RESUMEN
Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.
Asunto(s)
Angioedema/terapia , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bradiquinina/análogos & derivados , Omalizumab/uso terapéutico , Ácido Tranexámico/uso terapéutico , Bradiquinina/uso terapéutico , Humanos , Progestinas/uso terapéutico , Resultado del TratamientoRESUMEN
Helicobacter pylori is a common bacterium infecting about half the world's population. It is causally linked with a diverse spectrum of gastrointestinal clinical disorders including peptic ulcer disease, gastric cancer, and gastric MALT lymphoma. The principal reservoir is the human stomach, and transmission probably occurs by person-to-person passage. Prevalence rates are generally much higher in developing countries compared to developed countries, although there are subgroups within many regions with higher H. pylori prevalence than in the general population. The prevalence of H. pylori varies by geographical location, ethnic background, socioeconomic conditions, and age. Recent studies suggest decreasing prevalence in developed countries or those with rapidly improving socioeconomic conditions. Comparative studies of the two fully sequenced H. pylori genomes are providing understanding of its large genetic diversity and bacterial virulence factors. The discovery of the type IV secretion system in H. pylori and its role in translocation of the CagA protein from the bacterial cell into the host epithelial cell provides insight into how host-bacterial interaction may lead to host disease. Cytokine promoter polymorphisms are determinants important in host gastric acid secretion status. Understanding the changing trends in H. pylori epidemiology, details of its transmission pathways, and the bacterial and host determinants leading to gastroduodenal disease remain the challenges in this area. Global epidemiological studies, advances in technology, and medical interventions have converged to help clarify the mechanisms of interaction between this ubiquitous micro-organism and its host that result in its diverse clinical manifestations.
Asunto(s)
Antígenos Bacterianos , Enfermedades Gastrointestinales/microbiología , Infecciones por Helicobacter/transmisión , Helicobacter pylori/aislamiento & purificación , Adulto , Anemia Ferropénica/complicaciones , Proteínas Bacterianas/genética , Niño , Países Desarrollados , Países en Desarrollo , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Factores de Riesgo , Factores Socioeconómicos , Neoplasias Gástricas/etiología , Neoplasias Gástricas/microbiologíaRESUMEN
Helicobacter pylori infection is the world's most common chronic infection in humans and is the cause of most gastritis cases. This infection is accepted as the etiology of the majority of peptic ulcers. It has been implicated as a significant contributing factor in the development of gastric malignancy--both gastric MALT lymphoma and gastric adenocarcinoma. Both endoscopic and non-endoscopic tests are available for accurate diagnosis of the infection. Several multi-drug regimens are useful for effective eradication of the infection. Strategies have been developed for managing patients with gastric MALT lymphoma. Criteria to identify populations with increased risk for gastric malignancy are being developed. H. pylori induces gastritis; it is also involved in both apoptosis and cellular proliferation. The role of H. pylori infection in the pathogenesis of premalignant lesions, altered gastric acid secretion, and significant clinical presentations is the subject of numerous studies worldwide.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Úlcera Péptica , Neoplasias Gástricas , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/fisiopatología , Humanos , Úlcera Péptica/etiología , Úlcera Péptica/microbiología , Úlcera Péptica/fisiopatología , Neoplasias Gástricas/etiología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/fisiopatologíaRESUMEN
Peptic ulcer disease is a common gastrointestinal disease whose management and treatment has changed dramatically over the last 25 years. Treatment of peptic ulcer disease has evolved from dietary modifications and antacids to gastric acid suppression with H2-receptor antagonists and proton pump inhibitors to eradication of Helicobactor pylori infection. Treatment of patients infected with H pylori using antibiotics has changed the natural history of peptic ulcer disease. As a result of H pylori treatment and other unknown factors ulcer disease is declining and complications from ulcer disease have diminished significantly.
