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PubMed1988

Spontaneous passage of glass beads from the canine gallbladder: facilitation by sphincterotomy.

To investigate the mechanism by which ablation of the sphincter of Oddi prevents gallstone formation, we assessed passage of glass beads out of the gallbladders of dogs with sphincterotomy and sham sphincterotomy. One month after bead implantation, dogs with an intact sphincter passed 52%, 26%, 22%, 10%, 0%, and 0% of beads with diameters of 2, 3, 4, 5, 6, and 8 mm, respectively. For the same respective bead diameters, dogs with a sphincterotomy passed 90%, 90%, 88%, 75%, 75%, and 42% of beads (p less than 0.05 for all bead diameters). No beads were in the common bile duct of any dog. In separate dogs studied by cholescintigraphy, sphincterotomy significantly increased gallbladder ejection fraction from 0.46 to 0.76 (p less than 0.01). In addition, sphincterotomy significantly lowered resting gallbladder volume from 24.4 to 15.8 ml (p less than 0.025) and lowered cholecystokinin-stimulated gallbladder volume from 13.3 to 5.9 ml (p less than 0.025). These data indicate that even with an intact sphincter, small solids can pass from the gallbladder and into the duodenum. Sphincterotomy facilitates passage of solids, apparently by general improvement in gallbladder emptying. Facilitated passage of crystals, microliths, or small stones seems the most likely explanation for prevention of gallstone formation by sphincterotomy.

Animals↗

PubMed1989

Dietary intake and the prevalence of gallbladder disease in Mexican Americans.

Mexican Americans have a high prevalence of gallbladder disease. We examined the contribution of ethnic preferences in food intake to the risk of gallbladder disease in Mexican Americans and non-Hispanic whites. Participants in a population-based health survey were questioned about any history of gallbladder disease, and were interviewed to determine their dietary intake. After adjusting for age, body mass index, and ethnic group, we found that women with the highest intake of total fat and linoleic acid had reduced risks of gallbladder disease, although an opposite trend was observed in men. High levels of sucrose intake and low levels of cholesterol intake were associated with an increased risk for both sexes, but the odds ratios were not statistically significant. Although Mexican Americans and non-Hispanics differed in their intake of several nutrients, the elevated risk of gallbladder disease in Mexican American women was unchanged after ethnic differences in food intake were taken into account. Although the dietary preferences of Mexican Americans as reflected in 24-h diet recall interviews do not appear to explain their high prevalence of gallbladder disease, this finding should be interpreted with caution because of methodologic limitations in measuring habitual food intake.

Adult↗

PubMed1989

Subunit interactions and physical properties of bovine gallbladder mucin.

In this study the interaction of gallbladder mucin subunits was examined by gel permeation chromatography, quasielastic laser light scattering, and viscometry. Purified mucin eluted primarily in the void volume of a Sepharose 2B-Cl column, indicating a molecular weight above 2 x 10(6). Disaggregation of the mucin polymer resulted in the elution of glycoprotein in the included volume of the Sepharose 2B-Cl column. Gallbladder mucin had a hydrodynamic radius of 630 A that was independent of mucin concentration below 2 mg/ml. At mucin concentrations above 2 mg/ml, a concentration-dependent increase in both hydrodynamic radius and apparent viscosity of gallbladder mucin was observed. Mucin demonstrated a strong pH dependence in hydrodynamic radius and viscosity with the maximum occurring at approximately pH 5.5. These findings suggest that noncovalent interactions participate in bovine gallbladder mucin subunit associations. Furthermore, changes that occur in the physicochemical environment of the gallbladder during periods of stasis may enhance the viscoelastic properties of mucin and promote the accumulation of biliary sludge in the gallbladder.

Animals↗

PubMed1989

Release of substance P- and calcitonin gene-related peptide-like immunoreactivity and motor response of the isolated guinea pig gallbladder to capsaicin.

