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A T Axon

Publications and source records attributed to A T Axon.

At least 109 records · Page 6Linked to original sources
PubMed1995

Detection of c-Ki-ras mutations in bile samples from patients with pancreatic and biliary cancers.

Aim-To determine whether c-Ki-ras mutations can be detected in bile from patients with biliary strictures caused by pancreatic cancer and other biliary tumours, with a view to developing bile c-Ki-ras mutations as a non-invasive diagnostic marker of pancreatic cancer.Methods-Bile was collected from 89 subjects (47 controls (including patients with bile duct stones or benign stricture), 20 patients with pancreatic cancer, 11 with cholangiocarcinoma, five with ampullary cancer, and six with metastatic biliary obstruction) referred for endoscopic retrograde cholangiopancreatography. DNA was extracted from bile and c-Ki-ras codon 12 mutations were detected using PCR and a restriction enzyme digestion method.Results-c-Ki-ras mutations were detected in 10 (50%) of 20 patients with pancreatic cancer, in one (9%) of 11 with cholangiocarcinoma, and in two (33%) of six patients with metastatic biliary obstruction (primary tumours: colon and prostate). C-Ki-ras mutations were not detected in the controls and patients with ampullary cancer.Conclusions-The sensitivity of this test is too low at 50% to recommend its use clinically, but with refinement has potential as a diagnostic marker for pancreatic cancer.

Journal Article↗
PubMed1995

Non-ulcer dyspepsia: does Helicobacter pylori matter?

Non-ulcer dyspepsia is a heterogenous disorder characterised by chronic or recurrent abdominal or retrosternal discomfort lasting for more than four weeks for which no cause can be determined. Helicobacter pylori has been implicated as a potential cause in a subset of patients but the association has not been proven and H pylori eradication in patients with non-ulcer dyspepsia has had variable results. Large well-controlled studies are needed to clarify the relationship.

Dyspepsia↗
PubMed1995

Helicobacter pylori and recurrent ulceration after highly selective vagotomy.

OBJECTIVE: To examine the relationship between Helicobacter pylori and recurrent ulceration after highly selective vagotomy (HSV). SETTING: Academic Department of Surgery at a teaching hospital. PATIENTS: Thirty-eight patients (26 men and 12 women) were studied 2-21 years after HSV. Seven patients had recurrent ulceration. Each patient underwent tests of acid secretion before and 1 week after HSV together with later endoscopic examination of the stomach and duodenum. Four biopsies were taken from the duodenum and gastric antrum. RESULTS: There was no statistical difference in acid output between patients with and those without recurrent ulceration (peak acid output 46.9 versus 55.8 mmol/h, respectively; not significant) before operation. After operation, insulin stimulated acid secretion was significantly higher in patients who later developed recurrent ulceration (0.26 versus 4.1 mmol/h, respectively; P < 0.02). The endoscopic biopsies were tested for H. pylori infection (90 versus 86% for patients without and those with recurrent ulceration, respectively; not significant), gastric metaplasia within the duodenum (23 versus 14% for patients without and those with recurrent ulceration, respectively; not significant), antral gastritis (86 versus 71% for patients without and those with recurrent ulceration, respectively; not significant) and antral intestinal metaplasia (52 versus 43% for those without and those with recurrent ulceration, respectively; not significant). CONCLUSION: H. pylori infection is not influenced by HSV and ulcer recurrence is determined by the completeness of vagotomy rather than by H. pylori status.

Adult↗
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↗
PubMed1995

Helicobacter pylori, gastric cancer and gastric epithelial kinetics: a review.

AIM: To review the evidence that Helicobacter pylori promotes gastric carcinogenesis, with particular reference to gastric epithelial proliferation. MATERIALS AND METHODS: Gastric epithelial kinetics were reviewed and a series of studies of gastric mucosal proliferation in H. pylori-associated gastritis were performed in the intact and postsurgical stomach. In vitro bromodeoxyuridine labelling was performed on endoscopic antral biopsies from subjects with a normal gastric mucosa, with H. pylori-negative gastritis and with H. pylori-positive gastritis. The effect of eradication therapy was assessed. Corpus biopsies from the intact stomach were also examined and compared to body-type biopsies from the postsurgical stomach. RESULTS: Cell proliferation was increased in patients with H. pylori-positive gastritis and returned to normal levels following eradication therapy. The presence of H. pylori in the postsurgical stomach had a synergistic effect on gastric epithelial proliferation. CONCLUSIONS: H. pylori may promote gastric carcinogenesis by increasing epithelial proliferation. H. pylori and bile appear to have a synergistic effect on gastric cell proliferation.

Animals↗
PubMed1994

Patient and staff exposure to glutaraldehyde from KeyMed Auto-Disinfector endoscope washing machine.

