Aspirin concurrently administered with ranitidine does not delay healing of duodenal ulcer

Sixty-nine patients with endoscopically diagnosed duodenal ulcer were randomised to either Group I or Group II. Group I patients (n= 35) received tablet ranitidine 150 mg twice daily along with tablet aspirin 600 mg three times a day while Group II patients received only tablet ranitidine 150 mg twice daily. Eight patients (four in each group) dropped out of the trial but were included in the final analysis as failure of treatment. At the end of four weeks 51.4% ulcers healed in Group I compared to 58.8% in Group II. The difference between the two groups was not significant. There was also no statistical difference in the time required for relief of pain, number of patients relieved of pain and the complication rate. It is concluded that aspirin concurrently administered with ranitidine is safe and does not delay the healing of uncomplicated duodenal ulcers.     

The personality pattern of duodenal ulcer patients in relation to spontaneous ulcer healing and relapse

One hundred consecutive out-patients with duodenal ulceration from a hospital and a gastroenterological clinic were tested with the Minnesota Multiphasic Personality Inventory (MMPI). This was carried out in order to investigate whether neuroticism or other personality disorders were characteristics of duodenal ulcer patients, and whether the presence of such possible personality disorders might influence the prognosis of the disease. Neuroticism occurred in 53% of the patients, but only in 5% of controls (P less than 0.0001). Overall, personality disorders were present in 69% of the patients compared with 30% of the controls (P less than 0.0001). Neuroticism was connected with a high frequency of relapse (P less than 0.05) whereas failure of spontaneous ulcer healing had no certain relation to personality disorders. Patients with non-neurotic personality disorders had more frequently suffered stressful life events before entrance to the study (P less than 0.05) and, like the neurotic patients, they had lower ego-strength to cope with such events (P less than 0.05). The results indicate that personality assessments make it possible to distinguish between subgroups of duodenal ulcer patients with different course of the disease.     

A double-blind study of misoprostol (SC-29333) in the healing of duodenal ulcer

In a double-blind randomized placebo controlled trial, 50 patients with endoscopically confirmed duodenal ulcer were treated with either misoprostol 200 micrograms or placebo in q.i.d. doses for 4-8 weeks. Of 25 patients in the placebo group, four defaulted and two were withdrawn due to worsening of symptoms. Of 25 misoprostol-treated cases, 17 cases (68%) and 21 cases (84%) healed at 4 and 8 weeks respectively, compared with three (14%) and five (24%) of the 21 placebo-treated cases (P less than 0.001). Except for diarrhoea in 2 patients in each group and itching in one with misoprostol, no serious side effects were noted.     

Prostaglandin deficiency by itself is not the cause of mepirizole-induced duodenal ulcers in rats

The purpose of these studies was to determine the role played by endogenous prostaglandins in the development of gastric ulcers produced by indomethacin, and of duodenal ulcers produced by mepirizole in rats. Indomethacin (10 mg/kg subcutaneously) produced gastric ulcers, whereas mepirizole (100 mg/kg subcutaneously) produced exclusively duodenal ulcers. Both drugs, given at ulcerogenic doses, reduced the gastric and duodenal generation of PGE₂, PGF₂, 6-keto-PGF₁, and thromboxane B₂. In this regard, the extent of reduction was more pronounced after indomethacin than after mepirizole. Despite this greater inhibition of prostaglandin synthesis by indomethacin, this drug did not produce duodenal ulcers, whereas mepirizole was duodenoulcerogenic. In addition, mepirizole increased gastric acid secretion by 74%, whereas indomethacin had no effect on acid secretion. Oral administration of 16,16-dimethyl PGE₂, given at nonantisecretory doses (0.5–5 g/kg), prevented formation of indomethacin-induced gastric ulcers, whereas antisecretory doses were required to prevent formation of mepirizole-induced duodenal ulcers. We conclude that a reduction of prostaglandin formation in the duodenal mucosa is not by itself sufficient to induce duodenal ulcers. We hypothesize that three changes, produced by mepirizole, must be present for duodenal ulcers to develop: increased gastric acid secretion, decreased duodenal bicarbonate secretion (as demonstrated earlier), and decreased duodenal content of prostaglandins. The decreased prostaglandin formation, although not causing duodenal ulcers, may lower the resistance of duodenal mucosa to the hyperacidity induced by mepirizole. On the other hand, in the case of gastric ulcers following administration of indomethacin, a decrease in gastric mucosal levels of prostaglandins may play a more important role than changes in gastric acidity.These investigations were supported in part by a grant from the U.S.P.H.S. (AM RO1 37050)     

