- Urogynecology & Pelvic Reconstructive Surgery
- Obstetrics and Gynecology
Co-Chief, Division of Urogynecology and Pelvic Reconstructive Surgery, Stanford University (2011 - Present)
Honors & Awards
Faculty member, Educators-for-Care Program, Stanford University (2008)
Excellence in Teaching Award, Association of Professors of Gynecology and Obstetrics and Gynecology (2006)
One of America's Top Obstetricians and Gynecologists, Consumers' Research Council of America (2006-2007)
Outstanding Faculty Professor of Gynecology, Resident Staff of Obstetrics and Gynecology, Stanford University (2004-2005)
Top Doctor in Silicon Valley, San Jose Magazine (2000-2002)
Board Certification: Female Pelvic Medicine and Reconstructive Surgery, American Board of Obstetrics and Gynecology (2013)
Residency:Stanford University School of Medicine (1995) CA
Internship:Stanford University School of Medicine (1992) CA
Board Certification: Obstetrics and Gynecology, American Board of Obstetrics and Gynecology (1997)
Medical Education:Stanford University School of Medicine (1991) CA
Community and International Work
Stanford Eritrean Women's Health Project, Eritrea, Africa
Long-term outcomes of surgical treatment of vesicovaginal fistulas.
Stanford University and the Eritrean Ministry of Health, Eritrea, Africa
Women and girls of rural Eritrea, Africa
Opportunities for Student Involvement
Consulting gynecologist for Koko, the gorilla, Woodside, California
Performed first-ever complete gynecologic examination on Koko, the gorilla
The Gorilla Foundation of Woodside, California
Koko, the gorilla
Opportunities for Student Involvement
Medical mission, Neuvo Progreso, Guatemala
Urogynecologic and pelvic reconstructive surgery
Hospital de la Familia
Women and girls in an under-served area of Central America
Opportunities for Student Involvement
Current Research and Scholarly Interests
Dr. Chen’s research examines the molecular causes of urinary incontinence and pelvic floor dysfunction. Recognizing that urinary incontinence linked to demise of smooth muscle sphincter function, she is investigating the potential use of stem cell regeneration to restore muscle capacity.
Independent Studies (5)
- Directed Reading in Obstetrics and Gynecology
OBGYN 299 (Aut, Win, Spr, Sum)
- Early Clinical Experience in Obstetrics and Gynecology
OBGYN 280 (Aut, Win, Spr, Sum)
- Graduate Research in Reproductive Biology
OBGYN 399 (Aut, Win, Spr, Sum)
- Medical Scholars Research
OBGYN 370 (Aut, Win, Spr, Sum)
- Undergraduate Research in Reproductive Biology
OBGYN 199 (Aut, Win, Spr, Sum)
- Directed Reading in Obstetrics and Gynecology
Impact of the 2011 FDA transvaginal mesh safety update on AUGS members' use of synthetic mesh and biologic grafts in pelvic reconstructive surgery.
Female pelvic medicine & reconstructive surgery
; 19 (4): 191-8
To describe the frequency of use and recent change in use of synthetic mesh and biologic grafts in pelvic organ prolapse (POP) and stress urinary incontinence surgery by American Urogynecology Society (AUGS) members.An electronic survey of AUGS members was conducted between December 2011 and January 2012. Frequency of graft use in POP (overall and by transvaginal and transabdominal approaches) and stress urinary incontinence surgery was queried relative to the timing of the 2011 Food and Drug Administration (FDA) safety update. Rates of materials' use before and after the statement were compared using Wilcoxon signed rank test.Fifty-three percent (507/962) of AUGS members responded and were included in analysis; 79% were urogynecologists. Before the FDA warning, in POP surgery, most (90%) used synthetic mesh and fewer (34%) used biologic grafts; 99% used synthetic mesh slings. After the FDA statement, respondents reported an overall decrease in the percent of POP cases in which they used synthetic mesh (P < 0.001) but no change in biologic graft use for POP (P = 0.37) or synthetic mesh sling use (P = 0.10). Specifically, transvaginal mesh use decreased: 40% reported decreased use and 12% stopped use. However, transvaginal mesh was still used by 61% of respondents in at least some cases. No change (62%) or increased use (12%) of mesh was reported for transabdominal POP procedures.Synthetic mesh use in transvaginal POP surgery decreased after the 2011 FDA safety update, but synthetic mesh use for transabdominal POP repair and sling procedures and overall biologic graft use in POP surgery did not decrease.
View details for PubMedID 23797515
Proliferative behavior of vaginal fibroblasts from women with pelvic organ prolapse.
European journal of obstetrics, gynecology, and reproductive biology
2014; 183: 1-4
Pelvic organ prolapse (POP) significantly impacts quality of life of women, especially with advancing age. Cell proliferation is a critical parameter in both normal and pathophysiological processes. We sought to examine fibroblast proliferation in premenopausal women with and without POP and menopausal women with POP, and examine whether TGF-β1, a fibroblast mitogen, could stimulate proliferation in vaginal fibroblasts from these populations.Vaginal wall biopsies were obtained from asymptomatic women (controls) and women with POP (cases). Fibroblasts were cultured from these tissues. Vaginal fibroblasts were treated with or without TGF-β1. Cell proliferation rate (mitotic index) was measured with time-lapse dark-field microscopy. Cell mitosis was counted with ImageJ software after analysis of time-lapse images as Quick time movies.There was no significant difference in mitotic index throughout different time points of observation between premenopausal controls and cases of similar ages. However, a significant difference in mitotic index was seen between premenopausal and menopausal cases (p=0.01), with the menopausal group exhibiting significantly lower mitotic indices. When treated with different doses of TGF-β1, premenopausal control fibroblast proliferation increased with 5ng/ml of TGF-β1 compared to non-treated fibroblasts (p=0.04). TGF-β1 stimulation did not affect fibroblasts from either premenopausal or menopausal cases.Vaginal fibroblast proliferation decreases with age and this association does not appear to be affected by the presence of pelvic organ prolapse. TGF-β1 stimulation increased cell proliferation of premenopausal control fibroblasts. In contrast, there was no response seen in fibroblasts from premenopausal and menopausal cases.
View details for DOI 10.1016/j.ejogrb.2014.09.040
View details for PubMedID 25461341
A modified method for implantation of pluripotent stem cells under the rodent kidney capsule.
Stem cells and development
2014; 23 (17): 2119-2125
Teratoma formation, the standard in vivo pluripotency assay, is also frequently used as a tumorigenicity assay. A common concern in therapeutic stem cell applications is the tumorigenicity potential of a small number of cell impurities in the final product. Estimation of this small number is hampered by the inaccurate methodology of the tumorigenicity assay. Hence, a protocol for tumorigenicity assay that can deliver a defined number of cells, without error introduced by leakage or migration of cells is needed. In this study, we tested our modified transplantation method that allows for transplant of small numbers of pluripotent stem cells (PSCs) under the kidney capsule with minimal cell leakage. A glass capillary with a finely shaped tip and an attached mouth pipette was used to inject PSCs into the rodent kidney capsule. H9 embryonic and induced PSCs were tagged with Fluc and green fluorescence protein reporter genes and divided in different cell doses for transplantation. Bioluminescence imaging (BLI) on the day of surgery showed that the cell signal was confined to the kidney and signal intensity correlated with increasing transplant cell numbers. The overall cell leakage rate was 17% and the rodent survival rate was 96%. Teratoma formation was observed in rodents transplanted with cell numbers between 1×10(5)-2×10(6). We conclude that this modified procedure for transplanting PSCs under the kidney capsule allows for transplantation of a defined number of PSCs with significant reduction of error associated with cell leakage from the transplant site.
View details for DOI 10.1089/scd.2014.0099
View details for PubMedID 24800694
Challenges and future prospects for tissue engineering in female pelvic medicine and reconstructive surgery.
Current urology reports
2014; 15 (8): 425-?
With advances in material engineering there is now a wide array of new materials for augmentation of tissue repairs in Female Pelvic Medicine and Reconstructive Surgery (FPMRS). However, clinical outcomes are discrepant and long term complications debilitating. In this manuscript, we describe the molecular and cellular host environments and biomechanical considerations that affect optimal integration of implant materials. There is growing interest in biodegradable scaffolds with cellular implants. It is thought that the cellular component could regenerate host tissue while the scaffold provides temporary mechanical properties. Current findings are promising, but detailed in vivo and long term testing is needed before clinical applications.
