十二指肠溃疡患夜间酸突破现象初探

目的探讨十二指肠溃疡患者的夜间酸突破现象及其与Hp感染之间的关系.方法十二指肠溃疡患者随机分为三组,每组8例,分别接受①每12h一次静注奥美拉唑40mg(静注1组);②每24h一次静注奥美拉唑40mg(静注2组);③每日二次口服奥美拉唑20mg(口服组).均用药5日并于第5天早上7.30时起连续24小时监测其胃内pH值.结果三组的平均胃内pH、平均中位pH、夜间平均胃内pH、和夜间平均中位pH均升高,以静注1组显著高于其它二组静注2组的夜间pH＜4.0的时间占夜间监测时间的百分比(35.7%±40.3%)显著长于口服组(1.5%±1.9%)和静注2组(1.2±2.3)(p＜0.05);静注2组和口服组分别有4例(50.0%)和1例(12.5%)发生NAB,而静注1组无酸突破发生;合计9例Hp阴性中4例(44.4%)发生NAB,15例Hp阳性中只有1例(6.7%)出现NAB(p＜0.05).结论十二指肠溃疡患者中,中国人的NAB发生率低,可能与国人对奥美拉唑高敏感,且Hp感染率高有关.     

十二指肠溃疡患者夜间酸突破现象临床研究

目的　观察十二指肠溃疡患者夜间酸突破 (NAB)现象 ,以探讨不同治疗方案对NAB的控制效果。方法　将 2 0 0 2 - 0 6～ 2 0 0 3- 0 4大连医学院附属二院消化科 4 0例十二指肠溃疡患者随机分为 4组 ,每组 10例 ,A组 :口服奥美拉唑 2 0mg ,每日 2次 ,法莫替丁 2 0mg睡前口服 ;B组 :口服奥美拉唑 2 0mg ,每日 2次 ;C组 :口服奥美拉唑 2 0mg ,每日 1次 ,法莫替丁 2 0mg睡前口服 ;D组 :口服奥美拉唑 2 0mg ,每日 1次。用药 5d ,于第 5天监测 2 4h胃内pH值。结果　 (1)A组患者没有NAB发生 ,B、C组均分别只有 1例发生 ,D组发生 6例。A、B、C 3组显著低于D组 (P <0 0 5 )。 (2 ) 4组患者的平均胃内 pH值、平均中位pH、夜间平均胃内 pH、和夜间平均中位 pH比较 ,A组显著高于其他各组 (P <0 0 5 ) ;而B组与C组明显高于D组 (P <0 0 5 ) ,B、C组之间差异无显著性 ;D组各项指标均低于其他各组 (P <0 0 5 )。 (3)A组 pH <4 0的时间占总检测时间的百分比、夜间 pH <4 0的时间占夜间检测时间的百分比均显著低于其它各组 (P <0 0 1) ,而B组与C组均明显低于D组 (P <0 0 5 ) ,B、C组之间相比差异无显著性 ;D组明显高于其它各组 (P <0 0 5 )。结论　十二指肠溃疡患者治疗过程中单用奥美拉唑多发生NAB ,改变奥美拉唑用     

十二指肠溃疡患者夜间酸突破现象分析

目的探讨十二指肠溃疡患者(DU)的夜间酸突破(NAB)现象及其与幽门螺杆菌(Hp)感染之间的关系.方法十二指肠溃疡患者随机分为五组,每组8例,分别接受A组静脉注射奥美拉唑40 mg,每日2次;B组静脉注射奥美拉唑40 mg,每日1次;C组口服奥美拉唑20 mg,每日2次;D组口服奥美拉唑20 mg,每日1次;E组静脉注射西米替丁600 mg,每日2次.均用药5 d并于第5天早上8时起连续24 h监测其胃内pH值.结果五组患者的平均胃内pH、平均中位pH、夜间平均胃内pH和夜间平均中位pH均有不同程度升高,A组升高明显,显著高于B、D、E组,差异有显著性(P＜0.05);B、D、E组夜间pH＜4.0的时间占夜间监测时间的百分比显著高于A、C组(P＜0.05);五组分别有0例(A组,0%)、4例(B组,50.0%)、1例(C组,12.5%)、4例(D组,50.0%)、3例(E组,37.5%)患者发生NAB;奥美拉唑2次用药组(包括静脉和口服用药组)仅有1例NAB发生(6.3%),显著低于1次用药组(包括静脉和口服用药组,56.3%,P＜0.05);合计18例Hp阴性者中有10例(55.6%)发生NAB,22例Hp阳性者中只有3例(13.6%,P＜0.05).结论 DU患者中,中国人的NAB发生率低,NAB与奥美拉唑剂量、用药方法及Hp感染相关.     

