bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of ranitidine bismuth citrate plus clarithromycin with omeprazole plus clarithromycin for the eradication of Helicobacter pylori
Authors: Paré  , Farley  , Romãozinho  , Bardhan  , French  , Roberts  
Published: March 2003

Background: Many dual and triple therapy treatment regimens have been proposed for the eradication of Helicobacter pylori. However, assessing the relative efficacy of these regimens is complicated by differences in study design, and few well‐controlled comparative studies have been reported.Methods: This multicentre, randomized, double‐blind study involved 530 duodenal ulcer patients, of whom 520 had confirmed H. pylori infection. Patients received 14 days b.d. dual therapy of either ranitidine bismuth citrate (RBC) 400 mg or omeprazole 20 mg, both with clarithromycin 500 mg to eradicate H. pylori, followed by a further 14 days of treatment with RBC 400 mg b.d. or omeprazole 20 mg o.d. to facilitate ulcer healing. H. pylori eradication and ulcer healing were assessed at least 26 days after the end of treatment. Adverse events were recorded throughout the study.Results: H. pylori was eradicated in 90% of patients who received RBC with clarithromycin and in 66% of patients who received omeprazole with clarithromycin (per protocol; P < 0.001). intention‐to‐treat eradication rates were 77% and 60%, respectively (P < 0.001). Ulcer healing rates were 97% in the RBC treatment group and 95% in the omeprazole treatment group. Only 3% and 1% of patients in the RBC and omeprazole treatment groups, respectively, were withdrawn due to adverse events.Conclusions: RBC with clarithromycin is a simple and highly effective dual therapy regimen for the eradication of H. pylori, and is significantly more effective than omeprazole with clarithromycin. Both treatment regimens are well tolerated and effectively heal duodenal ulcers.
One‐week ranitidine bismuth citrate in combinations with metronidazole, amoxycillin and clarithromycin in the treatment of Helicobacter pylori infection: the RBC‐MACH study
Authors: Sung  , Chan  , Wu  , Leung  , Suen  , Ling  , Lee  , Cheng  , Chung S. C. Sydney 
Published: March 2003

Background: We have previously shown that ranitidine bismuth citrate (RBC)‐based triple therapy is comparable to proton pump inhibitor‐based triple therapy in eradicating Helicobacter pylori infection.Aim: To test the efficacy of different combinations of antimicrobials with RBC in the treatment of H. pylori infection.Methods: Dyspeptic patients with H. pylori infection were prospectively randomized to receive one of the following regimens: (i) RBC 400 mg, amoxycillin 1 g, clarithromycin 500 mg [RAC]; (ii) RBC 400 mg, metronidazole 400 mg, clarithromycin 500 mg [RMC]; (iii) RBC 400 mg, metronidazole 400 mg, tetracycline 1 g [RMT] (all given twice daily for 1 week); or (iv) RBC 400 mg plus clarithromycin 500 mg twice daily for 2 weeks [RC‐2]. Endoscopy (rapid urease test and culture) and 13C‐urea breath test (UBT) were performed before randomization. Four weeks after finishing medication, the 13C‐UBT was repeated in all cases and endoscopy was offered to patients with peptic ulcers.Results: Four hundred patients were randomized but in two (one in the RAC group and one in the RMC group) H. pylori infection was not confirmed. Successful eradication of H. pylori (intention‐to‐treat analysis and 95% CI) of RAC (86% [79–93%]), RMC (90% [84–96%]), RMT (79% [71–87%]) and RC‐2 (82% [75–90%]) were comparable, with a trend favouring clarithromycin‐containing triple therapy regimens. Among 276 isolates tested for antibiotic sensitivity, primary resistance to metronidazole, clarithromycin and amoxycillin was found in 56%, 2% and 0.4%, respectively. When given RMC or RMT, patients infected by metronidazole‐resistant H. pylori had success in eradicating H. pylori similar to patients infected by metronidazole‐sensitive H. pylori.Conclusion: One‐week RBC triple therapy is effective in curing H. pylori infection.
Injurious effect of Helicobacter pylori culture fluid to gastroduodenal mucosa, and its detoxification by sucralfate in the rat
Authors: Watanabe  , Joh  , Seno  , Takahashi  , Ohara  , Nomura  , Tochikubo  , Itoh  
Published: March 2003

