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1.
Am J Surg ; 215(2): 259-265, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29174772

ABSTRACT

BACKGROUND: The role of simulation-based education continues to expand exponentially. To excel in this environment as a surgical simulation leader requires unique knowledge, skills, and abilities that are different from those used in traditional clinically-based education. METHODS: Leaders in surgical simulation were invited to participate as discussants in a pre-conference course offered by the Association for Surgical Education. Highlights from their discussions were recorded. RESULTS: Recommendations were provided on topics such as building a simulation team, preparing for accreditation requirements, what to ask for during early stages of development, identifying tools and resources needed to meet educational goals, expanding surgical simulation programming, and building educational curricula. CONCLUSION: These recommendations provide new leaders in simulation with a unique combination of up-to-date best practices in simulation-based education, as well as valuable advice gained from lessons learned from the personal experiences of national leaders in the field of surgical simulation and education.


Subject(s)
Education, Medical, Graduate/organization & administration , General Surgery/education , Simulation Training/organization & administration , Accreditation , Curriculum , Education, Medical, Graduate/methods , Humans , Leadership , Simulation Training/methods , United States
2.
Surg Endosc ; 24(12): 3224, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20574857

ABSTRACT

INTRODUCTION: Single-incision laparoscopic surgery (SILS) is limited by the coaxial arrangement of the instruments. A surgical robot with "wristed" instruments could overcome this limitation but the "arms" collide when working coaxially. This video demonstrates a new technique of "chopstick surgery," which enables use of the robotic arms through a single incision without collision. METHODS: Experiments were conducted utilizing the da Vinci S® robot (Sunnyvale, CA) in a porcine model with three laparoscopic ports (12 mm, 2-5 mm) introduced through a single "incision." Pilot work conducted while performing Fundamentals of Laparoscopic Surgery (FLS) tasks determined the optimal setup for SILS to be a triangular port arrangement with 2-cm trocar distance and remote center at the abdominal wall. Using this setup, an experienced robotic surgeon performed a cholecystectomy and nephrectomy in a porcine model utilizing the "chopstick" technique. The chopstick arrangement crosses the instruments at the abdominal wall so that the right instrument is on the left side of the target and the left instrument on the right. This arrangement prevents collision of the external robotic arms. To correct for the change in handedness, the robotic console is instructed to drive the "left" instrument with the right hand effector and the "right" instrument with the left. RESULTS: Both procedures were satisfactorily completed with no external collision of the robotic arms, in acceptable times and with no technical complications. This is consistent with results obtained in the box trainer where the chopstick configuration enabled significantly improved times in all tasks and decreased number of errors and eliminated instrument collisions. CONCLUSION: Chopstick surgery significantly enhances the functionality of the surgical robot when working through a small single incision. This technique will enable surgeons to utilize the robot for SILS and possibly for intraluminal or transluminal surgery.


Subject(s)
Laparoscopy/methods , Robotics/methods , Animals , Swine
3.
Surg Endosc ; 21(3): 445-8, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17054006

ABSTRACT

BACKGROUND: As with new laparoscopic techniques, the ability to convince surgeons and gastroenterologists to embrace endolumenal techniques and the additional training required to perform the new procedures will correlate with how rapidly endolumenal therapies are adopted. The authors measured their ability to change attitudes among surgeons, who may or may not perform endoscopy as a part of their practice, toward endolumenal therapies. METHODS: As part of the endoluminal therapy postgraduate course presented at the annual Society of American Gastrointestinal Endoscopic Surgeons (SAGES) meeting in Ft. Lauderdale, Florida 2005, experts presented current literature and data on new endolumenal techniques. The participants, primarily of surgeons, were polled electronically about a number of case scenarios before and after their presentation. Each scenario was relevant to the topic presented and chosen to reflect potentially controversial disease processes with traditional or endolumenal treatment options. The responses were collected in real time and displayed to course participants. RESULTS: A panel of 10 experts presented data on a range of endolumenal therapies including endolumenal treatment for gastroesophageal reflux disease (GERD), endoscopic stenting, endoscopic treatments in bariatric surgery, intraoperative endoscopy, endoscopic mucosal resection (EMR), transanal endoscopic microsurgery (TEM), mucosal ablation for Barrett's esophagus, intralumenal resection, translumenal endoscopic surgery, and how to educate surgeons in new endolumenal techniques. Demographic data showed that 83.6% of the participants performed endoscopy as part of their practice. A comparison with traditional surgical options showed a statistically significant positive attitude change (p < 0.05) toward adoption of most endolumenal techniques after expert presentation. Only EMR and TEM did not show a statistically significant change in the participants' willingness to adopt these techniques. There was no significant change in the attitudes of how best to train surgeons. After presentation of the training options, 76% of the respondents believed that these techniques should be taught in residency. CONCLUSIONS: The education of surgeons in new endolumenal therapeutic techniques can have a significant impact in terms of changing practice attitudes and may accelerate adoption of new endoscopic techniques.


