Marina Ferrana

Do concomitant diseases and therapies affect the persistence of ulcer symptoms in the elderly

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study: 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size.

Absence of tolerance in duodenal ulcer patients treated for 28 days with a bedtime dose of roxatidine or ranitidine

Summary— There is much experimental work on the occurrence of tolerance to the antisecretory effect of H2‐receptor antagonists in healthy subjects, while data on its development in patients with duodenal ulcer are poor and conflicting. Moreover, this phenomenon has not been studied previously with 24 h gastric pH‐metry in patients with active duodenal ulcer. For these reasons, we carried out a prospective pharmacodynamic investigation in 48 patients with endoscopically proven duodenal ulcer using the well‐established once daily dosing schedule of H2 blockers. They were studied by means of 24 h continuous endoluminal pH‐metry which was performed before, on d1 and d28 after receiving an oral bedtime dose (2200 hours) of either roxatidine 150 mg or ranitidine 300 mg, given in randomized and single‐blind fashion. Eight patients did not complete the study for various reasons and 82% of ulcers healed after 4 weeks of therapy. Gastric pH was higher (P < 0.001) on d1 and d28 than basal values during all time periods, but the evening, with both H2 blockers. There was no significant difference between pH values of d1 and d28 in any time interval with both roxatidine and ranitidine. There was also no difference in pharmacodynamic data between the two active treatments. We conclude that tolerance does not develop after 1 months treatment with a bedtime dose of H2 antagonist in patients with active duodenal ulcer and therefore data gathered on this phenomenon in healthy subjects are not applicable to ulcer patients.

Markers of Slow-Healing Peptic Ulcer in the Elderly A Study on 1,052 Ranitidine-Treated Patients

Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearsons chi-squared tests and Coxs models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P=0.002) and persisting ulcer symptoms (P=0.0001); indicators of slow-healing DU were ulcer size (P=0.0001), persisting ulcer symptoms (P=0.0001), alcohol (P=0.0003), and NSAID (P=0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P=0.0352). Coxs models revealed that the persistence of ulcer symptoms is the most important factor predicting unhealing ulcers (GU,P=0.0008; DU,P=0.0002), while ulcer size is only important for DU (P=0.0215). Patients with ulcer disease onset before 65 years of age were more frequently males; DU subjects were more frequently smokers, with a family history of ulcer and no NSAID consumption. In conclusion, persistence of ulcer symptoms and ulcer size are indicators of slow-healing ulcer in the elderly; in the case of DU, NSAID and alcohol consumption may be additional factors.

Helicobacter pylori eradication and serum pepsinogens.

3 Chapman MAS, Grahn MF, Boyle MA, Hutton M, Rogers J, Williams NS. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut 1994; 35: 73-6. 4 Finnie IA, Taylor BA, Rhodes JM. Ileal and colonic epithelial metabolism in quiescent ulcerative colitis: increased glutamine metabolism in distal colon but no defect in butyrate metabolism. Gut 1993; 34: 1552-8.

Serum pepsinogens as markers of Helicobacter pylori eradication

Abstract Various methods, both invasive and noninvasive, are used to verify Helicobacter pylori eradication, with varying degrees of accuracy. The purpose of this study was to verify the relationship between H pylori eradication and serum levels of pepsinogen A (PGA) and pepsinogen C (PGC). The study involved 79 patients who tested positive for H pylori infection after histologic examination and the urease test. Patients were treated with various drug regimens for 7 to 25 days. Two months after discontinuing treatment, endoscopy was performed to verify H pylori eradication; 33 of 79 patients were found to be free of infection. Venous blood samples were taken to measure PGA and PGC levels before and after treatment. Patients in whom H pylori infection was eradicated had a significant drop in PGA and PGC levels, whereas in patients with persisting H pylori infection, there was a trend in which pepsinogen levels coincided with the quantity of bacteria detected. These preliminary data suggest that it may be possible to evaluate H pylori eradication by means of serum pepsinogen levels, sparing patients a follow-up endoscopy.