Background: Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer. Although several cytotoxins related to H. pylori have been reported, their effects on gastroduodenal mucosa have not been well evaluated in vivo.Aim: To investigate the effects of the combination of acid and toxic substances derived from H. pylori on gastroduodenal mucosa, and to observe the effect of sucralfate on such factors in the rat.Methods: Male Sprague–Dawley rats were fasted overnight and anaesthetized. The pylorus was ligated, and a double‐lumen cannula was inserted into the forestomach for gastric luminal perfusion. In other animals, a cannula was inserted to perfuse the proximal duodenum. 51Cr‐EDTA was administered intravenously and mucosal integrity was monitored by measuring the blood‐to‐lumen 51Cr‐EDTA clearance. After 72 h of culture of H. pylori (NCTC11637 and Sydney strain 1), Brucella broth containing 3% FBS was filtered to remove the bacteria (supernate of H. pylori culture fluid; HPsup). HPsup was acidified (pH=2.0) with HCl, and tested for its injurious action on gastric or duodenal mucosa by luminal perfusion. HPsup was incubated with sucralfate for 30 min. The supernate was collected by centrifugation and the pH was readjusted to 2.0. This sucralfate‐treated HPsup was used to test the effect of sucralfate against H. pylori‐related mucosal injurious factors.Results: Non‐acidified and acidified HPsup did not cause any detectable injury to the gastric mucosa. Non‐acidified HPsup did not cause injury in the duodenal mucosa. However, acidified HPsup induced a significantly greater increase in 51Cr‐EDTA clearance and greater histological damage than in controls. Sucralfate completely reversed this.Conclusion: These results suggest that an H. pylori‐related toxic substance may aggravate duodenal acid injury by acting on luminal surfaces, and that the detoxification of this substance by sucralfate may contribute to its anti‐ulcer action.
Seven‐day ‘rescue’ therapy after Helicobacter pylori treatment failure: omeprazole, bismuth, tetracycline and metronidazole vs. ranitidine bismuth citrate, tetracycline and metronidazole
Authors: Gisbert  , Gisbert  , Marcos  , Grávalos R. García , Carpio  , Pajares  
Published: March 2003

Background: Eradication therapy with omeprazole (O), amoxycillin (A) and clarithromycin (C) is used extensively, although it often fails. A ‘rescue’ therapy with a quadruple combination of O, bismuth (B), tetracycline (T) and metronidazole (M) has been recommended.Aim: To assess ranitidine bismuth citrate (Rbc) instead of O and B for treatment failure.Methods: Sixty consecutive patients (13 duodenal ulcer, 47 non‐ulcer dyspepsia) in whom a previous eradication trial with O, A and C had failed were randomized to receive one of two regimens for 7 days: O (20 mg b.d.), B (120 mg q.d.s.), T (500 mg q.d.s.) and M (250 mg q.d.s.) (group OBTM, n=30); or Rbc (400 mg b.d.), T (500 mg q.d.s.) and M (250 mg q.d.s.) (group RbcTM, n=30). Eradication was defined as a negative 13C‐urea breath test 1 month after completing therapy.Results: Mean age ± s.d. was 45 ± 12 years, 47% were males. Distribution of studied variables (age, sex, smoking, duodenal ulcer/non‐ulcer dyspepsia) was similar in both therapeutic groups. Per protocol eradication was achieved in 17 out of 29 patients (59%) in group OBTM and in 25 out of 29 patients (86%) in group RbcTM (P < 0.05). Intention‐to‐treat eradication was achieved, respectively, in 17 out of 30 (57%) and in 25 out of 30 (83%) (P < 0.05). In the multivariate analysis the variables which influenced on H. pylori eradication were the type of therapy (odds ratio, OR=3.9; 95%CI: 1.02–15; P < 0.05) and diagnosis (duodenal ulcer/non‐ulcer dyspepsia) (OR=0.1; CI: 0.02–0.4). Adverse effects were infrequent and mild with both regimens.Conclusion: Therapy with RbcTM is a promising option after H. pylori eradication failure with OCA, achieving a higher efficacy than quadruple therapy with OBTM.
The ulcer healing effect of protamine sulphate in rat stomach
Authors: Li  , Cho  
Published: March 2003