Subject(s)
Angioplasty/education , Education, Medical, Continuing/methods , Gastrointestinal Diseases/surgery , Health Knowledge, Attitudes, Practice , Angioplasty/instrumentation , Bariatrics/methods , Curriculum , Endoscopes, Gastrointestinal , Endoscopy, Gastrointestinal/methods , Humans , Laparoscopy , Microsurgery , Practice Patterns, Physicians'/statistics & numerical data , United States
4.
Surg Endosc ; 21(6): 838-53, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17180263

ABSTRACT

Several cultures, including the Egyptians, Greeks, Romans, and Arabs, made attempts to view accessible human body cavities using a variety of instruments such as spatulas and specula. The first endoscope was created in 1806 when Phillip Bozzini, a German-born urologist, constructed the lichtleiter, which used concave mirrors to reflect candlelight through an open tube into the esophagus, bladder, or rectum. Maximilian Carl-Friedrich Nitze, another German urologist, produced the first usable cystoscope in 1877 by using series of lenses to increase magnification. He was also the first to place light inside the organ of interest to aid visualization. In 1880 Mikulicz made the first gastroscope using a system similar to Nitze's cystoscope. Modern endoscopy was born with the introduction of the fiberoptic endoscope in the late 1950s. Over the ensuing 50 years endoscopy revolutionized many aspects of the surgeon's practice. Endoscopy can now be used to diagnose and often treat gastrointestinal cancer, hemorrhage, obstruction, and inflammatory conditions. This review was initiated by the SAGES Flexible Endoscopy Committee to chronicle the role of the surgeon in the development and introduction of flexible endoscopy into clinical practice, historically and in contemporary surgery. Flexible endoscopy evolved out of surgeons' need to overcome diagnostic and therapeutic challenges. There have been many recent technological advances that facilitate endoluminal therapies, and flexible endoscopy is now traversing new ground. Surgeons have been major contributors in the development of all aspects of endoscopy. There is a continually expanding list of therapeutic options available to patients. The difficult questions of which procedure, on which patient, and when can be answered best by the surgeon versed in endoscopic, laparoscopic, and open surgical techniques.


Subject(s)
Endoscopy/history , Endoscopy/trends , Fiber Optic Technology , Gastroenterology/history , General Surgery/history , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Physician's Role
5.
Surg Endosc ; 21(4): 560-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17180281

ABSTRACT

BACKGROUND: This study aimed to determine the optimal treatment parameters for the ablation of intestinal metaplasia (IM) containing high-grade dysplasia (HGD) using a balloon-based ablation system for patients undergoing esophagectomy. METHODS: Immediately before esophagectomy, patients underwent ablation of circumferential segments of the esophagus containing IM-HGD using the HALO360 system. The treatment settings were randomized to 10, 12, or 14 J/cm2 for two, three, or four applications. After esophagectomy, multiple sections from ablation zones were microscopically evaluated. Histologic end points included maximum ablation depth (histologic layer) and complete ablation of all IM-HGD (yes/no). RESULTS: Eight men with a mean age of 57 years (range, 45-71 years) were treated, and 10 treatment zones were created. There were no device-related adverse events. At resection, there was no evidence of a transmural thermal effect. Grossly, ablation zones were clearly demarcated sections of ablated epithelium. The maximum ablation depth was the lamina propria or muscularis mucosae. The highest energy (14 J/cm2, 4 applications) incurred edema in the superficial submucosa, but no submucosa ablation. Complete ablation of IM and HGD occurred in 9 of 10 ablation zones (90%), defined as complete removal of the epithelium with only small foci of "ghost cells" representing nonviable, ablated IM-HGD and demonstrating loss of nuclei and cytoarchitectural derangement. One focal area of viable IM-HGD remained at the margin of one ablation zone (12 J/cm2, 2 applications) because of incomplete overlap. CONCLUSION: Complete ablation of IM-HGD without ablation of submucosa is possible using the HALO360 system. Ablation depth is dose related and limited to the muscularis mucosae. In one patient, small residual foci of IM-HGD at the edge of the ablation zone were attributable to incomplete overlap, which can be avoided. This study, together with nonesophagectomy IM-HGD trials currently underway, will identify the optimal treatment parameters for IM-HGD patients who would otherwise undergo esophagectomy or photodynamic therapy.


