INTRODUCCION: La metaplasia intestinal gástrica (MI) es una etapa previa al cáncer gástrico. La apropiada identificación endoscópica con biopsia es vital para confirmación histológica. No conocemos en nuestro medio la relación entre los hallazgos endoscópicos sospechosos de metaplasia intestinal y su confirmación histológica, ni sus factores asociados con claridad. OBJETIVO: determinar la correlación entre los hallazgos endoscópicos de sospecha de metaplasia y su contraparte histológica en nuestro medio , dentro de ellos también determinar algunos factores asociados .a los pacientes con sospecha de metaplasia .Métodos: Estudio observacional analítico, realizado en el Hospital Nacional Hipólito Unanue en pacientes >= 18 años con sospecha endoscópica de MI, excluyendo pacientes con cáncer gástrico previo y pacientes con antecedentes previo de metaplasia . La evaluación estadística se realizó con el software estadístico SPSS. Resultados: 3398 pacientes sometidos a endoscopia alta se identificaron un total de 176 pacientes con sospecha endoscópica de metaplasia l. En 152 de ellos se encontró confirmación histológica MI equivalente a un 86,36% del total de la muestra. Los hallazgos histológicos frecuentes en el grupo fueron 51(29% pacientes ) pacientes presentaron gastropatía atrófica en alguna parte de su estómago , 28( 15,9%) pacientes presentaron gastritis superficial con la toma de biopsia , hiperplasia foveolar en Solo 2 (1,1%) pacientes demostrados por biopsia entre otros. Predominaron pacientes de sexo femenino con MI+ (90) .Los diferentes subgrupos generados por el reporte histológico de metaplasia intestinal incluyeron los siguientes: metaplasia completa (44,3%), metaplasia incompleta (17,6%), metaplasia inespecífica (13,6%), metaplasia mixta (11,4) % y la no presencia de metaplasia 13,1% . solo el 4 % de la población estudiada se reportó metaplasia intestinal con algún tipo de displasia . Con respecto al análisis bivariado se encontró asociación de riesgo con gastritis crónica atrófica OR : 3,733 (IC 95% 0,941-14,819,p = 0.051), gastritis crónica superficial OR 1,378 (ic 95% 0,382-4,973, p = 0.623) edad <=65 años con Helicobacter pylori (HP) y metaplasia intestinal + OR :2,706 (IC 95% 0,342-21,402, p = 0.327) edad <=65 años con hp+ y metaplasia intestinal completa vs mixta , se encontró OR 2,836 (IC 95% 0,341-23,574, p = 0.633), edad <=65 años con hp+ y MI completa vs incompleta OR 1,393 (IC 95% 0,356-5,447, p = 0.633). Entre reflujo y MI , se encontró un OR 1,164 (IC 95% 1,096 -1,238, p = 0.322) ,HP y MI OR 0.537 (IC 95% 0.226 -1,277, p = 0.155) no se puede afirmar que existe una tendencia de asociación entre presencia HP y MI . Conclusiones: Con respecto al diagnóstico histológico de metaplasia intestinal, 86,36 % de los pacientes sometidos a estudio 7 endoscópico con sospecha de metaplasia intestinal correspondientes a un total de 152 fueron confirmados mediante el estudio histológico, aunque la detección fue cercana al 86,36%,se encontró asociación de riesgo en los pacientes con gastritis atrófica , gastritis crónica superficial ,edad<=65años y HP+ ,reflujo biliar . No se encontró asociación en pacientes con Hp+ .Se requieren de estudios prospectivos, multicéntricos y con cromoendoscopia, con el fin de evaluar la concordancia respectiva entre los dos métodos y determinar variables endoscópicas predictoras de severidad, y tipo de metaplasia para determinar protocolos de seguimiento para este tipo de pacientes.

