Active Duodenal Ulcer Research Articles

Natural history of Campylobacter pylori in duodenal ulceration treated with an H2-antagonist.

Campylobacter pylori has been associated closely with active antral gastritis and duodenal ulcer but its pathogenetic role remains uncertain. The present longitudinal study examined, prospectively, the endoscopic antral biopsies of 45 patients with duodenal ulceration, taken before and after healing of the duodenal ulcer, during remission and at relapse. The biopsies were examined for the activity and degree of chronic inflammation of the gastritis and for the occurrence and density of C. pylori by Warthin-Starry stain. Before treatment the frequency of chronic active antral gastritis was 100% and the occurrence of C. pylori was 97%. Compared with the pre-treatment state, there was no significant change in either the frequency and severity of antral gastritis, or in the occurrence and density of the bacteria in the antral mucosa at the time the duodenal ulcer healed, during remission, or at relapse. The occurrence of the bacteria was significantly more frequent during remission, than at the time when the ulcer had healed initially (P less than 0.05). These results suggest that the bacterium may not play an important pathogenetic role in ulcer healing and relapse, when patients are managed using an H2-blocker.

Sucralfate suspension 1 g four times per day in the short-term treatment of active duodenal ulcer

Sucralfate suspension 1 g/10 ml four times per day was found to be significantly better than placebo for the healing of active duodenal ulcer. An eight-week, double-blind, randomized, placebo-controlled, parallel-group multicenter study was conducted. A total of 292 patients were evaluated. Ulcer healing was evaluated by endoscopy and symptom assessment occurred at baseline and at two, four, and eight weeks, or upon symptom worsening as determined by the investigator. Healing was defined as complete re-epithelialization of the crater, without residual erosion. Patients completed eight weeks of treatment regardless of whether or not they were healed at two or four weeks. Treatment groups were comparable with regard to age, sex, ulcer history, cigarette smoking, alcohol and caffeine consumption, ulcer size, and ulcer symptoms. Analysis of procedurally correct cases demonstrated that sucralfate suspension was significantly more effective in healing duodenal ulcers than placebo at two, four, and eight weeks. Ulcer-healing rates efficacy analysis are as follows. At two weeks, the healing rate of sucralfate suspension was 22 of 125 patients (18 percent) and the healing rate of placebo suspension was eight of 130 patients (6 percent; p = 0.006). At four weeks, 58 of 114 patients (51 percent) for sucralfate and 38 of 112 patients (34 percent) for placebo (p = 0.011) were healed. At eight weeks, 80 of 105 (76 percent) for sucralfate and 53 of 100 (53 percent) for placebo (p = 0.001) were healed. Sucralfate-treated patients experienced significantly greater reductions in both daytime and nighttime pain scores at two weeks. A significant difference between treatment groups was also found for daytime symptoms at four weeks. At four and eight weeks, patients who smoked cigarettes had significantly lower healing rates than those who did not, regardless of treatment group. Sucralfate suspension was found to be effective for the treatment of active duodenal ulcer.

Comparison between single morning and bedtime doses of 40 mg famotidine for the treatment of duodenal ulcer

The aim of this study was to compare the duodenal ulcer healing effects of morning (08.00 hours) vs. single bedtime (22.00 hours) doses of 40 mg famotidine, bearing in mind that the known efficacy of bedtime doses of H2-antagonists is regarded as evidence of the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer. This randomized double-blind multicentre trial was conducted in a total of 127 patients with endoscopically proven active duodenal ulcer. Nine patients dropped out and thus 118 were included in the final analysis. The duration of treatment was 4 weeks, and this was extended to 8 weeks in patients whose ulcers failed to heal by week 4. The patients in the two treatment groups were well matched for age and sex. The therapeutic efficacy parameters were endoscopic healing of the ulcer lesion and disappearance of pain. Results were compared using the chi-square method. The 4- and 8-week (cumulative) ulcer healing rates in the patients treated with the morning dose of famotidine were 77.2% and 86%, respectively, compared with 78.6% and 91.8% in those who received the bedtime dose. The differences failed to prove statistically significant either at week 4 (P = 0.85) or at week 8 (P = 0.31). The percentages of patients with ulcer pain, evaluated weekly, were similar in the two treatment groups. The equivalent efficacy of the morning and bedtime famotidine regimens raises doubts concerning the predominance of nocturnal gastric acidity in the pathogenesis of duodenal ulcer.

Abnormalities in the duodenal transit and motility in duodenal ulcer patients: studies with a new isotopic technique.

