Publications by authors named "Douglas Ewing"

21 Publications

  • Page 1 of 1

Depletion of Omega-3 Fatty Acids in RBCs and Changes of Inflammation Markers in Patients With Morbid Obesity Undergoing Gastric Bypass.

J Nutr 2021 Jun 10. Epub 2021 Jun 10.

Hackensack University Medical Center, Hackensack, NJ, USA.

Background: Bariatric surgery is considered the most effective treatment for severe obesity. Despite this wide success, bariatric surgery is associated with increased risks of nutritional deficiencies.

Objectives: To examine whether Roux-en-Y-gastric bypass (RYGB) alters essential fatty acid (FA) status and inflammation markers.

Methods: Subjects with obesity (n = 28; BMI > 40 kg/m2; mean age 48 years) were studied before and 1 year after RYGB. We collected blood samples before and 12 months after RYGB, and analyzed FA in RBCs and peripheral blood mononuclear cells (PBMC), and measured inflammation parameters in plasma. The proportion of total n-3 FAs was the primary outcome, while parameters related to other FAs and inflammation factors were the secondary parameters. In addition, PBMCs from 15 of the participants were cultured alone or with 100 and 200 μM DHA, and the production of IL-6, IL-1β, PGE2, and prostaglandin F2-alpha (PGF2α) was assayed after endotoxin (LPS) stimulation.

Results: RYGB induced a significant reduction of BMI (-30%) and improvement of insulin resistance (-49%). While the proportion of arachidonic acid was 15% higher after RYGB, the proportions of total and individual n-3 FAs were 50%-75% lower (P < 0.01). Consequently, the RBC omega-3 index and n-3:n-6 fatty acid ratio were 45% and 50% lower after surgery, respectively. In isolated PBMCs, LPS induced the production of IL-6, IL-1β, PGE2, and PGF2α in both pre- and post-RYGB cells, but the effects were 34%-65% higher (P < 0.05) after RYGB. This effect was abrogated by DHA supplementation.

Conclusions: This study presents evidence that RBC and PBMC n-3 FAs are severely reduced in patients with obesity after RYGB. DHA supplementation in PBMC moderates the production of inflammation markers, suggesting that n-3 FA supplementation would merit a trial in bariatric patients.
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http://dx.doi.org/10.1093/jn/nxab167DOI Listing
June 2021

Two cases of euglycemic diabetic ketoacidosis after bariatric surgery associated with sodium-glucose cotransporter-2 inhibitor use.

Obes Surg 2021 08 24;31(8):3848-3850. Epub 2021 Apr 24.

Center for Bariatric Medicine and Surgery, Hackensack University Medical Center, 20 Prospect Avenue, Suite 703, Hackensack, NJ, 07601, USA.

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http://dx.doi.org/10.1007/s11695-021-05391-0DOI Listing
August 2021

Insurance-Mandated Medical Weight Management Programs in Sleeve Gastrectomy Patients Do Not Improve Postoperative Weight Loss Outcomes at 1 Year.

Obes Surg 2020 Sep;30(9):3333-3340

Hackensack University Medical Center, Hackensack, NJ, USA.

Background/introduction: Qualification for bariatric surgery is based upon strict medical guidelines, but individual insurance companies may introduce additional requirements for approval and coverage as they deem necessary. A mandatory preoperative medical weight loss management (MWM) program is commonly such a requirement.

Objective: The primary objective of this study is to assess the effect of MWM programs on weight loss outcomes.

Methods: A retrospective review of all sleeve gastrectomies performed between 2012 and 2016 at our institution was conducted. Patients were divided into two groups: those who required a preoperative MWM program, and those who did not. A 1:1 greedy nearest-neighbor method matching algorithm was used to match patients based on age, BMI, smoking, gender, race, sleep apnea, and diabetes. Total weight loss and percent excess weight loss at 1 year for each group were compared.

Results: A total of 3059 sleeve gastrectomy patients were reviewed. Of these, 941 patients had adequate data points to be evaluated. The matching algorithm resulted in 530 patients for the final analysis, 265 patients in each group. There were no significant differences between the groups in terms of age, BMI, smoking, gender, race, sleep apnea, or diabetes. A paired t test found no significant differences between the MWM group and the control group at 1 year in both total weight loss (36.7 kg vs 36.2 kg) and in percent excess weight loss (56.5% vs 55.8%, p = 0.24).

