bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of angiotensin II and telmisartan, an angiotensin1 receptor antagonist, on rat gastric mucosal blood flow
Authors: HEINEMANN  , SATTLER  , JOCIC  , WIENEN  , HOLZER
Published: March 2003

Background:

Angiotensin II (ATII) has been suggested to contribute to shock‐induced dysfunction of the gastric circulation.

Aim:

To substantiate this conjecture, the effects on gastric mucosal haemodynamics and the hyperaemic response to acid back‐diffusion of ATII and the angiotensin AT1 receptor antagonist, telmisartan, were examined in normal rats and in animals subjected to haemorrhage.

Methods:

Gastric mucosal blood flow in phenobarbital‐anaesthetized rats was recorded with the hydrogen clearance technique, and acid back‐diffusion was induced by perfusing the stomach with ethanol (25%) in HCl (0.05 M).

Results:

Intravenous infusion of ATII (0.3–10 nmol/min/kg) led to dose‐dependent hypertension and a reduction of blood flow and vascular conductance in the gastric mucosa. The gastric hyperaemia caused by acid back‐diffusion was attenuated by ATII (1 nmol/min/kg). These effects of ATII were antagonized by intravenous injection of telmisartan (1–10 mg/kg) which per se caused hypotension and dilated the gastric mucosal vasculature, but did not modify the gastric mucosal hyperaemia evoked by acid back‐diffusion. Hypotension induced by haemorrhage (1.3 mL blood per 100 g body weight) failed to alter the hyperaemia due to acid back‐diffusion, but caused gastric mucosal vasoconstriction, an effect that was left unaffected by telmisartan.

Conclusions:

ATII constricts the rat gastric microvasculature via an action involving AT1 receptors. The effects of telmisartan indicate that endogenous ATII contributes to the homeostatic regulation of gastric vascular tone but does not compromise the ability of the gastric microvasculature to react to influxing acid. These results negate the concept that ATII contributes to the␣gastric vascular perturbances in haemorrhagic shock.
Low‐dose ranitidine for the relief of heartburn
Authors: PAPPA  , GOOCH  , BUARON  , PAYNE  , GIEFER  , SIRGO  , CIOCIOLA
Published: March 2003

Background

: Approximately 30% of adults in the USA suffer from heartburn or related symptoms monthly; more than 20% of these sufferers experience heartburn at least once per day. Although many rely on self‐medication with antacids for the relief of their symptoms, treatments that decrease gastric volume as well as increase the pH of refluxed material should be more effective in relieving heartburn.

Aim

: To compare the safety and efficacy of low‐dose regimens of ranitidine for the relief of heartburn.

Methods

: Adults with at least a 3‐month history of heartburn were eligible for this randomized, double‐blind, parallel group, multicentre dose‐ranging study. Following a 1‐week open‐label run‐in phase to document baseline heartburn frequency, subjects were randomized to receive treatment with one tablet of either ranitidine 75 mg (n = 491), ranitidine 25 mg (n = 504), or placebo (n = 494), to be taken as needed up to four times daily for 2 weeks for the relief of heartburn.

Results

: The ranitidine 75 mg regimen was clinically (> 10 percentage points) and statistically (P < 0.05) significantly more effective than placebo for all measured efficacy end‐points in relieving heartburn and reducing antacid consumption. In addition, the ranitidine 75 mg regimen was superior to placebo in providing heartburn relief within 30 min of dosing that lasted for up to 12 h. Ranitidine 25 mg was observed to be statistically superior (P < 0.05) but not clinically different from placebo, as defined a priori, in providing heartburn relief. All treatments were well tolerated and adverse events occurred no more frequently with the ranitidine regimens than with placebo.

Conclusions

: Ranitidine 75 mg provides prompt relief of heartburn that lasts for up to 12 h and has a safety profile comparable to that of placebo.
Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection
Authors: KASHIMURA  , SUZUKI  , HASSAN  , IKEZAWA  , SAWAHATA  , WATANABE  , NAKAHARA  , MUTOH  , TANAKA
Published: March 2003

Aim

: To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7‐day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori.

Methods

: Sixty‐six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment.

Results

: Five patients did not complete the treatment: no follow‐up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72–100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P < 0.05). On intention‐to‐treat analysis, the rates of eradication were 24 of 31 patients (77%; 95% CI: 62–93%) in the LAC group, and 33 of 35 patients (94%; 95% CI: 86–100%) in the LACP group (P < 0.05).

Conclusion

: A 7‐day triple therapy with lansoprazole, amoxycillin and clarithromycin is effective in H. pylori eradication, but this regimen is significantly improved by the addition of polaprezinc.
Altered oesophageal motility following the administration of the 5‐HT1 agonist, sumatriptan
Authors: Foster  , Houghton  , Whorwell  , Morris
Published: March 2003

Background

: The 5‐HT1 agonist sumatriptan, used in the treatment of migraine, can cause chest pain.

Aim

: To investigate the effect of a therapeutic dose of sumatriptan (6 mg s.c.) on oesophageal motility.

Methods

: In 16 normal healthy subjects aged 19–32 years (9 males), the manometric response of the lower oesophageal sphincter (sleeve sensor), oesophageal body (four sites), stomach and pharynx (to register swallows) to 5 mL water swallows was assessed before and after a subcutaneous injection of either sumatriptan (6 mg) or saline control. Symptoms and ECGs were also monitored.

