Intragastric Acidity Research Articles

2 - Peptic Ulceration and its Correlation with Symptoms

Studies in which the numbers of healed or unhealed ulcers and their correlation with symptoms are availabel are summarized in Table 1. A review of the data and inspection of the Table show that the correlation of GU or DU healing with symptomatic remission is generally poor. The reasons for this are unknown and reflect the very incomplete understanding of the mechanism of ulcer pain and of the pathways through which the pain is mediated. The pathogenesis of pain in GU or DU may be due to the action of acid and pepsin, or of bile, on the tissues exposed in the ulcer crater, to abnormal motility, to normal motility acting on inflamed tissue, to areas of inflammation surrounding the ulcer crater, or to a combination of these factors. The relative importance of each of these variables in DU or GU, or in individual patients (because the mechanism of pain may not be the same in each patient) is not known. Nor is it known how much the pathogenesis of ulcer pain is the result of local release of histamine, kinins, and prostaglandins. These biogenic factors are known to be associated with inflammation and produce, or enhance, somatic pain. Their importance in peptic ulcer in man needs to be studied. Relief of pain after neutralization or buffering of gastric contents with alkali or food suggests strongly that acid must play an important part in the pathogenesis of the ulcer symptoms. The rapidity with which relief of symptoms occurs points towards the direct involvement of hydrogen ions in at least one type of ulcer symptom. Lowering of intragastric acidity by histamine H2- receptor antagonists or high-dose alkali may contribute to the observed discrepancies between ulcer healing and the remission of pain, by creating an environment in the gastroduodenal lumen which favours symptomatic improvement, even in the presence of an unhealed crater. This idea, however, does not explain why there is a discordance between healing and symptoms in patients receiving placebo, or in those treated with other drugs, such as carbenoxolone sodium. In the absence of endoscopic evidence, the presence or absence of symptoms cannot be assumed to indicate with certainty the presence or the absence of a peptic ulcer.

Entry into occupational medicine

Omeprazole plus amoxicillin cures Helicobacter pylori infection. The hypothesis was tested that low acidity is a predictor of outcome. Fifty patients with relapsing or complicated, or both H pylori positive duodenal (n = 25) or gastric ulcer (n = 25) were randomly treated with either omeprazole 20 mg twice daily plus amoxicillin 1 g twice daily or with omeprazole 40 mg twice daily plus amoxicillin 1 g twice daily over two weeks. After one week of combined treatment, a 24 hour gastric pH measurement was performed in all patients. H pylori cure rate was 67%. Patients who later turned out to be cured had higher pH values during night time and after meals (p < 0.05). In an explorative analysis drug compliance, smoking, location of the ulcer (duodenum versus stomach), age, and grade of body gastritis were additional predictors of the outcome. Smoking (p = 0.006), compliance (p = 0.037), duodenal ulcer disease (p = 0.065), and young age (p = 0.021) were related to high acidity. In conclusion, the success of eradication treatment with omeprazole and amoxicillin in ulcer patients infected with H pylori depends on intragastric pH. Drug compliance, smoking habits, location of ulcer, age, and activity of body gastritis are other predictors and in part related to intragastric acidity.

Role of Intragastric Pressure, pH, and Pepsin in Gastric Ulceration in the Rat

A method of continuous gastric perfusion with "artificial gastric juice" was used in a study of individual factors (intragastric pressure, pH, and pepsin) known to participate in the pathogenesis of peptic ulcers. This method allowed change of only one factor at a time, while the other two remained constant. The gastric mucosa of normal rats, fasted for 48 hr, was found to be resistant to the ulcerogenic effects of artificial gastric juice perfused through the stomach for 6 hr without increasing the intragastric pressure. Perfusion of hydrochloric acid (pH 1.3) under increasing pressure produced ulceration of the corpus as well as forestomach portion of the stomach. The degree of gastric ulceration paralleled increases in intragastric pressure, acidity, and pepsin proteolytic activity. Inhibition of pepsin activity by a pepsin inhibitor protected the gastric mucosa even at the very low pH of 1.3. These results demonstrate that under the experimental conditions used, hydrochloric acid alone in the absence of pepsin does not produce ulceration of the rat stomach.

