A DEPARTMENT OF MEDICINE BULLETIN
UF UNIVERSITY of
College of Medicine
The Department of Medicine at the University of Florida
College of Medicine-Jacksonville is launching a quarterly
newsletter. This first issue coincides with the start of a new
season that we hope will bring peace and prosperity for all.
The purpose of this endeavor is to keep the UF & Shands
community and friends posted as to the developments
within a department that cares for almost 40% of patients admitted to the
hospital. It is understandable that the changes within the Department of
Medicine affect the operations of most of other departments and therefore it's
everyone's business to keep abreast of the accomplishments within Medicine.
In addition, to this strategic goal, the newsletter will also have an educational
goal and will serve as a vehicle to promote collegiality. To achieve these
goals, each issue will have an interesting case presentation, an update on a
new drug, highlight our ongoing efforts in clinical, teaching and research
missions and report on news and announcements of interest to our health care
community at large.
One of the early tasks at hand was to choose an appropriate name for this
newsletter. The decision of the editorial team was to call this newsletter
Academic Physician Quarterly to highlight the academic mission of the
Department. If you have other alternative suggestions please let me know and
we will share those suggestions with the readership for additional input.
As we celebrate the arrival of Spring please join me in welcoming the launch
of this new departmental vehicle of communication.
Arshag D. Mooradian, M.D.
Professor of Medicine
Chairman, Department of Medicine
Advanced Cardiovascular Care
Probing the Potential of Gene
Marco Costa, M.D.
Division of Cardiovascular Diseases
/ despite, and
of, decreases in
mortality associated with coronary
artery disease and acute myocardial
infarction in developed countries.
Recent advances in the pharmacological
and non-pharmacological therapies
of CHF including costly procedures,
such as surgical cardiomyoplasty, heart
transplantation, bi-ventricular pacing,
implantable cardioverter defibrillators
(ICD) and left ventricle assist devices,
have been unable to produce major
survival benefits for patients with CHF.
In recent years, angiogenesis, which
refers to the formation of new arteriolas
lacking developed media from pre-
existing vessels, has been proposed as
an alternative treatment for patients
with severe CAD, CHF and poor
candidates for current revascularization
strategies. Further, angiogenesis may
become an adjunctive strategy to other
revascularization strategies, such as
PCI and CABG, in patients with
The major physiologic stimuli to
angiogenesis include tissue hypoxia
and inflammation. Initial attempts
to promote angiogenesis used
laser or other mechanical means to
create multiple small holes in the
endocardium. The use of growth factor
proteins such as vascular endothelium
growth factors or genes encoding
these proteins to promote angiogenesis
has been under study for last decade.
There is increasing evidence that cell
transplantation may improve perfusion
and contractile function of the damaged
myocardium2-5. Whether the mechanism
of action involves myocardium
repopulation or neovascularization, or
ideally both, remains to be determined.
Transplanted cells may also stimulate
the resident myocites to improve their
contractility by the release of cytokines
and improvement in blood flow.
Our understanding on stem cell biology
has advanced considerably in the past
years. Ability to direct the plasticity
of precursor stem cells has lead to the
hope that severe heart disease might be
ameliorated by cell transplant therapy6.
The demonstration of both resident
and circulating stem cells committed to
cardiac cell lines opened a new avenue
in cardiovascular research7. Progenitor
endothelial cells (PEC), which express
CD34 and CD 133(AC133) antigens,
are high in the list of candidate cells
for promoting angiogenesis. These
cells have the potential to differentiate
into vascular endothelial cells and
blood cells and ultimately promote
vasculogenesis, a phenomenon not
yet demonstrated in adult human
hearts. PECs can be identified in adult
peripheral blood, bone marrow and
human umbilical cord blood.
The ability to delivery of high
concentrations of cells, angiogenic
proteins or genes within the target
myocardium represents another
important aspect of angiogenesis
therapy for cardiac disease.
Percutaneous approaches using
direct intramyocardial injection
catheters guided by 3D imaging and
mapping (NOGA, Biosensor Webster)4
offers the advantage to assess viability
of target sites prior to each injection and
assure precise intramural delivery in a
safe and minimally invasive manner.