View details for DOI 10.1007/s11934-014-0425-2
View details for PubMedID 24993035
Histologic Characteristics of Vaginal Cuff Tissue From Patients With Vaginal Cuff Dehiscence
JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY
2014; 21 (3): 442-446
To describe the histologic characteristics of vaginal tissue in patients with vaginal cuff dehiscence (VCD) after robotic hysterectomy and to compare this group with patients without dehiscence.Retrospective analysis (Canadian Task Force classification II-3).Academic center.Seven patients with VCD and 6 patients without VCD.Vaginal cuff tissue was obtained from all patients and was stained using hematoxylin-eosin and evaluated for acute and chronic inflammation markers including neutrophils, lymphocytes, and plasma cells. Immunohistochemical staining was performed and evaluated using the semiquantitative method for collagen types I and III, smooth muscle actin, and SM22α (myofibroblast) content. Grading was performed by 4 blinded investigators. The Mann-Whitney test was used to evaluate the 2 groups, and correlation coefficients for interobserver variability.The VCD group, compared with the non-VCD group, demonstrated significantly greater numbers of neutrophils (1.71 vs 1.0; p = .04), lymphocytes (2.85 vs 1.33; p = .002), and plasma cells (2.2 vs 1.0; p = .001). There was no statistical difference between the groups in amounts of collagen I (1.71 vs 1.27; p = .09) and collagen III (1.66 vs 1.38; p = .37), smooth muscle actin (1.23 vs 1.33; p = .65), and SM22α (1.85 vs 1.27; p = .09). Interobserver variability was low (κ = 0.86; p = .76).Compared with the control group, patients with VCD demonstrated significantly higher levels of acute and chronic inflammatory cells. This finding suggests that a prolonged inflammatory phase may be delaying normal progression to reparation in patients with dehiscence.
View details for DOI 10.1016/j.jmig.2013.11.013
View details for Web of Science ID 000336191700022
Concurrent Generation of Functional Smooth Muscle and Endothelial Cells via a Vascular Progenitor
STEM CELLS TRANSLATIONAL MEDICINE
2014; 3 (1): 91-97
Smooth muscle cells (SMCs) and endothelial cells (ECs) are typically derived separately, with low efficiencies, from human pluripotent stem cells (hPSCs). The concurrent generation of these cell types might lead to potential applications in regenerative medicine to model, elucidate, and eventually treat vascular diseases. Here we report a robust two-step protocol that can be used to simultaneously generate large numbers of functional SMCs and ECs from a common proliferative vascular progenitor population via a two-dimensional culture system. We show here that coculturing hPSCs with OP9 cells in media supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and bone morphogenetic protein 4 yields a higher percentage of CD31(+)CD34(+) cells on day 8 of differentiation. Upon exposure to endothelial differentiation media and SM differentiation media, these vascular progenitors were able to differentiate and mature into functional endothelial cells and smooth muscle cells, respectively. Furthermore, we were able to expand the intermediate population more than a billionfold to generate sufficient numbers of ECs and SMCs in parallel for potential therapeutic transplantations.
View details for DOI 10.5966/sctm.2013-0124
View details for Web of Science ID 000330014000010
View details for PubMedID 24311701
Improving the accuracy of prolapse and incontinence procedure epidemiology by utilizing both inpatient and outpatient data
INTERNATIONAL UROGYNECOLOGY JOURNAL
2013; 24 (11): 1939-1946
INTRODUCTION AND HYPOTHESIS: The epidemiologic description of pelvic organ prolapse (POP) and stress urinary incontinence (SUI) procedures is documented in several large studies using national database cohorts. These studies, however, may underestimate the number of procedures performed because they only capture procedures performed in either the inpatient or outpatient settings alone. We present a complete annual description of all inpatient and outpatient surgeries for POP and SUI in California. METHODS: We reviewed a record of all inpatient and outpatient POP and SUI surgeries performed in California in 2008 using data from the Office of Statewide Health Planning (OSHPD). RESULTS: In 2008, 20,004 and 20,330 women in California underwent POP and SUI procedures, respectively. Of these, 3,134 (15.6 %) and 9,016 (44.3 %) were performed in an outpatient setting. The age-adjusted rates of POP and SUI were 1.20 and 1.20 per 1,000 US females, respectively. This correlates to 186,000 POP and 186,000 SUI procedures per year nationally. Vaginal apical suspensions were more common in those undergoing surgery as an inpatient (45.1 vs 19.4 %). The use of mesh to augment prolapse repairs was similar (22.3 % inpatient vs 19.3 % outpatient). SUI procedures performed in the outpatient setting were more likely to be performed as stand-alone procedures (82.9 vs 18.8 %, respectively). CONCLUSIONS: In California, 16 % of POP and 44 % of SUI procedures were performed in an outpatient surgical setting in 2008. Epidemiologic studies of POP and SUI should account for the fact that a substantial number of repairs are performed in the outpatient setting in order to achieve accuracy.
View details for DOI 10.1007/s00192-013-2113-z
View details for Web of Science ID 000325828800020
To Sling or Not To Sling at Time of Abdominal Sacrocolpopexy: A Cost-Effectiveness Analysis
JOURNAL OF UROLOGY
2013; 190 (4): 1306-1312
OBJECTIVES: To compare the cost-effectiveness of three strategies for use of a mid-urethral sling (MUS) to prevent occult stress urinary incontinence (SUI) in those undergoing abdominal sacrocolpopexy (ASC). METHODS: Using decision-analysis modeling, we compared cost-effectiveness over a 1 year post-operative time period of three treatment approaches: 1) ASC alone with deferred option for MUS; 2) ASC with universal concomitant MUS; and 3) preoperative urodynamic study (UDS) for selective MUS. Using published data, we modeled probabilities of SUI after ASC with or without MUS, the predictive value of UDS to detect occult SUI, and the likelihood of complications after MUS. Costs were derived from Medicare 2010 reimbursement rates. The main outcome modeled was incremental cost effectiveness ratio (ICER) per quality-adjusted life years (QALY) gained. In addition to base-case analysis, one-way sensitivity analyses were performed. RESULTS: In our model, universally performing MUS at the time of ASC was the most cost-effective approach, with an incremental cost per QALY gained of $2867 when compared to performing ASC alone. Preoperative UDS was more costly and less effective than universally performing intraoperative MUS. The cost-effectiveness of ASC + MUS was robust to sensitivity analysis, with a cost-effectiveness ratio consistently below $20,000 per QALY. CONCLUSIONS: Universal concomitant MUS is the most cost-effective prophylaxis strategy for occult SUI in women undergoing ASC. The use of pre-operative UDS to guide MUS placement at the time of ASC is not cost-effective.
View details for DOI 10.1016/j.juro.2013.03.046
View details for Web of Science ID 000325091700058
View details for PubMedID 23524201
- Impact of the 2011 FDA Transvaginal Mesh Safety Update on AUGS Members' Use of Synthetic Mesh and Biologic Grafts in Pelvic Reconstructive Surgery FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY 2013; 19 (4): 191-198
Reprogramming of Fibroblasts From Older Women With Pelvic Floor Disorders Alters Cellular Behavior Associated With Donor Age
STEM CELLS TRANSLATIONAL MEDICINE
2013; 2 (2): 118-128
We aimed to derive induced pluripotent stem cell (iPSC) lines from vaginal fibroblasts from older women with pelvic organ prolapse. We examined the effect of donor age on iPSCs and on the cells redifferentiated from these iPSCs. Vaginal fibroblasts were isolated from younger and older subjects for reprogramming. iPSCs were generated simultaneously using an excisable polycistronic lentiviral vector expressing Oct4, Klf4, Sox2, and cMyc. The pluripotent markers of iPSCs were confirmed by immunocytochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spectral karyotyping was performed. The ability of the iPSCs to differentiate into three germ layers was confirmed by embryoid body and teratoma formation. Senescence marker (p21, p53, and Bax) expressions were determined by qRT-PCR and Western blot. The iPSCs were redifferentiated to fibroblasts and were evaluated with senescence-associated β-galactosidase (SA) activity and mitotic index using time-lapse dark-field microscopy. iPSCs derived from both the younger and older subjects expressed pluripotency markers and showed normal karyotype and positive teratoma assays. There was no significant difference in expression of senescence and apoptosis markers (p21, p53, and Bax) in iPSCs derived from the younger subject compared with the older subject. Furthermore, fibroblasts redifferentiated from these iPSCs did not differ in SA activity or mitotic index. We report successful derivation of iPSCs from women with pelvic organ prolapse. Older age did not interfere with successful reprogramming. Donor age differences were not observed in these iPSCs using standard senescence markers, and donor age did not appear to affect cell mitotic activity in fibroblasts redifferentiated from iPSCs.