Activated glutaraldehyde (2%) is the recommended agent for disinfection of endoscopic equipment. Exposure to the disinfectant is associated with side-effects and guidelines have been set to avoid these complications. Endoscope washing machines are used to provide automated high level disinfection of endoscopes as well as reduce exposure to the irritant aldehyde. We report a design fault in an endoscope washing machine which results in patients and staff being exposed to activated glutaraldehyde. The Auto-Disinfector (KeyMed) comprises a washing chamber supplied by three separate reservoirs (detergent, disinfectant, and rinse water) via a common channel. After the first cycle endoscopes are processed using previously used detergent and rinse water. Rinse water glutaraldehyde concentrations were measured in four machines during routine endoscopy lists on at least two occasions and showed a progressive rise in glutaraldehyde concentration up to 0.1% after two to six cycles. This results in staff being exposed to glutaraldehyde present on the processed instrument and the disinfectant being pumped from the internal channels of the endoscope into direct contact with the gastrointestinal mucosa during endoscopy at concentrations of 200-1000 ppm. The present atmospheric limit for glutaraldehyde is 0.2 ppm. Skin and mucosal irritation occur at concentrations of 0.3 ppm and severe synovitis in experimental animals at 100 pm. Tongue swelling and bloody diarrhoea with characteristic mucosal histological changes have been reported in patients exposed to activated glutaraldehyde on inadequately rinsed equipment. To reduce this problem the rinse water should be changed after every cycle and the endoscope should be dried thoroughly before use.

Disinfection↗
PubMed1994

Goseki histological grading of gastric cancer is an important predictor of outcome.

TNM (tumour, node, metastases) staging has thus far been the most important guide to prognosis in patients with gastric cancer. Histological grading, in contrast, has not provided any additional information. Recently a novel grading system based on tubular differentiation and mucus production has been proposed, which was correlated with patterns of tumour spread found at necropsy. This study set out to assess its value as a determinant of survival after gastric resection. In a consecutive series of 211 patients who had potentially curative resection for gastric cancer, five histological grading systems were assessed: the Lauren type, the WHO type, degree of differentiation, the type of tumour border, and the lymphocytic response to the tumour and compared with the Goseki grading (I-IV). When T and N stage were taken into account, using Cox's proportional hazards model, only the Goseki grading added further to the ability to predict survival. The proportional hazards ratios were: node negative v node positive 6.5 T1 v T3 2.45; Goseki I v Goseki IV 3.1. Five year survival of patients with mucus rich (Goseki II and IV) T3 tumours was significantly worse than that of patients with mucus poor (Goseki I and III) T3 tumours (18% v 53%, p < 0.003). Goseki grading identifies subgroups of patients with a poorer prognosis than is predicted by TNM staging alone. It could prove useful in the selection of patients for adjuvant therapy after potentially curative resection for gastric cancer.

Aged↗
PubMed1994

Comparison of labelling by bromodeoxyuridine, MIB-1, and proliferating cell nuclear antigen in gastric mucosal biopsy specimens.

AIMS: To compare proliferating cell nuclear antigen (PCNA) and MIB-1 with bromodeoxyuridine (BrdU) pulse labelling, a specific marker of cell proliferation, in endoscopic gastric biopsy specimens. METHODS: Twenty four biopsy specimens were obtained from 12 patients: 10 antral and eight body specimens were suitable. Each specimen was routinely processed and stained with haematoxylin and eosin. A modified Giemsa stain was used to detect the presence of Helicobacter pylori. Sections of the specimens were labelled with BrdU, MIB-1, and PC10. Gastric mucosa specimens were divided into three zones. The numbers of positively staining nuclei for 500 epithelial cell nuclei were counted in each zone and expressed as a percentage. RESULTS: The proportion of PCNA positive cells (range 0-90%) was much greater in all specimens (10 antrum, eight body). BrdU positive cells were virtually all confined to zone 2 (0-17% cells in this zone were positive) (zone 1 = surface and gastric pit, zone 2 = isthmus, zone 3 = gland base), while PCNA positive cells were present in all three zones (1 = 23-90%, 2 = 43-90%, 3 = 0-74%). Spearman's rank coefficient correlation of 0.57 confirmed that the percentage of positively staining cells varied in the same direction for both PCNA and BrdU (p < 0.001). PCNA, however, was overexpressed in all zones of the gastric epithelium compared with BrdU. In 38 biopsy specimens from 19 patients, of which 14 antrum and 11 body were suitable, the proportion of MIB-1 positive cells (0-59%) was greater than BrdU in most. As with BrdU labelling, the MIB-1 positive cells were confined to zone 2 (zone 1 = 1-11%); zone 2 = 21-59%; zone 3 = 0-13%) and the coefficient correlation for MIB-1 and BrdU was 0.63 (p < 0.001). CONCLUSIONS: MIB-1 accurately reflects the S-phase fraction in gastric mucosa, determined by BrdU labelling in conventionally processed gastric biopsy material. Caution is needed in the interpretation of PCNA labelling detected by PC10, which should not be accepted uncritically as a marker of cell proliferation in paraffin wax embedded material.

Antibodies, Monoclonal↗
PubMed1994

Mucosal interleukin-6 secretion in ulcerative colitis. Effects of anti-inflammatory drugs and T-cell stimulation.

