bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: stomach wars—a mucosal defence initiative
Authors: MATTHEWS J. B. , GARNER A. 
Published: July 2010

SUMMARYA model is presented which attempts to unify many of the processes identified in recent years as contributing to the maintenance of mucosal integrity in the stomach. Two concepts, namely acid disposal and rapid repair of superficial injury, are highlighted as being of particular physiological significance. The mechanisms involved in protection of the normal mucosa against luminal aggressors (e.g. acid/pepsin, ethanol, aspirin) must be distinguished from the factors which influence the healing of a pre‐existent ulcer. In this context, the relatively neglected topic of wound healing in the gastric mucosa is considered, and the implications for current therapeutic strategies and for the discovery of new anti‐ulcer drugs are explored.
Ranitidine in the treatment of duodenal ulcer disease: relationship between antisecretory effect and ulcer healing rate
Authors: McISAAC R. L. , DIXON J. S. , MILLS J. G. , WOOD J. R. 
Published: July 2010

SUMMARYThe relationship between drug‐induced suppression of intragastric acidity and the rate of duodenal ulcer healing was examined using data for a single drug, ranitidine, from 156 clinical trials involving 16362 patients together with data on acid suppression from 37 studies of intragastric acidity in 630 subjects. In these studies ranitidine was given in doses ranging from 150 mg to 1200 mg per day administered in 9 different dosage regimens. The overall percentage of patients whose duodenal ulcers healed at 2 and 4 weeks on the different regimens was highly correlated with the percentage suppression of 24‐hour intragastric acidity induced by different regimens. Thus the therapeutic benefit of a given ranitidine dosage regimen in healing duodenal ulcers relates directly to its antisecretory effect.
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

SUMMARYWater 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

SUMMARYIn 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

SUMMARYThe 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

SUMMARYTen 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

SUMMARYGR122311X (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

SUMMARYWe 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

SUMMARYFifty 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

SUMMARYThe 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

SUMMARYThe 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

SUMMARYDyspepsia 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

SUMMARYSerotonin (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

SUMMARYAcetorphan 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

SUMMARYThe 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.