Sulforaphane has an additive anticancer effect to FOLFOX in highly metastatic human colon carcinoma cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Patients with CRC may need chemotherapy (CTx) in a neoadjuvant, adjuvant or palliative setting through the course of the disease. Unfortunately, its effect is limited by chemoresistance and chemotoxicity. Novel more effective and non­toxic CTx regimens are needed to further improve CRC treatment outcomes. Thus, the present study was designed to test the hypothesis that non­toxic sulforaphane (SF) is effective against CRC and has additive effects in combination with conventional 5­fluorouracil, oxaliplatin and folinic acid (FOLFOX) CTx in vitro. Highly metastatic human colon cancer cells, CX­1, and fibroblasts were treated with FOLFOX ± SF. Cell viability was assessed using an MTT assay. The level of apoptosis and the expression of apoptotic proteins were measured by TUNEL assay and quantitative PCR analysis. Aldehyde dehydrogenase isoform 1 (ALDH1) and multidrug resistance protein 2 (MRP2) levels were evaluated. The ability of cells to form spheroids was measured in three­dimensional cell culture. SF alone and in combination with FOLFOX effectively decreased the viability of the CX­1 cells, promoted apoptosis within the CX­1 cells, prevented cellular spheroid formation and decreased ALDH1 activity. However, SF promoted MRP2 expression and protein levels. In conclusion, SF together with conventional FOLFOX has additive anticancer effects against highly metastatic human CRC in vitro.

Sulforaphane improves vascular reactivity in mouse and human arteries after "preeclamptic-like" injury.

INTRODUCTION: The widespread maternal endothelial dysfunction that underlies the manifestations of preeclampsia is thought to arise from excessive placental production of antiangiogenic factors and enhanced oxidative stress. Therefore, we assessed whether the natural antioxidant sulforaphane could improve vascular function. METHODS: Cell viability of human umbilical vein endothelial cells (HUVECs) was assessed after 24 or 48 h in normoxia (20% O2) or hypoxia (1% O2) with or without sulforaphane. To model vascular dysfunction associated with preeclampsia, mouse mesenteric arteries were incubated in trophoblast conditioned media (TCM), and human omental arteries incubated in preeclamptic explant media (PEM) with or without sulforaphane. Both media are rich in antiangiogenic compounds associated with preeclampsia. TCM was generated from primary cytotrophoblast cells from term placentae of normotensive, while PEM was generated from explants from preeclamptic women. Reactivity was assessed by wire myography. sulforaphane's actions as a vasodilator were also investigated. RESULTS: Under conditions of hypoxia, sulforaphane improved HUVEC viability. In mouse mesenteric arteries, sulforaphane reduced contraction evoked by potassium (p < 0.001), phenylephrine and endothelin 1 (all p < 0.001). Sulforaphane also inhibited Ca2+-induced contraction (p = 0.014). Sulforaphane prevented TCM-induced augmentation of phenylephrine and angiotensin II-mediated contraction of mouse mesenteric arteries. In human omental arteries, sulforaphane induced vasodilation (p < 0.001), and prevented PEM-induced endothelial dysfunction by restoring arterial sensitivity to the endothelium-dependent vasodilator bradykinin (p = 0.008). DISCUSSION: Sulforaphane causes relaxation in arteries and protects against arterial dysfunction induced by placental-derived antiangiogenic factors, which are known to contribute to the preeclampsia.

Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.

Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with short survival and limited therapeutic options. Broccoli sulforaphane is a promising new treatment due to the results of recent epidemiological, experimental and patient studies. Upon approval from the ethics committee and registration at ClinicalTrials.gov, 40 patients with palliative chemotherapy were placed into a placebo and treatment group in an unblinded fashion. Fifteen capsules with pulverized broccoli sprouts containing 90 mg/508 µmol sulforaphane and 180 mg/411 µmol glucoraphanin or methylcellulose were administered daily for up to 1 year. Twenty-nine patients were included in the treatment group and 11 patients were in the placebo group; these patients were followed for up to 1 year. The patient characteristics, overall survival and feasibility were assessed. Compared to those of the placebo group, the mean death rate was lower in the treatment group during the first 6 months after intake (day 30: 0%/18%, day 90: 0%/25%, and day 180: 25%/43%), and Kaplan-Meier analysis revealed a higher survival rate. There was a high drop-out rate (72% in the treatment group and 55% in the placebo group) after 1 year. We concluded from the Karnofsky index that the broccoli sprouts did not impact patient's self-care and overall abilities severely. The intake of 15 capsules daily was difficult for some patients, and the broccoli sprouts sometimes increased digestive problems, nausea and emesis. We did not obtain statistically significant results (p = 0.291 for the endpoint at day 180), but the knowledge about the feasibility is the basis for the development of new sulforaphane drugs.