Results

: Sumatriptan 6 mg s.c. altered oesophageal motility in all subjects. This was reflected by a significant increase in the amplitude of oesophageal body contractions (change from pre‐ to 1 h post‐injection: sumatriptan 9.9 (2.8, 17.1) mmHg vs. placebo – 0.8 (– 4.2, 2.6) mmHg, difference 10.8 (4.4, 17.1) mmHg; P=0.003) and a transient increase in lower oesophageal sphincter pressure (change from pre‐ to 5 min post‐injection: sumatriptan 10.9 (5.2, 16.6) mmHg vs. placebo 5.1 (1.8, 8.4) mmHg, difference 5.8 (– 0.7, 12.3) mmHg; P=0.08). Sumatriptan had no effect on the velocity of propagation of oesophageal contractions (change from pre‐ to 1 h post‐injection: sumatriptan – 0.1 (– 0.3, 0.1) cm/s vs. placebo – 0.1 (– 0.3, 0.0) cm/s, difference 0.1 (– 0.1, 0.2) cm/s; P = 0.40). One subject experienced chest symptoms following sumatriptan and, although motility was altered, this did not reach pathological levels. No ECG abnormalities were observed.

Conclusion

: Sumatriptan (6 mg s.c.) significantly alters oesophageal motor function without affecting the ECG. It is therefore possible that sumatriptan‐induced chest symptoms may have an oesophageal origin. The evaluation of similar therapeutic agents for migraine on oesophageal function may be justified.
Long‐term haemodynamic effects of octreotide on postprandial splanchnic hyperemia in humans: a placebo‐controlled echo–doppler study
Authors: Ludwig  , Terai  , Brüning  , Stange
Published: March 2003

Background

: Octreotide is a potent splanchnic hypotensive somatostatin analogue effective in the treatment of acute variceal bleeding.

Aim

: To study the effects of octreotide on basal and postprandial splanchnic and systemic haemodynamics, and hormonal changes in humans.

Methods

: Twenty‐four healthy volunteers were randomized to receive a liquid meal and either octreotide (OCT, 100 μg bolus) or placebo repeatedly every 4 h for 48 h. Splanchnic (Doppler ultrasound) and systemic haemodynamics (non‐invasive cardiac monitoring) were assessed for 2 h on four consecutive days: one control day and after doses 1 (0 h), 7 (24 h) and 13 (48 h).

Results

: The maximum postprandial increases in mean blood velocity of the superior mesenteric artery (SMA–Vmean + 72%), portal (PBF + 52%) and total hepatic blood flow (HBF + 50%) observed in the placebo group, were abolished after the first dose of octreotide (SMA–Vmean – 23%, P < 0.01; PBF – 22%, P < 0.01; HBF – 21%, P < 0.01). Postprandial hyperemia was restored at the end of the 48‐h study period, but baseline SMA–Vmean (placebo 40 ± 12, OCT 29 ± 11 cm/s, P < 0.05) and PBF (placebo 1200 ± 971, OCT 743 ± 449 mL/min, P < 0.05) remained significantly lower in the octreotide group. The postprandial decrease of systemic vascular resistance and increase of cardiac index were prevented by octreotide for 48 h.

Conclusions

: Repeated 4‐hourly bolus injections of octreotide reduce splanchnic blood flow for at least 48 h, but the prevention of food‐induced splanchnic hyperemia is short‐lasting.
Selective COX‐2 inhibitors and human inflammatory bowel disease
Authors: Mccartney  , Mitchell  , Fairclough  , Farthing  , Warner
Published: March 2003

Background

: Much recent effort has been made to produce selective inhibitors of cyclo‐oxygenase‐2 (COX‐2) in the belief that these will lack the gastrointestinal damaging effects of traditional non‐steroidal anti‐inflammatory drugs (NSAIDs). Inflammatory bowel disease is associated with increased local production of prostanoids. These prostanoids, particularly PGE2 and PGI2, may well be protective as inflammatory bowel disease is aggravated by NSAID use.

Aim

: To examine the effects of a traditional NSAID and a highly selective COX‐2 inhibitor on the production of these prostanoids in human inflammatory bowel disease.

Methods

: Colonic mucosal biopsies were obtained from patients undergoing routine colonoscopy and biopsy for diagnostic or surveillance purposes. Biopsies were incubated in culture medium containing 10% foetal calf serum and antibiotics, plus test drugs or vehicle for 24 h, after which time the medium was removed and the content of PGE2, PGI2 (measured as 6 keto‐PGF1α) and thromboxane (Tx) A2 (measured as TxB2) determined.

Results

: Biopsies obtained from diseased colonic mucosa produced significantly more PGE2, PGI2 and thromboxane A2 than did controls (for example, PGE2: ulcerative colitis, 4.17 ± 1.06; Crohn’s disease, 3.97 ± 1.66; control, 0.12 ± 0.13 ng/mL, n=8–12). These increases were inhibited to a similar extent by either a highly selective COX‐2 inhibitor (L‐745 337) or a traditional non‐selective NSAID (indomethacin).

Conclusions

: Until selective COX‐2 inhibitors have been assessed adequately in human inflammatory bowel disease, these compounds should not be assumed to be safe for the gastrointestinal tract in inflammatory bowel disease.
Early experience with intrasphincteric botulinum toxin in the treatment of achalasia
Authors: Greaves  , Mulcahy  , Patchett  , Gorard  , Fairclough  , Alstead  , Farthing
Published: March 2003

Background

: Recent reports have suggested that intrasphincteric injection of botulinum toxin is effective and long‐lasting in the treatment of achalasia.

Aim

: To report our experience of botulinum toxin injection in a prospective series of consecutive patients with achalasia.

