Long-term management of duodenal ulcer with pirenzepine and cimetidine: a double-blind controlled clinical trial

The effectiveness of pirenzepine in the prevention of duodenal ulcer relapses was assessed by means of a double-blind controlled trial versus cimetidine. Seventy duodenal ulcer out-patients endoscopically healed after a 6-week treatment with either pirenzepine or cimetidine were admitted to the trial. The former pirenzepine patients were treated again with pirenzepine: 1 tablet at breakfast and 2 tablets at bedtime (75 mg daily). The former cimetidine patients were treated again with cimetidine: 2 tablets at bedtime (400 mg daily). They received one placebo tablet at breakfast. Both treatments lasted 12 months. Tablets of a mild antacid were permitted only if necessary to relieve severe ulcer pain and heartburn. Patients underwent clinical and endoscopic assessments after 4, 8 and 12 months of treatment and whenever ulcer symptoms lasted more than 4-5 consecutive days. Only 47 out of the 70 patients that entered the trial underwent all clinical and endoscopic controls. Sixteen out of 23 patients on pirenzepine (70%) and 17 out of 24 patients on cimetidine (71%) did not relapse after 12 months. The difference is not statistically significant. Both treatments were well tolerated. The results show that pirenzepine was as effective as cimetidine in the prevention of duodenal ulcer relapses when administered at a dosage of 75 mg daily (of which 50 mg at bedtime) for one year.     

Clinical utility of electrogastrography and the water load test in patients with upper gastrointestinal symptoms.

We assessed gastric myoelectric functioning in patients with various gastrointestinal symptoms and to determine the utility of electrogastrography in differentiating specific disease entities. Electrogastrography with a water load was performed in 101 patients with reflux disease, 55 patients with active gastric ulcer, 59 patients with functional dyspepsia, and 30 controls. Upper gastrointestinal symptoms were assessed in each patient. Electrogastrography was abnormal in 41 (40.6%) patients with reflux disease, 31 (56.4%) patients with active gastric ulcer, and 26 (44.1%) patients with functional dyspepsia (P=NS). Water load tolerance was greater in controls than any patient group (all P<0.05). Symptoms predicted abnormal electrogastrography in reflux patents with satiety (OR=2.9; P<0.05) and in dyspeptic patients with nausea (OR=3.1; P<0.05). Although electrogastrography is helpful in differentiating subgroups of patients with nausea or satiety, it cannot directly differentiate disease states such as reflux disease, gastric ulcer, and functional dyspepsia.     

Healing of benign gastric ulcer with low-dose antacid or cimetidine. A double-blind, randomized, placebo-controlled trial

We conducted a 12-week, double-blind, randomized, placebo-controlled trial to determine whether cimetidine (300 mg with meals and at bedtime) or a convenient, liquid aluminum-magnesium antacid regimen (15 ml one hour after meals and at bedtime) would expedite healing or relief of symptoms in patients with benign gastric ulcer. Of the 101 patients who completed the trial according to protocol, 32 received the antacid, 36 cimetidine, and 33 placebo. At 4, 8, and 12 weeks after entry, ulcers had healed in a larger percentage of patients treated with cimetidine than of those treated with placebo: 53, 86, and 89 per cent of the cimetidine group versus 26, 58, and 70 per cent of the placebo group (P = 0.02, 0.01, 0.05), respectively. Healing at the three intervals had occurred in 38, 70, and 84 per cent, respectively, of the antacid-treated patients. Neither cimetidine nor antacid was more effective than placebo in relieving symptoms. The presence or absence of symptoms during the fourth and eighth treatment weeks was a poor predictor of the presence of absence of an ulcer crater. We conclude that cimetidine significantly hastens the healing of benign gastric ulcer.     

