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Biomedical subjects

D S Tompkins

Publications and source records attributed to D S Tompkins.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparison of one or two weeks of lansoprazole, amoxicillin, and clarithromycin in the treatment of Helicobacter pylori.

BACKGROUND: The simplest, most effective, and least expensive Helicobacter pylori therapy remains to be determined. Two weeks of 30 mg lansoprazole bid, 1 gm amoxicillin bid, and 500 mg clarithromycin bid (LAC2) had been shown to be an effective therapy for H. pylori. The aim of this study was to assess whether 1 week of this regimen (LAC1) would have a similar efficacy. MATERIALS AND METHODS: H. pylori-positive patients assessed histologically, by rapid urease test, microbiologically, and by a 13C-urea breath test (13C-UBT) were randomized to receive either LAC1 or LAC2 in a single-center open study. Patients were interviewed 1 to 3 days after completion of therapy to evaluate adverse events and compliance. Efficacy was determined by 13C-UBT at least 4 weeks after antibiotic therapy. RESULTS: Seventy evaluable patients were randomized to receive LAC1 (n = 33) LAC2 (n = 37). Of the 33 LAC1 patients, 30 (91%) were treated successfully (95% confidence interval (CI) = 76-98%), compared with 32 of 37 (86%) in the LAC2 group (95% CI = 71-96%). There was no difference in efficacy between the two groups (Fisher's exact test p = 1.0; 95% CI = -10.3%-19.2%). Patients taking LAC1 experienced significantly fewer severe adverse events than those taking LAC2 (Mann-Whitney U test). One of 64 patients had primary resistance to clarithromycin, and treatment was unsuccessful in this case. Six of the 7 remaining treatment failures developed secondary resistance to clarithromycin. CONCLUSIONS: LAC1 is as effective as LAC2 and is associated with less toxicity. Posttreatment clarithromycin resistance is common in patients who do not experience success with therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype.

AIMS: To use a range of natural phenotypically variant strains of Helicobacter pylori with disparate CagA and VacA (vacuolating cytotoxin) expression to determine which bacterial factors are more closely associated with epithelial interleukin-8 (IL-8) induction. METHODS: Gastric epithelial cells (AGS and KATO-3) were co-cultured with five H pylori strains which were variously shown to express the cagA gene/CagA protein, VacA and/or to exhibit biological cytotoxicity. Secreted IL-8 was assayed by enzyme leaked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) was assayed using a reverse transcription polymerase chain reaction based technique (RT-PCR). RESULTS: Strains expressing CagA, including a variant strain (D931) which is non-cytotoxic and does not express the VacA protein, were found to upregulate epithelial IL-8 secretion and gene expression. In contrast, strains with no CagA expression, even in the presence of VacA and/or biological cytotoxicity, (G104, BA142), failed to induce IL-8 protein or mRNA above control values. CONCLUSIONS: These results strongly support a role for H pylori CagA or coexpressed factors other than the cytotoxin in upregulation of gastric epithelial IL-8. Increased epithelial IL-8 secretion and concomitant neutrophil chemotaxis and activation in addition to direct cytotoxicity may be an important factor in tissue damage and ulceration.

Animals↗
PubMed1995

Induction of interleukin-8 secretion from gastric epithelial cells by a cagA negative isogenic mutant of Helicobacter pylori.

The ability of Helicobacter pylori strains to induce interleukin-8 (IL-8) gene expression and protein secretion from gastric epithelial cell lines in vitro is variable. This cellular response is associated with bacterial expression of the CagA protein present in type I H pylori strains. To determine the role of CagA in this host cell response, an isogenic cagA negative mutant, N6.XA3, was constructed. The cagA negative isogenic mutant and the wild-type parental cagA positive strain, N6, were cocultured with AGS, ST-42 and KATO-3 gastric epithelial cell lines and secreted interleukin-8 assayed by enzyme linked immunosorbent assay. In all three cell lines there was no significant difference in the IL-8 secretion induced by the cagA negative isogenic mutant, N6.XA3, and the wild-type parent strain, N6. These studies show that CagA is not the inducer of IL-8 secretion from gastric epithelial cells. As all wild-type CagA positive strains studied to date induce IL-8, the bacterial factor(s) inducing this inflammatory response is closely associated with the expression of CagA.

