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K-ras gene mutation in gall bladder carcinomas and dysplasia.

Epithelial dysplasia of gall bladder is an important precancerous lesion of gall bladder carcinogenesis. To investigate the frequency of K-ras gene mutation in gall bladder carcinoma and dysplasia, K-ras codon 12 mutations were investigated by the polymerase chain reaction/restriction enzyme based method following direct sequencing. Mutation was detected in 59% (30 of 51) of gall bladder carcinomas, in 73% (8 of 11) of gall bladder dysplasia in gall stone cases, and in 0% of the normal gall bladder epithelium. There was, however, no correlation between K-ras mutation and clinicopathological factors of gall bladder carcinoma. K-ras gene mutation occurs even in gall bladder dysplasia at an incidence similar to that in carcinomas, suggesting that testing for K-ras gene mutation may prove useful as an adjunct to bile cytological or biopsy analysis.

Base Sequence↗

Gall bladder emptying in severe idiopathic constipation.

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.

Adult↗

Increased sphincter of Oddi basal pressure in patients affected by gall stone disease: a role for biliary stasis and colicky pain?

BACKGROUND AND AIMS: Even if the motor activity of the gall bladder and sphincter of Oddi (SO) are integrated, it is not known if the presence of stones in the gall bladder affects SO function. The aim of the study was to compare SO motor activity in patients with and without gall stones. PATIENTS AND METHODS: In a series of 155 patients consecutively submitted to endoscopic retrograde cholangiopancreatography and SO manometry for suspected biliary or pancreatic disease, 23 gall stone patients had recurrent episodes of biliary or pancreatic pain (colicky group); 52 patients had non-biliary/pancreatic-type abdominal pain/discomfort, and of these, 15 had gall stones (non-colicky group), 25 were free of stones (controls), and 12 had undergone cholecystectomy. RESULTS: SO basal pressure in gall stone patients in the colicky or non-colicky group was significantly higher than in controls (p<0.001). SO basal pressure recorded in postcholecystectomy patients did not differ from controls. SO phasic activity did not differ between the patient groups. SO dysfunction was detected in more than 40% of gall stone patients irrespective of associated biliary/pancreatic pain but in none of the control subjects (p<0.001). CONCLUSIONS: Gall stones are frequently associated with increased SO tone which may obstruct bile flow thus acting to facilitate gall bladder stasis, and may play a role as a cofactor in biliary/pancreatic pain.

Adolescent↗

Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial.

BACKGROUND: Octreotide inhibits gall bladder emptying and prolongs intestinal transit. This leads to increases in the proportion of deoxycholic acid in, and cholesterol saturation of, gall bladder bile, factors that contribute to the pathogenesis of octreotide induced gall stones. AIMS: To see if an intestinal prokinetic, cisapride, could overcome these adverse effects of octreotide and if so, be considered as a candidate prophylactic drug for preventing iatrogenic gall bladder stones. METHODS: A randomised, double blind, placebo controlled, crossover design was used to examine the effects of cisapride (10 mg four times daily) on gall bladder emptying, mouth to caecum and large bowel transit times, and the proportions of deoxycholic acid and other bile acids, in fasting serum from: (i) control subjects (n=6), (ii) acromegalic patients not treated with octreotide (n=6), (iii) acromegalics on long term octreotide (n=8), and (iv) patients with constipation (n=8). RESULTS: Cisapride had no prokinetic effect on the gall bladder. In fact, it significantly increased both fasting and postprandial gall bladder volumes. However, it shortened mouth to caecum (from 176 (13) to 113 (11) minutes; p<0.001) and large bowel (from 50 (3.0) to 31 (3.4) h; p<0.001) transit times. It also reduced the proportion of deoxycholic acid in serum from 26 (2.3) to 15 (1.8)% (p<0.001), with a reciprocal increase in the proportion of cholic acid from 40 (3.5) to 51 (3.8)% (p<0.01). There were significant linear relationships between large bowel transit time and the proportions of deoxycholic acid (r=0.81; p<0.001) and cholic acid (r=-0.53; p<0.001) in fasting serum. INTERPRETATION/SUMMARY: Cisapride failed to overcome the adverse effects of octreotide on gall bladder emptying but it countered octreotide induced prolongation of small and large bowel transit. Therefore, if changes in intestinal transit contribute to the development of octreotide induced gall bladder stones, enterokinetics such as cisapride may prevent their formation.

