Simultaneous assessment of gallbladder emptying in the dog by real-time ultrasonography and strain gauge

Patterns of meal-and cerulein-induced gallbladder emptying (GBE) were compared in four dogs equipped with a force transducer implanted onto the body of the gallbladder, and in four unoperated animals. GBE was examined by real-time ultrasonography in conscious dogs. In two dogs the ultrasonographic measurement of GBE was performed simultaneously with the registration of the strain exerted on the force transducer fixed on the gallbladder body. Implantation of the force transducer onto the gallbladder impaired neither postprandial nor cerulein-induced GBE. The contractile response of the gallbladder exhibited a nonlinear relationship to the gallbladder volume. The reduction of gallbladder volume to 50% of its basal value was accompanied by an increase in strain amounting to about 16% of the maximum response, whereas a pronounced augmentation of the strain was observed with gallbladder volume ranging between 30% and 10% of the basal value. On the other hand, the contractile response of the gallbladder registered by means of a force transducer was linearly related to the angle α contained between two radii passing from the gallbladder center towards the edges of the strain gauge:y=0.852α−30.97 (r=0.959,P<0.001) in the case of i.v. cerulein infusion at stepwisely increasing doses (0.7–2.2–7.4–22.2–66.5 pmol·kg⁻¹h⁻¹), andy=0.640α−17.40 (r=0.869,P<0.001) for a 1-h constant-rate 22.2 pmol·kg⁻¹h⁻¹ cerulein infusion. Part of this work was recently presented at the First Congress of the European Federation of Physiological Societies (9–12 September 1995, Maastricht, The Netherlands) and was published in abstract form (Pflügers Arch-Eur J Physiol 1995; 430 (Suppl): R165)     

Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin

A reduction of gallbladder emptying in response to neural or hormonal stimulation has been reported in patients with diabetes mellitus. Decreased gallbladder emptying may be a key factor in the pathogenesis of gallbladder stones. Few drugs, if any, are able to stimulate gallbladder emptying. However, in a previous study we demonstrated that erythromycin, a macrolide antibiotic, stimulates gallbladder emptying and motilin release in healthy human subjects by an atropine-sensitive pathway. Therefore, the present study was designed to evaluate the effect of erythromycin on gallbladder emptying and motilin release in diabetic patients with or without cardiac autonomic neuropathy (AN). Thirteen diabetic patients, six with AN, and 10 healthy subjects were enrolled in the study protocol. Gallbladder emptying was determined by sonography after ingestion of a standard meal and during infusion of erythromycin alone or together with 6 g/kg/hr atropine. We found that 100 mg/hr erythromycin caused a significant reduction in gallbladder volume in both healthy subjects and diabetic patients. The ejection fraction (mean ±se) of 45.3±8.2% and 37.3±5.0% was similar. The presence of AN had no influence on gallbladder emptying induced by erythromycin. Basal motilin plasma levels were 111.5±14.5 pmol/liter in diabetic patients and 63.3 ±6.0 pmol/liter in healthy subjects (P<0.01). However, patients with AN had higher (130.0 ±11.9 pmol/liter) motilin plasma levels than patients without (74.0±9.4 pmol/liter,P<0.01). Erythromycin administration caused an approximately twofold increase in plasma motilin concentrations in healthy subject and patients withou AN, but did not stimulate motilin release in neuropathic patients. A negative correlation (r=–0.75,P<0.01) was found between basal plasma levels of motilin and peak of gallbladder emptying induced by erythromycin. Atropine completely inhibited the effects of erythromycin on gallbladder emptying and motilin release (P<0.001 by ANOVA). A negative correlation (r=–0.52,P<0.05) was also found between plasma glucose concentrations and peak of gallbladder emptying. Present results demonstrate that erythromycin could be used for treating alterations of gallbladder emptying in diabetic patients with or without AN.     

Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients

Impaired gallbladder emptying is one of the various factors suggested to be involved in the pathogenesis of gallstones. The present study was undertaken to determine whether gallbladder emptying, endogenous cholecystokinin (CCK) secretion, or their interrelation is altered in patients with gallstones. After intraduodenal administration of 60 ml corn oil, plasma CCK concentration was measured by a sensitive and specific radioimmunoassay and gallbladder emptying by cholescintigraphy. Patients with gallstones (N=20) produced significantly less endogenous CCK (105±17 pmol/liter 60 min; P <0.001) than control subjects (191±11 pmol/liter 60 min, N=20); gallbladder emptying in the patients was significantly decreased at 5, 10, 40, 45, and 50 min but the reduction in gallbladder emptying did not reach statistical significance at 60 min (patients 44±8%, control subjects 60±4%). In addition, the gallbladder responsiveness to intravenous infusion of the synthetic CCK analog cerulein was investigated. Based on the results of gallbladder emptying in response to endogenous and exogenous CCK, four subgroups of gallstone patients were identified: (1) a group (N=7) with normal gallbladder sensitivity to CCK, (2) a group (N=6) with significantly increased gallbladder sensitivity to CCK, (3) a group (N=6) with impaired gallbladder emptying after corn oil due to a significantly reduced endogenous CCK secretion but with normal gallbladder sensitivity to CCK, and (4) one patient whose gallbladder was unresponsive to CCK and was found to have chronic cholecystitis at surgery.     

Erythromycin stimulates gallbladder emptying and motilin release by atropine-sensitive pathways

The effect of administering different doses of erythromycin on gallbladder emptying and plasma concentrations of immunoreactive motilin was investigated in healthy volunteers. Erythromycin was infused for 30 min at four different doses: 20, 50, 100, and 1000 mg/hr. Gallbladder volume was determined by ultrasound scanning every 10 min for 60 min. All doses, except 20 mg/hr, provoked a significant reduction in gallbladder volume (P<0.01). The gallbladder emptying peak occurred after 20 min infusion. It was approximately 40–45% of basal volume and 60–70% of the emptying observed after a standard meal. At 100 mg/hr, erythromycin caused a 2.5-fold increase in plasma motilin concentration, which reached a peak after 30 min infusion. Plasma motilin peaked following maximum gallbladder emptying in all subjects. To evaluate whether cholinergic pathways were implicated in the action of erythromycin, 100 mg/hr erythromycin was infused together with 6 g/kg/hr atropine. Atropine inhibited both gallbladder emptying and motilin release (P<0.001). Infusion of 1 g/kg/hr somatostatin had the same inhibitory effects (P<0.001). Our results suggest that atropine acts by inhibiting an erythromycin-activated cholinergic neural mechanism. Somatostatin could exert its inhibitory effect by blocking the release of acetylcholine from neural terminations.     

Gallbladder dynamics in chronic pancreatitis

Gallbladder dynamics, cholecystokinin (CCK), and pancreatic polypeptide (PP) release were studied in 14 patients with chronic pancreatitis (CP) (2 females, 12 males; age range 24–56 years) and 12 control subjects (4 females, 8 males, 21–50 years). On day 1, gallbladder contractility was investigated after ceruletide intravenous infusion (2.5 ng/kg/min for 10 min). On day 2, a mixed standard test meal (1450 kJ) was administered orally. Gallbladder volume was assessed at three time intervals before (–30, –15, 0 min) and at 5, 10, 20, 30, 40, 50, 60, 80, 100 and 120 min after stimulation by means of ultrasonography. CCK and PP plasma levels were determined at each time interval.Exocrine pancreatic function was assessed using the pancreolauryl serum test (PLT). Six patients with CP had severe exocrine pancreatic insufficiency (EPI) (PLT<1.8 g/ml) with steatorrhea, eight patients had mild-moderate EPI. Fasting gallbladder volume was increased in CP (32.3±3.1 cm³) as compared to controls (20.5±1.2 cm³) (P<0.01). Peak gallbladder contraction (percent of initial volume) in CP ranged from 5 to 55% (controls: 8–46%) following ceruletide and from 17 to 86% (controls: 27–80%) following the test meal (NS). There was no correlation between the degree of EPI according to PLT and peak gallbladder contraction. Gallbladder emptying in CP patients was not different from controls, although the postprandial CCK response was significantly impaired (P<0.01). Postprandial PP response in CP was correlated with the PLT result (r=0.78;P<0.01) but not with gallbladder emptying or refilling time. We conclude that gallbladder emptying and refilling following the oral administration of a test meal or the stimulation with a pharmacological dose of ceruletide is normal in patients with chronic pancreatitis. Postprandial gallbladder emptying is not influenced by the degree of exocrine pancreatic insufficiency.     

