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secretion in leptin-resistant obese mice
S12
Surgical Forum Abstracts
trol of SGLT1, with the output loop mediated by either neural or hormonal factors.
Dorsal motor nucleus of the vagus (DMV): A CNS site that directly regulates activity of the lower esophageal sphincters Patrick G Jackson, MD, Mark Niedringhaus, Rebecca Pearson, Janell Richardson, Stephen Evans, MD, Richard Gillis, PhD, Niaz Sahibzada, PhD Georgetown University Hospital, Washington, DC INTRODUCTION: Concurrent transient relaxations of both the lower esophageal sphincters (LES) and crural diaphragm (CD) have been shown to be associated with gastroesophageal reflux. The purpose of the present study was to determine if the DMV regulates the activity of the both esophageal sphincters by a direct projection to these end organs. Additionally, since these sphincters act in tandem, we were interested to know the degree of their co-innervation by the DMV. METHODS: Experiments were performed in isoflurane anesthetized Ferrets (600-700 gm). Cholera Toxin (CTb) conjugated to HRP (n⫽4) or fluorescent label FITC or TRITC (n⫽3) was injected into either the LES or the CD, respectively. After 5 days, animals were perfused and their brains removed and prepared for immunohistochemistry. RESULTS: CTb-HRP injected into the LES or the CD retrogradedly labeled neurons with large somas (areas ⬃380-400mm2) only in the DMV. Similarly, CTb conjugated to FITC or TRITC labeled neurons throughout the rostrocaudal extent of the DMV some of which were double-labeled. CONCLUSIONS: Our data demonstrate that the DMV directly innervates both the LES and the CD. Furthermore, it shows that a subset of the DMV projection neurons innervates both sphincters via which this nucleus may simultaneously influence their activity. Whereas direct innervation of the LES by the DMV is well known, our data showing that the DMV directly innervates the CD is novel and unexpected.
Altered gallbladder absorption/secretion in leptinresistant obese mice Kyle Yancey, MD, Deborah Swartz-Basile, PhD, Abhishek Mathur, MD, Debao Lu, MD, Attila Nakeeb, MD, Henry Pitt, MD, FACS Indiana University School of Medicine, Indianapolis, IN INTRODUCTION: Obese hyperleptinemic humans are at increased risk for gallstone formation. Gallbladder absorption/secretion is a key factor in gallstone pathogenesis. We have previously demonstrated that obese leptin-resistant mice have enlarged gallbladders that do not empty normally and that leptin regulates multiple gallbladder genes related to ion and water flux. However, no data are available on the influence of obesity and an altered adipokine milieu on gallbladder fluid transport. Therefore, we tested the hypothesis
J Am Coll Surg
that obese leptin-resistant mice would have altered gallbladder absorption/secretion. METHODS: Eight lean (C57BL/6J) and eight obese leptin-resistant (Lep Db) female mice were fed a 25% fat diet for four weeks. At 12 weeks of age, the mice were fasted overnight, anesthetized and underwent laparotomy. The gallbladders were cannulated with a PE10 (0.61 mm) polyethylene tube and inflated with Krebs buffer to a pressure of 16mmHg. The gallbladder was then suspended in oxygenated Krebs buffer at 37 degrees centigrade and weighed at 10 minute intervals. Gallbladders were opened longitudinally and placed on a grid to determine surface area. Data were analyzed by Student’s t test. RESULTS: Results for weight change and fluid flux are presented in the table. Fluid Flux (l/cm2/hr)
Weight Change (%) Time (min)
10 20 30 40 50 60
Lean
Obese
97.6 ⫾ 0.9 94.8 ⫾ 1.3 92.6 ⫾ 1.7 90.2 ⫾ 1.9 88.0 ⫾ 2.0 86.0 ⫾ 2.3
102.0 ⫾ 0.9ⴱ 102.4 ⫾ 1.3† 102.2 ⫾ 1.7† 100.3 ⫾ 1.9† 98.2 ⫾ 1.4† 96.9 ⫾ 1.2†
Lean
Obese
⫺14.8 ⫾ 6.7 12.2 ⫾ 6.0ⴱ ⫺15.6 ⫾ 4.1 1.3 ⫾ 5.4§ ⫺12.7 ⫾ 3.2 ⫺1.2 ⫾ 3.4§ ⫺13.8 ⫾ 3.0 ⫺9.5 ⫾ 2.2 ⫺13.5 ⫾ 2.9 ⫺11.8 ⫾ 3.0 ⫺12.7 ⫾ 3.8 ⫺7.7 ⫾ 2.1
ⴱ p⬍0.01; † p⬍ 0.001; § p⬍ 0.02 vs lean.
