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.

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.

Orientador: Pedro Luiz Toledo de Arruda Lourenção / Resumo: Introdução: na prática clínica, nem sempre é fácil obter informações adequadas a respeito do padrão evacuatório. Na população pediátrica, os desafios para caracterização do aspecto das fezes são ainda maiores. Desta forma, é de fundamental importância a utilização de uma ferramenta adaptada para a linguagem e entendimento do público infantil. A Escala de Bristol para Consistência de Fezes Modificada para Crianças (“modified Bristol Stool Form Scale for Children – mBSFS-C”) foi recentemente criada e propõe a redução do número de tipos de fezes da Escala de Bristol original, de 7 para 5, e uma adaptação da linguagem utilizada nos descritores. O uso desta escala foi validado nos EUA, mas para que possa ser utilizada em países que possuam outros idiomas, é mandatória a realização de um processo de tradução, adaptação transcultural e validação. Objetivo: realizar o processo de tradução, adaptação transcultural e validação da mBSFS-C para a língua portuguesa do Brasil. Metodologia: a etapa de tradução e adaptação transcultural foi realizada segundo metodologia aceita internacionalmente que propõe a tradução, retro-tradução e pré-teste da versão traduzida da escala, em uma população de 74 crianças para avaliação do entendimento. A etapa de validação foi realizada através de um ensaio, que envolveu 64 crianças e 25 profissionais da saúde, estruturado para investigar a validade e confiabilidade da versão da escala traduzida. Resultados: a tradução e adaptação da mBSFS-C para o portugu... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Neonatal abstinence syndrome (NAS) is a syndrome of withdrawal symptoms in newborn infants that have a history of prenatal exposure to certain substances. Affected infants may have gastrointestinal (GI) issues, such as gassiness and diarrhea. Although infants with known exposures may be monitored in the first few days of life, it is unclear how long these symptoms persist. This poster will examine GI issues in the first six months of life across four groups of infants: those with prenatal opioid exposure, those with prenatal substance exposure that does not include opioids, those with polysubstance exposure, and those without substance exposure in a pediatric clinic in northeast TN. A retrospective chart review of 600 charts of infants born from 2017—2020 was conducted with IRB approval in a pediatric clinic in rural middle Appalachia. Of these, 300 charts were selected based on known prenatal substance exposure, and the other 300 charts were randomly selected. A REDCap extraction manual was created, research assistants were trained, and % agreement was determined. Data was collected about type of prenatal substance exposure, growth, and medical conditions in the first three years of life. Infants were divided into groups by type of prenatal substance exposure for analysis. The opioid-only group included exposure to buprenorphine, methadone, or other opiates. The other (non-opioid) exposure group included exposure to marijuana, cocaine, benzodiazepines, methamphetamines, and prescription ADHD medications. The polysubstance exposure group included exposure to both opiate and non-opiate substances. The control group had no prenatal substance exposure. Analyses were performed using SAS version 9.4. Descriptive statistics showed the demographics of the sample were representative of the population in rural middle Appalachia, with a predominantly Caucasian sample of 121 females and 123 males, mostly receiving TennCare. Chi-square results showed there was only a statistically significant difference between the prenatal substance exposure groups at 2 months, X2 (3, N = 176) = 8.03, p = 0.045, but not at hospital discharge, within the first few days of life, at 1 month, 4 months, or 6 months. Infants in the opioid-only exposure group were most likely to have GI issues. These findings suggest that GI issues are more likely to occur in infants with certain prenatal substance exposures. This poster also shows a longitudinal perspective of these issues, indicating that the symptoms may persist in the first few months of life. Thus, caregivers of infants at risk for NAS may benefit with information about the long-term effects. Because the retrospective chart review is still in progress, this poster only analyzes a preliminary number of charts. Future research should also take into consideration other factors that may be associated with GI issues in this population, such as nutrition.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24131号 / 医博第4871号 / 新制||医||1059(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 阪上 優, 教授 佐藤 俊哉, 教授 小杉 眞司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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.

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.

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 (&lt;50 years of age) reported GI symptoms more frequently than late-onset cases (70 % vs. 50 %, p &lt;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 &lt;0.01). Both upper and lower GI symptoms were significant negative predictors of nutritional status and health-related quality of life (p &lt;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 &lt;0.01) and parasympathetic (rs = -0.3, p &lt;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 &lt;0.01) and longitudinal (median density 0.0 vs. 1.8, p &lt;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 &lt;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.