Background: Protamine sulphate has been reported to stimulate nitric oxide production from blood vessels, which is a pivotal factor for gastric ulcer healing. Our preliminary study also showed that protamine sulphate potentiated the ulcer healing effect of heparin.Methods: Male SD rats with acetic acid‐induced gastric ulcers were given protamine sulphate (40–80 mg/kg, s.c.) twice daily for 4 or 7 days. L‐NG‐nitroarginine methyl ester (
L‐NAME, 5 mg/kg), an inhibitor of nitric oxide synthase (NOS), was given s.c. prior to protamine sulphate (80 mg/kg) treatment. Ulcer healing, angiogenesis, mucosal histological changes, NOS activity and growth factors were determined.Results: Protamine sulphate dose‐dependently accelerated gastric ulcer healing, which was accompanied by a significant increase in angiogenesis, mucosal regeneration and constitutive NOS activity. Inhibition of gastric secretion was observed. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), tumour necrosis factor‐α (TNF‐α) or inducible NOS activity was also affected.
L‐NAME completely blocked the beneficial effects of protamine sulphate.Conclusions: Protamine sulphate accelerates gastric ulcer healing through a mucosal nitric oxide‐dependent and possibly also the EGF‐and bFGF‐associated pathways, which are followed by an increase of angiogenesis and mucosal regeneration. Acid inhibition contributes in part to the ulcer healing action of protamine sulphate.
Oxyntic lesions may be provoked in the rat both by the process of acid secretion and also by gastric acidity
Authors: Waldum  , Mårvik  , Grønbech  , Sandvik  , Aase  
Published: March 2003

Background:Gastric ischaemia appears to be a common pathogenetic factor for stress ulcers. These ulcers occur predominantly in the oxyntic mucosa, suggesting that the acid secretory process or its stimulation is involved in the pathogenesis.Methods:We examined separately the role of the acid secretory process and gastric luminal acidity in the pathogenesis of gastric lesions using the isolated vascularly perfused acid‐secreting rat stomach.Results:Pentagastrin‐stimulated acid secretion induced submucosal bleeding in the oxyntic mucosa whether accompanied by perfusion of the gastric lumen with saline or a phosphate buffer at pH 7.0. On the other hand, acidity, whether endogenous or introduced by luminal perfusion, induced erosions in both the oxyntic and antral mucosa.Conclusion:It is concluded that the acid secretory process itself contributes to the particular vulnerability of the oxyntic mucosa to ischaemia. Histamine released upon stimulation of gastric acid secretion or shortage of energy due to the requirements for acid secretion may both contribute to this vulnerability. Furthermore, these findings suggest that inhibition of gastric acid secretion should be superior to antacids in preventing stress ulcers.
Limited exposure of the healthy distal colon to orally‐dosed formulation is further exaggerated in active left‐sided ulcerative colitis
Authors: Hebden  , Blackshaw  , Perkins  , Wilson  , Spiller  
Published: March 2003