The aim of this study was to assess whether a local motor response to capsaicin could be observed in the isolated guinea pig gallbladder and to discover the mechanism involved. Capsaicin produced a contraction of this organ that exhibited desensitization, suggesting a specific action on sensory nerves. In preparations preexposed to capsaicin to produce a functional blockade of the capsaicin-sensitive sensory fibers, the contractile response to field stimulation was unaffected as compared with controls. Tachykinins (substance P and neurokinin A) produced a concentration-related contraction of this organ, neurokinin A being more potent than substance P. Spantide, a tachykinin antagonist, markedly inhibited the capsaicin-induced gallbladder contraction, leaving the atropine-sensitive response to field stimulation unaffected. Calcitonin gene-related peptide (CGRP) produced a concentration-related relaxation, which was tetrodotoxin-resistant, suggesting a direct effect on muscle cells. Repeated administration of CGRP produced desensitization. At this stage, application of capsaicin produced a contractile response much larger than in controls. Both substance P- and CGRP-like immunoreactivity were detected in the guinea pig gallbladder by radioimmunoassay and were significantly reduced after systemic capsaicin desensitization. Capsaicin induced the simultaneous release of substance P- and CGRP-like immunoreactivity from superfused isolated gallbladders. These findings indicate that capsaicin-sensitive nerves in the guinea pig gallbladder can produce a local motor response involving the release of multiple neuropeptides. In the guinea pig gallbladder, tachykinins and CGRP might act as "physiologic antagonists," as observed in other viscera from rats and guinea pigs.

Animals↗

PubMed1989

Functional and biochemical characterization of the human gallbladder muscularis cholecystokinin receptor.

Gallbladders removed at cholecystectomy are a potentially useful source of human receptor for the gastrointestinal peptide hormone cholecystokinin (CCK). Seven healthy gallbladders (removed incidentally at time of resection of hepatic metastases) and 50 diseased gallbladders were studied. Cholecystokinin radioligand binding to an enriched plasma membrane preparation from these tissues was shown to be rapid, reversible, temperature-dependent, saturable, specific, and high-affinity. Computer analysis of equilibrium binding data using the Ligand program best fit a single class of binding sites with Kd = 1.0 +/- 0.1 nM (mean +/- SEM). This was similar in health and disease, with no apparent differences related to age, gender, or body habitus. The structural specificity for binding to this site correlated well with relative potencies for CCK-gastrin peptides to stimulate gallbladder contraction. To biochemically characterize this receptor, we used a battery of reagents, including "long" (125I-Bolton Hunter-CCK-33) and "short" 125I-D-Try-Gly-[(Nle28,31)CCK-26-33] probes that were cross-linkable through their amino terminus and a monofunctional probe with a photolabile group at its carboxyl terminus 125I-D-Tyr-Gly[(Nle28,31,pNO2-Phe33)CCK-26-33]. All probes specifically labeled a human gallbladder muscularis protein of Mr = 85,000-95,000, which was also independent of diagnosis. Labeling of this band was inhibited in a concentration-dependent manner by CCK-8 and by L-364,718. Thus, the CCK receptor present on the very common surgically removed human gallbladder is functionally and biochemically intact and is useful for further characterization.

Adult↗

PubMed1990

Intrinsic nerves affect gallbladder contraction in the guinea pig.

Muscarinic antagonists block gallbladder contraction induced by cholecystokinin in vivo but have little effect on gallbladder muscle strips. This study examined the effect of neural blockade on cholecystokinin-octapeptide-induced contraction of the intact guinea pig gallbladder in vitro using cholecystokinin-octapeptide applied to the gallbladder serosa, the lumen, or both compartments simultaneously. Simultaneous cholecystokinin stimulation of both the lumen and serosa was the most potent stimulus to contraction, and the responses were significantly inhibited by atropine and tetrodotoxin. Cholecystokinin in the gallbladder lumen alone evoked contraction by a dose-dependent mechanism that was entirely blocked by atropine or tetrodotoxin. Serosal application of cholecystokinin was the least potent, resulting in contractile responses and low sensitivity to neural blockers comparable to effects reported in muscle strips. The results suggest that cholecystokinin can cause gallbladder contraction by stimulating muscle receptors, neural receptors, or both, and combined neural and muscular stimulation is the most potent contractile stimulus.

Animals↗

PubMed1992

Calcium and carbonate ion concentrations in gallbladder and hepatic bile.

