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

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

published_or_final_version / abstract / Medicine / Master / Doctor of Medicine

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

Background and objectives: Physical fitness and stress resilience may influence the risk of gastrointestinal (GI) disease. High physical fitness level may reduce levels of systemic inflammation while psychosocial stress exposure can increase inflammation levels and intestinal permeability. The main objectives are to evaluate if poorer physical fitness and stress resilience in adolescence are associated with a raised risk of inflammatory bowel disease (IBD), peptic ulcer disease (PUD) and GI infections in adulthood and to assess evidence of causality. Materials and methods: Swedish registers provided information on a cohort of approximately 250,000 men who underwent military conscription assessments in late adolescence (1969 –1976) with follow-up until December 2009 (up to age 57 years). Cox regression evaluated the associations of physical fitness and stress resilience in adolescence with subsequent GI disease risk in adulthood. Results and conclusions: IBD: Poor physical fitness was associated with an increased risk of IBD. The association may be explained (in part) by prodromal disease activity reducing exercise capacity and therefore fitness. Low stress resilience was associated with an increased risk of receiving an IBD diagnosis. Stress may not be an important cause of IBD but may increase the likelihood of conversion from subclinical to symptomatic disease. PUD: Low stress resilience was associated with an increased risk of PUD. This may be explained by a combination of physiological and behavioural mechanisms that increase susceptibility to H. pylori infections and other risk factors. GI infections: Low stress resilience was associated with a reduced risk of GI infections, including enteric infections rather than the hypothesised increased risk.

Contexto: A hemorragia digestiva alta (HDA) resulta em 200 a 300 mil internações por ano nos Estados Unidos, com uma mortalidade de 2,5% a 10%. A úlcera péptica representa a causa mais comum de HDA, correspondendo por um terço a metade de todos os casos. Apesar das melhorias na compreensão de sua etiologia, a incidência de sangramento da úlcera péptica, sua complicação mais comum, não se alterou nas últimas décadas. A terapia endoscópica para HDA pode reduzir drasticamente o risco de ressangramento ou sangramento contínuo, a necessidade de cirurgia de urgência, o número de unidades de concentrado de hemácias para transfusão, o tempo de internação hospitalar e a mortalidade. O tratamento endoscópico da úlcera hemorrágica já percorreu um longo caminho desde injeções de adrenalina e outras soluções, o uso da termocoagulação, até a aplicação de dispositivos mecânicos, como o clipe metálico e a ligadura elástica. Objetivo: Permanece por esclarecer qual é a modalidade endoscópica (ou combinação de modalidades) que apresenta os melhores resultados no tratamento da hemorragia digestiva decorrente da úlcera péptica. Portanto, o objetivo desta revisão sistemática é comparar as diferentes modalidades de tratamento endoscópico da HDA decorrente da úlcera péptica, utilizando ensaios clínicos randomizados. Fontes de dados: Os estudos foram identificados através de pesquisa em bases de dados eletrônicas e listas de referência de artigos. As bases de dados pesquisadas foram Medline, Embase, Cochrane, LILACS, Dare e CINAHL. Critérios de elegibilidade de estudo, participantes e intervenções: Os estudos selecionados foram os ensaios clínicos randomizados comparando as diferentes modalidades endoscópicas para o tratamento de pacientes com hemorragia digestiva alta causada por úlcera péptica. Os estudos incluídos avaliaram técnicas endoscópicas contemporâneas de hemostasia: terapia de injeção endoscópica (todas as soluções, simples ou múltiplas), termocoagulação (heater probe, coagulação com plasma de argônio, coagulação com micro-ondas, eletrocoagulação monopolar, bipolar e multipolar), aplicação de clipes metálicos e tratamento combinado. Os desfechos avaliados foram as taxas de hemostasia inicial, ressangramento, cirurgia de urgência e de mortalidade. Avaliação de vieses: Ao nível de cada estudo, os revisores determinaram a adequação da randomização e da alocação; cegamento de pacientes, profissionais de saúde, coletores de dados e avaliadores de resultados; bem como o relato e a extensão das perdas de seguimento. Também foi avaliado se as técnicas de hemostasia endoscópica foram devidamente descritas e, se os desfechos foram adequadamente definidos em cada estudo. A análise de