View details for DOI 10.5966/sctm.2012-0092
View details for Web of Science ID 000314906400011
The Predictive Value of a Cystocele for Concomitant Vaginal Apical Prolapse
JOURNAL OF UROLOGY
2013; 189 (1): 200-203
Recent studies showing a correlation between descent of the anterior and apical vaginal compartments suggest that cystoceles may recur if associated apical prolapse is not corrected. However, to date the anatomical relationship of apical prolapse with respect to cystocele has been incompletely reported. We present the predictive value of a cystocele for clinically significant vaginal apical prolapse.We retrospectively reviewed the records of all new patient visits to a urogynecology clinic in a 30-month period. Women with a point Ba value of -1 or greater (stage 2 cystocele and above) were included in analysis. Predictive values of clinically significant apical prolapse, defined as point C -3 or greater, were calculated and stratified by cystocele stage.A total of 385 women were included in study. Point Ba was the leading edge of prolapse in 83.9% of cases. The position of Ba strongly correlated with that of the vaginal apex (Spearman ρ = 0.769, p <0.001). Overall 59.7% of patients had a point C of -3 or greater. The finding of clinically significant apical prolapse increased significantly with increasing Ba values. Of patients with stage 2, 3 and 4 cystocele point C was -3 or greater in 42%, 85% and 100%, respectively.The finding of stage 2 or greater cystocele is highly suggestive of clinically significant apical vaginal descent to -3 or greater. Furthermore, as cystocele stage increases, the predictive value of apical prolapse also increases. Surgeons contemplating cystocele repair should have high suspicion for vaginal apical prolapse and consider concomitant repair.
View details for DOI 10.1016/j.juro.2012.08.177
View details for Web of Science ID 000312604800066
View details for PubMedID 23174246
Trouble voiding in an adolescent girl. Diagnosis: Obstruced hemivagina and ipsilateral renal anomaly syndrome.
Obstetrics and gynecology
2012; 120 (4): 944-947
View details for PubMedID 22996114
Biomechanical Properties and Associated Collagen Composition in Vaginal Tissue of Women with Pelvic Organ Prolapse
JOURNAL OF UROLOGY
2012; 188 (3): 875-880
The pelvic tissue of women with pelvic organ prolapse is stiffer than that of controls but there are scant data on the collagen composition that corresponds to these mechanical properties. We evaluated human vaginal wall stiffness using the novel scanning haptic microscope and correlated these measurements to collagen expression in women with and without pelvic organ prolapse. In this simultaneous biomechanical and biochemical assessment we evaluated the usefulness of this measurement technology for pelvic floor disorder research and confirmed an association between mechanical properties and composition.The elastic constant (a measure of stiffness) of vaginal wall tissue was measured with the scanning haptic microscope. Protein expression of collagen types I and III of the same tissues were determined by Western blot. The Student t test was used for comparisons between groups.The anterior and posterior vaginal walls of premenopausal and postmenopausal women with pelvic organ prolapse were significantly stiffer than those of controls (p <0.05). Collagen III protein expression in the anterior vaginal wall in the control group was higher than in menopausal women. Collagen I expression was not significantly different between controls and cases.The scanning haptic microscope produced reliable mechanical measurements in small tissue samples without tissue destruction. Vaginal wall tissues are stiffer in women with pelvic organ prolapse than in controls. This vaginal wall stiffness was associated with lower protein expression of collagen III in the vaginal wall compared to that in asymptomatic controls.
View details for DOI 10.1016/j.juro.2012.05.017
View details for Web of Science ID 000307551200064
View details for PubMedID 22819408
The effect of raloxifene, a SERM, on extracellular matrix protein expression of pelvic fibroblasts
INTERNATIONAL UROGYNECOLOGY JOURNAL
2012; 23 (3): 349-355
We hypothesize that the abnormal extracellular matrix (ECM) turnover in pelvic tissues of women with prolapse may be attenuated by raloxifene. We examine the effect of raloxifene on ECM protein expression in pelvic fibroblasts.Pelvic fibroblasts were isolated from cases (N = 6) and controls (N = 3). Cells were treated with raloxifene. Dose-response analyses were performed by ANOVA. mRNA and protein expression of collagen I, III, MMPs, and TIMPs were determined by RT-PCR and Western blot. MMP activity was analyzed by zymography.The mRNA expression of TIMP-3 and protein expression of TIMP-1 and TIMP-3 were significantly increased by raloxifene in fibroblasts from both cases and controls (P < 0.05). Collagen I, III, and MMP mRNA and protein expressions were not affected.Raloxifene selectively attenuates abnormal matrix degradation by increasing inhibitors of proteases, TIMPs, in pelvic fibroblasts. This opens the possibility for SERMs to be used as preventive therapy for pelvic floor disorders.
View details for DOI 10.1007/s00192-011-1567-0
View details for Web of Science ID 000300552400014
View details for PubMedID 21935668
Robot-Assisted Versus Open Sacrocolpopexy: A Cost-Minimization Analysis
JOURNAL OF UROLOGY
2012; 187 (2): 638-643
Abdominal sacrocolpopexy is considered a standard of care operation for apical vaginal vault prolapse repair. Using outcomes at our center we evaluated whether the robotic approach to sacrocolpopexy is as cost-effective as the open approach.After obtaining institutional review board approval we performed cost-minimization analysis in a retrospective cohort of patients who underwent sacrocolpopexy at our institution between 2006 and 2010. Threshold values, that is model variable values at which the most cost effective approach crosses over to an alternative approach, were determined by testing model variables over realistic ranges using sensitivity analysis. Hospital billing data were also evaluated to confirm our findings.Operative time was similar for robotic and open surgery (226 vs 221 minutes) but postoperative length of stay differed significantly (1.0 vs 3.3 days, p <0.001). Base case analysis revealed an overall 10% cost savings for robot-assisted vs open sacrocolpopexy ($10,178 vs $11,307). Tornado analysis suggested that the number of institutional robotic cases done annually, length of stay and cost per hospitalization day in the postoperative period were the largest drivers of cost. Analysis of our hospital billing data showed a similar trend with robotic surgery costing 4.2% less than open surgery.A robot-assisted approach to sacrocolpopexy can be equally or less costly than an open approach. This depends on a sufficient institutional robotic case volume and a shorter postoperative stay for patients who undergo the robot-assisted procedure.
View details for DOI 10.1016/j.juro.2011.09.160
View details for Web of Science ID 000299070400102
View details for PubMedID 22177180
Identification of protein marker in vaginal wall tissues of women with stress urinary incontinence by protein chip array
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
2012; 38 (1): 89-96
We sought to investigate protein biomarkers for stress urinary incontinence (SUI) in vaginal tissues using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and examine if this is a reliable methodology to examine proteins in small tissue specimens.? We compared protein expression profile of vaginal tissue from women with SUI and continent controls. A 22.6kDa peak was identified by subsequent weak cation-exchange, reverse-phase fractionation, gel electrophoresis, and trypsin digestion, then analyzed by matrix assisted laser desorption/ionization mass spectrometry (MALDI MS) and MALDI MS-MS. Biomarker identity and expression level were confirmed by Western-blotting and immunohistochemistry.Expression of the 22.6kDa protein, identified as SM-22?, was significantly higher in women with SUI versus controls. A 3×3-mm tissue sample was sufficient for identification. Western-blot/immunohistochemistry confirmed the SELDI-TOS MS findings.SM-22?, a marker for myofibroblasts, was identified as a biomarker of SUI. Differential protein profiling by SELDI-TOF MS is a powerful and reliable tool for urogynecological research as it allows us to study an array of proteins simultaneously using small tissue samples.
View details for DOI 10.1111/j.1447-0756.2011.01690.x
View details for Web of Science ID 000298882800014
View details for PubMedID 22136672
Alterations in Connective Tissue Metabolism in Stress Incontinence and Prolapse
JOURNAL OF UROLOGY
2011; 186 (5): 1768-1772
We describe current knowledge about collagen/elastin and extracellular matrix metabolism in the genitourinary tract with special emphasis on stress urinary incontinence. We also explored the influence of genetics and reproductive hormones on extracellular matrix metabolism.We performed a MEDLINE® search from 1995 to February 2011 using the key words stress urinary incontinence, pelvic organ prolapse, extracellular matrix, collagen, elastin, matrix metalloproteinase, collagenase, tissue inhibitors of matrix metalloproteinase, elastin metabolism, elastase, connective tissue, supportive tissue, mechanical stress, biomechanical properties, selective estrogen receptor modulators, transforming growth factor-? and wound healing.The literature searched produced data on 4 areas of significance for extracellular matrix metabolism in patients with stress urinary incontinence and prolapse, including collagen, elastin and transforming growth factor-?. Data on collagen metabolism continue to support the hypothesis of increased turnover involving matrix metalloproteinases and serine proteases in pelvic tissues of affected individuals. Elastin metabolism studies suggest increased degradation but also abnormal elastin fiber synthesis. Epidemiological data indicate a genetic predisposition to abnormal extracellular matrix in affected individuals while human tissue and animal models reveal differential expression of candidate genes involved in structural proteins. Transforming growth factor-? pathways have been documented to be involved in stress urinary incontinence in human tissues and animal models. Finally, these extracellular matrix metabolisms are modulated by reproductive hormones and selective estrogen receptor modulators.Pelvic tissue from women with stress urinary incontinence and pelvic organ prolapse show a genetic predisposition to abnormal extracellular matrix remodeling, which is modulated by reproductive hormones, trauma, mechanical stress load and aging. This progressive remodeling contributes to stress urinary incontinence/pelvic organ prolapse by altering normal tissue architecture and mechanical properties.
