猫胃螺杆菌感染小鼠模型的研究

本研究建立了幽门螺杆菌的近缘苗猪胃螺杆菌的SPF级Balb／c小鼠模型，发现细菌可在其中长期定植并引起与人类Hp相关胃炎相似的组织学改变，提示该模型可用于幽门螺杆菌的研究。     

The Helicobacter felis Mouse Model in Assessing Anti-Helicobacter Therapies and Gastric Mucosal Prostaglandin E2 Levels

Background: The aims of the present study were to assess the usefulness of the Helicobacter felis mouse model in the evaluation of antimicrobial therapies and the effect of Helicobacter infection on gastric mucosal prostaglandin E₂ release. Methods: Barrier-maintained BALB/c mice were infected with H. felis and treated with different antibacterial therapies. H. felis status was determined by bacterial culture, urease test, and bacterial and histologic stainings. Release of prostaglandin E₂ from the gastric mucosa was measured by radioimmunoassay. Results: All triple-treated mice were cleared of bacteria both 24 h and 1 month after treatment. However, tinidazole alone also resulted in 100% eradication. Monotherapies with erythromycin acistrate, tetracycline, colloidal bismuth subcitrate, and nitecapone failed to eradicate the bacteria. The release of gastric prostaglandin E₂ was doubled in the infected mice (554 ± 39, mean ± SE) compared with the noninfected mice (270 ± 35) (p < 0.01). Conclusions: The H. felis mouse model proved satisfactory for assessing both anti-Helicobacter therapies and the prostaglandin E₂ release. The reliability of this method was improved when several methods to assess the H. felis status were used in parallel.     

沙土鼠感染幽门螺杆菌后胃粘膜病理学改变的研究

目的和方法:应用HP标准菌株ATCC43504,增菌培养后接种于6周龄沙土鼠胃内。分别于2周、12周后杀死实验鼠。鼠胃经过福尔马林固定,石蜡切片,进行HP组化染色、AB/PAS染色及Brdu.PCNA免疫组化染色。结果:接种HP2周后,胃粘膜上皮细胞间有中性粒细胞、淋巴细胞浸润,上皮细胞及腺窝内可见大量HP存在,AB/PAS染色处见肥大细胞增多。Brdu.PCNA呈阳性表达,明显高于对照组。接种HP12周后,胃窦部出现溃疡(2/3),胃粘膜上皮细胞可见核分裂相及淋巴滤泡。结论:①接种HP2周后的沙土鼠胃粘膜呈急性炎症改变,HP定植于胃窦粘膜呈慢性炎症改变。提示沙土鼠是研究HP感染性胃病有价值的动物模型;②HP感染性胃粘膜Brdu.PCNA呈阳性高表达,表明HP感染过程中,伴有细胞部增值性变化。     

在猪动物模型中检测幽门螺杆菌（HP）感染方法评价

用“中国1号小型猪”经口感染HP30天后取食管、胃体、胃窦、十二指肠、小肠、大肠标本行尿素酶试验、W-S银染色、HP培养、HP-PCR等检查。在15只猪中除对照组2只外,其余13只均有HP感染,胃窦HP阳性率最高,为12/13,小肠HP阳性率最低,为0/13。尿素酶试验的敏感性、特异性为88.1％、85.7％;W-S银染色的敏感性、特异性为57.l％、100％;HP培养的敏感性、特异性为31.0％、100％;HP-PCR的敏感性、特异性为100％、83.3％。提示本实验所用检测HP感染方法,其敏感性和特异性可相互补充,应同时应用。取材部位对诊断猪HP感染影响较大,应多部位取材。     

Dietary Analysis in Symptomatic Patients with Coeliac Disease on a Gluten-Free Diet: the Role of Trace Amounts of Gluten and Non-Gluten Food Intolerances

