Knowledge, attitudes and behaviours concerning cancer screening in Canada.

The Advisory Committee on Cancer Control funded a one-day workshop to discuss the surveillance of knowledge, attitudes/beliefs and behaviours concerning early cancer detection in Canada. Participants considered the need for such national surveillance and related methodological issues. Some exploratory work has been conducted in this regard. Results were presented from an inventory of existing survey questions and a summary of established cancer screening guidelines. There was overall agreement on the utility of collecting details of early cancer detection behaviours and their determinants. Explicitly, participants identified a need for site-specific information, highlighting cancers of the prostate and colon/rectum, as well as recognizing a need for qualitative information regarding the determinants that enable early cancer detection behaviours.

Effect of enprostil on amphibian gastroduodenal and human gastric bicarbonate secretion.

The protective and ulcer healing properties of prostaglandins are well established. We have explored the possible mode of action of enprostil, a synthetic dehydroprostaglandin E2, on amphibian gastroduodenal mucosal bicarbonate secretion in vitro and on human gastric bicarbonate secretion in vivo. Addition of enprostil (10(-6) M) to the luminal solution of isolated amphibian gastric mucosa produced a 28% increase in bicarbonate secretion without a change in transmucosal potential difference. The same concentration of enprostil added to the luminal solution of isolated amphibian duodenal mucosa produced a 37% increase in bicarbonate secretion and was associated with a rise in transmucosal potential difference. The gastric output of bicarbonate from the human stomach has been calculated using a perfusion technique before, during, and after perfusion with enprostil (35 micrograms) in six healthy volunteers. A significant 78% increase in bicarbonate secretion occurred during the period of enprostil perfusion, falling to normal during the postenprostil period. These changes were caused mainly by an increase in gastric secretory volume with insignificant increases in bicarbonate concentration. These results suggest that stimulation of gastroduodenal bicarbonate secretion by enprostil may play a role in its protective actions.

Effect of bismuth subcitrate on amphibian gastroduodenal bicarbonate secretion.

The ulcer healing and cytoprotective properties of colloidal bismuth (De-Nol) are well established although its mode of action is unclear. We have examined the action of bismuth subcitrate, the active ingredient of De-Nol, on gastroduodenal bicarbonate secretion by isolated amphibian mucosa. Addition of bismuth subcitrate (10(-6) to 10(-4) M) to the luminal solution produced a dose dependent increase in bicarbonate secretion from both gastric and duodenal mucosae without a change in transmucosal potential difference. The magnitude of this stimulation was greater for gastric than duodenal mucosae at all dose ranges. A second bismuth salt, bismuth oxynitrate, produced similar increases in bicarbonate secretion from gastric mucosae. Pretreatment of gastric mucosa with the cyclooxygenase inhibitor, indomethacin (10(-5) and 10(-4) M), did not abolish the secretory response to bismuth subcitrate. Similar treatment with the chloride transport inhibitor, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) (10(-3) M) prevented the secretory response to bismuth subcitrate.

Stimulation of amphibian gastroduodenal bicarbonate secretion by sucralfate and aluminium: role of local prostaglandin metabolism.

The present studies were designed to explore the possible mode of protective and ulcer healing actions of sucralfate by examining its effect on gastroduodenal bicarbonate secretion by isolated amphibian mucosa. Luminal sucralfate (0.5 g/l) significantly increased bicarbonate secretion by fundic and antral mucosa without influencing transmucosal potential difference. Significant stimulation of duodenal bicarbonate secretion occurred only at 1.0 g/l without change in potential difference. Aluminium, a component of sucralfate, produced similar increases in bicarbonate secretion, while the sucrose and sulphate components were without effect. Pretreatment of mucosae with the cyclooxygenase inhibitor, indomethacin (10 5M) did not abolish the secretory response to sucralfate or aluminium. The results suggest that stimulation of gastroduodenal bicarbonate secretion, possibly by the aluminium moiety of sucralfate, may play a role in its protective and ulcer healing actions.

Effect of luminal pH on the output of bicarbonate and PGE2 by the normal human stomach.

The gastric output of bicarbonate and prostaglandin E2 has been calculated using a perfusion technique before and after instillation of 100 mM hydrochloric acid into the stomach of seven healthy volunteers. A significant increase in bicarbonate output occurred from 258 +/- 38 mumol/30 min during the basal period to 531 +/- 86 mumol/30 min after return of the intragastric pH to neutral (p less than 0.05). Prostaglandin E2 output also increased significantly from 410 +/- 136 pmol/30 min to 1002 +/- 194 pmol/30 min (p less than 0.05). The changes were caused mainly by an increase in gastric secretory volume with only non-significant increases in concentrations of bicarbonate and prostaglandin E2. The results suggest that mechanisms exist to adjust the rate of gastric bicarbonate secretion to the prevailing intraluminal pH and that this may occur through the release of prostaglandin E2.

