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PubMed1994

Gastrin and colon cancer. Clarifying the controversy.

Controversy exists about the relationship between hypergastrinemia and colon cancer. Conflicting lines of evidence may be interpreted to support a variety of views regarding the link between the two. Although some experimental and clinical data suggest a strong correlation, other studies refute this. It is likely that the actual situation lies between these two viewpoints; the complex nature of the relationship between carcinogenesis and putative gut hormones makes a definitive answer unlikely. Nevertheless, a critical reading of the recent literature suggests that hypergastrinemia does not play a direct role in colorectal carcinogenesis. Certain subgroups of patients with elevated serum gastrin levels and tumors that possess gastrin receptors may have accelerated tumor growth. Further study of this issue is warranted to elucidate the role of the gastrointestinal hormonal milieu in colorectal neoplasia.

Colonic Neoplasms↗
PubMed1983

Pancreatic polypeptide: a unique model for vagal control of endocrine systems.

Pancreatic polypeptide (PP) is a hormone synthesized only in the duodenal pancreas where the PP cell is the dominating endocrine cell type. The secretion of PP is regulated by food-intake and by plasma glucose--in both cases through vagal cholinergic mechanisms. In vitro cholinergic stimulation is 4-10 times as potent as any other stimulatory mechanism, e.g. beta-adrenergic stimulation. Although other agents such as gastrointestinal hormones and neuropeptides are potent stimulators of PP secretion in vivo, their action is totally eliminated by blockade of the muscarinic receptor and in several cases also abolished by vagotomy. Furthermore, these peptides have no or only a weak effect in vitro. The stimulation of PP secretion by hypoglycemia and inhibition by hyperglycemia is mediated also through an efferent vagal mechanism. Under extreme hypoglycemia the stimulation of PP release becomes partially atropine resistant, although still totally dependent on the vagus; conceivably the release of other transmitters, like e.g. VIP, is activated under these circumstances. In the basal state, PP secretion is under oscillating cholinergic tone. Thus, the secretion of PP is unique in the way that the cholinergic, vagal stimulation is not only the most powerful stimulatory mechanism, but also the key through which other mechanisms act. PP secretion can be used, e.g. as a sensitive indicator of autonomic disorders in patients with diabetes.

Acetylcholine↗
PubMed1989

Gastrointestinal and pancreatic endocrine tumours.

The radiological diagnosis and interventional management of neuroendocrine tumours of the gastrointestinal tract and pancreas are challenging, demanding the complete gamut of available resources. Carcinoid tumours are most commonly found in the appendix and small bowel. Barium studies usually disclose a small solitary mucosal or submucosal mass in the distal ileum at times associated with smooth muscle hypertrophy and thickening of the mucosal folds. Intussusception and bowel obstruction may be the presenting finding. Mesenteric involvement may evoke a desmoplastic reaction with rigidity, fixation, angulation and tethering of small bowel loops. Angiography may demonstrate a hypervascular primary neoplasm but more frequently reveals vascular encasement and distortion from the mesenteric desmoplastic reaction. Pancreatic islet cell tumour is best defined radiologically by angiography and computed tomography as a well circumscribed hypervascular mass which enhances with contrast material. Portal venous sampling is of considerable assistance in localizing insulinoma. Metastases from neuroendocrine tumours to lymph nodes and to the liver are usually hypervascular. In the evaluation of the liver by CT scanning prior to contrast as well as dynamic scanning during the bolus intravenous injection of contrast material are necessary. At times the precontrast scan is more revealing. Computed tomography with the catheter in the superior mesenteric artery followed by selective hepatic arteriography is the most accurate combination for the detection of hepatic metastases. Interventional radiological management by sequential hepatic arterial embolization is the treatment of choice for multiple hepatic metastases from neuroendocrine tumours. Thus far, the maximum number of embolic episodes in a single patient has been 13. The carcinoid syndrome has been controlled in 87% while 79% of islet cell tumour hepatic metastases have responded. Contraindications to HAE includes a combination of all of the following: (i) replacement of more than 50% of the liver by tumour, (ii) serum lactic dehydrogenase above 425 mU/ml, (iii) serum glutamic oxaloacetic transaminase above 100 mU/ml, and (iv) bilirubin above 2 mg/dl. In the face of occlusion of the portal vein by intravascular neoplasm, HAE is contraindicated only if portal flow through collateral vein is away from the liver.