Background: Whereas many people with coeliac disease (CD) are asymptomatic when consuming a gluten-free diet (GFD), a proportion continues to experience symptoms. The reasons for this are unclear. Methods: Thirty-nine adult members of The Coeliac Society of New South Wales, all of whom had persistent gastrointestinal symptoms despite adhering to a GFD, were evaluated. Dietary analysis indicated that 22 (56%) were consuming a GFD as defined by the WHO/FAO Codex Alimentarius (Codex-GFD), in which foods containing up to 0.3% of protein from gluten-containing grains can be labelled as `gluten free'. The remaining 17 were following a no detectable gluten diet (NDG)-GFD, as defined by Food Standards Australia. All subjects were required to follow a NDG-GFD during the study. Those in whom symptoms persisted after changing from a Codex-GFD and those who entered the study already on a NDG-GFD began an elimination diet followed by open and double-blind challenges to identify specific non-gluten food or food chemical intolerances. Results: Of 22 patients who switched to a NDG-GFD symptoms resolved in 5 (23%) and were reduced in 10 others (45%). Thirty-one subjects commenced the elimination diet. Symptomatic improvement was experienced in 24 (77%). Subsequent food or food chemical challenges resulted in a mean of five positive challenges per individual. Diarrhoea was the most commonly provoked symptom, followed by headache, nausea, and flatulence. Symptoms were especially provoked by amine, salicylate and soy. Conclusion: The consumption of trace amounts of gluten, traditionally allowed in a Codex-GFD, may be responsible for the continuing symptoms seen in some patients with CD. Further investigation for non-gluten food intolerances should follow if symptoms persist after adherence to a NDG-GFD.     

幽门螺杆菌诱导蒙古沙鼠胃上皮细胞凋亡可能涉及线粒体途径

目的建立幽门螺杆菌(Hp)感染蒙古沙鼠模型,探讨线粒体途径在Hp诱导胃上皮细胞凋亡中的作用。方法 48只雄性蒙古沙鼠均分为Hp感染组和对照组,每组分别于1、3和6个月3个时相点各处死8只动物,取胃黏膜行组织学检查:用Warthin-Starry银染、PCR和快速尿素酶法检测 Hp;通过H-E染色,光镜下观察胃黏膜病理变化;流式细胞仪测定细胞凋亡、线粒体膜电位及胞内游离 Ca2+含量。结果 Hp感染蒙古沙鼠后,胃黏膜出现慢性胃炎、肠化生及异型增生改变,而对照组胃黏膜基本正常,Hp感染组肠化生及异型增生发生率明显高于对照组(P<0．05)。Hp感染胃上皮细胞1、3、 6个月后的凋亡率分别为(16．71±3．30)％、(5．90±0．82)％、(5．69±0．70)％,而对照组的凋亡率分别为(4．20±0．94)％、(3．17±0．43)％、(4．70±0．55)％。其中Hp感染1个月后胃上皮细胞的凋亡率高于其他各组(P<0．05)。Hp感染胃上皮细胞1、3、6个月后的线粒体膜电位分别为43．10±17．62、 71．19±38．03、80．56±32．90,而对照组分别为84．70±23．50、84．39±37．51、79．54±30．24,其中Hp 感染1个月后胃上皮细胞的线粒体膜电位低于其他各组(P<0．05);Hp感染1、3、6个月后胃上皮细胞内游离Ca2+含量分别为18．60±9．32、5．18±2．06、4．94±3．25,而对照组分别为4．82±3．70、6．86 ±2．34、5．28±3．13,Hp感染1个月后胃上皮细胞内游离Ca2+含量高于其他各组(P<0．05)。结论 Hp诱导蒙古沙鼠胃上皮细胞凋亡主要发生在Hp感染早期;线粒体膜电位的下降和胞内游离Ca2+含量的升高参与了Hp诱发蒙古沙鼠胃上皮细胞凋亡的过程。     