Methods

: Eleven consecutive patients with achalasia (eight male, mean age 55 years, range 20–87) were treated with 60 units of botulinum toxin (Dysport; Speywood Pharmaceuticals Ltd, UK) into each of four quadrants at the lower oesophageal sphincter. Patients were assessed pre‐treatment and 1 month after treatment using a symptom score and oesophageal manometry. Median follow‐up was 12 months (range 6–28).

Results

: The injection procedure was simple to perform and free of adverse effects. Although treatment had a beneficial effect on dysphagia (median pre‐treatment score 3 [interquartile range 3–3]; post‐treatment score 2 [0–3]: P=0.03) 1 month following therapy, there was no significant improvement in chest pain or regurgitation scores. Similarly, no significant reduction in median lower oesophageal sphincter pressure was observed (29.5 mmHg [21–42] pre‐treatment, 28.5 [17.5–55.5] post‐treatment P=0.67). Four patients (36%) required further therapy within 3 months and the overall relapse rate was 73% (eight of 11) within 2 years.

Conclusion

: Although botulinum toxin injection was well tolerated, these results using Dysport at a dose of 240 mouse units question its efficacy as a treatment for achalasia.
Reduction of the nociceptive response to gastric distension by nitrate ingestion in rats
Authors: Rouzade  , Anton  , Fioramonti  , Garcia‐Villar  , Theodorou  , Bueno
Published: March 2003

Background

: Dietary nitrates are known to produce nitric oxide in the stomach, which may influence gastric function.

Aim

: To investigate whether nitrate ingestion modifies gastric sensitivity to distension through a mechanism involving nitric oxide production.

Methods

: Nociception, associated with gastric distension ranging from 10 to 40 mmHg, was assessed in anaesthetized rats by the amplitude of cardiovascular depressor responses. Gastric volume corresponding to each distension was recorded. The following intragastric administrations (1 mL) were performed before distension: water (control), KNO3, NaNO3, KCl, NaCl (all at 0.1 mmol/kg), standard food (0.5 g), sodium nitroprusside, a nitric oxide donor (5 mg/kg), and haemoglobin, a nitric oxide scavenger (150 mg/kg) given either with water or KNO3.

Results

: In controls, the fall in blood pressure increased from 7.8 ± 2.0 to 31.6 ± 2.7 mmHg at distending pressures from 10 to 40 mmHg, respectively. KNO3 significantly reduced the amplitude of blood pressure response for the highest distending pressures (35 and 40 mmHg), while KCl induced a reduction in blood pressure response at all gastric pressures. NaNO3 and NaCl did not induce significant changes in distension‐induced depressor responses. Administration of 0.5 g of standard food or sodium nitroprusside reproduced the effect of KNO3, which was reversed by haemoglobin. None of the compounds modified the gastric pressure–volume relationship, except KNO3, which increased gastric volume for the lowest distending pressures, and haemoglobin, which reduced the volume for the highest pressure.

Conclusions

: Ingestion of potassium nitrate reduces the sensitivity to gastric distension, through a mechanism involving nitric oxide.
Mycophenolate mofetil: lack of efficacy in chronic active inflammatory bowel disease
Authors: Fellermann  , Steffen  , Stein  , Raedler  , Hämling  , Ludwig  , Loeschke  , Stange
Published: March 2003

Background:

Mycophenolate mofetil (MMF) is a new immunosuppressant with pharmacodynamic properties comparable to azathioprine. Recent reports found MMF to be effective in inflammatory bowel disease (IBD).

Methods:

An open‐label prospective and uncontrolled multicentre 6 month trial of MMF in combination with steroids was conducted in 24 chronic active IBD patients. A daily steroid demand of ≥ 10 mg prednisone in the preceding 2 months and a Crohn’s disease activity index (CDAI) > 150, or moderate to severe activity according to Truelove, served as criteria for chronic activity. The treatment consisted of a steroid pulse and tapering protocol in combination with MMF 2 g/day. A prednisone dose of 5 mg/day was maintained during months 4–6. The primary end‐point was induction and maintenance of remission.

Results:

Only 10 of 24 patients had achieved remission after 3 months. All but one Crohn’s disease patient had relapsed by the end of the study at 6 months. Depression and migraine necessitated drug withdrawal in two patients.

Conclusion:

In conclusion, MMF 2 g/day was unable to induce and maintain remission for a period of 6 months in 23 of 24 chronic active IBD patients. Further controlled investigations are required in view of recent conflicting reports.
Open label trial of oral clarithromycin in active Crohn’s disease
Authors: Leiper  , Morris  , Rhodes
Published: March 2003

Background:

Crohn’s disease seems likely to be due in some way to bacteria. Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn’s disease.

Methods:

Twenty‐five patients with active Crohn’s disease were treated with oral clarithromycin 250 mg b.d. in an open label study. Treatment was for an initial 4‐week period, continued to 12 weeks in patients who had shown a partial or complete response. The patients had a median age of 30 years (range 17–72), and disease duration of 5 years (range 2 months–28 years); 14 had ileocolonic, four small bowel, seven colonic disease and 10 had previous resections. Twenty patients were receiving a 5‐ASA preparation, 15 corticosteroids (prednisolone median dose 10 mg range 2–30 mg) and nine azathioprine. All patients receiving corticosteroids or azathioprine had been on unchanged treatment for at least 12 weeks.

