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The vagus, the duodenal brake, and gastric emptying
Abstract
It has been suggested that an intact vagal supply is essential for the normal function of the recptors in the duodenum and proximal small bowel, which influence the rate of gastric emptying. This paper reports the effect of vagal denervation on gastric emptying and also examines the site and mode of action of receptors in the proximal small bowel. It has been demonstrated in the dog that most, if not all, the receptors controlling gastric emptying lie in the proximal 50 cm of the small bowel. Following truncal vagotomy the emptying time of each instillation increased significantly and the differential rate of emptying of different instillations remained unchanged. The proximal 50 cm of small bowel was capable to differentiating between different instillates even after selective extragastric vagotomy, in which the duodenum was vagally denervated and, therefore, duodenal braking receptors function independently of vagal innervation.
... In the 1970s, Hunt and Stubbs (1975) proposed that the rate of calories transferred to the intestine is relatively constant, and the time taken to completely empty the stomach is regulated by the delivery of calories to the intestine. On the basis of energy dependent emptying, other researchers put forward the duodenal braking effect based on intestinal nutrient negative feedback (McHugh and Moran et al., 1979;Shahidullah, Kennedy, & Parks, 1975). In 1983, Brener (1983 further elaborated on the mechanism of calorie based gastric emptying and proposed that the pyloric sphincter controls the discharge of stomach contents into the duodenum according to the type and quantity of existing nutrients in the proximal small intestine, so as to ensure that rate of calories entering the small intestine is kept constant. ...
A safe and cost effective approach to reduce obesity and accompanying chronic disease would be through controlling appetite and energy balance. Konjac glucomannan (KGM), a soluble dietary fiber (DF) that hydrates gradually and develops high viscosity in solution, has been demonstrated in some preclinical and clinical studies to reduce appetite and obesity. KGM has the highest hydrated volume at the lowest concentration of any DF. Therefore, oral KGM can instill a filling of fullness at a lower dose than other fiber supplements. Appetite reduction may be through increasing gastric retention and delaying gastric emptying by the “mass effect” of a gel-like viscous mass forming in the stomach that triggers afferent vagal signals of fullness. Absorption of nutrients in the lumen is slowed and beneficially increases the levels of appetite related hormones. The intake of KGM either as a supplement or in foods has been shown to have a weight loss effect. However, the results of randomized clinical trials have not been consistent. Besides differences in dose, study duration, and participant selection, the molecular structure and hydration properties of KGM are not described. This may be part of the explanation for the inconsistent results. The current review collected published information related to the role of KGM supplementation in regulation of appetite and obesity, focused on the association between micro and macro physicochemical structures of KGMs with their functions as appetite regulator. Collective clinical data of KGM on long-term metabolic energy surplus and weight loss were also provided.
... In contrast, the celiac branches are connected to the jejunum, ileum, cecum, and entire colon, and along with other vagal branches, extend to the duodenum [5]. In humans, the celiac branch is connected to the celiac trunk, and a complex plexus is observed around the left gastric artery and common hepatic artery, which may connect the celiac branch to the duodenum or the hepatic branch [6,9]. ...
Purpose:
The perigastric vagus nerve may play an important role in preserving function after gastrectomy, and intraoperative neurophysiologic tests might represent a feasible method of evaluating the vagus nerve. The purpose of this study is to assess the feasibility of neurophysiologic evaluations of the function and viability of perigastric vagus nerve branches during gastrectomy.
Materials and methods:
Thirteen patients (1 open total gastrectomy, 1 laparoscopic total gastrectomy, and 11 laparoscopic distal gastrectomy) were prospectively enrolled. The hepatic and celiac branches of the vagus nerve were exposed, and grabbing type stimulation electrodes were applied as follows: 10-30 mA intensity, 4 trains, 1,000 µs/train, and 5× frequency. Visible myocontractile movement and electrical signals were monitored via needle probes before and after gastrectomy. Gastrointestinal symptoms were evaluated preoperatively and postoperatively at 3 weeks and 3 months, respectively.
Results:
Responses were observed after stimulating the celiac branch in 10, 9, 10, and 6 patients in the antrum, pylorus, duodenum, and proximal jejunum, respectively. Ten patients responded to hepatic branch stimulation at the duodenum. After vagus-preserving distal gastrectomy, 2 patients lost responses to the celiac branch at the duodenum and jejunum (1 each), and 1 patient lost response to the hepatic branch at the duodenum. Significant procedure-related complications and meaningful postoperative diarrhea were not observed.
Conclusions:
Intraoperative neurophysiologic testing seems to be a feasible methodology for monitoring the perigastric vagus nerves. Innervation of the duodenum via the celiac branch and postoperative preservation of the function of the vagus nerves were confirmed in most patients.
Trial registration:
Clinical Research Information Service Identifier: KCT0000823.
... It has been established that brake mechanisms in the proximal small intestine also control gastric emptying rate. Nutrient absorption in the duodenum and jejunum slows gastric emptying rate, although not to the extent observed in the ileum [28,29]. This would explain the delay, although not significant, in gastric emptying of the paste following the Polycose preload compared with the paste alone. ...
... The presence of a nutrient based feedback mechanism, also referred to as 'duodenal brake', has been observed by numerous researchers (Brener et al., 1983;Calbet and MacLean, 1997;McHugh and Moran, 1979;Shahidullah et al., 1975), by measuring gastric emptying rate with intraduodenal nutrient secretions. This mechanism allows for the pyloric sphincter to control the emptying of gastric content into the duodenum depending upon the amount of nutrient already present in the proximal small intestine, ensuring a constant rate of calories per minute entering the small intestine, and the nutrient type (Calbet and MacLean, 1997 receptors, similar to those found in the mouth and nasal cavity, e.g., the T1R family of receptors allows for the sensing of sugars (Depoortere, 2014;Young, 2011). ...
A comprehensive mathematical model of the digestive processes in humans could allow for better design of functional foods which may play a role in stemming the prevalence of food related diseases around the world. This work presents a mathematical model for a nutrient based feedback mechanism controlling gastric emptying, which has been identified in vivo by numerous researchers. The model also takes into account the viscosity of nutrient meals upon gastric secretions and emptying. The results show that modelling the nutrient feedback mechanism as an on/off system, with an initial emptying rate dependent upon the secretion rate (which is a function of the gastric chyme viscosity) provides a good fit to the trends of emptying rate for liquid meals of low and high nutrient content with varying viscosity.
... Bile and pancreatic juices are secreted in the duodenum and aid chemical digestion. Receptors in the duodenal wall regulate the rate at which the stomach empties [59] for different food compositions. ...
