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Biomedical subjects

A T Axon

Publications and source records attributed to A T Axon.

At least 91 records · Page 5Linked to original sources
PubMed1996

Antioxidants, Helicobacter pylori and stomach cancer in Venezuela.

A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Adult↗
PubMed1996

Eradication of Helicobacter pylori: omeprazole in combination with antibiotics.

Until recently, the mainstay of treatment for Helicobacter pylori infection was either dual therapy, using omeprazole with amoxycillin or clarithromycin, or traditional triple therapy comprising bismuth and two antibiotics. Success with these treatment strategies has, however, varied widely between centres. Furthermore, the side-effects reported for bismuth triple therapy and the 2-week treatment period recommended have limited its popularity. These drawbacks have thus stimulated research aimed at identifying better drug combinations, with a simpler dosage for a shorter period, fewer side-effects, and greater and more consistent efficacy. A number of studies have now been undertaken using an acid inhibitor in combination with two antibiotics. Omeprazole, a highly effective acid pump inhibitor, has been investigated most extensively in this context, and is markedly effective in eradicating H. pylori when combined with any two of clarithromycin, a nitroimidazole and amoxycillin. These omeprazole triple therapy combinations provide eradication rates that are usually in the range of 85-95%, when assessed on a per protocol basis. Side-effects are minor and rarely interfere with compliance. Increasingly, these combinations are being given in a twice-daily dosage, making them more acceptable for the patient, and the dosage of antibiotics, in some cases, can be reduced. Furthermore, 1 week of treatment has been shown to be effective. In a few patients, however, even these highly effective eradication regimens fails, and anecdotal reports suggest that, once this has happened, other treatments are often similarly ineffective. Failure is not simply a matter of antibiotic resistance because patients with resistant organisms are often cured. In some patients, poor compliance, antibiotic resistance, coccoid bacterial forms, or the presence of sanctuary sites may be the cause of failure, in others, it has been suggested that pretreatment with an acid inhibitor may be the explanation. Research into these particular areas will be required, unless a new and universally effective drug combination can be identified.

Anti-Bacterial Agents↗
PubMed1996

Eradication of Helicobacter pylori.

It has become clear over the past 10 years that Helicobacter pylori is responsible for two of the most common gastrointestinal diseases worldwide, gastric and duodenal ulcer, and that it plays an important role in the development of the second most common lethal malignancy affecting humankind, gastric cancer. At present eradication therapy is considered to be the most appropriate way of treating gastric and duodenal ulcer associated with infection. Treatment, however, remains a difficult area. Although the organism is sensitive to a wide variety of antibiotics in vitro, monotherapy in vivo is rarely successful. The first treatments used bismuth compounds, but results were variable and side-effects significant. When a single antibiotic, such as amoxycillin or clarithromycin, is combined with the proton pump inhibitor omeprazole, results are good but still with varied success and in the case of clarithromycin, the organism can develop resistance to macrolides. Triple therapy using omeprazole, 20 mg daily, in conjunction with clarithromycin, 250 mg twice daily, and tinidazole, 500 mg twice daily, and given for only one week, has had a 95% success rate. This regimen appears to be the most effective and acceptable combination described so far. However, the major difficulty facing most clinicians today is that even with the most effective therapies, infection in some patients would appear to be ineradicable, and this is an area in which further research is urgently required.

Drug Therapy, Combination↗
PubMed1995

Guidelines on appropriate indications for upper gastrointestinal endoscopy. Working Party of the Joint Committee of the Royal College of Physicians of London, Royal College of Surgeons of England, Royal College of Anaesthetists, Association of Surgeons, the British Society of Gastroenterology, and the Thoracic Society of Great Britain.

Upper gastrointestinal endoscopy is a valuable diagnostic tool, but for an endoscopy service to be effective it is essential that it is not overloaded with inappropriately referred patients. A joint working party in Britain has considered the available literature on indications for endoscopy, assessed standard practice through a questionnaire, and audited randomly selected cases using an independent panel of experts and an American database system. They used these data to produce guidelines on the appropriate and inappropriate indications for referral for endoscopy, although they emphasise that under certain circumstances there may be reasons to deviate from the advice given. The need for endoscopy is most difficult to judge in patients with dyspepsia, and this aspect is discussed in detail. Early endoscopy will often prove more cost effective than delaying until the indications are clearer.

Adult↗
PubMed1995

The role of pethidine in sedation for colonoscopy.