Abnormalities of duodenal motility have been described in patients with duodenal ulcer and in experimental ulcers in rats and it has been postulated that they could be pathogenic in peptic ulcer disease. We have investigated with an isotopic technique whether duodenal bulb clearance or duodenal transit are abnormal in duodenal ulcer. Six patients with inactive and six with active duodenal ulcers, all men, and six healthy male controls were studied. Motility of the duodenum was simultaneously monitored. A bolus of 99mTcDTPA was injected into the duodenum while water or acid were perfused on different occasions. Duodenal bulb clearance and transit to the ligament of Treitz were calculated. Duodenal transit in duodenal ulcer patients 108.8 (23) sec was faster than in controls, 194.9 (5.1) sec (p less than 0.05) during the quiescent period of the motility cycle. The frequency of duodenal bulb contractions during acid perfusion was higher in duodenal ulcer patients 1.7 (0.4) cont/min, than in controls 0.8 (0.1) cont/min (p less than 0.05). No other significant differences were observed between ulcer patients and controls. These data suggest that patients with duodenal ulcers do not have major abnormalities of duodenal bulb clearance, nor of duodenal transit and that duodenal motility does not play a primary role in the pathogenesis of the ulcer.

Reduction in index of oxygen saturation at margin of active duodenal ulcers may lead to slow healing.

This study tested the hypothesis that reduced perfusion of a duodenal ulcer margin (ie, the mucosa 1-2 mm from the edge of the ulcer base) is associated with slow healing. Reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and mucosal hemoglobin oxygen saturation (ISO2) were obtained endoscopically in 21 patients at the ulcer margin and the adjacent mucosa (ie, the mucosa 1-2 cm from the edge of the ulcer base). In 17 patients with adequate follow-up, stepwise multilinear regression analysis revealed a significantly negative correlation (r = -0.69, P less than 0.05) between ISO2 at the ulcer margin minus ISO2 at the adjacent mucosa (delta ISO)2 and ulcer healing time. In addition, smoking, being black, and early relapse since the last ulcer attack were found to be associated with increased duration required for healing. The results of this pilot study suggest factors, in addition to smoking, that may have to be considered in future studies concerned with duodenal ulcer healing.

A multicentre, randomized, double‐blind study comparing nocte famotidine or ranitidine for the treatment of active duodenal ulceration

The efficacy and safety of famotidine and ranitidine in the treatment of active duodenal ulcer were compared in a multicentre, randomized, double-blind study. The study was carried out in five centres which included a total of 143 patients with endoscopically documented active duodenal ulcer. The patients received either famotidine (one tablet of 40 mg at night) or ranitidine (two tablets of 150 mg at night). Endoscopic examinations were performed at 4 and 6 weeks of active treatment. Daytime and nocturnal pain were also monitored, and the laboratory and clinical profiles evaluated. One hundred and thirty-three patients fulfilled the evaluation criteria (66 patients in the famotidine group and 67 in the ranitidine group). Healing rates at 4 or 6 weeks of treatment showed no significant differences between the famotidine and ranitidine groups. The healing rates were 80% at week 4 and 97% at week 6 in the famotidine group, and 77% at week 4 and 96% at week 6 in the ranitidine group. Similar results were observed in both treatment groups with regard to pain resolution, decrease in antacid intake and safety profile.

Refractory duodenal ulcers (nonhealing duodenal ulcers with standard doses of antisecretory medication).

To evaluate possible differences between patients with refractory duodenal ulcers and those with duodenal ulcers that respond to standard doses of antisecretory medications, we determined basal acid outputs by nasogastric suction and daily smoking histories in 75 patients with endoscopically documented active duodenal ulcers. Patients were treated for at least eight weeks with standard doses of antisecretory medications and endoscopic healing or nonhealing was documented. Fifty-five patients that had complete healing of their duodenal ulcers had a mean basal acid output of 6.6 +/- 5.3 meq/hr, and 18/55 had daily cigarette smoking histories, whereas 20 patients that had nonhealing duodenal ulcers had a mean basal acid output of 20.0 +/- 9.6 meq/hr, and 8/20 had daily cigarette smoking histories. There were no significant differences between the two groups with regard to age, duodenal ulcer size, or cigarette smoking history. However, there were significant differences in male-female ratio (P less than 0.02) and in mean basal acid output (P less than 0.001), and all patients with nonhealing duodenal ulcers had basal acid outputs of greater than 10.0 meq/hr. Patients with nonhealing duodenal ulcers were treated with increased doses of ranitidine, mean 675 mg/day (range 600-1200 mg/day), and all had complete healing endoscopically documented. These results indicate that patients treated with standard doses of antisecretory medications with nonhealing duodenal ulcers have increased basal acid outputs of greater than 10.0 meq/hr, and the duodenal ulcers heal with increased doses of antisecretory medication.