View details for DOI 10.1016/j.juro.2011.06.054
View details for Web of Science ID 000296022200008
View details for PubMedID 21944102
Visualization of pelvic floor reflex and voluntary contractions.
Studies in health technology and informatics
2011; 163: 138-143
Visualization of the geometric deformation and associated displacement patterns of tubular abdominal organs to mechanical stimuli provides a quantitative measure that is useful in modeling their elastic properties. The origin of the stimulus may be the result of direct and voluntary muscle contraction or in response to a triggered reflex activity. Using trans-perineal 2D ultrasound imaging we examined the characteristics of deformation and displacement of these organs in response to voluntary activity, contraction, straining, and fast reflex responses to stimuli such as coughing. The relative time sequence in movement was examined by serially segmenting the outline of these structures and mapping their temporal characteristics.
View details for PubMedID 21335777
Expression of Apoptotic Factors in Vaginal Tissues From Women With Urogenital Prolapse
NEUROUROLOGY AND URODYNAMICS
2011; 30 (8): 1627-1632
Increased apoptotic activity in pelvic tissues may contribute to development of pelvic floor disorders. We evaluated expression of apoptotic factors (Bcl-2 family) in vaginal tissues from women with pelvic organ prolapse (POP) and how these factors correlate with severity of prolapse.mRNA and protein expression of anti-apoptotic and pro-apoptotic factors in vaginal tissues from subjects and controls were determined by real-time PCR and Western blot. Severity of prolapse was staged using POP-Q criteria.Differential expression of Bcl-2 family factors was observed in protein rather than in gene expression. During the secretory phase, the anti-apoptotic (Bcl-2, Bcl-xl) and pro-apoptotic protein (Bax) were upregulated in controls compared to cases (P?0.05). The ratios of Bcl-2/Bax and Bcl-2/Bad, which determine cellular sensitivity to induction of apoptosis, were higher in controls versus cases. Higher ratios indicate reduced cellular sensitivity to apoptosis. Protein expression of Bax and Bad was higher in women with severe compared to mild prolapse (P?0.05).Increased expression of Bad, Bax, and decreased ratios of Bcl-2/Bax, Bcl-2/Bad suggest increased apoptotic activity or sensitivity to induction of apoptosis in vaginal tissues of women with POP.
View details for DOI 10.1002/nau.21127
View details for Web of Science ID 000296425200046
View details for PubMedID 21674599
Preputial Epidermoid Cyst: An Atypical Case of Acquired Pseudoclitoromegaly
JOURNAL OF LOWER GENITAL TRACT DISEASE
2010; 14 (4): 382-386
Clitoromegaly and pseudoclitoromegaly are rare conditions with both congenital and acquired causes. Acquired causes of adult onset have most frequently been reported to occur in the setting of female genital cutting or neurofibromatosis.Case report.We describe the management of a 47-year-old postmenopausal woman who presented with a 1-year history of a progressive and painful enlargement of her clitoris. Surgical resection revealed an epidermoid, or follicular infundibular, cyst of the prepuce.A review of the etiology underlying acquired clitoromegaly and pseudoclitoromegaly is presented. Previously published cases of pseudoclitoromegaly secondary to cysts are reviewed, all of which were congenital or secondary to female genital cutting, abscesses, or puberty. We report the first case of a postmenopausal woman with no previous history of female genital cutting or infection with a preputial epidermoid cyst. Local cysts or tumors should be considered in the differential diagnosis as causes of pseudoclitoromegaly.
View details for DOI 10.1097/LGT.0b013e3181d85da9
View details for Web of Science ID 000282482600017
View details for PubMedID 20885168
Radiofrequency Treatment of Vaginal Laxity after Vaginal Delivery: Nonsurgical Vaginal Tightening
JOURNAL OF SEXUAL MEDICINE
2010; 7 (9): 3088-3095
All women who have given birth vaginally experience stretching of their vaginal tissue. Long-term physical and psychological consequences may occur, including loss of sensation and sexual dissatisfaction. One significant issue is the laxity of the vaginal introitus.To evaluate safety and tolerability of nonsurgical radiofrequency (RF) thermal therapy for treatment of laxity of the vaginal introitus after vaginal delivery. We also explored the utility of self-report questionnaires in assessing subjective effectiveness of this device.Pilot study to treat 24 women (25-44 years) once using reverse gradient RF energy (75-90 joules/cm(2) ), delivered through the vaginal mucosa. Post-treatment assessments were at 10 days, 1, 3, and 6 months.Pelvic examinations and adverse event reports to assess safety. The author modified Female Sexual Function Index (mv-FSFI) and Female Sexual Distress Scale-Revised (FSDS-R), Vaginal Laxity and Sexual Satisfaction Questionnaires (designed for this study) to evaluate both safety and effectiveness, and the Global Response Assessment to assess treatment responses.No adverse events were reported; no topical anesthetics were required. Self-reported vaginal tightness improved in 67% of subjects at one month post-treatment; in 87% at 6 months (P<0.001). Mean sexual function scores improved: mv-FSFI total score before treatment was 27.6 ± 3.6, increasing to 32.0 ± 3.0 at 6 months (P < 0.001); FSDS-R score before treatment was 13.6 ± 8.7, declining to 4.3 ± 5.0 at month 6 post-treatment (P < 0.001). Twelve of 24 women who expressed diminished sexual satisfaction following their delivery; all reported sustained improvements on SSQ at 6 months after treatment (P = 0.002).The RF treatment was well tolerated and showed an excellent 6-month safety profile in this pilot study. Responses to the questionnaires suggest subjective improvement in self-reported vaginal tightness, sexual function and decreased sexual distress. These findings warrant further study.
View details for DOI 10.1111/j.1743-6109.2010.01910.x
View details for Web of Science ID 000281550700015
View details for PubMedID 20584127
Transforming growth interacting factor expression in leiomyoma compared with myometrium
FERTILITY AND STERILITY
2010; 94 (3): 1078-1083
To investigate the expression of transforming growth interacting factor (TGIF), a Smad transcriptional corepressor, in leiomyoma and matched myometrial tissue samples and the effect of TGIF overexpression in myometrial cells.Experimental study.Tertiary university hospital.Uterine leiomyoma and myometrial tissues from 16 patients.None.The distribution of TGIF in leiomyoma and myometrial tissues by immunohistochemistry stain, mRNA, and protein expression levels by real-time quantitative polymerase chain-reaction (QPCR) and Western blot. Transcriptional regulation of TGIF in myometrial cells with overexpressed TGIF.Although TGIF is present in the smooth muscle cells of the leiomyoma and the myometrium, it is not found in the extracellular matrix. The TGIF mRNA and protein expressions were statistically significantly higher in the leiomyoma compared with the matched, unaffected myometrial tissues in both phases of the menstrual cycle. There were no differences in mRNA or protein expression throughout the menstrual cycle. Overexpression of TGIF protein in myometrial cells statistically significantly suppressed up-regulation of plasminogen activator inhibitor (PAI-1) induced by TGF-beta1 treatment.Expression of TGIF is increased in leiomyoma compared with myometrium. This increase in TGIF expression is not affected by endogenous ovarian hormones. Thus, TGIF is a potential repressor of TGF-beta pathways in myometrial cells.
View details for DOI 10.1016/j.fertnstert.2009.05.001
View details for Web of Science ID 000280407900038
View details for PubMedID 19524896
Imaging-Based Computation of the Dynamics of Pelvic Floor Deformation and Strain Visualization Analysis
ADVANCES IN VISUAL COMPUTING, PT III
2010; 6455: 604-612
View details for Web of Science ID 000290358400062
Is lysyl oxidase-like protein-1, alpha-1 antitrypsin, and neutrophil elastase site specific in pelvic organ prolapse?
INTERNATIONAL UROGYNECOLOGY JOURNAL
2009; 20 (12): 1423-1429
We investigated whether the expression of alpha-1 antitrypsin (ATT), neutrophil elastase (NE), and lysyl oxidase-like protein 1 (LOXL-1) vary within the vagina in subjects with pelvic organ prolapse (POP).Biopsies were obtained from the anterior and posterior vaginal wall of 22 women with POP (> or =stage 2 by POP-Q). The subjects were grouped by the most prominent defect: cystocele, cystocele plus uterine prolapse, and rectocele. Comparative real-time PCR, Western blotting, and NE enzyme activity assay were performed.The ratio of anterior and posterior vaginal wall ATT, NE, and LOXL-1 expression varied between individuals within the same defect group.ATT, NE, and LOXl-1 expression was variable among different biopsy sites in the vagina. No consistent pattern was present when the subjects were grouped by the most prominent defect. We recommend careful consideration of biopsy sites in future studies on POP to enhance reproducibility of data.
