Biomedical subjects

T Lind

Publications and source records attributed to T Lind.

At least 37 records · Page 2Linked to original sources

PubMed2001

Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastro-oesophageal reflux disease: a controlled trial of 'on-demand' therapy for 6 months.

BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.

Administration, Oral↗

PubMed2001

Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis.

BACKGROUND: Esomeprazole is a new proton pump inhibitor, which has been compared to omeprazole for the treatment of reflux oesophagitis in clinical trials. AIM: To compare the effectiveness of esomeprazole with the recommended dose of proton pump inhibitors in the healing of reflux oesophagitis, using omeprazole as a common comparator. METHODS: Systematic review of randomized controlled trials. Extraction and re-analysis of data to provide 'intention-to-treat' results. Meta-analysis using a Fixed Effects model. RESULTS: A meta-analysis of healing rates of esomeprazole 40 mg compared to omeprazole 20 mg gave the following results: at 4 weeks (relative risk 1.14; 95% CI: 1.10, 1.18) and 8 weeks (RR 1.08; 95%CI: 1.05, 1.10). Other proton pump inhibitors compared to omeprazole 20 mg are as follows: lansoprazole 30 mg at 4 weeks (RR 1.02; 95%CI: 0.97, 1.08) and 8 weeks (RR 1.01; 95%CI: 0.97, 1.06); pantoprazole 40 mg at 4 weeks (RR 0.99; 95%CI: 0.91, 1.07) and 8 weeks (RR 0.98; 95%CI: 0.93, 1.04); rabeprazole 20 mg at 4 weeks (RR 1.00; 95%CI: 0.87, 1.14) and 8 weeks (RR 0.98; 95%CI: 0.91, 1.05). CONCLUSIONS: Esomeprazole has demonstrated higher healing rates than omeprazole at 4 and 8 weeks. Other proton pump inhibitors (lansoprazole, pantoprazole and rabeprazole) have not shown higher healing rates when compared with omeprazole.

Administration, Oral↗

PubMed2001

The erythrocyte incorporation of absorbed non-haem iron in pregnant women.

Studies of Fe absorption in pregnancy often make unfounded assumptions of erythrocyte incorporation. Therefore, we measured the absorption and utilisation of Fe during early and late pregnancy by the erythrocyte incorporation of two stable isotopes. 8.5 mg 57Fe (oral) and 0.5 mg (58)Fe (intravenous) were given to five non-pregnant women, to five women in early gestation (12 weeks) and five women in late gestation (36 weeks). The stable isotope ratios in whole blood 14 d later were measured by MS. Together with estimation of body Fe mass, this enabled the calculation of Fe absorption and erythrocyte incorporation. In non-pregnant women, Fe absorption averaged 20.3 (range 10.2-34.3) %. It was not significantly different in early pregnancy (11.8 (range, 4.4-24.8) %), but during late pregnancy Fe absorption increased to 59.0 (range 38.2-77.2) %. All non-pregnant and early-pregnancy subjects had normal Fe status, but two women in late pregnancy had evidence of Fe insufficiency. During early and late pregnancy, mean erythrocyte incorporation was 63.4 (SD 12.1) % and 71.0 (SD 10.4) % respectively, significantly reduced compared with non-pregnant subjects (90.1 (SD 6.0) %). Decreased erythrocyte incorporation of absorbed Fe in early pregnancy is compatible with reduced Fe demand and low oral absorption. However, during late pregnancy decreased erythrocyte incorporation associated with high absorption and Fe insufficiency is different from the high erythrocyte incorporation which occurs in non-pregnant Fe-deficient women. This suggests that part of the aetiology of Fe deficiency during pregnancy may be the reduction of Fe utilisation.

Adult↗

PubMed2000

Identification that KfiA, a protein essential for the biosynthesis of the Escherichia coli K5 capsular polysaccharide, is an alpha -UDP-GlcNAc glycosyltransferase. The formation of a membrane-associated K5 biosynthetic complex requires KfiA, KfiB, and KfiC.

The Escherichia coli K5 capsular polysaccharide consists of the repeat structure -4)GlcA-beta(1,4)-GlcNAc-alpha(1- and requires the KfiA, KfiB, KfiC, and KfiD proteins for its synthesis. Previously, the KfiC protein was shown to be a beta-UDP-GlcA glycosyltransferase, and KfiD was shown to be a UDP-Glc dehydrogenase. Here, we demonstrate that KfiA is an alpha-UDP-GlcNAc glycosyltransferase and that biosynthesis of the K5 polysaccharide involves the concerted action of the KfiA and KfiC proteins. By site-directed mutagenesis, we determined that the acidic motif of DDD, which is conserved between the C family of glycosyltransferases, is essential for the enzymatic activity of KfiA. In addition, by Western blot analysis, we determined that association of KfiA with the cytoplasmic membrane requires KfiC but not KfiB, whereas the interaction of KfiC with the cytoplasmic membrane was dependent on both KfiA and KfiB. Likewise, KfiB was only detectable in cytoplasmic membrane fractions when both KfiA and KfiC were present. These data suggest that the interaction between the KfiA, KfiB, and KfiC proteins is essential for the stable association of these proteins with the cytoplasmic membrane and the biosynthesis of the K5 polysaccharide.

