[Dysfunction of the Oddi's sphincter].
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Common Bile Duct Diseases↗
Biomedical subjects
J Toouli
Publications and source records attributed to J Toouli.
Erythromycin and motilin stimulate sphincter of Oddi motility and inhibit trans-sphincteric flow in the Australian possum.
The actions of erythromycin lactobionate and porcine motilin on trans-sphincteric flow and simultaneous sphincter of Oddi motility were studied in 15 anaesthetized Australian Brush-tailed possums (Trichosurus vulpecula). Erythromycin (25-200 micrograms/kg) and motilin (25-200 ng/kg) were administered as graded doses by close intraarterial injection. Trans-sphincteric flow was measured as inflow and outflow. Both motilin and erythromycin decreased trans-sphincteric inflow (both P < 0.0001) and outflow (P < 0.0001 and P = 0.0017 respectively) in a dose-dependent manner. The highest dose of each agent abolished trans-sphincteric flow. These agents increased sphincter of Oddi phasic contraction frequency and basal pressure up to 2 and 3 fold respectively (P < 0.05). The amplitude of the sphincter of Oddi phasic contractions were not influenced in any consistent fashion by either agent. The durations of the responses (trans-sphincteric inflow) elicited by erythromycin and motilin were dose dependent (P = 0.0225 and P = 0.0001 respectively). The actions of erythromycin (200 micrograms/kg) or motilin (100 ng/kg) on trans-sphincteric flow and sphincter of Oddi motility were not influenced by neural blockade with tetrodotoxin. These findings support the hypothesis that erythromycin acts as a motilin agonist and both substances increase the resistance to flow through the sphincter of Oddi by raising the basal pressure and frequency of contractions.
Animals↗
Motilin and erythromycin enhance the in vitro contractile activity of the sphincter of Oddi of the Australian brush-tailed possum.
Erythromycin has been shown to interact with gastrointestinal smooth muscle in a similar manner to motilin, and has been postulated as a motilin receptor agonist. We report that in isolated preparations from the biliary tract of thirty one Australian Brush-tailed Possums (Trichosurus vulpecula) erythromycin acts in a similar manner to motilin. In all muscle strips from the sphincter of Oddi, prepared in both the circular and longitudinal orientation, both synthetic porcine motilin (10(-10) M-10(-6) M) and erythromycin (lactobionate) (10(-8) M-10(-4) M) stimulated contractile activity in a concentration dependent manner, via a direct effect on the smooth muscle (the response was unaffected by tetrodotoxin, omega conotoxin GVIA or atropine). In strips prepared from the gallbladder neither agonist affected the contractile activity in 7 of 8 animals. Motilin was approximately 1000 fold more potent in stimulating contractile activity than erythromycin in both sphincter of Oddi circular strips [pD2 for peak response to motilin 8.67 (mean) +/- 0.06 (SEM) compared with erythromycin 5.67 +/- 0.09] and sphincter of Oddi longitudinal strips [pD2 for peak response to motilin 8.64 (mean) +/- 0.28 (SEM) compared with erythromycin 5.45 +/- 0.23]. The concentration response curves for motilin and erythromycin were similar and both agonists required the presence of extracellular calcium to elicit responses (responses were diminished by verapamil and abolished in calcium free Krebs solution). Our results support the hypothesis that erythromycin mimics the action of motilin in stimulating the sphincter of Oddi in vitro.
Animals↗
Sphincter of Oddi regulates flow by acting as a variable resistor to flow.
