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1.
Eur J Dent Educ ; 20(2): 94-101, 2016 May.
Article in English | MEDLINE | ID: mdl-25891196

ABSTRACT

PURPOSE: To examine dentists' views of a novel video review technique to improve communication skills in complex clinical situations. MATERIALS AND METHODS: Dentists (n = 3) participated in a video review known as Video Interaction Guidance to encourage more attuned interactions with their patients (n = 4). Part of this process is to identify where dentists and patients reacted positively and effectively. Each dentist was presented with short segments of video footage taken during an appointment with a patient with intellectual disabilities and communication difficulties. Having observed their interactions with patients, dentists were asked to reflect on their communication strategies with the assistance of a trained VIG specialist. RESULTS: Dentists reflected that their VIG session had been insightful and considered the review process as beneficial to communication skills training in dentistry. They believed that this technique could significantly improve the way dentists interact and communicate with patients. The VIG sessions increased their awareness of the communication strategies they use with their patients and were perceived as neither uncomfortable nor threatening. DISCUSSION: The VIG session was beneficial in this exploratory investigation because the dentists could identify when their interactions were most effective. Awareness of their non-verbal communication strategies and the need to adopt these behaviours frequently were identified as key benefits of this training approach. One dentist suggested that the video review method was supportive because it was undertaken by a behavioural scientist rather than a professional counterpart. CONCLUSION: Some evidence supports the VIG approach in this specialist area of communication skills and dental training.


Subject(s)
Education, Dental , Communication , Dentist-Patient Relations , Dentistry , Humans , Teaching
2.
Ann Oncol ; 26(4): 731-736, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25628445

ABSTRACT

INTRODUCTION: KRAS and EGFR ectodomain-acquired mutations in patients with metastatic colorectal cancer (mCRC) have been correlated with acquired resistance to anti-EGFR monoclonal antibodies (mAbs). We investigated the frequency, co-occurrence, and distribution of acquired KRAS and EGFR mutations in patients with mCRC refractory to anti-EGFR mAbs using circulating tumor DNA (ctDNA). PATIENTS AND METHODS: Sixty-two post-treatment plasma and 20 matching pretreatment archival tissue samples from KRAS (wt) mCRC patients refractory to anti-EGFR mAbs were evaluated by high-sensitivity emulsion polymerase chain reaction for KRAS codon 12, 13, 61, and 146 and EGFR 492 mutations. RESULTS: Plasma analyses showed newly detectable EGFR and KRAS mutations in 5/62 [8%; 95% confidence interval (CI) 0.02-0.18] and 27/62 (44%; 95% CI 0.3-0.56) samples, respectively. KRAS codon 61 and 146 mutations were predominant (33% and 11%, respectively), and multiple EGFR and/or KRAS mutations were detected in 11/27 (41%) cases. The percentage of mutant allele reads was inversely correlated with time since last treatment with EGFR mAbs (P = 0.038). In the matching archival tissue, these mutations were detectable as low-allele-frequency clones in 35% of patients with plasma mutations after treatment with anti-EGFR mAbs and correlated with shorter progression-free survival (PFS) compared with the cases with no new mutations (3.0 versus 8.0 months, P = 0.0004). CONCLUSION: Newly detected KRAS and/or EGFR mutations in plasma ctDNA from patients refractory to anti-EGFR treatment appear to derive from rare, pre-existing clones in the primary tumors. These rare clones were associated with shorter PFS in patients receiving anti-EGFR treatment. Multiple simultaneous mutations in KRAS and EGFR in the ctDNA and the decline in allele frequency after discontinuation of anti-EGFR therapy in a subset of patients suggest that several resistance mechanisms can co-exist and that relative clonal burdens may change over time. Monitoring treatment-induced genetic alterations by sequencing ctDNA could identify biomarkers for treatment screening in anti-EGFR-refractory patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , ErbB Receptors/antagonists & inhibitors , Mutation/genetics , Neoplastic Cells, Circulating/pathology , Clone Cells , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , ErbB Receptors/blood , ErbB Receptors/genetics , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins/blood , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins B-raf/blood , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Survival Rate , ras Proteins/blood , ras Proteins/genetics
3.
Stud Mycol ; 80: 131-50, 2015 Mar.
Article in English | MEDLINE | ID: mdl-26955193