十二指肠溃疡患者夜间酸突破和幽门螺杆菌感染的关系

夜间酸突破现象(nocturnal acid breakthrough，NAB)是指在应用质子泵抑制剂(PPI)的情况下，夜间(当晚22时至次日早上8时)胃内pH值小于4．0的时间持续超过60min。NAB的发生与幽门螺杆菌(Hp)感染密切相关，为此我们对十二指肠溃疡患者的NAB发生情况，Hp感染对NAB产生的影响进行探讨。     

法莫替丁可抑制夜间胃酸分泌和酸突破

夜间酸突破 (NAB)指服用质子泵抑制剂 (PPI)后夜间pH <4持续 1h以上。国外有研究表明 ,正常人和胃食管反流病患者每日口服 2次PPI不足以完全控制夜间胃酸分泌 ,其中 3/4可发生NAB ,而H2 受体拮抗剂可有效地抑制NAB[1,2 ] 。为研究十二指肠溃疡 (DU)患者服用法莫替丁后NAB情况 ,我们比较服用奥美拉唑后 ,睡前加服法莫替丁和加服奥美拉唑对DU夜间胃酸分泌和NAB的影响。一、对象和方法1.研究对象 :2 0例患者 ,男 11例 ,女 9例 ,年龄 19～ 5 3岁 ,平均 38.6岁。胃镜诊断为活动性DU 1～ 2个 ,溃疡直径>3mm ,<2 0mm。近 4周未用抗溃疡…     

24小时胃内酸度监测评价多种抑酸剂静脉使用对十二指肠溃疡患者的抑酸效果

目的　对比各种常用抑酸剂对十二指肠溃疡出血患者胃酸的抑制效果。方法　运用随机、开放的方法分析５０ 例十二脂肠溃疡出血患者,分别使用奥美拉唑静脉滴注、法莫替丁静脉注射、雷尼替丁静脉注射、西咪替丁静脉注射或滴注。持续监测患者２４ 小时胃内ｐＨ 动态变化的情况、不同胃内ｐＨ值持续时间的百分率、２４ 小时平均胃内ｐＨ 和中位ｐＨ 值。结果　只有奥美拉唑８０ｍｇ／天组可达到胃内平均ｐＨ 和中位ｐＨ 均＞６ ,法莫替丁８０ｍｇ／天组可达到胃内平均ｐＨ 和中位ｐＨ 均＞ ４,其他治疗组均未达到ｐＨ＞ ４ 。２４ 小时胃内ｐＨ＜ ４ 、ｐＨ＜ ５、ｐＨ＜ ６ 时间所占百分比依次递增为：奥美拉唑８０ｍｇ／天组、法莫替丁８０ｍｇ／ 天组、雷尼替丁２００ｍｇ／天组、西咪替丁８００ｍｇ／天组。各Ｈ２ 受体拮抗剂组与奥美拉唑静脉滴注组比较,差异均有显著性。结论　静脉使用质子泵抑制剂的抑酸效果明显优于Ｈ２ 受体拮抗剂,尤其是奥美拉唑静脉滴注胃内ｐＨ 提高持续的时间较长。     