Diagnostic Imaging↗
PubMed1985

Medullary thyroid carcinoma and calcitonin.

Medullary carcinoma of the thyroid (MCT) develops from the thyroid C-cells. Thyroid C-cells and MCTs secrete calcitonin (CT), a 32 amino acid polypeptide hormone. The author has described a sensitive direct sequential radioimmunoassay of CT in human serum. The vast majority of healthy subjects had detectable values of serum immunoreactive calcitonin (iCT) and elevated levels were found in patients with MCT. Besides CT, several higher molecular weight substances contribute to CT-immunoreactivity. These substances may represent metabolic products in the processing of a glycosylated procalcitonin to CT. Calcium, several gastrointestinal hormones and ethanol increases CT secretion from normal and neoplastic C-cells, but the physiological regulation of CT secretion has not been firmly established. The author has shown that the levels of serum iCT vary little during day and nighttime. CT acutely reduces bone resorption and, in pharmacological doses, increases urinary electrolyte excretions. A lowering in serum calcium, magnesium and phosphorus levels result but the effect is pronounced only in disease states with a high bone turnover. The physiological role for CT may be preservation of the skeleton at times of increased need for calcium. A causal relationship between postmenopausal osteoporosis and CT deficiency has been proposed. The author has described increased serum 1,25-dihydroxyvitamin D levels and increased trabecular bone remodeling in patients with MCT and normalization of these parameters following surgical cure for MCT. These results were interpreted to indicate that chronic endogenous CT excess directly enhances the renal production of 1,25-dihydroxyvitamin D which, acting synergistically with parathyroid hormone, increases trabecular bone remodeling. Elevated serum iCT is almost invariably found in patients with clinically manifest MCT as well as in several patients with clinically occult MCT. An exaggerated increase in serum iCT levels after provocative testing with pentagastrin and/or calcium can disclose early C-cell neoplasia. Elevated serum iCT may be encountered in non-C-cell neoplasias and in renal insufficiency. Compared to MCT, circulating iCT may show a different immunochemical profile and the response to provocative testing is blunted in these conditions. MCT occurs in a sporadic variety, and in a familial variety as part of two related multiple endocrine neoplasia (MEN) syndromes. MEN IIa consists of MCT and often phaeochromocytomas and/or hyperparathyroidism and invariably exhibits an autosomal dominant mode of inheritance but a variable age of expression.(ABSTRACT TRUNCATED AT 400 WORDS)

APUD Cells↗
PubMed2000

Motility disorders of the small intestine: new insights into old problems.

Motility of the gastrointestinal tract is responsible for the orderly movement of food, in an oral-to-aboral direction, and allows for the digestion and absorption of nutrients and water, and the elimination of indigestible material. This complex series of events results from the integrated activity of enteric nerves, extrinsic nerves, the intrinsic properties of smooth muscle, and gastrointestinal hormones. Abnormalities in any of these components or in their integration can result in dysmotility: increased transit, decreased transit, or nonpropulsive activity. This review outlines the current understanding of the causes, pathophysiology, diagnostic evaluation, and treatment of motility disorders of the small intestine.

Gastrointestinal Motility↗
PubMed1975

Pharmaco-radiology in barium examinations with special reference to glucagon.

The reasons for and objections to the use of drugs as adjuncts in barium meal and follow-through examinations are briefly reviewed. Physiological factors related to gastric emptying are considered, including the volume, temperature and osmolarity. The drugs considered include those that speed gastric emptying and small bowel transit such as metoclopramide, those that delay gastric emptying such as propantheline and gastrointestinal hormones such as glucagon. Glucagon first produces gastric and duodenal dilatation and subsequently speeds transit through the small bowel. The indications, contra-indications and side effects of these drugs are also considered and tabulated.

Barium Sulfate↗
PubMed2006

Inhibitory effects of gastric electrical stimulation on ghrelin-induced excitatory effects on gastric motility and food intake in dogs.