[Evaluation of the effect of ilaprazole on intragastric pH in patients with duodenal ulcer].

OBJECTIVE: To evaluate the effect of ilaprazole enteric tablets on intragastric pH in duodenal ulcer patients. METHODS: A randomized, double blind, positive controlled clinical trial was carried out. A total of forty-two patients with duodenal ulcer were randomized into low dose ilaprazole group (5 mg/d), medium dose ilaprazole group (10 mg/d), high dose ilaprazole group (20 mg/d) and omeprazole group (20 mg/d). An ambulatory 24 hour intragastric pH study was performed at the fifth treatment day. Fraction time pH above 3, 4 or 5, median values of 24 hour diurnal pH and 12 hour nocturnal pH, the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours were evaluated. RESULTS: There were no significant differences of fraction time pH above 3 or 4, median values of 24 hour diurnal pH and 12 hour nocturnal pH and the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours among all the groups with different doses of ilaprazole and the omeprazole group. The fraction time pH above 5 in medium and high dose ilaprazole groups were (87.96 + or - 12.29)% and (89.86 + or - 15.18)% respectively, which was higher than that in low dose ilaprazole group [(67.17 + or - 30.16)%] and omeprazole group [(76.14 + or - 16.75)%], P < 0.05. CONCLUSION: Ilaprazole has a strong effect on intragastric acid control with a dose dependent trend.

Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: a U.S. multicenter randomized, double-blind study.

OBJECTIVES: No North American randomized study has compared ulcer rebleeding rates after endoscopic hemostasis in high-risk patients treated with high-dose intravenous (IV) proton pump inhibitors (PPIs) or IV histamine-2 receptor antagonists. Our hypothesis was that ulcer rebleeding with IV pantoprazole (PAN) would be lower than with IV ranitidine (RAN). METHODS: This was a multicenter, randomized, double-blind, U.S. study. Patients with bleeding peptic ulcers and major stigmata of hemorrhage had endoscopic hemostasis with thermal probes with or without epinephrine injection, then were randomly assigned to IV PAN 80 mg plus 8 mg/h or IV RAN 50 mg plus 6.25 mg/h for 72 h, and subsequently had an oral PPI (1/day). Patients with signs of rebleeding had repeat endoscopy. Rebleeding rates up to 30 days were compared in an intention-to-treat analysis. RESULTS: The study was stopped early because of slow enrollment (total N = 149, PAN 72, RAN 77). Demographics, APACHE II scores, ulcer type/location, stigmata, and hemostasis used were similar. The 7- and 30-day rebleeding rate was 6.9% (5 of 72 patients) with PAN and 14.3% (11 of 77) for RAN (p= 0.19). Rebleeds occurred within 72 h in 56% and between 4 and 7 days in 44% of patients. The 30-day mortality rate was 4%. Nonbleeding severe adverse events were more common in the RAN than in the PAN group (14 [18.1%]vs 7 [9.7%], p= 0.16). CONCLUSIONS: Because of the small sample size of this study, there was an arithmetic but not significant difference in ulcer rebleeding rates.

Extraesophageal manifestations of GERD: diagnosis and therapy.

Extraesophageal manifestations of gastroesophageal reflux disease (GERD) can include upper airway disorders, asthma and chronic cough. They have a common pathophysiology, involving microaspiration of acid into the larynx and pharynx, and vagally mediated bronchospasm and laryngospasm. The role of extraesophageal reflux (EER) in such disorders is underdiagnosed due to the often silent symptoms and difficult confirmation of diagnosis. Laryngeal examination and quantitative evaluation of findings using the reflux finding score are essential to diagnosis and treatment. Long-term high-dose proton pump inhibitor therapy is the first-line approach to controlling symptoms. Use of treatment algorithms is necessary to manage and accurately diagnose the cause of nonresponse to treatment.

