Intact Gallbladder Research Articles

Evaluation and management of functional biliary pain in patients with an intact gallbladder

The diagnosis and management of suspected functional biliary pain in patients with an intact gallbladder remains contentious. Major issues include the lack of a clear definition of what constitutes biliary pain, a poor understanding of its natural history and pathophysiology, and the all too common scenario of the patient who has persistent pain despite surgical removal of the gallbladder. As a consequence, symptoms alone have generally been considered to be unreliable in the diagnosis of gallbladder dysfunction, and this has led to a search for a reliable test to help confirm a clinical suspicion of gallbladder dysfunction prior to the definitive treatment, cholecystectomy. At present, cholecystokinin-cholescintigraphy with a calculation of the gallbladder ejection fraction is the most commonly used test; however, its utility in predicting symptom outcome after cholecystectomy has been questioned. The use of cholecystokinin-cholescintigraphy to determine the appropriateness for cholecystectomy appears to be most useful when performed using a slow infusion of cholecystokinin in a well-selected patient population. However, for reasons explained herein, consideration of cholecystectomy on the basis of high clinical suspicion after adequate follow-up with trials of pharmacological therapies and exclusion of other disease entities, together with counseling the patient on postoperative expectations, may be a reasonable alternative.

Percutaneous Cholecystolithotomy: A Case for Fulguration of the Gallbladder Wall

Percutaneous cholecystolithotomy (PC) has been described previously as an alternative to laparoscopic cholecystectomy in high-risk patients and in those with adherent gallbladders that are not amenable for laparoscopic cholecystectomy. However, it is associated with a high (41%) recurrence of cholelithiasis due to intact gallbladder mucosa. In this paper, we describe a case of PC with fulguration of the gallbladder mucosa to scar and defunctionalize the mucosa and thus prevent recurrence of stones. After 12 months of follow-up, the patient remains asymptomatic.

Impact of Food on Hepatic Clearance of Patients After Endoscopic Sphincterotomy

The recurrence rate of common bile duct stones (CBDS) is around 3-21% after treatment by endoscopic sphincterotomy (ES). Fatty meal has been shown to improve hepatic clearance in both patients with intact gallbladder and post-cholecystectomy after ES. This study tested the effects of different kinds of food on hepatic clearance by using quantitative cholescintigraphy (QC) in patients after ES. Forty-seven patients after ES with abnormal QC were enrolled in our study. Complete ablation of sphincter function was confirmed by sphincter of Oddi manometry. Fasting QC was done in every patient shortly after normalization of liver function, and then followed with low-fat and fatty-meal QC. Each of the 47 subjects was observed for the effect on hepatic clearance at 3 different levels of treatments (diets and fasting). Additionally, possible factors responsible for recurrent CBDS were investigated by means of logistic regression. Both fatty and low-fat meals could significantly improve hepatic clearance compared with fasting in most patients after ES. But the response to food types was individualized. All patients tolerated the meals well. There was no significant relationship between the recurrence of CBDS and sex, age, intact gallbladder and presence of juxtapapillary diverticulum, CBD size, and improvement in hepatic clearance (> or = 5%) by food. Both fatty and low-fat meals improved hepatic clearance in most of the patients with CBDS after ES, but the response to meals was individualized. Therefore, there is no need to restrict the amount of fat intake for patients who have undergone ES.

Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis

Microlithiasis has been identified as a cause of idiopathic acute pancreatitis in patients with an intact gallbladder. Microlithiasis has also been identified in the bile of some patients who have undergone cholecystectomy. However, it is unknown whether bile microlithiasis causes postcholecystectomy pain. To identify bile microlithiasis in patients with postcholecystectomy pain and to investigate the therapeutic effect of ursodeoxycholic acid (urso) on such patients with microlithiasis in the bile. Prospective randomized trial. Tertiary medical center. Patients with postcholecystectomy pain and bile crystals. Urso treatment. The severity and frequency of right upper-quadrant abdominal pain were compared with and without urso treatment, and before and after urso treatment. A total of 118 patients with postcholecystectomy pain were screened for the study. Twelve patients (10%) were identified with bile crystals. In the first phase, 6 of these patients received urso treatment, whereas the other 6 patients did not receive urso treatment. In the second phase, the latter 6 patients were given the urso treatment. After using urso for a few months, their biliary-type abdominal pain significantly improved or resolved. In the control group, there was no improvement in symptoms. There was a significant difference between the 2 groups (P = .01). Single-center, small number of patients. This study provided evidence that supports the hypothesis that bile microlithiasis is indeed a cause for postcholecystectomy pain. Patients with such postcholecystectomy pain may benefit from a microscopic examination of bile for crystals or microlithiasis, and urso treatment if bile crystals are identified.

The fate of patients who undergo “preoperative” ERCP to clear known or suspected bile duct stones

There is debate as to whether recurrent biliary complications are more common in patients who do not have elective cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) management of common bile duct (CBD) stones. The aim of this study was to determine the fate of patients with intact gallbladders who have had CBD stones removed at ERCP, and to assess their risk of recurrent biliary symptoms. We retrospectively identified all patients in our large tertiary center population with intact gallbladders who had an ERCP for CBD stones from December 1999 to March 2002. We determined which patients had subsequent elective cholecystectomy, and the outcomes of patients who did not have elective surgery. 309 patients had CBD stones at ERCP during the study period, of which 139 had intact gallbladders at the time of ERCP. Of these 139 patients 59 had subsequent elective cholecystectomy, 11 by open operation and 48 laparoscopically. Of these 139 patients, 27 had cholecystectomy planned; 47 patients were managed with a wait-and-see strategy, 30 of whom were poor surgical candidates. Of these 47 patients in whom a wait-and-see policy was adopted, 9 (19%) developed complications including recurrent pain and/or abnormal liver function tests (LFTs), recurrent biliary colic, and pancreatitis. Eight of these nine patients were from the poor surgical candidate group. Sphincterotomy had been performed at initial ERCP in all patients. Over half of our population of 139 patients with CBD stones at ERCP and intact gallbladders had actual or planned elective cholecystectomy. For those patients in whom a decision to wait-and-see was made, almost 20% developed complications. Elective cholecystectomy after a finding of choledocholithiasis is supported by many and is a common strategy in our experience. Recurrent biliary complications are relatively common in those who do not undergo elective cholecystectomy, especially those patients who represent a high operative risk.

Patient perception of natural orifice transluminal endoscopic surgery as a technique for cholecystectomy

Although the concept of natural orifice transluminal endoscopic surgery (NOTES) as a minimally invasive surgical technique is gaining increasing popularity, patient perception toward NOTES is unclear. Because cholecystectomy is the most common laparoscopic procedure, the concept of NOTES was examined in this context. To evaluate patient perception of NOTES as a potential technique for a cholecystectomy. Those patients with an intact gallbladder who were undergoing an EUS or an ERCP for evaluation of abdominal pain, pancreatitis, or suspected choledocholithiasis. Tertiary-referral center. Cross-sectional survey. One hundred patients were given a questionnaire that described the technique, the complication rates, and benefits of laparoscopic cholecystectomy (LC). The concept of NOTES was then described in detail, with possible orifices being the mouth, the rectum, and the vagina. Patients were queried about their preference for a cholecystectomy technique (LC vs NOTES), choice of orifice, and the risks that they were willing to undergo for NOTES. Of the 100 patients, 78% preferred NOTES, and 22% preferred LC. The mean age of the patients was 45 years; 36% of patients were men, 70% were white, and 83% had undergone a prior endoscopy; no significant differences were observed between the NOTES and LC groups for these characteristics. In multivariable modeling, those with age </= 50 years (odds ratio [OR] 1.3, P = .61), female sex (OR 2.1, P = .14), and prior endoscopy experience (OR 2.2, P = .19) were more likely to prefer NOTES than an LC. There was no difference in preference for NOTES between whites and nonwhites (OR 1.0, P = .98). The most common reasons for NOTES preference were lack of external pain (99%) and scarring (89%). Among the patients who preferred NOTES, for both men (23/25 [92%]) and women (43/53 [81%]), the oral route was the preferred orifice. A decreasing trend of patient preference for NOTES was observed with increased procedural complications: patient preference was 100% if complications were <3%, 97% if complications were equal to 3%, 15% if complications were 6%, and 6% if complications were 9%. A selective cohort of patients was evaluated. Patients preferred NOTES to laparoscopy as the technique for cholecystectomy as long as the complication rates were comparable with current standards of LC. The oral orifice appeared to be the preferred approach for most patients. Given this favorable perception, further innovations in NOTES-related technology and refinements in procedural technique are justified.