OBJECTIVE: To investigate the effects of ghrelin on food intake, gastric motility and whether gastric electrical stimulation (GES) is capable of reversing these effects of ghrelin in dogs. MATERIAL AND METHODS: Seven healthy dogs were equipped with a gastric cannula and electrodes for the measurement of antral motility and gastric myoelectrical activity (GMA). Both food intake and gastric motility studies were performed in three sessions (control, ghrelin, 20 microg and ghrelin plus GES) in randomized order, respectively. After a 28-h fast, the animals were provided with unlimited solid food for 1.5 h, 30 min after saline or ghrelin injection. Recordings of antral contractions and GMA in each session were recorded for 30 min at baseline and 45 min after ghrelin/saline injection in the fasting state. GES was performed throughout the experiment initiated 30 min prior to the injection. RESULTS: 1) Ghrelin significantly increased food intake from 475.6+/-75.5 g in the controls to 535.9+/-90.3 g with ghrelin (p=0.04); this excitatory effect was reversed by GES. 2) Ghrelin significantly increased the motility index from 8.6+/-1.6 in the controls to 16.1+/-2.4 with ghrelin (p=0.01) and this effect was also reversed by GES. 3). There were no effects of ghrelin on GMA. CONCLUSIONS: Ghrelin induces antral contractions and increases food intake. GES is capable of blocking these excitatory effects of ghrelin. These findings suggest that GES may inhibit the resistant effect of ghrelin on weight loss.

Animals↗
PubMedDate not supplied

Effect of the anastomosis-site after Billroth I gastrectomy on the motility of the remnant stomach.

BACKGROUND/AIMS: Gastric emptying, in healthy individuals, is a highly regulated process, and plasma cholecystokinin plays a major role in its feedback regulation. However, the hormonal regulation of postprandial gastric emptying of the remnant stomach after distal gastrectomy with Billroth I reconstruction procedure has not been well described. The aim of this study is to characterize the gastroduodenal motility and gastric emptying of the two anastomosis-methods after Billroth I gastrectomy, while assessing the effect of cholecystokinin on the motility of the remnant stomach. METHODOLOGY: Two types of anastomosis (end-to-end, side (posterior wall)-to-end) after Billroth I gastrectomy were measured with strain gauge force transducers, and evaluated as to gastroduodenal motility, gastric emptying, gastrointestinal hormones (cholecystokinin, gastrin), and blood glucose associated with food administration. RESULTS: Remnant stomachs with side-to-end anastomosis showed superior motility as compared to those with end-to-end anastomosis. Plasma cholecystokinin was higher in the end-to-end anastomosis group. No differences as to gastric emptying, levels of plasma gastrin, or blood glucose were observed between the two groups. CONCLUSIONS: Plasma cholecystokinin may explain the difference in motility index between the two groups.

Animals↗
PubMed1994

Decreased postprandial thermogenesis and fat oxidation but increased fullness after a high-fiber meal compared with a low-fiber meal.

The effect of a high-fiber (4.7 g/MJ) and an isoenergetic low-fiber (1.7 g/MJ) meal on 6-h postprandial thermogenesis, substrate metabolism, hormones, and satiety was investigated in 10 healthy, normal-weight male subjects. Diet-induced thermogenesis (DIT) was significantly reduced after the high-fiber meal (416.4 +/- 28.6 kJ/6 h) compared with the low-fiber meal (498.5 +/- 23.1 kJ/6 h; ANOVA: P < 0.0001), as was postprandial fat oxidation (P < 0.0001). The difference in DIT was correlated with the different palatability of the test meal (r = 0.89, P < 0.01). No differences were observed in plasma concentrations of glucose, insulin, norepinephrine, epinephrine, or gastrointestinal hormones, but C-peptide increased less (P < 0.05) and nonesterified fatty acids decreased more (P < 0.05) after the high-fiber meal. Finally, fullness was increased and desire to eat decreased after the high-fiber meal (P < 0.0001). In conclusion, a high-fiber meal decreased DIT and fat oxidation but increased fullness compared with a low-fiber meal.

Adult↗
PubMed1991

Metabolic effects and clinical value of beet fiber treatment in NIDDM patients.

