Search PubMed⌕ Search

Biomedical subjects

H T Debas

Publications and source records attributed to H T Debas.

At least 127 records · Page 7Linked to original sources
PubMed1979

Clinical implications of the gastrointestinal hormones.

The importance of the gastrointestinal hormones to the clinician is considered under three headings: in disease states, diagnostic applications and therapeutic implications. Pearse's APUD (Amine Precursor Uptake and Decarboxylation) theory is referred to, and single and multiple endocrinopathies are discussed with particular referrence to diagnostic criteria and principles of management. The field of gastrointestinal endocrinology is rapidly developing and these peptides will assume an even greater importance to the clinician who must keep abreast with these developments.

Endoscopy↗
PubMed1978

Control of gastric emptying: interaction of the vagus and pyloric antrum.

Gastric emptying of liquids and solids was evaluated in ten dogs with gastric fistula before and after either truncal vagotomy, antrectomy, or pyloroplasty. In subsequent operations, the vagotomy group underwent either antrectomy or pyloroplasty, and the antrectomy and pyloroplasty groups were vagotomized. Vagotomy significantly inhibited the emptying of both liquids and solids (p less than 0.001) when the pyloric antrum was intact. When the antropyloric mechanism was removed by antrectomy, the effect of vagotomy was to accelerate the emptying of liquids (p less than 0.05) but to impair the emptying of solids (p less than 0.001). When the pylorus was destroyed by pyloroplasty, vagotomy markedly accelerated the emptying of liquids but had little effect on the emptying of solids. Neither antrectomy nor pyloroplasty had any significant effect on the emptying of solids. Pyloroplasty caused minor acceleration of emptying of liquids while antrectomy had no effect.

Animals↗
PubMed1978

Cholecystokinin inhibits gastric emptying by acting on both proximal stomach and pylorus.

Cholecystokinin is a potent inhibitor of gastric emptying. It is known to both relax the proximal stomach and contract the pyloric sphincter, and either one or both of these actions could mediate inhibition of gastric emptying. We investigated the relative importance of these two actions by studying the effectiveness of the C-terminal octapeptide of cholecystokinin (OP-CCK) to inhibit the emptying of a liquid meal (300 ml saline) before and after operations that either remove or destroy the pyloric mechanism (antrectomy and pyloroplasty), or lead to loss of accommodation of the proximal stomach (vagotomy), and after both vagotomy and antrectomy, and vagotomy and pyloroplasty. The results show that OP-CCK causes dose-related inhibition of gastric emptying in the intact dog. After either pyloroplasty or antrectomy the effectiveness of low but not of high doses of OP-CCK is lost. After vagotomy, OP-CCK at any dose was ineffective. The findings suggest that cholecystokinin inhibits gastric emptying by acting both on the pylorus and on the proximal stomach.

Animals↗
PubMed1978

Evidence for pyloropancreatic reflux for pancreatic exocrine secretion.

In seven dogs provided with innervated pouch of the pyloric antrum, gastric fistula, and chronic pancreatic fistula, the effect of graded antral distenion on pancreatic exocrine secretion was studied. The effect of antral distension was tested both when gastrin release was promoted (alkaline distention) and when gastrin release was blocked (acid distension). These studies were performed both before and after transthoracic truncal vagotomy. Graded alkaline antral distension caused graded rise in protein-rich pancreatic secretion and graded increase in the concentration of serum immunoreactive gastrin. A similar pancreatic response was also seen with graded acid distention although this time no rise in serum gastrin concentration occurred. Pancreatic response to antral distension with either alkali or acid is completely inhibited by pretreatment of the animals with systemic atropine. Truncal vagotomy reduced pancreatic response to alkaline antral distension by 90% but completely abolished pancreatic response to distension of the antrum with acid. These studies provide evidence for a pyloropancreatic reflex mechanism for pancreatic secretion that is cholinergic and requires intact long vagal pathways.

