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M F Dixon

Publications and source records attributed to M F Dixon.

At least 73 records · Page 4Linked to original sources
PubMed1998

Choline acetyltransferase (ChAT) immunoreactivity in paraffin sections of normal and diseased intestines.

There is increasing interest in localizing nerves in the intestine, especially specific populations of nerves. At present, the usual histochemical marker for cholinergic nerves in tissue sections is acetylcholinesterase activity. However, such techniques are applicable only to frozen sections and have uncertain specificity. Choline acetyltransferase (ChAT) is also present in cholinergic nerves, and we therefore aimed to establish a paraffin section immunocytochemical technique using an anti-ChAT antibody. Monoclonal anti-choline acetyltransferase (1.B3.9B3) and a biotin-streptavidin detection system were used to study the distribution of ChAT immunoreactivity (ChAT IR) in paraffin-embedded normal and diseased gastrointestinal tracts from both rats and humans. Optimal staining was seen after 6-24 hr of fixation in neutral buffered formalin and overnight incubation in 1 microgram/ml of 1.B3.9B3, with a similar distribution to that seen in frozen sections. In the rat diaphragm (used as a positive control), axons and motor endplates were ChAT IR. Proportions of ganglion cells and nerve fibers in the intramural plexi of both human and rat gastrointestinal tracts were also ChAT IR, as well as extrinsic nerve bundles in aganglionic segments of Hirschsprung's disease. Mucosal cholinergic nerves, however, were not visualized. In addition, non-neuronal cells such as endothelium, epithelium, and inflammatory cells were ChAT IR. We were able to localize ChAT to nerves in formalin-fixed, paraffin-embedded sections. The presence of ChAT IR in non-neuronal cells indicates that this method should be used in conjunction with other antibodies. Nevertheless, it proves to be a useful technique for studying cholinergic neuronal distinction in normal tissues and pathological disorders.

Animals↗
PubMed1997

Randomised double blind controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection.

OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use.

Amoxicillin↗
PubMed1997

Assessment of microsatellite alterations in young patients with gastric adenocarcinoma.

BACKGROUND: Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome. METHODS: DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer. RESULTS: There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci. CONCLUSIONS: The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients.

Adenocarcinoma↗
PubMed1997

A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain.

BACKGROUND & AIMS: Currently available Helicobacter pylori models show variable and, in some instances, poor colonization. There is a need for a strain with high colonizing ability to act as a standard for animal studies. METHODS: After screening a range of fresh clinical isolates and long-term adaptation in mice, a strain of H. pylon has been isolated with a very good colonizing ability. RESULTS: This strain, named the Sydney strain of H. pylori (strain SS1), is cagA and vacA positive. High levels of colonization (10(6)-10(7) colony-forming units/g tissue) were achieved consistently in C57BL/6 mice. Colonization levels varied depending on the mouse strain used with BALB/c, DBA/2, and C3H/He, all being colonized but in lower numbers. In all strains of mice, bacteria were clearly visible at the junctional zone between the antrum and the body. The phenotype was stable with colonizing ability remaining after 20 subcultures in vitro. The bacterium attached firmly to gastric epithelium. During 8 months, a chronic active gastritis slowly developed, progressing to severe atrophy in both C57BL/6 and BALB/c mice. CONCLUSIONS: The Sydney strain of H. pylori is available to all and will provide a standardized mouse model for vaccine development, compound screening, and studies in pathogenesis.

Animals↗
PubMed1997

Prognostic significance of microsatellite instability in patients with gastric carcinoma.

A proportion of gastric adenocarcinomas exhibit replication errors manifested as microsatellite instability. The clinicopathological and prognostic significance of this abnormality remains uncertain. This study aimed to determine the importance of microsatellite instability by analysing a large series of gastric carcinomas from an English population. Using a novel fluorescent polymerase chain reaction technique, we amplified 11 microsatellite sequences from paired normal and carcinoma DNA from 101 patients who underwent a potentially curative resection for gastric carcinoma. Overall, 21% of cases demonstrated microsatellite instability in at least one locus. At least four loci were examined in each case. A replication error positive phenotype (minimum of 29% of loci affected) was detected in 9% of cases. There was no statistically significant association between the presence of microsatellite instability or replication error positive phenotype and the patient's age, sex, tumour site, stage, node status, histological subtype or grade. Carcinomas confined to the mucosa or submucosa (T1) showed a significantly higher frequency of instability and replication error positive phenotypes than T3 lesions (P = 0.03 and P = 0.05, respectively). A larger proportion of patients who were microsatellite instability or replication error positive were alive at 5 years compared with those who were negative but this did not reach statistical significance (P = 0.15 and P = 0.16, respectively). We identified a subset of gastric carcinomas from a relatively low-risk population which showed evidence of microsatellite instability. There were no statistically significant 5-year survival advantages in cases demonstrating microsatellite instability or replication error positive phenotypes. The detection of microsatellite instability is of limited prognostic value in gastric carcinoma.

Adult↗
PubMed1997

Histological classification of gastritis and Helicobacter pylori infection: an agreement at last? The International Workshop on the Histopathology of Gastritis.

