Biomedical subjects

C T Richardson

Publications and source records attributed to C T Richardson.

At least 37 records · Page 2Linked to original sources

PubMed1986

Effect of parietal cell vagotomy on acid secretory responsiveness to circulating gastrin in humans. Relationship to postprandial serum gastrin concentration.

To study the relationship between gastric acid secretion and serum gastrin concentration after vagotomy, gastric acid output and serum gastrin concentration were measured simultaneously during intravenous infusion of graded doses of human gastrin heptadecapeptide (G-17) in duodenal ulcer patients with parietal cell vagotomy and in unoperated patients with duodenal ulcer disease (controls). The curve relating serum gastrin concentration to gastric acid output was shifted downward and to the right after vagotomy; the peak acid output to G-17 was reduced by 50% (p less than 0.001). The serum gastrin concentration that produced half of peak acid output (EC50%) averaged 185.5 pg/ml after vagotomy and 74.1 pg/ml in controls (p less than 0.01). Mean basal and postprandial serum gastrin concentrations were twofold to threefold higher in vagotomy patients than in controls (p less than 0.005). However, when peak postprandial serum gastrin concentrations were used to predict acid secretion from curves relating serum gastrin to acid output, predicted acid secretion was only 12.6 mmol/h in vagotomy patients compared to 24.4 mmol/h in controls. Parietal cell vagotomy decreases "functional" parietal cell mass, as reflected by a 50% decrease in peak acid output, and also reduces the responsiveness of "functional" parietal cells to gastrin to such an extent that acid secretion is reduced after vagotomy despite basal and postprandial hypergastrinemia.

Duodenal Ulcer↗

PubMed1986

Role of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion in humans.

The relative importance of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion has not been studied systematically. We found that discussing appetizing food for 30 min (without sight, smell, or taste) increased acid secretion from 4 to 13 mmol/h in healthy human subjects (p less than 0.001) and also increased serum gastrin concentrations significantly (p less than 0.02). Discussing food resulted in an acid secretory response that averaged 66% +/- 10% of the response to modified sham feeding, which activates thought, sight, smell, and taste. Discussing topics other than food (e.g., current events, sports) did not increase acid secretion significantly. The sight of appetizing food (without smell or taste), the smell of appetizing food (without sight or taste), or the combination of sight and smell (without taste) also increased acid secretion and serum gastrin concentrations significantly. However, sight and smell were significantly less potent stimulants of acid secretion than sham feeding, with responses averaging only 23%-46% of the response to sham feeding. These studies indicate that thinking about food is a potent stimulant of gastric secretion in healthy humans. Moreover, the sight and smell of food increase gastric acid secretion and serum gastrin concentrations, probably by provoking thoughts related to food.

Adult↗

PubMed1986

Total 24-hour gastric acid secretion in patients with duodenal ulcer. Comparison with normal subjects and effects of cimetidine and parietal cell vagotomy.

The purposes of these studies were as follows: (a) to compare gastric acid secretion throughout an entire 24-h period in 8 patients with duodenal ulcer disease and in 7 normal subjects, and (b) to determine in duodenal ulcer patients to what extent total, 24-h acid secretion was reduced by oral cimetidine (n = 7) or parietal cell vagotomy (n = 7). Basal, interprandial, and nocturnal acid secretion were measured by gastric aspiration, whereas acid secretion in response to breakfast, lunch, and dinner was measured by in vivo intragastric titration. Total, 24-h acid secretion averaged 408.3 +/- 61.7 mmol in duodenal ulcer patients and 208.3 +/- 18.5 mmol in normal subjects (p less than 0.02). Acid secretion was higher in duodenal ulcer patients than in normal subjects during both day (p less than 0.01) and night (p less than 0.05). Cimetidine (400 mg twice daily) significantly (p less than 0.001) reduced total, 24-h acid secretion in duodenal ulcer patients to 235.3 +/- 58.6 mmol, a rate that was not significantly different from 24-h acid secretion in normal subjects. On the other hand, total, 24-h acid secretion averaged only 86.7 +/- 20.7 mmol after parietal cell vagotomy, a rate that was significantly lower than 24-h acid secretion in normal subjects (p less than 0.001) and in duodenal ulcer patients receiving cimetidine (p less than 0.05). These studies indicate that patients with duodenal ulcer disease secrete excessive amounts of gastric acid during the day and night and throughout an entire 24-h period. A twice-daily 400-mg dose of cimetidine reduces 24-h acid secretion in duodenal ulcer patients to nearly normal rates, whereas parietal cell vagotomy reduces acid secretion to well below normal rates.

