Comparison of serum, salivary, and rapid whole blood diagnostic tests for Helicobacter pylori and their validation against endoscopy based tests.

BACKGROUND: A rapid, reliable, and accurate test for the diagnosis of infection with Helicobacter pylori is needed for screening dyspeptic patients before referral for endoscopy. AIM: To compare a new rapid whole blood test (Helisal rapid blood, Cortecs), two serum enzyme linked immunosorbent assays (ELISAs; Helico-G, Shield and Helisal serum, Cortecs), and a salivary assay (Helisal saliva, Cortecs), with slide biopsy urease, 13C-urea breath test, and histology. METHODS: Three hundred and three consecutive dyspeptic patients attending for gastroscopy underwent two antral biopsies for histology, and one for rapid slide biopsy urease test for assessment of H pylori status. Blood and saliva were also collected. One hundred of the patients also underwent a 13C-urea breath test. Gold standard positives were defined as those with at least two positive tests among slide urease, breath test, or histology, and gold standard negatives as those with all these (or two when the breath test was not done) negative. RESULTS: Of 300 patients (median age 63, range 28-89) eligible for analysis, 137 (46%) were gold standard positives, of which Helisal rapid blood identified 116, Helico-G 129, Helisal serum 130, and Helisal saliva 120; 137 (46%) were gold standard negatives of which the number falsely identified as positive was 30 by Helisal rapid blood, 45 by Helico-G, 41 by Helisal serum, and 41 by Helisal saliva. Sensitivities and specificities were: for the whole blood test 85% and 78% respectively; for Helico-G 94% and 67%, for Helisal serum 95% and 70%, and for Helisal saliva 84% and 70%. CONCLUSIONS: If endoscopy had been undertaken only on patients with positive tests two of 16 duodenal ulcers would have been missed if the Helisal rapid blood test was used, and one if any of the ELISA tests were used. None of the blood tests would have missed any of six gastric ulcers, but the salivary test would have missed one.

Low-dose famotidine and ranitidine as single post-prandial doses: a three-period placebo-controlled comparative trial.

BACKGROUND: Low-dose H2-receptor antagonists are available without prescription for the self-medication of dyspepsia. METHODS: To investigate the relative abilities of low doses of famotidine and ranitidine to raise intragastric pH after a single post-prandial evening dose, 25 healthy volunteers completed a three-period cross-over trial of famotidine 10 mg, ranitidine elixir 75 mg and placebo. A standard meal was given at 18.30 h and drug or placebo at 19.30 h to subjects fasted for 5.5 h. Intragastric pH was recorded with nasogastric electrodes from 18.00 to 07.30 h by GastrograpH II recorder. RESULTS: The geometric mean area under the pH-time curve for the 5-9 h post-dose period was 1.49 pH units/h following placebo, 3.43 pH units/h following famotidine 10 mg (agent/placebo ratio 2.3; P < 0.001, ANOVA) and 2.6 pH units/h following ranitidine 75 mg (1.75; P < 0.001). The geometric mean area under the pH-time curve ratio of famotidine 10 mg to ranitidine 75 mg was 1.32 (P < 0.016). Median pH over the 5-9 h period was 1.1 following placebo, 2.7 following famotidine 10 mg (P < 0.05 by comparison with placebo) and 1.9 following ranitidine 75 mg (P < 0.05); comparison of median pH showed no significant difference between the active drugs. The percentage of pH values greater than 3.0 for the period 0-12 h post-dose was 9.7% following placebo, 30.0% following famotidine 10 mg (P < 0.05) and 24.9% following ranitidine 75 mg (P < 0.05); there was no significant difference between the active drugs. CONCLUSIONS: We conclude that both famotidine 10 mg and ranitidine 75 mg significantly raise intragastric pH when given as single post-prandial doses. Famotidine 10 mg may have a greater effect than ranitidine elixir 75 mg over the 5-9-h period after dosing.