An international workshop has assessed and revised the Sydney System for the reporting of gastritis. Much of the original approach was retained including division into acute, chronic and special forms, and grading of chronic inflammation, polymorph activity, atrophy, intestinal metaplasia and H. pylori density into mild, moderate and marked categories. Visual analog scales have been introduced as a simple guide to grading. The four biopsy sites have been changed to optimize detection of H. pylori, and supplemented by a fifth biopsy from the incisura angularis, the site which is most likely to yield premalignant changes. Chronic gastritis is classified into non-atrophic and atrophic forms with the latter divided into autoimmune (diffuse corpus atrophy) and multifocal. Histological reporting of gastritis should take into account the topographical pattern (antral or corpus predominant), and the final diagnostic term should ideally combine morphology and etiology to maximize the clinical value of gastric biopsy diagnosis.

Gastritis↗
PubMed1997

The endotoxin of Helicobacter pylori is a modulator of host-dependent gastritis.

Atrophic gastritis caused by Helicobacter pylori is the precursor lesion in the development of intestinal-type gastric adenocarcinoma. In animal models, atrophic gastritis induced by Helicobacter felis has been shown to be host dependent, developing in some mouse strains and not in others. The lipopolysaccharide (LPS) of H. pylori has been suggested to play a role in the induction of gastritis. The goal of this study was to compare the inflammation induced by long-term infection of the C3H/He and the C3H/HeJ strains of mice with H. felis. C3H/HeJ mice are unresponsive to LPS. Six months after infection, severe atrophic gastritis had developed in the body mucosae of all infected C3H/He mice, with replacement of parietal and chief cells. Atrophy was associated with a loss of the H. felis from the antral mucosa. In contrast, no atrophy was seen in the infected C3H/HeJ non-LPS responder animals, and heavy colonization of the antrum remained. There were no significant differences between both the quantitative and qualitative serum immunoglobulin G (IgG) and salivary IgA levels in both strains of mice. The main difference between the two strains of long-term-infected mice was a lack of macrophage infiltration in the lamina propria. Immunization induced good protective immunity to challenge with viable H. felis. Helicobacter-induced, host-dependent gastritis is likely to be cell mediated. The C3H/He and C3H/HeJ mouse model provides an excellent opportunity to investigate the cellular basis of atrophic gastritis.

Animals↗
PubMed1997

One week triple therapy for Helicobacter pylori: a multicentre comparative study. Lansoprazole Helicobacter Study Group.

BACKGROUND: Eradication of Helicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis. AIM: To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori. PATIENTS: Men or women with H pylori positive duodenal ulceration or gastritis, or both. METHODS: A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pylori status. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment. RESULTS: H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. CONCLUSIONS: All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Value of routine, non-targeted biopsies in the diagnosis of gastric neoplasia.

AIM: To explore how often a diagnosis of gastric neoplasia is made on routine, non-targeted biopsies taken for determination of Helicobacter pylori status, compared with directed biopsies from endoscopically abnormal mucosa. METHODS: Records of all patients with a biopsy diagnosis of gastric cancer or dysplasia during a two year period were reviewed to determine whether the biopsy had been targeted at an area of mucosal abnormality, and whether there was any evidence of dysplasia or malignancy before endoscopy. RESULTS: Of the 8907 endoscopic examinations that included biopsy, histology showed malignancy in 115 cases and dysplasia in 20. Of these, in 128 cases the biopsies were targeted from focal abnormal areas of mucosa, and six were from areas of diffuse mucosal thickening. In one case, adenocarcinoma was diagnosed in a patient with a "normal" endoscopic appearance; this patient was undergoing repeat endoscopy for previous dysplasia. CONCLUSIONS: Gastric malignancy or dysplasia was detected histologically in 1.5% of endoscopies that included biopsy. The performance of routine biopsies not targeted at a visible lesion from patients without previous diagnosis of neoplasia did not increase the detection of gastric malignancy. Such biopsies are indicated, however, if histological aspects of a patient's gastritis (such as atrophy or intestinal metaplasia) influence the clinical management, as in the treatment of helicobacter gastritis.

Adenocarcinoma↗
PubMed1997

Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin.

There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous architecture were studied. Small intestinal biopsies were obtained by Crosby capsule; small intestinal fluid was aspirated via the capsule. IEL counts were expressed per 100 epithelial cells, and intestinal IgA and IgM antigliadin antibody levels were measured by ELISA. Small intestinal permeability was measured by the lactulose:mannitol differential sugar permeability test. IEL counts were normal in all cases, median 17, range 7-30. Intestinal antigliadin antibodies were measured in six cases and were significantly elevated in two patients (both IgA and IgM). Intestinal permeability was measured in eight cases and was abnormal in two and borderline in one. These abnormalities did not overlap: four of nine patients had evidence of abnormal small intestinal function. Subclinical small intestinal disease is common in the two main forms of microscopic colitis.

Adult↗
PubMed1997

Significance of Helicobacter pylori infection and gastric cancer: implications for screening.

