Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

The Effect of Unenhanced MRI on the Surgeons' Decision-Making Process in Females with Suspected Appendicitis.

BACKGROUND: This prospective study evaluated the impact of the results of unenhanced magnetic resonance imaging (MRI) on the surgeon's diagnosis of acute appendicitis in potentially fertile females. METHODS: 112 female patients, aged 12-55, with suspected appendicitis underwent MRI of the abdomen. At three defined intervals; admission and clinical re-evaluation before and after revealing the MRI results, the surgeon recorded the attendance of each patient in operative treatment, observation or discharge. Appendicitis was confirmed or declined by pathology or by telephone follow-up in case of non-intervention. FINDINGS: Appendicitis was confirmed in 29 of 112 patients. At admission the surgeon's disposition had a sensitivity of 97 % and specificity of 29 %. After knowing the MRI results, sensitivity was 97 % and specificity 64 %. The sensitivity and specificity of MRI alone were 89 and 100 %, with a negative and positive predictive value of 96 and 100 %, respectively. CONCLUSION: We believe that MRI should perhaps be standard in all female patients during their reproductive years with suspected appendicitis. It avoids an operation in 32 % of cases and allows earlier planning for patients with an equivocal clinical picture. Trial number: OND1292733 (Narcis.nl).

Reproducibility of antroduodenal motility during prolonged ambulatory recording.

Ambulatory recording of antroduodenal manometry is a novel technique with several advantages over standard stationary manometry recording. Although the feasibility of this technique in clinical practice has been demonstrated, reproducibility of antroduodenal motility recorded by means of ambulatory manometry has not been investigated. To test whether antroduodenal motility recorded by ambulatory manometry is reproducible, we performed two 24-h ambulatory antroduodenal manometry recordings in 18 healthy subjects according to an identical protocol with a 1-week interval. Motility was recorded with a five-channel solid-state catheter. Postprandial motility was recorded after consumption of two test meals and interdigestive motility was recorded nocturnally. Postprandial antroduodenal motor characteristics were identical between the separate recordings. The number and duration of nocturnal cycles of the interdigestive migrating motor complex were also in the same range. Phase III characteristics in general were not different between the two recordings. Only minor alterations were observed in the duration of phase III motor fronts with duodenal onset and in the number of interdigestive cycles concluded by duodenal onset phase III. Parameters obtained by qualitative analysis were comparable between the two recordings. The antroduodenal motility pattern, when measured by ambulatory recording with solid state catheters under standardized conditions, is very reproducible.

Pancreatic polypeptide secretion in patients with chronic pancreatitis and after pancreatic surgery.

AIM: We investigated polypeptide (PP) secretion under basal conditions, in response to bombesin infusion and to meal ingestion in patients with chronic pancreatitis (CP) and patients after different types of pancreatic surgery. METHODS: Included were patients with CP without (n = 20) and with (n = 30) exocrine pancreatic insufficiency, patients after duodenum preserving resection of the head of the pancreas (DPRHP; n = 20), after Whipple's procedure (n = 19), following distal pancreatectomy (DP; n = 12), and healthy controls (n = 36). RESULTS: In CP patients basal and bombesin stimulated PP levels were significantly (p<0.01) reduced compared to controls only when exocrine insufficiency was present. Meal-stimulated PP secretion was significantly (p<0.01-0.05) reduced in CP patients both with and without exocrine insufficiency. Plasma PP peak increments after bombesin and meal ingestion correlated significantly with exocrine function. Basal PP, meal, and bombesin-stimulated PP secretion had low sensitivities of 22%, 42%, and 60% respectively, in detecting chronic pancreatitis. In patients after pancreatic surgery that included pancreatic head resection (DPRHP or Whipple operation) basal and stimulated PP secretion were significantly (p<0.01-0.05) reduced. CONCLUSION: Basal and meal or bombesin-stimulated PP levels are significantly reduced in patients with CP only when exocrine insufficiency is present. Determination of plasma PP levels has low sensitivity and is not useful in detecting chronic pancreatitis without exocrine insufficiency. In patients after pancreatic surgery, PP secretion is dependent on the type of operation (head vs tail resection).

Prolonged ambulatory recording of antroduodenal motility in slow-transit constipation.