夜间酸突破的影响

质子泵抑制剂（proton pump inhitor，PPI）自1989年问世以来，对消化系酸相关性疾病的治疗产生突破性的历史意义，一直以来被认为是治疗酸相关性疾病最有效的药物。随着PPI的广泛普及使用，近年来发现部分患者，尤其是胃食管反流病（GERD）患者在服用PPI治疗时症状仍得不到很好的控制。1998年Peghird等学者通过对胃食管反流病患者24h pH监测得出结果示，     

24小时胃内酸度监测评价多种抑制酸剂静脉使用对十二指肠溃疡 …

目的 对比各种常用抑酸剂对十二指肠溃疡出血患者胃酸的抑制效果。方法 运用随机,开放的方法分析５０例十二指肠溃疡出血患者,分别使用奥美拉唑静脉滴注,法莫替丁静脉注射,雷尼替丁静脉注射,西咪替丁静脉注射或滴注。     

夜间酸突破的临床意义和治疗措施

夜间酸突破现象(NAB)在应用质子泵抑制剂的人群中有很高的发生率,其发生机制复杂,与反流性食管炎、Barrett食管等酸相关性疾病有密切的联系。控制夜间酸突破是成功治疗上消化道酸相关性疾病的重要挑战,目前对其治疗主要以每日2次PPI联合睡前加服H2受体拮抗剂(H2RA)的方案为主,但疗效短暂。近年来对于NAB现象已有一定的认识,但仍处于探索阶段,还需要更多大样本的临床研究以寻求更好的治疗措施。     

夜间酸突破现象及治疗的研究

目的　了解夜间酸突破现象 (NAB)并寻求解决措施。方法　胃镜确诊十二指肠球部溃疡(DU)病人 4 0例 ,随机分为 5组 ,每组 8例 ,治疗方法 :A组奥美拉唑 2 0mg ,每日 1次口服 (晨起 ) ,B组奥美拉唑 2 0mg ,每日 2次口服 (晨起及下午 4时 ) ,C组奥美拉唑 4 0mg ,每日 2次静脉注射 (晨起及下午 4时 ) ,D组奥美拉唑 2 0mg ,每日 1次口服 (晨起 ) +雷尼替丁 15 0mg临睡前服 ,E组奥美拉唑 2 0mg ,每日2次口服 (晨起及下午 4时 ) +雷尼替丁 15 0mg临睡前服。所有病人于用药治疗第 5天连续 2 4h监测胃内pH值。结果　与A组 (4.8± 0 .7,4 .7± 0 .8)相比 ,后 4组病人的平均胃内pH值、夜间平均胃内pH值显著升高 ,B组为 6 .2± 0 .7,6 .4± 1.1;C组为 6 .9± 0 .7,6 .8± 0 .9;D组为 6 .0± 0 .7,5 .9± 0 .7;E组为 5 .8± 0 .5 ,6 .1± 0 .5 ,差异均有显著性 (P <0 .0 5 )。夜间 pH <4 .0的时间百分比A组 (2 8.4± 2 9.6 )较B组 (1.5± 1.9)、C组 (1.2± 1.3)、D组 (0 .1± 0 .3)、E组 (2 .9± 5 .1)明显增高 (P <0 .0 5 )。NAB发生情况A组 5例 ,较B组 1例 ,C组 0例 ,D组 2例 ,E组 0例明显增多 (P <0 .0 5 )。幽门螺杆菌 (Hp)阴性的病人NAB发生率显著高于阳性病人。结论　DU病人 ,NAB的发生与奥美拉唑的用药剂量、用     

A Pharmacodynamic Study of Two Omeprazole Regimens Suitable for Long-Term Treatment of Duodenal Ulcer

Vigneri S, Savarino V, Mela GS, Termini R, Di Mario F, Pantalena M, Zentilin P, Muratore F, Scialabba A, Badalamenti S. A pharmacodynamic study of two omeprazole regimens suitable for long-term treatment of duodenal ulcer. Scand J Gastroenterol 1994;29:488-492.