ABSTRACT

The pitch canker pathogen Fusarium circinatum has caused devastation to Pinus spp. in natural forests and non-natives in commercially managed plantations. This has drawn attention to the potential importance of Fusarium species as pathogens of forest trees. In this study, we explored the diversity of Fusarium species associated with diseased Pinus patula, P. tecunumanii, P. kesiya and P. maximinoi in Colombian plantations and nurseries. Plants displaying symptoms associated with a F. circinatum-like infection (i.e., stem cankers and branch die-back on trees in plantations and root or collar rot of seedlings) were sampled. A total of 57 isolates were collected and characterised based on DNA sequence data for the translation elongation factor 1-α and ß-tubulin gene regions. Phylogenetic analyses of these data allowed for the identification of more than 10 Fusarium species. These included F. circinatum, F. oxysporum, species within the Fusarium solani species complex and seven novel species in the Fusarium fujikuroi species complex (formerly the Gibberella fujikuroi species complex), five of which are described here as new. Selected isolates of the new species were tested for their pathogenicity on Pinus patula and compared with that of F. circinatum. Of these, F. marasasianum, F. parvisorum and F. sororula displayed levels of pathogenicity to P. patula that were comparable with that of F. circinatum. These apparently emerging pathogens thus pose a significant risk to forestry in Colombia and other parts of the world.

4.
Transplant Proc ; 46(7): 2406-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25242795

ABSTRACT

BACKGROUND: Pulmonary embolism (PE) is an uncommon, life-threatening complication after living donor nephrectomy (LDN), and is considered among the most common causes for donor mortality. Most cases of postoperative PEs are thought to originate in deep venous thrombosis (DVT) of the lower extremities. CASE REPORT: A 56-year-old, healthy woman underwent laparoscopic left LDN. Her postoperative course was complicated by PE, presenting at postoperative day 7. Doppler ultrasonography of her lower extremities did not demonstrate DVT. Both transthoracic echocardiogram and contrast-enhanced computed tomography demonstrated a floating thrombus within the inferior vena cava (IVC) originating from a thrombus in the left renal vein stump. Symptoms resolved with systemic anticoagulation. Repeat transesophageal echocardiography demonstrated resolution of the IVC thrombus. CONCLUSIONS: Thrombus originating in left renal vein stump should be considered in patients who develop PE after LDN, especially when lower extremity DVT is not demonstrated.


Subject(s)
Nephrectomy/adverse effects , Renal Veins , Vena Cava, Inferior , Echocardiography, Transesophageal , Female , Humans , Laparoscopy , Living Donors , Middle Aged , Nephrectomy/methods , Pulmonary Embolism/etiology , Tissue and Organ Harvesting/adverse effects , Tomography, X-Ray Computed , Vena Cava Filters , Venous Thrombosis/diagnosis
5.
Br J Radiol ; 85(1016): e514-22, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22374283

ABSTRACT

OBJECTIVES: Motion in images potentially compromises the evaluation of temporally acquired CT perfusion (CTp) data; image registration should mitigate this, but first requires validation. Our objective was to compare the relative performance of manual, rigid and non-rigid registration techniques to correct anatomical misalignment in acquired liver CTp data sets. METHODS: 17 data sets in patients with liver tumours who had undergone a CTp protocol were evaluated. Each data set consisted of a cine acquisition during a breath-hold (Phase 1), followed by six further sets of cine scans (each containing 11 images) acquired during free breathing (Phase 2). Phase 2 images were registered to a reference image from Phase 1 cine using two semi-automated intensity-based registration techniques (rigid and non-rigid) and a manual technique (the only option available in the relevant vendor CTp software). The performance of each technique to align liver anatomy was assessed by four observers, independently and blindly, on two separate occasions, using a semi-quantitative visual validation study (employing a six-point score). The registration techniques were statistically compared using an ordinal probit regression model. RESULTS: 306 registrations (2448 observer scores) were evaluated. The three registration techniques were significantly different from each other (p=0.03). On pairwise comparison, the semi-automated techniques were significantly superior to the manual technique, with non-rigid significantly superior to rigid (p<0.0001), which in turn was significantly superior to manual registration (p=0.04). CONCLUSION: Semi-automated registration techniques achieved superior alignment of liver anatomy compared with the manual technique. We hope this will translate into more reliable CTp analyses.