Food transport through different sections of the gastrointestinal tract for the purposes of digestion and waste removal is an essential physiological function for life. Mechanical and chemical breakdown of food takes place throughout the gastrointestinal tract. Periodic muscular contraction and relaxation of the intestinal walls agitate, mix and propel the multiphase digesta along the intestines. Experimental measurement of flow inside the intestines is difficult therefore understanding of food transport through the majority of the gut is limited. Computational models for predicting the transient behaviour of intestinal content subject to peristaltic activity offer the possibility for assessing the digestive performance of different foods. We present a numerical model for peristalsis in the duodenum using a suspension of rigid particulates in a viscous Newtonian fluid to represent simple digesta. This consists of a thin viscoelastic membrane representing the gut wall coupled to the particle-based methods Smoothed Particle Hydrodynamics (SPH) and Discrete Element Method (DEM) which are used to predict the motion of liquid and solids content respectively. Peristaltic waves travel along the gut wall resulting in active muscular contractions and relaxations of the gut. The bulk motion of the content shows both phases move together due to the laminar nature of the flow with only very short-term inter-phase differences found in the relaxation region and in the wake of the contraction. Propulsive events were found to cause significant non-homogeneity of the solids distribution along the length of the duodenum. The inclusion of solids mildly modifies the overall propulsive flow behaviour and the retrograde jet in the wake of the contraction. In the absence of solids and connective tissue constraints, a transverse wobbling instability in the fluid filled viscoelastic tube is observed.
... [159][160][161] Others reported that GE can be either delayed or accelerated in patients with CP, 162 an effect that may be more associated to underlying diabetes mellitus and autonomic neuropathy than to PEI. Changes in the control of GE via the duodenal 163 and ileal brake 164 can also be expected in PEI. Other patients with CP were found to develop a delayed GE after surgical intervention, for example, pancreaticojejunostomy or pancreaticoduodenectomy for severe pain 165,166 possibly due to morphological alterations or injury of the vagus innervation of the pylorus 167 rather than to PEI per se. ...
Modern therapy of pancreatic exocrine insufficiency (PEI) using pancreatic enzyme replacement therapy (PERT) has largely been very effective and has greatly helped in improving the nutritional status of patients with PEI and in increasing the life expectancy in cystic fibrosis. It is believed that the use of predictable large animal models could play an important role in assessing and developing new therapies. This article reviews the pancreatic duct ligated (adult) minipig as a chronic model of total PEI, with a detailed look at the influence of PEI and response to PERT on prececal compared to fecal digestibility, to directly investigate effects on protein and starch digestion and absorption. In addition, the piglet with PEI is reviewed as a model for PEI in young patients with the aim of further improving the therapy and nutritional status of young patients with cystic fibrosis.
... It also appears that this endogenous hormonal release by paracrine, neural, and endocrine functions is essential to the structural and functional intestinal adaptation seen in some SBS patients following intestinal resection; it is anticipated that these effects may be replicated or potentiated by exogenous hormonal therapy. The neuroendocrine feedback mechanisms of the gastrointestinal tract, often referred to as the 'gastric, jejunal, ileal, or colonic brakes', may be disrupted by the distal intestinal resections or mucosal disease [3][4][5][6]. The attenuation of the meal-stimulated secretion of hormones, such as the glucagon-like peptide 1 and 2 and peptide YY by L-cells, associated with the removal of the terminal ileum and the colon, may be associated with some of the possible pathophysiological features of SBS patients with distal bowel resections [7]: accelerated gastrointestinal motility, gastric and intestinal hypersecretion, diminished intestinal blood flow, disturbed immunological and barrier functions, impaired mucosal replacement, repair, and adaptation. ...
The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 teduglutide studies, and pilot studies employing GLP-1 and agonists for this orphan condition.
In a 3-week, phase 2, metabolic balance study, teduglutide increased the intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 Kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Adverse events were mainly of gastrointestinal origin and consistent with the known mechanism of action of teduglutide. Pilot studies suggest that GLP-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2.
Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation in these severely disabled short-bowel syndrome patients.
... 19,20 The mechanism for this would be the "duodenal braking mechanism," mediated through the hormonal mechanism. 21 Secretion of such duodenal hormones is induced by the sensation of gastric acid in the duodenum, which then inhibits gastrin secretion in the antral mucosa, which in turn brings about the inhibition of gastric acid secretion via a negative feedback mechanism. In the antral region in the patient presented in the current study, there was diffuse intraglandular proliferation of gastrin positive cells in the middle zone of the pyloric glands. ...
BACKGROUND
To the authors' knowledge, multiple carcinoid tumors of the duodenum have not been reported previously. However, multiple carcinoids in the stomach, ileum, and rectum, which were accompanied by the proliferation of endocrine cells, have been reported in the published literature.METHODSA patient with multiple carcinoids including argyrophilic cell hyperplasia of the duodenum and hypergastrinemia underwent surgery. The resected stomach and duodenum were analyzed histopathologically.RESULTSThere were 11 carcinoid lesions, each of which was accompanied by peripheral endocrine cell micronests (ECMs). Increasing gastrin positive cells in the antral region and chronic duodenitis in the duodenal bulb also were observed. The peripheral ECMs usually were adjacent to proliferating argyrophilic cells in the Brunner gland ducts or the crypts of Lieberkühn, which showed focal pyloric gland metaplasia.CONCLUSIONS
In the case presented in the current study, the development of the multiple carcinoid lesions may be strongly related to the presence of multifocal pyloric gland metaplasia, as well as to the trophic action of gastrin, which is present at high levels in the setting of chronic duodenitis. Cancer 2000;89:963–9. © 2000 American Cancer Society.
... Post-surgery, the animals were doubly-housed and monitored daily for loose sutures and blood in the stool. Due to the possibility of gastric bloat (212), body weight was measured daily to look for an unusual (i.e. greater than 20%) decrease in body weight. ...
Glucagon-like peptide-1(7-36NH2) (GLP-1) is secreted by the intestinal L cell in response to both nutrient and neural stimulation, resulting in enhanced glucose-dependent insulin secretion. GLP-1 is therefore an attractive therapeutic for the treatment of type 2 diabetes. The antidiabetic drug, metformin, is known to increase circulating GLP-1 levels, although its mechanism of action is unknown. Direct effects of metformin (5-2000 μm) or another AMP kinase activator, aminoimidazole carboxamide ribonucleotide (100-1000 μm) on GLP-1 secretion were assessed in murine human NCI-H716, and rat FRIC L cells. Neither agent stimulated GLP-1 secretion in any model, despite increasing AMP kinase phosphorylation (P < 0.05-0.01). Treatment of rats with metformin (300 mg/kg, per os) or aminoimidazole carboxamide ribonucleotide (250 mg/kg, sc) increased plasma total GLP-1 over 2 h, reaching 37 ± 9 and 29 ± 9 pg/ml (P < 0.001), respectively, compared with basal (7 ± 1 pg/ml). Plasma activity of the GLP-1-degrading enzyme, dipeptidylpeptidase-IV, was not affected by metformin treatment. Pretreatment with the nonspecific muscarinic antagonist, atropine (1 mg/kg, iv), decreased metformin-induced GLP-1 secretion by 55 ± 11% (P < 0.05). Pretreatment with the muscarinic (M) 3 receptor antagonist, 1-1-dimethyl-4-diphenylacetoxypiperidinium iodide (500 μg/kg, iv), also decreased the GLP-1 area under curve, by 48 ± 8% (P < 0.05), whereas the antagonists pirenzepine (M1) and gallamine (M2) had no effect. Furthermore, chronic bilateral subdiaphragmatic vagotomy decreased basal secretion compared with sham-operated animals (7 ± 1 vs. 13 ± 1 pg/ml, P < 0.001) but did not alter the GLP-1 response to metformin. In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 μg/kg, sc), reduced the GLP-1 response to metformin, by 55 ± 6% (P < 0.01) at 30 min. These studies elucidate the mechanism underlying metformin-induced GLP-1 secretion and highlight the benefits of using metformin with dipeptidylpeptidase-IV inhibitors in patients with type 2 diabetes.
