根除幽门螺杆菌对胃溃疡愈合质量及复发的影响研究

目的探讨幽门螺杆菌（Helicobacter pylori，Up）对胃溃疡愈合质量及复发的影响。方法120例坳阳性活动期胃溃疡患者，口服泮托拉唑、阿莫西林、甲硝唑一周后，继续口服泮托美拉唑5周。治疗结束后复查胃镜取病理组织学检查并检测Hp根除情况，对比却根除组与却根除失败组内镜下溃疡愈合形态差异和愈合质量（包括内镜下再生黏膜成熟度和再生黏膜组织学成熟度）。所有患者随诊1年以上了解溃疡复发情况。结果治疗后92例胃溃疡患者月p检测阴性，坳根除率为80．43％；却根除组与跏根除失败组在内镜下愈合率方面的差异无显著性意义（P〉0．05），但两组在再生黏膜成熟度和再生黏膜组织学成熟度方面的差异有显著性意义（P〈0．01）。坳根除组1年溃疡复发率为4．35％，却根除失败组为21．43％，两组差异有显著性意义（P〈0．05）。结论根除Hp可提高胃溃疡的愈合质量，减少溃疡病复发。     

蒲元和胃胶囊对消化性溃疡愈合质量的影响

[目的]研究蒲元和胃胶囊对消化性溃疡（PU）愈合质量的影响。[方法]选取PU患者167例,随机分为治疗组90例和对照组77例,2组患者均采用幽门螺杆菌（Hp）标准根除方案（雷贝拉唑、克拉霉素、阿莫西林）治疗1周,Hp阴性者不用。对照组继续服用雷贝拉唑钠肠溶片3周,治疗组服用雷贝拉唑钠肠溶片联合蒲元和胃胶囊3周。治疗4周后复查,观察胃镜下溃疡愈合情况和再生黏膜成熟程度。[结果]治疗组和对照组的胃溃疡总愈合率分别为89.47%和82.35%（P〉0.05）;瘢痕期（S期）Sc百分比分别为47.37%和23.53%（P〈0.05）。治疗组和对照组的十二指肠球部溃疡总愈合率分别为92.31%和86.05%（P〉0.05）;Sc百分比分别为48.08%和27.91%（P〈0.05）。[结论]蒲元和胃胶囊治疗PU能在溃疡愈合基础上显著提高愈合质量。     

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.     

Quality of gastric ulcer healing evaluated by endoscopic ultrasonography

AIM: To evaluate the quality of gastric ulcer healing after different antiulcer treatment by endoscopic ultrasonography (EUS). METHODS: The patients were divided into three groups, and received lansoprazole, amoxicillin and clarithromycin for 1 wk. Then group A took lansoprazole combined with tepreton for 5 wk, group B took lansoprazole and group C took tepreton for 5 wk. Endoscopy and EUS were performed before and 6 wk after medication. RESULTS: There was no significant difference in cumulative healing rate to S stage between the groups (89%, 82% vs 83%, P>0.05). The rate of white scar formation was significantly higher in group A than in groups B and C (67%, 36%, 50%, P<0.05). The average contraction rates of the width of ulcer crater, length of disrupted muscularis propria layer and hypoechoic area were higher in group A than in groups B and C (0.792±0.090, 0.660±0.105 vs 0.668±0.143, P<0.05). The hypoechoic area disappeared in four cases of group A, one of group B and two of group C. The percentage of hypoechoic area disappearance was higher in group A than in the other two groups (44%, 9% vs 17%, P<0.05). Gastric ulcer healing was better in group A. CONCLUSION: The combined administration of proton-pump inhibitors and mucosal protective agent can improve gastric ulcer healing.     

