Biomedical subjects

C T Richardson

Publications and source records attributed to C T Richardson.

At least 19 recordsLinked to original sources

PubMed1996

Laparotomy and proximal gastric vagotomy in Zollinger-Ellison syndrome: results of a 16-year prospective study.

OBJECTIVE: Pharmacological control of gastric acid hypersecretion in the Zollinger-Ellison syndrome has steadily improved, but medical treatment does not address the underlying tumor. The objective of this study was to evaluate the long-term effectiveness of a surgical approach to both tumor and acid hypersecretion in 22 patients with the Zollinger-Ellison syndrome. METHODS: Patients underwent laparotomy to resect tumors, combined with vagotomy to reduce acid secretion, followed by postoperative antisecretory therapy, if necessary. RESULTS: No surgical mortality or serious morbidity occurred. Tumor was found at laparotomy in nine patients (41%) and during long-term follow-up in an additional two patients (9%). Ten-year survival is 81%, with a long-term cure rate of at least 14%. Most patients (86%) have had long-term inhibition of acid secretion. Eight patients have discontinued regular use of acid-inhibiting medications. Patients requiring medication need less of it, and they have an improved acid inhibitory response to medication for up to 16 yr after surgery. CONCLUSION: Cure of the Zollinger-Ellison syndrome is possible in a minority of patients. Acid secretion can be safely reduced in almost all patients with laparotomy/vagotomy, usually allowing discontinuation, or reduced dose, of acid-inhibiting drugs. Long-term survival and quality of life are generally excellent.

Adolescent↗

PubMed1990

Role of aggressive factors in the pathogenesis of peptic ulcer disease.

Acid and pepsin are the major aggressive factors believed to play a role in the pathogenesis of peptic ulcer disease. On the average, patients with duodenal ulcer disease have higher than normal basal, nocturnal, and pentagastrin-stimulated acid secretion. Food-stimulated acid secretion, however, is normal in duodenal ulcer patients. The reason for higher basal and nocturnal acid secretion is not known but may be secondary to higher than normal basal serum gastrin concentrations in duodenal ulcer patients. Average serum pepsinogen levels also are higher than normal in patients with duodenal ulcer disease, suggesting that luminal pepsin concentrations also are higher. Patients with gastric ulcers have either normal or lower than normal acid secretion. This suggests that factors other than acid and pepsin may play a role in causing gastric ulcers. Reflux of bile and pancreatic juice into the stomach of patients with gastric ulcers has been suggested as one of the aggressive factors playing a role in the development of gastric ulcers.

Duodenogastric Reflux↗

PubMed1989

Effects of rioprostil on gastric acid and pepsin secretion in man: a review of studies in healthy volunteers.

The antisecretory effect of rioprostil on acid and pepsin secretion stimulated by pentagastrin or a meal, or on the 24-h intragastric acidity is tested in four different studies in 33 healthy male volunteers using a double-blind, crossover design. The oral doses of rioprostil used are 50 micrograms, 100 micrograms, 150 micrograms, 200 micrograms, 300 micrograms and 600 micrograms; these are the results obtained: Rioprostil reduces basal H+ and pepsin output by more than 50%. Rioprostil, 300 micrograms and 600 micrograms, significantly reduces the 3-h pentagastrin-stimulated acid output by 43.5% and 58.9%, respectively, and the 3-h stimulated pepsin output by 41.1% and 66.5%, respectively (p = 0.01). Depending on the method used for intragastric titration the following percentages of inhibition of acid secretion are observed, 40%, 65%, and 75% with 150 micrograms, 300 micrograms, and 600 micrograms rioprostil respectively, with one method and 32%, 34%, and 79% with 25 micrograms, 50 micrograms, and 200 micrograms rioprostil respectively, with a somewhat modified technique. The differences observed in % inhibition between these two studies can be explained by the use of a different intragastric titration technique. Rioprostil, 300 micrograms and 600 micrograms, significantly inhibits night-time acid secretion (AUC x h, 2400 h-0800 h) by 52% and 73.5% when compared with placebo (p = 0.03). The calculated ED50 for acid inhibition is 86.5 micrograms of rioprostil.