BACKGROUND: Slow-transit constipation may be part of a pan-enteric motor disorder. To test this hypothesis 24-h ambulatory antroduodenal manometry was performed and orocaecal transit time determined in patients with slow-transit constipation and in healthy controls. METHODS: Antroduodenal motility was recorded with a five-channel solid-state catheter. Postprandial motility was recorded after consumption of two standardized test meals and interdigestive motility was recorded nocturnally. Manometry tracings were analysed for quantitative and qualitative abnormalities. Orocaecal transit time was determined by means of the lactulose hydrogen breath test. RESULTS: Postprandial motility was no different between patients and controls. However, some minor changes of interdigestive motility were observed. The proportion of phase II activity of the nocturnal cycles of the interdigestive migrating motor complex was increased in patients while phase I activity was decreased. The total number of observed phase III fronts was no different in patients and controls, although the number of phase III fronts with antral onset was decreased. Furthermore, the amplitude of phase III activity of duodenal onset was also decreased. Specific motor abnormalities such as retrograde propagation of phase III fronts were more frequent in patients. Orocaecal transit time was delayed in patients. CONCLUSION: In patients with slow-transit constipation, orocaecal transit time is delayed but antro- duodenal motility is generally well preserved with only minor alterations. Presented as a poster to the Digestive Disease Week meeting in New Orleans, Louisiana, USA, May 1998, and published in abstract form as Gastroenterology 1998; 114: A820

Gallbladder motility in Crohn disease: influence of disease localization and bowel resection.

BACKGROUND: Patients with Crohn disease (CD) have an increased risk of developing gallstones. Among other factors, gallbladder motility may have a role in the pathogenesis of gallstone formation. We have evaluated whether gallbladder motor function is affected in Crohn disease with special emphasis on the influence of disease localization and previous bowel resection. METHODS: Thirty-seven patients (20 females and 17 males, age 36 +/- 2 years) with inactive Crohn disease (CDAI < 150) were studied: 15 patients after ileocecal resection and 22 non-operated patients; 12 had small bowel disease and 10 had large bowel disease. Nineteen healthy subjects (10 female; 9 male, age 30 +/- 2 years) served as controls. Gallbladder volumes were measured in the fasting state and at regular intervals for 2 h after ingestion of a solid meal (780 kcal). Blood samples were drawn at regular intervals for determination of cholecystokinin (CCK) and peptide YY (PYY). RESULTS: Fasting gallbladder volumes were significantly (P < 0.05) reduced in patients with large bowel disease (20.8 +/- 2.1 ml) or after ileocecal resection (18.3 +/- 2.4 ml) compared to patients with small bowel disease (28.0 +/- 2.1 ml) and controls (27.2 +/- 1.8 ml). Fasting plasma CCK levels were significantly (P < 0.05) higher in patients with large bowel disease or after ileocecal resection compared to patients with small bowel disease and controls. Postprandial gallbladder emptying and endogenous plasma CCK and PYY secretion in patients with Crohn disease were not different from controls. CONCLUSIONS: Fasting gallbladder volume is decreased and fasting plasma CCK levels are increased in patients with Crohn disease of the large bowel and patients after ileocecal resection. Postprandial gallbladder motility, CCK and PYY release were not affected in patients with Crohn disease.

Cholecystokinin secretion in patients with chronic pancreatitis and after different types of pancreatic surgery.

UNLABELLED: Cholecystokinin (CCK) secretion may be affected in patients with chronic pancreatitis (CP), but little is known on the effect of pancreatic surgery on CCK secretion. We measured CCK secretion (radioimmunoassay, RIA) in response to bombesin infusion (100 ng/kg/20 min) for 120 min to test CCK secretory capacity, to ingestion of a liquid diet (400 kcal) for 120 min, and in response to a solid fat-rich meal (500 kcal) for 120 min. These studies were performed in 45 patients with CP (25 with exocrine insufficiency), 15 patients after duodenum-preserving pancreatic head resection (DPRHP), 18 patients after the Whipple operation, 12 patients after distal pancreatectomy (DP), and 35 control subjects. In CP patients, the CCK secretory capacity was preserved, but the postprandial CCK response was reduced, depending on meal composition and the presence of exocrine insufficiency. In patients after Whipple's operation, CCK secretory capacity and postprandial CCK secretion were significantly (p < 0.05) reduced. In patients after DPRHP, CCK secretory capacity was not affected, but the postprandial CCK response was significantly (p < 0.05) reduced, depending on meal composition and the presence of exocrine insufficiency. In patients after DPRHP, fasting plasma CCK levels were significantly (p < 0.01) increased, pointing to the absence of feedback inhibition on CCK secretion by intraluminal enzymes. After DP, the CCK secretory capacity was not affected. IN CONCLUSION: alterations in CCK secretion are observed in patients with chronic pancreatitis and after pancreatic surgery. These alterations are related not only to the disease process (exocrine insufficiency) but also to the type of surgery and type of stimulus.

