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PubMed1989

Alterations in biliary motility correlate with increased gallbladder prostaglandin synthesis in early cholelithiasis in prairie dog.

Abnormal biliary motility has been observed in humans with gallstones and in animal models; however, the mechanism by which these abnormalities occur remains unknown. In this study we investigated the relationship between cholesterol gallstone formation, changes in biliary motility, and rates of gallbladder prostaglandin synthesis in prairie dogs receiving a 0.34% cholesterol diet for two, four, or six weeks. Gallstones did not occur until four weeks, when the incidence was 14%; after six weeks the incidence was 64%. Gallbladder emptying increased slightly at two weeks before becoming significantly decreased at four and six weeks. In contrast, there was a near linear increase in basal cystic duct resistance which began by two weeks of cholesterol feeding, although sphincter of Oddi resistances remained normal throughout the period of study. The synthesis of prostaglandins E and F2 alpha by the gallbladder was also increased beginning at two weeks and rose to a plateau at four and six weeks. In view of the potent effects of prostaglandins on biliary smooth muscle, these findings suggest that prostaglandins may mediate early changes in gallbladder and cystic duct motility which ultimately result in impaired gallbladder emptying.

Animals↗
PubMed2004

Bethanechol provocation testing does not predict symptom relief after cholecystectomy for acalculous biliary pain.

BACKGROUND: The currently accepted hypothesis to explain acalculous gallbladder pain is the lack of contractile co-ordination between the body and neck. We have previously shown that bethanechol, a muscarinic stimulant causes differential stimulation of these two regions. AIM: To evaluate the reliability of bethanechol-induced gallbladder contraction in predicting symptom relief after cholecystectomy in patients with acalculous gallbladder disease. METHODS: Fifty-one patients underwent a bethanechol provocation test together with serial ultrasound to determine gallbladder emptying. McGill pain questionnaires were completed, and patients positive for pain (bethanechol provocation test +ve) were offered cholecystectomy, and patients negative for pain (bethanechol provocation test -ve) were reassessed at 6 months and offered cholecystectomy if symptoms persisted. All patients answered pain questionnaires either 6 months after surgery or as follow-up. RESULTS: There was no difference in the percentage of gallbladder emptying between the bethanechol provocation test +ve and bethanechol provocation test -ve groups. Fifty-three percent of bethanechol provocation test +ve patients and 54% of bethanechol provocation test -ve patients still remained symptomatic 6 months after surgery. Conclusion. Gallbladder pain provoked by bethanechol does not predict symptom relief after cholecystectomy.

Adult↗
PubMed1999

Gallbladder hyporesponsiveness to an exogenous nitric oxide donor, glyceryl trinitrate, in patients with advanced liver cirrhosis.

OBJECTIVE: An increased production of nitric oxide (NO) in liver cirrhosis has been documented. NO could intervene in regulating gallbladder contraction, as suggested by clinical and experimental studies. Our aim was to investigate the influence of an NO donor on gallbladder motility in cirrhotic patients in relation to the severity of liver cirrhosis. METHODS: The subjects were six controls and 18 patients with liver cirrhosis (six in each Child class). Gallbladder emptying was monitored by ultrasound for 90 min after a mixed meal (14 g fat, 425 kcal). Fasting gallbladder volume, minimal residual volume, ejection fraction, area under emptying curve, and half contraction time of the gallbladder were assessed at 15-min intervals. The patients were evaluated on two consecutive days, with or without perlingual administration of 0.5 mg glyceryl trinitrate (GTN). Statistical analysis was performed by the two-tailed Student's t test and Pearson's correlation coefficient. RESULTS: GTN significantly reduced gallbladder motility in controls and compensated cirrhotics (p < 0.02), but had no effect upon gallbladder emptying in Child class B and C cirrhotics. CONCLUSIONS: Gallbladder hypocontractility in liver cirrhosis is related to the severity of the disease. This study is the first to show that GTN has no effect upon gallbladder motility in advanced liver cirrhosis when administered in doses that induce relaxation in controls and compensated cirrhosis.

