bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of water and solute absorption from experimental hypotonic and established oral rehydration solutions in secreting rat intestine
Authors: HUNT J. B. , CARNABY S. , FARTHING M. J. G.
Published: July 2010

Water and solute absorption from three experimental hypotonic oral rehydration solutions (HYPO‐ORS; sodium 45, 60 and 75 mmol/L, glucose 90 mmol/L), the World Health Organization recommended ORS (WHO‐ORS; sodium 90 mmol/L, glucose 111 mmol/L), and the British National Formulary recommended ORS (BNF‐ORS; sodium 35 mmol/L, glucose 200 mmol/L), have been assessed by perfusion studies in cholera toxin‐induced secreting rat intestine. Net water absorption was greatest from the most hypotonic solution (HYPO‐45; P < 0.05). UK‐ORS prevented net water secretion and WHO‐ORS promoted moderate net water absorption. Net sodium secretion was seen with all solutions but was least from WHO‐ORS and greatest with BNF‐ORS (P < 0.01). Glucose absorption was similar from BNF‐ORS, WHO‐ORS and HYPO‐45 and in each case was greater than glucose absorption from HYPO‐60 and HYPO‐75 (P < 0.05). These results suggest that net water and sodium absorption from ORS may be enhanced if osmolality is reduced by decreasing the glucose content.
Eradication of Helicobacter pylori abolishes 24‐hour hypergastrinaemia: a prospective study in healthy subjects
Authors: PREWETT E. J. , SMITH J. T. L. , NWOKOLO C. U. , HUDSON M. , SAWYERR A. M. , POUNDER R. E.
Published: July 2010

In a prospective study, eight young healthy subjects (five with an active H. pylori infection in the antral mucosa) were treated with a course of tripotassium dicitrato bismuthate, amoxycillin and metronidazole. The triple therapy eradicated infection when assessed 20–24 weeks later by antral biopsy (urease, histology, and 13C urea breath test [4 out of 5 subjects]). Twenty‐four hour intragastric acidity and plasma gastrin concentration were measured before treatment, and 4–6 weeks and 20–24 weeks post‐treatment. Treatment did not affect acidity in either the H. pylori‐positive or H. pylori‐negative groups, nor did it affect the plasma gastrin profile in the H. pylori‐negative group. Eradication of H. pylori infection in five subjects caused a drop of the median integrated 24‐hour plasma gastrin concentration from 558 pmol. h/L before treatment to 307 and 289 pmol.h/L at 4–6 and 20–24 weeks post‐treatment, respectively. It is concluded that H. pylori infection is associated with 24‐hour hypergastrinaemia, and that in apparently healthy subjects normal gastric physiology can be restored by eradication of the infection.
Inhibition of human gastric cyclic AMP production by Helicobacter pylori protein—possible involvement of mucosal prostaglandin E2
Authors: TAHA A. S. , FRASER W. D. , KELLY R. W. , GEMMELL C. G. , LEE F. D. , RUSSELL R. I.
Published: July 2010

The effect ofHelicobacter pyloriprotein on cAMP and prostaglandin (PGE2) production was studied in incubates of human gastric fundic mucosa.

At 24 hours, specimens incubated in the control fluid had a median cAMP value of 81 pmol/mg protein, compared to 28 pmol/mg (P< 0.05) when incubated inH. pyloriprotein, 155 pmol/kg (P< 0.006) in histamine, and 23 pmol/kg (P< 0.05) in histamine plusH. pyloriprotein. A similar trend was observed at 48 hours. AlthoughH. pyloriprotein had no direct effect on mucosal PGE2, it intensified the inhibitory effect of indomethacin and prevented the stimulatory effect of histamine on both PGE2and cAMP production.

Given the role of cAMP in various physiological responses, these results suggest thatH. pyloriprotein might alter those functional aspects of the human gastric mucosa which rely on cAMP as a second messenger. Assuming that PGE2is involved in mediating such effect, its role would appear to be either partial or indirect.
Effect of omeprazole on intestinal output in the short bowel syndrome
Authors: NIGHTINGALE J. M. D. , WALKER E. R. , FARTHING M. J. G. , LENNARD‐JONES J. E.
Published: July 2010

Ten patients with an end jejunostomy and one with a jejuno‐rectal anastomosis (jejunal length 30–140 cm) ate a constant chosen diet for 2 control days, and 2 test days when 40 mg omeprazole orally was taken each morning. In the 7 patients with a net secretory output of fluid, there was a mean reduction in wet weight of 0.66 kg/24 h (range –0.16 to 1.45 kg/24 h; P < 0.05) and sodium 46 mmol/24 h (– 51 to 135 mmol/24 h; N.S.); the four patients with net absorption of fluid showed no reduction in intestinal output. One patient with 30 cm jejunum responded little to oral but did so to intravenous 40 mg omeprazole twice a day with a reduction in wet weight of 3.00 kg/24 h and sodium 157 mmol/24 h. In one patient oral 40 mg omeprazole daily gave equivalent results to oral 300 mg ranitidine twice daily; in 2 others it was equivalent to intravenous 50 μg octreotide twice daily. Omeprazole reduces the intestinal output in patients with the short bowel syndrome and a net secretory output, but not enough to prevent the need for parenteral fluid and electrolyte replacement.
The effect of GR122311X, a bismuth compound with H2‐antagonist activity, on 24‐hour intragastric acidity
Authors: PREWETT E. J. , NWOKOLO C. U. , HUDSON M. , SAWYERR A. M. , FRASER A. , POUNDER R. E.
Published: July 2010