Two models of transsphincteric flow and a model evaluating pumping activity were established in the anesthetized Australian brush-tailed possum to determine whether the sphincter of Oddi (SO) acts as a resistor or as a pump. A simple model of transsphincteric flow (inflow only) demonstrated that at physiological common bile duct (CBD) pressure, 9.5 +/- 0.3 cmH2O (n = 7), transsphincteric flow occurred between SO pressure waves (n = 10). A second more complex transsphincteric flow model was established that permitted simultaneous measurements of inflow, outflow, CBD pressure, SO basal pressure, SO contraction frequency, and amplitude. At physiological CBD pressure, inflow always equaled outflow (157.0 +/- 11.2 and 156.4 +/- 11.4 microliters/min, respectively; n = 7). The SO displayed regular contractions superimposed on a basal pressure of 1.1 +/- 0.4 mmHg. Contraction amplitude was 12.6 +/- 3.0 mmHg and the frequency was 3.6 +/- 0.4 contractions/min (n = 7). Pressure waves recorded in the CBD corresponded to the SO contractions and reflected SO activity. Transsphincteric flow occurred between SO contractions and was obstructed by these contractions. Stimulation of SO activity (basal pressure and contraction frequency) with intra-arterial injections of motilin (200 ng/kg) or erythromycin (200 micrograms/kg) abolished transsphincteric flow. Reduction in SO contraction frequency to 72.7 +/- 7.2% (P < 0.01, paired t test) after administration of Cisapride (2 mg/kg iv) increased transsphincteric flow to 147.6 +/- 12.3% (n = 7, P < 0.05, paired t test). In six possums, possible SO pumping action was evaluated. A manometer was connected to the CBD, and a second manometer was connected to the duodenum surrounding the papilla.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Reproducibility of endoscopic sphincter of Oddi manometry.
Results from endoscopic sphincter of Oddi manometry are being used to support the diagnosis of sphincter dysfunction in patients with unexplained pain after cholecystectomy. However, there are few data on the reproducibility of manometric records or motility diagnosis during a second test. In this study, the reproducibility of manometric records was assessed in 12 patients with pain after cholecystectomy by performing a second study after three months. Manometric tracings were evaluated without access to patients details and scored for sphincter basal pressure, frequency and amplitude of phasic contractions, propagation of phasic contractions, and responses to intravenous injection of cholecystokinin octapeptide (20 ng/kg). At the initial manometric study, four patients were diagnosed as normal, four as stenotic, and four as dyskinetic. Those diagnosed as normal and stenotic at the first study had an identical diagnosis at the second study. However, the diagnosis of dyskinesia was reproduced only in two of the four patients. In the other two patients a diagnosis of "stenosis" and "normal" was made at the second study. Cholecystokinin octapeptide (20 ng/kg intravenous bolus) produced inhibition of phasic contractions in all studies, both initially and at three months. We conclude that endoscopic sphincter of Oddi manometry is reproducible when the initial diagnosis is either normal or stenosis. However, the diagnosis of dyskinesia is poorly reproducible, perhaps due to the episodic nature of this manometric disorder or to progression of sphincter of Oddi dysfunction.
Adult↗
Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy.
A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% +/- 1.9% (mean +/- SEM). A gallbladder ejection fraction greater than 40% (mean -3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13-54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction.
Adult↗
Innervation of the sphincter of Oddi: physiology and considerations of pharmacological intervention in biliary dyskinesia.
The sphincter of Oddi is a small sphincter which is strategically placed at the junction of the bile duct and pancreatic duct with the duodenum. It regulates the flow of bile and pancreatic juice into the duodenum and prevents reflux of duodenal contents into the ducts. The structure of the sphincter of Oddi differs from species to species and consequently its physiological action varies in different species. Anatomical and immunohistochemical investigations have demonstrated that the sphincter of Oddi is richly innervated by cholinergic, adrenergic and peptidergic neurons. In addition, neural connections exist between the sphincter, gallbladder and proximal gastrointestinal tract. These nerves in addition to hormones are important in the control of sphincter of Oddi motility and function. The normal human sphincter of Oddi is characterized by prominent phasic contractions which are superimposed on a modest basal pressure. These contractions are present throughout the interdigestive period. The contractions and basal pressure are inhibited by ingestion of a meal or infusion of cholecystokinin octapeptide, thus enhancing the flow of bile and pancreatic juice into the duodenum. Sphincter of Oddi dysfunction has been described in patients who present with recurrent biliary type pain and no evidence of a structural cause for the pain. Motility disorders characterized as an elevated basal pressure, rapid contraction frequency, paradoxical response to cholecystokinin octapeptide or excess of retrograde contractions have been identified. A number of pharmacologically active substances have been used in an attempt to treat these patients. Such pharmaceuticals include nitrites, Ca2+ channel blockers and smooth muscle relaxants. Their effect is transient and side effects relating to cardiovascular actions preclude their longterm use. Division of the sphincter either endoscopically or by open operation has been demonstrated by prospective clinical trials to be the most efficacious treatment for patients with a stenosed sphincter manometrically demonstrated by a high basal pressure. Improved understanding of the controlling mechanisms of sphincter of Oddi motility and the pathophysiology of sphincter of Oddi dysfunction should assist in the development of effective pharmacotherapy for these disorders.
