Levels of malondialdehyde in the gastric juice: Its association with Helicobacter pylori infection and stomach diseases.

BACKGROUND: Helicobacter pylori (H. pylori) infection causes elevation of lipid peroxidation product malondialdehyde (MDA) and this association may be due to the bacterium causing reactive oxygen species-mediated damage to DNA in the gastric epithelium. The aim of this study was to investigate the gastric juice MDA levels in relation to H. pylori infection and associated gastric diseases. METHODS: Gastric juice samples were obtained from 117 patients undergoing endoscopy, and gastric juice MDA levels were determined by high-performance liquid chromatography (HPLC) system. We compared the MDA levels between patients with and without H. pylori infection and assessed the differences of MDA levels between chronic gastritis, gastric intestinal metaplasia, and gastric cancer postsurgical resection. RESULTS: Malondialdehyde levels in gastric juice were significantly higher in chronic gastritis patients with H. pylori infection than in those without H. pylori infection (P < .0001). In patients without H. pylori infection, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection had significantly higher gastric juice MDA level than patients with chronic gastritis. As a whole, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection also had significantly higher MDA levels in gastric juice as compared to patients with chronic gastritis (P < .01). However, the difference of gastric juice MDA levels between gastric intestinal metaplasia and gastric cancer postsurgical resection was not significant. CONCLUSION: Malondialdehyde in gastric juice could be used as a potential diagnostic biomarker for H. pylori infection and associated gastric diseases. The gastric juice MDA levels increased proportionally with the severity of gastric diseases.

Reprogramming Antagonizes the Oncogenicity of HOXA13-Long Noncoding RNA HOTTIP Axis in Gastric Cancer Cells.

Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128.

Comparison of 10-day levofloxacin bismuth-based quadruple therapy and levofloxacin-based triple therapy for Helicobacter pylori.

OBJECTIVE: This was a prospective study aiming to investigate whether levofloxacin plus bismuth-based quadruple therapy was more effective than levofloxacin-based triple therapy after failed first-line eradication therapies for Helicobacter pylori (H. pylori) infection. METHODS: Sixty-seven patients infected with H. pylori were randomly assigned to two groups; the levofloxacin plus bismuth-based quadruple therapy group (RBAL [n = 33]; rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days) and the levofloxacin-based triple therapy group (RAL [n = 34]; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days). Endoscopy was performed 4-8 weeks after H. pylori eradication to assess treatment response. We followed up patient response and compliance and checked their resistance to antibiotics. RESULTS: Intention-to-treat analysis revealed that both groups had similar eradication rates (RBAL vs RAL: 84.8% [95% confidence interval {CI} 72.6-97.1%] vs 67.6% [95% CI 51.9-83.4%], P = 0.0987). No significant differences in compliance or adverse events were found (P = 0.9829 and 0.0720). Epsilometer test showed that most eradication failure cases were levofloxacin-resistant. CONCLUSIONS: Adding bismuth subcitrate to levofloxacin-based triple therapy was not more effective than not doing so, but no further side effects were noted. Both eradication therapies were equally safe and patients had the same tolerance to both regimens. Resistance rate to levofloxacin may be important when choosing second-line therapy.

Exploring the expression bar code of SAA variants for gastric cancer detection.

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.

Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer.

The network of stemness genes and oncogenes in human patient-specific reprogrammed cancer stem cells (CSCs) remains elusive, especially in liver cancer. HepG2-derived induced pluripotent stem cell-like cells (HepG2-iPS-like cells) were generated by introducing Yamanaka factors and the knockdown vector shTP53. They exhibited features of stemness and a higher tumorigenesis after xenograft transplantation compared with HepG2 cells. The cancerous mass of severe combined immunodeficiency (SCID) mice derived from one colony was dissected and cultured to establish reprogrammed HepG2-derived CSC-like cells (designated rG2-DC-1C). A single colony exhibited 42% occurrence of tumors with higher proliferation capacities. rG2-DC-1C showed continuous expression of the OCT4 stemness gene and of representative tumor markers, potentiated chemoresistance characteristics, and invasion activities. The sphere-colony formation ability and the invasion activity of rG2-DC-1C were also higher than those of HepG2 cells. Moreover, the expression of the OCT4 gene and the c-JUN oncogene, but not of c-MYC, was significantly elevated in rG2-DC-1C, whereas no c-JUN expression was observed in HepG2 cells. The positive-feedback regulation via OCT4-mediated transactivation of the c-JUN promoter and the c-JUN-mediated transactivation of the OCT4 promoter were crucial for promoting cancer development and maintaining cancer stemness in rG2-DC-1C. Increased expression of OCT4 and c-JUN was detected in the early stage of human liver cancer. Therefore, the positive feedback regulation of OCT4 and c-JUN, resulting in the continuous expression of oncogenes such as c-JUN, seems to play a critical role in the determination of the cell fate decision from iPS cells to CSCs in liver cancer. Stem Cells 2016;34:2613-2624.

