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Biomedical subjects

V Maxwell

Publications and source records attributed to V Maxwell.

At least 19 recordsLinked to original sources
PubMed1994

Somatostatin is released in response to cholecystokinin by activation of type A CCK receptors.

Cholecystokinin is a principal mediator of intestinal fat-induced inhibition of gastric acid secretion, indicating that it is an important physiological enterogastrone. Cholecystokinin has been shown to inhibit acid secretion by activation of type A CCK receptors and through a mechanism involving somatostatin. In the present study, we investigated the possibility that these two mechanisms are directly related such that activation of type A CCK receptors by CCK causes the release of somatostatin. We tested this hypothesis in vivo in a study of CCK-stimulated release of somatostatin in dogs and in vitro in a study of CCK-stimulated release of somatostatin from an enriched culture of canine fundic D cells. In dogs, IV infusion of CCK (50 pmol/kg/h, IV) significantly increased circulating somatostatin concentrations above basal. Further, systemic administration of somatostatin MAb F(ab)1 fragments of a somatostatin monoclonal antibody prevented most of CCK-induced inhibition of meal-stimulated acid secretion. In canine fundic D cells in culture, CCK-stimulated somatostatin release was blocked in a dose-dependent fashion by application of a type A CCK receptor antagonist. This study indicates that CCK activates type A CCK receptors to release somatostatin from canine fundic mucosal D cells, and accounts for somatostatin-dependent CCK-induced inhibition of acid secretion.

Acids↗
PubMed1993

Look through the parents' eyes. Helping parents of children with a learning disability.

1. The loss suffered by parents of children with learning disabilities is similar in some ways to a grief response, and must be clearly acknowledged. 2. While forming an identifiable group, parents of children with learning disabilities have individual abilities and needs both as people and as parents. 3. Adjusting to life with a child with a learning disability is often a long process marked by times of crisis, when extra professional intervention may be necessary. 4. Parents and professionals can work together, learning from each other and ultimately increasing the quality of life for the person with the learning disability.

Adaptation, Psychological↗
PubMed1992

Intestinal fat does not inhibit gastric function through a hormonal somatostatin mechanism in dogs.

In awake dogs with chronic gastric, duodenal, and jejunal fistulas, F(ab)1 fragments of somatostatin monoclonal antibody (mAb S607) were administered intravenously (IV) to test the hypothesis that intraintestinal lipid inhibits peptone-stimulated gastric acid secretion and emptying by a hormonal somatostatin mechanism. Plasma somatostatin was increased significantly by duodenal and jejunal perfusion with 20% lipid. Somatostatin administered IV caused dose-dependent inhibition of meal-stimulated gastric acid secretion and gastric emptying similar to that seen after intestinal perfusion with lipid. Administration of mAb S607 F(ab)1 fragments significantly reversed somatostatin (400 pmol.kg-1.h-1, IV)-induced inhibition of peptone-stimulated acid output and gastric emptying. Acid output inhibited by intraduodenal lipid was reversed partially after F(ab)1 administration, but the inhibitory effect of intrajejunal lipid was not altered. Inhibition of acid secretion by IV somatostatin and by intraintestinal fat was not caused by a decrease in circulating gastrin concentrations. Gastric emptying delayed by intraintestinal lipid was unaffected by antibody administration. Somatostatin does not appear to be a major hormonal mediator of intestinal fat-induced inhibition of gastric acid secretion or delayed gastric emptying in dogs.

Animals↗
PubMed1992

Cholecystokinin receptor antagonist MK-329 blocks intestinal fat-induced inhibition of meal-stimulated gastric acid secretion.