Background:Active distal ulcerative colitis is often resistant to topically acting oral formulations. We speculated that the left side of the colon is underexposed to orally‐dosed topical agents in patients with active distal colitis.Methods:Twenty‐two healthy volunteers (12 males, aged 22–47 years), and 10 patients (6 males, aged 33–73 years) with active left‐sided ulcerative colitis ingested a Eudragit‐coated gelatine capsule containing 111In‐labelled amberlite resin on four successive days. Regional colonic distribution, transit times and percentage of daily dose resident were calculated from the average of four serial gamma camera images on the 4th day.Results:(mean [95% CI]). When compared to controls, patients with colitis had significantly faster total colon transit (24.3 h [9.5–39.1] vs. 51.7 h [41.1–62.3]) as well as faster proximal colon transit (18.7 h [9.1–28.3] vs. 36.7 [28.5–44.9]), and distal colon transit (3.1 h [−0.5 to 6.8] vs. 15.0 h [10.5–19.5]), respectively (all P < 0.01). Material was asymmetrically distributed in health (proximal colon 69% [63–76] vs. distal colon 31% [24–37]). This asymmetry was more extreme in colitis, with corresponding values of 91% [85–96] vs. 9% [4–15]. As a result colitics had less material in the left‐sided colon (9% [4–15] vs. 31% [24–37]), P < 0.001. Colitics had a significantly lower percentage of the daily dose resident within the left side of the colon compared to controls (13% [−2 to 28] vs. 63% [44–81]), P < 0.01.Conclusions:Delayed release oral formulation is asymmetrically distributed within the colon in health. This asymmetry is exaggerated in active left‐sided ulcerative colitis and, together with faster colonic transit, results in reduced exposure of the distal colon to orally‐dosed topical agents.
Colorectal cancer prevention in ulcerative colitis: a case‐control study
Authors: Eaden  , Abrams  , Ekbom  , Jackson  , Mayberry  
Published: March 2003

Background:The risk of colorectal cancer (CRC) in ulcerative colitis (UC) increases with extent and duration of disease. Identifying other risk factors would allow targeting of sub‐groups at greatest risk, enabling more cost‐effective surveillance.Methods:We conducted a case‐control study comparing 102 cases of CRC in UC with matched controls. Odds ratios (OR) for cancer risk were estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables.Results:Regular 5‐aminosalicylic acid (5‐ASA) therapy reduces cancer risk by 75% (OR 0.25, 95% CI: 0.13–0.48, P < 0.00001). Adjusting for other variables, taking mesalazine regularly reduces risk by 81% (OR 0.19, 95% CI: 0.06–0.61, P=0.006) and visiting a hospital doctor more than twice a year also reduces risk (OR 0.16, 95% CI: 0.04–0.60, P=0.007). Considering variables independently, having a family history of sporadic CRC in any relative increases risk fivefold (OR 5.0, 95% CI: 1.10–22.82, P < 0.04).Conclusions:CRC risk among UC patients can be reduced by regular therapy with 5‐ASA medication. Colonoscopic surveillance may be best targeted on those unable to take 5‐ASAs (e.g. due to allergy) and those with a positive family history of CRC.
Pharmacoepidemiology of non‐steroidal anti‐inflammatory drug use in Nottingham general practices
Authors: Hawkey  , Cullen  , Pearson  , Holmes  , Doherty  , Wilson  , Garrud  , Garner  , Maynard  , Logan  
Published: March 2003