Conclusion: There was no significant difference in weight loss outcomes after 1 year in patients required by insurance to participate in MWM programs compared to those who were not. The necessity of these programs should be questioned.
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http://dx.doi.org/10.1007/s11695-020-04692-0DOI Listing
September 2020

Large series examining laparoscopic adjustable gastric banding as a salvage solution for failed gastric bypass.

Surg Obes Relat Dis 2018 Dec 13;14(12):1869-1875. Epub 2018 Sep 13.

Center for Bariatric Medicine and Surgery, Hackensack University Medical Center, Hackensack, New Jersey.

Background: The Roux-en-Y gastric bypass (RYGB) has long been considered the gold standard of weight loss procedures. However, there is limited evidence on revisional options with both minimal risk and long-term weight loss results.

Objective: To examine percent excess weight loss, change in body mass index (BMI), and complications in patients who underwent laparoscopic adjustable gastric banding (LAGB) over prior RYGB.

Setting: Academic hospital.

Methods: Retrospective analysis of a single-center prospectively maintained database. Three thousand ninety-four LAGB placements were reviewed; 139 were placed in patients with prior RYGB.

Results: At the time of LAGB, the median BMI was 41.3. After LAGB, we observed weight loss or stabilization in 135 patients (97%). The median maximal weight loss after LAGB was 37.7% excess weight loss and -7.1 change in BMI (P < .0001). At last follow-up visit, the median weight loss was 27.5% excess weight loss and -5.3 change in BMI (P < .0001). Median follow-up was 2.48 years (.01-11.48): 68 of 132 eligible (52%) with 3-year follow-up, 12 of 26 eligible (44%) with 6-year eligible follow-up, and 3 of 3 eligible (100%) with >10-year follow-up. Eleven bands required removal, 4 for erosion, 4 for dysphagia, and 3 for nonband-related issues.

Conclusions: LAGB over prior RYGB is a safe operation, which reduces the surgical risks and nutritional deficiencies often seen in other accepted revisional operations. Complication rates were consistent with primary LAGB. Weight loss is both reliable and lasting, and it can be considered as the initial salvage procedure in patients with failed gastric bypass surgery.
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http://dx.doi.org/10.1016/j.soard.2018.09.003DOI Listing
December 2018

A molecular guidance system based upon target genes, nuclear receptors and ligands applied to drug discovery and prediction of toxicity.

Mini Rev Med Chem 2008 Oct;8(12):1252-64

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta GA 30912, USA.

A molecular guidance system useful in drug design is described in which nuclear receptors position ligands in intercalation sites in responsive genes. Evidence is based upon positions of agonists in receptors and the transcriptional activity of a designed estrogen that is 3 times more potent than the steroid hormone estradiol.
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http://dx.doi.org/10.2174/138955708786140972DOI Listing
October 2008

One-year readmission rates at a high volume bariatric surgery center: laparoscopic adjustable gastric banding, laparoscopic gastric bypass, and vertical banded gastroplasty-Roux-en-Y gastric bypass.

Obes Surg 2008 Oct 2;18(10):1233-40. Epub 2008 May 2.

Surgery, New York University, Manhattan VA, 423 East 23rd St., New York City, NY, 10010, USA.

Background: An increasing importance has been placed on a bariatric program's readmission rates. Despite the importance of such data, there have been few studies that document 1-year readmission rates. There have been even fewer studies that delineate the causes of readmission. The objective of this study is to delineate the rates and causes of readmissions within 1 year of bariatric operations performed in a high-volume center.

Methods: Records for all patients undergoing bariatric operations during a 31-month period were harvested from the hospital electronic medical database. Readmissions for these patients were then identified within the hospital database for the year following the index operation. The electronic medical records of all readmitted patients were reviewed.

Results: The overall 1-year readmission rate for 1,939 consecutive bariatric operations was 18.8%. The laparoscopic adjustable gastric band (LAGB) had the lowest readmission rate of 12.69%. Next was the vertical banded gastroplasty-Roux-en-Y gastric bypass (VBG-RYGB) with a rate of 15.4%. The laparoscopic Roux-en-Y gastric bypass (LRYGB) had the highest readmission rate of 24.2%. Leading causes of readmission were abdominal pain with normal radiographic studies and elective operations. Independent factors predicting readmission were found to be LOS > 3 days (odds ratio 1.69 p = 0.004) and having a LRYGB (odds ratio of 1.49 p = 0.003). The previously reported reoperation rate for bowel obstruction of 9.7% had decreased to 3.7% due to changes in operative technique.

