Systematic review: noncoeliac gluten sensitivity.

BACKGROUND: Noncoeliac gluten sensitivity (NCGS) is a controversial emerging disorder. Despite reported symptoms related to the ingestion of gluten, NCGS remains a diagnosis based on the exclusion of coeliac disease, given the absence of reliable biomarkers. AIM: To evaluate the prevalence, diagnostic exclusion of coeliac disease and the efficacy of a gluten-free diet (GFD) for NCGS patients. METHODS: A PubMed search was performed up to December 2014. According to consensus diagnostic criteria, NCGS was defined as self-reported gluten intolerance, negative coeliac serology and absence of villous atrophy. Studies evaluating the impact of a GFD on patients with irritable bowel syndrome (IBS) were also included. RESULTS: Prevalence rates of NCGS (0.5-13%) differed widely. Seventeen studies, including 1561 patients (26 children), met the inclusion criteria for NCGS. HLA haplotypes could not be linked to histology [normal or lymphocytic enteritis (LE)] in 1123 NCGS patients. HLADQ2/DQ8 haplotypes were present in 44% of NCGS patients. After advanced diagnostic techniques in 189 NCGS patients combining LE and HLADQ2/DQ8 haplotypes, 39 (20%) were reclassified as coeliac disease. There was a higher than expected family history of coeliac disease and autoimmune disorders in NCGS patients. A GFD resulted in variable results for variable, but significantly improved stool frequency in HLADQ2 positive diarrhoea-predominant IBS patients. CONCLUSIONS: Prevalence rates for NCGS are extremely variable. A subset of NCGS patients might belong in the so-called 'coeliac-lite' disease. The benefit of a GFD for NCGS patients is currently controversial. HLADQ2 positive diarrhoea-type IBS patients might gain symptom improvement from a GFD.

Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding.

OBJECTIVES: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. RESULTS: Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. CONCLUSION: Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter pylori-related diseases.

Recent studies have revealed elevated expression of transforming growth factor beta1 (TGF-beta1) in gastric mucosa of patients with gastric cancer (GC) and those undergoing ulcer repair. As production of TGF-beta1 is genetically regulated, we aimed to assess whether functional polymorphisms of the TGFB1 gene are involved in susceptibility to and clinical characteristics of Helicobacter pylori-related diseases. DNA from 142 unrelated Spanish patients with GC, 200 with peptic ulcer and 342 healthy controls was typed for the MspA1I T+869C, and the Sau96I G+915C polymorphisms of the TGFB1 gene using polymerase chain reaction and RFLP analysis. H. pylori infection and CagA/VacA antibody status were determined by Western blot in patients and controls. H. pylori infection (odds ratio (OR): 11.44; 95% confidence interval (CI): 4.45-29.42; P<0.001) and non-steroidal anti-inflammatory drugs (OR: 5.07; 95% CI: 2.53-10.16; P<0.001) were identified as independent risks factors for duodenal ulcer (DU), whereas the TGFB1+869(*)C/C genotype was associated with reduced risk of developing the disease (OR: 0.32; 95% CI=0.15-0.68; P=0.003). Our results show that the TGFB1 T+869C gene polymorphism is involved in the susceptibility to DU and provide further evidence that host genetic factors play a key role in the pathogenesis of H. pylori-related diseases.

Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations.

BACKGROUND: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. OBJECTIVE: To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. METHODS: A hospital-based, case-control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. RESULTS: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. CONCLUSIONS: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.

No allelic variant associations of the IL-1 and TNF gene polymorphisms in the susceptibility to duodenal ulcer disease.