Female↗
PubMed2001

Absence of apolipoprotein E4 genotype, good gallbladder motility and presence of solitary stones delay rather than prevent gallstone recurrence after extracorporeal shock wave lithotripsy.

BACKGROUND/AIMS: Extracorporeal shock wave lithotripsy (ESWL) with adjuvant bile salt dissolution therapy may be successful in selected gallstone patients, but the considerable risk of recurrence is a major drawback. Apolipoprotein E4 genotype and impaired gallbladder motility have been identified as major risk factors for recurrence during short-term follow up. We have now examined their relevance during long-term follow up. METHODS: Eighty-four cholesterol gallstone patients (55 solitary and 29 multiple (two to ten) stones) were followed prospectively up to 10 years after complete stone disappearance. Various potential risk factors for recurrence were evaluated. RESULTS: Gallstone recurrence was found in up to 80% of patients at 10 years follow-up. Absence of the apolipoprotein epsilon4 allele, initial solitary stones, good gallbladder emptying (i.e. minimal postprandial volume < or = 6 ml) and 2-year postdissolution ursodeoxycholic acid prophylaxis (in ten patients) all delayed but did not prevent recurrence. In contrast, regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was identified as an independent protective factor, with greatly decreased recurrence (at 10 years: 58 vs 93% in non-NSAID users, P = 0.03). CONCLUSIONS: Non-apolipoprotein E4 genotype, presence of solitary stones and good gallbladder emptying delay rather than prevent recurrence after initially successful ESWL. Regular use of NSAIDs may prevent recurrence.

Adult↗
PubMed1995

Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis.

BACKGROUND & AIMS: Impaired gallbladder emptying is implicated in gallstone disease. Ultrasonography and scintigraphy have shown conflicting results because the former is influenced by postprandial refilling, whereas the latter is not influenced by refilling. The aim of this study was to measure postprandial refilling and turnover of bile by combining the two techniques. METHODS: Simultaneous scintigraphy and ultrasonography were used in 14 patients with gallstones and 11 healthy controls. Measurements were performed while the patients were fasting and at 10-minute intervals after a standard meal for 90 minutes, and the measurements were used to calculate postprandial refilling, turnover of bile (in milliliters), and turnover index. RESULTS: Ultrasonography and scintigraphy provided different gallbladder emptying patterns. Compared with controls, patients with gallstones had impaired emptying by both scintigraphy (P < 0.0001) and ultrasonography (P < 0.01). Postprandial refilling and turnover were both reduced between 60 and 90 minutes (P < 0.05), and the turnover index was markedly reduced (1.8 vs. 3.5; P < 0.001). CONCLUSIONS: Simultaneous scintigraphy and ultrasonography provide a new model of gallbladder motor function showing that refilling begins immediately postprandially. In healthy controls, the gallbladder postprandially handles up to six times its basal volume within a period of 90 minutes, but this turnover of bile is markedly reduced in cholelithiasis causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.

Analysis of Variance↗
PubMed1993

Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects.

Colorectal cancer is a disease of elderly subjects. A decreased ileal absorption of bile acids in elderly subjects may lead to an increased exposure of the colonic mucosa to secondary bile acids. This may contribute to an enhanced risk of colorectal cancer. In this study fasting and postprandial conjugated and unconjugated serum levels of cholic, chenodeoxycholic, and deoxycholic acid in 12 elderly and 12 younger subjects were investigated. Intestinal transit time, gallbladder emptying and jejunal bacterial flora were also studied in both age groups. Fasting levels of conjugated and unconjugated serum bile acids were similar in both age groups. Postprandial levels of all individual conjugated bile acids increased to a significantly higher extent in the younger subjects. Postprandial unconjugated serum bile acid levels did not differ significantly between both age groups, although unconjugated deoxycholic levels tended to increase to higher levels in the elderly. Results of jejunal bacterial counts, gallbladder emptying and intestinal transit time were similar in both groups. These data suggest that conjugated bile acids are reabsorbed less effectively in elderly subjects.