A Comparison of Nimatidine with the Three Other H istam i ne Receptor Antagonists for Duodenal Ulcer Therapy

Nizatidine (Axid) is the newest of four histamine receptor antagonists approved by the Food and Drug Administration for treatment of duodenal ulcer and maintenance therapy. It is as effective as the other histamine blockers in healing active duodenal ulcers and in the prevention of relapse. Nizatidine is comparable in price to cimetidine (Tagamet). Nizatidine does not interfere with the hepatic metabolism of other drugs. No significant central nervous system side effects have been reported. It is safe to use in elderly patients or in patients with renal insufficiency. The dosage, however, should be decreased when renal function is impaired.

Drug Safety of Rioprostil in Patients with Active Gastric or Duodenal Ulcer

Data from a large number of patients (1918) treated with rioprostil, H2-antagonists and placebo, are analysed to examine the safety profile of rioprostil in the treatment of active gastric ulcer or active duodenal ulcer. Rioprostil is administered to 1000 of those patients. Patients who dropped out of the studies and those with adverse drug reactions are classified and compared within different subgroups. The overall dropout rate for rioprostil patients is 8.8%: 2.3% of these because of adverse reactions. The incidence of adverse reactions during rioprostil treatment is 20.9%, with more than 60% of these having gastrointestinal symptoms, mainly appearing in the first week of therapy. Comparisons show a higher incidence of symptoms with rioprostil treatment than with ranitidine treatment because of the gastrointestinal symptoms. Possible differences are found between groups in sex, age, and drug dose. The analysis of laboratory variables does not show clinically important changes as a result of rioprostil treatment.

Interdigestive Gastroduodenal Motility in Patients with Active and Inactive Duodenal Ulcer Disease

The interdigestive gastroduodenal motility was studied by means of a manometric probe in 6 patients with active duodenal ulcer and acid hypersecretion, in 6 patients with ulcer disease in remission (inactive) and normosecretion and in 8 healthy subjects with normosecretion. After a basal recording period sufficient to record at least two activity fronts of the migrating motor complex (MMC), an intraluminal infusion of isotonic NaHCO3 was carried out for 180 min in patients with active duodenal ulcer, whereas in patients with ulcer in remission an HCl solution was infused for 180 min. Patients with active duodenal ulcer showed a basal motility with a longer than normal MMC cycle and a shorter than normal activity front, while patients with ulcer in remission showed a cyclic motor activity not significantly different from that of normal subjects. The NaHCO3 infusion in patients with active ulcer restored a near-normal motility, whereas the HCl infusion in patients with ulcer in remission induced a motility similar to that of patients with active ulcer. These data indicate that the increase in gastric acid secretion is responsible for the decrease in frequency and duration of MMC activity fronts, which have the function of cyclically clearing the gastroduodenal lumen. Consequently, acid and bacteria may remain a longer than normal time in contact with the gastroduodenal mucosa, which, in this manner, may be greatly exposed to the risk of peptic lesions.

Anatomic-functional profiles in duodenal ulcer.

Gastric acid secretion, gastrinemia, the type of gastritis of the fundic mucosa and the parietal cell mass, expressed by means of a 'parietal index', were considered in 70 patients with active duodenal ulcer. Hypersecretion was found in 60% of cases, normosecretion in 35.7% and hyposecretion in 4.3%, while achlorhydria was absent. Chronic fundic gastritis of the superficial or follicular type occurred at a similar rate in normosecretors (22%) and in hypersecretors (26%), being constantly of the preatrophic type in the 3 cases of hyposecretion. The parietal index was strictly correlated with maximal acid output but there was no correlation between gastrinemia and the secretory state or with the histological picture of the fundic mucosa. The results outline the prevalence of hypersecretion-hyperparietalism in duodenal ulcer but indicate also the frequent occurrence of normosecretion and normoparietalism and the rare finding of hypersecretion and hypoparietalism.

