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| Anne
Barbara Tietz |
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Home
Institution
Westfälische Wilhelms-Universität Münster
Host
Institution
Tufts University School of Medicine, Department of Cardiovascular Research,
St. Elizabeth's Hospital
Mentors: Jeffrey M. Isner, M.D., Douglas W. Losordo, M.D.
Clinical
Rotation
New England Medical Center, St. Elizabeth's Hospital (Anaesthesia)
E-Mail
annetietz@gmx.de
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Research
Topic
see Abstract |
Personal
Reactions to the U.S. Experience
It was an extremely enriching time getting to know the structural and practical
aspects of research in the US, not even to mention the personal contacts
and experiences. Doing three clinical rotations in the end, I was confronted
with the clinical life, which can be demanding because of the early starting
hours in the morning. However, you get fully compensated with extremely
good teaching. |
Greatest
Difficulties Encountered
This probably is what everybody will mention: finding an affordable room
in Boston! Plan on looking for a room for at least a week and even try to
check the web before you come over! Don't be shocked by the horrendous cost
of living. You will stop converting from $ to Euro soon! |
Most
humorous incident
This is something that cannot be summarized in one sentence. In general,
it is the discovery that it is a very small world and that no matter where
you go, someone will always know someone else that you also know from somewhere.
Other than that: our parties on Brattle Street, you could ever forget about
them!? Thanks, Carin! |
Helpful
Hints for Future Students
- Save some money beforehand or try to get additional financial support.
Boston is the best place to live but quite expensive. You could ask your
lab for support, apply for a Rotary stipend, etc.
- Try to work on your visa ahead of time. Call the responsible administrative
person if they don't get back to you.
- When looking for a room, the following websites might be helpful: www.bostonapartments.com,
http://euroclub.mit.edu/bboard/housing.html
(You can also get on their mailing list, a good link when you are looking
for furniture, etc). If you cannot find anything right away, it might be
worth calling Mrs.Clouser from 'At Home In Boston' who founded an organization
that matches students with families even on a short term basis. |
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Abstract
on Research Topic:
Cisplatin-induced peripheral neuropathy is the result of vascular injury
to the vasa nervorum and benefits from therapeutic angiogenesis by Vascular
Endothelial Growth Factor (VEGF) gene therapy |
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Authors:
Anne Barbara Tietz, Rudolf Kirchmair, Dirk H. Walter, Kilian Rittig, Jeffrey
M. Isner
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Institution
at which research was done:
Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts
University, Boston, MA |
Purpose:
Neuropathies induced by cisplatin or other chemotherapeutics occur with
high incidence, lack effective treatment and oftentimes represent the dose-limiting
factor for chemotherapies. Our hypothesis was that experimental toxic neuropathy
is a consequence of destruction of the vasa nervorum and can be reversed
by administration of VEGF. |
Materials
and Methods:
Male Sprague-Dawley rats were treated by intra-peritoneal injections of
cisplatin one a week for 9 weeks. Saline-injected animals served as a control
group. For VEGF gene transfer two groups were studied: One group of rats
received VEGF concomitantly with cisplatin treatment, the other was given
VEGF after 9 weeks of cisplatin. Sciatic nerve motor and sensory nerve conduction
velocity was measured before and after cisplatin/saline administration.
Vascularity of sciatic nerves was assessed by in situ fluorescent staining
using the endothelial cell-specific marker BS-1 lectin. Hindlimbs were perfused
with BS-1 lectin via the abdominal aorta. Afterwards sciatic nerves were
excised and fixed in 1% paraformaldehyde. Samples were analyzed using a
fluorescent microscope and labeled endoneurial vasa nervorum were counted
per cross section. Another group of immersion fixed nerves were subsequently
post-fixed with osmium tetroxide and embedded in epoxy resin for semi thin
sections and subsequent staining with methylene blue. |
Results:
Motor (MCV) and sensory (SCV) nerve conduction velocities (NCV) were stable
over the time of the study in control animals. Cisplatin treatment resulted
in a significant reduction of MCV and SCV (p< 0.05 vs. baseline) as measured
5 days after the last cisplatin injection. NCV showed a significant increase
in sensory as well as motor conduction velocity measured 3,6 and 12 weeks
after VEGF gene therapy. However, NCV did not increase after saline injection
in the control group. The subgroup of rats that received VEGF concomitantly
to cisplatin injections showed a significantly greater NCV than rats that
had not received VEGF gene therapy and neither sensory nor motor conduction
velocity declined compared to baseline values.Whole mount staining of sciatic
nerves showed markedly reduced vasa nervorum in cisplatin treated, saline
injected animals whereas VEGF gene transfer, performed after cisplatin treatment,
restored the nerve vasculature as judged by gross observation and counts
in nerve cross sections. The sciatic nerve histology revealed signs of axonal
degeneration, loss of myelinated fibers, fibrosis and myelin phagocytosis
by macrophages in cisplatin treated rats. In animals receiving VEGF treatment
after cisplatin therapy as well as in rats that received VEGF in parallel
with cisplatin, axonal damage was not detected. |
Conclusion:
We demonstrate that cisplatin-induced neuropathy is caused by vascular injury
to the vasa nervorum and is reversed and inhibited by gene therapy with
the angiogenic cytokine, VEGF. These data suggest a potential strategy to
preserve nerve function in patients undergoing chemotherapy and allow more
effective dosing of chemotherapeutic agents. |