Gall bladder emptying in severe idiopathic constipation.

BACKGROUND: It has been suggested that slow transit constipation (STC) may be part of a panenteric motor disorder. AIM: To evaluate motility of an upper gastrointestinal organ, the gall bladder, in 16 patients with STC and 20 healthy controls. METHODS: Gall bladder emptying (ultrasonography) was studied in response to neural, cephalic-vagal stimulation with modified sham feeding (MSF) for 90 minutes and in response to hormonal stimulation with cholecystokinin (CCK, 0.5 IDU/kg/h) for 60 minutes. RESULTS: Fasting gall bladder volume in patients with STC (17 (2) cm(3)) was significantly (p<0. 01) reduced compared with that in controls (24 (2) cm(3)). Gall bladder emptying in response to MSF was significantly reduced in patients with STC expressed both as percentage emptying (11 (5)% versus 22 (3)%; p<0.05) and as absolute emptying (2.1 (0.7) cm(3) versus 4.9 (0.7) cm(3); p<0.02). However, percentage gall bladder emptying in response to CCK was not different between patients and controls (73 (4)% versus 67 (4)%) although the absolute reduction in gall bladder volume was significantly (p<0.05) smaller in patients (10.7 (1.1) cm(3) versus 15.3 (1.4) cm(3)). CONCLUSIONS: Patients with slow transit constipation have smaller fasting gall bladder volumes, impaired gall bladder responses to vagal cholinergic stimulation, but normal gall bladder responses to hormonal stimulation with CCK. These results point to abnormalities in gastrointestinal motility proximal from the colon in slow transit constipation and more specifically, impaired neural responsiveness.

Post-prandial intragastric and duodenal acidity are increased in patients with chronic pancreatitis.

OBJECTIVES: Patients with chronic pancreatitis and exocrine insufficiency have lower intraduodenal pH compared to controls. It has been assumed that abnormal low intraduodenal pH in these patients not only results from impaired pancreatic bicarbonate secretion but also from an increased gastric acid load to the duodenum. METHODS: We have tested this hypothesis by combined intragastric and intraduodenal 24 h pH monitoring in nine chronic pancreatitis patients with exocrine pancreatic insufficiency and nine healthy control subjects during standardized test conditions. Postprandial gastrin and cholecystokinin release were also determined. RESULTS: Median 24-h intraduodenal pH (5.90 vs. 6.00) and intragastric pH (1.60 vs. 1.70) were not significantly different between patients and controls. However, in the 2-h postprandial periods intraduodenal pH was below five for a significantly higher percentage of time in chronic pancreatitis patients compared to controls (lunch: 14.5% vs. 0.17%, P=0.011; dinner: 24.1% vs. 5.75%, P=0.05). The post-dinner intragastric pH was below three for a significantly higher percentage of time in chronic pancreatitis patients vs. controls (72.2 vs. 48.9%, P=0.04). Postprandial gastrin release was not significantly different between the two groups. Postprandial secretion of cholecystokinin (CCK), as enterogastrone, was significantly (P < 0.01) reduced in chronic pancreatitis patients (78 +/- 13 pmol/L, 120 min) compared to controls (155 +/- 14 pmol/L, 120 min). CONCLUSIONS: Median intraduodenal and intragastric pH are not significantly decreased in patients with chronic pancreatitis and exocrine insufficiency but the postprandial time with an acidic pH in the duodenum (pH < 5) and in the stomach (pH < 3) is significantly (P

Effect of insulin and glucose on basal and cholecystokinin-stimulated exocrine pancreatic secretion in humans.

Pancreaticobiliary secretion is reduced during acute hyperglycemia. In nondiabetics, this inhibitory effect also may result from hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin (CCK)-stimulated pancreaticobiliary secretion. Nine healthy volunteers (age, 22-52 years) were studied on three occasions in random order during (a) intravenous saline (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mM), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/L, glucose at 4-5 mM). Duodenal outputs of bilirubin, amylase, trypsin, and bicarbonate were measured under basal conditions and during CCK infusion (0.25 and 0.5 IDU/kg/h). Basal pancreaticobiliary secretion was significantly (p < 0.05) reduced during both HG and HI. During low-dose CCK stimulation, HG significantly (p < 0.05) reduced bilirubin and trypsin output compared with control. In contrast, HI did not significantly reduce pancreatic enzyme and bilirubin output during low-dose CCK infusion. During high-dose CCK infusion, neither HI nor HG influenced pancreatic enzyme and bilirubin output. Pancreatic bicarbonate output was not influenced by CCK and remained significantly (p < 0.05) reduced during HI and HG compared with control. It is concluded that during both acute hyperglycemia and euglycemic hyperinsulinemia, basal pancreaticobiliary secretion is significantly reduced. CCK-stimulated pancreatic enzyme and bilirubin output is significantly reduced only during hyperglycemia. The inhibitory effect of hyperglycemia on pancreaticobiliary secretion in healthy volunteers may occur independent of insulin.