GR122311X (ranitidine bismuth citrate Glaxo Group Research Ltd) is a bismuth compound with histamine H2‐receptor antagonist activity. The gastric acid antisecretory activity of three oral dosage regimens of GR122311X was compared with placebo and 150 mg ranitidine b.d. The median 24‐h integrated intragastric acidity was 38, 26 and 18% of the median placebo value during dosing with GR122311X 196, 391 and 782 mg b.d., respectively. The 24‐h acid suppression with GR122311X 391 mg b.d. was not significantly different to that produced by 150 mg ranitidine b.d. (24% of placebo acidity). The median 24‐h urinary bismuth excretion increased with rising dosage of GR122311X from 19.2 μg with 196 mg b.d., to 36.4 μg with 391 mg b.d., to 68.7 μg with 782 mg b.d. In conclusion, GR122311X is an effective antisecretory agent with modest systemic bismuth absorption.
Tripotassium dicitrato bismuthate: absorption and urinary excretion of bismuth in patients with normal and impaired renal function
Authors: TREIBER G. , GLADZIWA U. , ITTEL T. H. , WALKER S. , SCHWEINSBERGS F. , KLOTZ U.
Published: July 2010

We have investigated the absorption and urinary excretion of tripotassium dicitrato bismuthate during a treatment course of 4 weeks in 7 patients with normal renal function (creatinine clearance 115 ± 29 ml/min; mean ± S. D.), in 7 patients with impaired renal function (creatinine clearance = 34 ± 19 ml/min) and in 4 dialysed patients. Following the first dose of tripotassium dicitrato bismuthate (216 mg bismuth b.d.), and after 2 and 4 weeks of treatment (dialysed patients received only 108 mg/b.d.), plasma and urine concentrations of bismuth were monitored for 2 and 24 h, respectively. After stopping therapy plasma and urine concentrations of bismuth were followed for 4 and 6 weeks, respectively. In all three groups of patients small amounts of bismuth (mean values 0.26 to 0.28% of dose) were rapidly (transient mean peak concentrations between 40 and 134 μg/L) reached within about 30 to 40 min, absorbed and alasma levels demonstrated a wide intra‐ and inter‐individual variability. Absorption profiles were not altered during the treatment course; however, the trough plasma concentration of bismuth demonstrated an about 3‐ to 5‐fold accumulation (correlated to creatinine clearance) from about 5 μg/L to 15 μ/L (normal renal function) or to 20–25 μ/L (impaired renal function). Pre‐study bismuth levels could be detected within 2 to 4 weeks after stopping therapy in all subjects whereas urinary concentrations were still elevated 6 weeks after the course of treatment.

Our results indicate that tripotassium dicitrato bismuthate is absorbed in very low amounts during standard therapy. However, dependent on renal function, accumulation to non‐toxic levels does occur during a course of treatment. It appears prudent to halve tripotassium dicitrato bismuthate dosage in patients with severe renal insufficiency (creatinine clearance ± 20 ml/min) to avoid any possible toxic risks. In such patients monitoring of the plasma bismuth concentration might be helpful, especially if longer or repeated treatment is anticipated.
Helicobacter pylori: treatment with combinations of pivampicillin and tripotassium dicitrato bismuthate
Authors: WEIL J. , BELL G. D. , POWELL K. , MORDEN A. , HARRISON G. , GANT P. W. , TROWELL J. E. , BURRIDGE S.
Published: July 2010

Fifty Helicobacter pylori‐ (H. pylori) positive patients entered an open study and were assigned to one of four treatment regimens comprising: pivampicillin (500 mg b.d.) for 2 weeks tripotassium dicitrato bismuthate (tablet or liquid form) for one month.

The 14C‐urea breath test was used to evaluate clearance (negative at the end of treatment) and eradication (negative at 1 month posttreatment) of H. pylori. Clearance rates were 20% (2/10) after pivampicillin alone, 86% (12/14) after tripotassium dicitrato bismuthate tablets (240 mg b.d.) plus pivampicillin, 67% (6/9) after tripotassium dicitrato bismuthate tablets (120 mg q.d.s.) plus pivampicillin, and 100% (13/13) after tripotassium dicitrato bismuthate liquid (120 mg in 5 ml q.d.s.) plus pivampicillin. The eradication rates were 0% (0/10), 13% (2/15), 0% (0/11) and 54% (7/13), respectively.

Combination of the results from the 2 tripotassium dicitrato bismuthate tablet/pivampicillin groups gave an eradication rate of 7.7% (2/26) which was significantly lower than the 53.9% (7/13) obtained with tripotassium dicitrato bismuthate liquid/pivampicillin (P < 0.02).

In conclusion, a liquid tripotassium dicitrato bismuthate pivampicillin combination may be of special use in the treatment of H. pylori‐positive patients when triple therapy is contraindicated (e.g. patient sensitivity/allergy to metronidazole) or when the H. pylori isolate is resistant to metronidazole.
Degrees of acid suppression and ulcer healing: dosage considerations
Authors: POUNDER R. E.
Published: July 2010

The human stomach has a normal circadian rhythm of intragastric acidity characterized by increasing acidity during the day and peaks in the early hours of the morning. Eating causes a transient decrease of intragastric acidity. Acid appears to be the permissive factor in peptic ulcer disease and to be responsible for symptoms; the patient with duodenal ulcer may secrete too much acid. Pharmacological control of gastric acid secretion will speed ulcer healing. Modern regimens, which typically use a bedtime dose of an H2‐receptor antagonist, produce a pulse of decreased acidity. Intragastric acidity is decreased during the night and early morning, leaving a normal profile of acidity during the day and early evening. Higher or more frequent doses of an antisecretory agent can produce a more profound decrease of 24‐h intragastric acidity. Theoretical problems associated with a sustained or profound decrease of 24‐h intragastric acidity include the threat of enteric infection and infestation, potential bacterial overgrowth with possible N‐nitrosamine formation, and drug‐induced hypergastrinaemia. In light of these potential problems, for the management of simple peptic ulceration, it appears sensible to use the minimum intervention required. Bedtime H2‐receptor blockade is one such regimen. The more potent antisecretory regimens can be used for difficult clinical problems such as the Zollinger–Ellison syndrome, intractable duodenal ulceration, and severe oesophagitis.
Safety profile of long‐term H2‐antagonist therapy
Authors: LEWIS J. H.
Published: July 2010