The association of ranitidine and sucralfate in the short-term treatment of duodenal ulcers, as compared to other forms of treatment

Results of the treatment of duodenal ulcer with ranitidine (150 mg X 2/die) and sucralfate (1 gr X 2/die) have been compared with other common schemes of therapy. Administration of the drugs was carried out for 8 weeks, and the evolution of the ulcer lesion was followed with endoscopic controls at the beginning and end of the treatment. Ulcer healing occurred in 92% of 25 patients, as compared with 83,3% of 30 cases treated with ranitidine only; 80% of 30 cases with cimetidine 1 g/day; 80% of 20 cases with cimetidine 800 mg/b.i.d.; 75% of 20 cases with sucralfate 3 g/day; 73,3% of 30 patients with pirenzepine 150 mg/day; 60% of 20 cases with sulglycotide 0.5-1 g/day; and 50% of 40 ulcerous patients treated with placebo. From these results it is concluded that the association of sucralfate with an H2-antagonist improves the possibility of short-term healing of duodenal ulcer.     

Treatment of gastroduodenal ulcers with cimetidine in combination with low-dose propantheline

Fifty-eight adult outpatients with endoscopically verified gastric, prepyloric or duodenal ulcers completed a double-blind trial of treatment with either cimetidine, 1 g daily, plus propantheline, 45 mg daily (group A) or cimetidine, 1 g daily, plus placebo (group B). After neither three nor six weeks of treatment was there any significant difference between the two groups with regard to ulcer healing or symptomatic relief. The ulcers of 22 (79%) of the 28 patients in group A and 25 (83%) of the 30 patients in group B were healed after six weeks, and 93% of the patients in both groups became painfree. We were thus not able to show any advantage in combining cimetidine treatment for ulcer healing with low-dose propantheline. In a small open trial the patients with healed ulcers received prophylactic treatment for 12 months with 1) cimetidine 800 mg daily, 2) cimetidine 400 mg at bedtime plus propantheline 45 mg daily or 3) propantheline 90 mg daily. No significant differences were found between the ulcer recurrence rates, but it cannot be excluded that a larger number of patients in each group might have yielded real differences.     

Cimetidine for anastomotic ulcers after partial gastrectomy. A randomized controlled trial.

In a randomized double-blind multicenter trial, 15 outpatients with endoscopically proved anastomotic ulceration after Billroth I or Billroth II partial gastrectomy received cimetidine, 1 g daily over eight weeks, or a placebo. All patients also received antiacid. The ulcer healed completely in all seven cimetidine-treated patients and in one of the eight placebo-treated patients (P less than 0.01). Ulcers not healed during the double-blind phase of the trial were all subsequently healed on open cimetidine treatment. There was a trend toward improvement of daytime symptoms in favor of cimetidine (P = 0.06), and nighttime symptoms were significantly relieved during the initial four weeks of cimetidine treatment P = 0.02). We conclude that cimetidine, 1 g daily, promotes healing of anastomotic ulcers after partial gastrectomy.     

Food intolerance in duodenal ulcer patients,non ulcer dyspeptic patients and healthy subjects

Summary In 50 duodenal ulcer out-patients and 50 non ulcer dyspeptic patients suffering from low to moderate epigastric painful symptoms the intolerance of 39 foods were significantly increased compared to a group of 50 healthy subjects. Food intolerance was not different between duodenal ulcer and non ulcer dyspeptic patients. Intolerance was related in the majority of nutrients to aversion and pain or to an increased incidence of aversion alone in patients and normals. In duodenal ulcer, coffee and fruit juice were associated with an elevated incidence of pain.Abbreviations DU Duodenal ulcer - NUD Non ulcer dyspepsia - N Normal Dedicated to Professor Dr. N. Zöllner on the occasion of his 65th anniversary     

The prevalence of anti-Helicobacter (Campylobacter) pylori antibodies in patients and healthy blood donors

An enzyme linked immunosorbent assay (ELISA) with a sonicated suspension of Helicobacter (Campylobacter) pylori as antigen was used to detect anti-H. pylori antibodies in 517 patients without dyspepsia or peptic ulcer symptoms and 401 healthy blood donors. The criterion of seropositivity was determined from a receiver operating curve computed with the values of optical densities of 48 sera from dyspeptic patients with proven helicobacter-associated gastritis and 16 sera from dyspeptic patients with normal antral mucosa and no microbiological or histological evidence of H. pylori infection. The 227 (44%) seropositive persons amongst the patient group appeared to be significantly higher than the 142 (35%) sera with antibodies in the blood donors tested (p less than 0.03), even when adjustment was made for increasing age. We conclude that the prevalence of antibodies against H. pylori increases with age and that although antibodies are more prevalent in patients attending a hospital than in healthy blood donors, seropositivity suggestive of current or past infection can be found in one third of a randomly chosen population of blood donors.     