View details for DOI 10.1007/s00192-009-0905-y
View details for Web of Science ID 000272796900006
View details for PubMedID 19763368
Retained Products of Conception Spectrum of Color Doppler Findings
JOURNAL OF ULTRASOUND IN MEDICINE
2009; 28 (8): 1031-1041
The purpose of this study was to characterize color Doppler imaging features of retained products of conception (RPOC) with gray scale correlation.Clinically suspected cases of RPOC between January 2005 and February 2008 were reviewed. Patient data and relevant color Doppler and gray scale features were recorded.A total of 269 patients referred for sonographic evaluation for RPOC were identified. Thirty-five patients had confirmed pathologic diagnoses, 28 of whom had RPOC. In those with RPOC, 5 (18%) were avascular (type 0); 6 (21%) had minimal vascularity (type 1); 12 (43%) had moderate vascularity (type 2); and 5 (18%) had marked vascularity (type 3). Peak systolic velocities ranged from 10 to 108 cm/s (average, 36.1 cm/s). Resistive indices in arterial waveforms ranged from 0.33 to 0.7 (average, 0.5). Five (45%) of the patients with type 0 vascularity had RPOC; 6 (86%) of those with type 1 had RPOC; and 17 (100%) of those with types 2 and 3 had RPOC. An echogenic mass had a moderate positive predictive value (80%) but low sensitivity (29%) for RPOC.Color Doppler evaluation of the endometrium is helpful in determining the presence of RPOC. Endometrial vascularity is highly correlated with RPOC, whereas the lack of vascularity can be seen in both intrauterine clots and avascular RPOC.
View details for Web of Science ID 000268556800008
View details for PubMedID 19643786
Relaxin increases elastase activity and protease inhibitors in smooth muscle cells from the myometrium compared with cells from leiomyomas
FERTILITY AND STERILITY
2009; 91 (4): 1351-1354
We investigated the effect of relaxin on extracellular matrix remodeling in cultured myometrial compared with leiomyoma smooth muscle cells. Relaxin increases elastase activity and protease inhibitor expressions in myometrial smooth muscle cells, but no effect was observed in leiomyoma cells.
View details for DOI 10.1016/j.fertnstert.2008.03.043
View details for Web of Science ID 000265132600018
View details for PubMedID 18554597
Emergency Gynecologic Imaging
SEMINARS IN ULTRASOUND CT AND MRI
2008; 29 (5): 353-368
Acute pelvic pain in the female patient can have myriad presentations and, depending on the diagnosis, profound consequences. In the pregnant patient with pelvic pain or bleeding, an ectopic pregnancy must be first excluded. Ultrasound is important in determining the size and location of the ectopic pregnancy, and presence of bleeding, which in turn helps guide treatment decisions. Subchorionic or subplacental bleeds in an intrauterine pregnancy may also present with vaginal bleeding with consequences dependent on gestational age and size of bleed. In the postpartum female suspected to have retained products of conception, sonographic findings may vary from a thickened endometrial stripe to an echogenic mass with associated marked vascularity, often mimicking an arterial-venous malformation. In the nonpregnant patient, early diagnosis and treatment of ovarian torsion can preserve ovarian function. Other causes of peritoneal irritation may also cause acute pelvic pain including a ruptured hemorrhagic cyst or ruptured endometrioma. When pelvic inflammatory disease is suspected, imaging is used to evaluate for serious associated complications including the presence of a tuboovarian abscess or peritonitis. While leiomyomas of the uterus are largely asymptomatic, a leiomyoma that undergoes necrosis, torsion or prolapse through the cervix may be associated with acute severe pain or bleeding. The imaging features of these and other important clinical entities in the female pelvis will be presented.
View details for DOI 10.1053/j.sult.2008.06.006
View details for Web of Science ID 000260064700006
View details for PubMedID 18853841
Effect of relaxin on TGF-beta 1 expression in cultured vaginal fibroblasts from women with stress urinary incontinence
2008; 15 (3): 312-320
The objective of this study is to compare relaxin's effect on transforming growth factor (TGF)- beta1 and latent TGF-beta1-binding protein (LTBP-1) in vaginal fibroblasts from women with stress urinary incontinence (SUI) to continent women (controls) in both phases of the menstrual cycle. Fibroblasts were treated with relaxin. TGF-beta1 levels were measured by enzyme-linked immunosorbent assay. LTBP-1 expression was evaluated by Western blot. In the proliferative phase, total TGF-beta1 level in the supernatant, cells, and extracellular matrix (ECM) of SUI fibroblasts decreased with increasing relaxin concentration (P < .05). Active TGF-beta1 levels increased at a low concentration of relaxin (P < .05) in the supernatant but decreased in the ECM of SUI fibroblasts at high concentration (P < .05). In the secretory phase, total TGF-beta1 levels decreased with relaxin treatment (P < .05) in the supernatant, cells and ECM of both women with SUI and controls. Relaxin decreased the levels of total and active TGF-beta1 in the ECM isolated from SUI vaginal fibroblasts.
View details for DOI 10.1177/1933719108315299
View details for Web of Science ID 000255410900012
View details for PubMedID 18421026
Is alpha 2-macroglobulin important in female stress urinary incontinence?
2008; 23 (2): 387-393
Loss of mechanical stability of the urethra and bladder is thought to be important in the development of stress urinary incontinence (SUI). The vaginal wall is the main supporting tissue for pelvic organs and changes in components of supporting tissues are known to be involved in the pathophysiology of SUI.We evaluated changes in expression of alpha2-macroglobulin (alpha2-M), a protease inhibitor, in vaginal wall tissues from premenopausal women (aged 42-45 years) with SUI (n = 28) compared with menstrual cycle-matched continent women (controls, n = 29). The distribution of alpha2-M in vaginal wall tissues and fibroblasts was analysed by immunohistochemistry and immunofluorescence. Expression levels of alpha2-M mRNA and protein was determined by relative real-time quantitative PCR and enzyme-linked immunosorbent assay, respectively. Protease inhibition was measured to assess bioactivity.Vaginal wall tissues do express alpha2-M. Expression of alpha2-M mRNA and protein was significantly higher in tissues from controls compared to women with SUI in both proliferative and secretory phases (P < 0.05). Protease inhibitory activity of alpha2-M was significantly higher in tissues from controls compared to women with SUI in the secretory phase (P < 0.05), but we found no difference in the proliferative phase between groups. alpha2-M protein level was lower in the proliferative phase than the secretory phase in both controls and SUI patients, while for alpha2-M mRNA this was found only in controls.Decreased expression of alpha2-M mRNA and protein and protease inhibitory activity in the vaginal wall tissues of women with SUI may contribute to the development of SUI.
View details for DOI 10.1093/humrep/dem370
View details for Web of Science ID 000252544300023
View details for PubMedID 18077315
Expression of CD9 in frozen-thawed mouse oocytes: preliminary experience
FERTILITY AND STERILITY
2007; 88 (2): 526-529
CD9 mRNA and protein expression levels in mouse slow frozen-rapid thawed oocytes were compared with those in fresh oocytes by using comparative quantitative real time reverse transcription-PCR and semiquantitative Western blot, respectively. The expression levels of both CD9 mRNA and protein in the frozen oocytes were significantly lower than those found in the fresh oocytes.
View details for DOI 10.1016/j.fertnstert.2006.11.130
View details for Web of Science ID 000248716000044
View details for PubMedID 17307168
Differences in mRNA and protein expression of small proteoglycans in vaginal wall tissue from women with and without stress urinary incontinence
2007; 22 (6): 1718-1724
To investigate changes in mRNA and protein levels of biglycan (BGN), decorin (DCN) and fibromodulin (FMOD) in vaginal wall tissue from women with stress urinary incontinence (SUI) compared to menstrual-cycle matched continent women.We determined mRNA expressions of BGN, DCN and FMOD by quantitative real-time PCR. They were localized in vaginal wall tissue by immunohistochemistry. We performed western blot analysis to examine protein expression.BGN, DCN and FMOD co-localized with collagen and elastin in the extracellular matrix (ECM) of vaginal wall tissue from both groups. The mRNA expression of FMOD was significantly lower in cases versus controls in the proliferative phase (P = 0.03). DCN mRNA expression in cases was higher in the proliferative (P = 0.05) and secretory phases (P = 0.02) versus controls. BGN mRNA expression showed no significant differences in either phase. Protein expression of FMOD in cases was lower in the proliferative phase versus controls (six out of nine pairs), whereas DCN and BGN protein expression in the secretory phase in cases was higher (seven out of nine pairs).BGN, DCN and FMOD expressions in vaginal wall tissue differ in women with SUI and are hormonally modulated. Differences in small proteoglycans may contribute to the altered pelvic floor connective tissues found in these women.