Adult↗

PubMed1988

Effect of placebo on meal-stimulated gastric acid secretion and serum gastrin concentration. Studies in healthy volunteers and duodenal ulcer patients.

The effect of placebos on gastric acid secretion in humans is unknown, even though placebo therapy is relatively effective in ulcer patients. Therefore, we evaluated the effect of a placebo capsule on meal-stimulated gastric acid secretion and serum gastrin concentrations in 10 healthy subjects and also in 10 patients with chronic duodenal ulcer. Each subject and patient was studied twice and in random order, once with placebo therapy prior to the meal and once without placebo. In either healthy subjects or duodenal ulcer patients, meal-stimulated acid secretion and serum gastrin concentrations were not significantly different with or without placebo administration. These studies demonstrate that a placebo capsule, administered by a physician just prior to a meal, has little, if any, effect on acid secretion or gastrin release in response to the meal. Any beneficial effects of placebos in treating patients with peptic ulcer disease are probably unrelated to inhibition of meal-stimulated gastric acid secretion.

Duodenal Ulcer↗

PubMed1988

Gastric adenocarcinoma masquerading endoscopically as benign gastric ulcer. A five-year experience.

The pathologic features and five-year survival of patients in whom gastric cancer masquerades at endoscopy as a benign gastric ulcer has been poorly characterized. We reviewed retrospectively all cases of gastric adenocarcinoma in three hospitals for a five-year period. Of 266 patients with gastric adenocarcinoma, 169 (63.5%) had endoscopy with biopsy prior to diagnosis of cancer. In 159 of these 169 patients (94.1%), the endoscopic findings suggested cancer, while in the remaining 10 patients (5.9%) the endoscopic appearance suggested benign ulcer. In six of these 10 patients, the initial endoscopic biopsies did not reveal cancer and correct diagnosis was delayed for as long as 14 months. Three of the 10 patients had "early gastric cancer" by pathologic criteria at gastrectomy, although one had lymph node metastasis. The other seven patients had pathologic criteria for advanced gastric cancer, and three had lymph node metastasis. In spite of advanced cancer and/or lymph node metastasis in eight of our 10 patients, five-year survival in these patients with benign-appearing ulcers was 70%, as compared to 17% in patients whose gastric lesions appeared malignant at endoscopy.

Adenocarcinoma↗

PubMed1988

Effect of proximal gastric vagotomy on serum pepsinogen I and II concentrations and acid secretion in duodenal ulcer patients.

Acid secretion and basal serum pepsinogen I and II concentrations were measured in 14 duodenal ulcer patients before and at intervals up to six years after proximal gastric vagotomy. Vagotomy led to significant and long-standing reductions in basal, vagally mediated (induced by sham feeding), and peak pentagastrin-stimulated acid secretion. Serum pepsinogen I concentrations also decreased significantly after vagotomy but to a significantly lesser extent than acid secretion. There was no correlation between serum pepsinogen I concentrations and peak acid secretion, either before or after vagotomy. Serum pepsinogen II concentrations decreased only slightly and transiently after vagotomy. Thus, proximal gastric vagotomy reduces acid hypersecretion and pepsinogen I hypersecretion, but not pepsinogen II hypersecretion, in duodenal ulcer patients.

Duodenal Ulcer↗

PubMed1988

Effect of terbutaline, a beta 2-adrenoreceptor agonist, on gastric acid secretion and serum gastrin concentrations in humans.

Because beta-adrenoreceptor agonists inhibit gastrin-stimulated gastric acid secretion in animals, we postulated that the beta 2-adrenoreceptor agonist, terbutaline, would inhibit pentagastrin-stimulated acid secretion in humans. Moreover, we hypothesized that terbutaline might inhibit food-stimulated acid secretion, as gastrin is a major mediator of food-stimulated acid secretion. Subcutaneous terbutaline (0.25 mg) reduced acid secretion during intravenous infusion of a submaximal dose of pentagastrin by 30%-40% (p less than 0.005), even though terbutaline increased serum gastrin levels (p less than 0.05). Furthermore, subcutaneous (0.25 mg) or oral (5 mg) terbutaline, given before a homogenized steak meal was infused into the stomach, lowered mean food-stimulated acid secretion rates, despite enhanced postprandial serum gastrin concentrations. Terbutaline also increased serum gastrin concentrations in patients with Zollinger-Ellison syndrome and in vagotomized individuals. Thus, beta 2-adrenoreceptor agonists enhance gastrin release while at the same time inhibiting gastrin-stimulated acid secretion in humans.