Suppression of IL-8-Src signalling axis by 17ß-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.

Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17ß -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17ß-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17ß-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.

Diagnosis of Helicobacter pylori infection: Current options and developments.

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.

The effect of Helicobacter pylori eradication on the levels of essential trace elements.

OBJECTIVE: This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. PATIENTS AND METHODS: We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. RESULTS: Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. CONCLUSION: H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327).

Acid suppressive agents and risk of Mycobacterium tuberculosis: case-control study.

BACKGROUND: The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported. METHODS: We conducted a case-control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed. RESULTS: TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended. CONCLUSIONS: Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.

Detection of genotypic clarithromycin-resistant Helicobacter pylori by string tests.

AIM: To evaluate the utility of the string test to detect genotypic clarithromycin-resistant Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR)-restriction fragment length polymorphism. METHODS: Patients undergoing endoscopic examinations were enrolled in the present study. String tests were done on the next day of endoscopy. Segments of 23S rRNA were amplified from DNA obtained from string tests. PCR-restriction fragment length polymorphism was accomplished by restriction enzymes BbsI and BsaI recognizing the mutation site A to G at 2143 or at 2142 of 23S rRNA domain V, respectively. RESULTS: One hundred and thirty-four patients with H. pylori infection underwent string tests. To compare phenotypic resistance, 43 isolates were successfully cultured in 79 patients in whom 23S rRNA was successfully amplified. Of five patients with clarithromycin-resistant H. pylori, 23S rRNA of H. pylori isolates from four patients could be digested by BsaI. In 38 susceptible isolates, 23S rRNA of H. pylori isolates from 36 patients could not be digested by either BsaI or BbsI. The sensitivity and specificity of the string test to detect genotypic clarithromycin resistance were 66.7% and 97.3%, respectively. Positive and negative predictive values were 80% and 94.7%, respectively. CONCLUSION: String test with molecular analysis is a less invasive method to detect genotypic resistance before treatment. Further large-scale investigations are necessary to confirm our results.

17ß-estradiol inhibits mesenchymal stem cells-induced human AGS gastric cancer cell mobility via suppression of CCL5- Src/Cas/Paxillin signaling pathway.

Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17ß-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17ß-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17ß-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.

Helicobacter pylori Infection and Anemia in Taiwanese Adults.

Background. Chronic Helicobacter pylori infection and iron-deficiency anemia (IDA) are common in adults. Although the most common causes of IDA usually arise from the gastrointestinal tract, the association between chronic Helicobacter pylori infection and anemia remains unclear. Aim. To evaluate the association of chronic Helicobacter pylori infection and IDA. Materials and Methods. We enrolled 882 patients from January 2010 to April 2013. The status of Helicobacter pylori (H.p) infection was confirmed and blood samples from the same participants were taken on the same day to check the level of hemoglobin, serum iron, ferritin, and total iron-binding capacity (TIBC). Results. No significant difference was noted from the demographic data. The average level of hemoglobin (Hb) was not different between negative and positive groups, pos 13.57 g/dL versus neg 13.65 g/dL (P = 0.699). Although the levels of serum IDA related parameters were expected in positive group (lower serum iron and ferritin and higher TIBC) these differences did not reach statistical significance (P = 0.824 for iron, P = 0.360 for ferritin, and P = 0.252 for TIBC). Conclusion. Chronic Helicobacter pylori infection is not attributed to IDA. The levels of hemoglobin, serum iron and ferritin, and TIBC remain unaffected after chronic H.p infection. Large-scale clinical studies are needed to prove the association.

Terlipressin-induced hyponatremic encephalopathy in a noncirrhotic patient.

