D. J. B. St. John

Regeneration of gastric mucosa after aspirin-induced injury in the rat

Regeneration of gastric mucosa damaged by aspirin was studied in 6-week-old rats, using histologic and autoradiographic technics. Aspirin (120 mg/kg) was given by esophageal intubation either in a single dose or each day for 14 days. After a single dose, two types of lesion were observed in the mucosa of the body of the stomach: (a) superficial erosions which were already present after 30 minutes and which completely healed within 24 hours; (b) deeper erosions, reaching maximal numbers at 4 hours, which healed slowly with a median disappearance time of 5 days and which were associated with a focal increase in3H-thymidine-labeled cells. The peak increase in labeling occurred between 16 and 48 hours. The pattern and rate of healing was not altered by repeated daily aspirin. The investigation has demonstrated slow healing of deep mucosal erosions caused by aspirin; the slow healing can be explained by destruction of the progenitor zone by the initial injury.Regeneration of gastric mucosa damaged by aspirin was studied in 6-week-old rats, using histologic and autoradiographic technics. Aspirin (120 mg/kg) was given by esophageal intubation either in a single dose or each day for 14 days. After a single dose, two types of lesion were observed in the mucosa of the body of the stomach: (a) superficial erosions which were already present after 30 minutes and which completely healed within 24 hours; (b) deeper erosions, reaching maximal numbers at 4 hours, which healed slowly with a median disappearance time of 5 days and which were associated with a focal increase in3H-thymidine-labeled cells. The peak increase in labeling occurred between 16 and 48 hours. The pattern and rate of healing was not altered by repeated daily aspirin. The investigation has demonstrated slow healing of deep mucosal erosions caused by aspirin; the slow healing can be explained by destruction of the progenitor zone by the initial injury.

Influence of achlorhydria on aspirin-induced occult gastrointestinal blood loss: studies in Addisonian pernicious anaemia.

The effect of aspirin (acetylsalicylic acid) ingestion on occult gastrointestinal blood loss has been studied in patients with treated Addisonian pernicious anaemia and proved achlorhydria and in control patients able to secrete hydrochloric acid. A highly significant increase in gastrointestinal blood loss (1·9 ml./day of treatment) occurred with aspirin ingestion in the achlorhydric patients. The control group had a significantly greater increase in blood loss (4·29 ml./day of treatment). Thus aspirin can produce occult gastrointestinal blood loss by a mechanism unrelated to hydrochloric acid. Half of the control patients had losses of similar magnitude to those in the pernicious anaemia group, and the degree of blood loss in individual control patients appeared unrelated to gastric acidity. Differences in gastric mucosal characteristics, in the rate of gastric emptying, or in systemic effects of aspirin may explain the variation between individuals in the degree of occult gastrointestinal blood loss after aspirin.

Ultrastructure and cytochemistry of the gastric mucosa of a reptile, Tiliqua scincoides.

SummaryThe gastric mucosa of a reptile, the lizard Tiliqua scincoides, has been examined by light and electron microscopy. The gastric pits lead into glands that are extensively coiled in the proximal stomach but become progressively shorter and straighter in the distal stomach. The following epithelial cell types have been identified: (i) Surface mucous cells (SMC) line the entire lumenal surface as well as the pits. They contain mucus granules that stain with periodic acid-Schiff and, like the granules of mammalian SMC, commonly contain an electron dense core that appears not to be mucus (periodic acid-chromic acid-silver methenamine nonreactive). (ii) Glandular mucous cells are present in glands throughout the mucosa. They are probably homologous with the mucous neck and antral gland cells of mammals; like SMC their mucus granules contain nonglycoprotein cores. (iii) Oxynticopeptic cells (OPC) are the predominant cell type in the proximal glands but become infrequent distally. Their fine structure resembles that of OPC in other nonmammalian vertebrates, with features like those of both parietal cells and zymogen cells of mammals, (iv) Endocrine cells of three different types have been identified. Two of these show close similarities to the EC and ECL cells of mammals.