Cost-effectiveness comparison of current proton-pump inhibitors to treat gastro-oesophageal reflux disease in the UK.

OBJECTIVE: Gastro-oesophageal reflux disease (GORD) is a recurring condition with many patients requiring long-term maintenance therapy. Therefore initial choice of treatment has long-term cost implications. The aim was to compare the costs and effectiveness of treatment of GORD the (unconfirmed by endoscopy) with seven proton pump inhibitors (PPIs: esomeprazole, lansoprazole (capsules and oro-dispersible tablets), omeprazole (generic and branded), pantoprazole and rabeprazole), over one year. DESIGN AND METHODS: A treatment model was developed of 13 interconnected Markov models incorporating acute treatment of symptoms, long-term therapy and subsequent decisions to undertake endoscopy to confirm diagnosis. Patients were allowed to stop treatment or to receive maintenance treatment either continuously or on-demand depending on response to therapy. Long-term dosing schedule (high dose or step-down dose) was based on current market data. Efficacy of treatments was based on clinical trials and follow-up studies, while resource use patterns were determined by a panel of physicians. MAIN OUTCOME MEASURES: The model predicts total expected annual costs, number of symptom-free days and quality-adjusted life-years (QALY). RESULTS: Generic omeprazole and rabeprazole dominated (i.e. cost less and resulted in more symptom-free days and higher QALY gains) the other PPIs. Rabeprazole had a favourable cost-effectiveness ratio of 3.42 pounds per symptom-free day and 8308 pounds/quality-adjusted life-year gained when compared with generic omeprazole. Rabeprazole remained cost-effective independent of choice of maintenance treatment (i.e. proportion of patients remaining on continuous treatment versus on-demand treatment). CONCLUSIONS: Economic models provide a useful framework to evaluate PPIs in realistic clinical scenarios. Our findings show that rabeprazole is cost-effective for the treatment of GORD.

Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett's esophagus.

BACKGROUND: Endoscopic ablation of Barrett's esophagus has been described in which various thermocoagulation modalities are used in combination with a high dose of a proton pump inhibitor. No randomized comparison of ablation strategies has been published. METHODS: Referred patients were screened to identify those with Barrett's esophagus 2 to 7 cm in length, without high-grade dysplasia or cancer. Included patients received pantoprazole (40 mg twice a day), followed by randomization to treatment with argon plasma coagulation (APC) or multipolar electrocoagulation (MPEC). The primary outcome measure was the number of treatment sessions required for endoscopic ablation. RESULTS: Of 235 patients screened, 52 were randomized. The mean length of Barrett's esophagus was 3.1 cm in the MPEC group vs. 4.0 cm in the APC group (p = 0.03). Otherwise, the treatment groups were similar with regard to baseline characteristics. The mean number of treatment sessions required for endoscopic ablation was 2.9 for MPEC vs. 3.8 for APC (p = 0.04) in an intention-to-treat analysis (p = 0.249, after adjustment for the difference in length of Barrett's esophagus). The proportion of patients in which ablation was endoscopically achieved proximal to the gastroesophageal junction was 88% for the MPEC group vs. 81% for the APC group (p = 0.68) and histologically achieved in 81% for MPEC vs. 65% for APC (p = 0.21). The mean time required for the first treatment session was 6 minutes with MPEC vs. 10 minutes with APC (p = 0.01) in per protocol analysis. There was no serious adverse event, but transient moderate to severe upper-GI symptoms occurred after MPEC in 8% vs. 13% after APC (p = 0.64). Conclusions Although there were no statistically significant differences, ablation of Barrett's esophagus with pantoprazole and MPEC required numerically fewer treatment sessions, and endoscopic and histologic ablation was achieved in a greater proportion of patients compared with treatment with pantoprazole and APC.

Results of triple eradication therapy in Japanese children: a retrospective multicenter study.