MRCP-secretin test–guided management of idiopathic recurrent pancreatitis: long-term outcomes

In patients with recurrent pancreatitis of unknown etiology and nondilated ducts, accurate morphofunctional evaluation of the pancreaticobiliary ductal system and sphincter of Oddi function is important in the diagnostic workup. However, ERCP and sphincter of Oddi manometry may be nondiagnostic and postprocedure complications may be frequent. Our purpose was to assess the diagnostic accuracy of the magnetic resonance cholangiopancreatography with secretin test (MRCP-S) in patients with recurrent acute pancreatitis of unknown etiology. Accuracy was established on the basis of ERCP findings and a minimum of 24 months' clinical follow-up. Thirty-seven consecutive patients with intact gallbladder and a nondilated pancreaticobiliary ductal system with nonpathologic EUS findings entered a prospective MRCP-S-guided and ERCP-guided diagnostic and therapeutic study protocol. Patients were followed up for a mean of 31.3 months (range 26-38 months). MRCP-S identified some pancreatic outflow impairment, suggesting morphofunctional dysfunction of either the major or minor papilla, in 12 of 37 patients (32.4%). The addition of ERCP to MRCP-S did not substantially improve the diagnostic yield for the etiology of recurrent pancreatitis, and 13.6% of cases had mild postprocedure pancreatitis. The S-test was abnormal in 12 of 20 cases (60%) in whom some dysfunction of the sphincter of Oddi or minor papilla was assumed on the basis of follow-up findings. The outcome was successful after biliary or pancreatic sphincterotomy in all patients with an abnormal S-test result. Sensitivity, specificity, and positive and negative predictive values of the S-test for the diagnosis of pancreatic outflow impairment at the major or minor papilla were, respectively, 57.1%, 100%, 100%, and 64%. When the test showed an abnormal result, we were unable to distinguish between biliary and pancreatic segment dysfunction of the sphincter of Oddi. In idiopathic recurrent pancreatitis with nondilated ducts, the MRCP-S-guided approach gave diagnostic accuracy comparable to ERCP with regard to morphologic lesions, and it can be used as an alternative, avoiding ERCP-related complications in the diagnostic phase. An abnormal S-test result showed an excellent positive predictive value and somewhat disappointing negative predictive value for sphincter of Oddi or minor papilla dysfunction and for clinical success of therapeutic endoscopic approach.

Difference of CBD width on US vs. ERCP

To investigate the relationship between US and ERCP in the measurement of common bile duct (CBD) width after application of Compound and Harmonic imaging on ultrasound. We prospectively evaluated the CBD width as measured on endoscopic retrograde cholangiopancreatography (ERCP) and ultrasonography (US), applying Compound and Harmonic US techniques, on 100 patients. Furthermore, we retrospectively re-examined US and ERCP images of 48 patients who underwent ERCP and US during the same hospitalization period. The average difference in measurements by US compared to ERCP was 2.3 mm (P < 0.01) in the retrospective and 1.9 mm in the prospective study (P < 0.001). The average difference in measurements between US and ERCP in post-cholecystectomy patients was 4.0 mm in the retrospective study (10 patients), and 3.8 in the prospective study (25 patients). The difference between the measurements on both examinations decreased with increasing CBD width. There was a good correlation between ERCP and US measurements of CBD width (r = 0.73 for all patients and r = 0.88 for patients with intact gallbladder, P < 0.001). There is a gap between measurement of CBD width on US and ERCP of about 2 mm. The application of Compound and Harmonic techniques in the prospective study probably enabled a more accurate sonographic measurement.