The Mallory-Weiss Syndrome

A policy of immediate investigation of patients with haematemesis or melaena or both led to the diagnosis of the Mallory-Weiss syndrome in 16 out of 121 patients admitted to a combined medical-surgical unit over three and a half years. A typical history suggestive of the diagnosis was obtainable in only nine of the 16 patients, though recent alcohol intake was high in another four. All patients survived the episode. Establishment of the diagnosis by oesophagogastroscopy was of special benefit when surgery was needed for control of continuing blood loss, but it also simplified the subsequent medical management of those patients in whom bleeding stopped spontaneously. The incidence of 13·2% in this series suggests that the Mallory-Weiss syndrome may be a relatively common cause of upper gastrointestinal bleeding.

Prescreening evaluation of a brush-based faecal immunochemical test for haemoglobin

OBJECTIVES To undertake a prescreening evaluation of a new brush-based faecal immunochemical test for haemoglobin, relative to a traditional spatula-sampling immunochemical test. METHODS SETTING Patients aged between 24 and 90 years, scheduled to undergo diagnostic colonoscopy in two major urban hospitals, for a range of clinical indications. DESIGN Patients sampled three stools using a spatula for the reference FlexSure OBT test and two stools using a brush for the InSure test; order of sampling was randomised. Faecal haemoglobin was quantified by a modified InSure in a subset of patients to determine whether brush-sampling allowed discrimination between groups. MAIN OUTCOME MEASURES Sensitivity for cancer or adenoma; false-positive rate in normals. Faecal haemoglobin levels. Preference for sampling method. RESULTS InSure and FlexSure OBT did not differ in their sensitivities for cancer (27/36, 75% vs 29/36, 80.5%, respectively), adenomas >or= 10 mm (12/29, 41.4% vs 13/29, 44.8%) or adenomas <10 mm (each 8/56, 14.3%). Likewise, false-positive rates in normals were similar: 4/179 (2.2%) and 5/179 (2.8%) respectively (specificities of 97.8% and 97.2%, respectively). Levels of faecal haemoglobin were highest in those with cancers; those with adenomas had intermediate levels which were also significantly higher than those in normals. The brush sampling method was preferred by 38/46 (82.6%), while 4/46 (8.7%) preferred the spatula (p<0.00001). CONCLUSIONS InSure is as sensitive and specific as FlexSure OBT for faecal haemoglobin. The novel stool-sampling method of InSure allows discrimination between normals and classes of neoplasia, and is highly preferred. The brush-sampling faecal immunochemical test InSure should now be evaluated in a screening population.

Effect of carbenoxolone sodium on aspirin-induced injury of the rat gastric mucosa

Investigations were performed in the rat to examine the effect of carbenoxolone sodium on aspirin-induced gastric mucosal injury. Mucosal damage was quantitated histologically in the body of the stomach (corpus) after a single dose of aspirin and after 2 weeks of daily aspirin. Over dosage ranges of 2–30 mg/kg/day of carbenoxolone and 10–120 mg/kg of aspirin, carbenoxolone treatment conferred no protection, despite evidence of a significant carbenoxolone effect on gastric mucus. This contrasts with the known protective action of carbenoxolone against injury by restraint stress and by corticosteroids. Much current evidence suggests that the mechanisms of erosion production by aspirin differ from those by restraint stress and corticosteroids, and it is likely that the present findings reflect such differences in pathogenesis.Investigations were performed in the rat to examine the effect of carbenoxolone sodium on aspirin-induced gastric mucosal injury. Mucosal damage was quantitated histologically in the body of the stomach (corpus) after a single dose of aspirin and after 2 weeks of daily aspirin. Over dosage ranges of 2–30 mg/kg/day of carbenoxolone and 10–120 mg/kg of aspirin, carbenoxolone treatment conferred no protection, despite evidence of a significant carbenoxolone effect on gastric mucus. This contrasts with the known protective action of carbenoxolone against injury by restraint stress and by corticosteroids. Much current evidence suggests that the mechanisms of erosion production by aspirin differ from those by restraint stress and corticosteroids, and it is likely that the present findings reflect such differences in pathogenesis.