BACKGROUND: Large-scale clinical trials in children are lacking concerning Helicobacter pylori eradication therapies. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapies in Japanese children. METHODS: This was a retrospective analysis of the first- and second-line PPI-based triple therapies from pediatric gastrointestinal units between 1996 and 2003. Data collected included doses and duration of regimens, drug compliance, success or failure of eradication, ulcer healing, and symptom response of those with dyspepsia and no ulcers. The results of antibiotic susceptibility tests were also reported in cases where these were performed. RESULTS: A total of 149 pediatric patients (mean age, 12.6 years) were studied, including 123 patients who received first-line therapy: 115 received a PPI plus amoxicillin and clarithromycin (PAC) and 8 received a PPI plus amoxicillin and metronidazole (PAM). Overall eradication rates of the first-line PAC and PAM therapies were 77.4% and 87.5%, respectively ( P = 0.68). All 14 patients with failed PAC therapy received the second-line PAM regimen, resulting in an eradication rate of 100%. Mild side effects were reported only in PAC regimens (13.8%). Primary resistance to amoxicillin, clarithromycin, and metronidazole was detected in 0%, 34.7%, and 12.5% of the strains, respectively. The PAC regimen showed a high eradication rate for clarithromycin-susceptible strains (91.7%), but was relatively ineffective for resistant strains (40.0%) ( P < 0.01). Eradication of H. pylori was associated with ulcer healing and symptomatic improvement among those with gastritis only (both; P < 0.001). Among 17 patients with iron-deficiency anemia, post-treatment hemoglobin levels were higher than the pretreatment levels ( P < 0.001). CONCLUSIONS: The PAC regimen is effective in children. Clarithromycin resistance is associated with eradication failure. Metronidazole is a good substitute for clarithromycin as the second-line option for children.

Masking of 13C urea breath test by proton pump inhibitors is dependent on type of medication: comparison between omeprazole, pantoprazole, lansoprazole and esomeprazole.

BACKGROUND: The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test. AIM: To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high-dose citric acid-based 13C urea breath test. METHODS: Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment. RESULTS: One hundred and seventy-nine patients, mean age 45.8 +/- 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05). CONCLUSIONS: Proton pump inhibitor-induced false negative results on high-dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.

Intravenous proton-pump inhibitors versus H2-antagonists for treatment of GI bleeding.

OBJECTIVE: To evaluate the evidence supporting the use of intravenous proton-pump inhibitors in the treatment of gastrointestinal (GI) hemorrhage in comparison with histamine(2) (H(2))-receptor antagonists. DATA SOURCES: Clinical literature was accessed through a MEDLINE search (1966-October 2002). Data from abstracts and fully published articles were retrieved for analysis. Key search terms included pantoprazole, omeprazole, proton-pump inhibitors, gastrointestinal hemorrhage, histamine(2)-receptor antagonists, ranitidine, and cimetidine. DATA SYNTHESIS: There are limited published clinical outcome data evaluating the use of intravenous pantoprazole in patients with upper GI hemorrhage. However, there are several gastric pH studies suggesting that intravenous pantoprazole is effective in quickly obtaining and maintaining a pH >6. When considering the results from studies of high-dose intravenous omeprazole, in addition to the pantoprazole data, the relative efficacy of intravenous proton-pump inhibitors appears to be superior to that of intravenous H(2)-receptor antagonists in providing a more predictable and sustained pH control. CONCLUSIONS: Intravenous proton-pump inhibitors are suitable, possibly superior, alternatives to intravenous H(2)-receptor antagonists in treatment of upper GI bleeding.

Onions--a global benefit to health.

Onion (Allium cepa L.) is botanically included in the Liliaceae and species are found across a wide range of latitudes and altitudes in Europe, Asia, N. America and Africa. World onion production has increased by at least 25% over the past 10 years with current production being around 44 million tonnes making it the second most important horticultural crop after tomatoes. Because of their storage characteristics and durability for shipping, onions have always been traded more widely than most vegetables. Onions are versatile and are often used as an ingredient in many dishes and are accepted by almost all traditions and cultures. Onion consumption is increasing significantly, particularly in the USA and this is partly because of heavy promotion that links flavour and health. Onions are rich in two chemical groups that have perceived benefits to human health. These are the flavonoids and the alk(en)yl cysteine sulphoxides (ACSOs). Two flavonoid subgroups are found in onion, the anthocyanins, which impart a red/purple colour to some varieties and flavanols such as quercetin and its derivatives responsible for the yellow and brown skins of many other varieties. The ACSOs are the flavour precursors, which, when cleaved by the enzyme alliinase, generate the characteristic odour and taste of onion. The downstream products are a complex mixture of compounds which include thiosulphinates, thiosulphonates, mono-, di- and tri-sulphides. Compounds from onion have been reported to have a range of health benefits which include anticarcinogenic properties, antiplatelet activity, antithrombotic activity, antiasthmatic and antibiotic effects. Here we review the agronomy of the onion crop, the biochemistry of the health compounds and report on recent clinical data obtained using extracts from this species. Where appropriate we have compared the data with that obtained from garlic (Allium sativum L.) for which more information is widely available.

Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit.

Stress-related mucosal disease develops in patients in the intensive care unit and can result in clinically important bleeding, which is associated with increased mortality. Patients in the intensive care unit without either mechanical ventilation or coagulopathy, which are the primary risk factors for such bleeding, do not seem to need or to benefit from prophylactic acid suppression for stress-related mucosal disease. Although histamine-2-receptor antagonists significantly reduce clinically important bleeding in patients in the intensive care unit and are widely used for prophylaxis, their benefits are limited by the rapid development of tolerance. Previous data suggested that agents that elevate the intragastric pH may increase the susceptibility of patients in the intensive care unit to nosocomial pneumonia. However, the largest study to date showed that intravenous histamine-2-receptor antagonists may not significantly increase the risk of ventilator-associated pneumonia or mortality compared with sucralfate, an agent that does not affect intragastric pH. Intravenous proton pump inhibitors are more potent and longer-acting inhibitors of gastric acid production than intravenous histamine-2-receptor antagonists. The ability of proton pump inhibitors to prevent stress-related mucosal disease and clinically important bleeding seems to be clinically meaningful. Preliminary findings have shown that intermittent administration of intravenous pantoprazole, the first proton pump inhibitor available by this route in the United States, is as effective in raising intragastric pH on the first day as a continuous infusion of a histamine-2-receptor antagonist in clinical trials conducted within an intensive care unit setting. This suggests that for stress ulcer prophylaxis, intermittent dosing with an intravenous proton pump inhibitor may be an alternative to high-dose continuous infusions of a histamine-2-receptor antagonist. These agents must be compared in clinical trials conducted in an intensive care unit setting.

Effect of aggressive therapy on laryngeal symptoms and voice characteristics in patients with gastroesophageal reflux.

Gastroesophageal reflux (GER) is associated with a variety of laryngopharyngeal signs and symptoms. Injury of the laryngopharynx as a result of GER can be refractory to conventional antireflux therapy. This prospective study was undertaken to evaluate the prevalence of laryngopharyngeal signs and symptoms in patients with documented GER and to assess the response to a high-dose combination antireflux therapy consisting of cisapride and pantoprazole. Twenty-two patients with symptoms of GER were enrolled. After baseline evaluation using a history questionnaire for symptoms, laryngeal endoscopy and vocal acoustic analysis, patients were started on treatment consisting of pantoprazole 40 mg b.d. and cisapride 20 mg twice daily. Repeat history and otolaryngologic evaluation was performed at 4 weeks. Laryngopharyngeal symptoms were frequent in most patients, with throat clearing and globus being the most prevalent symptoms followed by vocal fatigue and excess mucus production. Almost 90% of the patients had abnormal endoscopic laryngeal findings but the acoustic parameters did not show any abnormal results except for mild elevation in the shimmer. After treatment, all symptoms and endoscopic abnormalities improved significantly except for intermittent dysphonia and laryngeal mucosal redness. Acoustic abnormalities did not change significantly following therapy. Laryngeal symptoms and voice abnormalities are highly prevalent in patients with GER. Combination antireflux therapy with a proton pump inhibitor and a prokinetic agent results in rapid symptomatic and endoscopic response in the majority of patients.

Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study.