Amino Acid Sequence↗

PubMed2000

The human factor IX gene as germline mutagen test: samples from Mainland China have the putatively endogenous pattern of mutation.

Germline mutations are the major source of genetic variation that allows a species to evolve over time but at the cost of Mendelian disease and genetic predisposition to multifactorial diseases. Previous analyses have revealed that the pattern of germline mutations in the factor IX gene (F9) is similar among a variety of ethnically and geographically diverse populations and compatible with the ancient pattern that has shaped the mammalian genome. Here, we compare the pattern of germline mutation in a population of hemophilia B patients from Mainland China (n=66) to that in U.S. Caucasians, Blacks, and Mexican Hispanics and stratify by disease severity and ethnicity. The similar pattern of germline mutation in all ethnic groups studied to date provides additional data compatible with the inference that endogenous processes predominate in germline mutations.

China↗

PubMed2000

Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Esomeprazole (Nexium) is a new proton pump inhibitor for the treatment of acid-related diseases. METHODS: In this double-blind crossover study, 38 patients with gastro-oesophageal reflux disease (GERD) symptoms were randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5 days. On day 5 of each dosing period, 24-h intragastric pH and pharmacokinetic variables were measured. RESULTS: Thirty-six patients aged 29-58 (mean 45) years completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001 and P < 0. 01). Twenty-four-hour median intragastric pH was significantly higher with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P < 0.001 and P < 0.01). Area under the plasma concentration-time curve (AUC) was 80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40 mg was more than five times higher (each P < 0.0001). Interpatient variability in intragastric pH and AUC was less with esomeprazole than with omeprazole. Esomeprazole was well tolerated and there were no safety concerns. CONCLUSIONS: Esomeprazole provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid-related diseases.

Adult↗

PubMed2000

One-week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease.

BACKGROUND: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases. METHODS: Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication. RESULTS: Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%). Between-group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy. CONCLUSIONS: Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.

Adult↗

PubMed2000

The HOMER Study: the effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication with omeprazole, amoxycillin, and metronidazole is both effective and inexpensive. However, eradication rates with different dosages and dosing vary, and data on the impact of resistance are sparse. In this study, three different dosages of omeprazole, amoxycillin, and metronidazole were compared, and the influence of metronidazole resistance on eradication was assessed. METHODS: Patients (n = 394) with a positive H. pylori screening test result and endoscopy-proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada. After baseline endoscopy, patients were randomly assigned to treatment for 1 week with either omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 400 mg twice daily (low M); or omeprazole, 40 mg once daily, plus amoxycillin, 500 mg three times daily, plus metronidazole, 400 mg three times daily (medium M); or omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 800 mg twice daily (high M). H. pylori status at entry was assessed by a 13C urea breath test and a culture. Eradication was defined as two negative 13C-urea breath test results 4 and 8 weeks after therapy. Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy. RESULTS: The eradication rates, in terms of intention to treat (ITT) (population n = 379) (and 95% confidence interval [CI]) were as follows: low M 76% (68%, 84%), medium M 76% (68%, 84%), and high M 83% (75%, 89%). By per-protocol analysis (population n = 348), the corresponding eradication rates were: low M 81%, medium M 80%, and high M 85%. No H. pylori strains were found to be resistant to amoxycillin. Prestudy resistance of H. pylori strains to metronidazole was found in 72 of 348 (21%) of the cultures at entry (range, 10%-39% in the five countries). The overall eradication rate in prestudy metronidazole-susceptible strains was 232 of 266 (87%) and, for resistant strains, it was 41 of 70 (57%; p <.001). Within each group, the results were as follows (susceptible/resistant): low M, 85%/54%; medium M, 86%/50%; and high M, 90%/75%. There were no statistically significant differences among the treatment groups. 23 strains susceptible to metronidazole before treatment were recultured after therapy failed; 20 of these had now developed resistance. CONCLUSIONS: H. pylori eradication rates were similar (approximately 80%) with all three regimens. Metronidazole resistance reduced efficacy; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome. Treatment failure was generally associated with either prestudy or acquired metronidazole resistance. These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance.

Adolescent↗

PubMed2000

Changing surgical principles for gastro-oesophageal reflux disease--is laparoscopic fundoplication justified in the light of surgical complications?