sensibilidade foi realizada quando a heterogeneidade (I2) foi superior a 50% e uma nova meta-análise foi calculada excluindo o(s) estudo(s) discrepante(s). Uma análise adicional foi realizada em cada comparação, incluindo apenas os ensaios de qualidade metodológica mais elevada. Resultados principais: Um total de 28 ensaios clínicos randomizados (envolvendo 2988 pacientes) foram avaliados nesta revisão, eles foram divididos em sete grupos de comparação de acordo com as modalidades estudadas em cada estudo. A terapia de injeção endoscópica como modalidade única foi inferior à sua combinação com o clipe metálico e com a termocoagulação na avaliação de taxa de ressangramento (diferença dos riscos [DR] = -0,10, intervalo de confiança de 95% [IC95%] = -0,18 a -0,03 e [DR] = -0,08, [IC95%] = -0,14 a -0,02, respectivamente) e na necessidade de cirurgia de urgência ([DR] = -0,11, [IC95%] = -0,18 a -0,04 e [DR] = -0,06, [IC95%] = -0,12 para -0,00, respectivamente). A aplicação de clipes metálicos foi superior à terapia de injeção endoscópica na avaliação da taxa de ressangramento ([DR] = -0,13, [IC95%] = -0,19 para -0,08), e os resultados da comparação entre a aplicação de clipes metálicos como monoterapia e a sua combinação com a terapia de injeção endoscópica não apresentaram diferenças estatísticas. A comparação entre o clipe metálico e a termocoagulação encontrou uma considerável heterogeneidade entre as intervenções utilizadas em cada estudo e nos resultados encontrados das meta-análises. A comparação da termocoagulação com a terapia de injeção endoscópica não evidenciou qualquer diferença estatística entre as modalidades, e a combinação delas é superior à técnica de termocoagulação sozinha ao avaliar a taxa de ressangramento ([DR] = -0,11, [IC95%] = -0,21 para - 0,02). Conclusões: A terapia de injeção endoscópica não deve ser empregada isoladamente. A aplicação de clipes metálicos é superior à terapia de injeção endoscópica, e a associação da injeção endoscópica não melhora a eficácia hemostática do uso isolado do clipe metálico. Como modalidade única, uma técnica de termocoagulação tem uma eficácia hemostática semelhante à terapia de injeção endoscópica, e estas modalidades combinadas parecem ser superiores à técnica de termocoagulação sozinha. Portanto, recomendamos a aplicação de clipes metálicos ou o uso combinado de uma terapia de injeção endoscópica com um método de termocoagulação para o tratamento de pacientes com hemorragia digestiva alta por úlcera péptica / Background: Upper Gastrointestinal bleeding (UGIB) results in 200,00 to 300,000 hospital admissions annually in the United States, with a mortality of 2,5% to 10%. Peptic ulcer disease represents the most common cause of UGIB, accounting for a third to a half of all episodes. Despite improvements in the understanding of its etiology, the incidence of bleeding from peptic ulcer disease, the most common complication, has not changed. Endoscopic therapy for active UGIB can dramatically reduce the risk of rebleeding or continued bleeding, the need for surgery, the number of units of packed erythrocytes required for transfusion, the length of hospital stay and mortality. Endoscopic treatment for ulcer bleeding has come a long way from injections of epinephrine and other solutions, the use of thermocoagulation, to the application of mechanical devices such as hemoclips and banding ligator. Objective: It remains unclear which is the endoscopic modality (or combination of modalities) that presents the best results in the treatment of peptic ulcer bleeding. Therefore, the objective of this systematic review is to compare the different modalities of endoscopic hemostatic therapy, using randomized clinical trials. Data sources: Studies were identified by searching electronic databases and scanning reference lists of articles. The searched databases were Medline, Embase, Cochrane, LILACS, DARE and CINAHL. Study eligibility criteria, participants and interventions: The studies selected were the randomized clinical trials comparing different endoscopic modalities for the treatment of patients presenting with acute upper gastrointestinal bleeding caused by peptic ulcer disease. The included trials assessed contemporary endoscopic hemostatic techniques: endoscopic injection therapy (all injectates, single or multiple), thermal coagulation (heater probe, argon plasma and microwave coagulation, monopolar, bipolar and multipolar electrocoagulations), hemoclip placement and combination treatment. The outcomes measured were the rates of initial hemostasis, rebleeding, emergency surgery and overall mortality. Risk of bias assessment: At the study level, the reviewers determined the adequacy of randomization and concealment