Gallstones: an intestinal disease? (1/82)

Current evidence suggests that impaired intestinal motility may facilitate gallstone formation by influencing biliary deoxycholate levels or by modulating interdigestive gall bladder motility (fig 2), although a primary intestinal defect in gallstone pathogenesis has not yet been demonstrated. In the cold war period, most interesting events, from a political point of view, occurred at the border between capitalist and communist systems, near the iron curtain. Similarly, the gall bladder and biliary tract can be viewed as the border between liver and intestinal tract, where many interesting things occur with profound impact on both systems. Combined efforts by researchers in the field of hepatology and gastrointestinal motility should brake down the Berlin wall of ignorance of one of the most common diseases in the Western world.  (+info)

The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects. (2/82)

AIMS: Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release. METHODS: Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured. RESULTS: After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment. CONCLUSIONS: The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.  (+info)

SR146131: a new potent, orally active, and selective nonpeptide cholecystokinin subtype 1 receptor agonist. II. In vivo pharmacological characterization. (3/82)

SR146131 is a potent and selective agonist at cholecystokinin subtype 1 (CCK1) receptors in vitro. The present study evaluates the activity of the compound in vivo. SR146131 completely inhibited gastric and gallbladder emptying in mice (ED50 of 66 and 2.7 micrograms/kg p.o., respectively). SR146131 dose dependently reduced food intake in fasted rats (from 0.1 mg/kg p.o.), in nonfasted rats in which food intake had been highly stimulated by the administration of neuropeptide Y (1-36) (from 0.3 mg/kg p.o.), in fasted gerbils (from 0.1 mg/kg p.o.), and in marmosets maintained on a restricted diet (from 3 mg/kg p.o.). SR146131 (10 mg/kg p.o.) also increased the number of Fos-positive cells in the hypothalamic paraventricular nucleus of rats. Locomotor activity of mice was reduced by orally administered SR146131 (from 0.3 mg/kg p.o.). When administered intrastriatally, SR146131 elicited contralateral turning behavior in mice. Furthermore, orally administered SR146131 (0.3-10 mg/kg), also reduced the levels of cerebellar cyclic GMP. Finally, SR146131 (0.1 microgram/kg to 1 mg/kg, p.o.) significantly and dose dependently antagonized fluphenazine-induced mouth movements in rats. The CCK1 antagonist SR27897B prevented all the effects of SR146131. Conversely, SR146131 was unable to elicit any agonist or antagonist effects in a model of CCK2 receptor stimulation in vivo. SR146131 is a very potent and selective nonpeptide CCK1 agonist in vivo. SR146131 is more potent than any other CCK1 agonists reported to date. Because pharmacodynamic studies suggest that SR146131 should have a high absolute bioavailability, it may be a promising drug for the treatment of eating and motor disorders in humans.  (+info)

Gall bladder emptying in severe idiopathic constipation. (4/82)

BACKGROUND: It has been suggested that slow transit constipation (STC) may be part of a panenteric motor disorder. AIM: To evaluate motility of an upper gastrointestinal organ, the gall bladder, in 16 patients with STC and 20 healthy controls. METHODS: Gall bladder emptying (ultrasonography) was studied in response to neural, cephalic-vagal stimulation with modified sham feeding (MSF) for 90 minutes and in response to hormonal stimulation with cholecystokinin (CCK, 0.5 IDU/kg/h) for 60 minutes. RESULTS: Fasting gall bladder volume in patients with STC (17 (2) cm(3)) was significantly (p<0. 01) reduced compared with that in controls (24 (2) cm(3)). Gall bladder emptying in response to MSF was significantly reduced in patients with STC expressed both as percentage emptying (11 (5)% versus 22 (3)%; p<0.05) and as absolute emptying (2.1 (0.7) cm(3) versus 4.9 (0.7) cm(3); p<0.02). However, percentage gall bladder emptying in response to CCK was not different between patients and controls (73 (4)% versus 67 (4)%) although the absolute reduction in gall bladder volume was significantly (p<0.05) smaller in patients (10.7 (1.1) cm(3) versus 15.3 (1.4) cm(3)). CONCLUSIONS: Patients with slow transit constipation have smaller fasting gall bladder volumes, impaired gall bladder responses to vagal cholinergic stimulation, but normal gall bladder responses to hormonal stimulation with CCK. These results point to abnormalities in gastrointestinal motility proximal from the colon in slow transit constipation and more specifically, impaired neural responsiveness.  (+info)

Contrast material and gallbladder kinetics: implications for same day sonography after intravenous pyelography or CT scanning. (5/82)