Nizatidine accelerates gastric emptying of a solid meal in rats

Nizatidine, a new histamine-2-receptor antagonist, stimulates gastrointestinal motility in dogs and gastric emptying of liquids in rats. Effect of nizatidine on gastric emptying of a solid meal was investigated using a novel gastric emptying model in rats. Male Wistar rats (weighing 200–300 g) were supplied with powdered food containing 30 w/w% barium 14 hr before the beginning of the experiment and x-ray photography of rat stomach was taken under light ether anesthesia. Gastric emptying was assessed by percentage of a decrease in area 30 min after drug was injected intraperitoneally. There was a positive correlation between the area of the gastric outline and the weight of the gastric contents (r=0.94,P<0.01). Ether anesthesia itself did not affect gastric emptying. Nizatidine increased gastric emptying dose-dependently (emptied percentage; vehicle: 4.9±1.5%, 1 mg/kg: 7.2±0.4%, 3 mg/kg: 10.4±2.0%, 10 mg/kg: 16.7±4.9%, 30 mg/kg: 25.7±7.4%).N-Desmethyl nizatidine (NDM) also stimulated gastric emptying, but nizatidineS-oxide, cimetidine, an famotidine had no significant effects on gastric emptying. Nizatidine and neostigmine, but not NDM, at a subthreshold dose accelerated gastric emptying treated with a low dose of acetylcholine (0.1 mg/kg). Atropine (2 mg/kg, –30 min) did not modulate the gastroprokinetic action of nizatidine, but blocked that of NDM. These findings suggest that this noninvasive method may allow measurement of gastric emptying of solids accurately and that nizatidine and NDM facilitate gastric emptying probably mediated by a direct and/or an indirect (acetylcholinesterase inhibition) cholinergic mechanism.     

Postprandial gallbladder motility and plasma cholecystokinin at regular time intervals after injection of octreotide in acromegalics on long-term treatment

The increased risk of gallstone formation in acromegalics treated with the somatostatin analog octreotide has been related to an impaired gallbladder emptying. To determine the duration of these inhibitory effects, meal-stimulated gallbladder motility, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in five acromegalics treated for 6–32 months with 200–300 g octreotide daily. Meal tests were performed 45 min, 8 hr and two weeks after the last 100-g subcutaneous dose. Results were compared with those in normal subjects. Integrated postprandial gallbladder contraction (–125±194 cm³/120 min) and integrated PP secretion (–0.1±0.2 nmol/liter/120 min) were completely suppressed in the 45-min study, but significantly improved (P<0.05) when measured 8 hr (1376±322 cm³/120 min and 3.0±1.0 nmol/liter/120 min) and two weeks (1437±263 cm³/120 min and 10.6±1.6 nmol/liter/120 min) after the last dose of octreotide. The integrated gallbladder contraction in acromegalics at 8 hr was comparable to that at two weeks and to that in normal subjects, but the integrated PP response at 8 hr was significantly smaller (P<0.05 vs two weeks and vs normals). Integrated plasma CCK secretion at 45 min (0.13±0.06 nmol/liter/120 min) was not statistically significantly different from the response at 8 hr (0.15±0.02 nmol/liter/120 min) and from that in normal subjects, but it was significantly increased at two weeks after cessation of octreotide (P<0.05 vs 45 min and 8 hr). In conclusion, during long-term octreotide treatment in acromegalics, initial abolishment of postprandial gallbladder emptying is completely reverted to normal values 8 hr after the last subcutaneous dose. No major differences in postprandial plasma CCK at 45 min and at 8 hr were observed when compared with normal subjects, whereas plasma PP responses were diminished.     