幽门螺杆菌感染Balb/c 小鼠模型的建立及对N-甲基-N-亚硝基脲诱发胃癌的影响

目的建立一种稳定的造模周期短的幽门螺杆菌(Hp)感染模型,观察Hp对小鼠胃黏膜的损害程度,同时研究Hp感染是否促进亚硝基类化合物的致癌作用.方法 94只Balb/c小鼠分为4组.第1组单用N-甲基-N-亚硝基脲(MNU);第2、3组小鼠用灌胃法定植Hp,第3组小鼠加用MNU灌胃;第4组为正常对照.36周后处死全部小鼠,分别用尿素酶、Giemsa染色和微需氧细菌培养检测Hp定植;H-E染色进行鼠胃黏膜病理诊断.结果 Balb/c小鼠Hp定植率达93.9%.Hp单一处理组中度以上炎症占100.0%,其中萎缩性胃炎占20.0%;而Hp和MNU联合处理组中度以上炎症占100.0%,其中萎缩性胃炎占23.1%,不典型增生占42.3%和57.7%(胃体和胃窦),并发现2只小鼠有低分化腺癌,占7.1%.Hp处理组和Hp MNU联合处理组在炎症程度上与正常对照组相比,差异有统计学意义(P＜0.01).结论本实验成功建立了Hp感染小鼠模型,验证了Hp和胃癌的发生有高度相关性,证实Hp在协同MNU致癌性中的作用,提示胃癌的发生并非Hp感染单一因素的结果,而和多因素共同作用有关.     

长期饮酒合并幽门螺杆菌感染时胃黏膜损伤程度与EGF和PGE2的关系

目的探讨长期饮酒合并幽门螺杆菌感染时胃黏膜损伤的程度与胃液及血液中EGF及PGE2之间的关系。方法对2007年1月～2010年12月符合条件的长期饮酒合并幽门螺杆菌感染的56例患者进行内镜下胃黏膜活检组织的病理学观察,同时抽静脉血及胃液用ELISA法检测EGF及PGE2浓度。结果长期饮酒合并幽门螺杆菌感染胃黏膜中重度慢性炎症组患者血清和胃液EGF浓度明显高于轻度慢性炎症组患者血清和胃液EGF浓度(P=0.000;P=0.018);胃黏膜中重度萎缩组患者血清EGF浓度明显高于胃黏膜轻度萎缩组患者血清EGF浓度(P=0.000);胃黏膜中重度肠化组患者血清EGF浓度明显高于胃黏膜胃黏膜轻度肠化组患者血清EGF浓度(P=0.000),而胃黏膜中重度肠化组患者血清PGE2浓度明显降低(P=0.034);胃黏膜有不典型增生组患者血清和胃液中EGF浓度明显高于胃黏膜无不典型增生组患者血清和胃液中EGF浓度(P=0.000;P=0.044)。结论长期饮酒合并幽门螺杆菌感染引起血液中EGF升高与患者胃黏膜慢性炎症、萎缩和肠化加重及不典型增生的发生有关。而胃液中EGF浓度的升高仅与胃黏膜慢性炎症和不典型增生发生相关。在胃黏膜肠化患者中血清中PGE2明显降低。     

Resistance to metronidazole, clarithromycin and levofloxacin of Helicobacter pylori before and after clarithromycin-based therapy in Taiwan

Background and Aim:  Clarithromycin-based triple therapy has been commonly applied as the first-line therapy for Helicobacter pylori eradication. Levofloxacin could serve as an alternative in either first-line or second-line regimens. This study surveyed the prevalence of levofloxacin resistance of H. pylori isolates in naive patients and in patients with a failed clarithromycin-based triple therapy.
Methods:  The study collected the H. pylori isolates from 180 naive patients and 47 patients with a failed clarithromycin-based triple therapy. Their in vitro antimicrobial resistance was determined by E -test.
Results:  The naive H. pylori isolates had resistance rates for amoxicillin, levofloxacin, clarithromycin and metronidazole of 0%, 9.4%, 10.6% and 26.7%, respectively. An evolutional increase of the primary levofloxacin resistance was observed in isolates collected after 2004, as compared to isolates collected before 2004 (16.3% vs 3.2%, P  = 0.003). There was no evolutional increment of the primary clarithromycin resistance. The clarithromycin resistance elevated significantly after a failed clarithromycin-based triple therapy (78.7% vs 10.6%, P  < 0.001). The post-treatment isolates remained to have a levofloxacin resistance rate of near 17%, but the levofloxacin-resistant isolates were correlated with a higher incidence of metronidazole resistance ( P  = 0.023). No strain was found to be resistant to amoxicillin even after eradication failure.
Conclusion:  The levofloxacin resistance of naive H. pylori remains less than 10% in Taiwan. With relatively lower resistance to levofloxacin than to metronidazole of the H. pylori isolates collected after a failed clarithromycin-based therapy, proton pump inhibitor–levofloxacin–amoxicillin may be an alternative choice to serve as the second-line therapy.     