Subject(s)
Liver Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/standards , Aged , Female , Humans , Liver Neoplasms/blood supply , Male , Middle Aged , Movement , Observer Variation , Prospective Studies , Radiographic Image Interpretation, Computer-Assisted/standards , Reference Standards
7.
Surg Endosc ; 21(11): 2110, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17704879

ABSTRACT

The authors present the case of a 43-year-old women who underwent a laparoscopic gastric bypass in 2003 for morbid obesity. They report that 2 years later, she had maintained significant weight loss, but had developed acute abdominal pain, followed by nausea and emesis. In the emergency room, she had diffuse tenderness, tachycardia, and leukocytosis. After initial resuscitation, a computed tomography was performed, which showed free air above the liver and thickened small bowel loops. She was brought emergently to the operating room for laparoscopy. At surgery, turbid fluid and inflamed small bowel loops were seen. A perforated marginal ulcer was discovered in the Roux limb, approximately 2 cm distal to the gastrojejunal anastomosis. The perforation was oversewn primarily and patched with omentum. The repair was tested by intraoperative endoscopy. A gastrostomy tube also was placed within the gastric remnant for enteral access. The patient did extremely well postoperatively, and had an uneventful postoperative course. She was discharged on postoperative day 4. The gastrostomy tube was removed at 1 month, and at this writing, she remains well since surgery. An upper endoscopy at 2 months was completely normal, and the Helicobacter pylori test results were negative. The gastric pouch had not significantly enlarged since initial surgery, as indicated by both endoscopy and barium study. Marginal ulcer is reported to be 0.6% to 16% after laparoscopic gastric bypass. Etiologies include gastrogastric fistula, excessively large gastric pouch containing antral mucosa, H. pylori infection, nonsteroidal antiinflammatory use, and smoking. Unfortunately, none of these applied to the reported patient. Because her exact etiology remains unknown, she at this writing continues to receive proton pump inhibitor therapy.


Subject(s)
Gastric Bypass/adverse effects , Obesity, Morbid/surgery , Stomach Ulcer/etiology , Stomach Ulcer/surgery , Adult , Female , Humans , Laparoscopy/methods , Treatment Outcome
8.
Minerva Chir ; 61(2): 125-39, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16871144

ABSTRACT

The epidemic of obesity in the United States has triggered an exponential increase in the number of bariatric procedures performed. This has led to an elevated awareness of the complications of bariatric surgery. Several recent studies have suggested that the mortality rate from bariatric surgery is substantially higher than previously stated, particularly in the elderly and disabled population. As more complications from bariatric surgery occur, general surgeons, primary care doctors and emergency room personnel may be increasingly called upon to diagnose and treat them. This review describes the most commonly seen complications of bariatric surgery including anastomotic leak, thromboembolism, stricture formation, internal hernia, ulcer formation, cholelithiasis, hemorrhage, nutritional and metabolic derangements. Additionally, complications specific to the adjustable gastric band are addressed. The etiology, diagnosis and management of these complications is discussed. The long-term viability of bariatric surgery as a treatment for severe obesity will depend upon the prevention and appropriate treatment of bariatric complications.


