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Biomedical subjects

D L Hogan

Publications and source records attributed to D L Hogan.

At least 55 records · Page 3Linked to original sources
PubMed1989

Cyclooxygenase inhibition with indomethacin increases human duodenal mucosal response to prostaglandin E1.

In humans, prostaglandins of the E1 class stimulate duodenal mucosal bicarbonate secretion, whereas the cyclooxygenase inhibitor, indomethacin, decreases both mucosal PGE2 and bicarbonate production. The purpose of this study was to determine whether a synthetic prostaglandin E1, enisoprost, diminished the inhibitory effects of indomethacin on mucosal bicarbonate secretion. In seven healthy subjects the proximal 4 cm of duodenum was isolated by occluding balloons. The isolated test segment was perfused with 154 mM NaCl (2 ml/min, 37 degrees C). Each subject participated in four separate tests in random order. Indomethacin, 50 mg, or placebo was given 13 and 1 hr before testing. After measuring basal bicarbonate secretion, either 100 micrograms of prostaglandin E1 or placebo (in 154 mM NaCl) was perfused into the test segment over 30 min. As anticipated, PGE1 significantly increased duodenal mucosal bicarbonate secretion, and indomethacin decreased resting bicarbonate secretion. Indomethacin pretreatment significantly enhanced (P less than 0.03) the mucosa's response to PGE1 compared to PGE1 alone. These results further support the observations that endogenous prostaglandins, in part, regulate human proximal duodenal bicarbonate secretion. Furthermore, suppression of endogenous prostaglandin generation results in an increased sensitivity of the duodenal mucosa to PGE1.

Alprostadil↗
PubMed1989

Effect of VIP antagonist on VIP-, PGE2-, and acid-stimulated duodenal bicarbonate secretion.

Vasoactive intestinal peptide (VIP), prostaglandin E2 (PGE2), and luminal acidification are each potent stimulants of duodenal mucosal bicarbonate secretion. The present experiments were performed to determine whether the recently described VIP antagonist, [4Cl-D-Phe6,Leu17]VIP, suppresses VIP-stimulated duodenal mucosal bicarbonate secretion and to determine whether VIP serves as a mediator of bicarbonate secretion stimulated by acid or PGE2. In anesthetized rats, the effects of intravenous VIP, intraluminal PGE2, and intraluminal HCl on duodenal mucosal bicarbonate secretion both in the presence and absence of [4Cl-D-Phe6,Leu17]VIP were measured. The VIP antagonist inhibited duodenal bicarbonate secretion stimulated by both intravenous VIP and luminal acidification but not luminal PGE2. These findings suggest that VIP could be one mediator of acid-induced duodenal bicarbonate secretion and that the mechanism of PGE2-stimulated bicarbonate secretion is independent of VIP.

Animals↗
PubMed1989

The effect of vasoactive intestinal peptide, secretin, and glucagon on human duodenal bicarbonate secretion.

Duodenal luminal acidification increases duodenal mucosal bicarbonate production and also releases both secretin and vasoactive intestinal peptide (VIP). The effect of these two structurally similar peptides on human duodenal bicarbonate production has not been examined in humans. Our purpose was therefore to assess the effect of VIP and secretin and also glucagon, a homologous hormone, on human duodenal bicarbonate secretion. A 4-cm portion of either proximal or distal duodenum was isolated and perfused with iso-osmolar NaCl. Pure porcine VIP (200 and 400 pmol/kg-h intravenously) significantly increased proximal duodenal bicarbonate secretion. Although secretin (0.01 to 0.18 CU/kg-h intravenously) markedly increased pancreatic bicarbonate secretion, it failed to alter duodenal mucosal bicarbonate output in either the proximal or the distal duodenum. Glucagon (1 to 8 micrograms/kg-h intravenously) did not affect proximal duodenal mucosal bicarbonate output. It is concluded that VIP, but neither secretin nor glucagon, significantly stimulates human duodenal mucosal bicarbonate secretion.

Adult↗
PubMed1988

Damage and protection of the human gastric mucosa. A multiparameter assessment.

