Novel non-steroidal anti-inflammatory drugs: what we have learned from animal studies.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is frequently associated with serious adverse effects related to the inhibition of cyclooxygenase (COX) in tissues where prostanoids exert physiological effects, such as gastric mucosal defence, renal homeostasis and platelet aggregation. The discovery of a second COX isoform (COX-2) specifically induced in pathological tissues led to the development of selective COX-2 inhibitors, believed to have an improved safety profile compared to traditional NSAIDs. Animal studies, however, have revealed a protective role for the COX-2 enzyme in the stomach, kidney, heart, vasculature and reproductive system, and therefore, the safety of COX-2 selective inhibitors needs to be reassessed. On the other hand, new therapeutic indications have emerged as a result of the role played by COX-2 overexpression in cancer or Alzheimer's disease. A second approach aimed at obtaining safer NSAIDs is based on the gastroprotective effects of nitric oxide (NO). Traditional NSAIDs chemically linked to NO-releasing moieties retain the therapeutic efficacy, but not the adverse effects, of the parent NSAIDs. Moreover, additional therapeutic applications in cardiovascular diseases, Alzheimer's disease and cancer have been suggested. Animal data, however, need to be confirmed in large clinical trials. Finally, the increase in endogenous NO via a selective increase in inducible NO synthase in the gastric mucosa is the mechanism underlying the good gastric tolerability and the gastroprotective effects of the non-selective NSAID amtolmetin guacyl, documented to date in the rat.

The need for long-term treatment of peptic ulcer.

Some 10% of the population in Western countries will suffer a duodenal ulcer or gastric ulcer at some time in their lives. Although there has been an improvement in the survival rate of patients with peptic ulcer haemorrhage, the mortality is still approximately 10%. There is evidence to suggest that peptic ulcer disease is a life-long condition and that ulcers remain active with an unchanged potential for complications such as haemorrhage and perforation. Over the past 15 years anti-ulcer drugs with different mechanisms of action have been developed, and their use results in complete healing of an ulcer in four to eight weeks. However, most patients experience recurrence of their peptic ulcer after discontinuation of the healing therapy. Studies of continuous H2-receptor antagonist therapy have shown that recurrence occurs less frequently than in untreated patients, is largely asymptomatic, and is rarely characterized by haemorrhagic complications. Limited data on therapy for the eradication of Helicobacter pylori suggest that this may be an alternative approach for selected patients. As protection afforded by H2-receptor antagonists remains undiminished over the course of several years and is also observed in ulcers which have bled in the past, the implementation of long-term management with these agents constitutes a rational policy.

Ranitidine bismuth citrate with either clarithromycin 1 g/day or 1.5 g/day is equally effective in the eradication of H. pylori and healing of duodenal ulcer.

BACKGROUND: No randomized double-blind studies have been performed to compare clarithromycin 1 g/day with higher doses of the macrolide (1.5 g/day) when combined with ranitidine bismuth citrate (RBC). AIM: To compare H. pylori eradication and ulcer healing rates of RBC 400 mg b.d. for 4 weeks combined for the first 2 weeks either with clarithromycin 500 mg b.d. (Group A) or clarithromycin 500 mg t.d.s. (Group B). METHODS: Two hundred and seventy-three patients with H. pylori-positive active duodenal ulcer were included. H. pylori infection was detected by CLO-test and histology on antral and corpus biopsies before and at least 4 weeks after the end of therapy. Eradication was assumed if both CLO-test and histology results were negative for H. pylori. RESULTS: Eradication/healing rates according to intention-to-treat and per protocol analysis were 76/82% and 87/92% for Group A and 78/85% and 88/95% for Group B, respectively (P = N.S.). Adverse events were reported by 7% and 12% of patients in Groups A and B, respectively, and they were generally mild. CONCLUSIONS: RBC in co-prescription with clarithromycin 500 mg b.d. is as effective as RBC plus clarithromycin 500 t.d.s. in eradicating H. pylori and healing duodenal ulcers.

Treatment of gastroesophageal (acid) reflux with lansoprazole: an overview.