Conclusion: Rates of readmissions for patients undergoing bariatric surgery center at our high-volume center decreased over time and are comparable to other major abdominal operations.
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http://dx.doi.org/10.1007/s11695-008-9517-8DOI Listing
October 2008

Bariatric surgery: low mortality at a high-volume center.

Obes Surg 2008 Jun 3;18(6):660-7. Epub 2008 Apr 3.

Bariatric Surgery Center, Hackensack University Medical Center, Hackensack, NJ, USA.

Background: The American Society of Bariatric Surgery has initiated a Bariatric Surgery Center of Excellence Program and the American College of Surgeons has followed with their Bariatric Surgery Center Network Accreditation Program. These programs postulate that concentration of weight loss operations in high-volume centers will decrease surgical mortality and improve outcomes.

Methods: The purpose of this study was to calculate the in-hospital mortality for bariatric operations accomplished at the highest volume bariatric surgery center in the state of New Jersey. After receiving Institutional Revew Board approval, the revised surgical schedule was used to identify all patients undergoing weight loss surgery (WLS) at Hackensack University Medical Center from 1998 through June, 2006. Data for these patients were then harvested from the hospital's electronic medical record. Step-wise and univariate logistic regression analysis tested the impact of various factors on hospital length of stay and in-hospital mortality.

Results: Between 1998 and June, 2006, 5,365 patients underwent WLS surgery: 2,099 open vertical banded gastroplasty-Roux en Y gastric bypass (VBG-RYGB); 2,177 laparoscopic Roux en Y gastric bypass (LRYGB); and 1,089 laparoscopic adjustable gastric banding (LAGB). 75.5% of patients were women. Median age was 41 years old (13-79), median weight 128 kg (81.2-290.3), and median body mass index 46.1 kg/m2 (35.0-92.6). Median total operating room time for VBG-RYGB was 115 min (33-328); LRYGB 155 min (53-493), and LAGB 92 min (33-274). Median length of stay for VBG-RYGB was 3 days (1-39 days), LRYGB 2 days (1-46 days), and LAGB 1 day (1-20). Seven patients died in hospital after the 5,365 WLS operations (0.13%): four after VBG-RYGB (0.19%); three after LRYGB (0.14%); and none after LAGB (0%). The characteristics of the patients who died did not significantly differ from the group as a whole.

Conclusion: Surgeons at Hackensack University Medical Center, a high volume, accredited 1A American College of Surgeons Bariatric Surgery Center, achieved a 0.13% mortality among 5,365 patients undergoing weight loss operations between 1998 and June, 2006. This study supports the concept that high-volume centers perform bariatric operations with low mortalities.
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http://dx.doi.org/10.1007/s11695-007-9357-yDOI Listing
June 2008

Short-term outcomes for super-super obese (BMI > or =60 kg/m2) patients undergoing weight loss surgery at a high-volume bariatric surgery center: laparoscopic adjustable gastric banding, laparoscopic gastric bypass, and open tubular gastric bypass.

Surg Obes Relat Dis 2008 May-Jun;4(3):408-15. Epub 2008 Feb 1.

Bariatric Surgery Center, Hackensack University Medical Center, 20 Prospect Avenue, Hackensack, NJ 07601, USA.

Background: We previously reported significantly longer operating room times and a trend toward increased complications and mortality in the super-super obese (body mass index [BMI] > or =60 kg/m(2)) early in our experience with laparoscopic Roux-en-Y gastric bypass. The goal of this study was to re-examine the short-term outcomes for super-super obese patients undergoing weight loss surgery at our high-volume bariatric surgery center well beyond our learning curve.

Methods: The records for all patients who had undergone weight loss surgery at Hackensack University Medical Center from 2002 to June 2006 were harvested from the hospital's electronic medical database. This population was analyzed as 2 groups (those with a BMI <60 kg/m(2) and those with a BMI > or =60 kg/m(2)), as well as by type of operation. Step-wise and univariate logistic regression analyses assessed the effect of BMI on the outcome variables, including mortality, length of surgery, length of hospital stay, and disposition at discharge.