Effect of the mucolytic erdosteine on the success rate of PPI-based first-line triple therapy for Helicobacter pylori eradication: a prospective,double-blind,randomized, placebo-controlled study

Abstract

Objective. Because Helicobacter pylori creates a well-sheltered microenvironment within the gastric mucus layer, it has been speculated that the disruption of this space by a mucolytic agent may enhance the eradication rate. The aim of the present study was to investigate the effect of erdosteine, a strong mucolytic agent, on the effectiveness of PPI-based, first-line triple therapy in the eradication of H. pylori. Material and methods. Initially, 196 patients were enrolled to the study. Of these, 79 H. pylori-positive patients were randomized to the erdosteine group (triple therapy consisting of pantoprazole, amoxicillin and clarithromycin plus erdosteine; n = 40) or the placebo group (triple therapy plus placebo; n = 39) for 14 days. Endoscopic biopsies and ¹³C-urea breath tests were performed at entry and at 4–6 weeks after the completion of the treatment. Additionally, rapid urease tests were performed at entry. Results. The eradication of H. pylori was achieved in 30 (75%) of the 40 patients in the erdosteine group and in 20 (51.3%) of the 39 patients in the placebo group, according to the ITT analysis (p = 0.028). When the PP analysis was performed as well, H. pylori eradication was achieved in 30 (78.9%) of the 38 patients in the erdosteine group and in 20 (52.6%) of the 38 patients in the placebo group (p = 0.016). Conclusions. Erdosteine is an efficient adjuvant therapy that could be used in conjunction with first-line triple therapy in the treatment of H. pylori.     

三联疗法与序贯疗法在长期服用非甾体类抗炎药人群中根除幽门螺杆菌的疗效观察

目的 探讨长期服用非甾体类抗炎药(NSAID)的患者采用三联疗法与序贯疗法根除Hp的疗效.方法 以长期服用NSAID的患者为研究对象.将确诊的Hp感染者分为三联根除组和序贯根除组.三联根除组予埃索美拉唑+克拉霉素+阿莫西林治疗10 d;序贯根除组前5d予埃索美拉唑+阿莫西林,后5d予埃索美拉唑+克拉霉素+甲硝唑治疗.根除治疗结束后所有患者均予黏膜保护剂维持治疗,随访12周.随访前后行胃镜检查并检测Hp.对Hp根除率进行意向性分析和符合方案分析比较.结果 意向性分析显示,三联根除组和序贯根除组的Hp根除率分别为78.4％(40/51)和80.0％(40/50),两组差异无统计学意义(x2=0.038,P=0.846).符合方案分析显示,三联根除组和序贯根除组的Hp根除率分别为84.4％(38/45)和87.0％(40/46),两组差异无统计学意义(x2=0.117,P=0.732).结论 长期服用NSAID的患者采用三联疗法与序贯疗法根除Hp的疗效无显著差异.     

幽门螺杆菌长期感染蒙古沙土鼠建立胃癌模型的研究

目的：幽门螺杆菌（Hp）长期感染蒙古沙土鼠（MGs)发生胃癌鲜见报道。本实验旨在研究Hp长期定植于MGs导致胃黏膜病变及其致癌性。方法：36只交封闭MGs（雌雄各半）分别接种Hp标准株ATCC43504，或从胃癌患者胃内分离的Hp161株，10只MGs作为对照，接种后第8、20、28和84周分别处死，检查细菌定植及胃黏膜病变情况。结果：绝大多数MGs胃内Hp持续定植，胃黏膜炎症随时间逐渐加重，第84周组织学特征是胃黏膜中－重度胃炎，以淋巴细胞为主的单核细胞弥漫性浸润，黏膜，黏膜下，甚至浆膜下有大量淋巴滤泡浸润，偶见淋巴上皮病变，萎缩，肠化较少见，上皮增生明显，24％（4／17）发生增生性息肉，第84周时18％（3／17）发生高分化腺癌（Hp161组1例，ATCC43504组2例；1雄2雌），结论：单独感染Hp能诱导MGs发生胃癌，并提示可利用不同种属的MGs和不同Hp菌株进行相关研究，首次报道了雌性MGs感染也可发生胃癌。     