Diet and duodenal ulcer

BACKGROUND: Despite the fact that the main cause of duodenal ulcer incidence and recurrence is the Helicobacter pylori bacterium, more than 80% of Helicobacter pylori-infected people never develop an ulcer. Diet may be one of the most important environmental factors contributing to duodenal ulcer. AIMS: To explore the role of diet in causation, treatment and prevention of duodenal ulcer recurrence. METHODS: All research papers published in English from 1966 to October 1999 present in Medline, involving human subjects, and having duodenal ulcer as outcome, entered the review. RESULTS AND CONCLUSIONS: Soluble fibre from fruit and vegetables seem to be protective against duodenal ulcer and refined sugars a risk factor. The role of fibre in the treatment and prevention of recurrence of duodenal ulcer is uncertain, as is that of essential fatty acids. However, none of the epidemiological studies on the relationship between diet and duodenal ulcer disease controlled for Helicobacter pylori.     

Flow cytometric analysis of cell proliferation kinetics during duodenal ulcer healing

Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12 normal subjects were investigated. Biopsy samples were obtained during endoscopic examination and subjected to DNA analysis by flow cytometry. Thirty patients with duodenal ulcers were healed within 3 months with H₂ blockers (tractable or responsive ulcers), whereas 10 patients did not respond to treatment (intractable ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell proliferation, was constant in the adjacent duodenal mucosa 2cm from ulcer margin and antral mucosa during duodenal ulcer healing. The index at the margin of tractable ulcers was elevated during the active stage (12.9 ± 1.3), peaked during the healing stage (15.4 ± 2.8) and returned to the same level at the scarring stage (10.9 ± 2.0) as normal controls (10.3 ± 1.7). However, the index was not elevated in intractable ulcers (10.3 ± 1.7 in the healing stage) and was smaller than in tractable ulcers. These data indicate that augmented mucosal cell proliferation at the ulcer margin plays an important role in duodenal ulcer healing and intractable ulcers are characterized by an abnormal failure to accelerate DNA synthesis to achieve ulcer repair.     

愈疡止痛煎剂对十二指肠溃疡大鼠溃疡愈合质量的影响

[目的]探讨愈疡止痛(YYZT)煎剂对实验性大鼠十二指肠溃疡(DU)愈合质量的影响.[方法]用L-半胱胺酸盐酸盐复制大鼠DU模型,设立空白对照(A)组、病理模型(B)组、YYZT(C)组、雷尼替丁(D)组.3周后处死动物,观察溃疡愈合程度并评价溃疡愈合质量,测定胃液pH值及血清表皮生长因子(EGF)水平.[结果]C组胃酸较其余各组均降低(P＜0.05);C组胃液pH值及血清EGF较其余各组明显升高(P＜0.05,＜0.01).[结论]YYZT煎剂在提高溃疡愈合方面有明显优势,其作用机制可能与减少胃酸分泌、升高血清EGF有关.     