Helicobacter pylori ist ein an seine ökologische Nische hochgradig angepasstes Bakterium, das den Magen von mehr als 50% der Weltbevölkerung chronisch besiedelt. Bei 10 bis 20% der Infizierten können schwerere Krankheitsverläufe von Magengeschwüren bis hin zu Karzinomen auftreten. Die Chemotaxis-gesteuerte Motilität von H. pylori, vermittelt durch ein Bündel von 2-8 polaren Flagellen, ist für die Besiedelung und persistente Infektion des Wirtes essenziell. Mehr als 40 Komponenten des Flagellen- und Chemotaxissystems konnten mit Hilfe der beiden sequenzierten H. pylori-Genome identifiziert werden, wobei die Gene einzeln oder in kleinen transkriptionellen Einheiten über das gesamte Genom verteilt angeordnet sind. Mit der vorliegenden Arbeit sollte die Organisation und Vernetzung der transkriptionellen Regulation der Flagellenbiogenese und mögliche Querverbindungen zu anderen zellulären Funktionen in H. pylori umfassend charakterisiert werden. H. pylori verfügt über zwei unterschiedliche Flagellingene, flaA und flaB, deren Transkription von den beiden alternativen Sigma-Faktoren Sigma28 und Sigma54 kontrolliert wird. Um die transkriptionelle Regulation der beiden Gene in zwei unterschiedlichen Flagellenregulons zu untersuchen, wurde die Genexpression von flaA und flaB abhängig von der Wachstumsphase analysiert. Mit flaA- und flaB-Promotorfusionen wurde hier erstmalig ein sensitives, Biolumineszenz-basiertes Reportersystem für Expressionsstudien in H. pylori etabliert und genutzt. Die Transkriptmengen der beiden Flagellingene wurden weiterhin direkt mittels Northern Blot-Hybridisierungen und RT-PCR bestätigt. Es ergab sich eine Wachstumsphasen-abhängige, differentielle Regulation, bei der in Übereinstimmung mit der strukturellen Anordnung der Flagelline im Filament und der Zugehörigkeit der Gene zu zwei Regulationsklassen, das Verhältnis der flaA- zur flaB-Expression im Verlauf der Wachstumskurve stark anstieg. Um genomweite Analysen durchführen zu können, wurde in dieser Arbeit zunächst eine Plattform zur Untersuchung von H. pylori mit DNA-Microarrays etabliert. Hierzu wurde in Kooperation mit dem Max-Planck-Institut für Infektionsbiologie in Berlin ein PCR-Produkt-Microarray mit 1590 H. pylori-spezifischen Sonden produziert. Zusätzlich wurde ein industriell gefertigter, Oligonukleotid-basierter, H. pylori-Microarray erstmalig verwendet und validiert. Mit Hilfe der Microarray- Technologie wurden verschiedene zentrale Regulatoren der H. pylori-Flagellenbiogenese zum ersten Mal auf genomweiter Ebene untersucht. Hierzu zählten die beiden alternativen Sigma-Faktoren FliA und RpoN, der Anti-Sigma28-Faktor FlgM, das RpoN-spezifische Zwei-Komponenten System FlgS/FlgR und die Flagellen-Basalkörperkomponenten FlhA und FlhF. Bis auf die fliA- und flgM-Mutanten, die, in Übereinstimmung mit ihrer antagonistischen Funktion, Stummelflagellen bzw. eine leicht erhöhte Flagellenzahl aufwiesen, bewirkten die Mutationen in allen anderen untersuchten Genen einen flagellenlosen unbeweglichen Phänotyp. Die Klassen 2 und 3 des H. pylori-Flagellenregulons konnten durch die Analysen des FliA- und des RpoNRegulons neu definiert und um zehn neue Gene ergänzt werden. Für FlhA und FlhF konnte eine Funktion als übergeordnete Regulatoren der Klassen 2 und 3 des Flagellenregulons gezeigt werden. Des Weiteren wurden 24 Gene einer neuen regulatorischen Zwischenklasse zugeordnet. Diese Gene werden von mehr als einem Promotor kontrolliert und umfassen Flagellen- sowie Nicht-Flagellengene. Durch globale Untersuchungen von Doppelmutanten wurde die komplexe Einbindung des Anti-Sigma-Faktors FlgM in die FlhA- und FlhF-vermittelte transkriptionelle Rückkopplung nachgewiesen. Basierend auf den Ergebnissen der Arbeit konnte ein neues Modell der Regulation der Flagellenbiogenese für H. pylori entwickelt werden. Es beinhaltet drei regulatorische Genklassen mit einer intermediären Klasse, die von den drei H. pylori-Sigma-Faktoren Sigma80, Sigma54 und Sigma28 zusammen mit den assoziierten Regulatoren FlgS/FlgR und FlgM kontrolliert werden. FlgM vermittelt als Anti-Sigma28-Faktor die transkriptionelle Rückkopplung auf die Klasse 3- und, im Zusammenspiel mit FlhA, auch auf die Klasse 2-Flagellengene. FlhF kontrolliert die Expression der Klasse 2-Flagellengene durch einen FlgM-unabhängigen, bislang ungeklärten Mechanismus. Die Sigma80-abhängigen Klasse 1-Flagellengene werden, anders als bei vielen anderen Bakterien, mit Stoffwechselgenen koreguliert und beinhalten auch die Flagellenmotor- und Chemotaxisgene. Dies spiegelt die Anpassung von H. pylori an seine spezifische ökologische Nische wieder, mit der Notwendigkeit, während der gesamten Infektion die Motilität aufrecht zu erhalten. / The gastric human pathogen Helicobacter pylori is a fastidious bacterium, chronically colonizing the stomach of more than half of the world population, leading to severe diseases in some individuals such as ulcers or gastric cancer. H. pylori flagella-driven motility has been shown to be essential for the initial colonization of the human gastric mucosa and for the long-term persistence of the infection. The 2-8 flagella are arranged at one pole of the bacterium and covered by a membranous sheath. The flagella and chemotaxis system comprises more than forty genes. In contrast to the highly ordered gene organization in other organisms, they are scattered along the genome. The aim of this study was to comprehensively characterize the network of transcriptional regulation of flagellar biogenesis with possible links to other cell functions in H. pylori. H. pylori possesses two different flagellin genes, flaA and flaB, the transcription of the corresponding genes is controlled by sigma28 and sigma54 promoters respectively. To characterize the specific transcriptional regulation of these flagellar genes, which belong to two different regulons, transcript levels were monitored throughout the growth curve of H. pylori. A bioluminescence-based reporter gene system was successfully established