Subject(s)
Bariatric Surgery/adverse effects , Acute Disease , Cholelithiasis/etiology , Gastrointestinal Hemorrhage/etiology , Hernia/etiology , Humans , Intestinal Diseases/etiology , Nutrition Disorders/etiology , Pulmonary Embolism/etiology , Venous Thrombosis/etiology
9.
Surg Endosc ; 19(1): 34-9, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15529196

ABSTRACT

BACKGROUND: The aim of this study was to describe the occurrence and clinical characteristics of symptomatic internal hernias (IH) after laparoscopic bariatric procedures. METHODS: We conducted a retrospective review of cases of IH after 1,064 laparoscopic gastric bypasses (LGB) and biliopancreatic diversions with duodenal switch (LBPD-DS) performed from September 1998 to August 2002. RESULTS: We documented 35 cases of IH (overall incidence of 3.3%). The IH occurred in 6.0% of patients with retrocolic procedures and 3.3% of patients with antecolic procedures. Most were in the Petersen defect (55.9%) and at the enteroenterostomy site (35.3%). A bimodal presentation was observed, with 22.9% of patients with IH diagnosed in the early postoperative period (2-58 days) and 77.1% in a delayed fashion (187-1,109 days). A laparoscopic approach to the repair of IH was possible in 60.0% of patients. Complications occurred in 18.8% of patients, including one death (2.9%). CONCLUSION: Complete closure of all mesenteric defects is strongly recommended during laparoscopic bariatric procedures to avoid IH and their associated complications.


Subject(s)
Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Hernia/etiology , Laparoscopy/adverse effects , Hernia/epidemiology , Humans , Retrospective Studies
10.
Abdom Imaging ; 29(2): 231-8, 2004.
Article in English | MEDLINE | ID: mdl-15290952

ABSTRACT

Multidetector row computed tomography (CT) can acquire abdominal images of unprecedented thinness in a single breath-hold. This study investigated whether acquiring source axial images at 1.25 mm as opposed to 2.5 mm would result in a perceptible difference in image quality for coronal oblique reformations. Similarly, the hypothesis that a slice pitch of 3:1 would be superior to 6:1 was evaluated. Twenty-nine CT studies were retrospectively evaluated. The images were divided into four groups: 1.25-mm axial images, pitch 3:1; 2.5-mm axial images, pitch 3:1; 1.25-mm axial images, pitch 6:1; and 2.5-mm axial images, pitch 6:1. Three radiologists evaluated by consensus the coronal oblique reformations for overall image quality and image quality of structures in the hepatoduodenal ligament and of nodal groups. Use of 1.25-mm rather than of 2.5-mm source axial images resulted in statistically significant better scores for overall image quality and visualization of the hepatic artery, portal vein, pancreatic duct, and nodal groups. However, a pitch of 3:1 rather than of 6:1 did not result in significant differences in ratings of image quality. Use of 1.25-mm rather than of 2.5-mm source axial images improves image quality when creating coronal oblique reformations for abdominal anatomy.


Subject(s)
Image Processing, Computer-Assisted/methods , Ligaments/diagnostic imaging , Liver Diseases/diagnostic imaging , Pancreatic Diseases/diagnostic imaging , Tomography, Spiral Computed , Adult , Aged , Aged, 80 and over , Duodenum/diagnostic imaging , Female , Humans , Male , Middle Aged , Radiography, Abdominal , Retrospective Studies , Statistics, Nonparametric
11.
Australas Phys Eng Sci Med ; 26(1): 18-24, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12854621

ABSTRACT

A system has been developed for stimulation, recording and analysis of a wide range of eye movements. Eye movements are stimulated with an LED bar or a video projector under the control of a PC. The eye movements are measured using a scleral reflection technique (IRIS instrument), and sampled and stored on a PC. A range of tests have been developed to measure saccadic and smooth pursuit eye movements. A variety of tools have been developed to assist in the analysis of the data. Several research studies have ably demonstrated the utility and versatility of the system.