Acromegaly↗

Distribution and frequency of galls induced by Anisodiplosis waltheriae Maia (Diptera: Cecidomyiidae) on the invasive plant Waltheria indica L. (Sterculiaceae).

The frequency of galls induced by Anisodiplosis waltheriae Maia, a recently described species, on Waltheria indica L. was studied. W indica is an invasive weed in regeneration areas of Atlantic Forest in southeastern Brazil. Plants were collected in May 2004 and above-ground biomass, main stem length, number of leaves, number of galls per leaf and leaf area of each individual were recorded. Nearly 90% of all plants and 25% of all leaves were attacked by the gall midge, with an average of 0.67 galls/leaf. Leaf area had a weak effect on gall abundance while the number of leaves had no effect on gall abundance. Only 31% of the variation in gall abundance was explained by plant biomass. Natural enemies killed one third of the sampled galls. Predation accounted for 22.9% of gall mortality, unknown factors killed 7.6%, microhymenopteran parasitoids killed 2.5% and fungi only 1%. Mortality factors were not influenced by leaf area or gall density.

Animals↗

Diversity of galling arthropods and host plants in a subtropical forest of Porto Alegre, southern Brazil.

Many hypotheses have been proposed to explain diversity patterns of galling insects. However, there are contradictory evidences on the evolutionary and ecological factors responsible for the trends. Furthermore, questions such as arthropod seasonality, sampling sufficiency and sampling team experience have been almost ignored. This study records galling arthropod diversity while paying attention to these questions. Seasonal sampling of galling arthropods and host plants were conducted in a humid subtropical forest of southern Brazil. Four transects were sampled twice per season, with two persons searching the vegetation for galls during 1h30min. After 96h.persons of sampling, 130 gall morphotypes on 84 species of host plants were recorded. An analysis of the numbers of galls and gall morphotypes found per transect along time showed that sampling team experience influences galler richness results and the interpretation of galler seasonality patterns. Different species had distinct seasonal patterns. Galling arthropod richness was bound to plant richness. Our results suggest that sampling team experience is an important factor that must be explicitly considered, as well as seasonality patterns of different galling species, at least for tropical/subtropical areas. Although sampling sufficiency was not reached, fauna heterogeneity at small spatial scales seems substantial: despite the proximity of the sampled transects (500 m), they harboured significantly specific faunas. This work adds to the literature records suggesting that both plant richness and specific composition of the vegetation have a strong influence on galler richness at least for local scales.

Animals↗

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.

Adult↗

[Plasma endothelin levels in patients with multiple organ dysfunction syndrome caused by fish gall bladder poisoning].

OBJECTIVE: To investigate the correlation between the change of plasma endothelin (ET) and the occurrence and progress of multiple organ dysfunction syndrome (MODS) caused by fish gall bladder poisoning. METHODS: Plasma ET was measured in 85 patients with fish gall bladder poisoning and 30 healthy controls and comparison of the levels of plasma ET was carried out between patients groups with different severity of fish gall bladder poisoning. The relationship between plasma ET levels and enzymology as well as some biochemistry indexes in patients with fish gall bladder poisoning was then analyzed. RESULTS: Plasma ET in patients with fish gall bladder poisoning (150.5 +/- 90.5) ng/L was much higher than that in controls (52.8 +/- 9.3) ng/L. The concentration of plasma ET in slight poisoning group (61.2 +/- 13.6) ng/L increased a little, but it was not significantly different with that in controls (P > 0.05). The concentration of plasma ET was significantly higher in moderate poisoning group and severe poisoning group (162.3 +/- 82.3) ng/L and (232.6 +/- 92.7) ng/L as compared with that in the controls (P < 0.01), with the severe poisoning group much higher than the moderate poisoning group and the latter much higher than the normal. At the same time, plasma ET in MODS group and non-MODS group (210.2 +/- 98.7) ng/L and (126.3 +/- 68.3) ng/L were both notably higher than that in the controls. Furthermore plasma ET in the MODS group was much higher than that in the non-MODS (P < 0.01). It was also found that a positive correlation existed between plasma ET and creatine kinase-MB, cardiac troponin I, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and serum creatinine (P < 0.01) and a negative correlation between plasma ET and endogenous creatinine clearance rate (P < 0.01). CONCLUSION: Plasma ET may be involved in the process of fish gall ladder poisoning and later in the progress of MODS. It was shown that the higher the level of plasma ET, the severer the degree of poisoning and the higher the fatality rate. So monitoring plasma ET level dynamically may be an important clinical index in judging the patients condition and their prognosis in fish gall bladder poisoning. Simultaneously it is useful for earlier diagnosis of fish gall bladder poisoning and alertness of MODS caused by it as well as for proper management with antagonist and inhibitor against plasma ET for prevention and cure of fish gall bladder poisoning.

