The Department of Internal Medicine Brody School of Medicine East Carolina University presents the nd 22 Annual Yash P. Kataria IM Research Day - 2008 Thursday, May 29th, 2008 7:30 AM – 5:15 PM Allied Health Building 1102 and 1150 The Department of Internal Medicine Brody School of Medicine East Carolina University nd 22 Annual Yash P. Kataria IM Research Day – 2008 Laser Capture Microdissection (LCM) Paul Bolin, Jr., MD Interim Chair, Department of Internal Medicine Research Day Committee Granuloma positive sarcoidosis lung tissue section P ost laser capture microdissection Elizabeth McNeil Byrd, MD Roy Carlton Paul P. Cook, MD Randy Horton, MS (CME) Bobbie Harris Timothy A. Johnson, PhD Cindy Kukoly, MS Barbara J. Muller-Borer, PhD Belinda Perkinson George Sigounas, PhD Sarcoidosis – “Mystery Disease” • Sarcoidosis occurs when the body’s immune system overreacts to an unknown agent • Sarcoidosis "masquerades" as other diseases, such as hepatitis, dermatitis, arthritis, tuberculosis and asthma • About 50 percent of patients have at least some permanent organ damage • New ways of treating the disease are being developed that focus on controlling the immune system’s over-reaction Science Daily (Apr. 23, 1997) 1 The Yash P. Kataria IM Research Day is being established to honor the many contributions of Dr. Yash P. Kataria, and to support the educational and research program in the Department of Medicine at the Brody School of Medicine at ECU. This year, Research Day’s keynote will be delivered by Dr. Phil Bromberg, well known in pulmonary environmental medicine and former chief of pulmonary at UNC-CH, a mentor and friend of Dr. Yash P. Kataria. Dr. Kataria is Professor Emeritus of Medicine at BSOM and continues to contribute actively to the clinical, educational, and research mission of the pulmonary & critical care division at BSOM. He was the first pulmonologist in eastern NC and helped to establish the pulmonary specialty at BSOM 30 years ago and has been an integral force since the inception of the medical school. Yash was the first division chief of pulmonary medicine at BSOM and successfully recruited and established a clinical and active laboratory research program. Yash was the section head of pulmonary at BSOM / PCMH from 1978-1995, Vice Chair of the dept of Medicine 1987-1992, and interim chair 1986-87. Yash is of course known regionally, nationally, and internationally for his passion in translational research with a particular focus on sarcoidosis. He has authored over 70 publications, has received the Trudeau Award from the American Lung Association, lifetime achievement award by the NC Thoracic Society, on many occasions been listed on the “Best Doctors” list, has been a reviewer and/or on editorial board for numerous specialty journals. Over his 30 year career, he has cared for thousands of patients with sarcoidosis and he arguably has one of the largest sarcoid cohorts in the US. Yash is revered by his patients and families. Yash has literally trained hundreds of medical students and housestaff and is cherished by them as a role model and outstanding teacher at the bedside and in clinics. Yash has been a fixture in the international sarcoid community and has contributed actively at a leadership level at ACCP, ATS, and WASOG. Scientifically, Yash is perhaps best known for promulgating a paradigm shift in our understanding of sarcoid immunology. While it was accepted dogma in the 70s that sarcoidosis was a disease of “depressed immunity” and anergy, Yash proposed and championed the concept that it is a proinflammatory disease with involvement of activated T-cells, cytokines, etc. Yash and his group also proposed that the active “sarcoid factor” was localized to the cell walls of alveolar macrophages and monocytes or an “autologous kveim” model (this remains an intriguing hypothesis!). One of the missions of the medical school is community service in which medical school faculty plunged deeply. Yash lived in and loved Greenville where he raised two lovely children. He was actively involved in the J. H Rose Attendance Area Foundation Advisory Committee; also served as a Member Board of Academic Boosters Club, Rose High School, Greenville, NC and President, Parent Teacher Association, Greenville Middle School, Greenville, NC. He also helped to develop support groups for patients with sarcoidosis & COPD, and played leadership roles in the local American Lung Association of NC. We are honoring Dr. Kataria by dedicating our annual IM Research Day, which he started in 1987, to the Yash P. Kataria IM Research Day. We will continue to build on the tradition of encouraging research by inviting leading guest speakers and facilitating scholarship and interaction by our trainees and faculty. 2 Join us in thanking our sponsors for their support of IM Research Day - 2008 3 DISCLOSURE OF FACULTY RELATIONSHIPS WITH COMMERCIAL COMPANIES/ORGANIZATIONS 22ND ANNUAL YASH P. KATARIA IM RESEARCH DAY - 2008 The Brody School of Medicine at East Carolina University, the accredited provider of this activity, endorses the Standards of the Accreditation Council for Continuing Medical Education (ACCME) and Guidelines of the Association of American Medical Colleges (AAMC) that requires both sponsors and speakers to disclose relationships with commercial entities. Disclosure of a relationship is not intended to suggest or condone bias in any presentation, but is made to provide participants with information that might be of potential importance to their evaluation of a presentation. The following individuals have acknowledged that they have relationships with the companies/organizations identified below: CK Dunham Has not disclosed relationships with commercial entities. B Ramirez Has disclosed no relationships with commercial entities. GV Byrum III Has disclosed no relationships with commercial entities. H Dalrymple Has disclosed no relationships with commercial entities. J Jones Has disclosed no relationships with commercial entities. YA Midgette Has disclosed no relationships with commercial entities. S. Gerkin Has disclosed grant relationships with Fresenius Medical. AG Malur Has disclosed no relationships with commercial entities. LV Yang Has disclosed no relationships with commercial entities. S Arce Has disclosed no relationships with commercial entities. J Pender Has not disclosed relationships with commercial entities. CP Porterfield Has disclosed no relationships with commercial entities. Philip A. Bromberg Has disclosed no relationships with commercial entities. D Brescia Has disclosed no relationships with commercial entities. MA Gonzalez Has disclosed no relationships with commercial entities. EL Wilson Has disclosed no relationships with commercial entities. CM Wright Has disclosed no relationships with commercial entities. A Malur Has disclosed no relationships with commercial entities. KR Parker Has disclosed relationships with Novartis. DS Williams Has disclosed no relationships with commercial entities. S Kraemer Has not disclosed relationships with commercial entities. P Bolin Has disclosed relationships with Novartis and Astellas. D Liles Has disclosed no relationships with commercial entities. E McNeil Byrd Has not disclosed relationships with commercial entities. R Carlton Has disclosed no relationships with commercial entities. RP Cook Has not disclosed relationships with commercial entities. R Horton Has disclosed no relationships with commercial entities. B Harris Has disclosed no relationships with commercial entities. TA Johnson Has disclosed no relationships with commercial entities. C Kukoly Has disclosed no relationships with commercial entities. BJ Muller-Borer Has disclosed no relationships with commercial entities. G Sigounas Has disclosed relationships with Johnson and Johnson. 4 Department of Internal Medicine 22 nd Annual Yash P. Kataria IM Research Day Thursday, May 29, 2008 7:30am Continental Breakfast Allied Health 1102 8:00am Administrative Comments Allied Health 1102 Timothy A. Johnsons, PhD, Chair Internal Medicine Research Day Committee 8:05am Welcome Allied Health 1102 Paul Bolin, Jr., MD, Interim Chair Department of Internal Medicine First Oral Session, Allied Health 1102 Moderator: Barbara Muller-Borer, PhD 8:15am OV1 DO ANTIPSYCHOTIC DRUGS PROMOTE PROLACTINOMAS? A CASE REPORT AND REVIEW OF LITERATURE CK Dunham, FJ Cook and P Garcia 8:30am OV2 BROWN TUMORS: AN UNCOMMON MANIFESTATION OF PARATHYROID DISEASE B Ramirez, R Tanenberg, F Cook 8:45am OR1 THE EFFECT OF MECHANICAL STRAIN ON THE DIFFERENTIATION OF MESENCHYMAL STEM CELLS INTO A CARDIAC PHENOTYPE IN VITRO YA Midgette, MC Collins, PR Gunst, BJ MullerBorer 9:00am OR2 RITUXIMAB DEPLETES B-LYMPHOCYTES IN PULMONARY ALVEOLAR PROTEINOSIS H Dalrymple, A Malur, G Gagnon, I Marshall, S Arce, BP Barna, MS Kavuru, MJ Thomassen 9:15am OR3 PRISTANE INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS IN BALB/C MICE: AN ANIMAL MODEL J Jones, C Wright, I Marshall and EL Treadwell 9:30am OR4 ROLE OF THYMOSIN-β4 IN HUMAN MESENCHYMAL STEM CELL ENGRAFTMENT, SURVIVAL, AND DIFFERENTIATION IN MURINE MYOCARDIUM 5 GV Byrum III, MC Collins, BJ Muller-Borer, JI Virag 9:45am Break and Posters, Allied Health 1150 Visit the Exhibits Second Oral Session, Allied Health 1102 Moderator: Paul P. Cook, MD 10:15am OR5 OBESITY: THE MOST COMMON RISK FACTOR FOR KIDNEY DISEASE IN PITT COUNTY MEMORIAL HOSPITAL EMPLOYEES S. Gerkin, S. Johnson, C. Christiano, M. Hames, M. Locklear 10:30am OR6 IN VIVO REGULATION OF ABCG1 BY PPARγ IN ALVEOLAR MACROPHAGES OF GM-CSF KNOCKOUT (KO) MICE AG Malur, A Armstrong, A Malur, AJ McCoy, BP Barna, MS Kavuru, MJ Thomassen 10:45am OR7 REGULATION OF CELL RESPONSE TO ACIDOSIS BY THE PH-SENSING G PROTEINCOUPLED RECEPTOR GPR4 LV Yang, NR Leffler, AS Asch, ON Witte 11:00am OR8 DISTURBED PERIPHERAL B AND T CELL HOMEOSTASIS IN PATIENTS WITH SARCOIDOSIS NS Lee, H Dalrymple, A Malur, SA Joyner, I Marshall, BP Barna, MS Kavuru, MJ Thomassen, S Arce 11:15am OR9 IMPROVING BARIATRIC SURGERY OUTCOMES WITH A CENTERS OF EXCELLENCE PROGRAM J Pender, B Chapman, G Hughes, W Pories 11:30am OR10 IMPROVING PERFORMANCE IN PRACTICE: A QUALITY IMPROVEMENT PROJECT CONDUCTED AT THE ECU GENERAL INTERNAL MEDICINE RESIDENT CONTINUITY CLINIC R Mirza, CP Porterfield, MS Kraemer, B Johnson, B Bonnet 11:45am Lunch and Posters, Allied Health 1150 Visit the Exhibits Keynote Address, Allied Health 1102 12:45pm Introduction of Keynote Speaker Paul Bolin, Jr., MD, Interim Chair Department of Internal Medicine 12:50pm “TRANSLATIONAL RESEARCH: CLINICAL STUDIES OF OZONE INHALATION” Philip A. Bromberg, MD, Bonner Professor of Medicine and Scientific Director of the Center for Environmental Medicine, Asthma & Lung Biology at the University of North Carolina, Chapel Hill. 6 1:45pm Break and Posters, Allied Health 1150 Third Oral Session, Allied Health 1102 Moderator: Mary Jane Thomassen, PhD 2:15pm OR11 FELLOWSHIP EDUCATION IN MECHANICAL VENTILATION D Brescia, T Pancoast, M Mazer, MS Kavuru 2:30pm OR12 LONG-TERM OUTCOMES OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN EASTERN NORTH CAROLINA MA Gonzalez, D Eilen, RA Marzouq, S Awadallah, HR Patel, RA Bloomfield, JM Bennett, HM Lim, C Porterfield, AA Patel, LC Gilmore, S Nasir, JD Babb, JD Rose and WE Cascio for the MAPP investigators 2:45pm OR13 HEART FAILURE MANAGEMENT IN RURAL NORTH CAROLINA USING A HUB AND SPOKE MODEL; PILOT STUDY RESULTS MV Pizalis, EL Wilson, OC Elci, R Little, M Akpinar-Elci, A Mayo, GL Jones, L Novick, W Cascio 3:00pm OR14 PRELIMINARY ANALYSIS OF QUESTIONNAIRES USED IN THE EVALUATION OF KNEE PAIN CM Wright, WN Bronson, MA McLean, EL Treadwell 3:15pm OR15 LASER CAPTURE MICRODISSECTION: ADVANCED TECHNOLOGY FOR BIOMEDICAL RESEARCH A Malur, C Kukoly, L Dobbs, MJ Thomassen 3:30pm OR16 TWELVE MONTH FOLLOW UP OF GASTROINTESTINAL CO-MEDICATION DISCONTINUATION OR REDUCTION IN RENAL TRANSPLANT PATIENTS AFTER CONVERSION FROM MYCOPHENOLATE MOFETIL TO MYCOPHENOLATE SODIUM P Bolin, P Sullivan, SR Gerkin, KR Parker 3:45pm Break and Posters, Allied Health 1150 Fourth Oral Session, Allied Health 1102 Moderator: Hisham Barakat, PhD 4:00pm OR17 RELIABILITY OF ADVANCED GLYCATION END PRODUCT MEASUREMENT AT VARIOUS SITES IN SUBJECTS WITH DIABETIC PERIPHERAL POLYNEUROPATHY 7 EA Kidd, DS Williams, RJ Tanenberg 4:15pm OR18 RESIDENT PHYSICIAN CENTRAL VENOUS LINE PLACEMENT TRAINING REDUCES CENTRAL VENOUS LINE ASSOCIATED BACTEREMIA AT PITT COUNTY MEMORIAL HOSPITAL S Kraemer, MK Cochran, KM Ramsey, L Basnight, M Mazer, W Price, WC Robey, III 4:30pm OR19 OPTIMIZING TACROLIMUS THERAPY IN MAINTENANCE RENAL ALLOGRAFTS: A SINGLE CENTER ASSESSMENT OF CARDIOVASCULAR RISK FACTORS AND RENAL FUNCTION AT 36 MONTHS P Bolin, R Mirza, P Sullivan, KR Parke 4:45pm OR20 PREVALENCE OF VENOUS THROMBOEMBOLIC DISEASE IN PATIENTS WITH SICKLE CELL DISORDERS Indie Jones, D Liles, C Knupp Closing Remarks and Award Presentations Paul Bolin, Jr., MD, Interim Chair Department of Internal Medicine 5:00pm 8 Posters, Allied Health 1150 PR1 PREVALENCE AND ANTIBIOTIC RESISTANCE PROFILES OF COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IN A DERMATOLOGY CLINIC Eric Howell, Todd Nelson, Donald Holbert, Charles Phillips PR2 AN OBSERVATIONAL STUDY: PERIODIC AGITATION PROLONGS THE MINIMAL EFFECTIVE CONCENTRATION OF CIDEX® SOLUTION AG Waddell, DZ Stone, A Walston, BL West, CM Phillips PR3 MEDICAID PATIENTS WITH COLORECTAL CANCER ARE RARELY DIAGNOSED BY SCREENING COLONOSCOPY M Weed, A Rosenberg, L Burke, M Haque, P Vos, A Aravapalli, M Brinson PR4 PPAR-GAMMA DEFICIENCY: SURFACTANT ACCUMULATION AND LIPID DYSREGULATION IN ALVEOLAR MACROPHAGES AD Armstrong, A Malur, BP Barna, AG Malur, MS Kavuru, MJ Thomassen PR5 THE ROLE OF OXIDATIVELY-INDUCED CLUSTERED DNA LESIONS IN BREAST CELL TRANSFORMATION JW Hairr, CD Cooke, R Hudgins, JE Rhinehart, JE Wiley, G Sigounas PR6 ORAL GLUCOSE TOLERANCE IS IMPROVED FOLLOWING DUODENAL-JEJUNAL BYPASS IN LEAN DIABETIC RATS EZ Lukosius, RC Sloan, MA Reed, EB Tapscott, JR Pender IV, JJ Carter, V Boghossian, WH Chapman III, GL Dohm, WJ Pories, TP Gavin PR7 THE AMELIORATION OF TYPE 2 DIABETES MELLITUS FOLLOWING GASTRIC BYPASS SURGERY MA Reed, W Pories, W Chapman, J Pender, H Barakat, TP Gavin, T Green, E Tapscott, N Sharkley, R Ho, D Palidori, S Clark, SP Piccoli, L Brenner-Gati, GL Dohm PR8 DUODENAL-JEJUNAL BYPASS IMPROVES SKELETAL MUSCLE INSULIN SENSITIVITY IN A NON-OBESE DIABETIC ANIMAL MODEL RC Sloan, MA Reed, EZ Lukosius, EB Tapscott, GL Dohm, JR Pender, V Boghossian, JJ Carter, WJ Pories, WH Chapman, TP Gavin PR9 PARACRINE SUPPRESSION OF VEGF SECRETION BY ERYTHROPOIETIN INHIBITS TUMOR GROWTH CR Smith, KJ Salleng, A Asch, G Sigounas 9 PR10 THYMOSIN β4 TREATMENT OF HUMAN MESENCHYMAL STEM CELLS AND CARDIOMYOCYTES MC Collins, PR Gunst, JI Virag, BJ Muller-Borer PR11 GLUTATHIONE ACCENUATES TRANSNITROSATION IN THE EX VIVO RAT HEART AFTER BRIEF GLOBAL ISCHEMIA/REPERFUSION (I/R) JL Matthews, WE Cascio, MH Schoenfisch, NA Stasko, EL Holmuhomedov, CB Johnson, TA Johnson PR12 PPAR GAMMA DELETION IN ALVEOLAR MACROPHAGES UPREGULATES INFLAMMATORY MEDIATORS AJ McCoy, A Malur, BP Barna, MS Kavuru, MJ Thomassen PR13 IMPACT OF ADMISSION SURVEILLANCE SCREENING AND TOPICAL ANTIBIOTICS ON REDUCING VENTILATOR ASSOCIATED PNEUMONIAS DUE TO METHICILLINRESISTANT STAPHYLOCOCCUS AUREUS IN A SURGICAL INTENSIVE CARE UNIT T Das, MR Coogan, EA Toschlog, AD Bryant, MD Cochran, J Christie, A Blake, AA Pearson, KM Ramsey PR14 THE PREVALENCE OF VITAMIN D INADEQUACY IN MEDICAL INPATIENTS C Konduru, N Hernandez, AJ Drake, F Cook PR15 THE CROSSCUT PROJECT: FOCUS ON PRACTICE-BASED LEARNING AND IMPROVEMEN P Bolin, M Lateef, S Zadeh PR16 SIMULTANEOUS MEASUREMENT OF THREE DIMENSIONAL (3D) LEFT AND RIGHT VENTRICULAR VOLUMES AND EJECTION FRACTION DURING DOBUTAMINE CARDIOVASCULAR MAGNETIC RESONANACE S Mandapaka, K Lane, W Cascio, WG Hundley PV1 DIAGNOSIS OF SILENT RIGHT VENTRICULAR RUPTURE AFTER BLUNT TRAUMA TO CHEST BY IMAGING MODALITIES AND CONSERVATIVE MANAGEMENT WITH GOOD PROGNOSIS S Mandapaka, MA Newell, B Ferguson, B Kucysk, D Mann, J Campbell, WC Wood PV2 COCAINE INDUCED AORTIC DISSECTION S Mandapaka, J Gerardo, A Movahed PV3 UNUSUAL PRESENTATION OF HEREDITARY SIDEROBLASTIC ANEMIA W Badwan, S Changappa, Cl Weitz, C Lynch PV4 HYPERCALCEMIA AND ADRENAL INSUFFICIENCY ASSOCIATED WITH COCCIDIOIDOMYCOSIS AND HUMAN IMMUNODEFICIENCY VIRUS JM Bennett, AJ Drake, RJ Tanenberg 10 PV5 TRICHOLEMMAL CARCINOMA: CASE REPORT AND REVIEW OF A RARE CUTANEOUS TUMOR LD Briley, WA Burke, RH Schosser, VB Laing PV6 MALACOPLAKIA, A BLADDER MASS MIMICKING MALIGNANCY: A CASE REPORT NA Khan, BE Johnson, M McLean PV7 SARCOIDOSIS WITH INTRASCROTAL LESIONS Stephen Maxwell PV8 DRUG INDUCED AUTOIMMUNE BULLOUS DERMATOSES H Shaffer, C Phillips, R Schosser, W Burke PV9 GANGLIONEUROMA PRESENTING AS A RETROPERITONEAL MASS IN A YOUNG WOMAN TK Singh, L Dobbs, G Talente PV10 A CASE OF STREPTOCOCCAL TOXIC SHOCK SYNDROME V Slaughter, D Eilen, C Patel, M Mazer PV11 PREEXCITED ATRIAL FIBRILLATION IN THE PRESENCE OF ANTIDROMIC ATRIOVENTRICULAR RECIPROCATING TACHYCARDIA – A MIMICKER OF VENTRICULAR TACHYCARDIA TM Youmans, RW Kreeger PV12 ACUTE ST-ELEVATION MYOCARDIAL INFARCTION AFTER INFLIXIMAB INFUSION IN PATIENT WITH CROHN’S DISEASE N Peterson, A Nanjundappa, A Mayo PV13 THE IMPORTANCE OF BAL IN THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASE ASSOCIATED WITH ERLOTINIB FOR THE TREATMENT OF BRONCHOALVEOLAR CARCINOMA AS Carden, P Walker, D Liles, C Knupp, JL Finley PV14 PULMONARY AMYLOIDOSIS: A SECONDARY PROCESS WITH RADIOGRAPHIC VARIANTS MIMICKING ALMOST ALL INTERSTITIAL LUNG DISEASE PATTERNS AA Kanchwala, KD Kasa, TC Pancoast, MS Kavuru PV15 HEREDITARY HEMORRHAGIC TELANGIECTASIA: A FASCINATING CASE WHERE MULTIPLE DISEASES MIGHT HAVE A COMMON LINK AA Kanchwala, TC Pancoast, M Kavuru 11 PV16 GRANULAR CELL TUMORS: A RARE FINDING IN A COMPLICATED CASE OF FAILURE TO WEAN FROM MECHANICAL VENTILATION KD Kasa, TC Pancoast, M Kavuru PV17 HYPOGLYCEMIA AFTER GASTRIC BYPASS SURGERY: A NEWLY RECOGNIZED BUT IMPORTANT COMPLICATION C Konduru, N Hernandez, F Cook, RJ Tanenberg, AJ Drake PV18 HODGKIN TRANSFORMATION IN TWO PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA CA Lynch, D Liles PV19 SPINAL CORD INFARCTION AS A RARE COMPLICATION OF PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY JJ Felder, M Waqas OR = Oral Research OV = Oral Vignette PR = Poster Research PV = Poster Vignette Underlined author will present the abstract. Accreditation: The Brody School of Medicine at East Carolina University is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. CREDIT: The Brody School of Medicine designates this educational activity for a maximum of 6.5 AMA PRA Category 1 Credits™. Physicians should claim only those credits commensurate with the extent of their participation in the activity. AMERICANS WITH DISABILITIES ACT (ADA): Individuals requesting accommodation under the Americans with Disabilities Act (ADA) should contact the Department for Disability Support Services at least 48 hours prior to the event at (252) 737-1016. 