Asunto(s)
Úlcera Péptica/diagnóstico , Úlcera Péptica/terapia , Antiácidos/uso terapéutico , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Farmacorresistencia Microbiana , Medicina Familiar y Comunitaria/métodos , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Úlcera Péptica/epidemiología , Úlcera Péptica/etiología , Úlcera Péptica/fisiopatología , Atención Primaria de Salud/métodos , Inhibidores de la Bomba de Protones , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: Whether gastric infection with Helicobacter pylori increases the risk of gastric mucosal injury during long term/low dose aspirin therapy is unknown. We examined whether H. pylori infection enhances upper GI mucosal damage, assessed endoscopically, in volunteers given low dose aspirin. We studied 61 healthy men and women, 29 with and 32 without active H. pylori infection. METHODS: We treated volunteers for 45 days with a placebo or aspirin (either 81 mg every day or 325 mg every 3 days). Gastroduodenal mucosal damage was then assessed by endoscopy, as was gastric histology and ex vivo gastric mucosal prostaglandin E2 and F2alpha synthesis rates. RESULTS: Erosive disease from low dose aspirin (erosions and/or ulcers) occurred in 50% of H. pylori-infected volunteers and in 16% of their noninfected counterparts (p = 0.02). Aspirin caused a significantly higher average mucosal injury score in the gastric antrum in H. pylori-infected participants than in noninfected subjects (p = 0.03), and two H. pylori-infected subjects developed antral gastric ulcers. Subjects with H. pylori gastritis treated with the placebo had nearly 50% higher gastric mucosal prostaglandin (E2 plus F2alpha) synthesis rates than their noninfected counterparts (108 +/- 6 ng/g/min versus 75 +/- 6 ng/g/min, p < 0.001). Aspirin reduced mucosal prostaglandin synthesis to similar levels in infected and noninfected participants. CONCLUSIONS: Long term/low dose aspirin therapy led to more gastric mucosal damage when H. pylori gastritis was present than when it was absent, despite similar degrees of gastric mucosal prostaglandin depletion.
Asunto(s)
Aspirina/efectos adversos , Enfermedades Duodenales/inducido químicamente , Gastritis/complicaciones , Infecciones por Helicobacter/complicaciones , Prostaglandinas/biosíntesis , Gastropatías/inducido químicamente , Adolescente , Adulto , Anticuerpos Antibacterianos/biosíntesis , Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Plaquetas/enzimología , Ciclooxigenasa 1 , Método Doble Ciego , Enfermedades Duodenales/complicaciones , Enfermedades Duodenales/metabolismo , Enfermedades Duodenales/microbiología , Úlcera Duodenal/inducido químicamente , Úlcera Duodenal/complicaciones , Úlcera Duodenal/microbiología , Endoscopía Gastrointestinal , Femenino , Mucosa Gástrica/metabolismo , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/inmunología , Helicobacter pylori/aislamiento & purificación , Humanos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Isoenzimas/metabolismo , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Prostaglandina-Endoperóxido Sintasas/metabolismo , Estómago/efectos de los fármacos , Estómago/patología , Gastropatías/complicaciones , Gastropatías/metabolismo , Gastropatías/microbiología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/complicaciones , Úlcera Gástrica/microbiologíaRESUMEN
OBJECTIVES: Recent surveys of physician practice have suggested the existence of excessive, inappropriate use of the fecal occult blood test (FOBT). We studied the implementation of this test in hospitalized patients. METHODS: We performed a retrospective chart review of 1000 randomly selected patients who had been discharged from the Medicine service at four teaching hospitals. Patient demographics, clinical presentation, presence or absence of overt GI bleeding, and use of medications that might affect the FOBT were recorded. Reviewers assessed whether patients who had FOBT would have been candidates for colon resection if asymptomatic colon cancer had been found. RESULTS: Digital rectal examination was documented in 44.8% of patients; the findings were recorded in only 9%. A total of 421 patients had FOBT on admission, usually on stool obtained at digital rectal examination. Of the patients with a positive FOBT, 17% had active GI bleeding. Only 41.1% of patients with a positive FOBT were referred to the gastroenterology service. In 70.5% of patients, FOBT could be considered inappropriate because of factors such as age, active GI bleeding, or use of aspirin or other nonsteroidal anti-inflammatory drugs. CONCLUSIONS: The FOBT, which is validated only for colorectal cancer screening, is often performed inappropriately in patients admitted to the hospital. This test should be restricted in hospital practice. It would be preferable to identify patients who are appropriate candidates for colorectal cancer screening at the time of hospital discharge and to advise them about the appropriate performance of the FOBT at home.