Effect of Changes in the Intragastric Milieu on Competence of the Gastro-Oesophageal Region

Acid-reflux studies were carried out in 10 healthy subjects in the basal state, during continuous infusion of pentagastrin (0.015 mug/kg body-weight) after bolus injection of insulin (0.2 IU/kg bodyweight), and after intragastric instillation of 200 ml hydrochloric acid. Basal gastro-oesophageal sphincter pressure and rise in intragastric pressure on leg raising were measured by means of perfused catheters. The increase of intragastric acidity during infusion of pentagastrin and during insulin-induced hypoglycaemia was not accompanied by changes in the competence of the gastro-oesophageal region. Instillation of hydrochloric acid was followed by a significant enhancement of the reflux tendency. Changes in intragastric pressure-rise were not demonstrated in any of the series of investigation. Gastric acid secretion and its significance at the evaluation of the results of reflux studies by means of pH-measuring equipment has not been clarified in patients. It can therefore reasonably be demanded of future acid reflux studies that details have to be stated with regard to acid secretion, and that these should be taken into account at the assessment of the results of the study.

24-hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer during oral administration of cimetidine and atropine.

Cimetidine markedly inhibits gastric acid secretion, but from the therapeutic point of view it is important to know whether concurrent treatment with an anticholinergic increases its effect. This possibility has been investigated by measuring the 24 h intragastric acidity and nocturnal output of acid in four duodenal ulcer patients, each receiving on separate occasions cimetidine 1 g/day and placebo, atropine 2-4 mg/day and placebo, cimetidine and atropine, or two placebos. Cimetidine alone decreased mean hourly hydrogen ion activity by 63% of control values, decreased mean hourly hydrogen ion concentration (total acid) by 41%, inhibited nocturnal acid secretion by 83% and resulted in half the nocturnal samples being anacidic. Atropine alone had no effect when compared with control and combined treatment with both drugs was not superior to cimetidine alone. Atropine did not affect the absorption or urinary excretion of cimetidine. Fasting serum gastrin concentrations were not changed by any of the treatments. At the doses studied, the combination of cimetidine with an anticholinergic appears to offer no advantages over treatment with the H2-antagonist alone. Cimetidine is the only potent anti-secretory drug that does not cause acute side-effects and this important advantage would be lost if it were given with a maximal dose of an anticholinergic.

Stress and ulcer etiology in the rat

Shock predictability and dietary physical property were varied in an unavoidable shock situation for 48, 72, or 96 hr. Unpredictable shock did not markedly affect rumenal or corpus pH nor did it produce corpus ulcers. Animals in the liquid diet condition developed significantly more ulceration and had significantly lower pH in the rumen than animals in the solid diet groups. A strong correlation between ulceration and pH was found in the rumen. Under all experimental conditions, the rumenal portion of the stomach was consistently more acidic than the corpus. Although increased acidity is common to ulcer development in both portions of the rat stomach, the present results indicate that a uniform intra-gastric acidity increase may not result from exposure to a particular stressor.

24-HOUR CONTROL OF INTRAGASTRIC ACIDITY BY CIMETIDINE IN DUODENAL-ULCER PATIENTS

The effects of two dose regimens of cimetidine on 24 h intragastric acidity were investigated in six patients with duodenal ulcer. They received placebo capsules on the first day and cimetidine on the second day. Cimetidine 0·8 g/day decreased 24 h mean H + activity by 55% but 1·6 g/day decreased it by 67%, the difference being due to a greater nocturnal decrease in the high-dose group. Intragastric pH remained below 2·0 for much of the treatment day but similar values were found in four post-vagotomy patients. Cimetidine 0·8-1·6 g/day results in a decrease of intragastric acidity that is compatible with successful medical treatment of duodenal ulceration.

Canine pancreatic responses to intestinally perfused fat and products of fat digestion.

Canine pancreatic responses to intestinally perfused fat and products of fat digestion.

Serum gastrin in duodenal ulcer. II. Effect of insulin hypoglycaemia.