Discriminant factors of gastric ulcer healing by colloidal bismuth

One hundred and twelve patients with 49 corpus and 35 prepyloric gastric ulcers and 28 duodenal ulcers associated with gastric ulcers were entered into a stratified, controlled double-blind randomized study comparing the healing efficacy of colloidal bismuth suspension with placebo. Healing of corpus and prepyloric ulcers, but not duodenal-ulcer associated gastric ulcers, was significantly better with the bismuth compound than with placebo. The clinical, personal, ulcer and acid secretory data of these patients were prospectively collected and evaluated by stepwise discriminant analysis in two phases. In the first phase, the collected data of 91 consecutive patients were entered into computer analysis. The derived discriminant function classified patients into healed and unhealed categories with a sensitivity of 82%, specificity of 77%, positive diagnostic value of 73%, negative diagnostic value of 85% and diagnostic efficiency of 79%. In phase two, the discriminant function from phase 1 was applied prospectively to 21 patients to predict the outcome of treatment. Five out of five healed and 11/16 unhealed gastric ulcers were correctly predicted, giving a diagnostic efficiency of 76%. The present study shows that healing or non-healing of gastric ulcer can be predicted with reasonable accuracy by discriminant analysis. In addition, discriminant analysis identified, aside from the efficacious drug, ulcer size, young age, co-existing duodenal ulcer, and concomitant medical condition as adverse factors for gastric ulcer healing.     

Quality of ulcer healing influences the relapse of gastric ulcers in humans

The usefulness of dye-contrast endoscopy for the evaluation of the quality of gastric ulcer healing and the prediction of relapse was investigated. Sixty consenting patients whose ulcers healed during 3 months of treatment underwent endoscopy for the identification of the pattern of mucosal regeneration. Patients were monitored for relapses for up to 18 months after antiulcer therapy had ended. The pattern of regeneration was flat in 24 patients, nodular in 25 and intermediate in 11. Internal hypoechoic areas seen by endoscopic ultrasonography were less common and histological maturity was better in the patient group with the flat pattern compared with the patient group with the nodular pattern of mucosal regeneration. Prostaglandin E, synthesis was highest in the group with the flat pattern of mucosal regeneration and the relapse rate was lowest in this group. We conclude that the evaluation of the quality of ulcer healing is possible and that findings in individuals may aid the prediction of relapse for particular patients.     

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.     

Influences of Helicobacter pylori on gastric angiogenesis and ulcer healing in mice

BACKGROUND AND AIMS: Helicobacter pylori infection is associated with peptic ulcers; however, it is unclear whether the bacterium delays ulcer healing. We investigated the influence of H. pylori on ulcer healing in mice. We also examined the influence of H. pylori infection on angiogenesis. METHODS: An acetic acid ulcer was made in male BALB/c mice. Three days later (day 0), the animals were inoculated with H. pylori SS1 strain. The healing process of the ulcer was examined macroscopically and microscopically on days 0, 6 and 9. The index of angiogenesis was also determined using carmine dye injection. RESULTS: On day 0, angiogenesis began at the ulcer margin while the mucosal epithelia had not yet regenerated. On days 6 and 9, angiogenesis and epithelial regeneration developed and ulcer size reduced. These phenomena were significantly suppressed in mice infected with H. pylori. CONCLUSION: Helicobacter pylori infection significantly suppressed angiogenesis and delayed ulcer healing. These results indicate that H. pylori plays an important role in ulcer healing.     

兰索拉唑联合铝碳酸镁治疗消化性溃疡的长期疗效分析

目的：探讨溃疡愈合质量对消化性溃疡复发的影响。方法：将68例十二指肠球部溃疡合并幽门螺杆菌(H．Pylori)感染患者随机分为：试验组38例,对照组30例。2组均先给予标准3联疗法根除H．Pylori,1周后试验组,兰索拉唑30mg每日2次,联合铝碳酸镁(商品名,达喜)1000mg每日3次;对照组,兰索拉唑30mg每日2次;继续治疗4周。停药4周后观察内镜下溃疡愈合率、胃粘膜组织学改变;随访1年内溃疡复发情况。结果：停药4周后内镜下溃疡愈合率分别为,试验组94．7%,对照组80．0%,两者比较无显著性差异(P＞0．05)。组织学观察显示粘膜层厚度、腺体密度和腺管形态恢复,试验组显著优于对照组(P＜0．05);1年内溃疡复发率,试验组2．8%,对照组25．0%,两者比较有显著性差异(P＜0．05)。结论：兰索拉唑联用铝碳酸镁能提高溃疡愈合质量,减少溃疡复发,显著优于单用兰索拉唑。     

