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Invited presentations / International Journal of Gynecology & Obstetrics 107S2 (2009) S1–S92 S87
I350
Stem cells in drug discovery and development
A. Trounson. California Institute for Regenerative Medicine, San
Francisco, CA, USA
The California Institute for Regenerative Medicine (CIRM) was
established by Proposition 71 in 2004 to fund pluripotential
stem cell and progenitor cell research and their applications in
regenerative medicine, in response to the Bush Administration’s
Presidential proclamation to restrict US federal funding of
embryonic stem cell research. CIRM is provided with $US3 billion
from the sale of state bonds for funding a program which calls for
research applications (RFAs) from Californian research institutions,
medical centers and companies. In the first 3 years of grant
and facilities funding CIRM has committed around $US800mill.
CIRM has also negotiated duel funding arrangements for scientific
collaborations with a number of international funding bodies
(including the State of Victoria Australia, the Canadian Cancer
Consortium, MRC UK, MICINN Spain, JST Japan and Junior Diabetes
Research Foundation) for funding collaborative research with
California scientists.
New discoveries are rapidly occurring in stem cell biology and
directed differentiation. New pluripotent cell types have been
created by transduction using specific transcription factors (induced
pluripotent stem cells – iPS cells) integrated by viral constructs
of human genes and by recombinant proteins. This is enabling
determination of disease heterogeneity, cause of diseases and
the identification of small molecule candidates for control of
phenotype. Embryonic stem cells are moving forward to clinical
trials and biotechnology companies are partnering with researchers
to derive the risk and effectiveness data needed for INDs
(registrations for clinical trial). CIRM is supporting the team
approach to IND with substantial funding (up to $US20 mill). There
are more than 30 new proposals invited for review for support
for disease teams who are confident of achieving an IND within
4 years. This includes embryonic stem cell, iPS cell projects and new
candidate drugs that have been discovered using high throughput
screening using stem cell assays.
Cancer stem cells are also an important area for CIRM support.
These cells relate to pluripotent stem cells but have lost the
key regulatory machinery to control differentiation, apoptosis and
senescence, and have upgraded proliferation as a key phenotype. It
is proposed that the cancer stem cell is maintained in a protective
quiescent niche that enables them to escape conventional cancer
therapies aimed at rapidly proliferating cells. Consequently, cancer
can be reseeded by the cancer stem cell, often years after chemo-
or radiotherapy, with consequent multiple metastases. Identifying
and targeting the putative cancer stem cell requires recognition
of stable cancer stem cell biomarkers and targeting strategies. The
targeting of inoperable gliomas using the tropism of transplanted
neural stem cells containing engineered lethal cell substrates that
can kill existing tumors, is an example of the approaching cell
therapeutics in this area.
(see www. cirm.ca.gov).
I351
Caesarean section on demand – A psychosomatic challenge?
S. Tschudin
Background: The percentage of deliveries by cesarean section (CS)
increased during the last decades and might be partly due to a
rising number of CS performed on demand of pregnant women.
With regard to somatic consequences of performing CS without
medical reasons evidence remains controversial, current knowledge
on psychological effects and sequelae is limited. The talk aims at
discussing the psychosomatic impact of CS on demand.
Material and Method: Literature findings on prevalence and
reasons for CS on demand will be discussed and results of a
survey will be presented. The cross-sectional survey consisted
of an anonymous structured questionnaire and assessed pregnant
women’s awareness of and attitudes towards CS on demand and
identified medical and psychological predictors pertaining to the
decision for CS on demand.
Results: According to the literature the percentage of CS on demand
varies between less than 3% and up to 20% of all CS. Besides
mainly rational considerations, such as prevention of incontinence,
emotions, such as fear of pain or loss of control, concerns about the
baby’s well-being or a traumatically experienced preceding birth
are associated with the demand for elective CS. In our study 10% of
pregnant women seriously considered delivering by CS on demand
and a negative previous birth experience and a preceding CS were
predictors for the wish to deliver by CS.
Conclusion: From a psychosomatic perspective specific supportive
care during first pregnancy could play a pivotal role in preventing
negative birth experience resulting in CS on demand.
I352
Emergency obstetric hysterectomy
M. Turner. UCD Professor of Obstetrics and Gynaecology, Coombe
Women & Infants University Hospital and St. Vincent’s University
Hospital, Ireland
Obstetric hysterectomy is an unusual but serious complication
of childbirth. It is associated with considerable morbidity and
occasional maternal mortality. It abruptly limits family size. The
incidence varies depending on the healthcare setting and on clinical
practice. Estimates of 1.0 per 1000 deliveries have been reported
(Shah and Wright, 2009).
In a large Irish university hospital we had 31 obstetric
hysterectomies in 114,698 women who delivered a baby weighing
500 g or more, between 1992 and 2007 giving a rate of 0.27
per 1000 (1 in 3670). This compares with an incidence of 1 in
5953 deliveries in the hospital in the previous decade 1982–91.
There were only two cases in 46,276 primigravidas (1 in 23,143)
compared with 29 cases in 68,422 multigravidas (1 in 2259). The
two cases of hysterectomy in primigravidas were associated with
surgical complications of caesarean section and not uterine atony.
Of the 29 cases in multigravidas, 27 were associated with caesarean
section or a history of a previous section.
Obstetric hysterectomy worldwide is evolving and there are
conflicting trends. The more effective use of pharmacological
therapies and the introduction of balloon tamponade decreases
hysterectomies for uterine atony. Increasing caesarean section rates
increase hysterectomies for both pathological placentation and
uterine rupture.
Hysterectomies for uterine atony are usually unpredictable and
present as an emergency. They may be subtotal, which is technically
easier to perform than total. Staff drills for unpredictable massive
haemorrhage should minimise hysterectomies for uterine atony.
Hysterectomy for placentation pathology needs to be total if there
is haemorrhage from the placental bed involving the cervix.
They are often elective but the surgery may be highly complex
leading to serious complications. Involvement of colleagues
specialising in gynaecological cancer surgery should minimise
morbidity for hysterectomies associated with pathological placental
localisation.
I353
Virtual reality or boxtrainer: Does the investment make a
difference?
K.M. Uv
There are numerous laparoscopic simulators commercially
available. Basically they can be divided into two different kinds,
Virtual Reality (VR) and BoxTrainers, in addition there are hybrid
simulators. They all have pros and cons. In favour of the
VR is the possibility to simulate operations like, Adnexectomy,
Tubectomy, Hysterectomy, Ectopic pregnancy, etc. In addition the