Adult↗

Regional differences in constituents of gall stones.

The pathogenesis of pigment and mixed gall stone formation remains elusive. The elemental constituents of gall stones from southern states of Tamil Nadu, Kerala and Karnataka have been characterized. Our aim was to determine the elemental concentration of representative samples of pigment, mixed and cholesterol gall stones from Andhra Pradesh using proton-induced X-ray emission (PIXE) using a 3 MV horizontal pelletron accelerator. Pigment gall stones had significantly high concentrations of copper, iron and lead; chromium was absent. Except for iron all these elements were significantly low in cholesterol gall stones and intermediate levels were seen in mixed gall stones. Highest concentrations of chromium was seen in cholesterol and titanium in mixed gall stones respectively; latter similar to other southern states. Arsenic was distinctly absent in cholesterol and mixed gall stones. The study has identified differences in elemental components of the gall stones from Andhra Pradesh.

Cholesterol↗

Gall bladder dysmotility in diabetes mellitus--an ultrasound study.

Fifty two diabetic patients and 15 healthy control subjects were prospectively studied for their gall bladder function by ultrasound examination. The fasting gall bladder volume (FGBV) was calculated by using ellipse formula from the dimension of gall bladder shadow seen on ultrasound screen in two different cuts. The contractility of gall bladder was measured by calculating post prandial ejection fraction (EF) of the gall bladder. The mean FGBV and EF in 52 diabetic patients was found to be 20.7 +/- 10.7 cc and 47.5 +/- 20.1%, which was not significantly different from that in normal controls. Age, sex, obesity, diabetic control and presence of dyspeptic symptoms had no impact in FGBV and EF. Diabetic symptoms had no impact in FGBV and EF. However, diabetics with longer duration of disease had poorer gall bladder contractility (p < 0.05). Patients with autonomic neuropathy (AN) had significantly larger FGBV but normal contractility. Our results suggest that (a) long standing diabetics may have poor gall bladder emptying predisposing to gall stone formation (b) patients with autonomic neuropathy have reduced tone of fasting gall bladder but normal contractility.

Adult↗

Sympathetic and VIP-ergic control of calcium and bicarbonate transport in the feline gall bladder mucosa in vivo.

The regulation of calcium ion absorption by the gall bladder mucosa may be important for gall stone formation but this process is poorly understood. In this study performed in anaesthetized cats, the gail bladder lumen was perfused by a buffer equilibrated with 4% CO2 in air. During basal conditions, the pH and the [Ca2+] x [CO3(2-)] ion product decreased in the buffer when passing through the gall bladder lumen. The net absorption of calcium ions and fluid was significantly enhanced by stimulation of the splanchnic nerves. Intravenous infusion of vasoactive intestinal peptide (VIP) increased pH and the [Ca2+] x [CO3(2-)] ion product significantly in the buffer during the passage through the gall bladder lumen. Moreover, the basal fluid absorption was reversed to a net fluid secretion. In view of the presence of noradrenergic and VIP-immunoreactive nerve fibres in the gall bladder wall, and VIP-receptors on the gall bladder epithelial cells, the study suggests the existence of neural control mechanisms influencing the transport of Ca2+ by the gall bladder mucosa. These may be important to reduce potential calcium lithogenicity in the gall bladder lumen.

Animals↗

Effects of ethanol on contractile response of gall bladder isolated from guinea pig.

The effects of ethanol treatment in vitro and in vivo on gall bladder contraction were investigated using gall bladder strips isolated from guinea pigs. In vitro pretreatment of the strips with ethanol at a concentration of over 50 mM significantly attenuated the reactivity and sensitivity of contractile responses to KCl, acetylcholine and histamine in a concentration-dependent manner. Indomethacin treatment or removal of extracellular calcium remarkably reduced gall bladder contractile response to acetylcholine. The depressive effect of ethanol in vitro on gall bladder contraction was also noted in the presence of indomethacin or absence of calcium in the medium. The concentration-response curve of calcium-induced contraction in 40 mM KCl-depolarized gall bladder strip shifted to the right on pretreatment with ethanol. In the case of strips following the chronic administration of 3% ethanol solution ad libitum for 4 weeks, contractile responses to KCl, acetylcholine and histamine did not differ, compared to those in the pair-fed group. This chronic ethanol administration induced tolerance to the acute inhibitory effect of ethanol on gall bladder contractile responses to the agonists. Ethanol is thus shown to exert direct inhibitory action on gall bladder contraction by lowering the calcium sensitivity of the contractile apparatus of smooth muscle; it is unlikely that ethanol consumption would affect gall bladder motility in vivo, owing to the tolerance produced toward the acute inhibitory action of ethanol.