Gastric expression of inducible nitric oxide synthase and myeloperoxidase in relation to nitrotyrosine in Helicobacter pylori-infected Mongolian gerbils

Objective. For obscure reasons Helicobacter pylori infection of the gastric mucosa is maintained despite a pronounced host defence response. The present study elucidates possible H. pylori-related interference in the oxy- and nitro-radical formation pathways. Material and methods. Male Mongolian gerbils were infected with two different H. pylori strains, TN2GF4 and SS1. At 3, 6, 12 or 18 months after inoculation, gastric expressions of myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and nitrotyrosine were assessed by Western blotting. Results. Expression of both iNOS and MPO was markedly up-regulated in the H. pylori-infected animals compared with non-infected controls. The TN2GF4-infected animals initially (at 3 and 6 months) demonstrated pronounced expression of both iNOS and MPO. The SSI-infected animals exhibited a slower onset with significantly increased iNOS after 12 and 18 months. Nitrotyrosine expression was slightly elevated in the infected groups at 3 and 6 months compared with that in the controls. Nitrotyrosine levels then decreased and were no longer significantly different from those of controls (TN2GF4-infected animals) or were lower (SS1-infected animals) than in the controls. Conclusions. The results indicate that peroxynitrite formation as reflected by nitrotyrosine expression is low or even inhibited in chronic H. pylori infection despite pronounced expression of enzymes representing both the oxy- and nitro-radical formation pathways. The results support the theory that H. pylori survival is related to functional inhibition of mucosal enzymatic NO and/or oxy-radical formation.     

Recent trends in the antibiotic resistance of Helicobacter pylori in patient with dyspepsia

The aim of this study was to determine the resistance status and to identify the point mutations conferring resistance to clarithromycin and fluoroquinolones among dyspeptic patients in Manisa, Turkey.The study included a sample of 140 patients with an indication for upper gastrointestinal endoscopy randomly selected from 2100 dyspeptic patients attending to the Gastroenterology and Endoscopy Unit at Manisa Celal Bayar University Hafsa Sultan Hospital between April 2016 and May 2018. A commercially available GenoType Helico DR test was used to detect the presence of Helicobacter pylori and mutations associated with resistance to clarithromycin and fluoroquinolones in biopsy specimens.In total, 116 (82.9%) of 140 biopsies obtained from the same number of dyspeptic patients were positive for H pylori and 82 (approximately 71%) of them harbored resistance mutations in 23SrRNA and/or gyrA. Resistance to clarithromycin, levofloxacin, or both were detected in 43.1% (50/116), 27.6% (32/116), and 16/116 (13.8%) of tested biopsies, respectively. The most common mutation conferring resistance to clarithromycin was A2147G (96%, 48/50). Resistance to fluoroquinolones was frequently due to mutation in codon 91 and the most common mutation detected was D91G (34.4%). Heteroresistance patterns were observed in 48.0% (24/50) of clarithromycin-resistant samples and 28.1% (9/32) of levofloxacin-resistant samples.The resistance rates and detected mutations in this study are in line with the country data. However, to achieve better H pylori eradication and to prevent the spread of multidrug-resistant strains in Turkey, the molecular-based susceptibility tests should be considered routinely. Further studies are needed to determine the various mutations among resistant strains.     

Mucosal pharmacokinetics and pilot study of short course of parenteral imipenem in the eradication of Helicobacter pylori

