Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones.

The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P less than 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P less than 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P less than 0.05) and residual volume was 17.7 vs. 6.5 mL (P less than 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P less than 0.05) and residual volume was 17.2 vs. 5.0 mL (P less than 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P less than 0.001; residual volume, 3.7 mL, P less than 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects.     

Ultrasonographic assessment of gall bladder kinetics in the elderly.

BACKGROUND: The incidence of gallstones increases with age but the factors that influence gallstone formation in the elderly are poorly understood. Proposed factors include changes in bile composition and hypomotility of the gall bladder. Studies on gall bladder motility in the elderly have provided conflicting results, and none has been reported from India. AIM: To determine gall bladder contractility in healthy elderly subjects and compare it with that in young healthy volunteers. METHODS: Thirty healthy elderly (above the age of 60 years) and 30 young volunteers with no abdominal complaints were studied. Using real-time ultrasonography and the ellipsoid method, gall bladder volume was measured after overnight fast and at 10, 20, 30, 40, 50 and 60 minutes after a standard fatty meal. Residual volume, delta volume and ejection fraction were calculated. RESULTS: Mean fasting gall bladder volume in elderly subjects was higher than that in young subjects (13.5 [5.8] mL vs 10.9 [3.6] mL; p < 0.05). However, there was no difference in the 60-min postprandial residual gall bladder volumes in the two groups. Change in gall bladder volume and ejection fraction were also similar in the two groups. CONCLUSION: There was no difference in gall bladder emptying between elderly and young subjects though the fasting gall bladder volume was higher in the elderly.     

Gallbladder Contractility in Liver Cirrhosis: Comparative Study in Patients with and Without Gallbladder Stones

An increased prevalence of gallstones was demonstrated in patients with liver cirhosis, higher in the advanced stages of the disease. Some studies have found impaired emptying of the gallbladder in cirrhotic patients. Our aim here was to investigate gallbladder emptying in cirrhotic patients with and without gallstones to find out whether emptying is further impaired in the presence of gallstones. The study group comprised 24 patients with liver cirrhosis and gallstones, 8 in each Child class. The controls were represented by 18 cirrhotic patients without gallstones, 6 in each Child class. Fasting gallbladder volume was calculated by ultrasound using the ellipsoid formula. Gallbladder emptying was evaluated for 90 min after ingestion of a solid-liquid meal (14 g fat, 425 kcal), by assessing minimal residual volume, gallbladder ejection fraction, and area under emptying curve at 15-min intervals. Statistical analysis was performed using the two-tailed Students' t test and Pearson's correlation coefficient. In controls, gallbladder fasting and residual volumes increased with the severity of cirrhosis, but gallbladder emptying did not change significantly. In cirrhotics with gallstones, gallbladder emptying decreased in Child C compared with Child A class patients and, also, compared to Child C controls. The number or size of gallstones, as well as the thickness of the gallbladder wall, did not correlate with gallbladder emptying parameters. Gallbladder contractility is impaired in patients with liver cirrhosis and gallstones. Hypomotility is proportional to the severity of liver disease. Gallbladder hypomotility might contribute to the increased gallstone formation in patients with advanced cirrhosis.     

Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution

Gallbladder motility was evaluated by ultrasonography in 75 cholesterol gallstone patients and in 77 matched control subjects. All 75 gallstone patients were candidates for oral bile acid therapy (radiolucent gallstones, less than 2 cm in diameter, in well-opacified gallbladder), and 38 of them were also studied during ursodeoxycholic acid administration. An additional 20 gallstone patients were studied 1 year after confirmed gallstone dissolution with oral bile acids. Gallstone patients showed significantly greater fasting and residual volumes, a decreased percent of gallbladder emptying, but a similar absolute emptying and emptying rate compared with the control subjects. Greater fasting volumes and reduced percents of gallbladder emptying were also found in gallstone-free patients who achieved complete dissolution with oral bile acids. After ursodeoxycholic acid administration, fasting gallbladder volumes were greater, and percents of gallbladder emptying were further decreased than in untreated gallstone patients. In conclusion, greater fasting volumes, and not reduced gallbladder contractility, account for the defective gallbladder function in radiolucent (cholesterol-rich) gallstone patients. This condition is likely to precede, and possibly to promote, gallstone formation because it persists after gallstone dissolution. Ursodeoxycholic acid administration worsens the defect observed in gallstone patients. This finding also suggests, although indirectly, that the expected normalization of cholesterol saturation during oral bile acid administration is not paralleled by an improvement in gallbladder function.     

