Maintenance treatment with budesonide 6 mg versus 9 mg once daily in patients with Crohn's disease in remission.

BACKGROUND: In previous trials, budesonide 6 mg/day was able to prolong the time to relapse in patients with quiescent Crohn's disease and budesonide 9 mg/day was effective in active disease with limited side effects. The aim of this study was to compare the effectiveness of budesonide 9 mg vs 6 mg once daily on the maintenance of remission and occurrence of adverse events. METHODS: Double-blind, randomised trial in patients with Crohn's disease in remission. Patients were randomised to receive 6 mg/day or 9 mg/day of budesonide (Budenofalk) without concomitant treatment for Crohn's disease. Endpoints were the time to relapse and relapse rates after one year. RESULTS: Seventy-six patients were randomised to 6 mg/day and 81 patients to 9 mg/day. Survival analysis showed no differences in the time to relapse. One-year relapse rates were not significantly different (6 mg group 24%; 9 mg group 19%). Any adverse event was reported in 61 and 68% of patients in the 6 mg and 9 mg groups, respectively; none of the 12 serious adverse events were drug related. CONCLUSION: The one-year relapse rates were low and not significantly different between the group of patients treated with budesonide 6 mg vs 9 mg/day. Also, time to relapse and the number of adverse events were similar in both treatment groups.

Helicobacter pylori antibiotic resistance in a Dutch region: trends over time.

AIM: Most patients treated for H. pylori infection receive empirical therapy based on epidemiological data of antibiotic resistance. However, previous European studies indicate that resistance patterns may be changing. Therefore, the aim of this study was to investigate the prevalence of primary clarithromycin and/or metronidazole resistant H. pylori strains over a six-year period (1997-2002) in a regional hospital. METHODS: All patients visiting Slingeland Hospital in Doetinchem, the Netherlands between 1997 and 2002 with a positive H. pylori culture were included in this study. Susceptibility to metronidazole and clarithromycin was determined by disk diffusion. RESULTS: Of the 1355 patients with an H. pylori positive culture, 1127 did not have a history of H. pylori eradication, 58 did, and for 170 this information was not available. Mean rates of primary resistance to metronidazole and clarithromycin were 14.4% (162/1125) and 1.0% (11/1123), respectively. Primary metronidazole resistance was stable throughout the study period and primary clarithromycin resistance showed a decreasing trend. Patients of foreign descent and from secondary care had a higher chance of harbouring primary metronidazole-resistant H. pylori (adjusted OR (95% CI) 1.75 (1.1 to 2.8), and 1.60 (1.1 to 2.2), respectively). Patients with failed H. pylori eradication had a higher chance of harbouring metronidazole-resistant H. pylori (43 vs 14%, p<0.0001) and clarithromycin-resistantH. pylori (5.3 vs 1.0%, p=0.004) than untreated patients. CONCLUSION: Primary metronidazole resistance is stableat a low level, while primary clarithromycin resistance isvirtually absent in the eastern part of the Netherlands.Therefore, triple therapy with a proton pump inhibitor,clarithromycin and amoxicillin can remain the empiricaltreatment of choice in the Netherlands.

Comparison of four-day and seven-day pantoprazole-based quadruple therapy as a routine treatment for Helicobacter pylori infection.

