Sphincterotomy for biliary sphincter of Oddi dysfunction.

The review is withdrawn as it has not been maintained since its first publication in 2001 (searches date back to the year 2000). Since then, new trials have been published that may or may not change the conclusions of the review. A new team of authors overtook the review on 26.10.2020, and the new review is expected to be published by the beginning of 2022. The review will be prepared based on most recent Cochrane methods. Readers may still find the outdated review on the CDSR (the Cochrane Library).

Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial.

IMPORTANCE: Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE: To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS: One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES: The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS: In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE: Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01327976.

The islet-acinar axis of the pancreas: more than just insulin.

Although the role of the islets in the regulation of acinar cell function seemed a mystery to investigators who observed their dispersion among pancreatic acini, over time an appreciation for this intricate and unique structural arrangement has developed. The last three decades have witnessed a steadily growing understanding of the interrelationship of the endocrine and the exocrine pancreas. The islet innervation and vascular anatomy have been more fully characterized and provide an appropriate background for our current understanding. The interrelationship between the endocrine and exocrine pancreas is mediated by islet-derived hormones such as insulin and somatostatin, other humoral factors including pancreastatin and ghrelin, and also neurotransmitters (nitric oxide, peptide YY, substance P, and galanin) released by the nerves innervating the pancreas. Although considerable progress has been achieved, further work is required to fully delineate the complex interplay of the numerous mechanisms involved. This review aims to provide a comprehensive update of the current literature available, bringing together data gleaned from studies addressing the actions of individual hormones, humoral factors, and neurotransmitters on the regulation of amylase secretion from the acinar cell. This comprehensive view of the islet-acinar axis of the pancreas while acknowledging the dominant role played by insulin and somatostatin on exocrine secretion sheds light on the influence of the various neuropeptides on amylase secretion.

Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice.

BACKGROUND: We have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of a combined treatment of galantide and octreotide with the efficacy of each agent individually in experimental AP. METHODS: Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide and/or octreotide were co-administered with each caerulein injection commencing with the first injection. Control animals received galantide, octreotide or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma amylase and lipase activities were measured. RESULTS: Galantide significantly reduced AP-induced hyperenzymaemia by 39-45%. Octreotide alone, or in combination with galantide, did not significantly alter AP-induced hyperenzymaemia. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide and octreotide administered individually reduced MPO activity by 79% and 50%, respectively; however their combination was without effect. Galantide, octreotide and their combination significantly reduced the percentage of abnormal acinar cells by 28-45%. CONCLUSIONS: Treatment with galantide alone ameliorated most of the indices of AP studied, whereas treatment with octreotide reduced pancreatic MPO activity and acinar cell damage. Combining the two peptides appears to negate their individual benefits, which suggests an interaction in their mechanism of action.

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion.

BACKGROUND: Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy. METHODS: A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20-89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses. RESULTS: Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin

Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion.

Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin-dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured. Lobules were coincubated with galanin (10(-12)-10(-7) M) and caerulein (10(-7) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), diazoxide (10(-7) M), or the galanin antagonist galantide (10(-12)-10(-7) M) for 30 min followed by incubation with caerulein alone, or combined with galanin (10(-12) M). Lobules were also coincubated with combinations of galanin (10(-12) M), caerulein, octreotide (10(-12)-10(-7) M) or cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), a somatostatin receptor antagonist (10(-9) M). Amylase secretion was expressed as percent of total lobular amylase. Caerulein stimulated amylase secretion to 124% of control. Diazoxide pretreatment abolished the caerulein-stimulated amylase secretion, whereas atropine or tetrodotoxin caused a partial inhibition. Galanin (10(-12)-10(-7) M) potentiated caerulein-stimulated amylase secretion to 160% of control. Preincubation with a combination of atropine and diazoxide abolished the potentiating effect of galanin, indicating muscarinic receptor and insulin mediation. Preincubation with galantide abolished the galanin effect, implying galanin receptor involvement. Coincubation with caerulein, galanin, and octreotide significantly reduced the potentiating effect galanin. However, coincubation with the somatostatin receptor antagonist, alone or in combination with galanin, significantly increased caerulein-stimulated amylase secretion to a level comparable to the galanin potentiation. Taken together, these data suggest that, at supramaximal caerulein concentrations, galanin acts via its receptors to further increase caerulein-stimulated amylase secretion by inhibiting the caerulein-induced release of somatostatin.

Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin.

Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10(-12) M to 10(-7) M), carbachol (10(-6) M), or caerulein (10(-10) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), hexamethonium (10(-5) M), or diazoxide (10(-7) M and 10(-4) M) for 30 min followed by incubation with caerulein (10(-10) M) alone or combined with galanin (10(-12) M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2, and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of two- and 1.7-fold over control evoked at 10(-6) M and 10(-10) M, respectively. Galanin (10(-12) M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by approximately 80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release.

Sphincter of Oddi: Function, dysfunction, and its management.

The most common functional disorder of the biliary tract and pancreas relates to the activity of the Sphincter of Oddi. The Sphincter of Oddi is a small smooth muscle sphincter strategically placed at the junction of the bile duct, pancreatic duct, and duodenum. The sphincter controls flow of bile and pancreatic juices into the duodenum and prevents reflux of duodenal content into the ducts. Disorder in its motility is called Sphincter of Oddi dysfunction. Clinically this presents either with recurrent abdominal biliary type pain or episodes of recurrent pancreatitis. Manometry may identify the motility abnormalities, the most clinically significant being an abnormally elevated basal pressure. The most effective treatment once an abnormal basal pressure is identified is division of the sphincter. This is associated with good long-term results.

Selection of electrical algorithms to treat obesity with intermittent vagal block using an implantable medical device.

BACKGROUND: A laparoscopically implantable electrical device that intermittently blocks both vagi near the esophagogastric junction led to significant excess weight loss (EWL) in an initial clinical trial in obese patients. The study objective was to optimize therapy algorithms and determine the EWL achieved with a second-generation device at university hospitals in Australia, Norway, and Switzerland. METHODS: Data acquired during the initial clinical trial were analyzed and subsequently used to select alternative electrical algorithms. In the second trial, vagal blocking using one selected therapy algorithm was initiated 2 weeks after implanting the second-generation device. The patients were followed up for 6 months to assess the EWL and safety, including adverse events. RESULTS: In the initial clinical trial, vagal blocking algorithm durations of 90-150 s were associated with greater EWL compared with either shorter or longer algorithm durations (P<.01). The second trial enrolled 27 patients (mean body mass index 39.3+/-.8 kg/m2) to evaluate a 120-s blocking algorithm. At 6 months, greater EWL was achieved (22.7%+/-3.1%, n=24) compared with the initial study and first-generation device (14.2%+/-2.2%, n=29, P=.03). In both trials, an association was found between the number of 90-150-s algorithms delivered daily and greater EWL (P=.03). No deaths, unanticipated device-related adverse events, or medically serious adverse events were associated with the device. CONCLUSION: This second-generation vagal blocking device, using a therapy algorithm of 120-s duration, resulted in a clinically acceptable safety profile and significantly greater EWL compared with the first-generation device delivering a wider range of therapy algorithm durations.

Influence of Asian Ethnicities on Short- and Mid-term Outcomes Following Laparoscopic Sleeve Gastrectomy.

PURPOSE: Prevalence of obesity in Asia has been on the increasing trend, with corresponding increase in utilisation of bariatric surgery. The objective of this study was to examine differences in weight loss outcomes following bariatric surgery between Asian ethnicities. MATERIALS AND METHODS: A retrospective database review was conducted of patients undergoing primary laparoscopic sleeve gastrectomy between 2009 and 2013 in 14 centres from Singapore, Malaysia, Taiwan, Hong Kong, Japan, Korea, India, Australia, Switzerland, and the USA. All patients with available follow-up data at 12 months and 36 months post-surgery were included in this study. Outcome measures used were percentage excess weight loss (%EWL) and percentage total weight loss (%TWL). Differences in outcomes between ethnicities were analysed after adjusting for age, gender, baseline body mass index (BMI), and presence of diabetes. RESULTS: The study population (n = 2150) consisted of 1122 Chinese, 187 Malays, 309 Indians, 67 Japanese, 259 Koreans, and 206 Caucasians. 67.1% were female and 32.9% were male. Mean age was 37.1 ± 11.2 years. Mean pre-operative BMI was 40.7 ± 8.1 kg/m2. With the Caucasian population as reference, Japanese had the best %TWL (3.90, 95% CI 1.16-6.63, p < 0.05) and %EWL (18.55, 95% CI 10.33-26.77, p < 0.05) while the Malays had the worst outcomes. Both Chinese and Koreans had better %EWL but worse %TWL as compared to Caucasians and there were no significant differences with the Indian study group. CONCLUSION: There are differences in weight loss outcomes following bariatric surgery between Asian ethnicities.