Animals↗
Biliary tract motor dysfunction.
Gallbladder and sphincter of Oddi motility regulates the flow of bile from the liver to the duodenum. During the interdigestive period most secreted bile is diverted into the gallbladder where it is concentrated, but a significant minority of the biliary secretion passes directly into the duodenum. Regulation of this flow is mainly via the phasic contractions of the sphincter of Oddi and the sphincter basal tone. The phasic contractions expel small volumes of fluid into the duodenum, but most of the flow occurs between the contractions and is therefore not dependent on peristaltic pumping, but rather on a small pressure gradient. During fasting, just prior to duodenal phase III activity, the gallbladder expels up to 40% of its volume and the sphincter phasic contractions increase. Following a meal, the gallbladder empties its contents, and the sphincter of Oddi resistance is reduced via a fall in basal pressure and inhibition of the amplitude of phasic contractions. Control of this activity is via an interplay of both neuronal and hormonal factors which together have an effect on both gallbladder and sphincter of Oddi motility. Abnormalities in motility are recognized for both the gallbladder and the sphincter of Oddi. Gallbladder dyskinesia is objectively diagnosed using the radionuclide GBEF. In patients with a GBEF less than 40% cholecystectomy results in relief of symptoms. In postcholecystectomy patients sphincter of Oddi dysfunction presents as either biliary-like pain or idiopathic recurrent pancreatitis. Endoscopic sphincter of Oddi manometry provides the most objective diagnostic information. In patients with a sphincter of Oddi stenosis, characterized manometrically as an elevated basal pressure, division of the sphincter results in relief of symptoms. For patients with biliary-like pain, division is performed as an endoscopic sphincterotomy, whereas for patients with idiopathic recurrent pancreatitis, a sphincteroplasty and pancreatic duct septectomy are required.
Biliary Tract↗
Peri-operative colonoscopy detects synchronous tumours in patients with colorectal cancers.
The aim of this study was to assess the value of colonoscopy as a peri-operative investigation in patients treated for colorectal cancer by surgical excision. Patients (134 male, 83 female) undergoing curative resection for colorectal carcinoma between August 1984 and January 1989 had colonoscopy within 3 months of surgery. Eleven patients (5%) had a synchronous cancer, which was diagnosed by colonoscopy in eight. In six of these eight, the diagnosis was made after surgery and 3 patients needed a second colectomy. However, in 3 patients the synchronous cancer was removed endoscopically without the need for further surgical resection. Most synchronous cancers had an earlier pathological stage than the index tumour. The rate of synchronous cancers was higher in patients with synchronous benign polyps (16%) than in those without polyps (3%). Colonoscopy is clearly justified as a peri-operative investigation in all patients undergoing potentially curative resection of colorectal cancer. If possible, the examination should be carried out prior to surgery, to guide the extent of resection.
Adult↗
Management of splenic trauma: a new CT-guided splenic injury grading system.