BACKGROUND: H. pylori eradication is usually performed with three or four drugs for at least seven days. Recently four reports have shown a cure rate of approximately 90% using a four-day quadruple therapy. The objectives of this prospective study were: 1) to evaluate the efficacy of pantoprazole-based quadruple therapy, and 2) to compare the efficacy and tolerability of four-day with seven-day quadruple therapy. METHODS: The study was performed in a single centre. The first 56 consecutive patients with nonulcer dyspepsia or peptic ulcer disease and proven H. pylori infection received seven days of quadruple therapy (pantoprazole, bismuth, tetracycline and metronidazole). At least six weeks after treatment, endoscopy was repeated with six biopsies of the antrum and corpus for histology, urease test and culture. The next 59 consecutive patients followed the same protocol but received four-day quadruple therapy. RESULTS: Using an intention-to-treat analysis, the cure rate in the seven-day treatment group was 54/56 (96.4%, 95% confidence interval (CI) 87.7-99.6%). In the per protocol analysis the cure rate was 53/55 (96.3%, 95% CI 87.5-99.6%). Primary metronidazole resistance was observed in seven patients. All were cured. Using an intention-to-treat analysis, the cure rate in the four-day treatment group was 51/59 (86.4%, 95% CI 75.0-94.0%). In the per protocol analysis the cure rate was 50/58 (86.2%, 95% CI 74.6-93.8%). Primary metronidazole resistance was observed in seven patients, four of whom were cured. In three out of eight patients in whom four-day treatment failed, secondary metronidazole resistance was induced. Both treatment regimens were well tolerated. The difference between cure rates of both regimens did not reach statistical significance (p=0.0585). CONCLUSION: Routine use of both four-day and seven-day pantoprazole-based quadruple anti-H. pylori treatment is effective and well tolerated. The results of both regimens reach the required eradication standard, but results with the seven-day regimen were slightly but not significantly better. Seven-day treatment may be superior, especially in case of metronidazole resistance, and should be preferred.

Recurrent staphylococcal bacteraemia and subhepatic abscess associated with gallstones spilled during laparoscopic cholecystectomy two years earlier.

This is the first report of Staphylococcus aureus bacteraemia and subhepatic abscess in association with intraperitoneal gallstones spilled during laparoscopic cholecystectomy two years earlier. Spilled gallstones can lead to abscess formation in the late postoperative period by acting as foreign bodies that can become infected during bacteraemia and then become a source of recurrent bacteraemia.

Hyperglycaemia reduces gastrin-stimulated gastric acid secretion in humans.

BACKGROUND: Recent studies have pointed to the role of plasma glucose in the regulation of gastrointestinal function. METHODS: We have investigated the effect of acute hyperglycaemia on gastric acid secretion and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to intravenous infusion of gastrin-17 in two doses: 5 pmol kg-1 h for 60 min and 15 pmol kg-1 h for another 60 min. Seven healthy subjects were studied during normoglycaemia and during acute hyperglycaemia at 15 mmol L-1. Acid output was measured by continuous aspiration using phenol red as recovery marker. Plasma PP levels were determined at regular intervals. RESULTS: Gastrin infusion at 5 pmol kg-1 h significantly (P < 0.05) increased acid output both during normoglycaemia and during hyperglycaemia. Gastrin infusion at 15 pmol kg-1 h further and significantly (P < 0.05) increased the acid output during both experiments. Hyperglycaemia significantly (P < 0. 05) reduced basal acid output (2.5 +/- 0.9 vs. 6.3 +/- 1.9 mmol h-1), low-dose gastrin stimulated acid output (6.5 +/- 1.7 vs. 13.0 +/- 1. 8 mmol h-1) and high-dose gastrin stimulated acid output (11.7 +/- 3. 0 vs. 19.4 +/- 3.0 mmol h-1) compared with normoglycaemia. Plasma PP levels were not stimulated by gastrin-17 infusion and were significantly (P < 0.05) reduced during hyperglycaemia. CONCLUSIONS: (a) Basal and gastrin-17-stimulated gastric acid secretion are reduced during hyperglycaemia; (b) infusion of gastrin-17 to physiological post-prandial levels does not affect plasma PP levels; (c) plasma PP levels are reduced during hyperglycaemia, suggesting vagal-cholinergic inhibition of gastric acid secretion during hyperglycaemia.

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.

Effect of acute hyperglycemia on basal and cholecystokinin stimulated exocrine pancreatic secretion in humans.