of allocation; blinding of patients, of health care providers, of data collectors, and of outcome assessors; and the correct report and extent of loss to follow-up. It was also evaluated whether the endoscopic hemostatic techniques were properly described and if the outcomes were appropriately defined in each study. A sensitivity analysis was held when the heterogeneity (I2) was over 50% and a new meta-analysis was calculated excluding the outlier(s). An additional analysis was made at each comparison, including only the higher methodological quality trials. Main results: A total of 28 trials, involving 2988 patients were evaluated in this review, they were divided into seven comparison groups according to the modalities studied in each trial. Injection Therapy as single modality was inferior to its combination with Hemoclip and with Thermal Coagulation Therapy when evaluating rebleeding rate (risk difference [RD] = -0.10, 95% confidence interval [95%CI] = -0.18 to -0.03 and [RD] = -0.08, [95%CI] = -0.14 to -0.02, respectively) and need for emergency surgery ([RD] = -0.11, [95%CI] = -0.18 to -0.04 and [RD] = -0.06, [95%CI] = -0.12 to -0.00, respectively). Hemoclip was superior to Injection Therapy in the evaluation of rebleeding rate ([RD] = -0.13, [95%CI] = -0.19 to -0.08), and the results of the comparison between Hemoclip alone versus its combination with Injection Therapy did not present any statistical differences. The comparison between Hemoclip and Thermal Coagulation encountered a considerable heterogeneity between the trials in the interventions used and in the results found. The comparison of Thermal Coagulation versus Injection Therapy did not evidence any statistical difference between the modalities, and the combination of these is superior to the Thermal Coagulation alone when evaluating rebleeding rate ([RD] = -0.11, [95%CI] = -0.21 to -0.02. Conclusions: Injection therapy should not be used as single modality. The application of Hemoclip is superior to injection therapy, and the combined application of an injectate does not improve the hemostatic efficacy of the use of Hemoclip alone. As single modality, a thermal coagulation technique has a similar hemostatic efficacy as injection therapy, and these combined modalities appear to be superior to thermal coagulation technique alone. Therefore, we recommend the application of Hemoclips or the combined use of an Injection Therapy with a Thermal Coagulation method for the treatment of patients presenting with acute peptic ulcer bleeding

Song Jing-mei. / Thesis submitted in: December 1998. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 141-156). / Abstract also in Chinese. / Title page --- p.i / Acknowledgments --- p.ii / Table of contents --- p.iii / Abbreviations --- p.viii / Abstract --- p.x / 摘要 --- p.xii / Chapter Chapter1 --- Introduction --- p.1 / Chapter Chapter2 --- Evaluation of Antiulcer Effect Exhibited by Hippophae rhamnoides Using Different Ulcer Models / Chapter 2.1 --- Introduction --- p.20 / Chapter 2.1.1 --- Ethanol-induced gastric lesions --- p.24 / Chapter 2.1.2 --- NSAID-induced gastric lesions --- p.24 / Chapter 2.1.3 --- Stress-induced gastric lesions --- p.25 / Chapter 2.1.4 --- Pylorus ligation-induced gastric lesions --- p.25 / Chapter 2.1.5 --- Acetic acid-induced chronic gastric ulcer --- p.26 / Chapter 2.1.6 --- Necrotizing agent-induced lesion model --- p.27 / Chapter 2.2 --- Materials and Methods / Chapter 2.2.1 --- Plant materials --- p.28 / Chapter 2.2.2 --- Identification of the plant --- p.28 / Chapter 2.2.3 --- Preparation of crude extract for animal studies --- p.28 / Chapter 2.2.4 --- Experimental animals --- p.31 / Chapter 2.2.5 --- Ethanol-induced gastric mucosal lesions --- p.31 / Chapter 2.2.6 --- Acidified aspirin-induced gastric lesions --- p.32 / Chapter 2.2.7 --- Water immersion plus restraint-induced stress lesion model --- p.32 / Chapter 2.2.8 --- Pylorus ligation-induced gastric lesions --- p.32 / Chapter 2.2.9 --- Acetic acid-induced chronic gastric ulcer --- p.34 / Chapter 2.2.10 --- Necrotizing agent-induced gastric lesions --- p.34 / Chapter 2.2.11 --- Test of acute toxicity of Hippophae --- p.35 / Chapter 2.2.12 --- Statistical analysis --- p.35 / Chapter 2.3 --- Results / Chapter 2.3.1 --- Effect of Hr extract on ethanol-induced gastric lesions --- p.36 / Chapter 2.3.2 --- Effect of Hr extract on aspirin-induced gastric damage --- p.39 / Chapter 2.3.3 --- Effect of Hr extract on stress-induced gastric lesions --- p.40 / Chapter 2.3.4 --- Effect of Hr extract on pylorus ligation-induced gastric injury --- p.43 / Chapter 2.3.5 --- Effect of Hr extract on acetic acid-induced chronic ulcer --- p.48 / Chapter 2.3.6 --- Effect of Hr