Abstract Eradication of Helicobacter pylori infection is known to reduce the incidence of duodenal ulcer recurrence. The most commonly used regimen for H. pylori infection is triple antimicrobial therapy for 1-2 weeks. This treatment is associated with frequent side effects and hence unsatisfactory compliance. As in vitro data showed that H. pylori is sensitive to imipenem, the pharmacokinetics of this drug in the gastric milieu, and the clinical efficacy of imipenem with omeprazole in eradicating H. pylori infection were studied. Imipenem/cilastatin levels in serum, gastric secretion and gastric mucosa were assayed in four patients after intravenous injection of a bolus dose of 500 mg. The serum and gastric secretion levels of imipenem achieved were more than 10 times the minimum inhibitory concentration of the drug for H. pylori. Gastric mucosal levels of imipenem vary considerably with time, which probably indicates rapid elimination of the drug into the gastric lumen. In the second part of this study, imipenem/cilastatin was given intravenously for the first 2 days after diagnosis of H. pylori infection in patients with endoscopically confirmed duodenal ulcers. The patients were also treated with 4 weeks of omeprazole. Clearance of H. pylori was initially achieved at the end of 2 days in 20 out of 22 (91%) patients. However, when the biopsies were repeated at 8 weeks, recurrence of H. pylori infection was evident in 19 cases (86.3%) indicating a failure of eradication. It was concluded that imipenem/cilastatin in combination with omeprazole failed to eradicate H. pylori infection.     

Analysis of genetic variability,antimicrobial susceptibility and virulence markers in Helicobacter pylori identified in Central Italy

Objective. To assess the relationship between the presence of mixed infection of Helicobacter pylori and both antimicrobial susceptibility and virulence markers. Material and methods. Thirty-six patients with H. pylori infection were included in the study. Three colonies were selected from each positive biopsy sample collected from each host for a total of 108 H. pylori strains. The genetic variability was evaluated through the amplified fragment length polymorphism (AFLP) analysis; the antibiotic susceptibility to amoxicillin, clarithromycin, moxifloxacin, rifabutin and tinidazole was determined using the minimum inhibitory concentrations (MICs) with the agar dilution method. Moreover, the vacA, cagA, iceA and babA2 statuse were detected by polymerase chain reaction (PCR). Results. There was a strong connection between mixed H. pylori infection and antimicrobial resistance. In particular, H. pylori strains with genetic variability, in the same host, expressed more resistance to clarithromycin, moxifloxacin and tinidazole than that expressed in strains with a unique genetic host pattern. VacA s1m1/s1m2 genotypes were found in 70% of strains isolated in mixed infection, whereas the same allelic combinations were found in 42% of strains, isolated in single infection. The cagA⁺ status prevailed both in patients with mixed (97%) and in those with single infection (85%) without significant differences. The iceA1 status was more commonly found in patients with mixed infection, whereas the babA2 status was significantly prevalent in single H. pylori infection. Conclusions. Mixed H. pylori infection harbouring in one patient is significantly related to strains that are more resistant to antibiotics and with a more virulent genotype (vacA s1m1/s1m2, cagA, iceA1) than strains responsible for single infection.     

Comparison of three different second-line quadruple therapies including bismuth subcitrate in Turkish patients with non-ulcer dyspepsia who failed to eradicate Helicobacter pylori with a 14-day standard first-line therapy

Background and Aim: Many studies have reported poor results with standard first‐line treatment for Helicobacter pylori. Second‐line regimens that may overcome bacterial resistance can minimize side‐effects and optimize compliance. The aim of this study was to evaluate the efficacy of proton pump inhibitor (PPI) and bismuth subcitrate‐based quadruple therapy, after failure of a PPI plus clarithromycin and amoxicillin as first‐line therapy. Methods: Patients who failed to eradicate the infection after initial therapy were randomly separated into three groups. The first group received lansoprazole, bismuth subcitrate, metronidazole and amoxicillin (LBMA); in the second group metronidazole was replaced by tetracycline (LBTA); and the third group was given metronidazole and tetracycline in addition to same doses of lansoprazole and bismuth subcitrate (LBMT). Results: In the LBMA group, the eradication rate was 74.7% and was significantly related to sex, with no relationship to age. In the LBTA group the eradication rate was 81.5% with similar rates in males and females. No relation to sex or age was observed. In the LBMT group the eradication rate was 82.1% with no difference between women and men and it was not related to age, either. Eradication rates in study groups were similar (P > 0.05). Conclusion: A‐14‐day regimen of lansoprazole, bismuth subcitrate and antibiotic pairs, tetracycline–amoxicillin and tetracycline–metronidazole, is an effective quadruple therapy after one failed course of standard triple therapy. The evaluation of tolerability of and compliance with quadruple therapy needs further studies.     

