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Prolonged postprandial abdominal pain following Kawasaki syndrome with acute gallbladder hydrops: association with impaired gallbladder emptying.

Acute hydrops of the gallbladder is a well-recognized complication of Kawasaki syndrome. We report a case of a child with this syndrome whose gallbladder hydrops slowly resolved after intravenous gamma-globulin therapy. However, he continued to experience postprandial right upper quadrant abdominal pain. Hepatobiliary scintigraphy revealed normal filling of the gallbladder but marked impairment of meal-stimulated gallbladder emptying. Endoscopy with biopsy of the esophagus, stomach, and duodenum was normal, ruling out peptic complications of his aspirin therapy. This child's discomfort improved slowly over several months, finally ending approximately 6 months after the onset of his illness. A repeat gallbladder emptying study done ultrasonographically at that time revealed near-normal meal-stimulated gallbladder emptying. We conclude that poor emptying of the gallbladder may be associated with prolonged abdominal pain in Kawasaki syndrome. Meal-stimulated gallbladder emptying can be assessed by a simple ultrasonographic technique and should be considered in any patient with Kawasaki syndrome and abdominal pain.

Abdominal Pain

Effect of two new cholecystokinin antagonists on gallbladder emptying in opossums.

In this investigation we evaluated the effect of two new cholecystokinin (CCK) antagonists, CR 1409 and L364,718, on gallbladder emptying in the opossum. Gallbladder emptying was elicited by both exogenous and endogenous CCK. The three test challenges were 1) intravenous infusion of CCK octapeptide (OP) (10 ng.kg-1.min-1), 2) feeding, and 3) intraduodenal infusion of Isocal (0.4 ml/min), a fat-containing nutrient. During control conditions each test challenge elicited approximately 60% gallbladder emptying within 30 min and 70% emptying by 60 min. At given doses both CR 1409 and L364,718 substantially antagonized or abolished the gallbladder emptying elicited by each of the test challenges. The antagonism for postprandial gallbladder emptying was diminished between 30 and 50 min compared with that for CCK-OP infusion and intraduodenal infusion of Isocal. Unexpectedly, the gallbladder emptying induced by infusion of motilin (5 micrograms.kg-1.h-1) was antagonized by either CR 1409 or L364,718. In anesthetized animals, gallbladder contraction was induced by a variety of agonists, such as bethanechol, histamine phosphate, 5-hydroxytryptamine, and phenylephrine. In this later model CR 1409 and L364,718 functioned solely as selective antagonists. We conclude that for the opossum gallbladder 1) the CCK antagonists CR 1409 and L364,718 antagonize or abolish gallbladder emptying induced by exogenous or endogenous CCK; 2) the pattern of CCK antagonism after feeding suggests that the early phase of postprandial gallbladder emptying is mediated by a mechanism other than endogenous CCK, whereas late postprandial emptying is mediated by release of endogenous CCK; and 3) CR 1409 and L364,718 are not totally specific antagonists for gallbladder CCK receptors alone but also antagonize gallbladder contraction induced by motilin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

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 micrograms/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 without AN, but did not stimulate motilin release in neuropathic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Indomethacin and postprandial gallbladder emptying.

Patients with gallstone disease commonly have impaired gallbladder emptying. To see whether non-steroidal anti-inflammatory drugs (NSAIDs) prevent gallstone formation by improving gallbladder emptying, we assessed the effect of indomethacin on postprandial emptying in healthy subjects and in patients with gallstone disease. Subjects received indomethacin 25 mg three times a day for a week and matching placebo for another week. Compared with placebo, indomethacin improved postprandial gallbladder emptying in all 7 patients with gallstone disease. This finding was not recorded in healthy subjects with normal gallbladders. The prevention of gallstone formation associated with ingestion of NSAIDs may be due mainly to a prokinetic effect on the gallbladder since there is no evidence to suggest that these drugs affect cholesterol crystal nucleation at ordinary therapeutic doses in man or animals.

Adult

Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying.

In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.

