Addendum - VU

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Addendum
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Abbreviations
LIST OF ABBREVIATIONS
ACTA-2 AGEs
ANOVA ATFP
BMI
Col COL1α1
COL 3α1
CML
DES
ECM
ER
ET-1
FBs
FC
FDA FDR
GSEA
HP
HPLC
HYP
hUBC IL-6
IQR
LP
LOX
MMP POP
POP-Q
Pro
RIN
RT-PCR SAM
SD SMCs
TIMPs TNF-α
USL
USR
Ywhaz Alpha Smooth Muscle Actin
Advanced Glycation Endproducts
One-way Analysis Of Variance
Arcus tendineus fasciae pelvis
Body Mass Index
Collagen
Collagen 1α1
Collagen 3α1
Cyclic Mechanical Loading
Desmin
Extracellular Matrix
Estrogen Receptor
Endothelin-1
Fibroblasts
Fold Change
Food and Drug Administration
False Discovery Range
Gene Set Enrichment Analysis
Hydroxylysylyridinoline
High-Performance Liquid Chromatography
Hydroxyproline
Human ubiquitin C
Interleukine 6
Inter Quartile Range
Lysylpyridinoline
Lysyl Oxidases
Matrix Metalloproteinases
Pelvic Organ Prolapse
Pelvic Organ Prolapse Quantification
Proline
RNA Integrity Number
Reverse Transcription Polymerase Chain Reaction
Significance Analysis of Microarrays
Standard Deviation
Smooth Muscle Cells
Tissue derived inhibitors of metalloproteinases
Tumor Necrotic Factor-α
Uterosacral Ligaments
Uterosacral Ligament Resilience
Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase
activation protein, zeta polypeptide
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POP-Q
PELVIC ORGAN QUANTIFICATION SYSTEM (POP-Q)
Pelvic Organ Prolapse Quantification system (POP-Q) refers to an objective, site–
specific system for describing, quantifying, and staging pelvic support in women.1
It provides a standardized tool for documenting, comparing, and communicating
clinical findings with proven interobserver and intraobserver reliability.2 The POPQ system is being approved by the International Continence Society (ICS), the
International Urogynecology Association (IUGA), the American Urogynecologic
Society (AUGS), and the Society of Gynecologic Surgeons for the description of
female pelvic organ prolapse.
The system relies on specific measurements of defined points in the midline of
the vaginal wall. The hymen acts as the fixed point of reference throughout the
POPQ system. There are six defined points for measurement in the POPQ system
- Aa, Ba, C, D, Ap, Bp and three others landmarks: GH, TVL, PB. Each is measured
in centimeters above or proximal to the hymen (negative number) or centimeters
below or distal to the hymen (positive number) with the plane of the hymen being
defined as zero (0). The hymen was selected as the reference point rather the
introitus because it is more precisely identified.
There are three reference points anteriorly (Aa, Ba, and C) and three posteriorly
(Ap, Bp, and D). Points Aa and Ap are 3 cm proximal to or above the hymenal ring
anteriorly and posteriorly, respectively. Points Ba and Bp are defined as the lowest
points of the prolapse between Aa anteriorly or Ap posteriorly and the vaginal
apex. Anteriorly, the apex is point C (cervix), and posteriorly is point D (pouch of
Douglas). In women after hysterectomy, point C is the vaginal cuff and point D
is omitted. Three other measurements are taken: the vaginal length at rest, the
genital hiatus (gh) from the middle of the urethral meatus to the posterior hymenal
ring, and the perineal body (pb) from the posterior aspect of the genital hiatus to
the midanal opening (Figure 1).
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POP-Q
Figure 1. Points and landmarks
for POP–Q system examination.
Aa; point A anterior
Ap; point A posterior
Ba; point B anterior
Bp; point B posterior
C; cervix or vaginal cuff
D; posterior fornix (if cervix is
present)
gh; genital hiatus
pb; perineal body
tvl: total vaginal length.
The specific measurements at nine sites are recorded in a tic–tac–toe grid as shown
in Figure 2 where after the corresponding POP-Q stage is assigned (Table 1).
Table 1. Stages of POP–Q system measurement.
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Stage (0)
No prolapse is demonstrated.
Stage (I)
Most distal portion of the prolapse is more than 1 cm above the
level of the hymen
Stage (II)
Most distal portion of the prolapse is 1 cm or less proximal to or
distal to the plane of the hymen.
Stage (III)
The most distal portion of the prolapse is more than 1 cm below
the plane of the hymen.
Stage (IV)
Complete eversion of the total length of the lower genital tract
is demonstrated.
An example of measurements using the POP–Q system is shown in Figure 2. This
example represents a predominantly posterior support defect. Leading point of
prolapse is upper posterior vaginal wall, point Bp (+5). Point Ap is 2 cm distal to
hymen (+2) and vaginal cuff scar (after hysterectomy) is 6 cm above hymen (–6). Cuff
has undergone only 2 cm of descent because it would be at –8 (total vaginal length)
if it were properly supported. This represents stage III prolapse.1
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POP-Q
Figure 2. Example of measurements
using the POP–Q system.
REFERENCE LIST
1. 2. Bump RC, Mattiasson A, Bo K, Brubaker LP, Delancey JO, Klarskov P et al. The standardization
of terminology of female pelvic organ prolapse and pelvic floor dysfunction.
Am.J.Obstet.Gynecol. 1996;175:10-17:10-17.