in H. pylori for the first time. It was utilized to measure the activity of the newly constructed flaA- and flaB-promoter fusions. Furthermore growth-phase dependent transcript levels of the two flagellin genes were confirmed by Northern blot hybridizations and RT-PCR analysis. The results revealed a growthphase dependent differential transcriptional control of flaA and flaB in H. pylori. In agreement with the structural succession of FlaB and FlaA in the filament, as well as the affiliation of the genes to different flagellar regulons, flaA to flaB expression ratio was strongly increasing with the progression of the growth curve. An H. pylori microarray working platform was established to be able to perform genome-wide analyses on this organism. A custom made PCR-product microarray with 1590 H. pylori specific probes was constructed in cooperation with the Max-Planck-Institute for Infection Biology in Berlin. In addition, a commercially available H. pylori-specific oligonucleotide based microarray system was utilized for the first time and validated. By using the microarray technology, a set of different key regulators of the H. pylori flagellar system was analysed on a genome-wide scale for the first time. They are comprising the alternative sigma factors FliA and RpoN, the anti-sigma-factor FlgM, the RpoN specific two component system FlgS/R and the components of the flagellar basal body, FlhA and FlhF. While the fliA mutant revealed a phenotype with truncated flagella, the flgM mutant had a slightly enhanced number of flagella, correlating with their antagonistic function. Mutations in all other regulators lead to loss of flagella and motility. Based on the microarray analyses of the FliA and RpoN regulons, the flagellar regulatory classes 2 and 3 could be newly defined and enlarged by ten additional genes. The microarray studies on early flagellar components revealed a role for FlhA and FlhF as functional equivalents to master regulators. They are governing the transcription of flagellar regulatory classes 2 and 3 and a newly defined intermediate regulon. The latter comprised 24 flagellar and non-flagellar genes controlled by more than one promoter. Furthermore, studies on double mutants of the early regulators with the flagellar antisigma factor FlgM provided evidence for the complex regulatory interconnection of this factor with the determined flagellar feedback regulation of FlhA and FlhF. Based on the results of this study, a revised model of regulation pathways of flagellar biogenesis in H. pylori could be constructed. It is composed of three regulatory classes of flagellar genes and one intermediate class, governed by the three H. Pylori specific sigma factors sigma80, sigma54 and sigma28 and the associated regulators FlgS/R and FlgM. The transcriptional feedback regulation on class 3 genes is mediated by the anti-sigma factor FlgM, which is also involved in FlhA-dependent transcriptional control of class 2 flagellar genes. FlhF-dependent transcriptional control on class 2 genes is independent from FlgM. In contrast to other organisms, flagellar class 1 genes in H. pylori include flagellar motor and chemotaxis components and are coregulated with housekeeping genes. This coincides with the specific ecological adaptation of H. pylori to its niche and the necessity for the pathogen to be continuously motile to maintain a persistent infection.

Faculty of Health Scicence School of Medicine 0100107g johannes.geyer@wits.ac.za / The 14C and 13C labelled urea breath tests (UBT) for detecting Helico-bacter pylori infection are well established but scope for improvement exists in both to reduce some of their shortcomings. For this study, the 14C UBT investigation focussed on reducing the quantity of radioactive tracer that is administered to the subject un-dergoing this test, with the aim of lowering the radiation dose to the patient, reducing the impact to the environment and exempting the test from radioactive materials licensing. Wider acceptance, availabil-ity, affordability to lower socio-economic groups and third party medi-cal treatment payers and using readily available equipment were fac-tors considered when developing the method. The principle of the method developed is to collect larger volume breath sample, quantitatively absorbing a defined volume of extracted breath CO2 in an efficient CO2 trapping agent using a specifically de-signed apparatus and measuring the activity with a low background β-spectrometer. A reduction in the quantity of 14C labelled urea administered to the pa-tient was achieved. The method also reduced the counting error mar-gin at a lower detection limit, improving discrimination between H. py-lori positive and negative patients. iii The 13C UBT is a non-radioactive test however, it is substantially more expensive. The 13C UBT investigation aimed to determine whether commercially available un-enriched urea could be used thus reducing the cost of the 13C UBT. A simple protocol with Isotope Ratio Mass Spectrometry (IRMS) for the measurement was used as opposed to the well-established 13C UBT protocol. The principle of the 13C UBT investigation was to detect the change of the breath δ13C (13C/12C) ratio after the administration of un-enriched urea with a δ13C different to the exhaled breath. Theoretical calculations showed that an administered dose of 500mg un-enriched urea with at least a 10‰ δ13C difference may be detectable using IRMS. In vitro investigations confirmed that levels of 0.01 to 0.001‰ δ13C were detectable by IRMS. A change in the δ13C of a standard breath CO2 was confirmed for a range between 0.14 to 50% v/v mixed CO2 samples, i.e. the projected range for in-vivo investigation. Results from the in-vivo investigation however were not able to distinguish positive from negative H. pylori patients. The use of the 1000mg dose of urea appears to have caused saturation of the enzyme. It was con-cluded that some enrichment of the 13C is necessary or less urea be used.