Determinants of Gallbladder Kinetics in Obesity

Obese subjects are at risk of developing gallstones both by being overweight and by reducing their body weight. The aim of the present study was to investigate factors related to disturbances in gallbladder emptying measured by ultrasound. Detailed information about weight loss attempts, age at onset of obesity, parity, presence of menopause, use of contraceptive or hormonal replacement drugs, and phase of menstrual cycle was obtained. Smoking habits, alcohol use, dietary intake, and physical activity were recorded. Body composition and fat distribution were assessed by anthropometry. Blood samples were taken for CCK, lipids, glucose, and insulin. Mean (SD) fasting gallbladder volume was 30.0 (12.6) ml. The residual volume was 12.5 (9.8) ml 90 min after a test meal. CCK levels increased from a basal 1.64 (0.8) pM to a peak value of 2.9 (1.0) pM. Fasting gallbladder volumes were closely related to residual and ejection volumes. Body weight and fasting insulin levels explained 35.2% of the variance in fasting volume, lean body mass and insulin explained 28.1% of the residual volume, and waist circumference 23.6% of the ejection volume. None of the other factors were related to gallbladder emptying. Subjects with the largest fasting gallbladders had the largest residual and least emptying gallbladders, scored the highest in every aspect of body size, composition, and fat distribution, and also had the highest insulin levels. Body weight, lean body mass, central fat distribution, and insulin levels were the main determinants of gallbladder kinetics. Fasting and residual gallbladder volumes were closely related and both determined by obesity and its metabolic complication of hyperinsulinemia.     

Gallbladder emptying in patients with primary sclerosing cholangitis

AIM： To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis （PSC）. METHODS： Twenty patients with PSC and ten healthy subjects were investigated. Gallbladder fasting volume, ejection fraction and residual volume after ingestion of a test meal were compared in patients with PSC and healthy controls using magnetic resonance imaging. Symptoms, thickness and contrast enhancement of the gallbladder wall and the presence of cystic duct strictures were also assessed. RESULTS： Median fasting gallbladder volume in patients with PSC [67 （19-348） mL] was twice that in healthy controls [32 （16-55） mL] （P 〈 0.05）. The median postprandial gallbladder volume in patients with PSC was significantly larger than that in healthy controls （P 〈 0.05）. There was no difference in ejection fraction, gallbladder emptying volume or mean thickness of the gallbladder wall between PSC patients and controls. Contrast enhancement of the gallbladder wall in PSC patients was higher than that in controls; （69% ± 32%） and （42% ± 21%） （P 〈 0.05）. No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls.CONCLUSION： Patients with PSC have increased fasting gallbladder volume. Gallbladder Mucosal dysfunction secondary to chronic cholecystitis, may be a possible mechanism for increased gallbladder.     

Alterations in Gallbladder Emptying and Bile Retention in the Absence of Changes in Bile Lithogenicity in Postmenopausal Women on Hormone Replacement Therapy