View details for DOI 10.1093/humrep/dem039
View details for Web of Science ID 000247470700033
View details for PubMedID 17395685
Increased expression of latent TGF-beta binding protein-1 and fibrillin-1 in human uterine leiomyomata
MOLECULAR HUMAN REPRODUCTION
2007; 13 (5-6): 343-349
We compared latent TGF-ss binding protein-1 (LTBP-1) and fibrillin-1 (FBN-1) expression in leiomyomata and myometrium, correlated with leiomyomata size. We studied in vivo and in vitro effects of ovarian steroids using matched leiomyomata and myometrium samples from both phases of the menstrual cycle. Leiomyomata were divided into small (
or=6 cm) groups. We validated LTBP-1 and FBN-1 expression using QPCR, western blot and immunohistochemistry. LTBP-1 and FBN-1 mRNA and protein expressions were higher in the medium-sized group compared with myometrium in the proliferative phase (P = 0.01; P = 0.01). FBN-1 mRNA expression was higher in the secretory phase (P = 0.01). LTBP-1 mRNA and protein expression was higher in the medium group compared with the small and large groups in the proliferative phase (P = 0.04; P = 0.04). No differences between groups were seen in FBN-1 expression in either phase. 17Beta-estradiol (E2) increased mRNA and protein expression of LTBP-1 and FBN-1 in cultured leiomyoma smooth muscle cells (LSMC) (P < 0.05). No change in FBN-1 and LTBP-1 expression was observed when cells were treated with E2 plus progesterone. Estrogen may be involved in LTBP-1 and FBN-1 expression in leiomyomata. Extracellular matrix metabolism may be different in medium-sized leiomyoma.
View details for DOI 10.1093/molehr/gam007
View details for Web of Science ID 000247348500007
Acupuncture for postmenopausal hot flashes
2007; 56 (4): 383-395
To determine whether individually tailored acupuncture is an effective treatment option for reducing postmenopausal hot flashes and improving quality of life.In a randomized, placebo-controlled pilot study, 29 postmenopausal participants averaging at least seven moderate to severe hot flashes per 24h, with a baseline estradiol concentration of less than 50 pg/mL and a normal TSH level, were randomized to receive 7 weeks (nine treatment sessions) of either active acupuncture or placebo acupuncture (placebo needles that did not penetrate the skin at sham acupuncture points). Participants recorded hot flashes in logs that were reported daily. Global indices of the severity and frequency of hot flashes were derived from the participants' daily logs.Participants receiving the active treatment had a greater reduction in hot flash severity (24.5+/-30.7%) compared to those receiving placebo (4.4+/-17.1%, P=0.042). Within group repeated measures analyses of variance revealed a significant reduction in hot flash severity in the active (P=0.042), but not in the placebo treatment group (P=0.15). Although there was no significant group difference in the reduction of hot flash frequency between the active (42.4+/-32.2%) and placebo groups (32.0+/-26.5%; P>or=0.352), within group repeated measures analyses of variance revealed that the reduction was statistically significant in both groups (P
View details for DOI 10.1016/j.maturitas.2006.11.001
View details for Web of Science ID 000245757900006
View details for PubMedID 17182200
The role of neutrophil elastase in elastin metabolism of pelvic tissues from women with stress urinary incontinence
NEUROUROLOGY AND URODYNAMICS
2007; 26 (2): 274-279
Altered elastin metabolism is implicated in pelvic floor disorders. We studied neutrophil elastase (NE) and matrix metalloproteinase (MMP) activities in vaginal tissues from premenopausal women with stress urinary incontinence (SUI).Elastase and NE activities in vaginal tissues were assessed. Protein and mRNA expressions were determined by RT-PCR and Western blot. Total elastin and collagen contents were evaluated. To compare the relative elastolytic effect of NE and MMP-2, we used their respective antibodies to immunoprecipitate these proteins from vaginal fibroblast extracts prior to assessing elastase activity.Elastase activity in vaginal wall tissues was significantly higher in the secretory compared to the proliferative phase. NE mRNA and protein expressions were similar between control and SUI tissues from the secretory phase. However, NE activity in the SUI tissues was higher compared to control tissues. The mRNA expression of alpha-1 antitrypsin (ATT) was higher in control tissues from the proliferative phase compared to those from the secretory phase, while no difference was observed in SUI tissues between either phase. Protein expression of the active form of ATT was decreased in SUI tissues compared to controls during the secretory phase. Anti-NE antibody reduced total elastase activity by 60-70%, compared to less than 20% reduction with anti-MMP-2 antibody.During the secretory phase, elastolytic activity is increased in pelvic tissues from women with SUI, through an increase in NE activity and a concurrent decrease in ATT expression. The serine protease, NE, appears to be a more significant modulator of elastase activity compared to MMP-2.
View details for DOI 10.1002/nau.20347
View details for Web of Science ID 000245557300023
View details for PubMedID 17089373
Severe vaginal pain caused by a neuroma in the rectovaginal septum after posterior colporrhaphy
OBSTETRICS AND GYNECOLOGY
2006; 108 (3): 809-811
Traumatic vaginal neuromas are a rarely documented finding in the setting of vaginal pain after posterior colporrhaphy. They arise as a result of trauma or surgery and are often mistaken for scar tissue.After a total vaginal hysterectomy and posterior colporrhaphy, a 32-year-old woman presented with debilitating vaginal pain, presumed to be secondary to scar tissue formation. Excision of the tissue from the rectovaginal septum revealed a traumatic neuroma. After the removal of the neuroma, the patient's vaginal pain resolved.Traumatic neuromas may be a cause of significant point tenderness and thickened tissue after vaginal surgery or repair of obstetric lacerations. If conservative treatment methods have failed, surgical excision of the neuroma can be considered.
View details for Web of Science ID 000247038500042
View details for PubMedID 17018512
A randomized controlled pilot study of acupuncture for postmenopausal hot flashes: effect on nocturnal hot flashes and sleep quality
FERTILITY AND STERILITY
2006; 86 (3): 700-710
To assess the effectiveness of acupuncture on postmenopausal nocturnal hot flashes and sleep.Prospective randomized placebo-controlled study.Stanford University School of Medicine and private acupuncture offices.Active or placebo acupuncture was administered for nine sessions over seven weeks.Severity and frequency of nocturnal hot flashes from daily diaries and Pittsburgh Sleep Quality Index (PSQI).Twenty-nine postmenopausal women experiencing at least seven moderate to severe hot flashes daily, with E(2) <18 pg/mL and FSH 30.0-110.0 IU/L.Nocturnal hot-flash severity significantly decreased in the active acupuncture group (28%) compared with the placebo group (6%), P=.017. The frequency of nocturnal hot flashes also decreased in the active group (47%, P=.001), though it was not significantly different from the placebo group (24%, P=.170; effect size = 0.65). Treatment did not differentially influence sleep; however, correlations between improvements in PSQI and reductions in nocturnal hot flash severity and frequency were significant (P<.026).Acupuncture significantly reduced the severity of nocturnal hot flashes compared with placebo. Given the strength of correlations between improvements in sleep and reductions in nocturnal hot flashes, further exploration is merited.
View details for DOI 10.1016/j.fertnstert.2006.02.100
View details for Web of Science ID 000240998000036
View details for PubMedID 16952511
Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence?
2006; 21 (5): 1266-1273
To evaluate differential expression of transforming growth factor (TGF-beta1), latent transforming factor-binding proteins (LTBP-1, LTBP-2) and elastin microfibril components (fibrillin-1 and fibrillin-2) in vaginal tissue from women with stress urinary incontinence (SUI).In this case-control study, vaginal tissue from women in both phases of the menstrual cycle was obtained. Messenger RNA (mRNA) expressions of LTBP-1, LTBP-2, fibrillin-1, fibrillin-2 and TGF-beta1 were determined by relative real-time quantification PCR. Tissue localization was analysed by immunohistochemistry, and semiquantitative protein expression was evaluated by Western blot analysis.Vaginal wall fibroblasts synthesized all proteins tested. LTBP-1, LTBP-2 and TGF-beta1 co-localized with elastin microfibrils, fibrillin-1 and fibrillin-2 in the extracellular matrix. LTBP-1 mRNA and protein expressions were higher in control versus women affected with SUI in the proliferative phase (P = 0.04), while in the secretory phase, mRNA expression in cases was higher (P = 0.04). Fibrillin-1 mRNA was higher in women affected by SUI versus controls in both phases, but no statistical differences in fibrillin-1 protein expression were observed between the two groups in either phase. LTBP-2 and TGF-beta1 mRNA expressions showed the same trends as LTBP-1.LTBP-1, LTBP-2, TGF-beta1, fibrillin-1, and fibrillin-2 expressions are hormonally regulated in vaginal wall fibroblasts and differ in women affected by SUI when compared to controls. These data suggest a mechanism to regulate TGF-beta1 activity in pelvic connective tissue.