Subject(s)
Eye Movements/physiology , Photic Stimulation/instrumentation , Physical Examination/instrumentation , Equipment Design , Humans , Photic Stimulation/methods , Pursuit, Smooth/physiology , Saccades/physiology , Video Recording/methods
12.
Surg Endosc ; 17(7): 1055-60, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12728380

ABSTRACT

BACKGROUND: Increasing the length of the Roux limb in open Roux-en-Y gastric bypass (RYGB) effectively increases excess weight loss in superobese patients with a body mass index (BMI) >50 kg/m2. Extending the RYGB limb length for obese patients with a BMI < 50 could produce similar results. The purpose of this study was to compare the outcomes of superobese patients undergoing laparoscopic RYGB with standard (< or =100-cm) with those undergoing the procedure with an extended (150-cm) Roux limb length over 1-year period of follow-up. METHODS: Retrospective data over 2.5 years were reviewed to identify patients with a BMI < 50 who underwent primary laparoscopic RYGB with 1-year follow-up ( n = 58). Forty-five patients (sRYGB group) received limb lengths < or = 100 cm, including 45 cm ( n = 1), 50 cm ( n = 2), 60 cm ( n = 6), 65 cm ( n = 1), 70 cm ( n = 1), 75 cm ( n = 3), and 100 cm ( n = 31). Thirteen patients (eRYGB group) received 150-cm limbs. Postoperative weight loss was compared at 3 weeks, 3 months, 6 months, and 1 year. RESULTS: Comparing the sRYGB vs the eRYGB group (average +/- SD), respectively: There were no significant differences in age (41.5 +/- 11.0 vs 38.0 +/- 11.9 years), preoperative weight (119.2 +/- 11.9 vs 127.8 +/- 12.5 kg), BMI (43.7 +/- 3.0 vs 45.2 +/- 3.5 kg/m2), operative time (167.1 +/- 72.7 vs 156.5 +/- 62.4 min), estimated blood loss (129.9 +/- 101.1 vs 166.8 +/- 127.3 cc), or length of stay (median, 3 vs 3 days; range, 2-18 vs 3-19). Body weight decreased over time in both groups, except in the sRYGB group between 3 and 6 months and 6 and 12 months after surgery and in the eRYGB group between 6 and 12 months. BMI also decreased over time, except in the eRYGB group between 6 and 12 months. Absolute weight loss leveled out between 6 and 12 months in both groups, with no increase after 6 months. Percent of excess weight loss did not increase in the eRYGB group after 6 months. An extended Roux limb did not significantly affect body weight, BMI, absolute weight loss, or precent of excess weight loss at any time point when the two groups were compared. A trend toward an increased proportion of patients with >50% excess weight loss ( p = 0.07) was observed in the extended Roux limb group. CONCLUSIONS: In this series, no difference in weight loss outcome variables were observed up to 1 year after laparoscopic RYGB. Thus, extending Roux limb length from < or =100 cm to 150 cm did not significantly improve weight loss outcome in patients with a BMI < 50 kg/m2.


Subject(s)
Gastric Bypass , Laparoscopy , Obesity, Morbid/surgery , Adult , Anastomosis, Roux-en-Y , Body Mass Index , Female , Humans , Male , Retrospective Studies , Weight Loss
13.
Surg Endosc ; 15(4): 415-22, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11409412

ABSTRACT

Most minimally invasive surgical procedures are now performed in operating rooms that were originally designed for traditional open surgery. Laparoscopic instrumentation such as insufflators, light sources, and camera control units must be placed on one or more equipment carts. After the cart has been moved into place, insufflation tubing, video cables, light cords, cautery lines, and foot controls must be positioned and connected. This cart-based paradigm restricts the ergonomic configuration of the operating room and creates potential mechanical, electrical, and biological hazards to the patient and operating room staff. In order to decrease clutter, ease personnel movement, improve ergonomics, maintain the sterile field, and facilitate the use of advanced imaging, communication, and display devices, an appropriately designed operating environment is essential. Herein we detail both the theoretical and practical aspects of the design and describe the implementation and utilization of such a suite in our hospital. These design elements may prove to be critical to the next generation of minimally invasive surgical suites and will facilitate future advanced laparoscopic procedures.