Open access gastroscopy findings are unrelated to the use of aspirin and non-steroidal anti-inflammatory drugs.

This study aims to determine whether priority should be given to patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin when selecting which dyspeptic patients to refer for open access gastroscopy. A total of 8156 patients underwent gastroscopy, all of whom had upper gastrointestinal symptoms. Patients taking NSAIDs or aspirin showed no significant differences in the frequency of ulcer disease when age-matched groups were compared. Although NSAIDs and aspirin are frequently implicated in gastrointestinal bleeding in the elderly, patients referred for investigation of dyspepsia show no increase in major endoscopic pathology.     

Antacid treatment of duodenal ulcer

Sixty-seven consecutive outpatients with endoscopically verified duodenal ulcer were randomised to a double-blind treatment with either 10 ml of an antacid suspension (buffering capacity 85 mmol/10 ml, packed in single dosage pads) 1 and 3 h after each meal and at bedtime or cimetidine 400 mg b.i.d. The double-dummy technique was employed. Endoscopy was performed after 4 weeks treatment and, if the ulcer had not healed, after 8 weeks treatment. When ulcer healing had occurred, the patient entered a 1 year follow-up study. The cumulative healing rates after 4 and 8 weeks treatment were 83 and 97% vs. 69 and 94% in the antacid and cimetidine groups respectively. No significant differences were observed between the treatment groups regarding ulcer healing, symptom relief or compliance. Adverse reactions were few and only 3 (9%) patients in the antacid group had to discontinue the treatment due to diarrhoea. Of the cimetidine treated patients, 61% had symptomatic relapse during the 1 year follow-up compared to 71% of the antacid treated patients. There were no significant differences in recurrence rate or time to relapse. The moderate dose antacid treatment used here is efficient, well tolerated, safe, convenient and is a good alternative treatment of the duodenal ulcer patient.     

Cimetidine and placebo-cimetidine in the treatment of patients with chronic gastric ulcer (a multiclinical randomized double-blind comparative study)

The efficacy of a 4-week cimetidine treatment was examined by a double-blind randomized study in 37 outpatients with endoscopically verified chronic gastric ulcer. The patients received a daily dose of 3 times 1 tablet and, at night before going to bed 2 more tablet, thus a total amount of 1 g cimetidine, or cimetidine-placebo, but in case of complaints they could take in addition a mixed alkaline powder. Patients not recovering in response to a 4-week treatment, were then administered daily 5 tablets of cimetidine up to their complete recovery. Endoscopic, laboratory and clinical examinations were carried out every other week. As a result of a 4-week treatment, 56% of the cimetidine group recovered. The difference was not significant (P less than 0.2). The size of the ulcer and the intensity of the complaints were reduced significantly in both groups. The decrease in the size of the ulcer was significantly greater in the first two weeks of cimetidine treatment than in the cimetidine-placebo group (P less than 0.05). This favourable dynamics of ulcer healing was not felt in the second two weeks of treatment, and after four weeks there was no difference in the size of the residual ulcer to between the two groups. Cimetidine seemed to be a suitable drug for treating chronic gastric ulcer, since its healing rate proved to be better than that of placebo, the gain in weight also was favourable and there were no side-effects.     