Enzyme Activities in the Duodenal Mucosa in Duodenal Ulcer Patients

The mucosal enzyme activities of 11 marker enzymes from the brush border, basolateral membrane, and lysosomes of 45 patients with an active duodenal ulcer (DU) were determined by analysis of homogenized biopsy specimens obtained from the duodenal bulb and descending duodenum at endoscopy. They were compared with activities measured in 22 controls. In the duodenal bulb lactase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.0005), and monoamine oxidase (p less than 0.0005) were significantly decreased in DU patients. In the descending duodenum all the brush border enzymes except sucrase were significantly decreased when compared with controls. DU patients with inflammation in the biopsy specimens from the duodenal bulb had decreased levels of lactase (p less than 0.05), sucrase (p less than 0.05), neutral-alpha-glucosidase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), and acid phosphatases (p less than 0.05) when compared with DU patients with normal histology in this region. In the descending duodenum the activities of leucyl-beta-naphthylamidase (p less than 0.05) were decreased in patients with inflammation compared with those without such histologic changes. DU patients who had taken antacids before the investigation had decreased activities of lactase (p less than 0.05) in the descending duodenum when compared with those who had not taken antacids. Activities of lactase (p less than 0.005), sucrase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.05), and acid beta-glucuronidase (p less than 0.0005) in the descending duodenum were significantly lower in smokers than in non-smokers with active DU.

Chronic antral gastritis, Lewis(a+) phenotype, and male sex as factors in predicting coexisting duodenal ulcer.

Chronic antral gastritis, Lewis(a+) phenotype (Le(a+)), and male sex are common in patients with peptic ulcer. To approximate the relative risks (RR) and possible interactions of these factors in predicting coexisting active duodenal (DU) or gastric ulcer (GU), a consecutive endoscopic series of 140 ulcer patients and 215 non-ulcer controls was examined. The Lea phenotype (Le(a+) versus Le(a-)) was determined immunohistochemically as binding of Le(a)+-specific monoclonal antibody to surface epithelial secretory mucosubstances in gastric biopsy specimens. The presence versus absence of the gastritis was determined histologically from antral specimens. The RRs of the factors in the prediction of ulcer were approximated as age-adjusted RRs when the risk of ulcer in the absence of the factors--that is, in the absence of gastritis, in female sex and in Le(a-) phenotype--was applied as a base line (RR = 1). A case-control design, logistic linear modelling, and the maximal likelihood method were used in estimation of the risks. The RR of coexisting distal ulcer (DU or pyloric or prepyloric GU) was increased in the presence of gastritis (RR = 10.2), in male sex (RR = 3.0), and in Le(a+) phenotype (RR = 1.8). The RR of proximal ulcer (angular or corpus GU) was increased in the presence of gastritis (RR = 35) but decreased in the presence of male sex (RR = 0.5) and Le(a+) phenotype (RR = 0.7). As predictors of both distal and proximal ulcer, gastritis, sex, and Le(a) phenotype were independent of each other; that is, their joint value in prediction of ulcer is a multiplicand of the marginal risks. Thus, a 50-fold difference in the joint RR could be approximated between the extreme risk groups for distal ulcer--that is, between Le(a+) males with gastritis and Le(-a) females with normal antrum. In a consecutive series of outpatient endoscopies, 45% of females and 8% of males could be categorized to these extreme 'low'- and 'high'-risk groups, respectively. We conclude that sex, Le(a) phenotype, and gastritis are factors that, at least in ordinary outpatient endoscopy material, divide subjects to subgroups with very different risks and probabilities for having coexisting peptic ulcer.

Rioprostil, a New Prostaglandin E1Analogue, in the Once-Daily Treatment of Acute Duodenal Ulcer: A Comparison with Ranitidine

The efficacy of Rioprostil (a new prostaglandin E1 analogue) is compared with ranitidine in the once-a-day treatment in the evening for 4 or 6 weeks of active uncomplicated duodenal ulcer disease. A total of 255 patients are entered in this study; of these 243 have been statistically evaluated. One hundred and twenty (120) patients receive rioprostil 600 micrograms/daily, and 123 patients receive ranitidine 300 mg/daily. After 4 weeks 63.3% of the patients on rioprostil are endoscopically healed, as compared with 69.1% on ranitidine. After 6 weeks the cumulative cure rates are 87.3% and 89.9%, respectively, the difference not being statistically significant. Pain relief is similar for both drugs. Diarrhoea with rioprostil occurs in about 2% of the treatment days and is generally self-limiting.

Campylobacter pylori: Swedish Experiences

All patients referred for gastroscopy were investigated by Campylobacter pylori culture and antibody titration. An enzyme immunoassay was developed and found to have a negative predictive value of 0.997, which indicates that serologic tests could be used for screening of patients before gastroscopy. A close correlation was found between active and inactive duodenal and gastric ulcer and positive C. pylori culture. Small open treatment trials with the antibiotics doxycycline, tinidazole, amoxycillin, and norfloxacin were ineffective for the eradication of C. pylori. Treatment with the new anti-ulcer agents enprostil, rioprostil, and omeprazole had no effect on the presence of C. pylori.