extract on necrotizing agent-induced gastric damage --- p.54 / Chapter 2.3.7 --- Test of acute toxicity of Hr --- p.55 / Chapter 2.4 --- Discussion / Chapter 2.4.1 --- Cytoprotective effect of Hr against ethanol-induced lesions --- p.56 / Chapter 2.4.2 --- Preventive effect of Hr on NSAIDs-induced gastric lesions --- p.57 / Chapter 2.4.3 --- Inhibitory effect of Hr on stress-induced lesions --- p.58 / Chapter 2.4.4 --- Inhibitory effect of Hr extract on pylorus ligation-induced gastric lesions --- p.59 / Chapter 2.4.5 --- Healing effect of Hr extract on acetic acid-induced gastric ulcer --- p.60 / Chapter 2.4.6 --- Protective effect of Hr extract on necrotizing agent-induced gastric damage --- p.61 / Chapter 2.4.7 --- Summary --- p.61 / Chapter Chapter3 --- Study on Cytoprotective Effect of Hippophae rhamnoides on Ethanol-induced Gastric Damage / Chapter 3.1 --- Introduction --- p.63 / Chapter 3.2 --- Materials and Methods --- p.65 / Chapter 3.2.1 --- Chemicals and Instruments --- p.65 / Chapter 3.2.2 --- Test on effect of different concentrations of ethanol on gastric mucosa --- p.67 / Chapter 3.2.3 --- Examination of the gastric protective effect of Hr extract by different routes of administration --- p.68 / Chapter 3.2.4 --- Study on relationship between gastric protective effect of Hr extract and endogenous PGs --- p.68 / Chapter 3.2.5 --- Measurement of gastric mucosal blood flow (GMBF) --- p.69 / Chapter 3.2.6 --- Measurement of gastric secretion and acidity in gastric juice --- p.70 / Chapter 3.2.7 --- Measurement of gastric gastric emptying rate --- p.70 / Chapter 3.2.8 --- Measurement of pepsin content in gastric juice --- p.71 / Chapter 3.2.9 --- Measurement of protein content in gastric juice --- p.73 / Chapter 3.2.10 --- Measurement of mucus content on gastric wall --- p.75 / Chapter 3.2.11 --- Measurement of GSH content in gastric mucosa --- p.77 / Chapter 3.2.12 --- Measurement of PGE2 content in gastric mucosa --- p.79 / Chapter 3.2.13 --- Determination of protein content in gastric mucosa --- p.81 / Chapter 3.3 --- Results / Chapter 3.3.1 --- Test on gastric lesions induced by different concentrations of ethanol --- p.83 / Chapter 3.3.2 --- Effect of Hr extract on ethanol-induced gastric damage by different routes of administration --- p.83 / Chapter 3.3.3 --- Effect of Hr extract on GMBF and output of gastric acid --- p.85 / Chapter 3.3.4 --- Effect of Hr extract on gastric emptying rate --- p.87 / Chapter 3.3.5 --- Effect of Hr extract on gastric mucus --- p.88 / Chapter 3.3.6 --- Effect of Hr extract on gastric GSH content --- p.89 / Chapter 3.3.7 --- Influence of Hr extract on endogenous prostanglandin-E2 --- p.90 / Chapter 3.3.8 --- Antagonistic effect of indomethacin on the gastric protection of Hr extract --- p.91 / Chapter 3.4 --- Discussion / Chapter 3.4.1 --- Formation of gastric lesions induced by ethanol at different concentrations --- p.92 / Chapter 3.4.2 --- Different routes of administration --- p.92 / Chapter 3.4.3 --- "Role of GMBF, gastric acidity and acid output in the formation of gastric lesions" --- p.93 / Chapter 3.4.4 --- Effect of Hr extract on gastric motility --- p.95 / Chapter 3.4.5 --- Effect of Hr extract on gastric mucus --- p.96 / Chapter 3.4.6 --- Effect of Hr extract on gastric GSH content --- p.96 / Chapter 3.4.7 --- Effect of Hr extract on endogenous prostaglandins --- p.98 / Chapter 3.4.8 --- Summary --- p.99 / Chapter Chapter 4 --- Study on plant constituents of Hippophae rhamnoides / Chapter 4.1 --- Introduction --- p.100 / Chapter 4.2 --- Materials and Methods --- p.100 / Chapter 4.2.1 --- Plant Materials --- p.100 / Chapter 4.2.2 --- Plant Extraction --- p.101 / Chapter 4.2.3 --- Fractionation of hexane-extract by column chromatography --- p.103 / Chapter 4.2.4 --- Phytochemical identification and analyses of vitamin content in Hr extract --- p.104 / Chapter 4.2.4.1 --- Identification of vitamin A and vitamin C in the Hr extract by TLC --- p.104 / Chapter 4.2.4.2 --- Identification of α-tocopherol and γ-tocopherol by HPLC --- p.105 / Chapter 4.2.4.3 --- Analyses of the content of α-tocopherol in the Hr extract --- p.108 / Chapter 4.2.4.4 --- Identification and analysis of fatty acid in the Hr fractions --- p.111 / Chapter 4.2.4.4.1 --- Esterification of fatty acids --- p.111 / Chapter 4.2.4.4.2 --- Isolation and identification of FAME by GC-MS --- p.111 / Chapter 4.2.4.5 --- Quantitative analysis of composition and relative content of fatty acid in the Hr fractions --- p.112 / Chapter 4.3 --- Results / Chapter 4.3.1 --- Phytochemical analysis and identification --- p.114 / Chapter 4.3.1.1 --- Identification of vitamin A --- p.114 / Chapter 4.3.1.2 --- Identification of vitamin C --- p.115 / Chapter 