Preoperative routine magnetic resonance cholangiopancreatography before laparoscopic cholecystectomy: a prospective study.

OBJECTIVES: To assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) in detecting common bile duct stones in the preoperative investigation of patients electively referred for gallstone disease, to find out the incidence of asymptomatic common duct stones, and to correlate clinical symptoms and history and liver function tests (LFT) with the actual occurrence of common duct stones. DESIGN: Prospective study. SETTING: General hospital, Denmark. PATIENTS: 180 consecutive non-jaundiced patients referred with symptomatic gallstones for elective cholecystectomy. INTERVENTIONS: LFT, abdominal ultrasonography, MRCP, endoscopic retrograde cholangiopancreatography (ERCP), questionnaire. MAIN OUTCOME MEASURES: Positive and negative predictive values and accuracy of MRCP, number of patients with asymptomatic stones, and correlation of symptoms with the presence of stones. RESULTS: 26/180 patients had common duct stones (14%). Only one (<1%) had an asymptomatic stone. For detection of such stones, MRCP's positive predictive value was 0.95 (95% confidence interval (CI): 0.86 to 1.00), negative predictive value 0.96 (0.93 to 0.99), and accuracy 0.85 (0.93 to 0.99). MRCP missed 5 stones 1-4 mm in size in 5 patients; 17/64 patients with raised LFTs had stones (27%). The probability of stones was highest when the patients had both raised LFTs and a dilated common (>7 mm) bile duct (82%). There were no readmissions with ductal stones in the 6-month postoperative period. CONCLUSIONS: The predicive values of MRCP were fairly good, but MRCP misses some small stones <5 mm in size. Asymptomatic stones in the common duct are not common in this population and should not be screened for. The probability of stones increases with the number of predictive factors. Patients should be questioned carefully about signs of biliary obstruction, and only be offered preoperative MRCP should they have a suspicious history, raised LFTs, or a dilated common duct.

Transport of neutral, cationic and anionic amino acids by systems B, b(o,+), X(AG), and ASC in swine small intestine.

Amino acid influx across the brush border membrane of the intact pig ileal epithelium was studied. It was examine whether in addition to system B, systems ASC and b(o,+) were involved in transport of bipolar amino acids. The kinetics of interactions between lysine and leucine demonstrates that system b(o,+) is present and accessible also to L-glutamine. D-aspartate (K(1/2) 0.3 mM) and L-glutamate (K(i) 0.5 mM) share a high affinity transporter with a maximum rate of 1.3 micromol cm(-2) h(-1), while only L-glutamate with a K(1/2) of 14.4 mM uses a low affinity transporter with a maximum rate of 2. 7 micromol cm(-2) h(-1), system ASC, against which serine has a K(i) of 1.6 mM. In the presence of 100 mM lysine, L-glutamine (A), leucine (B), and methionine (C) fulfilled the criteria of the ABC test for transport by one and the same transporter. However, serine inhibits not only transport of L-glutamate but also of glutamine (K(i) 0.5 mM), and L-glutamate inhibits part of the transport of glutamine. The test does, therefore, only indicate that the three bipolar amino acids have similar affinities for transport by systems B and ASC. Further study of the function of system B must be carried out under full inhibition by lysine and glutamate.

Regional differences in neurogenic signal transduction pathway of cholera toxin-induced fluid, electrolyte and serotonin accumulation in the porcine jejunum.

Serotonin, acetylcholine and substance P are mediators involved in the secretory response to cholera toxin in the small intestine. The aim of this study was to investigate the regional difference in the effect of a serotonin receptor type 3 antagonist (ondansetron), a nicotinic receptor antagonist (hexamethonium), and a substance P antagonist (the neurokinin receptor type 1 antagonist, CP 99,994) on the cholera toxin-induced fluid accumulation in the porcine jejunum. A dose-range of cholera toxin (0.32-56.00 microg/loop) was instilled for 4 hr in ligated loops in two regions of the proximal jejunum in 6-8-week-old pigs. Ondansetron (200 microg/kg), hexamethonium (10 mg/kg), CP 99,994 (1 mg/kg), or saline alone (control) were given intravenously 10 min. before cholera toxin instillation. Cardiovascular parameters, blood gas data, net fluid accumulation, serotonin and electrolyte concentration in the accumulated fluid were measured. Cardiovascular and blood gas parameters were within the normal range in all treatments. The apparent maximal response in fluid accumulation was reduced 20% in case of ondansetron, and by 33% using CP 99,994 in the aboral region compared to control, whereas no effect was observed in the oral region. Hexamethonium reduced the apparent maximal secretory response in both the oral and aboral regions by 45%. None of the treatments with antagonists changed the luminal content of serotonin or the electrolyte concentrations in the accumulated fluid. The results demonstrate that the involvement of serotonin receptor type 3 and neurokinin type 1 receptors in the transductional pathway of cholera toxin-induced fluid accumulation vary significantly within the jejunum, while the cholinergic (nicotinic) transmission plays an even role.