Helicobacter pylori eradication in a clinical setting: success rates and the effect on the quality of life in peptic ulcer.

BACKGROUND: Helicobacter pylori eradication for peptic ulcer has been widely taken up. Evidence for the efficacy of different regimens is often derived from small series in clinical trials but there is little reporting of everyday practice with unselected patients. Freedom from ulcer relapse has been demonstrated, but not whether this equates with clinical success. METHODS: We report on a series of 706 patients with H. pylori infection who, between January 1991 and April 1995, received eradication therapy followed by assessment of H. pylori status. Two-hundred and seven of these patients were followed-up by postal questionnaire, validated by parallel questionnaires to their general practitioners, covering clinical outcome measures. RESULTS: The overall eradication rate was 81.7%, and a 1-week course of omeprazole plus two antibiotics was significantly better than a 2-week course of standard triple therapy (85.0% vs. 78.0%, P < 0.05). Amongst 21 first-time failures, a 7-day course of a clarithromycin-containing triple therapy succeeded in 18. The questionnaire replies indicate that, following successful H. pylori eradication, ulcer patients are less likely to consult with ulcer symptoms (P < 0.0005), take medication (P < 0.0005), require further prescription (P < 0.0005), or lose work-time because of their ulcer (P < 0.005). They are more likely to have a subjective sense of ulcer cure (P < 0.0005). CONCLUSIONS: In addition to clear cost savings, social benefits are now demonstrated when H. pylori is eradicated. A well-tolerated 1 week regimen is genuinely effective in everyday practice.

Low dose famotidine and cimetidine in single postprandial doses: a placebo controlled comparative study of overnight pH.

To investigate the relative abilities of low doses of famotidine and cimetidine to raise intragastric pH after a single postprandial evening dose, 16 healthy volunteers were recruited to a four period crossover trial of famotidine 10 mg, cimetidine 100 mg and 200 mg compared with placebo. Intragastric pH was monitored between 1800 and 0730 with a nasogastric pH electrode. Median gastric pH rose from 1.35 (interquartile range 1.1-1.65) with placebo to 1.95 (1.6-5.35, p < 0.001 Friedman rank) after dosing with famotidine 10 mg, to 1.46 (1.3-2.0, 0.05 < p < 0.1) after cimetidine 200 mg, and remained 1.35 (1.1-1.6, p > 0.2) after cimetidine 100 mg. Intragastric pH was above 3 for 34% (p < 0.005) of the time after dosing with famotidine, compared with 13.6% (p > 0.2) after cimetidine 200 mg, 9.5% (p > 0.2) after cimetidine 100 mg, and 4.7% after placebo. The rise of intragastric pH after famotidine 10 mg is significantly greater than that after either 200 mg or 100 mg cimetidine when the drugs are used postprandially.

Rising death rate from non-malignant disease of the oesophagus (NMOD) in England and Wales.

Between 1968 and 1991, the number of deaths from non-malignant oesophageal disease (NMOD) (International Classification of Diseases code 530), recorded by the Office of Population Censuses and Surveys (OPCS) in England and Wales, trebled in women, from 118 to 340 (5 to 13 per million) and doubled in men, from 131 to 251 (5.5 to 10 per million). Calculation of age specific death rates, shows the increase to result from a rise in mortality in those over 75 years and age standardised mortality confirms a rise in overall frequency from 2.9 to 7.0 deaths per million men and 5.2 to 13.1 per million women. Between 1974 and 1988 when specific diagnoses were coded, deaths from oesophageal ulcer rose from 1.5 to 2.5 per million. In men, the death rate from oesophageal stricture increased from 2.5 to 3 per million and in women from 3.5 to 6 per million. Mortality from oesophageal perforation did not change (1 per million). Some of these changes reflect the increasing age of the population in general, but further explanations are required. Review of 84 sets of case notes from a total of 281 inpatients whose coded diagnoses had included NMOD and who had died suggested that in 28 (33%) death was actually due to NMOD, and in seven of these endoscopic intervention was responsible. The certified underlying cause of death was compared with that suggested from case note review in 62 cases; death from NMOD was substantially underestimated. This study concludes that a rising death rate attributed to NMOD is underestimated on death certificates and that endoscopic intervention explains only a few of the cases.