Die vorliegende Arbeit befaßt sich mit Nachweismöglichkeiten von Helicobacter pylori und deren Vergleich. Hierfür ist eine genaue Kenntnis der Helicobacter-Proteine notwendig. Zu diesem Zweck wurde die humorale Immunantwort gegenüber Helicobacter pylori unter Anwendung der Methodik des zweidimensionalen Immunoblots analysiert. Zunächst wurden Proteine des autologen Helicobacter pylori-Stammes über zweidimensionale Gelelektrophorese aufgetrennt, auf Nitrocellulose-Membranen geblottet und sodann mit Antikörpern aus autologem Plasma sowie Antikörpern aus dem Überstand von in vitro kultiviertem autologem Biopsiematerial detektiert. Zur Bestimmung einer Helicobacter-Infektion wurden andere invasive und nicht invasive Tests genutzt. In einer prospektiven Untersuchung wurden über 200 konsekutive Patienten mit gastrointestinalen Beschwerden und unbekanntem H. pylori-Status, die für eine Gastroskopie vorgesehen waren, routinemäßig untersucht. Bei jeder Gastroskopie wurden zwei Antrum- und zwei Korpusbiopsien zur Gastritis-Diagnostik und zur Bestimmung des H. pylori-Status entnommen. Es wurden Assoziationen zwischen einer Infektion mit Helicobacter pylori und Erkrankungen wie akute und chronische Gastritis, gastraler und duodenaler Ulkus, Magenkarzinom und Folgeerkrankungen der Gastritis überprüft. Dabei wurden auch die eindeutig Helicobacter pylori-negativen Seren mit den positiven Seren verglichen. Trotz ungleichmäßiger Verteilung der Patientenzahlen über die einzelnen Krankheitsgruppen (Gastritis, Ulkus, Karzinom) wurden bestimmte Proteine nur bei einer der Erkrankungen erkannt. Einige Proteinspots kamen deutlich intensiver bei einer einzigen Krankheitsgruppe vor. Anzustreben sind Studien mit größeren Patientenzahlen innerhalb der einzelnen Krankheitsgruppen, um mögliche weitere Assoziationen bestimmter Helicobacter-Antigene mit Folgeerkrankungen zu analysieren und zu verifizieren. Ferner wurde das Vorliegen einer Assoziation des zweidimensionalen Immunoblots mit anderen invasiven und nicht invasiven Nachweisverfahren der H. pylori-Infektion analysiert. Dabei wurde das Antigenprofil des H. pylori, sowohl qualitativ als auch quantitativ, berücksichtigt. Durch die Charakterisierung und Identifizierung einer bedeutenden Anzahl von Helicobacter-Proteinen erhöht sich die Wahrscheinlichkeit für ein zukünftig beschleunigtes Screening in Richtung protektiver Vakzine-Kandidaten. / The present study is concerned with practicable methods of detecting Helicobacter pylori and comparing them. As a precondition, a precise knowledge of the proteins of Helicobacter is necessary. To this end the humoral immune response of Helicobacter pylori was analysed by using the method of two-dimensional immuno blots. First, the proteins of each autologous Helicobacter pylori strain were separated by two-dimensional electrophoresis, then blotted onto nitrocellulose membranes and eventually detected by using antibodies from autologous plasma and antibodies taken from the overflow of in vitro cultivated autologous biopsy material. For determining a Helicobacter infection various invasive and non-invasive tests were carried out. In a prospective study on more than 200 patients with gastrointestianal disorders but unknown H. pylori status were consecutively tested. At each gastroscopy two bioptic specimen each were taken from the antrum and from the corpus region in order to determine the H. pylori status. Associations were assessed between Helicobacter pylori infections and manifestations such as acute or chronic gastritis, gastric or duodenal ulcers, gastric carcinoma and gastritis induced disorders. In the process, clearly Helicobacter pylori negative sera were also compared with positive sera. Inspite of the unequal distribution of numbers of patients over different groups of disorders (gastritis, ulcers, carcinoma) certain proteins were only detected in connection with one group of disorder. Several of the protein spots only occurred in a single group of disorders. More studies will be necessary using greater numbers of patients within each group of diseases in order to analyse and verify associations between Helicobacter antigenes and other disorders. Further, evidences of an association between two-dimensional immunoblots and other invasive and non-invasive methods of assessing H. pylori were analysed with regard to respective antigene profiles, qualitatively as well as quantitatively. Based upon the presented characterizations and identifications of an unusually great number of Helicobacter proteins the probability is thus increased considerably with regard to improved screening methods towards protective vaccine candidates.