Serum gastrin has been measured by radioimmunoassay in normal subjects and patients with proven duodenal ulcer in response to insulin hypoglycaemia in conjunction with manoeuvres to decrease the intragastric acidity. Insulin hypoglycaemia alone caused a rise in the serum gastrin level from 5 +/- 1.0 to 49 +/- 2.9 pg/ml in duodenal ulcer and from 17 +/- 5.6 to 42 +/- 7.7 pg/ml in normals. With complete intragastric neutralization of acid and the same stimulus, the rise in duodenal ulcer was from 5 +/- 1.3 to 128 +/- 13.6 pg/ml and in normals from 13 +/- 2.6 to 84 +/- 2.6 pg/ml. These studies suggest an increased production rate of gastrin in response to vagal stimulation in duodenal ulcer, and indicate the precise role of acid inhibition in the control of gastrin release and support the concept of both an increased ;G cell' mass and parietal cell mass in duodenal ulcer. They have also offered an explanation of the variable vagal stimulation of gastrin release in normal subjects.

Serum gastrin and gastric acidity.

Summary: The relationship between serum levels of gastrin and intragastric acidity was studied using an immunoassay for gastrin which was specific for the biologically active C-terminal sequence of the gastrin molecules. Eighty-three combined serum gastrin and intragastric pH estimations were performed on 43 subjects (4 normal, 13 patients with gastric ulceration and 26 patients with duodenal ulceration). The serum gastrin response to gastric acidification by betazole hydrochloride was studied in 9 patients with duodenal ulceration. There was a highly significant (P <0.001) negative correlation (r=-0.37) of serum gastrin on basal intragastric pH, i.e. the patients with the higher gastrin levels had lower intragastric pH. Gastric acidification by betazole hydrochloride suppressed the hyper-gastrinaemia associated with duodenal ulceration. The correlation between serum gastrin and intragastric pH suggests that gastrin is a factor in maintaining basal gastric acid secretion. Suppression of the hypergastri-naemia associated with duodenal ulceration by gastric acidification is consistent with the concept of an increased vagal tone in these patients.

Suppression of gastric hydrochloric acid secretion by enzyme inhibitors; a new approach in research on the therapy of peptic ulcer.

According to our current ideas concerning the pathogenesis of peptic ulceration, this disease is essentially a matter of localized autodigestion of the wall of the digestive tract by active gastric juice. This process does not occur unless there is a breakdown of some kind in the normal defensive mechanism of the gastrointestinal mucosa, the two-component mucous barrier.1Since we do not yet know how to strengthen or repair this defensive structure directly, all the medications in general use today for the therapy of this disease are designed to reduce the intensity of the aggressive agent, acid-pepsin juice— directly, by way of the enzyme, and indirectly, by reducing the intragastric acidity, upon which peptic action is dependent. Many of the pharmacological agents which reduce gastric acidity also, in some measure, relieve muscle spasm which makes for prolonged retention of stomach contents. Hence, a review of all chemotherapeutic agents presently in

TREATMENT OF GASTRODUODENAL ULCERATIVE DISEASE WITH SODIUM ALKYL SULFATE

Our results from the treatment of gastroduodenal ulcerative disease with sodium alkyl sulfate are being reported now because this new therapy has already enabled patients with ulcer to enter the armed forces, and essential war workers previously incapacitated by this disease to return to industry. Palmer 1 has shown that gastroduodenal ulcerative disease is the major cause of medical disability in both the English and the American forces. Since it is usually present in male adults during the years of their greatest productivity, the impairment of war effort by this prevalent disease is of serious significance. Most patients with ulcer are now being treated by a routine which has for its goal reduction of intragastric acidity. This type of medication has not been completely satisfactory because a large number of patients with gastroduodenal ulcerative disease respond inadequately to this orthodox management. To date the emphasis has been placed on the

The influence of anxiety on gastric digestion

The study of the influence of emotional strain on digestion in man offers some difficulties due to the fact that the emotions cannot be readily controlled, nor are the subjects of extreme emotion readily amenable to experimentation. We were, however, able to obtain an interesting illustration of the profound effect of mental anxiety on gastric digestion in the case of one of our subjects. The man was a first-year medical student who had previously served as a subject of gastric tests. He was given one hundred grams of fried chicken on the morning of an important examination in chemistry, and was asked to write out his answers during the course of the test. He was plainly worried over the outcome of the examination and of his year's work. The resultant effect upon gastric digestion in prolonging evacuation for over two hours with high intra-gastric acidity is charted in the figure. Thesame chart gives the normal digestion curve for fried chicken on this subject as obtained a week later under the best menta...