Effect of i.v. amino acids on satiety in humans.

BACKGROUND: Parenteral nutrients suppress oral food intake. Separate i.v. infusion of amino acids (IVAA) at high doses affects gastrointestinal motility and secretion. However, little is known on the effects of separate i.v. infusion of amino acids at these high doses on satiety. Therefore, we have studied the effect of two different doses of a commercially available mixed amino acids solution on satiety and food intake. METHODS: Six healthy volunteers (ages 20 to 34 years) were studied on three separate occasions in random order during (a) i.v. saline (control), (b) low-dose IVAA ([LDA] 125 mg protein/kg/h, Vamin 18EF; Kabi Pharmacia BV, Woerden, The Netherlands), or (c) high-dose IVAA ([HDA] 250 mg protein/kg/h) for 360 minutes. Subjective criteria such as wish to eat, prospective feeding intentions, and feelings of hunger and fullness were scored on 100-mm visual analog scales at 30-minute intervals. Food preference also was measured every 60 minutes with food selection lists. At the end of the experiment a meal was presented. RESULTS: Feelings of fullness were significantly (p < .05) increased during both LDA and HDA. The wish to eat was significantly (p < .05) decreased during HDA compared with control and LDA. Prospective feeding intentions also tended to be reduced during HDA (not significant). Feelings of hunger were not significantly different between the three experiments. Total food selection was significantly (p < .05) decreased during LDA and HDA, mainly because of a significantly (p < .05) decreased preference for fat-rich items. However, the total amount of food consumed at the end of the experiment was not significantly different between the three experiments. CONCLUSIONS: The present study shows that in healthy volunteers, IVAA (1) increase satiety ratings, (2) increase feelings of fullness, (3) decrease preprandial food selection, and (4) have no effect on subsequent oral food intake.

Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time.

BACKGROUND: Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying. AIMS: To investigate whether intravenous amino acids also influence antroduodenal motility. METHODS: Eight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test. RESULTS: DCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control. CONCLUSIONS: Separate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.

Effect of gastrin on antroduodenal motility: role of intraluminal acidity.

The effect of gastrin on the migrating motility complex (MMC) was studied in seven healthy subjects. It was hypothesized that a potential effect of gastrin on the MMC may result from intraluminal acidification through increased gastric acid secretion. Therefore, antroduodenal manometry and intraluminal acidity were recorded simultaneously. The effect of gastric acid inhibition, with and without administration of gastrin, on antroduodenal motility and intraluminal acidity was also evaluated and compared with saline infusion (control). Continuous infusion of gastrin-17 (20 pmol. kg-1. h-1) increased intragastric and intraduodenal acidity and suppressed phase II and phase III motor activity in both antrum and duodenum. Concomitant gastric acid inhibition with intravenous famotidine, as demonstrated by intragastric neutralization of pH, completely antagonized the effect of gastrin on the MMC. In fact, famotidine infusion, both with and without administration of gastrin, significantly shortened MMC cycle length. It is concluded that the effect of gastrin on interdigestive antroduodenal motility results from increased intraluminal acidity.

Dose-dependent inhibition of postprandial gallbladder motility and plasma hormone secretion during acute hyperglycemia.