Indomethacin treatment during initial period of acetic acid-induced rat gastric ulcer healing promotes persistent polymorphonuclear cell-infiltration and increases future ulcer recurrence

The study was performed to examine whether indomethacin administered during the initial period of acetic acid-induced gastric ulcer healing affects future ulcer recurrence. Gastric ulcers were produced in rats by subserosal injection of acetic acid. Indomethacin (1 mg/kg/day, orally) administered either alone or concomitant with ornoprostil (50µg/kg/day, orally) was started on the fourth day and continued for 56 days. In rats whose ulcer healed at the 90th day after production of ulcer, endoscopy was done every 30 days to examine recurrence of ulcer. Gastric specimens were obtained 10, 30, 60, 90, and 240 days after ulcer production for histology, to quantitate the height of regenerated mucosa, thickness of fibrous tissue, degree of polymorphonuclear cell infiltration, and PAS-positive cells. Cumulative ulcer recurrence rate was significantly higher in rats initially treated with indomethacin than in controls. Increased polymorphonuclear cell infiltration was the major histologic abnormality persisting after cessation of indomethacin. Ornoprostil reversed these abnormalities caused by indomethacin. In conclusion, the administration of indomethacin during the initial period of the ulcer healing promoted persistent polymorphonuclear cell infiltration and increased ulcer recurrence rates, possibly via a prostaglandin-dependent mechanism.The work was supported by The Ministry of Education, Science and Culture of Grant-in-Aid for General Scientific Research 02454236 and by the DVA Medical Research Service.     

表皮生长因子治疗糖尿病足溃疡的研究进展

糖尿病足是糖尿病常见的慢性并发症之一,15%的糖尿病患者可能发生足部溃疡。溃疡创面局部生长因子及受体活性下降和数量的绝对或相对缺乏是其难以愈合的病理生理基础。表皮生长因子(EGF)通过促进细胞迁移、增殖及细胞外基质合成等参与溃疡创面愈合。外源性EGF作为一种新的治疗手段,局部应用于糖尿病足溃疡取得显著效果。通过组织工程学技术,EGF释药方式不断改善,并可与其他生长因子联合应用,具有广泛前景。     

Neutrophil elastase in pressure ulcer fluid degrades fibronectin in the exudates

Background:   Pressure ulcers are classified as chronic wounds, which do not heal in a timely fashion. Fibronectin is condensed in granulation tissue, and essential glycoprotein of wound healing. It has been proposed that fibronectin degradation may be involved in delaying wound healing. We have investigated whether pressure ulcer fluid (PUF) contains degraded fibronectin. In addition, we tried to identify the proteinase which contributes to fibronectin degradation in PUF.
Methods:   Fibronectin degradation and the presence of neutrophil elastase (NE) in PUF were determined by immunoblot analysis. Fibronectin degradation activity in PUF was determined in the presence of various proteinase inhibitors. NE activity was assessed using NE specific substrate.
Results:   Immunoblot analysis revealed that degraded fibronectin was observed in PUF samples but not in acute wound fluid (AWF). The PUF contained a proteinase capable of degrading freshly added fibronectin and its activity in PUF was blocked by a broad-spectrum serine proteinase inhibitor or sivelestat, a specific neutrophil elastase inhibitor, but not by metalloproteinase and cysteine proteinase inhibitors. Immunoblot analysis of PUF using an antineutrophil elastase antibody revealed that neutrophil elastase was detected as three bands at molecular weights of ∼30 kDa, ∼38 kDa, and ∼54 kDa, indicating that neutrophil elastase in the exudates existed not only as free monomers, but also in polymers or complexes with other molecules.
Conclusion:   These results suggest that PUF contains a high level of neutrophil elastase which may be involved in the delay of the healing of pressure ulcer through the fibronectin degradation.     