Despite the fact that reflux esophagitis is a multifactorial disease, inhibition of gastric acid secretion is the mainstay of medical treatment, both for moderate and severe cases. Antisecretory agents lower the acidity of the refluxate, thus decreasing its aggressive effect, which favors the mucosal healing process. The greater the acid inhibition, the greater will be the mucosal repair. This is the reason for a therapeutic gain for H2-receptor antagonists over anticholinergics and antacids, and for proton pump inhibitors over H2-receptor antagonists. The most recently developed proton pump inhibitor, lansoprazole, at doses of 15, 30, or 60 mg/day for 4 and 8 weeks of treatment, has proven to be significantly more effective than placebo (one multicenter study involving 292 patients) or ranitidine (three multicenter studies involving 653 patients) in terms of mucosal healing and symptom relief. In two comparative trials with omeprazole 20 mg vs lansoprazole 30 mg (in a total of 349 evaluable patients) healing rates were found to be similar, but in one trial the relief of heartburn proved to be significantly more pronounced in patients receiving lansoprazole who also used fewer antacids. The frequency of adverse events was comparable in the two treatment groups. Reflux esophagitis is a chronic condition and after stopping antisecretory treatment, including lansoprazole, most patients relapse in terms of symptoms and endoscopical lesions, which suggests the need for long-term treatment. However, a strategy for long-term control of reflux esophagitis remains to be defined (lower daily dose, alternate-day standard dose, or concomitant prokinetic drugs?). The safety of proton pump inhibitors given for prolonged periods also needs to be more thoroughly evaluated.

Lansoprazole versus omeprazole for duodenal ulcer healing and prevention of relapse: a randomized, multicenter, double-masked trial.

The aim of this randomized, multicenter, double-masked, parallel-group study was to compare the efficacy of lansoprazole with that of omeprazole monotherapy in duodenal ulcer healing and prevention of relapse. A total of 251 patients with duodenal ulcer were treated with either lansoprazole 30 mg/d (n = 167) or omeprazole 40 mg/d (n = 84). Patients with healed ulcers were then randomly allocated to 12 months of maintenance therapy with lansoprazole 15 mg/d (n = 74), lansoprazole 30 mg/d (n = 71), or omeprazole 20 mg/d (n = 73). Healing rates at 4 weeks (intent-to-treat analysis) were 93.9% (95% confidence interval [CI], 90.2% to 97.6%) with lansoprazole and 97.5% (95% CI, 93.7% to 100%) with omeprazole; there were no significant differences between groups. Endoscopic relapse rates after 6 months were 4.5% (95% CI, 0% to 10.6%) with lansoprazole 15 mg, 0% with lansoprazole 30 mg, and 6.3% (95% CI, 1.5% to 12.5%) with omeprazole 20 mg, compared with 3.3% (95% CI, 0% to 8.2%), 0%, and 3.5% (95% CI, 0% to 8.8%), respectively, at 12 months. Again, there were no significant differences between groups. The incidence of adverse events during acute treatment was 6.0% and 7.1% in the lansoprazole and omeprazole groups, respectively; during maintenance therapy, the incidences were 12.2% (lansoprazole 15 mg), 5.6% (lansoprazole 30 mg), and 11.0% (omeprazole 20 mg). Within treatment groups, pain was significantly ameliorated after the acute phase but not after maintenance therapy (P < 0.05); no differences were observed between groups. Gastrin values increased significantly after acute therapy (P < 0.05), persisted at these increased levels during maintenance therapy, and returned to normal after 6-month follow-up. Both lansoprazole and omeprazole were highly effective and well tolerated in the treatment of duodenal ulcer; relapse rates were similar for all doses studied. Thus no additional benefit is to be gained from using a proton-pump inhibitor at a dose > 15 mg lansoprazole to prevent relapse.

Short-term treatment of duodenal ulcer with a single nocturnal dose of ranitidine: an up-to-date overview of Italian experience.

