bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment options for Helicobacter pylori infection when proton pump inhibitor‐based triple therapy fails in clinical practice
Authors: LEE  , BRESLIN  , HYDE  , BUCKLEY  , O'MORAIN
Published: March 2003

Background

: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined.

Aims

: To evaluate proton pump inhibitor‐based triple therapies as first‐line eradication regimens in clinical practice, and to establish the efficacy of second‐line regimens in the context of an initial failed eradication attempt.

Methods

: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first‐line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2‐week proton pump inhibitor‐based triple therapy regimen as described, and 12 patients received a further 1‐week proton pump inhibitor‐based triple therapy regimen.

Results

: Including 308 patients, the intention‐to‐treat (ITT) eradication rates for OAC and OMC as first‐line regimens were 72% (95% CI: 63–80%) and 73% (95% CI: 67–79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow‐up gives an initial eradication rate of 78% (95% CI: 69–86%) for OAC and 79% (95% CI: 73–85%) for OMC. There were 60 patients (21%; 95% CI: 17–26%) in whom the initial eradication attempt was unsuccessful. With second‐line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58–73%) patients. The eradication rates with the quadruple regimen and 2‐week triple therapy regimens were 75% (95% CI: 56–94%) and 80% (95% CI: 63–98%) respectively (P = 0.71). The eradication rate with a repeat 1‐week regimen was 33% (95% CI: 7–60%).

Conclusions

: The eradication rates achieved in this `in practice' study with recommended first‐line 1‐week proton pump inhibitor‐based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1‐week proton pump inhibitor‐based triple therapy regimen was not successful as a salvage therapy. Both the 2‐week proton pump inhibitor‐based triple therapy regimen and the 1‐week quadruple therapy regimen were successful second‐line treatments in  ≥75% of patients.
Spiramycin is comparable to oxytetracycline in eradicating H. pylori when given with ranitidine bismuth citrate and metronidazole
Authors: OLAFSSON  , BERSTAD  , BANG  , NYSÆTER  , COLL  , TEFERA  , HATLEBAKK  , HAUSKEN  , OLAFSSON
Published: March 2003

Background

: We have consistently achieved about 90% eradication of H. pylori with liquid bismuth, metronidazole and oxytetracycline.

Aim

: To test eradication and adverse events of ranitidine bismuth citrate (RBC) when given with metronidazole and either oxytetracycline or spiramycin.

Methods

: One hundred and eighty‐three patients were randomized to one of four 10‐day regimens: RBC400OM: RBC 400 mg b.d., oxytetracycline 500 mg q.d.s.; RBC400SM: RBC 400 mg b.d., spiramycin 1 g q.d.s.; RBC200OM: RBC 200 mg q.d.s., oxytetracycline 500 mg q.d.s.; RBC200SM: RBC 200 mg q.d.s., spiramycin 1 g q.d.s. Additionally, all patients received metronidazole 400 mg q.d.s. A 14C‐urea breath test was performed at 8 weeks.

Results

: Intention‐to‐treat eradication rates were 94%, 91%, 94% and 89% with RBC400OM, RBC400SM, RBC200OM and RBC200SM, respectively (P = 0.81). Eradication was significantly higher in ulcer patients (97%) than in those with diagnoses other than ulcer (86%) (P = 0.009). There was a strong tendency to better eradication among those who had never smoked (100%) compared with ex‐smokers (93%) and smokers (89%) (P = 0.06). Fifty‐three per cent experienced at least one moderate or severe adverse event, and women had more adverse events than men (P = 0.0002).

Conclusions

: All four regimens had comparable efficacy and adverse events. Eradication was significantly better in ulcer patients but there was a trend to better eradication in those who smoked less, used less alcohol and exercised more. Adverse events were frequent, perhaps because of the large dose of metronidazole used, but few patients stopped treatment.
Dexamethasone inhibits IFNγ‐induced MHC class II expression of intestinal epithelial cells independently of the TGF‐β1 regulatory pathway
Authors: RUEMMELE  , DIONNE  , LEVY  , SEIDMAN
Published: March 2003

Background

: In the presence of inflammation, an increased expression of enterocyte MHC class II is observed, leading to altered mucosal antigen handling. Corticosteroids are potent anti‐inflammatory drugs, widely used in treating inflammatory bowel disorders. However, their diverse mechanisms of action are only partially understood.