Aim:To investigate the pharmacoepidemiology of NSAID usage in Nottingham general practices.Design:Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records.Setting:General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate.Subjects:Unselected patients receiving NSAIDs prescribed for all indications.Main outcome measures:Indication for treatment, differences in prescribing to different age groups, compliance and overall scheme drug exposure, drug effectiveness and tolerability, possible drug‐related adverse events, patients’ overall satisfaction with treatment and estimated costs of care.Results:NSAIDs were used for a wide range of conditions and only a small number of patients had rheumatoid arthritis. The main drugs used were ibuprofen, diclofenac and naproxen. Patients making short‐term use of NSAIDs had low compliance if they experienced adverse drug effects, whilst conversely in long‐term users, those with high compliance reported more adverse drug effects. Calculated compliance did not vary with age although older patients (over 65 years) claimed in their questionnaires to be more compliant than younger patients.Half the patients reported good or complete symptom relief. Half of those questions (and two thirds of those with good or complete symptom relief) rated their NSAID as the best treatment they had received for their current condition. The frequency of gastrointestinal adverse events was higher in the young and the old, which correlated with the use of anti‐ulcer drugs, and increased with the total number of medications used.Conclusions:NSAIDs are used for a wide‐range of conditions. They give symptom relief to, and are perceived as effective by, most patients taking them.
Plasma antioxidant levels in chronic cholestatic liver diseases
Authors: Floreani  , Baragiotta  , Martines  , Naccarato  , D’Odorico  
Published: March 2003

Bakcground:A predictable consequence of cholestasis is malabsorption of fat‐soluble factors, (vitamins A, D, E, K) and other free radical scavengers, such as carotenoids. It has been suggested that oxygen‐derived free radicals may be involved in the pathogenesis of chronic liver damage.Aims:(i) To evaluate retinol, α‐tocopherol and carotenoid plasma levels in two groups of patients with chronic cholestatic liver disease (primary biliary cirrhosis and primary sclerosing cholangitis); (ii) to compare the respective plasma levels with those of the general population; (iii) to correlate the plasma levels with disease severity.Methods:A total of 105 patients with chronic cholestasis were included in the study: 86 with primary biliary cirrhosis (81 female, five male, mean age 55.5 ± 11 years), 19 with primary sclerosing cholangitis (seven female, 12 male, mean age 35 ± 11 years; six patients had associated inflammatory bowel disease); 105 sex‐ and age‐matched subjects from the general population in the same geographical area (88 female, 17 male, mean age 51.3.5 ± 10 years) served as controls. Carotenoids (lutein zeaxanthin, lycopene, β‐carotene, α‐carotene, β‐cryptoxanthin), retinol and α‐tocopherol were assayed by high‐pressure liquid chromatography. A food frequency questionnaire was administered to each subject to evaluate the quality and the quantity of dietary compounds. Data were processed by analysis of variance and linear regression analysis, as appropriate.Results:Both primary biliary cirrhosis and primary sclerosing cholangitis patients had significantly lower levels of retinol, α‐tocopherol, total carotenoids, lutein, zeaxanthin, lycopene, α‐ and β‐carotene than controls (P < 0.0001). Among the cholestatic patients, no significant difference in the concentration of antioxidants was observed between primary biliary cirrhosis and primary sclerosing cholangitis subjects. Anti‐oxidant plasma levels were not affected by the severity of the histological stage in primary biliary cirrhosis, but a negative correlation was found between total carotenoids and both alkaline phosphatase (ALP) and gammaglutamyl transpeptidase (GGT) (P < 0.013 and P < 0.018, respectively). Within the primary sclerosing cholangitis group, no correlation was found between total carotenoids and cholestatic enzymes. Nutritional intake in cholestatic patients was comparable to controls, including fruit and vegetable intake.Conclusions:Although no clinical sign of deficiency is evident, plasma levels of antioxidants are low in cholestatic patients even in early stages of the disease. This is probably due to malabsorption of fat‐soluble vitamins, as well as other mechanisms of hepatic release, suggesting the need for dietary supplementation.
Cure of Helicobacter pylori infection in atrophic body gastritis patients does not improve mucosal atrophy but reduces hypergastrinemia and its related effects on body ECL‐cell hyperplasia
Authors: Annibale  , Aprile M. Rosaria , D’Ambra  , Caruana  , Bordi  , Fave G. Delle 
Published: March 2003