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No. of bitstreams: 3 license_text: 21244 bytes, checksum: 51d48429f9b12e63f6b08237f8c0eabe (MD5) license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) 2015HenriqueSulzbachdeOliveira.pdf: 1900803 bytes, checksum: b661d7808a3792bd808f143d5dd8e7a3 (MD5) / Helicobacter pylori é uma bactéria que infecta aproximadamente 50% da população mundial, podendo causar gastrite crônica e outras formas de dano celular. A relação entre inflamação e câncer é amplamente descrita. Estímulos patogênicos induzem a expressão do fator de necrose tumoral alfa (TNF-α) que, por sua vez, induz outros mediadores responsáveis pela resposta inflamatória e proliferação celular. O presente estudo teve como objetivo avaliar a expressão dos genes TNF-α, NFKΒ1 e p38α na mucosa gástrica humana e investigar a influência da presença de H. pylori na expressão destes em uma população do Vale do Taquari, Rio Grande do Sul, Brasil. As amostras foram coletadas por endoscopia digestiva alta, sendo o diagnóstico de H. pylori realizado através do teste rápido de urease, com posterior confirmação pelo exame anatomopatológico de rotina. O RNA total foi extraído e purificado para posterior síntese de DNAc (DNA complementar) e análise por qPCR (Reação em Cadeia da Polimerase em Tempo Real). O algoritmo NormFinder foi utilizado para a análise do gene de referência. Para análise estatística dos genes de interesse foram utilizados os testes de Mann-Whitney e Kruskal-Wallis seguido pelo teste de comparações múltiplas de Dunn. Das 100 amostras coletadas, 19% foram classificadas como normal, 46% como gastrite crônica não ativa, 27% como gastrite crônica ativa e 8% como metaplasia intestinal. Todas as amostras positivas para H. pylori apresentaram inflamação ativa, de acordo com o exame anatomopatológico. Utilizou-se como gene normalizador o SDHA, que foi classificado como mais estável em relação ao ACTB, GAPDH, B2M e HPRT1. A expressão do TNF-α foi significativamente superior nos grupo H. pylori Positivo (p < 0,0001, teste de Mann-Whitney) e Gastrite Crônica Ativa (p < 0,01, Teste de Kruskal-Wallis seguido pelo teste de comparações múltiplas de Dunn). No entanto, não foi detectada diferença na expressão gênica do NFKΒ1 e do p38α entre os grupos. Pode-se concluir que a presença de H. pylori pode estar relacionada ao aumento na expressão do TNF-α, demonstrando a sua influência no processo inflamatório do tecido gástrico. Apesar de não ter sido encontrada alteração na expressão do NFKΒ1 e do p38α em nível de RNAm, estudos adicionais devem ser realizados para verificação da influência destes genes nesta via. / Helicobacter pylori infects about 50% of the world’s population, causing chronic gastritis and other forms of cellular damage. The relationship between inflammation and cancer is well known. Pathogenic stimuli induce the expression of tumor necrosis factor alpha (TNF-α), which, in turn, induce other mediators responsible for inflammation response and cell proliferation. The present study aimed to evaluate the gene expression of TNF-α, NFKB1 and p38α in human gastric mucosa and investigate the H. pylori influence in the expression of these genes in a population of Vale do Taquari, Rio Grande do Sul, Brazil. The samples were collected by upper endoscopy and the H. pylori diagnosis was performed through rapid urease test and histological analysis. The total RNA was extracted and purified for subsequent cDNA synthesis and qPCR analysis. The NormFinder algorithm was used for reference gene analysis. For the statystical analysis of the studied genes were used the Mann-Whitney test and the Kruskal-Wallis test followed by the Dunn’s test for multiple comparisons. From the 100 samples collected, 19% were classified as normal, 46% as non-active chronic gastritis, 27% as active chronic gastritis, and 8% as intestinal metaplasia. All samples positive for H. pylori demonstrated active inflammation, according to hystological analysis. SDHA was classified as the most stable gene when compared to ACTB, GAPDH, B2M and HPRT1, being chosen to be used as reference gene for qPCR normalization. The TNF-α expression was significantly higher in the H. pylori (p < 0,0001, Mann-Whitney’s test) and the Active Chronic Gastritis groups (p < 0,01, Kruskal Wallis test followed by Duncan’s multiple comparisons test). However, it wasn’t detected any difference in NFKΒ1 and p38α expression in the studied groups. It can be concluded that the presence of H. pylori can be related to TNF-α upregulation, demonstrating its influence in the inflammatory response of the gastric tissue. Although it has not been found changes in the NFKΒ1 and p38α expression at mRNA levels, additional studies are needed to verify the influence of these genes in this pathway.