This study was undertaken to investigate the effect of acute hyperglycemia on pancreatico-biliary secretion in healthy subjects. Duodenal outputs of bilirubin, amylase, trypsin and bicarbonate were measured by aspiration using a recovery marker under basal condition for 75 min and during continuous infusion of CCK (0.5 IDU/kg.h for 60 min). Seven healthy subjects participated in two experiments performed in random order during normoglycemia and during acute hyperglycemic clamping at 15 mmol/l. At regular intervals plasma PP levels were determined as an indirect measure of vagal-cholinergic tone. Basal pancreatico-biliary secretion was significantly (p<0.05) reduced during acute hyperglycemia. CCK significantly (p<0.05) increased bilirubin, amylase and trypsin output both during normo- and hyperglycemia. During the initial 30 min of CCK infusion the bilirubin, amylase and trypsin outputs were significantly (p<0.05) inhibited in the hyperglycemic experiment compared to normoglycemia. In the following 30 min of CCK infusion the bilirubin, amylase and trypsin output were not different between hyper- and normoglycemia. Basal and CCK-stimulated plasma PP concentrations were significantly (p<0.05) reduced during hyperglycemia. In summary: 1) basal pancreatico-biliary secretion is significantly reduced during acute hyperglycemia 2) during hyperglycemia CCK-stimulated pancreatico-biliary secretion is also significantly reduced with the pattern of a delayed response 3) hyperglycemia inhibits basal and CCK-stimulated PP secretion suggesting impaired vagal-cholinergic activity during hyperglycemia.

Four-day quadruple therapy as a routine treatment for Helicobacter pylori infection.

BACKGROUND: H. pylori eradication usually involves treatment with three or four drugs for at least 7 days. Possible advantages of short treatment regimens are better patient compliance and tolerability. and less adverse effects. Recently two reports have shown a cure rate of > 90% using a 4-day quadruple therapy. AIM: To confirm these data and to evaluate the efficacy and tolerability of 4-day quadruple therapy in a single centre. METHODS: Thirty-eight consecutive patients with non-ulcer dyspepsia or peptic ulcer disease, and proven H. pylori infection, received 4 days of quadruple therapy (bismuth, tetracycline, metronidazole, lansoprazole). At least 6 weeks after treatment, endoscopy was repeated with six biopsies of antrum and corpus for histology and culture. RESULTS: The intention-to-treat cure rate was 34/38 (89.5%, 95% CI: 79.7-99.2%). In the per protocol analysis the cure rate was 34/37 (91.9%, 95% CI: 83.1-100%). Primary metronidazole resistance was observed in two patients; both were cured. Metronidazole resistance induction was observed in one patient in whom therapy failed. The treatment was generally well tolerated. CONCLUSION: Routine use of 4-day quadruple anti-H. pylori treatment is effective and well tolerated.

The role of cholecystokinin and the cholinergic system in intravenous amino acid-induced gallbladder emptying.

BACKGROUND: Recent studies have demonstrated that separate intravenous infusion of amino acids (IVAA) at high doses induces gallbladder emptying. However, little is known about the mechanisms mediating IVAA-induced gallbladder contraction. OBJECTIVE AND METHODS: To investigate whether the effect of IVAA on gallbladder motility is mediated by the cholinergic system and/or cholecystokinin (CCK), the major hormonal stimulus for gallbladder contraction. Six healthy male volunteers were studied in random order on five occasions using: (a) IVAA, (b) loxiglumide (CR 1505, a selective CCK-A receptor antagonist), (c) IVAA plus loxiglumide, (d) atropine and (e) IVAA plus atropine. Gallbladder volumes (ultrasonography) and plasma CCK levels (radioimmunoassay) were determined every 15 min for 60 min before and for 120 min during intravenous infusion of amino acids (Vamin 18EF; 250 mg protein/kg/h) and/or loxiglumide (10 mg/kg/h) and/or atropine (0.005 mg/kg/h). RESULTS: IVAA significantly (P < 0.05) reduced gallbladder volume from 32 +/- 5 ml to 17 +/- 2 ml but induced only a small and transient increase in plasma CCK levels. Loxiglumide given alone significantly (P < 0.05) increased fasting gallbladder volume to 190% of the basal value. IVAA-induced gallbladder emptying was completely abolished by loxiglumide. Maximal gallbladder relaxation during IVAA plus loxiglumide was not significantly different compared to loxiglumide given alone. Concomitant administration of atropine also significantly (P < 0.05) inhibited IVAA-induced gallbladder emptying. CONCLUSION: In healthy volunteers intravenous infusion of high doses of amino acids results in a significant gallbladder contraction, which is inhibited by CCK-A receptor blockade and by atropine.

