Héctor J. Maldonado-Garza

Role of the polymorphic IL‐1B, IL‐1RN and TNF‐A genes in distal gastric cancer in Mexico

Several cytokine gene polymorphisms have been associated with increased risk of distal gastric cancer (GC) and its precursor histological markers in Caucasian, Asian and Portuguese populations although little is known about their role in other ethnic groups. Our study investigates the role of the IL‐1B‐31, IL‐1RN and TNF‐A‐308 gene polymorphisms as risk factors for the development of GC in a Mexican population. We studied 278 patients who were enrolled at the Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León. The subjects were divided into 2 groups. Sixty‐three patients with histologically confirmed distal GC (mean age = 58.8 years, range = 22–84, F:M = 0.56), and 215 patients with no evidence of distal or proximal GC (mean age = 56.1 years, range = 18–92, F:M = 1.17). The IL‐1B‐31 and the TNF‐A‐308 polymorphisms were determined by PCR‐RFLP and pyrosequencing, respectively, in all cases and controls. The VNTR polymorphism in intron 2 of the 1L‐1RN gene was typed by PCR in 25 cases and 201 controls. The H. pylori status was determined by histology, rapid urease test, culture and serology for non‐cancer controls and by histology for the GC cases. The carriage of the proinflammatory IL‐1B‐31*C allele was associated with increased risk of distal GC (odds ratio [OR] = 7.63, 95% confidence interval [CI] = 1.73‐46.94, p = 0.003). When cases and controls were matched by age and gender, the OR value was higher (OR = 8.05, 95% CI = 1.8–50.22, p = 0.001). When only H. pylori GC cases and controls were compared, the OR value was 7.8 (95% CI = 1.05–161.8, p = 0.04). No association was found between any of the other polymorphisms studied and distal GC. In this Mexican population, the IL‐1B proinflammatory genotype increases the risk of distal GC. These findings are similar to previous reports in Caucasian populations and underscore the importance of cytokine gene polymorphisms in the development of distal GC.

Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer

BackgroundThe intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC). The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses.Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population.MethodsWe studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS)-PCR.ResultsThe non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly [the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82)] and for TLR4 Thr399Ile [the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1–4.2) (p = 0.023).ConclusionThis study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population.

A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication

Helicobacter pylori (H. pylori) affects nearly half of the worlds population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patients clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.

Predictors of in-hospital mortality in patients with non-variceal upper gastrointestinal bleeding

OBJECTIVE to determine the independent predictors of in-hospital death of Hispanic patients with nonvariceal upper gastrointestinal bleeding (NVUGB). EXPERIMENTAL DESIGN prospective and observational trial. PATIENTS in a period between 2000 and 2009, all patients with NVUGB admitted to our hospital were studied. Demographical and clinical characteristics, endoscopic findings and laboratory tests were evaluated χ² and Mann-Whitney U analyses were per-formed for comparisons, and binary logistic regression was employed to identify independent predictors of in-hospital mortality. RESULTS 1,067 patients were included, 65% male with a mean age of 58.8 years. Mean number of comorbidities per patient was 1.6 ± 0.76. The most frequent cause of bleeding were gastric and duodenal ulcers (55.4%); 278 patients (25.8%) received endoscopic treatment of which 69.1% had combined therapy. Rebleeding occurred in 36 patients (3.4%) of which 50% died. In-hospital mortality was 10.2%, of which only 3.1% was associated to bleeding. When comparing causes of death among patients with and without comorbidities, only hypovolemic shock was found significative (48.3 vs. 25%; p = 0.020). Binary logistic regression found that the number of comorbidities, Rockall scale score; serum albumin < 2.6 g/dL on admission; rebleeding and length of hospital stay were independent risk factors of in-hospital mortality. CONCLUSION the number of comorbidities, the Rockall scales core, an albumin level < 2.6 g/dL, the presence of rebleeding and hospital stay were predictors of in-hospital mortality in patients with NVUGB.

Antibiotic Susceptibility Patterns of Helicobacter pylori Strains Isolated from Northeastern Mexico

Abstract There are reports of increased antibiotic resistance rates in Helicobacter pylori strains around the world. The aim of this study was to determine the susceptibility patterns in H. pylori strains isolated in Monterrey, Mexico. We studied 62 strains isolated from the same number of symptomatic adult patients. Metronidazole (Mtz), clarithromycin (Cla), amoxicillin (Amx) and tetracycline (Tet) were tested by the E-test method. We observed that 37.1% of the strains were resistant to Mtz (MIC ≥8 mg/L), and 8.1% to Cla (MIC ≥8 mg/L), but we did not observe resistance to Amx (MIC ≥2 mg/L) or Tet (MIC ≥4 mg/L). In northeastern Mexico, the percentage of resistant strains was similar to that observed in developed countries. These results confirm that it is necessary to evaluate the susceptibility patterns of H. pylori strains by geographic area.

The treatment of diabetes mellitus of patients with chronic liver disease.

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.