Antigens, Bacterial↗
PubMed1995

Efficacy and optimum dose of omeprazole in a new 1-week triple therapy regimen to eradicate Helicobacter pylori.

OBJECTIVE: To assess the efficacy of a 1-week course of omeprazole, clarithromycin and tinidazole for the eradication of Helicobacter pylori and the optimum dose of omeprazole required. DESIGN: The study was divided into two sequential phases. The first phase was an open, two-centre study. The second phase was a single-blind, single-centre study. METHODS: Patients found to be infected with H. pylori at endoscopy were enrolled in the study. In phase 1, patients were prescribed 20 mg omeprazole, 250 mg clarithromycin and 500 mg tinidazole twice daily for 1 week. In phase 2, all patients were prescribed 250 mg clarithromycin and 500 mg tinidazole twice daily for 1 week. In addition, patients were randomly assigned to receive 20 mg omeprazole twice daily (group A), 20 mg omeprazole daily (group B) or no omeprazole (group C). Eradication was assessed in all patients by 13C-urea breath testing 4 weeks after the completion of therapy. RESULTS: In phase 1, H. pylori eradication was achieved in 132 (88%) of 150 evaluable patients. In phase 2, eradication was achieved in 44 (88%) of 50 individuals in group A, 47 (88.7%) of 53 in group B and 30 (63.8%) of 47 in group C. In the omeprazole groups, 22 patients harboured metronidazole-resistant strains of H. pylori and all were cured by the omeprazole regimen. One patient harboured a strain of H. pylori that was resistant to clarithromycin alone but which was successfully eradicated. Treatment failed in two out of three patients harbouring H. pylori strains resistant to both clarithromycin and tinidazole. CONCLUSION: One week of omeprazole, clarithromycin and tinidazole is effective in eradicating H. pylori. There is no advantage in increasing the dose of omeprazole from once to twice daily. This regimen is effective in patients with 5-nitroimidazole-resistant strains of H. pylori.

Adult↗
PubMed1994

Adaptation of Helicobacter pylori to aerobic growth.

Two of 23 strains of Helicobacter pylori adapted from microaerobic to aerobic growth on blood agar plates incubated in humidified air. The air-adapted strains remained urease and phenylalanine deaminase positive and did not require the buffering effect of an enriched CO2 atmosphere for growth. The significance of this phenomenon remains to be determined as the two strains capable of aerobic metabolism were laboratory-adapted.

Aerobiosis↗
PubMed1994

A multicentre study of the in-vitro activity of cefotaxime, cefuroxime, ceftazidime, ofloxacin and ciprofloxacin against blood and urinary pathogens.

The in-vitro susceptibilities of aerobic bacteria isolated from 1804 blood and 4529 urine specimens collected at nine hospitals in the UK were examined. An agar dilution method was used to determine the MICs of each isolate to three cephalosporins, cefotaxime, cefuroxime and ceftazidime, and to two fluoroquinolones, ofloxacin and ciprofloxacin. Sensitivities were then calculated using British Society for Antimicrobial Chemotherapy recommended breakpoints. Of the cephalosporins tested cefotaxime was the most active against the Enterobacteriaceae. All the systemic staphylococcus isolates collected were sensitive to both cefotaxime and cefuroxime. As expected, ceftazidime was the only cephalosporin active against the Pseudomonas isolates. Both quinolones were highly active against the Enterobacteriaceae and Pseudomonas spp. They also demonstrated good Gram-positive activity, particularly against Staphylococcus aureus and Enterococcus spp.

Anti-Infective Agents↗
PubMed1994

CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines.