Subject(s)
Barrett Esophagus/pathology , Barrett Esophagus/surgery , Catheter Ablation/instrumentation , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagectomy/instrumentation , Aged , Barrett Esophagus/mortality , Biopsy, Needle , Catheterization/instrumentation , Equipment Design , Equipment Safety , Esophageal Neoplasms/mortality , Esophagectomy/methods , Follow-Up Studies , Humans , Immunohistochemistry , Male , Metaplasia/pathology , Middle Aged , Neoplasm Invasiveness/pathology , Risk Assessment , Survival Analysis , Treatment Outcome
6.
Surg Endosc ; 20(8): 1179-92, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16865615

ABSTRACT

The field of minimally invasive surgery has seen tremendous growth since the first laparoscopic cholecystectomy was performed in 1987. The key question is not how successful these techniques are currently, but rather where may they lead in the future? New technologies promise to usher in an era of even less invasive procedures. The terms being coined in the literature include "incisionless," "endoluminal," "transluminal," and "natural orifice" transluminal endoscopic surgery. These techniques certainly have the potential to become the next wave of minimally invasive procedures. A recent editorial in Surgical Endoscopy by Macfadyen and Cuschieri highlighted the ongoing developments in endoscopic surgery and stressed the critical importance of surgeons being involved in future applications and permutations of these techniques [1]. There are early signs of such involvement. The work of numerous investigators in the field was presented recently at the 2005 Digestive Disease Week. The American Society for Gastrointestinal Endoscopy and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), in collaboration with the American College of Surgeons, recently organized a postgraduate course in endoluminal therapy at the spring 2005 meeting held in Hollywood, Florida. The course is being offered again at the 2006 SAGES annual meeting. Similar courses are being offered at other regional and national meetings. This review attempts to highlight some of the available and evolving endoluminal therapies reviewed at that forum, including techniques for the management of gastroesophageal reflux disease, endoscopic mucosal resection, endoluminal bariatric surgery, transanal endoscopic microsurgery, and transgastric endoscopic surgery, as well as new technologies and possible future directions in luminal access surgery.


Subject(s)
Endoscopy, Digestive System/trends , Bariatric Surgery/trends , Humans , Suture Techniques/trends
7.
Surg Endosc ; 20(1): 125-30, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16333533

ABSTRACT

BACKGROUND: The goal of this study was to determine the optimal treatment parameters for the ablation of human esophageal epithelium using a balloon-based bipolar radiofrequency (RF) energy electrode. METHODS: Immediately prior to esophagectomy, subjects underwent esophagoscopy and ablation of two separate, 3-cm long, circumferential segments of non-tumor-bearing esophageal epithelium using a balloon-based bipolar RF energy electrode (BARRX Medical, Inc., Sunnyvale, CA, USA). Subjects were randomized to one of three energy density groups: 8, 10, or 12 J/cm2. RF energy was applied one time (1x) proximally and two times (2x) distally. Following resection, sections from each ablation zone were evaluated using H&E and diaphorase. Histological endpoints were complete epithelial ablation (yes/no), maximum ablation depth, and residual ablation thickness after tissue slough. Outcomes were compared according to energy density group and 1x vs 2x treatment. RESULTS: Thirteen male subjects (age, 49-85 years) with esophageal adenocarcinoma underwent the ablation procedure followed by total esophagectomy. Complete epithelial removal occurred in the following zones: 10 J/cm2 (2x) and 12 J/cm2 (1x and 2x). The maximum depth of injury was the muscularis mucosae: 10 and 12 J/cm2 (both 2x). A second treatment (2x) did not significantly increase the depth of injury. Maximum thickness of residual ablation after tissue slough was only 35 microm. CONCLUSIONS: Complete removal of the esophageal epithelium without injury to the submucosa or muscularis propria is possible using this balloon-based RF electrode at 10 J/cm2 (2x) or 12 J/cm2 (1x or 2x). A second application (2x) does not significantly increase ablation depth. These data have been used to select the appropriate settings for treating intestinal metaplasia in trials currently under way.