Small Intestinal Malabsorption of Vitamin B12 In Iron-Deficient Rats

Summary Rats were rendered iron deficient by a combination of diet and bleeding to study its effects on vitamin B12 absorption. Small intestinal loops were isolated in vivo and the absorption of 57Co‐vitamin B12 bound to a known quantity of intrinsic factor was measured. Iron deficiency resulted in the impairment of both uptake and transport of B12. This malabsorption was corrected within 5 days by parenteral iron repletion. The findings were not due to a non‐specific effect of anaemia since no correlation existed between haemoglobin levels and B12 absorption in rats anaemic as a result of acute blood loss. No evidence was found for an altered small‐intestinal microflora, bacterial counts being similar in iron‐deficient and control rats. It is concluded that iron deficiency in the rat results in impaired absorption of B12 by the small intestine, probably as a result of some defect produced in the enterocyte.

Measurement of occult upper gastrointestinal tract blood loss: A direct comparison of radiochromium and haem-porphyrin assay techniques

Faecal haem‐porphyrin assay by the HemoQuantTM method has many practical advantages over the well‐validated, radiochromium (51Cr‐tagged red cell) method for measuring gastrointestinal blood loss. Because haem may be absorbed but the chromic ion is not, the two measures were directly compared in low‐grade bleeding from the proximal gastrointestinal tract. Blood loss was measured by both methods simultaneously in 40 patients with osteoarthritis before and during medication with aspirin preparations. Mean (geometric) daily blood loss before aspirin usage measured 0.60 mL by radiochromium (range 0.13–1.62) and 0.47 mL (0.14–1.40) by HemoQuantTM (P= 0.042). On aspirin, bleeding rose to 1.57 mL/day (0.43–4.85) by radiochromium and to 0.72 mL/day (0.23–3.0) by HemoQuantTM (P≤ 0.0001). The two measures correlated well, r= 0.847 (P≤ 0.0001), but the regression coefficient was 0.417, reflecting the lower estimates of bleeding by HemoQuantTM. In four normal subjects who ingested 51Cr‐labelled red cells (26–41 mL) over 3 days, recovery of 51Cr was complete (103 ± 2%, ± s.e.), but recovery of haem‐porphyrins was only 63 ± 13% (P= 0.01), presumably because of absorption of haem. Although faecal haem‐prophyrin assay is of considerable clinical utility, it is a quantitative index rather than an absolute measure when low amounts of bleeding originate from the proximal gastrointestinal tract.

Screening tests for colorectal neoplasia

.. I he Working Party reviewed the tests that are currently available for screening for colorectal neoplasia (Table 1) and the technical factors that affect selection of a screening test and outcome of screening programmes (Table 2). Although technical PdctorS have an important role in influencing recommendations, selection of screening tests also depends upon the ~ y p r of risk and the level of’ risk that an individual has for colorectal cancer. Special strategies for patients with ulcerative colitis and for at-risk members of families with familial adenomatous polvposis will be presented later in this report. In most situations, screening is based on regglar Cdccal occult blood testing, preferably combined with flexible sigmoidoscopy performed once every 3-5 years. When Family medical history indicates an increased level of risk for colorectal cancer, greater security can he provided by starting screening at an earlier age (e.g. at 40 years rather than at 50 years), by increasing the frequency of testing and/or by combining occult blood testing with periodic colonoscopy rather than sigmoidoscopy. Another option is to change the type of faecal occult blood test, using a more sensitive test for groups with a higher prevalence of disease.

Managing Surveillance for Colorectal Cancer: The Importance of Microcomputers

Large scale screening programmes for colorectal cancer based on genetic risk are difficult to administer because of the need to identify at-risk family members and ensure that surveillance proceeds in an orderly fashion over a lifetime. As at August 1989, 1100 high risk persons have been registered with the Royal Melbourne Hospital Surveillance Programme. Categorisation of risk is done after evaluation of the family’s history of cancer. Surveillance protocols are then defined based on the intensity of cancer in the family. Annual occult blood testing is performed in all groups. Colonoscopy is performed every 2 years on at-risk members of families with hereditary non-polyposis colon cancer syndromes (n = 35 families) and 3 to 5 yearly for individuals with two or more first-degree relatives with sporadic colorectal cancer. Flexible sigmoidoscopy is performed every 3 years on some individuals with one affected first-degree relative, particularly where there are other affected relatives more remotely placed in the family. Patients who have had an adenoma/cancer undergo 3-yearly colonoscopy.