Results:

Median pre‐treatment Harvey Bradshaw index (HBI) was 9 (range 5–16) and median serum C‐reactive protein was 21.5 mg/L (range < 5–117). By 4 weeks the median HBI had decreased to 5 (range 0–18) (P < 0.001) and median CRP to 17 mg/L (range < 5–157) (P=0.16). Sixteen patients (64%) had at least a 3 point fall in HBI and remission (defined as a HBI less than or equal to 4) was achieved in 12 patients (48%). By 12 weeks median HBI was 5 (range 0–18) (P < 0.001) and median CRP was 14.5 mg/L (range < 5–157) (P=0.05). Eleven of the 25 patients studied continued on oral clarithromycin after 12 weeks for a median of 28 weeks (range 20–60). Eight (73%) remained in remission on treatment. When treatment with clarithromycin was stopped three remained in remission and five relapsed after a median of 5 months (range 4–9). Two patients withdrew due to non‐serious side‐effects. Treatment was well tolerated in the remaining patients.

Conclusion:

This open label study has shown an impressive response to clarithromycin in a group of patients with active Crohn’s disease, many of whom had been resistant to other therapy. A formal randomized controlled trial of clarithromycin in active Crohn’s disease is needed.
Tepoxalin inhibits inflammation and microvascular dysfunction induced by abdominal irradiation in rats
Authors: Panés  , Mollà  , Casadevall  , Salas  , Sans  , Conill  , Anderson  , Roselló‐Catafau  , Granger  , Piqué
Published: March 2003

Background:

Inflammatory cells contribute to the acute and sub‐acute sequelae of radiation therapy. Tepoxalin, an inhibitor of cyclooxygenase and 5‐lipoxygenase that suppresses NF–κB activation, has potent anti‐inflammatory activity.

Aims:

To assess the effects of tepoxalin on radiation‐induced inflammatory damage, and determine its mechanisms of action.

Methods:

Leucocyte rolling, adhesion and emigration, and albumin leakage were determined by intra‐vital microscopy in rat mesenteric venules. NF–κB activation was measured by electrophoretic mobility shift assays, and endothelial intercellular adhesion molecule‐1 expression by the radiolabelled antibody technique. Groups of irradiated rats were treated with tepoxalin, N‐acetyl‐ L‐cysteine, zileuton (lipoxygenase inhibitor), or vehicle.

Results:

Irradiated animals had a marked increase in the number of rolling, adherent and emigrated leucocytes in mesenteric venules, and in microvascular permeability. Tepoxalin prevented leucocyte adhesion and the increase in permeability after radiation. Tepoxalin did not inhibit radiation‐induced NF–κB activation or intercellular adhesion molecule‐1 up‐regulation, while N‐acetyl‐ L‐cysteine, which attenuated NF–κB activation, had no effect on leucocyte recruitment. In contrast, tepoxalin inhibited the increase in leukotriene B4 levels after radiation, and the anti‐inflammatory effects of the drug were mimicked by zileuton.

Conclusions:

Tepoxalin affords significant protection against radiation‐induced inflammation and microvascular dysfunction in splanchnic organs through a mechanism dependent on leukotriene synthesis inhibition.
Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study
Authors: Katelaris  , Adamthwaite  , Midolo  , Yeomans  , Davidson  , Lambert
Published: March 2003

Background:

The efficacy of omeprazole‐based eradication therapies has been determined mostly in populations with low to moderate prevalence of metronidazole resistant Helicobacter pylori, yet resistance is high in many regions.

Aim and Methods:

The H. pylori eradication and duodenal ulcer healing rates after 1 week of either omeprazole 40 mg mane, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM) or omeprazole 20 mg b.d., metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC) were compared in a randomized trial in Australia and New Zealand. Patients had a further 1 week of omeprazole 20 mg. Outcome was assessed at 6 weeks with stringent criteria (endoscopy, biopsies and 13C‐urea breath test).

Results:

Of 220 subjects randomized, the H. pylori eradication rates (all patients treated/per protocol) were 82%/85% for OMC and 58%/63% for OAM (P= 0.001). Pre‐treatment metronidazole resistance was present in 56% and clarithromycin resistance in 6%. The eradication rate for primary metronidazole resistance isolates treated with OMC was 80% (CI: 65–90%) compared with 45% (CI: 29–62%) for OAM, whereas for sensitive organisms, the eradication rates were 94% (CI: 79–99%) and 79% (CI: 62–91%), respectively. Duodenal ulcer healing was 96% for OMC and 87% for OAM. Compliance was excellent and both treatments were well‐tolerated.

Conclusions:

OMC is a well‐tolerated, effective therapy for H. pylori eradication and duodenal ulcer healing in this region despite the high metronidazole resistance rate. OAM is less effective, largely due to the impact of metronidazole resistance.
Eradication of Helicobacter pylori with pantoprazole and two antibiotics: a comparison of two short‐term regimens
Authors: Frevel  , Daake  , Janisch  , Kellner  , Krezdorn  , Tanneberger  , Wack
Published: March 2003

Background:

High rates of Helicobacter pylori eradication can be achieved by combining proton pump inhibitors with two antibiotics. However, in the search for an optimal therapy a direct comparison of different regimens is necessary.

Methods:

For this open study, 331 patients with duodenal ulcer were screened and randomly allocated to either pantoprazole 40 mg b.d., clarithromycin 500 mg b.d., and metronidazole 500 mg b.d. (PCM) or pantoprazole 40 mg b.d., amoxycillin 1000 mg b.d., and clarithromycin 500 mg b.d. (PAC) for 7 days. Both combinations were followed by a 7‐day therapy with pantoprazole 40 mg o.d. alone. Eradication of H. pylori was assessed by use of a 13C‐urea breath test 4 weeks after the intake of the last medication.