BACKGROUND: Actual blood glucose concentrations influence gastrointestinal function. We investigated whether in healthy subjects the inhibitory effect of acute hyperglycemia on gallbladder motility is dose-dependent. METHODS: Seven healthy volunteers were studied on four separate occasions in random order during euglycemia and during hyperglycemic clamping, at 4 mmol/l, 8 mmol/l, 12 mmol/l, and 16 mmol/l, respectively. Gallbladder volumes (ultrasonography) and plasma hormone release were studied before and after ingestion of a meal. RESULTS: Postprandial gallbladder contraction was significantly (P < 0.05) and dose-dependently inhibited during the hyperglycemic experiments at 8, 12, and 16 mmol/l (56%+/-8%, 49%+/-8%, and 30%+/-5%, respectively) compared with euglycemia (68%+/-6%). Postprandial cholecystokinin release was significantly (P < 0.05) reduced compared with euglycemia only at a plasma glucose level of 16 mmol/l (116+/-28 versus 159+/-13 pmol x l(-1) x 120 min). Plasma pancreatic polypeptide secretion, as an indirect measure of vagal-cholinergic tone, was significantly (P < 0.05) and dose-dependently reduced during hyperglycemia at 8, 12, and 16 mmol/l. CONCLUSION: In healthy subjects acute hyperglycemia significantly and dose-dependently inhibits postprandial gallbladder motility. Future studies on gallbladder motility should take into account the influence of plasma glucose, because already at postprandial glucose levels gallbladder motility is reduced.

Interdigestive antroduodenal motility and gastric acid secretion.

BACKGROUND: In humans, interdigestive acid secretion and antroduodenal motility are closely related with cyclic variations in acid secretion, synchronous with the various phases of the migrating motor complex (MMC). Duodenal acidification inhibits antral motility, but little is known about the effect of acute acid inhibition on antroduodenal motility. AIM: To study the effect of acute acid inhibition on antroduodenal motility. SUBJECTS: Ten healthy volunteers (four men and six women: age range 20-31 years). METHODS: Antroduodenal motility (perfusion manometry) and gastric acid secretion (continuous aspiration with recovery marker) were measured simultaneously. Each subject was studied twice in random order during (1) intravenous infusion of saline for one-two complete MMC cycles and (2) during acute acid inhibition with intravenous famotidine (bolus 20 mg, continuous infusion 4 mg/h) for one-two complete MMC cycles or at least 240 min. RESULTS: In the saline study, acid output in phase III (2.1 +/- 0.3 mmol/10 min) and late phase II (1.7 +/- 0.2 mmol/10 min) was significantly (P<0.05) increased over early phase II and phase I (1.2 +/- 0.2 and 1.2 +/- 0.2 mmol/10 min, respectively). Famotidine increased gastric pH to above pH 6 within 30 min. After acid inhibition, duration of MMC cycle during famotidine (106 +/- 8 min) was not significantly different from the saline experiment (133 +/- 14 min). Phase distribution of the MMC cycle was not significantly different between famotidine (I, II and III: 12 +/- 3, 82 +/- 3 and 5 +/- 1%) and saline (I, II and III: 13 +/- 3, 83 +/- 3 and 4 +/- 1%). CONCLUSIONS: Gastric acid secretion varies cyclically with interdigestive antroduodenal motility. Acute acid inhibition with intravenous famotidine does not significantly affect interdigestive antroduodenal motility.

Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans.

BACKGROUND/AIMS: Acute hyperglycemia inhibits gallbladder contraction. In non-diabetic subjects this inhibitory effect may result from endogenous hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin-stimulated gallbladder motility. METHODS: Gallbladder volume (ultrasonography) and duodenal bilirubin output were studied simultaneously in nine healthy volunteers (age 20-52 years) on 3 separate occasions in random order during: (a) saline infusion (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mmol/l), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/l, glucose at 4-5 mmol/l). After a 2-h basal clamp period, cholecystokinin was infused intravenously for 60 min at 0.25 IDU x kg(-1) x h(-1), followed by another 60 min at 0.5 IDU x kg(-1) x h(-1). RESULTS: HI and HG significantly (p<0.05) reduced basal duodenal bilirubin output compared to control, while basal gallbladder volume did not change. At the low dose cholecystokinin, gallbladder emptying during HG (25+/-3%) and HI (39+/-4%) was significantly (p<0.01) reduced compared to control (61+/-4%). The inhibitory effect of HG was significantly (p<0.05) stronger compared to HI. Duodenal bilirubin output during the low dose cholecystokinin was significantly (p<0.05) reduced by HG, but not by HI. No inhibitory effect of HG and HI on gallbladder emptying and duodenal bilirubin output was observed with the high dose of cholecystokinin. CONCLUSIONS: In healthy subjects acute hyperglycemia and euglycemic hyperinsulinemia reduce basal duodenal bilirubin output and inhibit gallbladder emptying stimulated by low dose cholecystokinin. These results suggest that insulin is involved in the inhibitory effect of hyperglycemia on basal and cholecystokinin-stimulated gallbladder motility.

