Reducing overnight secretion of acid to heal duodenal ulcers. Comparison of standard divided dose of ranitidine with a single dose administered at night.

This study was undertaken to assess the clinical usefulness of a single nighttime dose of ranitidine in the short-term healing of duodenal ulcer. One hundred and nine patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with ranitidine, either 150 mg twice daily or 300 mg as a single nighttime dose for four weeks, in a prospective double-blind, double-placebo trial. Of the 102 patients who completed the study, 48 of 57 (84 percent) healed endoscopically on ranitidine 150 mg twice daily, and 43 of 45 (96 percent) healed on 300 mg at nighttime (Mantel-Haenszel test without continuity correction: X2 = 2.9, p = 0.09). One patient treated with ranitidine 150 mg twice daily had a transient episode of cholestatic hepatitis that did not necessitate stopping the drug; in this patient the ulcer healed after 28 days of treatment. There were no other unwanted effects in either group and no significant abnormal biochemical or hematologic changes. This study shows that ranitidine 300 mg given as one nighttime dose is as safe as 150 mg twice daily, and equally as effective. Three hundred milligrams at night appear to confer protection against the adverse effect of smoking in ulcer healing.

The assay of gastrin using the perfused rat stomach.

1. A method is described for the bio-assay of gastric secretagogues using the perfused rat stomach in which the acid output can be readily and accurately quantified.2. This technique increases the sensitivity of the perfused rat stomach so that 10-20 ng of synthetic human gastrin I can be detected.3. It is possible to assay secretagogues, relative to a standard with fiducial limits of less than +/-30%.4. The use of this system is illustrated by assays comparing synthetic human gastrin I with pentagastrin, pure hog gastrin and gastrin added to plasma.

The role and limitations of H2-receptor antagonists in the treatment of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GERD) occurs in up to 44% of adults in the USA. Most individuals do not seek medical help, self-medicating with antacids. Manifestations of GERD range from symptoms without oesophagitis, which constitute the bulk of patients who self-medicate, to active oesophagitis and then to complications such as stricture and ulceration. It is the more severe cases who tend to come to the gastroenterologist, but it must be remembered that reflux symptoms are probably around 5-10 times more common than actual oesophagitis. Since acid in the refluxate is responsible for the bulk of the symptoms and mucosal damage, antacids are often used for quick relief--which of course may not be sustained. More prolonged suppression of acid secretion, such as by a histamine H2-receptor antagonist (H2RA) or a proton pump inhibitor (PPI), is required to give long-lasting symptomatic relief and heal any inflammatory change. H2-receptor antagonists inhibit acid secretion with an effect that lasts for 4-8 h with a single dose, decreasing stimulated acid secretion by around 70%. When treating oesophagitis, the H2RAs suffer from the disadvantage of their relatively short duration of action (compared with PPIs), development of tolerance, and incomplete inhibition of acid secretion in response to a meal. Therefore, it is not easy for the H2RAs to achieve optimum conditions for healing the more severe forms of oesophagitis--even very high doses may fail. In mild GERD the H2RAs have been shown to be effective in relieving symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

When should endoscopy (or radiology) be used in dyspepsia and peptic ulcer disease?

It is now possible readily to investigate dyspeptic symptoms using either a double-contrast barium meal or upper gastrointestinal endoscopy. The accuracy of endoscopy makes it preferable for routine use. As oesophagogastro-duodenoscopy (OGD) is invasive, some risks (albeit very small) are involved. Moreover, this technique has some weaknesses. For these reasons, selection of patients is important. Organic disease is most likely to occur in older patients: anyone presenting with dyspepsia for the first time over the age of 40 years should be investigated automatically. In individuals under 40 years of age, organic disease is less common and some selection criteria should be applied to reduce the number of negative investigations. After age, smoking is probably the single most important adverse factor. For gastric ulcer, endoscopy with biopsy, repeated after a course of therapy, is routine, but for duodenal ulcer repeat examination need not normally be undertaken owing to the effectiveness of modern healing drugs. Methods for improving the diagnostic accuracy of patient histories and clinical examinations need to be developed in order to utilize diagnostic investigations more efficiently for the patients' benefit.

Safety of lansoprazole.