BACKGROUND: We have studied modulation of mucosal interleukin-6 (IL-6) secretion by T-cell activation and by anti-inflammatory agents in inflammatory bowel disease. METHODS: In vitro secretion of IL-6 by biopsy specimens from patients with active ulcerative colitis was investigated in the presence of cyclosporin-A (CsA) and drugs that have other anti-inflammatory actions. Biopsy specimens from patients with quiescent ulcerative colitis or controls were stimulated with anti-CD3 antibody to activate mucosal T cells. RESULTS: Stimulation of control specimens increased IL-6 secretion (median increase, 147%; p < 0.003), which was prevented by CsA. In quiescent ulcerative colitis there was enhanced spontaneous secretion of IL-6 but a smaller, non-significant increase after T-cell activation (125%). Dexamethasone inhibited secretion in active ulcerative colitis (p < 0.006). 5-Aminosalicylic acid, 6-mercaptopurine, methotrexate, and indomethacin had no effect. There also tended to be a small reduction with CsA, but this just failed to reach statistical significance. CONCLUSIONS: In quiescent ulcerative colitis the enhanced spontaneous secretion of IL-6 may be a consequence of mucosal T-cell or macrophage activation: the smaller increase after T-cell stimulation suggests that one or both of these two cell types are already pre-activated.

Anti-Inflammatory Agents↗
PubMed1994

The role of omeprazole and antibiotic combinations in the eradication of Helicobacter pylori--an update.

When omeprazole is given with an appropriate antibiotic, a high rate of Helicobacter pylori eradication can be achieved. To date, most studies have used omeprazole and amoxycillin, and an analysis of the results suggests that, at present, the most effective treatment regimen comprises omeprazole, 20 mg twice daily, and amoxycillin, 1 g twice daily, for 14 days. This regimen provides an eradication rate of about 85%. Results using omeprazole plus bismuth or tetracycline have been disappointing; however, preliminary studies of omeprazole plus clarithromycin show promise, although further data are needed. Treatment with omeprazole plus two different antibiotics has also been used in a number of studies. The results thus far have been variable, although increases in the omeprazole dose/regimen might improve eradication rates. Moreover, one recent study that used omeprazole, a low dose of clarithromycin and tinidazole gave 100% H. pylori eradication after 1 week. If the effectiveness of this regimen is confirmed, it will prove to be the most effective treatment for the eradication of H. pylori identified to date.

Amoxicillin↗
PubMed1994

The role of acid inhibition in the treatment of Helicobacter pylori infection.

The recognition that Helicobacter pylori is a causal factor in the development of most peptic ulcers (and may play a role in the pathogenesis of gastric cancer) has provided an impetus to the search for a suitable regimen that will eradicate the organism. Combinations of antibiotics with bismuth (triple therapy) eradicate the organism in around 90% of cases, but the regimens are complicated, and poor compliance and significant side effects are frequently seen. The observation that omeprazole in combination with a single antibiotic provides eradication rates of over 80% is an important advance, as this combination is a simple regimen and is well tolerated. In this article, the role of omeprazole in eradication therapy is discussed, the published data are reviewed and hypotheses relating to the mode of action of omeprazole are presented. Although the optimum therapy has yet to be identified, acceptable results should be obtained by using omeprazole, 40 mg twice daily, plus amoxycillin, 500 mg four times daily, for 2 weeks.

Amoxicillin↗
PubMed1993

Gastric cancer: a curable disease in Britain.

OBJECTIVE: To determine whether more vigorous efforts aimed at earlier diagnosis allied to radical surgical resection lead to improved survival of patients with gastric cancer. DESIGN: Prospective audit of all cases of gastric cancer treated during 1970-89. SETTING: Department of surgery, general hospital. SUBJECTS: 493 consecutive patients with gastric adenocarcinoma. MAIN OUTCOME MEASURES: Operative mortality, postoperative morbidity, and five year survival after radical potentially curative resection. RESULTS: 207 (42%) patients underwent potentially curative resection. The proportion of all patients in whom this was possible increased significantly (p < 0.01) from 31% in the first five year period to 53% in the last five year period. The proportion of patients who had early gastric cancer rose from 1% to 15% (p < 0.01) and stage I disease rose from 4% to 26% (p < 0.001). After potentially curative resection, mortality 30 days after operation was 6%. Operative mortality decreased from 9% in the 1970s to 5% in the 1980s. Likewise, the incidence of serious postoperative complications decreased from 33% in the 1970s to 17% in the 1980s (p < 0.01). Five year survival was 60% in patients who underwent curative resection, 98% in patients with early gastric cancer, and 93%, 69%, and 28% in stage I, II, and III disease respectively. By the late 1980s five year survival after operation was about 70%. CONCLUSIONS: These findings suggest that an increasing proportion of patients with gastric cancer could be diagnosed at a relatively early pathological stage when about two thirds are curable by means of radical surgery.

Adenocarcinoma↗