Calcium carbonate is a major component of gallstones, but there are few data on calcium and carbonate (CO3(2-)) concentrations in human bile. Therefore, in patients undergoing cholecystectomy for gallstones, total [CaTOT] and free ionized [Ca2+] calcium concentrations, pH, PCO2, and total [CO2] were measured and [CO3(2-)] was derived in gallbladder and hepatic bile (aspirated anaerobically at surgery or from T tubes). Gallbladder bile had lower pH (6.96 vs. 7.30) and total [CO2] (14.1 vs. 21.6 mmol/L), higher PCO2 (53.8 vs. 40.2 mm Hg), lower [CO3(2-)] (2.52 vs. 6.11 x 10(5) mol/L) and lower [Ca2+] x [CO3(2-)] ion product (1.88 vs. 4.74 x 10(-8) mol/L) than did hepatic bile. Gallbladder bile pH correlated positively with total [CO2], [CO3(2-)], and [Ca2+] x [CO3(2-)] but negatively with PCO2. Patients with surface gallstone calcification had similar gallbladder bile [CaTOT] and [Ca2+] but higher gallbladder bile pH (7.30 vs. 6.90), lower PCO2 (42.9 vs. 57.2 mm Hg), higher [CO3(2-)] (7.29 vs. 1.84 x 10(-5) mol/L), and higher [Ca2+] x [CO3(2-)] ion product [4.73 vs. 1.45 x 10(-8) (mol/L)2] than those with radiolucent gallstones. There were no differences in these parameters between patients with cholesterol stones and those with pigment stones. These data suggest that the human gallbladder acidifies bile by secreting hydrogen ion and that impairment of this secretion is one cause of calcified gallstone formation in humans.

Adult↗

PubMed1993

Characterization of muscarinic receptors on guinea pig gallbladder smooth muscle.

BACKGROUND: Cholinergic agonists are of major importance for the regulation of gallbladder motility. However, the gallbladder muscarinic receptors have not been localized or characterized directly using radioligands, and it has not been clearly established which subtype of muscarinic receptor mediates contraction. The aim of the present study was to characterize the gallbladder muscarinic receptors. METHODS: Binding studies to guinea pig gallbladder sections were performed using 1-[N-methyl-3H] scopolamine methyl chloride. Carbachol-induced contraction was measured using muscle strips. RESULTS: Binding of 1-[N-methyl-3H] scopolamine methyl chloride was reversible, dependent on time, temperature, and pH. Autoradiography showed binding only over the smooth muscle. Binding and carbachol-induced contractions were inhibited by muscarinic receptor antagonists with the following potencies: atropine > N-methyl-scopolamine > silahexocyclium-methylsulfate > AF-DX 384 [(+-)-5,11-dihydro-11-([(2-(2-[(dipropylamino)-methyl]-1- piperidinyl)ethyl)amino]carbonyl)-6H-pyrido (2,3b) (1,4)-benzodiazepine-6-one] > hexahydro-siladifenidol hydrochloride > AF-DX 116 [(+-)-11-([2-[(diethylamino)methyl]-1- piperidinyl]-acetyl)-5,11-dihydro-6H-pyrido (2,3b)(1,4)benzodiazepine-6-one] > pirenzepine. Carbachol inhibited binding to gallbladder sections over the same range of concentrations that caused contractions. The concentration-contraction curves for carbachol were not altered by tetrodotoxin. CONCLUSIONS: Gallbladder smooth muscle cells possess muscarinic receptors of the M3 type. These receptors mediate carbachol-induced contraction.

Animals↗

PubMed1995

Gallbladder emptying in vivo, bile composition, and nucleation of cholesterol crystals in patients with cholesterol gallstones.