Prevalence of Helicobacter pylori infection in duodenal ulcer and gastro‐duodenal ulcer diseases in Taiwan

Background and Aim: The prevalence of Helicobacter pylori‐negative duodenal ulcer (DU) is increasing in Western countries but is rare in Japan. We aimed to examine the prevalence of H. pylori infection and the characteristics in DU and gastro‐duodenal ulcer (GDU) diseases in Taiwan. Study: All patients with an endoscopic diagnosis of DU or GDU from September 2003 to May 2004 at Taipei Veterans General Hospital were included. Rapid urease test was done for all patients, while urea breath test was carried out on those with negative rapid urease tests. A patient was considered infected if either test was positive. Results: The prevalence of H. pylori was 88.7% (555/626) in DU and 90.5% (95/105) in GDU patients. There was no difference in sex and prevalence of H. pylori between the two groups but age was higher in the GDU patients (60.1 ± 15.5 vs. 55.4 ± 15.5, P = 0.005). Of H. pylori‐negative DU patients, 28.2% (20/71) reported using non‐steroidal anti‐inflammatory drugs (NSAIDs)/aspirin, which were used by all 10 H. pylori‐negative GDU patients (100%) (P < 0.001). There was no difference in sex and age between H. pylori‐positive and negative DU patients. The prevalence rate of H. pylori in DU was not statistically different among outpatients, inpatients, and physical check‐up subjects (86.8% vs. 93.3% vs. 90.7%, P = 0.163). Conclusion: The prevalence of H. pylori infection in DU appears to be decreasing in Taiwan. Thus, eradication therapy without confirming the presence of H. pylori in DU patients cannot be recommended. NSAIDs/aspirin is the major risk factor for H. pylori‐negative DU patients, especially those with co‐morbid gastric ulcer.     

胃、十二指肠溃疡患者内皮素Ⅰ水平初步探讨

本文研究３２例胃、十二指肠溃疡患者血浆、胃液及胃、十二指肠溃疡缘与正常胃粘膜组织中内皮素Ⅰ的水平，并以１９例健康人作对照。结果表明：胃溃疡患者血浆内皮素Ⅰ水平为４．４８±０．７８ｐｇ／ｍｌ，明显高于健康对照组血浆水平２．５６±０．１７ｐｇ／ｍｌ，Ｐ＜０．０５。胃溃疡缘组织中内皮素Ⅰ含量为４１．６３±４．３６ｐｇ／ｍｇ，明显高于自身正常胃粘膜２１．８４±１．７３ｐｇ／ｍｇ和健康对照组内皮素Ⅰ含量２１．７８±１．６８ｐｇ／ｍｇ，Ｐ值均＜０．００１。提示内皮素Ⅰ可能作为局部因素参与胃溃疡的形成，并说明胃溃疡患者有血管收缩和舒张因子的代谢不平衡。而十二指肠溃疡患者血浆、胃液、组织中内皮素Ⅰ水平与健康对照组无明显差异，提示内皮素Ⅰ在十二指肠溃疡发病中并不起重要作用。     