Morbidity and mortality after surgical treatment for gastro-oesophageal reflux disease (GORD) can be considerable. During the past decade the dynamic evolution of laparoscopic surgery has seen this technique applied for GORD. In this chapter I will discuss perioperative and postoperative morbidity and mortality. I base my remarks on publications from all over the world, a national questionnaire, and a restricted national register. Only one randomised study has been reported, which concluded that there was no difference between conventional open and laparoscopic operations. A number of non-randomised studies have reported complications and clinical results in the same range as previously reported after open operations. More than half the surgical units in Sweden do laparoscopic fundoplications. In the questionnaire complications were reported in >2%, but the mortality was extremely low, <0.2%. These complications included postoperative paraoesophageal herniation, perforations, and reoperations for other reasons. There is a learning curve before complication rates are reduced.

Clinical Trials as Topic↗

PubMed2000

The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis.

The D-glucuronyltransferase and N-acetyl-D-glucosaminyltransferase reactions in heparan sulfate biosynthesis have been associated with two genes, EXT1 and EXT2, which are also implicated in the inherited bone disorder, multiple exostoses. Since the cell systems used to express recombinant EXT proteins synthesize endogenous heparan sulfate, and the EXT proteins tend to associate, it has not been possible to define the functional roles of the individual protein species. We therefore expressed EXT1 and EXT2 in yeast, which does not synthesize heparan sulfate. The recombinant EXT1 and EXT2 were both found to catalyze both glycosyltransferase reactions in vitro. Coexpression of the two proteins, but not mixing of separately expressed recombinant EXT1 and EXT2, yields hetero-oligomeric complexes in yeast and mammalian cells, with augmented glycosyltransferase activities. This stimulation does not depend on the membrane-bound state of the proteins.

Animals↗

PubMed1999

The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies.

BACKGROUND & AIMS: The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established. This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance. METHODS: Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori screening test result were randomized into 4 groups. OAC group received 20 mg omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg, and clarithromycin, 250 mg) groups received no omeprazole. All doses were administered twice daily for 1 week. H. pylori status was assessed before and after therapy by 13C-urea breath test. Susceptibility testing was performed at entry and in patients with persistent infection after therapy. RESULTS: Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001). Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and clarithromycin resistance each developed in 12 patients: 8 treated with omeprazole and 16 without omeprazole. CONCLUSIONS: Addition of omeprazole achieves high eradication rates, reduces the impact of primary resistance, and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics.

Amoxicillin↗

PubMed1999

The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy.

AIM: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer. METHODS: This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months. RESULTS: The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high. CONCLUSION: The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.

Acute Disease↗

PubMed1999

The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer.

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

Adult↗

PubMed1999

On demand therapy with omeprazole for the long-term management of patients with heartburn without oesophagitis--a placebo-controlled randomized trial.

AIM: To observe the natural course of gastro-oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long-term management of these patients. METHODS: We investigated the efficacy of on-demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double-blind, randomized multicentre trial. It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short-term treatment. Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6-month period. They also had access to antacids. The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue. RESULTS: According to life-table analysis, after 6 months the remission rates were 83% (95% CI: 77-89%) with omeprazole 20 mg, 69% (61-77%) with omeprazole 10 mg, and 56% (46-64%) with placebo (P < 0.01 for all intergroup differences). The mean (s.d.) number of study medications used per day in these groups was 0.43 (0.27), 0.41 (0.27) and 0.47 (0.27), respectively. The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group. Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life. CONCLUSIONS: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life. On-demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients.

Adult↗

PubMed1999

Purification and characterization of fetal bovine serum beta-N-acetyl-D-galactosaminyltransferase and beta-D-glucuronyltransferase involved in chondroitin sulfate biosynthesis.

beta-N-Acetylgalactosaminyltransferase II and beta-glucuronyltransferase II, involved in chondroitin sulfate biosynthesis, transfer an N-acetylgalactosamine (GalNAc) and glucuronic acid (GlcA) residue, respectively, through beta-linkages to an acceptor chondroitin oligosaccharide derived from the repeating disaccharide region of chondroitin sulfate. They were copurified from fetal bovine serum approximately 2500-fold and 850-fold, respectively, by sequential chromatographies on Red A-agarose, phenyl-Sepharose, S-Sepharose and wheat germ agglutinin-agarose. Identical and inseparable chromatographic profiles of both glycosyltransferase activities obtained through the above chromatographic steps and gel filtration suggest that the purified enzyme activities are tightly coupled, which could imply a single enzyme with dual transferase activities; beta-N-acetylgalactosaminyltransferase and beta-glucuronyltransferase, reminiscent of the heparan sulfate polymerase reaction. However, when a polymerization reaction was performed in vitro with the purified serum enzyme preparation under the polymerization conditions recently developed for the chondroitin-synthesizing system, derived from human melanoma cells, each monosaccharide transfer took place, but no polymerization occurred. These results may suggest that the purified serum enzyme preparation contains both beta-N-acetylgalactosaminyltransferase II and beta-glucuronyltransferase II activities on a single polypeptide or on the respective polypeptides forming an enzyme complex, but is different from that obtained from melanoma cells in that it transfers a single GalNAc or GlcA residue but does not polymerize chondroitin.

