The significance of cagA and vacA subtypes of Helicobacter pylori in the pathogenesis of inflammation and peptic ulceration.
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AIMS: To assess the significance of cagA and vacA subtypes of Helicobacter pylori in relation to inflammation and density of bacterial colonisation in vivo within a dyspeptic UK population. METHODS: Dyspeptic patients who were Helicobacter pylori positive had antral samples taken for histology and culture. Gastroduodenal pathology was noted. The grade of bacterial density and inflammation was assessed using the Sydney system. Bacterial DNA was extracted and the vacA alleles and the cagA/gene typed using PCR. RESULTS: 120 patients were studied. There was high rate of cagA positive strains in this population. Bacterial density did not correlate with the presence of peptic ulceration. There was a significant association between cagA positive strains and increased inflammation and bacterial density. The vacA s1 type independently correlated with extensive chronic inflammation but there was no association with bacterial density. The vacA m type did not correlate with extent of inflammation or bacterial density. CONCLUSIONS: The results suggest that cagA is important in the pathogenesis of inflammation and peptic ulceration. These findings are in keeping with the hypothesis that cagA acts as a marker for a cag pathogenicity island which encodes several genes involved in inflammation. The vacA s1 allele correlates with inflammation independently of cagA, possibly through its enhanced ability to produce the vacuolating cytotoxin. (+info)
Can restrictions on reimbursement for anti-ulcer drugs decrease Medicaid pharmacy costs without increasing hospitalizations?
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OBJECTIVE: To examine the impact of a policy restricting reimbursement for Medicaid anti-ulcer drugs on anti-ulcer drug use and peptic-related hospitalizations. DATA SOURCES/STUDY SETTING: In addition to U.S. Census Bureau data, all of the following from Florida: Medicaid anti-ulcer drug claims data, 1989-1993; Medicaid eligibility data, 1989-1993; and acute care nonfederal hospital discharge abstract data (Medicaid and non-Medicaid), 1989-1993. STUDY DESIGN: In this observational study, a Poisson multiple regression model was used to compare changes, after policy implementation, in Medicaid reimbursement for prescription anti-ulcer drugs as well as hospitalization rates between pre- and post-implementation periods in Medicaid versus non-Medicaid patients hospitalized with peptic ulcer disease. PRINCIPAL FINDINGS: Following policy implementation, the rate of Medicaid reimbursement for anti-ulcer drugs decreased 33 percent (p < .001). No associated increase occurred in the rate of Medicaid peptic-related hospitalizations. CONCLUSIONS: Florida's policy restricting Medicaid reimbursement for anti-ulcer drugs was associated with a substantial reduction in outpatient anti-ulcer drug utilization without any significant increase in the rate of hospitalization for peptic-related conditions. (+info)
Management and outcome of patients undergoing surgery after acute upper gastrointestinal haemorrhage. Steering Group for the National Audit of Acute Upper Gastrointestinal Haemorrhage.
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Most patients with acute upper gastrointestinal haemorrhage are managed conservatively or with endoscopic intervention but some ultimately require surgery to arrest the haemorrhage. We have conducted a population-based multicentre prospective observational study of management and outcomes. This paper concerns the subgroup of 307 patients who had an operation because of continued or recurrent haemorrhage or high risk of further bleeding. The principal diagnostic group was those with peptic ulcer. Of 2071 patients with peptic ulcer presenting with acute haemorrhage, 251 (12%) had an operative intervention with a mortality of 24%. In the non-operative group mortality was 10%. The operative intervention rate increased with risk score, ranging from 0% in the lowest risk categories to 38% in the highest. Much of the discrepancy between operative and non-operative mortality was explainable by case mix; however, for high-risk cases mortality was significantly higher in the operated group. In 78% of patients who underwent an operation for bleeding peptic ulcer there had been no previous attempt at endoscopic haemostasis. For patients admitted to surgical units, the operative intervention rate was about four times higher than for those admitted under medical teams. In patients with acute upper gastrointestinal haemorrhage operative intervention is infrequent and largely confined to the highest-risk patients. The continuing high mortality in surgically treated patients is therefore to be expected. The reasons for the low use of endoscopic treatment before surgery are not revealed by this study, but wider use of such treatments might further reduce the operative intervention rate. Physicians and surgeons have not yet reached consensus on who needs surgery and when. (+info)
Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: possible effect of age, liver disease and length of therapy.
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AIMS: To evaluate the reliability of the omeprazole hydroxylation index as a marker for polymorphic CYP2C19 activity in a Japanese population of healthy young subjects (n = 78) and patients with peptic ulcer (n = 72). METHODS: Healthy subjects were administered a single dose of omeprazole (20 mg), whereas patients received 20 mg daily for at least 1 week. The ratio of the serum concentration of omeprazole to hydroxyomeprazole at 3 h postdose was determined and used as a measure of CYP2C19 activity. The CYP2C19 wild type (wt) gene and four mutant alleles associated with the poor metaboliser phenotype of (S)-mephenytoin, CYP2C19*2 in exon 5, CYP2C19*3 in exon 4, CYP2C19m4 in exon 9, and CYP2C19m3 in the initial codon were analysed. RESULTS: In the healthy volunteer study there was complete concordance between genotype and phenotype. However, eight of the patients who had the EM genotype had a high value for their hydroxylation index, and were classified as phenotypic PMs. No CYP2C19m4 and CYP2C19m3 mutations were detected in the eight mismatched patients. They were all genotypic heterozygous EMs, elderly (> or = 65 years) and/or had hepatic disease. Therefore, impaired CYP2C19 activity combined with partial saturation of omeprazole metabolism during multiple dosing may have contributed to the discrepancy between CYP2C19 genotyping and phenotyping. CONCLUSION: Although omeprazole has been used instead of mephenytoin as a probe for polymorphic CYP2C19, it does not appear to be reliable enough for clinical application in Japanese patients. (+info)
PCR-based restriction pattern typing of the vacA gene provides evidence for a homogeneous group among Helicobacter pylori strains associated with peptic ulcer disease.
