VIP-antiserum inhibits fluid secretion by the inflamed gallbladder mucosa.

The inflammatory fluid secretion by the gallbladder mucosa in experimental cholecystitis is induced by an increased prostaglandin formation and is mediated by intramural nerves. In the present study the effect of VIP-antiserum on the inflammatory fluid secretion in the gallbladder was tested in a validated experimental model in cats. The animals were studied in acute experiments 6 weeks after a procedure when the cystic duct was tied and gallstones were implanted in the gallbladder. During basal conditions there was a continuous secretion of fluid into the lumen of the inflamed gallbladder averaging 0.43 +/- 0.18 ml/h. Injection of VIP antiserum, obtained from immunized rabbits and diluted with saline 1:10 in a bolus of 4 ml into the coeliac artery reversed this secretion into an absorption of 1.72 +/- 0.44 ml h-1 (P < 0.001). VIP-antiserum did not affect the fluid adsorption in control animals with an intact gallbladder and injection of control serum from rabbits not immunized to VIP did not affect fluid secretion in the inflamed gallbladders. The results support the idea that the inflammatory fluid secretion in the gallbladder mucosa is mediated by VIP-ergic nerve fibres.

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.

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.

Management of acute cholecystitis in the laparoscopic era: results of a prospective, randomized clinical trial.

The aim of this prospective, randomized study was to determine whether laparoscopic cholecystectomy should be performed as an early or a delayed operation in patients with acute cholecystitis. After diagnostic workup, patients were randomized to one of two groups: (1) early laparoscopic cholecystectomy (i.e., within 7 days after onset of symptoms) or (2) initial conservative treatment followed by delayed laparoscopic cholecystectomy 6 to 8 weeks later. Seventy-four patients were placed in the early-operation group, and 71 patients were assigned to the delayed-operation strategy. There was no significant difference in conversion rates (early 31% vs. delayed 29%), operating times (early 98 [range 30 to 355] minutes vs. delayed 100 [45 to 280] minutes), or complications. Failure with the conservative treatment strategy was noted in 26% of these patients. The total hospital stay was significantly shorter in the early group (5 [range 3 to 63] days) vs. the delayed group (8 [range 4 to 50] days; P<0.05). Despite a high conversion rate, early laparoscopic cholecystectomy offered significant advantages in the management of acute cholecystitis compared to a conservative strategy. The greatest advantage was a reduced total hospital stay.

Randomized clinical trial of day-care versus overnight-stay laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy has been performed as a day-care procedure for many years. Few studies have been conducted with primary focus on patient acceptance and preferences in terms of quality of life for this practice compared with overnight stay. METHODS: Data from 100 patients with symptomatic gallstones randomized to laparoscopic cholecystectomy performed either as a day-care procedure or with overnight stay were analysed. Complications, admissions and readmissions, quality of life and health economic aspects were assessed. Two instruments were used to assess quality of life, the Hospital Anxiety and Depression Scale (HADS) and the Psychological General Well-Being Index (PGWB). RESULTS: Forty-eight (92 per cent) of 52 patients in day-care group were discharged 4-8 h after the operation. Forty-two (88 per cent) of 48 in the overnight group went home on the first day after surgery. The overall conversion rate was 2 per cent. Two patients had complications after surgery, both in the day-care group. No patient in either group was readmitted. There was no significant difference in total quality of life score between the two groups. The mean direct medical cost per patient in the day-care group (3085 Euros) was lower than that in the overnight group (3394 Euros). CONCLUSION: Laparoscopic cholecystectomy can be performed as a day-case procedure with a low rate of complications and admissions/readmissions. Patient acceptance in terms of quality of life variables is similar to that for cholecystectomy with an overnight stay. The day-care strategy is associated with a reduction in cost.

Randomized clinical trial of open versus laparoscopic cholecystectomy in the treatment of acute cholecystitis.

BACKGROUND: The aim of this prospective trial was to determine whether surgical approach (open versus laparoscopic) had an impact on morbidity and postoperative recovery after cholecystectomy for acute cholecystitis. METHODS: Seventy patients who met the criteria for acute cholecystitis were randomized to open or laparoscopic cholecystectomy. The type of operation was unknown to the patient and all hospital staff involved in the postoperative care. RESULTS: The two groups were similar with respect to demographic and clinical characteristics. There were no significant differences in rate of postoperative complications, pain score at discharge and sick leave. In eight patients a laparoscopic procedure was converted to open cholecystectomy. Median operating time was 90 (range 30-155) and 80 (range 50-170) min in the laparoscopic and open groups respectively (P = 0.040). The direct medical costs were equivalent in the two groups. Although median postoperative hospital stay was 2 days in each group, it was significantly shorter in the laparoscopic group (P = 0.011). CONCLUSION: Cholecystectomy for acute cholecystitis can be performed by either laparoscopic or open techniques without any major clinically relevant differences in postoperative outcome. Both techniques offer low morbidity and rapid postoperative recovery.

