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Objectives:
The investigators hypothesize that the valves of dogs
with mitral valve disease (MVD) possess inherently
different geometrical characteristics when compared to
those of non-affected dogs. They propose to use a novel
3-D echocardiographic technique to correlate the valve
geometry with disease severity, ventricular function and
geometry, and conventional 2-D echocardiographic
measurements of mitral valve disease.
Background:
It is not known whether breeds (like CKCS) that are
predisposed to spontaneous mitral valve disease (MVD)
have inherent abnormalities in valve geometry that lead
to, or promote, development of the disease. Any such
geometric abnormalities cannot be adequately evaluated
by currently standard techniques, such as 2-D
echocardiography. The investigators plan to use new 3-D
echocardiography techniques and specialized image
reconstruction to visualize the geometry of the valve
annulus and valve leaflets in greater detail. They will
study Cavaliers with MVD, Cavaliers without clinical MVD
(a “non-affected, predisposed” dog population), and
unaffected dogs from other, large breeds (a
“non-affected, non-predisposed” population). These
results will be correlated with clinical and
echocardiographic parameters of disease severity, and
will be compared between the three study groups to
determine whether dogs predisposed to MVD have inherent
mitral valve abnormalities that predispose them to
development of the disease. |
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Grant 105
Institution:
The Ohio State University
Title of Project:
The Study of Caudal Occipital Malformation Syndrome (COMS)
in Cavalier King Charles Spaniels
Investigators: Carley J. Abramson, DVM and Phil March, DVM.
Duration:
2005-2007
Objectives:
The goals of this study were to assess the correlation
between the severity of clinical signs and the MRI
findings in dogs affected with caudal occipital
malformation syndrome (COMS) and to evaluate potential
objective, non-invasive markers of COMS that might be
used to detect the disease, assess its severity, select
patients for surgical correction, and follow the
effectiveness of surgery.
Findings:
COMS is a serious condition in dogs that can have severe
neurological consequences. At present, reliable
diagnosis is only possible with magnetic resonance
imaging (MRI), which is expensive, requires sedation,
and adds complexity to the evaluation of dogs suspected
of having COMS. The investigators evaluated seven other
non-invasive tests and parameters in 52 dogs and
compared those results to MRI findings. Analysis so far
indicates that none of the proposed non-invasive,
non-sedation-requiring screening tests for COMS that
were hoped to evolve out of this study will produce
sufficiently reliable results. However, they also
evaluated novel MRI techniques to assess the patterns of
flow of the cerebrospinal fluid around and within the
spinal cord in Cavaliers with COMS. These results may be
important in understanding this disease and assessing
the effectiveness of surgery or other therapies. Dr.
March is currently at Tufts University, where he hopes
to continue these investigations. |
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Grant 104
Institution:
The Stone Lion Veterinary Centre, Wimbledon, England
The Centre for Applied
Genomics, Hospital for Sick Children in Toronto
The Centre for Research in
Neuroscience, McGill University in Montreal
The Comparative Neuromuscular
Laboratory, UC San Diego
Title of Project:
The Study of the
Successful Collection and Archiving of DNA from Cavalier
King
Charles Spaniels, Enabling a Genome Scan to be
performed.
Investigators:
Clare Rusbridge, BVMS; Penny Knowler, BSc; Berge A
Minassian, MD, CM; Guy
A. Rouleau, MD, PhD; Diane Shelton, DVM, PhD.
Duration:
2005-2007
Objectives:
This was a pilot study of the collection and archiving
of DNA from Cavalier King Charles Spaniels, with the
eventual goal of enabling a genome scan to be performed.
This study is part of a much larger investigation that
is aimed at performing large-scale DNA archiving, and
genomic and genealogical analysis, with the goal of
localizing the genes associated with syringomyelia,
mitral valve degeneration, and epilepsy. This is a large
study, funded by several organizations and involving
multiple breeds. The portion of this study funded by the
Cavalier Health Foundation was the
collection and archival of DNA
samples for 400 CKCSs in North America, to supplement
the investigators’ ongoing data collection in the United
Kingdom and Australia.
Findings:
The
investigators have collected DNA samples from over 1500
CKCS dogs, including the 400 funded by the Foundation.
They have also constructed a genealogy of over 10600
related CKCS dogs from over 600 MRI-confirmed
syringomyelia dogs, as well as 273 with mitral valve
disease and 62 with epilepsy. Preliminary results have
suggested six interesting regions on six associated
chromosomes that warrant further investigation. The
investigators are currently investigating these six
candidate regions by further genetic analysis in
additional affected sibling-pair dogs with syringomyelia.