Long-term efficacy of a low-pressure adjustable gastric band in the treatment of morbid obesity.

OBJECTIVE: To determine the long-term efficacy and safety of a low-pressure adjustable gastric band in the treatment for morbid obesity and to detect whether age, gender, or preoperative body mass index (BMI) has an impact on the outcome. BACKGROUND: It is well known that low-pressure adjustable gastric bands such as the Swedish adjustable gastric bands (SAGB) lead to weight loss. However, very few long-term studies have been published and questions remain regarding long-term efficacy and safety, and whether any of the patient's demographic parameters including age, gender, or initial BMI impact the long-term outcome. METHODS: Six hundred consecutive patients who had a SAGB inserted between August 1996 and October 2005 were evaluated with regard to their initial BMI, age, and sex. RESULTS: There were 488 females and 112 males, with mean age 45.3 +/- 9.1, mean BMI 42.9 +/- 7.2 kg/m2, and mean weight 119.6 +/- 23.9 kg. Overall morbidity was 25.7% (10.4% perioperative, whereas 15.3% on long term). The following data represents 2, 3, 5, and 7 years of follow-up respectively. Mean BMI decreased to 30.9, 30.5, 32.7, and 31.2 kg/m2, whereas mean percentage excess weight loss (%EWL) was 60.5%, 61.5%, 53.2%, and 61.2%. Patients with BMI (<40 kg/m2) lost 63.7%, 61.2%, 45.5%, and 66.1% of their excess weight, whereas patients with BMI (40-49.9 kg/m2) lost 60.1%, 61.3%, 59.4%, and 66.6%, patients with BMI (50-50.9 kg/m2) lost 57.5%, 67.5%, 49.3%, and 40.2%, and patients with BMI (>60 kg/m2) lost 42.2%, 46.3%, 38.7%, and 40.2%. Female patients %EWL were 62.2%, 62.1%, 55.1%, and 62.3%, whereas male %EWL were 54.1%, 59.1%, 42.1%, and 51.3%. Patients <40 years %EWL were 61.8%, 62.5%, 57.1%, and 86.2%, whereas >40 years %EWL were 60.1%, 61.2%, 52.4%, and 60.1%. CONCLUSION: The SAGB is effective in achieving long-term sustainable weight loss with an acceptably low complication rate. Bands are effective regardless of patients' age and gender. Furthermore, preoperative BMI up to 60 kg/m2 does not influence the outcome.

Treatment of common bile duct stones discovered during cholecystectomy.

BACKGROUND: Several techniques of laparoscopic bile duct exploration and intraoperative endoscopic sphincterotomy (ES) have been developed to treat patients with common bile duct (CBD) stones in one session and avoid the complications of ES. With all these options available, very few randomized controlled trials (RCTs) have been undertaken. This review analyzes those studies. METHODS: We searched PubMed. Four RCTs and a Cochran Database Systematic Review were found. RESULTS: Two RCTs compared preoperative ES and laparoscopic CBD exploration (E) for known CBD stones. Laparoscopic CBDE had shorter length of hospitalization. Two RCTs compared immediate and delayed treatment and found that length of stay was less with laparoscopic CBDE, but clearance rates and morbidity/mortality were similar. CONCLUSIONS: Studies suggest that CBD stones discovered at the time of cholecystectomy are best treated during the same operation. The transcystic approach is safest if applicable. Individual surgeons must be aware of their own capabilities and those of the available endoscopists and perform the safest technique.

Intermittent Vagal Nerve Block for Improvements in Obesity, Cardiovascular Risk Factors, and Glycemic Control in Patients with Type 2 Diabetes Mellitus: 2-Year Results of the VBLOC DM2 Study.