Intraluminal prostaglandin E2 affects gallbladder function by activation of intramural nerves in the anaesthetized cat.

Gallbladder mucosal net fluid transport and motility were measured in vivo by a continuous perfusion technique in the anaesthetized cat. Prostaglandin E2, administered to the perfused gallbladder lumen, caused a contraction decreasing gallbladder volume capacity, and induced a secretory response by the mucosa. These effects by prostaglandin E2 were abolished by the nerve-blocking agent tetrodotoxin (administered close intraarterially) and somatostatin (administered intravenously), but not by intravenous hexamethonium. Atropine (administered intravenously) reduced the order of magnitude of the gallbladder contraction in response to prostaglandin E2 but did not affect the secretory response by the mucosa. Neither of these drugs significantly affected gallbladder volume capacity or mucosal fluid transport during basal conditions. Tetrodotoxin did not abolish the gallbladder responses to intravenous cholecystokinin or vasoactive intestinal peptide, peptides known to act directly upon smooth muscle and epithelial cell receptors, respectively. It is suggested that prostaglandin E2 affects gallbladder function in vivo mainly by activation of postganglionic non-cholinergic intramural nerve cells.

[Externalizing the problem--a method in psychiatric treatment]. / Eksternalisering av problemet--en metode i psykiatrisk behandling.

Michael White is an Australian family therapist. He has developed a therapeutical method which he calls "externalizing the problem". According to this method, the patient's problem is given a linguistic designation, for example "the tyrant of anguish", "the tempter of drugs", "the black voice", and is kept outside the dominant identity of the patient. The patient, in time also the family, is invited to a dialogue on the effect of this problem and how to develop strategies to beat "the problem tyrant". The authors have based their work on the thoughts and methods of Michael White. They have used these methods to address a wide range of psychiatric problems. The paper describes the theory behind the methods, and presents a number of clinical examples where they have been used.

Reflex regulation of flow resistance in the feline sphincter of Oddi by hydrostatic pressure in the biliary tract.

Despite wide variations in bile secretion and biliary tract capacitance, the pressure in the bile ducts is fairly constant. Recent studies have demonstrated that both inhibitory and excitatory nerves regulate the activity of the sphincter of Oddi. In the present study, it was consistently found that the resistance by the choledochoduodenal junction to a constant flow, within the physiologic range of hepatic bile output, is reduced when the hydrostatic pressure in the gallbladder and bile ducts is increased from 0 to 10, 0 to 15, and 0 to 20 cmH2O. This response was eliminated by tetrodotoxin or infiltration of the junction between the common bile duct and the cystic duct by mepivacaine, a local anesthetic. The results suggest a homeostatic mechanism during the interprandial periods, when the activity of the sphincter of Oddi is regulated by the distending pressure in the biliary tract. This reflex regulation is mediated by modulation of the activity of inhibitory nerves running along the common bile duct.

Prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. A prospective randomized study of metoclopramide and transdermal hyoscine.

OBJECTIVE: To compare the antiemetic effects of metoclopramide and hyoscine in patients after laparoscopic cholecystectomy. DESIGN: Prospective, randomised trial. SETTING: University hospital, Sweden. SUBJECTS: 100 consecutive patients median age 49 years (range 21-79) of whom 9 were withdrawn after randomisation. INTERVENTIONS: Patients were randomised to receive either four doses of metoclopramide 10 mg intravenously starting at the induction of anaesthesia (n = 44), or hyoscine transdermally through a patch placed behind the ear at 0600 h on the day of operation (n = 47). MAIN OUTCOME MEASURES: The incidence of nausea and vomiting. RESULTS: Metoclopramide was significantly more effective at preventing both nausea and vomiting (20/44 (45%) compared with 32/47 (68%), p < 0.05, and 10/44 (23%) compared with 21/47 (45%), p < 0.05). Women were significantly more likely to become nauseated than men (46/66 (70%) compared with 5/25 (20%), p < 0.001). Two patients in the metoclopramide group developed dizziness, and one patient in the hyoscine group had a disturbance of vision. About 20% in each group required additional antiemetic treatment. The median hospital stay in both groups for patients who did not develop complications was 2 days. CONCLUSION: There was a high incidence of nausea and vomiting after laparoscopic cholecystectomy even after treatment with metoclopramide. Further measures are indicated, particularly for women.

Flow resistance in the feline choledocho-duodenal sphincter as studied by constant-pressure and constant-perfusion techniques.