Adult↗
PubMed1989

Postdissolution gallstone recurrence. A clinical perspective.

The intuitive assumption that gallstones will rapidly recur in all patients is clearly incorrect. At least 50% of patients do not develop stones within three to five years of complete dissolution, and the risk may decrease after the first two or three years. This is not so surprising when one considers the complexity of the pathogenic process. Bile must be sufficiently supersaturated with cholesterol, an imbalance in nucleating and antinucleating factors must occur, at least transiently, and, for some patients, a defect in gallbladder emptying may be necessary. Occasionally, pathogenic mechanisms that had been present, eg, estrogens, obesity, or medications such as clofibrate, may no longer be active. The best method to reduce the risk of recurrence is to reverse one or more of the essential pathogenic mechanisms. Desaturating bile in cholesterol by oral therapy with a bile acid such as ursodiol should be effective. A search for other safe, effective, and cost-effective approaches persists, eg, for novel bile acids resistant to bacterial degradation and for various dietary regimens. Alteration of cholesterol nucleation with nonsteroidal antiinflammatory agents is also under investigation. In addition, enhancement of gallbladder emptying is an interesting approach that is worth studying. If stones do recur, the course of action is not always clear. Recurrent stones are usually "silent," and we do not usually treat asymptomatic stones. These small cholesterol stones are temptingly easy to dissolve, however. At least in those patients whose level of surgical risk would be high if symptoms developed, prophylactic dissolution therapy may be desirable.

Bile↗
PubMed1995

Abnormalities in gallbladder dynamics of type 1 (insulin-dependent) diabetic patients with autonomic neuropathy.

The aim of this study was to evaluate gallbladder dynamics in insulin-dependent diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was studied by a scintigraphic method after a test meal in 26 insulin-dependent diabetic patients and 10 normal individuals. The presence and severity of autonomic neuropathy were defined according to the number of abnormal cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal tests), and severe (4-5 abnormal tests). The time from the moment when the patient started to take the test meal to the beginning of gallbladder emptying was longer (P = 0.01) in diabetic patients with mild (N = 11, 12.1 +/- 7.6 min) and severe neuropathy (N = 8, 11.0 +/- 10.6 min) than diabetic patients without autonomic neuropathy (N = 7, 3.9 +/- 4.4 min) and controls (N = 10, 4.8 +/- 4.2 min). The ejection rate was higher (P = 0.02) in the group with severe autonomic neuropathy (N = 8, 5.1 +/- 3.3%/min) than diabetic patients with mild (N = 11, 2.0 +/- 1.0%/min) or without autonomic neuropathy (N = 7, 1.8 +/- 0.8%/min) and controls (N = 10, 2.6 +/- 1%/min). Thirty-two percent of the diabetic patients with autonomic neuropathy presented increased perspiration, nausea and urgency to defecate after the ingestion of the test meal. A significant positive correlation of ejection rate with the presence of these symptoms (biserial point correlation test = 0.67, P < 0.01) was also observed. These data suggest that insulin-dependent diabetic patients with autonomic neuropathy present abnormalities of gallbladder emptying that could be related to specific gastrointestinal symptoms.

Adult↗
PubMed1994

[Ultrasonographic evaluation of gallbladder and gastric emptying after ingestion of water with various saline compositions].

