RESUMO
Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium, compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.
Assuntos
Etnicidade , Microbioma Gastrointestinal , Esclerose Múltipla/microbiologia , Adulto , Negro ou Afro-Americano , Estudos de Casos e Controles , Clostridium/classificação , Clostridium/genética , Clostridium/isolamento & purificação , Feminino , Microbioma Gastrointestinal/genética , Hispânico ou Latino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Masculino , Metagenoma , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , RNA Ribossômico 16S/genética , População Branca , Adulto JovemRESUMO
Important advances have been made since the last Mexican consensus on the diagnosis and treatment of Helicobacter pylori (H. pylori) infection was published in 2007. Therefore, the Asociación Mexicana de Gastroenterología summoned 20 experts to produce "The Fourth Mexican Consensus on Helicobacter pylori". From February to June 2017, 4 working groups were organized, a literature review was performed, and 3 voting rounds were carried out, resulting in the formulation of 32 statements for discussion and consensus. From the ensuing recommendations, it was striking that Mexico is a country with an intermediate-to-low risk for gastric cancer, despite having a high prevalence of H. pylori infection. It was also corroborated that peptic ulcer disease, premalignant lesions, and histories of gastric cancer and mucosa-associated lymphoid tissue lymphoma should be considered clear indications for eradication. The relation of H. pylori to dyspeptic symptoms continues to be controversial. Eradication triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor should no longer be considered first-line treatment, with the following 2 options proposed to take its place: quadruple therapy with bismuth (proton pump inhibitor, bismuth subcitrate, tetracycline, and metronidazole) and quadruple therapy without bismuth (proton pump inhibitor, amoxicillin, clarithromycin, and metronidazole). The need for antimicrobial sensitivity testing when 2 eradication treatments have failed was also established. Finally, the promotion of educational campaigns on the diagnosis and treatment of H. pylori for both primary care physicians and the general population were proposed.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Educação em Saúde , Infecções por Helicobacter/microbiologia , Humanos , México , Médicos de Atenção PrimáriaRESUMO
BACKGROUND: Helicobacter pylori prevalence in Western countries has been declining simultaneously with increases in childhood asthma and allergic diseases; prior studies have linked these phenomena. AIMS: To examine the association between H. pylori colonisation in children and risk of asthma and related conditions at school age. We secondly examined additional effects of maternal H. pylori status by pairing with children's status. METHODS: This study was embedded in a multi-ethnic population-based cohort in Rotterdam, The Netherlands. We measured anti-H. pylori and anti-CagA antibodies in serum of children obtained at age 6 years, and of their mothers obtained during midpregnancy. Asthma or related conditions were reported for children at age 6 years. We used multivariate logistic regression analyses among 3797 subjects. RESULTS: In children, the H. pylori positivity rate was 8.7%, and 29.2% of these were CagA-positive. A child's colonisation with a CagA-negative-H. pylori strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60), but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. When taking into account maternal H. pylori status, only H. pylori-positive children with an H. pylori-negative mother had increased risk of asthma (2.42; 1.11-5.27), accounting for 3.4% of the asthma risk. CONCLUSIONS: Colonisation of a European child with a CagA-negative-H. pylori strain at age 6 was associated with an increased prevalence of asthma, but there was no association for non-European children. The underlying mechanisms for the observed risk differences require further research.