Continued on vaqe 3
FOCUS continued from page 2
Areas supplied by totally occluded epicardial vascular beds
can be targeted by this method. However, this technology is
costly and available in limited centers worldwide.
The division of cardiology at the University of Florida,
College of Medicine Jacksonville is committed to advance
our knowledge and develop new therapeutic modalities
for patients with advanced cardiac and peripheral vascular
disease. We have developed a comprehensive research
program in the field of angiogenesis and cell therapy.
The molecular component of the program is dedicated to
understanding the functional profile of endothelial progenitor
cells (EPC = CD34+ cells) in patients with diabetes mellitus
and/or CAD and we have conducted an initial clinical
investigation which involved 54 patients. Our group is
also exploring new approaches to stimulate angiogenesis.
We proposed the concept of injecting antibodies against
circulating progenitor cells directly into the myocardium to
recruit cells in situ. A pilot experimental study was performed
in collaboration with investigators (Dr Emerson Perin) at the
Texas Heart Institute, Houston, TX.
We recently initiated collaboration with Professor Takayuki
Asahara, MD, PhD, Director of Regenerative Medicine
and Research Kobe Institute of Biomedical Research and
Innovation, who first described the presence of circulating
progenitor cells in humans. We are currently supporting
clinical trials testing PECs for the treatment of cardiac disease
and peripheral vascular disease in Japan. Future plans are
to establish a center for expansion of progenitor cells which
would facilitate the implementation of angiogenesis therapy
in clinical practice.
Our Institution was the first in Florida to apply
transmyocardial injection of gene therapy to promote
angiogenesis in patients with advanced coronary artery
disease. We recently started the first U.S. multicenter study
for transmyocardial injection of bone marrow derived CD34+
stem cells to promote angiogenesis in patients with advanced
CAD. This clinical study uses the NOGA catheter technology
to guide and monitor cell delivery.
Finally, our division, through a collaborative effort between
the Cardiovascular Imaging Core Laboratories and the
department of Radiology developed a systematic approach
to quantify MRI data, which is currently being applied
to various angiogenesis clinical trials. The MRI data from
the first US trial testing the feasibility of intramyocardium
injection of BMC in patients with CHF, conducted at the Texas
Heart Institute, is being analyzed by our Core Laboratory.
Another collaborative clinical effort has been initiated with the
Minneapolis Heart Institute (Dr Timothy Henry) to evaluate
myocardial perfusion and function using MRI in patients who
underwent different forms of angiogenesis therapy.
1. Sousa JE, Costa MA, Tuzcu EM, Yadav JS, Ellis S. New frontiers in
interventional cardiology. Circulation. 2005;111:671-81.
2. Simons M, Bonow RO, Chronos NA, Cohen DJ, Giordano FJ, Hammond HK,
Laham RJ, Li W, Pike M, Sellke FW, Stegmann TJ, Udelson JE, Rosengart TK.
Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert
panel summary. Circulation. 2000;102:E73-86.
3. Menasche P, Hagege AA, Vilquin JT, Desnos
M, Abergel E, Pouzet B, Bel A, Sarateanu S,
Scorsin M, Schwartz K, Bruneval P, Benbunan
M, Marolleau JP, Duboc D. Autologous skeletal
myoblast transplantation for severe postinfarction
left ventricular dysfunction. J Am Coll Cardiol.
o 4. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa
AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS,
Dohmann HJ, Silva GV, Belem L, Vivacqua R, Rangel
FO, Esporcatte R, Geng YJ, Vaughn WK, Assad
JA, Mesquita ET, Willerson JT. Transendocardial,
autologous bone marrow cell transplantation for
severe, chronic ischemic heart failure. Circulation.
5. Schachinger V, Erbs S, Elsasser A, Haberbosch
W, Hambrecht R, Holschermann H, Yu J, Corti R,
Mathey DG, Hamm CW, Suselbeck T, Assmus B,
Tonn T, Dimmeler S, Zeiher AM. Intracoronary bone
marrow-derived progenitor cells in acute myocardial
infarction. N Engl J Med. 2006;355:1210-21.