Calcium waves in intact guinea pig gallbladder smooth muscle cells

Intracellular Ca(2+) waves and spontaneous transient depolarizations were investigated in gallbladder smooth muscle (GBSM) whole mount preparations with intact mucosal layer [full thickness (FT)] by laser confocal imaging of intracellular Ca(2+) and voltage recordings with microelectrodes, respectively. Spontaneous Ca(2+) waves arose most often near the center, but sometimes from the extremities, of GBSM cells. They propagated regeneratively by Ca(2+)-induced Ca(2+) release involving inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] receptors and were not affected by TTX and atropine (ATS). Spontaneous Ca(2+) waves and spontaneous transient depolarizations were more prevalent in FT than in isolated muscularis layer preparations and occurred with similar pattern in GBSM bundles. Ca(2+) waves were abolished by the Ins(1,4,5)P(3) receptor inhibitors 2-aminoethoxydiphenyl borate and xestospongin C and by caffeine and cyclopiazonic acid. These events were reduced by voltage-dependent calcium channels (VDCCs) inhibitors diltiazem and nifedipine, by PLC inhibitor U-73122, and by thapsigargin and ryanodine. ACh, CCK, and carbachol augmented Ca(2+) waves and induced Ca(2+) flashes. The actions of these agonists were inhibited by U-73122. These results indicate that in GBSM, discharge and propagation of Ca(2+) waves depend on sarco(endo)plasmic reticulum (SR) Ca(2+) release via Ins(1,4,5)P(3) receptors, PLC activity, Ca(2+) influx via VDCCs, and SR Ca(2+) concentration. Neurohormonal enhancement of GBSM excitability involves PLC-dependent augmentation and synchronization of SR Ca(2+) release via Ins(1,4,5)P(3) receptors. Ca(2+) waves likely reflect the activity of a fundamental unit of spontaneous activity and play an important role in the excitability of GBSM.

Functional Gallbladder and Sphincter of Oddi Disorders

The functional disorder of the gallbladder (GB) is a motility disorder caused initially either by metabolic abnormalities or by a primary motility alteration. The functional disorders of the sphincter of Oddi (SO) encompass motor abnormalities of either the biliary or the pancreatic SO. Dysfunction of the GB and/or biliary SO produce similar patterns of pain. The pain caused by a dysfunction of the pancreatic SO can be similar to that of acute pancreatitis. The symptom-based diagnostic criteria of motility dysfunction of the GB and biliary SO are episodes of moderate to severe steady pain located in the epigastrium and right upper abdominal quadrant that last at least 30 minutes. GB motility disorder is suspected after gallstones and other structural abnormalities have been excluded. This diagnosis should then be confirmed by a decreased GB ejection fraction induced by cholecystokinin at cholescintigraphy and after disappearance of the recurrent biliary pain after cholecystectomy. Symptoms of biliary SO dysfunction may be accompanied by features of transient biliary obstruction, and those of pancreatic SO dysfunction are associated with elevation of pancreatic enzymes and even pancreatitis. Biliary-type SO dysfunction is more frequently recognized in postcholecystectomy patients. SO manometry is valuable to select patients with sphincter dysfunction; however, because of the high incidence of complications, these patients should be referred to an expert unit for such assessment. Thus invasive tests should be performed only in the presence of compelling clinical evidence and after noninvasive testing has yielded negative findings. The committee recommends that division of the biliary or pancreatic sphincters only be considered when the patient has severe symptoms, meets the required criteria, and other diagnoses are excluded.