Adult

Duodenal osmolality drives gallbladder emptying in humans.

The effect of duodenal osmoreceptor stimulation on gallbladder motility was evaluated in 18 normal subjects during intraduodenal infusion of 280, 560 and 840 mosm/liters NaCl solutions. Gallbladder emptying was found to be dose-dependent between 560 and 840 mosm/liter (P less than 0.01 vs basal volume). The effect of duodenal infusion of hypertonic saline on gallbladder emptying was prevented by atropine and partially antagonized by naloxone, indicating that cholinergic and endorphinergic pathways may be involved in regulating this reflex. Since proglumide, a cholecystokinin (CCK) antagonist, did not affect gallbladder emptying induced by hypertonic saline, it seems likely that CCK is not released by increasing duodenal osmolality. A significant reduction in gallbladder volume was obtained when hyperosmolar saline was delivered into the duodenum, whereas no emptying was seen when infused into the gastric antrum or the jejunum, suggesting that osmoreceptors that activate gallbladder emptying are located only in the duodenum. Additionally, all subjects manifested central symptoms (nausea or vomiting) during duodenal infusion of hypertonic saline, suggesting that central mechanisms might be activated by a change in duodenal osmolality. Our data indicate that the osmolality of duodenal contents might regulate gallbladder motility by neural atropine- and naloxone-sensitive pathways.

Adult

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 micrograms/kg/hr atropine. Atropine inhibited both gallbladder emptying and motilin release (P < 0.001). Infusion of 1 microgram/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.

Adult

Postprandial gallbladder emptying is related to intestinal motility at the time of meal ingestion.

The characteristics of meal-induced gallbladder emptying in healthy individuals are subject to wide variation. We hypothesized that some of the observed variation might relate to ingestion of the meal during different phases of the migrating motor complex (MMC). Recording of gastrointestinal pressure was combined with scintigraphic recording of bile kinetics during infusion of 99mTc-HIDA. The material consisted of 12 healthy men. Group 1 (n = 6) had a fat-rich meal in phase I, and group 2 (n = 6) had the meal in a phase II. With the end of the meal ingestion as zero, the following results emerged. The subjects in group 1 had a median (range) lag period before beginning of gallbladder emptying of 13.5 (9.0-22.5) min. In group 2 gallbladder emptying began during the meal ingestion in four subjects, and the median lag period was 0 min (minimum, -9.0; maximum, 13.5 (p = 0.02)). The median percentage change of gallbladder counts during the observation period of 54 min in group 1 was 11.5% (from 19% filling to 25% emptying). The corresponding figures in group 2 were 41% (from 2% to 91% emptying (p less than 0.05)). This difference was due to the difference in duration of lag periods, as the emptying rates measured from the end of the lag periods were equal. In conclusion, the onset of postprandial gallbladder emptying relates to the phase activity of the MMC at the time of ingestion.

Adult

Adrenergic influences on the gallbladder emptying.

Dihydroergotamine (dhe) (or phentolamine), an alpha-adrenergic blocking agent, induced important changes on the CCK-stimulated gallbladder emptying of 70 volunteer subjects. Two cholecystograms were performed with 10-day intervals in each subject. The first cholecystogram showed gallbladder emptying provoked by a test meal (35 subjects or by 0.5 U. CCK Kg. injected intravenously (35 subjects). During the second cholecystogram 1 mg. of DHE was injected intramuscularly 45 minutes befor the cholecystokinetic stimulus. The drug counteracted the gallbladder emptying induced by both endogenous and exogenous CCK. The effect was more pronounced when DHE was administered prior to the test meal stimulus than before CCK administration. This difference could be explained by a delayed gastric emptying induced by the alpha-adrenergic blockade. Our results suggest that the lack of gallbladder emptying could be due to the relaxation of this organ, in addition to a duodenal spasticity induced by DHE (or phentolamine).

Adolescent

Gallbladder emptying in patients with primary achalasia.