The role of female sex hormones in the pathogenesis of gallstones is well established. Pregnancy, contraceptive use, estrogen replacement therapy in postmenopausal women, and estrogen therapy in men for the treatment of prostatic carcinoma have been found to be associated with increased risk of cholesterol gallstones. Alterations in gallbladder emptying and in bile lithogenicity in postmenopausal women receiving hormone replacement therapy (HRT) have not been studied to date. The present study was undertaken to study the effect of HRT on gallbladder emptying and bile lithogenicity. Sixteen postmenopausal women were included in the study. None of the patients had gallstone disease and none had received prokinetic drugs, such as, erythromycin, metoclopramide, domperidone or cisapride, aspirin, and nonsteroidal antiinflammatory drugs. Gallbladder emptying (n = 16), bile microscopy (n = 7), cholesterol saturation index (CSI) (n = 7), and nucleation time (n = 7) were studied before and 3 months after HRT (conjugated estrogen, 0.625 mg, + medroxyprogesterone acetate, 2.5 mg, everyday). Fasting and residual volumes increased (fasting volume, 18.2 +/- 2.2 mL pre-HRT vs 27.6 +/- 3.2 mL post-HRT, P = 0.0003; residual volume, 3.9 +/- 0.6 mL pre-HRT vs 10.3 +/- 2.0 mL post-HRT, P = 0.00009) and ejection fraction decreased (78.2 +/- 2.5% pre-HRT vs 62.2 +/- 3.8% post-HRT; P = 0.0017) after 3 months of HRT. There was no change in CSI (2.32 +/- 0.36 pre-HRT vs 2.60 +/- 0.51 post-HRT; P = NS) or in nucleation time (19.0 +/- 1.2 days pre-HRT vs 17.6 +/- 1.3 days post-HRT; P = NS). None of the bile samples either pre-HRT or post-HRT showed cholesterol monohydrate crystals. Though impairment of gallbladder emptying occurs in the short term with HRT in postmenopausal women, there is no change in CSI and nucleation time.     

Gallbladder motility and lithogenicity of bile in patients with choledocholithiasis after endoscopic sphincterotomy

Background/Aims: Ablation of the sphincter of Oddi has been shown to inhibit gallstone formation in the prairie dog model, probably by allevaiting gallbladder bile stasis. The effect of endoscopic sphincterotomy (ES) on gallbladder emptying and lithogenicity of bile has not been studied adequately in humans. We, therefore, studied the changes in gallbladder emptying and lithogenicity of bile following ES in patients with choledocholithiasis and gallbladder in situ.Methods: Thirteen patients with choledocholithiasis with intact gallbladder underwent ES and common bile duct clearance. Eight patients had concomitant gallstones. Gallbladder emptying was studied by real time ultrasonography after stimulation by ceruletid infusion. Fasting gallbladder bile was collected during endoscopic retrograde cholangiography by placing a 7F or 8F catheter in the common bile duct and after ceruletid stimulation of gallbladder for bile microscopy and cholesterol nucleation time determination. Gallbladder emptying, nucleation time and bile microscopy were performed before ES and again between 4 and 8 weeks after ES after cholangiographic confirmation of clearance of common bile duct stones.Results: Fasting and residual gallbladder volumes decreased and ejection fraction increased significantly following ES, suggesting decreased stasis and improved emptying of gallbladder. Nucleation time was prolonged and cholesterol crystal index in bile decreased after ES, suggesting decreased lithogenicity. The decrease in gallbladder volumes and increase in ejection fraction after ES were observed in both groups of patients, with or without concomitant gallstones.Conclusions: ES decreases the stasis of gallbladder bile, improves gallbladder emptying and decreases the lithogenicity of bile in patients with gallstone disease as reflected by prolongation in nucleation time. ES may find a role as an adjunct to oral bile acid therapy and extracorporeal shock wave lithotripsy in addition to a prophylactic role of preventing gallstone formation in high risk groups.     

Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones

Hormonal control of gallbladder motility is still unclear in patients with cholelithiasis. In a case-control study, we determined the characteristics of gallbladder emptying evaluated sonographically and the hormone levels of somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal in 10 gallstone patients compared with 20 healthy subjects. Patients with lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects. During fasting, plasma pancreatic polypeptide concentrations were significantly higher in lithiasis patients (P < 0.03). In contrast, no differences between the two groups of patients were observed during the post prandial period. Somatostatin and gastrin plasma levels were similar in the two groups. Lastly, the serum bile salt levels were in the normal range and were not different between groups both during fasting and postprandial states. We conclude that large basal plasma concentrations of pancreatic polypeptide, a gut peptide inducing gallbladder relaxation, may constitute a factor facilitating lithogenesis.     