Omeprazole versus placebo in duodenal ulcer healing

The study objective was to study the ulcer healing effects and safety of the proton pump inhibitor, omeprazole, given in a dose of 20 mg once daily before breakfast. The study design was a randomized, double-blind, multicenter comparison of omeprazole and placebo using endoscopy to assess ulcer healing after two or four weeks of therapy. One hundred fifty-three patients with endoscopically documented active duodenal ulcer were studied. One hundred two patients received omeprazole and 51 received placebo. Patients in both groups were similar with regard to age, sex, duration of disease, initial ulcer size, smoking history, and alcohol use. A per protocol analysis of healing rates showed a significant advantage for omeprazole (P<0.01) at both week 2 (41% vs 13%) and week 4 (75% vs 27%). Concomitant factors (including smoking and ulcer size) did not alter the significance of the differences in healing rates between omeprazole and placebo. Complete relief of day and night pain was more often achieved (P<0.01) in the omeprazole group. All-patients treated analyses for healing and pain relief gave results similar to the respective per protocol analyses. Omeprazole was well tolerated; fewer patients had clinical and laboratory adverse experiences in the omeprazole group than in the placebo group. Fasting serum gastrin levels increased with omeprazole therapy (mean 34.9 to 73.5 pg/ml) but exceeded the normal range (>150 pg/ml) in only 12.3% of patients. Two weeks after therapy was stopped, serum gastrin levels showed a decrease toward baseline but had not yet completely returned to pretreatment levels (mean 49.7 pg/ml). Observations from Europe and Australia of >90% healing of duodenal ulcers after four weeks of omeprazole therapy were not confirmed in this study. No single factor explains this difference. Considerable variation in the degree of suppression of acid secretion has been demonstrated with the 20-mg daily dose of omeprazole; it is possible that, in US populations, a greater degree of antisecretory effect may be required to achieve the healing rates observed in Europe and Australia. In conclusion, omeprazole was more effective than placebo in the treatment of active duodenal ulcer, as determined by ulcer healing and relief of pain, and was well tolerated in the short-term treatment of patients with duodenal ulcer.     

Seasonal changes in symptomatic duodenal ulcer activity in Taiwan: a comparison between subjects with and without haemorrhage

Abstract. Tsai C-J, Lin C-Y (Chi Mei Foundation Hospital, Tainan, Taiwan). Seasonal changes in symptomatic duodenal ulcer activity in Taiwan: a comparison between subjects with and without haemorrhage. J Intern Med 1998; 244 : 405–10.

Objectives

To examine if climatic changes may influence the presentation of pain and haemorrhage in patients with duodenal ulcers.

Design

Cross-sectional study.

Setting

Tertiary referral centre.

Subjects

A total of 10 331 symptomatic duodenal ulcer diseases were diagnosed from 1989 to 1996. The patients who had any extrinsic factors that might influence the exacerbation of duodenal ulcer were not included. Patients were divided into those whose ulcer bled once or repeatedly as distinct from those whose ulcers caused pain without haemorrhagic complications. Patients with acute cholangitis diagnosed in the same period were studied as controls.

Results

During the 7-year period, 10 331 symptomatic duodenal ulcer diseases were diagnosed. Amongst these, 5328 showed active duodenal ulcer without haemorrhage, 2088 showed acute duodenal ulcer with stigmata of recent haemorrhage, and 2915 showed a deformed bulb. The incidence of total duodenal ulcers showed significant monthly variation and was found to be more common from November to March (P < 0.001). The monthly incidence of total episodes of upper gastrointestinal tract bleeding peaked from November to March (P < 0.001) with significant variation. The monthly incidence of bleeding episodes from duodenal ulcer only was the same (P < 0.001). In patients whose duodenal ulcers repeatedly caused pain without haemorrhage, there were significant monthly fluctuations, with peak months from December to March (P < 0.001). In the control diagnosis, there were no significant calendar variations (P = 0.85).

Conclusions

Our study has shown that both groups of patients demonstrated similar monthly fluctuations. The incidence is significantly higher during the cold seasons. These data suggest that climatic changes may influence the presentation of pain and haemorrhage in duodenal ulcer patients.

     

Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients

High-affinity and saturable membrane-bound dopamine binding sites have been characterized in rat and human gastrointestinal tissues. Although their role in experimental ulcerogenesis has been suggested, dopamine receptor activity in peptic ulcer disease has not been investigated. Radioligand binding studies were performed with mucosal tissue homogenates obtained from the antrum and duodenum of six male healthy volunteers and six male duodenal ulcer patients. The binding assay was performed in triplicate with a crude membrane fraction using [³H] dopamine as a ligand at a final concentration of 1 nM at 22 °C in the dark. Nonspecific binding (which usually comprised about 30% of total binding) was determined in the presence of a 100-fold excess of unlabeled dopamine. A significant (P<0.05) increase of [³H]dopamine binding was found in duodenal mucosa of duodenal ulcer patients. [³H]Dopamine binding in stomach (antrum) of normal and duodenal ulcer patients did not differ significantly. These findings provide preliminary evidence for a role of dopamine receptors in duodenal ulcer and suggest that biochemical abnormalities of gut dopamine function may be operative in the pathogenesis of peptic ulcer disease.     