Assuntos
Asma/microbiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Anticorpos Antibacterianos/sangue , Criança , Feminino , Helicobacter pylori/imunologia , Humanos , Masculino , Mães , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos , RiscoRESUMO
La displasia broncopulmonar (DBP) es la secuela más prevalente del recién nacido pretérmino, y sigue suponiendo un motivo frecuente de consulta en las unidades de Neumología Pediátrica. La decisión del alta de la unidad neonatal debe apoyarse en una valoración exhaustiva de la situación clínica del paciente y en el cumplimiento de unos requisitos, que incluyen la estabilidad respiratoria y nutricional, y la instrucción a los cuidadores en el manejo domiciliario. Para un control adecuado de la enfermedad, es necesario que quede establecido, previamente al alta, un calendario de visitas y de exploraciones complementarias, y deben aplicarse las pautas de prevención de exacerbaciones y el tratamiento apropiados. El concepto de DBP como enfermedad multisistémica es fundamental en el seguimiento de los pacientes y debe ser tenido en cuenta para un buen control de la enfermedad. En este documento, el Grupo de Trabajo de Patología Respiratoria Perinatal de la Sociedad Española de Neumología Pediátrica propone un protocolo que sirva como referencia para unificar el seguimiento de los pacientes con DBP entre los diferentes centros y ámbitos asistenciales. Se revisan los aspectos a tener en cuenta en la evaluación previa al alta de la Unidad Neonatal y las principales complicaciones durante el seguimiento. Seguidamente, se detallan las recomendaciones en materia de tratamiento de la enfermedad y prevención de complicaciones, los controles tras el alta y su cronología
Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, and remains a major problem in pediatric pulmonology units. The decision of discharging from the Neonatal Unit should be based on a thorough assessment of the condition of the patient and compliance with certain requirements, including respiratory and nutritional stability, and caregiver education on disease management. For proper control of the disease, a schedule of visits and complementary tests should be established prior to discharge, and guidelines for prevention of exacerbations and appropriate treatment should be applied. In this paper, the Working Group in Perinatal Respiratory Diseases of the Spanish Society of Pediatric Pulmonology proposes a protocol to serve as a reference for the follow up of patients with BPD among different centers and health care settings. Key factors to consider when planning discharge from the Neonatal Unit and during follow up are reviewed. Recommendations on treatment and prevention of complications are then discussed. The final section of this guide aims to provide a specific schedule for follow-up and diagnostic interventions to be performed in patients with BPD
Assuntos
Humanos , Masculino , Feminino , Criança , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/prevenção & controle , Protocolos Clínicos , Recém-Nascido de muito Baixo Peso , Doenças do Prematuro/diagnóstico , Gasometria/métodos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Seguimentos , Recém-Nascido Prematuro/fisiologia , Indicadores Básicos de SaúdeRESUMO
Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, and remains a major problem in pediatric pulmonology units. The decision of discharging from the Neonatal Unit should be based on a thorough assessment of the condition of the patient and compliance with certain requirements, including respiratory and nutritional stability, and caregiver education on disease management. For proper control of the disease, a schedule of visits and complementary tests should be established prior to discharge, and guidelines for prevention of exacerbations and appropriate treatment should be applied. In this paper, the Working Group in Perinatal Respiratory Diseases of the Spanish Society of Pediatric Pulmonology proposes a protocol to serve as a reference for the follow up of patients with BPD among different centers and health care settings. Key factors to consider when planning discharge from the Neonatal Unit and during follow up are reviewed. Recommendations on treatment and prevention of complications are then discussed. The final section of this guide aims to provide a specific schedule for follow-up and diagnostic interventions to be performed in patients with BPD.
Assuntos
Displasia Broncopulmonar/diagnóstico , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Guias de Prática Clínica como AssuntoRESUMO
El síndrome del lóbulo medio es una patología frecuente en el niño, sobre todo en relación con el asma y/o la hiperreactividad bronquial, aunque existen otras muchas causas, como los cuerpos extraños, la tuberculosis endobronquial, etc. Presentamos el caso de un niño de 5 años de edad, con atelectasia persistente en la base derecha con participación del lóbulo medio, que se diagnosticó de tuberculosis. La tomografía computarizada confirmó la lesión y, ante una prueba de la tuberculina positiva, se realizó una fibrobroncoscopia para descartar una tuberculosis endobronquial, que demostró la presencia de una lesión polipoidea en el bronquio intermediario a la entrada del lóbulo medio. Se describen las diversas formas de tuberculosis endobronquial, así como el tratamiento con corticoides sistémicos. Se aconseja la realización de una fibrobroncoscopia en los casos de tuberculosis pulmonar con alteraciones radiológicas persistentes (atelectasia, atrapamiento aéreo, etc.) y/o falta de mejoría clínica pese al tratamiento adecuado(AU)