Optimizing acid suppression for treatment of acid-related diseases.

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.

Lack of effect of H2-receptor antagonists on the pharmacokinetics of alcohol consumed after food at lunchtime.

The possibility of a pharmacokinetic interaction between H2-receptor antagonists and alcohol consumed at lunchtime, was investigated in 24 healthy non-alcoholic male subjects, each receiving ranitidine 150 mg four times daily, cimetidine 400 mg four times daily, famotidine 20 mg four times daily and placebo in an open, four-way cross-over study. The subjects consumed 50 g alcohol after a standard lunch on the eighth day of dosing with study medication. Blood samples taken during the 6 h after alcohol consumption were analysed for alcohol concentrations by gas liquid chromatography using head space analysis. None of the H2-receptor antagonists had any statistically significant effects on any of the pharmacokinetic parameters for alcohol. Mean Cmax (95% CI) results for ranitidine were 547 (516, 580), cimetidine 531 (501, 563), famotidine 563 (530, 598) and placebo 529 (499, 561) mg l-1.

Duodenal ulcer treatment: progress from pH to HP.

The treatment of duodenal ulcer has evolved from ineffective medical treatments through an era of surgical management, back to increasingly effective medical treatment. The advent of H2-receptor antagonists changed the outlook for ulcer patients. More recently, Helicobacter pylori, an organism which inhabits gastric mucosa exclusively, has been implicated in the pathogenesis of peptic ulcer. This bacterium is found in the stomachs of around 95% of duodenal ulcer patients. Its eradication is shown dramatically to improve the rate at which ulcers relapse. The mechanisms whereby it may cause ulceration are not established--we review current hypotheses. No method of eradication is 100% effective, and many different dual or triple therapy regimens have been tried. Metronidazole resistance is reported but its importance is not yet known. Helicobacter eradication is likely to prove a cost-effective and acceptable treatment for duodenal ulcer, and once its value has gained acceptance widespread uptake of this option is anticipated.

Current management of bleeding peptic ulcer. A review.

In the United Kingdom, acute bleeding from peptic ulcer is estimated to account for 25 admissions to hospital per 100,000 population annually. Overall mortality has been reported at around 10%. Accurate initial assessment for the identification of high risk groups, prompt resuscitation, close monitoring and timely intervention for rebleeding improves survival. In patients not responding to initial resuscitation and those who rebleed, emergency endoscopy identifies the source of bleeding in the majority and is essential to enable endoscopic therapy. Injection of a vasoconstrictor and/or sclerosant into a visible or bleeding vessel, or thermal coagulation, reduces the incidence of rebleeding and probably decreases mortality. In general terms, 'early' surgical intervention is indicated for those aged over 60 years in whom bleeding recurs or continues despite endoscopic measures. The low mortality (< 5%) reported from specialist units and units adhering to strict protocols of management should become the norm. The use of antacids, histamine H2-receptor antagonists or omeprazole does not influence mortality or the incidence of early rebleeding in patients with acute haemorrhage from peptic ulcer. Although not used routinely, tranexamic acid has been shown to have significant benefit.

Continuous intravenous famotidine for haemorrhage from peptic ulcer.

