Quadruple Group Research Articles

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

This study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian gerbils infected with H. pylori received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of H. pylori. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (P = 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in H. pylori eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on H. pylori collectively. Thus, pronase may enhance the level of antibiotics for eradication of H. pylori in the clinic.

Efficacy of triple versus quadruple furazolidone-based eradication regimens for Helicobacter pylori infection

To explore the eradication efficacies of triple versus quadruple furazolidone-based regimens for Helicobacter pylori (H. pylori) infection. A total of 357 outpatients with H. pylori infection were enrolled from June to December 2010. There were 200 males and 157 females with an average age of (42 ± 12) years. A diagnosis of duodenal ulcer was made according to their endoscopic examination results. They were randomly assigned into 4 treatment groups: 7-day triple (n = 89) and 10-day triple (n = 91), rabeprazole 10 mg, amoxicillin 1 000 mg and furazolidone 100 mg twice daily for 7 and 10 days respectively. 7-day quadruple (n = 88) and 10-day quadruple (n = 89), rabeprazole 10 mg, bismuth 220 mg, amoxicillin 1 000 mg and furazolidone 100 mg twice daily for 7 and 10 days respectively.H. pylori status was re-assessed with (14)C-urea breath test after 4-week therapy. Among them, 323 cases completed the study. According to the analysis of intention-to-treat (ITT), the H. pylori eradication rates were 71.91% (64/89) in 7-day triple, 81.32% (74/91) in 10-day triple, 78.41% (69/88) in 7-day quadruple and 83.15% (74/89) in 10-day quadruple groups. No significant deviation existed among all groups (P > 0.05). According the per-protocol (PP) analysis, H. pylori eradication rates were 78.05% (64/82) in 7-day triple, 88.10% (74/84) in 10-day triple, 87.34% (69/79) in 7-day quadruple and 94.87% (74/78) in 10-day quadruple groups. Significant deviation existed among all groups (P = 0.017). The H. pylori eradication rate in 10-day quadruple group was significantly higher than that in 7-day triple group (P = 0.002). The total adverse reaction rate was 7.00% (25/357). No significant difference existed among all groups (P > 0.05). Quadruple treatments provide higher H. pylori eradication rates than triple therapies. A 10-day treatment may improve H. pylori eradication rate. And 10-day quadruple regimen with furazolidone and bismuth may be effective for H. pylori infection.

The Effect of Concomittent Therarpy and Quadruple Therapy for Patients Who Had 23S Ribosomal Ribonucleic Acid MutatedHelicobacter pyloriin Daegu and Kyoungpook Area

Background/Aims: Proton pump inhibitor (PPI) and two types of antimicrobial agents, amoxicillin, and clarithromycin have been widely used for the eradication of Helicobacter pylori. However, antibiotic resistant strains has rapidly increased and has emerged as an important factor for eraducation failure. Materials and Methods: Patients diagnosed with chronic gastritis, peptic ulcer disease or gastric epithelial neoplasm was examined by H. pylori PCR for mutation at 23S rRNA. Positive H. pylori PCR without 23S rRNA mutation was eradicated by standard triple therapy. Patients with 23S rRNA mutation was eradicated by standard triple therapy or concomittent therapy with amoxicillin, PPI, clarithromycin and metronidazol or quadruple therapy with bismuth, PPI, tetracycline and metronidazol. We evaluated the predictors of eradication failure with regards to 23S rRNA mutation and initial eradication regimen. Results: Nine hundred sixty-one patients were studied. H. pylori PCR was positive in 35.0% of the patients and 23S rRNA mutatation was found in 22.2% of the patients. The eradication rate of H. pylori for the A2143G point mutated group with standard triple therapy was 28.5% and significantly lower than 93.1% of the wild type group and 100% of the concomitant therapy group, 66.6% of one week quadruple group and 100% of two week quadruple group (P＜0.005). Conclusions: When 23S rRNA point mutation was positive, the standard triple therapy was not effective and the eradication rates was only 22.2%. Alternative regimens should be considered when 23S rRNA point mutation is detected, especially when A2143G point mutation is detected because A2143G point mutation is highly related to eradication failure. (Korean J Helicobacter Up Gastrointest Res 2014;14:249-254)