BACKGROUND/AIMS: Impaired postprandial gallbladder emptying may provide time for progressive bile concentration with formation of instable cholesterol-rich vesicles and fast nucleation of cholesterol crystals. The aim of this study was to assess postprandial gallbladder emptying, bile composition, and nucleation of cholesterol crystals in the same patient. METHODS: In 30 patients with cholesterol gallstones, postprandial gallbladder emptying was measured ultrasonographically. In each patient, gallbladder bile composition (obtained at cholecystectomy) and nucleation of cholesterol crystals was determined. Patients were divided in 22 strong contractors (> 50% postprandial gallbladder emptying) and 8 weak contractors. RESULTS: In weak contractors, bile salt and phospholipid concentrations were much higher than in strong contractors (234.6 +/- 24.7 vs. 130.3 +/- 10.8 mmol/L [P < 0.001] and 44.5 +/- 3.5 vs. 30.2 +/- 3.1 mmol/L [P < 0.05], respectively). Cholesterol concentrations were comparable in strong and weak contractors. Consequently, total lipid concentration was significantly higher (15.5 +/- 1.4 and 9.2 +/- 0.7 g/dL; P < 0.001) and cholesterol saturation index significantly lower (0.90 +/- 0.08 and 1.61 +/- 0.17; P < 0.001) in weak contractors. Nucleation time, percentage of cholesterol in vesicles, bile salt species, and molecular species of phosphatidylcholine were not significantly different. CONCLUSION: Differences in bile composition can be linked to different patterns of postprandial gallbladder emptying and may point to two different pathways of gallstone formation.

Adult↗

PubMed1991

Heterotopic gastric mucosa in the gallbladder: a cause of chronic abdominal pain in a child.

A 12-year-old boy presented with a 7-year history of intermittent colicky epigastric pain. Serial abdominal ultrasound studies showed a contracted gallbladder, and single and double dose oral cholecystograms demonstrated nonfunction. All other investigation results were normal. At cholecystectomy, there was a fibrotic stricture at the junction of the gallbladder neck and cystic duct. The small, thin-walled gallbladder contained white bile. Histologically, the gallbladder was lined with normal mucous secreting columnar epithelium. The area of stricture showed diffuse fibrosis with islands of heterotopic gastric mucosa containing all gastric mucosal cell types. One year postoperatively, there have been no further episodes of abdominal pain. This is the seventh reported case of heterotopic gastric mucosa in the gallbladder of a child causing symptoms necessitating cholecystectomy. We recommend that a child with abdominal pain and a nonfunctioning gallbladder be considered for cholecystectomy even in the absence of cholelithiasis.

Abdominal Pain↗

PubMed1991

Histopathology of the donor gallbladder removed at orthotopic liver transplantation: correlation with graft function.

The histopathology of 50 consecutive donor gallbladders removed during orthotopic liver transplantation was reviewed and correlated with graft function. Multiple sections of the gallbladders were examined for the presence of mucosal congestion, hemorrhage, and necrosis, without prior knowledge of the clinical outcome. Each pathologic feature was graded as absent (0), involving less than 10% (1+), 10% to 50% (2+), or more than 50% (3+) of the histologically examined mucosa. Graft function was determined by two transplant surgeons, a poor diagnosis being worsening of liver function tests associated with declining mental status and resulting in immediate retransplantation or early postoperative death; all others were categorized as good. Of 39 patients with good graft function, 18 had normal donor gallbladders, 11 had congestion only, and 10 had hemorrhage and/or necrosis. Of 11 patients with poor graft function, eight had hemorrhage and/or necrosis (2+ in seven), three had congestion only, and none had a normal gallbladder mucosa. Congestion alone was found to be a poor predictor of graft damage. Presence of any grade of hemorrhage and/or necrosis in donor gallbladders as related to poor liver graft function had a sensitivity of 73%, a specificity of 74%, a positive predictive value of 44%, and a negative predictive value of 91%. When hemorrhage and/or necrosis of 2+ severity was separately grouped and correlated with poor graft function, the specificity rose to 97% and the positive predictive value to 88%, and the negative predictive value was similar at 90%. We conclude that donor gallbladders often show mucosal abnormalities consisting of varying degrees of congestion, hemorrhage, and necrosis. The finding of hemorrhage and/or necrosis affecting more than 10% of the mucosa appears to be a specific lesion of ischemic damage that correlates highly with poor liver graft function.

Gallbladder↗

PubMed1993

Effect of neurotensin on the canine gallbladder motility: in vivo and in vitro experiments.