The investigators are pursuing additional funding to
extend and expand their project. |
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Grant 103
Institution:
University of Tennessee
Title of Project:
Quantitative, Functional, and Morphologic
Characterization of Platelets in the
Cavalier King Charles Spaniel
Investigator: Sarah M. Cowan, DVM
Duration:
2002-2003
Objectives:
This was a pilot study designed as an effort to
characterize the commonly reported, inherited
abnormalities of platelets (macrothrombocytosis and
thrombocytopenia) in Cavalier King Charles Spaniels.
Findings:
Thrombocytopenia (low platelet count) and
macrothrombocytosis (abnormally large platelet cells)
are commonly-encountered blood-count abnormalities in
Cavaliers. This study was aimed at quantifying this
problem and assessing its clinical significance.
Thrombocytopenia was present in 51% of the 69 CKCSs in
the study, and macrothrombocytes were present in
one-third. Co-incidentally, 38% of the dogs in this
study had cardiac murmurs, though any linkage between
the two will require much further study. However,
overall platelet function appeared normal. The
investigators termed the disorder “Benign Inherited
Giant Platelet Disorder” (IGPD). Significantly, the
investigators noted that platelet counting by automated
instruments is particularly prone to error in this
condition and that platelet counts in affected animals
should always be performed manually.
Several abstracts and one published paper have
originated from this study, which won the award for best
resident abstract at the 2002 Meeting of the
American College of Veterinary Internal Medicine. Dr.
Cowan is now located at The Veterinary Specialist Centre
in Sidney, Australia and is continuing her research on
platelet function in Cavaliers and the possible genetic
relationship of this abnormality with mitral valve
disease.
Awarded Best Resident Abstract at the ACVIM Forum in
2002 |
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Grant 102
Institution:
North Carolina State University
Title of Project:
Identification of Mitogenic Receptors Associated with
Chronic Valvular Heart
Disease in Cavalier King Charles Spaniels
Investigators:
Bruce W. Keene, DVM, MSc; Natasha J. Olby, VetMB, PhD;
Sharon C. Hinkle PhD;
David Malarkey, DVM, PhD; Francis W.K. Smith III, DVM;
Teresa C. DeFrancesco,
DVM; William Rausch, DVM; Jens Haggstrom, DVM; Clarke E.
Atkins, DVM.
Duration:
2001-2002
Objectives:
This was a pilot study designed to identify specific
receptors on heart valves that may be involved in the
development of Cavalier heart valve disease.
Findings:
Special microscopic staining of heart valve tissues from
dogs with and without mitral valve disease was performed
to assess the levels of several types of receptors.
These types of receptors are triggered by a variety of
specific molecules that play many roles within the body,
including the regulation of cell numbers within tissues,
cell activity, and the balance between cell division and
programmed cell death. Such molecules, called mitogens,
have been implicated by some investigators in human
valvular disease associated with certain drugs, like
fenfluramine. The investigators in this study found
mitogen receptor levels in valvular tissues somewhat
different from those reported in earlier publications by
other authors. The investigators have proposed several
possible causes for the discrepancy between their
results and previous studies. They suggest that further
studies be performed, using valvular tissues from larger
numbers of affected and control animals, as well as
testing for additional subtypes of these mitogenic
receptors |
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Grant 101
Institution:
Texas A&M University
Title of Project: Effect of Carvedilol in Dogs with Chronic Degenerative Valve Disease
Investigators:
Sonya G. Gordon, BSc, DVM, DVSc; Dawn M. Boothe, DVM,
PhD; Matthew W.
Miller, DVM, MS; Anne Bahr, DVM, MS; and Wendy
Arsenault, DVM.
Duration:
2001-2004
Objectives:
This study was a pilot project to evaluate the use of a
beta-blocker, carvedilol, in Cavaliers with mitral valve
disease (MVD). Beta blockers are often used in humans
to improve the heart's pumping ability. The primary
goal of this study was to determine the most effective
dosing for carvedilol in CKCS dogs, and to lay a
foundation for future studies to determine if carvedilol
will slow the progression of MVD in affected dogs.
Findings:
The
investigators have completed the assessment of the
biological effects and metabolism of carvedilol in
normal dogs, and have established safe and effective
dosage regimens. They have developed an oral suspension
of carvedilol that allows for precise dosing of canine
cardiac patients – a requirement for rigorous clinical
trials. Their early clinical results suggest that
carvedilol improves the heart’s pumping action in
Cavaliers with MVD that have not yet developed symptoms.
So far, six abstracts and two scientific papers have
been published from this work. One of these abstracts
was awarded “Best Resident Abstract” at the 2003
American College of Veterinary Internal Medicine Forum.
The investigators are continuing their research in this
field and are planning a larger study to determine
whether treatment of asymptomatic Cavaliers with MVD
will delay onset of clinical signs and symptoms of
congestive heart failure.
Awarded
Best Resident Abstract at the ACVIM Forum in 2003 |
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