Recent studies have reported the association of a pro-inflammatory profile of genetic polymorphisms in IL-1B, IL-1RN, TNF-A, and IL-10 genes with an increased risk of non-cardia gastric cancer. Because gastric cancer and duodenal ulcer are mutually exclusive outcomes of Helicobacter pylori infection, we aimed to investigate possible allelic variant associations of several functional polymorphisms in the IL-1B, IL-1RN, TNFA, and LTA genes in the susceptibility to duodenal ulcer. Genomic DNA from 118 patients with duodenal ulcer and 97 healthy controls was typed for the IL-1B polymorphisms at positions -511, -31, and +3954, the VNTR polymorphism in intron 2 of the IL-1RN gene, the TNFA-308, TNFA -238, and the NcoI and BsI LTA polymorphisms by PCR, SSCP and TaqMan assays. H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) use was investigated in patients and controls. Logistic regression analysis identified H. pylori infection (OR: 12.86; 95%CI: 3.85-43), NSAID use (OR: 11.95; 95%CI: 4.19-34.05), and family history-ulcer (OR: 3.79; 95%CI: 1.68-8.54) as independent risk factors for duodenal ulcer. When the effect of the combinations of IL-1 and TNF genotypes was studied we found that the distribution of all possible combinations of these eight polymorphisms was similar in duodenal ulcer patients and controls. The simultaneous carriage of alleles IL-1RN*2/IL-1B -31T/IL-1B -511C/IL-IB +3954C/TNF-HaplotypeE negative (termed in some studies as 'low-producing' alleles) was increased in H. pylori-positive duodenal ulcer patients compared to H. pylori-infected healthy controls (10.5% vs. 5.9%) although the difference did not reach statistical significance (OR: 1.85; 95%CI: 0.57-5.99, P = 0.41). Moreover, no differences were found with respect to H. pylori status, NSAID use, age, gender, smoking habit, type of complication, recurrence of the ulcer, and need for surgical treatment. Our data show no association between allelic variants of IL-1 and TNF gene polymorphisms in the susceptibility to and final outcome of duodenal ulcer.

Association of interleukin 1 gene family polymorphisms with duodenal ulcer disease.

Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among cytokines, interleukin (IL)-1beta and its natural specific inhibitor, the interleukin-1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL-1B and IL-1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL-1B-511, IL-1B-31, and IL-1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL-1RN gene by polymerase chain reaction (PCR)-based methods and TaqMan assays. H. pylori status and non-steroidal anti-inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9.74; 95%CI = 3.53-26.89) and NSAIDs use (OR: 8.82; 95%CI = 3.51-22.17) as independent risk factors for DU. In addition, the simultaneous carriage of IL-1RN*2, IL-1B-511*C, IL-1B-31*T and IL-1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3.22; 95%CI = 1.09-9.47). No significant differences in IL-1RN and IL-1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.

Breath test is very reliable for diagnosis of Helicobacter pylori infection in real clinical practice.

AIMS: To determine the accuracy of the most common available tests for the diagnosis of Helicobacter pylori infection in an unselected and untreated population of patients. PATIENTS AND METHODS: Prospective study including 314 unselected patients from a population of 814 patients referred for upper endoscopy at one hospital. H. pylori infection was diagnosed by rapid urease test (RUT), histology, culture and 13C-urea-breath test (UBT) and serum IgG (EIA). H. pylori infection was defined as positive if culture or at least two of the other tests were positive. RESULTS: The prevalence of H. pylori infection in this population was 72%. The diagnostic test with the greatest combination of sensitivity (97%) and specificity (100%) was the UBT. EIA had a good sensitivity (96%), but it was the test with the least specificity (71%). RUT, histology and culture showed a high specificity (>98%) but a sensitivity lower than 90%. In elderly patients (>65 years old, n=120), UBT was also the test with the greatest combination of sensitivity (94%) and specificity (100%). CONCLUSIONS: In conditions of real clinical practice the 13C-urea-breath test is a reliable test for H. pylori diagnosis, both in young and elderly patients.

Low frequency of upper gastrointestinal complications in a cohort of high-risk patients taking low-dose aspirin or NSAIDS and omeprazole.