Subject(s)
Adenocarcinoma/surgery , Catheter Ablation/instrumentation , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagus/surgery , Aged , Aged, 80 and over , Electrodes , Epithelium/surgery , Equipment Design , Esophagoscopy , Esophagus/pathology , Humans , Male , Middle Aged , Postoperative Period , Reoperation , Treatment Outcome
8.
Surg Endosc ; 16(1): 112-4, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11961618

ABSTRACT

BACKGROUND: No consensus exists concerning the utility of a full diagnostic upper endoscopy during percutaneous endoscopic gastrostomy (PEG) tube placement. We evaluate the effect of a complete survey on identifying and treating unsuspected gastrointestinal pathology. METHODS: During a 10-year period (1990-2000), 1,706 patients underwent attempted PEG tube placement by five different surgical endoscopists at one institution. A complete survey of the esophagus, stomach, and proximal duodenum was attempted in all cases. Endoscopic findings and recommendations were recorded in a computerized log and patient charts. Pathology results were obtained from a computerized pathology database and patient charts. RESULTS: Placement of a PEG tube was successful in 97%, and a full survey was possible in 99% of the cases. Pathologic findings were found in 38% of the surveyed patients (esophagus, 7%; stomach, 24%; duodenum, 7%). One group with gastrointestinal polyps or gastric ulcers (5.7%) was identified as possible candidates for endoscopic intervention. In 30% of this group (1.8% of the total) a biopsy was performed, or bleeding was treated endoscopically. In a second group pathology was identified in the duodenum (6.4%) that would not have been recognized without a full survey. These duodenal findings resulted in a recommendation for treatment change in 38% of this group (2.4% of the total). CONCLUSIONS: Upper endoscopic survey before PEG tube placement showed a significant amount of unsuspected gastrointestinal pathology. Findings requiring biopsy, immediate treatment, or a change in medical treatment occurred in 4.2% of the cases, and these findings did not prevent PEG tube placement in any patient.


Subject(s)
Endoscopes, Gastrointestinal , Endoscopy, Gastrointestinal/methods , Gastrostomy/instrumentation , Gastrostomy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Retrospective Studies
9.
Surg Endosc ; 15(12): 1390-4, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11965452

ABSTRACT

BACKGROUND: Laparoscopic donor nephrectomy (LDN) preferentially involves the left kidney to optimize vessel length, but occasionally, right nephrectomy is preferred. Right LDN differs markedly in anatomic relations and the need for a fourth port. This retrospective study compares donor outcomes and graft function of right and left LDN and describes the technique. METHODS: Consecutive patients undergoing right LDN from March 26, 1996 to December 31, 2000 were compared with those undergoing left LDN. Age, height, weight, body mass index, creatinine, creatinine clearance, operative time, warm ischemia time, analgesic requirements, serial postoperative creatinine, time to diet resumption, and hospital stay were compared. A second cohort matched for age, gender, race, and temporal left LDN also were compared with the group undergoing right LDN. RESULTS: No significant differences were found for any of the parameters measured. CONCLUSION: This study demonstrates that despite substantial differences in the procedures, donor outcome and graft survival are similar for right and left LDN.


Subject(s)
Kidney Transplantation/methods , Laparoscopy/methods , Living Donors , Nephrectomy/methods , Adult , Female , Humans , Male , Retrospective Studies , Treatment Outcome
10.
Surg Laparosc Endosc Percutan Tech ; 10(5): 275-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11083208

ABSTRACT

This study reports the histologic changes seen in the biliary ductal system and pancreas as a result of endobiliary stenting. Ten mini pigs underwent endoscopic placement of suprapapillary endobiliary stents. The animals were killed and the liver, biliary tree, and pancreas were resected en bloc and prepared for histologic examination. Endobiliary stenting was found to result in significant chronic inflammation in the biliary system within 4 weeks of stent placement. These changes were present throughout the entire extrahepatic biliary ductal system and persisted throughout the 15-week study period. There was no significant acute inflammation in the biliary tree nor acute or chronic inflammation in the pancreatic duct. Further study is indicated to determine whether these changes will result in fibrosis and stricture.