Effects of sucralfate on gastroduodenal bicarbonate secretion and prostaglandin E2 metabolism.

The mechanism of action of sucralfate has been investigated. Using homogenized rabbit mucosa, the drug increased arachidonic acid conversion to prostaglandin E2 without affecting catabolism. Luminal administration of sucralfate (0.5 g/liter) caused marked stimulation of bicarbonate secretion by isolated amphibian gastric mucosa but not duodenal mucosa. In a higher dose (1 g/liter), duodenal bicarbonate secretion was also stimulated. These effects are likely to be due to endogenous prostaglandin formation since they are inhibited by indomethacin. The results suggest that the cytoprotective action of sucralfate is due to stimulation of endogenous prostaglandin formation and may involve various mucosal defensive factors.

Simultaneous measurement of in vitro gastroduodenal prostaglandin E2 synthesis and degradation in peptic ulcer disease.

The ability of mucosal specimens from the stomach and duodenum to synthesize and degrade prostaglandin E2 has been determined in normal subjects and peptic ulcer patients. Significant reduction in fundic PGE2 synthesis capacity was observed in gastric ulcer patients. There was also significant reduction in the PGE2 degradation capacity of antral, fundic, and duodenal mucosal specimens in gastric ulcer patients. Patients with gastritis showed significant elevation of both antral and fundic PGE2 synthesis capacity compared with normal but no alteration in PGE2 degradation. No differences were observed in PGE2 synthesis and degradation rates in patients with duodenal ulcer. The results argue in favour of an association between impairment of PGE2 metabolism in the mucosa of patients with gastric but not duodenal ulceration.

Effect of sucralfate on gastroduodenal bicarbonate secretion and mucosal prostaglandin E2 metabolism.

The effect of sucralfate on gastroduodenal bicarbonate secretion has been examined using isolated amphibian mucosa. Significant increases in gastric bicarbonate secretory rate were seen following addition of 0.5 milligram sucralfate to the luminal solution. Duodenal alkali secretion was stimulated only by a higher concentration of 1 milligram. Pretreatment with indomethacin prevented the increases in gastric and duodenal bicarbonate secretion observed after sucralfate. Other experiments indicated that sucralfate caused stimulation of prostaglandin E2 formation by mucosal homogenates. These studies demonstrate that sucralfate is a potent stimulant of gastroduodenal bicarbonate secretion and that the action is dependent on mucosal prostaglandin formation. These effects are likely to play an important role in the mode of action of the drug.

Influence of opiates on alkali secretion by amphibian gastric and duodenal mucosa in vitro.

Experiments were performed to study the effects of opiates on gastric and duodenal alkali secretion in amphibian mucosa in vitro. Alkali secretion by fundic mucosa of Rana temporaria, or antral mucosa of Rana catesbeiana, was unaffected by morphine, methionine-enkephalin and leucine-enkephalin, two enkephalin analogues, or the opiate antagonist naloxone. Acid secretion by fundic mucosa in vitro was not influenced by 10(-5) and 10(-4) M morphine, or by 10(-7) to 10(-5) M naloxone. However, duodenal alkali secretion in Rana catesbeiana was stimulated by opiates while the electrical potential difference was unaffected. Morphine stimulated secretion, maximally at 10(-5) M, by 33% over basal values, 30 min after exposure to the drug, whereas the maximal response to methionine-enkephalin occurred at 10(-6) M and was obvious within the first 15 min after administration. The effects of these opiates were prevented by pretreatment with naloxone or with the more specific opiate receptor antagonist ICI 154129. The response to morphine was inhibited when bicarbonate in the nutrient-side solution was replaced by the impermeant anion HEPES or by removal of chloride from the bathing media. Furosemide (10(-3) M) also inhibited the response of duodenal mucosa to morphine. The nerve-blocker tetrodotoxin (10(-7) M) prevented the morphine-induced response. These data suggest that opiates can stimulate duodenal alkali secretion, probably by activating an electrically neutral Cl-/HCO3- exchange. It seems likely that the effect of opiates is mediated by a neurologic intermediary, and the results suggest the possibility that duodenal alkali secretion may be under some neurologic control.

Effect of certain ulcer-healing agents on amphibian gastroduodenal bicarbonate secretion.