BACKGROUND AND STUDY AIMS: As sedation with a combination of benzodiazepines and opioids has been associated with an increased risk of serious cardiorespiratory events, it is rarely used in upper gastrointestinal endoscopy. The combination is, however, still commonly used in sedation for colonscopy and endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to determine the benefits and disadvantages of adding pethidine to diazepam (Diazemuls) in the sedation for colonoscopic examinations. PATIENTS AND METHODS: Seventy-one consecutive patients attending for routine colonoscopy were randomized in a double-blind, placebo-controlled manner to sedation with Diazemuls alone or Diazemuls with pethidine. The colonoscopist was at liberty to administrate any dose of Diazemuls considered appropriate for the patient's age and size, following which the patient was given an injection of pethidine 50 mg or a placebo. Both the patient and the endoscopist were blind to whether pethidine or a placebo was used. Adequacy of sedation was assessed and oxygen saturation recorded throughout the procedure. Oxygen was administered if the oxygen saturation fell below 92%. Patient satisfaction with sedation and recall of the procedure was recorded, by questionnaire, one day after examination. RESULTS: A total of 71 patients were entered into the trial. The two groups were similar with respect to age, sex, weight, alcohol intake, and state of health. An average of 18 mg of Diazemuls was given in the pethidine group and 19 mg in the placebo group. There was no statistically significant difference in the level of sedation obtained with the two regimens, although there was a tendency for the combination of Diazemuls with pethidine to give deeper sedation. Three patients were inadequately sedated with Diazemuls alone, requiring the code to be broken for pethidine to be given. Nine colonoscopies had to be abandoned due to patient intolerance in the group receiving Diazemuls, compared to five in the group receiving the combination regimen (p = 0.22). Twice as many patients receiving the combination of Diazemuls with pethidine required oxygen supplementation to maintain oxygen saturation during the procedure. This difference was highly statistically significant (p = 0.008). With the administration of supplemental oxygen, the average drop in oxygenation was similar in both groups. Satisfaction with sedation and recall for the procedure were similar in both groups. CONCLUSIONS: Although the patients had no preference for either regime, there may be an advantage in using the combination of Diazemuls and pethidine, as there was a trend for this combination to be preferred by the colonoscopists. The combination of a benzodiazepine with an opiate should be used with caution, however, as there was a greater requirement for oxygen in the group sedated by Diazemuls and pethidine.

Adolescent↗
PubMed1995

Endoscopy and gastric ulcers.

Upper gastrointestinal endoscopy plays a key role in the diagnosis and management of gastric ulceration, and is the only investigation that allows histology to distinguish benign from malignant disease. Therapeutic endoscopy is becoming increasingly important in the management of bleeding gastric ulcers, and further research in this field should provide insights into the most effective technique for reducing the mortality from this condition.

Gastroscopes↗
PubMed1995

The potential value of lansoprazole in Helicobacter pylori eradication.

Most anti-Helicobacter pylori (Hp) regimens available have drawbacks. Standard triple therapy using bismuth, metronidazole, and tetracycline gives good eradication rates but at the expense of a long, complicated regimen associated with significant side effects, and results are not as good in areas where there is a high resistance to nitroimidazoles. The introduction of eradication regimens based on acid suppression in combination with antibiotics has yielded promising results. Dual therapy using a proton pump inhibitor (PPI) with either amoxicillin or clarithromycin has yielded eradication rates above 80% with relatively few side effects, but results have been somewhat inconsistent from center to center. The combination of acid suppression with two antibiotics has provided better results, with centers achieving eradication rates of over 90%. The new PPI lansoprazole possesses some theoretical advantages as an acid-suppressing drug, and its preliminary use in a number of studies suggests that it may have an important role to play in Hp eradication regimens. Considerably more work, however, is required to identify the ideal dosage and combination that will give the best eradication rates with the simplest regimen and fewest side effects.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double-blind, randomized trial.

AIMS: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen. METHODS: In this double-blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 60). H. pylori status was assessed by 13C-urea breath test at entry and at 4 weeks post-treatment. RESULTS: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: +30 to +62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side-effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05). CONCLUSIONS: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.

Administration, Oral↗
PubMed1995

Review article: is Helicobacter pylori transmitted by the gastro-oral route?