Background: The experience with long-term treatment of peptic ulcer with omeprazole is still scant, but the possibility cannot be excluded that its better pharmacodynamic effect on gastric acidity also has a positive result in the relapse rate. Moreover, this drug acts via a mechanism other than receptorial binding, and therefore its efficacy should not dissipate with time. This study was carried out to assess the pharmacodynamic properties and the possible changes with time of two dose regimens of omeprazole that could be suitable for long-term treatment in duodenal ulcer.

Methods: Twenty patients with endoscopically proven duodenal ulcer were studied by means of 24-h gastric pH-metry both in basal conditions and on the 5th day of acute treatment with 40 mg omeprazole in the morning. All the ulcers healed after 4 weeks, and thereafter 10 patients were randomized to receive orally 20 mg omeprazole daily at 0800 h in single-blind fashion (group A) and 10 to receive 20 mg omeprazole every other day (group B) for up to 6 months. At the end of the 1st, 3rd, and 6th month of these maintenance treatments 24-h gastric pH-metry was repeated to assess the antisecretory effect of each regimen over time. In group-B patients the test was performed on 2 consecutive days (without and with medication) at each time interval. The fasting gastrin values were also determined. The patients underwent esophago-gastroduodenoscopy every 2 months.

Results: Three patients in group B were lost to follow-up for various reasons, and only seven remained elegible for final analysis. The two long-term regimens of omeprazole were able to increase significantly pH values (p < 0.02-0.001) and the times spent at and above pH 3.0 (p < 0.001) over 24 h compared with basal conditions. In group A the 24-h pH value obtained in the 6th month was higher (p < 0.02) than that in the 3rd month of maintenance treatment. In group B the pharmacologic effect tended to decrease on the day without medication compared with the day with medication, but the difference between them was significant (p < 0.05) only at the 6-month interval. There was no significant difference between the gastrin levels of the two groups in the long-term treatment. No ulcer relapse was detected at any long-term endoscopic control in the two groups of patients.

Conclusions: The two omeprazole regimens we tested are effective in reducing gastric acidity, and their pharmacodynamic action does not decrease with time. They are therefore suitable for maintenance treatment in acid-related disorders.     

Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study

Background/AimsTegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects.MethodsIn a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation.ResultsAll 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration–time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing.ConclusionsAll the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.     

Gastric Acid Secretion and Duodenal Ulcer Healing during Treatment with Omeprazole

Twenty-seven duodenal ulcer patients were treated with omeprazole, 40 mg daily for 4 weeks. The peak acid output to pentagastrin measured 24 h after dosing was reduced by 54% on day 3 of the study and by 74% on day 14. The ulcers in 25 of 26 patients had healed by the end of the treatment period, and 1 patient was unable to attend the final endoscopy. Ulcer symptoms were relieved rapidly. The drug was well tolerated, and few adverse reactions were reported.     

胃食管反流病夜间酸突破与食管酸暴露的关系探讨

目的探讨胃食管反流病(GERD)患者夜间酸突破(NAB)与食管酸暴露的关系。方法将45例GERD患者随机分为两组,对照组(21例)给予雷贝拉唑钠10 mg早晚各1次口服,试验组(24例)治疗同对照组外晚间睡前另加服雷尼替丁150 mg,疗程共7 d。两组治疗前后行24 h食管、胃pH监测,及反流诊断问卷评分(RDQ),并进行比较。结果加服雷尼替丁组夜间酸突破的发生率为20.83%,单用雷贝拉唑钠组为57.14%,两组比较差异有统计学意义(P0.05)。结论食管酸暴露和食管反流症状的控制不依赖于夜间酸突破的缓解,更大程度上取决于食管动力异常的改善。     

Inhibition by Pirenzepine of Nocturnal Gastric Acid Secretion in Duodenal Ulcer Patients

Ten patients with endoscopically proven duodenal ulcers participated in a double-blind, placebo-controlled, cross-over trial to investigate the effect of pirenzepine on nocturnal gastric acid secretion. Pirenzepine, 50 mg orally at bedtime, inhibited acid secretion all night long: the overall volume secreted and acid output (midnight to 7 a.m.) were significantly less than after placebo. The decrease in acid output per hour was significant at 1, 2, 3, 6, and 7 a.m. and the decrease in acid concentration of gastric juice at 2, 6, and 7 a.m. It was concluded that controlled clinical trials of maintenance therapy for prevention of relapse of healed duodenal ulcers should be carried out with the pirenzepine taken at bedtime.     