Middle lobe syndrome is a common condition in children, mainly related to asthma and/or bronchial hyperresponsiveness, although there are many other causes, such as foreign bodies, endobronchial tuberculosis, etc. We report a 5-year-old child with persistent atelectasis involving the right middle lobe, and diagnosed with tuberculosis. Computed tomography confirmed the injury and after a positive tuberculin skin test, fiberoptic bronchoscopy is performed to rule out endobronchial tuberculosis showing a polypoid lesion in the bronchus intermedius at the entrance of the middle lobe. It describes the various forms of endobronchial tuberculosis, and treatment with systemic corticosteroids. Fiberoptic bronchoscopy is recommended in cases of pulmonary tuberculosis with persistent radiographic abnormalities (atelectasis, air trapping, etc.) and/or a lack of clinical improvement with an adequate treatment(AU)
Assuntos
Humanos , Masculino , Pré-Escolar , Síndrome do Lobo Médio/diagnóstico , Tuberculose Pulmonar/diagnóstico , Síndrome do Lobo Médio/complicações , Tuberculose Pulmonar/complicações , Atelectasia Pulmonar/diagnósticoRESUMO
La neumonía adquirida en la comunidad (NAC) es una enfermedad frecuente en la infancia, en cuyo diagnóstico y tratamiento participan diversas especialidades pediátricas. Esto ha motivado que la Sociedad Española de Neumología Pediátrica (SENP) y la Sociedad Española de Infectología Pediátrica (SEIP) elaboren un documento de consenso sobre el diagnóstico de la NAC, revisando mediante la medicina basada en la evidencia aquellos aspectos prácticos sobre el mismo. Se analizan la etiología y la epidemiología, con los cambios actuales, así como la validez de ciertas pruebas complementarias, como los reactantes de fase aguda, los métodos microbiológicos y los métodos de imagen, orientando al pediatra en la utilidad real de los mismos(AU)
Community Acquired Pneumonia (CAP) is a common childhood disease, involving several paediatric subspecialties in its diagnosis and treatment. This has prompted the Spanish Society of Paediatric Pulmonology (SENP) and the Spanish Society of Paediatric Infectious Diseases (SEIP) to prepare a consensus document on the diagnosis of CAP, assessing the practical aspects by means of evidence-based medicine. It discusses the aetiology and epidemiology, with the current changes and the validity of certain laboratory tests, such as acute phase reactants, microbiological and imaging techniques, guiding the paediatricians in the real value of these tests(AU)
Assuntos
Humanos , Infecções Comunitárias Adquiridas/diagnóstico , Pneumonia/diagnóstico , Fatores de Risco , Surtos de Doenças , Derrame Pleural/epidemiologia , Biomarcadores/análise , Técnicas MicrobiológicasRESUMO
INTRODUCTION: The aim of this study was to characterize the mutations types present in the 23S rRNA gene related to H. pylori clarithromycin-resistance strains in Spain and evaluate a novel PCR-RFLP method for detection of the most frequent point mutation in our population. METHODS: Gastric biopsies were obtained by endoscopy from patients with gastric symptoms. H. pylori was cultured according to standard microbiological procedures and clarithromycin resistance was determined by E-test. DNA extraction was performed by NucliSens platform with the NucliSens magnetic extraction reagents (bioMérieux) according to the manufacturer instructions. Analyses for point mutations in 23S rRNA gene strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using BsaI enzyme to detect restriction sites that correspond to the mutation (A2143G). RESULTS: We found 42 out of 118 (35.6%) strains resistant to clarithromycin by E-test. E-test results were confirmed for the presence of point mutation in 34 (88.1%) of these strains. Mutation A2143G was found in 85.3% of the strains. Analyses with the restriction enzyme BsaI was able to confirm the presence of A2143G mutation. There were 8 H. pylori strains resistant to clarithromycin by E-test but without any point mutation in the 23 rRNA gene. CONCLUSIONS: We conclude that PCR-RFLP is a reliable method to detect clarithromycin-resistance H. pylori strains in countries with a high prevalence of clarithromycin-resistance as Spain. It may be useful before choosing regimens of H. pylori eradication.
Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adolescente , Adulto , Idoso , Criança , DNA Bacteriano/genética , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação Puntual/genética , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 23S/genética , Espanha , Adulto JovemRESUMO
The purpose of this study was to assess the role of Helicobacter pylori and several genetic polymorphisms in relation to inflammatory bowel disease (IBD). We studied 44 unrelated patients with IBD and 75 subjects with no history of IBD as controls. Using pyrosequencing technology, we identified gene polymorphisms in IL-10, TNF-A, ILB-31, and TLR4. H. pylori status was determined by serology. Individuals homozygous for IL10-592 A or IL10-1082 A genotypes show significantly lower occurrence of IBD (P=0.03 and P<0.01, respectively). Individuals heterozygous at IL10-1082 have significantly increased occurrence of IBD, both ulcerative colitis and Crohn's disease (P<0.01). There was no difference in the prevalence of H. pylori infection between cases and controls. This study provides evidence that variation in IL10 is correlated with IBD occurrence in this Mexican population.
Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Adulto , Idoso , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/genética , Doença de Crohn/epidemiologia , Doença de Crohn/genética , Feminino , Predisposição Genética para Doença , Haplótipos , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Doenças Inflamatórias Intestinais/complicações , Interleucina-10/genética , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto JovemRESUMO
La displasia broncopulmonar (DBP) es la enfermedad pulmonar crónica más frecuente en niños prematuros. Con la introducción de corticoides prenatales, la administración de agente tensioactivo y las nuevas estrategias de ventilación mecánica, se ha incrementado la supervivencia de neonatos cada vez más inmaduros, por lo que la incidencia de la DBP no sólo no ha descendido, sino que ha aumentado en este grupo de niños nacidos extremadamente pretérmino. Condiciona una gran morbilidad respiratoria en los 23 primeros años de vida, con numerosos ingresos hospitalarios y agudizaciones respiratorias provocados en su mayoría por infecciones víricas. Aunque hay una tendencia hacia la mejoría, en la edad escolar y la adolescencia persisten los síntomas respiratorios, así como alteraciones en la función pulmonar, y con cierta frecuencia estos niños presentan menor capacidad para el ejercicio. Aunque los síntomas de la DBP son muy parecidos a los del asma, ya que existe limitación al flujo aéreo e hiperrespuesta bronquial (HRB), el mecanismo fisiopatológico podría ser distinto en las 2 enfermedades. Por otra parte, la prematuridad aislada desempeña un papel importante en la enfermedad respiratoria crónica del niño y ya desde los primeros meses de vida se demuestran alteraciones en la función pulmonar de niños pretérmino sanos. Se ha observado que estos niños también tienen mayor morbilidad respiratoria que los nacidos a término no sólo en los primeros años de vida, sino en edades posteriores. En este artículo analizaremos distintos aspectos de la enfermedad respiratoria crónica asociada a la prematuridad, deteniéndonos en la sintomatología clínica, las alteraciones de la función pulmonar, la HRB y la capacidad de ejercicio. Haremos un recorrido desde la primera infancia hasta la adolescencia y la edad adulta joven. También veremos las similitudes y las diferencias entre la DBP y el asma (AU)
Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in premature children. With the inclusion of antenatal steroid therapy, surfactant use and novel mechanical ventilation strategies, survival of premature newborns has increased, whereupon the incidence of BPD has not only decreased but has also risen in extremely premature newborns. This has led to a high respiratory morbidity in the first 23 years of life, with numerous admissions to hospital and respiratory exacerbations mostly due to viral infections. Although there is a trend towards improvement, during school age and adolescence, respiratory symptoms may persist, due to changes in pulmonary function often showing a lower exercise capacity. Although BPD symptoms are similar to those of asthma, as there is limitation in airflow and bronchial hyperresponsiveness (BHR), pathophysiological mechanisms could be different in both diseases. On the other hand, isolated prematurity plays an important role in the child's respiratory pathology, proving that pulmonary function alterations in preterm children are present since the first months of life. A higher respiratory morbidity has also been observed in these children when compared to full-term newborns, not only during the first years of life but also subsequently. In this study, different aspects of chronic respiratory disease associated with prematurity will be analysed, drawing special attention to clinical symptoms, respiratory function changes, BHR and exercise capacity. All these aspects will be reviewed from early childhood until adolescence and young adult age. Similarities and differences between BPD and asthma will also be discussed (AU)
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , /fisiologia , Corticosteroides/uso terapêutico , Fatores de Risco , Sons Respiratórios/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Doenças do Prematuro/diagnóstico , Recém-Nascido Prematuro , /fisiologia , Morbidade , Broncodilatadores/uso terapêuticoRESUMO
Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in premature children. With the inclusion of antenatal steroid therapy, surfactant use and novel mechanical ventilation strategies, survival of premature newborns has increased, whereupon the incidence of BPD has not only decreased but has also risen in extremely premature newborns. This has led to a high respiratory morbidity in the first 2-3 years of life, with numerous admissions to hospital and respiratory exacerbations mostly due to viral infections. Although there is a trend towards improvement, during school age and adolescence, respiratory symptoms may persist, due to changes in pulmonary function often showing a lower exercise capacity. Although BPD symptoms are similar to those of asthma, as there is limitation in airflow and bronchial hyperresponsiveness (BHR), pathophysiological mechanisms could be different in both diseases. On the other hand, isolated prematurity plays an important role in the child's respiratory pathology, proving that pulmonary function alterations in preterm children are present since the first months of life. A higher respiratory morbidity has also been observed in these children when compared to full-term newborns, not only during the first years of life but also subsequently. In this study, different aspects of chronic respiratory disease associated with prematurity will be analysed, drawing special attention to clinical symptoms, respiratory function changes, BHR and exercise capacity. All these aspects will be reviewed from early childhood until adolescence and young adult age. Similarities and differences between BPD and asthma will also be discussed.