AIMS: To investigate: (1) whether Helicobacter pylori directly induces interleukin-8 (IL-8) message expression and protein secretion in established gastric epithelial cell lines; and (2) if CagA/cytotoxin positive and negative strains of H pylori differ in their ability to induce epithelial IL-8. METHODS: Gastric epithelial cell lines were co-cultured with H pylori NCTC 11637 and 10 clinical isolates (four cytotoxic, six non-cytotoxic) and secreted IL-8 was measured by enzyme linked immunosorbent assay (ELISA). Specific induction of gastric epithelial IL-8 mRNA was examined by reverse transcription and polymerase chain reaction (RT-PCR) amplification. RESULTS: H pylori (NCTC 11637) induced IL-8 secretion from three gastric epithelial cell lines (KATO-3, ST42, AGS) but not from MKN 45 (gastric) or intestinal (SW480, HT29) cell lines. H mustelae did not stimulate IL-8 secretion from KATO-3, ST42, and AGS cells. H pylori induced IL-8 secretion was reduced by heat killing, sonication, freeze thawing or formalin fixation of the bacteria. CagA/cytotoxin positive strains of H pylori induced significantly higher IL-8 secretion than CagA/cytotoxin negative strains in the three positive gastric epithelial cell lines (KATO-3, ST42: p < 0.01; AGS: p < 0.02). A significant increase (p < 0.01) in the expression of IL-8 mRNA relative to G3PDH mRNA was observed in KATO-3 cells after three hours of co-culture with CagA/cytotoxin positive strains. CONCLUSIONS: H pylori directly increases gastric epithelial IL-8 mRNA expression and IL-8 protein secretion in a strain specific manner. Induction of epithelial IL-8 by CagA/cytotoxin positive strains is likely to result in neutrophil chemotaxis and activation and thus mucosal damage. These observations on epithelial IL-8 may explain the association between CagA/cytotoxin positive strains and gastroduodenal disease.

Animals↗
PubMed1993

Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer.

The systemic IgG response to Helicobacter pylori was examined in 70 patients with gastric cancer. H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA), and serological recognition of H pylori antigens was characterised by western blotting. A percentage of 78.5 were seropositive by ELISA. Two of five patients under age 50 were seronegative. Positivity was unrelated to age, sex, tumour type, or site. Ninety one per cent of ELISA positive cancer patients recognised the H pylori cytotoxin associated 120 kilodalton (kD) protein, significantly more than a control group of 47 ELISA positive patients with non-ulcer dyspepsia (72%). Four of 15 ELISA negative cancer patients also showed recognition of this protein in western blots. Mucosal IgA responses to H pylori were examined by immunoblotting supernatants of in vitro cultured resected antral mucosa in an overlapping group of 19 gastric cancer patients. Eighteen had a positive response, including 10 of 11 negative for H pylori by biopsy urease testing. The systemic and local immunoblotting results show that the high seroprevalence of H pylori antibodies detected by ELISA is nevertheless an underestimate of past infection. Dyspepsia screening policies based solely on H pylori ELISA would miss some young patients with gastric cancer. Further study of the relation of the H pylori cytotoxin to gastric precancerous lesions is warranted.

Adenocarcinoma↗
PubMed1993

Identification of Helicobacter pylori DNA in the mouths and stomachs of patients with gastritis using PCR.

AIMS: To determine the prevalence of Helicobacter pylori colonisation in the mouths of patients with H pylori gastritis. METHODS: A nested polymerase chain reaction test for the 16S ribosomal RNA gene of H pylori was used on saliva, dental plaque, gastric juice and gastric biopsy specimens from patients attending a dyspepsia clinic. RESULTS: Thirteen patients had histologically confirmed Helicobacter associated gastritis. Twelve of these had positive gastric aspirates by PCR. Five had at least one positive oral specimen. Eight patients with normal gastric biopsy specimens had no PCR positive oral specimens or gastric aspirates. All, however, had PCR positive gastric biopsy specimens. In an attempt to determine the origin of these positive results in normal patients, it was shown that biopsy forceps could contaminate specimens with DNA from previous patients. CONCLUSION: The demonstration of the organism in the mouths of a substantial proportion of dyspeptic patients has major implications for the spread of H pylori and identifies a potential source for reinfection following eradication of the organism from the stomach.

Base Sequence↗
PubMed1993

Clinical value of microbiological investigations in general practice.

The clinical value of many laboratory tests has frequently been queried. A short questionnaire was attached to individual microbiology reports issued to general practitioners in Bradford for an eight week period. Of the 2386 questionnaires sent out 1847 (77%) were returned. The general practitioners indicated that 34% of reports gave unexpected findings, 28% resulted in a change of therapy and most of the investigations (83%) were seen as beneficial to the patients. The majority of the specimens (56%) were mid-stream urine samples of which 77% gave negative findings. This study indicates that conventional microbiology test results are more valuable in general practice than previous hospital based surveys might suggest. Alternative strategies for investigation to reduce the number of tests of low value are discussed.

Bacteriological Techniques↗
PubMed1992

Effect of physical environment on survival of Helicobacter pylori.