Adult↗

PubMed1988

Soy protein meals stimulate less gastric acid secretion and gastrin release than beef meals.

Soy protein is a widely used, inexpensive, and nutritious source of dietary protein. In contrast to beef protein, the effects of soy protein on gastric acid secretion and serum gastrin concentration have not been evaluated. We compared the effects of meals containing the same amounts of either isolated soy or beef protein on acid secretion and serum gastrin concentration in normal humans. Acid secretion measured by in vivo intragastric titration was 30%-40% less with soy than beef protein (p less than 0.05), whether isolated soy protein alone was compared with a mixed beef meal containing carbohydrate and fat or whether soy or beef meals containing similar amounts of fat were compared. Average gastrin rises were 65%-75% less with soy than with beef (p less than 0.01). The explanation for less gastrin release with soy than with beef is unclear, but lower serum gastrin concentrations with soy probably accounted for reduced acid secretion. These results indicate that the source of dietary protein in a meal may be an important determinant of gastric acid secretion and gastrointestinal hormone release.

Adult↗

PubMed1988

Comparison of gastric acid secretion rates and serum pepsinogen I and II concentrations in Occidental and Oriental duodenal ulcer patients.

The purpose of these controlled studies was to determine the prevalence of acid-pepsinogen hypersecretion in 173 patients with duodenal ulcer disease [88 Americans (75 men, 13 women) and 85 Chinese (66 men, 19 women)]. One-half to two-thirds of duodenal ulcer patients of either sex had acid hypersecretion or hyperpepsinogenemia, or both. When Chinese and American duodenal ulcer patients were compared, the two ethnic groups had similar serum pepsinogen I and II concentrations and similar maximal acid outputs per kilogram body weight. In contrast, Chinese duodenal ulcer patients had significantly lower basal acid outputs per kilogram body weight than American duodenal ulcer patients. We conclude that acid-pepsinogen hypersecretion is present in the majority of American and oriental duodenal ulcer patients.

Adult↗

PubMed1988

Basal and sham-feeding-stimulated salivary flow in duodenal ulcer patients and healthy subjects.

Increased vagal (parasympathetic) stimulation of gastric secretion has been postulated in patients with duodenal ulcer disease. Since salivary secretion is influenced by parasympathetic nerves, we reasoned that duodenal ulcer patients also might have increased salivary secretion. Furthermore, if salivary secretion in duodenal ulcer patients is under nearly maximal parasympathetic stimulation basally, salivary volume might not increase with additional parasympathetic activation induced by sham feeding. To test these hypotheses, we measured basal and sham-feeding-stimulated salivary flow in duodenal ulcer patients and healthy subjects. Contrary to our hypotheses, both basal salivary flow and the salivary response to sham feeding were almost identical in duodenal ulcer patients and healthy subjects. Also, urogastrone concentrations in saliva were approximately the same in duodenal ulcer patients and normal subjects.

Duodenal Ulcer↗

PubMed1987

Positive intravenous secretin test in patients with achlorhydria-related hypergastrinemia.

The intravenous secretin test is widely used to distinguish gastrinoma (Zollinger-Ellison syndrome) from other causes of fasting hypergastrinemia. We report 2 patients with fasting hypergastrinemia and a rise of greater than 200 pg/ml in serum gastrin concentration after intravenous injection of 2 CU/kg body wt of pure natural secretin. Both patients had pentagastrin-fast achlorhydria. Thus, the intravenous secretin test may be positive in patients with achlorhydria-related hypergastrinemia. Gastric acid secretion should be measured in hypergastrinemic patients before embarking on a secretin test.

Achlorhydria↗

PubMed1987

Variable contribution of gastrin to gastric acid secretion after a meal in humans.