The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet to date no satisfactory explanation has been advanced to account for its spread from person to person. This is surprising for a disease that affects 50% of the world's population. Attempts to culture H. pylori from faecal material and saliva have met with difficulty, casting some doubt on the likelihood of a faeco-oral or oro-oral route of transfer. The infection is easily passed from person to person by gastric intubation. The hypothesis advanced in this paper is that the natural route of transmission is by gastric juice, specifically as a result of epidemic vomiting in childhood. This theory is supported by literature indicating that acute infection with H. is characterized by vomiting of achlorhydric mucus that may serve as a vehicle for transmission. The hypothesis is consistent with most of the epidemiological data that have been published on H. pylori infection, including its association with childhood overcrowding, the lack of a fixed hot water supply and disadvantaged social conditions.

Gastric Juice↗
PubMed1995

Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy.

Helicobacter pylori causes chronic (type B) gastritis. The 'intestinal' form of gastric cancer arises against a background of chronic gastritis, and prospective epidemiological studies have shown that H pylori is a major risk factor for this. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging where there is chronic epithelial cell injury associated with H pylori gastritis. In vitro bromodeoxyuridine labelling of endoscopic antral biopsy specimens was used to measure mucosal cell proliferation in H pylori associated gastritis before and after therapy for H pylori triple infection. Cell proliferation was increased in H pylori associated gastritis patients compared with normal controls and patients with H pylori negative chronic gastritis (p = 0.0001; Tukey's Studentised range). There was no difference in antral epithelial cell proliferation between duodenal ulcer and non-ulcer subjects infected with H pylori (p = 0.62; Student's t test). Antral mucosal cell proliferation fell four weeks after completing triple therapy, irrespective of whether or not H pylori had been eradicated (p = 0.0001). At retesting six to 18 months later (mean = 12 months), however, those in whom H pylori had not been successfully eradicated showed increased mucosal proliferation compared with both H pylori negative subjects at a similar follow up interval and all cases (whether H pylori positive or negative) four weeks after completion of triple therapy (p = 0.024). These findings suggest that H pylori infection causes increased gastric cell proliferation and in this way may play a part in gastric carcinogenesis.

Adult↗
PubMed1995

Cell proliferation in the gastric corpus in Helicobacter pylori associated gastritis and after gastric resection.

Patients who have undergone gastric resection are at higher risk of developing gastric carcinoma than normal subjects, and bile reflux is believed to play a role in carcinogenesis. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging, particularly where there is chronic epithelial injury associated with bile reflux. Helicobacter pylori is considered a major risk factor for gastric cancer in the intact stomach. It has been shown previously that antral cell proliferation is increased in H pylori gastritis and falls to normal levels after eradication of the organism. Little is known of corpus cell proliferation in H pylori gastritis or after gastric resection. Using in vitro bromodeoxyuridine labelling of endoscopic biopsy specimens we have found that corpus cell proliferation is increased in H pylori gastritis. Cell proliferation was greater in corpus biopsy specimens of resected stomachs than in H pylori gastritis. Subgroup analysis of patients who had undergone gastric resection indicated that those positive for H pylori had higher levels of cell proliferation than those negative for the organism. These findings provide further evidence that H pylori and bile have a role in gastric carcinogenesis and suggest that their presence has a synergistic effect on gastric epithelial cell proliferation.

Adult↗
PubMed1995

Preservation of the spleen improves survival after radical surgery for gastric cancer.

One hundred and ninety five consecutive, potentially curative resections for adenocarcinoma of the stomach were performed in one surgical department between 1970 and 1989: 76 patients underwent gastrectomy with splenectomy and 119 gastrectomy without splenectomy. Operative mortality was 12% after gastrectomy with splenectomy, but only 2.5% after gastrectomy without splenectomy (p < 0.05). Postoperative complications were also significantly more common when splenectomy was combined with gastrectomy (41% v 14%, p < 0.01). Cumulative five year survival was 45% after gastrectomy with splenectomy, compared with 71% after gastrectomy alone (p < 0.01). When the results of the two groups of patients were compared, stage for pathological stage, no evidence was found that splenectomy improved survival. Application of Cox's proportional hazards model, which makes allowance for other variables such as the T and N stages, showed that splenectomy had an adverse influence on patients' survival. Splenectomy does not benefit the patient and its routine use in the course of radical resections for carcinoma of the stomach should be abandoned.

Adenocarcinoma↗
PubMed1995

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.

Acute Disease↗
PubMed1995

Helicobacter pylori infection and dental care.