Neurotensin (NT) (10(-8)-10(-6)) exerted a dose-dependent increase in the tone and release of [3H]ACh in the guinea-pig gallbladder muscle strips but was inefficient in the canine gallbladder muscle strips. However, in conscious dogs NT (2.5-20 ng/kg intravenously (i.v.)) dose-dependently increased the gallbladder pressure. Similar was the effect of CCK8 (1-10 ng/kg i.v.) and carbachol (0.5-2 micrograms/kg i.v.). The NT- or CCK8-induced gallbladder pressure was inhibited by atropine (10-50 micrograms/kg i.v.) or hexamethonium (0.5-3 mg/kg i.v.). Somatostatin (1-2 micrograms/kg i.v.) or VIP (0.5-1 microgram/kg i.v.) also reduced or even abolished the NT- or CCK8-induced gallbladder pressure. The NT-induced increase of the tone of guinea-pig gallbladder preparations was accompanied by an increase of [3H]ACh release, suggesting the involvement of cholinergic innervation.

Acetylcholine↗

PubMed1996

MRI of acute cholecystitis: comparison with the normal gallbladder and other entities.

Our purpose was to prospectively compare MRI findings with histopathologic findings in the evaluation of suspected acute cholecystitis. Fourteen patients with clinically suspected acute cholecystitis were entered into the study. MR sequences included T1-weighted fat-suppression and breath-hold spoiled gradient echo (SGE) before and after intravenous gadolinium chelate administration. Percent contrast enhancement (%CE) of the gallbladder wall and gallbladder wall thickness (WT) were measured and liver enhancement patterns determined prospectively on MR images. Correlation was obtained with pathological findings at cholecytectomy in all patients. In a second phase of the study MR images on 10 additional subjects who underwent MR examination for reasons other than hepatobiliary disease were analyzed to determine normal values for %CE and gallbladder wall thickness. Mean %CE was 124.0% in patients with acute cholecystitis (10 patients), 58.0% in patients with chronic cholecystitis (2 patients), and 73.0% in patients with gallbladder malignancy (2 patients). Mean gallbladder WT was 6.1 mm in acute cholecystitis, 4.5 mm in chronic cholecystitis, and 6.0 mm in malignant disease. There was a significant difference in %CE between acute and chronic cholecystitis (p = 0.03); no other significant differences in %CE or WT were observed among the patients with gallbladder disease. Patients without biliary disease had %CE of 37.3% and WT of 2.9 mm, which were both significantly less (p < 0.001) than in patients with acute cholecystitis. Transient enhancement of pericholecystic hepatic parenchyma on immediate postgadolinium SGE images was seen in 7 of 10 patients with acute cholecystitis, and not observed in other patients. Patients with acute cholecystitis had increased %CE and WT on MR images that were significantly greater than normal and %CE that was significantly greater than in patients with chronic cholecystitis. Transient increased pericholecystic hepatic enhancement was observed in 70% of acute cholecystitis patients and in no other patient groups.

Acute Disease↗

PubMed1991

The effect of vasoactive intestinal polypeptide (VIP) on the canine gallbladder motility.

1. VIP at doses of 10(-9) to 10(-8) M was ineffective and at doses of 5 x 10(-8) to 10(-7) M exerted a slight inhibitory effect on the tone of the canine gallbladder muscle strip. However, VIP (0.1-1 micrograms/kg) injected intravenously (i.v.) in conscious dogs dose-dependently decreased the gallbladder pressure. 2. VIP did not influence significantly the acetylcholine (ACh)- or carbachol- induced contractions of canine gallbladder under in vitro or in vivo conditions, but it decreased the electrically-induced, atropine-sensitive contractions of gallbladder muscle strips. 3. VIP (5 x 10(-9) to 5 x 10(-8) M) did not influence significantly the dose-response curve for cholecystokinin octapeptide (CCK OP) of canine and guinea-pig gallbladder muscle strips. VIP injected i.v. (0.1-0.5 micrograms/kg) in conscious dogs greatly decreased the CCK OP-induced gallbladder pressure.

Adult↗

PubMed2006

Apolipoprotein E genotype and gallbladder disease risk in a large population-based cohort.