Effect of extracorporeal shock wave lithotripsy and ursodeoxycholic acid on gallbladder motility

Extracorporeal shock wave lithotripsy and dissolution agents are useful nonsurgical therapies for gallstones. Their effect on gallbladder emptying is unclear. We evaluated emptying by ultrasonography before and after lithotripsy in 50 patients on ursodeoxycholic acid or placebo and in nine controls. At baseline, patients had normal (68.8±3.2%) or delayed emptying (14.5±3.3%). In a subset of 24 patients, lithotripsy increased fasting volume (26.6±3.0 to 43.8±5.0 ml,P<0.005), postprandial volume (11.3±3.1 ml to 22.9±3.0 ml,P<0.05), and decreased ejection fraction (70.0±4.1% to 42.7±6.0%,P<0.0005). There was an inverse linear correlation between power and ejection fraction,r=–0.43,P<0.005. Ursodeoxycholic acid increased fasting (23.3±2.2 ml to 36.7±4.6 ml,P<0.005) and postprandial volume (11.1±1.8 to 17.6±2.5,P<0.005). Treatment with ursodeoxycholic acid resulted in a greater decrease in fragment size compared to placebo after lithotripsy in patients with fragment size greater than 6 mm. In conclusion, both lithotripsy and ursodeoxycholic acid have an effect on gallbladder emptying.     

Effect of nifedipine on interdigestive gallbladder volume and postprandial gallbladder emptying in man

The effect of two oral doses (10 and 20 mg) of nifedipine versus placebo on the fasted gallbladder volume and on the meal-induced gallbladder emptying was assessed according to a double-blind study protocol in 12 healthy volunteers. Eight subjects underwent three studies (with placebo and with both nifedipine doses), whereas in two subjects the effect of a 10-mg nifedipine dose, vs placebo and in two others the effect of a 20-mg nifedipine dose vs placebo was examined. The studies were performed on separate days, and the gallbladder volume was measured by means of real-time ultrasonography. Neither placebo nor 20 mg nifedipine per os elicited any significant change in the fasted gallbladder vlume. With 10 mg nifedipine per os a significant increase in the interdigestive gallbladder volume was observed: 22.9±2.9 cm³ before and 26.2±3.2 cm³ after the drug receipt (P<0.005). A trend towards an inhibition of the postprandial gallbladder emptying was observed with 10 mg nifedipineper os without, however, reaching the level of statistical significance. Following 20 mg nifedipineper os, a marked delay in the meal-stimulated gallbladder emptying occurred as reflected by a decrease in the gallbladder ejection fraction from 48.1±4.5% (placebo) to 26.4±5.0% (nifedipine) (P<0.02) at 30 min and from 54.0±3.6% (placebo) to 33.2±4.6% (nifedipine) (P<0.02) at 40 min after the test meal. We conclude that a therapeutic oral dosage of nifedipine has a significant relaxing effect on the human gallbladder.     

GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon,inhibit gastric acid secretion in humans

Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively, into eight volunteers to study pharmacokinetics and effects on pentagastrin- stimulated gastric acid secretion (plateau stimulation with pentagastrin at D ₅₀:100ng/kg/hr). The concentration of GLP-1 in plasma increased from 64±12 to 189±23 and 631±76 pmol/liter, respectively. The concentration of truncated GLP increased from approximately 7 pmol/liter to 28±3 pmol/liter during the high rate of infusion. A similar increase was seen in response to a mixed meal in eight normal volunteers. The metabolic clearance rate (MCR) of GLP-1 was 2.2±0.3 and 2.6±0.3 ml/kg/min, respectively, and the half- life in plasma was 17±2 min. The MCR of truncated GLP-1 was 13±2.8 ml/kg/min and the half- life 11.4±2.1 min. GLP-1 reduced the pentagastrin- stimulated acid secretion 16±9% during the low-rate infusion and 23±12% during the high rate (P<0.05). Truncated GLP-1 caused a 36±3% inhibition during the high infusion rate. Thus truncated GLP-1, a naturally occurring peptide, is a potent inhibitor of acid secretion in man and more so than GLP-1.This study was supported by the Danish Medical Research Council, Novo's Fond and Owesen's Fond.     

Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying

The effect of a single oral dose of loxiglumide, a cholecystokinin antagonist, on postprandial gallbladder contraction and on gastric emptying was evaluated in humans. Following a 12-hr fasting period, two tablets of loxiglumide (400 mg each) or placebo was administered on different days, in random order and in a double-blind fashion to 10 healthy volunteers 15 min before the ingestion of a 1050-kcal standard meal. Gallbladder and antral volumes were measured by real-time ultrasonography in basal conditions and at fixed time intervals after the meal. Oral loxiglumide administration was followed by a total inhibition of the gallbladder contraction for 60 min after the end of the meal ingestion. Thereafter, up to the end of the study period, gallbladder volume was larger than that of the placebo study (at 300 min after the meal 2.7±1.6 ml after placebo and 8.2±3.5 ml after loxiglumide; P<0.008). No difference between placebo and loxiglumide was found in the antral volumes at any time interval (postprandial 63.5±16.5 ml after placebo and 59.4±24 ml after loxiglumide; at 300 min after the meal 20.8±13.3 ml after placebo and 18.9±9.5 ml after loxiglumide). In conclusion, a single oral dose of loxiglumide at the dose of 800 mg can inhibit postprandial gallbladder contraction without affecting gastric emptying. It would therefore appear that in man endogenous CCK, released after a solid-liquid, caloric, nutrient-balanced meal, plays a major role in the contraction of the gallbladder but does not affect gastric emptying.     

Effect of extracorporeal shock-wave lithotripsy on gallbladder emptying in patients with solitary and multiple gallbladder stones

In a prospective study, we investigated the effect of extracorporeal shock-wave lithotripsy (ESWL) on gallbladder contractility and on fasting and residual gallbladder volume in patients with solitary and multiple gallbladder stones with stone densities<100 Hounsfield units (HU) and adequate gallbladder function. Twenty-five patients (seven males and 18 females, mean age 48.5±11.7 years) treated with ESWL were assigned to either group I, consisting of 13 patients with solitary stones<20 mm diameter, or group II, including patients with two to three stones and maximum stone diameter of 30 mm. ESWL was performed with the MPL 9000 lithotripter. Gallbladder ejection fraction was determined using the method of Dodds after a 12-hr fast and following application of a standard stimulative meal. Gallbladder volume was measured by ultrasound over 90 min at 10-min intervals before ESWL, then at 1, 30, 120, and 210 days after ESWL. At 24 hr after ESWL, residual gallbladder volume increased in group I from 7.4 ml to 13.9 ml (P=0.0567) and in group II from 6.5 ml to 20.2 ml (P=0.0076). Thereafter, residual volumes returned to pre-ESWL levels. In group II, post-ESWL fasting volumes were significantly increased over initial values at all time intervals. Correspondingly, only at 24 hr after ESWL, ejection fractions decreased from 73.1% to 64.9% in group I and from 76.5% to 62.7% in group II. No statistically significant differences in gallbladder contractility between the two groups were observed at any point of the follow-up period. ESWL exerts a no more than transient effect on gallbladder motility, regardless of stone count prior to ESWL. We postulate that changes in residual gallbladder volume and reductions in ejection fraction may be due to transitory disturbances in the gallbladder epithelium and resultant gallbladder wall edema.     