Helicobacter pylori infection delays the healing of acetic acid-induced gastric ulcer in Japanese monkeys

To clarify the relationship between Helicobacter pylori and the healing of gastric ulcers, we investigated the healing of acetic acid-induced gastric ulcers in the antral mucosa of Japanese monkeys (n=5) infected with H. pylori and in control monkeys without H. pylori infection (n=6). Using H. pylori-infected Japanese monkeys as an experimental model, gastric ulcers were induced endoscopically with acetic acid. Healing of ulcers and factors that influenced healing were studied. Continuous colonization with H. pylori was confirmed in the infected group throughout the observation period; no H. pylori were isolated from the gastric mucosa of the control group. White scarring was not observed in any infected monkeys 4 weeks after ulcer formation, but was observed in one (20%) of five monkeys at 6 weeks and in all five monkeys eight weeks after ulcer formation. In the control group, white scarring was observed in one (16.7%) of six monkeys at 4 weeks and in six monkeys at 6 (P< 0.01 vs infected group) and 8 weeks. The ammonia concentration of the gastric secretions and the grade of inflammation were significantly increased in the H. pylori-infected group compared with the control group (P< 0.01 and P< 0.001, respectively). The volume of intracellular PAS-positive substance was decreased (P< 0.025–0.01) at the ulcer margin in the infected group compared with the ulcer margin in the control group. The proliferation of gastric epithelial cells was markedly accelerated at the ulcer margin in the infected group compared with the ulcer margin in control group (P< 0.025–0.01). Our results strongly suggest that H. pylori infection delays the healing of gastric ulcers.     

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.     

A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide

Background and Aim: Controversies remain over the need for antiulcer treatment following 1‐week eradication triple therapy for Helicobacter pylori‐positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. Methods: The study was conducted in 52 H. pylori‐positive patients with an endoscopically‐proven open gastric ulcer. All patients received 1‐week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7‐week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and ¹³C‐urea breath test. Results: The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non‐eradicated patients. The overall gastrointestinal symptom‐free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. Conclusions: The results suggested that the combination therapy for open gastric ulcer was safe, well‐tolerated and effective. However, data from a double‐blind placebo‐controlled study is necessary to confirm these findings.     

胶体果胶铋联合泮托拉唑三联治疗H.pylori阳性胃溃疡的疗效分析

目的观察胶体果胶铋联合泮托拉唑三联对H.pylori阳性胃溃疡的溃疡愈合质量的影响以及根除H.pylori的疗效。方法将经胃镜检查及14C呼气试验确诊的90例H.pylori阳性胃溃疡患者随机分为两组:对照组45例,口服泮托拉唑40 mg bid+左氧氟沙星200 mg bid+阿莫西林1 000 mg bid,连续口服10 d后,停服阿莫西林及左氧氟沙星,继续口服泮托拉唑40 mg qd维持3周;试验组45例,在对照组的基础上加用胶体果胶铋干混悬剂150 mg qid。停药4周后复查14C呼气试验,观察H.pylori根除情况;疗程结束后,胃镜复查评估溃疡愈合情况。结果试验组和对照组H.pylori根除率分别为88.89%、71.11%,两组相比,差异有统计学意义(P0.05);溃疡愈合率分别为86.67%、68.89%,两组相比,差异有统计学意义(P0.05)。试验组溃疡愈合S2期获得率57.78%,显著高于对照组的33.33%(P0.05)。结论胶体果胶铋联合泮托拉唑三联治疗H.pylori阳性胃溃疡是一种高效、简便、安全的临床方案,胶体果胶铋在抗H.pylori、提高溃疡愈合质量上起着重要作用。     