... The shortening of MCTT is also in agreement with animal studies showing desensitization of the ileal brake to chronic infusion of fat (Brown et al., 1994). Other mechanisms such as duodenal brake may also explain these observations (Shahidullah et al., 1975). The number and distribution of fatty acid-sensitive receptors along the GI tract (Engelstoft et al., 2008) means that classifications into gross anatomical structures may be less useful than actual nutrient sensitivity. ...
High-fat (HF) diets of 2 weeks have been shown to accelerate gastric emptying (GE). To date, no studies have shown any alteration in GE following shorter HF diets. The aim of this study was to assess if an HF, high-energy diet of 3 days can adapt gastrointestinal (GI) transit, blood lipids and satiety.
Eleven male volunteers participated in a study consisting of three, 3-day interventions each separated by a test day. During the first intervention, volunteers recorded their diet. In the second and third interventions, volunteers repeated their food diary plus either a low-fat yogurt or HF yogurt supplement in randomized order. Test days involved measurement of GE using the (13)C octanoic-acid breath-test, mouth-to-caecum transit time (MCTT) using the inulin H(2) breath test and satiety using visual analogue scales. Blood samples for measurement of lipaemia were taken using a venous cannula.
MCTT was different between the three test days (P=0.038), with the shortest MCTT following the HF intervention. GE was shortest following the HF intervention. There were no differences in satiety between the interventions. The HF intervention reduced triglycerides, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol.
This study shows that changes in GI transit owing to an HF diet can occur in a time period as short as 3 days.
... However, the mechanism by which physical activity affects gastric motility remains elusive. The parasympathetic nervous system may greatly influence gastric motility (Shahidullah et al. 1975). The vagal nerve has been traditionally considered as a parasympathetic efferent nerve that regulates autonomic functions such as heart rate and gastric motility. ...
It has been shown that mild to moderate exercise can accelerate gastric emptying in humans. However, understanding of the underlying mechanism is hampered by the lack of appropriate animal models. To investigate the effects of mild exercise on gastric motility, we developed an animal model, in which strain gauge transducers were surgically planted on the antral surfaces of female Sprague-Dawley rats. We continuously recorded the contractions of gastric circular muscle in unrestrained conscious rats, divided into four groups: sham-operated exercise, sham-operated sedentary, vagotomized exercise, and vagotomized sedentary. The rats were trained for 3 weeks, and gastric motility was monitored before and after exercise. Although exercise accelerates gastric antral contraction in sham-operated rats, this effect was absent in the vagotomized exercise group, indicating the involvement of the vagal nerve in the exercise-mediated increase in gastric motility. Among the four groups, daily food intake was highest in the sham-operated exercise group. In contrast, the vagotomized exercise group exhibited the smallest body weight gain. Severe gastric retention was observed in vagotomized rats, suggesting a role of the vagal nerve in facilitating food movement and digestion in the stomach. Moreover, at the end of the 3-week exercise, there were no differences in plasma levels of growth hormone, peptid YY, and ghrelin among the four groups. These results indicate that in response to a mild physical exercise challenge, the vagal nerve stimulates gastric motility and enhances the ability of the stomach to process food. Our findings highlight the significance of neuronal control of stomach function.
... Similarly the role of the vagi in the emptying of liquid meals is unclear. In humans, the emptying of hypertonic saline meals was accelerated after truncal vagotomy [Hall and Read, 1970] while in dogs after vagotomy a small meal still emptied more slowly than one of isotonic saline [Shahidullah, Kennedy and Parks, 1975]. Our results support a potential role for the pyloric antrum and vagal stimulation in the control of the gastric emptying of liquid meals. ...
The emptying of a liquid test meal from the stomach was studied during, and in the absence of, electrical stimulation of cut ends of a thoracic branch of the vagus in anaesthetized cats. The test meal (154 mmol.1-1 NaCl and 30 mg.1-1 phenol red) was measured by collecting effluent from a duodenal fistula over a 30 min period. The stomach emptied about 60% of the meal under control conditions compared with over 90% during efferent stimulation of the vagus. The increased volumes emptied during efferent stimulation were not accounted for by secretion of gastric acid. Coincident with the vagally evoked antral contractions there was a gush of liquid from the duodenal cannula. Afferent vagal stimulation resulted in an initial marked delay of emptying followed by an acceleration so that the volume emptied after 30 min was similar to that in control experiments. Antral contractions, evoked by efferent vagal stimulation, accelerated the emptying of a liquid test meal from the stomach.
... 37 However, other studies in gastric ®stulated dogs claim an inhibition after truncal vagotomy. 10,12 These differences might originate from the surgical preparation, involving a gastric cannulation, which is known to alter gastric relaxation. 38 Truncal vagotomy has also been reported to increase liquid emptying in dogs, 6 but to a lesser extent than selective (proximal) vagotomy. ...
The role of vagal innervation on emptying patterns and intragastric distributions of liquid and semisolid meals is still controversial. We aimed to record these features after dorsal, ventral and truncal vagotomies, using external gamma scintigraphy in conscious pigs in which the dorsal vagus specifically innervates the proximal stomach. Imaging of the stomach was performed for all experimental situations and before surgery using 99mTc-labelled glucose and porridge meals. Emptying of liquids was faster after dorsal vagotomy, whereas it was unchanged after ventral and truncal vagotomies (T1/2 = 57 +/- 8.5, 31 +/- 14.4, 54 +/- 9.1 and 42 +/- 14.9 min for intact, dorsal, ventral and truncal vagotomies, respectively). On the other hand, truncal vagotomy significantly reduced the emptying rate of semisolids whereas dorsal and ventral vagotomies had no significant effect (T1/2 = 96 +/- 7.2, 113 +/- 8.1, 75 +/- 9.9 and 260 +/- 56.6 min for intact, dorsal, ventral and truncal vagotomies). Morphological analysis of the gastric shape confirmed an overdistended proximal stomach after truncal vagotomy only. For semisolids, proximal stomach emptying followed the same emptying pattern as the entire stomach, irrespective of the surgical procedure. We concluded that the proximal stomach is the main control for the emptying of liquids and semisolids. The vagal control of overall gastric emptying for semisolids is probably identical to that modulating the intragastric distribution of the meal.