Gallbladder hypokinesia and normal gastric emptying of liquids in patients with dyspeptic symptoms

Gastric and gallbladder emptying after a standard liquid meal were studied in 65 patients with early satiety, bloating, pain at the right hypochondrium or the epigastrium, nausea, and occasionally vomiting. Fifty normal subjects were studied as a control group. Gastric and gallbladder emptying were evaluated by means of real-time ultrasonography (RUS). Serial RUS scans were made after a 12-hr fast and every 15 min after a standard meal for 2 hr. Patients were considered to have delayed gastric emptying or hypokinetic gallbladder when gastric diameters and gallbladder volume evaluated 45 min after meal were 2sd above the corresponding mean values of the normal subject group. Fifteen patients (23%) were found with delayed gastric emptying and 20 (30.7%) a reduced gallbladder emptying. None of our patients showed delayed gastric emptying and hypokinetic gallbladder simultaneously. The 20 patients with reduced gallbladder emptying were included in a double-blind randomized, placebo controlled, change-over study with cisapride (10 mg three times a day) for 30 days. Cisapride treatment reversed the gallbladder hypomotility within the normal range while placebo did not change the response to meal. Symptom score improved significantly after cisapride and placebo. It is concluded that in dyspeptic patients with reduced gallbladder response to a meal, cisapride may be of help in improving the kinetic abnormality. Dyspeptic symptoms, however, do not seem to be corrected with the described gallbladder motor abnormality.Part of this study was presented at the 1990 Meeting of the American Gastroenterological Association in San Antonio, Texas, and published in abstract form in the May 1990 issue ofGastroenterology.     

Study of the effect of neurotensin on meal- and cerulein-induced gallbladder contraction.

We studied the effect of a low dose of neurotensin (2.5 pmol/kg/min) on meal- and cerulein-induced gallbladder contraction in 11 healthy volunteers by means of real-time ultrasonography. Ingestion of a meal caused a significant reduction in gallbladder volume which reached a maximum of 57 +/- 2% of the basal value at 60 min after the meal. The infusion of neurotensin caused a slight but not significant attenuation of the contractile response of the gallbladder to the meal (maximal reduction of 49 +/- 6%). Increasing doses of cerulein (10, 20 and 40 ng/kg/h, for 30 min at each dose) caused progressive reductions in gallbladder volume of 18 +/- 5, 72 +/- 5 and 89 +/- 4% with the three respective doses of cerulein used. The simultaneous administration of neurotensin did not significantly modify the gallbladder response to cerulein. The results indicate that neurotensin, at a dose of 2.5 pmol/kg/min, does not influence the gallbladder contraction stimulated by food or cerulein.     

Gall Bladder Emptying in Patients with Corrosive-Induced Esophageal Strictures

Ingestion of corrosive substances can lead to strictures of the esophagus and stomach. Cicatrization of the lower part of the esophagus can entrap vagal fibers in the process of fibrosis. The aim of the present study was to evaluate gallbladder dysfunction as a sequel to vagal damage in patients with corrosive-induced esophageal strictures. The cephalic phase of gallbladder emptying was stimulated by modified sham feeding according to the chew-and-spit method. Gallbladder volume was measured by ultrasonography using the ellipsoid method after an overnight fast and every 15 min for a period of 90 min after sham feeding in 22 patients and 10 controls. Mean fasting gallbladder volume was significantly greater in patients than in controls (22.09± 9.78 vs. 14.61± 4.42 ml; P = 0.025). After sham feeding the gallbladder ejection fraction was significantly lower in patients than in controls (32.86± 17.21 vs. 49.40± 7.86%; P = 0.007). Patients with cicatrization in the distal one-third of the esophagus had a greater basal gallbladder volume (24.57± 9.2 ml) and significantly lower ejection fraction (20.47± 8.9%) than patients with strictures at other sites (gallbladder volume, 18.50± 10.69 ml; ejection fraction, 47.48± 13.3%; P = 0.001). In conclusion, patients with corrosive-induced esophageal strictures, especially those in the distal one-third, had an increased fasting gallbladder volume and decreased cephalic phase of gallbladder emptying, pointing to impaired vagal cholinergic transmission, possibly due to vagal entrapment in the cicatrization process.     