BACKGROUND: One-week triple therapy is currently regarded as the reference of anti-Helicobacter pylori treatment. However, antibiotic-associated gastrointestinal side effects are among the major pitfalls of such regimens. Probiotic supplementation may be regarded as a therapeutic tool to prevent or reduce these troublesome drug-related manifestations. AIM: To determine whether the addition of the probiotic Lactobacillus GG to an anti-H. pylori standard triple therapy could help to prevent or minimize the occurrence of gastrointestinal side effects. METHODS: One hundred and twenty healthy asymptomatic subjects screened positive for H. pylori infection and deciding to receive eradication therapy were randomized either to 1-week pantoprazole (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), tinidazole (500 mg b.i.d.) or to the same regimen supplemented with Lactobacillus GG for 14 days. Patients filled in validated questionnaires during follow-up to determine the type and severity of side effects and to judge overall tolerability. RESULTS: Bloating, diarrhea and taste disturbances were the most frequent side effects during the eradication week and were significantly reduced in the Lactobacillus GG-supplemented group (RR = 0.4, CI 0.2-0.8; RR = 0.3, CI 0.1-0.8; RR = 0.3, CI 0.1-0.7, respectively). The same pattern was observed throughout the follow-up period. Overall assessment of treatment tolerability showed a significant trend in favor of the Lactobacillus GG-supplemented group (p = 0.03). CONCLUSIONS: Lactobacillus GG supplementation beneficially affects H. pylori therapy-related side effects and overall treatment tolerance.

Efficacy of a 1-week pantoprazole triple therapy in eradicating Helicobacter pylori in Asian patients.

BACKGROUND: The aim of the present paper was to determine the efficacy and tolerability of a 1-week treatment regimen consisting of pantoprazole and two antibiotics: clarithromycin and amoxycillin, in the eradication of Helicobacter pylori. METHODS: The patients selected had unequivocal evidence of H. pylori infection based on urease test, culture and histology on antral and corpus biopsies obtained at endoscopy. Patients received pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day and amoxycillin 1 g twice a day for 1 week and were assessed for successful eradication at least 4 weeks after completion of therapy by repeat gastroscopy and gastric biopsies. Eradication was defined as absence of bacteria in both antral and corpus biopsies tested by culture, histology and urease test. RESULTS: One hundred and six patients were recruited for the study. The mean age was 48.0 years (range: 23-74 years). Four patients defaulted follow up and five patients were not compliant (taking less than 85%) with medications. Eradication rates on per-protocol analysis were: 88/97 (90.7%; 95% CI: 83.1-95.7); and on intention-to-treat analysis they were: 88/106 (83.0%; 95% CI: 75.9-90.2). Side-effects were in general mild and tolerable: 57 of 106 (53.7%) patients complained of a bitter taste; 15 (14.1%) complained of giddiness; 10 (9.4%) complained of increased abdominal pain; 11 (11.5%) complained of lethargy and 16 (15.1%) complained of loose motions. Pre-treatment metronidazole resistance was encountered in 57/74 strains (77.0%). Clarithromycin resistance was not encountered in any of the strains. CONCLUSIONS: The pantoprazole 1-week triple therapy with amoxycillin and clarithromycin is effective in H. pylori eradication. The treatment was well tolerated by patients. Metronidazole resistance was reported in a high percentage of strains isolated from patients. Clarithromycin resistance was, however, not detected in any of the strains.

Triple therapy for Helicobacter pylori eradication: a comparison of pantoprazole once versus twice daily.

BACKGROUND: Proton pump inhibitor-based triple therapy is recommended as treatment for Helicobacter pylori eradication. The proton pump inhibitor may be given once or twice daily. However, little information is available on how these two treatment strategies compare. METHODS: H. pylori-positive patients (two positive test results) with endoscopy-proven healed duodenal ulcer or non-ulcer dyspesia were randomly allocated to 1 week of double-blind treatment with pantoprazole 40 mg once or twice daily, plus clarithromycin 250 mg and metronidazole 400 mg twice daily. Eradication was defined as a negative 13C-urea breath test (13C-UBT) and histology, 4-5 weeks post-treatment. The follow-up phase comprised 12 months off therapy, with 13C-UBT at 6 and 12 months. RESULTS: Two hundred and four patients received treatment: pantoprazole once daily (x1), n=104; twice daily (x2), n=100. Eradication rates were 84% in both the pantoprazole x1 and pantoprazole x2 groups by modified intention-to-treat analysis and 89% and 87%, respectively, by per protocol analysis. Metronidazole resistance was found in 44% of pre-treatment cultures of H. pylori. Eradication rates were similar in susceptible (72%) and resistant (75%) strains. During follow-up, recrudescence of infection occurred in 3/118 patients. CONCLUSION: When using pantoprazole plus clarithromycin and metronidazole, the proton pump inhibitor can be used once daily without loss of efficacy.