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The results of PCR-based molecular typing of Helicobacter pylori strains by restriction fragment length polymorphism analysis of a 1, 161-bp nucleotide sequence of the midregion of the vacA gene are reported. A total of 48 H. pylori strains isolated from gastric biopsy specimens obtained from 18 patients with peptic ulcer dyspepsia, 15 patients with nonulcer dyspepsia, and 15 asymptomatic H. pylori-infected subjects were studied. Highly heterogeneous restriction patterns were obtained by digestion of PCR products with SauII, BglII, and HhaI, whereas HaeIII digestion resulted in a strictly homogeneous profile for H. pylori strains isolated from 14 of 18 (77.7%) patients with peptic ulcer dyspepsia, but a strictly homogeneous profile was found for strains from only 8 of 15 (53.3%) patients with nonulcer dyspepsia (P = 0.163) and 5 of 15 (33.3%) asymptomatic H. pylori-infected subjects (P = 0.014). A potentially important aspect of the results obtained is the clinical relevance, since a single restriction pattern seems to be able to identify the majority of H. pylori strains associated with peptic ulcer disease. (+info)
Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene in South Africa: rarity of the vacA s1a genotype and natural occurrence of an s2/m1 allele.
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We describe the rarity of Helicobacter pylori strains of vacuolating cytotoxin type s1a (the type most commonly associated with peptic ulceration in the United States) among black and mixed-race South Africans. We also provide the first description of a naturally occurring strain with the vacA allelic structure s2/m1. (+info)
Relationship between mucosal levels of Helicobacter pylori-specific IgA, interleukin-8 and gastric inflammation.
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Mucosal IgA is important in local immune defence. Helicobacter pylori induces a specific IgA response in antral mucosa, but its immunopathology is unknown. Interleukin-8 (IL-8) has been suggested to be important in H. pylori-induced inflammation. Current information on the relationship between H. pylori-induced IgA and mucosal inflammation is limited. To investigate possible associations between mucosal-specific IgA, the toxinogenicity of H. pylori, mucosal levels of IL-8 and gastric inflammation, 52 endoscoped patients were studied. These comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer dyspepsia. Antral biopsies were taken for histology, H. pylori culture and measurement of mucosal levels of IL-8 (pg/mg) and specific IgA (A450x1000) by ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H. pylori infection, with a median (interquartile) level of 220 (147, 531) units. There was no significant difference in mucosal levels of the IgA antibodies between patients infected with cytotoxin-positive or cagA-positive strains of H. pylori and those with toxin-negative or cagA-negative strains. The IgA levels in those patients with severe neutrophil infiltration were lower than in those with mild or moderate infiltration (P<0.05). There was a weak inverse correlation between antral mucosal IgA and IL-8 in infected patients (r=-0.36; P=0.04). H. pylori infection induced a significant local mucosal IgA response in most infected patients. The level of IgA antibodies does not appear to be correlated with the toxinogenicity of H. pylori. However, patients with severe active inflammation appear to have decreased levels of IgA. An inverse correlation between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation compromises the mucosal IgA defence and renders the mucosa susceptible to further damage. (+info)
High cure rate of Helicobacter pylori infection using tripotassium dicitrato bismuthate, furazolidone and clarithromycin triple therapy for 1 week.
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BACKGROUND: When metronidazole is used in bismuth-based or proton pump inhibitor-based triple therapy, the cure rate of Helicobacter pylori is usually high. However, metronidazole-resistant H. pylori strains, which are increasing in frequency, are a major cause of failed H. pylori eradication. AIM: To evaluate the efficacy of non-metronidazole containing bismuth-based triple therapy for H. pylori infection. METHODS: One-hundred and eighty H. pylori-positive patients with endoscopically documented peptic ulcer disease or functional dyspepsia were randomly assigned to one of three 1-week regimens containing tripotassium dicitrato bismuthate (also called colloidal bismuth subcitrate) 240 mg b.d. and two antibiotics: furazolidone 100 mg b.d. plus clarithromycin 250 mg b.d. (Group A); or clarithromycin 250 mg b.d. plus amoxycillin 1000 mg b.d. (Group B); or furazolidone 100 mg b.d. plus josamycin 1000 mg b.d. (Group C). H. pylori status was assessed by rapid urease test, histology and culture of gastric biopsy specimens taken from both the antrum and corpus, both before and at least 4 weeks after completion of therapy. RESULTS: Thirteen patients dropped out (3 in group A, 5 in group B and 5 in group C). Based on an intention-to-treat analysis, the eradication rates achieved in groups A, B and C were 88% (53/60), 58% (35/60) and 77% (46/60), respectively. These differences were significant between groups A and B (P < 0.001), as well as between groups B and C (P < 0.05). Side-effects occurred in 7 (12%) patients in group A, 3 (5%) in group B and 8 (13%) in group C, and were mild, with the exception of vomiting in one patient (group C) that resulted in withdrawal from the study. CONCLUSION: One-week triple therapy, consisting of tripotassium dicitrato bismuthate, low-dose furazolidone and low-dose clarithromycin, achieves a high cure rate of H. pylori. (+info)