Aim

: To evaluate effect and mechanisms of corticosteroids on intestinal crypt epithelial cell MHC class II.

Methods

: The effect of dexamethasone treatment on cytokine‐induced MHC class II expression was measured in IEC‐6 cells by immunofluorescence and flow cytometry. To determine the role of the TGF‐β1 regulatory pathway in mediating the effects of dexamethasone, neutralizing anti‐TGF‐β antibodies were used. Additionally, endogenous and dexamethasone‐stimulated IEC‐6 cell TGF‐β1 production was measured by ELISA.

Results

: Dexamethasone potently down‐regulated IFNγ‐induced class II expression on IEC‐6 cells, in a dose‐dependent manner. TGF‐β1 had a similar inhibitory effect on class II expression. However, neutralizing anti‐TGF‐β antibodies did not alter the effect of dexamethasone. Furthermore, dexamethasone reduced endogenous TGF‐β1 synthesis.

Conclusions

: Corticosteroids inhibit cytokine‐induced MHC class II expression on IEC‐6 cells in a TGF‐β1 independent way. This effect may markedly alter enterocytic antigen presentation, reducing the aberrant state of activation of mucosal immune cells.
Post‐prandial intragastric and duodenal acidity are increased in patients with chronic pancreatitis
Authors: Geus  , Eddes  , Gielkens  , Gan  , Lamers  , Masclee
Published: March 2003

Objectives

: Patients with chronic pancreatitis and exocrine insufficiency have lower intraduodenal pH compared to controls. It has been assumed that abnormal low intraduodenal pH in these patients not only results from impaired pancreatic bicarbonate secretion but also from an increased gastric acid load to the duodenum.

Methods

: We have tested this hypothesis by combined intragastric and intraduodenal 24 h pH monitoring in nine chronic pancreatitis patients with exocrine pancreatic insufficiency and nine healthy control subjects during standardized test conditions. Postprandial gastrin and cholecystokinin release were also determined.

Results

: Median 24‐h intraduodenal pH (5.90 vs. 6.00) and intragastric pH (1.60 vs. 1.70) were not significantly different between patients and controls. However, in the 2‐h postprandial periods intraduodenal pH was below five for a significantly higher percentage of time in chronic pancreatitis patients compared to controls (lunch: 14.5% vs. 0.17%, P=0.011; dinner: 24.1% vs. 5.75%, P=0.05). The post‐dinner intragastric pH was below three for a significantly higher percentage of time in chronic pancreatitis patients vs. controls (72.2 vs. 48.9%, P=0.04). Postprandial gastrin release was not significantly different between the two groups. Postprandial secretion of cholecystokinin (CCK), as enterogastrone, was significantly (P < 0.01) reduced in chronic pancreatitis patients (78 ± 13 pmol/L, 120 min) compared to controls (155 ± 14 pmol/L, 120 min).

Conclusions

: Median intraduodenal and intragastric pH are not significantly decreased in patients with chronic pancreatitis and exocrine insufficiency but the postprandial time with an acidic pH in the duodenum (pH < 5) and in the stomach (pH < 3) is significantly (P ≤ 0.05) increased.
Helicobacter pylori infection and gastric cancer: systematic review of the epidemiological studies
Authors: Danesh
Published: March 2003

Background

: The published epidemiological studies of chronic Helicobacter pylori infection and gastric cancer yield conflicting results, so there is uncertainty as to whether any material association exists and, if so, how strong it is.

Aim

: To review these studies quantitatively.

Methods

: A systematic review of sero‐epidemiological studies published before 1998 of H. pylori and gastric cancer, as identified by computer‐assisted literature searches of relevant journals, reference lists and discussions with authors. All relevant studies identified were included, subdivided by study design. The following was abstracted from published reports: adjusted odds ratio (or, in prospective studies, the risk ratio) and confidence interval, study design, type of controls, mean age, mean duration of follow‐up, assay methods, location of study, and degree of adjustment for confounders.