Effects of parenteral nutrients on gastrointestinal motility and secretion.

BACKGROUND: The stimulation of gastrointestinal motility and secretion during nutrient digestion is generally divided into a cephalic, gastric and intestinal phase. Little is known about the effects of macronutrients on gastrointestinal function during the postabsorptive or circulatory phase of digestion. METHODS: Review of studies investigating the effects of circulating macro-nutrients such as fat, amino acids and glucose on gastrointestinal motility and secretion. RESULTS: Intravenous infusion of fat emulsions delays gastric emptying and interrupts the interdigestive intestinal motor pattern. Intravenous amino acids, administered in high doses, stimulate gastric acid secretion, pancreatic secretion, gallbladder contraction, and intestinal motility. Patients receiving total parental nutrition (TPN) have inert gallbladders and are at risk of developing gallbladder sludge and stones. Administering a proportion of the daily amino acid requirement by rapid intravenous infusion may prove useful in the prevention of sludge and stone formation during TPN by promoting gallbladder contraction. Intravenous infusion of glucose, already at physiological postprandial plasma levels, inhibits gastrointestinal motility and secretion. The inhibitory effect of glucose is dose-dependent, that is, more pronounced at higher plasma glucose levels. Recent studies have indicated that in patients with diabetes mellitus alterations in gastrointestinal function are related to the degree of hyperglycaemia. CONCLUSIONS: Nutrients during the circulatory phase of digestion influence gastrointestinal motility and secretion. Knowledge of these effects is relevant for conditions with increased plasma levels of macro-nutrients such as in patients with diabetes mellitus or during total parenteral nutrition.

Effect of intravenous glucose on intravenous amino acid-induced gallbladder contraction and CCK secretion.

The present study was undertaken to investigate the effect of acute hyperglycemia on the gallbladder contraction induced by intravenous administration of high doses of amino acids (Vamin 18, 250 mg protein/kg/hr). Six healthy volunteers were studied in random order on two occasions during normoglycemia and hyperglycemia with blood glucose levels stabilized at 15 mmol/liter. Gallbladder volumes, measured with ultrasonography, were studied for 60 min before and for 120 min during intravenous infusion of amino acids (IVAA). Administration of IVAA resulted in a significant reduction (P < 0.05) in gallbladder volume from 32 +/- 5 cm3 to 17 +/- 2 cm3 during normoglycemia. During hyperglycemia no significant changes in gallbladder volume were observed in response to IVAA. No significant changes in plasma CCK concentration, the major hormonal stimulus for gallbladder contraction, occurred in response to IVAA. During hyperglycemia, pancreatic polypeptide (PP) secretion, as an indirect measure of vagal cholinergic tone, in response to IVAA was significantly (P < 0.05) reduced compared to normoglycemia. It is concluded that: (1) administration of high doses of IVAA results in significant gallbladder contraction, (2) high doses of IVAA do not stimulate CCK secretion, (3) acute hyperglycemia inhibits IVAA-induced gallbladder contraction, and (4) acute hyperglycemia inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal-cholinergic tone during hyperglycemia.

Effect of hyperglycaemia on gallbladder motility in type 1 (insulin-dependent) diabetes mellitus.