Asunto(s)
Pruebas Hematológicas/estadística & datos numéricos , Auditoría Médica , Sangre Oculta , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/diagnóstico , Colonoscopía , Femenino , Estudios de Seguimiento , Hospitales de Enseñanza , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , Procedimientos Innecesarios , Revisión de Utilización de RecursosRESUMEN
Discussion continues on the role of Helicobacter pylori. The following debate provides a venue to examine 2 sides of this complicated issue. Dr. Vakil presents evidence that the eradication of H pylori will improve patients' health, while Dr. Go introduces evidence that suggests the presence of H pylori can be beneficial in particular cases. These clinicians also discuss the issue of whether to test and treat for H pylori and the role of H pylori in patients with gastroesophageal reflux disease.
Asunto(s)
Úlcera Duodenal/complicaciones , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Antiinflamatorios no Esteroideos , Dispepsia/complicaciones , Reflujo Gastroesofágico/complicaciones , Infecciones por Helicobacter/patología , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Neoplasias Gástricas/complicaciones , Estados UnidosRESUMEN
Bacterial and host response factors play significant roles in the pathogenicity of H. pylori-related disease manifestations. The complete DNA sequences for two H. pylori strain genomes have been published. The differences in the sequences between these two unrelated strains may enable clinicians to identify rapidly other conserved and potentially virulent genes and products. Whether these two DNA sequences are sufficient representation of the H. pylori genetic heterogeneity is unknown. The host immune response and the cascade of events that occurs with H. pylori infection are being clarified rapidly. Understanding the role of this gastric bacterium in apoptosis and cellular proliferation would enable clinicians to understand its relationship to ulcerogenesis and gastric malignancy. Piecing together many observations related to H. pylori would result in understanding the interaction of H. pylori factors and host responses that lead to the variety of disease manifestations associated with this chronic infection. The development of animal models with H. pylori and other Helicobacter species has set the stage in which in vitro observations can be tested in the in vivo model.
Asunto(s)
Úlcera Duodenal/microbiología , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidad , Úlcera Gástrica/microbiología , Enfermedad Crónica , Úlcera Duodenal/fisiopatología , Femenino , Humanos , Masculino , Medición de Riesgo , Sensibilidad y Especificidad , Úlcera Gástrica/fisiopatología , Virulencia/fisiologíaRESUMEN
The discovery of Helicobacter pylori and its relationship to upper gastrointestinal tract diseases has emphasized the significance of infectious pathogens in clinical disease. Severe manifestations of H. pylori-associated diseases include gastric adenocarcinoma and the recently described gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Ongoing worldwide investigations of the interactions of H. pylori and the host response are rapidly clarifying the role of this bacterium in multiple gastrointestinal diseases. This review will address diagnosis, management, and follow-up of the patient presenting with gastric MALT lymphoma, including a discussion of the issues related to premalignant lesions associated with gastric adenocarcinoma. Prospective trials and long-term follow-up studies are in progress and will guide appropriate management of these diseases.
Asunto(s)
Adenocarcinoma/microbiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Linfoma de Células B de la Zona Marginal/microbiología , Neoplasias Gástricas/microbiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Progresión de la Enfermedad , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/terapia , Humanos , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/terapia , Masculino , Persona de Mediana Edad , Lesiones Precancerosas , Inducción de Remisión , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMEN
OBJECTIVE: Despite recently published national guidelines, many physicians have only limited knowledge about Helicobacter pylori infection. We conducted this study to assess internal medicine residents' knowledge about H. pylori. METHODS: Two hundred and nineteen residents in seven accredited internal medicine training programs completed a self-administered questionnaire on personal demographics and practices related to testing for-and treating-H. pylori infection. RESULTS: Noon conferences (82%), ward teaching (66%), journals (70%), and sponsored symposia (27%) were their major sources of H. pylori-related information. Forty-eight percent had used office-based tests for the infection. Testing for (and treatment of) Helicobacter pylori infection was recommended by 97% (97%) for newly diagnosed duodenal ulcer, but by only 61% (63%) for a past history of duodenal ulcer. Many recommended testing in unproven conditions and might not have offered treatment to an infected patient. A proton pump inhibitor-based triple-drug regimen was the treatment of first choice of 55%; 20% recommended proton pump inhibitor-based dual regimens. Sixty-six percent and 80%, respectively, underestimated the rates of resistance to clarithromycin and metronidazole. In the absence of gastrointestinal symptoms, 22% would have ordered Helicobacter pylori testing but only 33% of these would undergo treatment if positive. CONCLUSIONS: Internal medicine residents usually test for Helicobacter pylori infection in appropriate conditions, but may not always treat the infection when the result is positive. Most use efficacious treatment regimens although many have inaccurate knowledge of resistance rates, which may adversely influence prescribing. Education should focus on practical issues surrounding Helicobacter pylori testing and treatment such as those contained in the American College of Gastroenterology's 1998 practice guidelines.