Adult↗

PubMed1986

Effects of transdermal scopolamine, alone or in combination with cimetidine, on total 24 hour gastric acid secretion in patients with duodenal ulcer.

Transdermal scopolamine is an antimuscarinic preparation approved for use in the United States for prevention of motion sickness. A recent study using this drug (0.5 mg/patch) suggested that enough scopolamine was absorbed through the skin to reduce basal gastric acid secretion in patients with duodenal ulcer. We have compared the effect of transdermal scopolamine and oral cimetidine (400 mg twice daily) in seven men with chronic duodenal ulcer, both alone and in combination, on acid secretion throughout an entire 24 hour period in a placebo-controlled, randomised, double blinded cross over study. The effect of these drugs on basal, interprandial, and nocturnal gastric juice volume and hydrogen ion concentration also was measured. Transdermal scopolamine had no significant effect on mean 24 hour acid secretion (placebo, 409.4 mmol/day; scopolamine, 364.0 mmol/day) nor did it have a significant effect on gastric juice volume or hydrogen ion concentration. The combination of transdermal scopolamine plus cimetidine was not more effective than cimetidine alone in reducing total 24 hour acid secretion (mean, 231.8 versus 235.3 mmol/day) nor in reducing gastric juice volume or hydrogen ion concentration.

Administration, Cutaneous↗

PubMed1986

Salivary response to food in humans and its effect on gastric acid secretion.

The purpose of these studies was to determine the amount of saliva secreted in response to food in humans and to evaluate the effect of saliva on postprandial gastric acid secretion. Subjects chewed and spat out an appetizing steak and french-fried potato meal (modified sham feeding), with the increase in the weight of the meal during sham feeding taken to represent salivary secretion. Mean salivary flow rose from basal rates of 37.1 ml/h to 167.3 ml/h during modified sham feeding (P less than 0.001). Chewing gum increased salivary secretion to approximately the same extent as modified sham feeding, whereas chewing on plastic tubing caused a much smaller increase in salivary flow. Intravenous infusion of bethanechol (50 micrograms . kg-1 . h-1) was approximately half as potent as modified sham feeding or gum chewing in stimulating salivary flow. The salivary response to sham feeding was completely blocked by 15 micrograms/kg intravenous atropine. Salivary secretion increased approximately 20 ml/h when a 700-ml amino acid meal was infused directly into the stomach (P less than 0.01), whereas gastric distension with 700 ml saline had no effect. These findings suggested that food in the stomach or upper small intestine may activate a reflex or release a hormone into the circulation that augments salivary flow. Although intravenous gastrin-17 infusion had no effect on salivary flow, somatostatin-14 infusion increased salivary flow 15 ml/h (P less than 0.02). Saliva contained approximately 2,000 pg/ml immunoreactive urogastrone, an inhibitor of acid secretion when administered parenterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Inhibitory effects of beta-adrenergic agonists on gastric acid secretion in dogs.