Patients with diabetes mellitus are at increased risk of developing gallstones. This has been attributed, among other factors, to alterations in gallbladder motility in the presence of autonomic neuropathy. Since high blood glucose concentrations impair gastric emptying in diabetic patients, we have investigated the effect of acute hyperglycaemia on gallbladder motility. Seven Type 1 (insulin-dependent) diabetic patients were studied twice during euglycaemia (blood glucose 5 mmol/l) and hyperglycaemia (blood glucose 15 mmol/l) using a clamp technique. In addition, seven healthy volunteers were studied during euglycaemia and hyperglycaemia. Gallbladder volumes, measured with ultrasonography, were studied before and during infusion of step-wise increasing doses of cholecystokinin-33, 0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1, each dose for 30 min. Mean basal gallbladder volumes were not significantly different in the four experiments. Administration of cholecystokinin resulted in significant (p < 0.05) dose-dependent reductions in gallbladder volume in all experiments. During euglycaemia the gallbladder contraction in diabetic patients was not significantly different from the control subjects. During hyperglycaemia the gallbladder contraction in the diabetic patients was significantly (p < 0.05) reduced compared to euglycaemia only during infusion of 0.25 Ivy Dog Unit.kg-1.h-1 of cholecystokinin (19 +/- 6% vs 33 +/- 6%). Compared to euglycaemia, during hyperglycaemia the gallbladder contraction in the control subjects was significantly (p < 0.05) reduced during infusion of 0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1 of cholecystokinin (14 +/- 4% vs 31 +/- 3%; 42 +/- 6% vs 65 +/- 5%; 74 +/- 4% vs 90 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperglycemia modulates gallbladder motility and small intestinal transit time in man.

The aim of the present study was to investigate the effect of acute hyperglycemia on (1) the intestinal phase of gallbladder contraction induced by the intraduodenal administration of emulsified fat, and (2) the small intestinal transit time measured by the lactulose breath hydrogen test. Six healthy volunteers were studied in random order during normoglycemia and hyperglycemia (blood glucose levels 15 mmol/liter). Gallbladder volumes were measured with ultrasonography. Administration of 1 and 2 g/hr of fat resulted in significant reductions in gallbladder volumes from 24 +/- 2 cm3 to 11 +/- 1 cm3 (P < 0.05) and 8 +/- 1 cm3 (P < 0.05), respectively during normoglycemia, and from 24 +/- 2 cm3 to 21 +/- 2 cm3 (P < 0.05) and 16 +/- 2 cm3, respectively (P < 0.05) during hyperglycemia. Compared to normoglycemia, the gallbladder contraction was significantly (P < 0.05) reduced during hyperglycemia. No significant differences in CCK secretion were observed between experiments. Small intestinal transit time during hyperglycemia (101 +/- 12 min) was significantly (P < 0.05) prolonged compared to normoglycemia (57 +/- 12 min). During hyperglycemia, basal PP levels and PP secretion in response to intraduodenal fat were significantly (P < 0.05) reduced compared to normoglycemia. It is concluded that (1) low doses of intraduodenal emulsified fat result in significant gallbladder contraction and CCK secretion, (2) acute hyperglycemia inhibits intraduodenal fat induced gallbladder contraction, (3) acute hyperglycemia does not affect the intraduodenal fat induced CCK secretion, (4) small intestinal transit is significantly prolonged during acute hyperglycemia, and (5) acute hyperglycemia inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal-cholinergic tone during hyperglycemia.

Effect of acute hyperglycaemia on gall bladder contraction induced by cholecystokinin in humans.

This study examined the effect of acute hyperglycaemia, induced by intravenous glucose, on gall bladder motility. Six healthy volunteers were studied in random order on three occasions during normoglycaemia and hyperglycaemia with blood glucose concentrations stabilised at 8 and 15 mmol/l. Gall bladder volumes, measured with ultrasonography, were studied before and during infusion of stepwise increasing doses of cholecystokinin (CCK-33; 0.25, 0.5, and 1.0 IDU.kg-1.h-1). Each dose was given for 30 minutes. Pancreatic polypeptide (PP) secretion was determined as an indirect measure of cholinergic tone. Infusion of CCK-33 resulted in significant dose dependent reductions in gall bladder volume in all three experiments. Compared with normoglycaemia the gall bladder contraction was significantly (p < 0.05) reduced during infusion of 0.25 and 0.5 IDU kg-1.h-1 CCK-33 in the 8 mmol/l hyperglycaemic experiment, and during infusion of 0.25, 0.5, and 1.0 IDU kg-1.h-1 CCK-33 in the 15 mmol hyperglycaemic experiment. During hyperglycaemia basal plasma PP concentrations and PP secretion in response to CCK-33 were significantly (p < 0.05) reduced. It is concluded that blood glucose concentrations affect gall bladder motility, that an acute hyperglycaemia at 8 and 15 mmol/l reduces the gall bladder responsiveness to CCK-33 in a dose dependent manner, and that hyperglycaemia reduces basal and CCK-33 stimulated plasma PP concentrations, suggesting impaired cholinergic activity during hyperglycaemia.