Subject(s)
Facility Design and Construction/standards , Minimally Invasive Surgical Procedures/methods , Operating Rooms/standards , Surgery Department, Hospital/organization & administration , Accident Prevention , Facility Design and Construction/trends , Humans , Laparoscopy/methods , Operating Rooms/trends , Surgical Equipment/standards , Video-Assisted Surgery/instrumentation , Video-Assisted Surgery/methods
14.
Arch Surg ; 136(6): 700-4, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11387013

ABSTRACT

Patients with metastatic colorectal cancer limited to the liver are candidates for regional chemotherapy with implantable hepatic artery infusion (HAI) pumps. The poor prognosis of these patients, and the requirement of a laparotomy for placement, has deterred many oncologists from referral for HAI pump implantation. Minimally invasive surgical techniques are particularly well suited for the task of HAI pump placement in patients who may not tolerate the additional physiologic stress of a major surgical intervention. Advances in laparoscopic techniques allow pumps to be implanted safely and effectively, replicating the well-described tenets of open pump placement. The principal steps of the operation include a thorough laparoscopic evaluation to exclude extrahepatic disease, complete vascular isolation of the hepatic and gastroduodenal arteries, ligation of aberrant hepatic vessels, secure cannulation of the gastroduodenal artery, and confirmation of complete hepatic perfusion without extrahepatic perfusion. We describe the procedure and briefly review our clinical experience. We believe that the benefits typically derived from minimally invasive approaches (less pain, fewer perioperative complications, shorter hospitalization, faster recovery, and potentially less immune suppression) will be seen in these patients as well. If so, a completely laparoscopic approach to regional treatment of the liver may extend survival and improve the quality of life of patients whose prognosis is poor regardless of treatment. Controlled trials will be required to evaluate the added value of a laparoscopic approach to the placement of the hepatic artery pump.


Subject(s)
Colorectal Neoplasms/pathology , Hepatic Artery , Infusions, Intra-Arterial/instrumentation , Infusions, Intra-Arterial/methods , Laparoscopy/methods , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Ultrasonography, Interventional/instrumentation , Ultrasonography, Interventional/methods , Humans , Infusions, Intra-Arterial/adverse effects , Laparoscopy/adverse effects , Length of Stay/statistics & numerical data , Liver Neoplasms/mortality , Prognosis , Time Factors , Treatment Outcome , Ultrasonography, Interventional/adverse effects
15.
J Org Chem ; 66(8): 2822-7, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11304207

ABSTRACT

A diastereoselective synthesis of 1-methyl-2-alkyl- and 2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylic esters has been developed from methyl (2-nitrophenyl)acetate (1). The method involves alkylation of 1 with an allylic halide, ozonolysis of the double bond, and catalytic hydrogenation. The final hydrogenation initiates a tandem sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the aniline or hydroxylamine(8) nitrogen with the side chain carbonyl, (3) reduction of the resulting nitrogen intermediate, and (4) reductive amination of the tetrahydroquinoline with formaldehyde produced in the ozonolysis to give a methyl (+/-)-1-methyl-2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylate. Removal of the formaldehyde prior to hydrogenation gives the simple (+/-)-2-alkyl derivatives. The products are isolated in high yield as single diastereomers having the C-2 alkyl group cis to the C-4 carboxylic ester. The reaction has been extended to the synthesis of tricyclic structures with similar high diastereoselection.


Subject(s)
Esters/chemical synthesis , Quinolines/chemical synthesis , Stereoisomerism
16.
Arch Surg ; 135(9): 1055-61; discussion 1061-2, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10982510