国产法莫替丁治疗胃、十二指肠溃疡病双盲多中心的临床研究

为评价国产法英替丁(Famotidine,FT)治疗消化性溃疡的疗效和安全性,在北京和上海15所医院进行了一项多中心研究。FT的剂量为40mg/日;对照组雷尼替丁(Ramitidine,RT)为300mg/日,共完成十二指肠溃疡的疗效观察480例,胃溃疡123例,分为FT胶囊组,片剂组和RT组。经胃镜判断疗效,结果显示:FT治疗胃溃疡六周的愈合率,不论胶囊组(79％)或片剂组(86.7％)均明显高于RT组(61.3％,P<0.05)。十二指肠溃疡四周的愈合率,胶囊组为66.7％,片剂组为67.5％,与RT组(70.8％)比较无显著差别,本药无严重副作用,仅少数病人有轻度口干、便秘、头晕、失眠,与对照组相似,也未发现对肝、肾功能有毒性反应。     

伴特发性肺纤维化的胃食管反流病患者夜间酸暴露特点

背景:胃食管反流是特发性肺纤维化(IPF)发生的危险因素之一,夜间反流在胃食管反流病(GERD)食管外表现中起重要作用。目的:研究伴IPF的GERD患者夜间食管酸暴露的特点。方法:选取2006年12月～2008年1月北京朝阳医院收治的16例IPF-GERD患者、32例GERD患者和16例健康志愿者(非GERD)。各组患者行24 h食管pH监测,对夜间8 h内(10pm-6am)的酸暴露程度,包括pH4的时间百分比、酸清除时间、反流次数、长反流(5 min)次数、最长反流时间等指标进行分析。结果:14例(87.5%)IPF-GERD患者存在夜间酸暴露,其程度高于非GERD组(P0.05),而与GERD患者无明显差异(P0.05)。IPF-GERD组患者前半夜pH4的时间百分比显著高于后半夜(12.2%±3.9%对1.1%±0.5%,P0.05),GERD组两者无明显差异(10.8%±2.7%对5.1%±1.8%,P0.05)。结论:大部分IPF-GERD患者存在夜间酸暴露,其主要发生于前半夜。     

胃酸和十二指肠胃食管反流在非糜烂性反流病中的作用

背景:胃酸和十二指肠胃食管反流(DGER)在我国非糜烂性反流病(NERD)患者发病中的作用尚不清楚。目的:探讨胃酸和DGER在NERD发病中的作用。方法:选取在消化专科门诊连续就诊的具有烧心和(或)反酸等反流症状的所有患者为研究对象,所有入选者填写一份问卷后,依顺序行胃镜检查、24h食管pH监测和24h食管胆汁联合监测。结果:共有82例NERD患者入选,平均年龄为42.7岁±11.7岁。其中,24例(29.3%)24h食管pH监测阳性[NERDpH(+)],58例(70.7%)24h食管pH监测阴性[NERDpH(-)];43例(52.4%)为DGER阳性,39例(47.6%)为DGER阴性。联合监测结果为,82例患者中15例(18.3%)病理性酸反流与DGER并存,9例(11.0%)存在单一的病理性酸反流,28例(34.1%)存在单一的DGER,30例(36.6%)则无病理性酸反流,且DGER阴性。采用24h食管pH监测组对NERD的诊断率为29.3%,而联合24h食管胆汁监测,则NERD的诊断率升高到63.4%。24例NERDpH(+)者中,15例(62.5%)存在DGER;58例NERDpH(-)者中,28例(48.3%)存在DGER;NERDpH(+)组与NERDpH(-)组DGER发生率无显著性差异(χ2=1.377,P=0.241)。结论:NERD的病理性酸反流比例相对较低,联合24h食管pH和胆汁监测可明显提高NERD的诊断率,DGER在NERD中的作用地位不容忽视。     