The aim of this study was to assess a newly developed computerized tomography (CT)-based splenic injury index in predicting the outcome of splenic injury. Twelve patients with isolated splenic injuries were studied. Splenic parenchymal injury was graded from 1 to 4 based on CT. The splenic injury index was obtained by multiplying the parenchymal score by the volume haemoperitoneum, which was measured on the CT scanner. The 12 patients with CT-proven splenic injuries had a mean injury index of 193.5 +/- 191 (mean +/- s.d.). The 3 patients who failed conservative management had a mean index of 475 +/- 50, compared with an index of 99.5 +/- 100 in the nine managed non-operatively (P less than 0.001). This new CT-based splenic injury index allows morphological assessment of splenic injury and may predict the outcome of splenic trauma.
Adolescent↗
A prospective evaluation of the management of bleeding peptic ulcer.
Bleeding from a peptic ulcer is associated with significant morbidity and mortality, particularly in the elderly. The results of a management policy of early endoscopy and close monitoring of patients were prospectively evaluated to assess whether major stigmata of recent haemorrhage (SRH) helped to identify patients who were likely to rebleed. Early endoscopy allowed the diagnosis of the most likely site of haemorrhage in 94% of the 190 patients. The nature and site of SRH (visible vessel, fresh clot, red or black spot) was recorded. Ninety-three of 167 patients in whom the presence or absence of SRH were recorded, had major SRH (visible vessel, fresh clot) and 51% of these patients rebled while only 10 of 74 (14%) patients without major SRH rebled. Overall, 80% of those with further haemorrhage had major SRH. Operation was performed on 28% of patients and the main indication for operation was further haemorrhage. Major morbidity in the surgical patients was strongly correlated with vascular instability at the time of further haemorrhage. Significant morbidity occurred in 16 of 28 patients (57%) with vascular instability, compared with only 1 of 18 patients (6%) without vascular instability (P less than 0.001). The overall low mortality of 5.3% was attributed to an approach of joint medical and surgical management with early operation for further haemorrhage. Although major SRH identified a group of patients most likely to suffer further haemorrhage, the positive predictive value of major SRH was only 51%.
Adult↗
Distension of the gall bladder inhibits sphincter of Oddi motility in humans.
Studies in animals have suggested a neural reflex between the gall bladder and the sphincter of Oddi. The aim of this study was to investigate whether sphincter of Oddi motility is altered by distension of the gall bladder in humans. Sphincter of Oddi motility was recorded intraoperatively in 10 patients undergoing elective cholecystectomy for gall stones. The manometry was performed by a triple lumen constantly perfused catheter which was introduced through the cystic duct and positioned across the sphincter of Oddi to record sphincter basal pressure, wave amplitude, and frequency of contractions. In five patients a separate catheter was introduced into the gall bladder after ligation of the cystic duct. This catheter was used to distend the gall bladder. Sphincter of Oddi pressures were measured before, during, and after the distension. In a separate control group of patients (n = 5) basal sphincter of Oddi activity was recorded without distension of the gall bladder. Distension of the gall bladder decreased sphincter of Oddi basal pressure from (mean (SD] 22.8 (8.5) mmHg to 18.6 (6.5) mmHg (p = 0.01, paired t test) and frequency of sphincter of Oddi contractions decreased from 2.6 (1.6) to 1.1 (1.3) contractions/min (p = 0.003, paired t test). The results were significantly different from those of the control group (p less than 0.05, unpaired t test) during the same time period (four minutes). Pulse rate and blood pressure were not affected by the gall bladder distension. The results suggest a local reflex between the gall bladder and the sphincter of Oddi that might be important in the regulation of the pressure within the bile ducts and flow across the sphincter. This reflex is likely to be neurally mediated and injuries to it may be important in the aetiology of postcholecystectomy sphincter of Oddi dysfunction.
Adult↗
Symptomatic gallstones: management options for the 1990s.
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Bile Acids and Salts↗
Contrast cholangiography versus ultrasonographic measurement of the "extrahepatic" bile duct: a two-fold discrepancy revisited.