Being more evident that primary achalasia is not confined to the esophagus and that it may involve other organs in the digestive tract, gallbladder emptying was ultrasonographically evaluated in 10 patients affected with primary achalasia and in 10 controls. An intravenous cerulein infusion was used to induce gallbladder contraction. Eight out of 10 achalasic patients had a lower gallbladder emptying, and 6 out of 10 had a markedly delayed gallbladder emptying compared with the controls. Achalasic patients, taken as a whole, showed a significantly lower and delayed mean gallbladder emptying when compared with the controls. Such a finding confirms the possible extra-esophageal extension of primary achalasia. In this study, the hypothesis of impaired cholinergic gallbladder innervation in primary achalasia is discussed.

Ceruletide

Relationship between interdigestive gallbladder emptying, plasma motilin and migrating motor complex in man.

The aim of this study was to elucidate the importance of biliary output for the regulation of migrating motor complex and the release of plasma motilin. Gallbladder emptying was monitored by hepatobiliary scintigraphy, plasma motilin concentration by radioimmunoassay and gastrointestinal motility by a perfused catheter system. During a total recording time of 46 h and 20 min in 16 volunteers, we observed 29 episodes of gallbladder emptying, 27 plasma motilin peaks and 23 activity fronts (phase 3 activity) of the migrating motor complex (MMC). Twelve episodes of gallbladder emptying started in phase 1 and continued into phase 2 of the MMC. The remaining 17 episodes of gallbladder emptying started in phase 2, and three of these continued into phase 3 of the MMC. Biliary output was associated with a significant rise in plasma motilin concentration, whereas plasma motilin significantly decreased after the activity fronts. These observations may explain the well-known fluctuations of plasma motilin concentration in the fasted state. Motilin is released into the circulation as a result of biliary output, while the ensuing activity front of the MMC removes this stimulant from the proximal small bowel, resulting in a fall in plasma motilin. In conclusion, we have confirmed a temporal relationship between biliary output into the duodenum and the release of plasma motilin. The observed transition from phase 1 to phase 2 and from phase 2 to phase 3 of the MMC during gallbladder emptying episodes suggests that biliary output stimulates gastrointestinal motility in the fasted state.

Adolescent

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison.

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.

Adult

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 volume. 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 less than 0.005). A trend towards an inhibition of the postprandial gallbladder emptying was observed with 10 mg nifedipine per os without, however, reaching the level of statistical significance. Following 20 mg nifedipine per 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 less than 0.02) at 30 min and from 54.0 +/- 3.6% (placebo) to 33.2 +/- 4.6% (nifedipine) (P less than 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.

Adult

[Effects of bicarbonated-alkaline water (Uliveto) on gastric and gallbladder emptying in normal subjects. Ultrasonic evaluation].

In 10 healthy patients gastric and gallbladder emptying after a standard meal (800 cal, 60% glucides, 20% protides, 20 lipids) associated with 400 ml alkaline bicarbonated water or tap water were evaluated by ultrasonography. An increase of gastric emptying was noted after alkaline bicarbonated water versus tap water with significant differences at 30' (p less than 0.05), 60' (p less than 0.01) and 120' (p less than 0.05). No significant differences exist in final gastric emptying time. Alkaline bicarbonated water induced less intensive gallbladder emptying with statistical difference versus tap water at 60' and 120' from the standard meal (p less than 0.01).

Adult

Effect of a synthetic prostaglandin E1 derivative, misoprostol, on fasted gallbladder volume and on meal-induced gallbladder emptying in man.