We evaluated the effect of two beta-adrenergic agonists, isoproterenol (nonselective agonist) and terbutaline (selective beta 2-agonist), on gastric acid secretion stimulated by intravenous pentagastrin, bethanechol, or histamine in dogs with gastric fistulas. Intravenous infusion of isoproterenol or terbutaline inhibited pentagastrin-stimulated acid secretion to a significantly greater extent than they inhibited bethanechol- or histamine-stimulated acid secretion. For example, isoproterenol (12 micrograms X kg-1 X h-1) reduced mean pentagastrin-, bethanechol-, and histamine-stimulated acid output by 86, 63, and 14%, respectively. Percent inhibition of acid secretion with terbutaline (30 micrograms X kg-1 X h-1) averaged 60, 17, and 24% for pentagastrin, bethanechol, and histamine, respectively. Terbutaline also inhibited pentagastrin-stimulated acid secretion from vagally denervated fundic pouches in a dose-related manner. Plasma somatostatin-like immunoreactivity was significantly higher during infusion of terbutaline plus pentagastrin than during infusion of pentagastrin alone. However, an intravenous infusion of 0.3 microgram X kg-1 X h-1 somatostatin-14 had no effect on pentagastrin-stimulated acid secretion from the gastric fistula, even though this infusion increased plasma somatostatin-like immunoreactivity to the same extent as terbutaline plus pentagastrin infusion. Thus the amount of somatostatin released during terbutaline infusion was not sufficient to explain the inhibition of pentagastrin-stimulated acid secretion observed.

Adrenergic beta-Agonists↗

PubMed1986

Comparison of acid secretory responsiveness to gastrin heptadecapeptide and of gastrin heptadecapeptide pharmacokinetics in duodenal ulcer patients and normal subjects.

Serum gastrin concentrations and gastric acid secretion were measured during intravenous infusion of gastrin heptadecapeptide (G-17) (0, 7, 22.1, 70, 221, and 700 pmol/kg X h) in 15 duodenal ulcer patients and 15 healthy controls. Ulcer patients developed higher serum gastrin concentrations during G-17 infusion due to nearly twofold slower clearance of gastrin (8.8 vs. 15.7 ml/kg X min; P less than 0.01). Despite slower clearance of G-17, ulcer patients had plasma elimination half-times for G-17 similar to controls (6.0 vs. 6.1 min, respectively). Thus, calculated volume of distribution for G-17 was lower in ulcer patients than controls (78.5 vs. 140.7 ml/kg; P less than 0.025). For any serum gastrin during gastrin-17 infusion, acid secretion (millimoles per hour) was higher in ulcer patients than in controls. However, when acid secretion was expressed as a percentage of peak acid output to G-17 (to correct for differences in parietal cell mass), curves relating acid secretion to serum gastrin were identical in ulcer patients and controls.

Adult↗

PubMed1986

Effect of doxepin on basal gastric acid and salivary secretion in patients with duodenal ulcer.

We compared the effect of 50- or 100-mg doses of oral doxepin or a placebo on basal gastric acid secretion, salivary flow, and pulse rate in seven asymptomatic patients with chronic duodenal ulcer disease. Acid secretion and salivary flow were measured for four 1-hour periods beginning at 3.5, 5.5, 7.5, and 9.5 hours after medication, with plasma sampling for measurement of doxepin at the midpoint of each collection period. Compared to placebo, the 50- and 100-mg doses of doxepin reduced mean basal acid output by 46% and 37%, respectively. There was no significant difference in the effect of the 50- or 100-mg dose on acid secretion even though mean plasma concentrations of doxepin were higher with the 100-mg than with the 50-mg dose (p less than 0.01). Salivary flow was reduced by 62% and 84% with the 50- and 100-mg doses, respectively, whereas doxepin had no effect on mean pulse rate.

Adult↗

PubMed1986

Intravenous cimetidine or two regimens of ranitidine to reduce fasting gastric acidity.

Fasting gastric pH (acidity) was measured over a 10-hour period in six patients with duodenal ulcer disease. Fasting pH was measured in a control study during which no medications were administered and in response to 300 mg of intravenous cimetidine given every 6 hours or 50 mg of intravenous ranitidine given every 6 or 8 hours. Each regimen produced gastric pH levels significantly higher than those obtained when no medication was given. Although patterns of gastric pH differed among the medication regimens, and although the ranitidine regimens maintained pH at or above 5.0 more reliably than cimetidine, there were no significant differences in mean pH, median pH, or mean hydrogen ion concentration.