Helicobacter pylori infection is a major cause of premature mortality. Methods for diagnosing and treating this infection are now simple and reliable. A screening program to eradicate H. pylori is relatively straightforward to implement and is financially viable. This strategy initially involves a large capital outlay, however, and cannot be recommended until it is proven that H. pylori eradication reduces gastric cancer risk. It is also important to assess the magnitude of benefit of a screening program against the harm that might be engendered in terms of anxiety and adverse events from antibiotic treatment. If screening is beneficial, then in developed countries it could make death from H. pylori infection in the next century as uncommon as mortality from tuberculosis has been in this century.

Health Care Costs↗
PubMed1996

The significance of B-cell clonality in gastric lymphoid infiltrates.

The significance of the demonstration of a clonal B-cell population in gastric lymphoid infiltrates was investigated by analysis of immunoglobulin heavy chain (IgH) gene rearrangements using sensitive polymerase chain reactions, employing fluorescently labelled primers to target the FR3 and FR1 regions. Tissue blocks were studied showing different histological features (high-grade lymphoma, low-grade lymphoma, and chronic gastritis) from 12 gastrectomies for primary gastric lymphoma, together with blocks showing chronic gastritis from 13 cases of gastric adenocarcinoma and biopsies from 33 patients with active Helicobacter-associated chronic gastritis. Clonal IgH gene rearrangements were detected in lymphoma samples from eight of the gastrectomies for lymphoma (67 per cent). In four of these eight specimens, clonal rearrangements were also detectable in the samples showing only chronic gastritis. Three of 28 (11 per cent) informative biopsies showing active Helicobacter-associated chronic gastritis had detectable clonal populations. Clonal rearrangements were also demonstrated in two of eight (25 per cent) informative blocks showing chronic gastritis from eight gastrectomies for adenocarcinoma. It is concluded that the detection of a clonal population in a suspicious lymphoid infiltrate does not confirm the diagnosis of lymphoma, nor does the absence of such a population imply benignity.

B-Lymphocytes↗
PubMed1996

Gastric metaplasia: its role in duodenal ulceration.

There is good evidence to suggest that gastric metaplasia in the proximal duodenum and Helicobacter pylori gastritis are essential requirements for the development of duodenal ulceration in most cases. Gastric metaplasia is most likely to be a defence response or adaptation to excess acid reaching the duodenum. The appearance of gastric-type epithelium over the duodenal villi probably results from substitution by cells migrating from Brunner's gland ducts. These metaplastic foci provide sites for colonization by H. pylori passing through the duodenum; the organisms do not attach to native duodenal epithelial cells. Having colonized the metaplastic areas, H. pylori provokes an active chronic inflammatory response akin to that seen in the gastric mucosa. Active chronic duodenitis leads to a weakening of mucosal defence against acid-peptic attack, and erosion and ulceration may ensue. Healing of ulcers by conventional acid-reducing treatments does not influence the extent of gastric metaplasia, (although there may be some reduction with long-term proton pump inhibitors); nor do such regimens affect the background duodenitis. Only with eradication of H. pylori is there resolution of inflammation, but studies to date indicate that eradication alone has no substantial effect on the prevalence or extent of gastric metaplasia. Nevertheless the elimination of H. pylori appears to remove one of the essential co-factors for duodenal ulceration and the patient can be considered cured, despite the persistence of gastric metaplasia.

Duodenitis↗
PubMed1996

Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals.

High dietary ascorbic acid intake appears to protect against gastric cancer. This may be due to its action as a scavenger of reactive radical species formed in the gastric mucosa, resulting in a reduced level of radical-mediated DNA damage. We have studied 82 patients, of whom 37 had Helicobacter pylori-associated gastritis, a condition which predisposes to gastric cancer. Using electron paramagnetic resonance (EPR) spectroscopy we have demonstrated, for the first time, that ascorbyl radicals are generated in human gastric mucosa, presumably as a result of scavenging of free radicals by ascorbic acid. Quantification of ascorbyl radicals demonstrates that there is a higher concentration in those patients with H.pylori gastritis compared with subjects with normal histology (P < 0.01). We also found gastric mucosal luminol-enhanced chemiluminescence and malondialdehyde concentrations (which are believed to be markers of radical generation and tissue damage) to be higher in patients with H.pylori gastritis compared with those with normal histology (P < 0.001 and P < 0.01 respectively). The observed concentrations of the ascorbyl radical correlate with the level of luminol-enhanced chemiluminescence (r = 0.41, P < 0.001), but not with malondialdehyde concentrations (r = 0.08, P = 0.47). Mucosal ascorbic acid and total vitamin C concentrations did not vary between histological groups, nor did they correlate with mucosal levels of the ascorbyl radical, chemiluminescence or malondialdehyde. These data suggest that ascorbic acid is acting as a scavenger of free radicals generated in human gastric mucosa. The experiments therefore provide direct supportive evidence for the hypothesis that ascorbic acid protects against gastric cancer by scavenging reactive radical species which would otherwise react with DNA, with resultant genetic damage.

Adult↗