Acetylcholine↗

Isolation of Escherichia coli O157:H7 from the gall bladder of inoculated and naturally-infected cattle.

To determine if Escherichia coli O157:H7 is capable of residing in the gall bladder of cattle, inoculation studies were conducted with O157:H7 strain 86-24 in weaned Holstein calves. Strain 86-24 was isolated from the gall bladders of five calves 36 days after inoculation. Two other calves contained the inoculation strain in the distal colon but the organism was absent in their gall bladders. A second trial in which the calves were euthanized 15 days after inoculation found strain 86-24 in six of seven inoculated calves but only in colon and/or rumen samples. In a third trial that inoculated eight calves with a four-strain cocktail of O157:H7 strains, the gall bladders from all eight animals were positive 9 days after inoculation. The colon and rumen samples from these calves were also positive. E. coli O157:H7 isolates recovered from bile samples and subtyped by pulsed field gel electrophoresis found that three of the four inoculation strains were present in one or more of the calves. Thus, residence in the gall bladder is not restricted to a single strain. Additional evidence of the ability to localize in the gall bladder of cattle was provided by testing the bile from 150 gall bladders (five collection dates, 30 samples each) obtained at an abbatoir and the isolation of E. coli O157:H7 from four samples (2.7%). This study establishes that E. coli O157:H7 can reside transiently or permanently at a low level in the gall bladder of cattle.

Animals↗

Radiological aspects of solvent dissolution of gall-stones.

Twenty-five patients were referred for solvent dissolution of gall-stones using methyl tertiary butyl ether (MTBE). All patients were assessed beforehand by ultrasound and oral cholecystography. Computed tomography was performed in 23 patients to assess stone calcification and gall-bladder anatomy. Successful stone dissolution was achieved in 15 patients and partial dissolution in six patients. Failure to catheterize the gall-bladder occurred in four patients. There were four biliary leaks, two requiring cholecystectomy. The CT appearances of the gall-bladder may have predicted problems with catheterization in three of the four cases, and the results suggest that cover of the gall-bladder by the liver of greater than 50% is a favourable predictor of successful catheterization. A thick-walled gall-bladder and excess fat between the liver and the lateral abdominal wall are adverse predictors of successful gall-bladder catheterization. Both tubography and ultrasound should be used to assess progress of dissolution. Newer, more effective solvents together with increased expertise in interventional techniques may encourage the more widespread use of solvent dissolution of gall-stones as an alternative to surgery in a selected population.

Adult↗

Tension and stress calculations in a 3-D Fourier model of gall bladder geometry obtained from MR images.

Biliary tract obstruction results in dilatation of the biliary tract including the gall bladder and induction of symptoms such as abdominal pain. Since the pain receptors are likely mechano-sensitive receptors, it is important to develop tools for studying the distributions of tension and stress in the wall of the gall bladder. Wall tension and stress can be determined using Laplace's equation and the three-dimensional (3-D) geometry of a thin walled organ under equilibrium conditions. The objective of this study was to develop an analytical method to describe the 3-D geometry of the porcine gall bladder. The Fourier series method was used to describe the organ surface geometry obtained from magnetic resonance (MR) images. MR images of nine normal and three obstructed porcine gall bladders were analyzed. The curvature was computed throughout the gall bladder surface and the wall tension was computed using Laplace's equation. The spatial distributions of principal curvatures, tensions, and stresses were nonhomogeneous in the gall bladder because of its complex geometry. The extremum values of curvatures did not differ between normal and 2-day obstructed gall bladders. The pressure, tension, and stress were significantly higher, however, in the obstructed gall bladders (p < 0.05). This study provides an analytical tool for characterizing the complex 3-D geometry of an organ obtained from a clinical imaging modality.

Anatomy, Cross-Sectional↗

Naloxone increases mucosal fluid secretion in the inflamed and distended feline gall bladder: evidence for a possible protective mechanism by endogenous opioids.