四联疗法根治幽门螺旋杆菌感染疗效分析

目的探讨四联疗法治疗幽门螺杆菌(Hp)所致消化性溃疡和胃炎的疗效。方法将317例消化性溃疡和慢性萎缩性胃炎患者随机分为标准三联疗法组、四联7d组和四联10d组。四联疗法组采用左氧氟沙星+阿莫西林+奥美拉唑+枸橼酸铋钾胶囊,治疗周期分别为7d和10d。三联疗法采用奥美拉唑+克拉霉素+阿莫西林,治疗周期14d。结果采用PP分析法计算Hp根除率三联疗法组为78.43%,四联7d组为85.71%,四联10d组为91.00%,差异有统计学意义(P<0.05);采用ITT分析法计算3组的Hp根除率分别为76.19%、83.33%和87.50%,差异无统计学意义(P>0.05);总有效率分别为81.37%、85.71%和89.00%,差异无统计学意义(P>0.05)。三联疗法、四联7d组和四联10d组的成本-效果比分别为4.12、2.58、3.47,四联7d组与四联10d组相对于标准三联组的增量成本-效果比值分别为-14.11和-0.64。结论四联7d及10d方案均具有较高的Hp根除率,两种方案均为安全、有效、经济的一线治疗方案,符合我国国情,值得临床推广。     

Gastrin release and gastric acid secretion in the rat infected with either Helicobacter felis or Helicobacter heilmannii

Helicobacter pylori infection in humans has been shown to be associated with changes in gastric physiology, including exaggerated basal and meal-stimulated gastrin levels. This has been suggested to be due to the direct effects of the bacterium through inflammation and its urease enzyme. The gastric bacteria Helicobacter felis and Helicobacter heilmannii colonize the antrum of rats in large numbers and induce no significant inflammatory response. Thus, the direct effect of Helicobacter infection on gastric physiology, independent of gastritis, could be studied. Basal, freely fed and stimulated acid and gastrin levels were recorded from animals infected with H. felis, H. heilmannii or uninfected controls over a 30 week period. No significant difference was found between freely fed gastrin over 7 weeks or fasting gastrin over 24 weeks or basal and stimulated acid over 30 weeks between all three groups. Triple therapy did not alter gastrin or acid output. The antrum of all Helicobacter-infected rats was well colonized; triple therapy cleared H. felis but not H. heilmannii. Very little inflammation was seen in control or Helicobacter-infected animals. In conclusion, Helicobacter-induced effects on gastric physiology are unlikely to be due to direct bacterial effects, but are best explained by other factors (i.e. inflammatory damage).     

治疗的依从性、年龄、性别对胃溃疡患者使用三联7天疗法根除幽门螺杆菌治疗的影响

目的研究胃溃疡患者使用三联7天疗法治疗幽门螺杆菌（Helicobacter pylori,H.pylori）感染的根除率,评估患者依从性、年龄、性别对于此类人群根除H.pylori治疗的影响。方法将经胃镜检查确诊为新发胃溃疡,并经活组织病理学检查明确有H.py-lori感染的1 075例患者纳入研究范围,所有入选患者均接受三联（洛赛克或耐信20 mg/次、2次/天,联合克拉霉素500 mg/次、2次/天,与阿莫西林1 000 mg/次、2次/天）7天疗法行根除H.pylori治疗,之后予以耐信或洛赛克20 mg/次、1次/天、治疗49天。所有入选患者系统治疗完成后6-8周复查胃镜。结果40-59岁与60岁以上人群的胃溃疡患者对治疗的依从性差异无显著性,而40岁以下人群对治疗的依从性较差（P〈0.05）。〈40岁、40-59岁和≥60岁胃溃疡患者的H.pylori根除率分别为61.0%、72.7%和81.9%。〈40岁与40-59岁和≥60岁患者的H.pylori根除率差异有统计学意义（P〈0.05）。不同性别胃溃疡患者的H.pylori根除率差异无显著性（P〉0.05）。结论使用三联7天疗法治疗胃溃疡患者的H.pylori感染,H.pylori的根除率较低,患者对治疗的依从性、年龄是影响胃溃疡患者H.pylori根除率的重要因素,而性别对此无影响。