The author compares the efficacy of ranitidine 300 mg in a single bedtime dose, and ranitidine 150 mg twice daily, in 509 duodenal ulcer patients treated in two Italian multicentre trials. In the first of these trials the treatment period was 4 weeks plus a further 4 weeks in patients whose ulcers failed to heal, as against 2 plus 4 weeks in the other trial. Given the homogeneity of the patient entry and exclusion criteria, and the fact that identical clinical and endoscopic evaluation criteria were used in the two trials, the results are grouped together for analysis purposes. This permits detailed evaluation of the therapeutic effects of the two ranitidine regimens at two-weekly intervals over a total period of 8 weeks. With the single bedtime dose regimen, healing rates were 47.2% after 2 weeks, 81.7% after 4 weeks, 83.6% after 6 weeks and 94.8% after 8 weeks, while the corresponding rates for the twice-daily regimen were substantially similar (51.9%, 84.1%, 89.5% and 95.8%). The two regimens also produced comparable results in terms of relief of daytime and nocturnal ulcer pain. The Italian experience confirms, in a fairly large patient population, that the simpler ranitidine regimen represented by the single bedtime dose fully preserves its therapeutic efficacy in duodenal ulcer. Moreover, the fact that no differences were noted in responses of patients from the various different regions of Italy with their greatly differing constitutional, environmental and alimentary characteristics, appears to suggest that such factors are not sufficient in themselves to affect the therapeutic results obtained with the drug.

Endoscopic double-blind controlled trial of ranitidine vs placebo in the short-term treatment of duodenal ulcer.

The aim of the present study was to investigate the effectiveness of ranitidine in the treatment of duodenal ulcer. Fourty patients with endoscopically proven pyloric or duodenal ulcer were treated with ranitidine 40 mg t.d. with meals and 80 mg nocte, or identical placebo tablets under double-blind conditions. Endoscopy after four weeks of treatment revealed complete healing in 15 out of 18 (83.3%) ranitidine-treated patients and in 5 out of 17 (29.4%) of the placebo patients (P less than 0.01). Ulcer symptoms were significantly less in ranitidine-treated patients, while the difference in antacid consumption between the two groups was found to be only arithmetical. No side effects or significant hematological or biochemical abnormalities were found. Four-week treatment with 200 mg of ranitidine daily seems to correspond to that of 6-8 weeks with 1-1, 6 g of cimetidine.

Pirenzepine and exocrine secretions: a selective agent for gastric glands?

Nineteen healthy volunteers were studied to investigate whether or not muscarinic receptors of different exocrine glands could be distinguished from one another by the use of pirenzepine. A simultaneous evaluation of lacrimation, salivation and gastric secretion was carried out, bethanechol (80 micrograms/kg/hr) being used as a stimulant and pirenzepine (10 or 5 mg i.v.) as an inhibitor. Bethanechol increased salivation significantly and the volume of gastric juice, and non-significantly increased lacrimation and total acid output. Pirenzepine abolished the hypersecretion induced by bethanechol, and decreased the basal level of the exocrine secretions, to approximately the same extent. These experiments seem to demonstrate that if there is a difference among the muscarinic receptors of lacrimal, salivary and gastric oxyntic glands, pirenzepine is unable to discriminate them from one another, at least under the experimental conditions of this investigation.

Urinary PABA recovery after oral N-benzoyl-L-tyrosyl-PABA administration combined with various exocrine pancreatic stimulants.

Eleven healthy volunteers (C) and nine patients affected by chronic relapsing pancreatitis (CP) were administered N-Benzoyl-L-Tyrosyl-PABA orally, at a dose of 150 mg combined, on different days, with: 1) water alone (schedule a); 2) Lundh meal (schedule b); 3) Secretin-Caerulein by i.v. infusion (0.5 CU/kg/hr and 75 ng/kg/hr respectively) (schedule c); 4) Caerulein by i.m. injection (300 ng/kg) (schedule d). The mean urinary PABA recovery in CP was lower than in C with all the schedules, but this was statistically significant only with schedules a and c (P less than 0.02 and P less than 0.05 respectively). With respect to b, c, and d, the mean urinary PABA recovery seemed to increase both in C and in CP as compared with schedule a, but only in the CP group with schedule b was the increase statistically significant (P less than 0.05). The present data show that the exocrine pancreatic stimulants do not improve the reliability of the PABA test.

