J. Spencer

Histamine and duodenal ulcer: effect of omeprazole on gastric histamine in patients with duodenal ulcer.

Gastric mucosal concentrations of histamine and of its metabolic enzyme, histamine methyltransferase activity, were measured in patients with duodenal ulcer disease and patients with an apparently normal stomach and duodenum. Patients with duodenal ulcer had significantly less (p less than 0.05) mucosal histamine (median 204 nmol/g) than control subjects (median 252 nmol/g). There was no significant difference between the two groups in their histamine methyltransferase activity values. Omeprazole therapy did not significantly change mucosal histamine (+23%), histamine methyltransferase activity (+5%), histamine release before (+5%) or during (+7%) pentagastrin infusion. It significantly decreased acid secretion during pentagastrin stimulation (median -73%, p less than 0.001). Omeprazole, like cimetidine, does not stop histamine release during pentagastrin stimulation.

Drug-Induced Colonic Pseudo- Obstruction Report of a Case

Colonic pseudo-obstruction may have many possible causes. Some of these are well described and pose no diagnostic problems. Drug-related colonic pseudo-obstruction remains underreported, but is of importance in modern society where drugs are endemically abused. This case highlights the importance of drugs in altering colonic motility and emphasizes the nonsurgical management of this condition.

Acid blockade by omeprazole or ICI 162846 in a chronic duodenal ulcer model

Oral treatment with the H2-antagonist ICI 162,846 or omeprazole for five days inhibited both basal and pentagastrin stimulated acid secretion by 50% or more in mice. Either treatment increased the luminal secretion of histamine in the basal (12-fold) and stimulated (9-fold) states. Mice treated with the H2-antagonist had a 27% reduction (p<0.05) in mural histamine in the acid-producing area of the stomach. Mice were treated so as to induce duodenal ulcers (abscopal model) and were then treated with the H2-antagonist ICI 162,846, omeprazole or vehicle, orally for one week. Fewer duodenal ulcers were found in animals receiving drug treatments than in the oral vehicle group. Both the H2-receptor antagonist and the proton pump blocker inhibit acid production; acid blockade by either drug is accompanied by a massive increase in secretion of histamine. This rise was associated with depletion of the gastric histamine store only with H2-receptor blocker. Both means of acid inhibition reduced the formation of ulcers in this model.

Effect of gastric irradiation on gastric secretion and histamine in mice.

Gastric irradiation selectively inhibits acid secretion. Histamine may have a role in the inhibitory process. Seven days after gastric irradiation with 9 Gy X-rays, mice underwent a stomach perfusion and secretion test. Under pentagastrin stimulation (62.5 μg/kg), acid and histamine secretion was significantly lower than that of the unirradiated controls, while pepsin and potassium outputs were unchanged. Histamine concentration in the oxyntic region of the stomach assayed after the perfusion test was significantly lower than that of controls. It is postulated that the fall in the endogenous histamine store may contribute to the reduction in acid production.

Embolisation in colonic bleeding

Although therapeutic embolisation has been employed extensively in the control of upper gastrointestinal bleeding (Athanasoulis, 1982), considerable caution has been exercised with regard to its use in colonic bleeding because of the risk of bowel ischaemia. The following case illustrates the successful application of colonic embolisation in a particularly difficult clinical situation. A 50-year old man was admitted as an emergency with profuse rectal bleeding. On examination he was shocked (BP 90/60; pulse 110/min; respiration 40/min). The abdomen was normal to palpation and there was bright red blood on rectal examination. There was a history of two previous similar episodes in the past six years; on both occasions the bleeding had stopped spontaneously, and a barium enema after the second episode had revealed diverticula throughout the colon.

Duodenal ulcer: a model of impaired mucosal defence.

There is a new model of chronic duodenal ulcer in which the ulcer is generated by irradiating the lower mediastinum of mice with a single dose of 18 Gy 250 kV x rays. Single ulcers develop in the proximal duodenum of about half the animals. Previous studies have shown a remarkable morphological and behavioural similarity to duodenal ulcer in man. Ulceration occurs because of an imbalance between aggressive and defensive forces within the duodenum and an attempt has been made to elucidate the pathomechanism of this ulcer by determining acid and pepsin secretion. The basal and pentagastrin stimulated secretion of acid, pepsin, and histamine were measured and no changes in acid or pepsin secretion were shown to occur (risk of type II error < 1%). It is therefore concluded that this chronic ulcer is a model of impaired duodenal defence.