Hyperglycemia reduces gallbladder emptying and plasma hormone secretion to modified sham feeding and regular feeding.

The purpose of this study was to investigate the effect of acute stable hyperglycemia on gallbladder motility, plasma cholecystokinin level and pancreatic polypeptide secretion. Gallbladder emptying in response to modified sham feeding and regular feeding was determined in six healthy subjects on two separate occasions during normoglycemia (serum glucose = 5 mmol/L) and during hyperglycemia (serum glucose = 15 mmol/L). Pancreatic polypeptide secretion was determined as an indirect measure of cholinergic tone. Gallbladder contraction in response to sham feeding during hyperglycemia (9% +/- 2%) was significantly (p < 0.05) reduced compared with that in normoglycemia (22% +/- 1%). During hyperglycemia, gallbladder emptying after meal ingestion (29% +/- 9%) was significantly (p < 0.05) less than that in normoglycemia (60% +/- 10%). Sham feeding did not affect plasma cholecystokinin levels. Regular feeding induced significant (p < 0.05) increases in plasma cholecystokinin levels in both experiments. However, integrated postprandial plasma cholecystokinin secretion was significantly (p < 0.05) reduced during hyperglycemia compared with that in normoglycemia (29 +/- 5 pmol.60 min vs. 58 +/- 10 pmol.60 min). Modified sham feeding-and feeding-stimulated pancreatic polypeptide secretion during hyperglycemia (235 +/- 95 pmol.90 min and 1,035 +/- 267 pmol.60 min, respectively) were significantly (p < 0.05) less than levels seen in normoglycemia (434 +/- 71 pmol.90 min and 1,961 +/- 219 pmol.60 min, respectively). This study indicates that gallbladder emptying and plasma hormone secretion in response to sham feeding and regular feeding are affected by blood glucose levels.

Hyperglycemia reduces gastric secretory and plasma pancreatic polypeptide responses to modified sham feeding in humans.

We have investigated the effect of acute stable hyperglycemia on gastric acid secretion and serum gastrin and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to modified sham feeding (MSF) in 7 healthy volunteers on two separate occasions: during normoglycemia (serum glucose 5 mmol/l) and during hyperglycemia (serum glucose 15 mmol/l). PP secretion was determined as an indirect measure of vagal-cholinergic tone. Basal acid output during hyperglycemia (4.7 +/- 1.0 mmol/h) was not significantly different from euglycemia (5.4 +/- 0.6 mmol/h), but MSF-stimulated acid output during hyperglycemia (14.7 +/- 3.3 mmol/90 min) was significantly (p < 0.05) reduced compared to euglycemia (24.7 +/- 3.2 mmol/90 min). Serum gastrin levels were not affected by MSF. During hyperglycemia, the integrated PP secretion in response to MSF (235 +/- 95 pmol/l.90 min) was significantly (p < 0.05) reduced compared to euglycemia (434 +/- 71 pmol/l.90 min). This study indicates that (1) serum glucose affects cephalic-stimulated gastric acid secretion, and (2) PP secretion after MSF is significantly reduced during hyperglycemia suggesting impaired vagal-cholinergic activity during hyperglycemia.

Effect of acute hyperglycemia on esophageal motility and lower esophageal sphincter pressure in humans.