MK-329, a selective type A cholecystokinin (CCK) receptor antagonist, was given to dogs to test the hypothesis that CCK is one of the principal physiological enterogastrones mediating fat-induced decreases in gastric acid secretion. Gastric acid secretion in response to 300 mL 8% peptone meals was measured by intragastric titration to pH 5.5 in six awake dogs with chronic gastric, duodenal, and jejunal fistulas. Gastric emptying was measured by a dye-dilution technique. During the last hour of peptone stimulation, the intestine was perfused with either control solution or 20% lipid (Intralipid; Kabi Vitrum, Alamedo, CA) intraduodenally or intrajejunally. Compared with control perfusions, mean gastric acid outputs were decreased significantly after lipid perfusion of the duodenum (47% of control) and jejunum (24% of control). Similarly, mean gastric emptying rates were significantly less after lipid perfusion of the duodenum (56%) and jejunum (26%). Oral pretreatment with MK-329 (1 mg/kg) significantly reversed the inhibition of gastric acid output caused by lipid perfusion of the duodenum and jejunum, but fat-induced inhibition of gastric emptying was not significantly affected. These studies provide evidence for an important inhibitory role for CCK as an enterogastrone but do not implicate CCK as being important in fat-induced delayed gastric emptying of a liquid meal in dogs.

Animals↗
PubMed1992

Regulation of gastric acid secretion by gastrin in duodenal ulcer patients and healthy subjects.

To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol.kg-1.h-1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2-8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach.

Adult↗
PubMed1990

Prolonged inhibition of acid secretion causes hypergastrinaemia without altering pH inhibition of gastrin release in humans.

Hypergastrinaemia induced by potent inhibitors of acid secretion is thought to occur as a result of the elimination of the inhibitory effects of intragastric acid on gastrin release. The present study was designed to determine if the mechanisms responsible for feedback inhibition of gastrin release and acid secretion by intragastric acid are preserved during four weeks of varying degrees of drug-induced acid inhibition. Forty-eight healthy male volunteers were randomly assigned to one of four treatments for four weeks: 10 mg omeprazole o.m., 20 mg omeprazole o.m., 40 mg omeprazole o.m. or 150 mg ranitidine b.d. Gastrin release and acid secretion in response to peptone meals maintained at pH 2.5 and pH 5.5 by intragastric titration, and 24-hour gastrin profiles in response to standard meals were determined before treatment, at the fourth week of treatment and two weeks after discontinuing treatment. As expected, omeprazole produced dose-related effects on acid secretion and gastrin concentrations that were largely reversed after treatment was discontinued. Gastrin release in response to pH 5.5 peptone meals remained significantly greater than gastrin release in response to pH 2.5 meals during treatment with all doses of omeprazole. The ratio of pH 5.5/pH 2.5 peptone meal-stimulated gastrin release was approximately 1.5, and remained constant for all treatment groups throughout the study period. These data indicate that four weeks of drug induced hypochlorhydria causes an apparent increase in overall G-cell function, but it does not interfere with normal feedback inhibition of gastrin release and acid secretion mediated by intragastric acidity.

Adolescent↗
PubMed1989

Gastrin is a major mediator of the gastric phase of acid secretion in dogs: proof by monoclonal antibody neutralization.

We developed a monoclonal antibody, 28.2, that binds specifically to the amidated carboxyl terminal region common to gastrin and cholecystokinin. This immunoglobulin G1 antibody has high affinity (ID50 = 30-70 pM for gastrin and cholecystokinin peptides), binds labeled gastrin similarly at 37 degrees C and 4 degrees C, and shows minimal inhibition of binding in the presence of 40% canine serum. Antibody 28.2 was used to carry out in vivo immunoneutralization studies in 8 dogs previously prepared with chronic gastric fistulas. Preliminary studies revealed that a single intravenous dose of 0.75 mg of partially purified immunoglobulin G of monoclonal antibody 28.2 completely inhibited the acid stimulatory effect of exogenous gastrin-17 given intravenously at 200 pmol/kg.h, a physiologic dose, and inhibited by 70% the acid response to a supraphysiologic dose, 800 pmol/kg.h. The same dose of antibody decreased the acid secretory response obtained during distention of the stomach with 300 ml of 5.8% glucose solution by 98% and decreased the response to distention with 300 ml of 8% peptone solution by 68%. A 10-fold higher dose of antibody decreased the acid response to peptone by 96%. The gastrin antibody had no effect on the acid response to exogenous histamine. A control antibody, specific for the biologically inactive glycine-extended gastrin/cholecystokinin peptapeptide region, had no significant effect on gastric acid secretion stimulated by gastrin or by gastric distention with nutrients. These studies indicate that circulating gastrin is of major importance in the gastric phase of gastric acid stimulation caused by distention of the stomach with nutrients.