Factors predicting the therapeutic outcome of duodenal ulcer treatment with H2-receptor antagonists

Summary In a prospective trial 37 duodenal ulcer patients were treated daily with 1 g cimetidine. Personal and clinical data were obtained for all patients, acid secretion studies performed before and during treatment, and pharmacokinetic parameters of cimetidine determined. The healing rate after 4 weeks was 64.9% (24 patients). Non-Responders included a higher proportion of smokers, patients with a history of ulcer and previous treatment with H₂-receptor antagonists than Responders. Basal acid output (BAO) and peak acid output (PAO) values were not different between the two groups, nor was the reduction of BAO and PAO under cimetidine. However, more Responders had complete suppression of BAO than Non-Responders. A correlation existed in both groups between cimetidine plasma concentration and PAO suppression but not with BAO suppression. Regular drug intake (compliance) was found in about 90% in both groups. Cimetidine bioavailability parameters were identical in both groups, but Non-Responders had a higher peak concentration and a shorter time of peak concentration. Discriminant analysis enabled a prediction of treatment response in 89.2% of the patients by using five factors: time of peak concentration of cimetidine, previous H₂-receptorantagonist treatment, peak concentration, smoking, and alcohol use. Prediction of treatment response is increased by use of drug related variables.Abbreviations BAO basal acid output - C_max peak concentration - PAO peak acid output - T_max time of peak concentration - T>0.5 time of effective plasma concentrations Dedicated to Professor Dr. Hans J. Dengler on the occasion of his 60th birthday     

Seropositivity to a major allergen of Anisakis simplex, Ani s 1, in dyspeptic patients with Helicobacter pylori infection: histological and laboratory findings and clinical significance

Previous studies have demonstrated a high prevalence of seropositivity to the Ani s 1 protein in dyspeptic patients with Helicobacter pylori infection, but it is not known whether this represents episodes of anisakiasis misdiagnosis or previous exposure to the parasite without clinical relevance. To investigate the clinical significance of seropositivity to the Ani s 1 protein, a cohort study was performed with 87 consecutive dyspeptic patients who were treated for H. pylori infection. Fourteen (16.5%) patients were seropositive for the Ani s 1 protein, which was associated with the consumption of uncooked fish (p 0.0002). There were no differences in histological findings between subjects seropositive or seronegative for Ani s 1, but seropositive patients had increased eosinophil and basophil leukocyte counts (p < 0.05). Anti-Ani s 1 IgE was associated with a lack of improvement in the group of patients with non-ulcer dyspepsia after successful eradication of H. pylori (p 0.016). Thus, in at least a subset of patients with H. pylori infection, seropositivity to Ani s 1 could have clinical relevance. In addition, these data highlight that only anisakiasis associated with severe allergic or gastric symptoms is currently being diagnosed.     

Prevalence of Helicobacter pylori vacuolating cytotoxin and its allelic mosaicism as a predictive marker for Iranian dyspeptic patients

Helicobacter pylori infects the majority of the population in the developing countries. However, the rate of gastrointestinal complications such as peptic ulcers and gastric malignancies has no parallel with the infection. In order to determine whether cytotoxin (vacA) and its allelic polymorphism can serve as screening markers for such a population, H. pylori strains were isolated from one hundred and thirty two dyspeptic patients. H. pylori genomic DNA was extracted and underwent PCR-amplification for the cytotoxin alleles. Genotyping of the signal sequence region of the vacA gene identified 68% (70 out of 103) of patients with non ulcer dyspepsia (NUD) and 79% (23 out of 29) of the patients with peptic ulcer disease (PUD) possessing the s1 genotype. S1 strains were significantly more prevalent among patients with PUD as compared to the NUD (p < 0.05). In regard to the middle region, 55% of the patient isolates belonged to the m2 genotype with no correlation to disease. The s1m2 genotype was the most prevalent among all patients and significantly correlated with the PUD group (p < 0.05).     

How well do general practitioners manage dyspepsia?