Effect of antispasmodic agents, alone or in combination, in the treatment of Irritable Bowel Syndrome: Systematic review and meta-analysis

INTRODUCTION Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit. AIMS To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS. METHODS We carried out a systematic review and meta-analysis of randomized controlled clinical trials on antispasmodic agents for IBS treatment. Clinical trials identified from January 1960 to May 2011 were searched for in MEDLINE, the Cochrane Library, and in the ClinicalTrials.gov registry. Treatment response was evaluated by global improvement of symptoms or abdominal pain, abdominal distention/bloating, and frequency of adverse events. The effect of antispasmodics vs placebo was expressed in OR and 95% CI. RESULTS Twenty-seven studies were identified, 23 of which fulfilled inclusion criteria. The studied agents were pinaverium bromide, mebeverine, otilonium, trimebutine, alverine, hyoscine, alverine/simethicone, pinaverium/simethicone, fenoverine, and dicyclomine. A total of 2585 patients were included in the meta-analysis. Global improvement was 1.55 (CI 95%: 1.33 to 1.83). Otilonium and the alverine/simethicone combination produced significant values in global improvement while the pinaverium/simethicone combination showed improvement in bloating. As for pain, 2394 patients were included with an OR of 1.52 (IC 95%: 1.28 a 1.80), favoring antispasmodics. CONCLUSIONS Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations.

Hypertriglyceridemia-induced pancreatitis and risk of persistent systemic inflammatory response syndrome.

Background:The mechanisms responsible for the development of acute pancreatitis (AP) and its complications are not fully understood. Aim:To assess the role of clinical and host molecular factors for the development and outcome of persistent systemic inflammatory response syndrome (SIRS) in patients with AP. Methods:We included 191 patients with AP in the study. The considered variables were demographic characteristics, prognosis and outcome, etiology, laboratory findings and complications. Interleukin (IL) 10 (−1082 G/A, −592 C/A), TNFA-308 (G/A) and ILB-31 (C/T) polymorphisms were determined by pyrosequencing. An amplification refractory mutation system-polymerase chain reaction method was used to genotype the IL8-251 (A/T) polymorphism. Results:Demographic characteristics were not statistically significant risk factors for the acquisition of persistent SIRS in patients with AP. Patients with hypertriglyceridemia were more likely to develop persistent SIRS (P < 0.05). No association with the TNFA, ILB, IL8-251 (A/T) and IL10 single-nucleotide polymorphisms was detected from the allele, genotype or haplotype frequencies. Conclusions:Patients with hypertriglyceridemia-induced AP were more likely to develop persistent SIRS.

Comparision of endoscopy-based and serum-based methods for the diagnosis of Helicobacter pylori

UNLABELLED Available commercial tests for the diagnosis of Helicobacter pylori infection are based on different types of antigen preparations and hence the diagnostic utility differs substantially. OBJECTIVE To assess the diagnostic value of the determination of Immunoglobulin (Ig) A and IgG antibodies to H pylori whole cell (WC) and IgG antibodies to cytotoxin associated gene A (CagA) using an in-house ELISA in relation to the results obtained with different invasive methods. METHODS The study population consisted of 251 Mexican adults, mean age 53 years, age range 15 to 92 years and female to male ratio of 1.5. Peptic ulcer disease was present in 10.8% of these patients, 5.2% had gastric cancer, 11.2% had esophagitis and 72.9% had nonulcer dyspepsia. Biopsy specimens from the body and the antrum of the stomach were obtained for culture, histology and rapid urease test. ELISAs to detect IgA and IgG WC and CagA antibodies were performed using serum. RESULTS H pylori status was established by the results of the invasive tests. Eighty (31.9%) patients positive to the three tests and 38 (15.1%) negative to all the tests were identified. Based on this result, the sensitivity and specificity of the serology assays were 97.5% and 78.9% for the IgG WC and 70% and 73.7% for the IgA WC, respectively. However, if H pylori status was defined by the positive result of at least one or two invasive diagnostic tests, the sensitivity for the IgG WC decreased to 87.3% and 66.7% respectively, but the specificity was essentially the same. Similar results were obtained for the sensitivity and specificity of IgA using the same criteria. A low CagA prevalence was observed (39%). CONCLUSIONS Testing for serological IgG antibodies to H pylori WC was the best to assess whether infection by H pylori was present. Neither the IgA WC nor the IgG CagA ELISAs add significant value in the diagnosis of H pylori.

Subclinical abnormal glucose tolerance is a predictor of death in liver cirrhosis

AIM To determine if subclinical abnormal glucose tolerance (SAGT) has influence on survival of non-diabetic patients with liver cirrhosis. METHODS In total, 100 patients with compensated liver cirrhosis and normal fasting plasma glucose were included. Fasting plasma insulin (FPI) levels were measured, and oral glucose tolerance test (OGTT) was performed. According to OGTT results two groups of patients were formed: those with normal glucose tolerance (NGT) and those with SAGT. Patients were followed every three months. The mean follow-up was 932 d (range of 180-1925). Survival was analyzed by the Kaplan-Meyer method, and predictive factors of death were analyzed using the Cox proportional hazard regression model. RESULTS Of the included patients, 30 showed NGT and 70 SAGT. Groups were significantly different only in age, INR, FPI and HOMA2-IR. Patients with SAGT showed lower 5-year cumulated survival than NGT patients (31.7% vs 71.6%, P = 0.02). Differences in survival were significant only after 3 years of follow-up. SAGT, Child-Pugh B, and high Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were independent predictors of death. The causes of death in 90.3% of cases were due to complications related to liver disease. CONCLUSION SAGT was associated with lower survival. SAGT, Child-Pugh B, and high Child-Pugh and MELD scores were independent negative predictors of survival.