Efficacy of furazolidone-based quadruple therapy as rescue treatment for refractory Helicobacter pylori infection

To evaluate the efficacy and tolerability of a furazolidone-based quadruple rescue regimen in patients with previously failed Helicobacter pylori (H.pylori) eradication treatment. A total of 156 patients were recruited from July 2011 to June 2013 at Beijing Hospital and randomized into one of the following 10-day treatment regimens: (1) Esomeprazole 20 mg twice daily, furazolidone 100 mg twice daily, amoxicillin 1000 mg twice daily, bismuth salts 150 mg thrice daily for 10 days. (2) Esomeprazole 20 mg twice daily, levofloxacin 500 mg daily, amoxicillin 1000 mg twice daily, bismuth salts 150 mg thrice daily for 10 days. H.pylori status was re-assessed with the (13)C-urea breath test at 4 weeks after the end of therapy. The intention-to-treat (ITT) and per-protocol (PP) H.pylori eradication rates were 83.8% (67/80) and 88.2% (67/76) in the furazolidone-based quadruple group, and 69.7% (53/76) and 73.6% (53/72) in the levofloxacin-based quadruple group respectively (χ(2) = 4.311, 5.100; P = 0.038, 0.024). The 10-day furazolidone-based quadruple therapy is an efficacious rescue strategy in patients with previously failed eradication therapy.

Sequential Therapy vs Quadruple Therapy for Helicobacter pylori Eradication in South West of Iran.

ABSTRACTAim To compare the efficacy of quadruple and sequential therapy in eradication of Helicobocter pylori (H. pylori) in a randomized study.Method Three hundred H. pylori positive patients were enrolled into the study. These patients were randomly divided into two groups: group I (n = 150) received quadruple therapy (20 mg omeprazole bid, 240 mg bismuth subcitrate bid, 1,000 mg tetracycline bid and 500 mg metronidazole bid) for 14 days, group II (n = 150) received sequential therapy (20 mg omeprazole bid, 1,000 mg amoxicillin bid for 5 days, followed by 20 mg omeprazole bid, 500 mg metronidazole bid, 500 mg clarithromycin for the other 5 days). H. pylori status was assessed by histology and rapid urease test at baseline. Follow-up breath test by 14C urea breath test (UBT) was performed 4 weeks after completion of treatment. Eradication was defined as negative results on UBT.Results Successful eradication was achieved in 245 patients. In each group, five patients did not tolerate the regimen and were excluded from analysis. About 29 (20%) patients who received sequential therapy and 21 (14.5%) of the quadruple group tolerated mild side effects (p = 0.21).Per-protocol analysis demonstrated eradication rates of 86.9% for sequential therapy and 82.7% for quadruple therapy (p = 0.26). Results according to the intention to treat analysis were 84 and 79.5% in the sequential and quadruple group respectively. Eradication rate differences were not significant.Conclusion The success rate of sequential therapy is comparable with quadruple therapy. Sequential therapy due to the short duration and lesser drug usage is a good alternative for eradication of H. pylori in the country.How to cite this article: Masjedizadeh AR, Hajiani E, Hashemi SJ, Alavinejad P, Dalvand H. Sequential Therapy vi Quadruple Therapy for Helicobocter pylori Eradication in South West of Iran. Euroasian J Hepato-Gastroenterol 2014;4(2):63-66.

Levofloxacin, Metronidazole, and Lansoprazole Triple Therapy Compared to Quadruple Therapy as a Second-Line Treatment ofHelicobacter pyloriInfection in Korea