Pancreatic arteriovenous malformation with duodenal ulcer

Summary We report the color Doppler ultrasonography features of arteriovenous malformation (AVM) of the pancreas, a very rare disease. The patient was a 52-year-old man with congenital AVM of the pancreas and a duodenal ulcer that had been resistant to medication. Endoscopic color Doppler ultrasonography (color Doppler EUS) revealed many abnormal color signals showing pulsatile wave form at the portion of the duodenal wall involving the duodenal ulcer. Extracorporeal color Doppler ultrasonography revealed a mosaic-like color signal, caused by turbulent flow, in the portal trunk. Angiography demonstrated a vascular network with extensive proliferation at the pancreatic head and early portal filling. It is possible that the pancreatic AVM had caused the duodenal ulcer. Color Doppler EUS can be a useful modality for detection of vessel abnormalities of the gastrointestinal tract.     

Catecholamine concentrations in biopsied gastroduodenal tissue specimens of patients with duodenal ulcer

We measured dopamine and norepinephrine concentrations in the biopsied gastroduodenal mucosa obtained from 12 ulcer-free dyspeptic patients, nine patients with active duodenal ulcer, and eight patients with inactive (or healed) duodenal ulcer using a high-performance liquid chromatography with electrochemical detection method. Biopsy specimens were taken from endoscopically normal-appearing mucosa in the gastric body and antrum as well as in the duodenal bulb. Additional specimens were obtained from the outer edge of the ulcer margin in patients with active duodenal ulcer. The mean (±SD) mucosal dopamine concentrations in the gastric body and duodenum (7.6±2.8 and 6.8±2.6 pg/mg tissue) obtained from patients with inactive duodenal ulcer were significantly (P<0.05) lower than those from dyspeptic patients (13.6±6.9 and 10.9±3.5 pg/mg tissue, respectively). In contrast, no significant differences were observed in the mean norepinephrine concentrations in these gastroduodenal tissues among the three study groups. However, the mean mucosal norepinephrine concentration in the outer edge of duodenal ulcer (86.2±125.6 pg/mg tissue) was significantly (P<0.05 and 0.01) reduced as compared with that in the ulcer-free area of duodenum obtained from patients with inactive duodenal ulcer (257.1±188.2 pg/mg tissue) and from dyspeptic patients (276.8±138.3 pg/mg tissue). The results suggest that an alteration in the catecholaminergic system may be associated with one of the pathogenic factors of duodenal ulcer.This study was supported by a grant-in-aid from the Ministry of Human Health and Welfare, Tokyo.     

Reducing meal-stimulated acid secretion versus reducing nocturnal acid secretion for healing of duodenal ulcer

Both meal-stimulated and nocturnal acid secretions have been shown to be abnormally increased in patients with duodenal ulcer. The relative efficacy of an acid-reducing regimen aimed specifically at controlling postprandial acid secretion compared with one that controls nocturnal acid secretion is, however, not known. The endoscopic healing rates at weeks 2, 4, 6, 8, 10, and 12 of three cimetidine regimens with identical total daily dose—bedtime (1200 mg), mealtime (400 mg three times a day with meals), and reference (200 mg three times a day with meals and 600 mg at bedtime)—were compared in a randomized study on 141 patients with endoscopically proven duodenal ulcer. Evaluating endoscopists were blinded to patients' form and duration of treatment and their clinical progress; patients were unaware of the comparative design of the study. Life-table analysis for the 12 weeks of observation revealed that the mealtime regimen resulted in significantly (P<0.05) better healing rates than either the bedtime or the reference regimen. The differences were accounted for largely by the significantly (P<0.04) better healing rate at two weeks with the mealtime regimen (68%) than with either the bedtime (47%) or the reference (45%) regimen. These findings indicate that a regimen that aims at controlling meal-stimulated acid secretion achieves a faster healing rate than one that aims at controlling nocturnal acid secretion in the treatment of duodenal ulcer, and they suggest that postprandial acid secretion plays a greater role than nocturnal acid secretion in the pathophysiology of this condition.This study was supported by the Peptic Ulcer Research Fund (311/041/0372), and by grants (311/030/8009/31, 311/030/8010/12, 335/041/0006, 311/030/8010/69) of the University of Hong Kong.     

