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Overlap of reflux and eosinophilic esophagitis in two patients requiring different therapies:A review of the literature

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World Journal of Gastroenterology 2008年第9期14卷 1463-1466页

作者： Javier Molina-Infante Lucía Ferrando-Lamana Jose María Mateos-Rodríguez Belén Pérez-Gallardo Ana Beatriz Prieto-Bermejo Unit of Gastroenterology Hospital San Pedro de Alcantara Avda. Pablo Naranjo s/n 10003 Caceres Spain department of Pathology. hospital san pedro de alcantara Avda. Pablo Naranjo s/n 10003 Caceres Spain

Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have overlapping clinical, manometric, endoscopic and histopathologic features. The diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per high power field (eo/HPF) in esophageal biopsies. We report the cases of two young males suffering from dysphagia and recurrent food impaction with reflux esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of which became asymptomatic on proton pump inhibitor (PPI) therapy. The first patient also achieved a histologic response, while EE remained in the other patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring. Topical steroid therapy combined with PPI led to complete remission in this latter patient. GERD and EE may be undistinguishable, even by histology, so diagnosis of EE should only be established after a careful correlation of clinical, endoscopic and pathologic data obtained under vigorous acid suppression. These diagnostic difficulties are maximal when both diseases overlap. Limited data are available about this topic, and the interaction between EE and GERD is a matter of debate. In this setting, upper-mid esophagus step biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to evaluate the role of each disease. A PPI trial is mandatory in patients with a histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE should be suggested. However, a clinical response to PPI may not rule out quiescent EE, as shown in this report.

关键词： Eosinophils Eosinophilic esophagitis Gastroesophageal reflux Proton pump inhibitors Overlap

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Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance

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World Journal of Gastroenterology 2014年第30期20卷 10338-10347页

作者： Javier Molina-Infante Javier P Gisbert department of Gastroenterology Hospital San Pedro de Alcantara10003 CaceresSpain department of Gastroenterology Hospital Universitario de la PrincesaInstituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas28006 MadridSpain

The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade,largely related to increasing clarithromycin resistance *** a microbiological standpoint,bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its ***,several obstacles such as availability,complexity or tolerance prevent a general implementation of bismuth quadruple therapy,so nonbismuth quadruple regimens remain the best firstline treatment in clinical practice in many geographical *** review the rationale and efficacy of several optimization tools(increasing the length of duration,high-dose acid suppression,probiotics),which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple ***,we update available evidence on the effectiveness of several non-bismuth quadruple therapies(sequential,concomitant,hybrid,miscellaneous therapy),which have gained interest *** also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and,finally we provide a novel regionalized therapeutic algorithm,based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens,upon local antibiotic resistance rates.

关键词： Helicobacter pylori Eradication Clarithromycin Sequential Concomitant Hybrid Antibiotic resistance Bismuth

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Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

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Cell Research 2001年第1期11卷 44-54页

作者： ZAMORANO JOSE,Unidad de Investigacion, hospital san pedro de alcantara, Avda Millan Astray, 10003 Caceres ANN E KELLY, JONATHAN AUSTRIAN, HELEN Y WANG, ACHSAH D KEEGAN (department of Immunology, Jerome Holland Labs, American Red Cross, Rockville, MD, USA department of Immunology Jerome Holland Labs American Red Cross Rockville USA Unidad de Investigacion Hospital San Pedro de Alcantala Avda Millan Astray Caceres

IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3’ kinase in both resting and activated cells. By contrast, association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2 in B cell blasts. The pattern of IL-4- induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEKI inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts. These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

关键词： B lymphocytes IL-4 survival proliferation.

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Nicotinic cholinergic receptors in esophagus:Early alteration during carcinogenesis and prognostic value

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World Journal of Gastroenterology 2016年第31期22卷 7146-7156页

作者： Marina Chianello Nicolau Luis Felipe Ribeiro Pinto pedro Nicolau-Neto Paulo Roberto Alves de Pinho Ana Rossini Tatiana de Almeida Simao Sheila Coelho Soares Lima departamento de Bioquímica Instituto de Biologia Roberto Alcantara GomesUniversidade do Estado do Rio de Janeiro Programa de Carcinogênese Molecular Instituto Nacional de CancerCoordenacao de Pesquisa Gastroenterologia Hospital Universitário Pedro ErnestoUniversidade do Estado do Rio de Janeiro