Prevalence of resistance to clarithromycin and its clinical impact on the efficacy of Helicobacter pylori eradication.

BACKGROUND: Triple therapy with a proton-pump inhibitor (PPI) in combination with metronidazole and clarithromycin is the method of choice for eradication of Helicobacter pylori. Failures have been primarily blamed on the development of resistance to clarithromycin. The present study investigated the prevalence and clinical significance of resistance to clarithromycin and metronidazole in determining therapeutic success of both triple therapy as a primary eradication method and high-dose dual therapy in non-responders. METHODS: On the basis of prior therapy, H. pylori-positive patients were assigned to one of two groups in the present prospective study. Group A (n = 93) included patients who had not undergone any prior eradication treatment, whereas group B (n = 15) consisted of patients who had received clarithromycin but in whom eradication had been unsuccessful. All patients underwent endoscopy with biopsy for bacterial culture and resistance studies. Patients in group A were treated with a 7-day regimen of pantoprazole (40 mg twice daily), metronidazole (500 mg twice daily), and clarithromycin (250 mg twice daily), whereas those in group B received omeprazole (40 mg three times a day) and amoxycillin (1000 mg three times a day ) for 14 days. Success of the eradication treatment was ascertained by means of the 13C urea breath test. RESULTS: In group A resistance to clarithromycin and metronidazole was identified in 3 patients (4.9%) and in 14 patients (22.9%), respectively. Eradication proved successful in 78 of 84 patients (92.6%) followed up. Two of the 3 patients with primary clarithromycin resistance and 1 of the 14 patients with metronidazole resistance did not respond to treatment. In group B isolated or combined resistance to clarithromycin was found in seven patients, whereas another four showed isolated resistance to metronidazole. Eradication proved successful in 10 of 13 controlled patients (76.9%) followed up, and only 2 patients reported severe side effects. CONCLUSION: Determination of antibiotic resistance before initiating therapy is not necessary, since primary resistance to clarithromycin is rare. The Italian triple therapy remains a highly effective primary therapeutic method. Further, routine determination of resistance in non-responders also seems to be superfluous because high-dose dual therapy is an effective and well-tolerated second-line therapy regardless of the patients' resistance status.

Two-week course of pantoprazole combined with 1 week of amoxycillin and clarithromycin is effective in Helicobacter pylori eradication and duodenal ulcer healing.

BACKGROUND: Experience with proton pump inhibitor-based triple therapy is predominantly with omeprazole-containing regimens. AIM: To investigate the efficacy of a pantoprazole-based regimen, with either a 1 or 2-week course of antibiotic co-therapy, in eradicating H. pylori, healing duodenal ulcers and to assess the antibiotic sensitivity profiles of isolated H. pylori strains. METHODS: A single-blind, multicentre, parallel group comparison of patients with endoscopically proven, H. pylori associated, active duodenal ulceration. All patients received pantoprazole, 40 mg b.d. for 2 weeks. Patients were randomized to receive either 1 or 2 weeks of therapy with amoxycillin, 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry, at 14 days and a minimum of 4 weeks after cessation of all therapy. H. pylori status was determined by urease reaction, histological assessment and culture from antral and body biopsies. Antibiotic sensitivity was determined using the agar dilution technique. RESULTS: Sixty-seven patients were randomized. One week co-therapy (n=33): eradication efficacy, ITT= 79% (95% CI: 61-91%); ulcer healing efficacy (at 6-week visit)=88% (95% CI: 72-97%). Two-week co-therapy (n=34): eradication efficacy, ITT=91% (95% CI: 76-98%: ulcer healing efficacy= 88% (95% CI: 73-97%). Both regimens were well tolerated and no primary antibiotic resistance was noted. CONCLUSION: Pantoprazole-based triple therapy, with either 1 or 2 weeks of co-therapy with amoxycillin and clarithromycin, is effective in eradicating H. pylori and healing duodenal ulceration.