4.3.1.3 --- Identification of α-tocopherol and γ-tocopherol --- p.116 / Chapter 4.3.1.4 --- Quantitative analysis of α-tocopherol content in the Hr extract --- p.117 / Chapter 4.3.1.5 --- Identification of fatty acid composition --- p.117 / Chapter 4.3.1.6 --- Analysis of relative content of fatty acids in the Hr extract --- p.122 / Chapter 4.3.1.7 --- Study on phytosterols of Hr --- p.124 / Chapter 4.3.2 --- Examination of antiulcer effect of Hr fractions against ethanol-induced gastric lesions --- p.124 / Chapter 4.3.2.1 --- Effect of different extracts of Hr seed on ethanol-induced gastric lesions --- p.125 / Chapter 4.3.2.2 --- Effect of fractions of hexane-extract of Hr on gastric lesions induced by ethanol --- p.126 / Chapter 4.3.2.3 --- Effect of Hr components on gastric lesions induced by different ulcer models --- p.127 / Chapter 4.3.2.3.1 --- Effect of Hr components on ethanol-induced lesions --- p.127 / Chapter 4.3.2.3.2 --- Effect of Hr components against stress-induced gastric lesions --- p.128 / Chapter 4.3.2.3.3 --- Effect of β-sitosterol against gastric lesions induced by pylorus ligation --- p.129 / Chapter 4.4 --- Discussion / Chapter 4.4.1 --- Role of fatty acids in the stomach protection --- p.130 / Chapter 4.4.2 --- Role of vitamins in the gastric protection --- p.133 / Chapter 4.4.3 --- Role of plant terpenoids in the stomach --- p.134 / Chapter 4.4.4 --- Summary --- p.135 / Chapter Chapter 5 --- General discussion --- p.136 / References --- p.141

Orientador: Clélia Akiko Hiruma-Lima / Banca: Caden Souccar / Banca: Miriam Sannomiya / Banca: Mirtes Costas / Banca: Cláudia Helena Pellizon / Resumo: Este trabalho visou estudar os efeitos farmacológicos do extrato metanólico (BiMeOH) e partições acetato de etila (AcoEt) e aquosa (AcoAq) das folhas de Byrsonima intermedia A. Juss, espécie do Cerrado brasileiro. A partir de sua indicação popular para gastrite e distúrbios do trato gastrintestinal, foram realizados ensaios in vivo que comprovaram seu potencial terapêutico como antiulcerogênico. Análise fitoquímica do extrato resultou na caracterização de BiMeOH que possui majoritariamente taninos condensados na partição AcoAq e flavonóides derivados de quercetina em AcoEt. A avaliação de toxicidade aguda revelou que BiMeOH causou morte de alguns camundongos fêmeas, indicando cautela em sua utilização. Embora a ação gastroprotetora de BiMeOH não envolva a participação do Óxido Nítrico (NO), as partições testadas apresentaram envolvimento dessa via, bem como de grupamento sulfidrilico (SH). Além disso, apenas a AcoAq apresentou gastroproteção frente às úlceras induzidas por DAINEs, com redução dos níveis de mieloperoxidase (MPO). Também foi mostrada a participação dos neurônios sensitivos à capsaicina tanto da BiMeOH quanto da AcoEt em sua ação gastroprotetora. O extrato e partições também foram efetivos na redução dos danos gástricos no teste de isquemia-reperfusão, com redução da atividade de MPO e aumento dos níveis de glutationa total (GSH) apenas para AcoEt. No duodeno, BiMeOH e AcoAq apresentaram atividades protetoras frente à lesão induzida por cisteamina. Nenhum tratamento agudo (24 hs) do extrato e partições foi capaz de reduzir as lesões promovidas pela isquemia-reperfusão, após a instalação da lesão. Porém, o tratamento de 6 dias com BiMeOH e AcoEt apresentou redução das lesões, acompanhada por diminuição de MPO e interleucina 1-β (IL 1-β) e aumento de interleucina 10 (IL-10). A AcoEt apresentou, ainda... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study evaluated the pharmacological effects of the methanolic extract (BiMeOH) and the ethyl acetate (AcoEt) and aqueous (AcoAq) partitions from the leaves of Byrsonima intermedia A. Juss, a medicinal species of the brazilian Cerrado, in rodent models of gastrointestinal diseases. Although nitric oxide (NO) did not participated in gastroprotective action of BiMeOH the involvement of NO as well as sulfhydril compounds (SH) in the gastroprotection of AcoAq and AcoEt was shown in acute lesion induced by ethanol. Furthermore, only the AcoAq protected against NSAID-induced ulcers, with reduced levels of myeloperoxidase (MPO). It was also shown the involvement of capsaicin-sensitive neurons in the gastroprotection of BiMeOH and AcoEt. The gastric damage induced by ischemia-reperfusion were not affect by acute (24h) treatment with BiMeOH or partitions but the treatment for 6 days reduced the lesions and the MPO activity and increased levels of total glutathione (GSH). However, treatment with AcoEt and BiMeOH for 6 days decreased lesion accompanied by reduction in MPO and interleukin 1-β (IL 1-β) and increase in interleukin 10 (IL-10). The AcoEt also showed increased GSH and reduction