Subject(s)
Bile Ducts, Extrahepatic/pathology , Pancreatic Ducts/pathology , Stents , Animals , Chronic Disease , Inflammation/pathology , Prospective Studies , Swine , Swine, Miniature
11.
J Urol ; 164(5): 1494-9, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11025690

ABSTRACT

PURPOSE: We determined whether laparoscopic living donor nephrectomy decreases the morbidity of renal donation for the donor, while providing a renal allograft of a quality comparable to that of open donor nephrectomy. MATERIALS AND METHODS: In a 3-year period laparoscopic donor nephrectomy was performed via the transperitoneal approach. We evaluated donor and recipient medical records for preoperative donor characteristics, intraoperative parameters and complications, and postoperative recovery and complications. RESULTS: Of the 320 laparoscopic donor nephrectomies performed the left kidney was removed in 97.5%. Intraoperative complications, which developed in 10.4% of cases, tended to occur early in the experience and required conversion to open nephrectomy in 5. Average operative time was 31/2 hours and warm ischemia time was 21/2 minutes. As the series progressed, blood loss as well as laparoscopic port size and number decreased but extraction site size remained constant at 7 cm. Urinary retention, prolonged ileus, thigh numbness and incisional hernia were the most common postoperative complications. Postoperative analgesic requirements were low and average hospitalization was 66 hours. CONCLUSIONS: Laparoscopic donor nephrectomy appears to be safe and decreases morbidity in the renal donor. Allograft function is comparable to that in open nephrectomy series. The availability of laparoscopic harvesting may be increasing the living donor volunteer pool.


Subject(s)
Kidney Transplantation/methods , Laparoscopy , Living Donors , Nephrectomy/methods , Adult , Aged , Female , Humans , Intraoperative Complications , Male , Maryland , Middle Aged , Nephrectomy/adverse effects
13.
Urology ; 56(6): 926-9, 2000 Dec 20.
Article in English | MEDLINE | ID: mdl-11113733

ABSTRACT

OBJECTIVES: To determine whether laparoscopic living donor nephrectomy is safe and efficacious in markedly obese renal donors. METHODS: From 1996 to 1999, 431 laparoscopic living donor nephrectomies were performed. The markedly obese group consisted of 41 patients with a body mass index (BMI) greater than 35. Forty-one controls with a BMI less than 30 were matched to the obese donors by sex, age, race, and date of surgery. RESULTS: The markedly obese and control groups were closely matched in sex, race, age, serum creatinine level, creatinine clearance, HLA match to recipient, side of donated kidney, and experience level of the surgeons. The obese patients had a BMI range of 35.2 to 53.9 (mean 39.3), and the control patients had a BMI range of 18.4 to 29.0 (mean 24.3). Donor operations in the markedly obese were significantly longer by an average of 40 minutes. The greater intraoperative blood loss and longer extraction incision length seen in the markedly obese did not reach statistical significance. More and larger laparoscopic ports were used in the markedly obese. Obese donors were more likely to require conversion from laparoscopic nephrectomy to open nephrectomy than ideal-sized donors. The postoperative recovery of the gastrointestinal tract, hospitalization time, analgesic requirements, and total complications were equal in the two groups, although the obese donors' complications tended to be cardiopulmonary problems. The recipient graft function was equivalent between the two groups. CONCLUSIONS: Laparoscopic living donor nephrectomy is more difficult to perform in the markedly obese but is associated with an equivalent donor morbidity and recipient renal outcome.


Subject(s)
Kidney Transplantation/methods , Laparoscopy/methods , Living Donors , Nephrectomy/methods , Obesity/complications , Blood Loss, Surgical/statistics & numerical data , Body Mass Index , Body Weight , Humans , Obesity/diagnosis , Postoperative Complications/epidemiology
15.
Surg Endosc ; 12(12): 1426-9, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9822472

ABSTRACT

The incidence of pseudocysts in patients with chronic pancreatitis ranges from 20-40%. Unlike pseudocysts associated with acute pancreatitis, these do not usually resolve spontaneously. Traditionally, these cysts were drained surgically. More recently, however, they have been successfully managed with endoscopic drainage. This report reviews the history and results of nonsurgical pseudocyst management and describes a case of drainage obtained using an alternative method of ultrasound-directed percutaneous endoscopic cyst-gastrostomy.