Terlipressin, an analogue of vasopressin, is frequently used for the management of esophageal varices bleeding and hepatorenal syndrome. Terlipressin therapy in portal hypertensive patients is frequently associated with hyponatremia, but is rarely accompanied with serious neurological manifestations. A 39-year-old female with pancreatic neuroendocrine tumor, liver metastasis, main portal vein thrombosis, and a history of esophageal varices presented to the emergency room because of hematemesis. Terlipressin was given with a loading dose of 2 mg followed by 1 mg every 6 hours. After a total of 6 mg terlipressin injection, she suffered from acute delirium. Pertinent examinations showed there was no gross brain lesion by computed tomography, whereas her serum sodium level dropped from baseline (136 mmol/L) to 116 mmol/L with a serum osmolality of 256 mOsm/kg. At that time, urine sodium and urine osmolality were 142 mmol/L and 488 mOsm/kg, respectively. Under the tentative diagnosis of terlipressin-induced hyponatremic encephalopathy, terlipressin was withheld and hypertonic saline infusion was given. Within 12 hours, her serum sodium level recovered to 130 mmol/L and she gradually regained her cognitive functions. Although symptomatic hyponatremic encephalopathy is a rare complication of terlipressin treatment, close monitoring of serum electrolyte level is warranted in patients receiving terlipressin.

Long-Term Use of Probiotic-Containing Yogurts Is a Safe Way to Prevent Helicobacter pylori: Based on a Mongolian Gerbil's Model.

Background. The suppression of Helicobacter pylori (H. pylori) decreases H. pylori-related diseases. The probiotics have an inhibitory effect on H. pylori. Aim. We investigated the effects of long-term use of yogurt on H. pylori based on Mongolian gerbils' model. Materials and Methods. Yogurt (containing a supplement of Lactobacillus acidophilus, Bifidobacterium lactis, etc.) was used. Forty-six gerbils were divided into five groups. All groups were inoculated with H. pylori for 5 to 8 weeks. The yogurt was given as follows: Group (Gr.) A: from 1st to 4th week; Gr. B from 5th to 8th week; Gr. C: from 17th week to sacrifice; Gr. D: from 5th week to sacrifice. Gerbils were sacrificed on the 52nd week. Histology was evaluated according to the Sydney system. Results. The positive rates of H. pylori were 60% (Gr. A), 75% (Gr. B), 67% (Gr. C), 44% (Gr. D), and 100% (Gr. E). Gr. D showed lower inflammatory score. Only Gr. E (60%) had intestinal metaplasia. Gr. D showed higher IL-10 and lower TNF- α expression than Gr. E. Conclusion. Long-term intake of yogurt could decrease H. pylori infection. The long-term use of yogurt would be an alternative strategy to manage H. pylori infection.

Current pharmacological management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD), a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment.

Helicobacter pylori infection associated with high HbA1c and type 2 diabetes.

BACKGROUND: Although the association between chronic Helicobacter pylori infection and type 2 diabetes has been suggested, findings have been inconsistent. This study evaluated the association between chronic H. pylori infection and glucose regulation. MATERIALS AND METHODS: We evaluated H. pylori infection status of participants recruited from the gastroenterology clinic at our hospital. At baseline, we performed blood tests including fasting plasma glucose, insulin, glycated haemoglobin A1c (HbA1c) and other biochemical measurements. Insulin resistance and beta-cell function were assessed by homoeostasis model assessment (HOMA-IR and HOMA-B, respectively). RESULTS: A total of 2070 participants were recruited. Those who had H. pylori infections had higher serum HbA1c levels and lower HOMA-B than those who did not (5.78% vs. 5.69%, P = 0.01 and 53.85 + 38.43 vs. 60.64 + 43.40, P = 0.009, respectively). They also had a significantly higher prevalence of type 2 diabetes (8.97% vs. 5.57%, P= 0.02). Chronic H. pylori infection was significantly associated with high levels of HbA1c and type 2 diabetes in participants above 65 years old (P = 0.001) and decreased insulin secretion and sensitivity in those under 45 years (P = 0.05). CONCLUSIONS: Long-term H. pylori infection is significantly associated with high levels of HbA1c and decreased insulin secretion in this Chinese population. Proper screening for H. pylori infection combined with regular monitoring of blood glucose and HbA1c levels might be effective for the early detection of glucose dysregulation and prevention of type 2 diabetes.

Differentiation of virulence of Helicobacter pylori by matrix-assisted laser desorption/ionization mass spectrometry and multivariate analyses.

BACKGROUND: The ability to determine the virulence of a Helicobacter pylori strain would be helpful for predicting the development of gastrointestinal disease and suggesting medical treatment. METHODS: A protocol based on matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) was established for the efficient detection of peptides and proteins in extracts of H. pylori cells. Two multivariate statistical methods-principal component analysis (PCA) and hierarchical clustering analysis-were used to analyze the resulting MALDI mass spectra of reference strains and clinical isolated/inoculated strains. RESULTS: Based on differences in their peptide and protein profiles, H. pylori strains having similar virulence genotypes were grouped together on the PCA score plot. Hierarchical cluster analysis revealed high conformity between the protein profiles and the respective virulence genotypes. The inoculated H. pylori strain, which was clustered in the same group with the high-virulence reference strains, also resulted in severe histopathological lesions in gerbils. CONCLUSIONS: MALDI-TOF MS combined with multivariate analyses shows the ability to rapidly differentiate H. pylori strains in terms of their virulence.