Retrospective review of the preoperative biliary and gastrointestinal evaluation for gastric bypass surgery

The purpose of this study was to analyze the frequency and results of preoperative biliary and gastrointestinal (GI) evaluation of patients undergoing Roux-en-Y gastric bypass (RYGB). Retrospective review of the preoperative evaluation of 144 consecutive RYGB patients. Cholecystectomy had already been performed in 43 (30%) patients; 22% of those patients with an intact gallbladder had cholelithiasis. Ten patients (7%) had an upper GI x-ray (UGI), and 94 patients (65%) had an esophagogastroduodenoscopy (EGD). Abnormalities were found in 40% of the UGIs and 84% of the EGDs. A total of 96 patients (67%) were tested for Helicobacter pylori; 11% were positive. Twenty-one patients (15%) underwent preoperative colonoscopy; 48% were abnormal, but most of the abnormalities were not clinically significant. Three patients had barium enema x-ray, which was normal in all cases. The preoperative biliary and GI evaluation of bariatric surgery patients should include a routine ultrasound of the gallbladder. Routine preoperative EGD will detect a significant number of abnormalities that should be treated, but should rarely alter the bariatric surgical procedure or result in denial of bariatric surgery. Many abnormalities will be asymptomatic. Patients should be routinely screened for H. pylori and, if positive, treated before bariatric surgery. Lower GI evaluation should be performed selectively based on the patient's symptoms, physical findings, and guidelines for colorectal cancer and polyp screening.

Routine gallbladder screening not necessary in patients undergoing laparoscopic Roux-en- Y gastric bypass

Background Management of the gallbladder in patients undergoing laparoscopic Roux-en- Y gastric bypass (LRYGBP) is controversial. We reviewed our experience in patients undergoing LRYGBP without routine gallbladder screening. Methods The data of 644 patients who underwent LRYGBP at our institution were analyzed. Preoperative ultrasonography was routinely obtained early in our series and selectively thereafter in patients with suspected symptomatic biliary disease. Cholecystectomy at LRYGBP was performed in symptomatic patients with positive ultrasound findings. Postoperatively, patients with intact gallbladders were prescribed ursodiol for 6 months. Results Of the 644 patients, 155 (24%) had history of cholecystectomy. A total of 104 patients underwent preoperative ultrasonography. Of the 104 patients, 20 had positive ultrasound findings and symptoms consistent with biliary disease and underwent concomitant cholecystectomy. Twelve patients had positive ultrasound findings and no biliary symptoms and did not undergo cholecystectomy. At a mean follow-up of 26.4 months, only 1 (8.3%) of the 12 patients had required cholecystectomy. Of the 104 patients, 72 had negative ultrasound findings. At a mean follow-up of 21.2 months, 5 of them (6.9%) had required cholecystectomy. The remaining 385 patients did not undergo any gallbladder screening. At a mean follow-up of 14 months, 32 (8.3%) of 385 patients had required cholecystectomy. Compliance with ursodiol for >4 months was only 39%. A time-to-event analysis did not reveal a significant difference in the cholecystectomy rate between asymptomatic patients with preoperative gallbladder screening and patients with no screening. Conclusion Omission of gallbladder screening in asymptomatic patients undergoing LRYGBP is a reasonable approach that spares the patient a potentially unnecessary procedure with all its associated risks.

Endoscopic sphincterotomy for bile duct stones in patients with intact gallbladders.