Animals↗
PubMed1989

Prolonged inhibition of meal-stimulated acid secretion and gastrin release following single subcutaneous administration of octreotide (SMS 201-995) in man.

Single subcutaneous doses of the somatostatin analogue, SMS 201-995, were evaluated for the degree and duration of effects on acid secretion, serum gastrin levels, and gastric emptying in eight human male subjects (mean age 44 years) over an 8-h period. All the subjects received subcutaneous 50-micrograms and 100-micrograms doses of SMS 201-995 and placebo on three separate days in a double-blind random order. Drug or placebo was administered at time 0 followed by peptone meals at time 0, 2, 4, and 6-h. Peptone meals were evacuated at time 1, 3, 5 and 7-h to create 'basal' conditions between alternate hours. Gastric acid secretion was determined hourly beginning at time--1. Both the 50-micrograms and 100-micrograms doses of SMS 201-995 significantly inhibited 'basal' and peptone meal-stimulated gastric acid secretion throughout the 8-h measurement period. The minimum effective plasma concentration of SMS 201-995 for inhibition of peptone meal-stimulated gastric acid secretion was approximately 1000 pg/ml. Peptone meal-stimulated plasma gastrin concentrations were inhibited for 5 and 7 h after 50-micrograms and 100-micrograms doses of SMS 201-995, respectively, whereas 'basal' plasma gastrins were inhibited for 4 and 6 h, respectively. Gastric emptying determined by marker dilution was not significantly enhanced compared to placebo. These results indicate prolonged and potent effects of single subcutaneous doses of SMS 201-995 on peptone-meal stimulated acid secretion and gastrin release.

Adult↗
PubMed1988

Somatostatin may not be a hormonal messenger of fat-induced inhibition of gastric functions.

The present study was designed to evaluate somatostatin as a hormonal inhibitor of gastric functions in humans. Seven healthy volunteers were investigated on 6 separate days. Peptone meal-stimulated gastric acid secretion was measured by intragastric titration for 2 h and gastric emptying was estimated with a dye-dilution technique. The effect of intravenous administration of somatostatin at 0, 12.5, 50, 100, and 200 pmol/kg.h was investigated and related to the effect of intragastric administration of 100 ml of vegetable oil. Plasma somatostatinlike immunoreactivity was elevated during intravenous administration of somatostatin at 100 and 200 pmol/kg.h, whereas no increase was detected in response to the oil. Somatostatin infusion at 100 and 200 pmol/kg.h significantly inhibited the acid secretion by 25% and 65%, and the oil reduced the acid output by 41%. Somatostatin at 100 and 200 pmol/kg.h significantly enhanced gastric emptying, whereas the oil inhibited gastric emptying. These observations suggest that somatostatin may not be an important hormonal messenger of fat-induced inhibition of acid secretion or gastric emptying.

Adult↗
PubMed1987

Gastric acidification inhibits meal-stimulated gastric acid secretion after prostaglandin synthesis inhibition by indomethacin in humans.