Results

: The 34 retrospective studies included in total 3300 gastric cancers, but their controls were of uncertain validity. The 10 ‘nested’ case–control comparisons in prospective studies included in total only 800 gastric cancers, and combined analysis of them yielded a risk ratio of 2.5 (95% CI: 1.9–3.4; 2P < 0.00001) for gastric cancer in people seropositive for H. pylori antibodies.

Conclusions

: The prospective studies suggest that gastric cancer is 2 or 3 times as common in those chronically infected by H. pylori, but to help investigate causality, further observational studies are still needed, as are large‐scale randomized trials of whether antibacterial regimens reduce the eventual incidence of gastric cancer.
On demand therapy with omeprazole for the long‐term management of patients with heartburn without oesophagitis—a placebo‐controlled randomized trial
Authors: Lind  , Havelund  , Lundell  , Glise  , Lauritsen  , Pedersen  , Anker‐Hansen  , StubberÖD  , Eriksson  , Carlsson  , Junghard
Published: March 2003

Aim

: To observe the natural course of gastro‐oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long‐term management of these patients.

Methods

: We investigated the efficacy of on‐demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double‐blind, randomized multicentre trial. It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short‐term treatment. Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6‐month period. They also had access to antacids. The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue.

Results

: According to life‐table analysis, after 6 months the remission rates were 83% (95% CI: 77–89%) with omeprazole 20 mg, 69% (61–77%) with omeprazole 10 mg, and 56% (46–64%) with placebo (P < 0.01 for all intergroup differences). The mean (s.d.) number of study medications used per day in these groups was 0.43 (0.27), 0.41 (0.27) and 0.47 (0.27), respectively. The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group. Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life.

Conclusions

: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life. On‐demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients.
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.
Non‐absorbable antibiotics for managing intestinal gas production and gas‐related symptoms
Authors: Di Stefano M. , Strocchi A. , Malservisi S. , Veneto G. , Ferrieri A. , Corazza G. R.
Published: March 2003

Background:

Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas‐related symptoms with conflicting results.

Aim:

To study the relationship between gaseous symptoms and colonic gas production and to test the efficacy of rifaximin, a new non‐absorbable antimicrobial agent, on these symptoms.

Methods:

Intestinal gas production was measured by hydrogen (H2) and methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34 functional patients. Only the 34 functional patients took part in a double‐blind, double‐dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7 days), or activated charcoal (400 mg b.d per 7 days). The following parameters were evaluated at the start of the study and 1 and 10 days after therapy: bloating, abdominal pain, number of flatus episodes, abdominal girth, and cumulative breath H2 excretion.

Results:

Hydrogen excretion was greater in functional patients than in healthy volunteers. Rifaximin, but not activated charcoal, led to a significant reduction in H2 excretion and overall severity of symptoms. In particular, in patients treated with rifaximin, a significant reduction in the mean number of flatus episodes and of mean abdominal girth was evident.

Conclusions:

In patients with gas‐related symptoms the colonic production of H2 is increased. Rifaximin significantly reduces this production and the excessive number of flatus episodes.
Endoscopic injection of botulinum toxin in patients with recurrent acute pancreatitis due to pancreatic sphincter of Oddi dysfunction
Authors: Wehrmann T. , Schmitt T. H. , Arndt A. , Lembcke B. , Caspary W. F. , Seifert H.
Published: March 2003

Aim:

To evaluate the technical feasibility, safety, and short‐term efficacy of botulinum toxin injection for pancreatic sphincter of Oddi dysfunction and to analyse whether the symptomatic response to botulinum toxin might be a predictor of outcome for endoscopic sphincterotomy.