Assuntos
Displasia Broncopulmonar/fisiopatologia , Doenças do Prematuro/fisiopatologia , Pulmão/fisiopatologia , Fatores Etários , Asma/complicações , Displasia Broncopulmonar/complicações , Exercício Físico , Humanos , Recém-Nascido , Respiração , Fatores de TempoRESUMO
The prevalence and mechanisms of antibiotic resistance of Helicobacter pylori have not yet been investigated in Uruguay. The objective of this study was to assess the susceptibility of H. pylori to the most frequently used antibiotics and to determine the mechanism of resistance to clarithromycin. Seventy-nine isolates were obtained from gastric biopsies of 50 adult patients during two periods, 2001 and 2006. The former group enrolled the general population (GP), the latter group Afro-descendant (AD) subjects. The minimum inhibitory concentrations of clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin were determined using the E-test technique. Amplification was achieved through PCR and nucleic acid sequencing to detect mutations in the site of action of clarithromycin in the rRNA gene 23S. No amoxicillin or tetracycline-resistant strains were found. Clarithromycin resistance was found in 12% of the patients overall: 19.4% resistance in AD patients and no resistance in the GP group. This difference was statistically significant. The highest resistance was seen with metronidazole (36%), present in similar proportions in the two groups: 36.8% (GP) and 35.5% (AD). One GP patient and one AD patient had levofloxacin-resistant strains. Sequencing analysis of gene 23S rRNA showed that only mutation in position 2143 was presented in all clarithromycin-resistant strains.
Assuntos
Claritromicina/farmacologia , Helicobacter pylori/efeitos dos fármacos , Farmacorresistência Bacteriana , Helicobacter pylori/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Uruguai , Adulto JovemRESUMO
The prevalence and mechanisms of antibiotic resistance of Helicobacter pylori have not yet been investigated in Uruguay. The objective of this study was to assess the susceptibility of H. pylori to the most frequently used antibiotics and to determine the mechanism of resistance to clarithromycin. Seventy-nine isolates were obtained from gastric biopsies of 50 adult patients during two periods, 2001 and 2006. The former group enrolled the general population (GP), the latter group Afro-descendant (AD) subjects. The minimum inhibitory concentrations of clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin were determined using the E-test technique. Amplification was achieved through PCR and nucleic acid sequencing to detect mutations in the site of action of clarithromycin in the rRNA gene 23S. No amoxicillin or tetracycline-resistant strains were found. Clarithromycin resistance was found in 12% of the patients overall: 19.4% resistance in AD patients and no resistance in the GP group. This difference was statistically significant. The highest resistance was seen with metronidazole (36%), present in similar proportions in the two groups: 36.8% (GP) and 35.5% (AD). One GP patient and one AD patient had levofloxacin-resistant strains. Sequencing analysis of gene 23S rRNA showed that only mutation in position 2143 was presented in all clarithromycin-resistant strains(AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Claritromicina/uso terapêutico , Omeprazol/uso terapêutico , Claritromicina/biossíntese , Antibacterianos/uso terapêutico , Resistência a Medicamentos , Resistência Microbiana a Medicamentos , Uruguai/epidemiologiaRESUMO
BACKGROUND: Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis. AIMS: To determine whether leptin receptors are present in the oesophagus, and whether serum or gastric leptin levels are associated with oesophageal inflammation and metaplasia. METHODS: From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal oesophagus, and serum samples were collected. Patients were classified as having normal, inflamed or Barrett's oesophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay. RESULTS: Of 269 individuals enrolled, 105 were Helicobacter pylori-negative. Of the 88 patients with complete oesophageal biopsies, 44 were normal, 24 were inflamed and 20 were Barrett's oesophagus. Receptors for leptin were highly expressed on oesophageal epithelial cells, with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett's had significantly (p = 0.01) higher fundic leptin levels (median 202 (interquartile range 123-333) pg/mg) compared with normal (126 (78-221) pg/mg) or inflamed (114 (76-195) pg/mg) oesophagus. In multivariate analysis, for every twofold increase in fundic leptin, the odds of having Barrett's was 3.4 times (95% CI 1.5 to 7.6) higher compared with having a normal oesophagus. CONCLUSIONS: Leptin receptor expression on oesophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential oesophageal healing and metaplasia progression.