6. Caplice NM, Gersh BJ. Stem cells to repair the heart: a
clinical perspective. Circ Res. 2003;92:6-8.
7. Asahara T, Murohara T, Sullivan A, Silver M, van der
Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM.
Isolation of putative progenitor endothelial cells for
angiogenesis. Science. 1997;275:964-7.
N. Stanley Nahman, Jr., M.D. (Program Director),
Olga Petrucelli, M.D. and Arpitha Ketty, M.D.
(Associate Program Directors)
The office of Graduate Medical Education seeks to advance
all facets of the academic mission, but with particular
emphasis on education. Part of the educational program
includes development of critical thinking through literature
reviews in monthly journal clubs, and facilitating the
acquisition of analytic tools for research and investigation.
In the latter area, the institution offers Dean's Fund Research
Grants for trainees that may award up to $5,000 in support.
In August 2006, the Department received five 5 such grants,
all of which were spearheaded by resident investigators. The
spectrum of funded studies was diverse and included an
assessment of kidney function in older patients with sickle
cell disease, production of a video articulating an approach to
end-of-life decisions, and the role of hepatitis C in promoting
bacteremia in dialysis patients. All projects are funded for
one year and are currently in progress.
In other areas of research, the program's mega-team approach
to the allocation of resident manpower was highlighted in
an oral presentation at the Southern Society of the American
Federation of Medical Research's Regional Meeting on
February 8 through the 10th in New Orleans. We anticipate
that this presentation will provide the basis for a follow-up
publication documenting the Department's experiences with
this novel approach to organizing resident ward teams on
inpatient medicine services.
In summary, the office of Graduate Medical Education offers
a variety of research opportunities, all of which are designed
to provide a meaningful exposure to the challenges and
rewards of original research, as well as groom forward-
thinking clinicians who will always seek improved, and
novel, approaches to patient care or education.
A CLINICAL CASE
Erik Lowman, D.O., Chief Resident
Macromelia Masquerading as an Acromegaloid
Syndrome in an Adult with Klippel-Trenaunay
Klippel-Trenaunay syndrome (KTS) is a rare congenital
condition that belongs to a family of human disorders
characterized by tissue overgrowth1. Classically the
syndrome presents as a triad of vascular malformations,
cutaneous hemangiomas and bone or soft-tissue
hypertrophy usually affecting one extremity. The tissue
hypertrophy in this syndrome is typically localized and
asymmetrical. In this communication we describe a
case of this disease in an adult patient with symmetrical
macromelia suggestive of an acromegaloid syndrome. The
serum levels of growth hormone and insulin like growth
factor one (IGF-1) were normal.
In a series of 252 patients with KTS, capillary malformations
(port-wine stains) were found in 98%, varicosities or
venous malformations in 72%, and limb hypertrophy in
67%. All three features of KTS were present in 63% of
patients studied, and 37% had two of the three features'.
Our patient had all the three components of the syndrome.
In addition he had substantial lymphedema in left lower
extremity. Lymphedema is not common although it has
been previously described.
In patients with vascular disease two mutations have been
described that have pathogenetic significance. One mutation
is the chromosomal translocation t(5;11) which increases
the transcription of VG5Q, a protein that acts as a potent
Continued on page 5
Figure: The hands of the patient shown in comparison to an average adult hand
in : ... :- ;: the symmetrical macromelia, a common feature of
A CLINICAL CASE continued from page 4
angiogenic factor2. The second is a functional mutation
of E133K that enhances the angiogenic effect of VG5Q.
Thus, VG5Q is a susceptibility gene for KTS, and increased
angiogenesis is a molecular pathogenic mechanism of this
syndrome2. The IGF2 over expression has been implicated
in the etiology of the tissue hypertrophy observed in KTS3.
The recognition of this syndrome will help avoid any
unnecessary and extensive work up for acromegaly.
1. Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW,
Clay RP, Gloviczki P. Klippel-Trenaunay syndrome:
spectrum and management. Mayo Clin Proc.