12 Keynote Address: “Translational Research: Clinical Studies of Ozone Inhalation” Philip A. Bromberg, MD Bonner Professor of Medicine and Scientific Director of the Center for Environmental Medicine, Asthma and Lung Biology at the University of North Carolina School of Medicine in Chapel Hill, NC Philip Bromberg, MD (Harvard 1953) is Bonner Professor of Medicine (Pulmonary) and Scientific Director of the Center for Environmental Medicine, Asthma and Lung Biology at the University of North Carolina School of Medicine in Chapel Hill, NC. Dr. Bromberg's research is supported principally by a Cooperative Agreement with the U.S. EPA and by NIH grants to Professor David Peden (Department of Pediatrics and Director of the Center) of which he is (Co-Investigator). Dr. Bromberg's current research interests are in signal transduction pathways and gene activation responses to air pollutants (such as ozone Zn and PM) which underlie inflammation, using primary cultures of human airways epithelial cells and macrophages exposed in vitro, as well as controlled exposures of healthy and diseased volunteers. Dr. Bromberg has served on various committees at UNC-CH including the Chancellor's Advisory Committee. He is a member of the Faculty Advisory Committee of the Carolina Institute for the Environment. He is the former Chairman, External Advisory Board of the NIEHS Center in Urban Environmental Health, The Johns Hopkins University (John D. Groopman, Ph.D., Director). He has served on various Editorial Boards and on Study Sections and Advisory Committees for the American Thoracic Society, the American Heart Association and the NIH. He served on the Subspecialty Board on Pulmonary Diseases, American Board of Internal Medicine. Dr. Bromberg is a member of numerous Professional Societies, such as the American Thoracic Society, American Physiological Society and the European Respiratory Society, among others. Dr. Bromberg has received many distinctions including Distinguished Lecturer at the Annual NC Lung Association & Thoracic Society; Norma Berryhill Distinguished Lecturer at the School of Medicine, UNC-CH; Heineman Distinguished Lecturer at the University of California @ Davis; Invited Lecturer (Commemoration of David V. Bates) at the Annual Meeting of the Health Effects Institute; and most recently the honor of being invited as the keynote speaker for the Annual Yash P. Kataria Research Day in the Brody School of Medicine at East Carolina University. 13 W. James Metzger, Jr., MD Award The W. James Metzger, Jr., M.D. award is presented to the most outstanding presentation by a junior faculty member in the Department of Internal Medicine. A peer-review process selects the winner. The recipient of the award receives a certificate and has his/her name engraved on a plaque that is displayed in the Department of Internal Medicine Library. The recipient also receives recognition on the Department of Internal Medicine web site. Dr. Metzger, a native of Pittsburgh, Pennsylvania, was a graduate of Stanford University and Northwestern University Medical School, Chicago, Illinois. He completed his residency and research fellowship in Allergy-Clinical Immunology at Northwestern University. After serving in the United States Air Force, he came to Greenville in 1984 to join the East Carolina University School of Medicine. During his tenure at East Carolina University, Dr. Metzger rose to the rank of Professor of Medicine. He was Section Head of the Section of AllergyImmunology and held the appointments of Vice Chairman of Research, Department of Internal Medicine; Executive Director, the Center for Asthma, Allergy, and Immunology; Assistant Vice Chancellor for Clinical Research; Assistant Dean for Clinical Research; and Director, Clinical Trials Office. He was the recipient of the East Carolina University Award for Excellence in Research and Creative Activity and the Distinguished Research Professor of Medicine. His research was published in the New England Journal of Medicine, Nature, and other journals. Dr. Metzger had mentored numerous faculty and fellows. In August 2000 Dr. Metzger accepted a position as Professor of Allergy, Asthma, and Immunology at the National Jewish Medical and Research Center and was a faculty member at the University of Colorado Medical School, Denver, Colorado. He died on November 11, 2000 at the age of 55. Dr. Metzger represented excellence in research. 2001 Recipients: Carlos A. Estrada, MD, MS Paul Mehlhop, MD 2003 Recipient: Lisa Staton, MD 2004 Recipient: Cassandra Salgado, MD 2005 Recipient: Barbara J. Muller-Borer, PhD 2006 Recipient: Timothy P. Gavin, PhD 2007 Recipient: Christopher Newton, MD 14 Abstracts of Oral and Poster Presentations (Abstracts are listed in the order in which they are presented.) 15 OV1 OV2 DO ANTIPSYCHOTIC DRUGS PROMOTE PROLACTINOMAS? A CASE REPORT AND REVIEW OF LITERATURE CK Dunham, FJ Cook and P Garcia BROWN TUMORS: AN UNCOMMON MANIFESTATION OF PARATHYROID DISEASE B Ramirez, R Tanenberg, F Cook LEARNING OBJECTIVES 1) Review psychiatric symptoms of pituitary tumors 2) Understand the interactions between antipsychotic medications and the pituitary gland 3) Review the link between antipsychotic medications and prolactinmediated tumorigenesis 4) Identify antipsychotics that are prolactin stimulating and prolactin sparring Introduction: Brown tumors are rare focal giant-cell lesions that arise in settings of excess osteoclast activity as a direct effect of high levels of parathyroid hormone on bone tissue. The characteristic brown coloration results from hemosiderin deposition into osteolytic cysts. Patients with severe untreated primary, secondary or tertiary hyperparathyroidism are at risk of developing this disorder. Brown tumors commonly affect the mandible, maxilla, clavicle, ribs, and pelvis. If located in the mandible, they disrupt normal dental occlusion and make the chewing process difficult. If located in the maxilla, they can produce nasal obstruction and epistaxis. If located in the spine, they can cause spinal cord compression and pathological fractures with subsequent paralysis. In view of these important complications, and the increased likelihood for brown tumors to occur in the dialysis population, physicians should be familiar with this disorder. An early diagnosis may prevent the untoward sequela of brown tumors. Case: In May 2007, a 41-year-old African American male with a 15 year history of dialysis for end stage renal disease was admitted to the surgery service at Pitt County Memorial Hospital for elective parathyroid resection. He had long standing secondary hyperparathyroidism with PTH levels > 4000 pg/ml in 2006. He reported progressive difficulty in mastication associated with enlargement of the mandible for at least one year. Preoperative labs included: corrected calcium 7.1 mg/dL, intact PTH level 8,633 pg/mL, serum phosphorus 2.9 mg/dL and an alkaline phosphatase of 1,218 U/L. Imaging demonstrated subperiostial bone resorption in a hand radiograph and salt and pepper appearance of the skull on a head CT. A maxillofacial CT Scan revealed only brown tumors and no normal bone tissue. The patient underwent subtotal parathyroidectomy with removal of 3 ½ glands. An intraoperative PTH monitoring technique confirmed a drop in the PTH level to 79.1 pg/mL after resection. Pathology reported that “histologically, there were no reliable features that helped differentiate adenoma from hyperplasia.” Conclusion: As a consequence of the precipitous drop in the PTH, he developed the Hungry Bone Syndrome. He was treated successfully with intravenous calcium infusion, parenteral vitamin D and Cinacalcet. This case illustrates the potential medical and postoperative complications of brown tumors in patients with severe secondary hyperparathyroidism from CKD. CASE INFORMATION: We present a man with paranoid schizophrenia who developed an invasive prolactin secreting pituitary macroadenoma after five years of risperidone therapy. Prior to antipsychotic use, he had a brain MRI that showed a normal pituitary. His psychotic symptoms were well controlled before clinical symptoms of headache and vision loss led to his diagnosis of prolactinoma. While on risperidone maintenance therapy his prolactin levels remained elevated despite pharmacologic, surgical and radiation therapy for his aggressive prolactinoma. Only after his risperidone was changed to another agent did his prolactin level become close to normal. Our case raises questions regarding the use of antipsychotics during prolactinoma treatment in general. We question if risperidone is a complicating factor in prolactinoma treatment and wonder if it contributed to pituitary tumorigenesis. To answer these questions, current literature is reviewed. SUMMARY: In animal models antipsychotics have caused tumorigenesis of the pituitary tumor. In humans, treatment with potent D2-receptor antagonists has been associated with lactrotroph proliferation and prolactinoma formation. We conclude that prolactin sparing antipsychotics should be considered in patients with prolactinomas since prolactin stimulating medications complicate treatment. More research is needed to investigate the impact of prolactin stimulating medications in this population. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 16 OR2 OR1 RITUXIMAB DEPLETES B-LYMPHOCYTES IN PULMONARY ALVEOLAR PROTEINOSIS H Dalrymple, A Malur, G Gagnon, I Marshall, S Arce, BP Barna, MS Kavuru, MJ Thomassen THE EFFECT OF MECHANICAL STRAIN ON THE DIFFERENTIATION OF MESENCHYMAL STEM CELLS INTO A CARDIAC PHENOTYPE IN VITRO YA Midgette, MC Collins, PR Gunst, BJ Muller-Borer Background: Transplantation of bone marrow derived stem cells is being studied as a therapeutic approach to repair damaged heart tissue. Yet, cardiomyoplasty is limited by low levels of stem cell engraftment, survival, and myocardial tissue regeneration. While it is recognized that the modulation of the stem cell microenvironment plays a critical role in the derivation of cardiomyocytes, the molecular mechanisms controlling stem cell fate are not well understood. The goal of this study was to begin to elucidate the role of “cardiac-like” biomechanical signals on the differentiation of human mesenchymal stem cells (hMSCs) to a cardiac phenotype. Methods: Female hMSCs from the Tulane Center for Gene Therapy were seeded on laminin-coated flexible plates. To mimic the cardiac microenvironment, uniform uniaxial strain (3% elongation at 3 Hz) was applied to the hMSCs and maintained at 370 C in 5% CO2. Control hMSCs were unstrained. The acquisition of cardiac structural proteins, sarcomeric α-actinin (Sα-a) and connexin 43 (Cx43) and transcription factors, Nkx2.5, Tbx5, Mef2C (strained activated), and co-factor myocardin were evaluated at 24 hrs and 7days after the initiation of strain. Changes in hMSC morphology were assessed with photomicroscopy. Results: The expression of Sα-a and Cx43 decreased at 24 hrs (38% and 50% of control, respectively), but returned to control levels by day 7 (88% and 81% of control, respectively). Preliminary results showed an increase in Nkx 2.5 in the strained hMSCs at 24 hrs and a decrease at 7 days (49% and 28%, respectively). Mef2C showed a slight increase at 24 hrs and an 87% increase at 7 days. Myocardin showed a gradual decrease to 46% over 7 days. Cell morphology measurements revealed that 64% of the strained hMSCs aligned perpendicular to the direction of strain vs. 22% of the unstrained hMSCs at 24 hrs with no change in hMSC alignment after 7 days. Conclusion: This study revealed temporal effects of pulsatile strain on the expression of cardiac structural proteins in hMSCs. This study also showed a decrease in cardiac specific transcription factors at 7 days. These results suggest that biomechanical strain in the in vivo cardiac microenvironment may contribute to the low rate of survival and engraftment after hMSC transplantation. In addition, pulsatile strain alone may not be effective in committing hMSCs toward a cardiac fate prior to transplantation. Background: Pulmonary Alveolar Proteinosis (PAP) is an autoimmune disorder characterized by autoantibodies to GM-CSF. Rituximab, a chimeric murine-human monoclonal antibody, directed against the B lymphocyte specific antigen CD20, has shown promise in a number of autoimmune disorders. We hypothesized that Rituximab would deplete B-lymphocytes in PAP and thus improve clinical condition. Methods: As part of an open label proof-of-concept Phase II clinical trial of 10 patients, to date, 7 PAP patients received two infusions (1mg/ml) of Rituximab, fifteen days apart. Peripheral blood samples were collected from patients both pre- and post-Rituximab infusion. Lymphocyte activation was determined by measurement of ATP using CD4 magnetic bead assays (Cylex). Peripheral blood mononuclear cells (PBMC) were also isolated from both PAP patients and healthy controls and analyzed by flow cytometry. Oxygenation of PAP patients was measured by PaO2. Results: B-lymphocytes decreased by 15±2 % (n=7) by fifteen days post therapy and persisted for 6 months. T-lymphocyte activity increased by 55% following administration of Rituximab, persisting three months post therapy (n=5), as compared to <1% increase in activity of T-lymphocytes from healthy controls (n=4). Oxygenation was also determined to be improved by 14±5 mmHg in 4/5 patients. Conclusions: Administration of Rituximab to PAP patients effectively depleted B- lymphocytes and enhanced T-lymphocyte activity, suggesting that in PAP, Rituximab affects both humoral and cellular immune systems. Rituximab also improved clinical symptoms, indicating that therapy directed at the autoimmune pathogenesis of PAP represents an effective and beneficial approach. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 17 _________________________________________________ OR4 OR3 ROLE OF THYMOSIN-β4 IN HUMAN MESENCHYMAL STEM CELL ENGRAFTMENT, SURVIVAL, AND DIFFERENTIATION IN MURINE MYOCARDIUM GV Byrum III, MC Collins, BJ Muller-Borer, JI Virag PRISTANE INDUCED SYSTEMIC LUPUS ERYTHEMATOSUS IN BALB/C MICE: AN ANIMAL MODEL J Jones, C Wright, I Marshall and EL Treadwell BACKGROUND AND OBJECTIVES: We previously reported clinical features of pristane (2, 6, 10, 14-Tetramethylpentadecane) in Balb/c mice as a possible animal model for systemic lupus erythematosus (SLE) and related connective tissue diseases (CTDS). In this study, our objective was to determine if pristane or similar hydrocarbons could induce SLE related antibodies in normal or non-SLE related mice. METHODS: One hundred twenty Balb/c 7 month old female mice, divided into 10 separate groups with 12 / group, were intraperitoneally injected respectively with 0.5ml of phosphate buffered saline (PBS), mineral oil, cod liver oil, shark liver oil, pristane (0.1 – 0.5ml) and hexane / cod liver oil (1:9 parts). Mice were bleed pre-injection, and twice at 5 month intervals. Total mice survival was 118 at Bleed #1, 117 at Bleed #2 and 111 at Bleed #3. Serum was frozen at -30˚ C until assayed by double immunodiffusion (ID) against an antigen extract of rabbit (RTE) or calf thymus (CTE) using (NH4)2SO4 precipitation. ID plates were read up to 4 weeks for identification of precipitin reactions using predefined antibody controls for SLE related antigens; anti-Sm, RNP, SS-A, SS-B and anti-Su. RESULTS: No precipitin reactions were noted in the pre-bleed group or Bleed #1 using CTE or RTE. In Bleed #2, 8/12 (66%) of only the pristane treated mice had SLE associated antibodies (Abs) to RTE. In Bleed #3, 1/12 mineral oil, 5/12 (42%) of the pristane group and 3/12 (25%) of the Hexane / cod liver oil group had RTE Abs. In the CTE group, 4/12 mice in the pristane group had Abs in Bleed #3. The treated group with positive antibodies were associated with the groups previously reported with the highest decrease survival, increase in major organ size and proteinuria; the pristane and hexane / cod liver oil groups. CONCLUSION: Pristane and related long chain carbon compounds are cable of inducing autoantibodies associated with SLE and related CTDs, and are associated with the clinical features of these diseases. The exact mechanism is currently unknown. Background: Heart transplantation remains the only viable treatment for endstage heart failure but is limited by the availability of donor hearts. This limitation has fueled the interest in cellular cardiomyoplasty to treat damaged heart tissue. However, the microenvironment of transplanted stem cells plays a crucial role in the efficiency of stem cell engraftment and differentiation, with successful transplantation often limited by low cell survival rates. Research suggests that the protein thymosin beta-4 (Tβ4) promotes cardiac cell survival and demonstrates a cardioprotective role in injured myocardium. The goal of this study was to determine the effect of a cellular and systemic Tβ4-treatment on human mesenchymal stem cell (hMSC) engraftment, survival, and differentiation in murine myocardium. Methods: Female hMSCs transfected with a mitochondrial red fluorescent protein (dsRed) were obtained from the Tulane Center for Gene Therapy. Tβ4-treated and untreated dsRed hMSCs were cultured for RNA analysis. Treated and untreated cells were also injected into the anterior surface of the left ventricle of nude mice that either received or did not receive a systemic Tβ4 treatment. Fluorescent microscopy was used to locate the injected cells in paraffin embedded sections of the heart at 1 and 4 week time points. The graft area with dsRed hMSCs was evaluated using ImageJ software. A TUNEL assay was used to detect apoptotic dsRed hMSCs. Subsequent sections were stained with ULEX to identify dsRed hMSC differentiation to endothelial cells. Results: RT-PCR showed a significant increase in expression of Tie-2 (endothelial protein growth factor) in the dsRed hMSCs with a 24-hr Tβ4 treatment. In vivo, there was an increase in dsRed hMSC engraftment in animals receiving cellular and systemic Tβ4-treatment at 1 and 4 weeks. However, the overall number of dsRed hMSCs found in the graft region decreased from 1 to 4 weeks. Conclusion: The increase in Tie-2 with a 24-hour Tβ4 treatment suggests the potential for dsRed hMSCs to differentiate into mature endothelial cells, promoting angiogenesis and improved heart function. Preliminary data suggests that Tβ4 can increase dsRed hMSC engraftment in the myocardium. However, there is a decreased presence of dsRed hMSCs from 1 to 4 weeks. Conditioning the cells and/or tissue may help to enhance cell engraftment, providing a more suitable microenvironment for transplantation. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 18 OR5 OR6 OBESITY: THE MOST COMMON RISK FACTOR FOR KIDNEY DISEASE IN PITT COUNTY MEMORIAL HOSPITAL EMPLOYEES S. Gerkin, S. Johnson, C. Christiano, M. Hames, M. Locklear IN VIVO REGULATION OF ABCG1 BY PPARγ IN ALVEOLAR MACROPHAGES OF GM-CSF KNOCKOUT (KO) MICE AG Malur, A Armstrong, A Malur, AJ McCoy, BP Barna, MS Kavuru, MJ Thomassen Background: Obesity represents a growing problem in the US and is a risk factor for chronic kidney disease (CKD). Early detection and education regarding kidney disease has become a major focus for Internists and Nephrologists around the world. The purpose of this study is to demonstrate that risk factors for CKD, especially obesity, are prevalent in a population of hospital employees. We submit that health screens are a useful tool to identify CKD risk. Objectives: Two health screens of 158 University Health Systems employees were performed looking for CKD risk factors such as diabetes, hypertension, hyperlipidemia, and obesity. An ongoing data registry was created to convince other institutions of the utility of health screens. Methods: After informed consent was obtained, participants were asked to fill out a questionnaire pertaining to medical history, education and perceived fitness level. Blood tests for serum creatinine, lipids and glucose were obtained. Blood pressure, height and weight measurements were also taken. A urine sample for a dipstick urinalysis was obtained assessing protein, white blood cells, and blood. At the conclusion of the screen, participants met with a health professional to discuss results. Results: 147 of 158 (93.0%) employees screened had at least one risk factor for CKD. 134 of 158 (84.8%) had a BMI that was above 25 and 49 of those 134 (36.6%) had a BMI greater than 35. 44 of 158 (27.8%) had a systolic blood pressure ≥ 140 mmHg or a diastolic pressure ≥ 90mmHg. In addition, 24 of 158 (15.2%) employees screened did not report having a primary care doctor. Conclusions: In this continuous study of hospital employees our data indicates the overwhelming presence of CKD risk factors. It is disheartening to find that the number one CKD risk factor in PCMH employees is obesity. An 84.8% obesity rate of is well above the national average of 66%. Enhancing public awareness of: 1) obesity as a CKD risk factor, and 2) the extent of CKD in the general population is a priority. This evolving data demonstrates the need for more expansive early detection programs and education. Background: Pulmonary alveolar proteinosis (PAP) is a rare autoimmune lung disease characterized by neutralizing autoantibodies to granulocytemacrophage colony stimulating factor (GM-CSF). The loss of functional GMCSF results in an extensive filling of the alveolar spaces of the lungs with surfactant and lipid-engorged, Oil Red O positive alveolar macrophages. The nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARγ), a key regulator of lipid metabolism, is expressed in alveolar macrophages and is known to be up-regulated by GM-CSF. We have recently demonstrated decreased levels of PPARγ and ATP-binding cassette transporter G1 (ABCG1) in the alveolar macrophages from both PAP patients and GM-CSF knockout (GM-CSF KO) mice, suggesting the involvement of PPARγ and ABCG1 in surfactant catabolism (J Lipid Res 2007). We hypothesize that upregulation of PPARγ will lead to an increase in mRNA levels of ABCG1. Methods: The upregulation of PPARγ was achieved using a lentivirus expression system in vivo. GM-CSF KO mice were intratracheally instilled with 100ng lenti-PPARγ or control lenti-eGFP (enhanced Green Fluorescence Protein) virus and the bronchoalveolar macrophages were harvested 7-30 days post-instillation. Results: Real-Time PCR analysis demonstrated significant increases in PPARγ (3.1 fold ± 0.2 SEM, p=0.02) and ABCG1 (1.9 fold ± 1.6, p=0.02) gene expression in alveolar macrophages of mice instilled with lenti-PPARγ (n=4), while PPARγ and ABCG1 levels remain unchanged in control groups instilled with lenti-eGFP (n=4) and sterile PBS (n=3). Fluorescence microscopy indicated that 79±3% (n=3) of alveolar macrophages contained eGFP. Oil Red O positivity was reduced within the alveolar macrophages of mice treated with lenti-PPARγ virus. Conclusions: Results with lenti-PPARγ instillations demonstrate: (1) efficient in vivo transduction of alveolar macrophages with persistence up to 30 days; (2) up-regulation of ABCG1 by PPARγ; (3) a reduction in macrophage lipid accumulation. These studies suggest that PPARγ and ABCG1 are important in surfactant catabolism. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 19 OR8 OR7 DISTURBED PERIPHERAL B AND T CELL HOMEOSTASIS IN PATIENTS WITH SARCOIDOSIS NS Lee, H Dalrymple, A Malur, SA Joyner, I Marshall, BP Barna, MS Kavuru, MJ Thomassen, S Arce REGULATION OF CELL RESPONSE TO ACIDOSIS BY THE PH-SENSING G PROTEIN-COUPLED RECEPTOR GPR4 LV Yang, NR Leffler, AS Asch, ON Witte Background: Hypoxia and metabolic glycolysis frequently lead to tissue acidosis, which is associated with a variety of pathological conditions including tumor and ischemia. Acidotic tissue microenvironment plays important roles in disease development such as promoting tumor metastasis and aggravating ischemic tissue injury. However, the mechanisms by which cells respond to acidic pH are not well understood. Recent studies show that a family of proton-sensing G protein-coupled receptors (GPCRs), including GPR4, OGR1, TDAG8 and G2A, can be activated by acidic extracellular pH. We have investigated the roles of GPR4 in angiogenesis, tumor cell motility, and acidosis-induced cytotoxicity. Methods: Angiogenesis was examined in an aortic ring assay and in tumor xenograft models. Tumor cell motility was assessed by transwell assay. Acidosis-induced cytotoxicity was measured by MTT assay and protein expression was detected by Western blotting. Results: GPR4 was responsive to pH changes to regulate angiogenesis. In the aortic ring assay, microvascular outgrowth from GPR4-null aortas, compared to wild-type controls, was less inhibited by acidosis. Microvessel density was higher in tumor xenografts in GPR4-null mice. Consistently, overexpression of GPR4 in endothelial cells inhibited cell migration and in vitro tube formation at acidic pH. Enhanced expression of GPR4 in malignant B16 melanoma cells also reduced tumor cell motility in the transwell assay. Using C2C12 muscle cells to model the effects of tissue acidosis, acidic pH/GPR4 signaling significantly increased cytotoxicity and decreased the expression of anti-apoptotic protein Bcl-xL. Conclusion: GPR4 is a functional pH-sensing GPCR for various cells to respond to acidotic microenvironment. Our results implicate that potential agonists of GPR4 may inhibit angiogenesis and tumor cell invasion. On the other hand, antagonists of GPR4 may be used to protect acidosis-induced injury in tissue ischemia. Background: Sarcoidosis is a granulomatous disorder characterized by an accumulation of activated Th1 cells and macrophages at sites of disease activity. Inflammation in sarcoidosis is considered a cell-mediated immune process in which B cells play no role. Since activated B-cells act as antigenpresenting cells to elicit potent Th1 responses and produce inflammatory cytokines, we hypothesize that B-cells may exert important pathogenic roles in this disease. To study the peripheral B-cell compartment in sarcoidosis will be crucial to elucidate the possible involvement of B-cells in the pathogenesis of this inflammatory disorder. Methods: Venous blood from 10 sarcoid patients and 10 healthy control individuals was collected. Peripheral blood mononuclear cells were isolated by Ficoll-Hypaque. The following monoclonal antibody combinations were used to characterize the lymphocyte compartments: anti-CD19-PE-Cy5/antiIgD-FITC/anti-CD27-PE; anti-CD19-PE-Cy5/anti-IgD-FITC/anti-CD38-PE; anti-CD19-PE-Cy5/anti-CD20-FITC/anti-CD27-PE and anti-CD62L-PECy5/anti-CD4-FITC/anti-CD45RA-PE. Sample acquisition and analysis were performed using a FACS-Scan flow cytometer and the CellQuest software. Results: In the majority of sarcoid patients, the frequency of CD19+CD27+ (memory B cells) and CD19+/CD20-/CD27++ (plasmablasts) were increased compared to healthy subjects. Frequencies of CD19+/CD38+ (activated B cells), CD4+/CD45RA-/CD62L+ (central memory), CD4+/CD45RA-/CD62L(effector memory) and CD4+/CD45RA+/CD62L- (effector differentiated) Th cells were also increased in most of the sarcoid patients analyzed. Conclusions: Our results reflect disturbances in B- and T-cell homeostasis suggesting ongoing, antigen-driven immune response, accelerated differentiation of B- and T-lymphocytes into effector cells and cooperation between B- and T-cells. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 20 OR9 OR10 IMPROVING PERFORMANCE IN PRACTICE: A QUALITY IMPROVEMENT PROJECT CONDUCTED AT THE ECU GENERAL INTERNAL MEDICINE RESIDENT CONTINUITY CLINIC R Mirza, CP Porterfield, MS Kraemer, B Johnson, B Bonnet IMPROVING BARIATRIC SURGERY OUTCOMES WITH A CENTERS OF EXCELLENCE PROGRAM J Pender, B Chapman, G Hughes, W Pories BACKGROUND: Bariatric surgery, the only effective therapy for severe obesity and its co-morbidities is technically challenging and requires meticulous care in high risk patients. Prior to 2003, outcomes in the US were so spotty that carriers refused to cover the procedures and malpractice litigation soared. As a result, patients lost access to the only effective treatment. Objectives: Eastern North Carolina has seen a dramatic increase in the number of people with Diabetes over the past several decades. This holds especially true in the East Carolina University Internal Medicine Outpatient Resident Clinic. In order to better care for diabetic patients of this practice, a quality initiative was implemented. Improving Performance in Practice (IPIP) is a project that is financially supported by the Robert Wood Johnson Foundation and initiated in North Carolina and Colorado, with East Carolina University being one of first sites utilized. Specific objectives were to (a) Improve the quality of Diabetic care in our Continuity Clinic, by establishing standard care orders and evaluations for every Diabetic patient; (b) Teach residents how to approach system based problem solving and analysis; (c) Establish the Resident Continuity Clinic systems based practice curriculum. Methods: We systematically approached different American Diabetic Association guidelines, and used the PDSA model (Plan, Do, Study, Act) cycle to implement change. Measures studied included: (i)Aspirin usage in Diabetic patients (ii) Regular recommended HbA1c checks (iii) % of HbA1c < 7 (iv) BP < 130/80 (v) LDL <100 (vi) Foot Exams on every diabetic visit (vii) Yearly Retinal Eye referrals (viii) Diabetic Education. The data for these measures were self reported by each resident from February 2007 thru October 2007, then switched to computer generated data from the electronic medical records. The following were specific interventions to improve patient care outcomes: reviewing the current ADA guidelines; changing templates in electronic medical record; physician reminder cards for every diabetic visit; automated nursing protocols for every diabetic visit including removing shoes and socks, checking FSBS and HbA1c. A specialized Diabetic nurse was added to provide education to noncompliant, uncontrolled and/or new patients automatically without physician orders. Results: As of 02/2008 aspirin usage in Diabetic patients: Initially 57% 2/07 now 91%; Regular recommended HbA1c checks: 92% to 96%; % of HbA1c < 7: 41% to 50%; BP < 130/80: 38% to 31%; LDL <100: 35% to 47%; Foot Exams on every diabetic visit: 39% to 66%; Yearly Retinal Eye referrals: 25% to 44%. Conclusions: After implementing this quality initiative, there has been sustained improvement in the care of our diabetic patients, as proven by the results above. METHODS: With the leadership of ECU faculty and support of the ECU IRB, the Association for Metabolic and Bariatric Surgery developed a program to certify those surgeons and hospitals with favorable outcomes as Centers of Excellence. A non-profit corporation, the Surgical Review Corporation, with a broadly representative Board, was founded to manage the program. National standards, site inspections, a uniform data base constitute the essential elements. RESULTS: 323 US hospitals have earned the certification. The hospital mortality of bariatric surgery has been reduced to 0.14%, the 90 day mortality to 0.34% based on over 110,000 patients. Bariatric surgery in centers is as safe as cholecystectomy and compares favorably to the national statistics for colectomy (5%), esophagectomy (9%). CONCLUSION: Centers of Excellence programs can lead to improved outcomes surgery. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 21 OR12 OR11 LONG-TERM OUTCOMES OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN EASTERN NORTH CAROLINA MA Gonzalez, D Eilen, RA Marzouq, S Awadallah, HR Patel, RA Bloomfield, JM Bennett, HM Lim, C Porterfield, AA Patel, LC Gilmore, S Nasir, JD Babb, JD Rose and WE Cascio for the MAPP investigators FELLOWSHIP EDUCATION IN MECHANICAL VENTILATION D Brescia, T Pancoast, M Mazer, MS Kavuru BACKGROUND AND OBJECTIVES: Managing patients requiring mechanical ventilation is complicated requiring integration of many different factors. There is no universally accepted method or curriculum used to teach mechanical ventilation. Teaching practices vary widely between fellowship training programs. Management practices vary considerably between physicians and new evidence can take years to be put into practice. As a first step towards developing a formal structured program for teaching mechanical ventilation to fellows, we surveyed program directors and fellows to determine how fellows are currently educated and to identify potential barriers to learning this skill. METHODS: Separate surveys were sent via e-mail to program directors, selected faculty and fellows in pulmonary and or critical care fellowships using surveymonkey.com. The surveys consisted of 42 (faculty survey) or 45 (fellow survey) multiple choice questions with comment fields included for most questions. Data was collected and statistical analysis was performed with GraphPad Prism. RESULTS: Responses were received from 108 of 155 programs (81program directors, 27 other faculty) and 331 of 1440 fellows. Only 50% of fellows reported satisfaction with their education in mechanical ventilation. Presence of formal educational activities (longitudinal programs, hands on sessions, and an introduction course) correlated with fellow satisfaction in mechanical ventilation education (p</=0.0005). Similarly, confidence with management of secondary ventilator settings, waveform analysis, and identification and treatment of patient-ventilator asynchrony also correlated with fellow satisfaction in mechanical ventilation education (p<0.0001). Additionally, teaching methods, supervision, knowledge of respiratory physiology (p<0.0001), and active presence of respiratory therapists (p=0.0039) all correlated with fellow satisfaction in mechanical ventilation education. CONCLUSIONS: Fellowship education in mechanical ventilation is not uniform and fellow satisfaction with the process is suboptimal. The key finding of this study is that formal education programs and knowledge leading to confidence in specific areas are desirable, yet not consistently offered nor taught. We conclude that a well-structured formal education program is necessary to teach fellows mechanical ventilation. Background: Acute myocardial infarction (AMI) is the dominant cause of mortality and growing disability in Eastern North Carolina. Yet, in this geographical region the long-term outcomes and the characteristics of these patients are largely unknown. Objectives: This study determines the rates of fatal and non-fatal stroke and AMI [major adverse cardiovascular events (MACE)], re-hospitalization, revascularization interventions, new heart failure (HF), prevalence of uncontrolled cardiovascular risk factors (UCVRF), utilization of cardioprotective medications (UCPM) and compliance with national guidelines in patients presenting with AMI to Pitt County Memorial Hospital (PCMH). Method: We studied, in a prospective clinical cohort (“MAPP-Registry”), 540 consecutives patients with AMI presenting to PCMH from December 1st 2004 to December 31, 2005 and followed for 2 years until December 31, 2007. Patients with AMI, both ST elevation myocardial infarction (STEMI) and nonST elevation myocardial infarction (NSTEMI) according to the AHA/ACC clinical definition, who met the specific inclusion and exclusion criteria were included in the study. The primary outcome was the rate of MACE. We performed univariate and multivariate logistic regression analysis of the primary outcome measurement. Results: Of the540 patients with AMI, 103 were STEMI and 437 were NSTEMI. The average length of stay for STEMI and NSTEMI was 2.7 and 5.2 days respectively. The rate of MACE in patients with AMI was 12.6% at 2 years of follow up. More specifically, the rate of mortality was 5.1%, stroke was 2.2%, first recurrent MI was 4.4%, second recurrent AMI was 0.5% and third recurrent AMI was 0.1%. The number of UCVRF, vascular beds involved, UCPM, ejection fraction, and the TIMI and GRACE risk scores were the main independent predictors of MACE. Statistical analysis is ongoing. Conclusions: Patients presenting with AMI to PCMH have a 12.6% rate of MACE at 2 years of follow-up. Improving the UCVRF, increasing the UCPM and adherence with the national guidelines may improve the long-term outcomes of patient with AMI in Eastern North Carolina. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 22 OR14 OR13 PRELIMINARY ANALYSIS OF QUESTIONNAIRES USED IN THE EVALUATION OF KNEE PAIN CM Wright, WN Bronson, MA McLean, EL Treadwell HEART FAILURE MANAGEMENT IN RURAL NORTH CAROLINA USING A HUB AND SPOKE MODEL; PILOT STUDY RESULTS MV Pizalis, EL Wilson, OC Elci, R Little, M Akpinar-Elci, A Mayo, GL Jones, L Novick, W Cascio BACKGROUND AND OBJECTIVES: Multiple questionnaires (QSs) have been developed and validated for the evaluation of knee pain for osteoarthritis (OA) and rheumatoid arthritis (RA). Questions still remain on the readability and understandability of these QSs due to the high variability of educational status in diverse populations and cultures. Our goal was to determine the frequency of misunderstood words or phrases (MUWP) in 8 QSs designed for understanding patients’ knee pain and its affect on daily life function. METHODS: A set of 50 packets composed of 8 QSs each was given to local geographical non-patient subjects (Subs) for review. QSs were transcribed in 14mm font using a Microsoft Word processor. QSs were obtained from various published sources (seven) except one self designed (Rheumatology Arthritis Patient’s survey or RAPS). Subs were asked to draw a line through MUWP. RESULTS: 36/50 (72%) QS packets were returned: 28/36 (78%) female, 20/36 (56%) black, 8/36 (22%) white; 8/36 (22%) male, 6/36 (17%) black and 2/36 (5%) white. The number and (%) of Subs with MUWP from each QS and total number and (%) of MUWP for each QS are reported: QSs PGAA VAS APS WM RAPS SFKOOS AIMS MPQ Background and Objectives: Heart failure (HF) at the community level is associated with high mortality and morbidity despite the outcome improvements shown in clinical studies. Geographical barriers and the lack of specialized centers delivering care contribute to the dimensions of the problem. We hypothesized that HF patient outcome could improve if health care providers at the community level (Spokes) worked collaboratively with a specialized HF Clinic (Hub). Methods: We established a telemedicine network where the Spokes (Ahoskie Center; Heritage Hospital, Tarboro and ECU Cardiology, Greenville) consult the Hub (Health Steps, BSOM/PCMH) regarding pharmacist, dietician, psychological and cardiologist evaluations. Results: Six African-American patients were recruited (demographics shown below in Table 1). The following parameters were evaluated 6 months before and 6 months after entering the study: hospital admissions, New York Heart Association (NYHA) score, and quality of life (QOL) using the Minnesota Living with Heart Failure Questionnaire. Hospital admissions decreased from a mean of 2 to a mean of 0.5 for 5 patients and stayed the same for 1 patient. NYHA scores decreased for all patients from 3 to 2. QOL scores improved for all patients, with an average decrease of 26 in life activity limitations related to HF. Conclusions: In conclusion, it is possible to create a reliable network to improve HF patient outcomes by reducing hospital admissions and reducing HF symptoms, thereby managing patients at the community level in rural North Carolina. Subs 8(22) 0 3(8) 4(11) 8(22) 6(17) 10(28) 7(19) N=36 MUWP 13(12) 0 7(6) 9(8) 29(27) 13(12) 17(16) 21(19) N=109 PGAA=Patient’s Global Assessment of Arthritis; VAS=Visual Analog Scale; APS=American Pain Society; WM=Western Ontario McMaster University (WOMAC) Osteoarthritis Index; RAPS=Rheumatology Arthritis Patients Survey; SF-MPQ=Short Form McGill Pain Questionnaire; KOOS= Koos Knee Survey; AIMS=Arthritis Impact Measurement Scale CONCLUSION: Our participants were predominately female and African American. MUWP were present among QSs of similar length but of a low frequency. The 41-50 age groups tended to have the lowest number of MUWP. This study will need to be translated to a larger population. Table1: Demographic Characteristics of Patients (N=6) Frequency Percentage Characteristic 67 Gender Male 4 33 Female 2 100 Race African-American 6 33 Age Aged < 60 2 50 Aged 60-80 3 17 Aged > 81 1 Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 23 _________________________________________________ OR16 OR15 TWELVE MONTH FOLLOW UP OF GASTROINTESTINAL COMEDICATION DISCONTINUATION OR REDUCTION IN RENAL TRANSPLANT PATIENTS AFTER CONVERSION FROM MYCOPHENOLATE MOFETIL TO MYCOPHENOLATE SODIUM P Bolin, P Sullivan, SR Gerkin, KR Parker LASER CAPTURE MICRODISSECTION: ADVANCED TECHNOLOGY FOR BIOMEDICAL RESEARCH A Malur, C Kukoly, L Dobbs, MJ Thomassen Background: Biological research at the molecular level is the focus of modern science and critical to solving the problems of human disease. One of the most exciting new developments in biomedical research is laser capture microdissection (LCM), a technique which allows for the isolation of single cells or populations of cells from human or animal tissue sections. This technique enables the researcher to investigate DNA and proteins from specific cells or groups of cells free of adjacent tissue or contact contaminants. Such cutting-edge technologies as DNA microarrays and proteomics depend upon the isolation of single cells or pure populations of cells with specific phenotypes for meaningful results. Background: To evaluate if successful discontinuation or reduction of GI comedication use is sustainable 12 months after conversion from MMF to ECMPS. Methods: Fifty-four renal transplant patients on a GI co-medication were recruited from a single center cohort of 93 patients who had successfully converted from MMF to EC-MPS in a previous study. These patients were placed on a protocol to reduce or discontinue their GI co-medication. Additional follow up was conducted at one year. At baseline, patients on twice a day GI co-medication were reduced to daily dosing and at 30 day visit further reduced to PRN. Patients on daily dosing at baseline were reduced to PRN. All patients were given pocket diaries to record GI co-medication use and potential cost savings. Assessments for GI symptoms were performed using Gastrointestinal Symptom Rating Scale (GSRS), Gastrointestinal Quality of Life Index (GIQLI) and Psychological General Well-Being Index (PGWBI) at each visit. Results: Successful discontinuation or reduction of GI co-medication was achieved in 42 (78%) patients after 30 days and maintained through day 90. There was no significant change in assessments from baseline to day 30 or 90 despite discontinuation or reduction in GI comedication. Twenty-four patients (44%) were taking Proton Pump Inhibitors (PPIs) and 30 (56%) were taking H-2 blockers at enrollment. Twelve month follow up demonstrated sustained improvement in 32 (91%) of these patients. Estimated cost savings per patient for H-2 blockers are $925-$1850 and PPIs are $1861-$3722 annually. Conclusions: This study supports successful long term minimization of GI co-medications in maintenance renal transplant patients after conversion to EC-MPS. These data suggest that after conversion to EC-MPS renal transplant patients can successfully reduce or discontinue GI co-medication without worsening of symptom burden, while maintaining their health-related quality of life and overall well-being. Considering graft survival rates of 72% at 5 years this could translate into significant long term savings for renal transplant patients. In addition, avoidance of GI co-medication is important considering the multiple potential complications recently described in this class of medication. Methods: The Zeiss PALM MicroBeam System is a non-contact sampling technique for medical and biological materials for recovery of DNA, RNA and protein. This system also enables the manipulation of both fixed and living cells. LCM opens entirely new perspectives in scientific research. Unique to this system is Laser Microdissection and Pressure Catapulting (LMCPC), a break-through technology that combines laser microdissection with laser-assisted transfer. Results: Specific advantages of the PALM MicroBeam System include the following: (a) Gentle, contact-free handling of specimens; (b) Standard slides may be used with no intermediate steps; and (c) Contamination-free transport against gravity. Conclusions: This technique allows the isolation of distinct cell types which have a signature molecular fingerprint under normal and pathological conditions. Isolating these cells may provide new insights and potential therapies to a host of human conditions including cancer, cardiovascular disease, pulmonary inflammatory diseases, and others. Funded by: NCBC Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 24 OR18 OR17 RELIABILITY OF ADVANCED GLYCATION END PRODUCT MEASUREMENT AT VARIOUS SITES IN SUBJECTS WITH DIABETIC PERIPHERAL POLYNEUROPATHY EA Kidd, DS Williams, RJ Tanenberg RESIDENT PHYSICIAN CENTRAL VENOUS LINE PLACEMENT TRAINING REDUCES CENTRAL VENOUS LINE ASSOCIATED BACTEREMIA AT PITT COUNTY MEMORIAL HOSPITAL S Kraemer, MK Cochran, KM Ramsey, L Basnight, M Mazer, W Price, WC Robey, III Background: Diabetes mellitus (DM) has become an epidemic in the U.S. and much of the world. Prevention of diabetic microvascular complications is an essential area for new research efforts. Diabetic peripheral polyneuropathy (DPN) is a common and important microvascular complication that often leads to ulceration of the foot and loss of extremity. It has been postulated that there is an association between the differences in lower extremity kinematics and increased plantar pressures in individuals with DPN. Increased glycation and, in particular, accumulation of advanced glycation end products (AGE) in the tissues have been shown to play an important role in the pathogenesis of DM complications. AGE accumulation in specific tissue could contribute to increased stiffness in the lower extremity which may alter lower extremity kinematics. AGE, measured by skin autofluorescence in the forearm, has been found to correlate strongly with measurements in the lower leg of DM subjects. People with DPN have been found to have increased AGE compared to individuals without DPN. The purpose of this study was to determine if subjects have increased levels of AGE in the lower leg compared to the forearm secondary to DPN. Methods: Using the AGE-Reader with an excitation light source of 345-410nm, autofluorescence of the skin was measured at the forearm and lower leg in 47 subjects with a history of DM. Nine subjects had DPN as determined by a reading of ≥ 5.07 with Semmes Weinstein Monofilaments, and 38 were nonneuropathic. Emission light and reflected excitation light from the skin were measured by a spectrometer within the AGE-Reader and then recorded by computer software. Results: The study shows an excellent relationship of skin autofluorescence between the forearm and lower leg measurements in people with DPN. Conclusions: The results of this study have suggest that autofluorescence measures in the lower leg is an effective method for evaluating levels of AGE in individuals with DPN compared to the forearm. Future studies involving AGE measurements need to be performed in order to relate gait changes in diabetic patients to levels of AGE. BACKGROUND: Resident physicians place the majority of central venous lines (CVL) in patients admitted to PCMH. The Institute for Healthcare Improvement recommends a CVL Bundle, which includes guidelines for the placement and preferred site of CVLs. In 2005-06, the CVL-associated Bloodstream Infection (BSI) rates were above the mean of the Center for Disease Control’s National Nosocomial Infection Survey (NNIS) rates for comparable teaching hospitals in the US. Existing literature reports improved resident confidence in CVL placement following any type of training and fewer procedure related complications. OBJECTIVE: To decrease CVL-associated BSIs at PCMH following training of the resident physicians on CVL placement. METHODS: PGY1 internal medicine, emergency medicine, and surgery residents completed a Graduate Medical Education Office sponsored 3 step sequential central line training program in January 2007. Session #1 is a DICON web based course. Session #2 involves simulation lab for instruction and practice of subclavian and internal jugular CVL insertion. Step 3 consists of an Observed Clinical Skills Exercise during which residents simulate communication skills required for informed consent for CVL placement. The institution also promotes compliance with CVL bundles and the use of a CVL insertion procedure note. CVL-associated BSIs were detected during the 2006-07 fiscal year using the NNIS definitions, and were calculated house-wide with the CVLassociated BSI rates per 1000 line days. These data were compared with the BSIs for fiscal year 2005-06. RESULTS: Since the initiation of this standardized training, CVL-associated BSIs declined from 5.21 per 1000 line days, to 3.51 per 1000 line days (i.e., 33% decrease) overall at PCMH. CONCLUSIONS: The CVL insertion resident training program has contributed to a decrease of CVL infections at PCMH. CVL training promotes a standardization of technique and mandated use of quality bundles. This quality initiative is one of the first GME education programs revealing a link between resident education and improved patient outcomes within an entire institution. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 25 OR20 OR19 PREVALENCE OF VENOUS THROMBOEMBOLIC DISEASE IN PATIENTS WITH SICKLE CELL DISORDERS Indie Jones, D Liles, C Knupp OPTIMIZING TACROLIMUS THERAPY IN MAINTENANCE RENAL ALLOGRAFTS: A SINGLE CENTER ASSESSMENT OF CARDIOVASCULAR RISK FACTORS AND RENAL FUNCTION AT 36 MONTHS P Bolin, R Mirza, P Sullivan, KR Parker There is little literature presently available regarding thrombosis in Sickle cell disorders. A study of patients hospitalized for DVT recently found an excess of patients with sickle trait (1) Another recent study utilizing data from the National Hospital Discharge Survey found an increased prevalence of pulmonary embolism (PE) but not deep venous thrombosis in patients with Sickle cell disorders as compared to age matched African Americans (2). The prevalence of PE and DVT in that review seemed much lower than what we have observed in the population of adult patients with Sickle cell disorders seen at our institution (0.44% in patients younger than 40 years old; 0.5% for PE and 0.61% for DVT in older patients). As a result, we performed a retrospective chart review to determine the incidence of venous thromboembolism in our patient population. A retrospective chart review of outpatient and hospital records of all 250 adult patients enrolled in the adult Sickle cell clinic since its inception from 1997 to 2007 was performed. The paper or electronic outpatient clinic records, hospital discharge summaries, inpatient and outpatient radiology reports were reviewed for evidence of PE, DVT and other venous thrombotic events. Only those subjects with radiographic documentation of thrombotic diagnoses were included in the tabulation of thrombotic events. Twenty nine out of 250 patients had at least one episode of DVT (9.6%) documented by venous duplex Doppler ultrasound or venography. Eleven patients had at least one episode that involved a catheter/line (4.4%), and thirteen cases were unprovoked (5.2 %). Eight patients had at least one recurrence (33%). Five cases of PE were diagnosed by either CT or CTA (2%). The prevalence of PE and DVT was similar in patients 40 years of age or older (1.2% vs. 1.6% respectively). The prevalence of PE in patients less than 40 years was similar to the older group; however the prevalence of DVT in this group was higher than those older than 40 years of age (8% vs. 0.8%). Our review suggests venous thromboembolic disease is more common in patients with Sickle cell disorders than is recognized in the medical literature. Establishing the prevalence of venous thrombotic problems, especially in the setting of an acute pain crisis is important to be certain that venous thromboembolic problems are recognized and treated appropriately. Background: To determine the effect of conversion from Cyclosporine (CsA) to Tacrolimus (TAC) based therapy on cardiovascular risk factors and renal function at 36 months assessed by cholesterol, low density lipoprotein (LDL) and Cystatin C. Methods: OPTIMA, a 12 month randomized, open label, multicenter study of 323 stable renal transplant recipients currently receiving CsA were randomized 1:1:1 to continue CsA (50-250ng/mL); or convert to reduced TAC (3.0-5.9ng/mL) or standard TAC (6.0-8.9ng/mL). Improvement in total cholesterol (p<0.004) and LDL cholesterol (p<0.004) was observed in both TAC groups compared with CsA group at 12 months. Renal function improved in the reduced TAC group compared to CsA (p<0.001). Sixty patients from our center completed the 12-month OPTIMA trial and were followed for an additional 2 years to determine if these benefits could be sustained for 3 years. Patients were assessed for renal function and cardiovascular risk factors at year 24 and 36 months. Results: Our population consisted of 70% males, 53% African American (AA), 43% Caucasian and 42% diabetic. Mean transplant vintage was 7.5 years. An improvement in total cholesterol, LDL cholesterol and Cystatin C was seen in each TAC group over the course of 36 months compared to CsA group. Conclusions: Results seen in the multi-center trial at 12 months were sustained in our single center trial at 36 months. Improvement in renal function was maintained at 36 months in patients converted from CsA to TAC. These data suggest that reduced TAC dosing provides long term improvement in cardiovascular risk factors to renal transplant patients. These benefits were seen in a cohort of patients who were 53% AA and 42% diabetic and more than 7 years post transplant. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 26 PR2 PR1 AN OBSERVATIONAL STUDY: PERIODIC AGITATION PROLONGS THE MINIMAL EFFECTIVE CONCENTRATION OF CIDEX® SOLUTION AG Waddell, DZ Stone, A Walston, BL West, CM Phillips PREVALENCE AND ANTIBIOTIC RESISTANCE PROFILES OF COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IN A DERMATOLOGY CLINIC Eric Howell, Todd Nelson, Donald Holbert, Charles Phillips Background: Cidex® Activated Dialdehyde Solution is used in medical offices as a sterilant for semi-critical instruments. Our office replaces Cidex solution every 7 days, but the manufacturer states that it is effective for 14days. Objective: To determine if Cidex in our clinic is effective for 14 days. Methods: Phase 1: Activated Cidex was placed into 9 instrument bins. The minimal effective concentration (MEC) was checked with a test strip to make sure that it was effective (day 1). If the strip turned purple, the solution passed the MEC of 1.5% glutaraldehyde. If it turned orange or speckled, the MEC was not met, and the solution was replaced. Instruments removed and deposited into each bin were recorded. For 10 weeks, the MEC of each bin was checked on day 7, 11, and 14. Failures were recorded. Phase 2: The MEC of Cidex in each bin was checked on day 4 and 7 for 4 weeks. The Cidex was agitated by briefly stirring the solution prior to checking the MEC and was replaced every 7 days. We observed that the Cidex met the MEC at every checkpoint. In order to test if agitating the solution kept it effective longer, we compared Phase 1 to Phase 3. Phase 3: The MEC of Cidex in each bin was checked on day 7, 11, and 14 for 10 weeks. The solution was agitated briefly by stirring prior to checking the MEC. Failures were recorded. Results: During Phase 1, there were 14 times that the MEC was less than 1.5%. The bin used least failed 4 times. This observation led us to perform Phase 2 which included solution agitation prior to checking the MEC. During Phase 2, the Cidex met the MEC at every checkpoint. During Phase 3, there were only 3 failures. Once we began agitating the solution prior to testing it, no bins failed to reach the MEC prior to or on day 7. Conclusions: Our standard of practice is to change Cidex weekly. Even though our parameters fall within the manufacturer’s recommendations, several bins failed prior to day 14. However, we did not determine the pH of the solution in our study. Periodic agitation lengthened the effectiveness of the solution. To our knowledge, there have been no infections transmitted to our patients through instrument use. This was a small observational study, but emphasizes the manufacturer’s recommendation for periodic monitoring of Cidex to verify its effectiveness. Background: Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly important in community-acquired skin and soft tissue infections in a variety of medical settings, with significant implications for the treatment of commonly encountered skin infections. While generally acknowledged as an increasing problem, the actual prevalence of CA-MRSA is highly variable across different geographic and clinical settings Objective: To determine the prevalence of MRSA in a dermatology outpatient setting and the current antibiotic resistance profiles. Methods: We reviewed bacterial culture results from all cultures obtained in our clinic in the past five years. In addition to culture results, patient information was obtained from the medical chart and compiled to evaluate for potential associations with positive MRSA cultures. Results: MRSA culture rates changed from 0% in the first year of study to 30% by the final year. While all MRSA isolates were susceptible to trimethoprim-sulfamethoxazole, only 43% were sensitive to clindamycin. Limitations: The overall numbers in the study were small, making analysis of relevant risk factors difficult. Conclusions: MRSA prevalence has increased in our dermatology outpatient clinic, and the antibiotic sensitivities in our cohort differed from those recently reported in the literature from other geographic and clinical settings. Prospective studies evaluating optimal therapies for various skin and soft tissue infections will be useful, but it will remain important to understand the local patterns of resistance and how they are changing to provide optimal therapy for skin infections caused by Staphylococcus aureus. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 27 PR4 PR3 MEDICAID PATIENTS WITH COLORECTAL CANCER ARE RARELY DIAGNOSED BY SCREENING COLONOSCOPY M Weed, A Rosenberg, L Burke, M Haque, P Vos, A Aravapalli, M Brinson PPAR-GAMMA DEFICIENCY: SURFACTANT ACCUMULATION AND LIPID DYSREGULATION IN ALVEOLAR MACROPHAGES AD Armstrong, A Malur, BP Barna, AG Malur, MS Kavuru, MJ Thomassen Background: Periodic screening for colorectal cancer is recommended for all patients over age 50. However, many patients are diagnosed when symptomatic, resulting in decreases in survival and cure rates. We wished to identify patients more likely to present with symptomatic disease, in order to target outreach efforts. Methods: Patients, aged > 50 years, diagnosed with colorectal cancer during the years 2001 – 2006 were identified through the Tumor Board Registry of University Health Systems (UHS), a regional referral center in rural eastern North Carolina. Charts were reviewed to determine what prompted the diagnosis of colorectal cancer (i.e. through symptoms versus screening while asymptomatic). Demographic data were obtained from the registry. The demographic characteristics of patients who presented with symptoms were compared to those of patients who were diagnosed through a screening colonoscopy using univariate and multivariate analysis (logistic regression). Results: Hospital and clinic charts of 705 patients were reviewed. Of the patients, 519 (74%) were symptomatic at diagnosis, while 186 (26%) were asymptomatic. Symptomatic patients were more likely to present with metastatic disease (21% vs. 6%). On univariate analysis, patients with symptoms were less likely to be men (OR 0.68; 95% CI 0.48 to 0.97; p= 0.032) and had a higher mortality (OR=2.9; 95% CI=1.9 to 4.4; p=0.0001). As expected, multivariate analysis showed patients with symptoms were likely to have advanced disease at presentation (p=0.00001). Medicaid patients were more likely than other patients to be symptomatic (p=0.034) as were older patients (p=0.028). Sex was not significant once other factors were taken into account (p=0.12). Conclusion: Patients who presented with symptomatic colorectal cancer were more likely to be on Medicaid and older. The increased rate of symptomatic presentation of Medicaid patients is not explained by reimbursement policies since NC Medicaid will cover screening colonoscopies. Outreach to these at-risk groups, and especially to the Medicaid population, would be expected to improve survival by increasing the likelihood of screening leading to early diagnosis of colorectal cancer. Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of lipid-rich surfactant within alveolar macrophages. The alveolar macrophages from PAP patients exhibit low levels of peroxisome proliferator-activated receptor-gamma (PPARγ), a key regulatory molecule that is involved in lipid metabolism. We hypothesize that a deficiency of PPARγ leads to the dysregulation of lipid metabolism genes thereby resulting in surfactant accumulation within the alveolar macrophages. Methods: To investigate PPARγ deficiency in the macrophage, we utilized floxed PPARγ X CRE M lysozyme mice on a C57/BL6 background, effectively knocking out PPARγ in the macrophages and neutrophils. Alveolar macrophages were harvested by bronchoalveolar lavage (BAL). All results were compared to C57 wildtype controls. Results: Analysis of PPARγKO alveolar macrophages for neutral lipid accumulation revealed a 90% increase in oil red O positive staining. Investigation into cholesterol (a component of surfactant) content within the PPARγKO BAL fluid revealed a 2.7 fold increase (p=0.002) in extracellular cholesterol levels. Moreover, preliminary studies demonstrated a 4 fold increase (p=0.05) of intracellular cholesterol in PPARγKO alveolar macrophages. Immunofluorescence analysis also confirmed the increase in accumulation of surfactant associated protein A (SP-A) within the PPARγKO alveolar macrophages. Additionally, real time PCR analysis demonstrated dysregulation of genes specifically involved in lipid metabolism and regulated by PPARγ: ATP binding cassette ABC transporters G1 (ABCG1) decreased 1.5 fold (p=0.04) and ABCA1 increased 5.8 fold (p=0.002), and transcription factors Liver X receptors alpha (LXRα) decreased 1.7 fold (p=0.02) and LXRβ increased 34.4 fold (p=0.02). Conclusions: PPARγ-deficient alveolar macrophages have altered expression of genes involved in lipid metabolism and accumulate neutral lipid, cholesterol, and SP-A, all of which are components of surfactant. These results support our hypothesis that the accumulation of surfactant in the alveolar macrophages from PAP patients may be due to the decreased expression of PPARγ. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 28 PR5 PR6 TTHE ROLE OF OXIDATIVELY-INDUCED CLUSTERED DNA LESIONS IN BREAST CELL TRANSFORMATION JW Hairr, CD Cooke, R Hudgins, JE Rhinehart, JE Wiley, G Sigounas ORAL GLUCOSE TOLERANCE IS IMPROVED FOLLOWING DUODENALJEJUNAL BYPASS IN LEAN DIABETIC RATS EZ Lukosius, RC Sloan, MA Reed, EB Tapscott, JR Pender IV, JJ Carter, V Boghossian, WH Chapman III, GL Dohm, WJ Pories, TP Gavin Background: Breast cancer is the most common non-skin malignancy and the second leading cause of cancer-related mortality in women in the United States. Several environmental and genetic risk factors are associated with the disease. Oxidative stress and DNA damage have been associated with a variety of human pathophysiological conditions, including cancer and aging. Complex DNA damage may be manifested in double strand breaks (DSBs) and non-DSB, bi-stranded, oxidatively-induced clustered DNA lesions (OCDLs). These lesions are hypothesized to present challenges to cellular repair mechanisms. Polycyclic aromatic hydrocarbon carcinogens, such as benzo[α]pyrene (B[α]P), may play a role in the initiation of breast cancer and have been shown to induce chromosomal aberrations and transformation of normal breast cells. We hypothesized that unstable DNA adducts and reactive oxygen species induce multiple complex clustered DNA lesions, including single strand breaks (SSBs), DSBs and OCDLs in breast cancer cells exposed to benzo[a]pyrene. Methods: To assess the role of complex DNA damage in breast cell transformation, normal primary breast tissuederived cells were treated with B[α]P and the levels of DNA lesions were determined using alkaline single-cell gel electrophoresis and an adaptation of pulse-field gel electrophoresis. Results: We found elevated levels of several types of complex DNA damage in treated cells, including OCDLs, in primary breast cells exposed to B[α]P compared to the control (p<0.05). After exposure to B[α]P, there was a dose-dependent increase in the number of chromosomal aberrations, which have been reported to be directly linked to genetic instability, mutagenesis and cancer. In addition, a strong positive correlation (r=0.91) between number of OCDLs and number of chromosomal aberrations was observed. Finally, total antioxidant capacity was decreased by 2-fold in cells treated with 8 μM B[a]P compared to the control group (p<0.001). Conclusions: These findings provide a strong indication that oxidatively-induced clustered DNA damage may play a significant role in the transformation of normal primary breast cells. BACKGROUND: Diabetes currently affects 200 million people worldwide and this number is expected to reach 333 million by 2025. Gastric bypass surgery (RYGBP) for the treatment of obesity, reverses type 2 diabetes (T2DM) in 80-90% of obese diabetic patients, however whether this reversal is due to weight loss, food restriction, or bypassing of the duodenum and proximal jejunum is poorly understood. In patients, RYGBP increases glucose stimulated small intestine production of incretins, which are responsible for greater insulin secretion in response to oral compared to intravenous glucose. PURPOSE: To investigate whether bypassing of the duodenum and proximal jejunum (DJB) improves oral (OGTT) and intraperitoneal (IPGTT) glucose tolerance in Goto-Kakizaki (GK) rats, a lean animal model of T2DM. METHODS: GK rats underwent either DJB (N=9) or sham (N=8) operations and non-diabetic Wistar Kyoto (WKY) rats underwent sham operation (N=7) at 14 weeks of age. At 2-3 weeks post-operatively, glucose was measured before and at 30, 60, and 120 min following an oral or intraperitoneal glucose (2.0 g/kg) challenge. RESULTS: Our preliminary data suggest that blood glucose at each time point of the OGTT and the area under the curve (AUC) for glucose were lower in GK-DJB compared to GKSham, but higher than WKY-Sham. For the IPGTT no difference was observed at any time point or for total area under the curve (AUC) between the GK-DJB and GK-Sham while WKY-Sham is lower. CONCLUSION: Bypassing of the duodenum and proximal jejunum alone improves oral, but not intraperitoneal glucose tolerance. Since this improvement was only seen in response to an oral glucose challenge it suggests that incretin-induced pancreatic insulin secretion accounted for the improvements. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 29 PR7 PR8 THE AMELIORATION OF TYPE 2 DIABETES MELLITUS FOLLOWING GASTRIC BYPASS SURGERY MA Reed, W Pories, W Chapman, J Pender, H Barakat, TP Gavin, T Green, E Tapscott, N Sharkley, R Ho, D Palidori, S Clark, SP Piccoli, L Brenner-Gati, GL Dohm DUODENAL-JEJUNAL BYPASS IMPROVES SKELETAL MUSCLE INSULIN SENSITIVITY IN A NON-OBESE DIABETIC ANIMAL MODEL RC Sloan, MA Reed, EZ Lukosius, EB Tapscott, GL Dohm, JR Pender, V Boghossian, JJ Carter, WJ Pories, WH Chapman, TP Gavin BACKGROUND AND OBJECTIVES Gastric bypass surgery (RYGBP) for the treatment of obesity has proven to clinically reverse type 2 diabetes mellitus (T2DM). RYGBP involves both gastric reduction and bypass of the proximal small intestine. Duodenal-Jejunal Bypass (DJB) is a surgical procedure that bypasses the proximal small intestine without gastric reduction and has been proposed to improve insulin sensitivity via Akt phosphorylation in T2DM. The PURPOSE of the current study was to determine if DJB improves phosphorylation of Akt in a non-obese animal model of T2DM. Akt is an essential protein involved in the insulin stimulated uptake of glucose. METHODS DJB was performed on non-obese diabetic Goto-Kakizaki (GK) rats (n=4), and sham operations were performed on GK rats (n=5). Akt phosphorylation was determined using Western immunoblot analysis. RESULTS Akt phosphorylation was higher in DJB operated GK rats when compared to sham operated GK rats. CONCLUSIONS Bypassing of the proximal small intestine (DJB) improves insulin signaling in a nonobese animal model of T2DM suggesting that the defect in insulin sensitivity observed in diabetic patients may be reversible with surgical treatment. Twenty years ago our research group demonstrated that Type 2 diabetes mellitus can be ameliorated following gastric bypass surgery, but the mechanisms associated with this resolution are largely unknown. It was our goal to determine what factors may be responsible for the improvement in diabetes one week and three months post gastric bypass surgery. An intravenous glucose tolerance test and a mixed meal challenge to measure glucose and insulin response as well as various gut incretins such as glucagon-like peptide 1 (GLP-1) were performed. Tests were performed on diabetic and non-diabetic patients pre-surgery, and one week and three months post-surgery. Prior to surgery, the diabetic group exhibited fasting hyperglycemia and remarkably, one week following surgery they were euglycemic. Insulin sensitivity was significantly increased in both diabetic and nondiabetic patients following surgery. In response to IV glucose in the nondiabetic group one week post-surgery, the insulin area under the curve (AUC) decreased and diminished even further three months post-surgery. Conversely, in the diabetic group there was a very small insulin response to IV glucose pre-surgery and one week post-surgery. Only at three months postsurgery did the AUC appear to increase suggesting a recovery of insulin secretion. In response to the mixed meal challenge, there was a significant increase in insulin production one week and three months post-surgery in both groups. Corresponding to the increase in insulin production there was also a remarkable enhancement in GLP-1 production in both groups suggesting GLP-1 may be assisting in the improvement of diabetes. These data indicate there may be multiple factors contributing to the amelioration of Type 2 diabetes following gastric bypass surgery. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 30 PR10 PR9 THYMOSIN β4 TREATMENT OF HUMAN MESENCHYMAL STEM CELLS AND CARDIOMYOCYTES MC Collins, PR Gunst, JI Virag, BJ Muller-Borer PARACRINE SUPPRESSION OF VEGF SECRETION BY ERYTHROPOIETIN INHIBITS TUMOR GROWTH CR Smith, KJ Salleng, A Asch, G Sigounas Background: The low rate of stem cell survival, engraftment and differentiation after cardiomyoplasty presents a technical challenge in cardiac regenerative therapy. Recent in vivo studies suggest that pre-conditioning stem cells and/or the myocardium with the protein thymosin beta-4 (Tβ4) results in increased stem cell survival and engraftment after transplantation. The goal of this study was to begin to elucidate the mechanisms of Tβ4 treatment on human mesenchymal stem cells (hMSCs) and cardiomyocytes (CMs) prior to cell transplantation. Methods: Confluent hMSC and neonatal rat CM cultures were treated with Tβ4 (0.0 μg/ml, 1.0 μg/ml) for 24 hours or 7 days, respectively, corresponding with concurrent in vivo studies. The cytokine and angiogenic response, expression of cardiac proteins, connexin 43 (Cx43), and cardiac troponin T (CTnT), and proliferation were evaluated in hMSCs. Cx43 expression, functional cell-cell communication, beat frequency and wound healing were evaluated in CMs. Results: A proteomic microarray analysis showed a 2.5-fold upregulation of Angiopoietin-1 (Ang-1) and Endostatin from Tβ4 treated hMSCs. A downregulation in expression was reported in other angiogenic mediators and pro-inflammatory cytokines. Expression of Cx43 and CTnT decreased in hMSCs and no change in hMSC proliferation was observed afterTβ4 treatment. Cx43 expression increased 2.7 fold in Tβ4 treated CMs (p<0.05). Observations made, over 24 hours, of a wound healing assay showed overall wound size to decrease more rapidly in Tβ4 treated CMs vs. control (47% vs. 30%). No differences were observed in functional cell-cell coupling or beat frequency in the CMs. Conclusion: This study highlights several mechanism relevant to hMSC survival, engraftment and differentiation with Tβ4 treatment. The robust increase in Ang-1 and decrease in pro-inflammatory cytokines may contribute to increased hMSC survival through increased angiogenesis and reduced myocardial injury. In addition, the increased rate in CM wound closure with Tβ4 treatment implies a more favorable environment for hMSC transplantation. Increased Cx43 expression in CMs and decreased expression in hMSCs would contribute to variable cell-cell communication, hMSC survival, engraftment and differentiation. We are currently investigating the implications of these results in the context of the in vivo model. Background: Several studies have reported that erythropoietin (Epo) is a pleiotropic cytokine with biological properties in addition to its primary function in regulating maturation, growth and survival along the erythroid lineage. Recently, a number of investigators have reported that various neoplastic tissues and human cancer cell lines express Epo and the Epo receptor (EpoR), raising suspicion for the presence of an autocrine-paracrine Epo-EpoR system. It has been shown that inhibition of vascular endothelial growth factor (VEGF) results in an increase of Epo secretion and increased hematocrit in vivo. In this study, we used an in vivo Lewis lung carcinoma model to examine a converse Epo effect on VEGF production and metastasis. Methods: Lewis lung carcinoma (LLC) cells were injected subcutaneously into C57BL mice. The plasma levels of VEGF, the tumor vessel formation, the size of the primary tumors and the extent of lung metastatic disease were determined. In addition, intravenously injected LLC cells seeded in the lungs were assessed. Results: Tumor-bearing animals treated with Epo had 23.6% less VEGF in the plasma compared to saline treated mice (p<0.04). Tumor sections indicated that the number of blood vessels was higher (10.7% for inner and 23.8% for outer, respectively) in tumors obtained from animals treated with saline compared to Epo-treated mice (p>0.05). Using non-parametric analysis, we found that there was a statistically significant difference in tumor growth between saline-treated and Epo-treated animals (p<0.05). However, the number of lung metastases derived from primary tumors was similar in both groups. In assessing size of the metastatic tumors, we found that the average volume of lung nodules was 24.2% higher in saline-injected animals compared to Epo-treated mice. The number of tumors seeded in the lungs following intravenous injection of LLC cells was similar in animals treated with a high dosage of Epo, low dosage of Epo or saline. In addition, the average volume of the nodules was reduced by 42% in animals treated with high and low concentrations of Epo compared to the control group (p = 0.03). Conclusions: These results suggest that Epo exerts a paracrine suppressive effect on VEGF secretion resulting in slower tumor growth in this model. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 31 PR11 PR12 GLUTATHIONE ACCENUATES TRANSNITROSATION IN THE EX VIVO RAT HEART AFTER BRIEF GLOBAL ISCHEMIA/REPERFUSION (I/R) JL Matthews, WE Cascio, MH Schoenfisch, NA Stasko, EL Holmuhomedov, CB Johnson, TA Johnson PPAR GAMMA DELETION IN ALVEOLAR MACROPHAGES UPREGULATES INFLAMMATORY MEDIATORS AJ McCoy, A Malur, BP Barna, MS Kavuru, MJ Thomassen Background: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of a superfamily of intracellular ligand-activated receptors that function as transcription factors. PPARγ is constitutively expressed at high levels in healthy alveolar macrophages(Bonfield et.al 2003: Am.J. Respir.Cell.Mol.Biol ) in contrast to the other tissue macrophages and blood monocytes. Our studies suggest PPARγ is essential in the maintenance of lung homeostasis. We hypothesized that deletion of PPARγ would result in upregulation of inflammatory mediators in the lung in vivo. To test this hypothesis we utilized floxed PPAR (FJ Gonzalez) X CRE M lysozyme mice on a C57/BL6 background. Introduction: Previous studies from our laboratory demonstrated that reperfusion of ischemic isolated Langendorff-perfused hearts with a solution containing nitric oxide (NO) decreases cellular injury. Moreover, tissue salvage by NO is dose-dependent having an optimal concentration affording maximal protection. Lower or higher concentrations show attenuated protection. When engineered dendrimers serve as the delivery vehicle for NO donor chemistry is not affected and protection persists. Although, recent data suggests a key role of glutathione in the NO cascade, standard reperfusion solutions do not typically include glutathione at physiologically relevant concentrations. Our aim was to assess the protective and dose-dependent effects of dendrimer-delivered NO in a clinically relevant model of I/R injury using reperfusion solutions containing glutathione. Methods: Isolated rat hearts were perfused using the Langendorff apparatus with Krebs-Henseleit solution (KHS) or KHS amended with glutathione (500µM, KHS+G). Global, no-flow ischemia was induced for 20min, followed by reperfusion with KHS or KHS+G for 20min with PAMAM-G4 dendrimers engineered to contain the NO-donor SNAP (S-nitroso-N-acetylpenicillamine) or its control NAP (N-acetylpenicillamine) across a broad range of concentrations. Hearts were reperfused for an additional 40min without the dendrimer in KHS or KHS+G. The hearts were removed, sliced into multiple transverse sections, stained with TTC, dissected, sorted by viability and wetweighed. Ischemia-reperfusion injury was characterized as percent infarct. Results: In the presence of glutathione, we found a highly significant reduction in optimal dose (2mM dendrimer-SNAP without glutathione versus 0.015mM dendrimer-SNAP in the presence of glutathione). Statistical analysis demonstrated a benefit of glutathione alone as well as a benefit of NO-donor chemistry in the presence of glutathione. Conclusion: Our data demonstrates improved transnitrosation using these thiol-NO donors in the presence of glutathione and portends the further utility of NO-donors in the salvage of tissue following a clinically relevant ischemic challenge. Methods: Alveolar macrophages were harvested by bronchoalveolar lavage (BAL) from 3-5 mice and pooled. RNA was extracted from BAL cells and analyzed by real time PCR for inducible nitric oxide synthase (iNOS), inflammatory and proinflammatory genes. Results: iNOS expression was upregulated 24.3 ± 3.1 fold in the PPARγ conditional knock out (KO) (n=5) as compared to wild type c57/BL6 (p=0.008). Interestingly, pro-inflammatory cytokine genes were also upregulated including GM-CSF (23.8 fold, p=0.01) and MCP-1 (39.4 fold, p<0.0001). In contrast, thioglycollate-elicited peritoneal macrophage gene expression was not different from wild type. Conclusions: The upregulation of inflammatory genes in the PPARγ KO alveolar macrophages suggests that PPAR γ plays a role in lung homeostasis. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 32 PR13 PR14 IMPACT OF ADMISSION SURVEILLANCE SCREENING AND TOPICAL ANTIBIOTICS ON REDUCING VENTILATOR ASSOCIATED PNEUMONIAS DUE TO METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS IN A SURGICAL INTENSIVE CARE UNIT T Das, MR Coogan, EA Toschlog, AD Bryant, MD Cochran, J Christie, A Blake, AA Pearson, KM Ramsey THE PREVALENCE OF VITAMIN D INADEQUACY IN MEDICAL INPATIENTS C Konduru, N Hernandez, AJ Drake, F Cook Background: Methicillin- resistant Staphylococcus aureus (MRSA) is an important cause of ventilator-associated pneumonias (VAP) in Surgical intensive care units (SICU). Objective: To determine if active surveillance screening for MRSA among all admissions, plus contact precautions and eradication therapy for nasal carriers of MRSA reduces MRSA ventilatorassociated pneumonias (VAP) among admissions to a SICU. Methods: This is an interrupted time series study of data collected from all patients admitted to 24-bed SICU in a University affiliated tertiary care hospital. Prior to the intervention, active surveillance cultures were performed only on high risk patients for MRSA with barrier precautions utilized. We compared the VAP rates per 1000 ventilator days due to MRSA during 12 months before and after implementation of the active surveillance and MRSA eradication program. Active surveillance screening was initiated for of all admissions via nasal swabs using PCR with same day results. Positive carriers were placed in contact isolation and initiation of eradication via mupirocin ointment to anterior nares plus whole body washing with chlorhexidine every other day for 5 days. VAPs were defined using the National Nosocomial Infection Survey (NNIS) criteria, and rates of VAP per 1000 ventilator days were calculated for the study period. VAPs due to Acienetobacter baumannii, Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus during the study period served as the control group. Results: In the 12 month pre-intervention, the rate of VAP due to MRSA was 1.84/1000 ventilator days (SD 1.19; 95%CI 1.10-2.58). In the post-intervention period, the rate fell to 0.65/ 1000 ventilator days (SD 1.04; 95%CI 0.00-1.30). The MRSA VAP rates decreased by 65% during the intervention period which was statistically significant p= 0.025). VAPs caused by other control group of pathogens remained stable during the study period. Conclusions: Active Surveillance screening, initiation of contact precautions and eradication of carriage of MRSA with topical antibiotics was associated with statistically significant reductions in the rate of MRSA ventilator-associated pneumonia in a SICU. Background: Vitamin D deficiency constitutes an unrecognized epidemic worldwide. Vitamin D is now known to be important in both skeletal and extra skeletal health. A major source of Vitamin D comes from exposure to sunlight. Dietary sources of vitamin D are limited. The risk factors for Vitamin D deficiency include inadequate vitamin D in the diet, increased use of sunscreens, increased skin pigmentation, decreased outdoor activity, advanced age, fat malabsorption, liver and kidney disease and certain medications. The optimal range of circulating 25(OH) D (vitamin D) for skeletal health is proposed as 30ng/mL as this reduces PTH(Parathyroid hormone) levels to a minimum steady state and calcium absorption to maximum. A level > or = 30ng/mL is considered as sufficient vitamin D and a level of 21ng/mL to 29ng/mL indicates relative insufficiency for vitamin D. Methods: We studied 52 patients admitted consecutively to hospitalist service in August, 2006. Within 24 hrs of admission, each patient’s record was reviewed. The data collected included age, sex, race, diagnosis and risk factors associated with vitamin D inadequacy. Each patient was classified as ambulatory, housebound, or living in a Nursing home. Dietary history, Multivitamin use, vitamin D or calcium supplements and sun exposure history was obtained. 25 OH (D) levels were done by Enzyme Immunoassay, which has a reference value of 32-100ng/mL. Results: The prevalence of hypovitaminosis D is 77% if the cut off is taken as 32ng/mL. The prevalence is 58% if the cut off is 20ng/mL. If we stratify the patients on risk factors, 81% with risk factors and 75% without risk factors were insufficient. Three out of 4 patients (75%) on anticonvulsants and 4 out of 5(80%) on glucocorticoids had insufficiency. 75% of nursing home patients were insufficient. There were 3 patients whose job involves working outside and they had normal Vitamin D levels. Conclusions: Despite evidence of its profound importance to human health, vitamin D inadequacy is not recognized as a problem by physicians and patients. These observations highlight the need for greater awareness of the high prevalence of vitamin D inadequacy and more aggressive screening in high-risk population. A periodic measurement of 25 OH (D) levels and supplementation is prudent not only to maximize bone health but also to prevent chronic diseases that may be linked with vitamin D deficiency. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 33 PR16 PR15 THE CROSSCUT PROJECT: FOCUS ON PRACTICE-BASED LEARNING AND IMPROVEMENT P Bolin, M Lateef, S Zadeh SIMULTANEOUS MEASUREMENT OF THREE DIMENSIONAL (3D) LEFT AND RIGHT VENTRICULAR VOLUMES AND EJECTION FRACTION DURING DOBUTAMINE CARDIOVASCULAR MAGNETIC RESONANACE S Mandapaka, K Lane, W Cascio, WG Hundley Background: Competency based training has become the paradigm of graduate medical education. The competencies appear to be inherent to the practice of medicine however they can be effectively taught and therefore enhanced. The care of chronic renal transplant patients requires a multidisciplinary approach and involves all elements of the core competencies identified by the Accreditation Council of Graduate Medical Education. The Crosscut Project was designed to formally address these competencies with particular focus on practice-based learning and improvement by increasing awareness in nephrology fellows, faculty, and staff. Methods: Given the frequency of visits within the first year of transplantation, chronic transplant providers often assume primary care roles, in addition to the management of chronic immunosuppressive regimens. The Crosscut Project was devised as an educational tool to focus upon practice based learning and improvement in this additional role as primary provider. The project was designed to focus evaluation of one co-morbidity across an entire population in a setting specifically removed from a clinic visit. The co-morbidities evaluated included traditional cardiovascular risk factors which were blood pressure management, LDL measurement and control, and hemoglobin A1C measurement. The more nontraditional risk factors included evaluation of metabolic syndrome, proteinuria, and vitamin D levels. Multidisciplinary meetings were conducted monthly to address the monthly clinical interest. These meetings focused on practice based learning and improvement but incorporated additional core competencies such as interpersonal skills and communication. Results and Conclusion: As a result of the Crosscut Project, fellows, faculty, and staff developed an increased awareness and ability to identify elements of competency based training. This goal was achieved by focusing on practice based learning in a multidisciplinary setting. Interactive chart review and discussion of current management guidelines resulted in improved patient care. Practice based changes such as the development of patient letters detailing overall progress and specific cardiovascular parameters enhanced patient communication. This project has been successfully incorporated into our clinical practice and now will be utilized for data collection and reporting of outcomes. Background: Appropriate displacement of blood volume from the right into the left ventricle via the pulmonary circulation is necessary to maintain forward cardiac output during stress and prevent inappropriate displacement of blood into the lungs by the right ventricle during left ventricular (LV) failure. Objectives: Cardiovascular magnetic resonance (CMR) has been used to quantify LV and right ventricular (RV) volumes, and ejection fraction (EF) simultaneously at rest, but the feasibility of CMR to quantify simultaneous measures of RV and LV volumes and EF throughout the course of cardiovascular stress testing in humans is unknown. Methods: Thirteen healthy subjects (5 women; 42%), without medical conditions and taking no medications, aged 53 + 10 years, underwent 2 CMR studies separated by 4 to 8 weeks in which dobutamine and atropine were infused to achieve 85% of the maximum predicted heart rate response (MPHRR) for age. Images were acquired with a 1.5 T Excite (General Electrical Medical Systems, Milwaukee, Wisconsin) whole body imaging system using a phased array a cardiac surface coil over the chest. Multislice, steady state free precession cine white blood images were acquired spanning the cardiac base to the apex. Two slices were acquired in the multislice stack during 10 second periods of breath-holding. RV and LV volumes, and EF were determined using a Simpson’s Rule technique. Results: All data are expressed as mean + standard deviation. At rest, low dose dobutamine (7.5 mcg/kg/min), and peak stress, the heart rates, systolic, and diastolic blood pressures for the participants were similar. RV and LV SV were highly correlated at each level of stress (rest, r=0.98, Ttest=0.92, p= 0.0006; low dose, r=0.87, Ttest=0.96, p = 0.0243 ; peak stress, r=0.88, Ttest=0.99, p= 0.0207). Conclusions: Simultaneous change in RV and LV stroke volume can be assessed in a highly reproducible manner throughout the course of pharmacologic stress. This noninvasive methodology will be useful to further study the interdependence of RV and LV stroke volume during various forms of stress, and identify inappropriate displacement of blood flow into the lungs in patients with dyspnea. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 34 PV2 PV1 DIAGNOSIS OF SILENT RIGHT VENTRICULAR RUPTURE AFTER BLUNT TRAUMA TO CHEST BY IMAGING MODALITIES AND CONSERVATIVE MANAGEMENT WITH GOOD PROGNOSIS S Mandapaka, MA Newell, B Ferguson, B Kucysk, D Mann, J Campbell, WC Wood COCAINE INDUCED AORTIC DISSECTION S Mandapaka, J Gerardo, A Movahed Learning Objectives: Aortic dissection is defined by the presence of an intimal flap, a double lumen, an entry tear, and one or more re-entry sites. Established risk factors for acute aortic dissection include hypertension, inherited disorders of connective tissue – Marfan’s syndrome, and EhlerDanlos syndrome type 1V, bicuspid aortic valve disease, coarctation of aorta, aortitis, pregnancy, surgical manipulation, and cardiac catheterization. Recently, cocaine exposure is being noted to be a cause for aortic dissection. Learning objectives: Right ventricular rupture is associated with higher mortality and morbidity than other cardiac complications associated with blunt trauma. Established risk factors for right ventricular ruptures include previous myocardial infarction, coronary artery bypass graft surgery, pacemaker or defibrillator insertion, mediastinitis, and blunt chest trauma. Most patients with cardiac ruptures present with dramatic symptoms of hemodynamic compromise, but occasionally can be silent and can be conservatively managed without the risk of increased mortality or morbidity. Case information: A 79-year-old, Caucasian male with past medical history including hypertension, myocardial infarction, and known coronary artery disease with coronary artery bypass grafting was involved in a motor vehicle collision and sustained multiple injuries, including pulmonary contusions, bilateral rib fractures, sternal fracture, and mesenteric contusion. He had elevated cardiac enzymes. An echocardiogram was performed to determine if there was evidence of myocardial contusion versus infarction. A small right ventricular rupture was seen on microbubble saline contrast study. The rupture was within the right ventricular free wall. Bidirectional flow into a self contained extracardiac cavity contiguous with the right ventricular free wall rupture was identified using color flow examination. This injury was further evaluated with a 3D echocardiographic examination and chest computer tomography (CT). Summary: Free wall rupture of the right ventricle should be suspected in all cases of significant blunt chest trauma. In unusual cases with previous intrathoracic procedures, a free wall rupture of the right ventricle could be contained. Surface echocardiographic study with saline microbubble study and color flow examination can visualize right ventricular free wall extensively as seen in our case. Three dimensional echocardiographic studies may have a potential role along with chest CT in further evaluation of the heart. . Usual management recommendation for RV rupture is open heart surgery and repair. But as seen in our case report conservative management with good follow-up may be considered. Case information: We report a patient with aortic dissection secondary to cocaine use, 51-years-old, African-American female with past medical history of hypertension x 10 years, history of TIA x 2, asthma, and active tobacco smoker presented with dyspnea of sudden onset with associated continuous chest pain (8/10), retrosternal for one day, no radiation. On PE, the BP 238/54, pulse 123/min RR, 24, Temp 96.1, pulse Ox sat: 88% on RA. The lungs were clear bilaterally. Cardiac exam demonstrated 3/6 diastolic rumble at LSB. Neurologic exam demonstrated the patient was getting increasing confused with passage of time, but with no gross motor or sensory focal deficits. A diagnosis was made with 2D echo – Proximal ascending aorta dissection, descending aorta dissection, dilated aortic root 4.3 cm, and prolapse of the non-coronary cusp in diastole with moderate AI. Patient was emergently taken to surgery, but patient subsequently expired in next few hours. Summary: In an inner city population, acute aortic dissection in the setting of crack cocaine use is common, as a consequence of abrupt, transient, severe hypertension and catecholamine release. It is a highly lethal disorder with mortality rate of 1% per hour during the first 24 hours after onset. Early diagnosis and intervention can alter the outcome, morbidity and mortality associated with aortic dissection. In spite of the confounding factors that may have resulted in this clinical scenario, we believe that the added stress of catecholamine release tipped the scale for resulting aortic dissection. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 35 PV4 PV3 UNUSUAL PRESENTATION OF HEREDITARY SIDEROBLASTIC ANEMIA W Badwan, S Changappa, Cl Weitz, C Lynch HYPERCALCEMIA AND ADRENAL INSUFFICIENCY ASSOCIATED WITH COCCIDIOIDOMYCOSIS AND HUMAN IMMUNODEFICIENCY VIRUS JM Bennett, AJ Drake, RJ Tanenberg Introduction: Sideroblastic Anemia is a condition characterized by a slow, progressive anemia. There are hereditary, idiopathic, and acquired causes. Ineffective erythropoiesis can accelerate iron absorption from the gut. As a result, iron accumulates in the mitochondria of red blood cells, giving a ringed appearance to the nucleus, called a ringed sideroblast. Hereditary sideroblastic is transmitted by X-linked inheritance. Normally females are carriers, who usually show no signs of the disorder. This form usually responds after several weeks of treatment with high doses of pyridoxine (vitamin B6). Discussion: Most hereditary sideroblastic anemias are rare and usually present in childhood. Females are carriers since the majority have an Xlinked pattern of inheritance. There have been instances of autosomal recessive inheritance which is why F.B. was sent for genetic testing. The hereditary form of sideroblastic anemia is the most responsive to pyridoxine therapy. Ms. FB likely has a mild form of the disease which had been indolent for a long period of time leading to the accumulation of iron in the liver and spleen. The Iron deposition likely affected the Beta Islet cells leading to the development of Type I Diabetes. LEARNING OBJECTIVES: Recognize the clinical signs, symptoms and laboratory findings associated with adrenal insufficiency. Effectively treat hypercalcemia and adrenal insufficiency associated with certain infections. CASE INFORMATION: A 33 year-old male Mexican immigrant presented to clinic with complaints of weakness, fatigue and backache. Laboratory evaluation revealed hypercalcemia of 13.2 mg/dL. Upon hospital admission, the patient additionally complained of nausea and vomiting, he was hypotensive, appeared cachetic and had increased pigmentation of his skin especially in sun-exposed areas. He was treated with intravenous fluids, diuretics and did received 4 mg of zoledronic acid. In evaluation of etiology of the patient’s signs and symptoms, he underwent a cosyntropin stimulation test, with a baseline cortisol of 9 μg/dL and stimulated level of 11.2 μg/dL, indicating a very poor adrenal reserve. His ACTH level was elevated at 511 pg/mL and PTH suppressed at 3.0 pg/mL. For his adrenal insufficiency he was prescribed corticosteroid therapy. He improved clinically, had improvement of his calcium level and was discharged from the hospital in good condition. The patient’s past medical history was significant for human immunodeficiency virus diagnosed six months prior when he sought medical care for persistent cough, weight loss and fevers. At diagnosis his CD4 count was 24 and viral load was greater than 100,000. Due to findings of pulmonary nodules on chest CT, the patient underwent open lung biopsy which revealed infection with Coccidioides immitis. The patient was prescribed a regimen of fluconazole along with efavirenz-emtricitab-tenofovir. SUMMARY: Hypercalcemia is often a clue to the presence of unsuspected illness and may be an associated marker of certain infections. The majority of patients with hypercalcemia will have either primary hyperparathyroidism or malignancy. However it is crucial to recognize the signs and symptoms of hypercalcemia associated with granulomatous processes and chronic infections. Increased production of 1,25-dihydroxyvitamin D by activated macrophages has been shown to be the cause in most cases. Presented is a case report of an HIV positive patient with coccidioidomycosis demonstrating classic clinical manifestations of adrenal insufficiency and resulting hypercalcemia. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ Case: Ms. F.B., a 40 year old African American female with a past medical history of lymphoma in remission, Type 1 Diabetes diagnosed at age 32, and history of anemia. She initially had a hemoglobin of 4.3. F.B. was transferred to a tertiary care hospital after failing to respond to more than a dozen blood transfusions for an assumed hemolytic anemia. A bone marrow biopsy revealed predominately erythroid precursors many of which appeared dysplastic myeloid cells and ringed sideroblasts. F.B was started on folic acid and pyridoxine with dramatic changes in her reticulocyte count, hemoglobin, and iron. On further questioning her about her family history, she had several family members who have been anemic including her mother. She also has an 18 month old daughter who is anemic and requires iron supplementation. She was referred for further genetic testing. 36 PV5 PV6 TRICHOLEMMAL CARCINOMA: CASE REPORT AND REVIEW OF A RARE CUTANEOUS TUMOR LD Briley, WA Burke, RH Schosser, VB Laing MALACOPLAKIA, A BLADDER MASS MIMICKING MALIGNANCY: A CASE REPORT NA Khan, BE Johnson, M McLean Learning Objectives: Tricholemmal carcinoma is the malignant counterpart of a tricholemmoma. It is a rare neoplasm that is often mistaken clinically for more common tumors such as squamous cell carcinoma and basal cell carcinoma. It behaves more aggressively than these more common tumors and must be treated differently. Background: Malacoplakia (soft plaque) is an unusual granulomatous inflammatory disease which involves mostly genitourinary tract. Though, majority of the cases had been reported involving the genitourinary tract, include bladder, ureter and renal parenchyma but involvement of other organs has also been reported including gall bladder, liver, nasopharynx, skin, and subcutaneous tissue. The etiology of malacoplakia is unknown, but it may present in association with anemia, weight loss and may mimic features of malignancy. We reported a case of malacoplakia with extensive spread into the bladder, leading to bilateral ureteral obstruction. However, no obvious etiology was identified except for a smoking history. This case is possibly the third case in English literature with similar features on presentation; first two cases were reported more than two decades ago. Case Information: The patient was a 45 year old female who presented with worsening abdominal pain for seven months and hematuria for one month. She had a 50 lb weight loss, anemia and kidney failure. Imaging of the abdomen/pelvis revealed moderate hydronephrosis secondary to a mass involving the trigone with obstruction of bilateral ureteral orifices. It was thought be a transitional carcinoma of the bladder. A bilateral percutaneous nephrostomy tube was placed to relieve obstructive uropathy. When subsequent transurethral tumor resection and bilateral ureteral stent placement was performed, the obstructing tissue turned out to be malacoplakia upon histopathology. No malignancy was identified via pathology. Patient was discharged on ciprofloxacin and vitamin C for one month. Approximately four months later, repeat cystoscopy and biopsy was negative for any persistent disease or malignancy. She was asymptomatic and her renal status improved back to her baseline. Conclusions: Although, malacoplakia is a benign inflammatory process but it may present with hallmark features of malignancy, so it must be diagnosed by biopsy. It is often treatable by antibiotics alone but surgical resection may be needed to reduce the burden of disease and it may facilitate recovery. Our patient was treated with surgical resection followed by adjuvant antibiotics which lead to a complete recovery. Case Presentation: 66 year old male presented with an erythematous scaling plaque just posterior to the right ear. This area had been treated in the past with both cryotherapy plus electrodessication and curretage. Shave biopsy at the previous visit was consistent with the Favre-Racouchot syndrome. Ultimately, a 3mm punch biopsy performed established the diagnosis of tricholemmal carcinoma. The follicular epithelium had been replaced by atypical cells many of which demonstrated clear cell change. Cells were negative for CEA. Glycogen was demonstrated by PAS stain, and there was patchy positivity for EMA. The cells in the neoplasm were AE1:3 positive. The patient was treated Mohs surgery. Discussion: Tricholemmal carcinoma is an extremely rare tumor that has been described as an invasive atypical clear cell neoplasm of adnexal keratinocytes. It stays contiguous with the epidermis as its pushing inferior border invades the dermis. While it can act locally aggressive with perineural invasion and local recurrence, it rarely metastasizes with only one report of distant metastases in the literature. Mohs surgery or wide local excision with regular follow up is the treatment of choice. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 37 PV7 PV8 DRUG INDUCED AUTOIMMUNE BULLOUS DERMATOSES H Shaffer, C Phillips, R Schosser, W Burke SARCOIDOSIS WITH INTRASCROTAL LESIONS Stephen Maxwell Objectives: To describe the clinical and pathologic findings of two patients with autoimmune drug induced bullous disorders and review current literature. One presents with penicillamine induced epidermolysis bullosa acquisita-like reaction while the other displays vancomycin induced linear IgA bullous dermatosis. Case Information: Case 1: A 46 year old female presents with a one year history of recurrent tender violaceous plaques and purpuric patches studded with hemorrhagic vesicles on the buttocks, knees, elbows and lower legs with no systemic symptoms. These lesions healed with scarring and milia. Her past medical history was significant for long-term use of high dose d-penicillamine for cystinuria. The clinical presentation was consistent with EBA while the initial biopsy was inconclusive. DIF and IIF were negative. Treatment including corticosteroids and dapsone were unsuccessful. Few case reports indicate that long term d-penicillamine may cause an EBA-like reaction in which clinical presentation is identical to idiopathic disease while immunofluorescence tends to be negative. Resolution of the eruption occurred within 6 months of discontinuing the medication. Case 2: A 43 year old female presents with two days of painful, pruritic 2-4 mm tense bullae with surrounding excoriations on her trunk and a single oral mucosal erosion with no systemic complaints. This eruption began 10 days following administration of IV vancomycin for a mixed gram positive wound infection following dehiscence of a posterior spinal fusion site. Labs were unremarkable. Skin biopsy reveals a subepidermal bullae with DIF showing a linear IgA band consistent with linear IgA bullous dermatosis. Summary: EBA-like reaction and LABD are two autoimmune bullous dermatoses that may be caused by medications. These cases highlight the pathologic and immunofluorescent findings in both and describe differences between idiopathic and drug induced variants while also emphasizing the most common drugs known to cause these reactions. Learning objectives: Sarcoidosis is a systemic inflammatory disorder that may involve virtually every organ in the body, but most commonly affects the lung, skin, liver, and eyes. Involvement of other organs is far less common, and the unusual clinical presentation of sarcoidosis in these rare cases may make the diagnosis difficult. The clinician must be familiar with these uncommon manifestations to prevent delayed diagnosis and avoid exposing patients to unnecessary and perhaps dangerous treatments and procedures. Here, a case of sarcoidosis presenting as a testicular mass is described to illustrate this point. Additionally, a brief discussion on the diagnosis and management of testicular sarcoidosis is given. Case Information: A previously healthy 22 year old African American male presented with a history of generalized malaise, weight loss, painful left scrotal swelling, and diffuse lymphadenopathy. A testicular ultrasound revealed a left intrascrotal mass and CT scan of the chest and abdomen showed diffuse lymphadenopathy. When the patient failed to improve with empiric treatment of infectious etiologies, a right antecubital lymph node biopsy was done and found to be consistent with sarcoidosis. The patient was treated with prednisone with resolution in his testicular pain and swelling and significant overall improvement. Summary: Sarcoidosis is a multi system disorder that is usually localized to the chest, but can less commonly affect the testicles. Due to the low prevalence of genital sarcoidosis many physicians may misdiagnose these lesions leading to unnecessary procedures that might be harmful to the patient. This case describes a patient with findings that I believe are consistent with genital sarcoidosis. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 38 PV10 PV9 A CASE OF STREPTOCOCCAL TOXIC SHOCK SYNDROME V Slaughter, D Eilen, C Patel, M Mazer GANGLIONEUROMA PRESENTING AS A RETROPERITONEAL MASS IN A YOUNG WOMAN TK Singh, L Dobbs, G Talente INTRODUCTION: Streptococcus pyogenes is a Group A Streptococci (GAS) that causes multiple cutaneous and systemic diseases of varying severity. Significant mortality has been reported from Streptococcal Toxic Shock Syndrome (TSS). This organism typically invades via the skin, lungs and mucus membranes. CASE PRESENTATION: A 43 year old white man with well controlled diabetes mellitus type II presented to the emergency department complaining of fever, sore throat, cough, and myalgias of increasing severity over five days. Vomiting and generalized abdominal pain were also reported. He had increasing pain in the left great toe. Initial evaluation revealed a toxic appearing male in mild distress with fever, tachypnea, and tachycardia. Pharyngitis and a petechial rash were noted on physical exam. The left great toe had evidence of an ingrown toenail and was swollen and erythematous. The ED physician performed an incision and drainage of purulent material from the toe. Initial laboratory data: WBC- 3.8k/uL with left shift, lactate 8.2 mmol/L, pH 7.26, and PT/PTT - >100/>200. The patient developed progressive hypotension refractory to intravenous fluids and vasopressors were started. Empiric antibiotics were initiated, a surgery consult was requested and he was admitted to the MICU. Despite appropriate and aggressive resuscitative efforts, disseminated intravascular coagulation and hypotension progressed. He developed fulminant acute respiratory distress syndrome and was intubated. Six hours after admission to the MICU, the patient went into cardiac arrest and expired. The blood cultures were positive for Group A Streptococcus. CONCLUSION: GAS has enormous clinical variability. This case is an example of a probable streptococcal soft tissue infection and/or pharyngitis leading to rapidly progressive and fatal TSS. Previous studies have clearly shown that early recognition and prompt intervention in septic patients has a positive effect on mortality. Fluid resuscitation, vasopressors and inotropes should be used to restore oxygen delivery and systemic perfusion. Source control is paramount for survival. Due to its highly aggressive nature, this appears to be especially true for patients with GAS sepsis and TSS. Mortality has been reported to be as high as 40% in one study of intensive care patients with GAS sepsis. Learning Objectives: Ganglioneuromas are rare tumors that arise in association with autonomic nerve cells, which may be in any part of the body. It is important to increase awareness of symptoms, diagnosis, management and prognosis of these rare, but typically benign tumors. Ganglioneuroma should be suspected in cases of incidentally discovered retroperitoneal masses, especially those causing symptoms. Case Information: We present a case of a 26 year old female presenting with intermittent abdominal pain. Imaging of abdomen by CT scan revealed a retroperitoneal mass. A laparotomy was performed to obtain biopsy of the mass. Histology revealed features of a ganglioneuroma, with mature ganglion cells scattered within a background of wavy spindle cells (Schwann cells). The biopsy did not reveal any immature cells (eg. neuroblasts) to suggest a malignant neoplasm. However, there did appear to be involvement of a lymph node by the neoplasm, suggesting that this neoplasm could possibly be more aggressive than the typically benign ganglioneuroma. The patient was scheduled for a complete resection of the tumor. Summary: Ganglioneuromas are benign tumors that are composed of ganglion cells and nerve fibers. They frequently occur in people between age 10 and 40. They are generally asymptomatic and most commonly discovered in the course of a normal exam or during treatment for some other condition. Ganglioneuroma is relatively difficult to distinguish from other tumors because of the lack of imaging findings specific for these type of tumors. Therefore a histologic diagnosis is essential. The management of ganglioneuromas is mainly surgical resection. The prognosis of these benign tumors is usually good. There are rare reports of metastatic ganglioneuromas. Therefore, long-term follow-up postoperatively is necessary to assess the malignant potential of these tumors. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 39 PV12 PV11 ACUTE ST-ELEVATION MYOCARDIAL INFARCTION AFTER INFLIXIMAB INFUSION IN PATIENT WITH CROHN’S DISEASE N Peterson, A Nanjundappa, A Mayo PREEXCITED ATRIAL FIBRILLATION IN THE PRESENCE OF ANTIDROMIC ATRIOVENTRICULAR RECIPROCATING TACHYCARDIA – A MIMICKER OF VENTRICULAR TACHYCARDIA TM Youmans, RW Kreeger Objective: We report a case of coronary thrombosis provoking anterior ST-elevation myocardial infarction (STEMI) after infliximab therapy for treatment of Crohn’s disease. Comprehensive literature review yields several case reports of thrombotic events, but none causing coronary thrombosis in patients without risk factors for cardiovascular disease. CASE REPORT: Patient is a 40 year-old white male with a history of Crohn’s Disease who has been receiving treatment with infliximab. Patient developed retrosternal chest pain after Infliximab infusion. ECG revealed evidence of ST-elevation in anterior leads. Emergent cardiac catheterization revealed left anterior descending (LAD) proximal segment to have large thrombus burden and the mid-segment to be totally occluded with thrombus (Image 1). Patient received intra-coronary eptifibatide 180mcg/kg times two boluses and 5mg of intravenous reteplase. Initially, AngioJet was used for thrombectomy. Two successful embolectomies were performed and subsequently the patient received intracoronary adenosine and nitroglycerin. Angiogram revealed patent proximal LAD, midsegment with mild thrombus burden, and distal segment with clot in the apical region. Patient was returned to the cardiac intensive care unit and treated with IV heparin overnight. Repeat coronary angiography the next morning revealed widely patent LAD in the proximal and mid-segment. The distal LAD in apical segment showed diffuse moderate amount of thrombus with TIMI 2 flow. No further intervention was performed. SUMMARY: This report describes a patient with no history of cardiac disease who experienced acute ST-elevation myocardial infarction with thrombus in the left anterior descending artery following infliximab infusion. To our knowledge, this is the first report of such an event associated with infliximab infusion in a patient without cardiovascular risk factors. This rare event of coronary thrombosis provoking anterior STEMI after Infliximab therapy for Crohn’s disease raises the question of whether increased cardiac surveillance is needed in this patient population. Learning Objectives: Atrioventricular reciprocating tachycardia (AVRT) is caused by the presence of an accessory pathway (AP), or bypass tract in which the AV node is used as the antegrade limb and the AP as the retrograde limb. Antidromic AVRT in which an AP is used as the antegrade limb of an AVRT is rare occurring in 5-10% of patients with Wolff-ParkinsonWhite syndrome (WPW). The purpose of this case report is to review the diagnostic evaluation, and treatment of a patient with this phenomenon. Case Information: 25 year old soldier in the Air National Guard with a history of enlarged heart, heart murmur, and near syncope awoke at home with complaints of midsternal chest pain, rapid palpitations, nausea and vomiting. In the emergency department, the patient complained of dizziness and then suddenly became unresponsive. An electrocardiogram (ECG) showed AF with a wide QRS and very rapid ventricular response (RVR). The patient was cardioverted due to hemodynamic instability. An ECG after cardioversion revealed preexcitation suggesting a left lateral pathway. He was transferred to Pitt County Memorial Hospital to the Electrophysiology service. An electrophysiological study revealed dual accessory pathway conduction and easily inducible wide QRS tachycardia resembling VT. Successful left lateral AP ablation was performed with no inducibility after ablation. Summary: Catheter ablation of the AP is first line therapy in symptomatic patients with AF who have WPW, particularly those with syncope due to rapid heart rate. Immediate direct current cardioversion is recommended to prevent ventricular fibrillation (VF) in patients with AF with RVR and hemodynamic instability. Intravenous procainamide or ibutilide is recommended to restore sinus rhythm in patients with WPW in whom AF occurs without hemodynamic instability as they block AP conduction. Rapid antegrade AP conduction during AF can stimulate VT since it is a wide QRS complex tachycardia. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 40 PV14 PV13 PULMONARY AMYLOIDOSIS: A SECONDARY PROCESS WITH RADIOGRAPHIC VARIANTS MIMICKING ALMOST ALL INTERSTITIAL LUNG DISEASE PATTERNS AA Kanchwala, KD Kasa, TC Pancoast, MS Kavuru THE IMPORTANCE OF BAL IN THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASE ASSOCIATED WITH ERLOTINIB FOR THE TREATMENT OF BRONCHOALVEOLAR CARCINOMA AS Carden, P Walker, D Liles, C Knupp, JL Finley LEARNING OBJECTIVES: Pulmonary involvement in Amyloidosis is rare and has many clinical, radiographic and pathologic variants. Radiographic variants described in literature include diffuse interstitial lung disease with or without mediastinal adenopathy, isolated mediastinal adenopathy, pleural disease, diaphragmatic involvement and nodular variant also known as Amyloidomas. Amyloidomas, in the majority are clinically silent. CASE INFORMATION: We report a case of a 72 year old Caucasian female with a history significant for diabetes mellitus, hypertension and dyslipidemia, being evaluated for an episode of transient aphasia. Routine chest x-ray (CXR) showed multiple pulmonary nodules. Commuted tomography (CAT) of the chest showed multiple bilateral nodules of varying sizes, largest being 4.5 x 2.2 centimeters (cm). No mediastinal or hilar lymphadenopathy was noted. A 10 pound weight loss in 2 months was observed. Bronchoscopy revealed yellow tinged nodularities in the right upper and left lower lobe sub segments and a black endobronchial mass obstructing one of the left lower lobe sub segments. Bronchoalveolar lavage, brushings, and endobronchial and transbronchial biopsy showed dense lymphocytic infiltrate, anthracosis, and amorphous eosinophillic material, staining positive for Congo red, consistent with amyloid deposition. Further classification was not possible but light chain (AL) amyloid was excluded. Diagnostic dissatisfaction led to repeat bronchoscopy with similar results. Further workup including connective tissue disease and age related cancer screening were negative. Pulmonary function tests were normal. SUMMARY: Pulmonary involvement in Amyloidosis is rare and extremely variable. Our patient had Amyloidomas which varied in size, shape and number, and for the most part were clinically silent. Rarely symptoms like dyspnea, chest discomfort and hemoptysis may occur. Amyloidomas are mostly associated with the AL variant. The challenge is to differentiate from other more common diseases, like cancers, fungal infections, hamartomas and nodular sarcoidosis. Diagnosis is usually incidental on biopsy via bronchoscopy or surgery. Diagnostic workup is another challenge. In our case, after excluding all other causes we suspect the lung findings to be either due to diabetes mellitus or senility, (precursor protein: Islet amyloid, amyloid type: AIAPP, Protein: Amylin). Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/tyrosine kinase inhibitor. It is approved as the standard of care for second and third line therapy for patients with stage IV non-small cell lung cancer. It has been shown to have higher response rates in women, Asians, patients with adenocarcinoma, and those who have little to no smoking history. Despite erlotinib's favorable safety profile, rare adverse events such as interstitial lung disease have been reported. This is a case report of a patient with no pre-existing lung disease who was treated with erlotinib for non-small cell lung cancer and subsequently developed interstitial pneumonitis. Accurate diagnosis of interstitial lung disease is often difficult to differentiate from disease progression on computed tomography particularly in patients with bronchoalveolar carcinomas where interstitial patterns of both entities resemble each other. Nevertheless, BAL and bronchoscopy may be useful tools to aid in the diagnosis. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 41 PV15 PV16 HEREDITARY HEMORRHAGIC TELANGIECTASIA: A FASCINATING CASE WHERE MULTIPLE DISEASES MIGHT HAVE A COMMON LINK AA Kanchwala, TC Pancoast, M Kavuru GRANULAR CELL TUMORS: A RARE FINDING IN A COMPLICATED CASE OF FAILURE TO WEAN FROM MECHANICAL VENTILATION KD Kasa, TC Pancoast, M Kavuru LEARNING OBJECTIVES: Hereditary Hemorrhagic Telangiectasia (HHT), an autosomal dominant (AD) disease, causes vascular malformations on skin, mucous membranes, lungs, liver and brain leading to recurrent hemorrhage causing varying degrees of morbidity. The two main subtypes, HHT-1 and HHT-2, are characterized by different mutations found respectively on chromosome 9 in the Endoglin gene, and chromosome 12 in the Activin Receptor Like Kinase-1 gene. Both gene products are members of the Transforming Growth Factor-Beta (TGF-ß) receptor family, and are involved in regulation of angiogenesis. There is variable penetrance leading to differences in disease phenotype. CASE INFORMATION: The patient is a 32 year old man with recurrent nose bleeds, pulmonary arteriovenous malformations (AVM), rheumatoid arthritis with fibrosing alveolits and pituitary macroadenoma, followed since age 8. His first symptoms were dyspnea, weakness and joint pain. A chest X-ray and computed tomography (CT) demonstrated areas of fibrosis without active alveolits in the lower lobes, and a right lower lobe AVM. The AVM was treated by coil embolization. He was also diagnosed with Rheumatoid Arthritis and treated with low dose prednisone and hydroxychloroquine. Since 2000 he has had daily nose bleeds leading to multiple admissions for blood transfusion. In September 2007 he developed worsening dyspnea. A CT scan showed a 12mm left upper lobe AVM. Echocardiogram showed a pulmonary shunt with a 16% shunt fraction. The AVM was coil embolized with minimal improvement in shunt fraction. He has had numerous pulmonary function tests revealing moderate to severe restriction. Genetic analysis revealed a mutation in the Endoglin gene. Parental testing is underway. SUMMARY: This patient has an aggressive phenotype with normal parents. While unusual in AD diseases, heterogeneity of disease severity is seen in HHT and mirrored in its murine model. While most mutations are null alleles, modifier genes or epigenetic phenomenon are required to produce disease, making this case much more plausible. An alternative is a new mutation. The presence of multiple diseases in the patient leads to speculation of a link between these diseases, possibly involving the TGF-B receptor. Endoglin has been implicated in rheumatoid arthritis. Learning Objectives: Granular Cell Tumors are rare benign tumors of the lung that cause severe pulmonary complications that arise due to bronchial obstruction. Granular cell tumors, with their prodrome of symptoms, are a very rare cause of failure to wean from mechanical ventilation. Case Information: We report a case of a 47-year-old African American female with a history only significant for hypertension who was admitted to the intensive care unit with a hemorrhagic stroke. The patient had recurrent extubation failure resulting in the need for tracheotomy. Chest radiographs demonstrated recurrent right middle lobe consolidation. Bronchoscopy revealed copious mucoid secretions and pus with an endobronchial lesion at the right middle lobe takeoff point with friable, hyperemic, inflamed mucosa and a fish mouth opening. Biopsies were obtained and demonstrated the presence of a granular cell tumor. Discussion: Granular Cell tumors of the lung are very rare in the setting of failure to wean from mechanical ventilation. Our patient has a benign disease with a debilitating process that is compromising her airway by an obstructive process resulting in recurrent pneumonias. Her tumor is a major reason for respiratory failure and long-term mechanical ventilatory support. From further review of literature, this is rare condition that is associated with failure to wean from mechanical ventilation. Conclusion: A challenging aspect of this case was the diagnostic process. Granular Cell Tumors can cause significant obstructive pathophysiology. In review of literature, there are several case reports documenting treatment options that can alleviate the obstruction. Treatment options include Laser therapy and cryotherapy to resection the tumor via bronchoscopy or surgical resection. Surgical resection is usually recommended for lesions greater than 8 mm in diameter in order to prevent recurrence. References: 1. 2. Multicentric Endobronchial Granular Cell Myoblastoma. Redjaee et al. CHEST Oct. 1990:98:945-948 Symptomatic Solitary Granular Cell Tumor. Thaller et al. CHEST Dec. 1985:88:925-928 Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 42 PV18 PV17 HYPOGLYCEMIA AFTER GASTRIC BYPASS SURGERY: RECOGNIZED BUT IMPORTANT COMPLICATION C Konduru, N Hernandez, F Cook, RJ Tanenberg, AJ Drake A NEWLY HODGKIN TRANSFORMATION IN TWO PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA CA Lynch, D Liles Learning objectives: The increasing prevalence of obesity has led to increased bariatric surgery of which the gastric bypass (GOP) is the most common procedure. Severe postprandial hypoglycemia with hyperinsulinemia is a recently recognized rare complication of GOP. Case information: A 47 year old Caucasian female with a past medical history of morbid obesity underwent laparoscopic GOP in July 2006. About 9 months later she was treated in an ER for hypoglycemia with IV 50% dextrose. A 3 hr glucose tolerance test was ordered: fasting glucose - 89, 1hr -89, 2hr- 32 (associated with symptoms) and 3hr- 64 mg/dL. She was referred to the ECU Endocrine Clinic. She noted frequent episodes of diaphoresis, weakness and dizziness associated with fingerstick glucose levels in the 40s and 50s on a glucometer. These symptoms are promptly relieved with glucose tablets or juice. These episodes are not related to mealtimes or exercise. She had no history of diabetes prior to her GOP. Postoperatively, she lost ~100 pounds but recently her weight has been stable. Physical exam was unremarkable. Labs drawn in December 2007 when she was symptomatic included plasma glucose of 61 mg/dL, insulin level 7.9 uIU/mL and C-peptide 2.3ng/mL. A sulfonylurea screen was negative. An abdominal ultrasound and CT were normal. She was treated with acarbose 10mg tid with meals. She had no further visits to the ER but follow-up revealed that the patient was still having symptomatic hypoglycemic episodes with fingerstick glucose levels in the 40’s Since she did not benefit from acarbose it was discontinued and she was advised to continue to eat small frequent meals and avoid foods with a high glycemic index. Summary: At present it remains unclear whether patients who develop hyperinsulinemic hypoglycemia after bypass surgery have an unrecognized predisposition to this condition predating bariatric procedures. Furthermore, it should be emphasized that patients who have undergone gastric bypass surgery may have a myriad of postprandial symptoms, which could be incorrectly attributed to hypoglycemia. The clinical criteria of Whipple’s triad need to be fulfilled to accurately diagnose hypoglycemia. With the increase in bariatric surgery, this condition will likely become more common. Further investigation is needed to elucidate the hormonal, metabolic, genetic and neural mechanisms and to explore potential treatments for this syndrome. LEARNING OBJECTIVES: Chronic Lymphocytic Leukemia (CLL) is a low grade malignancy and the most common adult leukemia. It is associated with increased risk of second malignancy. The most common secondary malignancy is a Richter transformation, in which CLL transforms to a high grade lymphoma. This occurs in approximately 2-8% of patients. We describe two cases of unusual transformation to Hodgkin lymphoma (HD). CASE INFORMATION: A 58 year old male with CLL presented with increasing supraclavicular adenopathy following completion of treatment with rituxan and fludarabine. Biopsy of the neck mass revealed HD. He was treated with two cycles of ABVD followed by two cycles of COPP and attained a complete remission. He subsequently underwent involved field radiation and remains in remission five months post-therapy. The second patient, a 78 year old female, was diagnosed with CLL in 2000, but did not require any therapy until 2005 when she developed neutropenia and thrombocytopenia. At that time, she received treatment with Fludarabine. In 2007, she presented with complaints of abdominal pain. A CAT scan demonstrated right hydronephrosis with aortocaval adenopathy and multiple bilateral lung nodules. Bladder and lung biopsies were consistent with HD. She began therapy with Chlorambucil, Vinblastine, Procarbazine, Prednisone, Adriamycin, Bleomycin and Vincristine (ChlVPP/ABV hybrid). Repeat imaging after two cycles of therapy was consistent with a partial response. However, she developed cytopenias with rapid progression of disease and succumbed to her illness just four months after her diagnosis. SUMMARY: While transformation to an aggressive lymphoma is seen with some frequency, review of the literature reveals that transformation into HD is much less common. While the de novo development of HD has an excellent cure rate, the presence of this transformation in CLL heralds a poor prognosis. A median survival of 0.8 years has been reported from one published series. While Hodgkin transformation is rare, it should be considered in a CLL patient with evidence of a new high grade malignancy. Despite the poor prognosis reported in the literature, our patients demonstrate it is possible to obtain a response to HD directed therapies, but with uncertain duration of response. Other case reports have reported a duration of response and overall survival of less than one year. Notes: _________________________________________________ Notes: _________________________________________________ _________________________________________________ _________________________________________________ _________________________________________________ 43 _________________________________________________ PV19 SPINAL CORD INFARCTION AS A RARE COMPLICATION OF PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY JJ Felder, M Waqas Learning Objectives: Spinal cord infarction is uncommon, typically presenting with sudden onset of paralysis and sensory disturbances. Concurrently, infarction of the spinal cord as a complication of coronary angiography is exceedingly rare and should be diagnosed accurately, as it is an event of significant consequence. Case Information: We report the case of a 67-yearold Caucasian male with significant cardiac risk factors who was airlifted from Carteret General Hospital for the treatment of an acute inferolateral STEMI. The patient received thrombolysis with TNKase, along with aspirin and plavix, en route to Pitt County Memorial Hospital for PTCA. In the catheterization laboratory vascular access was obtained using a modified Seldinger technique to the right femoral artery through which 6F JR-4 and JL-4 diagnostic catheters were passed. Coronary angiogram revealed triple vessel disease with 60% and 70% lesions in the mid and distal portions of the RCA respectively, which were subsequently repaired using ballooning and Vision bare metal stent placement. The patient was returned to the cardiac intensive care unit pain free and in stable condition. A few hours later, the patient complained of bilateral leg weakness and inability to move his feet. Neurological exam revealed 0/4 deep tendon reflexes and 0/5 motor strength in the lower extremities bilaterally with absent pinprick sensation below L2 and absent rectal sensation without tone. An MRI of the throacolumbar spine showed a 9x9x15cm abdominal aortic aneurysm from L1-L5 and abnormal T2 weighted signaling, within the spinal cord, extending from the conus to the level of T8 consistent with ischemic changes secondary to an anterior spinal cord infarction. The patient also developed notable ischemic changes in the first and second toe of the left foot suggestive of a thromboembolic phenomenon, which improved during the hospital stay. His paraplegia, however, remained permanent. Summary: A spinal infarction as a complication of invasive vascular studies, such as angiographies, is at present very atypical, but should be remembered as a possible adverse outcome that can greatly affect patient morbidity and mortality. Spinal cord infarction may be suspected in cases of acute thoracic or lumbar pain with motor and sensory defects, which reflect a spinal level distribution, and can be confirmed on magnetic resonance studies of the spinal cord. Notes: _________________________________________________ _________________________________________________ _________________________________________________ 44 Notes: 45
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