The purpose of these experiments was to determine the contribution of gastrin to the acid secretory response to eating in healthy human subjects. To simulate the gastric and intestinal phases of eating, a meal was homogenized and then infused into the stomach through a nasogastric tube. At the same time, the cephalic phase of acid secretion was activated by sham feeding. With this simulated meal, mean serum gastrin concentration increased from a basal value of 43 +/- 9 pg/ml to an average postprandial gastrin concentration over 2 h of 121 +/- 25 pg/ml. Gastrin release after this simulated meal was similar to gastrin release after a normally eaten meal in the same 12 subjects. Gastric acid secretion in response to the simulated meal, which was measured by in vivo intragastric titration, averaged 24.2 +/- 2.4 mmol/h. To determine how much of this postprandial acid secretion could be attributed to gastrin, gastrin 17 I was infused intravenously in the same subjects on a separate day and acid secretion and serum gastrin concentrations were measured. By relating serum gastrin concentration during gastrin 17 infusion to concomitant acid secretion, we determined that an average postprandial serum gastrin concentration of 121 pg/ml could result in an acid secretion rate of 21.5 mmol/h, 89% of the actual acid secreted after the simulated meal in these subjects. However, in individual subjects, the amount of gastrin released after a meal could produce as little as 51% or as much as 162% of actual postprandial acid secretion. Thus, in individual human subjects the contribution of gastrin to acid secretion after a meal is variable.

Adult↗

PubMed1987

Comparison of two antimuscarinic drugs, pirenzepine and propantheline, on gastric acid secretion, serum gastrin concentration, salivary flow and heart rate in patients with duodenal ulcer disease.

Effects of orally-administered pirenzepine and propantheline bromide on food-stimulated gastric acid secretion, serum gastrin concentration, salivary flow and heart rate were compared in 10 duodenal ulcer patients in a placebo-controlled, double-blind study. Pirenzepine inhibited acid secretion by 25, 36 and 44% at doses of 50, 100, and 150 mg, respectively, while propantheline inhibited acid secretion by 32 and 41% at doses of 15 and 45 mg, respectively. None of the doses of pirenzepine affected food-stimulated serum gastrin concentrations, whereas 45 mg propantheline increased serum gastrin concentration significantly above placebo control. Enhancement of gastrin release by propantheline was not due to its antisecretory effect since intragastric pH after the meal was held constant at 5.0 by intragastric titration in vivo. Pirenzepine had no significant effect on heart rate and little or no inhibitory effect on salivary volume, depending on the dose administered. By contrast, both doses of propantheline increased heart rate and reduced salivary volume significantly (P less than 0.05). Thus, pirenzepine and propantheline in the doses administered inhibited acid secretion to approximately the same extent but pirenzepine had fewer effects on other organs.

Adult↗

PubMed1987

Detailed comparison of basal and food-stimulated gastric acid secretion rates and serum gastrin concentrations in duodenal ulcer patients and normal subjects.

We measured basal and peak acid outputs, food-stimulated acid secretion, and basal and food-stimulated serum gastrin concentrations in a large group of duodenal ulcer patients and normal subjects. Basal and peak acid outputs were significantly higher in ulcer patients. In contrast, acid secretion was similar in the groups when food was infused into the stomach and when sham feeding was combined with meal infusion to simulate normal eating. Meal-stimulated acid secretion, expressed as a percentage of peak acid output to correct for differences in secretory capacity, was lower in ulcer patients (P less than 0.002). Basal serum gastrin concentrations were higher in ulcer patients, which may have contributed to higher basal acid output. However, increases in serum gastrin after food were similar in the groups. Duodenal ulcer patients, as a group, have increased basal and maximal acid secretion, but the amount of acid secreted and gastrin released after eating is normal.

Adult↗

PubMed1987

Effect of proximal gastric vagotomy on calculated gastric HCO3- and nonparietal volume secretion in man. Studies during basal conditions and gastrin-17 infusion.

We calculated gastric HCO3- and H+ secretion, as well as nonparietal and parietal volume secretion, in 15 duodenal ulcer patients who had previously undergone successful proximal gastric vagotomy, 15 unoperated duodenal ulcer patients, and 15 normal control subjects. Basal HCO3- secretion was not significantly altered after vagotomy, while basal H+ secretion, parietal volume and nonparietal volume secretion were reduced significantly. Intravenous gastrin-17 infusion reduced gastric HCO3- secretion by approximately 50% in both unoperated ulcer patients and normal subjects (P less than 0.05). Gastrin-17 infusion did not inhibit gastric HCO3- secretion after vagotomy. In fact, mean gastric HCO3- secretion increased to a nearly significant extent in response to gastrin (P = 0.06). These findings indicate that gastrin inhibits gastric HCO3- secretion in humans and that the gastrin-induced reduction in gastric HCO3- secretion is dependent upon intact vagal innervation to the oxyntic mucosa.