AIM: To compare expression of nicotinic cholinergic receptors(CHRNs) in healthy and squamous cell carcinoma-affected esophagus and determine the prognostic ***: We performed RT-q PCR to measure the expression of CHRNs in 44 esophageal samples from healthy individuals and in matched normal surrounding mucosa, and in tumors from 28 patientsdiagnosed with esophageal squamous cell carcinoma(ESCC). Next, we performed correlation analysis for the detected expression of these receptors with the habits and clinico-pathological characteristics of all study participants. In order to investigate the possible correlations between the expression of the different CHRN subunits in both healthy esophagus and tissues from ESCC patients, correlation matrices were generated. Subsequently, we evaluated whether the detected alterations in expression of the various CHRNs could precede histopathological modifications during the esophageal carcinogenic processes by using receiver operating characteristic curve analysis. Finally, we evaluated the impact of CHRNA5 and CHRNA7 expression on overall survival by using multivariate ***: CHRNA3, CHRNA5, CHRNA7 and CHRNB4, but not CHRNA1, CHRNA4, CHRNA9 or CHRNA10, were found to be expressed in normal(healthy) esophageal mucosa. In ESCC, CHRNA5 and CHRNA7 were overexpressed as compared with patient-matched surrounding non-tumor mucosa(ESCC-adjacent mucosa; P dentified as an independent prognostic factor in ESCC; patients with high CHRNA5 expression showed an increased overall survival, in comparison with those

关键词： Nicotinic cholinergic receptors Esophagus Esophageal squamous cell carcinoma Tobacco Alcohol Gene expression

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Low prevalence of germline hMSH6 mutations in colorectal cancer families from Spain

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World Journal of Gastroenterology 2005年第37期11卷 5770-5776页

作者： Ana Sánchez de Abajo Miguel de la Hoya Alicia Tosar Javier Godino Juan Manuel Fernández Jose Lopez Asenjo Beatriz Perez Villamil pedro Perez Segura Eduardo Diaz-Rubio Trinidad Caldes Laboratorio de Oncología Molecular hospital Clinico san Carlos Madrid Spain Servicio de Anatomía Patológica hospital Clinico san Carlos Madrid Spain Servicio de Oncología Médica hospital Clinico san Carlos Madrid Spain

AIM: To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or ***: We used PCR-based DGGE assay and direct Sequencing to screen for hMSH6 gene in 91 HNPCC ***: we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort,8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X ***: Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.

关键词： HNPCC MMR hMSH6 MSI IHC SPANISH

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Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits

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World Journal of Gastroenterology 2016年第48期22卷 10477-10481页

作者： Alberto Lué Angel Lanas Digestive Diseases Service University Clinic Hospital Lozano Blesa Avenida San Juan Bosco IIS Aragon Avenida San Juan Bosco University of Zaragoza Calle de Pedro Cerbuna CIBERehd Av. Monforte de Lemos

Proton pump inhibitors(PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal antiinflammatory drugs(NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding(LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.

关键词： Proton pump inhibitor Small bowel Small bowel Lower gastrointestinal bleeding Nonsteroidal anti-inflammatory drugs

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Effectiveness and safety of first-generation protease inhibitors in clinical practice:Hepatitis C virus patients with advanced fibrosis

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World Journal of Gastroenterology 2015年第30期21卷 9163-9174页

作者： Javier Salmeron Carmen Vinaixa Ruben Berenguer Juan Manuel Pascasio Juan Jose sanchez Ruano Miguel angel Serra Ana Gila Moises Diago Manuel Romero-Gomez Jose Maria Navarro Milagros Testillano Conrado Fernandez Dolores Espinosa Isabel Carmona Jose Antonio Pons Francisco Jorquera Francisco Javier Rodriguez Ramon Perez Jose Luis Montero Rafael Granados Miguel Fernandez Ana Belen Martin Paloma Munoz de Rueda Rosa Quiles CIBERehd Instituto de Salud Carlos Ⅲ28029 MadridSpain Unit for Clinical Management of Digestive Diseases Complejo Hospitalario Universitario de Granada Instituto de Investigacion Biosanitaria de Granada University hospital Politecnico La Fe Unit for Clinical Management of Digestive Diseases University Hospital Virgen Del Rocio hospital Toledo University Clinic hospital of Valencia University General hospital of Valencia Unit for Clinical Management of Digestive Diseases University Hospital Nuestra Senora de Valme department of Gastroenterology and Hepatology Agencia sanitaria Costa del Sol University hospital Cruces Gastroenterology Unit University Hospital Fundacion Alcorcon University hospital Virgen Macarena University hospital Virgen de la Arrixaca hospital of Leon University General hospital Reina Sofia department Gastroenterology and Hepatology University Hospital Central de Asturias University hospital Reina Sofia University hospital de Gran Canaria Dr. Negrin hospital san pedro de alcantara

AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow ***:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was

关键词： Hepatitis C Boceprevir Telaprevir First-generation protease inhibitors Advanced fibrosis

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Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

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World Journal of Gastroenterology 2024年第29期30卷 3479-3487页

作者： Miriam López-Gómez Maria Morales Rebeca Fuerte Marta Muñoz pedro-David delgado-López Jorge Francisco Gómez-Cerezo Enrique Casado department of Medical Oncology Precision Oncology LaboratoryInfanta Sofía University HospitalSan Sebastián de los Reyes 28231MadridSpain department of Medical Oncology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain department of Internal Medicine Infanta Sofía University HospitalSan Sebastián de los Reyes 28703MadridSpain department of Pathology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain department of Neurosurgery Burgos University HospitalBurgos 09006Spain department of Internal Medicine Infanta Sofía University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain department of Medical Oncology Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain

BACKGROUND Helicobacter pylori(***)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between *** infection and esophageal *** mechanisms underlying this supposedly protective effect remain *** To determine the prevalence of *** infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our *** We retrospectively reviewed the prevalence of *** infection in a cohort of patients diagnosed with esophageal *** or previous proton pump inhibitor(PPI)usage was also *** A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were *** was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal ***,54 patients(60.7%)presented at stages III and *** *** infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous *** infection had stage *** one patient had received prior *** eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI *** In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous *** *** also reviewed the medical history of the patients,concluding that the majority had received or were on PPI *** minimal prevalence of *** infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

关键词： Helicobacter pylori Eradication Esophageal tumor Dysbiosis Proton pump inhibitors Carcinogenesis Microbiota Incidence

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Local renin angiotensin system and sperm DNA fragmentation

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Asian Journal of Andrology 2022年第2期24卷 139-146页

作者： María Victoria Aparicio Prieto María Victoria Rodríguez Gallego Asier Valdivia Palacín Yosu Franco Iriarte Gotzone Hervás Barbara Enrique Echevarría Orella Luis Casis Saenz Human Reproduction Unit Cruces University HospitalBarakaldo 48903Spain Human Reproduction Unit San Pedro HospitalLogroño 26006Spain department of Physiology Faculty of Medicine and NursingUniversity of the Basque Country(UPV/EHU)Leioa 48940Spain Human Reproduction Unit Ruber International HospitalMadrid 28034Spain

The renin angiotensin system(RAS)appears to influence male fertility at multiple *** this work,we analyzed the relationship between the RAS and DNA *** male volunteers were divided into two groups(25 each):control(DNA fragmentation≤20%)and pathological(DNA fragmentation>20%)*** of five peptidases controlling RAS were measured fluorometrically:prolyl endopeptidase(which converts angiotensin[A]I and A II to A 1–7),neutral endopeptidase(NEP/CD10:A I to A 1–7),aminopeptidase N(APN/CD13:A III to A IV),aminopeptidase A(A II to A III)and aminopeptidase B(A III to A IV).Angiotensin-converting enzyme(A I to A II),APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays,as were the receptors of all RAS components:A II receptor type 1(AT1R),A II receptor type 2(AT2R),A IV receptor(AT4R or insulin-regulated aminopeptidase[IRAP]),(pro)renin receptor(PRR)and A 1–7 receptor or Mas receptor(MasR)None of the enzymes that regulate levels of RAS components,except for APN/CD13(decrease in fragmented cells),showed significant differences between both *** of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented *** of AT1R(94.3%normozoospermic vs 84.1%fragmented),AT4R(96.2%vs 95.3%)and MasR(97.4%vs 87.2%)was similar between the ***2R(87.4%normozoospermic vs 63.1%fragmented)and PRR(96.4%vs 48.2%)were higher in non-fragmented *** findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.

关键词： DNA fragmentation local renin angiotensin system sperm fertility

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Is it enough to eliminate hepatitis C virus to reverse the damage caused by the infection?

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World Journal of Clinical Infectious Diseases 2017年第1期7卷 1-5页

作者： Patricia Pérez-Matute José A Oteo Infectious Diseases de-partment Center for Biomedical Research of La Rioja(CIBIR)-Hospital San Pedro

Hepatitis C virus(HCV) infection represents one of themajor causes of chronic liver disease, hepatocellularcarcinoma and morbidity/mortality worldwide. It is alsoa major burden to the healthcare systems. A complete elimination of the HCV from the body through treatment is now possible. However, HCV not only alters the hepatic function. Several extra-hepatic manifestations are present in HCV-infected patients, which increase the mortality rate. Liver and gut are closely associated in what is called the "gut-liver axis". A disrupted gut barrier leads to an increase in bacterial translocation and an activation of the mucosal immune system and secretion of inflammatory mediators that plays a key role in the progression of liver disease towards decompensated cirrhosis in HCV-infected patients. In addition, both qualitative and quantitative changes in the composition of the gut microbiota(GM) and states of chronic inflammation have been observed in patients with cirrhosis. Thus, a successful treatment of HCV infection should be also accompanied by a complete restoration of GM composition in order to avoid activation of the mucosal immune system, persistent inflammation and the development of long-term complications. Evaluation of GM composition after treatment could be of interest as a reliable indicator of the total or partial cure of these patients. However, studies focused on microbiota composition after HCV eradication from the body are lacking, which opens unique opportunities to deeply explore and investigate this exciting field.

关键词： Hepatitis C infection Inflammation Virus eradication Direct-acting antivirals Gut microbiota

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