BACKGROUND: There is very little information available on the incidence of complications and on the best prevention therapy in high-risk patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or aspirin. Randomized-controlled trials in such patients are rare for ethical reasons. We studied the incidence of gastrointestinal complications in high-risk patients taking long-term low-dose aspirin or non-aspirin-NSAIDs combined with omeprazole in a real-life clinical setting. METHODS: This was a multicentre, prospective and observational study including 247 consecutive high-risk patients who had a clinical indication for long-term treatment with either low-dose aspirin or non-aspirin NSAIDs and omeprazole therapy. The occurrence of gastrointestinal complications was measured. RESULTS: In addition to a recent history of peptic ulcer bleeding, all patients had at least 1 other risk factor and 112 (45.3%) had 3 or more risk factors; 78.9% were taking low-dose aspirin and the remainder non-aspirin NSAIDs. Mean follow-up was 14.6 +/- 10.38 months. Three patients taking low-dose aspirin developed upper gastrointestinal bleeding (1.2%; 95% CI 0.3-3.5; 1.0 event/100 patients/year). This was similar to the rate observed in studies involving non-high-risk patients taking low-dose aspirin and higher than that observed in patients not taking low-dose aspirin. Two additional patients developed a lower gastrointestinal bleeding event (0.81% (0.04%-3.12%); 0.67 events/100 patients/year), which was within the range expected in NSAID users. CONCLUSIONS: The use of omeprazole in the high-risk patient taking low-dose aspirin or NSAIDs seems to be a safe therapeutic approach in this population and is associated with a low frequency of upper gastrointestinal complications.

Validation of the 13c-urea breath test for the initial diagnosis of helicobacter pylori infection and to confirm eradication after treatment.

OBJECTIVES: the breath test with 13C-urea (UBT) is a method widely used in Spain, but its diagnostic accuracy has not been evaluated in a clinical trial until now. Our objective was to validate the UBT (TAU-KIT) both as an initial diagnostic method for the detection of H. pylori infection and as a method to confirm eradication. METHODS: a multi-centre study in 7 Spanish hospitals was performed. A group of dyspeptic patients who had not previously received eradication treatment was included, and a second group of patients with gastric ulcer or upper gastrointestinal bleeding due to peptic ulcer was also included (eradication of H. pylori was confirmed 6 to 8 weeks after treatment completion with omeprazole, clarithromycin and amoxycillin). In both groups an endoscopy was performed with biopsies for histology and rapid urease test. Patients were considered infected if both tests yielded positive results, and not infected when both tests were negative. The UBT 13C-urea (TAU-KIT, Isomed S.L., Madrid, Spain) was performed with citric acid and 100 mg of 13C-urea. The pathologist and persons responsible for endoscopy, urease test and UBT were all unaware of the results from the other diagnostic methods. RESULTS: in the pre-treatment group (36 patients) the prevalence of H. pylori was 72%, the area under the ROC curve for the diagnosis of infection with the UBT was 0.99, and the best cut-off point was 5 units, with the following results: sensitivity= 96% (95% CI = 81-99%), specificity= 100% (69-100%), positive predictive value (PPV) = 100% (87-100%), negative predictive value (NPV) = 92% (59-100%), likelihood ratio (LR) + = infinity, and LR- = 0.04. In the post-treatment group (85 patients) the prevalence of H. pylori was 16%, the area under the ROC curve was 0.99, and the best cut point was 4.6, with the following results: sensitivity= 100% (77-100%), specificity = 97% (90-99%), PPV = 88% (62-98%), NPV = 100% (95-100%), LR+ = 35, and LR- = 0. CONCLUSION: UBT provides excellent accuracy both for the initial diagnosis of H. pylori infection and to confirm eradication after treatment.

Validación de la prueba del aliento con 13C-urea para el diagnóstico inicial de la infección por Helicobacter pylori y la confirmación de su erradicación tras el tratamiento / Validation of 13 C-urea breath test for the initial diagnosis of Helicobacter pylori infection and for the confirmation of its eradication after treatment