of tumor necrosis factor α (TNF-α). On the other hand, AcoAq only increased levels of GSH and IL-10. Chronic treatment with BiMeOH, AcoAq or AcoEt for 14 days, but not for 7 days, reduced significantly the acetic acid-induced gastric lesions in rats with AcoAq and AcoEt increasing significantly the GSH levels in this model. In the duodenum, BiMeOH and AcoAq protected against injury induced by cysteamine administration. Mucosal lesions the evaluation of duodenal mucosa by 7 and 14 days of treatment was also observed reduction of injuries by the extract and partitions, up to GSH in AcoEt the period observed. The BiMeOH and AcoAq prevented the diarrhea induced by the castor oil decreasing... (Complete abstract click electronic access below) / Doutor

Contexto: A hemorragia digestiva alta (HDA) resulta em 200 a 300 mil internações por ano nos Estados Unidos, com uma mortalidade de 2,5% a 10%. A úlcera péptica representa a causa mais comum de HDA, correspondendo por um terço a metade de todos os casos. Apesar das melhorias na compreensão de sua etiologia, a incidência de sangramento da úlcera péptica, sua complicação mais comum, não se alterou nas últimas décadas. A terapia endoscópica para HDA pode reduzir drasticamente o risco de ressangramento ou sangramento contínuo, a necessidade de cirurgia de urgência, o número de unidades de concentrado de hemácias para transfusão, o tempo de internação hospitalar e a mortalidade. O tratamento endoscópico da úlcera hemorrágica já percorreu um longo caminho desde injeções de adrenalina e outras soluções, o uso da termocoagulação, até a aplicação de dispositivos mecânicos, como o clipe metálico e a ligadura elástica. Objetivo: Permanece por esclarecer qual é a modalidade endoscópica (ou combinação de modalidades) que apresenta os melhores resultados no tratamento da hemorragia digestiva decorrente da úlcera péptica. Portanto, o objetivo desta revisão sistemática é comparar as diferentes modalidades de tratamento endoscópico da HDA decorrente da úlcera péptica, utilizando ensaios clínicos randomizados. Fontes de dados: Os estudos foram identificados através de pesquisa em bases de dados eletrônicas e listas de referência de artigos. As bases de dados pesquisadas foram Medline, Embase, Cochrane, LILACS, Dare e CINAHL. Critérios de elegibilidade de estudo, participantes e intervenções: Os estudos selecionados foram os ensaios clínicos randomizados comparando as diferentes modalidades endoscópicas para o tratamento de pacientes com hemorragia digestiva alta causada por úlcera péptica. Os estudos incluídos avaliaram técnicas endoscópicas contemporâneas de hemostasia: terapia de injeção endoscópica (todas as soluções, simples ou múltiplas), termocoagulação (heater probe, coagulação com plasma de argônio, coagulação com micro-ondas, eletrocoagulação monopolar, bipolar e multipolar), aplicação de clipes metálicos e tratamento combinado. Os desfechos avaliados foram as taxas de hemostasia inicial, ressangramento, cirurgia de urgência e de mortalidade. Avaliação de vieses: Ao nível de cada estudo, os revisores determinaram a adequação da randomização e da alocação; cegamento de pacientes, profissionais de saúde, coletores de dados e avaliadores de resultados; bem como o relato e a extensão das perdas de seguimento. Também foi avaliado se as técnicas de hemostasia endoscópica foram devidamente descritas e, se os desfechos foram adequadamente definidos em cada estudo. A análise de sensibilidade foi realizada quando a heterogeneidade (I2) foi superior a 50% e uma nova meta-análise foi calculada excluindo o(s) estudo(s) discrepante(s). Uma análise adicional foi realizada em cada comparação, incluindo apenas os ensaios de qualidade metodológica mais elevada. Resultados principais: Um total de 28 ensaios clínicos randomizados (envolvendo 2988 pacientes) foram avaliados nesta revisão, eles foram divididos em sete grupos de comparação de acordo com as modalidades estudadas em cada estudo. A terapia de injeção endoscópica como modalidade única foi inferior à sua combinação com o clipe metálico e com a termocoagulação na avaliação de taxa de ressangramento (diferença dos riscos [DR] = -0,10, intervalo de confiança de 95% [IC95%] = -0,18 a -0,03 e [DR] = -0,08, [IC95%] = -0,14 a -0,02, respectivamente) e na necessidade de cirurgia de urgência ([DR] = -0,11, [IC95%] = -0,18 a -0,04 e [DR] = -0,06, [IC95%] = -0,12 para -0,00, respectivamente). A aplicação de clipes metálicos foi superior à terapia de injeção endoscópica na avaliação da taxa de ressangramento ([DR] = -0,13, [IC95%] = -0,19 para -0,08), e os resultados da comparação entre a aplicação de clipes metálicos como monoterapia e a sua combinação com a terapia de injeção endoscópica