Studies in animals and humans have indicated that endogenous prostaglandins as well as synthetic prostaglandin analogues can prevent gastric mucosal damage induced by various agents. Methods were developed to assess induced damage and the effects of potentially protective agents (synthetic prostaglandin analogues and the histamine [H2]-receptor antagonist cimetidine) on the human gastric mucosa by measuring ion fluxes and transmucosal potential difference, as well as by observations with gastrointestinal endoscopy. Commonly ingested agents, such as aspirin, 1,300 mg, and 20 percent ethanol increased hydrogen ion and sodium ion fluxes, decreased potential difference, and caused gross mucosal damage, as observed by endoscopy. Conversely, acetaminophen, 2,600 mg, and 10 percent ethanol did not have any significant effects. Hyperosmolar solutions (1,800 and 3,600 mOsm/kg) also produced acute damage. Sodium taurocholate (10 mmol/liter) when instilled into the stomach, either at pH 1.1 or 7.0, produced both functional and structural damage. When given as a single dose, neither 15(R)15-methyl PGE2 nor the synthetic PGE1 analogue, misoprostol, prevented mucosal damage induced by aspirin and taurocholate (pH 1.1), respectively. Cimetidine, 400 mg orally, however, did reduce aspirin-induced mucosal damage, and this effect was independent of gastric acid inhibition.

Arbaprostil↗
PubMed1987

Impaired proximal duodenal mucosal bicarbonate secretion in patients with duodenal ulcer.

The defensive factors that prevent the human duodenal mucosa from acidic and peptic damage have not been fully evaluated. To determine whether duodenal mucosal bicarbonate production was altered in patients with inactive duodenal ulcer, we measured basal and acid-stimulated bicarbonate output from the duodenal bulb and the distal duodenum in healthy subjects and patients with inactive duodenal ulcer. As compared with 16 normal subjects, the 12 patients had significantly less mean (+/- SE) basal proximal duodenal mucosal bicarbonate secretion (185 +/- 13 vs. 107 +/- 18 mumol per centimeter per hour; P less than 0.001). Moreover, in response to a physiologic amount of hydrochloric acid (2 mmol per five minutes) instilled directly into the duodenal bulb, peak proximal duodenal bicarbonate output in the patients was 41 percent of the normal response (263 +/- 65 vs. 642 +/- 77 mumol per centimeter per hour; P less than 0.01). There was little overlap between groups. In contrast, bicarbonate outputs in the distal duodenum were similar in the two groups. We conclude that most patients with duodenal ulcer disease have decreased proximal duodenal mucosal bicarbonate production at rest, in response to hydrochloric acid, and in relation to peak gastric acid secretion. Impaired proximal duodenal mucosal bicarbonate secretion may be an important factor in the development and natural history of duodenal ulcer.

Adult↗
PubMed1987

Cimetidine decreases aspirin-induced gastric mucosal damage in humans.

Aspirin induces gastric mucosal damage in animals and humans. The purpose of this study was to examine whether cimetidine protects the human gastric mucosa from acute aspirin-induced damage. Eight healthy subjects were studied on 4 separate days. Cimetidine, 400 mg, or placebo was given orally 1 hour before initial endoscopy. The stomach was isolated and atropine given to suppress basal acid secretion. Each study consisted of four 15 min periods during which an acidic test solution was instilled into the stomach. During the second period only, either aspirin (1300 mg, 36 mmol) or control for aspirin (36 mmol HCl) was added to the test solution. Ion fluxes and gastric mucosal potential difference were measured, and endoscopy performed following each test. After placebo, aspirin significantly altered hydrogen ion flux and potential difference versus basal and control. Cimetidine decreased the damaging effect of aspirin. Endoscopic scores increased after aspirin plus placebo, whereas they remained unchanged after aspirin plus cimetidine. Therefore, cimetidine decreased aspirin-induced gastric mucosal damage in humans. As gastric acidity was identical during all studies, the effect of cimetidine was independent of gastric acid secretion.

Adult↗
PubMed1987

Indomethacin inhibits duodenal mucosal bicarbonate secretion and endogenous prostaglandin E2 output in human subjects.