Results: A total of 3692 patients were studied. Of these patients, 3401 had a BMI <60 kg/m(2) and 291 had a BMI > or =60 kg/m(2). Of the 291 super-super obese patients, 130 underwent vertical banded gastroplasty-Roux-en-Y gastric bypass, 116 laparoscopic Roux-en-Y gastric bypass, and 45 laparoscopic adjustable gastric banding. The proportion of male patients, black patients, and patients with sleep apnea was increased in the BMI > or =60 kg/m(2) group. The number of co-morbid diseases per patient correlated with age but not BMI. The BMI > or =60 kg/m(2) group required a significantly longer total operating room time (136 versus 120 min). Hospital length of stay was significantly longer only in the laparoscopic Roux-en-Y gastric bypass patients (3 d for the BMI > or =60 kg/m(2) group versus 2 d for the BMI <60 kg/m(2) group). A significantly greater percentage of patients in the super-super obese group were discharged to chronic care facilities. The overall in-hospital mortality rate was 0.15% (5 of 3692) but did not significantly differ between the 2 groups: BMI <60 kg/m(2), rate of 0.12% (4 of 3401 patients), and BMI > or =60 kg/m(2), rate of 0.34% (1 of 291 patients). The type of operation did not significantly affect the disposition at discharge or in-hospital mortality.

Conclusion: Super-super obese patients required longer total operating room times, a longer hospital length of stay, and were more likely to be discharged to chronic care facilities than were patients with a BMI <60 kg/m(2); however, the in-hospital mortality was similar for both groups.
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http://dx.doi.org/10.1016/j.soard.2007.10.013DOI Listing
October 2008

30-day readmission rates at a high volume bariatric surgery center: laparoscopic adjustable gastric banding, laparoscopic gastric bypass, and vertical banded gastroplasty-Roux-en-Y gastric bypass.

Obes Surg 2007 Sep;17(9):1171-7

Bariatric Surgery Center, Hacekensack University Medical Center, Hackensack, NJ 07601, USA.

Background: Recent studies suggest that weight loss operations may actually increase the costs to society due to increased hospital readmission rates. The purpose of this study was to determine the 30-day readmission rates following bariatric operations at a high volume bariatric surgery program.

Methods: Records for all patients undergoing bariatric operations during a 3-year period were harvested from the hospital electronic medical database. All hospital readmissions within 30 days of surgery were reviewed to determine the cause, demographics, and patient characteristics. Logistic regression analysis assessed the impact of various factors on the risk of readmission.

Results: 2,823 consecutive patients were identified using the corrected operative log. Of these patients, 165 (5.8%) patients required 184 (6.5%) readmissions within 30 days of their index bariatric operation. Laparoscopic adjustable gastric banding (LAGB) had the lowest patient readmission rate of 3.1%; vertical banded gastroplasty-Roux-en-Y gastric bypass (VBG-RYGBP) 6.8% and Laparoscopic Roux-en-Y gastric bypass (LRYGBP) 7.3%. Technical considerations were the most common cause for readmission (41% of readmissions). White race and undergoing LAGB decreased the odds for readmission, while total operating-room time >120 minutes, initial hospital stay of >3 days and deep venous thrombosis increased the odds for readmission.

Conclusion: This study found an overall 30-day readmission rate of 6.5% following bariatric operations at a high volume bariatric surgery program. This study supports the concept of bariatric surgery Centers of Excellence and accreditation of Bariatric Surgery Programs based on hospital volume of bariatric operations.
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http://dx.doi.org/10.1007/s11695-007-9210-3DOI Listing
September 2007

Laparoscopic medial-to-lateral colon dissection: how and why.

J Gastrointest Surg 2007 Jun;11(6):778-82

Department of General and Oncologic Surgery, City of Hope National Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA.