Peptic ulcer bleeding often stops spontaneously but rebleeding may be catastrophic. Emergency surgery carries risks so safe medical therapies are needed. Since platelet function and plasma coagulation are both pH sensitive and since pepsin lyses clot at low pH the maintenance of gastric pH close to neutrality might influence rebleeding rates. Previous trials with H2 antagonists have been inadequate although a 1985 meta-analysis did support an important clinical effect. We report here a large multicentre trial of famotidine in ulcer bleeding. 1005 patients admitted to one of sixty-seven hospitals in the UK or Eire with haemorrhage from peptic ulcer with endoscopic signs of oozing, black slough, fresh clot or visible vessel were randomly allocated to famotidine (10 mg bolus followed by 3.2 mg/h intravenously) or matching placebo for 72 h. This famotidine regimen had previously been shown to maintain pH near 7 in such patients. 497 patients received famotidine and 508 placebo. The treatment groups were similar in respect of age, sex, ulcer site, and signs and severity of bleeding. Case fatality (6.2% famotidine vs 5.0% placebo), rebleeding (23.9% vs 25.5% placebo), and surgery (15.5% vs 17.1% placebo) rates were not significantly different between the two groups. This trial suggests that potent inhibition of gastric secretion does not influence the natural history of peptic ulcer haemorrhage.

Co-administration of misoprostol or ranitidine with indomethacin: effects on pharmacokinetics, abdominal symptoms and bowel habit.

This three-way randomized crossover study in 18 healthy male volunteers compared the pharmacokinetics of 50 mg indomethacin b.d. during concomitant twice daily dosing with 400 micrograms misoprostol, 150 mg ranitidine or placebo. Plasma indomethacin concentrations were determined by HPLC assay of samples collected over 12 h after the first dose, and over 14 h after the last dose on Day 8 of each dosing period. A daily diary of bowel habits, and the occurrence and severity of abdominal symptoms, was kept by each subject throughout the study. Statistical comparisons were made by analysis of variance. In the presence of misoprostol there was a 13% decrease in the area under the plasma concentration-time curve of indomethacin over one dosing interval on Day 1 (P less than 0.01), and at steady state there was a 24% decrease in the maximum plasma concentration (P less than 0.02). The pharmacokinetics of indomethacin were not affected by co-administration of ranitidine. Accumulation of indomethacin after repeated oral dosing was not significantly altered by the co-administration of either misoprostol or ranitidine. The frequency and severity of abdominal symptoms was significantly increased (P less than 0.01) during misoprostol dosing, compared with either ranitidine or placebo plus indomethacin. When the dosing phase (Days 1-8) was compared with the washout phase (Days 9-15) in each period, misoprostol, but not ranitidine or placebo, plus indomethacin resulted in an increase (P less than 0.001) in abdominal symptom severity, frequency of bowel motions and a decrease in faecal consistency.

Effects of oral pantoprazole on 24-hour intragastric acidity and plasma gastrin profiles.

Pantoprazole selectively blocks gastric parietal cell H+,K(+)-ATPase. To define a dosage regimen for clinical trials we compared the effect of pantoprazole 40 and 60 mg daily on 24-h intragastric acidity and plasma gastrin concentrations using a double-blind, randomized, cross-over design. Eleven men took each of the three regimens (placebo, 40, 60 mg) for 5 days. On Day 5, 24-h pHmetry and plasma gastrin profile were performed. A consistent decrease in intragastric acidity with each dosage regimen was shown by a rise in 24-h median pH from 1.4 (1.2-1.8, IQR) on placebo to 2.3 (1.8-4.4, P = 0.0022) during pantoprazole 40 mg and to 3.5 (2.6-4.9, P = 0.0017) during 60 mg. Pantoprazole 40 and 60 mg maintained the intragastric pH above 3 for 33% and 58% of time, respectively, compared with 15% time with placebo. Twenty-four-hour integrated plasma gastrin concentration rose from 478 to 1798 and 1962 pmol.h/L, respectively. The drug was well tolerated. The decrease of acidity was dose related and should result in clinical efficacy similar to other antisecretory drugs. It is not known whether higher doses might abolish acid secretion. The optimal dose of pantoprazole is yet to be established.