Nonsteroidal anti-inflammatory drugs are a frequent cause of gastric and duodenal mucosal injury. We examined the effect of indomethacin on duodenal mucosal bicarbonate secretion and prostaglandin output in healthy subjects. Subjects received either 50 mg of indomethacin or placebo orally 13 hours and 1 hour before study. A 4-cm segment of proximal (the duodenal bulb) or distal (10 to 14 cm beyond the pylorus) duodenum was isolated and perfused with 154 mM NaCl containing a nonabsorbable marker. In the proximal duodenum indomethacin reduced both basal and acid-stimulated bicarbonate secretion by approximately 65% (p less than 0.01); in the distal duodenum indomethacin decreased basal and acid-stimulated bicarbonate output by approximately 45% (p less than 0.01). Oral indomethacin inhibited basal and acid-stimulated duodenal prostaglandin E2 output in both the proximal and distal duodenum. We conclude that, by decreasing duodenal mucosal bicarbonate production and prostaglandin output in humans, oral indomethacin, in two doses of 50 mg each, impairs an important duodenal defense mechanism.

Administration, Oral↗
PubMed1986

Enprostil, a synthetic prostaglandin E2 analogue, inhibits meal-stimulated gastric acid secretion and gastrin release in patients with duodenal ulcer.

The effect of enprostil, a synthetic dehydro-prostaglandin E2, on meal-stimulated gastric acid secretion and gastrin release was studied in six patients with inactive duodenal ulcer disease. Each subject underwent seven tests in random order on separate days: placebo intragastrically and intraduodenally; enprostil 35 and 70 micrograms both intragastrically and intraduodenally; and ranitidine 150 mg intragastrically. After measuring basal gastric acid secretion and gastrin release, a liquid meal (500 ml, pH 5.5, 40 g protein, 30 g fat, 30 g carbohydrate, 550 Kcal, 768 mOsm) was given. Gastric acid secretion and gastrin release were measured over the next four hours. A second identical meal was instilled and both parameters were measured for an additional four hours. Thirty-five and 70 micrograms of enprostil administered intragastrically reduced total eight-hour gastric acid secretion by 58 percent and 82 percent, respectively (p less than 0.05). The 35 and 70 microgram doses administered intraduodenally decreased gastric acid secretion by 67 percent and 91 percent, respectively (p less than 0.05 compared with placebo). Ranitidine suppressed gastric acid secretion by 95 percent, which was similar to the suppression achieved with the 70 microgram dose of enprostil. The total meal-stimulated integrated gastrin response was significantly suppressed by both intragastric doses of enprostil and by the 70 microgram dose given intraduodenally (p less than 0.05). Compared with placebo, the 35 microgram intragastric and intraduodenal doses decreased the integrated gastrin response by 73 percent and 72 percent, respectively. The 70 microgram intragastric and intraduodenal doses of enprostil reduced the integrated gastrin response by 90 percent and 125 percent, respectively. Ranitidine did not alter the integrated gastrin response. It is concluded that enprostil significantly inhibited both meal-stimulated gastric acid secretion and gastrin release. The response to enprostil occurred in a dose-dependent manner and was similar regardless of the route of administration.

Duodenal Ulcer↗
PubMed1986

Effect of 11R, 16, 16-trimethyl prostaglandin E2 on meal-stimulated gastric acid secretion in duodenal ulcer subjects.

The effect of varying oral doses of 11R, 16, 16-trimethyl prostaglandin E2 (TmPGE2) on meal-stimulated gastric acid secretion and serum gastrin concentrations was studied in 10 male subjects with asymptomatic duodenal ulcer disease. A liquid protein meal was infused intragastrically 0.5 h and 3.5 h after drug administration. TmPGE2 inhibited gastric acid secretion in a dose dependent manner during the first meal and no significant effect was observed during the second meal. Except for the highest dose, no TmPGE2 was detected in plasma 3 h after drug administration. The degree of inhibition of meal-stimulated gastric acid was positively correlated with the plasma level of TmPGE2, but it was not due to inhibition of postprandial gastrin release. The results indicate that oral TmPGE2 inhibits meal-stimulated gastric acid secretion but not gastrin release in humans with asymptomatic duodenal ulcer disease.

Adult↗
PubMed1986

The effect of sodium bicarbonate versus aluminum-magnesium hydroxide on postprandial gastric acid in duodenal ulcer patients.