Clinical applicability of shortenedd-Xylose breath test for diagnosis of intestinal malabsorption

Urinary and/or plasmaticd-xylose tests are broadly used in clinical practice for the diagnosis of intestinal malabsorption. A 5-hr hydrogen breath test (H₂ BT) has also proven useful. Our goal was to determine whether a shorter, hence more efficient, 3-hr test would perform as well as the 5-hr test. We studied 33 patients with proven malabsorption, 44 patients with irritable bowel syndrome (IBS), and 27 healthy subjects. Each individual ingested 25 g ofd-xylose, and alveolar breath samples were obtained thereafter at 30 min intervals for 5 hr. Breath samples were analyzed for H₂ by gas chromatography. Individual peak delta changes and area under the curve (AUC) were calculated. Simultaneously, the 5-hr cumulative urinary excretion ofd-xylose was measured by colorimetry. Results of 5-hr tests were compared with those of the first 3 hrs. In the malabsorption group, the 5-hr test showed a markedly enhanced production of H₂ relative to healthy controls (delta: 60.7±6.4 vs 7.7±1.5 and AUC: 8465.0±985.4 vs 393.2±232.6,P<0.001 for both) and a reduced urinary excretion ofd-xylose (2.8±0.3 g/5 hr vs 6.3±0.2,P<0.001). Results in IBS patients did not differ from those in healthy controls. Three-hour analysis also reflected an enhanced production of H₂ in the malabsorption group (delta: 45.4±6.4 and AUC: 3700.0±545.6,P<0.001 vs healthy controls). Correlation between 3-hr and 5-hr tests was significant in healthy controls (r=0.9), IBS (r=0.9), and malabsorption (r=0.8). The sensitivity of the 3-hr test was lower than of the 5-hr test (0.72 vs 0.91). The loss of sensitivity of the 3-hr test was attributed to a delayed appearance of the delta peak in the malabsorption group. In conclusion, the H₂ breath test withd-xylose is a useful test for the diagnosis of the intestinal malabsorption, but requires a 5-hr monitoring period to be reliable.     

5-Hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin

In the present study we evaluated the effect of ondansetron (formerly indicated as GR38032F), a potent and selective type-3 5-hydroxytryptamine receptor antagonist, on erythromycin-induced gallbladder emptying and motilin release, as well as gallbladder emptying induced by a regular meal in healthy volunteers. Gallbladder emptying was evaluated by sonography. Ondansetron, at the dose of 0.05 mg/kg, significantly reduced (P<0.001 by ANOVA) the gallbladder emptying induced by 2 mg/kg/hr erythromycin, but did not increase basal gallbladder volume or inhibit gallbladder emptying induced by a regular meal. Ondansetron also inhibited the motilin release induced by erythromycin (P<0.001, by ANOVA). These results suggest that serotoninergic mechanisms modulate the effects of erythromycin on the gastrointestinal tract. The exact site of action of ondansetron remains to be identified.     

Effect of aspirin on gallbladder motility in patients with gallstone disease

Patients with gallstone disease have impaired gallbladder motility. Prostaglandins are thought to be important mediators of gallbladder hypomotility. We assessed the effect of aspirin, a prostaglandin inhibitor on gallbladder resting volume and ejection fraction according to a double-blind study protocol in 20 healthy volunteers and 30 patients with gallstone disease. Healthy volunteers had a higher ejection fraction compared to patients with gallstone disease (73.9±0.9% vs 60.4±1.0%,P<0.05). Aspirin in a dose of 350 mg/day for two weeks did not alter gallbladder motility in the healthy volunteers. Thirty patients with gallstone disease were randomized into three treatment groups: group I (placebo), group II (aspirin 350 mg/day), and group III (aspirin 1400 mg/day). After two weeks of treatment, gallbladder ejection fraction was improved in group II (74.0±1.7% vs 62.0±1.7%,P<0.01) and group III (69.8±3.8% vs 61.2±1.3%,P<0.01) but not in group I (60.4±2.6% vs 59.0±1.9%,P=NS). The higher dose of aspirin did not induce a greater increase in gallbladder emptying. It is concluded that impaired gallbladder motility in patients with gallstone disease is corrected by short-term oral aspirin even in low dosage. This may be clinically useful in secondary prophylaxis after nonsurgical therapy for gallstone disease.     