Laparoscopic colectomy is a difficult procedure with a long learning curve. We describe in this study our technique for right- and left-sided laparoscopic medial-to-lateral colectomy. The medial approach involves division of the vascular pedicle first, followed by mobilization of the mesentery toward the abdominal wall, and finally freeing of the colon along the white line of Toldt. This approach allows immediate identification of the plane between the mesocolon and the retroperitoneum and renders the dissection fast and safe. Our series of 50 consecutive laparoscopic colectomies supports this concept. We believe that surgeons familiar with this technique will have an important tool in their armamentarium to circumvent some of the challenges of laparoscopic colectomy.
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http://dx.doi.org/10.1007/s11605-007-0120-4DOI Listing
June 2007

Small molecule intercalation with double stranded DNA: implications for normal gene regulation and for predicting the biological efficacy and genotoxicity of drugs and other chemicals.

Mutat Res 2007 Oct 24;623(1-2):53-71. Epub 2007 Mar 24.

Accelerated Pharmaceuticals Inc., Augusta, GA, United States.

The binding of small molecules to double stranded DNA including intercalation between base pairs has been a topic of research for over 40 years. For the most part, however, intercalation has been of marginal interest given the prevailing notion that binding of small molecules to protein receptors is largely responsible for governing biological function. This picture is now changing with the discovery of nuclear enzymes, e.g. topoisomerases that modulate intercalation of various compounds including certain antitumor drugs and genotoxins. While intercalators are classically flat, aromatic structures that can easily insert between base pairs, our laboratories reported in 1977 that a number of biologically active compounds with greater molecular thickness, e.g. steroid hormones, could fit stereospecifically between base pairs. The hypothesis was advanced that intercalation was a salient feature of the action of gene regulatory molecules. Two parallel lines of research were pursued: (1) development of technology to employ intercalation in the design of safe and effective chemicals, e.g. pharmaceuticals, nutraceuticals, agricultural chemicals; (2) exploration of intercalation in the mode of action of nuclear receptor proteins. Computer modeling demonstrated that degree of fit of certain small molecules into DNA intercalation sites correlated with degree of biological activity but not with strength of receptor binding. These findings led to computational tools including pharmacophores and search engines to design new drug candidates by predicting desirable and undesirable activities. The specific sequences in DNA into which ligands best intercalated were later found in the consensus sequences of genes activated by nuclear receptors implying intercalation was central to their mode of action. Recently, the orientation of ligands bound to nuclear receptors was found to match closely the spatial locations of ligands derived from intercalation into unwound gene sequences suggesting that nuclear receptors may be guiding ligands to DNA with remarkable precision. Based upon multiple lines of experimental evidence, we suggest that intercalation in double stranded DNA is a ubiquitous, natural process and a salient feature of the regulation of genes. If double stranded DNA is proven to be the ultimate target of genomic drug action, intercalation will emerge as a cornerstone of the future discovery of safe and effective pharmaceuticals.
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http://dx.doi.org/10.1016/j.mrfmmm.2007.03.009DOI Listing
October 2007

Endoscopic resection of thoracic paravertebral and dumbbell tumors.

Neurosurgery 2006 Dec;59(6):1195-201; discussion 1201-2

Minimally Invasive Spine Surgery Center, Department of Neurosurgery, St. Luke's/Roosevelt, and Beth Israel Medical Centers, New York, New York 10019, USA.

Objective: Neurogenic paravertebral tumors are uncommon neoplasms arising from neurogenic elements within the thorax. These tumors may be dumbbell shaped, extending into the spinal canal or exclusively paraspinal. Generally encapsulated, they are located in the posterior mediastinum. In this report, we present our experience in the thoracoscopic resection of these tumors, including surgical technique and potential pitfalls.

Methods: A retrospective review of patients undergoing endoscopic surgery for paravertebral tumors was undertaken. Patient demographics, charts, operative reports, and pre- and postoperative images were reviewed.

Results: Between 1997 and 2004, 13 patients were treated thoracoscopically for paravertebral tumors in our departments. Our population consisted of four men and nine women. The median age was 44.9 years (range, 29-66 yr). Eight patients presented with pain, dyspnea, cough, and weakness. Five patients had tumors found incidentally. Sizes of the tumors varied from 3 to 9 cm. Final pathology included four neurofibromas, eight schwannomas, and one unclassified granular cell tumor. Gross total resection was achieved endoscopically in all cases. Three patients required a hemilaminectomy for resection of the intraspinal dumbbell component of the tumor during the same operation. The mean operative time was 229.5 minutes. The mean estimated blood loss was 371.1 ml. Postoperative morbidities included one each of tongue swelling, ulnar neuropathy, and intercostal hyperesthesia. The mean hospital stay was 2.8 days.