OBJECTIVE: Evaluation of gallbladder and gastric emptying after ingestion of a saline enriched water ("Acqua Santa" di Chianciano) in comparison with a commercial oligomineral water. STUDY DESIGN: A 40-minute blind prospective study. LOCATION: The study was performed at the Terme of Chianciano (Siena) for subjects of group A and at the Institute of Clinica Medica Generale and Terapia Medica of the University of Bologna for subjects of group B. PATIENTS OR PARTICIPANTS: Two groups of healthy subjects were studied. Each group consisted of 12 subjects without gallbladder disease. EXPERIMENTAL PROTOCOL: Fasting subjects of group A ingested alternatively, for two consecutive mornings, 400 ml of the saline enriched water at the natural temperature of 33 degrees C or 400 ml of oligomineral water warmed to the same temperature. Subjects of group B ingested the same waters at 18 degrees C. METHODS: Gastric and gallbladder emptying were evaluated, after ingestion of the different waters, by means of ultrasonography. RESULTS: In both groups gallbladder emptying was significantly higher after ingestion of the saline enriched water. On the other hand gastric emptying was similar with both waters. CONCLUSIONS: This study demonstrated that saline enriched water determines a greater emptying of the gallbladder in comparison with an oligomineral water. This effects is not related to gastric emptying but rather it is due to a higher concentration of saline components and thus to their possible effect on gallbladder motility.

Adult↗
PubMed1997

Safety and efficacy of repeated shockwave lithotripsy of gallstones with and without adjuvant bile acid therapy.

BACKGROUND & AIMS: The value of adjuvant bile acid dissolution therapy after extracorporeal shockwave lithotripsy (ESWL) of gallbladder stones is under debate. A double-blind, randomized, multicenter trial was conducted to determine the safety and efficacy of repeated ESWL with and without adjuvant bile acid therapy. METHODS: At five centers, 153 patients with gallstones and good gallbladder emptying were randomized to undergo up to six high-energy lithotripsy sessions combined with ursodeoxycholic acid (UDCA, 750 mg/day; n = 77) or placebo (n = 76). RESULTS: Six months after the initial treatment, 77% of patients with small single stones (< or = 20 mm in diameter), 60% with large single stones (> 20 mm in diameter), and 41% with multiple stones were free of stones. Administration of UDCA had no effect on stone disappearance in the whole study group but tended to improve stone disappearance rates in patients with large single stones and tended to decrease biliary adverse effects in patients with multiple stones. CONCLUSIONS: Repeated high-energy ESWL without adjuvant bile acid therapy represents a safe and effective treatment in patients with small single stones and good gallbladder emptying. In patients with large single stones and multiple stones, adjuvant bile acid therapy may be beneficial.

Adjuvants, Pharmaceutic↗
PubMed1994

Contractile mechanisms of gallbladder filling and emptying in dogs.

BACKGROUND/AIMS: The mechanisms of gallbladder filling and emptying during the fasting state, postprandial state, and after intravenous administration of cholecystokinin, motilin, and morphine were investigated in conscious dogs. METHODS: Bile flow in the cystic and common bile ducts was measured by miniature flow probes. RESULTS: The gallbladder showed brief alternating excursions of filling and emptying in the fasting and fed state. The emptying excursions exceeded the filling excursions during phase II and for about 4 hours after a meal. The filling excursions exceeded the emptying excursions during phase I, phase III, and the latter half of the postprandial state. Most gallbladder emptying occurred when its pressure was high, and most filling occurred when its pressure was low. The duodenal contractions played a major role in gallbladder filling and emptying during phase III. CONCLUSIONS: Gallbladder filling and emptying are not monotonous during the fasting and postprandial states. The brief alternating excursions of filling and emptying would almost continually mix the concentrated gallbladder bile with the fresh dilute hepatic bile to prevent supersaturation of the gallbladder bile during the fasting state and extend the delivery of a small volume of concentrated gallbladder bile for a period of several hours after a meal.

Animals↗
PubMed2005

Gallbladder motor function, plasma cholecystokinin and cholecystokinin receptor of gallbladder in cholesterol stone patients.

AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease. METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30). Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls. RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases) and non-contractor group (19 cases). The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86+/-3.86 pmol/L vs 37.85+/-0.88 pmol/L and 37.95+/-0.74 pmol/L, P<0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27+/-0.94 fmol/mg vs 24.59+/-2.39 fmol/mg and 22.66+/-0.55 fmol/mg, P<0.01). The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683, P<0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0.9627, P<0.01). CONCLUSION: The distinctive interactive relationship of gallbladder emptying, plasma CCK and CCK-R in gallbladder from this study suggested that the defect of CCK-R may be a key point leading to the impairment of gallbladder motor function and the pathogenesis of cholesterol gallstone formation may differ in two subgroups of gallstone patient, gallbladder non-contractor group or contractor group.