Subject(s)
Gastroscopy/methods , Gastrostomy/methods , Pancreatic Pseudocyst/therapy , Pancreatitis/complications , Chronic Disease , Drainage/methods , Follow-Up Studies , Gastroscopes , Gastrostomy/instrumentation , Humans , Male , Middle Aged , Pancreatic Pseudocyst/diagnosis , Pancreatic Pseudocyst/etiology , Pancreatitis/diagnosis , Tomography, X-Ray Computed , Treatment Outcome
16.
Gastrointest Endosc ; 48(2): 180-3, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9717784

ABSTRACT

BACKGROUND: The role of oxygen-derived free radicals in the pathogenesis of pancreatitis has been supported by data from previous studies using animal models. This study was conducted to determine whether prophylaxis with the xanthine oxidase inhibitor allopurinol would decrease the incidence and severity of pancreatography-induced pancreatitis in a canine model. METHODS: Thirty-two dogs were randomized to receive either placebo or oral allopurinol 1 hour before the procedure. A laparotomy and duodenotomy were performed and a pancreatogram was obtained. Postoperatively, pancreatic enzymes were drawn for 5 days. The animals were then euthanized, and the pancreas was weighed and evaluated histologically. RESULTS: The histologic incidence of pancreatitis was significantly reduced in the allopurinol pretreatment group (6.7%) as compared with the placebo group (41.2%, p < 0.01). A significant decrease in postoperative serum amylase levels among dogs pretreated with allopurinol was also noted. A similar trend was observed in lipase levels. The pancreas weight index was decreased in the allopurinol pretreatment group as well (control = 0.00246 vs. allopurinol = 0.00195, p < 0.02). CONCLUSIONS: Pretreatment with oral allopurinol decreases the incidence of pancreatography-induced pancreatitis. These results support the role of xanthine oxidase inhibitors in the prevention of endoscopic retrograde cholangiopancreatography-induced pancreatitis.


Subject(s)
Allopurinol/therapeutic use , Disease Models, Animal , Enzyme Inhibitors/therapeutic use , Pancreas/diagnostic imaging , Pancreatitis/prevention & control , Premedication/methods , Xanthine Oxidase/antagonists & inhibitors , Animals , Dogs , Drug Evaluation, Preclinical , Pancreas/drug effects , Pancreas/enzymology , Pancreas/pathology , Pancreatitis/etiology , Pancreatitis/pathology , Radiography , Random Allocation , Time Factors
18.
J Surg Res ; 61(2): 348-54, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8656607

ABSTRACT

Despite improved antimicrobials and advances in caring for critically ill patients, mortality from sepsis is still unacceptably high. Upregulation of the cellular immune system is one strategy for decreasing mortality in subjects with severe sepsis, which appears to be promising. Granulocyte colony stimulating factor (G-CSF) has been used successfully to decrease mortality in neutropenic subjects with sepsis. In this study, we have investigated whether pretreatment with G-CSF decreases mortality in non-neutropenic rodents with lethal Escherichia coli peritonitis. We implanted agar pellets impregnated with 5 x 10(8) cfu of Escherichia coli into the peritoneal cavities of rats pretreated with 50 micrograms/kg of G-CSF or an equal volume of 5% dextrose in water (D5W). Survival of these animals increased from 38 to 78% with G-CSF pretreatment. We also demonstrated an 11-fold increase in the number of polymorphonuclear leukocytes (PMNs) in animals treated with G-CSF. This increase in cells was seen initially only in the peripheral circulation. Twenty-four hours after induction of peritonitis, however, there was a three-fold greater increase in number of PMNs recovered from the peritoneal cavities of animals pretreated with G-CSF as compared to those treated with D5W. PMNs recovered from the peritoneal cavities of these animals had significantly elevated bactericidal activity (74% killing vs 53% killing) as compared to those cells recovered from the peritoneal cavities of control animals. These results indicate that G-CSF pretreatment improves survival of non-neutropenic animals with lethal Escherichia coli peritonitis by enhancing the cellular arm of the immune response.