Animals↗
PubMed1977

Regulation of gastric acid secretion.

The advent of the H2-histamine-receptor antagonists has given new life to the old hypothesis that histamine might be the final common chemical mediator of acid secretion. The available evidence, however, does not prove this hypothesis but does confer on histamine a role in the regulation of acid secretion in normal physiology. Evidence is mounting that, in addition to its stimulatory action, the vagus may play an inhibitory role in acid secretion and gastrin release. Our concepts of the gastric phase of acid secretion have been extended by the discovery of cross distension reflexes in the stomach: the pyloro-oxyntic reflex for acid secretion and the oxyntopyloric reflex for gastrin release. In addition, digested protein has been shown to stimulate directly the oxyntic gland mucosa, but the evidence is against a role for this mechanism in the intact stomach. The hormone(s) responsible for the intestinal phase have not been isolated but the physiological characteristics of entero-oxyntin (a nongastrin, enteric substance that acts on the oxyntic cell) have been defined. Gastric inhibitory polypeptide is an excellent candidate for the entero-gastrone released by fat, but whether it is the sole enterogastrone released is yet to be determined.

Gastric Juice↗
PubMed1976

After vagotomy atropine suppresses gastrin release by food.

Changes in serum gastrin in response to feeding a meal of beef liver (15 g kg(-1)) were studied in 5 gastric fistula dogs with and without administration of atropine sulfate (0.2 mg kg(-1) intravenously). The studies were repeated after a truncal vagotomy that abolished acid secretion in response to 2-deoxyglucose. Before vagotomy atropine had little effect on the gastrin response to a meal. After vagotomy the gastrin response to feeding was greatly enhanced, but now atropine depressed the gastrin response at all times after the meal. It is concluded that vagotomy enhances the serum gastrin response to feeding and that atropine counteracts this enhancement.

Animals↗
PubMed1976

The vagus.

The surgical physiology of the vagus is reviewed with respect to vagotomy in the treatment of duodenal ulcer. All types of vagotomy (truncal, selective gastric, or proximal gastric) produce similar reduction in acid secretion and comparable elevation in serum gastrin. The evidence is mounting that the vagus may have opposing influences on gastrin release: stimulation and inhibition. Division of only the extragastric vagal branches leads to withdrawal of an inhibitory mechanism rendering the denervated stomach more sensitive to the action of gastrin. The loss of this vagally controlled inhibitory mechanism, rather than more meticulous dissection, may explain the higher incidence of more complete vagotomies in selective than in truncal vagotomy. Proximal gastric vagotomy may be the ideal elective operation yet devised for duodenal ulcer. It does, however, cause elevation in serum gastrin and more than 90 per cent of patients after this operation will have positive insulin test in two to four years. This is higher than the positivity seen with truncal vagotomy. Results of controlled trials are needed before this operation becomes fully established.

Animals↗
PubMed1975

Effect of extragastric and truncal vagotomy on pancreatic secretion in the dog.

In four dogs with chronic pancreatic and gastric fistulas, dose-response studies of pancreatic bicarbonate and protein secretion were done with intravenous infusions of secretin, octapeptide of cholecystokinin (OP-CCK), and 2-deoxyglucose (2-DG). The pancreatic response to a meal and to duodenal perfusion of graded concentrations of HCl, sodium oleate, and tryptophan were also studied. These observations were repeated after division of both the hepatic and celiac vagal branches to produce extragastric vagotomy, and subsequently after transthoracic truncal vagotomy. The responses to secretin, OP-CCK, and to duodenal perfusion of HCl were either unaltered or only slightly decreased by either extragastric or truncal vagotomy. Basal pancreatic secretion and the responses to duodenal perfusion of oleate and tryptophan were markedly depressed by extragastric vagotomy. These findings indicate that tonic vagal activity contributes to basal pancreatic secretion but has little effect on the response of the pancreas to secretin or CCK or on the release of secretin from the intestine. The decreased pancreatic response to intestinally perfused oleate and tryptophan seen after extragastric vagotomy could be caused either by interruption of reflex paths between gut and pancreas or by interference with CCK release. Extragastric vagotomy reduced pancreatic responses to a meal and to 2-DG and subsequent truncal vagotomy caused still further reduction, possibly, at least in part, by depressing release of antral gastrin.