Somatostatin in gastric juice in normal subjects and patients with duodenal ulcer

Somatostatin in gastric juice was determined in normal subjects and patients with duodenal ulcer. Gel exclusion chromatography of gastric juice revealed that the main immunoreactivity existed at the position of somatostatin-14. A large amount of somatostatin was present in gastric juice, and the quantity increased following tetragastrin stimulation. Furthermore, there was a good inverse correlation between somatostatin concentration and acidity of gastric juice; however, there was no difference between normal subjects and patients with duodenal ulcer in the amount of somatostatin released into gastric juice.     

Hypersomatostatinaemia in duodenal ulcer

Abstract A sensitive and specific radioimmunoassay of serum somatostatin has been developed that overcomes the problems encountered in earlier assays of peptide disintegration and the need for prior plasma extraction, which is known to result in artifactual loss of somatostatin. In 37 normal controls, a significant positive correlation between fasting serum gastrin and somatostatin concentrations, and a significant negative correlation between pentagastrin-stimulated maximal acid output and fasting serum somatostatin levels were observed. In the majority of 134 patients with active duodenal ulcer in whom the fasting serum somatostatin levels were normal, these relationships were absent. In the remaining 25% in whom the fasting serum somatostatin levels were abnormally raised, these relationships were retained. Following a mixed meal, circulating somatostatin levels remained unchanged in controls and patients as a group. These results suggest that: (i) in the normal state, fasting levels of circulating gastrin and somatostatin are closely related, and that acid secretion may paradoxically exert an inhibitory effect on fasting somatostatin levels; (ii) hypersomatostatinaemia identifies a subgroup of patients with duodenal ulcer in whom these relationships are retained; and (iii) somatostatin may not have a significant hormonal role in the postprandial state in man.     

Regression of duodenal gastric metaplasia in Helicobacter pylori positive patients with duodenal ulcer disease

Background. It is unclear whether the extent of duodenal gastric metaplasia is due to Helicobacter pylori and/or acid.Aims. To investigate the role of Helicobacter pylori eradication in the regression of duodenal gastric metaplasia in patients with duodenal ulcer maintained in acid suppression conditions.Methods. Duodenal (anterior, superior, inferior walls of first part of duodenum) and gastric antrum biopsies were obtained from 44 Helicobacter pylori positive duodenal ulcer patients. Helicobacter pylori infection was diagnosed by rapid urease test, histology and ¹³C-Urea Breath Test. Patients were treated with 20 mg omeprazole tid associated with 250 mg clarithromycin and 500 mg amoxycillin four times daily for 10 days and maintained with 20 mg omeprazole daily for 18 weeks. Control endoscopies were performed at 6 and 18 weeks after beginning treatment.Results. Duodenal gastric metaplasia regression was observed in all ( ) patients in whom Helicobacter pylori was eradicated, but in only 3 out of 6 patients in whom eradication was not achieved (p<0.001).Conclusions. The present results suggest that Helicobacter pylori eradication associated with prolonged acid suppression may represent a good therapeutic strategy to achieve duodenal gastric metaplasia regression and highlight the combined role of acid and Helicobacter pylori in the pathogenesis of duodenal gastric metaplasia.