Objetivos: el test del aliento con l3C-urea (TAU) es un método ampliamente utilizado en España, pero su validez diagnóstica no ha sido evaluada hasta hoy en un ensayo clínico. Nuestro objetivo fue validar el TAU-KIT® tanto para el diagnóstico inicial de H. pylori como para la confirmación de su erradicación. Métodos: estudio multicéntrico realizado en 7 hospitales españoles. Se incluyó un grupo de pacientes dispépticos en los que no se había administrado tratamiento erradicador previo y otro grupo con úlcera gástrica o hemorragia digestiva por úlcera gastroduodenal en el que se confirmaba la erradicación de H. pylori 6 a 8 semanas después de finalizar el tratamiento con omeprazol, claritromicina y amoxicilina. En ambos grupos se realizó gastroscopia con biopsias para histología y test rápido de la ureasa. Se consideró infectado a un paciente cuando ambas pruebas eran positivas, y no infectado cuando ambas eran negativas. Se realizó el TAU (TAU-KIT®, Isomed S.L., Madrid) con ácido cítrico y 100 mg de 13C-urea. El endoscopista, el patólogo y la persona responsable de la lectura del test de la ureasa y del TAU desconocían el estado de infección por los demás métodos diagnósticos. Resultados: en el grupo pretratamiento (36 pacientes) la prevalencia de H. pylori fue del 72 por ciento, el área bajo la curva ROC para el diagnóstico de la infección con el TAU fue de 0,99 y el mejor punto de corte se situó en 5 unidades , con los siguientes resultados: sensibilidad (S)=96 por ciento (IC 95 por ciento=81-99), especificidad (E)=100 por ciento (69-100), valor predictivo positivo (VPP)=100 por ciento (87100), valor predictivo negativo (VPN)=92 por ciento (59-100), cociente de probabilidades (CP) += y CP-=0,04. En el grupo postratamiento (85 pacientes) la prevalencia de H. pylori fue del 16 por ciento, el área bajo la curva ROC de 0,99 y el punto de corte óptimo de 4,6, con los siguientes resultados: S=100 por ciento (77-100), E=97 por ciento (90-99), VPP=88 por ciento (62-98), VPN=100 por ciento (95-100), CP+=35 y CP-=0.Conclusión: el TAU posee una excelente exactitud tanto para el diagnóstico inicial de la infección por H. pylori como para la confirmación de su erradicación después del tratamiento (AU)

The polymorphic IL-1B and IL-1RN genes in the aetiopathogenesis of peptic ulcer.

Besides environmental factors, the genetic background of an individual may contribute to the development and final outcome of peptic ulcer disease. Interleukin-1beta (IL-1beta) and the interleukin-1 receptor antagonist (IL-1ra) are cytokines that play a key role in modulating the inflammatory response in the gastrointestinal mucosa. This study aimed to investigate whether polymorphisms in the IL-1B and IL-RN genes are involved in the susceptibility to and final outcome of peptic ulcer disease. DNA from 179 unrelated Spanish Caucasian patients with peptic ulcer diseases and 99 ethnically matched healthy controls was typed for the TaqI polymorphism at position + 3954 in the IL-1B gene and the variable number of tandem repeats polymorphism in intron 2 of the IL-1RN gene. The determination of Helicobacter pylori status and non-steroidal anti-inflammatory drug (NSAIDs) use was studied in all patients and in controls. H. pylori infection and NSAID use were more frequent in ulcer patients than in controls. There were no significant differences in carriage rate, genotype and allele frequencies of the IL-1RN and the IL-1B(+3954) gene polymorphisms between peptic ulcer patients and controls. However, a strong allelic association between IL-1B and IL-1RN genes was found in duodenal ulcer patients (P < 0.0006). Logistic regression identified H. pylori infection and NSAIDs use as independent risk factors for peptic ulcer diseases whereas the simultaneous carriage of IL-1B(+3954) allele 2 and IL-1RN allele 2 was associated with reduced risk for duodenal ulcer disease (OR: 0.37, 95% CI = 0.14-0.9). Our data suggest that IL-1B and IL-1RN genes in addition to bacterial and environmental factors play a key role in determining the final outcome of peptic ulcer disease.

[CagA and VacA cytotoxin antibodies and risk for peptic ulcer disease in patients with Helicobacter pylori infection]. / Anticuerpos frente a las citotoxinas CagA y VacA y riesgo de úlcera péptica en pacientes con infección por Helicobacter pylori.