Can colonoscopy diagnose transmural ischaemic colitis after abdominal aortic surgery? An evidence-based approach.

OBJECTIVES: to assess the diagnostic value of colonoscopy in ischaemic colitis following abdominal aortic surgery, based on a literature review, and to introduce the concept of evidence-based medicine. METHOD: a review of the literature according to evidence-based principles was made by all doctors of our department. RESULTS: seven prospective non-randomised reports on routine colonoscopy after abdominal aortic surgery were found. None of the participants found all the reports, and the last was identified by the reviewer. CONCLUSIONS: Endoscopy may disclose ischaemic colitis, but cannot separate transmural from the clinically less important mucosal ischaemia. Endoscopy had no impact on mortality in any of the prospective series. The evidence-based conference was an inspiring teaching modality, and illustrated for the participants the difficulty in performing a targeted literature search.

Effect of age on vasoactive intestinal polypeptide-induced short-circuit current in porcine jejunum.

Vasoactive intestinal polypeptide is a transmitter at the neuroepithelial junction of the small intestine in cholera toxin-induced secretion. We investigated whether the secretory effect in vitro of vasoactive intestinal polypeptide in porcine jejunum was changed with age. Stripped tissue preparations from three age groups, neonatal (7-11 days), young (6-8 weeks) and adult (13-15 weeks) pigs, were mounted in Ussing chambers and short-circuited. Vasoactive intestinal polypeptide produced concentration dependent increases in short-circuit current in all three age groups with EC50 values (in nM) of 14.5 +/- 1.9, 16.2 +/- 2.0 and 147 +/- 0 in neonatal, young and adult pigs, respectively. The peak increases in short-circuit current in adult pigs were significantly decreased compared with the other two age groups. To evaluate the secretory capacity, theophylline was added to tissue preparations in which baseline short-circuit current again was established. Theophylline caused a significantly lesser increase in short-circuit current in adult pigs (25.4 +/- 2.0 microA.cm-2) than neonatal (57.1 +/- 3.6 microA.cm-2) and young pigs (63.1 +/- 2.9 microA.cm-2). In conclusion, vasoactive intestinal polypeptide showed a marked decrease in the secretory response with age in porcine jejunum, at least partly caused by a reduced secretory capacity of the enterocytes.

Functional characterisation of tachykinin receptors mediating ion transport in porcine jejunum.

In the present study, tachykinin receptors (designated NK 1, NK2 and NK3) involved in regulation of ion transport in porcine jejunum were characterised. Stripped tissue preparations were mounted in Ussing chambers and short-circuited. Substance P produced a concentration dependent increase in short-circuit current, the relationship showing a double sigmoidal form. The non-peptide NK1 receptor antagonist, CP 99,994 ((2S,3S)-3-(2-methoxybenzyl)amino-2-phenylpiperidine), caused a dextral shift of the first sigmoidal response, indicating the involvement of an NK1 receptor. This was further supported by a concentration-dependent response of the NK1 receptor agonist [Sar9Met(O2)11]substance P with an EC50 value of 235.0+/-53.9 nM. Increasing concentrations of CP 99,994 (0.1, 0.3 and 1 microM) produced a parallel dextral shift of the [Sar9Met(O2)11]substance P curve with a slope of the Schild regression significantly different from unity (1.59). The neurokinin A concentration-response curve, with an EC50 value of 68.87+/-16.23 nM, was not significantly changed by the non-peptide NK2 receptor antagonist SR 48,968 ((S)-N-methyl-N-(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophe nyl)butyl)bezamide). In additional studies, the peptide NK2 receptor antagonists, GR 94,800 (PhCO-Ala-Ala-DTrp-Phe-DPro-Pro-NleNH2) and PD 147,714 ((2,3-diOMeZ)-(S)Trp(S)alphaMePheGlyNH2), did not change the response to neurokinin A. However, CP 99,994 totally inhibited neurokinin A responses at 0.5 microM and above. The NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), caused only an increase in short-circuit current in microM concentrations, whereas the NK3 receptor agonist, senktide, did not elicit a response. These results indicate, that substance P and neurokinin A mediate ion transport in porcine jejunum through NK1 receptors. However, tachykinins seem to activate another receptor. Two active conformers of the NK1 receptor might be present.

Tachykinins mediate changes in ion transport in porcine jejunum through release of prostaglandins and neurotransmitters.