Results:

Eradication rates were 90% in intention‐to‐treat patients from the PCM (132 out of 147; 95% CI: 84–94%) and the PAC group (135 out of 150; 95% CI: 84–94%). H. pylori was eradicated in 112 out of 117 per protocol patients of the PCM group (96%; 95% CI: 90–99%) and in 119 out of 126 patients of the PAC group (94%; 95% CI: 89–98%). Rapid relief from ulcer pain and a decrease in the mean intensity of other gastrointestinal symptoms was observed. Sixty‐nine patients reported adverse events, none of which were related to the intake of pantoprazole. Four serious adverse events, none related to the trial medication, were observed.

Conclusions:

Both pantoprazole‐based short‐term triple therapies are highly effective and well‐tolerated treatment regimens in the eradication of H. pylori.
Impaired contractile response of mesenteric arteries in Crohn’s disease
Authors: Lebuffe G. , Haddad E. , Desreumaux P. , Gambiez L. , Colombel J. F. , Vallet B.
Published: March 2003

Background:

Crohn’s disease is associated with vascular injury and dysregulation of the intestinal immune system which together can provide disturbance of mesenteric circulation functional properties.

Aim:

To evaluate the vascular reactivity of mesenteric arteries from patients with Crohn’s disease.

Methods:

Phenylephrine‐induced contractions were assessed from 10 patients with Crohn’s disease and 8 control organ donors. NG‐nitro‐L‐arginine‐methyl‐ester (L‐NAME) was used to test the presence of inducible NO synthase. Endothelium dependent and independent relaxation was assessed using acetylcholine, bradykinin, calcium ionophore A23187 and sodium nitroprusside.

Results:

The contractile response to phenylephrine was significantly decreased in arteries without endothelium from patients with Crohn’s disease. Exposure to the NO synthase inhibitor L‐NAME restored the contractile response to phenylephrine. Relaxation remained unaltered in both groups.

Conclusion:

These data provide direct evidence for fading of contraction caused by phenylephrine in Crohn’s disease. The restored mesenteric artery tone by a specific NO synthase inhibitor suggests that an increased production for NO in vascular smooth muscle might be responsible of this altered vascular reactivity.
Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study
Authors: Zullo A. , Rinaldi V. , Hassan C. , Diana F. , Winn S. , Castagna G. , Attili A. F.
Published: March 2003

Background:

Intestinal type metaplasia plays a role in intestinal type gastric carcinoma development. Ascorbic acid demonstrates a protective effect against gastric carcinogenesis, due to its ability to inactivate oxygen free‐radicals as well as its nitrite‐scavenging effects.

Aim:

To assess whether long‐term ascorbic acid administration following Helicobacter pylori eradication could affect intestinal metaplasia regression in the stomach.

Methods:

Sixty‐five patients were included in the study. The inclusion criterion was the presence of intestinal metaplasia on the gastric mucosa after H. pylori eradication. An upper gastrointestinal endoscopy was performed and 3 biopsy specimens were taken in the antrum, 3 in the gastric body, and 2 in the incisura angularis. Patients were randomized to receive 500 mg of ascorbic acid o.d., after lunch (32 patients) for 6 months or no treatment (33 patients). All patients underwent to endoscopic control at the end of the 6 months.

Results:

H. pylori infection recurrence was detected in 6 (9.4%) patients (three from each group), and these patients were excluded from further analysis. We were unable to find evidence of intestinal metaplasia in any biopsied site of the gastric mucosa in 9/29 (31%) patients from the ascorbic acid group and in 1/29 (3.4%) of the patients from the control group (P=0.006). Moreover, a further six (20.7%) patients from the ascorbic acid group presenting chronic inactive pangastritis with widespread intestinal metaplasia at entry, showed less extensive antritis with intestinal metaplasia at control, whilst a similar finding was only seen in one patient from the control group (P=0.051).

Conclusion:

The administration of ascorbic acid significantly helps to resolve intestinal metaplasia of the gastric mucosa following H. pylori eradication, and its use as a chemoprevention treatment should be considered.
Omeprazole 40 mg once a day is equally effective as lansoprazole 30 mg twice a day in symptom control of patients with gastro‐oesophageal reflux disease (GERD) who are resistant to conventional‐dose lansoprazole therapy—a prospective, randomized, multi‐centre study
Authors: Fass R. , Murthy U. , Hayden C. W. , Malagon I. B. , Pulliam G. , Wendel C. , Kovacs T. O. G.
Published: March 2003

Background:

Comparative studies of omeprazole and lansoprazole are scarce and even scarcer are comparisons of higher doses. Most of the comparative studies have assessed the effect of the two proton pump inhibitors (PPIs) on gastric acid secretion or gastric pH. Few studies have compared clinical end‐points such as oesophageal healing and symptom control.

Aim:

To determine the clinical efficacy of omeprazole 40 mg daily as compared to lansoprazole 30 mg twice a day in symptom control of patients with severe symptomatic GERD.

Methods:

Ninety‐six patients who failed a standard dose of lansoprazole (30 mg once daily), were enrolled in a prospective fashion from three VA medical centres and were randomized to receive 6 weeks of either omeprazole 40 mg daily or lansoprazole 30 mg twice daily. Patients reported daily on symptom severity and frequency, antacid consumption and side‐effects.