Conclusion: Paravertebral tumors in the posterior mediastinum are amenable to endoscopic removal, even in hard to reach locations. Tumors with intraspinal extension can be removed concurrently by performing a hemilaminectomy, followed by thoracoscopy, without the need for a thoracotomy.
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http://dx.doi.org/10.1227/01.NEU.0000245617.39850.C9DOI Listing
December 2006

Telerobotic-assisted laparoscopic right hemicolectomy: lateral to medial or medial to lateral dissection?

Surg Laparosc Endosc Percutan Tech 2006 Dec;16(6):406-10

Division of Minimally Invasive and Telerobotic Surgery, Hackensack University Medical Center, Hackensack, NJ 07601, USA.

Background: We previously reported that telerobotic-assisted laparoscopic colectomy was feasible and could be accomplished safely. Nonetheless, we found that the current iteration of da Vinci was not well suited to a lateral to medial (LtM) dissection of the colonic mesentery. The motion scaling made the large excursion arcs required for adequate exposure in a LtM dissection cumbersome to achieve.

Aim: As a result, the aim of this study was to compare the ability of the da Vinci telerobotic surgical system to perform telerobotic-assisted laparoscopic right hemicolectomy using a LtM dissection with a medial to lateral (MtL) dissection technique.

Methods: We compared 8 consecutive da Vinci-assisted laparoscopic right hemicolectomies performed using a LtM dissection to 8 consecutive operations using a MtL dissection technique. Results were compared using analysis of variance.

Results: Age for the 2 groups were not significantly different: LtM 64 (43 to 71) years and MtL 56 (39 to 68) years. Body mass index was similar: LtM 27 (22 to 34) and MtL 25 (20 to 32) kg/m. Total surgical time (including cystoscopy and intraoperative colonoscopy) were similar: LtM 212 (188 to 610) minutes and MtL 203 (135 to 220) minutes. There was no significant difference in lymph node harvest: LtM 12 (3 to 20) lymph nodes and MtL 18 (3 to 35) lymph nodes. There were no deaths or anastomotic leaks in either groups. Median length of stay was similar for both groups: LtM 5 (3 to 10) days and MtL 4 (2 to 9) days.

Conclusions: da Vinci-assisted laparoscopic right hemicolectomy using a MtL dissection technique achieves similar outcomes as a LtM dissection approach.
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http://dx.doi.org/10.1097/01.sle.0000213732.03204.50DOI Listing
December 2006

DNA intercalative potential of marketed drugs testing positive in in vitro cytogenetics assays.

Mutat Res 2006 Oct 20;609(1):47-59. Epub 2006 Jul 20.

Schering-Plough Research Institute, Department of Genetic and Molecular Toxicology, Summit, NJ, USA.

We have previously noted that the Physicians' Desk Reference (PDR) contains over 80 instances in which a drug elicited a positive genotoxic response in one or more in vitro assays, despite having no obvious structural features predictive of covalent drug/DNA interactive potential or known mechanistic basis. Furthermore, in most cases, these drugs were "missed" by computational genotoxicity-predicting models such as DEREK, MCASE and TOPKAT. We have previously reported the application of a V79 cell-based model and a 3D DNA docking model for predicting non-covalent chemical/DNA interactions. Those studies suggested that molecules that are very widely structurally diverse may be capable of intercalating into DNA. To determine whether such non-covalent drug/DNA interactions might be involved in unexpected drug genotoxicity, we evaluated, using both models where possible, 56 marketed pharmaceuticals, 40 of which were reported as being clastogenic in in vitro cytogenetics assays (chromosome aberrations/mouse lymphoma assay). As seen before, the two approaches showed good concordance (62%) and 26 of the 40 (65%) drugs exhibiting in vitro clastogenicity were predicted as intercalators by one or both methods. This finding provides support for the hypothesis that non-covalent DNA interaction may be a common mechanism of clastogenicity for many drugs having no obvious structural alerts for covalent DNA interaction.
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http://dx.doi.org/10.1016/j.mrgentox.2006.06.001DOI Listing
October 2006

Transcriptional inhibition of the estrogen response element by antiestrogenic piperidinediones correlates with intercalation into DNA measured by energy calculations.