Sonographic examination of the gallbladder has allowed us to study the effects of various substances on this organ. A prospective study involving 77 patients was undertaken to evaluate the effects of intravenous or oral contrast agents on gallbladder volume changes in patients without known gallbladder disease. A mean volume after contraction of 24.8% was observed after administration of intravenous contrast agent (P < 0.01) and of 31.9% after oral administration (P < 0.01). This phenomenon of contraction of the gallbladder should therefore be recognized when sonographic or computed tomographic evaluation of the gallbladder is undertaken after imaging procedures that use radiographic contrast agents either intravenously or orally.  (+info)

Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle. (6/82)

Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with intracellular recordings from intact gallbladder and whole cell patch-clamp recordings from isolated cells. Cholesterol significantly attenuated the spontaneous action potentials of intact tissue. Furthermore, calcium-dependent action potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyperpolarizations induced by the ATP-sensitive potassium channel opener, pinacidil, nor voltage-activated outward potassium currents were affected by cholesterol. Hyperpolarizations elicited by calcitonin gene-related peptide were reduced by cholesterol enrichment, indicating potential changes in receptor ligand binding and/or second messenger interactions. These data indicate that excess cholesterol can contribute to gallbladder stasis by affecting calcium channel activity, whereas potassium channels remained unaffected. In addition, cholesterol enrichment may also modulate receptor ligand behavior and/or second messenger interactions.  (+info)

Differing effects on gall-bladder motility of lanreotide SR and octreotide LAR for treatment of acromegaly. (7/82)

BACKGROUND: Octreotide treatment may be associated with gall stone development in up to 50% of patients with acromegaly. Two new sustained-release formulations of somatostatin analogue have been recently developed: lanreotide SR (Somatuline) and octreotide LAR (Sandostatin LAR). The incidence of gall-stone development in patients receiving these drugs has been shown to be less than 20%, but the duration of follow-up has been limited. OBJECTIVE: Prospectively to assess and compare the effects of the two new long-acting somatostatin agonists on gall bladder motility in patients with acromegaly. METHOD AND PATIENTS: Eleven patients with active acromegaly were studied. Three patients had asymptomatic gall stones at the start of the study. Ultrasound scans were performed before commencement of the treatment, and repeated during treatment with lanreotide SR and octreotide LAR. The presence of gall stones, fasting gall bladder volume (FV), residual volume (RV) and maximal percentage gall bladder emptying were measured. RESULTS: One patient developed asymptomatic small gall stones after treatment with octreotide LAR for 4 months. FV and RV were both significantly larger when patients received treatment with lanreotide SR or octreotide LAR compared with pretreatment values (P<0.05 for both). Maximal percentage gall bladder emptying was significantly reduced in patients receiving lanreotide SR or octreotide LAR compared with pretreatment (P<0.01), but was less impaired in patients receiving lanreotide SR than in those receiving octreotide LAR (P<0.01). CONCLUSIONS: Gall bladder motility is impaired in patients receiving either of these new long-acting preparations, and long-term follow-up will be needed to establish the true incidence of gall stones.  (+info)

Cholecystokinin cholescintigraphy: victim of its own success? (8/82)

Numerous publications have reported that a low gallbladder ejection fraction (GBEF) determined by cholecystokinin (CCK) cholescintigraphy has a high positive predictive value for the diagnosis of chronic acalculous cholecystitis (CAC). Clinicians and surgeons have found this test to be clinically useful as an objective method to confirm their clinical diagnosis. However, an abnormally low GBEF is not specific for CAC. For example, numerous other diseases have been associated with a low GBEF, and various therapeutic drugs can cause poor gallbladder contraction. Importantly, improper CCK infusion methodology can result in an erroneously low GBEF. More than one third of healthy subjects and patients who receive sincalide, 0.02 microg/kg infused over 1-3 min, will have an erroneously low GBEF but will have a normal GBEF with a slower infusion (30-60 min) of the same total dose. Because of enthusiastic acceptance of CCK cholescintigraphy by clinicians, the types of patients referred for this test have changed over time. Patients investigated in publications confirming the usefulness of CCK cholescintigraphy had a high pretest likelihood of disease. They underwent extensive workup to rule out other diseases and were followed up for months or years before CCK cholescintigraphy was performed, allowing other diseases to become manifest or symptoms to resolve. However, CCK cholescintigraphy is now being used by clinicians to shorten the workup and follow-up time based on the rationale that CCK cholescintigraphy can quickly confirm or exclude the diagnosis. This new group of referral patients has a lower likelihood of the disease. Many will ultimately be diagnosed with diseases other than CAC. The positive predictive value of this test will likely be lower and the false-positive rate will likely be higher. Nuclear medicine physicians must work to minimize false-positive studies to maintain the confidence of referring clinicians. First, we can educate referring physicians as to the proper use of this study. Next, we must perform CCK cholescintigraphy using optimal methodology that will result in the lowest possible false-positive rate. And finally, we must interpret CCK cholescintigraphy in light of the patient's history, prior workup and clinical setting.  (+info)