Bicarbonates↗

PubMed1987

Effect of sham feeding on acid secretion in patients with Zollinger-Ellison syndrome with or without proximal gastric vagotomy.

In dogs, vagal stimulation by sham feeding inhibits gastrin-stimulated gastric acid secretion from vagally denervated fundic pouches. To investigate this in humans, we sham fed patients with endogenous hypergastrinemia secondary to the Zollinger-Ellison syndrome. Whether these patients had been treated previously by proximal gastric vagotomy or not, sham feeding did not reduce basal acid secretion. Thus, sham feeding did not inhibit acid secretion in humans with hypergastrinemia, even when the fundus of the stomach had been vagally denervated.

Adolescent↗

PubMed1987

Lack of effect of parathyroidectomy or calcium channel blockade on serum gastrin concentration and gastric acid secretion in a patient with hyperparathyroidism and Zollinger-Ellison syndrome.

Management of patients with multiple endocrine neoplasia type I (Wermer's syndrome) who have concurrent hypercalcemia and hypergastrinemia is controversial. The usual therapeutic approach has been to perform parathyroidectomy first before surgery for ulcer disease in an effort to decrease serum calcium concentration and presumably remove one of the stimuli for both gastrin and gastric acid secretion. We present the history of a 48-year-old man with primary hyperparathyroidism and Zollinger-Ellison syndrome who underwent acid secretory studies and secretin stimulation tests before and after parathyroidectomy. We also studied the effect of calcium channel blockade on gastrin and gastric acid secretion, since calcium influx into endocrine cells, such as the gastrinoma cell, is thought to be critical in hormone secretion. Although parathyroidectomy reduced serum calcium and parathormone levels to normal, basal serum gastrin concentration and basal acid output remained unchanged. The peak rise in serum gastrin concentration after secretin injection was less after parathyroidectomy than before parathyroidectomy but was still abnormal. During administration of verapamil, a calcium channel antagonist, no change was seen in the serum gastrin concentration, secretin test response, or acid secretion. Basal acid output was 45.4 mmol/hr before parathyroidectomy or verapamil and 54.0 and 50.4 mmol/hr after parathyroidectomy or verapamil, respectively. In contrast, a small but significant decrease (p less than 0.05) in serum parathormone concentration occurred during treatment with verapamil, an observation that to the best of our knowledge has not been previously reported in humans.

Calcium Channel Blockers↗

PubMed1986

Cimetidine blocks antacid-induced hypergastrinemia.

The effects on fasting serum gastrin concentrations of hourly doses of magnesium and aluminum hydroxide antacid, with and without intravenous cimetidine, were determined in 8 patients with duodenal ulcer disease. Gastrin levels rose significantly over 10 h when antacid was given either as a bolus of 30 ml every hour or as a constant infusion of 0.5 ml/min (36 +/- 5 pg/ml and 33 +/- 6 pg/ml to 108 +/- 32 pg/ml and 109 +/- 22 pg/ml, respectively, p less than 0.05). This effect was specific for some component of the antacid and not for neutralization of acid per se, inasmuch as sodium bicarbonate, infused to keep gastric pH at levels at or above those of antacid, produced no significant rise in serum gastrin concentration. When intravenous cimetidine was administered simultaneously with intragastric antacid, gastrin levels did not rise. This occurred even though intragastric pH levels were actually higher with cimetidine plus antacid than with antacid alone. The ability of intravenous cimetidine to block antacid-induced hypergastrinemia was counteracted by infusing simultaneously both hydrochloric acid and antacid into the stomach. Since hydrochloric acid reacts with magnesium and aluminum hydroxide to form ionic magnesium and aluminum chloride, cimetidine most likely blocks antacid-induced hypergastrinemia by reducing acid secretion from the stomach and thereby limiting the generation of ionic magnesium and aluminum.

Adult↗