I NTRODUÇÃO: A refratariedade aos inibidores da bomba de prótons (IBP) tem sido o grande desafio dos gastroenterologistas. Este trabalho visa caracterizar os pacientes que persistem com sintomas típicos de doença do refluxo gastroesofágico (DRGE), em uso de inibidores de bomba de prótons em doses de, pelo menos 40mg/dia, quanto aos aspectos demográficos, clínicos e laboratoriais, determinando-se a freqüência da persistência de refluxo ácido pela pH-metria esofágica de 24h. Secundariamente procurouse determinar a freqüência da esofagite eosinofílica nessa população. MÉTODO: Foram entrevistados 110 pacientes que apresentavam persistência de sintomas de pirose e/ou regurgitação em uso de pelo menos 40 mg de IBP por pelo menos 6 semanas. Os mesmos foram submetidos à endoscopia digestiva alta (EDA) com biópsia esofágica, manometria, pHmetria esofágica de duplo canal e exames laboratoriais. RESULTADOS: Dos pacientes avaliados, 77,3% eram do sexo feminino, com média de 46 anos e predomínio de baixa escolaridade. Apenas 10,9% eram tabagistas, 55% apresentavam índice de massa corpórea (IMC) acima de 25Kg/m2, sendo o IMC médio de 27Kg/m2. Entre as comorbidades, as mais freqüentes foram: alergias (72,7%); hipertensão arterial (34,5%), asma (18,2%), depressão (29,1%) e fibromialgia (8,2%), sendo estas duas últimas maiores que a encontrada na população geral. Observou-se freqüência elevada de sintomas dispépticos (70% dos pacientes relataram epigastralgia e 70% plenitude pós-prandial), disfagia (60,9%); globus (37,3%), tosse (37,3%) e dor torácia não cardíaca (30,9%). Apenas 16,4% evidenciavam à endoscopia, lesão em corpo esofágico e 23,6% hérnia de hiato. A maioria dos pacientes (61,8%) apresentava alguma alteração à manometria esofágica. Encontrou-se, entre os pacientes estudados, 24,6% com pHmetria positiva (8,1% no canal distal e 16,45% no proximal) e 75,4% com pH-metria normal. Comparando-se os resultados desses dois grupos de pacientes (pH-metria positiva e normal), segundo as variáveis estudadas, apenas a presença de lesão no corpo esofágico à endoscopia e a elevada escolaridade evidenciaram associação com persistência de pH-metria positiva (p: 0,0061 OR: 4,11 IC: 1,43:11,84 e p: 0,0237 OR: 2,74 IC: 1,13: 6,67 respectivamente). Ao se comparar presença de sintomas atípicos com a presença de refluxo ácido (no esôfago proximal versus distal), apenas globus apresentou associação com pH-metria positiva no canal proximal. Foi diagnosticado um único caso de esofagite eosinofílica entre os pacientes com sintomas típicos de DRGE refratários ao IBP. CONCLUSÃO: DRGE refratária predomina em mulheres de meia idade, associada à alta freqüência de história de alergia, depressão, fibromialgia e sintomas dispépticos. Segundo os resultados da pH-metria, a presença de esofagite erosiva em uso do IBP ou elevada escolaridade foram os únicos fatores de risco para a persistência de refluxo ácido nos dois canais, e globus no canal proximal. Não se observou diferença entre os pacientes com pH-metria positiva ou normal quanto às demais variáveis, até mesmo sintomas dispépticos. É baixa a freqüência de esofagite eosinofílica entre pacientes com pirose e/ou regurgitação refratários ao inibidor da bomba de próton / BACKGROUND: Proton pump inhibitor (PPI) refractory patients have been a big challenge to gastroenterologists. The aim of this study was to characterize the patients that had gastroesophageal reflux disease (GERD) persistent typical symptoms, undergoing PPI medication, administered at a dose of at least 40 mg/day, according to demographic, clinical and laboratory aspects. The primary outcome was to determine the frequency of acid reflux persistence based on the 24-hour esophageal pH-metry result. The secondary outcome was to determine, the