Results:

Forty‐six patients received omeprazole and 44 lansoprazole. Although not statistically significant, there was a consistent trend of better symptom control in the omeprazole group for daytime and night‐time heartburn and acid regurgitation. There was no statistical difference between the two groups in mean antacid consumption overall and at the end of each of the 6 weeks of the study. In addition, there was no significant difference in the overall frequency of side‐effects between the two groups nor for each individual side‐effect.

Conclusion:

Omeprazole 40 mg once daily is equally effective and tolerated as lansoprazole 30 mg twice daily in symptom control of patients with GERD.
Review article: cyclooxygenase – a target for colon cancer prevention
Authors: Dubois R. N.
Published: March 2003

Use of nonsteroidal anti‐inflammatory drugs such as aspirin, which are known to inhibit cyclooxygenase activity, reduces the relative risk of colorectal cancer in humans by 40–50%. Animal and human studies have shown a 50–80% reduction in tumour multiplicity following treatment with a variety of nonsteroidal anti‐inflammatory drugs. Two isoforms of cyclooxygenase have been described, cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2). In 85% of colorectal adenocarcinomas taken from humans, COX‐2 levels are 2–50‐fold higher than levels in adjacent normal intestinal mucosa, while COX‐1 levels are unchanged. These observations raise the question: Does COX‐1 or COX‐2 provide a useful target for prevention or treatment of colorectal cancer?
Review article: the stages of gastrointestinal carcinogenesis – application of rodent models to human disease
Authors: Pitot H. C. , Hikita H. , Dragan Y. , Sargent L. , Haas M.
Published: March 2003

The development of gastrointestinal cancer in humans and animals occurs through a consecutive series of stages termed initiation, promotion and progression. The characterization of each of these stages has been elucidated in several model systems as well as in human neoplasms.

Both single, putatively initiated cells and preneoplastic foci have been identified by marker protein differences as well as by mutational changes.

The promotion stage involves the clonal expansion of single initiated cells. Such expansion can be rapidly reversed by a variety of means, of which acute fasting (as exemplified in rat hepatocarcinogenesis) is among the most rapid and efficient. This reversal involves a selective apoptosis of preneoplastic cells and preneoplastic lesions, associated with a marked increase in expression of the proto‐oncogene c‐myc.

Transition of cells from the stage of promotion to that of progression initially involves specific karyotypic alterations, as noted in both the rat liver model and human colon carcinogenesis. In the former, the transition appears to be associated with enhanced expression of the H119 imprinted putative tumour suppressor gene.

Thus, the use of model systems may be applied directly to the human circumstance, increasing the potential both for rational prevention of gastrointestinal neoplasia and for new approaches to the therapy of neoplastic disease in the progression stage.
Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cells
Authors: Mutoh H. , Ratineau C. , Ray S. , Leiter A. B.
Published: March 2003

Secretin‐producing enteroendocrine cells arise from a multipotential endocrine progenitor in the crypts of the small intestine. As these cells migrate up the crypt‐villus axis, they produce secretin and stop dividing as they terminally differentiate and die. Transcription of the secretin gene is controlled by a complex enhancer binding to multiple transcription factors. The basic helix‐loop‐helix protein, BETA2, binds to an E box sequence and associates with the p300 coactivator to activate transcription of the secretin gene. Basic helix‐loop‐helix proteins appear to play a pivotal role in the control of cellular differentiation. BETA2 induces cell cycle arrest and apoptosis in addition to activating secretin gene expression. Thus BETA2 may function as a master regulatory gene to coordinate terminal differentiation of secretin cells.
A novel in vitro effect of the mucosal protective agent sofalcone – inhibition of chemotactic motility in Helicobacter pylori
Authors: Yoshiyama H. , Nakamura H. , Okamoto T. , Okita K. , Nakazawa T.
Published: March 2003

Background: Motility of Helicobacter pylori is essential for colonization. H. pylori has been shown to exhibit chemotactic activity toward urea and sodium and bicarbonate ions, which are secreted from the gastric epithelia. The importance of urease activity for chemotactic motility of H. pylori in a viscous environment has also been shown. Consequently, application of drugs inhibiting chemotactic motility has been proposed as a strategy for H. pylori eradication. This inhibitory effect can be evaluated through assay of chemotaxis and swarming.

Materials and methods: H. pylori CPY3401 and ATCC43504 were grown on brucella agar plates/broth supplemented with 3% horse serum under microaerobic conditions (N2, 85%; O2, 5%; CO2, 10%). For motility assay, H. pylori cells grown on brucella‐serum agar were stabbed into motility agar containing 0.35% refined agar in brucella‐serum broth and the swarming zone was measured. For the chemotaxis assay, cells were suspended in 10 m
m potassium phosphate buffer, pH 7.0, with 3% polyvinyl‐ pyrrolidone and assayed as described previously. Bacterial swimming in the fluid environment was observed under dark‐field microscopy.

Results: Numbers of bacteria attracted toward 1 μm flurofamide were reduced with increasing con‐ centrations of sofalcone (0.2–222 μm). In addition, the size of the swarming zone was reduced in motility agar containing 22 and 222 μm sofalcone. On the other hand, 22 μm sofalcone did not inhibit bacterial growth on day 3. Bacterial swimming speed in brucella broth was slower in the presence of 22 and 222 μm sofalcone than in its absence.