Hall AF, Theofrastous JP, Cundiff GW, Harris RL, Hamilton LF, Swift SE et al. Interobserver and
intraobserver reliability of the proposed International Continence Society, Society of Gynecologic
Surgeons, and American Urogynecologic Society pelvic organ prolapse classification system.
Am.J.Obstet.Gynecol. 1996;175:1467-70.
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Flexercell Device
FLEXERCELL DEVICE
Fibroblasts Flexercell Cultured for 3-‐5 passages Loading post Elas3c membrane +/-‐ Collagen type I Vacuum force Morphological changes Extracellular matrix (ECM) remodeling factors Cyclic mechanical loading (CML) mimicking normal breathing cycle (sinus wave, 10%, 0.2 Hz) Acknowledgement: A.M. Ruiz-Zapata for designing the figure.
The Flexercell FX4000 system (Flexcell International Corp., McKeesport, PA, USA)
is a device which is extensively used to study the effects of mechanical loading on
cultured cells. It has a vacuum pump that pulls down the elastic membrane of the
bioflex plates stretching the cells that are seeded on top accordingly. The elastic
membranes can be uncoated or coated with different types of collagens, elastin,
pronectin and laminin (BioFlex, Flexcell International Corp.).
In our study (Chapter 5 and 6) fibroblasts from healthy and women with pelvic
organ prolapse, were subjected to cyclic mechanical loading mimicking continuous
respiration on artificial polymeric membranes uncoated as well as coated with
collagen I. Changes in morphology and anabolic/catabolic compounds that may
affect the remodeling of the extracellular matrix were analysed.
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Authors and affiliations
AUTHORS AND AFFILIATIONS
Jeroen A.M. Belien, PhD
Maaike C.G. Bleeker, MD, PhD
Herman Bril, MD, PhD
Hans A.M. Brölmann, MD, PhD
Marco N. Helder, PhD
Linda Hendriks, MD Alejandra M. Ruiz-Zapata, MSc
Theo H. Smit, PhD
Reinout Stoop, PhD
Saskia Vosslamber, PhD
Behrouz Zandieh-Doulabi, PhD
Department of Pathology,
VU University medical center,
Amsterdam, The Netherlands.
Department of Pathology,
VU University medical center, Amsterdam, The Netherlands.
Department of Pathology,
Kennemer Gasthuis Hospital, Haarlem, The Netherlands.
Department of Obstetrics & Gynecology,
VU University medical center,
Amsterdam, The Netherlands.
Department of of Orthopedics,
VU University medical center,
Amsterdam, The Netherlands.
Department of Obstetrics & Gynecology,
VU University medical center,
Amsterdam, The Netherlands.
Department of of Orthopedics and
Oral Cell Biology,
ACTA- University of Amsterdam and
VU University, Research Institute MOVE,
Amsterdam, The Netherlands.
Department of of Orthopedics,
VU University medical center,
Amsterdam, The Netherlands.
Department of Metabolic Health Research,
TNO, Leiden, The Netherlands.
Department of Pathology,
VU University medical center, Amsterdam, The Netherlands.
Department of of Orthopedics and
Oral Cell Biology,
ACTA- University of Amsterdam and
VU University, Research Institute MOVE,
Amsterdam, The Netherlands.
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List of publications
LIST OF PUBLICATIONS
M.H. Kerkhof, A.M. Ruiz-Zapata, H. Bril, M.C.G. Bleeker, J.A.M. Belien, R. Stoop and
M.N. Helder. Changes in tissue composition of the vaginal wall of premenopausal
women with prolapse.
Am J Obstet Gynecol. 2013. 210, 168.e1-9.
A.M. Ruiz-Zapata, M.H. Kerkhof, B. Zandieh-Doulabi, H.A.M. Brölmann, Th.H. Smit
and Marco N. Helder. Fibroblasts from women with pelvic organ prolapse show
differential mechano-responses depending on surface substrates.
Int Urogynecol J Pelvic Floor Dysfunct. 2013 Sep: 24(9):1567-75.
M.H. Kerkhof. Hoeveel rek zit er in een prolaps?
Linneaus medisch Journaal (2011) 19:2:54-56.
M.H. Kerkhof, L. Hendriks, H.A.M. Brölmann. Changes in connective tissue in
patients with pelvic organ prolapse, a systematic review of literature. Urogynecol J
Pelvic Floor Dysfunct. 2009 Apr: 20(4): 461-74.
M.H. Kerkhof. Verzakking, een bindweefselziekte?
Linneaus medisch Journaal (2009) 17:1:1-33.
M.H. Kerkhof. Urine incontinentie.
Merck Manual. Leeftijd en gezondheid. 2008 p745-75.
M.H. Kerkhof and I. Scholten. POP leading to end stage renal failure.
J Fam Pract. In press.
M.H. Kerkhof, A.M. Ruiz-Zapata, B. Zandieh-Doulabi, H.A.M. Brölmann, Th.H. Smit,
S. Vosslamber, Marco N. Helder. Gene expression in anterior vaginal wall from
premenopausal patients with pelvic organ prolapse (submitted).
M.H. Kerkhof, A.M. Ruiz-Zapata, Zandieh-Doulabi, H.A.M. Brölmann, Th.H.
Smit and Marco N. Helder. Functional characteristics of vaginal fibroblasts from
premenopausal women with pelvic organ prolapse (submitted).
D.M. Koppes, R.P. Schellart RP, M.I. Withagen, M.H. Kerkhof. Anterior vaginal wall
prolapse, the comparison of three different surgical techniques (submitted).
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