Subject(s)
Escherichia coli Infections/therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Peritonitis/therapy , Animals , Escherichia coli Infections/blood , Escherichia coli Infections/mortality , Leukocyte Count/drug effects , Male , Neutrophils/drug effects , Neutrophils/physiology , Peritonitis/blood , Peritonitis/mortality , Rats , Rats, Sprague-Dawley
19.
J Surg Res ; 59(2): 236-44, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7543631

ABSTRACT

The failure of chronic wounds to heal remains a major medical problem. Recent studies have suggested an important role for growth factors in promoting wound healing. We investigated the mitogenic effect of basic fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF), comparing their effects with those of media alone (MEM) in a human skin explant model. A stable organ culture system for maintaining the histologic structure of human epidermis for 10 days in vitro was developed. DNA synthesis was measured on Days 1, 3, and 7 of organ culture using [3H]thymidine ([3H]thy) uptake and expressed as cpm/mg dry weight (mean +/- SEM). FGF, IGF-1, and EGF were each capable of stimulating [3H]thy uptake on Day 1 of culture (2372 +/- 335 FGF, 2226 +/- 193 IGF-1, 4037 +/- 679 EGF vs 1108 +/- 70 MEM, P < 0.05). IGF-1 and EGF also stimulated [3H]thy uptake on Days 3 and 7 of culture. The organ culture system was further employed to observe epidermal outgrowth. Longest keratinocyte outgrowth from the explant periphery (simulating epithelial regeneration from the wound edge) was observed on Day 7. EGF resulted in maximum stimulation of epithelial outgrowth (440 +/- 80 microns), followed by FGF (330 +/- 56 microns), IGF-1 (294 +/- 48 microns), and MEM (189 +/- 50 microns). We postulate, therefore, that FGF, IGF-1, and EGF are important mitogens for wound healing and that EGF in particular is capable of stimulating epithelialization.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Epidermal Growth Factor/pharmacology , Fibroblast Growth Factor 2/pharmacology , Insulin-Like Growth Factor I/pharmacology , Skin/cytology , Wound Healing/physiology , Cell Division/drug effects , Cell Division/physiology , Culture Techniques , DNA/biosynthesis , Dose-Response Relationship, Drug , Epithelial Cells , Epithelium/drug effects , Epithelium/ultrastructure , Humans , Immunohistochemistry , Keratins/analysis , Keratins/metabolism , Microscopy, Electron , Microscopy, Electron, Scanning , Skin/drug effects , Skin/ultrastructure , Thymidine/metabolism , Tritium , Wound Healing/drug effects
20.
Ann Surg ; 222(2): 186-92, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7639585

ABSTRACT

BACKGROUND/AIMS: Esophageal mucosal blood flow is a dynamic phenomenon that is altered by luminal content that probably represents an important intrinsic method of defense. This study investigated the role played by endogenous nitric oxide in the regulation of esophageal mucosal blood flow at rest and in response to luminal capsaicin, a specific stimulant for visceral afferent nerves, as well as calcitonin gene-related peptide, and the bile salt deoxycholate. METHODS: The L-arginine analog L-NAME was used to block nitric oxide synthesis. Radiolabeled microspheres were used to measure blood flow in a well-characterized rabbit model. Phenylephrine was used to mimic the hemodynamic effects of L-NAME to show the specificity of positive findings. RESULTS: Administration of L-NAME led to a significant reduction in mucosal blood flow at rest, an effect that was not shared by phenylephrine. The blood flow responses to luminal capsaicin, intra-arterial calcitonin gene-related peptide (CGRP), and luminal deoxycholate, however, were not diminished in the presence of L-NAME. CONCLUSIONS: Although nitric oxide may play a role in the maintenance of normal resting esophageal mucosal blood flow, the reactive responses to luminal capsaicin, luminal deoxycholate, and intra-arterial CGRP are not nitric oxide dependent.


Subject(s)
Calcitonin Gene-Related Peptide/pharmacology , Capsaicin/pharmacology , Deoxycholic Acid/pharmacology , Esophagus/blood supply , Nitric Oxide/physiology , Administration, Topical , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Calcitonin Gene-Related Peptide/administration & dosage , Capsaicin/administration & dosage , Deoxycholic Acid/administration & dosage , Esophagus/drug effects , Esophagus/innervation , Hyperemia/chemically induced , Hyperemia/physiopathology , Infusions, Intra-Arterial , Male , Microspheres , Mucous Membrane , NG-Nitroarginine Methyl Ester , Neurons, Afferent/drug effects , Nitric Oxide/antagonists & inhibitors , Phenylephrine/pharmacology , Rabbits , Regional Blood Flow/drug effects
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