When ingested 1 hour after a meal, conventional liquid antacids have a buffering effect of approximately 2 hours, while in the fasting state their effect is brief, lasting less than 1 hour. We tested the hypothesis that equal doses of antacid, one water soluble (sodium bicarbonate) and the other water insoluble (aluminum hydroxide plus magnesium hydroxide, MaaloxR), would have similar durations of postprandial buffering if the water soluble antacid regenerates the particulate protein buffer of the meal that leaves the stomach more slowly than liquids. Tests were conducted in random order on three separate days in 10 patients with duodenal ulcer. The effects of 30 ml of 2.39 M sodium bicarbonate (6.17 g, about 1 teaspoonful), the aluminum-magnesium antacid, each equivalent to 71.7 mmol of in vitro buffer, and water as a control on pH, hydrogen ion activity, and titratable acidity were compared. Thirty milliliters of each was swallowed 1 and 3 hours after ingestion of a standard solid plus liquid. Compared to the water control each dose of sodium bicarbonate significantly increased intragastric pH and decreased hydrogen ion activity and titratable acidity for only 1 hour. Each dose of the aluminum-magnesium antacid significantly buffered intragastric contents for 2 hours. These findings indicate that sodium bicarbonate transiently buffers postprandial intragastric contents. Therefore, sodium bicarbonate fails to reconstitute the protein buffer of the meal effectively, and the observations suggest that it leaves the stomach rapidly with the liquid phase of the meal. However, the water insoluble, aluminum-magnesium antacid has a longer duration of buffering, probably because it leaves the stomach more slowly, largely with the solid portion of the meal.

Adult↗
PubMed1986

Duodenal mucosal bicarbonate secretion in humans: a brief review.

The human proximal duodenum serves as the crucible for the neutralization of gastric acid. Methods have been developed and validated that permit isolation of 4-cm segments of either the proximal or distal duodenum. These isolated segments were free of contamination from gastric, pancreatic, and biliary secretions. At rest the healthy human proximal duodenum produced approximately 175 mumol cm-h: or, assuming that the duodenal bulb is approximately 4 cm in length, 700 mumol h. The distal duodenum (the third part) produced significantly less bicarbonate, approximately 25 mumol/cm-h. HCl produced a prompt and sustained increase in bicarbonate output from both duodenal segments. Bicarbonate output was less in the distal duodenum, indicating a proximal-to-distal gradient. Synthetic prostaglandin E1 caused a dose-related increase in output. Substitution of the NaCl perfusate with Na2SO4 produced a brief decrease, suggesting a chloride bicarbonate exchange mechanism. Vasoactive intestinal polypeptide significantly increased proximal duodenal bicarbonate output. Bicarbonate production by the duodenal mucosa is probably an important defensive factor in maintaining mucosal integrity.

Alprostadil↗
PubMed1986

Human duodenal mucosal bicarbonate secretion. Evidence for basal secretion and stimulation by hydrochloric acid and a synthetic prostaglandin E1 analogue.

The factors responsible for prevention of duodenal mucosal injury are not known. This series of experiments was performed to determine whether the human duodenum secretes bicarbonate that could prevent mucosal damage. To isolate a 4-cm segment of proximal (i.e., the duodenal bulb) or distal duodenum free of contamination from either gastric or pancreaticobiliary secretion, or both, methods were developed using occlusive balloons. The test segment was perfused with NaCl (2 ml/min, 37 degrees C) containing [14C]PEG as a nonabsorbable marker, and bicarbonate output was quantitated. Mean (+/- SE) basal proximal duodenal bicarbonate output was 143 +/- 17 mumol/cm X h. A 5-min infusion of 25, 50, and 100 mM HCl directly into the isolated proximal duodenal test segment increased bicarbonate output to 167 +/- 29, 199 +/- 19, and 278 +/- 49 mumol/cm X h, respectively, during the hour after acidification. Distal duodenal acidification (25, 50, and 100 mM) also increased bicarbonate output from the isolated proximal duodenal test segment. A synthetic prostaglandin E1 analogue, misoprostol (1.67-13.3 micrograms/min), infused directly into proximal or distal test segments significantly stimulated bicarbonate outbreak; peak responses were 644 +/- 35 mumol/cm X h and 171 +/- 20 mumol/cm X h (p less than 0.001), respectively. Thus, in humans, the proximal and distal duodenal mucosa secretes bicarbonate at rest; direct acidification of the proximal duodenum stimulates bicarbonate output; acidification of the distal duodenum beyond the isolated test segment also increased proximal duodenal bicarbonate output; and a synthetic prostaglandin E1 analogue stimulated both proximal and distal bicarbonate output; however, distal duodenal bicarbonate output was significantly less, indicating a proximal-to-distal gradient in bicarbonate secretion.