The safety profile of low‐dose maintenance therapy with H2‐antagonists for duodenal ulcer disease suggests that these agents can be given safely for several years and probably much longer. Because information regarding the use of these compounds for more than 10 years in large numbers of patients is lacking, the safety of these drugs should continue to be monitored. The safety profiles of famotidine and nizatidine will require several additional years of postmarking surveillance data to match the depth of our knowledge regarding cimetidine and ranitidine. Compared to a surgical approach to ulcer disease, continuous H2‐blocker maintenance therapy is cost‐effective and is associated with significantly less morbidity. Patents with a history of bleeding or other ulcer complication should be encouraged to remain on maintenance therapy if they do not undergo surgery. The need for extended maintenance therapy also applies to individuals with frequent symptomatic ulcer relapses, reflux oesophagitis, and a range of less common disorders.

Currently, H2‐blockers and sucralfate are the only agents approved by the Food and Drug Administration for maintenance therapy of duodenal ulcer disease. Experience with omeprazole is still limited, and its longterm safety profile must await the completion of controlled trials of maintenance therapy. Given the apparent long‐term safety of the H2‐blockers for maintenance therapy, any new agent must prove to be equally safe in the clinical arena, a task that may be indeed formidable.
Non‐ulcer dyspepsia: myths and realities
Authors: TALLEY N. J.
Published: July 2010

Dyspepsia can be defined as the presence of upper abdominal pain or discomfort; other symptoms referable to the proximal gastrointestinal tract, such as nausea, early satiety, and bloating, may also be present. Symptoms may or may not be meal related. To be termed chronic, dyspepsia should have been present for three months or longer. Over half the patients who present with chronic dyspepsia have no evidence of peptic ulceration, other focal lesions, or systemic disease and are diagnosed as having non‐ulcer (or functional) dyspepsia. Non‐ulcer dyspepsia is a heterogeneous syndrome. It has been proposed that this entity can be subdivided into a number of symptomatic clusters or groupings that suggest possible underlying pathogenetic mechanisms. These groupings include ulcer‐like dyspepsia (typical symptoms of peptic ulcer are present), dysmotility (stasis)‐like dyspepsia (symptoms include nausea, early satiety, bloating, and belching that suggest gastric stasis or small intestinal dysmotility), and reflux‐like dyspepsia (heartburn or acid regurgitation accompanies upper abdominal pain or discomfort).

The aetiology of non‐ulcer dyspepsia is not established, although it is likely a multifactorial disorder. Motility abnormalities may be important in a subset of dyspepsia patients but probably do not explain the symptoms in the majority. Epidemiological studies have not convincingly demonstrated an association between Helicobacter pylori and non‐ulcer dyspepsia. Other potential aetiological mechanisms, such as increased gastric acid secretion, psychological factors, life‐event stress, and dietary factors, have not been established as causes of non‐ulcer dyspepsia. Management of non‐ulcer dyspepsia is difficult because its pathogenesis is poorly understood and is confounded because of a high placebo response rate. Until more data are available, it seems reasonable that treatment regimens target the clinical groupings described above. Antacids are no more effective than placebo in non‐ulcer dyspepsia, although a subgroup of non‐ulcer dyspepsia patients with reflux‐like or ulcer‐like symptoms may respond to H2‐receptor antagonists. However, there is no significant benefit of these agents over placebo in many cases. Bismuth has been shown to be superior to placebo in patients with H. pylori in a number of studies, but these trials had several shortcomings and others have reported conflicting findings. Sucralfate was demonstrated in one study to be superior to placebo, but this finding was not confirmed by another group of investigators. Prokinetic drugs appear to be efficacious, and may be most useful in patients with dysmotility‐like and reflux‐like dyspepsia.
Review article: 5‐hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications
Authors: TALLEY N. J.
Published: July 2010

Serotonin (5‐hydroxytryptamine; 5‐HT) is found in the enteric nervous system where it has been implicated in controlling gastrointestinal motor function. A number of receptor or recognition sites have been identified in the gut, but recently most attention has focused on the 5‐HT3and 5‐HT4receptors. The functional role of the 5‐HT3receptor remains incompletely understood, but it is probably involved in the modulation of colonic motility and visceral pain in the gut. A number of selective 5‐HT3antagonists have been developed including ondansetron, granisetron, tropisetron renzapride and zacopride. While the substituted benzamide prokinetics (for example, metoclopramide, cisapride) also block 5‐HT3receptors in high concentrations, their prokinetic action is believed to be on the basis of their agonist effects on the putative 5‐HT4receptor. Some 5‐HT3antagonists have 5‐HT4agonist activity (for example, renzapride, zacopride) and others do not (for example, ondansetron, granisetron), while tropisetron in high concentrations is a 5‐HT3antagonist. Based on the pharmacological data, it has been suggested that specific 5‐HT antagonists and agonists may prove to be beneficial in a number of gastrointestinal disorders including the irritable bowel syndrome, functional dyspepsia, non‐cardiac chest pain, gastrooesophageal reflux and refractory nausea. In this review, the rationale for the use of these compounds is discussed, and the available experimental evidence is summarized.
Effects of acetorphan, an antidiarrhoeal enkephalinase inhibitor, on oro‐caecal and colonic transit times in healthy volunteers
Authors: BERGMANN J. F. , CHAUSSADE S. , COUTURIER D. , BAUMER P. , SCHWARTZ J. C. , LECOMTE J. M.
Published: July 2010