Sixty two patients (mean age 45.6 years) were assessed for oral hygiene and periodontal disease by dental examination before endoscopy. Information about oral care, smoking, and dentures was obtained and samples of dental plaque collected. The presence of Helicobacter pylori in plaque as sought by culture and polymerase chain reaction (PCR), and gastric antral biopsy specimens were taken for histological examination. Although H pylori was detected in the antral specimens of 34 patients (54%) all of the cultures of dental plaque were negative, and PCR was only positive from the dentures of one patient. Smokers had poor oral hygiene, visited their dentist less often, and brushed their teeth less frequently. There was no correlation of H pylori gastritis with either dental hygiene or periodontal disease. These results suggest that dental plaque or dentures are not an important reservoir for H pylori and are probably not a significant factor in transmission of the organism. The conflicting results in published works may be caused by differences in sample collection, culture techniques, or oral contamination from gastric juice as a result of gastro-oesophageal reflux at the time of endoscopy.

Adult↗
PubMed1995

The perfect pelvic pouch--what makes the difference?

The aim of this study was to determine what factors are important for the achievement of perfect anal continence after restorative proctocolectomy. One hundred patients underwent paired studies of anorectal physiology before and one year after restorative proctocolectomy with pelvic ileal reservoir (11 S, 25 J, 64 W) with stapled ileoanal anastomosis, without mucosectomy. Fifty seven patients attained perfect anal continence and were able to discriminate flatus from faeces with such confidence that they were able to release flatus safely without fear of faecal soiling. The remaining 43 patients experienced minor problems in this regard. Four factors were found to correlate significantly with a perfect functional result (median, perfect v imperfect): maximum resting anal pressure (72 v 57 cm H2O, p < 0.02), the sensory threshold in the upper and mid-anal canal (7.3 v 8.6 and 5.3 v 7.0 mA, p < 0.05 and p < 0.02), compliance of the ileal reservoir (12.4 v 7.6 ml/cm H2O, p < 0.01), and the presence of a pouch-anal inhibitory reflex (56 of 57 patients v 29 of 43 patients, p < 0.01). The quality of anal continence depends on several factors: a complaint ileal reservoir, a strong sensitive anal sphincter, and normal reflex coordination of the activities of the reservoir and the sphincter. Excellent pouch-anal coordination is obtainable irrespective of the design of the reservoir, provided that these criteria are satisfied.

Adolescent↗
PubMed1995

Lymphocytic gastritis and associated small bowel disease: a diffuse lymphocytic gastroenteropathy?

AIM: To investigate the natural history of lymphocytic gastritis (LG) and its relation to Helicobacter pylori infection and to coeliac disease using serology, duodenal biopsy and a small intestinal permeability test. METHOD: Twenty two patients diagnosed as having LG between 1984 and 1994 were investigated by upper gastrointestinal endoscopy at which gastric and duodenal biopsy specimens were taken for histological assessment and immunohistology. Serum was collected for measurement of anti-H pylori, anti-gliadin and anti-endomysial antibodies. A lactulose/mannitol absorption test was performed within one week of endoscopy. Control groups were studied by histology, serology and permeability tests. RESULTS: Three patients had been recently diagnosed as having LG while 15 still had the condition after a mean of 13.9 (range two to 38) months. LG involved the antrum alone in three patients, antrum and body in seven, body alone in six, and gastric remnant in two. Gastroduodenal intraepithelial lymphocytes (IELs) were T cells and predominantly of T suppressor (CD8) type. Duodenal IELs were increased compared to age/sex matched controls with chronic gastritis. Four patients had duodenal villous atrophy. Four patients no longer had LG after a mean of 29.3 (10-70) months but had increased gastroduodenal IELs. H pylori was present in four (22%) of 18 patients with LG but H pylori serology was positive in 11 (61%) of 18. There was no difference in seropositivity when compared with age/sex matched controls with dyspepsia. Eleven of 20 patients with LG tested had abnormal lactulose/mannitol absorption (v none of 22 controls with chronic gastritis). Four patients with LG, all with villous atrophy, were seropositive for IgA endomysial antibody. CONCLUSIONS: The persistence of LG with time, the association with increased duodenal IELs and abnormal small intestinal permeability suggests LG may be a manifestation of a diffuse lymphocytic gastroenteropathy related to sensitivity to gluten or some other agent.

Adult↗