J Steroid Biochem Mol Biol 2005 Sep 28;96(5):335-45. Epub 2005 Jul 28.

Department of Gynceology and Obstetrics, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.

The energy of interaction of antiestrogenic ligands bound to DNA derived from molecular modeling was compared to the capacity of the ligands to directly inhibit the transcriptional activity of an estrogen responsive gene. 3-Phenylacetylamino-2,6-piperidinedione (A10) and related compounds were intercalated into a partially unwound DNA site in a canonical estrogen response element (ERE). The piperidinedione/ERE complexes were subjected to energy minimization and the strength of interaction of the ligands with the DNA was measured. The ability of the ligands to inhibit transactivation was assessed using a reporter gene constructed with the ERE of the vitellogenin gene promoter (ERE(v)-tk-Luc) transiently transfected into the human estrogen receptor-positive MCF-7 breast cancer cell line. The results demonstrate a direct correlation between the calculated energetic fit of the compounds in the ERE and inhibition of ERE(v) transactivation. The order of potency of the compounds to suppress estrogen-dependent reporter gene activity was identical to that previously shown for inhibiting the growth of MCF-7 cells. To our knowledge, these results provide the first direct experimental evidence that the predicted fit of a class of compounds into a defined DNA binding site correlates with the ability of the compounds to modulate specific gene functions regulated at that site.
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http://dx.doi.org/10.1016/j.jsbmb.2005.04.040DOI Listing
September 2005

The learning curve measured by operating times for laparoscopic and open gastric bypass: roles of surgeon's experience, institutional experience, body mass index and fellowship training.

Obes Surg 2005 Feb;15(2):172-82

Bariatric Surgery Center, Hacekensack University Medical Center, Hackensack, NJ 07601, USA.

Background: Surgeons must overcome a substantial learning curve before mastering laparoscopic Roux-en-Y gastric bypass (LRYGBP). This learning curve can be defined in terms of mortality, morbidity or length of surgery. The aim of this study was to compare the learning curves in terms of surgical time for the first 3 surgeons performing LRYGBP in our hospital with the length of surgery for open gastric bypass (CONTROLS).

Methods: We compared 494 primary LRYGBPs performed by 3 surgeons (393 by 1st SURGEON, 57 by 2nd SURGEON and 44 by 3rd SURGEON) to 159 open vertical banded gastroplasty-Roux-en-Y gastric bypasses (CONTROLS). Data for LRYGBP patients were prospectively obtained. Factors that significantly affected the length of surgery were identified by univariate and multivariate linear regression analysis.

Results: LRYGBP and CONTROL patients were similar in age, height, weight and BMI, although more CONTROLS were male. Median time for the 1st SURGEON performing LRYGBP dropped for each subsequent 100 operations: 1st 100 - 190 min, 2nd 100 - 135 min, 3rd 100 - 110 min and 4th 100 - 100 min. Median time for 2nd SURGEON performing LRYGBP was 120 min, 3rd SURGEON 173 min and CONTROLS 64 min. Length of surgery significantly correlated with surgical experience in terms of numbers of operations and BMI of patient. Times for 2nd SURGEON, a fellowship trained laparoscopic surgeon, started significantly faster than 1st SURGEON's, but did not significantly improve with experience. 3rd SURGEON's initial times were similar to 1st SURGEON's, but his times improved more rapidly with experience. Times for CONTROLS were significantly faster than all laparoscopic groups and did not correlate with operation number or patient BMI.

Conclusions: The length of surgery for LRYGBPs continued to shorten beyond 400 operations for the first surgeon performing LRYGBP in our hospital. Previous fellowship training in LRYGBP shortened surgical times during initial clinical experience as an attending for the second surgeon. The learning curve was truncated because of the already established LRYGBP program.
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http://dx.doi.org/10.1381/0960892053268507DOI Listing
February 2005

Evaluation of DNA intercalation potential of pharmaceuticals and other chemicals by cell-based and three-dimensional computational approaches.

Environ Mol Mutagen 2004 ;44(2):163-73

Department of Genetic and Reproductive Toxicology, Schering-Plough Research Institute, Lafayette, New Jersey 07848, USA.