Background:The effects of H. pylori eradication on atrophic body gastritis are controversial.Aim:To investigate the effect of triple therapy on atrophic body gastritis in H. pylori‐positive patients and its effect on morpho‐functional gastric parameters.Methods:Thirty‐five consecutive atrophic body gastritis patients with histological/serological evidence of H. pylori infection were treated. Before and 6 and 12 months after H. pylori eradication the patients were evaluated for fasting gastrinemia and pepsinogen I, basal and peak acid output, and detailed histological assessment including the ECL cell proliferative patterns.Results:Six months after treatment, 25 out of 32 patients were cured (78%). Cure of infection was associated with improvement in both basal (basal acid output mean 0.23 ± 0.14 mmol/h vs. 1.75 ± 0.7 mmol/h, P < 0.005) and stimulated acid secretion (peak acid output mean 3.0 ± 1.06 mmol/h vs. 16.6 ± 4.1 mmol/h, P=0.0017) as well as with reduction in hypergastrinemia (mean gastrin levels 444.1 ± 110.7 pg/mL vs. 85.3. ± 28 pg/mL; P < 0.005). In contrast, the eradication had no effect on body corporal atrophy and intestinal metaplasia, or pepsinogen I levels (mean 16.6 ± 2.9 ng/mL vs. 14.2 ± 2.1 ng/mL, N.S.). These results were confirmed at 12 months after eradication. A statistical inverse correlation was obtained (r=–0.3635, P < 0.05) between the corporal chronic infiltrate score and peak acid output values. A total of 53% of atrophic body gastritis patients showed a regression in severity of body ECL cell hyperplastic change.Conclusion:Cure of H. pylori infection in patients with atrophic gastritis reverses some adverse effects on gastric function and ECL cell hyperplasia. H. pylori infection may be cured in atrophic body gastritis patients with partial reversion of its negative consequences on acid secretion and body ECL cell hyperplasia.
Botulinum toxin injected in the gastric wall reduces body weight and food intake in rats
Authors: Gui  , De Gaetano  , Spada P. Luigi , Viggiano  , Cassetta  , Albanese  
Published: March 2003

Background:Botulinum toxin is a powerful, long‐acting inhibitor of muscular contractions in both voluntary and smooth muscle. It acts by blocking the release of the neurotransmitter acetylcholine. In the stomach, propulsive contractions of the antrum are necessary for the gastric contents to pass into the duodenum.Aims:To investigate whether intramuscular injections of botulinum toxin type A into the gastric antrum of rats would cause a reduction in food intake and hence body weight, by inhibition of gastric emptying.Materials and methods:This was a prospective, randomized, 3‐way parallel group study in rats. The first group was anaesthetized, laparotomized and given 20 U of botulinum toxin type A by intramuscular injection into the gastric antrum (botulinum toxin type A group, n=14). The second group was anaesthetized, laparotomized and injected with saline (sham group, n=14) and the third group did not have any intervention (control group, n=5). Food intake was measured daily for 7 weeks and body weight was measured daily for 10 weeks.Results:There was a significant difference in loss of body weight between the two treated groups (14.0 ± 8.2% botulinum toxin type A group, 4.4 ± 2.7% sham group; P < 0.001). Further, the time to reach the weight nadir was significantly longer in the botulinum toxin type A group (8.7 ± 3.9 days) compared with the sham group (5.3 ± 3.8 days; P < 0.04). There were no significant differences between the sham and control groups for any of the body weight parameters. The minimum dietary intake was significantly lower in the botulinum toxin type A group than in the sham group (37.8 ± 21.8% of the basal value in the botulinum toxin type A group, vs. 65.5 ± 32.0 in the sham group, P < 0.05). In addition, the time to reach the nadir was significantly prolonged (8.2 ± 3.5 days, botulinum toxin type A group vs. 4.9 ± 1.7 days, sham group, P < 0.001).Conclusions:The parallel reduction of body weight and food intake in botulinum toxin type A treated animals is consistent with a long lasting inhibition of the antral pump. This is probably due to slowed gastric emptying leading to early satiety. Patients with morbid obesity might benefit from endoscopic injections of botulinum toxin type A into the stomach wall.