Assuntos
Esôfago de Barrett/metabolismo , Esofagite/metabolismo , Esôfago/metabolismo , Refluxo Gastroesofágico/metabolismo , Leptina/metabolismo , Receptores para Leptina/metabolismo , Esôfago de Barrett/etiologia , Esôfago de Barrett/patologia , Endoscopia do Sistema Digestório , Esofagite/patologia , Esôfago/patologia , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/patologia , Humanos , Masculino , Metaplasia/etiologia , Metaplasia/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: to assess the efficacy of rabeprazole (RPZ), amoxicillin (Am), and clarithromycin (Cla) (7 vs. 14 days) in the eradication of H. pylori, and to determine the effect of strain-specific antibiotic resistance and host CYP2C19 status. MATERIAL AND METHODS: first, we determined the CYP2C19 status of 100 healthy subjects to establish a sample size for the clinical trial. Then, 59 H. pylori-infected patients were randomized to receive RPZ (20 mg daily) plus Cla (500 mg b.d.) and Am (1,000 mg b.d.) for 7 vs. 14 days. The MIC for Am and Cla were determined using the agar dilution method. The CYP2C19 genotype was determined by the PCR-RFLP method. RESULTS: In the per-protocol analysis (PP) eradication rates were 89.7 and 72% for the 7- and 14-day groups (p = 0.159). In the intention to-treat analysis (ITT) eradication rates were 86.7 and 62.1% in the 7- and 14-day groups, respectively (p = 0.06). None of the strains was resistant to Am, and 4 strains were resistant to Cla: 3 (11.1%) in the 14-day group and 1 (4%) in the 7-day group. Neither strain-specific antibiotic resistance nor host CYP2C19 status influenced eradication rates. CONCLUSIONS: both 7- and 14-day therapies were effective for H. pylori eradication. Strain resistance and CYP2C19 status do not seem to influence eradication rates in the studied population.
Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Hidrocarboneto de Aril Hidroxilases , Claritromicina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Oxigenases de Função Mista , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/farmacologia , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Hidrocarboneto de Aril Hidroxilases/genética , Claritromicina/administração & dosagem , Claritromicina/farmacologia , Citocromo P-450 CYP2C19 , Interpretação Estatística de Dados , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Genótipo , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Oxigenases de Função Mista/genética , Rabeprazol , Fatores de TempoRESUMO
In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies.
Assuntos
Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/imunologia , Neoplasias Gástricas/epidemiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/imunologia , Adulto , Idoso , Índice de Massa Corporal , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/imunologia , Cárdia , China/epidemiologia , Estudos de Coortes , Comorbidade , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/imunologia , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/imunologiaRESUMO
Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed.
Assuntos
Interleucina-1/genética , Idoso , Costa Rica , Feminino , Triagem de Portadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Multiple Helicobacter pylori strains may colonize an individual host. Using enzyme-linked immunosorbent assay and line probe assay (LiPA) techniques, we analyzed the prevalence of mixed H. pylori colonization in 127 subjects from Venezuela, a country of high H. pylori prevalence, from three regions representing different population groups: the Andes (Merida), where Caucasian mestizos predominate, a major city near the coast (Caracas), where Amerindian-Caucasian-African mestizos predominate, and an Amazonian community (Puerto Ayacucho), where Amerindians predominate and mestizos reflect Amerindian and Caucasian ancestry. Among 121 H. pylori-positive persons, the prevalence of cagA-positive strains varied from 50% (Merida) to 86% (Puerto Ayacucho) by LiPA. Rates of mixed colonization also varied, as assessed by LiPA of the vacA s (mean, 49%) and m (mean, 26%) regions. In total, 55% of the individuals had genotypic evidence of mixed colonization. vacA s1c, a marker of Amerindian (East Asian) origin, was present in all three populations, especially from Puerto Ayacucho (86%). These results demonstrate the high prevalence of mixed colonization and indicate that the H. pylori East Asian vacA genotype has survived in all three populations tested.