Cholecystokinin↗
PubMed1978

Nocturnal gallbladder storage and emptying in gallstone patients and healthy subjects.

Nocturnal hepatic bile is supersaturated with cholesterol, and increased storage of this "lithogenic" bile in gallstone patients might explain why they more frequently have supersaturated fasting state gallbladder bile than patients without gallstone disease. To test this possibility, we measured the fraction of nocturnal hepatic bile stored in the gallbladder in 5 patients whose gallstones had been previously dissolved by chenodeoxycholic acid, in 5 control subjects without gallstone disease matched for age, sex, and weight, and in 5 young healthy males. We developed a new method based on the use of indocyanine green as a bile marker. The hourly rate of input into the duodenum of indocyanine green was measured during its constant, prolonged intravenous infusion. When gallbladder storage occurred, indocyanine green input was less than the infusion rate; when gallbladder emptying occurred, input exceeded the infusion rate. The method was validated by showing that duodenal output of indocyanine green was identical to intravenous input of indocyanine green in 2 cholecystectomized patients. When the method was applied, emptying of the gallbladder with meals was documented, and calculations showed that more than half of the bile secreted at night bypassed the gallbladder in both gallstone patients and control subjects. No difference in "cholecystodynamics" was observed between gallstone patients, matched control subjects, and young healthy men. Our results validate a method for quantitating gallbladder storage and emptying in men, but fail to support the speculation that an important pathogenetic step in gallstone formation is increased storage of supersaturated nocturnal bile in the gallbladder.

Adult↗
PubMed1995

[Gallbladder motility following intake of mineral bicarbonate-alkaline water. Ultrasonographic assessment].

Sonographic measurement of gallbladder volume has allowed us to assay the influence of many substances (hormones, drugs, etc.) on gallbladder kinetics playing a pivotal role in digestive mechanisms. The aim of the present study has been to evaluate the effect of an alkaline bicarbonate water (Donata) on gallbladder emptying. The study was performed in cross-over. Ten healthy volunteers randomly assumed alkaline bicarbonate water or saline (400 ml). Gallbladder volumes were measured by ultrasonography, according to ellipsoid method, before and 15', 30', 45', 60', 90', 120' after water or saline intake. A week later the test was repeated. Gallbladder kinetics was evaluated referring to fasting volume, residual volume, absolute emptying and maximum percent emptied. Student's "t" test for paired data was used for statistical evaluation of the results. Gallbladder volumes were significantly reduced 15', 30', 45' and 60' after alkaline bicarbonate water administration, whereas saline did not induced gallbladder emptying. The present results suggest that Donata water may be employed in order to ameliorate dyspepsia due to biliary dyskinesia, moreover it may play a complementary role in the prevention and in the medical treatment of biliary lithiasis.

Adult↗
PubMed1995

Cholesterol gallstone formation in man and potential treatments of the gallbladder motility defect.

Cholelithiasis affects 10-15% of the adult population in Western society, and about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of cholesterol with the formation of instable cholesterol-rich vesicles in bile, an imbalance between nucleation-inhibiting and nucleation-promoting proteins with further aggregation of cholesterol crystals in a gallbladder with a motility defect (stasis), all play a role in the pathogenesis of cholesterol gallstones. Experimental animal models suggest that gallstone formation can be prevented by improving gallbladder emptying. Thus, a better understanding of the causes underlying the impaired gallbladder motor function in patients with gallstones might lead to the selection of therapeutic approaches for those individuals who are at increased risk for the formation or recurrence of gallstones. The present article focuses on current concepts and theories on the pathogenesis of cholesterol gallstones with emphasis on the gallbladder motility defect. Several treatment strategies for the correction of gallbladder hypomotility are also discussed.

Adult↗