ABSTRACT

HYPOTHESIS: Based on retrospective, uncontrolled studies, it has been claimed that Nissen fundoplication should be performed over an esophageal bougie to minimize postoperative dysphagia. We hypothesized that a surgeon experienced in laparoscopic fundoplication will have similar rates of postoperative dysphagia whether or not an esophageal bougie is used. DESIGN: A patient and observer blinded, randomized, prospective clinical trial to assess the effect of intraoperative bougie use. SETTING: A tertiary care teaching hospital that is a regional referral source for complex laparoscopic foregut surgical procedures. PATIENTS: Three hundred thirty-six consecutive patients referred for laparoscopic fundoplication between March 1, 1996, and July 31, 1998, were evaluated for eligibility based on inclusion criteria and, if applicable, were offered randomization for fundoplication with or without a 56F bougie. One hundred seventy-one patients were enrolled in this study. INTERVENTIONS: All patients underwent laparoscopic Nissen fundoplication, 81 with a bougie (hereafter referred to as the bougie group) and 90 without a bougie (hereafter referred to as the no bougie group). MAIN OUTCOME MEASURES: Dysphagia severity and frequency were assessed by a blinded observer using a standardized scoring system. Incidence of complications related to the use or absence of a bougie, operative times, and postsurgical recovery was also assessed. RESULTS: The mean operating time was 148 minutes (range, 65-295 minutes). The overall operative morbidity was 9% (7. 4% in the bougie group and 11% in the no bougie group, P=.41). One esophageal injury (1.2%) occurred in the bougie group. The 30-day mortality was 0. Long-term dysphagia assessment was completed in 90% of patients, with a mean follow-up of 11 months. Overall, long-term postoperative dysphagia was present in 13 patients (17%) in the bougie group and 24 patients(31%) in the no bougie group (P=.047). Severe dysphagia occurred in 5% of patients in the bougie group and 14% in the no bougie group. CONCLUSION: This study confirms the dogma that use of a large-caliber stent during the creation of a fundoplication decreases the long-term incidence of dysphagia; albeit at the risk of injury from the introduction of a bougie.


Subject(s)
Deglutition Disorders/prevention & control , Fundoplication/adverse effects , Laparoscopy , Adult , Double-Blind Method , Female , Fundoplication/methods , Humans , Male , Middle Aged , Prospective Studies
20.
J Med Chem ; 43(5): 859-72, 2000 Mar 09.
Article in English | MEDLINE | ID: mdl-10715153

ABSTRACT

High-throughput screening of a combinatorial library of diamidophenols yielded lead compounds with the ability to inhibit human factor Xa (fXa) at micromolar concentrations (e.g. compound 4, fXa apparent K(ass) = 0.64 x 10(6) L/mol). SAR studies in this novel structural series of fXa inhibitors showed that the phenolic hydroxyl group was not essential for activity. The best activity was found in substituted 1,2-dibenzamidobenzenes in which the phenyl group of one benzoyl group (A-ring) was substituted in the 4-position with relatively small lipophilic or polarizable groups such as methoxy, vinyl, or chloro and the phenyl group of the other benzoyl group (B-ring) was substituted in the 4-position with larger lipophilic groups such as tert-butyl or dimethylamino. The central phenyl ring (C-ring) tolerated a wide variety of substituents, but methoxy, methanesulfonamido, hydroxyl, and carboxyl substitution produced slightly higher levels of activity than other substituents when present in combination with favorable B-ring substitution. Methylation of the amide nitrogen atoms was found to greatly decrease activity. Compound 12 is the highest affinity fXa inhibitor in this group of compounds, having fXa apparent K(ass) = 25.5 x 10(6) L/mol, about 40x more active than the original lead. This lead series does not show potent inhibition of human thrombin. A model for the binding of these ligands to the fXa active site is proposed. The model is consistent with the observed SAR and can serve to guide future SAR studies.


Subject(s)
Anticoagulants/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Factor Xa Inhibitors , Phenylenediamines/chemical synthesis , Sulfonamides/chemical synthesis , Thrombin/antagonists & inhibitors , Anticoagulants/chemistry , Anticoagulants/metabolism , Binding Sites , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Factor Xa/chemistry , Factor Xa/metabolism , Humans , Models, Molecular , Phenylenediamines/chemistry , Phenylenediamines/metabolism , Phenylenediamines/pharmacology , Serine Proteinase Inhibitors/chemical synthesis , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/metabolism , Structure-Activity Relationship , Sulfonamides/chemistry , Sulfonamides/metabolism , Sulfonamides/pharmacology , Thrombin/metabolism
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