View details for DOI 10.1093/humrep/dei485
View details for Web of Science ID 000236818600026
View details for PubMedID 16452154
Female urinary incontinence in China: experiences and perspectives.
Health care for women international
2006; 27 (2): 169-181
We sought to understand the perceptions and experiences of Chinese women living with urinary incontinence (UI), a problem that has not yet been characterized in China. We conducted the study using semistructured interviews with 15 women, aged 24-81, diagnosed with UI at the Obstetrics and Gynecology Clinic of Fuzhou General Hospital, Fujian, China. We conducted and analyzed the interviews according to the Interpretative Phenomenological Analysis model. The five core themes we derived from the participants' responses were uncertainty about UI, self-blame, avoidance, emotional isolation, and desire for treatment. The negative impacts of UI we documented, such as limiting exercise and causing embarrassment, demonstrated that UI is a problem for the affected women in China. Our study was limited by the small sample size and the need for additional reliability/validity measures, but we believe it presented a strong foundation and justification for more rigorous research into UI in China.
View details for PubMedID 16484160
Metastatic mantle cell lymphoma presenting as a vaginal mass - A case report
GYNECOLOGIC AND OBSTETRIC INVESTIGATION
2006; 62 (4): 217-219
Vaginal masses are an uncommon finding in well-woman gynecologic examinations. The differential diagnosis includes cysts, leiomyomata, ectopic ureteroceles, infected granuloma, and malignancy.A 74-year-old woman with a history of mantle cell lymphoma was referred for vaginal prolapse. Examination revealed a vaginal mass, with MRI confirming 3 masses. Fine needle aspiration confirmed metastatic mantle cell lymphoma which later regressed with radiation therapy.Although vaginal masses are often rare and incidental findings during routine gynecologic examinations, a comprehensive differential diagnosis is required to avoid delays in treatment. Fine needle aspiration should be included as part of the arsenal of diagnostic tools because of its low cost and the ease with which it can be performed in a clinical setting.
View details for DOI 10.1159/000094006
View details for Web of Science ID 000241776600005
View details for PubMedID 16785735
Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women
2006; 21 (1): 22-29
The pathophysiology of pelvic floor dysfunction resulting in stress urinary incontinence (SUI) in women is complex. Evidence suggests that there is also a genetic predisposition towards SUI. We sought to identify differentially expressed genes involved in extracellular matrix (ECM) metabolism in vaginal tissues from women with SUI in the secretory phase of menses compared with asymptomatic women.Tissue samples were taken from the periurethral vaginal wall of five pairs of premenopausal, age-matched SUI and continent women and subjected to microarray analysis using the GeneChip Human Genome U133 oligonucleotide chip set.Extensive statistical analyses generated a list of 79 differentially expressed genes. Elafin, keratin 16, collagen type XVII and plakophilin 1 were consistently identified as up-regulated ECM genes. Elafin, a serine protease inhibitor involved in the elastin degradation pathway and wound healing, was expressed in pelvic fibroblasts and confirmed by Western blot, quantitative competitive PCR and immunofluorescence cell staining.Genes involved in elastin metabolism were differentially expressed in vaginal tissue from women with SUI, suggesting that elastin remodelling may be important in the molecular aetiology of SUI.
View details for DOI 10.1093/humrep/dei276
View details for Web of Science ID 000233846700003
View details for PubMedID 16126751
Elastin metabolism in pelvic tissues: Is it modulated by reproductive hormones?
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2005; 192 (5): 1605-1613
The purpose of this study was to investigate the effect of relaxin on extracellular matrix protein expression in pelvic fibroblasts that were cultured from women with stress urinary incontinence compared with asymptomatic control subjects.Periurethral vaginal wall fibroblasts from premenopausal women with stress urinary incontinence and continent women (in both the proliferative and secretory phase of the menstrual cycle) were stimulated with increasing concentrations of relaxin (0-500 ng/mL). The supernatant was sampled for matrix metalloproteinase-2 and -9 by zymography. Tissue inhibitors of metalloproteinase-1 and -2 and alpha-1 antitrypsin were evaluated with Western blot. Total elastase activity was measured by generation of free amino groups from succinylated elastin. Increasing concentrations of alpha-1 antitrypsin were added to cell lysate to evaluate total elastase activity inhibition.Proliferative-phase stress urinary incontinence fibroblasts demonstrated an increase in matrix metalloproteinase-2 and no change in matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 and -2 expressions with increasing relaxin concentrations. Cells from control subjects showed increased expression of matrix metalloproteinase-2 and -9, but no change in tissue inhibitors of metalloproteinases. Secretory-phase stress urinary incontinence fibroblasts showed no response in matrix metalloproteinase or tissue inhibitors of metalloproteinase expressions with relaxin stimulation. Secretory-phase control fibroblasts reacted by increasing matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2. With respect to total elastase activity and alpha-1 antitrypsin expression, increasing doses of relaxin appear to increase elastolytic activity in stress urinary incontinence cells by decreasing the expression of alpha-1 antitrypsin in proliferative phase cells or increasing the total elastase activity in secretory phase cells. Fibroblast total elastase activity was inhibited by increasing concentrations of alpha-1 antitrypsin.Elastase activity appears to be increased in relaxin-stimulated stress urinary incontinence fibroblasts by either decreased inhibitor (alpha-1 antitrypsin) production or increased elastase activity.
View details for DOI 10.1016/j.ajog.2004.11.027
View details for Web of Science ID 000229384100057
View details for PubMedID 15902165
Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse
NEUROUROLOGY AND URODYNAMICS
2004; 23 (2): 119-126
Weakening of pelvic supportive tissues is thought to be a contributing etiology in female pelvic floor disorders such as stress urinary incontinence and/or pelvic organ prolapse (SUI/POP). Since elastin modulates the mechanical properties of supportive tissues, we examined elastase activity in vaginal tissue from women with pelvic floor dysfunction compared to asymptomatic controls, by comparing overall elastase activity, human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin (a serine protease inhibitor) mRNA and protein levels.Full-thickness peri-urethral vaginal wall tissues were collected from age and menstrual-phase matched SUI/POP and control women at the time of pelvic surgery. Elastolytic activity in the homogenized tissue was determined by the generation of amino groups from succinylated elastin. To quantify mRNA levels of each protein, quantitative competitive-PCR and confirmatory Western blot analyses were performed on the samples for human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin.The mean elastolytic activity in vaginal tissues from the SUI/POP group was similar to that in the control group. With respect to the proteolytic enzymes, neither human neutrophil elastase nor cathepsin K differed between the two groups. However, alpha-1 antitrypsin mRNA and protein levels were significantly decreased in tissues from affected women.A significant decrease in alpha-1 antitrypsin expression was seen in tissues from women with SUI/POP compared to controls. This data suggest that altered elastin metabolism may contribute to the connective tissue alterations observed in pelvic floor dysfunction. Future investigations are warranted to help define the role of elastin turnover in pelvic floor dysfunction.
View details for DOI 10.1002/nau.20012
View details for Web of Science ID 000220085600008
View details for PubMedID 14983422
- Bench to bedside: clinical opportunities for microarray analysis FERTILITY AND STERILITY 2003; 80 (2): 291-292
Distinctive proliferative phase differences in gene expression in human myometrium and leiomyomata
FERTILITY AND STERILITY
2003; 80 (2): 266-276
To gain a comprehensive view of the gene expression and regulation involved in uterine leiomyomata and matched normal myometrium using oligonucleotide microarray-based hybridization analysis.Retrospective analyses of tissue obtained in a prospective randomized clinical study.Academic institution.Seven patients with leiomyomata scheduled for surgery during the proliferative phase.Seven paired samples of leiomyomata and adjacent myometrium were obtained from patients undergoing hysterectomy.The total RNA extracted from leiomyomata and myometrium was used for gene expression profiling of 6800 human genes using high-density oligonucleotide microarrays. In addition, reverse transcriptase-semiquantitative polymerase chain reaction and immunohistochemistry were used to validate tumor-specific gene expression.A comparison of expression patterns in each paired sample revealed 68 genes significantly up- or down-regulated in each paired tissue sample, of which 23 genes showed increased expression and 45 showed decreased expression in leiomyomata compared with normal myometrium. Cluster analysis supported the relevance of these candidate genes for distinguishing between normal myometrium and leiomyomata biologic activity.Expression profiling of uterine leiomyomata using high-density oligonucleotide microarrays yields signature patterns that reflect the distinctive differences between normal human myometrium and leiomyomata during the proliferative phase. These observations suggest that a number of genes are involved in the tumorigenesis of leiomyomata.