Effect of amino acids on lower esophageal sphincter characteristics and gastroesophageal reflux in humans.

The effect of a commercially available mixed amino acids solution, when given either intravenously or intragastrically, on lower esophageal sphincter (LES) pressure, frequency of transient LES relaxations (TLESRs) and gastroesophageal reflux (GER) was investigated in six healthy volunteers. LES pressure and esophageal pH were simultaneously recorded on three separate occasions 1 hr before (basal) and 3 hr during intravenous or intragastric infusion of amino acids (250 mg protein/kg/hr) or saline (control). No significant changes in LES pressure were seen in the control experiment. Intravenous amino acids caused a rapid and sustained (P < 0.01) decrease in LES pressure whereas intragastric amino acids decreased LES pressure only gradually and temporarily (P < 0.01). In the three experiments no significant differences were observed in TLESR frequency, the number of GER episodes, the mechanism of reflux, or duration of acid exposure. In healthy subjects both intragastric and, especially, intravenous infusion of amino acids significantly decrease LES pressure but do not affect the frequency of TLESRs or GER episodes during a continuous liquid gastric load.

Effects of hyperglycemia and hyperinsulinemia on satiety in humans.

Hyperglycemia may influence satiety. One mechanism by which glucose could influence food intake is hyperinsulinemia. Therefore, we investigated the short-term effects of acute hyperglycemia and euglycemic hyperinsulinemia on satiety. Six healthy volunteers (aged 20 to 26 years) were studied for 240 minutes on three separate occasions in random order during (1) intravenous (i.v.) saline (control), (2) acute hyperglycemic hyperinsulinemia (HG) with plasma glucose at 15 mmol/L, and (3) euglycemic hyperinsulinemia (HI) with plasma insulin at 80 mU/L and glucose at 4 to 5 mmol/L. Subjective criteria for appetite like the wish to eat, prospective feeding intentions ("How much food do you think you can eat?"), and feelings of hunger and fullness were scored on a 100-mm visual analog scale (VAS) at 30-minute intervals. Appetite was also measured every 60 minutes with the use of a food selection list (FSL). Appetite (prospective feeding intentions, feelings of hunger, and the wish to eat) gradually increased over basal levels during control conditions and HI. In contrast, prospective feeding intentions and feelings of hunger gradually decreased during HG and were significantly (P < .05) reduced versus basal and control levels during the last hour of the experiment. The wish to eat followed the same pattern. Feelings of fullness did not significantly change in all three experiments. Total food selection was not significantly decreased during HG, but the preference for fat-rich or carbohydrate-rich items tended to be reduced. The study suggests that in humans hyperglycemia induces satiety. This effect seems not to be mediated by insulin, since HI had no effect on appetite. However, a potentiating effect of endogenous insulin on the satiating effect of high blood glucose levels cannot be excluded.

Influence of hyperglycemia on the satiating effect of CCK in humans.

In the present study the effects of intraduodenal (i.d.) fat (endogenous CCK) and of CCK infusion on satiety were studied during normo-and hyperglycemic conditions. Eight healthy subjects participated in two protocols consisting of two experiments each. First protocol: (a) normoglycemia (control) with i.d. emulsified fat (i.d. fat) infusion, (b) acute hyperglycemia (HG) with plasma glucose levels stabilized at 15 mmol/L and i.d. fat infusion. In the second protocol the effect of exogenous cholecystokinin (CCK) on satiety was studied during normo- and hyperglycemia. Intraduodenal fat (Intralipid 10%) was infused at a dose of 1 g/h via a nasoduodenal tube in the first protocol, whereas in the second protocol CCK-33 was infused intravenously at a dose of 0.5 IDU/kg x h. Satiety was scored using visual analog scales (VAS). Plasma CCK levels were determined at regular intervals. During infusion of i.d. fat and i.v. CCK the VAS scores of wish to eat, hunger, and prospective feeding decreased significantly (p<0.05) in the normoglycemic experiments. During hyperglycemia satiety did not significantly change in the basal period; however, the scores of wish to eat, hunger, and prospective feeding increased significantly (p<0.05) when i.d. fat or i.v. CCK was administered. Plasma CCK levels in the basal and the stimulated period were not significantly different between normo- and hyperglycemia. In summary, the present study shows that in healthy humans volunteers 1) during normoglycemic conditions satiety can be induced by very low dose of i.d. fat and by CCK infusion, 2) during hyperglycemia the effect of i.d. fat and CCK on satiety are reversed, resulting in increased appetite.