Fundamentos: a rosácea é uma dermatose freqüente que possui multiplicidade de fatores envolvidos no seu desencadeamento. Na literatura recente, há autores que apontam o Helicobacter pylori como um possível agente etiológico da doença. Porém os poucos estudos publicados sobre o assunto que utilizaram pacientes controles não encontraram evidências de que esta associação seja importante. No Brasil, não há trabalhos publicados quanto à exposição ao Helicobacter pylori em pacientes com rosácea, e mesmo o perfil geral dos pacientes com rosácea, no país, é pouco conhecido. Objetivos: o principal objetivo do estudo foi avaliar se a exposição ao Helicobacter pylori constitui um fator de risco para o desenvolvimento da rosácea. Os outros objetivos do trabalho foram: avaliar uma possível diferença da presença de distúrbios dispépticos entre casos de rosácea e controles, analisar se a exposição ao Helicobacter pylori ocorre homogeneamente nos diferentes estágios evolutivos da rosácea, e descrever o perfil clínico-epidemiológico dos pacientes com rosácea. Metodologia: foi realizado um estudo caso-controle no Serviço de Dermatologia do Hospital de Clínicas de Porto Alegre I Universidade Federal do Rio Grande do Sul e no Laboratório Faillace (Porto Alegre, RS), no período entre 15 de abril de 1996 e 18 de maio de 1998. Os casos de rosácea (n=62) foram definidos de acordo com o critério clínico de Marks ( 1992) e classificados de acordo com os critérios de Plewig e Kligman (1993). Em situações de dúvidas clínicas, foram realizadas biópsias cutâneas, e a histopatologia foi utilizada para definir os diagnósticos. Os pacientes controles (n=124) foram selecionados entre pacientes não portadores de rosácea, atendidos no mesmo Serviço. Houve pareamento para idade, sexo e raça e apenas pacientes acima de 18 anos foram incluídos. As variáveis aferidas em ambos os grupos foram renda familiar mensal, grau de escolaridade, uso prévio de medicamentos sistêmicos, presença de distúrbios dispépticos e sorologia (IgG por enzimaimunoensaio) para Helicobacter pylori. Foram realizadas análise de risco bivariada e análise estatística estratificada. Resultados: houve uma fraca associação entre a exposição ao Helicobacter pylori e a rosácea (OR= 1,41 p=0,367), porém a análise estratificada demonstrou que o uso de medicamentos prévios e a renda familiar mensal inferior a 10 salários mínimos agiram de modo a modificar a relação entre o fator em estudo e o desfecho. No estrato em que essas variáveis modificadoras de efeito não interferiram, verificou-se uma forte associação entre a bactéria e a dermatose (OR=8,0 p""0,023). Não ocorreram diferenças importantes entre casos e controles quanto à presença de distúrbios dispépticos; também não ocorreram diferenças importantes quanto à freqüência de reagência sorológica ao Helicobacter pylori entre os diferentes estágios evolutivos da rosácea. O perfil dos pacientes com rosácea da amostra mostrou-se semelhante aos já descritos na literatura mundial. Conclusão: a freqüência da sorologia reagente para Helicobacter pylori em casos e em controles demonstrou não existir uma forte associação de risco entre o bacilo e a dermatose, exceto quando as variáveis modificadoras de efeito são removidas. Portanto, a principal conclusão do estudo é que, provavelmente, o Helicobacter pylori constitua um fator de risco para a rosácea em determinados grupos de indivíduos. / Background: rosacea is a frequent dermatosis triggered by multiple factors. In recent literature there are authors who indicate Helicobacter pylori as a possible etiological agent of the disease. However, the few studies published on this subject using control patients did not find evidence that this association is important. In Brazil, no studies have been published regarding exposure to Helicobacter pylori in patients with rosacea, and even the general profile of the patients with rosacea in the country is little known. Objectives: the main objective of the study was to assess whether the exposure to Helicobacter pylori constitutes a risk factor for the development of rosacea. The other objectives ofthe study were: to assess a possible difference in the presence of dyspeptic disorders between cases of rosacea and the controls; to analyze whether exposure to Helicobacter pylori occurs homogeneously in the different stages of evolution of rosacea, and; to describe the clinical-epidemiological profile o f rosacea patients. Methodology: a case-control study was perfomed at the Dermatology Service of Hospital de Clínicas de Porto Alegre I Universidade Federal do Rio Grande do Sul, and at Laboratório Faillace (Porto Alegre, RS), in the period from April 15, 1996 to May 18, 1998. The rosacea cases (n=62) were defined according to the clinicai criterion of Marks (1992) and classified according to the criteria ofPlewig and Kligman (1 993). In situations of clinicai doubt, skin biopsies were perfomed, and the histopathology was used to define the diagnoses. The control patients (n= l24) were selected among patients who did not have rosacea, seen at the same Service. Matching was perfomed for age, sex and race, and only patients over 18 years of age were included. The variables measured in both groups were monthly family income, schooling, previous use of systemic medications, presence of dyspeptic disorders and serology (lgG by enzyme immunoassay) for Helicobacter pylori. Bivariate risk analysis and stratified statistical analysis were perfomed. Results: a weak association was found between exposure to Helicobacter pylori and rosacea (OR= l ,41 p=0,367), but stratified analysis showed that the use of previous medications and family in come below 1 O rninimum wages modified the relationship between the factor studied and outcome. In the stratum where these effect-modifying variables did not interfere, a strong association was found between the bacteria nad dermatosis (OR=8,0 p=0,023). No significant ditferences were found as to frequency of serological reaction to Helicobacter pylori among the different evolutionary stages of rosacea. The profile ofthe rosacea patients in the sample proved similar to those already described in world literature. Conclusion: the frequency of serology reagent for Helicobacter pylori in cases and controls showed that there is not strong risk association between the bacillus and dermatosis, except when the effect-modifying variables are removed. Thus, the main conclusion o f the study is that, probably Helicobacter pylori constitues a risk factor for rosacea in certain groups o f individuais.