BACKGROUND: One-year results of the VBLOC DM2 study found that intermittent vagal blocking (VBLOC therapy) was safe among subjects with obesity and type 2 diabetes mellitus (T2DM) and led to significant weight loss and improvements in glycemic parameters and cardiovascular risk factors. Longer-term data are needed to determine whether the results are sustained. METHODS: VBLOC DM2 is a prospective, observational study of 28 subjects with T2DM and body mass index (BMI) between 30 and 40 kg/m(2) to assess mid-term safety and weight loss and improvements in glycemic parameters, and other cardiovascular risk factors with VBLOC therapy. Continuous outcome variables are reported using mixed models. RESULTS: At 24 months, the mean percentage of excess weight loss was 22% (95% CI, 15 to 28, p < 0.0001) or 7.0% total body weight loss (95% CI, 5.0 to 9.0, p < 0.0001). Hemoglobin A1c decreased by 0.6 percentage points (95% CI, 0.2 to 1.0, p = 0.0026) on average from 7.8% at baseline. Fasting plasma glucose declined by 15 mg/dL (95% CI, 0 to 29, p = 0.0564) on average from 151 mg/dL at baseline. Among subjects who were hypertensive at baseline, systolic blood pressure declined 10 mmHg (95% CI, 2 to 19, p = 0.02), diastolic blood pressure declined by 6 mmHg (95% CI, 0 to 12, p = 0.0423), and mean arterial pressure declined 7 mmHg (95% CI, 2 to 13, p = 0.014). Waist circumference was significantly reduced by 7 cm (95% CI, 4 to 10, p < 0.0001) from a baseline of 120 cm. The most common adverse events were mild or moderate heartburn, implant site pain, and constipation. CONCLUSIONS: Improvements in obesity and glycemic control were largely sustained after 2 years of treatment with VBLOC therapy with a well-tolerated risk profile.

Inguinal hernia repair with the Kugel patch.

BACKGROUND: The Kugel hernia patch (Davol, Cranston, RI, USA) for treatment of inguinal hernias is a minimal access technique of inguinal herniorrhaphy, which aims to combine the utility of the open operation with the advantages of the laparoscopic procedures. The aim of the present study is to report an initial experience of a cohort of patients with inguinal hernias undergoing repair using this technique. METHODS: A prospective series of 107 inguinal hernia repairs performed between January 2000 and October 2003 in 96 patients, using the Bard Kugel hernia patch were entered into the study. Patient comfort, complications, activity levels postoperations and early recurrence were evaluated. RESULTS: The median age was 76 years (range 23-88 years). There were 107 inguinal hernias repaired. There were 11 bilateral, 39 left and 46 right sided hernias, 12 were recurrent. There were no major complications. There were no early recurrences. At 6 and 12 months there were one and two hernia recurrences, respectively. A further recurrence was noted at 2 years. There was no consistent relationship between having hernia surgery and loss of mobility. There was no difference in straight leg raising noted following surgery compared to the patients' preoperative score. Ability to shower, dress, reach the toilet or perform housework by day 7 returned to normal. Shopping activities were resumed by day 30 in all patients. CONCLUSIONS: The Kugel hernia operation is associated with minimal postoperative pain and rapid return to normal activity. There is a modest hernia recurrence rate, which needs to be addressed.

Effect of a post-operative structured exercise programme on short-term weight loss after obesity surgery using adjustable gastric bands.

BACKGROUND: Exercise has been recommended as an adjunct to diet control to achieve weight loss. No previous studies in the area had formal exercise guidelines or education [1, 2]. Unique to our practice is Bandfit, a personal trainer-led exercise programme for patients following bariatric surgery. METHODS: We analysed the effect of Bandfit on short-term weight loss. A retrospective review of a prospectively collected database of consecutive patients between 2007 and 2008 was undertaken. Patients were educated about appropriate exercises for obese people with active participation. Percentage excess weight loss was calculated at 12 and 36 months. Weights were accepted ±3 months following the gastric banding. Patients were divided into subgroups based on zero, one or greater than one session attended. Patients without available records, 12-month data or a rural address were excluded. Data were statistically analysed utilising a two-sample t test and an analysis of variance (ANOVA) calculation. RESULTS: One hundred sixty-three patients were eligible for inclusion with 26 excluded as described in the methods. In the remaining 137 patients, 49 (36 %) did not attend any sessions, 28 (20 %) attended one, and 60 (44 %) attended more than one session. CONCLUSIONS: Analysis of the %EWL and sessions attended demonstrated a significant difference between those who attended more than one Bandfit session (p < 0.03), compared to those who did not attend any. However, this effect was not seen at 36 months. Attendance at a dedicated educational exercise programme significantly enhances short-term weight loss, but the effect is not seen at 36 months.

Characterization of circular muscle motor neurons of the duodenum and distal colon in the Australian brush-tailed possum.