BACKGROUND: The presence of cagA antibodies constitutes a serum marker of infection caused by virulent strains of Helicobacter pylori. The objective of this study was to determine the risk of peptic ulcer in patients with H. pylori infection, in relation to the detection of CagA and VacA antibodies. PATIENTS AND METHOD: Prospective case-control study including 104 peptic ulcer patients with active H. pylori infection (positive urease test and/or histology, or positive urea breath test) and 104 age- and sex-matched controls, without peptic ulcer history, with active H. pylori infection (positive urea breath test). Serum CagA and VacA antibodies were determined by Western blot. Non-steroidal antiinflamatory drugs (NSAID) use was determined by structured data collection. A multivariate analysis (logistic regression) was carried out to determine the odds ratio (OR). RESULTS: Presence of serum antibodies against CagA was higher in peptic ulcer patients (74%) than in controls (46.2%) (OR = 5.7; 95% CI = 2.1-15.6). However, presence of serum antibodies against VacA in patients (46.2%) was similar to that in controls (36.5%). NSAID use was also more frequent in patients (51.9%) than in controls (21,2%) (OR = 6.5; 95% CI = 2.2-19,5). CONCLUSIONS: Serum antibodies against CagA and use of NSAID are the most important risk factors for peptic ulcer disease.

[Helicobacter pylori and immunogenetic factors of the host: relevance of the HLADQA1 *0102 and *0301 alleles in peptic ulcer]. / Helicobacter pylori y factores inmunogenéticos del huésped: relevancia de los alelos HLADQA1 *0102 y *0301 en la úlcera péptica.

AIM: To investigate the potential contribution of the *0102 and *0301 alleles of the HLADQA1 gene in Helicobacter pylori infection and peptic ulcer disease in a Spanish Caucasian population. PATIENTS AND METHODS: We studied 163 patients with peptic ulcer (117 duodenal ulcers and 46 gastric ulcers; 111 with recent upper gastrointestinal hemorrhage) and 90 controls. The *0102 and *0301 alleles of the HLADQA1 gene were typed by polymerase chain reaction using genomic DNA. H. pylori infection were determined by breath test and/or serology. The cytotoxins CagA and VacA were investigated using serology (Western-blot) in 98 patients and 48 controls with H. pylori infection. RESULTS: H. pylori infection was found in 94.6% of patients with duodenal ulcer, in 84.4% of those with gastric ulcer and in 67.4% of controls (p < 0.001). The distribution of the *0102 allele of the HLADQA1 gene was similar in patients (31.9%) and in controls (36.7%). The *0301 was more frequent in patients with gastric ulcer (32.6%) than in those with duodenal ulcer (16.2%) (p < 0.05) but no differences were found on comparison with the control group (24.4%). No differences were found when the groups were analyzed according to H. pylori infection, CagA- and VacA-positive strains, consumption of non-steroidal antiinflammatory drugs or previous history of ulcer or hemorrhage. CONCLUSION: The *0102 and *0301 alleles of the HLADQA1 gene did not alter susceptibility to H. pylori infection or the evolution of peptic ulcer disease in a Caucasian population in Spain.

Diaphragm disease of the small bowel: a case without apparent nonsteroidal antiinflammatory drug use.

BACKGROUND: Diaphragm-like strictures of the small bowel are an infrequent complication of the treatment of patients with nonsteroidal antiinflammatory drugs (NSAIDs). STUDY: We report a patient with this condition in whom the use of NSAIDs was ruled out by both clinical history and objective blood testing of current aspirin use. RESULTS: He reported a history of recurrent episodes of colic abdominal pain during the past 25 years; he underwent three surgical operations for this condition. Before these symptoms, he had an undefined abdominal process with diarrhea, weight loss, and diffuse edema, which resolved spontaneously without reaching a diagnosis. CONCLUSIONS: We suggest that diaphragm-like strictures might be developed as a nonspecific response to different damaging insults to the intestine and are not necessarily associated with NSAID use.