During interdigestive periods, there is a resistance to flow in the biliary tract exerted by the sphincter of Oddi, resulting in a pressure gradient between the common bile duct and the duodenum. In this experimental study, this flow resistance was studied with both a constant-flow and a constant-perfusion technique in fasted, anaesthetized cats. The flow resistance exerted by the sphincter is higher when it is perfused by a constant flow compared to when the common bile duct pressure is kept constant and the flow varies in response to its muscular activity. It was demonstrated with each method that the flow resistance in the choledocho-duodenal junction is reduced in response to distension of the biliary tree and gallbladder and also by distension of the duodenum. Cholecystokinin was shown to reduce the flow resistance in the choledocho-duodenal junction as estimated with either method.

Cholecystectomy in the cat damages pericholedochal nerves and impairs reflex regulation of the sphincter of Oddi. A mechanism for postcholecystectomy biliary dyskinesia.

A recent study demonstrated the activity of the feline sphincter of Oddi to be regulated by the distending pressure in the biliary tract via inhibitory nerves running along the common bile duct. In the present study this mechanism was investigated in cats previously subjected to cholecystectomy. An increment in the hydrostatic pressure in the biliary tree from 0 to 20 cmH2O did not affect the function of the sphincter of Oddi in cholecystectomized cats, but relaxed the sphincter in controls and in cats with sham operation. Morphologic study of the nerve arrangement in the feline extrahepatic biliary tract revealed that cholecystectomy is likely to damage pericholedochal nerves. These experimental observations may have relevance for the development of biliary dyskinesia following cholecystectomy in some patients, and suggest that when performing biliary-tract surgery it is important to preserve nerve fibers running along the common bile duct.

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.

A comparative retrospective study of thoracoscopy versus thoracotomy for the treatment of spontaneous pneumothorax.

Thoracoscopic surgery has been claimed to reduce patient disability, recovery time, and hospital costs compared with open surgery. We analyzed 25 patients who had undergone thoracoscopic surgery and compared the outcome to 24 patients who had undergone conventional surgery for spontaneous pneumothorax. The thoracoscopic group was able to return to work and daily activities earlier and had less impairment of shoulder movement. There was a loss of sensation corresponding to the dermatomes where the thoracoscopic ports were placed, which could have resulted from compression of the intercostal nerves by the instruments. However, a similar loss of sensation was found in the thoracotomy group. We conclude that thoracoscopy may be the method of choice for the treatment of spontaneous pneumothorax, although further methodological development should be done.

Medication with ursodeoxycholic acid enhances the biliary clearance of polyethylene glycol 900, but not mannitol.

Ursodeoxycholic acid (UDCA) is a nontoxic bile acid currently used in the treatment of different cholestatic diseases. This bile acid is also considered to be a 'hypercholeretic bile acid'. The effects of daily administration of UDCA on bile flow and the bile acid secretion rate in man are not fully known. The aim of this study was to explore the effects by UDCA on bile flow and its different functions. The biliary clearances of polyethylene glycol 900 (PEG 900) and mannitol were measured simultaneously in patients with an indwelling T tube after cholecystectomy. One group (n = 6) were given UDCA (10 mg/kg/day) for at least 14 days before the investigation and a control group (n = 8) received no bile acid treatment. The bile secretion was studied in acute experiments where bile was drained for 6 h. The bile plasma ratio for PEG 900 was 31 and that for mannitol was 0.7 which corresponds well with the results obtained in different animal species. The relationship between bile flow and the bile salt secretion rate, as expressed by linear regression analysis, showed no difference between the 2 groups (control y = 0.22 + 0.012x, r = 0.61, p < 0.001; UDCA y = 0.20 + 0.016x, r = 0.88, p < 0.001). The relationship between the biliary clearance of PEG 900 and the bile salt secretion rate, as expressed with linear regression analysis, showed a significantly steeper slope for the UDCA-treated patients (control y = 8.1 + 0.34x, r = 0.41, p < 0.05; UDCA y = 5 + 1.58x, r = 0.78, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Functional and morphological relationships between the feline main pancreatic and bile duct sphincters.

To analyze the relationships between the bile duct and main pancreatic duct sphincters, the resistance to flow through these sphincters was studied simultaneously with perfusion techniques in anesthetized cats. Basal flow resistance was higher in the pancreatic sphincter than in the bile duct sphincter. The pressure in one duct system was not affected by the flow in the other. The muscular activities in the sphincters were usually well coordinated. Distention of the upper biliary tract or the pancreatic duct system reduced the flow resistance in both sphincters. Cholecystokinin-8 (0.01 micrograms), duodenal distention, and sublingual glyceryl trinitrate (0.4 mg) also relaxed both sphincters, whereas secretin in a dose that induced pancreatic secretion had no consistent effect. Morphine increased flow resistance in both systems. These functional studies indicate that the 2 sphincters share smooth muscle fibers at the level where the flow resistances arise, and there are thus no grounds for separate control of the sphincters. There was no evidence of a functionally common sphincter ampulla. The conclusions drawn from the manometric results were supported by morphological findings in this study.

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.

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.