Gallstone disease in an elderly population: the Silea study

BACKGROUND: Little is known on gallbladder emptying and gallstone composition in the elderly. AIMS AND SUBJECTS: Cross-sectional survey on the prevalence of gallstone disease and associated factors, gallstone characteristics and gallbladder emptying in a population aged > or = 60 years. METHODS: Gallstone number and size as well as gallbladder motor function were assessed by ultrasound. Gallstone composition and pattern were evaluated by conventional radiology and computed tomography (CT) based on Hounsfield units (HU). RESULTS: Gallstones were found in 148/1,065 subjects (13.9%), while 136 subjects (12.8%) were cholecystectomized with an overall prevalence of gallstone disease of 26.7% (sex ratio: F > M). Multiple gallstones (62.7%) and small gallstones (52%, diameter < or = 15 mm) were seen; silent gallstones accounted for 93.9% of the total. Only diabetes mellitus in women was significantly associated with cholelithiasis. Gallbladder fasting volumes were larger in gallstone carriers than in controls (P < 0.01); residual and ejection volumes were also significantly greater in gallstone carriers, whereas ejection fractions were similar in the two groups (50.3% +/- 2.4 versus 54.9% +/- 3.0; not significant). Gallstone calcifications were detected in 29/91 gallstone carriers by X-ray and in another 20 by CT (HU > 90). Moreover, 35 gallstone carriers had a score < or = 50 HU and six had attenuation values between 50 and 90 HU. Six gallstone patterns were identified: hypo-isodense, homogeneously dense, rimmed, laminated, core-hyperdense, gas-containing. CONCLUSIONS: In the elderly, the prevalence of gallstone disease is very high, especially in women, but gallstone size, number and pattern and gallbladder emptying do not differ from those reported in the middle-aged gallstone population. Advanced age is associated with a high rate of calcified, probably pigment stones.     

Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. A cholescintigraphic study

We studied gallbladder bile flow before, during, and after cholesterol gallstone formation in the prairie dog using infusion cholescintigraphy with 99mTc-diethyl iminodiacetic acid. In 18 fasting animals partitioning of bile between gallbladder and intestine was determined every 15 min for 140 min, and gallbladder response to cholecystokinin (5 U/kg X h) was calculated from the gallbladder ejection fraction. Ten prairie dogs were then placed on a 0.4% cholesterol diet and 8 on a regular diet, and the studies were repeated 1, 2, and 6 wk later. The proportion of hepatic bile that entered the gallbladder relative to the intestine varied from one 15-min period to the next, and averaged 28.2% +/- 5.1% at 140 min. Partial spontaneous gallbladder emptying (ejection fraction 11.5% +/- 5.6%) was intermittently observed. Neither the number nor the ejection fraction of spontaneous gallbladder contractions changed during gallstone formation. By contrast, the percent of gallbladder emptying in response to cholecystokinin decreased from 72.1% +/- 5% to 25.9% +/- 9.3% (p less than 0.025) in the first week and was 14.3% +/- 5.5% at 6 wk (p less than 0.01 from prediet values, not significant from first week). Gallbladder filling decreased from 28.2% +/- 5.1% to 6.7% +/- 3% (p less than 0.01), but this change was only observed after 6 wk, when gallstones had formed. This study shows that bile flow into the gallbladder during fasting is not constant; the gallbladder contracts intermittently; gallbladder emptying in response to exogenous cholecystokinin is altered very early during gallstone formation; and gallbladder filling remains unaffected until later stages, when gallstones have formed.     

Changes in gallbladder motility and gallstone formation following laparoscopic gastric banding for morbid obestity.

Morbid obesity is associated with cholesterol gallstone formation, a risk compounded by rapid weight loss. Laparoscopic gastric banding allows for a measured rate of weight loss, but the subsequent risk for developing gallstones is unknown. METHOD: Twenty-six normal-weight volunteers (body mass index [BMI] less than 30) were compared with 14 morbidly obese patients (BMI greater than 40). Gallbladder volumes were measured ultrasonographically, after fasting and following stimulation with intravenous cholecystokinin-octapeptide (CCK-8) RESULTS: Preoperatively, fasting gallbladder volume and residual volume after CCK stimulation were both two times greater in the obese group (P<0.02 versus controls). Per cent gallbladder emptying was not different. Gallbladder refilling was four times higher in the obese patients (P<0.01). By six weeks postoperatively, the obese patients lost 1.4+/-0.1% body weight per week. Gallbladder emptying decreased 18.4% (80.3+/-3.9% to 65.5+/-6.9%; P<0.05); residual volume rose one-third (not significant), and refilling fell 60.5% (0.43+/-0.09 to 0.26+/-0.04 mL/min; P=0.07). Three patients with weight losses of greater than 1.7% per week developed gallstones; gallbladder emptying fell outside the 95 percentile. By six months, weight loss slowed to 0.5+/-0.1% per week; gallbladder motility improved modestly. No further stones developed. CONCLUSION: Rapid weight loss following laparoscopic gastric banding impairs gallbladder emptying and when pronounced, gallstones form by six weeks postoperatively. The accompanying reduction in gallbladder emptying, increased gallbladder residual volume and decreased refilling promote gallbladder stasis and hence stone formation.     

Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus

BACKGROUND AND AIMS: Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). METHODS: Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. RESULTS: Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3 +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0 vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs 20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/- 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/- 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. CONCLUSION: Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.     

Misoprostol induces gallbladder contraction during fasting,but does not influence postprandial emptying: an ultrasound study in healthy subjects

OBJECTIVE: The aim of this study was to evaluate the effect of the PGE1 analogue, Misoprostol, on gallbladder fasting volume and meal-stimulated emptying. Prostaglandins' effects on the gallbladder were studied principally regarding mucus production during lithogenesis. In the few in vitro and in vivo studies, contradictory results concerning their influence upon gallbladder motility were obtained. SUBJECTS: 13 healthy subjects, 8 females, 5 males, aged 23.4 years (ranges 22-25). METHODS: Gallbladder volumes were assessed by ultrasound, after measuring the three diameters of the gallbladder in two perpendicular planes, using a conventional 2D equipment and a 3D equipment, after the 3D-reconstruction of the gallbladder. The volumes were calculated by means of the ellipsoid formula. Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were assessed during 90 minutes after a test meal (14 g fat, 425 kcal). Gallbladder emptying was evaluated in each subject on three different days: without prior Misoprostol administration, after 200 mg Misoprostol, and after 400 mg Misoprostol. Misoprostol was given orally as a single dose, 60 minutes before the meal. The two-tailed Student's t test for paired observations was used to compare the results. RESULTS: Misoprostol induced a significant decrease of the gallbladder fasting volume: from 12.8 +/- 4.4 (SD) ml (controls) to 9.1 +/- 3.6 ml (200 mg Misoprostol) and 5.4 +/- 2.6 ml (400 mg Misoprostol). Gallbladder meal-stimulated emptying was not influenced by Misoprostol. CONCLUSIONS: Our results indicated that, in healthy subjects, misoprostol induced a dose-dependent gallbladder emptying in the fasting state, but did not influence gallbladder postprandial emptying. Pre-prandial Misoprostol administration might be useful to treat gallbladder stasis in patients with chronic constipation, thus preventing gallstone formation.     

Simultaneous quantitative measurements of absolute gallbladder storage and emptying during fasting and eating in humans

We have carried out simultaneous, quantitative measurements of absolute gallbladder (GB) storage and emptying in 6 subjects with gallstones, using a modified duodenal perfusion technique that incorporates technetium 99m-labeled diethyl phenylcarbamomethyl iminodiacetate (99mTc-HIDA) as a GB bile marker in addition to indocyanine green as a hepatic bile marker. The technique was validated by measuring duodenal recovery of 99mTc-HIDA (mean +/- SEM, 101% +/- 4%), and also by studying 2 subjects who had undergone cholecystectomy. During the first hour following an evening meal, cumulative GB ejection of 99mTc-HIDA in the 6 subjects with gallstones was 43% +/- 12%. This was accompanied by GB storage of most hepatic indocyanine green (70% +/- 5%) during each 10-min interval of that hour. During subsequent overnight fasting, storage of hepatic indocyanine green (89% +/- 2%) was accompanied by ejection of 99mTc-HIDA from the GB in 33 of the 66 hourly intervals. Since 'simultaneous' filling and emptying cannot occur through the cystic duct, the results suggest frequent alternations in absolute GB storage and emptying, a phenomenon more analogous to a bellows than to the conventional concept of a simple pump.     

Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects

Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5+/-10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7+/-8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student's t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin (P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.     