Omeprazole vs. ranitidine in the short-term treatment of duodenal ulcer: an Italian multicenter study.

A double-blind, double-dummy, randomized Italian multicenter trial was carried out to compare the efficacy and safety of omeprazole 20 mg in the morning and ranitidine 150 mg b.i.d. in short-term treatment of acute duodenal ulcer. One hundred and twenty-one patients (61 in the omeprazole and 60 in the ranitidine group) with endoscopically proven active duodenal ulcer, completed the study. The healing rates after 2, 4 and 6 weeks were 66, 97 and 100%, respectively, with omeprazole and 53, 85 and 92%, respectively, with ranitidine. The difference was statistically significant (p less than 0.05) at weeks 4 and 6. Night and day pain were markedly reduced during both treatments, as also antacid consumption. Both drugs were well tolerated, and the adverse events were infrequent and moderate. In our experience, omeprazole 20 mg once daily seems to be superior to ranitidine 150 mg b.i.d. in the short-term treatment of duodenal ulcer.

Comparison of pirenzepine and carbenoxolone in the treatment of chronic gastric ulcer. A double-blind endoscopic trial.

The purpose of the present study was to compare the effectiveness of pirenzepine and carbenoxolone in accelerating the healing of chronic gastric ulcer. Sixty-six out-patients with endoscopically proven gastric ulcer, without major systemic diseases, were admitted to the study. Patients were randomly allocated to either pirenzepine, 50 mg three times a day for 6 weeks, or carbenoxolone, 100 mg three times a day for one week followed by 50 mg three times a day for the remaining five weeks. At 6 weeks, the ulcers had healed in 20 out of 34 patients (59%) treated with pirenzepine, and in 15 out of 29 patients (52%) treated with carbenoxolone. Symptomatic improvement was similar with both drugs. Some major side effects (oedema, hypokalaemia and hypertension) occurred in approximately 30% of patients treated with carbenoxolone; of those receiving pirenzepine 25% complained of minor symptoms (e.g. dry mouth, headache, tachycardia). It is concluded that pirenzepine and carbenoxolone are of similar, but rather limited, efficacy in speeding the healing of chronic gastric ulcer, but show important differences with respect to tolerability.

Is ethanol metabolism affected by oral administration of cimetidine and ranitidine at therapeutic doses?

The aim of this study was to compare the ethanol serum concentration curve, the area under the curve and subjective response after acute ingestion of ethanol (red wine, 13 degrees proof, at a dose of 0.8 g/kg of ideal weight in 6 healthy volunteers with a mean habitual alcohol intake of 20 g/day. All the subjects underwent the test a total of three times, after pre-treatment with cimetidine (400 mg X 2/day/7 days) and ranitidine (150 mg X 2/day/7 days), respectively, and after receiving no pre-treatment. The wine was taken orally within the space of 15 min, four hours after taking a standard-weight ham sandwich. Blood samples were drawn at the following times: 0, 30, 60, 90, 120, 180, 240 and 360 minutes. The plasma ethanol curve of the subjects pre-treated with cimetidine lies above that of the subjects pre-treated with ranitidine, and largely coincides with the curve obtained in those who received no pre-treatment, with the exception of the initial hour-and-a-half, when the later show a slightly higher mean plasma concentration. The differences between the three treatment groups are merely arithmetical, but not statistical, with respect to peak plasma ethanol concentrations, time elapsing before peaking, and areas under the curves. These results are at variance with some published data suggesting a significant interaction of cimetidine with the metabolism of alcohol by way of interference either with the hepatic oxidative metabolizing enzymes, or with the activity of alcohol dehydrogenase.

Short-term treatment of reflux oesophagitis with ranitidine 300 mg nocte. Italian multicentre study.