Plasma histamine in pig: Effect of food and pentagastrin

Histamine may have a role in the physiological control of gastric acid secretion. We aimed to detect histamine release into the circulation during food and pentagastrin. Non-parametric statistical analysis was used. Seven pigs bearing iliac artery, iliac vein and portal vein cannulae were given a standard meal. Blood samples were collected at 10-minute intervals over a period of 2 hours for histamine assay. There were no significant changes in whole blood and plasma histamine concentrations in the iliac arterial or venous blood. In portal venous blood, no significant changes were observed in whole blood histamine, but there were signficant increases in plasma histamine 40 minutes after food (basal median: 149.0; range: 50.3–258.6 pmol ml−1; 40 minutes, median 214.9; range: 64.2–319.6 pmol ml−1).Four pigs were given pentagastrin, 6 μ kg−1 h−1 i.v. Iliac and portal venous bloods were collected for histamine assay before and 15 minutes after pentagastrin infusion. There were no significant changes in the whole blood histamine concentration in either iliac or portal venous blood. A small increase, mean 5%, of plasma histamine concentration was detected in the iliac venous blood (basal mena 242.9±21.7 pmol ml−1; stimulated mean 256.9±39.1 pmol ml−1). A 20% increase in the portal plasma histamine concentration was observed after pentagastrin (basal mean 240.1±13.2; stimulated mean 288.4±18.8 pmol ml−1).Both food and pentagastrin increase plasma histamine concentration in the portal vein. Pentagastrin has a greater effect than food.

The effect of some gastrointestinal peptides on pentagastrin-stimulated acid secretion and oxyntic mucosal histamine in rats

In addition to gastrin many incretin hormones are capable of regulating gastric acid secretion, particularly the glucagon-like family ofpeptides such as glucagon-like peptide (7-36)amide (GLP-l) and oxyntomodulin (OXM) from the L-cell of the ileal mucosa. Both peptides have been reported to be potent inhibitors of stimulated acid secretion in vivo and vitro, in man and in the conscious rat [1, 2]. This effect may involve several pathways, including stimulation of somatostatin (SMS) release [3]. The aims of this study were to investigate the effect of the glucagon-like peptides and related gastrointestinal hormones on pentagastrin-stimulated acid secretion and on oxyntic mucosal histamine in anaesthetized rats.

Effect of gastric stimulants on histamine release and circulatory responses

The effects of pentagastrin (6 μg/kg/h) or insulin (0.15 U/kg/h) on histamine release and blood circulation in nine anaesthetized dogs were studied by measuring (1) plasma histamine concentrations in the iliac artery, iliac vein, hepatic vein and portal vein, (2) the corresponding blood pressures, and (3) blood flow in the hepatic artery and the portal vein. In the portal vein, pentagastrin induced an overall 204% rise (p<0.01) in plasma histamine and a 28% rise (p<0.01) in blood flow while other measurements did not change significantly. Insulin did not induce similar rises. Three patients with duodenal ulcer (DU) undergoing proximal gastric vagotomy (PGV) were given pentagastrin (6 μg/kg) by bolus injection. Plasma histamine concentrations in the gastric veins draining the oxyntic cell area rose by 68%, 15 min after injection. Thus, specific histamine release may act as a mediator for pentagastrin-stimulated gastric acid secretion and as a vasodilator to facilitate gastric circulation. Insulin did not promote histamine release in the present study.

Gastrointestinal histamine and histamine formation capacity after gastric irradiation in mice

Mice were exposed to a single dose of 9 or 15 Gy of X rays directed to the stomach. Histamine and histamine formation capacity (HFC) in the oxyntic region of the stomach were assayed at regular intervals for 7 weeks. After 9 Gy, mean gastric mural histamine fell to 61% of the control value (p less than 0.01) 7 days after irradiation while HFC rose to 172% (p less than 0.05). Both histamine and HFC returned to control values within 2 weeks after irradiation. With 15 Gy, on Day 7, histamine fell to 46% (p less than 0.01) and HFC rose to 260% (p less than 0.05). Histamine concentration remained low (less than half of the control value) while HFC returned to normal. These dose-dependent changes in histamine were observed neither elsewhere in the gut nor in the circulating blood. Further groups of mice were exposed to 3, 6, 9 or 15 Gy to the stomach, with gastric histamine and HFC assayed on Day 7. Histamine concentration was inversely related to dose (r = -0.59, p less than 0.001) and HFC was directly dose dependent (r = 0.52, p less than 0.001). These results suggest that irradiation of the stomach may reduce gastric histamine without inducing a general histamine release. The depletion of the gastric histamine store may explain the inhibitory effect of irradiation of the stomach on gastric acid secretion.