Animals↗
PubMed1975

Molecular forms of gastrin in antral mucosa and serum of dogs.

Instillation of liver extract into antral pouches produced an increase in the serum concentrations of both little (G-17) and big (G-34) gastrins. The molar fraction of G-17 plus G-34 represented by G-17 was about 0.9 in antral mucosa and about 0.3 in serum 3 hr after initiating release with liver extract. The predominance of G-34 in serum can be accounted for only in part by its slower rate of removal from the blood so other factors probably also contribute. Although G-17 contributed only about 30% of the total molar concentration of gastrins in serum, it accounted for about 70% of the acid stimulatory activity because on a molar basis it is about five times more bioactive than G-34.

Animals↗
PubMed1975

Inhibition of gastric emptying is a physiological action of cholecystokinin.

This study was designed to determine whether cholecystokinin (CCK) plays a physiological role in the inhibition of gastric emptying. Physiological conditions were simulated by giving CCK by continuous intravenous infusion rather than by bolus injection, by using doses known to be distinctly submaximal for pancreatic protein secretion, and for gallbladder contraction, and by releasing endogenous CCK. The rate of gastric emptying was determined in 4 dogs with gastric fistulas by measuring the volume of fluid remaining in the stomach 10 min after instillation of 300 ml of 0.15 M NaCl. Rate of emptying was studied during intravenous infusion of saline (control) and of different doses of 98% pure CCK, commerically available 20% pure CCK, synthetic COOH-terminal octapeptide of CCK (OP-CCK), pentagastrin, and heptadecapeptide gastrin. The effect of endogenously released CCK was studied by measuring the rate of emptying of solutions in which different concentrations of tryptophan replaced equiosmolar amounts of NaCl. The d50's of 20% pure CCK (3 U kg minus-1 hr minus-1) and of OP-CCK (125 ng kg minus-1 hr minus-1) for inhibition of gastric emptying were about the same as their D50's for cholecystokinetic and pancreozyminic actions. By contrast, although both pentagastrin and heptadecapeptide gastrin inhibited gastric emptying, the doses required for this action were much higher than the D50's required for stimulation of gastric acid secretion. The effectiveness of OP-CCK indicates that inhibition of gastric emptying is attributable to CCK itself and not to an impurity in the CCK preparation. We have confirmed this directly by showing that pure CCK is a potent inhibitor of gastric emptying. Tryptophan also inhibited gastric emptying. In other dogs pancreatic protein secretion and gallbladder contraction were shown to be stimulated during the time tryptophan was inhibiting gastric emptying. This evidence supports the view that inhibition of gastric emptying is one of the physiological actions of CCK, but in the case of gastrin it must be regarded as a pharmacological action.

Animals↗
PubMed1975

Chemicals bathing the oxyntic gland area stimulate acid secretion in dog.