The effects of cyclooxygenase inhibition by indomethacin on gastric acid secretion were studied in 8 healthy men. Oral doses of indomethacin (200 mg), administered 15 and 2 h before testing, were known to inhibit prostaglandin synthesis by 90% in 3 of the subjects as determined by prostaglandin E2 generation assay on endoscopically obtained gastric mucosal biopsy specimens. Acid-induced inhibition of gastric acid secretion was evaluated in a randomized and blinded study in which acid output was measured for 2 h during basal conditions by aspiration, for the next 2 h by intragastric titration during distention with isotonic glucose, and for the following 2 h by intragastric titration during meal stimulation with peptone. The studies were done on separate days, and intragastric pH was maintained at either 2.5 or 5.5 after administration of indomethacin or placebo. Basal acid output was not altered by indomethacin treatment. Distention of the stomach stimulated acid output significantly to a similar degree in all groups, without affecting plasma gastrin. Meal stimulation increased plasma gastrin and acid output significantly more at pH 5.5 (47 +/- 12 pM, 13 +/- 2 mmol/30 min) than at pH 2.5 (30 +/- 8 pM, 6 +/- 2 mmol/30 min). No effect of indomethacin treatment was observed. It is concluded that the participation of cyclooxygenase products in the mechanisms by which acid inhibits the gastric phase of acid secretion in humans is likely to be minor. These results also cast doubt on an important physiologic role for cyclooxygenase products in the regulation of basal acid secretion or of acid secretion stimulated by distention or a peptone meal.

Adult↗
PubMed1987

Regulation of gastric acid secretion by neurotensin in man. Evidence against a hormonal role.

The present study was designed to evaluate neurotensin as a hormonal regulator of gastric acid secretion in man. After a fat-rich meal, the strongest known stimulus of neurotensin release, plasma neurotensin-like immunoreactivity (NTLI) was elevated from 7.6 +/- 1.9 to 15.5 +/- 2.5 pM. Plasma NTLI was measured with antiserum L170, which requires the biologically active carboxyl-terminal hexapeptide of the neurotensin molecule for recognition and does not crossreact significantly with any known natural catabolite in human plasma. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 resulted in a plasma level of 14.7 +/- 2.1 pM, similar to the maximal physiological level observed after the fat-rich meal. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 during 2 h, however, failed to significantly inhibit peptone meal-stimulated gastric acid secretion measured by intragastric titration. The 2-h acid output to peptone was 40.8 +/- 6.2 and 41.3 +/- 6.9 mmol during the vehicle and the neurotensin infusion, respectively. Intravenous infusion of neurotensin at 100 or 400 pmol X kg-1 h-1 did not affect acid output, whereas at 1,600 pmol X kg-1 h-1, which resulted in a plasma neurotensin concentration of 725 +/- 80 pM, significantly reduced peptone meal-stimulated gastric acid secretion. The neurotensin-induced inhibition of acid output was independent of the hormone gastrin. The present results provide evidence against a hormonal role for neurotensin in the regulation of meal-stimulated gastric acid secretion in man.

Adolescent↗
PubMed1987

Fat inhibits meal-stimulated gastric acid secretion after prostaglandin synthesis inhibition by indomethacin in man.

The effect of cyclooxygenase inhibition by indomethacin on the mechanism by which fat inhibits gastric acid secretion was studied in eight healthy men. Oral 200-mg doses of indomethacin administered 15 h and 2 h before testing is known to inhibit prostaglandin synthesis by 90%, as determined by prostaglandin E2 generation assay on endoscopically obtained gastric mucosal biopsy specimens. Fat-induced inhibition of gastric acid secretion was evaluated by intragastric administration of 200 ml vegetable oil or glucose (control) for 30 min, followed by intragastric titration with peptone at pH 5.5 for 2 h. The mean acid output was significantly lower after fat (8 +/- 0.2 mmol 30 min-1) as compared with control (12 +/- 0.5 mmol 30 min-1). The fat-induced inhibition was unaffected by indomethacin treatment, and the plasma gastrin responses were similar in all groups. It is concluded that the participation of cyclooxygenase products such as prostaglandins in the mechanisms by which fat inhibits the gastric phase of acid secretion in man is likely to be minor.