In the present study a randomized cross-over design was used to determine the clinical usefulness of adding 16 g of beet fiber to the ordinary diet of non-insulin dependent diabetic (NIDDM) out-patients. In addition, fiber effects on the gastrointestinal hormone responses to a standardized test meal were evaluated. The study included five patients treated with diet alone and eight patients treated with diet and sulphonylurea (SU). Beet fiber supplementation resulted in a 10% reduction (P less than 0.01) of serum cholesterol in SU-treated patients. No differences were found for fasting blood glucose, glycated hemoglobin, serum triglycerides or body weight. In the diet-treated patients, fasting plasma somatostatin was elevated during the fiber period. However, postprandial responses of insulin, C-peptide, glucagon, gastric inhibitory peptide and somatostatin were not influenced by an increased fiber intake in any group. All patients experienced mild gastrointestinal discomfort during the fiber period. In view of the limited metabolic benefit of beet fiber treatment we conclude that there is little use for this type of dietary fiber in the routine treatment of patients with NIDDM.

Blood Glucose↗
PubMed2000

Review article: gall-bladder motility after intestinal surgery.

There is a close relationship in humans between gall-bladder motility and gastrointestinal motility during the fasting state, as well as in the post-prandial period. Only a minority of publications take this relationship into account in the description of biliary dysmotility after various surgical procedures. Most publications deal with post-prandial gall-bladder motility or with stimulation of gall-bladder contraction from various prokinetic drugs or gastrointestinal hormones. Impaired gall-bladder motility has been demonstrated after Billroth II gastric resection, pyloroplasty and colectomy, but the epidemiological data on the risk of gallstone formation in these patients are too scarce and equivocal to recommend prophylactic cholecystectomy. Future studies on gall-bladder motility after surgical procedures should include measurements of gall-bladder motility during the fasting state, as well as in the post-prandial period. The measurements should be related to the migrating motor complexes, and this necessitates a simultaneous recording of gastrointestinal motility.

Cholelithiasis↗
PubMed2001

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon.

BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2. METHODS: Balance studies were performed before and after treatment with GLP-2, 400 microg subcutaneously twice a day for 35 days, in 8 patients (4-17 years from last bowel resection; 6 with Crohn's disease). Four patients received home parenteral nutrition (mean residual jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and body composition was measured by dual-energy x-ray absorptiometry. RESULTS: Treatment with GLP-2 improved the intestinal absorption of energy 3.5% +/- 4.0% (mean +/- SD) from 49.9% to 53.4% (P = 0.04), wet weight 11% +/- 12% from 25% to 36% (P = 0.04), and nitrogen 4.7% +/- 5.4% from 47.4% to 52.1% (P = 0.04). Body weight increased 1.2 +/- 1.0 kg (P = 0.01), lean body mass increased 2.9 +/- 1.9 kg (P = 0.004), fat mass decreased 1.8 +/- 1.3 kg (P = 0.007), and 24-hour urine creatinine excretion increased (P = 0.02). The time to 50% gastric emptying of solids increased 30 +/- 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel transit time was not changed. Crypt depth and villus height were increased in 5 and 6 patients, respectively. CONCLUSIONS: Treatment with GLP-2 improves intestinal absorption and nutritional status in short-bowel patients with impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon have been resected.

Adult↗
PubMed1988

Growth factors and intestinal neoplasms.

Signals that control normal and neoplastic epithelial proliferation are not completely understood. We have reviewed the importance of the possible roles of the following control mechanisms: polyamine biosynthesis, intraluminal nutrients, gastrointestinal hormones and growth factors, bowel resection, carcinogens, and oncogenes. The mechanisms by which these agents act and the precise roles they play in normal and abnormal proliferation of intestinal mucosa have not yet been clearly defined. Peptide hormones and growth factors exert their mitogenic effects by first interacting with specific receptors in the cell membrane. Oncogenes induce production of growth factors or replace growth factors and, by themselves, stimulate growth. We believe that no single agent is likely to be responsible; rather, multiple agents are involved in stimulation of growth of normal and neoplastic intestinal epithelial cells. A clear understanding of the factors responsible for regulation of normal and abnormal intestinal cell growth will greatly facilitate the development of therapeutic strategies for the prevention and treatment of gastrointestinal cancers.