Gastroesophageal reflux disease (GERD): current agents and future perspective.

The objectives of medical treatment of patients with gastroesophageal reflux disease (GERD) are relief of symptoms and healing of esophagitis, which can be achieved, at least in part, by drugs which suppress acid secretion. In patients with GERD symptoms and/or mild esophagitis, the best and most cost-effective therapeutic strategy is to start with a proton pump inhibitor with subsequent trial of step down of the intensity of therapy (e.g. H2-receptor antagonists). In patients with moderate or severe esophagitis, proton pump inhibitors are the mainstay of treatment and the most effective in preventing symptoms and esophagitis. In patients with mild disease, the recurrence of symptoms is less frequent and many patients may not need continuous maintenance therapy or may require treatment with either low dose proton pump inhibitors, H2-receptor antagonists or cisapride only. H. pylori eradication might be needed in GERD patients on long-term treatment with proton pump inhibitors, but the benefit of this strategy has not yet been adequately demonstrated. Antireflux surgery is a maintenance option for the young patient on long-term medical therapy. Improved medical therapy for GERD might depend on future agents with different therapeutic targets, including GABA inhibitors and nitric oxide modulating drugs in the control of the lower sphincter esophagus and in motility disorders, free radical scavengers in the prevention of mucosal damage and COX-2 specific inhibitors in the prevention of the progression of Barret's esophagus to adenocarcinoma. Finally, the modulation of some growth factors might have a potential role in delayed esophageal ulcer healing, refractory esophagitis and in Barrett's esophagus.

TNF and LTA gene polymorphisms reveal different risk in gastric and duodenal ulcer patients.

A small proportion of patients infected with Helicobacter pylori or using non-steroidal anti-inflammatory drugs (NSAIDs) develops peptic ulcer disease. Since family studies have shown the importance of the genetic background of the host in the development of gastric and duodenal ulcers, immunogenetic factors involved in the regulation of inflammation deserve further study. Polymorphisms in the genes encoding tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA) have been shown to contribute to the severity of infectious disease. Our aim was to study four bi-allelic polymorphisms in the TNF and LTA genes, which occur as five haplotypes, in patients with peptic ulcer disease. A total of 130 patients with duodenal ulcer, 50 with gastric ulcer and 102 ethnically-matched Spanish Caucasian healthy controls were studied. H. pylori infection was determined by invasive and non-invasive tests. Odds ratios were obtained by logistic regression analysis. H. pylori was detected in 91.8% of peptic ulcer patients and in 73.3% of controls (P < 0.001). Patients with gastric ulcer had a lower frequency of the TNF-308 allele 2 and a higher frequency of the LTANcoI 2.2 genotype when compared with duodenal ulcer patients (P < 0.01 and P = 0.03, respectively). Carriers of haplotype TNF-I were more frequent in gastric ulcer patients (49%) than in controls (28%) (P < 0.05) and the haplotype TNF-E was significantly more frequent in duodenal ulcers than in gastric ulcers (27% vs 8.2%; P < 0.01). Logistic regression analysis identified haplotype TNF-I carrier status as an independent risk factor for peptic ulceration in H. pylori-infected patients (OR: 4.2; 95%CI: 1.7-10.2). These results suggest that TNF and LTA gene polymorphisms are related to the development of gastric and duodenal ulcer and may determine disease outcome in H. pylori infection.

Factors affecting the variation in antibiotic resistance of Helicobacter pylori over a 3-year period.

Strains of Helicobacter pylori, isolated from 300 patients between 1996 and 2000 were tested for their sensitivity to clarithromycin, metronidazole and amoxycillin. Primary resistances (95% CI) were 9. 7% for clarithromycin and 21.7% for metronidazole. No strains were resistant to amoxycillin. There was no significant difference between the number of resistant strains in the male and female groups. Clarithromycin resistance was more common in older patients (P<0.01) and metronidazole resistance was more common in patients with peptic ulcer compared with patients with chronic gastritis (P<0. 05). Logistic regression analysis confirmed these results.