Acetorphan is a potent enkephalinase inhibitor displaying antidiarrhoeal activity attributable to its intestinal antisecretory action mediated by endogenous enkephalins. The effect of acetorphan on digestive motility was studied in 12 healthy volunteers. Oro‐caecal transit time was evaluated using the sulphasalazine/sulphapyridine method and colonic transit times using radiopaque markers. These measurements were successively performed after one week treatment with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was no significant modification in transit time linked to acetorphan treatment: total orocaecal times were 303 ± 32 minvs.287 ± 27 min and colonic transit times 25.8 ± 5.8 hvs. 31.3 ± 5.5 h after acetorphan and placebo, respectively (means ± S.E.M.). There was no significant modification either in right colonic, left colonic or rectosigmoid segmental transit times, or in the mean number of stools. These results, consistent with those from animal studies, confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which act by delaying intestinal transit, acetorphan does not affect the transit. Antidiarrhoeal activity not accompanied by a delayed intestinal transit could have beneficial therapeutic consequences in the management of infectious diarrhoea. In addition, we show that the sulfphasalazine and radiopaque markers methods can be simultaneously applied in the same study.
Review article: adrenergic control of motor and secretory function in the gastrointestinal tract
Authors: McINTYRE A. S. , THOMPSON D. G.
Published: July 2010

The role that the sympathetic nervous system plays in modulating physiological processes in the gastrointestinal tract is becoming clearer. It is now known that motor, secretomotor and vasomotor activity are all modulated independently by the system. Adrenoreceptor stimulation appears to reduce intestinal contraction (except at sphincters), both via alpha‐receptors which inhibit neurotransmitter release and also by a direct beta‐receptor mediated action on smooth muscle. There is also evidence for tonic activity in the beta‐adrenergic pathway, since betaantagonists tend to increase contraction pressures. In animals alphareceptor‐mediated pathways modulate fluid and electrolyte absorption, and alpha‐adrenergic agonists enhance net absorption and reduce net secretion. In man there is also evidence for a beta‐adrenergic pathway which controls secretomotor function. Carbohydrate absorption appears to be dependent on activity in a beta‐adrenergic pathway, although this may be an indirect effect of changes in motor function. The time course of changes of both secretomotor and motor activity, induced by modulating sympathetic or adrenergic input, differ from the vascular changes indicating that the effects occur independently of each other. The gastrointestinal response to stressors is mediated, in part at least, by the sympathetic nervous system. Differences between individuals are likely to prove important.

Since the sympathetic nervous system regulates gastrointestinal function both in the basal state and under stressful conditions, it will have effects on pathophysiological responses. Modification of such responses is likely to ameliorate symptoms, as has already been found for alpha‐2‐adrenergic agonists which have an antidiarrhoeal action.
Review article: non‐steroidal, antiinflammatory drugs—the extending scope of gastrointestinal side effects
Authors: AABAKKEN L.
Published: July 2010

The gastrointestinal side effects of non‐steroidal, anti‐inflammatory drugs extend beyond the duodenal bulb, and comprise a variety of lesions in all parts of the gut. Gastroduodenal ulceration is quantitatively dominant, although a major part of these lesions probably go unnoticed and heal spontaneously. Adaptation has been demonstrated for acetylsalicylic acid, and may be of importance for other substances as well. Non‐steroidal anti‐inflammatory drugs (NSAIDs) may induce relapse of inflammatory bowel disease. Permeability changes and mucosal inflammation are found in the small and large bowel in the majority of subjects taking NSAIDs, although the clinical significance is still not clear. Ulceration and perforation do, however, occur in this part of the gut as well. Treatment of NSAID‐associated ulceration is similar to traditional ulcer treatment, possibly with extended treatment duration if the NSAID is continued. Prophylaxis is of some value, but is not required for every patient receiving an NSAID.
Short report: the effect of ranitidine on the post‐prandial absorption of a low dose of alcohol
Authors: FRASER A. G. , HUDSON M. , SAWYERR A. M. , ROSALKI S. B. , POUNDER R. E.
Published: July 2010

Twenty healthy male subjects were studied twice using a double‐blind, randomized placebo controlled, cross‐over study design. Alcohol absorption (integrated 2‐h plasma alcohol concentration, peak plasma alcohol concentration, and time to reach peak concentration) was measured after 8 daily doses of either placebo or 300 mg ranitidine. They were given alcohol, 0.15 g/kg of body weight by month after an evening meal. Compared with placebo, there was a trend towards higher integrated 2‐h plasma alcohol concentrations (3.17 and 3.89 mg. h/dL, respectively, P= 0.07), and a statistically significant increase in mean peak plasma alcohol concentration after dosing with ranitidine (4.92 and 6.47 mg/dL, respectively, P= 0.05).
Review article: maintenance treatment with H2‐receptor antagonists for peptic ulcer disease
Authors: PENSTON J. G. , WORMSLEY K. G.
Published: July 2010

In recent years a number of different strategies for managing patients with peptic ulcer disease have become available. The present review discusses the relative merits of each form of treatment. Intermittent treatment (whether given in response to symptoms or as a prophylactic regimen prescribed seasonally or at weekends) fails to prevent ulcer recurrence and leaves patients at risk of haemorrhage and perforation. Anti‐Helicobacter pylori therapy, although useful in certain circumstances, cannot be recommended for all patients with ulcer disease because of side effects and, in any case, requires further assessment of efficacy. Gastric surgery reduces ulcer recurrence and complications, but operations which have a low incidence of side effects are associated with higher rates of ulcer recurrence, particularly when patients are followed up for more than 10 years. Long‐term continuous maintenance treatment with H2‐receptor antagonists for 5 or more years effectively prevents ulcer recurrence in the majority of patients and significantly reduces the risk of ulcer complications. In addition, maintenance treatment has proved to be safe and is well tolerated by patients.