frequency of eosinophilic esophagitis in the same population. METHODS: We interviewed 110 patients that presented persistence of heartburn and/or regurgitation symptoms and were undergoing treatment with PPI at a minimum dose of 40 mg/day for at least six weeks. They underwent upper gastrointestinal endoscopy with esophageal mucosa biopsy, esophageal manometry and double probe 24- hour esophageal pH-metry, as well as laboratory tests. RESULTS: 77.3% of the evaluated patients were female, with mean age of 46 years old, and most of them with low educational level. Only 10.9% were tobacco smokers and 55% had body mass index (BMI) greater than 25Kg/m2, showing mean BMI of 27Kg/m2. The most frequent comorbidities were allergy (72.7%), arterial systemic hypertension (34.5%), asthma (18.2%), depression (29.1%) and fibromyalgia (8.2%). Comparing the general population and the group of patients, a higher frequency of depression and fibromyalgia was observed. Some symptoms were found in high frequency: dyspeptic symptoms (70% associated with epigastric pain and 70% with postprandial fullness), dysphagia (60.9%), globus and cough (37.3% each) and no-cardiac chest pain (30.9%). By endoscopy, only 16.4% showed esophageal body lesion and 23.6% hiatal hernia. Most patients (61.8%) presented some alteration in esophageal manometry. Among studied patients, 24.6% had abnormal pHmetry (8.1% in distal probe and 16.45% in the upper probe) and 75.4%, a normal result. When comparing normal to abnormal pH-metry patients according to studied variables only the presence of esophageal body lesion, observed by endoscopy, and high educational level were associated to the persistence of abnormal pH-metry (p: 0.0061; OR: 4.11; IC: 1.43:11.84; and p: 0.0237; OR: 2.74; IC: 1.13: 6.67; respectively). When comparing atypical symptoms with the presence of acid reflux (proximal versus distal esophagus) only globus was associated with abnormal upper probe pHmetry. Only one patient was diagnosed with eosinophilic esophagitis among the total sample with typical gastroesophageal reflux symptoms refractory to PPI treatment. CONCLUSION: Refractory GERD was predominant in middleaged females, associated with high frequency of previous allergy, depression, fibromyalgia and dyspeptics symptoms. The risk factors to the persistence of acid reflux in the two pH-metry probes and to the symptom of globus in the upper pH-metry probe were the persistence of erosive esophagitis in patients undergoing treatment with PPI an a higher educational level. No differences between abnormal or normal pH-metry results patients were found regarding the other variables, such as dyspeptic symptoms. The frequency of eosinophilic esophagitis was low in heartburn and/or regurgitation in PPI refractory patients

Introdução: A doença do refluxo gastroesofágico (DRGE) é definida pela intensidade e/ou qualidade de refluxo do conteúdo gástrico ou duodenal para o esôfago. O tratamento cirúrgico da DRGE tem mostrado resultados conflitantes e índices inaceitáveis de recidiva, principalmente devido a migração da válvula anti-refluxo para o tórax. Variações técnicas têm sido propostas com objetivo de diminuir a recidiva da DRGE, inclusive com uso rotineiro de prótese na hiatoplastia. A prevalência de DRGE em portadores de HH pode chegar a 94%. A membrana frenoesofágica (MFE) que atua na estabilização da junção esofagogástrica no abdômen pode ser um fator etiológico da hérnia hiatal (HH)? Conduzimos um estudo para avaliar o colágeno na constituição da MFE de pacientes com HH e cadáveres sem HH. Métodos: Foram coletadas amostras da MFE de 29 pacientes com HH e DRGE (casos) e amostras de 32 cadáveres sem HH (controles). O colágeno total foi quantificado pela técnica histoquímica de Picrossirius e o colágeno