Methods:

Fifteen consecutive patients (nine female, aged 38 ± 12 years) with frequent attacks (median four) of acute pancreatitis within 6 months, and manometrically proven pancreatic sphincter of Oddi dysfunction underwent endoscopic injection of 100 units of botulinum toxin into the major papilla. All patients underwent prospective follow‐up thereafter and in cases of recurrent pancreatitis manometry this was repeated and pancreatic sphincterotomy was performed.

Results:

No side‐effects occurred after botulinum toxin injection in any patient. Within 3 months after botulinum toxin treatment, 12 out of 15 patients remained asymptomatic (80% primary response). Only one out of three patients without symptomatic benefit showed continued elevated pancreatic sphincter pressure at manometry and only this patient benefited from pancreatic sphincterotomy later on. Eleven of the 12 patients initially responding to botulinum toxin injection developed a symptomatic relapse 6 ± 2 months after botulinum toxin treatment. These patients then achieved long‐term clinical remission from pancreatic or combined (biliary and pancreatic, n=5) sphincterotomy (median follow‐up, 15 months).

Conclusion:

Endoscopic botulinum toxin injection into the papilla of Vater is a safe procedure for treatment of pancreatic sphincter of Oddi dysfunction that may provide short‐term relief in about 80% of the patients. Those patients who respond to botulinum toxin may subsequently gain definitive cure from sphincterotomy.
Multicentre randomized placebo‐controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis
Authors: Almasio P. L. , Floreani A. , Chiaramonte M. , Provenzano G. , Battezzati P. , Crosignani A. , Podda M. , Todros L. , Rosina F. , Saccoccio G. , Manenti F. , Ballardini G. , Bianchi F. P. , Scheuer P. J. , Davies S. E. , Craxì A.
Published: March 2003

Aim:

To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cirrhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilirubin exceeding 2 mg/mL.

Methods:

A total of 90 patients were randomly assigned to ursodeoxycholic acid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid at the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritus, bilirubin, and Mayo score. All patients underwent clinical, ultrasonographic, and biochemical examinations at entry and then every 6 months up to 3 years of follow‐up. Patients with cirrhosis underwent endoscopy every 12 months. In a sub‐group of patients without cirrhosis, who consented, liver biopsy was repeated at the end of the study.

Results:

The number of treatment failures (i.e. dead, orthotopic liver transplantation (OLT), complications of cirrhosis, doubling of bilirubin, untreatable pruritus) was 11 (25%) in the UDCA group and four (9%) in the UDCA/C group (P < 0.05). No significant differences were observed in terms of improvement of liver enzymes related to cholestasis and cytolysis and of amelioration of pruritus. The Mayo score values increased less above the baseline values at 24 and 36 month‐intervals in the UDCA/C group than in the UDCA group. Histological evaluation at baseline and at the end of the study was available for 15 patients with pre‐cirrhotic stage. A significant reduction in histological grading score was observed in patients from the UDCA/C group, whereas no changes in these histological scores were observed in the UDCA group.

Conclusions:

The addition of colchicine to ursodeoxycholic acid in patients with symptomatic primary biliary cirrhosis results in a small but significant reduction of disease progress.
Role of antimicrobial susceptibility testing on efficacy of triple therapy in Helicobacter pylori eradication
Authors: Toracchio S. , Cellini L. , Di Campli E. , Cappello G. , Malatesta M. G. , Ferri A. , Ciccaglione A. F. , Grossi L. , Marzio L.
Published: March 2003

Background:

Helicobacter pylori treatment failure may be due to resistance to macrolides and 5‐nitroimidazoles.

Aim:

To test whether a preliminary in vitro susceptibility test of H. pylori to tinidazole and clarithromycin and a consequent specific regimen could improve the eradication rate.

Methods:

A total of 109 consecutive H. pylori‐positive patients with dyspeptic symptoms were included. At endoscopy, biopsy from the antrum was obtained for H. pylori culture and antimicrobial susceptibility testing. Fifty‐six patients were treated with omeprazole, tinidazole and clarithromycin for 10 days (group OTC) and 53 patients received therapy on the basis of the susceptibility test (group SUSC). Treatment success was evaluated by the 13C‐urea breath test 1 month after the end of therapy.