Asunto(s)
Recolección de Datos , Conocimientos, Actitudes y Práctica en Salud , Infecciones por Helicobacter , Helicobacter pylori , Medicina Interna/educación , Internado y Residencia , Adulto , Farmacorresistencia Microbiana , Quimioterapia Combinada , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/fisiología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de ProtonesRESUMEN
Combination antimicrobial therapies for the effective eradication of Helicobacter pylori infection have been identified and are commercially available. Ongoing studies to improve eradication rates are based on modification of currently approved treatments. Management of H. pylori infection now focuses on which patients should be treated and, by extension, which should be tested, because all patients should have a positive test result for H. pylori before starting antimicrobial therapy. Peptic ulcer disease was believed to be caused by acid abnormalities until about two decades ago, when H. pylori was successfully cultured; the clinical records of an early proponent of an infectious cause of peptic ulcer disease were recently discovered. The role of H. pylori infection in gastroesophageal disease and in ulcer disease associated with nonsteroidal anti-inflammatory drugs have become intensely investigated topics. Consensus conferences among pediatric physicians are establishing practice guidelines for H. pylori management in children and adolescents.
RESUMEN
OBJECTIVE: Whether Helicobacter pylori infection and use of nonsteroidal antiinflammatory drugs (NSAIDs) are independent risk factors for ulcerogenesis remains unclear. We undertook this study to evaluate H. pylori isolates from gastric ulcer patients to determine whether the genotype of the infecting isolate could be correlated with the use or nonuse of NSAIDs. METHODS: Fifty-two patients presenting with gastric ulcer and infected with H. pylori were included; 26 patients were taking NSAIDs or aspirin (ASA) regularly at the time of ulcer diagnosis. Polymerase chain reaction (PCR) was employed to assess the presence and mosaicism of the following H. pylori genes: cagA, vacA, iceA, and picB. RESULTS: We found no statistical differences in the presence of these genes in H. pylori isolates from gastric ulcer patients taking or not taking prescription NSAIDs or ASA. A 297-bp fragment of the cagA gene was detected in 96% of the isolates from the NSAID and ASA users and 100% from the non-NSAID users (p = 1.0). A larger and more variable region of the cagA gene was detected more frequently among the isolates from non-NSAID users than those from NSAID users (p = 0.05). Ninety-two percent of the isolates were identified as vacA genotype s1. The dominant vacA subtype was s1b, 76.9% and 65.4% in isolates from non-NSAID-taking or NSAID-taking patients, respectively (p = 0.4). iceA1 genotype was not correlated with gastric ulcer as this allele was only detected in 17.3% of all isolates. CONCLUSIONS: No significant differences in the presence of the candidate virulence genes vacA, cagA, picB, or iceA were detected in isolates from gastric ulcer patients taking prescription NSAIDs or ASA, compared with those not taking these drugs, indicating that single gene presence does not allow discrimination of isolates that may be important in NSAID-induced ulcerogenesis. A variable region of the cagA gene was more frequently detected in isolates from patients not taking NSAIDs or ASA, suggesting that this gene may be modified by NSAID- or ASA-related factors or that certain strains may be selected for in patients taking these medications.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antígenos Bacterianos , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/microbiología , Adulto , Anciano , Aspirina/uso terapéutico , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Femenino , Genes Bacterianos/genética , Genotipo , Helicobacter pylori/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Mosaicismo/genética , Reacción en Cadena de la PolimerasaRESUMEN
Chronic Helicobacter pylori infection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation by H. pylori strains obtained from patients with different clinical presentations. Bacterial sonicates from 12 strains were used to stimulate phagocyte upregulation of CD11b/CD18 adherence molecules assessed by fluorescence flow cytometry and oxidative burst responses assessed by chemiluminescence. A dose-dependent activation of CD11b/CD18 adherence molecules was observed with all strains on both neutrophils and monocytes. The activities were similar for strains from patients with duodenal ulceration and for strains from asymptomatic volunteers irrespective of histopathologic grades of the biopsy specimens from the antral mucosa. The neutrophil chemiluminescence response correlated with histopathologic severity. We conclude that upregulation of neutrophil and monocyte adherence molecules by H. pylori sonicates is not associated with clinical presentation of the infection.