tipo I e tipo III por imuno-histoquímica (anticorpo monoclonal). As imagens das lâminas coradas foram fotografadas, armazenadas em arquivo.tiff e quantificadas por programa de computador (Image Pro Plus) para contagem de pixels por campo. Resultados: A média de idade dos casos foi de 49,5 (±11,5) anos e dos controles foi de 38,5 (±13) (p<0,01). Em relação ao gênero, 58,6% (17) dos casos e 18,75% (6) dos controles eram do sexo feminino (p<0,01). A quantidade, em pixels por campo, de colágeno total (p<0,01), tipo I (p<0,01) e tipo III (p<0,05) foi significativamente menor, em torno de 60%, nos pacientes com HH em relação aos controles. Conclusão: Nossos dados demonstram que a constituição da MFE dos pacientes com HH e DRGE tem menor quantidade de colágeno total, tipo I e tipo III que a MFE de cadáveres sem HH. A qualidade da MFE pode ser um fator etiológico para o desenvolvimento da HH. / Background: Gastroesophageal reflux disease (GERD) is defined by the intensity and/or quality of the reflux of gastric or duodenal contents into the esophagus. Surgical treatment of GERD has shown conflicting results and unacceptable recurrence rates, mainly due to herniation of the antireflux valve into the chest. A variety of techniques have been proposed to reduce GERD recurrence, including routine use of prosthesis in cruroplasty. The prevalence of GERD in patients with hiatal hernia (HH) can reach 94%. It is possible that the phrenoesophageal ligament (POL) engaged in the stabilization of the gastroesophageal junction in the abdomen may be an etiologic factor of HH. We conducted a study to evaluate collagen in the constitution of the POL in patients with HH and cadavers without HH. Methods: POL samples were collected from 29 patients with HH and GERD (cases) and 32 samples from cadavers without HH (controls). Total collagen was quantified through the Picro-Sirius histochemical technique, and type-I and type-III collagens were quantified immunohistochemically using a monoclonal antibody. The stained slides were photographed, and images were quantified by computer software (Image Pro Plus) to count the pixels per field. Results: The mean age was 49.5 (±11.5) years for the cases and 38.5 (±13) years for the controls (p < 0.01). Seventeen cases (58.6%) and 6 controls (18.75%) were female (p < 0.01). The quantity of total (p < 0.01), type-I (p < 0.01), and type-III (p < 0.05) collagen was significantly lower, about 60%, in patients with HH compared to controls. Conclusion: Our data indicate that the composition of POL for patients with GERD and HH has fewer total, type I and type III collagen than that of the POL of cadavers without HH. The quality of the POL may be an etiological factor in the development of HH.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-04-12Bitstream added on 2014-06-13T19:07:28Z : No. of bitstreams: 1 correa_mccsf_me_botfm_prot.pdf: 1406876 bytes, checksum: 2e2f4ae9e757377b79aeedad040ad016 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / A doença do refluxo gastroesofágico (DRGE) é uma infecção de elevada incidência no qual o refluxo gastroduodenal reflui para o esôfago e/ou orgãos adjacentes, inclusive a cavidade oral, podendo causar lesões ou nos tecidos duros e moles. Foram estudados 100 pacientes, sendo 50 portadores da DRGE (Grupo 1) e 50 controles... / Gastroesophageal reflux disease, or GERD is a high incidence condition in which gastro duodenal contents leak back, or refluz, into the esophagus and/or adjancent organs including the oral cavity and the therefore possibly causing lesions on the soft and hard tissue structures... (Complete abstract, click eletronic address below)