Campylobacter pylori and ulcer disease--a causal connection?

A strong positive correlation has been demonstrated between the (antral mucosal) presence of Campylobacter pylori and active duodenal and gastric ulceration. Moreover, both duodenal and gastric ulcers heal, and remain in remission, as a consequence of therapeutic measures which eradicate C. pylori. However, the Henle-Koch postulates have not been fulfilled, because C. pylori has not been shown to produce ulcers. As for the claim that ulcer disease represents an infection with C. pylori because therapeutic eradication heals ulcers, it has been shown that antibiotics and metronidazole, as well as bismuth subcitrate, exert antiulcer actions by mechanisms which do not involve their antibacterial effects. The association between C. pylori and ulcer disease, which was noted half a century ago, remains unexplained now as it did then.

A Multicenter, Randomized, Double-Blind Study Comparing Famotidine with Cimetidine in the Treatment of Active Duodenal Ulcer Disease

The efficacy and safety of famotidine (40 mg at night), a new potent H2-receptor antagonist, has been studied in 119 patients by four investigators in four Spanish hospitals in a randomized double-blind comparative study with cimetidine (800 mg at night). Antacid tablets were allowed as additional treatment, if needed for pain relief. There were no significant differences between the groups in baseline characteristics, including duodenal ulcer size. Efficacy parameters included daytime and nocturnal symptom relief and duodenal ulcer healing, documented by endoscopy, and defined as complete reepithelization of the ulcer crater. Endoscopy was performed at baseline and after 4 and 6 weeks of treatment. One hundred and five patients fulfilled the evaluation criteria (51 patients in the famotidine group and 54 in the cimetidine group). After 4 weeks, in 91.6% of the patients receiving famotidine and 82.3% of the patients receiving cimetidine ulcers were healed. After 6 weeks, healing rates were 96% (famotidine) and 85.1% (cimetidine) (p = 0.056). Pain relief was rapid in both treatment groups, with a tendency to better response during the day in the famotidine group. The intake of antacids, as well as the clinical and laboratory safety profile were similar for both groups.

The Potential Impact of Campylobacter pylori on the Treatment of Duodenal Ulcer Disease

In most studies the association between Campylobacter pylori infection, Type B gastritis and duodenal and gastric ulceration is extremely strong. The best evidence for it having an aetiological role is at present in Type B gastritis. It should be remembered, however, that serological studies show carriage of the organism to be common also in the general population. An attempt is made here to gain some idea of the clinical impact of C. pylori infection in duodenal ulcer disease by analysing clinical trials, and in particular relapse data, in which an agent which suppresses C. pylori is used (colloidal bismuth subcitrate) and compared with one which does not (an H2-receptor antagonist). A mathematical model based on the data from these studies predicts that the prevalence of active duodenal ulceration will be twice as common in a group of subjects treated repeatedly upon relapse with an H2-receptor antagonist as in a group treated with colloidal bismuth. Other possible mechanisms are discussed but the ability of bismuth to suppress C. pylori infection is perhaps the best available explanation at present. Early data from several centres suggest that patients who can be rendered C. pylori negative over a prolonged period of time are relatively immune from relapse of their duodenal ulcers. If confirmed this observation may well transform the long-term management of duodenal ulcer disease.

24-hour ambulatory dual gastroduodenal pH monitoring. The role of acid in duodenal ulcer disease.

A new system for long-term, 24-hour, ambulatory dual gastroduodenal pH monitoring is described. Eighteen patients with active duodenal ulcers and ten healthy subjects were studied. Simultaneous gastric and duodenal bulb pH were measured during fasting, the ingestion of a solid meal, and for the remainder of the 24-hour period. The gastric pH profile was similar for both groups. There was no significant difference between the fasting duodenal bulb pH of the duodenal ulcer (DU) patients and controls. The daytime and nocturnal duodenal acid exposure was similar for both groups. The meal caused a similar pattern of duodenal acidification in both controls and DU patients, and acid neutralization appeared to be effective in DU patients. The role of acid in the duodenal bulb does not appear to be of primary pathophysiologic importance in duodenal ulcer disease.

Sucralfate in Duodenal Ulcer Disease: A Double-Blind Trial

ABSTRACT Seventy-five patients with endoscopically confirmed duodenal ulcer disease received either sucralfate (34 patients) or placebo (41 patients) for 6 weeks in a double-blind clinical trial. N...