This chapter reviews data on the pathways by which luminal, mainly duodenal, chemoreceptors modulate gastro-pyloro-duodenal motor function to control emptying of nutrients into the small intestine. The vagus mediates proximal gastric relaxation caused by nutrient stimulation of duodenal/jejunal mucosal chemoreceptors. Modulation of the spatial patterning and inhibition of antral contractions during duodenal chemoreceptor activation are somewhat conflicting: both vagal control and ascending intramural nerves appear to play a role. Intraduodenal nutrients stimulate the localized pyloric contractions that prevent transpyloric flow via ascending duodenal intramural nerve pathways. Though not yet formally investigated, patterns of activation of the duodenal brake motor mechanism suggest that duodenal loop mucosal chemoreceptors signal to a brake mechanism at the most aborad region of the duodenum via descending intramural duodenal nerves. Intrinsic intramural pathways are important in the control of the first stages of digestion.
Coordinated contractions across the small and large intestine via the ileocecal junction (ICJ) are critical to healthy gastrointestinal function, and are in part governed by myoelectrical activity. In this study, the spatio-temporal characteristics of the bio-electrical conduction across the ICJ and its adjacent regions were quantified in anesthetized rabbits. High-resolution mapping was applied from the terminal ileum (TI) to the sacculus rotundus (SR), across the ICJ and into the beginning of the large intestine at the caecum ampulla coli (AC). Orally propagating slow wave patterns in the SR did not entrain the TI. However, aborally propagating patterns from the TI were able to entrain the SR. Bio-electrical activity was recorded within the ICJ and AC, revealing complex interactions of slow waves, spike bursts and bio-electrical quiescence. This suggests involvement of myogenic coordination when regulating motility between the small and large intestine. Mean slow wave frequency between regions did not vary significantly (13.74-17.16 cpm). Slow waves in the SR propagated with significantly faster speeds (18.51±1.57 mm/s) compared to the TI (14.05±2.53 mm/s, P = 0.0113) and AC (9.56±1.56 mm/s, P = 0.0001). Significantly higher amplitudes were observed in both the TI (0.28±0.13 mV, P = 0.0167) and SR (0.24±0.08 mV, P = 0.0159) within the small intestine compared to the large intestine AC (0.03±0.01 mV). We hypothesize that orally propagating slow waves facilitate a motor-brake pattern in the SR to limit outflow into the ICJ, similar to those previously observed in other gastrointestinal regions.
The most frequent diseases involving the small bowel and requiring surgery are Crohn’s disease and postoperative or post inflammatory adhesion. Less frequently small bowel resection is performed because of ischemia for mesenteric artery thrombosis or embolism and for neoplastic diseases arising in the small bowel (rare) or compressing or infiltrating the small bowel from outside (desmoid tumors, sarcomas, lymphomas, etc.). Furthermore, the small bowel is often interested by penetrating wounds (stab wounds or gunshot wounds) or can be strangulated in inguinal hernia, ventral hernia, or volvulus. Another rare small bowel disease requiring surgery is intussusception often associated to pedunculated polyps.
Effect of tetragastrin on gastric emptying was studied in 20 normal subjects and 14 patientswith gastric ulcer scar. All subjects were tested with following examinations:
1) Gastric analysis with intramuscular injection of tetragastrin 4γ/kg.
2) Gastric emptying test by the double sampling method after George and Mizuno, using 300ml of 5% glucose solution as a test meal, for 20 minutes.
3) Gastric emptying test, described in 2), added with intramuscular injection of tetragastrin2γ/kg at instillation of test meal. Thirteen of 20 normal subjects were additionarilytested with gastric emptying using 4γ/kg tetragastrin injection instead of 2γ/kg.
Results were as follows:
Tetragastrin generally delayed gastric emptying with mode of dose-response. It wassuggested that delay of gastric emptying by tetragastrin might be caused by its direct affectionto the gastric muscles.
In hyposecretory cases with OAO less than 6mEq/h among normal subjects, stimulationof tetragastrin 2γ/kg rather accelerated gastric emptying. It was speculated that theduodenal brake mechanism could be important in control of gastric emptying.
In hyposecretory cases among patients with gastric ulcer scar, there were a few caseswho showed delay of gastric emptying by injection of tetragastrin 2γ/kg. Duodenal brakemight etiologically reffer to gastric ulcer.
The relationship between the lipid content of the intestinal lumen and gastric motor activity was studied in anesthetized cats. For this purpose the electromyographic activity was recorded in the antrum whereas the small intestine (duodenum and first part of jejunum or ileum) was perfused with various solutions including calcium propionate, tributyrin, sodium caprylate, potassium oleate, mixtures containing linoleic acid, monolein, triolein, mixture of triglycerides, and glycerol. Long-chain lipids and glycerol both induced a decrease in the rate of basal antral activity. This effect was found to depend on the state of lipid hydrolysis (triglycerides, monoglycerides, and fatty acids) and was most marked with monolein, linoleic acid, and glycerol. With the middle-chain lipids used, these effects were only slight; short-chain lipids did not induce any visible changes in gastric activity. All these effects were prevented by cervical bivagotomy. It was concluded that the two types of lipid-sensitive vagal receptors, which we recently showed to exist in the small intestine, trigger an inhibitory enterogastric reflex that contributes to the regulation of gastric emptying.
Teduglutide, a recombinant analog of human glucagon-like peptide 2, has recently been approved in the US and Europe (Gattex and Revestive, respectively) as the first targeted treatment of short bowel syndrome-associated intestinal failure (SBS-IF). Glucagon-like peptide 2 improves structural and functional intestinal adaptation following intestinal resection by decelerating a rapid gastric emptying, by decreasing gastric hypersecretion, by increasing intestinal blood flow and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 studies preceding the US Food and Drug Administration and the European Medicines Agency approval of subcutaneous teduglutide for this orphan condition.
In a 3-week, phase 2, metabolic balance study, teduglutide increased intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Teduglutide had an acceptable tolerability profile, where adverse events generally were of gastrointestinal origin consistent with the known mechanism of action.
Teduglutide will add incremental benefit to the limited medical treatment armamentarium in SBS patients by maximizing intestinal absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. Future research should target and implement other key hormones with similar and possible additive or synergistic effects, thereby further promoting structural and functional adaptation and intestinal rehabilitation in these severely disabled SBS patients.
Nutritional therapy following small intestinal and pancreatic resection will be dependent upon the extent of resection. As far as small intestinal resection is concerned the type of dietary advice will also be dependent on whether residual small intestine is anastomosed to functionally active segments of colon. The dietary advice given to patients following pancreatic resection will also depend on whether there is co-existing exocrine pancreatic insufficiency.
Intragastric distribution of solids and liquids is far from uniform but until recently technical limitations have prevented detailed study. Echo planar imaging (EPI), which can provide high-quality images of intragastric contents, has been used in this study to assess the intragastric distribution of oil and water and gastric emptying in subjects lying on either their left or right side. Eight healthy volunteers underwent four gastric emptying studies after consuming either an aqueous meal (400 mL beef consomme soup + 100 mL water) or a fat/aqueous meal (400 mL soup + 100 mL olive oil) lying on either their left or right side.