não apresentaram diferenças estatísticas. A comparação entre o clipe metálico e a termocoagulação encontrou uma considerável heterogeneidade entre as intervenções utilizadas em cada estudo e nos resultados encontrados das meta-análises. A comparação da termocoagulação com a terapia de injeção endoscópica não evidenciou qualquer diferença estatística entre as modalidades, e a combinação delas é superior à técnica de termocoagulação sozinha ao avaliar a taxa de ressangramento ([DR] = -0,11, [IC95%] = -0,21 para - 0,02). Conclusões: A terapia de injeção endoscópica não deve ser empregada isoladamente. A aplicação de clipes metálicos é superior à terapia de injeção endoscópica, e a associação da injeção endoscópica não melhora a eficácia hemostática do uso isolado do clipe metálico. Como modalidade única, uma técnica de termocoagulação tem uma eficácia hemostática semelhante à terapia de injeção endoscópica, e estas modalidades combinadas parecem ser superiores à técnica de termocoagulação sozinha. Portanto, recomendamos a aplicação de clipes metálicos ou o uso combinado de uma terapia de injeção endoscópica com um método de termocoagulação para o tratamento de pacientes com hemorragia digestiva alta por úlcera péptica / Background: Upper Gastrointestinal bleeding (UGIB) results in 200,00 to 300,000 hospital admissions annually in the United States, with a mortality of 2,5% to 10%. Peptic ulcer disease represents the most common cause of UGIB, accounting for a third to a half of all episodes. Despite improvements in the understanding of its etiology, the incidence of bleeding from peptic ulcer disease, the most common complication, has not changed. Endoscopic therapy for active UGIB can dramatically reduce the risk of rebleeding or continued bleeding, the need for surgery, the number of units of packed erythrocytes required for transfusion, the length of hospital stay and mortality. Endoscopic treatment for ulcer bleeding has come a long way from injections of epinephrine and other solutions, the use of thermocoagulation, to the application of mechanical devices such as hemoclips and banding ligator. Objective: It remains unclear which is the endoscopic modality (or combination of modalities) that presents the best results in the treatment of peptic ulcer bleeding. Therefore, the objective of this systematic review is to compare the different modalities of endoscopic hemostatic therapy, using randomized clinical trials. Data sources: Studies were identified by searching electronic databases and scanning reference lists of articles. The searched databases were Medline, Embase, Cochrane, LILACS, DARE and CINAHL. Study eligibility criteria, participants and interventions: The studies selected were the randomized clinical trials comparing different endoscopic modalities for the treatment of patients presenting with acute upper gastrointestinal bleeding caused by peptic ulcer disease. The included trials assessed contemporary endoscopic hemostatic techniques: endoscopic injection therapy (all injectates, single or multiple), thermal coagulation (heater probe, argon plasma and microwave coagulation, monopolar, bipolar and multipolar electrocoagulations), hemoclip placement and combination treatment. The outcomes measured were the rates of initial hemostasis, rebleeding, emergency surgery and overall mortality. Risk of bias assessment: At the study level, the reviewers determined the adequacy of randomization and concealment of allocation; blinding of patients, of health care providers, of data collectors, and of outcome assessors; and the correct report and extent of loss to follow-up. It was also evaluated whether the endoscopic hemostatic techniques were properly described and if the outcomes were appropriately defined in each study. A sensitivity analysis was held when the heterogeneity (I2) was over 50% and a new meta-analysis was calculated excluding the outlier(s). An additional analysis was made at each comparison, including only the higher methodological quality trials. Main results: A total of 28 trials, involving 2988 patients were evaluated in this review, they were divided into seven comparison groups according to the modalities studied in each trial. Injection Therapy as single modality was inferior to its combination with Hemoclip and with Thermal Coagulation Therapy when evaluating rebleeding rate (risk difference [RD] = -0.10, 95% confidence interval [95%CI] = -0.18 to -0.03 and [RD] = -0.08, [95%CI] = -0.14 to -0.02, respectively) and need for emergency surgery ([RD] = -0.11, [95%CI] = -0.18 to -0.04 and [RD] = -0.06, [95%CI] = -0.12 to -0.00, respectively). Hemoclip was superior to Injection Therapy in the evaluation of rebleeding rate ([RD] = -0.13, [95%CI] = -0.19 to -0.08), and the results of the comparison between Hemoclip alone versus its combination with Injection Therapy did not present any statistical differences. The comparison between Hemoclip and Thermal Coagulation encountered a considerable heterogeneity between the trials in the interventions used and in the results found. The comparison of Thermal Coagulation versus Injection Therapy did not evidence any statistical difference between the modalities, and the combination of these is superior to the Thermal Coagulation alone when evaluating rebleeding rate ([RD] = -0.11, [95%CI] = -0.21 to -0.02. Conclusions: Injection therapy should not be used as single modality. The application of Hemoclip is superior to injection therapy, and the combined application of an injectate does not improve the hemostatic efficacy of the use of Hemoclip alone. As single modality, a thermal coagulation technique has a similar hemostatic efficacy as injection therapy, and these combined modalities appear to be superior to thermal coagulation technique alone. Therefore, we recommend the application of Hemoclips or the combined use of an Injection Therapy with a Thermal Coagulation method for the treatment of patients presenting with acute peptic ulcer bleeding

Orientador: Giovanni Faria Silva / Banca: Pedro Achilles / Banca: Luiza Maria Filomena Romanello / Banca: José Luiz Pimenta Modena / Banca: Ciro Garcia Montes / Resumo: A Hemorragia Digestiva Alta (HDA) é uma das desordens digestivas mais comumente diagnosticadas no mundo. As principais causas são a úlcera peptica gastroduodenal (UPGD) e a lesão aguda da mucosa gastroduodenal (LAMGD). Apesar dos avanços tecnológicos ocorridos nas últimas décadas, não se observou um declínio das taxas de mortalidade, que variam entre 11% e 33%. Esforços consideráveis tem sido realizados para a identificação precoce dos preditores de mau prognóstico, possibilitando à equipe médica a identificação dos grupos de alto risco e, com isso, uma intervenção mais agressiva e precoce. Análise comparativa dos preditores de recidiva hemorrágica ou óbito nos pacientes com HDA por UPGD ou LAMGD e análise de sobrevida dos grupos. Análise retrospectiva dos pacientes adultos com HDA por UPGD ou LAMGD submetidos a endoscopia digestiva alta (EDA) no período de jan/01 a dez/04 no HC da Faculdade de Medicina de Botucatu - UNESP. Critérios de inclusao: pacientes com HDA por UPGD ou LAMGD submetidos à EDA. Critérios de exclusão: HDA de outra etiologia. Análise estatística: testes de associação (Qui- Quadrado e teste exato de Fisher), testes de comparação entre os grupos, regressão logística múltipla, teste de Log Rank e regressão de Cox. 255 casas de HDA, sendo 57 por LAMGD e 198 por UPGD. Os grupos foram homogêneos com relação à idade, gênero, uso de anti-inflamatórios não esteroides (AINES), presença de comorbidades, níveis de hematócrito e hemoglobina e índices de recidiva hemorragica e óbito. No grupo com LAMGD,a idade media foi 60,4 anos (±18,7) e 64% dos doentes eram homens. O uso de AINES foi relatado por 46% dos doentes e 58% apresentavam comorbidades. Recidiva hemorrágica ocorreu em 3,5% dos pacientes e óbito em 10%. O preditor de ressangramento foi a necessidade de grande volume de transfusão sanguínea (OR: 2,03; IC:1,07-3,83)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The upper gastrointestinal bleeding (UGIB) is one of the most commonly diagnosed digestive disorders in the world. The main causes are the peptic ulcer disease (PUD) and erosive disease. Despite technological advances occurring in recent decades there was not a decline in mortality rates, ranging between 11% and 33%. Considerable efforts have been made to identify early predictors of poor prognosis, allowing the medical team to identify high risk patients and, thus, a more aggressive and early intervention. Comparative analysis of predictors of rebleeding or death in patients with UGIB by PUD or erosive disease and analysis of survival of groups. Retrospective analysis of adult patients with UGIB by PUD or erosive disease underwent endoscopy from January 2001 to December 2004 in the Botucatu Medical School - UNESP. Inclusion criteria: patients with UGIB by PUD or erosive disease underwent endoscopy. Exclusion Criteria: UGIB by another etiology. Statistical analysis: chisquare and Fisher exact test, tests for comparison between groups, multivariate logistic regression models, Log Rank test and Cox proportional hazards regression. 255 cases of UGIB, being 57 by erosive disease and 198 by PUD. The groups were homogeneous with respect to age, gender, use of nonsteroidal anti-inflammatory drugs (NSAIDS)... Complete abstract click electronic access below) / Doutor