Adult↗
PubMed1987

The effect of an oral evening dose of nizatidine on nocturnal and peptone-stimulated gastric acid and gastrin secretion.

An evening oral dose of nizatidine, a new H2-receptor antagonist, was tested for its ability to suppress nocturnal gastric acid secretion and to inhibit food stimulated acid secretion the following day. Using a double-blind, randomized, cross-over design, nizatidine 30, 100, and 300 mg and placebo were compared in 8 male subjects with basal acid secretion greater than or equal to 3 mmol/h. Continuous nasogastric suction was started 2 h after oral dosing, and acid secretion was measured hourly overnight. Phenol red was used to determine the completeness of gastric aspiration. The following day, food stimulated acid secretion in response to 8% peptone meals was measured by intragastric titration to determine the carry-over effect of nizatidine. Serum gastrin levels were measured by RIA. Nizatidine inhibited overnight acid secretion in a dose-related manner with 30, 100, and 300 mg producing 57, 73, and 90% suppression. The effect was long-lasting, with nizatidine 300 mg decreasing acid secretion by 52% 10 h after administration. Peptone stimulated acid secretion on the following day was not inhibited by nizatidine. Gastrin levels did not differ significantly among the treatment groups. Nizatidine's effects on nocturnal acid secretion therefore resemble other H2-receptor antagonists.

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↗
PubMed1985

Somatostatin inhibits gastric acid secretion after gastric mucosal prostaglandin synthesis inhibition by indomethacin in man.

The inhibitory effect of indomethacin, 200 + 200 mg administered per os over 24 hours, on the prostaglandin E2 generative capacity of gastric mucosal tissue was determined in healthy male volunteers. The effect of prostaglandin synthesis inhibition on somatostatin induced suppression of food-stimulated acid secretion was tested. Peptone meal stimulated acid secretion was quantified in five healthy volunteers by intragastric titration with and without indomethacin pretreatment. Somatostatin doses of 200, 400, and 800 pmol/kg/h each significantly inhibited the peptone stimulated acid output. Indomethacin treatment, resulting in 90% inhibition of prostaglandin E2 synthesis, did not affect glucose- or peptone-stimulated acid output or modify the inhibitory action of somatostatin. Clinically, acid inhibition by somatostatin has been used to treat bleeding peptic ulcers. Ulcer haemorrhage may be preceded by an excessive use of drugs that inhibit prostaglandin synthesis such as aspirin or other non-steroidal anti-inflammatory agents. Recent observations in the rat indicate that prostaglandins mediate the inhibitory action of somatostatin on gastric acid secretion. The present results suggest that prostaglandins are not required for inhibition of gastric acid secretion by somatostatin in man.

Adult↗
PubMed1984

Glucose perfusion intragastric titration.

A comparison was made between use of isotonic 0.15 M sodium chloride and 5.8 g/100 ml glucose solutions for measurement of gastric acid secretion by intragastric titration in normal and ulcer subjects. Glucose distention did not cause significantly different acid secretion than saline distention in either group. The total amounts of glucose entering the duodenum over the 3.5-hr study period were 99 g in normal subjects and 122 g in ulcer subjects. In normal subjects, circulating gastrin-related acid secretion curves were not significantly different during endogenous peptone and exogenous G-17 stimulation using either the glucose or the saline meals. This finding provides evidence that glucose meals of this size do not alter sensitivity to gastrin. With glucose meals, inhibition of gastric emptying caused retention of a sufficient volume in the stomach to permit accurate continuous intragastric titration. Saline meals caused pronounced diarrhea which was not seen after glucose meals. Glucose distention intragastric titration allows reliable comparisons of endogenously and exogenously stimulated gastric acid secretion without serious side effects and is especially suitable for studying acid secretion in duodenal ulcer subjects.

Adult↗