A multicentre study involving 9 Italian institutions was carried out to compare the efficacy and safety of ranitidine 150 mg b.i.d. and ranitidine 300 mg nocte in the treatment of reflux oesophagitis. 117 patients with histologically proven oesophagitis were randomly allocated to two comparable treatment groups. Efficacy and reliability were evaluated by clinical and laboratory tests at the beginning of the study, and at 3 and 6 weeks; endoscopy and biopsies were performed at the beginning and at 6 weeks. Treatment with ranitidine for 6 weeks led to total disappearance of gastro-oesophageal reflux symptoms in 60% of patients, with percentages of partial improvement varying between 85% and 95% of cases. Improvement in the results of endoscopic examination was 85%, of which 55% were cured. Microscopic examination revealed an improvement of 36% and 44%, with a cure rate of 18% and 26% respectively. With regard neither to the regression of symptoms nor to the macroscopic and microscopic inflammation of the oesophageal mucosa did statistical examination show significant differences in the therapeutic efficacy of ranitidine 150 mg b.i.d. or 300 mg nocte for treatment of reflux oesophagitis.

Ranitidine vs cimetidine: short-term treatment of gastric ulcer.

We compared the clinical effectiveness and endoscopic results of ranitidine and cimetidine treatment; 71 outpatients, all affected with benign gastric ulcer, were selected for the study (43 type I, 7 type II and 21 type III, according to Johnson's classification). The patients were treated randomly for 4 weeks with ranitidine (300 mg daily) or cimetidine (1 g daily). An endoscopic examination was repeated within 3 days after the end of the treatment. Clinical checks were performed weekly in order to monitor the clinical course of pain and antacid consumption, according to the patient's needs. The patients who did not demonstrate complete healing on endoscopic examination were treated for an additional 4 week period. At the end of this 4 week period, another endoscopic examination was done. Thirty-six patients treated with ranitidine and 33 with cimetidine completed the first period of therapy. The two groups were homogeneous with regard to sex, age, duration of disease, smoking habits, alcohol consumption, and type and size of ulcer. Ranitidine and cimetidine treatments did not demonstrate any significant difference with regard to ulcer healing after the 4th or the 8th week of therapy. Both ranitidine and cimetidine were less effective in healing type I than type II and III G.U., at the 4th week of treatment. No significant differences between the two groups were noted with regard to pain or weekly antacid consumption. No significant side effects were reported.

[NSAID-induced gastroduodenal damage: strategies for prevention]. / Danno gastroduodenale da FANS: strategie di prevenzione.

The improved knowledge of the mechanism by which NSAIDs work and damage the gastrointestinal (GI) mucosal suggested a series of measures for the prevention of NSAIDs-induced GI lesions, apart from the use of those proved to be less toxic. PPI have now been definitively shown to be more effective in the relief of symptoms and in the healing and prevention of ulcers/erosions than H2-antagonists and also better tolerated than misoprostol. Other more innovative approaches include selective and highly selective COX-2 inhibitors, NSAIDs containing NO or stimulating the gastric endogenous biosynthesis of NO, and chiral NSAIDs. Clinical usefulness of other compounds, including NSAIDs associated with zwitterionic phospholipids or fibroblast growth factor, is still under investigation.

[Diet and drugs in the therapy of nonorganic dyspepsia: the hypothesis and factual data]. / Dieta e farmaci nella terapia della dispepsia non organica: ipotesi e dati di fatto.