To what extent noncovalent chemical-DNA interactions, in particular weak nonbonded DNA intercalation, contribute to genotoxic responses in mammalian cells has not been fully elucidated. Moreover, with the exception of predominantly flat, multiple-fused-ring structures, our ability to predict intercalation ability of novel compounds is nearly completely lacking. Computational programs such as DEREK and MCASE recognize primarily those molecules that can form irreversible covalent adducts with DNA since their learning sets, for the most part, have not been populated by compounds for which a relationship between noncovalent interaction and genotoxicity exists. We describe here a novel three-dimensional (3D) computational DNA-docking model for prediction of DNA intercalative activity of molecules with both classical and nonclassical intercalating structures. The 3D docking results show a remarkable concordance with results obtained from testing these molecules directly in the Chinese hamster V79 cell-based bleomycin amplification system suggesting that either or both of these approaches may have utility in defining noncovalent chemical-DNA interactions. The ability to predict and/or demonstrate cellular DNA intercalation of novel molecules may well provide fresh insights into the nature and mechanistic basis of structurally unexpected genotoxicity observed during safety testing.
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http://dx.doi.org/10.1002/em.20036DOI Listing
September 2004

Robots in the operating room--the history.

Semin Laparosc Surg 2004 Jun;11(2):63-71

Minimally Invasive and Telerobotic Surgery Institute, Hackensack University Medical Center, Hackensack, New Jersey 07601, USA.

The history of robotics can be traced back to the automata of ancient Greece, but it has only been within the last 50 years that machines have been made to mimic human actions in order to perform labor rather than to entertain and amuse. Furthermore, it has been only within the last 20 years that robotic technology has been applied to the practice of surgery. The goal of this technology has not been to replace the surgeon, but rather to enhance his or her performance with highly advanced tools. We present a brief history of some of the key points in the development of surgical robotics and discuss the advantages and disadvantages of the various US Food and Drug Administration-approved robotic surgical systems and surgical robots in general.
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http://dx.doi.org/10.1177/107155170401100202DOI Listing
June 2004

Totally endoscopic robotic thymectomy for myasthenia gravis.

Ann Thorac Surg 2003 Feb;75(2):569-71

St. Luke's Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, New York 10019, USA.

The current recommendations for treating myasthenia gravis include surgical thymectomy for patients between puberty and 60 years of age. This is a report of a new method for surgical thymectomy using the robotic da Vinci surgical system for a totally endoscopic approach. This new procedure combines the potential advantages of minimally invasive methods with the efficacy of open procedures.
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http://dx.doi.org/10.1016/s0003-4975(02)04296-0DOI Listing
February 2003

The transposed forearm loop arteriovenous fistula: a valuable option for primary hemodialysis access in diabetic patients.

Ann Vasc Surg 2002 Jan 17;16(1):89-94. Epub 2002 Jan 17.

St Luke's-Roosevelt Hospital Center New York, NY, USA.

The distal forearm is the site of first choice for creation of an arteriovenous fistula for hemodialysis. The archetypal procedure, the primary radial-cephalic fistula as described by Brescia, yields excellent functional patency for many patients. Results are much less favorable in patients with diabetes mellitus, for whom non-maturation rates as high as 70% have been reported. This is likely due to inadequate inflow caused by atherosclerotic disease of the forearm arteries in diabetics. Secondary autologous access procedures often involve upper arm configurations such as transposed brachial-basilic fistulas. The present study focuses on a valuable alternative for hemodialysis access in diabetic patients, the transposed forearm loop arteriovenous fistula. Over a 2-year period, 16 forearm loop fistulas were created in 16 diabetic patients who either had a failed radial-cephalic fistula or had arterial anatomy deemed inadequate for wrist fistula formation. In each case, the forearm segment of the basilic or cephalic vein was transposed to form a U-shaped loop and anastomosed to the brachial, proximal radial, or proximal ulnar artery distal to the antecubitai fossa. Functional patency was defined as usability for dialysis. Patency rates were calculated by Kaplan-Meier survival analysis. From our results we determined that the forearm loop fistula is an excellent but underutilized technique that exploits the forearm veins while circumventing the distal arterial supply, thus preserving the upper arm vasculature for future use.
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http://dx.doi.org/10.1007/s10016-001-0141-5DOI Listing
January 2002
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