Results:

Eight patients dropped out. Overall primary resistance to clarithromycin, tinidazole and both antibiotics was 13%, 33% and 4%, respectively. In group OTC, H. pylori was eradicated in 81% and 75% of patients by per protocol and intention‐to‐treat analysis, respectively. Per protocol and intention‐to‐treat eradication rates for group SUSC were 98% and 91% (P < 0.05 vs. group OTC).

Conclusions:

These data show that in H. pylori infection, antibiotic therapy based on the results of culture and susceptibility testing gives, in comparison to standard therapy, a significant improvement in eradication rate.
Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia
Authors: May B. , Köhler S. , Schneider B.
Published: March 2003

Aim:

To assess the efficacy and safety of enteric coated capsules containing a fixed combination of 90 mg peppermint oil and 50 mg caraway oil (PCC; Enteroplant) in patients with functional dyspepsia.

Methods:

A total of 96 out‐patients received one capsule twice daily of PCC or placebo for 28 days. Primary efficacy variables were the intra‐individual change in (i) pain intensity and (ii) sensation of pressure, heaviness and fullness between days 1 and 29, and the investigators’ rating of (iii) global improvement (Clinical Global Impressions [CGI] item 2) on day 29. A global type I error of α=0.05 was controlled by a priori ordering of hypotheses.

Results:

All patients were evaluable for efficacy and safety. On day 29, the average intensity of pain was reduced by 40% vs. baseline in the PCC group and by 22% in the placebo group. With regards to pressure, heaviness and fullness, a 43% reduction was observed for PCC vs. 22% for placebo. In CGI item 2, 67% (PCC) vs. 21% (placebo) of the patients were described as much or very much improved. In all three target parameters, the superiority of PCC over placebo was statistically significant. Six patients (PCC: 5; placebo: 1) reported adverse events, either unrelated to the trial, or attributable to an aggravation of the disease under investigation. Eructation with peppermint taste did not occur.

Conclusion:

These results demonstrate the good tolerability and the favourable risk–benefit ratio of PCC for the treatment of functional dyspepsia.
Rat CXC chemokine GRO/CINC‐1 paradoxically stimulates the growth of gastric epithelial cells
Authors: Suzuki H. , Mori M. , Seto K. , Shibata F. , Nagahashi S. , Kawaguchi C. , Suzuki M. , Matsui H. , Watanabe K. , Miura S. , Ishii H.
Published: March 2003

Background: CXC chemokines such as interleukin (IL)‐8 are neutrophil chemoattractants, the levels of which increase in Helicobacter pylori‐infected gastric mucosa. Many investigators have focused on the chemotactic aspects of IL‐8; however, CXC chemokines are also reported to have angiogenic activity and to serve as remodelling factors. Rat GRO/CINC‐1 is a rodent counterpart of human GROα, a member of the family of CXC chemokines. Gastric mucosa infected with H. pylori is in a state of hyperproliferation, with increases in the amounts of growth factors such as hepatocyte growth factor (HGF).

Aim: To investigate whether rat GRO/CINC‐1 had growth‐stimulating activity for gastric epithelial cells.

Methods: The rat gastric epithelial cell line RGM‐1 was incubated in serum‐free medium for 12 h to adjust the cell cycle to the G0 phase, and GRO/CINC‐1 was then added for 24 h. The total cell number was determined by fluorogenic analysis after propidium iodide staining, and cell proliferation was assessed by measuring 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation. The activity of p42/p44 mitogen‐activated protein kinase (MAPK) was measured 5–20 min after the start of GRO/CINC‐1 exposure.

Results: Cultures treated with GRO/CINC‐1 showed a significant increase in cell number and BrdU incorporation in a concentration‐dependent fashion. The MAPK activity increased within 5 min after GRO/CINC‐1 application and returned to the control level at 20 min.

Conclusion: The growth‐stimulatory effect of GRO/CINC‐1 on rat gastric epithelial cells suggests a dual function of this chemokine: proinflammatory action and induction of epithelial proliferation.