CONCLUSIONS: These data suggest that 1) lean mice absorb gallbladder fluid at a constant rate, but 2) obese mice initially secrete fluid into the lumen and do not absorb normally. We conclude that the adipokine milieu of leptin-resistant obese mice may alter gallbladder absorption/secretion and, thereby, enhance gallstone formation.
Re-operating on gastric bypass patients: High incidence of mesenteric defects Sharon L Bachman, MD, Timothy Geiger, MD, Peter Rippey, BS, Archana Ramaswamy, MD, Roger de la Torre, MD, Stephen Scott, MD University of Missouri-Columbia, Columbia, MO INTRODUCTION: The aim of this study was to evaluate the incidence of mesenteric defects (MD) and internal hernias (IH) in patients status-post gastric bypass (GBP), who presented to the OR again for any other reason. METHODS: The operative reports of two bariatrics surgeons were retrospectively examined. All patients who had previous GBP underwent intraoperative examination of their anastamoses to detect the presence of MD and IH. RESULTS: The population was 86.5% female and 13.5% male; median time elapsed was 1.13 years. Median weight change was 109 lbs, with median change in BMI of 17.6. The most common pre-op diagnosis was biliary disease (28.4%), abdominal pain (18.4%), ventral hernia (16.3%) and internal hernia (12.1%). The most common procedures were laparoscopic exploration (47.9%), laparoscopic cholecystectomy (28.6%) and ventral hernia repair (15.7%). Any
Surgical Forum Abstracts
trol of SGLT1, with the output loop mediated by either neural or hormonal factors.
Dorsal motor nucleus of the vagus (DMV): A CNS site that directly regulates activity of the lower esophageal sphincters Patrick G Jackson, MD, Mark Niedringhaus, Rebecca Pearson, Janell Richardson, Stephen Evans, MD, Richard Gillis, PhD, Niaz Sahibzada, PhD Georgetown University Hospital, Washington, DC INTRODUCTION: Concurrent transient relaxations of both the lower esophageal sphincters (LES) and crural diaphragm (CD) have been shown to be associated with gastroesophageal reflux. The purpose of the present study was to determine if the DMV regulates the activity of the both esophageal sphincters by a direct projection to these end organs. Additionally, since these sphincters act in tandem, we were interested to know the degree of their co-innervation by the DMV. METHODS: Experiments were performed in isoflurane anesthetized Ferrets (600-700 gm). Cholera Toxin (CTb) conjugated to HRP (n⫽4) or fluorescent label FITC or TRITC (n⫽3) was injected into either the LES or the CD, respectively. After 5 days, animals were perfused and their brains removed and prepared for immunohistochemistry. RESULTS: CTb-HRP injected into the LES or the CD retrogradedly labeled neurons with large somas (areas ⬃380-400mm2) only in the DMV. Similarly, CTb conjugated to FITC or TRITC labeled neurons throughout the rostrocaudal extent of the DMV some of which were double-labeled. CONCLUSIONS: Our data demonstrate that the DMV directly innervates both the LES and the CD. Furthermore, it shows that a subset of the DMV projection neurons innervates both sphincters via which this nucleus may simultaneously influence their activity. Whereas direct innervation of the LES by the DMV is well known, our data showing that the DMV directly innervates the CD is novel and unexpected.