Using a water suppressed imaging mode the lipid phase was clearly seen layering above the aqueous phase with little evidence of mixing. Gastric emptying of the aqueous meal (A) was not significantly different when lying on the left compared to the right side. However, gastric emptying of the aqueous phase of the fat/aqueous meal (B) was considerably slower when lying on the left compared to the right side, gastric volumes actually increasing over the 90 min of the study P ≤ 0.05. When lying on the right side the aqueous phase of meal B emptied significantly slower than meal A. Oil was clearly observed to layer above the water and fill the duodenal cap when subjects lay on their left and the fundus when they lay on their right side.
EPI clearly demonstrates the intragastric layering of oil which causes posture to strongly influence gastric emptying. EPI is a tool with great potential to describe the intragastric events following ingestion of complex multiphase meals.
The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.
1. Methods of measuring and sampling the flow of digesta passing through intestinal cannulas in preruminant calves were studied and compared. 2. The effect of collecting digesta from a duodenal cannula on abomasal emptying in a calf given whole milk was determined. When digesta were collected and returned to the duodenum manually in large amounts (about 200 g) the outflow of abomasal contents was intermittent. When digesta were returned to the animal either manually or automatically in amounts of less than about 50 g abomasal emptying was smooth. 3. An automatic apparatus for measuring and sampling the flow of digesta continuously was developed. The device allowed effluent to be returned smoothly to an ingoing cannula at the same rate that digesta left the outgoing cannula. After a feed of whole milk abomasal contents were observed to enter the duodenum in an orderly series of gushes. Each gush consisted of about 5--30 g of digesta. 4. The apparatus was rearranged to measure the effects of composition of duodenal digesta on abomasal emptying. Replacement of duodenal digesta with a suspension containing heated soyabean flour slowed the abomasal outflow of a feed containing casein. 5. Automatic apparatus was used to collect digesta arriving at the distal ileum. Withholding effluent from the large intestine did not affect the movement of digesta from the ileum.
The relationship between the lipid content of the intestinal lumen and gastric motor activity was studied in anesthetized cats. For this purpose the electromyographic activity was recorded in the antrum whereas the small intestine (duodenum and first part of jejunum or ileum) was perfused with various solutions including calcium propionate, tributyrin, sodium caprylate, potassium oleate, mixtures containing linoleic acid, monolein, triolein, mixture of triglycerides, and glycerol. Long-chain lipids and glycerol both induced a decrease in the rate of basal antral activity. This effect was found to depend on the state of lipid hydrolysis (triglycerides, monoglycerides, and fatty acids) and was most marked with monolein, linoleic acid, and glycerol. With the middle-chain lipids used, these effects were only slight; short-chain lipids did not induce any visible changes in gastric activity. All these effects were prevented by cervical bivagotomy. It was concluded that the two types of lipid-sensitive vagal receptors, which we recently showed to exist in the small intestine, trigger an inhibitory enterogastric reflex that contributes to the regulation of gastric emptying.
In anesthetized cats, the unitary activity of 53 sensory vagal neurons was recorded in nodose ganglia by means of extracellular glass microelectrodes. All the neurons had non-medullated fibres, with conduction velocities ranging from 0.8 to 1.2 m/s. Forty of these cells were stimulated by perfusion of the small intestine with lipids. Two types of receptors were identified: 21 endings were activated by glycerol and short chain lipids, and 19 endings were activated by long chain lipids. These receptors did not respond to either mechanical or osmotic stimulation. The discharge frequency generally increased with the concentration. The short latency suggested that they were located close to the enterocyte. The role of vagal intestinal receptors sensitive to lipids is discussed. Their functional characteristics along with previous experimental data suggest that they may be involved in the regulation of gastric emptying and alimentary behaviour, particularly satiety mechanisms.
The pattern of gastric emptying after truncal vagotomy and drainage is usually biphasic. An early rapid phase is followed by a characteristically abrupt transition to slow emptying. The mechanisms responsible for this pattern were studied in six dogs with truncal vagotomy and pyloroplasty, fitted with a proximal duodenal cannula. Gastric emptying was measured using gamma camera imaging of a radiolabelled 15% dextrose test meal. Sixty one hour studies were done using five designs. (1) With the cannula closed gastric emptying was initially rapid, followed by stasis (emptying at 15 min - 32% (5.3), 60 min - 34% (4.8); mean (SE)). (2) With the cannula open emptying was very rapid (15 min - 76% (4.2) p less than 0.001, 60 min - 88% (2.6) p less than 0.001 ANOVA). (3) Distal duodenal instillation of isotonic saline, at a rate equivalent to gastric emptying with the cannula closed, did not retard this rapid emptying (15 min - 78% (10.6), 60 min - 90% (5.4)). (4) With duodenal instillation of 15% dextrose, gastric emptying remained faster than in studies without diversion (15 min - 50% (7.0) NS, 60 min - 65% (6.8) p less than 0.01), but was slower than during diversion alone (p less than 0.05). (5) Finally, duodenal instillation of 15% dextrose before administration of the test meal produced slower initial emptying without subsequent stasis (15 min - 24% (4.5), 60 min - 47% (10.6)), although the amounts emptied were not significantly different from those with the cannula closed. These results indicate that after truncal vagotomy and pyloroplasty small bowel resistances play a significant role in controlling gastric emptying. Osmoreceptor responses persist after truncal vagotomy, but sympathetic inhibitory responses to small bowel distension are not involved in the regulatory process.
We investigated the impact of direct jejunal delivery of various meals on gastric emptying, glucose tolerance, and insulin response in a chronic dog model following duodenojejunostomy. Ten beagle dogs underwent duodenal transection 2 cm distal to the pylorus and end-to-side duodenojejunostomy 20 cm distal to the ligament of Treitz. Three months after operation each dog underwent gastric emptying studies using radiolabeled normal saline, 20% glucose solution, and standardized mixed solid meal. Glucose tolerance tests with plasma insulin determinations were obtained using the glucose meal. After duodenojejunostomy both the rapid exponential pattern of emptying of normal saline and the slower linear pattern of glucose emptying seen in intact dogs were preserved. The linear gastric emptying of the solid meal which was slower than gastric emptying of either of the liquid meals was also preserved. Although integrated plasma glucose levels over 2 hr were 484.8 +/- 40.4 and 456.6 +/- 30.4 mg X hr/dl in intact and duodenojejunostomy dogs, respectively (P greater than 0.05), the initial rate of rise of plasma glucose was significantly delayed in the duodenojejunostomy dogs. But integrated plasma insulin levels over 2 hr differed significantly (P less than 0.05) between the intact (71.6 +/- 9.2 microU X hr/nl) and duodenojejunostomy (48.3 +/- 6.2 microU X hr/nl) dogs. We conclude that duodenojejunostomy (jejunal delivery) preserved the patterns of gastric emptying of saline, glucose, and mixed solid meals; retarded initial plasma glucose response to the glucose meal; and blunted plasma insulin response to the glucose load.
Functional diarrhoea remains an elusive and a difficult condition to diagnose and treat; however, with careful history-taking a logical approach to management can be made. Each patient must be considered individually and sub-classification should be attempted. It is very important to rule out organic disease. Unfortunately treatment remains empirical in the majority of cases, but more is now known about functional disorders and there is hope for the future.