The effect of a single oral dose of 400 micrograms of misoprostol versus placebo on the fasted gallbladder volume and on meal-induced gallbladder emptying was assessed in 10 healthy subjects according to a double-blind study protocol. Gallbladder volumes were measured by means of real-time ultrasonography. The fasted gallbladder volume before drug administration was 18.9 +/- 1.1 cm3 on the placebo day, and 18.8 +/- 1.4 cm3 on the misoprostol day. No significant change in the gallbladder volume was observed 30 minutes after drug administration (18.3 +/- 1.3 cm3 placebo vs 20.2 +/- 1.8 cm3 misoprostol). The gallbladder volume 10 min after the test meal was significantly larger after misoprostol (16.9 +/- 1.7 cm3) than after placebo (12.8 +/- 1.6 cm3), p less than 0.02. However, the differences at subsequent time points (i.e. 20, 30, and 40 min after the test meal) proved to be insignificant. An insignificant effect of misoprostol on gallbladder emptying was revealed also by the analysis of the respective gallbladder ejection fractions. We conclude that misoprostol does not have any significant effect on fasted gallbladder volume or on meal-induced gallbladder emptying in humans.

Adult

Gallbladder emptying stimuli in obese and normal-weight subjects.

Gallbladder stasis may be an important factor in the pathogenesis of cholesterol-gallstone formation in some individuals. We investigated gallbladder function in a group of nondieting, gallstone-free, healthy subjects with normal (22 +/- 1 kg/m2) and high (36 +/- 1 kg/m2) body mass indexes. Fasting gallbladder volume (28.2 +/- 4.4 ml) and residual volume after maximal emptying (8.4 +/- 2.3 ml) in high-body-mass index subjects were not significantly different from those of normal-body-mass index subjects (20.5 +/- 2.5 ml and 4.2 +/- 1.3 ml, respectively). The percentage of gallbladder emptying (71% +/- 5%) and the rate of gallbladder emptying (-1.9 +/- 0.3 x 10(-2) min-1) in high-body-mass index subjects in response to a maximal emptying stimulus was similar to the percentage of emptying (78% +/- 6%) and rate of emptying (-2.3 +/- 0.6 x 10(-2) min-1) in normal-body-mass index subjects. A liquid meal containing less than 1 gm fat, 14 gm protein and 6 gm carbohydrate resulted in both a decreased rate of gallbladder emptying and an increased residual gallbladder emptying and an increased residual gallbladder volume in both groups. The addition of 10 or 20 gm (but not 4 gm) of fat to the liquid meal restored gallbladder emptying to the maximal-stimulus level. These results demonstrate that gallbladder emptying in response to a single liquid meal stimulus is not altered in obesity and that dose-response relationships to fat are similar in obese and normal-weight individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Gallbladder emptying following cholecystokinin and fatty meal in normal subjects.

A quantitative study of gallbladder emptying using 99mTc-HIDA as a bile tracer was performed with either CCK or a fatty meal as gallbladder stimulant. Its aims were to establish; (1) the reproducibility of CCK- and fatty-meal-induced gallbladder contraction, and (2) temporal patterns of gallbladder emptying following a physiological meal. Nineteen healthy, fasted volunteers were selected for 3-minute CCK administration (IV Boots Pancreozymin 2CHR units/kg) or a 40 g fatty meal. Each underwent repeat scans not less than 14 days after the first. Quantitative activity/time curves were drawn with computer analysis establishing gallbladder ejection fractions (GBEF) for each stimulus. Our results demonstrated: (1) poor reproducibility of CCK-induced gallbladder contraction precluding its diagnostic use, (2) improved but still variable meal-induced gallbladder contraction, and (3) evidence for a neurocephalic emptying response with a fatty meal stimulus.

Adult

Postprandial gallbladder emptying in patients after pancreatoduodenectomy. A preliminary report.

The study was undertaken to establish the pattern of gallbladder emptying in patients after pancreato-duodenectomy with the gallbladder preserved. 14 patients were examined. The preliminary examination revealed pathologic changes of the gallbladder in 5 patients, they were excluded from further investigations. The mean initial gallbladder volume, and the mean gallbladder maximum ejection fraction in patients after pancreatoduodenectomy were significantly lower as compared with controls. The pattern of gallbladder emptying was markedly flattened in the majority of patients, accompanied by alternate emptying and refilling of the gallbladder. On the basis of the above-mentioned observations we confirm the necessity to remove the gallbladder during pancreatoduodenectomy.

Adult