AIMS: To determine the effects of physical conditions on survival of Helicobacter pylori in aquatic environments. Survival for prolonged time intervals would implicate environmental water as a possible source of infection. METHODS: The effect of ionic strength, pH, urea, protein and composition of incubation atmosphere on the survival of H pylori NCTC 11637 and two clinical isolates (CI 82 and 92) was investigated. RESULTS: H pylori strains survived for longer periods in physiological (0.15M) saline than in 0.05M or 0.6M saline solution. Optimal pH range for survival was between pH 5.8 and 6.9. Addition of urea (final concentration 100 microM/l-1 and 5 mM/l-1) to neutral unbuffered 0.15M saline resulted in a reduction in survival; addition of bovine serum albumin (1%) or gelatin (1%) resulted in variable survival times compared with saline alone. Incubation in a microaerobic gas mixture prolonged survival compared with incubation in air. CONCLUSION: H pylori survival in water over a prolonged period is possible for a range of physical variables. The results indicate that H pylori could survive in environmental water which may thus act as a potential reservoir of infection.

Disease Reservoirs↗
PubMed1992

Expression of 120 kilodalton protein and cytotoxicity in Helicobacter pylori.

Antral biopsy culture supernatants from 14 subjects with chronic gastritis, known to have IgA antibodies to the 120 kilodalton protein, showed positive recognition of this antigen in western blots against a cytotoxin positive strain of Helicobacter pylori but gave negative reactions with two cytotoxin negative strains. Control immunoblots with culture supernatants from 13 non-responders to the protein were all negative. This indicates a direct association between expression of the 120 kilodalton protein in H pylori strains and cytotoxicity.

Aged↗
PubMed1991

Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology.

The gastric IgA response to Helicobacter pylori was examined in 100 dyspeptic patients by means of immunoblotting of supernatants from antral biopsy and gastric mononuclear cell cultures. 76 of 78 patients with chronic gastritis, 2 of 8 with reactive gastritis, and 1 of 14 subjects with normal mucosa showed positive responses. Of patients with chronic gastritis, 75%, 83%, 97% and 76%, respectively, showed responses to the 120 kDa, 90 kDa, 61 kDa, and 31 kDa proteins. None of the 19 patients with chronic gastritis who did not recognise the 120 kDa protein had peptic ulcers, whereas 25 of 57 with positive recognition had peptic ulcers (p less than 0.001). Mucosal recognition of the H pylori 120 kDa protein was also positively associated with the activity of gastritis (polymorph infiltration) (p less than 0.002) and with the extent of surface degeneration (p less than 0.01). These findings suggest that 120-kDa-positive strains of H pylori have pathogenic features associated with active gastritis and peptic ulceration. Infection with 120-kDa-negative strains may explain why peptic ulceration develops in only a proportion of subjects infected with H pylori.

Adult↗
PubMed1991

Direct polymerase chain reaction test for detection of Helicobacter pylori in humans and animals.

We designed a polymerase chain reaction (PCR) for amplifying the Helicobacter pylori gene encoding 16S rRNA. Primers for the specific detection of H. pylori were designed for areas of the 16S rRNA gene in which there is the least sequence homology between H. pylori and its closest relatives. The specificity of detection was confirmed by ensuring that the primers did not amplify DNA extracts from the campylobacters H. cinaedi, H. mustelae, and Wolinella succinogenes, which are the closest relatives of H. pylori, as determined by 16S rRNA sequencing. Serial dilution experiments revealed the detection of as little as 0.1 pg of DNA by PCR and 0.01 pg by nested PCR. H. pylori DNA was detected successfully in clinical paraffin-embedded and fresh gastric biopsy specimens from patients positive for the bacterium and also in fecal suspensions seeded with the organism. The DNA from the nonculturable coccoid form of H. pylori was also identified by the primers. Universal primers designed for highly conserved areas on the 16S rRNA gene enabled large amplification products to be produced for direct sequencing analysis. Gastric bacteria resembling H. pylori have been isolated from animals. DNA of these animal gastric bacteria amplified with H. pylori-specific primers yielded PCR products identical to those from human isolates of H. pylori, as confirmed by the use of a 20-base radiolabelled probe complementary to an internal sequence flanked by the H. pylori-specific primers. The results of PCR amplification and partial 16S rRNA gene sequence analysis strongly support the contention that the gastric organisms previously recovered from a pig, a baboon, and rhesus monkeys are H. pylori.

Animals↗