Animals↗
PubMed1976

A fraction isolated from porcine upper small intestine stimulating pepsin secretion in the cat.

The preliminary purification of a material, apparently distinct from any hitherto isolated gastrointestinal hormone, with pepsin release stimulating activity in the cat is described. This material has shown no inhibitory effect on pentagastrin-stimulated secretion of acid, no effect of its own on gastric acid secretion and antral motility, and only a weak stimulatory effect on pancreatic secretion of bicarbonate.

Animals↗
PubMed1981

[Motility disturbances of the large intestine].

Motility disturbances of the large intestine, which appear in various conditions of a disease, are based on a reduction, the loss or an intensivation of the contractility as well as on a disorganization of the motor activity. Also in the region of the large intestine the normal motoricity can underlie such disturbances, such as retarded or accelerated passage, passage in wrong direction as well as increased turbulence or increased content. Retarded passage of the large intestine leads to obstipation and in advanced form to ileus. The leading symptom in accelerated passage is the diarrhoea. The passage in wrong direction disturbs the motoricity of the colon in the case of a lesion of the ileocaecal valves. Increased turbulence of the content of the large intestine is one of the causes of obstipation, particularly, when it appears in a retarded passage. The disturbances of the laminary flow are characteristic for a diverticulosis. The motor activity of the colon is influenced by many factors, mainly by the central nervous system, the gastrointestinal hormones (cholecystokinin, gastrin, serotonin, insulin and prostaglandins), the diet and the way of life. The motor disturbances are accompanied by bioelectric disturbances of the colon. In the second part of the lecture some pathogenetic and clinical aspects of the most frequently appearing motor disturbance of the large intestine, the irritable colon, are discussed.

Colitis↗
PubMed1998

Effects of prostaglandin F2alpha and cisapride on small intestinal activity during the early postoperative period in humans.

The relationship between intestinal motor activity and the influence of prostaglandin F2alpha (PGF) and cisapride were investigated during the early postoperative period in 26 patients who underwent abdominal surgery. Records of intestinal motility were made using an infusion catheter. PGF, 0.4 microg/kg per minute, given intravenously over 60 min, and cisapride, 5 mg, given intraintestinally, were administered to 13 patients each, first immediately after the operation, and then after the migrating motor complexes (MMCs) had reappeared following a period of intestinal quiescence. The MMCs were reestablished within the first postoperative day. Both PGF and cisapride stimulated irregular, high-amplitude contractions; however, the MMCs reappeared following these induced contractions only if the drugs were administered just after the postoperative MMCs became evident. These prokinetic drugs did not affect gastrointestinal hormone concentrations, but induced contractile activity even in the early postoperative period. Although the findings of this study demonstrate that these drugs may be useful as prokinetic agents to promote recovery from postoperative ileus just after the reappearance of MMCs in the early postoperative period, their precise mode of action has not been established.

Abdomen↗
PubMed1979

Effect of secretin and cholecystokinin-pancreozymin on plasma CEA concentration in patients with pancreatic carcinoma and pancreatitis.

Plasma CEA concentration before and after administration of secretin and cholecystokinin-pancreozymin has been determined in 89 patients with neoplastic or inflammatory pancreatric disease and other neoplastic and nonneoplastic disorders. The purpose of the study was to expore the specificity and sensitivity of such a provocation tests. Some rise of the plasma CEA concentration after hormonal stimulation could be observed in several patients in the various groups. However, none of the 37 patients with nonpancreatic disease who had a basal CEA concentration of 6 micrograms/l or less had a maximal CEA concentration above 13 micrograms/l after the stimulation whereas 7 out of 31 patients with pancreatic disease (3 with pancreatic carcinoma and 4 with chronic pancreatitis) showed such an elevation of plasma CEA concentration. Thus, the provocation test showed a satisfactory specificity for pancreatic disease but a low sensitivity. It is suggested that the possibility of an effect of physiologically released gastrointestinal hormones should be considered when "unexplained" high CEA values are found in plasma samples from nonfasting patients.

Animals↗