by Wu Che-yuen Justin. / "September 2000 (amendment)." / Thesis (M.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 237-267). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Orientador: Maria Aparecida Marchesan Rodrigues / Resumo: Introdução: A infecção por Helicobacter pylori (H. pylori) é o principal fator etiológico da gastrite e úlcera péptica. O diagnóstico e tratamento adequados são importantes para prevenir essa evolução. Objetivo: Investigar o padrão de colonização da mucosa gástrica por H. pylori em crianças e adolescentes com dor abdominal crônica e dispepsia não ulcerosa. Casuística e Métodos: Foram analisadas retrospectivamente 94 biópsias endoscópicas de mucosa gástrica, 47 do antro e 47 do corpo gástrico, de crianças e adolescentes com diagnóstico de pan-gastrite associada à infecção por H pylori. Foram avaliados o padrão de colonização da mucosa por H pylori e a densidade de colonização, por análise imuno-histoquímica. A intensidade da resposta inflamatória e a frequência de folículos linfóides também foram investigados. Resultados: A frequência de colonização profunda do H pylori na mucosa do corpo foi de 72,3%, em contraste com a colonização predominantemente superficial no antro gástrico (95,7%). A densidade de colonização por H pylori foi alta no antro (83%) e no corpo gástrico (68,1%). A frequência de agregados linfoides foi significativamente maior na mucosa do antro (68,1%), quando comparada à do corpo gástrico (34%) e apresentou boa correlação com a intensidade da inflamação e a densidade de colonização por H pylori no antro gástrico. Conclusão: O padrão de colonização por H. pylori diferiu entre as regiões do estômago, sendo predominantemente superficial no antro e profundo no c... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation and peptic ulcer disease. Diagnosis and treatment are important to prevent these outcomes. Aim: To investigate colonization pattern of H pylori in gastric mucosa of children and adolescents with chronic nonulcer dispepsy. Methods: Gastric endoscopic biopsies, 47 from antrum and 47 from corpus, were retrospectively analysed to determine H. pylori colonization pattern and density by immunohistochemistry. Inflammation grade and presence of lymphoid aggregates were also evaluated. Results: High frequency of deep H pylori colonization was found in gastric corpus (72,3%), in contrast to the superficial colonization identified in the antral mucosa (95,7%). H pylori density was high in the antrum (83%) and corpus (68,1%). High grades of gastric inflammation were detected in both antrum (89,4%) and corpus (76,6%). The frequency of lymphoid aggregates was significantly higher in the antral mucosa (68,1%) than in the corpus (34%) and presented a good correlation with H pylori density and grade of inflammation. Conclusion: H. pylori colonization pattern is predominantly superficial in both antrum and corpus mucosa, but deep H pylori colonization can be found in gastric corpus. / Mestre

A metaplasia intestinal gástrica (MIG) é considerada como lesão precursora para o câncer gástrico, mas isto não tem levado a um controle maior dos portadores. Estudamos uma população dispéptica adulta e detectamos a prevalência de MIG. Vários marcadores têm sido testados para indicar qual paciente portador de metaplasia intestinal deva ser acompanhado com exames periódicos. Um destes marcadores é a pesquisa da proteína de membrana CD44v6 em lesões pré-malignas. Objetivo: estudar a expressão da CD44v6 em pacientes dispépticos com Helicobacter pylori (H. pylori) e metaplasia intestinal gástrica. Local: Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul. Pacientes: 642 pacientes dispépticos dos quais foram estudados 56 pacientes com MIG e comparados com outros dois grupos, um de pacientes com H. pylori e outro, sem H. pylori e sem MIG. Métodos: estudo da MIG com colorações HE (hematoxilina-eosina), PAS/AB (periodic acid-Schiff/ Alcian blue), HID (high iron diamine) e, para estudar a expressão da CD44v6, empregou-se a imuno-histoquímica. Resultados: De 642 pessoas avaliadas, 424 eram portadoras de Helicobacter pylori e 218 não. Das portadoras, 77 tinham MIG (18,2%) e das não portadoras, 15 (6,9%). Das pessoas com MIG, estudamos 56 casos, sendo MIG do tipo I em 55% (31/56) dos casos, 22% (12/56) do tipo II e 23% (13/56) do tipo III. A MIG teve igual proporção entre os sexos, foi mais frequente no antro, o tipo de MIG não teve relação com a extensão da metaplasia e não houve aumento proporcional com a idade. Na nossa população de estudo, a MIG foi de baixa frequência relativa (14,4%). Quanto à CD44v6, todos os nossos casos foram negativos para esta proteína. Conclusões: 1) Os nossos casos foram todos negativos para CD44v6 e não vemos utilidade de utilizar este marcador no nosso meio no rastreamento de pacientes com metaplasia intestinal gástrica que mereceriam um acompanhamento subsequente. 2) Biópsias do antro e da incisura detectaram quase a totalidade (93%) dos casos de metaplasia intestinal gástrica nos nossos casos e isto pode ser uma indicação para a prática clínica. 3) A distribuição da metaplasia intestinal gástrica entre os sexos seguiu a proporção no grupo estudado, concluindo-se que não há diferença entre os sexos. 