Conclusion: Sofalcone was found to inhibit chemotactic motility of H. pylori. This drug may be useful for inhibiting the bacterium's ability to colonize the human stomach.
Effect ofLactobacillusingestion on the gastrointestinal mucosal barrier alterations induced by indometacin in humans
Authors: Gotteland M. , Cruchet S. , Verbeke S.
Published: March 2003

Background:

Chronic nonsteroidal anti‐inflammatory drug (NSAID) ingestion strongly affects the gastrointestinal mucosa as a first stage before ulceration. SomeLactobacillusstrains may stabilize the mucosal barrier by increasing mucin expression, reducing bacterial overgrowth, stimulating mucosal immunity and synthetizing antioxidant substances; these events are altered in NSAID‐associated gastroenteropathy.

Aim:

To determine whether ingestion of the probioticLactobacillusGG (LGG) protects the gastrointestinal mucosa against indometacin‐induced alterations of permeability.

Subjects and methods:

Four gastrointestinal permeability tests were carried out in random order in 16 healthy volunteers: (i) basal; (ii) after indometacin; (iii) after 5 days of living LGG ingestion before indometacin administration; (iv) after 5 days of heat‐killed LGG ingestion before indometacin administration.

Results:

Indometacin significantly increased basal sucrose urinary excretion (29.6 mg [17.1–42.1] vs. 108.5 mg [68.2–148.7],P=0.0030) (means [95% CI]) and lactulose/mannitol urinary excretion (1.03% [0.73–1.32] vs. 2.93% [1.96–3.90],P=0.00012). Heat‐killed LGG did not modify the indometacin‐induced increase of gastrointestinal permeability, while live bacteria significantly reduced the alteration of gastric (47.8 mg [31.1–64.6],P=0.012) but not intestinal permeability induced by NSAID.

Conclusions:

Regular ingestion of LGG protects the integrity of the gastric mucosal barrier against indometacin, but has no effect at the intestinal level.
Validation of a new immunoblot assay for the diagnosis of Helicobacter pylori in the Asian population
Authors: Leung W. K. , Chow T. P. , Ng E. K. W. , Chan F. K. L. , Chung S. C. S. , Sung J. J. Y.
Published: March 2003

Background:

Performance of commercial serological tests for Helicobacter pylori varies in different populations, largely due to strain heterogeneity and variations in antigenic preparations. Currently available serology tests often show sub‐optimal accuracy when used for Asian patients.

Aim:

This study evaluated a recombinant antigen‐based immunoblot for the diagnosis of H. pylori infection in Chinese patients, and compared it with a conventional ELISA test.

Methods:

Dyspeptic patients referred for diagnostic endoscopy were recruited. The gold standard for H. pylori infection was based on two or more positive results among rapid urease test, histology and 13C‐urea breath test. Serological diagnosis of H. pylori infection was conducted by an ELISA test (pylori DTect; Diagnostic Technology) and an immunoblotting against a novel recombinant antigen (C1S; Genelab), which was constructed by immunological screening of the genomic DNA library of H. pylori.

Results:

A total of 87 patients were evaluated and H. pylori infection was diagnosed in 40 (46%) by the reference tests. The sensitivities of the ELISA and immunoblot were 80% (95% CI: 64–91%) and 90% (95% CI: 76–97%), whilst the specificities were 96% (95% CI: 86–96%) and 87% (95% CI: 74–95%), respectively. The respective likelihood ratios of the two tests were 18.6 and 7.0.

Conclusions:

Satisfactory performance is obtained by the use of the new recombinant antigen‐based immunoblot for diagnosing H. pylori infection in Chinese patients.
Effect of food on the pharmacokinetics of budesonide controlled ileal release capsules in patients with active Crohn’s disease
Authors: Lundin P. , Naber T. , Nilsson M. , Edsbäcker S.
Published: March 2003

Aim:

To study the influence of food on the systemic availability of budesonide in patients with active Crohn’s disease.

Methods:

Eight patients with an established diagnosis of Crohn’s disease each received 9 mg budesonide controlled ileal release (CIR) capsules (Entocort capsules) orally on two separate occasions: once in a fasting state and once after a heavy breakfast. For reference, deuterium‐labelled (2H8) budesonide, 0.5 mg, was given intravenously. Plasma concentrations of budesonide and 2H8‐budesonide were determined for 12 h, and their pharmacokinetic parameters were calculated.

Results:

Average systemic availability of budesonide during fasting conditions was 10.7%, area under the curve was 27.5 nmol/L × h and peak plasma concentration was 4.1 nmol/L. Corresponding postprandial values were 13.2%, 27.0 nmol/L × h and 3.8 nmol/L. Food increased the mean absorption time from 4.5 to 6.8 h (P=0.0012). Body clearance of budesonide was about 25% higher after eating (P=0.0015).

Conclusions:

Food had little influence on systemic availability and peak plasma concentrations of budesonide administered in CIR capsules. Absorption was retarded postprandially, likely due to delayed gastric emptying. Budesonide in CIR capsules can be administered at the same dose regardless of prandial status in patients with Crohn’s disease.
Changing patterns of sedation use for routine out‐patient diagnostic gastroscopy between 1989 and 1998
Authors: Mulcahy H. E. , Hennessy E. , Connor P. , Rhodes B. , Patchett S. E. , Farthing M. J. G. , Fairclough P. D.
Published: March 2003

Background:

Knowledge of sedation trends for upper gastrointestinal endoscopy is important for health service planning, particularly in view of rapidly increasing demands on endoscopy services. However, no data are available on sedation trends in Britain over the past 10 years.

Aim:

To determine sedation use for routine gastroscopy in a single endoscopy unit between 1989 and 1998.

Methods:

This was a retrospective study of 9795 consecutive adults (mean age 56 years, range 18–100 years; 4512 females) who had undergone a gastroscopy between 1989 and 1998. Clinical, pharmacological and endoscopic data were retrieved from a computerized database.