Altered gallbladder absorption/secretion in leptinresistant obese mice Kyle Yancey, MD, Deborah Swartz-Basile, PhD, Abhishek Mathur, MD, Debao Lu, MD, Attila Nakeeb, MD, Henry Pitt, MD, FACS Indiana University School of Medicine, Indianapolis, IN INTRODUCTION: Obese hyperleptinemic humans are at increased risk for gallstone formation. Gallbladder absorption/secretion is a key factor in gallstone pathogenesis. We have previously demonstrated that obese leptin-resistant mice have enlarged gallbladders that do not empty normally and that leptin regulates multiple gallbladder genes related to ion and water flux. However, no data are available on the influence of obesity and an altered adipokine milieu on gallbladder fluid transport. Therefore, we tested the hypothesis
J Am Coll Surg
that obese leptin-resistant mice would have altered gallbladder absorption/secretion. METHODS: Eight lean (C57BL/6J) and eight obese leptin-resistant (Lep Db) female mice were fed a 25% fat diet for four weeks. At 12 weeks of age, the mice were fasted overnight, anesthetized and underwent laparotomy. The gallbladders were cannulated with a PE10 (0.61 mm) polyethylene tube and inflated with Krebs buffer to a pressure of 16mmHg. The gallbladder was then suspended in oxygenated Krebs buffer at 37 degrees centigrade and weighed at 10 minute intervals. Gallbladders were opened longitudinally and placed on a grid to determine surface area. Data were analyzed by Student’s t test. RESULTS: Results for weight change and fluid flux are presented in the table. Fluid Flux (l/cm2/hr)
Weight Change (%) Time (min)
10 20 30 40 50 60
Lean
Obese
97.6 ⫾ 0.9 94.8 ⫾ 1.3 92.6 ⫾ 1.7 90.2 ⫾ 1.9 88.0 ⫾ 2.0 86.0 ⫾ 2.3
102.0 ⫾ 0.9ⴱ 102.4 ⫾ 1.3† 102.2 ⫾ 1.7† 100.3 ⫾ 1.9† 98.2 ⫾ 1.4† 96.9 ⫾ 1.2†
Lean
Obese
⫺14.8 ⫾ 6.7 12.2 ⫾ 6.0ⴱ ⫺15.6 ⫾ 4.1 1.3 ⫾ 5.4§ ⫺12.7 ⫾ 3.2 ⫺1.2 ⫾ 3.4§ ⫺13.8 ⫾ 3.0 ⫺9.5 ⫾ 2.2 ⫺13.5 ⫾ 2.9 ⫺11.8 ⫾ 3.0 ⫺12.7 ⫾ 3.8 ⫺7.7 ⫾ 2.1
ⴱ p⬍0.01; † p⬍ 0.001; § p⬍ 0.02 vs lean.
CONCLUSIONS: These data suggest that 1) lean mice absorb gallbladder fluid at a constant rate, but 2) obese mice initially secrete fluid into the lumen and do not absorb normally. We conclude that the adipokine milieu of leptin-resistant obese mice may alter gallbladder absorption/secretion and, thereby, enhance gallstone formation.
Re-operating on gastric bypass patients: High incidence of mesenteric defects Sharon L Bachman, MD, Timothy Geiger, MD, Peter Rippey, BS, Archana Ramaswamy, MD, Roger de la Torre, MD, Stephen Scott, MD University of Missouri-Columbia, Columbia, MO INTRODUCTION: The aim of this study was to evaluate the incidence of mesenteric defects (MD) and internal hernias (IH) in patients status-post gastric bypass (GBP), who presented to the OR again for any other reason. METHODS: The operative reports of two bariatrics surgeons were retrospectively examined. All patients who had previous GBP underwent intraoperative examination of their anastamoses to detect the presence of MD and IH. RESULTS: The population was 86.5% female and 13.5% male; median time elapsed was 1.13 years. Median weight change was 109 lbs, with median change in BMI of 17.6. The most common pre-op diagnosis was biliary disease (28.4%), abdominal pain (18.4%), ventral hernia (16.3%) and internal hernia (12.1%). The most common procedures were laparoscopic exploration (47.9%), laparoscopic cholecystectomy (28.6%) and ventral hernia repair (15.7%). Any