Endoscopic sphincterotomy was performed in 121 patients (age ranged 34-92 years; median 80 years) with intact gallbladders and bile duct stones. Clearance of the duct by basket or balloon extraction was attempted in 97 patients (80 per cent) and achieved in 93 of these patients (96 per cent). In 24 patients the duct was left to empty spontaneously and this occurred in 22 patients. Immediate complications due to endoscopic sphincterotomy occurred in five patients (two haemorrhage, two perforation, one haemorrhage and perforation). Of the 101 patients reviewed 12-72 months (median 24 months) after endoscopic sphincterotomy, 76 (75 per cent) have remained asymptomatic throughout the follow-up period. Eighteen patients (18 per cent) required cholecystectomy for recurrent gallbladder symptoms 1-24 months after endoscopic sphincterotomy. One of the asymptomatic patients underwent cholecystectomy on the advice of his consultant. A further seven had recurrent biliary colic or cholangitis necessitating enlargement of the sphincterotomy and further stone retrieval in three of these patients. Endoscopic sphincterotomy is an effective treatment for bile duct stones in high risk patients, but subsequent cholecystectomy is required in a significant number of patients owing to continuing gallbladder symptoms.

Endoscopic sphincterotomy for bile duct stones in patients with intact gallbladders

Endoscopic sphincterotomy for bile duct stones in patients with intact gallbladders

Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells

Spontaneous action potentials and Ca(2+) transients were investigated in intact gallbladder preparations to determine how electrical events propagate and the cellular mechanisms that modulate these events. Rhythmic phasic contractions were preceded by Ca(2+) flashes that were either focal (limited to one or a few bundles), multifocal (occurring asynchronously in several bundles), or global (simultaneous flashes throughout the field). Ca(2+) flashes and action potentials were abolished by inhibiting sarcoplasmic reticulum (SR) Ca(2+) release via inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] channels with 2-aminoethoxydiphenyl borate and xestospongin C or by inhibiting voltage-dependent Ca(2+) channels (VDCCs) with nifedipine or diltiazem or nisoldipine. Inhibiting ryanodine channels with ryanodine caused multiple spikes superimposed upon plateaus of action potentials and extended quiescent periods. Depletion of SR Ca(2+) stores with thapsigargin or cyclopiazonic acid increased the frequency and duration of Ca(2+) flashes and action potentials. Acetylcholine, carbachol, or cholecystokinin increased synchronized and increased the frequency of Ca(2+) flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did not affect Ca(2+) flash or action potential activity but inhibited the excitatory effects of acetylcholine on these events. These results indicate that Ca(2+) flashes correspond to action potentials and that rhythmic excitation in the gallbladder is multifocal among gallbladder smooth muscle bundles and can be synchronized by excitatory agonists. These events do not depend on PLC activation, but agonist stimulation involves activation of PLC. Generation of these events depends on Ca(2+) entry via VDCCs and on Ca(2+) mobilization from the SR via Ins(1,4,5)P(3) channels.

Duct of Luschka Leak with an Intact Gallbladder Following EUS

Duct of Luschka Leak with an Intact Gallbladder Following EUS

Cholecystectomy After Endoscopic Sphincterotomy for Common Bile Duct Stones: Is Surgery Necessary?

It has been more than 30 years since the introduction of endoscopic sphincterotomy for the management of choledocholithiasis. Once introduced, this endoscopic intervention subsequently enabled clinicians to witness the natural history of leaving the gallbladder in situ once the common duct calculi were removed. Because many people were free of symptoms once the common bile duct was cleared of stones, patients and physicians alike soon questioned whether it was necessary to remove the gallbladder at all. Despite more than two decades of clinical research and numerous published reports, the answer to this question remains elusive. Similarly, the management algorithm for choledocholithiasis in patients with an intact gallbladder remains controversial. We review the available key data regarding this question. Importantly, there are only three prospective, randomized trials that have examined the need for cholecystectomy after endoscopic sphincterotomy, with case studies constituting most of the published reports. Consequently, the literature on this topic remains inconclusive, weakened by its retrospective approach, considerable variability between the patients studied, inconsistent inclusion and exclusion criteria, and frequently poor patient follow-up. Nonetheless, the preponderance of data favor removing the gallbladder after endoscopically clearing the common bile duct of gallstones because an estimated 25% of patients will experience recurrent symptoms within a 2-year follow up period. Recognizing the existence of various mitigating clinical factors, we advocate adopting a selective wait-and-see approach for high-risk patients, especially those with a life expectancy of less than 2 years or severely debilitating comorbidities.