Complete gastric emptying time using barium sulfate mixed with commercial canned dog food was measured radiographically in 29 mature mixed breed dogs before and 3 to 4 weeks after Fredet-Ramstedt pyloromyotomy (FRP) (6 dogs), Heineke-Mikulicz pyloroplasty (HMP) (6 dogs), Finney pyloroplasty (FP) (6 dogs), Jaboulay's gastroduodenostomy (JG) (6 dogs), and antral gastrojejunostomy (AG) (5 dogs). The dogs were observed for clinical evidence of side effects. Postoperative endoscopic examination and double contrast gastrography were performed to subjectively evaluate the diameter of the gastrointestinal communication and the amount of enterogastric reflux. Although none of the procedures significantly (p less than 0.05) altered gastric emptying time, the overall tendency was toward slowing down gastric emptying time. The severity of gastrointestinal side effects and enterogastric reflux appeared to be related to the size and/or location of the gastrointestinal opening.
The relationship between osmotic pressure in the intestinal lumen and gastric motor activity was studied in anesthetized cats. For this purpose the EMG was recorded in the antrum while the small intestine (duodenum and the first part of jejunum) was perfused with various solutions: tap water (5 mOsm), NaCl, mannitol and glucose having an osmotic pressure of 70, 138, 275, 550 or 1100 mOsm. Hypotonic and hypertonic solutions both induced a decrease in the gastric activity, i.e. an increase in period of electrical control activity. This effect was found to depend both on the osmolarity value (the osmotic pressures furthest removed from the isotonic value produced the greatest effect) and on the substance used (glucose, mannitol and NaCl, in decreasing order of efficiency). The isotonic solution of glucose and, to a lesser extent, of mannitol was also active, unlike the isotonic solution of NaCl. All these gastric changes were prevented by cervical bivagotomy. It was concluded that the vagal osmosensitive receptors located in the small intestine trigger this inhibitory enterogastric reflex which probably constitutes an important part in the regulation of gastric emptying.
In anesthetized cats, the unitary activity of 66 sensory vagal neurones was recorded with extracellular glass microelectrodes implanted in the nodose ganglia. These neurones had non-medullated afferent fibres with conduction velocities between 0.8 and 1.2 m/s, as do most of the intestinal vagal fibres, and were silent or fired at low frequencies before any simulation. They were activated by perfusion of the small intestine (duodenum and first part of jejunum) with tap water and various solutions (glucose, NaCl and mannitol, in particular) having osmotic pressures ranged between 4 and 1100 mOsm. In general, hypotonic solutions and tap water induced the more marked responses, but differences were observed according to the solution used. Most of these neurones were also excited by other forms of stimulation including stroking of the mucosa and perfusion with warm (39-55 degrees C) and acid (HCl at pH 1) solutions. Therefore they must be considered to be polymodal receptors sensitive to osmotic pressure. The short latency of responses elicited by osmotic stimulations, the marked sensitivity to mucosal stroking and the disappearance of nervous activity after local anesthesia indicate that these receptors are located close to the epithelium. The role of these osmosensitive endings is discussed. Analysis of their general characteristics suggests that they may be involved in the inhibitory entero-gastric reflex modulating gastric emptying.
The gastric emptying of a fluid standard meal labelled with 99mTc-DTPA has been studied in dogs, using a scintillation detector. The method was assessed in a series of in vivo and in vitro experiments. The gastric emptying patterns were visualized as time-activity curves. In the initial phase, the typical curves showed a rapid emptying within 2-5 min after start of the meal, followed by a more varied emptying and a subsequent steady emptying in the basic phase. Duplicate tests showed acceptable reproducibility. The initial emptying varied among individuals, whereas the basic emptying did not vary significantly. Combined evacuation/isotope gastric emptying studies showed that the external counting technique produced results comparable to those obtained by evacuation. Short-lasting spikes and plateau-like dislocations were observed in the curves, indicating peristalsis and duodenogastric reflux, respectively. The observed data are comparable with those obtained in man when using a gamma camera. Gastric emptying tests, carried out during continuous infusion of distilled water, 20% soya bean oil, or 25% glucose into various parts of the proximal gastrointestinal tract, showed that in dogs inhibitory 'receptors' for fat and glucose were located in the small intestine distal to the ligament of Treitz.
Prolonged (18-24 hours) recordings of the pattern of small intestinal motor activity have been made, using radiotelemetry, in seven patients before surgery for chronic duodenal ulcer, seven after truncal vagotomy, and four with persistent post-vagotomy diarrhoea. There was no difference in the pattern of fasting cyclical activity between the three groups but the duration of feeding activity after a standard meal was reduced in asymptomatic truncal vagotomy patients compared with duodenal ulcer controls (p less than 0 . 05). In patients with post-vagotomy diarrhoea, the duration of the feeding pattern was further reduced compared with the asymptomatic post-vagotomy patients (p less than 0 . 001). It is suggested that altered emptying of food from the stomach in these patients together with duodenal receptor insensitivity is the probable explanation of these changes.
The effect of transthoracic vagotomy and a conventional pylorotomy on gastric emptying of a hyperosmolar glucose meal was evaluated in four dogs by means of an isotope technique. The measurements were made preoperatively and 1 month and 3-6 months after each operation. Vagotomy significantly increased the initial rate of gastric emptying, whereas the total fraction of the meal emptied in 60 min was the same as before operation. The pylorotomy did not alter the emptying. Approximately 50% of the meal was still retained in the stomach at the end of the tests. The abnormal gastric emptying of the glucose meal after vagotomy was normalized by drinking an 'aperitif' of 20% soya bean oil 15 min before the ingestion of the glucose meal. It is concluded that a vagotomy alters the pattern but not the 60-min fraction of gastric emptying of a liquid meal, whereas a pylorotomy alters neither the pattern nor the 60-min fraction of gastric emptying. The vagally denervated gastrointestinal tract has maintained mechanisms for control of the gastric emptying.
The results of reconstruction of the pylorus in 12 patients with disabling diarrhoea and/or dumping after vagotomy and pyloroplasty are reported. Eight patients, primarily operated on with a truncal vagotomy and pyloroplasty, all indicated frequent diarrhoea as their principal symptom. After the reconstruction operation the stools were normalized in five, and the frequency of diarrhoea was reduced considerably in two patients. Three of four patients who had had a selective vagotomy and pyloroplasty complained of severe dumping after all kinds of food; after the reconstruction these symptoms were milder and provoked by sweets and milk only. The fourth patient with heavy diarrhoea as the principal symptom had postoperatively a slight reduction of the frequency. The operation is easy to perform, and no complication was encountered. The pathogenesis of the symptoms is discussed, and it is recommended that patients with disabling diarrhoea and/or dumping after vagotomy and pyloroplasty undergo a reconstruction of the pylorus.
Gastric emptying of 5 per cent and 10 per cent glucose test meals has been measured in 43 patients with a duodenal ulcer prior to surgery and in 52 patients with an unsatisfactory result following truncal vagotomy and a drainage procedure. Seventeen patients had a recurrent ulcer and incomplete vagotomy while 35 patients were symptomatic with complete vagotomy. In both the preoperative and postoperative patients the 10 per cent glucose test meal emptied significantly more slowly than the 5 per cent glucose test meal regardless of the completeness of vagotomy. Thus, osmotic control of gastric emptying persists after vagotomy.