Non-organic dyspepsia, although not frequently reported, is still a disorder which is difficult to classify in nosographic and physiopathological terms, a fact which inevitably influences the indications for its treatment. Non-pharmacological treatment of non-organic dyspepsia includes changes in dietary and behavioural habits which, even if established on empirical grounds, play a far from ancillary role. When considered appropriate, pharmacological treatment must be formulated solely on the basis of controlled clinical trials vs placebo given the well-known significance of the placebo effect in this and other so-called "functional" diseases. The therapeutic strategies which are most subject to verification are based on the one hand on the neutralisation or inhibition of gastric acid secretion and, on the other, on the improvement of gastrointestinal motility. Surprisingly, the widely used antacid drugs are among those which have been less well studied and show the lowest efficacy. Among the anti-secretory drugs, pirenzepine is approximately 25% more effective than placebo. H2-antagonists, the drugs which have been most closely studied both in terms of the number of trials and the size of the sample populations studied, produce contradictory results. However, a meta-analysis of the trials shows an overall 18% improvement in efficacy compared to placebo. The overall results of studies on prokinetic compounds are "good" in meta-analytical terms, with an improved efficacy of 50% compared to placebo. This is not necessarily due to the superiority of prokinetic compared to anti-secretory drugs and can be explained by the reduced placebo effect in trials using prokinetic drugs or a greater presence in the latter of dyspepsia which is physiopathologically correlated to motor discord. Among the future drugs still being studied, it is particularly worth mentioning fedotozine, a specific K opioid receptor agonist which appears to have provided extremely interesting results in preliminary studies. The role of barrier drugs, such as sucralfate and colloidal bismuth, continues to remain unclear and in particular the latter might be of increased use if evidence of a relationship between Helicobacter pylori and non-organic dyspepsia were reinforced; this relationship may in fact not exist in all dyspeptic patients but only in a subgroup. Lastly, the problem of the duration of pharmacological treatment still remains unsolved, as do the questions of whether longterm treatment should be conceived once acute symptoms have disappeared and whether it is possible to hypothesise differentiated pharmacological treatment depending on the clinical variants of functional dyspepsia which have been defined with greater attention over the course of the past decade.

Placebo in the evaluation of antiulcer drugs.

According to the most recent definition, "placebo" is any substance devoid of specific activity, which nevertheless is given in order to obtain an effect. It is used to advantage in identifying active drugs (controlled clinical trials). It has an effect which is usually (though not always) favourable and has its own pharmacology closely resembling that of active substances. In view of the consistency of the placebo effect, any substance tried in the treatment of the various diseases of the alimentary tract must prove superior to placebo in order to be considered an "active" substance. It is only on the basis of this criterion that we may accept the risk of side-effects which, though they may be slight, are nevertheless unjustified if the drugs we are administering are inactive. This drug vs placebo comparison classically takes the form of so-called "double-blind" controlled studies, but for digestive diseases these are far less numerous than the many unreliable, uncontrolled studies available. Generally, the use of a placebo control has led to the elimination of numerous substances characterized by purely alleged efficacy, and to the identification of efficacious compounds or acceptable therapeutic trends. In peptic ulcer, controlled studies vs placebo have also contributed towards the acquisition and definition of useful pathophysiological, clinical and therapeutic notions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Helicobacter pylori and the treatment of gastric ulcer. Reflections and uncertainties]. / Helicobacter pylori y tratamiento de la úlcera gástrica. Reflexiones e incertidumbres.

The authors examine the relationship between Helicobacter pylori and gastric ulcer therapy, analyzing both the data suggesting that eradication of the organism renders the gastric mucosa less susceptible to development of gastric ulcer and the substantial body of evidence to the contrary. They review the results reported in clinical trials with colloidal bismuth subcitrate, antimicrobial agents (furazolidone), and combinations of antiulcer and antimicrobial agents (H2-antagonist + cefixime, H2-antagonist + metronidazole). Also analyzed is the relationship between Helicobacter pylori eradication and ulcer recurrence; only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing. The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of Helicobacter pylori facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.

[No acid, no ulcer: such a simple axiom?]. / No ácido, no úlcera: un axioma tan simple?

According to the traditional view gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanisms of action--antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents--thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing yield contradictory clinical results; morning and bedtime single administrations of H2-antagonists prove equiactive on ulcer healing, leading to a reappraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby apparently undermining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the protonpump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility.

[Functional dyspepsia in the aged]. / La dispepsia funzionale nell'anziano.

Functional dyspepsia (FD) is a very common syndrome in general population which does not spare the elderly. To define the pathophysiology of FD (GI secretion and motility, visceral sensitivity, psyche) in the elderly proves to be a difficult task, because it is hard enough in itself to discriminate between troubles due to "normal" ageing and manifestations of diseases to which the elderly are particularly susceptible. At any event, unlike in non-elderly dyspeptics, in elderly patients thorough GI investigations are always absolutely mandatory. Dietary recommendations should be simple and reasonable. Drug therapy by antisecretory and prokinetic agents should not be too strong, because the elderly are particularly sensitive to drugs, and are often taking other drugs for extra-intestinal pathology.