Maintenance treatment with H2‐receptor antagonists is the preferred option for the management of patients with peptic ulcer disease.
Clinical tolerance to three 5‐aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine
Authors: GIAFFER M. H. , O'BRIEN C. J. , HOLDSWORTH C. D.
Published: July 2010

The clinical tolerance to three 5‐aminosalicylic acid (5‐ASA) releasing preparations (mesalazine, olsalazine and balsalazide) was assessed in a consecutive series of 43 patients with inflammatory bowel disease who were intolerant to sulphasalazine. The relative contributions to the side‐effects of sulphasalazine made by its two components, 5‐ASA and sulphapyridine, were also assessed in these patients. Thirty‐nine (91%) patients were able to tolerate at least one of the three 5‐ASA preparations. Only four (9%) patients were intolerant to all preparations, having adverse reactions previously experienced with sulphasalazine and presumably related to 5‐ASA rather than sulphapyridine. The clinical tolerance to mesalazine (63%), olsalazine (70%) and balsalazide (70%) was similar, and tolerance to one drug only was found in nine (18%) patients. The commonest adverse reactions associated with 5‐ASA preparations were gastrointestinal. Diarrhoea was a problem in five patients during treatment with olsalazine and three each while on mesalazine and balsalazide. Allergic reactions from 5‐ASA preparations were uncommon; of ten patients with rash following sulphasalazine only one developed a rash with mesalazine. The results of this study indicate that the vast majority of patients with inflammatory bowel disease can be managed with at least one of these four 5‐ASA containing preparations and that the side‐effects of sulphasalazine are multifactorial in aetiology, some being due to the parent molecule, and some to one of its two metabolites, 5‐ASA and sulphapyridine.
Lansoprazole versus famotidine: efficacy and tolerance in the acute management of duodenal ulceration
Authors: HOTZ J. , KLEINERT R. , GRYMBOWSKI T. , HENNIG U. , SCHWARZ J. A.
Published: July 2010

Lansoprazole (AG 1749/CG 4801) is an inhibitor of gastric acid secretion by blocking H+,K+‐ATPase. In this 2:1 randomized, double‐blind, multicentre trial lansoprazole 30 mg am was compared to 40 mg famotidine nocte in 264 out‐patients suffering from uncomplicated duodenal ulcer. After 2 weeks of treatment ulcer healing was confirmed endoscopically in a significantly higher proportion (P= 0.027) of patients treated with lansoprazole (94/174 = 54.0%) compared to patients receiving famotidine (35/90 = 38.9%). Cumulative healing rates after 4 weeks were 91.4% for the lansoprazole group and 83.3% for the famotidine group (P= 0.065). Pain relief and decrease of concomitant antacid consumption during treatment were comparable in both groups. Both compounds were well tolerated. Rates of recurrent duodenal ulcer in the 6 months after trial treatment were 45/158 (28.5%) after lansoprazole, and 18/69 (26.1%) after famotidine.
Omeprazole (20 mg) daily given in the morning or evening: a comparison of effects on gastric acidity, and plasma gastrin and omeprazole concentration
Authors: CHIVERTON S. G. , HOWDEN C. W. , BURGET D. W. , HUNT R. H.
Published: July 2010

Although omeprazole has a long duration of action and has usually been given in the morning, there are theoretical advantages in administering antisecretory drugs in the evening as has been shown for the H2‐receptor antagonists. The aim of this study was to compare the effects of placebo and 20 mg omeprazole given either in the morning or evening, on gastric acidity, plasma gastrin levels and plasma omeprazole in 6 duodenal ulcer patients. The 24‐hour mean pH (± S.E.M.) was: placebo 1.7 ± 0.1; morning doing, 3.9 ± 1.8 (P < 0.01); evening dosing, 2.9 ± 1.1 (N.S.). There was a large inter‐individual variability of intragastric acidity in response to omeprazole, which was reflected both in the plasma gastrin and in the area under the plasma omeprazole concentration–time curve. Morning administration of omeprazole is optimal, but variability in the patient response to 20 mg omeprazole is still seen.
Short report: short‐term triple therapy for H. pylori‐associated duodenal ulcer disease
Authors: PATCHETT S. , BEATTIE S. , KEANE C. , O'MORAIN C.
Published: July 2010

Thirty consecutive patients with endoscopically proven duodenal ulceration who had Helicobacter pylori infection on culture and histology, were treated with tripotassium dicitrato bismuthate (1 tablet q.d.s., 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. for one week, followed by the bismuth salt for a further 3 weeks. All patients were endoscoped at entry and 4 weeks after cessation of treatment, to check for ulcer healing and H. pylori eradication. Two antral biopsies were taken at each endoscopy for histological and microbiological evidence of H. pylori infection. Complete healing of duodenal ulcers was observed in 27/30 patients (90%). Gastritis improved or completely resolved in 26 patients. Eradication of H. pylori was achieved in 27 patients. Of the three patients who failed to heal, two were H. pylori‐positive at follow‐up and one was H. pylori‐negative.
Helicobacter pylori clearance in the treatment of non‐ulcer dyspepsia
Authors: HOLCOMBE C. , THOM C. , KALUBA J. , LUCAS S. B.
Published: July 2010