The fat component of meals has been thought to make a major contribution to the colonic response to feeding. We have combined gamma scintigraphy and radiotelemetry to noninvasively study the response of the normally inaccessible proximal colon after ingestion of either a high or low fat meal. Separate studies were performed to measure the rate of passage of the same meals through the whole gut. Gastric emptying and small bowel transit of the two meals to the colon was similar, 50% of meal marker reaching the ascending colon 4.8 +/- 0.2 and 4.5 +/- 0.3 hr after the high and low fat meals respectively (N = 8, difference not significant). The low fat meal caused a consistent increase in motility index, which rose from a basal value of 1.0 +/- 0.3 to 2.6 +/- 0.7 mm Hg in the 2 hr after the meal (N = 8, P < 0.01). Response to the high fat meal was less consistent, motility index increasing from 1.6 +/- 0.6 basally to 2.3 +/- 0.7 mm Hg postprandially (N = 8, P = 0.21). Despite these increases in motor activity there was no net caudal propulsion of colonic contents after either meal. The geometric center was comparable, being 3.2 +/- 0.4 and 3.7 +/- 0.4 before the high and low fat meals. This did not change significantly after either meal, being then 3.5 +/- 0.4 and 3.6 +/- 0.4 2 hr after the high and low fat meals, respectively. We conclude that in normal subjects equicaloric high and low fat meals transit the whole gut at a similar rate.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of our study was to test the hypothesis that the better absorption of sorbitol when ingested with glucose could be related to a delayed gastric emptying. We tested the effect of the ingestion of glucose and lipids on the gastric emptying and intestinal absorption of sorbitol in six healthy volunteers, using gastric scintigraphy and hydrogen breath test. After an overnight fast, subjects ingested in random order, on 48-h test periods separated by at least one week, the following solutions: (a) 20 g sorbitol alone; (b) 20 g sorbitol and 20 g glucose; (c) 20 g sorbitol and 9 g lipids. Isotopic acquisitions were taken for 3 h following the ingestion of sorbitol labelled with 111Indium. Hydrogen concentration was measured in end-expiratory samples during 5 h, and the areas under the breath hydrogen curve, reflecting the amounts of sorbitol unabsorbed in the small bowel, were compared between periods. Mean area under the curve was 397 +/- 159 when sorbitol was ingested alone, and this was significantly lower when ingested with glucose or lipids (313 +/- 181 and 337 +/- 135, respectively; P < 0.05). The three curves of sorbitol gastric emptying differed significantly from each other, the gastric emptying being the slowest for sorbitol plus lipids, and the fastest for sorbitol taken alone. We found a positive correlation between the half-emptying time and the hydrogen areas under the curve (r = 0.46, P = 0.05). In conclusion, our study demonstrates that adding glucose or lipids to a solution of sorbitol slows the gastric emptying of sorbitol, resulting in a better intestinal absorption of sorbitol.
Various nutrients are known to alter small intestinal motility patterns although their effect on transit of fluids and solids in man is not clear.
To determine small intestinal transit of solids and liquids during perfusion with lipids, protein, and non-energy solutions.
Twenty eight healthy volunteers received a jejunal infusion (1 ml/minute for 30 minutes) of one of four solutions: a lipid or a protein solution (4.18 J/ml), a non-absorbable electrolyte solution containing polyethylene glycol, or 0.9% sodium chloride. As solid phase marker 1 g of amberlite resin pellets labelled with 111InCl3 was added; 99mTc DTPA was used as a fluid phase marker. Images were obtained on a gamma camera at 10 minute intervals for four hours or until all radiolabel was detected in the colon.
Intestinal transit of solids and liquids from the duodenojejunal junction to the caecum was simultaneous, and independent of the energy content of the solution infused. Lipid infusion accelerated transit through the small intestine but delayed transport of chyme along the ileocolonic junction. After protein small intestinal transit was slowest; ileocolonic transit on the other hand was fastest with protein. Transit of the non-energy solutions was in between that of the nutrient solutions.
Transit times through the small intestine and the ileocolonic junction were influenced by the luminal contents. In the small intestine fat induced significantly faster transit compared with proteins, but delayed ileocolonic transit. Once in the small intestine, solids and liquids transit the small bowel together, independent of the luminal content.
To the authors' knowledge, multiple carcinoid tumors of the duodenum have not been reported previously. However, multiple carcinoids in the stomach, ileum, and rectum, which were accompanied by the proliferation of endocrine cells, have been reported in the published literature.
A patient with multiple carcinoids including argyrophilic cell hyperplasia of the duodenum and hypergastrinemia underwent surgery. The resected stomach and duodenum were analyzed histopathologically.
There were 11 carcinoid lesions, each of which was accompanied by peripheral endocrine cell micronests (ECMs). Increasing gastrin positive cells in the antral region and chronic duodenitis in the duodenal bulb also were observed. The peripheral ECMs usually were adjacent to proliferating argyrophilic cells in the Brunner gland ducts or the crypts of Lieberkühn, which showed focal pyloric gland metaplasia.
In the case presented in the current study, the development of the multiple carcinoid lesions may be strongly related to the presence of multifocal pyloric gland metaplasia, as well as to the trophic action of gastrin, which is present at high levels in the setting of chronic duodenitis.
The "ileal brake" is the primary inhibitory feedback mechanism to control transit of a meal through the gastrointestinal tract in order to optimize nutrient digestion and absorption. Neurohormonal factors mediating this response continue to be identified. Recently, additional brakes that fine-tune transit have been described. When gut traffic control is disrupted, pathologic states characterized by malabsorption and impaired drug bioavailability manifest as diarrhea and malnutrition. An understanding of the importance of these nutrient-triggered brakes provides essential clues to future treatments of chronic diarrhea, malnutrition, and drug malabsorption.
The vagus is involved in the cephalic phase of insulin secretion but its role in the meal absorption phase of insulin release remains to be defined. The aim of this study was therefore to evaluate the role of the vagus in the early and the late meal absorption phases of insulin secretion. In six pigs, venous insulin profiles were compared in intact animals, after ventral or dorsal vagal trunk section, and after section of both vagal trunks (truncal vagotomy). Since gastric emptying could be modified by vagotomy, it was recorded concomitantly by gamma scintigraphy. Semi-solid (porridge) and liquid (glucose 10%) meals were tested. Truncal vagotomy significantly increased insulin release compare to intact animals after glucose (63.8%) and porridge (174.4%) meals in the early and the late absorption phases of insulin secretion, respectively. For the glucose meal, this effect could be explained by a vagally mediated change in gastric emptying rate, since insulin concentrations for a similar amount of nutrient propelled to the duodenum were not different in intact and truncal vagotomized animals. In contrast, after the porridge meal, truncal vagotomy was associated with a second, later occurring increase in circulating insulin, which could not be explained by changes in gastric emptying rate. These results demonstrate for the first time an inhibitory role of the vagus in the late meal absorption phase of insulin release.