Acid Gastroesophageal Reflux Reports in Infants: A Comparison of Esophageal pH Monitoring and Multichannel Intraluminal Impedance Measurements

Twenty-four-hour tracings generated from combined esophageal pH and multichannel intraluminal impedance measurements of 14 infants (nine males, median age 3.5 months) were examined retrospectively. For each tracing, two acid reflux assessment reports were generated using either pH monitoring alone or pH monitoring combined with impedance. Significantly fewer acid reflux episodes were detected using pH monitoring combined with impedance when compared to pH monitoring alone (25.1±4.0 versus 99.9±18.3 episodes/patient, p=.001). Estimates of esophageal acid exposure using pH monitoring alone were two-fold higher (137.4±23.7 versus 66.6±15.9 min/patient, p=.002) than estimates derived using both techniques. Of the total acid reflux episodes detected by pH monitoring alone, 71.8% could not be confirmed by combined pH and impedance. Detection of significant numbers of “pH-only” episodes raises concerns regarding possible over-estimations of acid exposure that may occur when estimates are based solely on esophageal pH monitoring.This study was funded in part by a grant from the National Institutes of Health (NIH 5R03DK62755-02) (HM) issued on July 1, 2002 (NIH, 900 Rockville Pike, Bethesda, MD).     

Effects of Omeprazole and Eradication of Helicobacter pylori on Gastric and Duodenal Mucosal Enzyme Activities and DNA in Duodenal Ulcer Patients

Vetvik K, Schrumpf E, Mowinckel P, Aase S, Andersen K-J. Effects of omeprazole and eradication of Helicobacter pylori on gastric and duodenal mucosal enzyme activities and DNA in duodenal ulcer patients. Scand J Gastroenterol 1994;29:995-1000.

Background: Duodenal and gastric content of mucosal enzymes in duodenal ulcer (DU) patients differs from that of controls. The purpose of this study has been to examine the effect of omeprazole and eradication of Helicobacter pylori on mucosal enzymes in DU patients

Methods: The enzyme activities of seven gastric and duodenal mucosal marker enzymes from the brush border, lysosomes, and mitochondria have been studied. In study I the measurements were made in 29 patients with an active DU before and after 14 days of omeprazole treatment. In study II 22 duodenal ulcer patients were given bismuth subnitrate, oxytetracycline, and metronidazole (triple therapy) for 2 weeks to eradicate H. pylori. Biopsy specimens were taken from the duodenum and the stomach for enzyme measurements and histologic assessment. In study II additional specimens were obtained from the prepyloric region for urease tests and culture of H. pylori.

Results: The ulcer healing rates were more than 90% after both omeprazole and triple therapy. H. pylori was eradicated in 86% after triple therapy. The activities of the brush-border enzymes lactase, neutral-α-glucosidase, alkaline phosphatase, leucyl-β-naphthylami-dase, and γ-glutamyltransferase (γ-GT) increased significantly in the duodenal bulb and the descending duodenum during treatment with omeprazole. No changes in duodenal enzyme activity were detected after triple therapy, whereas a significant fall in γ-GT and acid phosphatase activities was seen in the stomach. The mucosal DNA in the gastric antrum decreased both after treatment with omeprazole and after triple therapy.

Conclusions: A similar decrease in mucosal DNA of the gastric antrum was demonstrated after both omeprazole and triple therapy with bismuth subnitrate, oxytetracycline, and metronidazole. Omeprazole also affects the content of duodenal mucosal enzymes, whereas triple therapy particularly affects the gastric mucosal enzyme activity.