux de ventre, l’enfant exprime ses limites corporelles et sociales. À l’intérieur de la famille, l’expression de cette limite peut être parfois dérangeante, confrontante, et même entraîner des rapports conflictuels. C’est ainsi qu’est « négociée » une approche appropriée à la douleur qui redéfinit les rôles de chacun par rapport à cette dernière. Le ventre devient le médiateur qui permet le compromis nécessaire au « vivre ensemble » ou au « vivre dans le monde ». À l’issue de ii cette négociation qui implique la participation du médecin traitant, les rapports sont parfois reconstruits et la relation au monde et aux autres peut devenir différente.
This study in medical anthropology is an exploration of the sociocultural dimension of functional gastrointestinal disorders (FGID) considering the experience of six frenchspeaking families of Québec where a pre-teenager suffers from symptoms associated with FGID. The anthropological perspective that allowed us to approach these experiences of pain is based mainly on work from tanscultural psychiatry, as well as on the influences of the anthropology of the body and phenomenology. Through this view, somatization is considered to be a form of communication of distress, modulated in an important way by sociocultural context and reflecting social suffering. This language punctuated with idioms of distress and metaphors allows individuals to express their suffering and to mobilize an efficient social support. From then on, the body must be seen as a lived body; as a place of social marking, but also as an instrument of social positioning and a border where movements of belonging and divergence are expressed. By exploring, in each of these families, different ways of describing the symptoms, interpret them and respond to them, we proceeded to the reconstruction of particular stories to find how these symptoms were part of the individual’s and family’s biography. Through the analysis of how those families make sense of the pain and adopte practices to control it, abdominal pain appeared to us as intimately linked to social experience and the medicalization as a basis for a better apprehension of this suffering. While telling his or her pain, the child is also expressing his or her bodily and social boundaries. Within the family, the expression of this limit can sometimes be disturbing, confrontational, even lead to conflict. Thus was “negociated” an appropriate approach to pain that redefines the roles of each in relation to it. The abdomen becomes the mediator who allows the compromises needed to “live together” or to “live in the world”. Following this “negociation” that involves the participation of the attending physician, bonding within the family is sometimes positively transformed and the relation to the world and to the others can become different.