To explore whether endemic fluorosis in Tibet is related to local factors, an epidemiological survey of fluorosis was conducted in 3 districts in Tibet. The survey used the WHO and FAO established "Guideline for the study of dietary intake of chemical contaminants" and the Horowitz suggested criteria for children dental fluorosis examination. The fluorine in the local environment of the 3 selected districts was studied in detail. The possible fluorine sources examined indicated that only the brick-tea carried a high content of fluoride; water, other food materials, and fuel contents were insignificant. The children daily fluorine intake was high, where Naqu was 8.03 mg, Lahsa was 6.93 mg, Dingri was 7.68 mg. All the dietary fluoride was come from the brick-tea processed foods: the buttered-tea and zamba, these two contributed 99.74%, 98.70% and 99.60% of their daily fluorine intake respectively. The dental fluorisis index indicated that Naqu and Dingri were severe epidemic and Lahsa was moderate epidemic. The endemic fluorosis that occurs in Tibet was essentially due to heavy consumption of foodstuffs prepared with brick-tea, however, the high altitude, harsh living conditions, and poor nutritional status aggravated the fluorosis. Brick-tea type fluorosis is a new type of fluorosis recently discovered in China. Compared with the drinking water type and coal combustion type of fluorosis, it covered extensive area, more covert, and difficult to control. Decrease the fluorine content of brick-tea might be the most promising measure.
The rate of gastric emptying was measured by means of a new method, in which the stomach was scanned at intervals after a standard breakfast containing Cr-51 had been given. Most of the meal left the stomach in an exponential manner. The rate of gastric emptying can be expressed as the half-life of the meal in the stomach.
Investigations were carried out in man and dog to study the validity of Cannon's law of denervation supersensitivity in relation to parasympathetic denervation of the stomach. Subthreshold doses of carbachol did not accelerate gastric emptying before vagotomy but caused a significant increase in the rate of gastric emptying after vagotomy. These findings may be relevant to aberrations of gastrointestinal motility after vagotomy and may provide the basis of a test for completeness of gastric vagotomy.
1. Test meals of solutions and suspensions of potassium and sodium salts of a series of saturated fatty acids, from C 2 to C 18 , were given to healthy subjects.
2. From the volume of these meals recovered after a fixed interval the relative effectiveness of the salts of the acids in slowing gastric emptying was assessed.
3. On a molar basis the salts of fatty acids from acetic up to decanoic were relatively ineffective in slowing gastric emptying.
4. The salts of fatty acids with 12‐18 carbon atoms were much more effective than those with up to 10 carbon atoms. Myristate was the most effective of the salts.
5. Buffering the test meals with 33 m M sodium citrate increased the effectiveness of the salts in slowing gastric emptying.
The effects of Peptavlon on gastric acid secretion and gastric emptying before and after vagotomy and pyloroplasty are reported. Patients were submitted to two Hunt quantitative test meals before, and two after, selective vagotomy and Finney pyloroplasty. The test meals were paired, one being a control meal and the other being performed during continuous intravenous infusion of pentagastrin at a dose rate of 6 μg./kg/hr. Pentagastrin markedly increased acid output over the control level both before and after vagotomy, and the response before operation was greater than that reported by some other workers. There was a significant, but not major, reduction in response to pentagastrin following vagotomy, and control secretion was reduced 36% by vagotomy. Pentagastrin did not appear to affect the rate of gastric emptying. However, vagotomy and pyloroplasty resulted in increased gastric emptying after both control and pentagastrin meals. © 1969 Hoeber Medical Division • Harper & Row, Publishers, Incorporated.
After an experience of seven years during which 620 vagotomies for various types of intractable peptic ulcer have been performed by the attending and resident staff of this clinic, we are persuaded that this is a relatively safe, efficient and practical method of surgical treatment and should replace subtotal gastrectomy as the initial, definitive, surgical treatment for duodenal, gastrojejunal and certain esophageal ulcers. It should regularly be combined with a posterior gastroenterostomy of small size to facilitate the emptying of the stomach and simplify postoperative management. Crile1 has employed pyloroplasty and Beattie2 partial pylorectomy instead of gastroenterostomy with success.Surgical methods have been successful in the treatment of peptic ulcer, depending directly on the extent to which these procedures reduce the secretion of the pepsin and hydrochloric acid of the gastric juice. The most important of these methods in use at the present time are subtotal gastrectomy and
The effect of vagotomy and a drainage procedure on the rate of gastric emptying Regulation of gastric emptying
- P Goodall
Goodall, P. (1966). The effect of vagotomy and a drainage procedure on the rate of gastric emptying. Brit. J. Surg., 53, 995. Hunt, J. N., and Knox, M. T. (1968a). Regulation of gastric emptying. In Handbook of Physiology, Sect. 6, edited by C. F. Code, Vol. IV, pp. 1917-1935. American Physiological Society Washington, D.C.
Parks Hospital Group Research Sub-Committee for a grant to one of us (M.S.) from their endowment funds which has made it possible to undertake this work. Professor A. D. Roy has kindly provided facilities for the study in the Department of Surgery, Queen's University
- M Shahidullah
- T L Kennedy
M. Shahidullah, T. L. Kennedy, and T. G. Parks Hospital Group Research Sub-Committee for a grant to one of us (M.S.) from their endowment funds which has made it possible to undertake this work. Professor A. D. Roy has kindly provided facilities for the study in the Department of Surgery, Queen's University, Belfast. We also wish to thank Mr H.
El ritmo de apertura pilorica en el ulcus gastroduodenal
- Tamarit Torres
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Tamarit Torres, J., Enriquez de Salamanca, F., Jr., and Castro-Rial Canosa, M. (1954). El ritmo de apertura pilorica en el ulcus gastroduodenal. Arch. Med. exp. (Madr.), 12, 99-118.
Walker for secretarial help Gastric secretion and emptying before and after vagotomy and pyloroplasty, with and without continuous infusion of peptavlon pentagastrin. Amer
- Nevin
- J Mr
- White
- E Sister
- Craw-Ford
- S Assistance
- Mrs J Leonard
- P Wastell
- C Wise
Nevin, Mr J. White, and Sister E. Craw-ford for technical assistance, and Mrs S. Leonard and Mrs J. Walker for secretarial help. References Aylett, P., Wastell, C., and Wise, I. (1969). Gastric secretion and emptying before and after vagotomy and pyloroplasty, with and without continuous infusion of peptavlon pentagastrin. Amer. J. dig. Dis., 14, 245-252.
Appraisal of va-otomy for peptic ulcer after seven years New clinical method for measuring the rate of gastric emptying: The double sampling test meal
- L R Dragstedt
- E R Woodward
Dragstedt, L. R., and Woodward, E. R. (195 1). Appraisal of va-otomy for peptic ulcer after seven years. J. Amer. med. Ass., 145, 795. George, J. D. (1968). New clinical method for measuring the rate of gastric emptying: The double sampling test meal. Gut, 9, 237-242.
The effect of vagotomy and a drainage procedure on the rate of gastric emptying
- P Goodall
- Goodall, P.