Adult↗

PubMed1985

Pathogenetic factors in peptic ulcer disease.

Peptic ulcers are believed to develop because of increased acid and pepsin secretion, a reduced mucosal defense mechanism, or a combination of these two abnormalities. Environmental factors such as use of nonsteroidal and steroidal anti-inflammatory drugs, smoking, and emotional stress may play a role in the pathogenesis of ulcer disease in some patients. The exact mechanisms whereby these factors cause ulcers is unknown, although it is likely that non-steroidal drugs cause ulcers by reducing mucosal defense mechanisms whereas emotional stress may lead to ulceration by increasing acid secretion and/or decreasing mucosal defense mechanisms. Genetic factors may be important in the pathogenesis of ulcers in some patients.

Alcoholic Beverages↗

PubMed1985

In vivo and in vitro evaluation of magnesium-aluminum hydroxide antacid tablets and liquid.

The effect of magnesium-aluminum hydroxide antacid tablets or liquid on food-stimulated gastric acidity was evaluated in vivo in eight duodenal ulcer patients. Experiments were performed also in vitro. Although in vitro neutralizing capabilities of the two preparations were the same (28.3 +/- 0.1 mmol/liter), the duration of effect of tablets was longer in vivo. For example, at 3 3/4 hr after an eaten meal, mean hydrogen ion concentration with three tablets was 29.8 +/- 9.9 mmol/liter while with 15 ml liquid it was 59.6 +/- 10.3 mmol/liter (P less than 0.05). Additional studies were performed in vitro to explain the longer duration of effect of tablets compared with liquid in vivo. These experiments suggested that tablets reacted more slowly with acid than did liquid and that saliva, which was mixed with tablets during chewing, also contributed to the prolonged duration of effect.

Aluminum Hydroxide↗

PubMed1985

Sustained fasting achlorhydria: a comparison of medical regimens.

The effects on fasting gastric pH of eight medical regimens were evaluated during a 10-h period in 8 duodenal ulcer patients. Our goal was to find a regimen that would produce sustained, fasting achlorhydria (pH greater than 7.0) in every patient. The effects of commonly prescribed bolus doses of cimetidine, antacid, or their combination were studied first. Mean gastric pH with cimetidine (300 mg/6 h intravenously), antacid (30 ml/h intragastrically), and their combination was 3.5, 4.6, and 6.8, respectively. Although mean pH with the combination was significantly higher than with either drug alone (p less than 0.05), sustained achlorhydria was not achieved. Next we tested constant-infusion regimens of cimetidine (50 mg/h intravenously), antacid (0.5 ml/min intragastrically), and their combination. Whereas infusions of cimetidine or antacid alone produced mean pH levels of 4.3 and 5.2, respectively, not significantly different from their bolus counterparts, the combination regimen resulted in a mean pH of 7.4. However, sustained achlorhydria was still not produced in each patient. Only when the dose of cimetidine infusion was doubled to 100 mg/h and administered with a constant infusion of antacid was sustained achlorhydria achieved in each patient.

Adult↗

PubMed1985

Treatment of Zollinger-Ellison syndrome with exploratory laparotomy, proximal gastric vagotomy, and H2-receptor antagonists. A prospective study.