4) Não encontramos alteração da freqüência da metaplasia intestinal gástrica conforme a idade. 5) O achado de borda em escova ou células de Paneth não exclui que naquela lâmina haja glândulas metaplásicas do tipo incompleto. 6) Não houve relação entre o local da metaplasia intestinal gástrica e seu tipo. 7) Não houve relação entre extensão e tipo de metaplasia intestinal gástrica. 8) A população estudada tem baixa prevalência de metaplasia intestinal gástrica. / The gastric intestinal metaplasia (GIM) is considered a premalignant lesion for gastric cancer, but this has not led to greater control of the carriers. We studied a dyspeptic adult population and detected the prevalence of GIM. Several markers have been tested to indicate which patients with intestinal metaplasia should be followed with periodic examinations. One of these markers is the membrane protein CD44v6. Objective: To study the expression of CD44v6 in dyspeptic patients with Helicobacter pylori (H. pylori) and gastric intestinal metaplasia. Location: Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Patients: 642 dyspeptic patients of which 56 patients with GIM and compared with two other groups, one of patients with H. pylori and another without H. pylori. Methods: A study of GIM with HE staining (hematoxylin-eosin), PAS / AB (periodic acid-Schiff / Alcian blue), HID (high iron diamine). We used immunohistochemistry (IHC) to study the expression of CD44v6. Results: Of 642 patients evaluated, 424 were carriers of Helicobacter pylori and 218 did not. The carriers had 77 MIG (18.2%) and noncarriers, 15 (6.9%). Of those GIM 56 study cases, GIM type I by 55% (31/56) cases, 22% (12/56) Type II and 23% (13/56) of Type III. GIM had equal sex ratio, was more frequent in the antrum, the type of GIM was not related to the extent of metaplasia and there was no proportional increase with age. In our study population, the GIM has low relative frequency (14.4%). As to CD44v6, all our cases were negative for this protein. Conclusions: 1 ) Our cases were all negative for CD44v6 and we do not see the usefulness of using this marker in screening patients with gastric intestinal metaplasia that merit a subsequent follow-up. 2) Biopsies of the antrum and incisura detected almost all (93 %) cases of gastric intestinal metaplasia in our cases and this can be an indication for clinical practice. 3) The distribution of gastric intestinal metaplasia between the sexes followed the proportion in the group studied, and so there is no difference between the sexes. 4) No change was found in the frequency of gastric intestinal metaplasia according to age. 5) The finding of brush border and Paneth cells does not preclude that metaplastic glands is not of the incomplete type. 6) There was no relationship between the location of gastric intestinal metaplasia and its type. 7) There was no relationship between the extent and type of gastric intestinal metaplasia. 8) The population has a low prevalence of gastric intestinal metaplasia.

Determina la prevalencia y las características del Helicobacter pylori en pacientes con diagnóstico de úlcera péptica que acuden al Hospital Nacional Dos de Mayo en el periodo 2010. Este estudio es de tipo observacional, con diseño descriptivo, retrospectivo y de corte transversal. La población estudiada fueron los pacientes que acudieron al centro endoscópico del hospital que tenían diagnóstico de úlcera péptica e informe de biopsia, se recolectó los datos de los informes endoscópicos y de las biopsias de los pacientes incluidos en el estudio, mediante la ficha de recolección de datos, estos se ordenaron y procesaron utilizando el programa SPSS versión 18. La prevalencia de la infección por Helicobacter pylori en pacientes con úlcera péptica fue de 74,1%. Se observa una predominancia del sexo masculino. Los pacientes con úlcera péptica Helicobacter pylori positiva tenían una edad promedio 57,8+/-18,9. La úlcera duodenal fue la más común en los pacientes con infección por Helicobacter pylori (33,9%). Concluye que la enfermedad ulcerosa péptica Helicobacter pylori positiva tiene una alta prevalencia en el Hospital Nacional Dos de Mayo en el 2010. Se observa con más frecuencia en personas de mayor edad, sexo masculino, localizada en el duodeno y, a nivel gástrico la úlcera ubicada en el antro fue la más frecuente. / Tesis

2009 wurde die deutsche S3-Leitlinie „Helicobacter pylori und gastroduodenale Ulkuskrankheit“ publiziert, in der klare Empfehlungen für die Diagnostik, die Indikationen für eine Eradikation, die Therapie und das Follow-Up beschrieben sind. Das Management der H. pylori Infektion im praktischen Alltag zeigt nach dieser Arbeit indessen ein anderes Bild. Ein Optimierungsbedarf für die Zukunft kann daraus abgeleitet werden. Diese Arbeit beschäftigt sich mit dem poststationären Management von Patienten mit einer H. pylori Infektion im Raum Aschaffenburg. Hierzu wurden 199 Patienten identifiziert, bei denen im Rahmen eines stationären Aufenthaltes im Klinikum Aschaffenburg im Jahr 2011 eine H. pylori Infektion diagnostiziert worden war. Aus den Patientenakten wurden alle relevanten Daten entnommen, wie zum Beispiel Diagnose, Indikation zur H. pylori Eradikation und deren stationäre Initiierung beziehungsweise Empfehlung an den Hausarzt. Nachfolgend wurden die 97 Hausärzte der 199 Patienten angeschrieben und um das ausfüllen eines Fragebogens gebeten. Dieser enthielt sechs Fragen zum poststationären Management der Patienten mit H. pylori Infektion. Während des stationären Aufenthaltes war bei 88/199 Patienten (44,2%) die Eradikationstherapie begonnen und bei 24 von ihnen (12,1%) bereits abgeschlossen worden. Bei den anderen 64 Patienten sollte die Medikation ambulant fortgeführt werden. Bei 77 Patienten (38,7%) wurde dem Hausarzt die Einleitung einer ambulanten Eradikationsbehandlung empfohlen. 