Release of gastrin is the only recognized mechanism by which chemicals in the stomach stimulate acid secretion. We report here that dietary components coming in contact only with oxyntic gland mucosa stimulate near maximal acid secretion through a local, H-sensitive mechanism that does not involve gastrin. In 4 dogs with gastric fistula and Heidenhain pouch (HP), 10% liver extract, 10% peptone, 0.4 M glycine, or Tris buffer, as control, was instilled into the HP in volumes of 40, 80, or 160 ml every 30 min. Instilled solutions were adjusted to pH 8.0 and HP acid secretion was measured by titrating a sample of the fluid recovered from the HP back to pH 8.0 with 0.2 M NaOH. Instillation of liver extract into the HP stimulated acid secretion from the HP but caused no change in serum gastrin and no change in acid secretion from the gastric fistula. The maximal response to liver extract occurred with the largest volume instilled and was 80% of the maximal response to histamine and 188% of the maximal response to pentagastrin. Expressed as per cent of maximal response to histamine, the maximal response to Tris buffer was 8%, to peptone 44%, and to glycine 14%. Intact bovine serum albumin gave no response, but after digestion by pepsin it stimulated acid secretion moderately. At pH 2.0, liver extract caused no stimulation of acid secretion. The pH threshold was about 2.5, and at pH 4.5 acid secretion was 55% of the response at pH 8.0. The response to liver extract at pH 8.0 was only minimally decreased by topical lidocaine or by intravenous atropine or metiamide. Since atropine and metiamide almost totally abolish the acid response to food in the main stomach, but do not inhibit secretion of acid evoked by instilling liver extract into the HP, there is reason to doubt whether this new mechanism operates under physiological conditions.

Animals↗
PubMed1974

Pure human minigastrin: secretory potency and disappearance rate.

Minigastrin, a gastrin with 13 amino-acid residues, was recently isolated from tissues by Gregory and Tracy (1974). In this study, pure human natural nonsulphated minigastrin (HG-13-I) and pure human natural nonsulphated heptadecapeptide gastrin (HG-17-I) were compared with regard to acid-stimulating potency and rate of disappearance from blood. Three dogs with gastric fistulae and Heidenhain pouches were given these gastrins by continuous intravenous infusion in doses of 100, 200, 400, and 800 pmol/kg-hr. Equimolar infusion rates of HG-13-I and HG-17-I caused equimolar increases over basal of serum immunoreactive gastrin but HG-13-I- was less than half as potent as HG-17-I in stimulating acid secretion (potency ratio 0.4, 95% confidence limits 0.2 to 0.6). The half time for disappearance of HG-13-I from blood was 1.8 minutes and its volume of distribution was calculated to be 0.17 1/kg, values similar to those found for HG-17-I in an earlier study. The role of minigastrin in health and disease awaits further study.

Animals↗
PubMed1974

Pure human big gastrin. Immunochemical properties, disappearance half time, and acid-stimulating action in dogs.

Biological properties of pure natural human "big gastrin" (designated G-34 because it contains 34 amino acid residues) were compared with those of pure natural heptadecapeptide gastrins (G-17) from human and porcine sources. Radioimmunoassay inhibition curves indicated that G-17 was nearly 1.5 times more potent than G-34 with the antibody used in this study. This difference was confirmed by demonstration of increased immunoreactivity generated when G-34 was converted to G-17 by trypsinization. When infused intravenously into dogs with gastric fistulas and Heidenhain pouches in equimolar doses, G-34 produced slightly higher acid secretory responses than G-17. Responses to sulfated and nonsulfated forms were not significantly different, nor were responses to human and porcine G-17. During infusion of equimolar doses, steady-state serum gastrin concentrations were more than fivefold higher with G-34 than with G-17. The difference in steady-state blood concentrations could be accounted for by a corresponding difference in removal rates. The half times of the G-34 preparations averaged 15.8 min and the half times of the G-17 preparations averaged 3.2 min. The calculated spaces of distribution for G-17 and G-34 were similar, about 25% of body weight. When the increment in serum gastrin was plotted against acid secretory response it was found that nearly five times greater increments in molar concentrations of G-34 than of G-17 were required to produce the same rate of acid secretion. The potency of these two molecular forms of gastrin can be expressed in two different ways. Based on exogenous molar doses, the potencies of G-34 and G-17 were similar. However, based on molar increments in serum gastrin concentration, G-17 was approximately five times more potent than G-34. Hence, fractionation of these gastrin components may be important in estimation of the acid-stimulating action represented by total serum gastrin as measured by radio-immunoassay.

Animals↗