Twenty-two patients with Zollinger-Ellison syndrome were managed by a combined medical and surgical approach. Patients were treated initially with cimetidine or ranitidine. A laparotomy was performed to remove easily resectable tumors and to carry out a proximal gastric vagotomy. Tumors were found in 9 patients (41%) and all visible tumors were removed from 6 of the 9 patients. Fasting serum gastrin concentrations and serum gastrin responses to intravenous secretin were normal 6 wk after surgery in each of the patients from whom all visible tumors were resected and are normal in 4 patients, 6 wk to 5 yr after surgery. Acid secretion was reduced after vagotomy in each patient, even when tumors were not found or completely resected. Thus, vagotomy decreased the acid secretory response to endogenous hypergastrinemia. In addition, vagotomy augmented the inhibitory effect of H2-receptor antagonists on acid secretion. Follow-up has ranged from 6 wk to 6 yr (median, 2 yr). Dosages of cimetidine or ranitidine have been reduced, compared with preoperative amounts, in all but 1 patient. Two patients are taking no antisecretory drugs. Only 3 patients have had occasional symptoms of ulcer disease. Complications such as bleeding, perforation, or obstruction have not occurred in any patient. Endoscopy was performed in all patients to estimate the point prevalence of active ulcers and an ulcer was found in 1 patient. Based on these results, it is our opinion that this combined medical and surgical approach is an effective treatment for patients with Zollinger-Ellison syndrome.

Adolescent↗

PubMed1985

Effect of histamine and cimetidine on amino acid meal-stimulated gastrin release at a controlled intragastric pH in healthy human beings.

Results of several experiments have suggested that histamine-2 receptors play an inhibitory role in regulating gastrin release. We evaluated this prospectively in healthy human beings by infusing intravenously either histamine (0.33 micrograms/kg/min) or cimetidine (3.33 mg/min) during a continuous 3-h intragastric infusion of a 3% mixed amino acid meal, a potent stimulus of gastrin release. In order to be certain that effects of histamine or cimetidine on gastrin release were independent of their known effects on gastric acid secretion, intragastric pH was maintained at 5.0 by in vivo intragastric titration with sodium bicarbonate or hydrochloric acid. Although histamine and cimetidine had significant effects on gastric acid secretion, neither significantly affected the rises in serum gastrin concentrations during intragastric amino acid infusion. For example, mean gastrin rises above basal concentrations were 39 +/- 9 pg/ml on the control day, 39 +/- 9 pg/ml on the histamine day and 44 +/- 11 pg/ml on the cimetidine day (P greater than 0.05). Thus, blockade or stimulation of H2-receptors at the doses tested had no effect on gastrin release in response to an amino acid meal in humans when intragastric pH was maintained at 5.0.

Adult↗

PubMed1985

Effect of pentagastrin on gastric mucosal histamine in dogs.

We studied the effect of pentagastrin on histamine content of gastric mucosa obtained from dogs with gastric fistulas to determine whether pentagastrin mobilizes cellular stores of histamine. Experiments were also performed on canine gastric mucosa in vitro to investigate the effects of pentagastrin on histamine release, per se. During in vivo studies basal histamine content averaged 0.9 nmol/mg wet wt tissue or 18.8 nmol/mg tissue prot. No significant difference in gastric mucosal histamine content occurred during intravenous administration of pentagastrin (6 or 16 micrograms . kg-1 . h-1) or saline (control), even though acid output from the gastric fistula increased significantly above control during pentagastrin infusion. Moreover, pentagastrin (10(-5) and 10(-8)M) did not release more histamine from gastric mucosa in vitro than the buffer (control), whereas Triton X-100 and the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, alone and in combination with calcium ionophore A23187, released significant amounts of histamine above control values. From these experiments we conclude that pentagastrin did not alter histamine content of canine gastric mucosa in vivo, even though acid secretion was stimulated maximally, nor did pentagastrin release histamine in vitro.

Animals↗

PubMed1984

Effect of a new potent H2-receptor antagonist on meal-stimulated gastric acid secretion and serum gastrin concentration in duodenal ulcer patients.