One hundred and thirty north Nigerian patients with non‐ulcer dyspepsia were treated with tripotassium dicitrato bismuthate and amoxycillin, or antacid. Symptoms resolved in 28 (33%) of bismuth and amoxycillin recipients completing the trial compared with 1 (4%) of the antacid recipients. Symptomatic improvement did not relate to clearance of Helicobacter pylori.
The effect of alpha‐1‐adrenoreceptor agonist and antagonist administration on kumun upper gastrointestinal transit and motility
Authors: McINTYRE A. S. , THOMPSON D. G. , BURNHAM W. R. , WALKER E.
Published: July 2010

To explore the role of alpha‐1‐adrenoreceptor‐mediated pathways on human upper gut motor function in vivo, we studied the effects of the alpha‐1‐agonist phenylephrine and the alpha‐1‐antagonist thymoxamine on oro‐caecal transit and antroduodenal motor activity. Transit was measured using a standard exhaled‐breath hydrogen method, and motility was measured by intraluminal manometry.

Oro‐caecal transit was unaffected by 80 mg thymoxamine [median 63 min (range 35–164 min) vs. control, 65 min (range 30–155 min), P > 0.1]. However, phenylephrine (2.4 μg/kg/min) consistently delayed oro‐caecal transit time to 103 min (50–215 min), P > 0.005. Co‐administration of thymoxamine abolished this phenylephrine‐induced delay.

The mean amplitude of antral postprandial contractions was reduced by phenylephrine from 29 (13–37) to 10 (3–13) mmHg (P < 0.02). In contrast, neither the pattern nor the mean inter‐contraction interval was altered. Responses to phenylephrine in the duodenum were similar to those in the antrum, with reduction in amplitude from 12 (3–18) to 6 (5–13) mmHg without alteration in the pattern or interval between contractions.

Nutrient transit through the upper gut can thus be inhibited via activation of an alpha‐1‐adrenoreceptor‐mediated pathway. Failure of alpha‐1‐antagonist administration to alter oro‐caecal transit suggests that this pathway is not tonically active, and it is therefore unlikely to play a major role in nutrient passage under normal circumstances.
Experience with‘triple’ anti‐Helicobacter pylori eradication therapy: side effects and the importance of testing the pre‐treatment bacterial isolate for metronidazole resistance
Authors: BELL G. D. , POWELL K. , BURRIDGE S. M. , PALLECAROS A. , JONES P. H. , GANT P. W. , HARRISON G. , TROWELL J. E.
Published: July 2010

At the 1990 World Congresses of Gastroenterology, the Working Party on Helicobacter pylori (H. pylori) recommended that, in suitable patients, the bacterium should be eradicated using a therapeutic regimen comprising a bismuth salt, tetracycline and metronidazole for two weeks. We have treated 40 patients infected with H. pylori with‘triple’ therapy consisting of 120 mg tripotassium dicitrato bismuthate q.d.s., 500 mg tetracycline q.d.s. and 400 mg metronidazole t.d.s. for two weeks.

The success rate, in terms of bacterial eradication, was 19/21 (90.5%) in patients with metronidazole‐sensitive organisms, compared with only 6/19 (31.6%) in patients whose H. pylori were resistant to metronidazole (P < 0.01). Side effects, particularly diarrhoea and vomiting/nausea, were common: 23/40 patients reported such symptoms during the 14‐day course of therapy. Fifteen of these 23 patients completed the entire 14‐day course, although suffering from significant side effects, while the remaining eight patients had to discontinue the treatment because side effects became intolerable.

If a form of triple therapy is going to be widely used to eradicate H. pylori infection, the regimen will have to be simpler, shorter, produce fewer side effects and be more effective in patients with metronidazole‐resistant bacteria.
An artificial stomach‐duodenum model for the in‐vitro evaluation of antacids
Authors: VATIER J. , MALIKOVA‐SEKERA E. , VITRE M. T. , MIGNON M.
Published: July 2010

To improve the dynamic in‐vitro evaluation of the effects of antacids, we have developed the‘artificial stomach’ model by adding a‘duodenal reservoir’ to receive the gastric emptying flux and simulated bicarbonate secretion, thus constituting an‘artificial stomach‐duodenum’ model. With this model we measured antacid‐induced resistance to gastric acidification, and simultaneously evaluated the effect of antacid activity on the duodenal milieu. The model also permitted evaluation of the antacid effects of proteins (as natural antacids), and of drugs containing aluminium phosphate, alone or combined with magnesium oxide, or aluminium and magnesium hydroxides. At the gastric site, these drugs, as well as the proteins (that is, meat extract), induced a strong resistance to acidification due to the gastric emptying flux and to antacid composition. At the duodenal site, the decrease of the acid load penetrating into the duodenum varied, depending on the efficacy of gastric antacid activity. Duodenal pH was related to the equilibrium between bicarbonate secretion and the emptying of acid load. Proteins and aluminium phosphate induced the same duodenal pH as in the control tests without antacids, but magnesium‐containing antacids increased it, thus decreasing bicarbonate consumption. The antacid mechanisms within the stomach, and the fate of antacids in the duodenal milieu, might explain the variation in duodenal pH in response to antacid administration.
Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin
Authors: LANGHOLZ E. , BRYNSKOV J. , BENDTZEN K. , VILIEN M. , BINDER V.
Published: July 2010

Fusidic acid is an antibiotic with T‐cell specific immunosuppressive effects similar to those of cylosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy‐resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea, Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre‐treatment levels after cessation of treatment.