The care with which patients are monitored during clinical trials provides an excellent database to assess the tolerability and safety of drugs. Additional information can be obtained from knowledge of the compound itself, its metabolism and its pharmacological action. Other compounds from the same class can highlight areas that need particular study. All these factors have been used to assess the safety of lansoprazole. Lansoprazole has been administered to 4749 subjects and has been well tolerated. Only 1.2% of patients have been withdrawn from trials because of suspected drug-related events but there was no pattern and no relationship to drug dosage. Diarrhoea (3.2%) and headache (4.7%) were the most commonly reported adverse events.

Review article: over-the-counter drugs and the gastrointestinal tract.

An increasing number of drugs are becoming available over-the-counter, empowering patients to treat them- selves. Although drugs presently available over-the-counter are generally safe, there are issues of safety and possible delays in diagnosis of serious conditions. Therefore it is vital that patients are made aware of the indications and limitations of over-the-counter drugs through improved communication and education. Pharmacists and drug companies will have an increasingly important role in giving information and advice to patients. This review looks at the present and future of over-the-counter medication, highlighting the safety aspects.

Pharmacological response to cimetidine and healing of duodenal ulceration: effects of high-dose cimetidine and combination of cimetidine with pirenzepine.

Overnight gastric secretion was studied in 32 patients with acute duodenal ulcers before treatment and whilst taking cimetidine 400 mg b.d. After 6 weeks of treatment with cimetidine 400 mg b.d. 13 patients had healed ulcers, seven patients had healed ulcers but a persistent erosive duodenitis, and 12 patients had persisting ulceration. Inhibition of nocturnal gastric secretion by cimetidine 400 mg b.d. was most profound in patients who healed their ulcers completely; a less profound inhibition of nocturnal gastric secretion was seen in the non-healing and duodenitis groups. In patients with persisting ulcers and poor inhibition of nocturnal gastric secretion by cimetidine, gastric secretion could be suppressed by either cimetidine 400 mg b.d. in combination with pirenzepine 50 mg b.d., or by cimetidine 1600 mg nocte, but suppression of nocturnal gastric secretion was more effective with cimetidine 1600 mg than cimetidine with pirenzepine.

Helicobacter pylori and non-steroidal anti-inflammatory drugs: lone agents or partners in crime?

A variety of mechanisms are responsible for the gastric and duodenal mucosal injury known to result from the consumption of non-steroidal anti-inflammatory drugs (NSAIDs). Many of these mechanisms may be influenced by coexistent infection with Helicobacter pylori. However, evidence of increased risk from NSAIDs in patients with this bacterium is contradictory. While some authors have reported that symptoms, severity and prevalence of mucosal damage are higher in H. pylori-positive individuals taking NSAIDs than in those who are H. pylori negative, others have noted no significant difference. Reasons for this conflict may include the age of the subjects studied, duration of treatment, toxicity of the NSAID employed and pathogenicity factors related to different strains of H. pylori.

Guidelines for the management of dyspepsia.

Dyspepsia is a common problem necessitating strategies for investigation and management because of the scarcity of available resources for investigation, i.e. endoscopy, and the need to focus on those at risk of serious disease. It is agreed that those in the older age group, with the presence of alarm symptoms or non-steroidal anti-inflammatory drug use require prompt endoscopy, but there remains a significant proportion of patients in whom the underlying diagnosis is unclear, presenting a management problem. Unfortunately, no universally applicable approach to investigation and management is available. Each major community needs to modify its guidelines for the management of dyspepsia based upon such factors as the local incidence of organic disease, prevalence of Helicobacter pylori infection and lifestyle. Endoscopy off acid suppressive therapy remains the only way of making a certain diagnosis. A diagnosis of gastrooesophageal reflux disease can now be made confidently by endoscopy, with selective use of 24 h pH study of the lower oesophagus. The same cannot be said for other groups with dyspepsia where symptoms alone are a poor guide to diagnosis. Evidence is beginning to emerge, however, that further stratification of dyspeptics on the basis of symptoms and other risk factors, e.g. H. pylori status, may help in management. In addition, there is a clinical need for accurate, inexpensive tests of foregut motility. Integrating clinical data with specific investigation in dyspepsia is required in order for the practising clinician to better define the dyspeptic so that patients can be managed effectively and simply.

