association between the corrected pressure and the random zero was examined for each site. The simple linear regression coefficients
were 0.02 (95 % confidence interval - 0.05 to 0.10), - 0.08 ( - 0.18 toO.02),and -0-16(-0-25to -0-06) in the arm and right and left ankles, respectively. We obtained closely similar results in another study of systolic pressures in 600 patients with intermittent claudication. The association with the random zero was much weaker than that reported by Kronmal and colleagues, who showed a regression coefficient of - 0-869 for systolic blood pressure. We have found the random zero sphygmomanometer satisfactory to use but the slow-release valve and random zero wheel are prone to sticking so that frequent maintenance is required. We can confirm, however, that observer bias is negligible.1 Wolfson Unit for Prevention of Peripheral Vascular Diseases. Department of Community Medicine, Edinburgh University Medical School, Edinburgh EH8 9AG, UK
C. C. A. MACINTYRE F. G. R. FOWKES
Macintyre CCA, Prescott RJ, Ruckley CV. Variability of systolic pressures in the measurement of atherosclerotic peripheral arterial disease. J Epidemiol Community Health 1988; 42: 128-33.
1. Fowkes FGR, Housley E,
ankle and brachial
Helicobacter gastritis and intestinal metaplasia in a gastric cancer family SiR,—Familial clustering of carcinoma of the gastrointestinal tract is well known. In some families the cancer forms part of the spectrum of the cancer family syndrome, which in Warthin’s original account1 contained a large number of stomach neoplasms, though large bowel cancers are more frequent, accounting for about 50% of cancers in these families.2 We have investigated a family, in which two of four siblings presented at an early age (under 40 years) with gastric cancer. A third had antrectomy for gastric dysplasia, and the fourth sibling has extensive chronic atrophic gastritis and intestinal metaplasia at age 36. We investigated their eight children by endoscopy and biopsy. The following biopsy specimens were taken from each child-one from the duodenum, two from the gastric antrum, and four from the fundus. Specimens were examined histologically for the presence of chronic gastritis, intestinal metaplasia, and Helicobacter pylori, with a modified giemsa technique. Of the eight children, five (63%) have H pylori-positive, chronic atrophic gastritis (age at diagnosis 10-26 years) and in three of the five (60%) intestinal metaplasia developed, at 21, 23, and 34 years of age, respectively (see figure). In all three intestinal metaplasia was found in the gastric antrum but not in the body. H pylori infection and intestinal metaplasia are unusual before age 30. Seropositivity was shown in less than 20% of a random population of blood donors aged under 30 with an ELISA technique3 and in a recent combined serological and histological study of 113 symptom-free volunteers H pylori infection was documented in 10% (histological) to 20% (serological) of the 18-29 year age group."* Intestinal metaplasia was present in only 4% of an unselected rural population in Sweden.s In Leeds, we have found
this condition in one of sixty-one dyspeptic patients under age 30 with Hpylori-associated gastritis (unpublished data), and in a large multicentre study6 in which a mean of 37 biopsy specimens were examined per case intestinal metaplasia was found in only 4% of individuals aged under 30. The early occurrence of gastritis and intestinal metaplasia in members of our family may reflect a genetic predisposition to the metaplasia/dysplasia/carcinoma sequence described by û>rrea.1 More specifically, intestinal metaplasia arising in three out of five H pylori infected offspring would be consistent with a dominant pattern of inheritance for a gene concerned with the development of intestinal metaplasia. We postulate that H pylori acts as a promoter in the progression from normal to metaplastic epithelium, possibly by inducing a hyperproliferative state in the inflamed gastric mucosa. Eradication of the organism under these circumstances may remove a potential promoter and thus reduce the risk of gastric cancer.
Susceptibilty to cancer and gastritis in relatives of gastric cancer patients has been well documented. In most cases, however, increased risk has been confined to tumours classified as "diffuse" by Lauren’s histological criteria.8 Both tumours in the present study were of the "intestinal" type. This is in keeping with the carcinogenic sequence we propose and may reflect neoplastic development on a genetic basis different from that in diffuse type carcinomas. Departments of Pathology, Surgery, and Gastroenterology, Leeds General Infirmary, Leeds LS2 9JT, UK; ICRF Genetic Epidemiology Unit, University of Leeds; and Department of Pathology, St James’ Hospital
N. SCOTT M. LANSDOWN R. DIAMENT B. RATHBONE V. MURDAY J. I. WYATT M. MCMAHON M. F. DIXON P. QUIRKE
1. Warthin AS. Heredity with reference to carcinoma. Arch Intern Med 1913; 12: 546-55. 2. Lynch HT, Lynch PM, Albano WA, Lynch JF. The cancer syndrome: a status report.
Dis Col Rect 1981; 24: 311-22. 3.
Wyatt JI, Rathbone BJ. The role of serology in the diagnosis of Campylobacter pylori infection. Scand J Gastroenterol 1989; 24 (suppl 160): 27-34. 4. Dooley CP, Cohen H, Fitzgibbons PL, et al. Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med 1989; 23: 1562-66. 5. Siurala M, Isokoski M, Varis K, Kekki M. Prevalence of gastritis in a rural population Scand J Gastroentrol 1968; 3: 211-23. 6. Filipe MI, Potet F, Bogomoletz WV, et al. Incomplete sulphomucin-secreting intestinal metaplasia for gastric cancer: preliminary data from a prospective study from three centres. Gut 1985; 26: 1319-26. 7. Correa P. A human model of gastric carcinogenesis. Cancer Res 1988; 48: 3554-60. 8. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. Acta Path Microbiol Scand 1965; 64: 31-49.
Helicobacter pylori, mucus, and ulcer
SIR,—Dr Sidebotham and Dr Baron (Jan 27, p 193) propose that Helicobacter pylori promotes gastric ulcer formation by means of its deleterious effect on gastric mucus. Their hypothesis closely resembles my suggestion that the microorganism alters the quality of mucus by means of urease production and that impaired mucus secretion may play a part in ulcer recurrence.1 Experiments support the view that H pylori does include changes in the structure of mucus, degrading both mucus glycoprotein2 and gastric mucosal lipids,3with a consequent reduction in the viscosity of the mucus
0=female, 0’=deceased, C=heHcobacter gastritis,
(3= gastric carcinoma, (gastric dysplasia, C’ltestinai metaplasia, -
biopsy material available.
We should concede, however, that the observations on mucus permeability to H + ions under the effect of H pylori are somewhat conflicting2,4 and that the sequence of events can take place in reverse. I certainly concur that in gastric ulcer patients gastric mucus is qualitatively altered,5 but whether this is secondary to H pylori infection rather than a primary occurrence remains uncertain. In fact, my experience is that the quality of mucus in chronic non-erosive gastritis-a disorder closely associated with H pylori infection-is normal. It is possible that in gastric ulcer a primary defect in mucus structure allows colonisation of the mucosa by H pylori, which in turn can further alter mucus characteristics and lead to yet more damage to gastric mucosa."* This would