The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.
Short report: comparison of two orally administered bowel preparations for colonoscopy—polyethylene glycol and sodium picosulphate
Authors: DAKKAK M. , AZIZ K. , BENNETT J. R.
Published: July 2010

Fifty‐nine consecutive patients admitted for colonoscopy were randomized to receive polyethylene glycol or sodium picosulphate. Patients expressed their opinion in a questionnaire and the endoscopists, blinded to the preparation, assessed the cleanliness of different segments of the colon.

There was no statistically significant difference in the taste‐acceptability of the preparations, frequency of nausea, abdominal pain, peri‐anal soreness or sleep disturbance between the two groups. Polyethylene glycol caused vomiting in 13% of patients while this was absent in those who received sodium picosulphate (P< 0.05).

The average number of stools passed was 12.4 in the polyethylene glycol and 8.6 in the sodium picosulphate groups; mean difference 3.8 (95% C.I. 0.7–6.9) withP< 0.02. The overall cleanliness of the colon was better in the polyethylene glycol group (P= 0.002) as judged by the blinded colonoscopist. There was less delay (P= 0.06) and more completed colonoscopies (P= 0.01) in this group. Polyethylene glycol was a better preparation in all segments of the colon except the rectum.

We conclude that polyethylene glycol is the choice of the colonoscopist and should be given to all patients; sodium picosulphate would be a good alternative if patients are intolerant. If a limited colonoscopy or flexible sigmoidoscopy is intended, sodium picosulphate may be preferred because of its acceptable efficacy and slightly advantageous side‐effect profile.
Review article: the pathophysiology and pharmacological treatment of portal hypertension
Authors: GROSE R. D. , HAYES P. C.
Published: July 2010

The pathogenesis of portal hypertension remains poorly understood. Similarly, pharmacological manipulation for the prevention and treatment of variceal haemorrhage has not fulfilled the promise of the 1980s. This article reviews current concepts in the pathophysiology of portal hypertension and considers pharmacotherapy for the treatment of variceal bleeding.
A comparison of gastro‐oesophageal reflux in volunteers assessed by ambulatory pH and gamma monitoring after treatment with either Liquid Gaviscon or Algicon Suspension
Authors: WASHINGTON N. , GREAVES J. L. , IFTIKHAR S. Y.
Published: July 2010

This study was designed to compare the effectiveness of single doses of either Liquid Gaviscon or Algicon Suspension in the suppression of food and acid reflux into the oesophagus after a test meal in volunteers.

After the pH electrode and gamma detector were positioned 5 cm above the cardia, the volunteers received a refluxogenic radiolabelled meal. The subjects then remained untreated, or thirty minutes later they were given a dose of unlabelled Algicon Suspension, or Liquid Gaviscon and a recording was made for a minimum of 3 hours. Allocation to the treatment group was randomized with the cross‐overs performed 1 week apart.

Liquid Gaviscon suppressed gastro‐oesophageal reflux of both food and acid whereas only an insignificant reduction in reflux was seen after Algicon Suspension. The oesophageal pH remained below 4 for 3.21 ± 0.92% (S.E.M.) of the recording period in the control study, 0.88 ± 0.33 after Gaviscon and 2.91 ± 0.68 after Algicon. The reflux of food was reduced from 17070 ± 103± 4713 ± 103 counts in the control study to 224 ± 103± 93 ± 103 counts after the Gaviscon and 16080 ± 103± 7131 ± 103 counts after Algicon. The suppression of reflux by Liquid Gaviscon was significantly better than that produced by Algicon Suspension.
A new model of human secretory diarrhoea using cholera toxin
Authors: HUNT J. B. , THILLAINAYAGAM A. V. , CARNABY S. , FAIRCLOUGH P. D. , CLARK M. L. , FARTHING M. J. G.
Published: July 2010

Secretory diarrhoea is a major cause of morbidity and mortality worldwide. However, there is no biologically relevant test system in man for assessing new anti‐diarrhoeal therapies prior to clinical trial. We have used highly purified cholera toxin in combination with the triple lumen jejunal perfusion technique to establish a subclinical model of cholera in man. Cholera toxin was administered either by mouth with sodium bicarbonate or directly into a 30 cm‘open’ or‘closed’(isolated between two inflated balloons) jejunal segment in healthy adult volunteers. Both oral dosing and direct delivery into an‘open’ jejunal segment failed to produce consistent secretion of water and electrolytes. In contrast 15 μg or 25 μg of cholera toxin elicited secretion of water and sodium 3 h after instillation into the balloon occluded‘closed’ jejunal segment (P < 0.05 vs. controls). The rate of secretion was constant over the maximal period studied (4.5 h) and was similar to that reported in human cholera. None of the subjects experienced troublesome diarrhoea. We believe this model offers a relevant test system for assessing anti‐diarrhoeal therapy in man.
Ranitidine: differential effects on gastric bleeding and mucosal damage induced by aspirin
Authors: COLE A. T. , BRUNDELL S. , HUDSON N. , HAWTHORNE A. B. , MAHIDA Y. R. , HAWKEY C. J.
Published: July 2010