The evaluation of a gastric bile probe.

The purpose of this study was to validate a new technique for measuring duodenogastric bile reflux in the human subject. A custom built cadmium telluride gamma detector (Radiation Monitoring Devices, Mass), small enough to be passed into the oesophagus and stomach, was developed and tested for sensitivity to 99Tcm and 75Se radioisotopes. When immersed in radiolabelled water, the detector was capable of measuring gamma radiation in quantities as low as 0.1 microCi (0.0037 MBq) per ml. Two patients (A and B) with endoscopically proven bile reflux, and three normal volunteers (C, D and E) underwent oesophageal manometry to map the position of the lower oesophageal sphincter (LOS). The gamma probe was passed via the nose, to a position in the gastric fundus, 5 cm below the LOS. Each subject was placed supine under a gamma camera (Siemens LFOV 37 ZLC head), centred on the epigastrium. A 4 mCi (148 MBq) dose of radiolabelled 99Tcm-HIDA was administered intravenously, and simultaneous internal/external scanning was performed for between 45 and 90 min. Internal gamma probe data was transferred by a screened cable to a Memolog 600 portable recorder, using a 5 s counting interval, and from the gamma camera to a Nodecrest Micas III computer, using a 15 s counting interval. Gamma camera counts from a region of interest over the fundus of the stomach were then correlated with counts from the internal probe using a linear regression analysis program on the Nodecrest. The internal gamma probe functioned well at body temperature in the acidic gastric environment. Radiolabelled bile refluxed into the stomach during HIDA scanning in three out of the five subjects (one patient and two normal volunteers). There was a strong correlation between internal and external gamma counts (A, r = +0.79; C, r = +0.53; E, r = +0.54; P greater than 0.01). In the other two cases, there was no bile reflux, but still a significant correlation between internal and external gamma counts (B, r = +0.89; D, r = +0.75; P greater than 0.01). The mean correlation coefficient for the series of five cases was +0.70. We conclude firstly that the newly developed internal gamma detector is capable of measuring the reflux of radiolabelled bile into the human stomach and, secondly, that bile reflux may occur in normal subjects as well as those with upper gastrointestinal pathology.

Acid-related disorders: what are they?

'Acid-related disorders' is a term used to describe a whole range of conditions from the Zollinger-Ellison syndrome, where acid is entirely responsible for the problems, to aerophagia and motility-type non-ulcer dyspepsia, where acid plays little if any role in the dyspeptic symptoms. Careful evaluation of the patient's symptoms is required to establish the basis for the dyspepsia and from that, careful selection can be made for any investigations that might be needed. These symptoms are the basis for advising on the most effective management--but as many doctors and patients erroneously attribute dyspepsia solely to acid, it is all too easy for inappropriate treatment to be offered. Acid is not the only cause of dyspeptic symptoms. Dyspepsia is a very common complaint with many causes. Acid and pepsin are often held responsible for these symptoms, by both the medical profession and the lay public. The term, 'acid-related disorders' is used to embrace this wide variety of conditions in which acid may play a part. However, in spite of current folklore, it is a spectrum of conditions ranging from situations where acid is crucial to conditions where acid may play little part.

Dyspepsia update.

BACKGROUND: Non-Ulcer Dyspepsia (NUD) is a very common problem which has many causes. Trying to group dyspeptic patients according to symptoms has been proposed in order to improve our understanding of the problem and to aid both clinical trials and indeed practice by studying and treating homogeneous groups. REVIEW: The literature has been reviewed to see if sub-groups of dyspepsia are standing up to scrutiny and clinically relevant. RESULTS: Reflux-like dyspepsia may now be identified accurately in a high proportion by a combination of careful history and the use of intra-oesophageal 24-h pH monitoring. Acid suppressing therapy is often useful in this group. Dysmotility-like dyspepsia is currently an area of active investigation with growing evidence that there is abnormal gastric emptying. Response to pro-kinetic drugs looks encouraging. Ulcer-like dyspepsia: Appears to be the largest dyspeptic group. Acid secretion is normal. Helicobacter pylori does not correlate with any group of dyspepsia. CONCLUSION: Separating NUD into groups is becoming useful in both investigation and treatment, but more specific simple tests are needed to take this further.