The motor innervation of the duodenum and distal colon remains uncharacterized within the same species. Our aim was to compare the projections and neurochemical properties of duodenal and distal colon circular muscle motor neurons. Circular muscle motor neurons were retrogradely traced by using a neural tracer in vitro, processed for choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity and then visualized by using indirect immunofluorescence. A mean of 372 +/- 64 and 156 +/- 23 neurons (mean +/- SEM) were tracer-labeled within the duodenum and colon, respectively. The ChAT+/NOS- neurons comprised 57.6 +/- 6.6% and 39.6 +/- 4.4% of all labeled cells in the duodenum and colon, respectively, and projected mainly in the oral direction. Of all labeled cells, the ChAT-/NOS+ neurons comprised 8.5 +/- 2.3% in the duodenum and 46.6 +/- 5.0% in the distal colon and projected mainly in the anal direction. Of the remainder, 20.6 +/- 5.0% and 8.2 +/- 2.4% were ChAT+/NOS+ and 13.2 +/- 0.9% and 5.6 +/- 1.4% were ChAT-/NOS- in the duodenum and distal colon, respectively. Within both regions, the distribution of the ChAT+/NOS- and ChAT-/NOS+ neurons are consistent with the ascending excitatory and descending inhibitory reflexes. The proportion of ChAT-/NOS+ neurons is greater within the colon in comparison with the duodenum. A considerable proportion of duodenal motor neurons were ChAT+/NOS+ and ChAT-/NOS-. These two classes may underlie nonperistaltic motor patterns, which predominate within the duodenum. These findings demonstrate regional differences in the innervation of intestinal circular muscle.

Endothelins induce gallbladder contraction independent of elevated blood pressure in vivo in the Australian possum.

Endothelin levels are elevated in shock, sepsis, and cholestatic jaundice, and an effect on biliary motility may be postulated. The aim of this study was to determine whether (1) endothelin-1 and endothelin-3 induce gallbladder contraction in vivo, (2) the response is caused by changes in blood pressure, and (3) the response is nerve mediated. Gallbladder pressure and blood pressure were measured in 38 anesthetized possums. Endothelin-1 or endothelin-3 (5 to 200 pmol/kg) was administered by close intra-arterial injection. Tetrodotoxin (9 microg/kg) or the mixed endothelin antagonist tezosentan was infused at a rate of 10 or 100 nmol/kg/min (close intra-arterial injection). Maximum changes in gallbladder pressure (% of carbachol-induced contraction) and blood pressure (mm Hg) were determined. Statistical analysis was carried out by means of repeated-measures analysis of variance and Kruskal-Wallis test. Both endothelin-1 and endothelin-3 induced dose-dependent increases in gallbladder pressure and blood pressure (P < 0.05), which were unaffected by pretreatment with tetrodotoxin. The endothelin-1-induced gallbladder pressure but not blood pressure was reduced by the higher dose of tezosentan (P < 0.03). The lower dose of tezosentan also produced a decrease in the endothelin-3-induced gallbladder pressure (P < 0.02) but not in blood pressure, whereas the higher dose reduced the blood pressure with no further reduction in gallbladder pressure (P < 0.05). Endothelins increase gallbladder motility in vivo, acting directly on the smooth muscle and independent of changes in blood pressure.

Second-generation recombinant hemoglobin molecules do not stimulate sphincter of Oddi, gallbladder or duodenal motility in the Australian brush-tailed possum.

BACKGROUND: Several studies have investigated the effects of hemoglobin-based oxygen carriers on gastrointestinal motility. Diaspirin cross-linked hemoglobin reduces sphincter of Oddi trans-sphincteric flow and increases duodenal motility in the Australian brush-tailed possum, effects attributed to nitric oxide (NO) scavenging. Recently, second-generation recombinant hemoglobin molecules with reduced NO scavenging ability have been developed. AIM: To determine the effects of two second-generation recombinant hemoglobin solutions and the prototype recombinant hemoglobin with high NO binding, on duodenal and biliary motility in the Australian brush-tailed possum. METHOD: Blood pressure; duodenal, sphincter of Oddi and gallbladder motility; and trans-sphincteric flow were recorded. The effects of recombinant hemoglobin or human serum albumin (control) solutions on these parameters were investigated. Each solution was infused intravenously at 1 mL/kg/min to deliver 250 mg/kg or 500 mg/kg. RESULTS: Duodenal contraction frequency was stimulated by the high dose of prototype recombinant hemoglobin, but not by a comparable dose of second-generation recombinant hemoglobin. The induced duodenal activity occurred in the later phase of the experimental period. In contrast, biliary motility and trans-sphincteric flow were not altered by any hemoglobin solution. The high dose of all the hemoglobin solutions elevated blood pressure, whereas the low dose solutions did not alter any parameter measured. CONCLUSION: At the doses studied, the second-generation recombinant hemoglobin with reduced NO binding capacity did not significantly alter duodenal and biliary motility, supporting the need for further studies to evaluate their potential usefulness as blood substitutes.