The effect of acute hyperglycemia on esophageal motility and lower esophageal sphincter pressure (LESP) was investigated. Esophageal manometry was performed for 120 minutes in seven healthy volunteers on two separate occasions during euglycemia and during hyperglycemia with blood glucose levels stabilized at 15 mmol/L. At 90 minutes, motility was stimulated with edrophonium chloride (0.08 mg/kg intravenously). Pancreatic polypeptide (PP) secretion was determined as an indirect measure of vagal-cholinergic tone. During hyperglycemia the LESP decreased significantly (P less than 0.05) from 20.1 +/- 1.6 mm Hg to 10.7 +/- 0.6 mm Hg; plasma PP levels were also significantly (P less than 0.05) decreased during hyperglycemia. Edrophonium induced significant (P less than 0.05) increases in LESP and PP levels in both experiments. However, LESP and PP levels after edrophonium stimulation remained significantly (P less than 0.05) reduced during hyperglycemia compared with euglycemia. During hyperglycemia a significant (P less than 0.05) increase in peristaltic wave duration and a decrease in peristaltic velocity were observed in the distal part of the esophagus. It is concluded that blood glucose levels affect esophageal motility, acute hyperglycemia reduces LESP and impairs esophageal motility under both basal and edrophonium-stimulated conditions, and hyperglycemia reduces plasma PP levels, suggesting impaired vagal-cholinergic activity during hyperglycemia.

Effect of hyperglycemia on gastrointestinal and gallbladder motility.

Gastrointestinal motor abnormalities occur frequently in patients with diabetes mellitus. The gastrointestinal motor dysfunction in these patients has been associated with the presence of autonomic neuropathy. Recently, however, several studies have shown that the gastrointestinal motor responses to various stimuli are impaired during acute hyperglycemia in both healthy subjects and diabetic patients. It has been demonstrated that acute hyperglycemia impairs esophageal peristalsis, reduces the lower esophageal sphincter pressure, delays gastric emptying, slows intestinal transit, and reduces the gallbladder contraction in response to various stimuli in healthy subjects. In diabetic patients gastric emptying and gallbladder contraction have been shown to be impaired during hyperglycemia. With regard to the mechanisms of action, it has been suggested that hyperglycemia may affect gastrointestinal function through vagal-cholinergic inhibition, by alterations in serum osmolality, or perhaps by alterations in gastrointestinal hormone secretion.

Effect of intravenous fat on cholecystokinin secretion and gallbladder motility in man.

During total parenteral nutrition (TPN) gallbladder bile stasis and hypomotility have been well documented. Little is known, however, about the effect of the separate components of TPN on gallbladder motor function. Inasmuch as fat, administered intraduodenally, is a potent stimulus of cholecystokinin (CCK) secretion and gallbladder contraction we have investigated whether intravenous (IV) fat affects gallbladder motility. Six healthy volunteers were studied on two separate occasions, during infusion of Intralipid 10%, 200 mL/h or saline infusion (control) for 3 hours, to evaluate the effect of IV infusion of fat on (1) plasma CCK concentration and gallbladder volume and (2) CCK-induced gallbladder emptying. Intravenous infusion of Intralipid resulted in significant increases in serum triglycerides from 0.9 +/- 0.1 to 5.1 +/- 1.3 mmol/L (at 90 min). During fat infusion no significant changes in plasma CCK and gallbladder volume were noted when compared with basal values or to the control experiment. During IV fat, concomitant infusion of 0.25, 0.5, and 1.0 Ivy dog unit (IDU) per kilogram per hour of CCK-33 resulted in a significant reduction in gallbladder volume from 26 +/- 6 cm3 (basal) to 15 +/- 4 cm3 (p less than .05), 6 +/- 2 cm3 (p less than .05) and 2.5 +/- 1 cm3 (p less than .05), respectively. No significant differences in CCK-induced gallbladder emptying were observed between IV fat and saline infusion (control). It is concluded that, in contrast to intraduodenal fat, IV infusion of fat does not affect (1) basal plasma CCK and gallbladder volume and (2) CCK-induced gallbladder contraction.