Submitted by Anderson Roberto Guerra null (andersonrguerra@hotmail.com) on 2017-03-24T15:51:27Z No. of bitstreams: 1 Dissertação Anderson Roberto Guerra.pdf: 1591587 bytes, checksum: 988e12ad9846b8f241313fe2038e610c (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-03-24T18:04:27Z (GMT) No. of bitstreams: 1 guerra_ar_me_bot.pdf: 1591587 bytes, checksum: 988e12ad9846b8f241313fe2038e610c (MD5) / Made available in DSpace on 2017-03-24T18:04:27Z (GMT). No. of bitstreams: 1 guerra_ar_me_bot.pdf: 1591587 bytes, checksum: 988e12ad9846b8f241313fe2038e610c (MD5) Previous issue date: 2017-02-24 / A doença do refluxo gastroesofágico (DRGE) é uma das mais importantes afecções digestivas, tendo em vista as elevadas e crescentes incidências, a intensidade dos sintomas e a gravidade das complicações. Existem alguns grupos de riscos independentes para o desenvolvimento desta doença e a obesidade está entre os principais fatores de risco para a DRGE. A DRGE pode acarretar em algumas complicações como o desenvolvimento de esôfago de Barrett, estenose, úlcera e sangramento esofágico, além de perda da qualidade de vida. Síndrome metabólica (SM) é uma associação central da obesidade, definido por medidas de circunferência abdominal em relação ao IMC, seguido por outros parâmetros como triglicérides alto, colesterol HDL baixo, pressão sistólica e/ou diastólica elevadas e glicemia em jejum acima de 100 mg/dL ou ainda algum tratamento prévio para uma ou mais dessas doenças citadas. A observação da possível associação de alterações clínicas às disfunções celulares e moleculares em pacientes com DRGE e/ou SM, torna-se crucial para o melhor entendimento da doença, bem como fornecer subsídios para a busca de novas alternativas terapêuticas. O objetivo deste trabalho foi avaliar a relação dos aspectos clínicos e celulares da DRGE e SM. Os resultados encontrados sugerem que há uma relação entre DRGE e a presença de SM ou obesidade central e ainda sugere que pessoas com circunferência abdominal, triglicérides e HDL alterados, podem apresentar DRGE. Também foram encontrados marcadores moleculares diferentes nos grupos DRGE+SM e SM, o que pode levar a possível diagnóstico diferencial no futuro além de ser um alvo potencial para intervenções ou diagnósticos. / Gastroesophageal reflux disease (GERD) is one of the most important digestive disorders, due to the high and increasing incidence, the intensity of the symptoms and the severity of the complications. There are some groups of independent risks for the development of this disease and obesity is among the main risk factors for GERD. GERD can lead to complications such as the development of Barrett's esophagus, stenosis, ulcer and esophageal bleeding, and loss of quality of life. Metabolic syndrome (MS) is a central association of obesity, defined by measures of waist circumference in relation to BMI, followed by other parameters such as high triglycerides, low HDL cholesterol, elevated systolic and / or diastolic blood pressure and fasting glycemia above 100 mg/dL or some previous treatment for one or more of these diseases. The observation of the possible association of clinical alterations to cellular and molecular dysfunctions in patients with GERD and / or MS is crucial for a better understanding of the disease, as well as providing subsidies for the search for new therapeutic alternatives. The aim of this study was to evaluate the relationship between clinical and cellular aspects of GERD and MS. The results suggest that there is a relationship between GERD and the presence of MS or central obesity and also suggests that people with altered abdominal circumference, triglycerides and HDL may present GERD. Different molecular markers were also found in the GERD + MS and MS groups, which may lead to a possible differential diagnosis in the future besides being a potential target for interventions or diagnoses.