Background/AimsSeveral rescue therapies have been recommended to eradicate Helicobacter pylori infection in patients with a failure of first-line eradication therapy, but they still fail in more than 20% of cases. The aim of this study was to evaluate the efficacy and safety of levofloxacin, metronidazole, and lansoprazole (LML) triple therapy relative to quadruple therapy as a second-line treatment.MethodsIn total, 113 patients who failed first-line triple therapy for H. pylori infection were randomly assigned to two groups: LML for 7 days and tetracycline, bismuth subcitrate, metronidazole and lansoprazole (quadruple) for 7 days.ResultsAccording to intention-to-treat analysis, the infection was eradicated in 38 of 56 patients (67.9%) in the LML group and 48 of 57 (84.2%) in the quadruple group (p=0.042). Per-protocol analysis showed successful eradication in 38 of 52 patients (73.1%) from the LML group and 48 of 52 (92.3%) from the quadruple group (p=0.010). There were no significant differences in the adverse effects in either treatment group.ConclusionsLML therapy is less effective than quadruple therapy as a second-line treatment for H. pylori infection. Therefore, quadruple therapy should be considered as the primary second-line strategy for patients experiencing a failure of first-line H. pylori therapy in Korea.

Sa1922 Superiority of Acid Suppression for Esomeprazole-Based Helicobacter pylori Eradication Therapy in Japanese CYP2C19 Rapid Metabolizers

Background/Aims: The increasing trend of antibiotic resistance requires effective secondline Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori that would determine the effect of the eradication therapy in long-term follow up period after second-line treatment. Methods: During 2003-2011, 898 patients who had failed previous H. pylori eradication on standard triple therapy were treated with either of two regimens: 1, esomeprazole (20 mg b.i.d), tripotassum dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (40 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, follow-up H. pylori tests were performed with 13C urea breath test or invasive tests (Giemsa histology, CLO test, and culture). In patients who were maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. Results: Mean follow-up periods were 34.1 months and 35.6 months in the quadruple therapy group (n = 65) and moxifloxacin group (n = 177), respectively. H. pylori reappeared in 9 (13.8%) of EBMT and in 31 (17.5%) of MEA, resulting in the annual reinfection rate of 4.88% and 3.13% per year, respectively (P = 0.496). In addition, recrudescence rate of EBMT and MEA group was found to be 1.52% and 3.28% (MEA), respectively (P = 0.679). Multivariate analysis showed that there was no association with any clinical risk factor for H. pylori reinfection. Conclusion: This long-term reinfection rate of H. pylori stayed rather low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy, thus reinfection cannot affect the choice of second-line treatment.

Prediction of tensile capacity of adhesive anchors including edge and group effects using neural networks

AbstractAdhesive anchors are widely used in seismic strengthening applications to add new structural members or sections to existing concrete members due to their high tensile and compressive strengths, low cost, and easy and fast installation. To safely design such anchors, it is very important to know their pullout capacity under axial tensile forces. This paper explores the pullout capacity of both single and groups of adhesive anchors loaded in tension in uncracked concrete. Quadruple anchor groups were considered for group effect. To this end, 142 single anchor tests including edge effect (located near a concrete edge) and 175 quadruple group anchor tests (totally 317 tests) were obtained from literature. The formulated three-layered artificial neural network method (ANN) was trained using 75% of the data set by using different learning algorithms. The methods were tested with the remaining 25%. The variables taken into account in this study are anchor diameter, embedment length, concrete compressive strength, concrete body height, edge distance (for single anchors), and anchor spacing (for group anchors). It was determined that experimental data can be estimated to a notably close extent via the ANN model.

Efficacy of bismuth-based quadruple therapy as first-line treatment for Helicobacter pylori infection

To evaluate the efficacy of bismuth-based quadruple therapy as the first-line treatment for H.pylori infection. A total of 136 patients with H.pylori related peptic ulcer or chronic gastritis were randomized into two groups: 67 patients in bismuth-based quadruple group received esomeprazole 20 mg, clarithromycin 0.5 g,amoxicillin 1.0 g,and bismuth potassium citrate 220 mg for 7 d; 69 patients in standard triple group received esomeprazole 20 mg, clarithromycin 0.5 g and amoxicillin 1.0 g for 7 d. Outcome of eradication therapy was assessed by (14)C-UBT. On ITT and PP analysis, calculating the cost-effectiveness ratio (C/E) and the incremental cost-effectiveness ratio (delta C/delta E). On ITT and PP analysis, the eradication rates of the quadruple therapy group were 82.09% and 88.71%, and those of the triple therapy group were 66.67% and 73.02% (P<0.05). The cost-effectiveness ratio of two groups was 4.15 and 4.82; The incremental cost-effectiveness ratio of quadruple therapy group was 1.02 as against triple therapy group. Compared to the standard triple therapy regimen, the bismuth-containing quadruple therapy regimen has higher eradication rate and cost-effectiveness, which can be recommended as the fist-line treatment for H.pylori infection.

Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second‐line treatment of resistant Helicobacter pylori infection

To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by (13)C-urea breath test. Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P=0.34). Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains.

Quadruple Therapy with CsA, MTX, MMF and ATG and Triple Therapy with CsA, MTX and ATG for Preventing Graft-Versus-Host Disease in Unrelated Donor Hematopoietic Stem Cell Transplantation.

Objective To explore the effective protocol for graft-versus-host disease (GVHD) prophylaxis in unrelated donor hematopoietic stem cell transplantation (URD-HSCT).Methods 31 patients with leukemia received URD-HSCT, of whom 16 received quadruple therapy (quadruple group) with CsA, MTX, MMF and ATG for GVHD prophylaxis and 15 received triple therapy (triple group) with CsA, MTX and ATG. 22 patients were matched in all HLA genetic loci with donors, seven were mismatched in one HLA genetic locus, 1 in two HLA genetic loci, and 1 in three HLA genetic loci. Total body irradiation (TBI) plus cyclophosphamide (CTX) was adopted in 17 cases and modified BuCY conditioning regimen (hydroxyurea, busulfan, Ara-C, Cyclophosphamide) in the other 14 cases. Immune reconstitution of quadruple group and triple group at 1,3, 6, 9,12 month after transplantation were examined by flow cytometer, and the diference of the two group were estimated with Independent-Samples T test. The incidence of GVHD of the two group was esitimated with Mann-Whitney Test. Kaplan-Meier survival analysis model was used to estimate the overall survival and the disease-free survival (DFS).Results Immune reconstitution after transplantation of quadruple group and triple group have no significant difference (P>0.05). Acute GVHD (aGVHD) occurred in 9 patients (56.25%) of the quadruple group and in 11 (73.33%) of the triple group, respectively. The incidence of acute GVHD (aGVHD) differed little between the two group (P=0.238). The incidence ofIII~IV°aGVHD in the two group were 6.30% and 26.67%, respectively, and there was no significant difference (P=0.122). 6 patients had chronic GVHD (cGVHD), in the16 cases who could be followed up in quadruple group, 3 of the 11 patients who could be followed up in triple group developed cGVHD postoperatively (P=0.580). Four patients of quadruple group died of hemorrhagic cystitis, mycotic pneumonia, tuberculosis and relapse, respectively. 3 patients of triple group died of GVHD, and the other 3 died of GVHD associated interstitial pneumonia, cytomegalovirus (CMV) pneumonia and pneumocystis carinii infection. The lethality of GVHD of quadruple group and triple group were 0%,26.7%, respectively, and there was significant difference(P=0.027). The one-year disease-free survival rate was 75% and 60% in patients of the quadruple and the triple group, respectively, and significant difference was not noted (P= P=0.188).Conclusion Compared with triple therapy with CsA, MTX and ATG, CsA+MTX+MMF+ATG procedure dose not worsen the immune reconsititution after transplantation. It can't decrease the incidence and severity of aGVHD, but can lower the lethality of GVHD in URD-HSCT. The quadruple procedure may lead to higher relapse rate after URD-HSCT.

Quadruple therapy with lactoferrin for Helicobacter pylori eradication: A randomised, multicentre study