2. Tian XL, Kadaba R, You SA, Liu M, Timur AA, Yang
L, Chen Q, Szafranski P, Rao S, Wu L, Housman
DE, DiCorleto PE, Driscoll DJ, Borrow J, Wang Q.
Identification of an angiogenic factor that when
mutated causes susceptibility to Klippel-Trenaunay
syndrome. Nature. 2004;427:592-4.
3. Sperandeo MP, Ungaro P, Vernucci M, Pedone PV,
Cerrato F, Perone L, Casola S, Cubellis MV, Bruni
CB, Andria G, Sebastio G, Riccio A. Relaxation of
insulin-like growth factor 2 imprinting and discordant
methylation at KvDMR1 in two first cousins affected by
Beckwith-Wiedemann and Klippel-Trenaunay Weber
syndromes. Am J Hum Genet. 2000;66:841-7.
NEWS AND NOTES
Gliptins: A New Therapeutic Option for
These agents are selective inhibitors of dipeptidyl peptidase
4 (DPP-4), the enzyme that degrades incretins as well as
other select peptides. The incretins, such as glucagon -like
peptide-1 (GLP- 1) or glucose-dependent insulinotropic
peptide (GIP) are secreted by the gut following nutrient
ingestion and have multiple biologic effects including,
augmentation of insulin secretion, inhibition of glucagon
secretion, inhibition of gastric emptying and enhancing
Vildagliptin and sitagliptin (approved by FDA 10/2006) are
two agents that belong to this class. In clinical trials they
have been shown to be effective as either monotherapy or
as an adjuvant therapy to metformin, thiazolidenediones
and possibly with insulin in a select group of patients.
The advantages of these agents include lack of significant
risk of hypoglycemia, lack of weight gain and possibly
preservation of pancreatic beta cells. The disadvantages
include cost, lack of long term safety data, and uncertainty
as to the optimal patient population to target.
Internal Medicine Residency Program Receives
The Anne and Max Michael, Jr. Education fund is founded by
Mrs. Anne Michael in memory of her late husband, Dr. Max
Michael, Jr. who was the first Dean in the Jacksonville campus
This fund awards a hand crafted wood lacquered rocker with
a gold screen printed seal of the University of Florida from
1873, to our graduates who complete a three year residency
training program in Internal Medicine.
Mrs. Michael was at the Department of Medicine Annual
Award Banquet on June 2, 2006 at The River Club, to present
to the first graduating class to receive these special rockers
with Dr. Stan Nahman.
Figure N. Stanley Nahman, Jr., M.D. ( ; Director) and Mrs. Anne Michael
UF Shands From ancient times
U & when stone masons
Ta 0'1on clle began cutting their
~Jao v flL trademark signatures
The University Of Florida Health System into the house facades
they created, branding has been essential to society. But
unlike those ancient artisans, a modern brand is not just a
logo. Instead, a brand is more of a "feeling" than anything
tangible. This "feeling" is what a properly developed brand
represents to its audience and how successful brands are
built. Brands like Volvo or Nike have been carefully crafted
over the years to symbolize "safety" and "competitive
sports" respectively. Those carefully created brands enjoy
a loyal audience as well as a higher value relative to a
lesser-known competitor. What the UF&Shands brand is
now doing is no different. In 2004, we began an awareness
campaign of the brand which was the combination of the
two entities The University of Florida Health Science
Center and Shands HealthCare.
The next phase of the branding campaign will spotlight
the power of "&", and what we have accomplished by
working together. Amazing stories are being told every day
in our corridors stories of medical breakthroughs, better
treatment options and strong patient relationships. Just as
the ampersand links our organizations, the symbol is used
as a visual theme throughout the campaign to highlight our
important connections. Filming and photography took place
in October and November 2006, and the campaign launched
in January. Television and radio spots will run on local
broadcast and cable channels, supported by ads in major
newspapers and regional magazines.
Next time you see the ads, perhaps you'll see yourself or
one of your colleagues and feel your contributions to the
"Science of Hope".
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