34 Patienten verließen das Krankenhaus ohne Therapie und auch ohne entsprechende Therapieempfehlung. Die Rücklaufquote der Fragebögen betrug 46,2% (92 von 199 Patienten). Die nachfolgenden Ergebnisse beziehen sich auf diese 92 Patienten (entspricht 100%). Zwei Drittel der Patienten (n=61) stellten sich direkt im Anschluss an die Entlassung aus stationärer Behandlung ihrem Hausarzt vor. Bei 30 Patienten führte der Hausarzt die stationäre begonnene Eradikationstherapie fort (32,6%) oder initiierte sie bei 28 Patienten selbst (30,4%). 17 Patienten erhielten keine Eradikation (18,5%). Die Gründe hierfür waren unterschiedlich, am häufigsten lag ein Informationsdefizit zwischen Klinik und Hausarzt vor. Die französische Triple-Therapie wurde mit 39 mal am häufigsten verordnet, die italienische Triple-Therapie wurde 20 Patienten verschrieben. Andere Behandlungsprotokolle fanden nur vereinzelt Anwendung. Eine Kontrolle des Eradikationserfolges wurde bei 35 Patienten (38%) vorgenommen. Bezieht man die Eradikationskontrolle ausschließlich auf die therapierten Patienten erfolgte diese in der Hälfte der Fälle (49,3%). Von den Patienten mit H. pylori Eradikation und Kontrolle des Eradikationserfolges (n=35) konnten 31 (88,6%) erfolgreich behandelt werden. Die Vorgehensweise nach erfolgloser H. pylori Eradikation umfasste den Versuch einer Zweitlinientherapie, die Überweisung zum Gastroenterologen und den Verzicht auf weitere Maßnahmen. Zusammenfassend zeigt diese Erhebung, dass es einen klaren Optimierungsbedarf in der Anwendung der Empfehlungen aus der Leitlinie bedarf. Dieser Aspekt sollte zukünftig vermehrt Berücksichtigung finden, nicht zuletzt in der Aktualisierung der Leitlinie 2016. / In 2009, the German S3-guideline "Helicobacter pylori and gastroduodenal ulcer disease" was published, in which clear recommendations for diagnosis, the indications for eradication, therapy and follow-up are described. However, the management of H. pylori infection in everyday practice shows a different picture. An optimization requirement for the future can be derived from this. This thesis deals with post-hospital management of patients with H. pylori infection in the area of Aschaffenburg. 199 patients were identified who had been diagnosed with H. pylori infection during their inpatient stay at Aschaffenburg Hospital in 2011. All relevant data were taken from the patient records, such as diagnosis, indication for H. pylori eradication and their inpatient therapy initiation or recommendation to the family doctor. Subsequently, the 97 general practitioners of the 199 patients were contacted and asked to complete a questionnaire. This included six questions about post-hospital management of patients with H. pylori infection. During inpatient treatment, eradication therapy had started in 88/199 patients (44.2%) and had already been completed in 24 of them (12.1%). For the other 64 patients, the medication should be continued on an outpatient basis. In 77 patients (38.7%) the family doctor received a recommended to initiate an eradication therapy. Thirty-four patients left the hospital without therapy and without appropriate therapy recommendation. The response rate of the questionnaires was 46.2% (92 out of 199 patients). The following results refer to these 92 patients (equivalent to 100%). Two-thirds of the patients (n = 61) presented themselves to their family doctor immediately after discharge from hospitalization. In 30 patients, the family doctor continued inpatient eradication therapy (32.6%) or initiated it in 28 patients (30.4%). 17 patients received no eradication (18.5%). The reasons for this varied, with the most common being an information deficit between the clinic and the family doctor. The French triple therapy was prescribed most often in 39 times, the Italian triple therapy was prescribed to 20 patients. Other treatment protocols were used only sporadically. A control of eradication success was made in 35 patients (38%). If the eradication control was exclusively applied to the treated patients, this was done in half of the cases (49.3%). Of the patients with H. pylori eradication and control of eradication success (n = 35), 31 (88.6%) were successfully treated. The procedure after unsuccessful H. pylori eradication included the attempt of a second-line therapy, the referral to the gastroenterologist and the renunciation of further steps. In summary, this scientific work shows that there is a clear need for optimization in the application of the Guideline recommendations. This aspect should be taken more into account in the future, not least in the update of the upcoming guideline update 2016.