间充质干细胞凝胶对大鼠四期压疮创面愈合的作用及机制

目的探讨人间充质干细胞(MSCs)凝胶对大鼠四期压疮创面在不同环境中愈合的效果及作用机制。方法选择126只大鼠,按照随机数字表法选取6只作为正常组;其余120只大鼠造模后随机分为对照组、干性-临床组(GL组)、湿性-临床组(SL组)、干性-干细胞组(GG组)及湿性-干细胞组(SG组),每组各24只。对照组无治疗措施,自然愈合;GL组予以涂抹碘伏+纱布包扎;SL组予以涂抹清创胶+水胶体覆盖;GG组予以涂抹MSCs凝胶+纱布包扎;SG组予以涂抹MSCs凝胶+水胶体覆盖。治疗第3、6、9、15天时,测量各组大鼠创面面积并计算创面愈合率,采用ELISA法测定血清VEGF、TNF-α及IL-10表达水平。结果治疗6 d、9 d、15 d时,SL组创面愈合率均高于GL组(P均<0.05),GG组创面愈合率均高于SG组(P均<0.01)。治疗9 d、15 d时,SL组血清TNF-α水平均低于GL组,GG组血清TNF-α水平均低于SG组(P均<0.05)。治疗3 d、6 d、9 d、15 d时,GG组血清IL-10、VEGF水平均高于SG组(P均<0.05)。结论MSCs凝胶可提高四期压疮大鼠的创面愈合率,且在干性愈合环境中的作用能力优于湿性环境,其机制可能为减轻创面炎症反应、促进血管新生。     

Quality of ulcer healing in gastrointestinal tract: Its pathophysiology and clinical relevance

In this paper, we review the concept of quality of ulcer healing (QOUH) in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease (PUD) has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori (H. pylori), which is also the cause of ulcer recurrence. However, H. pylori-negative ulcers are present in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macrophages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer recurrence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a deficiency and/or an imbalance of endogenous growth factors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn’s disease and ulcerative colitis.     

铝碳酸镁联合奥美拉唑治疗活动期胃溃疡的随机、平行对照、多中心临床研究

目的比较铝碳酸镁咀嚼片（商品名：达喜）联用奥美拉唑或单用奥美拉唑治疗成人活动期胃溃疡患者的临床症状改善情况、内镜下溃疡愈合率以及组织学溃疡愈合质量。方法采用多中心、随机、平行对照研究、将88例经胃镜证实伴幽门螺卡下菌感染的成人活动期胃溃疡患者，随机分为试验组（45例）和对照组（43例）。治疗第1周．两组均予幽门螺杆菌根除三联疗法．试验组同时给予铝碳酸镁咀嚼片每次1000mg．每日4次嚼服。第2～6周，试验组给予铝碳酸镁（剂量服法同前）联合奥美拉唑胶囊20mg．每晨1次口服。对照组仅给予奥美拉唑胶囊20mg．每晨1次口服。第7～8周．试验组继续给予铝碳酸镁咀嚼片（剂量服法同前），对照组停药。结果首次服药后上腹痛消失时间对照组为2d．试验组仅0．5d．两组间差异有统计学意义（P〈0．001）。治疗第1周末，试验组改善腹痛、腹胀、反酸、暖气、呕吐的发生频率显著优于对照组（P〈0．05）．试验组改善腹痛程度亦显著优于对照组（P〈0．01）。治疗8周后，两组内镜下溃疡愈合总有效率差异无统计学意义（P〉0．05）。病理组织学检查显示试验组腺体密度和腺管形念恢复显著优于对照组（P〈0．05）。结论治疗活动期胃溃疡，在质子泵抑制剂有效抑酸基础上．联合应用兼有抗酸、抗胆汁作用的胃黏膜保护剂铝碳酸镁，能更快缓解多种临床症状，尤其是迅速缓解胃痛。加用铝碳酸镁能显著促进胃黏膜组织形态结构的恢复，提高溃疡愈合质量。     

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.