Biliary microlithiasis: A neglected cause of recurrent pancreatitis and biliary colic?

Biliary microlithiasis: A neglected cause of recurrent pancreatitis and biliary colic?

Long-Term Effects of Endoscopic Papillary Balloon Dilation on Gallbladder Motility

We prospectively studied long-term (5 years) effects of endoscopic papillary balloon dilation (EPBD) on gallbladder motility. Thirteen patients with intact gallbladders (six with and seven without gallbladder stones) who had undergone EPBD for choledocholithiasis were enrolled in this study. Gallbladder volumes, while fasting and after dried egg yolk ingestion, were determined by ultrasonography, before and at 7 days, 1 month, and 1, 2, and 5 years after EPBD. Before EPBD, the gallbladder had a larger fasting volume and lower yolk-stimulated maximum contraction than in normal controls. Seven days after EPBD, fasting volume was decreased and maximum contraction was increased, regardless of whether the patient had gallbladder stones, showing significant differences from the pre-EPBD values. At 1 month to 5 years after EPBD, these changes were far less evident and gallbladder function did not differ significantly from baseline. EPBD does not adversely affect gallbladder motility in the long-term (5 years).

CNTF restores gallbladder contractility in leptin-resistant obese diabetic mice

Background. Obesity and diabetes are major risk factors for the development of cholesterol gallstones, and the majority of obese people have leptin-resistant obesity. Previous studies from our laboratory have demonstrated that both leptin-deficient (Lep ob) and leptin-resistant (Lep db) obese diabetic mice have decreased in vitro gallbladder motility. We have also shown that leptin administration to leptin-deficient (Lep ob) animals restores gallbladder motility and reverses obesity and hyperinsulinemia. However, the administration of additional leptin to leptin-resistant (Lep db) mice would not be expected to ameliorate their physiologic parameters. In contrast, recent studies have demonstrated that ciliary neurotrophic factor (CNTF) can reduce weight and hyperinsulinemia in leptin-resistant obesity. Hypothesis. CNTF would cause weight loss, lower blood sugars, and restore gallbladder contractility in leptin-resistant (Lep db) mice. Methods. To test this hypothesis, 20 C57b/6J and 20 Lep db 8-week-old mice were injected intraperitoneally daily with either saline or 0.3 μg/g CNTF Ax15 for 17 days. At 11 weeks, mice were weighed and underwent cholecystectomy. Intact gallbladders were mounted in 3 mL muscle baths and stimulated with acetylcholine (ACh) and cholecystokinin (CCK). Serum glucose levels were measured. Data were analyzed by two-way ANOVA. Results are shown in the table. Conclusions. These data suggest that daily administration of ciliary neurotrophic factor (CNTF) causes (1) significant weight loss, (2) improvement of diabetes, and (3) significant alterations in gallbladder motility which is decreased in lean nondiabetic mice and improved in obese diabetic mice. We conclude that ciliary neurotrophic factor may improve gallbladder contractility in leptin-resistant obese diabetes. TABLE—ABSTRACT 48 Strain Wt (g) Glucose (mg/dL) ACh 10 −5 M (N/cm 2) CCK 10 −8 M (N/cm 2) Saline C57 17 ± 0 110 ± 12 .39 ± .04 1.14 ± .13 CNTF C57 13 ± 0 ∗ 101 ± 7 .20 ± .04 ∗ 0.59 ± .08 ∗ Saline Lep db 41 ± 2 † 440 ± 26 † .13 ± .03 ∗ 0.46 ± .08 ∗ CNTF Lep db 22 ± 1 ‡ 200 ± 33 † .54 ± .10 ‡ 1.02 ± .09 ‡ ∗ P < 0.05 versus Saline C57; † P < 0.01 versus other groups; Ddagger; P < 0.001 versus Saline lep db.