Asunto(s)
Úlcera Duodenal/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Monocitos/inmunología , Activación Neutrófila/inmunología , Neutrófilos/inmunología , Antígenos CD18/inmunología , Úlcera Duodenal/sangre , Úlcera Duodenal/microbiología , Infecciones por Helicobacter/sangre , Humanos , Antígeno de Macrófago-1/inmunologíaRESUMEN
H pylori infection is so common as to seem ubiquitous in many areas of the world. Transmission is believed to be primarily person to person. The pathogen invariably damages the gastric mucosa, resulting in both structural and functional abnormalities. It causes histologic gastritis and is critical in the pathogenesis of the gastritis-associated diseases, namely, gastric ulcer, duodenal ulcer, gastric adenocarcinoma, and primary gastric lymphoma. Elimination of the infection results in healing of gastritis and cure of peptic ulcer disease.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Úlcera Péptica , Reflujo Gastroesofágico/microbiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Humanos , Úlcera Péptica/epidemiología , Úlcera Péptica/microbiología , Prevalencia , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
An algorithmic approach to evaluation of dyspepsia or abdominal discomfort begins with differentiation between peptic ulcer disease and gastroesophageal reflux disease as well as recognition of alarm signs and symptoms for gastric cancer, which are indications for early endoscopy. In the absence of alarm symptoms, most patients should undergo noninvasive testing for H pylori infection with a serologic, urea breath, or stool antigen test. Factors to consider in selection of appropriate testing include reliability, specificity, sensitivity, cost, and local access and expertise. As a general rule, physicians should choose a test that has the best accuracy for the level of testing expertise available. The basic principle underlying testing for H pylori is that patients should not undergo testing unless the physician is willing to treat on the basis of a positive test result. In patients who receive treatment, confirmation of cure is important for preventing further morbidity and reducing risk of transmission of infection.
Asunto(s)
Úlcera Péptica/diagnóstico , Antiinflamatorios no Esteroideos/efectos adversos , Diagnóstico Diferencial , Reflujo Gastroesofágico/diagnóstico , Humanos , Úlcera Péptica/etiología , Factores de RiesgoRESUMEN
Peptic ulcer disease associated with H pylori infection is curable. The important factors in selecting therapy are efficacy of eradication, prevention of resistance, avoidance or minimization of adverse effects, patient compliance, and cost. The most effective regimens include a bismuth preparation or antisecretory drug (proton pump inhibitor or H2 receptor antagonist) plus two antibiotics administered for 14 days. Dual-drug therapies are not recommended. Triple-drug regimens are more likely to eradicate H pylori and less likely to generate resistant strains among surviving organisms. In general, cure of the infection should be confirmed 4 weeks after completion of the treatment. Antibiotic resistance is an important consideration in choosing therapy, and patients should be taught the importance of compliance. When treatment fails, antibiotic combinations should not be repeated. Considerations for anti-H pylori treatment in a managed care environment mirror those for good medical practice in general, with special attention to stringent cost-control or outcomes-driven measures.