Comparison of 10 day bismuth quadruple therapy with high-dose metronidazole or levofloxacin for second-line Helicobacter pylori therapy: a randomized controlled trial.

OBJECTIVES: This prospective study was designed to compare the efficacies of levofloxacin-containing and high-dose metronidazole-containing quadruple therapies after failure of standard triple therapies. METHODS: A total of 150 Helicobacter pylori-infected patients were enrolled in our study and randomly assigned to levofloxacin-containing quadruple therapy (EBTL group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of levofloxacin once daily for 10 days) (n = 76) or high-dose metronidazole-based quadruple therapy (EBTM group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of metronidazole four times daily for 10 days) (n = 74). Follow-up endoscopy or urea breath test was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes and antibiotic resistances were also examined. All participants, caregivers and those assessing the outcomes were blinded to group assignment. RESULTS: Intention-to-treat analysis revealed that both groups showed similar eradication rates: EBTL, 78.9% (60/76) (95% CI 69.7%-88.1%) and EBTM, 79.7% (59/74) (95% CI 70.5%-88.7%) [risk ratio (RR) 0.97, 95% CI 0.44-2.14]. Per-protocol results were EBTL = 87.0% (60/69) (95% CI 79.4%-94.9%) and EBTM = 90.8% (59/65) (95% CI 83.8%-97.8%) (RR 0.68, 95% CI 0.23-2.0). We did not find significant differences in compliance (RR 0.5, 95% CI 0.54-2.3) and adverse events (RR 1.11, 95% CI 0.54-2.3) between the two groups. Logistic regression analysis showed that only compliance was an important predictor for eradication failure. CYP2C19 polymorphism did not influence the eradicating effect. CONCLUSIONS: The 10 day bismuth quadruple therapies with high-dose metronidazole or levofloxacin were effective even in areas with high resistance. These two therapies were equally safe and tolerated. Besides this, the metronidazole-containing therapy was cheaper. So it is persuasive that high-dose metronidazole-containing quadruple therapy could be a good choice for second-line H. pylori eradication in areas with high resistance.

Low effect-site concentration of propofol target-controlled infusion reduces the risk of hypotension during endoscopy in a Taiwanese population.

OBJECTIVE: Target-controlled infusion (TCI) of propofol is an effective way of delivering propofol during endoscopy. However, the ideal effect-site concentration (Ce) of propofol has not yet been defined in an Asian population. This study aimed to determine the ideal Ce of propofol in painless gastrointestinal endoscopy in a Taiwanese population. METHODS: A total of 121 consecutive patients undergoing diagnostic endoscopy were recruited for this study. The endoscopic procedure was carried out within 1 h. TCI of propofol was utilized during the procedure. All patients received the same regimen to induce conscious sedation, including a bolus of midazolam (0.04 mg/kg) and fentanyl (0.5 µg/kg). The Ce of propofol was calculated using the Schneider model. Patients were randomly assigned to either the low Ce group (1.5-2.5 µg/mL) or high Ce group (3.0-4.0 µg/mL). Their cardiovascular and respiratory events were monitored during the procedure and the patients' post-procedure satisfaction was evaluated. RESULTS: The mean requirement for propofol was 232.02 mg in the low Ce group and 329.56 mg in the high Ce group, respectively (P < 0.0001). No unexpected event was observed in either group. However, more episodes of hypotension were observed in the high Ce group (P = 0.026). The post-procedure satisfaction rate between the two groups was comparable. CONCLUSION: A low Ce of propofol TCI (1.5-2.5 µg/mL) achieved adequate anesthesia, reduced the risk of hypotension, and attained a high satisfaction rate in a Taiwanese population undergoing diagnostic painless endoscopy.

The Optimal First-Line Therapy of Helicobacter pylori Infection in Year 2012.

This paper reviews the literature about first-line therapies for H. pylori infection in recent years. First-line therapies are facing a challenge because of increasing treatment failure due to elevated antibiotics resistance. Several new treatment strategies that recently emerged to overcome antibiotic resistance have been surveyed. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, and hybrid therapy. Levofloxacin-based therapy shows impressive efficacy but might be employed as rescue treatment due to rapidly raising resistance. Rifabutin-based therapy is also regarded as a rescue therapy. Several factors including antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports. It is recommended that triple therapy should not be used in areas with high clarithromycin resistance or dual clarithromycin and metronidazole resistance.