Animals↗

PubMed1999

cDNA cloning and expression of UDP-glucose dehydrogenase from bovine kidney.

We have isolated a cDNA encoding UDP-glucose dehydrogenase from a bovine kidney cDNA-library, the first mammalian cDNA clone published. [After submission of the manuscript, a study appeared describing the molecular cloning and characterization of the human and mouse UDP-glucose dehydrogenase genes (Spicer et al., 1998).] The enzyme catalyzes the conversion of UDP-glucose to UDP-glucuronic acid, an essential precursor in glycosaminoglycan biosynthesis. The cDNA has an open reading frame of 1482 nucleotides coding for a 55 kDa protein. Expression of the enzyme in COS-7 cells showed a 3-fold increase in UDP-glucose dehydrogenase activity; also, the C-terminal 23 amino acids was shown not to be necessary for enzyme activity. Northern blots from human and mouse tissues reveal high expression in liver and low in skeletal muscle. Human tissues have a major transcript size of 3.2 kilobases and a minor of 2.6 whereas mouse tissues have a single 2.6 kilobase transcript. We have also developed a sensitive and direct assay using UDP-[14C]Glc as a substrate for detection of small amounts of UDPGDH activity.

Amino Acid Sequence↗

PubMed1999

Omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection.

OBJECTIVE: In two studies, different regimens of omeprazole-amoxycillin-metronidazole were assessed for the eradication of Helicobacter pylori. DESIGN: Randomized, international, multicentre studies with parallel groups. SETTING: The studies were performed at centres in Canada, Czech Republic, France, Germany, Hungary, Sweden and UK. PARTICIPANTS AND INTERVENTIONS: H. pylori-positive patients with duodenal ulcer disease (active or in remission) were randomized to 7-day treatment with: omeprazole 40 mg once daily, amoxycillin 500 mg three times daily and metronidazole 400 mg three times daily (OAMtid; n = 242); omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 800 mg twice daily (OAM800; n = 247); or omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 400 mg twice daily (OAM400; n = 127). MAIN OUTCOME MEASURES: Eradication of H. pylori. RESULTS: Intention-to-treat analysis revealed H. pylori eradication rates of 76% (184/242) with OAMtid, 80% (198/247) with OAM800, and 76% (97/127) with OAM400. There was considerable variation in the levels of primary resistance to metronidazole in different countries. The overall eradication rate in patients infected with metronidazole-sensitive H. pylori strains was 85% (313/370), compared with 60% (56/94) in patients harbouring metronidazole-resistant strains (P<0.001). All regimens were generally well tolerated, with mild adverse events occurring in 4-26% of patients (mainly diarrhoea, reversible increase in liver enzymes and headache). CONCLUSION: The OAM combination is effective in curing H. pylori infection. Primary metronidazole resistance may reduce its effectiveness, but an increased daily dosing of metronidazole may partly overcome this problem.

Amoxicillin↗

PubMed1999

Quality of life in patients with heartburn but without esophagitis: effects of treatment with omeprazole.

OBJECTIVE: Because improvement in quality of life (QoL) is an important therapeutic goal in patients with heartburn but without esophagitis, the aim of the present study was to compare the impact of omeprazole 20 mg or 10 mg daily with that of placebo on QoL in patients with heartburn as the predominant symptom. METHODS: QoL was measured at baseline and after 4 wk using two validated questionnaires, the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptom Rating Scale. RESULTS: The two questionnaires were completed by 163 patients in the omeprazole 20 mg group, 163 in the omeprazole 10 mg group, and 82 in the placebo group. The reflux dimension of the Gastrointestinal Symptom Rating Scale showed a significant improvement in terms of reflux symptoms on omeprazole 20 mg versus omeprazole 10 mg and placebo, and on omeprazole 10 mg compared with placebo. The total score of the PGWB index improved significantly more on both doses of omeprazole than on placebo. The mean scores rose from 96.8 to 103.9 on omeprazole 20 mg, from 98.4 to 106.0 on omeprazole 10 mg, and from 98.0 to 100.6 on placebo. All dimensions of the PGWB index improved on treatment with omeprazole, but the improvements were most pronounced in the dimensions depicting anxiety, depressed mood, and self-control. CONCLUSIONS: It is concluded that treatment with omeprazole 20 mg and omeprazole 10 mg restores QoL to a level comparable with that observed in a healthy population.

Adolescent↗