2 A n

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)
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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.
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Join us in thanking our sponsors for their
support of IM Research Day - 2008
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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
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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.
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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.
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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:
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17
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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:
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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:
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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:
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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:
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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:
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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
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23
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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
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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:
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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:
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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:
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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:
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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:
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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:
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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:
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Notes:
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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:
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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:
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Notes:
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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:
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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:
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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:
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Notes:
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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:
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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:
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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:
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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:
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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:
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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
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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:
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43
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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.
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