Adult↗
PubMed1985

Intestinal phase of gastric acid secretion in humans with and without portacaval shunt.

To examine the effect of proximal small intestinal stimulants of gastric acid secretion in cirrhotic patients with portacaval shunt, unshunted cirrhotics, and normal subjects, a mixture of L-amino acids was administered intraduodenally, into the proximal jejunum, or intravenously to 8 cirrhotic patients with portacaval shunt and to 8 unshunted subjects (4 cirrhotic and 4 healthy volunteers). In addition, the effect of intrajejunally administered hyperosmolar mannitol (850 mosmol/kg) and intrajejunal balloon distention (40 mmHg) was determined. In the shunted and unshunted groups gastric acid secretion significantly increased equally in response to intravenous and intraduodenal amino acid infusion, whereas amino acids administered intrajejunally did not significantly alter acid secretion. Perfusion of the jejunum with hyperosmolar mannitol resulted in significant stimulation of acid secretion in the shunted subjects, whereas in the unshunted subjects it caused significant inhibition. In addition, jejunal balloon distention significantly stimulated secretion in the shunted subjects, but not in the unshunted group. Serum gastrin did not change significantly during any of the experiments and plasma amino acids were not different after jejunal compared with duodenal perfusion. These studies indicate the following: Enteral and parenteral amino acids increase gastric acid secretion similarly in subjects with and without portacaval shunt. The intestinal phase of gastric acid secretion is initiated by intraduodenal, but not intrajejunal, amino acids. As plasma amino acid concentrations were similar regardless of the route used, this suggests that the intestinal phase of acid secretion cannot be fully explained by the postabsorptive stimulation by amino acids. Intrajejunal distention with a balloon or infusion of hyperosmolar mannitol into the proximal jejunum stimulates acid secretion only in subjects with portacaval shunt.

Adult↗
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↗
PubMed1984

A new method for quantitation of ion fluxes across in vivo human gastric mucosa: effect of aspirin, acetaminophen, ethanol, and hyperosmolar solutions.

A new, sensitive, and reproducible method for measuring hydrogen and sodium ion fluxes across the human gastric mucosa was developed and validated. By the use of a double-balloon tube that obstructed the pylorus, the stomach was converted into an in vivo Pavlov-type pouch. Duodenogastric reflux was prevented, and emptying of gastric contents into the duodenum was, on the average, 6%, thereby eliminating two important sources of error in quantitative gastric ion fluxes in humans. Transmucosal potential difference and endoscopic appearance of the gastric mucosa were also evaluated during each experiment. The mean percentage variation between duplicate tests for hydrogen ion was 3.2%, for sodium 17.5%, and the potential difference was 2.5%. Instillation of acetylsalicylic acid (36 mM, 1300 mg) in 200 ml of 100 mM hydrochloric acid for just 15 min resulted in a mean net hydrogen ion loss of 3.4 mmol/15 min, a net sodium ion gain of 1.9 mmol/15 min, a decrease in the potential difference of 23 mV, and marked gastric mucosal changes. Furthermore, exposure for 15 min to 20% ethanol (vol/vol, in 200 ml of 100 mM hydrochloric acid) and two separate hyperosmolar solutions (3600 mosmol/kg and 1800 mosmol/kg, both in 200 ml of 100 mM hydrochloric acid) also resulted in marked changes of net hydrogen ion loss (3.1, 4.8, 5.2 mmol/15 min, respectively), net sodium ion gain (2.4, 3.3, 2.4 mmol/15 min, respectively), decrease in potential difference (32, 30, 36 mV, respectively), and gross damage to the gastric mucosa. Each parameter was significantly different from the control test. Acetaminophen (86 mM, 2600 mg) or 10% ethanol (vol/vol) in 200 ml of 100 mM hydrochloric acid did not significantly alter ion fluxes or potential difference. Acetaminophen also did not significantly alter the endoscopic appearance of the gastric mucosa, whereas 10% ethanol had only a modest effect. In the control, aspirin, and acetaminophen experiments, maximal changes in the four parameters (i.e., hydrogen and sodium ion fluxes, potential difference, and endoscopic score) were significantly correlated with one another.

Acetaminophen↗