Omeprazole in the maintenance treatment of duodenal ulcer: results after 6 months of 20 mg daily, 20 mg every other day, or 40 mg on weekends

Abstract An open, prospective, randomized, 6-month, clinical trial was performed on 198 patients with healed duodenal ulcers (DUs) to compare three omeprazole schedules for the prevention of ulcer relapse—20 mg daily (group 1), 20 mg every other day (group 2), and 40 mg on Saturday and Sunday (group 3). Patients were followed up at 3-month intervals; endoscopy and laboratory screening (including basal serum gastrin measurement) were performed at baseline, after 6 months, and in the event of any symptomatic replase. One-way analysis of variance, the chi-square test, and Students t test on paired data were used for statistical analysis of the study data. Per protocol analysis (PPa) and a more restrictive analysis (Ra) considering all dropouts as treatment failures were also used. Patients were randomly assigned to one of three treatment groups: 67 to group 1, 69 to group 2, and 62 to group 3. Thirty-two patients dropped out of the study, 14 in group 1, 3 in group 2, and 15 in group 3. Confirmed ulcer relapse rates were 3.8% in group 1, 19.7% in group 2, and 23.4% in group 3 (PPa, P P

A PRELIMINARY REPORT ON HELICOBACTER PYLORI AND ANTRAL GASTRIN CONCENTRATION IN PATIENTS WITH DUODENAL ULCER

This study analyzed the relationship between Helicobacter pylori infection, mucosal gastrin concentration, and basal serum gastrin levels in duodenal ulcer patients with dyspepsia. Patients with duodenal ulcers who were H pylori positive showed higher antral gastrin concentrations than either H pylori-positive patients with dyspepsia or H pylori-negative patients with duodenal ulcers. No correlation was found between serum gastrin and antral gastrin concentrations. The increased antral gastrin concentrations were not correlated with an inhibition of acid-gastrin feedback. These preliminary data confirm that H pylori infection impairs gastrin physiology.

H2 antagonists and gastric ulcer: A multicenter, randomized, double-blind, controlled study comparing nizatidine with ranitidine*

An 8-week, multicenter, randomized, double-blind study was performed with the aim of comparing nizatidine 300 mg at bedtime with nizatidine 150 mg twice daily (BID) and with ranitidine 150 mg twice daily in 114 patients with benign acute gastric ulcer. Healing rates did not significantly differ among groups at 4 weeks, but they were lower in the once-daily group (53%) than in the BID groups (approximately 69%). At 8 weeks, healing rates with nizatidine 150 mg BID (97%) were significantly higher than those observed in the groups that received nizatidine 300 mg at bedtime (78%) or ranitidine 150 mg BID (83%). Smoking was found to affect the therapeutic efficacy of the bedtime dosing. The results of this study show that nizatidine is an efficacious and safe drug in the treatment of benign acute gastric ulcer when given twice daily, especially in smokers.

HEMORRHAGIC DUODENAL ULCER DISEASE: CLINICAL AND BIOCHEMICAL FINDINGS IN A CASE-CONTROL PILOT STUDY

Abstract A retrospective study of 31 consecutive bleeding duodenal ulcer (DU) patients and, as controls, 62 active DU subjects without bleeding episodes was conducted in order to ascertain whether bleeding DU patients have particular clinical or functional characteristics. The patients were followed for 15.6 and 17.4 months, respectively, after diagnosis. The following parameters were taken into account: sex, age, family history of ulcer, blood group (ABO system), ulcer pain, nonsteroidal anti-inflammatory drug (NSAID) consumption, cigarette smoking, alcohol and coffee consumption, ulcer site, fasting serum gastrin and pepsinogen group A, basal acid output (BAO), and maximal acid output (MAO). Statistics were gathered using the Students t test and Fishers exact test. Bleeding DU patients had less ulcer pain ( P P

CYTOPROTECTIVE EFFECTS OF COLLOIDAL BISMUTH SUBCITRATE IN PATIENTS WITH ULCER DISEASE

Abstract Helicobacter pylori is capable of altering the structure of the mucus gel adhering to the surface of the gastric antral wall. Thirty patients (22 men and 8 women) with endoscopic evidence of active duodenal ulcer and histologically confirmed H pylori antral gastritis participated in this prospective study. The study objective was to evaluate the effects of 6 weeks of treatment with colloidal bismuth subcitrate (two 120-mg tablets twice daily) on peptic secretion and the gastric mucosal barrier. Samples of gastric juice were collected during endoscopy to measure pepsin levels. Also during endoscopy, four biopsies were taken (two antral and two from the body/fundus) for histological examination, H pylori detection, and the quantification of pepsinogen group A (PGA), gastrin, and pepsin in the tissues. All of the above parameters were repeated with endoscopy after 6 weeks of treatment. Ulcer healing was obtained in 26 (87%) of 30 patients after treatment. H pylori infection was cleared in 15 (50%) patients. No significant changes were detected in concentrations of pepsin in the gastric juice or concentrations of PGA, gastrin, or pepsin in the tissues. Mucus depletion was visibly lower after treatment, suggesting that colloidal bismuth subcitrate may alter the bacterial microenvironment, regenerating the quantity of mucus.