Effects of Glucose or Insulin Infusions on Growth Hormone Secretion in Male Red Deer

The growth hormone (GH) secretory pattern in male red deer is associated with the seasonal growth cycle. During this cycle metabolic state changes from weight gain in spring to weight loss in winter. However, short-term metabolic changes due to feeding could also alter the GH pattern. To investigate the effect of such changes on GH secretion, the acute feedback of blood glucose level on the GH secretory pattern was examined. Six yearling male red deer were infused iv with glucose (G; 150 mg/kg/hr) or insulin (I; 30 mU/kg/hr) for a 12-hr period, 1 week apart. GH was measured in jugular venous blood every 10 min, for 12 hr before, during, and 6 hr after the infusions. Glucose, insulin, IGF-1, and haematocrit were also measured. There was no difference (P > 0.05) in glucose levels between G and I prior to infusions (5.8 vs 6.0 mmol/liter, SED = 0.42). Glucose levels rose to 8.7 mmol/liter during G and fell to 3.4 mmol/liter (SED = 0.72,P <0.001) during I, then returned towards normal postinfusion. Insulin levels increased during G and I (P < 0.01) with no difference (P > 0.05) between G and I during preinfusion (163 ± 7.6 pmol/liter) or infusion (259 vs 264 ± 16.5 pmol/liter) periods. There were no differences (P > 0.05) in GH secretory characteristics, mean IGF-1, or haematocrit between G and I. However, there were significant effects of infusion within the treatments. Mean GH declined (P < 0.05) from 1.8 ng/ml (both treatments) preinfusion to 1.13 and 1.31 ng/ml during G and I infusion, respectively. GH pulse amplitude was lower during I infusion (5.6 ng/ml vs 8.2 ng/ml preinfusion,P < 0.05, SED = 1.0) and the change in amplitude from preinfusion to infusion differed (P > 0.05) with an increase in G and a decrease in I (+0.6 and −2.6, SED = 1.1). IGF-1 levels were stable and averaged 555 and 520 ng/ml (SED = 34.9) for G and I, respectively. Haematocrit declined from 34.3 ± 1.85% over the first 4 hr of sampling to 25.7 ± 0.97% for the remainder of the sampling period. The finding that there were no major alterations in GH secretory patterns during 12 hr of hypoglycemia and hyperglycemia suggests that GH secretion in the male red deer is relatively insensitive to short-term changes in metabolic state.     

Effect of nitric oxide on gallbladder motility in patients with acalculous biliary pain: a cholescintigraphic study

The aim of the present study was to evaluate the influence of the exogenous nitric oxide donor glyceryl trinitrate on cerulein-induced gallbladder contraction in patients with acalculous biliary pain. Quantitative hepatobiliary scintigraphy was performed on 33 patients. From the 60th min cerulein (1 ng/kg body wt/min for 10 min intravenous) then from the 90th min the same dose of cerulein plus glyceryl trinitrate (0.5 mg sublingually) (21 patients) or placebo (12 patients) were administered and the gallbladder ejection fraction was measured repeatedly. After the first dose of caerulein, the gallbladder ejection fraction was less than 35% in 23 of 33 patients (nonresponders), while it was more than 35% in the remaining 10 patients (responders). After the second dose of cerulein in 16 nonresponder patients glyceryl trinitrate administration significantly increased the previously impaired gallbladder ejection fraction while in 7 nonresponder patients placebo administration had no effect. In conclusion, normalization of the gallbladder ejection fraction in the majority of patients following glyceryl trinitrate administration suggests that impairment of gallbladder emptying is caused by a functional motility disorder rather than any organic disease.