The effect of luminal application of aluminum sulphate, sucralfate, and bismuth subcitrate on gastroduodenal alkali secretion has been studied with isolated amphibian mucosa. The mucosa, stripped of its external muscle layer, was mounted in chambers that allowed titration of alkali secretion and measurement of transmucosal potential difference and electrical resistance. Neutral aluminum sulphate (3 X 10(-3) M) increased bicarbonate secretion by fundic (mean +/- SEM = 144 +/- 48%, n = 5, P less than 0.05), antral (mean +/- SEM = 214 +/- 63%, n = 4, P less than 0.05), and duodenal (mean +/- SEM = 133 +/- 44%, n = 6, P less than 0.005) mucosa. Sucralfate (0.5 g/l) stimulated fundic (mean +/- SEM = 183 +/- 87%, n = 4, P less than 0.05) and antral (mean +/- SEM = 156 +/- 58%, n = 5, P less than 0.005) alkali secretion and, at a concentration of 1 g/l, duodenal output (mean +/- SEM = 42 +/- 15%, n = 6, P less than 0.05). Bismuth subcitrate (10(-4) M) produced a significant rise in fundic (mean +/- SEM = 80 +/- 21%, n = 5, P less than 0.05) and duodenal (mean +/- SEM = 62 +/- 7%, n = 6, P less than 0.05) alkali secretion. None of these agents altered transmucosal potential difference or electrical resistance. The actions of these agents on gastroduodenal bicarbonate secretion may be important in their ulcer healing effects.

Alkali secretion by isolated rabbit gastric mucosa: effects of non-steroidal anti-inflammatory drugs and prostaglandins.

The effects of aspirin, indomethacin and prostaglandins E2 and F2 alpha on the secretory and electrical activity of isolated rabbit gastric mucosa have been studied. Serosal side application of indomethacin (10(-5) M) or aspirin (3 X 10(-3) M) inhibited alkali secretion by fundic mucosa (mean +/- SE: 0.55 +/- 0.06 to 0.12 +/- 0.06 mumol X cm-2 X h-1, n = 6, p less than 0.01 and 0.28 +/- 0.06 to 0.11 +/- 0.03 mumol X cm-2 X h-1, n = 7, p less than 0.02 respectively) and antral mucosa (0.80 +/- 0.03 to 0.53 +/- 0.21 mumol X cm-2 X h-1, n = 5, p less than 0.01 and 0.75 +/- 0.23 to 0.47 +/- 0.20 mumol X cm-2 X h-1, n = 8, p less than 0.01 respectively). Mucosal and serosal side application of prostaglandin E2 or F2 alpha (10(-10) to 10(-4) M) had no effect on gastric alkali secretion. Serosal side 16,16 dimethyl E2 (10(-6) M) stimulated alkali secretion by fundic mucosa (0.90 +/- 0.20 to 1.50 +/- 0.30 mumol X cm-2 X h-1, n = 6, p less than 0.01) and abolished the inhibition of alkali production caused by indomethacin in fundic and antral mucosae. Inhibition of alkali secretion by aspirin was not modified by 16,16 dimethyl E2 pretreatment. The findings suggest that mucosal damage by aspirin and indomethacin may be mediated by inhibition of alkali secretion and that the protective action of various prostaglandins are only partly related to effects on this secretion.

Effects of non-steroidal anti-inflammatory drugs and prostaglandins on alkali secretion by rabbit gastric fundus in vitro.

The effects of non-steroidal anti-inflammatory drugs and prostaglandins E(2) and F(2alpha) on the secretory and electrical activity of isolated rabbit fundic mucosa have been studied. Spontaneous acid secretion was inhibited by serosal side application of sodium thiocyanate (6x10(-2)M) and the resulting alkali secretion measured by pH stat tiration. Serosal side application of indomethacin (10(-5)M) or aspirin (3x10(-3)M) inhibited alkali secretion (0.55+/-0.06 to 0.12+/-0.06 mumol/cm(2)/h, n=6, p<0.01 and 0.28+/-0.06 to 0.11+/-0.03 mumol/cm(2)/h, n=7, p<0.02 respectively). Mucosal or serosal side prostaglandin E(2) (10(-5) to 10(-10)M) and F(2alpha) (10(-4) to 10(-10)M) failed to alter the rate of alkalinisation but secretion was significantly increased by serosal side 16,16-dimethyl-prostaglandin E(2) (10(-6)M) (0.90+/-0.20 to 1.50+/-0.30 mumol/cm(2)/h, n=6, p<0.01). Serosal side application of 10(-6)M prostaglandin E(2) to fundic mucosae pretreated with either aspirin (5x10(-3)M) or indomethacin (10(-5)M), to reduce endogenous E(2) formation, also failed to alter alkali secretion. Pretreatment of the mucosa with 16,16-dimethyl-E(2) (10(-6)M) abolished the inhibitory effect of indomethacin (10(-5)M) on alkali secretion (n=6) but did not modify the secretory response to aspirin (3x10(-3)M) (fall in alkali secretion with aspirin = 81+/-11% and with aspirin plus 16,16-dimethyl-E(2) = 72+/-10%, n=7). In the doses used, none of the prostaglandins or non-steroidal anti-inflammatory drugs altered transmucosal potential difference or electrical resistance. These results show that the damaging agents, aspirin and indomethacin, both inhibit gastric alkali secretion but that modes of action may differ. The observation that prostaglandins, E(2) and F(2alpha) failed to increase alkali production suggests that their protective activity against a variety of damaging agents as shown by others, may be mediated by another mechanism.