We evaluated the effect of 20-, 40-, 60-, and 80-mg doses of SKF 93479, a new H2-receptor antagonist, on food-stimulated gastric acid secretion in duodenal ulcer patients. Medications were given as a single oral dose in the morning with a breakfast meal, and acid secretion was measured by in vivo intragastric titration in response to four blended steak meals infused into the stomach at intervals over a 24-hr period. A breakfast meal was infused immediately after medication; a luncheon meal was given 5 hr after drug, and a dinner meal was instilled 10 hr later. A second breakfast meal was infused 24 hr after medication. For comparison, the effect of 300 mg cimetidine, given as normally prescribed (with meals and at bedtime), on acid secretion was also studied. Food-stimulated acid secretion was inhibited in a dose-related manner by each of the four doses of SKF 93479. The antisecretory effect was most dramatic following the luncheon meal, and there was still significant (P less than 0.05) inhibition of acid secretion at the dinner meal with all doses of SKF 93479. With the second breakfast meal 24 hr after medication, the 80-mg dose alone achieved significant (P less than 0.05) inhibition of acid secretion. Inhibition of acid secretion was correlated positively with blood SKF 93479 levels. When compared with placebo results, serum gastrin concentration, measured 5 and 10 hr after medication, was significantly higher (P less than 0.05) with SKF 93479.

Adult↗

PubMed1983

Sex-related differences in gastrin release and parietal cell sensitivity to gastrin in healthy human beings.

We compared serum gastrin concentrations and gastric acid secretion basally and in response to a mixed meal in age-matched women and men. Women had significantly higher basal serum gastrin concentrations (P < 0.01) and two- to threefold higher food-stimulated serum gastrin concentrations (P < 0.001) than men. Basal and food-stimulated serum gastrin concentrations in women did not fluctuate significantly during the menstrual cycle. Sex-related differences in food-stimulated serum gastrin concentrations were not due to differences in antral pH because pH after the meal in women and men had been kept constant at 5.0 by in vivo intragastric titration with sodium bicarbonate. Studies using an antibody that reacts only with potent gastrin heptadecapeptide species (G-17-I and II) indicated that women also had threefold higher serum G-17 concentrations after the meal than men (P < 0.005). Elevated serum G-17 concentrations after the meal in women were due to increased release of G-17 rather than slower clearance of G-17 from the circulation.Despite elevated serum gastrin concentrations in response to food, women secreted approximately the same amount of acid relative to their maximal secretory capacity as men. Furthermore, during exogenous G-17 infusion, which led to identical serum gastrin concentrations in women and men, the dose-response curve for acid secretion in women was shifted significantly to the right of the G-17 dose-response curve in men (P < 0.02). The dose of G-17 that stimulated half of peak acid secretion was two to three times higher in women than in men, reflecting significantly reduced sensitivity of parietal cells to gastrin in women (P < 0.05). Our studies suggest that, compared with men, women release greater amounts of gastrin but are at the same time less sensitive to stimulation of acid secretion by gastrin.

Adult↗

PubMed1983

Effect of gastric alkalinization on serum gastrin concentrations in humans.

Previous studies have shown that alkalinizing the stomach with sodium bicarbonate for periods up to 3 h does not cause an increase in serum gastrin concentration. We evaluated the effect of a 5-h period of continuous intragastric alkalinization on serum gastrin concentration in 12 healthy humans and 12 asymptomatic duodenal ulcer patients. On the first day, intragastric pH was maintained between 6.0 and 7.0 for 5 h by infusing 0.3 N sodium bicarbonate into the stomach. On the second day, an identical amount of sodium bicarbonate was infused intravenously while intragastric pH was permitted to remain at its natural level for 5 h. Serum gastrin concentration was also measured in each subject and patient after infusion of a homogenized steak meal. In both healthy subjects and duodenal ulcer patients, mean serum gastrin concentrations were significantly (p less than 0.05) higher after 5 h of intragastric bicarbonate infusion than after 5 h of intravenous bicarbonate infusion during which intragastric pH remained at its natural level. Increases in serum gastrin concentration with alkalinization averaged 23% and 30% of the increases in serum gastrin after a homogenized steak meal in the same subjects and patients, respectively. We conclude that continuous gastric alkalinization for 5 h increases serum gastrin concentrations in humans.

Bicarbonates↗