Gallbladder and gastric motility in obese newborns, pre-adolescents and adults

Background and Aim: Impaired gallbladder and gastric motility have been associated with obesity in adults. The timing of appearance of this dysfunction, however, is unclear. Methods: Lean and obese subjects from three different age groups were studied noninvasively: 50 newborns (1–12 months old, six obese), 18 pre‐adolescents (7–8 years old, seven obese), and 99 adults (22–80 years old, 32 obese) classified according to standard normal tables and body mass index. Changes of fasting/postprandial gallbladder and gastric motility were assessed simultaneously by functional ultrasonography in response to milk (newborns and pre‐adolescents) and to a liquid test meal (adults). Results: In newborns, fasting and postprandial gallbladder volumes and gastric emptying were similar between obese and lean subjects. In pre‐adolescents, obese subjects had a larger fasting gallbladder volume, with slower postprandial gastric emptying than lean subjects. In obese adults, the most evident dysfunction emerged, with larger fasting and postprandial residual gallbladder volume, and slower postprandial gastric emptying than lean subjects. Conclusions: Obese subjects display abnormal gallbladder and gastric motility patterns, which first appear in pre‐adolescents and deteriorate in adults. Such abnormalities are absent in obese newborns. Functional ultrasonography can detect altered cholecysto‐gastric motility at the earliest stage. Our findings suggest an age‐related decline of motility, probably secondary to excessive fat and insulin‐resistance.     

Gallbladder Motility and Lithogenesis in Obese Patients During Diet-Induced Weight Loss

Obesity and weight loss are important risk factors for gallstone development. The mechanisms involved are unknown. We prospectively studied changes in gallbladder (GB) emptying and bile composition during weight loss. We studied 12 alithiasic obese subjects who entered a six-month diet program (800–1200 kcal/day, 26 g fat/day). As controls we evaluated 12 healthy nulliparous nonobese young women. GB volumes were studied by ultrasonography (fasting volume, GBFV; residual volume after a liquid meal, GBRV) at entry and after 4 and 20 weeks of dieting. Bile acid pool size, biliary lipid composition, presence of cholesterol crystals, and nucleation time were also studied. Of 12 obese subjects studied (mean BMI 35.1 kg/m²), 10 remained in the program for six months, but only six completed the entire study protocol, obtaining a significant weight loss (BMI: 31.2 kg/m², P < 0.001). GBFV was greater in obese subjects than in nonobese controls (27.5 ± 10.7 vs 11.7 ± 6 ml; P < 0.05). GBRV and GB emptying curves were similar in both groups and did not change during weight loss. The obese subject who developed gallstones (1/10) was the only one who had cholesterol crystals in bile and a sluggish initial GB emptying. In conclusion: (1) obese subjects had a greater GBFV than controls; however, the GB emptying was adequate. (2) During weight loss we did not observe significant changes in GB kinetics or the bile parameters studied. (3) We observed a relatively low frequency of gallstone formation, which can be explained by a high fat content of the diet (26 g/day) and by the adequate GB emptying of our group of patients. (4) An abnormal GB contractility and cholesterol crystals in bile could be considered premonitory to gallstone formation.     

Increased Prevalence of Gallstone Disease and Impaired Gallbladder Motility in Patients with Barrett’s Esophagus

The prevalence of gallstones in patients with Barrett's esophagus (BE) and their gallbladder motility relative to that of healthy volunteers and GERD patients without BE were investigated. Of the 707 patients reviewed, 203 (125 males and 78 females) had BE. The prevalence of gallstones was significantly higher in the patients with BE than in those without BE (34 vs. 20%, respectively). The gallbladder functions of 22 patients with GERD, 27 patients with BE and 21 healthy volunteers were assessed by ultrasonography before and after a test meal. The patients with BE had significantly higher fasting volume and residual volume, but lower ejection volume, ejection fraction and ejection rate values than those of the healthy controls. None of the ultrasonographic parameters of patients without BE were significantly different from those of the controls. Patients with BE have a more complex gastrointestinal motility disorder that involves the gallbladder, and this makes this subset of patients with GERD more prone to gallstone disease.     

The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study

OBJECTIVE: Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls. METHODS: Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain. RESULTS: Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients. CONCLUSIONS: Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized patients.