1. Endogenous opioid peptides are found in the enteric nervous system in the gastrointestinal tract. The opioid peptide enkephalin, which has anti-secretory action in the small intestine, is also contained in nerves in the gall-bladder wall. 2. In experimental cholecystitis, there is active fluid secretion by the epithelial cells into the gall-bladder lumen, when the intraluminal hydrostatic pressure is low. This fluid secretion to the lumen was abolished by intravenous administration of enkephalin, an effect that was blocked by naloxone pretreatment. The flux of fluid into the lumen was also abolished when the intraluminal hydrostatic pressure was raised to the level initially observed in the inflamed and obstructed gall bladder. Fluid absorption in the normal gall bladder was unaffected by enkephalin. 3. In experimental cholecystitis, naloxone, used as a non-specific antagonist of opiate action, did not affect the gall-bladder mucosal fluid transport observed at a low intraluminal hydrostatic pressure, but it induced fluid secretion when this pressure was high. 4. It is suggested that a raised intraluminal hydrostatic pressure in experimental cholecystitis, which distends the gall bladder, releases endogenous opioids that inhibit active fluid secretion by the gall-bladder epithelial cells. This response may represent a defence mechanism that could be present also in the gastrointestinal tract. In the obstructed and inflamed gall bladder it may prevent progressive distension, ischaemia and perforation of the wall.

Animals↗

Naloxone-reversible inhibition of gall-bladder mucosal fluid secretion in experimental cholecystitis in the cat by acetorphan, an enkephalinase inhibitor.

1. Enkephalin immunoreactive nerve fibres have been demonstrated in the gall bladder of various mammals including man. In various tissues, enkephalins are partly degraded by a membrane metallo-endopeptidase, enkephalinase (EC 3.4.24.11). 2. Using 3H-labelled [D-Ala2,Leu5]enkephalin as a substrate, enkephalinase activity, immunoprecipitated by a monoclonal antibody directed against the rabbit kidney enzyme, was demonstrated in the feline gall bladder. Using the same antibody in 125I-labelled form, the peptidase was immunolocalized by autoradiography, mainly in the epithelium. 3. In experimental cholecystitis, elicited by implantation of human gall-stones into the cat gall bladder, the continuous fluid secretion into the lumen was inhibited by exogenous enkephalins. 4. Acetorphan, an enkephalinase inhibitor, was found to block fluid secretion by the inflamed gall bladder via a naloxone-sensitive mechanism, but not to affect fluid transport in the normal gall bladder. The drug also transiently contracted the gall bladder and increased bile outflow from the liver. 5. It is suggested that acetorphan, by reducing the degradation of endogenous enkephalins in the inflamed gall bladder, decreases fluid secretion by the epithelium and that enkephalinase inhibitors may find clinical applications in acute cholecystitis.

Animals↗

Review article: control of gall-bladder motor function.

Muscular contraction of the gall-bladder is the primary determinant of bile delivery into the duodenum. Where bile goes following its secretion by the liver depends upon a co-ordinated series of pressure interrelations between the hepatic secretory pressure at the entrance to the biliary system, a low pressure conduit, and the pressure differences between the gall-bladder, cystic duct and sphincter of Oddi. During fasting, the relatively higher tone in the sphincter of Oddi fosters the entry of bile into the gall-bladder. The gall-bladder accommodates this influx without an increase in intravesicular pressure through its compliance or distensibility, which consists of active muscle relaxation and passive fibroelastic components. The concentrating function of the gall-bladder keeps the volume small. Once about every 120 min during the interdigestive period, gall-bladder emptying occurs coincident with intense duodenal contractions; all part of the migratory myoelectric complex. This helps maintain the enterohepatic circulation of bile salts. Motilin, which mediates these events during fasting, acts by stimulating intrinsic cholinergic nerves. Cholecystokinin is the major determinant of gallbladder emptying with eating. Cholecystokinin acts through pre-ganglionic cholinergic nerves, to initiate gall-bladder contraction. Agonists like cholecystokinin and acetylcholine cause contraction of gall-bladder smooth muscle through signal transduction, which increases intracellular calcium levels and so initiates the contractile machinery. Cholecystokinin also acts on the sphincter of Oddi via pre-ganglionic cholinergic nerves to release vasoactive intestinal polypeptide and nitric oxide, and so lower tone. These events are co-ordinated with motility and secretory events in the upper gastrointestinal tract, delivering bile at appropriate times into the duodenum.

Cholecystokinin↗