The upper limit of the normal extrahepatic duct diameter when measured by sonography in our institution is less than half that when measured by endoscopic retrograde cholangiopancreatography (ERCP). The objective of this study was to locate possible sources of this discrepancy by comparing measurements obtained on the same patient by sonography, before and after ERCP. Thirty consecutive patients referred for ERCP were entered into a prospective trial; bile duct measurements were obtained independently by both techniques in 19 patients. Correcting for radiographic magnification, the ERCP measurement was more than twice that obtained by ultrasonography. Among the possible reasons for diverse results that we considered, radiographic magnification, ultrasonic underestimation, and distending effects of retrograde cholangiography (ERCP) were not found to be prominent causes for the marked discrepancy that we observed. The most likely explanation is that the duct in individual patients was being measured at a different level by the two techniques. A retrospective comparison of the studies obtained by each method suggests that the sonographic measurement is most often of the right hepatic duct. If this is the case, the two measurements show no statistically significant difference (P greater than 0.05). A prospective trial is needed to test this hypothesis.
Bile Ducts↗
Clinical relevance of sphincter of Oddi dysfunction.
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Ampulla of Vater↗
Differing effects of pethidine and morphine on human sphincter of Oddi motility.
The aim of this study was to evaluate the effects of morphine and pethidine on human sphincter of Oddi motility. The action of these opioids on the sphincter of Oddi was evaluated by means of intraoperative manometry in 36 patients undergoing elective cholecystectomy. Both opioids were given in intravenous cumulative equipotent doses up to a maximum of 10 micrograms/kg morphine or 100 micrograms/kg pethidine. At these doses, morphine increased the mean(s.d.) frequency of contractions from 2.4(1.0) to 7.9(1.6) (P less than 0.001); this effect was reduced by naloxone (0.04 mg bolus, P less than 0.05). Pethidine inhibited the frequency of contractions from 1.5(0.8) to 0.8(0.5) (P less than 0.05); this response was blocked by atropine (0.6 mg bolus, P less than 0.01). Pretreatment with atropine or naloxone reduced the frequency of contractions significantly (P less than 0.05). The results illustrate different responses to pethidine and morphine of the sphincter of Oddi, and provide a pharmacological explanation for the suitability of pethidine over morphine as the analgesic of choice in patients experiencing biliary pain.
Adult↗
Cisapride inhibits motility of the sphincter of Oddi in the Australian possum.
Cisapride has been shown in a number of recent studies to have prokinetic effects on the gastrointestinal tract. Studies of its action on the biliary tract have been limited. In this study we determined the effect of cisapride on sphincter of Oddi motility of the Australian brush tailed possum in vivo, and evaluated possible mechanisms for its effect. Cisapride produced a dose-dependent inhibition of sphincter of Oddi phasic contractions. The inhibitory effect was not blocked by atropine, phentolamine, propranolol, methysergide, or hexamethonium administration, or after cervical truncal vagotomy. Tetrodotoxin, however, abolished the sphincter response to cisapride. We conclude that cisapride has an inhibitory effect on the possum sphincter of Oddi. This inhibitory effect is mediated via nonadrenergic, noncholinergic inhibitory neurons and is similar to the inhibitory effect of cholecystokinin on the sphincter of Oddi.
Ampulla of Vater↗
Endoscopic decompression for acute cholangitis due to stones.
The prognosis in patients with acute cholangitis is poor, particularly when the cholangitis is 'severe' as defined by the presence of hypotension and/or confusion. This prospective study evaluates 16 elderly patients with acute cholangitis ('severe' in 11) due to stones in whom endoscopic biliary decompression was attempted. It was technically successful on 13 (81%) of the 16 occasions and the cholangitis rapidly resolved in these patients. In seven of 13, this was the definitive treatment while six underwent subsequent surgery consisting of: cholecystectomy or cholecystostomy (five) and secondary bile duct exploration (one). Two patients died following laparotomy for stones that were not amendable to endoscopic removal. Urgent endoscopic retrograde choledochography is recommended in elderly patients with acute cholangitis, because it confirms the diagnosis and allows decompression of the biliary tract by sphincterotomy. This stabilizes the patient's general condition and facilitates subsequent open surgery when required.
Aged↗