PURPOSE: The aim of the study is to describe the association between apolipoprotein E (apoE) genotype and gallbladder disease incidence. METHODS: Cases of incident hospitalized gallbladder disease were ascertained in nearly 13,000 middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study in four US communities. RESULTS: Between the ARIC baseline examination (1987 to 1989) and December 31, 2001, a total of 639 participants were hospitalized for gallbladder disease. After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes, the relative risk for hospitalized gallbladder disease associated with the presence of an epsilon4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by race showed that the inverse association with epsilon4 was stronger in whites (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk, 0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, epsilon2 (i.e., genotypes E2/2, E2/3, and E2/4 versus others) was associated with a modest increased risk for gallbladder disease (relative risk, 1.28; 95% CI, 1.05-1.57). CONCLUSIONS: These results suggest that independent of traditional risk factors, apoE genotype may influence gallbladder disease risk, particularly in whites. The exact biologic mechanism for such an association remains unclear and requires further investigation.

Apolipoproteins E↗

PubMed2006

Arsenic trioxide induces gallbladder carcinoma cell apoptosis via downregulation of Bcl-2.

Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of apoptotic stimuli. Here, we report for the first time the pro-apoptosis role of arsenic trioxide (As2O3) in gallbladder carcinoma and identify the contribution of Bcl-2 in the As2O3-induced apoptosis. The treatment of As2O3 in gallbladder carcinoma cells could induce apoptosis in a dose-dependent manner and downregulate the expression of anti-apoptotic protein Bcl-2 at mRNA level. Moreover, Bcl-2 overexpression could protect gallbladder carcinoma cells from As2O3-induced apoptosis, indicating the contribution of Bcl-2 in As2O3-induced apoptosis. Taken together, these results suggest that arsenic trioxide induces gallbladder carcinoma cell apoptosis via downregulation of Bcl-2, which may have important therapeutic implications in gallbladder carcinoma patients.

Antineoplastic Agents↗

PubMed2005

Resection of lung metastasis from gallbladder carcinoma: immunohistochemistry of RCAS1 and CD8+T cells in primary and metastatic tumors.

Advanced Gallbladder cancer has an extremely poor prognosis. We examined a patient with resectable gallbladder cancer with associated lung metastasis. A 64-year-old female patient, diagnosed with gallbladder cancer and a solitary benign lung tumor by imaging, was subjected to extensive cholecystectomy and extrahepatic bile duct resection. After one year, a follow-up CT indicated enlargement of the lung tumor; video-assisted right middle lobectomy was then performed. The lung tumor was diagnosed as a metastasis derived from the gallbladder cancer by pathology and immunohistochemistry. Expression of RCAS1, an independent unfavorable prognostic indicator in gallbladder cancer, was observed in both the gallbladder and lung tumors. However, infiltration of CD8+T cells was only seen in the lung metastatic tumor. She has remained free of any evidence of recurrence in the 10 months and 4 years after the first surgery. The results that metastasis is solitary and infiltrated by CD8+T cells correspond with the present clinical history.

Adenocarcinoma, Papillary↗

PubMed2006

Contrast enhanced sonography of the gallbladder: a tool in the diagnosis of cholecystitis?

RATIONALE AND OBJECTIVES: To evaluate if contrast enhanced sonography (CES) can help to detect gallbladder inflammation and differentiate between acute and chronic cholecystitis. MATERIALS AND METHODS: Thirty-three patients with clinical suspicion of acute cholecystitis were examined with CES before cholecystectomy. Thirty patients with no history of gallbladder disease served as control. CES was performed using 2.5 mL SonoVue. A small mechanical index was chosen (0.1). The enhancement pattern of the gallbladder was ranked in a three-point scale: no enhancement, low enhancement and strong enhancement. 28/33 patients underwent surgery. Sonographic findings were compared to histological results. RESULTS: In 16/20 cases with histological proven acute cholecystitis, the gallbladder wall showed a strong enhancement. Low enhancement was found in four patients with acute and in six patients with chronic cholecystitis. The gallbladder wall of two patients with chronic inflammation and all patients (30/30) of the control group showed no enhancement. CONCLUSION: CES is a feasible tool for detecting gallbladder inflammation. Differentiating between acute and chronic cholecystitis seems to be possible.

Acute Disease↗