This paper reports the incidence of dyspepsia in general practice, the characteristics of patients, the types of complaints presented and the management of the dyspeptic patient by general practitioners. Fourteen general practitioners in the Maastricht region of the Netherlands studied 318 consecutive patients presenting with dyspepsia. Two questionnaires were used: one filled in by the patient (82% response), the other by the physician (100% response). The diagnostic conclusions which were established after three months of follow-up were compared with the diagnostic hypotheses at the initial consultation. The annual consultation rate for dyspepsia was calculated as 27 per 1000 registered subjects. One third of the patients had an earlier history of dyspepsia. Almost all patients (95%) complained of pain, and 37% had been suffering from pain for more than three months before consulting the general practitioner. The general practitioner prescribed medication in 70% of cases; less commonly the patient was referred for x-ray (14%), endoscopy (13%) or to a specialist (11%). A higher age was associated with a higher probability of referral, and with the finding of organic disease. A history of ulcer disease was strongly correlated with the diagnosis of an ulcer during the current episode. The overall concordance between the general practitioner's diagnostic hypothesis at the initial consultation and the diagnostic conclusion after three months of follow-up was 78%; it was highest when minor pathology was suspected. We conclude that dyspepsia is managed well in general practice and is only rarely associated with major lesions. Dyspeptic patients referred to a specialist therefore constitute a highly selected population.     

Long-term follow up of patients with gastritis associated with Helicobacter pylori infection.

The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later. Gastric antral biopsies had been taken routinely at endoscopy and were subsequently re-examined for the presence of H pylori. The patients' medical records were examined to establish their consulting rates over the follow-up period and whether they suffered from any other medical conditions. Patients were interviewed to assess the course of their dyspeptic symptoms. Comparison of patients who were unequivocally H pylori positive with those who were negative revealed no significant differences in the consultation rate for gastroenterological symptoms, in the proportion of patients referred to a hospital consultant or for further gastroenterological investigations or in the proportion reporting that their symptoms had improved. However, a statistically highly significant relationship was found between H pylori infection and hypertension. The results of this study have shown that there is a good prognosis for non-ulcer dyspepsia whether or not H pylori infection is present. The association between H pylori gastritis and hypertension clearly merits further investigation.     

Successful treatment of intractable gastric ulcers with acetazolamide

An open-controlled trial performed in gastric ulcer cases resistant to previous cimetidine, antacids, vitamin A and polyvinylbutylether therapy applied for at least 4 weeks. A group of 21 patients treated with acetazolamide was compared with 16 patients treated with cimetidine (controls). The period of management was 3 weeks. The number of healed patients (P = 0.009), the surfaces of ulcers after treatment (P = 0.0166) and the duration of complaints (P = 0.0003) differed favourably and significantly in the acetazolamide group as compared to the cimetidine group. In the acetazolamide group, however, several side effects (in 11 cases metabolic acidosis, in 9 cases tingling of extremities) were registered. Side effects were not seen in the control group. It is supposed that in the treatment of gastric ulcers a compound with less carbonic anhydrase inhibition but with the same or more cytoprotective effect would have wider clinical perspectives than acetazolamide alone.     

The role of screening for Helicobacter pylori in patients with duodenal ulceration in the primary health care setting.

BACKGROUND: It is known that at least 90% of duodenal ulcers are caused by infection with the bacterium Helicobacter pylori. Eradicating this organism usually results in complete resolution of the disease. Testing for H pylori was introduced relatively recently, and thus, many patients known to have uncomplicated peptic ulcer disease who continue to need long-term treatment with ulcer-healing drugs have never been tested for the infection or offered eradication therapy. In modern computerized practices, this subgroup of patients can readily be identified by reference to morbidity and repeat prescribing data. Eradication of H pylori infection in this group of patients has great potential benefit for the individuals concerned as well as cost-saving benefit for the National Health Service. AIM: The aim of this prospective study was to determine whether it is worthwhile screening for and treating H pylori infection in patients in a general practice population with previously diagnosed duodenal ulcer disease taking ulcer-healing drugs long term. METHOD: In 1994, in a practice of 7100 patients, morbidity and repeat prescribing data were used to identify 40 patients (0.6%) with proven duodenal ulcer disease taking ulcer-healing medication long term and with uncertain H pylori status. Twenty-nine of the 40 subjects agreed to undergo serology testing for H pylori antibodies. Of 20 (69%) who were positive, 18 (eight women, median age 63.8 years) were given eradication therapy. Seventeen patients received omeprazole 40 mg once daily and amoxycillin 500 mg three times daily for 14 days with metronidazole 400 mg three times daily for the first 7 days; for the remaining patient metronidazole was inadvertently omitted. [13C]Urea breath testing was carried out at the local hospital at least one month after therapy to determine whether eradication treatment had been successful. Subjects were also personally followed up by telephone after 1 and 4 months to assess the success of treatment subjectively. RESULTS: [13C]Urea breath testing showed that H pylori eradication was successful in all 17 patients (100%) who received the intended eradication regimen. Helicobacter pylori was not eradicated in the patient who received only omeprazole and amoxycillin. Four months after successful H pylori eradication, 13 of the 17 (76%) patients remained completely asymptomatic. Two of the four patients who had some recurrent dyspepsia had known gastro-oesophageal reflux and their ongoing symptoms after eradication therapy seemed, on close questioning, to be more attributable to this than to duodenal ulcer disease. CONCLUSION: Testing for and eradication of H pylori is worthwhile in general practice in those patients with previous proven duodenal ulceration who need long-term ulcer-healing medication. The high rate of eradication of H pylori achieved with the regimen used in this study compares very favourably with that of other treatment regimens. However, in patients with duodenal ulcers there may be coexisting pathology, and H pylori eradication does not necessarily result in complete disappearance of dyspeptic symptoms. Thus, when monitoring the outcome of treatment it is important to assess improvement of symptoms as well as objective evidence of eradication.     