Objetivo: Avaliar o perfil funcional do esôfago e a prevalência de refluxo gastroesofágico (RGE) em pacientes candidatos a transplante pulmonar. Métodos: Foram analisados prospectivamente entre Junho de 2005 a Novembro de 2006, 55 pacientes candidatos a transplante pulmonar da Santa Casa de Misericórdia de Porto Alegre. Os pacientes foram submetidos a esofagomanometria estacionária e pHmetria esofágica ambulatorial de 24 horas de um e dois eletrodos antes de serem submetidos ao transplante pulmonar. Resultados: A esofagomanometria foi anormal em 80% dos pacientes e a pHmetria revelou RGE ácido patológico em 24%. Os sintomas digestivos apresentaram sensibilidade de 50% e especificidade de 61% para RGE. Noventa e quatro por cento dos pacientes com DPOC apresentaram alteração à manometria, sendo a hipotonia do esfíncter inferior o achado mais frequente (80%). Pacientes com bronquiectasias apresentaram a maior prevalência de RGE (50%). Conclusões: RGE é achado freqüente em pacientes com doença pulmonar avançada. Na população examinada, a presença de sintomas digestivos de RGE não foi preditiva de refluxo ácido patológico. A contribuição do RGE na rejeição crônica deve ser considerada e requer estudos posteriores para seu esclarecimento. / Objective: To assess the prevalecence of gastro-esophageal reflux (GER) and esophageal motor profile in lung transplant candidates. Methods: Between July 2005 and November 2006, a prospective study was conducted in 55 candidates for lung transplantation. Patients underwent esophageal manometry and 24-hour pH testing before undergoing transplantation as an attempt to obtain the prevalence of reflux in this subset. Results: Abnormal esophageal manometry was documented in 80% of the patients and abnormal GER was documented in 24% of the patients. Reflux-related symptoms presented sensitivity and specificity of 50% and 61% for GER, respectively. Ninety-four per cent of the patients with COPD presented an abnormal esophageal manometry, and hipotensive lower esphincter was the most common finding (80%). Bronchiectasis patients presented the highest prevalence of GER (50%). Conclusions: GER is highly prevalent in end-stage lung disease. Reflux-related symptoms was not preditive of gastroesophageal reflux. The contribuition of GER to chronic rejection and allograft dysfunction must be considered and needs to be addressed in future studies.

Background. Obstructive Sleep Apnoea (OSA) is associated with an increase in nocturnal gastro-oesophageal reflux (nocturnalGOR) events and symptoms, however the mechanism for this remains undefined. Treatment of OSA with continuous positive airway pressure (CPAP) has been shown to reduce nocturnalGOR in individuals with OSA however the reasons for this reduction are not clear. The combination of OSA and nocturnalGOR could be particularly problematic for individuals who have had a lung transplant in whom Bronchiolitis Obliterans Syndrome (BOS) limits survival. It is thought that GOR plays a role in the development of BOS in these individuals. Methods and Results. Five interrelated studies were undertaken. The first two studies sought to determine and compare the prevalence and risk factors of nocturnalGOR in OSA patients with the general population. To do this, a GOR questionnaire was completed by 2,042 members of the general community as part of the Busselton Health Survey and by 1,116 patients with polysomnography-diagnosed OSA. Risk of OSA in the general population was determined using a standardised sleep questionnaire. 137 of the OSA patients completed the questionnaire before and after treatment with CPAP. The prevalence of nocturnalGOR symptoms reported more than once a week (frequent symptoms) was greater in OSA patients (10.1%) than the general population (5.8%) (p<0.001), in individuals from the general population at high (11.2%) than low risk of OSA (4.5%) (p<0.001) and in patients with severe (14.7%) than mild OSA (5.2%) (p<0.001). Treatment of OSA with CPAP decreased the prevalence of frequent nocturnalGOR from 9.0% to 3.8% (p=0.04). In the general population, high risk of OSA was independently associated with a 2.4-fold increased risk of frequent ABSTRACT vi nocturnalGOR symptoms than low risk. In the OSA group, disease severity was independently associated with nocturnalGOR symptoms, with an adjusted odds ratio of 1.7 for frequent nocturnalGOR symptoms.

Thesis (M.Med.)--University of Natal, Durban, 1997.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 5 uppsatser.