This study investigated the influence of ranitidine on mucosal injury and gastric bleeding in 20 normal volunteers taking 600 mg aspirin q.d.s. This study was a double‐blind placebo controlled crossover study comparing ranitidine, as 150 mg b.d., 300 mg q.d.s. and 600 mg b.d. with placebo. Gastric mucosal injury was assessed at unsedated endoscopy by counting haemorrhagic and non‐haemorrhagic erosions; bleeding was measured in gastric washings. Aspirin alone increased mucosal injury from 0 to 11.4 erosions (mean, P < 0.01) and bleeding from 1.77 to 9.11 μl blood/10 min (mean P < 0.001). Ranitidine prophylaxis reduced bleeding to 5.34, 3.18 and 3.47 μl/10 min with 150 mg b.d., 300 mg q.d.s. and 600 mg b.d. respectively (overall effect of ranitidine P < 0.001) and also reduced haemorrhagic erosions though it had no effect on the total number of erosions. Ranitidine is effective at reducing aspirininduced gastric bleeding and whilst not reducing aspirin‐induced gastric erosions, it does reduce the number that appear haemorrhagic. Ranitidine may have a role in the prophylaxis of aspirin‐induced gastric bleeding.
Is oropharyngeal anaesthesia with topical lignocaine useful in upper gastrointestinal endoscopy?
Authors: JAMESON J. S. , KAPADIA S. A. , POLSON R. J. , McCARTHY P. T. , MISIEWICZ J. J.
Published: July 2010

The aim of this study was to determine whether patients' tolerance of upper gastrointestinal endoscopy is related to the dose of lignocaine spray used for oropharyngeal anaesthesia and to measure plasma concentrations at these doses. Sixty consecutive patients undergoing routine upper gastrointestinal endoscopy with sedation were randomized to receive lignocaine spray 50 mg (Group A), 100 mg (Group B) or 200 mg (Group C). Patient, endoscopist and endoscopy nurse were unaware of the variation in dose used. Each patient's tolerance of the intubation and of the remainder of the gastroscopy was assessed independently by the patient, endoscopy nurse, and endoscopist using a visual analogue scale. Plasma lignocaine concentration was measured at 20, 40, 60 and 80 min after administration of the spray. Fifty (83 %) patients were unable to recall either the intubation, or the procedure. On the endoscopy nurse's assessment, the patients in Group B tolerated the intubation better than those in Group A, and Groups B and C tolerated the remainder of the gastroscopy better than those in Group A. On the endoscopist's assessment, Groups B and C tolerated the remainder of the gastroscopy better than Group A. There were fewer gags per min in Groups B and C compared to Group A. Mean plasma Lignocaine concentrations showed a dose—dependent absorption of the spray, but none exceeded the potentially toxic level of 5 mg/L.
Review article: S‐Adenosyl‐L‐Methionine–a new therapeutic agent in liver disease?
Authors: OSMAN E. , OWEN J. S. , BURROUGHS A. K.
Published: July 2010

The established biochemical effects of exogenous S‐Adenosyl‐l‐Methionine (SAMe) are diverse and are still being explored in liver disease. Putative therapeutic effects could be exerted via different mechanisms. The established deficiency of SAMe synthetase in cirrhosis could by bypassed by exogenous SAMe, leading to increased levels of sulphur‐containing amino acids and glutathione which would protect against oxidant stress and drug‐induced hepatotoxicity (for example, paracetamol). Furthermore SAMe could act by improving membrane fluidity, and thus potentially improve or restore the function of receptors, enzymes and transporters in the cell surface. Membrane fluidity is known to be affected by alterations in cell membrane lipid composition in chronic liver disease.

Very few therapeutic agents are effective for the symptomatic or specific treatment of chronic liver disease. SAMe has established biochemical and biophysical effects which in pilot studies ameliorate symptoms and biochemical parameters of cholestasis. Moreover, abnormalities in liver function tests (including transaminase values) also improve. Before SAMe can be considered as an established therapy for patients with hepatic disease, long‐term controlled clinical trials of SAMe are needed to assess the benefit for patients' symptoms, well being, histological changes and progression of liver disease.
Gastric and duodenal mucosal blood flow in patients receiving non‐steroidal anti‐inflammatory drugs—influence of age, smoking, ulceration and Helicobacter pylori
Authors: TAHA A. S. , ANGERSON W. , NAKSHABENDI I. , BEEKMAN H. , MORRAN C. , STURROCK R. D. , RUSSELL R. I.
Published: July 2010

Using laser Doppler flowmetry, we measured gastric and duodenal mucosal blood flow in 70 patients who had taken non‐steroidal anti‐inflammatory drugs (NSAIDs) for longer than 4 weeks, and studied the correlation with demographic factors, ulceration, andHelicobacter pylori. Blood flow was also measured in 17 other subjects not taking any drugs. Measurements were taken from healthy‐looking mucosa in the gastric antrum and the first part of the duodenum.

Both gastric and duodenal blood flow values were significantly lower in patients taking NSAID than in those who did not. In the NSAID group, the median duodenal mucosal blood flow was 150 perfusion units in smokers (n =29) compared with 175 in non‐smokers (P= 0.024), 123 units in patients with duodenal ulcers (n =12) compared with 160 in those without duodenal ulcers (P= 0.020), 135 units in patients withH. pylori(n= 30) compared with 168 in patients without H.pylori(P= 0.033), and 118 in smokers infected withH. pyloricompared with 175 units in non‐smokers not infected with H.pylori(F= 13.4, P = 0.0005). There was no correlation with age. Gastric blood flow was not significantly influenced by any of the above variables.

These results suggest that chronic NSAID intake is associated with reduced blood flow in both the stomach and duodenum. However, amongst NSAID patients, duodenal, but not gastric, mucosal blood flow is reduced in smokers, and in those with duodenal ulcers andH. pylori. Multivariate analysis showed that only the simultaneous presence of smoking and H.pylorihad an independent suppressive effect, and when combined, lower blood flow values are observed which might suggest a synergistic relationship between these two factors.