A randomised controlled trial of four management strategies for dyspepsia: relationships between symptom subgroups and strategy outcome.

BACKGROUND: The first step in the management of uncomplicated dyspepsia in primary care often consists of prescribing empirical therapy, but in certain cases prompt endoscopy might be preferred. Any decision is usually based on the patient's symptoms and the presumed underlying pathology that causes these symptoms. AIM: To assess the relationship between symptom subgroups and the effect of management strategies on primary care patients with dyspepsia. DESIGN OF STUDY: Randomised controlled trial. SETTING: All patients presenting successively with a new episode of dyspepsia between January 1995 and November 1997. METHOD: The results of four management strategies in dyspeptic primary care patients were compared and the value of subgrouping within this trial was estimated. Patients were allocated to one of either (a) empirical treatment in which therapy was based on the presented symptoms, or empirical treatment with (b) omeprazole or (c) cisapride regardless of the presented symptoms, or (d) prompt endoscopy followed by the appropriate treatment. Patients were retrospectively classified into the subgroups for each strategy using baseline data. The yield of each strategy was measured by counting the number of strategy failures in the first year. RESULTS: Of the 349 included patients, 326 were analysed. No statistically significant difference could be demonstrated between the strategies or between the symptom subgroups. However, patients in the reflux-like subgroup showed a trend towards a better outcome in all empirical strategies. Ulcer-like dyspepsia seemed to benefit from omeprazole. The non-specific subgroup seemed to benefit from cisapride but also had the highest proportion of strategy failure. Prompt endoscopy did not appear especially useful in any subgroup. CONCLUSION: Although this study has relatively low power, we conclude that the use of symptom subgroups seems to be a sensible approach when choosing empirical therapy in dyspepsia. Patients with reflux-like symptoms seem to have the best prognosis in the first year in every strategy.     

Effect of omeprazole and cimetidine on duodenal ulcer. A double-blind comparative trial

We conducted a double-blind randomized study of 132 patients to determine whether the new, investigational proton-pump inhibitor, omeprazole (30 mg per day), would accelerate healing and pain relief, as compared with cimetidine (1 g per day), in patients with duodenal ulcer. After two weeks of treatment, which was completed by all patients, the healing rates were 73 per cent in the omeprazole group and 46 per cent in the cimetidine group (P less than 0.01). After four weeks of treatment, which was completed by 118 patients, the corresponding figures were 92 and 74 per cent (P less than 0.05). In the omeprazole group 55 per cent of the patients were free of pain after the first week, as compared with 40 per cent of those treated with cimetidine (P greater than 0.05). No major clinical or biochemical side effects of omeprazole or cimetidine were noted. A six-month follow-up study revealed no significant difference between the recurrence rates after omeprazole and after cimetidine treatment. In May 1984 clinical trials with omeprazole were temporarily suspended, since a study of long-term toxicity in rats had shown the development of gastric carcinoid tumors.