Background. Helicobacter pylori eradication rate with standard triple therapies is decreasing. Recently, lactoferrin administration has been shown to significantly increase the cure rate of 7-day rabeprazole, clarithromycin and tinidazole triple therapy. We assessed whether lactoferrin also increases the eradication rate of 7-day esomeprazole, clarithromycin and amoxycillin triple therapy as first-line treatment. Methods. Overall, 133 consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomised to receive either a standard 7-day triple therapy with esomeprazole 20 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxycillin 1 g b.i.d. (68 patients) or a quadruple therapy comprising of the same regimen plus lactoferrin 200 mg b.i.d. (65 patients). H. pylori at entry was assessed by endoscopy, while bacterial eradication was checked by 13C urea breath test 4–6 weeks after treatment. Results. H. pylori eradication following standard triple therapy was achieved in 53/68 (77.9%; 95% CI = 68–88) and in 53/66 (80.3%; 95% CI = 71–89) patients at ITT and PP analyses, respectively. Following the quadruple regimen, the infection was cured in 50/65 (76.9%; 95% CI = 67–87) and 50/64 (78.1%; 95% CI = 68–88) patients at ITT and PP analyses, respectively. No statistically significant difference emerged between the two therapeutic regimens, both at ITT ( p = 0.9) and PP analyses ( p = 0.9). Side effects were complained by seven (10.3%) patients and six (9.2%) patients following the triple and quadruple regimens, respectively ( p = 0.9), with only one patient in the quadruple group interrupting the treatment due to side effects. Conclusions. Quadruple therapy with lactoferrin did not significantly increase the H. pylori cure rate of standard 7-day clarithromycin–amoxycillin based triple therapy in non-ulcer dyspepsia patients.

Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study

Various immunosuppressive regimens aim to reduce the incidence of acute rejection after liver transplantation. The efficacy of antithymocyte globulin (ATG) induction therapy and short-term effects on the cellular response have been demonstrated in several studies. Nevertheless, information about long-term effects of ATG therapy on cellular responses and frequency of complications is limited. Therefore, we analyzed the effect of ATG administration within a cyclosporine-based induction therapy, including azathioprine and prednisolone, on lymphocyte subsets and activation markers. We divided 35 liver transplant recipients into two groups according to their initial postoperative immunosuppression: a triple group without ( n=15) and a quadruple group with ATG ( n=20). The minimum observation time (flow cytometry analysis, clinical follow-up) was 2 years. Patients treated with ATG had persistently lower percentages of T cells for at least 2 years postoperatively ( P<0.001). The CD4/CD8 ratios were lower in the quadruple group ( P<0.005). The patients in the ATG group revealed a drop in CD25(+) T cells within 2 years ( P<0.05). However, the percentage of CD71(+) and HLA-DR(+) T cells was temporarily higher in patients with ATG treatment ( P<0.05). Patients with ATG treatment showed persistently higher levels of CD8(+)/CD57(+) double positive cells in the late postoperative phase ( P<0.05). In contrast, no differences could be observed between the two groups for major parameters of clinical outcome (acute rejections, severe infections, patient survival). We conclude that ATG therapy induces long-lasting alterations in T-cell subset composition. However, no beneficial clinical effect could be confirmed after liver transplantation.

Studies on the structure of hair-forming groups in Finnsheep

Recognition of hair-forming groups in the skin of sheep was dealt with by many scientists on almost all breeds of sheep in the world and in some particular countries. To the few breeds not yet investigated up to now in this respect belongs Finnsheep (F), and this substantiates the present attempt. The histological analysis was performed on skin sections taken by the biopsy method from 7 F of the Experiment Station Koluda Wielka. Upon fixing and staining skin preparations by the method generally applied, the microscopic examination of kinds of groups, number of primary (P) and secondary(S) follicles per 1 mm2 (nS/mm2 +nP/mm2) in all kinds of groups as well as density of follicles, i.e.nS/nP per 1 mm2, was carried out. In microscopic pictures of skin, documented by means of photographs, superiority of triple groups, the share of which amounted to 74.2 %, has been found. The share of quadruple groups was 11.4 %, of double groups 8.6 % and of hexal groups 5.1 %. The mean density of follicles, measured by the number of primary and secondary follicles per 1mm2 of skin, amounts to 14.1, which results from the share of 2.0 primary + 12.2 secondary follicles per 1 mm2. The value of the nS/nP ratio in particular groups was as follows: the highest ratio was for the triple group (6.0), in the double group it amounted to 5.8, in quadruple group to 5.6 and in the hexal group to 5.3. Thus, the mean density for this sheep breed amounts to 5.84. Differences in the above values between singles and groups appeared to be small and not proved statistically. The obtained results concerning the studied F skin traits are characteristics for the hair cover of longwoolled type.