Results:

Over the 10‐year study period, the sedation rate remained constant for patients undergoing therapeutic endoscopy (P=0.99) and those undergoing in‐patient diagnostic examinations (P=0.63). In contrast, the sedation rate for out‐patient diagnostic endoscopy decreased by 54%, from a high of 70% in 1990 to 32% in 1998 (P < 0.0001). Logistic regression analysis showed that the decline in sedation use was greater in females (P < 0.0001) than males and in procedures performed by non‐consultant compared to consultant staff (P=0.01).

Conclusions:

If our results form part of a national trend, they will have important implications for cardiopulmonary monitoring strategies, recovery room practices and for complication rates due to the use of sedation for upper gastrointestinal endoscopy.
Sildenafil inhibits gastroduodenal motility
Authors: Bortolotti M. , Mari C. , Lopilato C. , La Rovere L. , Miglioli M.
Published: March 2003

Background:

Sildenafil shows an intense and prolonged inhibitory effect on the smooth muscle cells of corpus cavernosum arterioles by blocking phosphodiesterase‐type 5, which inactivates the nitric oxide‐stimulated cyclic guanosine monophosphate.

Aim:

To investigate whether this inhibitory effect is also displayed on the musculature of the gastroduodenal tract.

Methods:

In 16 normal subjects, antroduodenal motility was recorded by means of a low‐compliance manometric system. Ten minutes after the appearance of a phase III of the migrating motor complex, a tablet of sildenafil 50 mg, dissolved in 20 mL of water, was infused in the gut of eight patients, or a placebo in the other eight patients, randomly and in a double‐blind manner, continuing the recording for 90 min. The frequency and amplitude of antral and duodenal waves, measured during the first 60 min after infusion in the two groups, were compared statistically. In addition, the duration of antral and duodenal phases I, and the number of phases III occurring during the whole 90 min after infusion, were compared in the two groups.

Results:

Antral and duodenal wave frequency and amplitude were significantly lower during the first 60 min after sildenafil administration. Both antral and duodenal phases I were significantly longer after sildenafil than after placebo, and the number of phases III which occurred during the 90 min after sildenafil was significantly lower than after placebo.

Conclusions:

Sildenafil inhibits interdigestive motor activity of the antrum and duodenum.
Five‐day proton pump inhibitor‐based quadruple therapy regimen is more effective than 7‐day triple therapy regimen for Helicobacter pylori infection
Authors: Nagahara A. , Miwa H. , Yamada T. , Kurosawa A. , Ohkura R. , Sato N.
Published: March 2003

Background:

There have been no reports that describe whether 5‐day quadruple therapy (rabeprazole + amoxicillin + clarithromycin + metronidazole; RACM) could substitute for standard 7‐day triple therapy as a first‐line therapy for Helicobacter pylori.

Patients and methods:

This study was designed as a randomized prospective single centre study. A total of 160 H. pylori‐positive patients who had not received therapy were given either a 5‐day RACM regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d.) or a 7‐day RAC regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d. and clarithromycin 200 mg b.d.). Cure of the infection was assessed by a 13C urea breath test 1 month after the completion of therapy.

Results:

The eradication rates of the 5‐day RACM regimen and the 7‐day RAC regimen were 93% (95% CI: 84–97%) and 81% (95% CI: 71–89%) by intention‐to‐treat analysis, 94% (95% CI: 86–98%) and 83% (95% CI: 73–91%) by all‐patients‐treated analysis analysis and 95% (95% CI: 87–98%; P < 0.05) and 82% (95% CI: 72–90%) by per protocol analysis, respectively. No serious adverse effect was observed, and 99% of the patients reported complete compliance.

Conclusions:

The cure rate of the 5‐day RACM regimen was more effective than the 7‐day RAC regimen, suggesting that this regimen could be preferable as a first‐line therapy for H. pylori infection.
Clarithromycin vs. furazolidone in quadruple therapy regimens for the treatment of Helicobacter pylori in a population with a high metronidazole resistance rate
Authors: Fakheri H. , Malekzadeh R. , Merat S. , Khatibian M. , Fazel A. , Alizadeh B. Z. , Massarrat S.
Published: March 2003

Background:

The eradication of Helicobacter pylori plays a pivotal role in the treatment of peptic ulcer disease. Metronidazole resistance, common in Iran, is claimed to be a major reason for the failure of metronidazole‐containing regimens. Both clarithromycin and furazolidone are potential alternatives for metronidazole.

Aim:

To assess and compare the effectiveness of clarithromycin‐ and furazolidone‐based regimens in eradicating H. pylori in a population with a high metronidazole resistance rate.

Methods:

Patients with proven duodenal ulcer and H. pylori infection were randomly assigned to one of two groups. The patients received 2 weeks of omeprazole 20 mg b.d., amoxicillin 1000 mg b.d, bismuth subcitrate 240 mg b.d. and either clarithromycin 500 mg b.d. (the OABC group) or furazolidone 200 mg b.d. (the OABF group).

Results:

A total of 118 patients were randomized, 55 in the OABC group and 63 in the OABF group. The intention‐to‐treat eradication rate was 84% and 85% for the OABF and OABC groups, respectively. The per protocol eradication rates were 90% for both groups.

Conclusions:

OABC and OABF are both effective in eradicating H. pylori in areas where metronidazole resistance is a problem. OABF is a good alternative in the face of growing resistance to clarithromycin in developed countries, and is attractive for developing countries where clarithromycin is not readily available.