In the present study, we investigated the mediators involved in substance P (SP) and neurokinin A (NKA) induced ion transport. Stripped preparations of porcine jejunal tissue were mounted in Ussing-chambers and short-circuited. The cyclo-oxygenase inhibitor, piroxicam (10 microM) and the neuronal conduction blocker, tetrodotoxin (TTX) (0.1 microM) both significantly decreased the SP (0.1 microM) (66% and 36%, respectively) and NKA (1 microM) (64% and 31%, respectively) induced increase in short-circuit current (SCC). Pretreatment with both piroxicam and TTX totally abolished the SP and NKA response. SP (0.1 microM) caused a significant release of prostaglandin E2 (PGE2), whereas the release of PGE2 induced by NKA was not significant. Experiments were performed to clarify if vasoactive intestinal polypeptide (VIP) was mediating SP or NKA responses. VIP caused a TTX-insensitive and a concentration-dependent increase in SCC. Two VIP antagonists did not change the response to VIP (10 nM and 0.1 microM). Thus, these antagonists could not be used to further elucidate the role of VIP. We were unable to measure a significant release of VIP after SP or NKA treatment. These results indicate, that SP and NKA regulate ion transport in porcine jejunum, entirely through the release of prostaglandins and enteric neurotransmitters.

Regional differences in the effect of cholera toxin and enterotoxigenic Escherichia coli infection on electrolyte and fluid transport in the porcine small intestine.

The regional differences in secretory and absorptive responses to cholera toxin (CT) and to infection by enterotoxigenic Escherichia coli (ETEC), producing heat-stable enterotoxins, were studied in the porcine small intestine. Proximal, mid and distal small intestine from newly weaned piglets were used. Na+ and Cl- fluxes and electrical parameters in CT-stimulated and ETEC-infected intestine were measured by the Ussing chamber technique. In addition, CT-induced fluid accumulation in ligated loops was measured. CT induced fluid accumulation, which was highest in the proximal segment and decreased in the aboral direction of the small intestine. In addition, CT induced a net Cl- secretion in the proximal and mid segments, while net Na+ absorption was reduced only in the proximal segment. The ETEC-infected intestine showed a net increase in Cl- secretion in the proximal part and abolished the net Na+ absorption in the distal segment. These results demonstrate segmental differences in the epithelial transport responses to enterotoxin from Vibrio cholerae and to ETEC infection. This needs to be taken into consideration in relation to oral rehydration studies.

Secretory response to cholera toxin in the porcine jejunum under different types of general anaesthesia.

Investigations of intestinal secretion are often performed under anaesthesia. This study evaluates the influence of anaesthetic agents on the intestinal secretion induced by cholera toxin (CT) in the pig. CT was instilled for 4 h in ligated jejunal loops under anaesthesia with halothane, saffan, alpha-chloralose, or propofol. Cardiovascular parameters, blood gas data, plasma cortisol levels, net fluid accumulation, intraluminal mediators (serotonin (5-HT), prostaglandin E2 (PGE2)) and electrolyte concentrations in the accumulated fluid were determined. The systolic blood pressure and heart rate was highest for saffan-anaesthetized pigs (blood pressure: saffan > alpha-chloralose > propofol = halothane; heart rate: saffan > alpha-chloralose = propofol = halothane), while blood gases and cortisol levels were within the same range. CT induced a dose-dependent fluid accumulation under all four anaesthetics. The fluid accumulation was significantly higher in pigs treated with saffan, alpha-chloralose and propofol than in halothane-treated pigs (saffan = alpha-chloralose > propofol > halothane). There was no significant difference in electrolyte concentrations in the accumulated fluid or in the luminal content of 5-HT and PGE2 between anaesthetics. The results demonstrate that anaesthetic agents profoundly influence the secretory response in the small intestine and indicate the importance of the choice of anaesthetic in this type of experiment.

The effect of histamine on ion transport in porcine jejunum.

Histamine is present in the gastrointestinal tract, and is an important mediator in gastrointestinal type I hypersensitivity reactions. The effect of histamine on ion transport in "stripped" porcine jejunal preparations was investigated. Histamine caused a transient increase in short-circuit current (SCC), which seemed to be concentration dependent. A maximum response was obtained at 0.1 mM. The histamine response was attenuated (44.8%) by the neuronal conduction blocker, tetrodotoxin (TTX), indicating that enteric neurotransmitters are involved. The neurokinin-1 antagonist, CP 99,994, did not alter the response to histamine (0.1 mM). Thus, tachykinins acting at NK-1 receptors do not seem to be involved in the histamine response.

Serotonin-induced short-circuit current in pig jejunum.

