A tale of two sisters.

Hereditary haemochromatosis is the most common inherited disorder in white populations, whereas non-alcoholic steatohepatitis (NASH) is becoming the most common reason for referral for investigation of abnormal liver function tests (LFTs). This report describes two sisters, from similar environments, who were referred to the clinic after being found to be C282Y homozygotes and to have abnormal LFTs. One sister had developed features of haemochromatosis and the other had developed NASH. These cases illustrate the potential non-penetrance of HFE gene mutations and the need to investigate abnormal LFTs fully, even when there is a positive genetic test at the outset.

Low-dose famotidine and effervescent cimetidine in healthy subjects: a placebo-controlled overnight pH study.

BACKGROUND: Amongst the low-dose H2-receptor antagonists available for the self-medication of dyspepsia, both famotidine 10 mg and cimetidine 200 mg have been shown to raise intragastric pH, but there is a delay after ingestion before significant effects can be demonstrated. A new effervescent preparation of cimetidine 200 mg releases an acid buffer which has a more rapid effect on intragastric pH. AIM: To investigate the relative abilities of low-dose famotidine and effervescent cimetidine to raise intragastric pH after a single postprandial evening dose. METHODS: Twenty-four healthy subjects (12 men, 12 women, median age 32 years) completed a three-period crossover trial of famotidine 10 mg, effervescent cimetidine 200 mg and placebo. After a standard meal was given at 18.30 h to subjects fasted for 5.5 h, drug or placebo was given at 19.30 h. Intragastric pH was recorded with combined glass electrodes from 18.00 to 07.30 h by digital recorders. RESULTS: Over the 12 h post-dose period the mean area under the pH/time curve (AUC) after famotidine 10 mg was 3.73, after cimetidine 200 mg effervescent 2.79, and after placebo 2.07. Over the same period the median pH and percentage of time that recordings were above pH 3 were 3.45 and 52.5 after famotidine 10 mg, 2.40 and 33.8 after cimetidine 200 mg effervescent, and 1.68 and 15.9 after placebo. Both active treatments were significantly different from placebo by each measure (P < 0.001), and famotidine 10 mg was significantly more effective than cimetidine 200 mg effervescent by each measure over the 0-12 h period (P < 0.001). Comparisons of mean AUCs for each 15 min period after dosing showed that decrease in acidity was significantly greater after cimetidine 200 mg effervescent than after famotidine 10 mg for the first 60 min. In the later post-dose period only famotidine 10 mg raised pH for all time points to 12 h, whilst the effect of effervescent cimetidine 200 mg was detectable to = 8 h. CONCLUSIONS: Inhibition of gastric acidity over the 12 h post-dose period was significantly greater and endured longer after famotidine 10 mg than after effervescent cimetidine 200 mg, but for the 60 min period immediately after dosing the effect on intragastric pH was significant following effervescent cimetidine 200 mg but not famotidine 10 mg. This suggests effervescent formulations of H2-receptor antagonists with an acid buffer have a more rapid effect on intragastric pH than film-coated tablets.

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.

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.