Asunto(s)
Antiulcerosos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/microbiología , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Farmacorresistencia Microbiana , Quimioterapia Combinada , Helicobacter pylori/efectos de los fármacos , HumanosRESUMEN
OBJECTIVE: Few studies have examined the genetic relationships of Helicobacter pylori strains affecting family members. Our aim was to do so. METHODS: We characterized H. pylori isolates obtained from members of a single family presenting with various gastroduodenal diseases to examine H. pylori bacterial genetic similarity. Endoscopic evaluation with gastric mapping was performed on each individual to establish clinical and histological disease. Genomic DNA extracted from each H. pylori isolate was used to generate DNA fingerprints for each strain by REP-PCR. vacA genotypes and cagA presence were established by PCR. RESULTS: Gastrointestinal diseases among the five members of this family included gastric adenocarcinoma in a 52-yr-old man (index patient), gastric MALT-lymphoma in the 73-yr-old mother; intestinal metaplasia (IV) and atrophic gastritis in the 48-yr-old brother; intestinal metaplasia (I-III) in the 47-yr-old brother, and a duodenal ulcer scar in the 42-yr-old sister. REP-PCR DNA fingerprints of H. pylori isolates from the index patient, his mother, and both of his brothers were identical or highly similar. By contrast, the H. pylori DNA fingerprint from the sister was markedly different from the H. pylori DNA fingerprints from the other family members. All isolates had the genotype cagA-positive and vacA slb/ml mosaic genotype. CONCLUSIONS: The DNA fingerprints of H. pylori strains obtained from members of this family with malignancy or premalignant histological disease were identical or highly similar and markedly different from the H. pylori DNA fingerprint from the sibling with duodenal ulcer disease. All H. pylori isolates within the family possessed genetic markers of enhanced virulence (presence of the cagA gene and vacA sl/ml mosaicism). In addition to host genetics and environmental factors, these findings suggest that infection with genetically similar H. pylori strains is a significant factor in determining the clinical outcome of an infection with H. pylori.
Asunto(s)
Adenocarcinoma/microbiología , Antígenos Bacterianos , Úlcera Duodenal/microbiología , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Linfoma de Células B de la Zona Marginal/microbiología , Neoplasias Gástricas/microbiología , Adulto , Anciano , Proteínas Bacterianas/genética , Dermatoglifia del ADN , ADN Bacteriano/genética , Femenino , Helicobacter pylori/aislamiento & purificación , Humanos , Intestinos/patología , Masculino , Metaplasia , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
In each of six gastric cancer patients, repetitive extragenic palindromic PCR DNA fingerprints of 18 single colonies of Helicobacter pylori from the gastric antrum, corpus, and cardia were identical and matched that of the parental isolate. In three additional gastric cancer patients, 17 of 18 single-colony DNA fingerprints were identical to each other and to the DNA fingerprint of the corresponding parental isolate.
Asunto(s)
Adenocarcinoma/complicaciones , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Neoplasias Gástricas/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Dermatoglifia del ADN , ADN Bacteriano/análisis , ADN Bacteriano/genética , Femenino , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Secuencias Repetitivas de Ácidos Nucleicos/genéticaRESUMEN
Chronic Helicobacter pylori infection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation induced by H. pylori strains with different virulence genotypes. Bacterial sonicates from 12 strains were used to induce phagocyte up-regulation of adherence molecule CD11b, assessed by fluorescence flow cytometry, and oxidative burst responses, assessed by chemiluminescence. A dose-dependent induction of the expression of CD11b was observed with sonicate from all H. pylori strains on both neutrophils and monocytes. Strains negative for cagA and picB genes had the same inducing activity of upregulation of CD11b as strains positive for these genes. A vacA-S2 type strain had the same activity as vacA-S1 type strains. The induction of toxic oxygen radicals by H. pylori-activated neutrophils gave higher median values for the cagA-positive strains than for the cagA-negative strains. For the monocyte chemiluminescence response, cagA-negative strains gave higher median values compared to cagA-positive strains. We conclude that upregulation of the neutrophil and monocyte adherence molecule CD11b induced by H. pylori sonicates is not associated with the presence of cagA, picB or mosaic pattern of vacA, and that cagA, picB-negative strains and vacA-S2 strains retain their inflammatory capacity.