This paper presents the effects of serotonin (5-HT) on short-circuit current (SCC), sodium and chloride fluxes, and prostaglandin E2 release in pig jejunum, using the Ussing-chamber technique. 5-HT elicited a dose-dependent increase in SCC, yielding an EC50 of 6 +/- 4 microM and EMAX of 77 +/- 8 microA.cm-2 using about 100 microM. Inhibited sodium absorption and stimulated chloride secretion carried part of the 5-HT-induced SCC. 5-HT caused a dose-independent PGE2 release, and indomethacin reduced the SCC-inducing effect of 5-HT by 40%. Octreotide, a long-lasting somatostatin analogue, also reduced 5-HT-induced SCC by about 40%, while tetrodotoxin (TTX) did not alter the effect of 5-HT. In conclusion, 5-HT causes a dose-dependent indomethacin and octreotide-sensitive, and TTX-insensitive increase in SCC, and a chloride secretion and inhibited sodium absorption and an increased release of PGE2 in pig jejunum in vitro.

5-Hydroxytryptamine2 and 5-hydroxytryptamine3 receptors mediate serotonin-induced short-circuit current in pig jejunum.

The purpose of this study was to determine the effect of methysergide, ketanserin, granisetron, cisapride, and renzapride on serotonin (5-hydroxytryptamine-evoked short-circuit current in muscle and myenteric plexus-stripped pig jejunum using the Ussing chamber technique. Ketanserin, granisetron, cisapride, and renzapride all reduced the 5-hydroxytryptamine-induced increase in short-circuit current by about 50%. Combination of ketanserin and granisetron only reduced the 5-hydroxytryptamine-induced peak increase in short-circuit current by 25%. Cisapride caused a small concentration-dependent increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Ketanserin, granisetron, methysergide, and renzapride did not alter the basal short-circuit current. These results suggest that 5-hydroxytryptamine elicits an increase in short-circuit current by activating epithelial and submucosal 5-hydroxytryptamine2 and 5-hydroxytryptamine3 receptor subtypes. Furthermore, the short-circuit current-increasing effect of cisapride, is due to activation of at least muscarinic and nicotinic receptors.

Effect of indomethacin, renzapride, methysergide, ketanserin, granisetron and citalopram on serotonin-induced fluid accumulation in pig jejunum.

The purpose of this study was to elucidate the intestinal serotonin (5-HT) receptor subtypes involved in fluid transport in the pig jejunum in vivo. The fluid accumulating effect of intraluminally administered 5-HT, renzapride, methysergide, ketanserin, granisetron, citalopram and intravenous indomethacin, was tested in tied-off loops in vivo. 5-HT caused a dose-dependent fluid accumulation, which was reduced by indomethacin by about 30%. Renzapride, methysergide, ketanserin, granisetron and citalopram all caused fluid accumulation. Taking into account these fluid accumulating effects, renzapride, methysergide, ketanserin and granisetron reduced the fluid accumulating effect of 5-HT, giving a maximal reduction of 70, 46, 76, and 80%, respectively. These data suggest the existence of intestinal 5-HT receptor subtypes involved in fluid transport in the pig jejunum. The antagonistic effects of indomethacin, ketanserin and granisetron, suggest the involvement of prostaglandins, as well as the 5-HT2 and the 5-HT3 receptor subtypes in the fluid accumulating response of 5-HT.

Opioid involvement in the perception of pain due to endurance exercise in trained man.

The purpose of this study was to evaluate the role of endogenous opiates in modulating physical performance during dynamic exercise in conscious man. The plasma concentration of beta-endorphin (BEP) and of adrenocorticotropic hormone (ACTH) along with muscle pain (McGuill Pain Questionnaire) were assessed in 17 trained, male runners before and after running the longest possible distance within 12 min (i.e., the Cooper test). Each runner participated twice in the test (double-blind cross-over design), with a 1-week interval--with or without an injection of the opiate antagonist naloxone (0.8 mg i.v.). The average (SEM) distance reached was 3,198 (45) m in the naloxone test and 3,240 (38) m in the placebo test. The BEP increased significantly during the tests by a factor of 4.1 on naloxone and by 2.8 on placebo (from the normal resting averages of 1.7 and 2.1 pmol/l, respectively). The ACTH also increased significantly by a factor of 2.0 on naloxone and 2.5 on placebo (from the normal resting averages of 19.3 and 16.8 pmol/l, respectively). There were no significant differences between the naloxone and the placebo test with respect to the increments of BEP or ACTH by exercise. However, the perception of muscle pain was enhanced with naloxone. The increased perception of pain did not decrease the athletes ability to perform in terms of the distance run. We conclude that endogenous opiates are involved in the perception of pain associated with exhaustive exercise and may subserve psychological rather than physiological functions during exercise.