View details for DOI 10.1016/S0015-0282(03)00730-1
View details for Web of Science ID 000184634700007
View details for PubMedID 12909484
Menstrual phase-dependent gene expression differences in periurethral vaginal tissue from women with stress incontinence
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2003; 189 (1): 89-97
The mechanical stability of the genitourinary tract is dependent on intact collagen fibers that support the bladder neck, urethra, and pelvic organs. We hypothesize that genetic differences in collagen metabolism may contribute to stress urinary incontinence. Because sex hormones have substantial influence on the female lower urinary tract throughout adult life, we investigated the gene expression of vaginal tissue of women with stress incontinence compared with women with no stress incontinence in the proliferative phase of the menstrual cycle.Quantitative competitive polymerase chain reaction was used to verify that the gene expressions were similar between periurethral vaginal tissue and pelvic ligamentous tissue. Labeled complementary RNA was obtained from periurethral vaginal tissue in five pairs of age- and menstrual phase-matched, premenopausal women with and without stress urinary incontinence. The vaginal tissues were then hybridized on HuGeneFL arrays that contained probes representing 6800 full-length human genes. The Student t test and Mann-Whitney ranking were used independently to select candidates with probability values <.05. Hierarchical clustering analysis was performed on the selected candidates to assess the ability of these genes to discriminate between normal and affected individuals.Tissue inhibitor of metalloproteinases-1 and estrogen receptor-alpha messenger RNA expressions were found to be similar between uterosacral ligament and periurethral vaginal tissue in six participants. Of the 90 candidate genes that were identified, 62 genes were up-regulated and 28 were down-regulated in the stress urinary incontinence group. Genes that were involved in extracellular matrix activity in the up-regulated group include transforming growth factor-beta3, laminin, and collagen type VI. Down-regulated genes that may participate in collagen metabolism include laminin-related protein, collagen XVII, serine/threonine protein kinase, type II interleukin-1 receptor, and platelet-derived growth factor-associated protein.In this preliminary study, we identified differential gene expressions that may contribute to extracellular matrix remodeling in pelvic tissue from women with stress urinary incontinence in the proliferative phase versus continent control subjects. The alteration in expression of these candidate genes suggests that they should be targets for further investigation.
View details for DOI 10.1067/mob.2003.373
View details for Web of Science ID 000184296400016
View details for PubMedID 12861144
Differences in estrogen modulation of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-1 expression in cultured fibroblasts from continent and incontinent women
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2003; 189 (1): 59-65
The purpose of this study was to investigate the effect of increasing estrogen concentrations on metalloproteinase and tissue inhibitors of metalloproteinase protein expressions in cultured pelvic fibroblasts that were obtained from continent and incontinent women.Periurethral vaginal wall tissues were taken from four stress incontinent and three continent premenopausal women who underwent gynecologic surgery for benign indications. Protein was extracted from these tissues, and Western blot analysis was performed to document that fibroblasts from continent and incontinent women differed with respect to metalloproteinase and tissue inhibitors of metalloproteinase production. One age-matched tissue pair was prepared for fibroblast culture. Cells were cultured with increasing concentrations of estradiol (0-500 pg/mL). Extracellular metalloproteinase and tissue inhibitors of metalloproteinase were assessed semiquantitatively with Western blotting.Periurethral vaginal tissues from incontinent women expressed less tissue inhibitors of metalloproteinase when compared with tissue from the control subjects; there was no difference in the expression of cleaved, active metalloproteinase protein. Tissue inhibitors of metalloproteinase expression from fibroblasts of continent women significantly increased with increasing estradiol concentrations (0-100 pg/mL, P <.05). No significant dose response was seen in fibroblasts from an incontinent woman. Metalloproteinase expression was not altered by increasing estradiol concentrations in fibroblasts from either continent or incontinent women.This preliminary in vitro study suggested that, in fibroblasts that were derived from the continent woman, tissue inhibitors of metalloproteinase protein production increases with increasing estrogen levels and that, in stress incontinent fibroblasts, no similar increase occurs. Neither group demonstrated a change in metalloproteinase production in response to varying estrogen levels, which suggests that estrogen may inhibit collagen degradation in continent women by increasing tissue inhibitors of metalloproteinase production but exerts a reduced inhibitory effect on collagenolysis in women with stress urinary incontinence.
View details for DOI 10.1067/mob.2003.378
View details for Web of Science ID 000184296400011
View details for PubMedID 12861139
Abdominal myomectomy versus uterine fibroid embolization in the treatment of symptomatic uterine leiomyomas
AMERICAN JOURNAL OF ROENTGENOLOGY
2003; 180 (6): 1571-1575
The purpose of this study was to compare treatment efficacy and complications of abdominal myomectomy with those of uterine fibroid embolization in women with symptomatic uterine fibroids.We analyzed the outcomes of 111 consecutive patients who underwent abdominal myomectomy (n = 44) or fibroid embolization (n = 67) over a 30-month period. The mean ages of the two groups were 37.7 years (range, 28-48 years) and 44.2 years (range, 31-56 years), respectively. A questionnaire and review of medical records assessed all procedure-related complications and changes in symptoms. Length of hospital stay, time until resumption of daily activities, and pain medication requirements after the procedure were also analyzed.Follow-up times for the myomectomy and embolization groups were 14.6 and 14.3 months, respectively. The respective observed success rates in abdominal myomectomy and uterine fibroid embolization patients were 64% versus 92% for menorrhagia (p < 0.05), 54% versus 74% for pain (not significant), and 91% versus 76% for mass effect (p < 0.05). The complication rates were 25% (abdominal myomectomy) and 11% (uterine fibroid embolization) (p < 0.05). The respective secondary end points for the two procedures were 2.9 versus 0 days mean hospital stay, 8.7 versus 5.1 days of narcotics use, and 36 versus 8 days until resumption of normal activities. These differences were all statistically significant.Uterine fibroid embolization is a less invasive and safer treatment option in women with symptomatic leiomyomas than myomectomy. Menorrhagia may be better controlled with embolization, and myomectomy may be a better option in patients with mass effect. Both procedures were equally effective in controlling pain.
View details for Web of Science ID 000183149200013
View details for PubMedID 12760922
Collagen metabolism and turnover in women with stress urinary incontience and pelvic prolapse
INTERNATIONAL UROGYNECOLOGY JOURNAL
2002; 13 (2): 80-87
The aim of this study was to investigate quantitative mRNA expression of matrix metalloproteinases MMP-1, MMP-2, MMP-9, and their inhibitors, the tissue inhibitors of metalloproteinases TIMP-1, TIMP-2 and TIMP-3, in vaginal wall tissue from women with stress urinary incontinence compared to continent controls. Vaginal wall tissues were obtained from 7 women with stress urinary incontinence/severe pelvic prolapse and 15 continent controls. RNA was then extracted and quantified. Quantitative competitive reverse transcription (QC-RT-PCR) was carried out with oligonucleotide primers to quantify MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 mRNA expression. Stress continent women demonstrated a significant decrease in TIMP-1 and mRNA expression (P = 0.03). There was no difference in TIMP-2, TIMP-3, MMP-2 or MMP-9 mRNA expression between stress incontinent women and controls. However, MMP-1 mRNA expression was significantly increased (P = 0.05) in the incontinent group and the MMP-1/TIMP-1 ratio (P = 0.04) was consistent with increased collagen degradation in the stress incontinence. Stress incontinent women demonstrated an increase in MMP-1 mRNA expression and a decrease in the inhibitor TIMP-1 mRNA expression. Both these findings are consistent with increased collagen breakdown as a pathologic etiology of incontinence.
View details for Web of Science ID 000175825400004
View details for PubMedID 12054187
Virtual endoscopy using perspective volume-rendered three-dimensional sonographic Data: Technique and clinical applications
AMERICAN JOURNAL OF ROENTGENOLOGY
1999; 172 (5): 1193-1197
We present a technique for obtaining three-dimensional external and virtual endoscopy views of organs using perspective volume-rendered gray-scale and Doppler sonographic data, and we explore potential clinical applications in the carotid artery, the female pelvis, and the bladder.Using the proposed methods, radiologists will find it possible to create virtual endoscopy and external perspective views using sonographic data. The technique works well for revealing the interior of fluid-filled structures and cavities. However, expected improvements in computer performance and integration with existing sonographic equipment will be necessary for the technique to become practical in the clinical environment.
View details for Web of Science ID 000079919700005
View details for PubMedID 10227488
Dysfunctional uterine bleeding
WESTERN JOURNAL OF MEDICINE
1998; 169 (5): 280-284
Abnormal uterine bleeding is a common, debilitating condition. Dysfunctional uterine bleeding (DUB) is the diagnosis given to women with abnormal uterine bleeding in whom no clear etiology can be identified. DUB has been observed in both ovulatory and anovulatory cycles. Medical treatments include nonsteroidal anti-inflammatory drugs, oral contraceptive pills, progestins, danazol (a synthetic androgen), GnRH agonists, and antifibrinolytic drugs. The drawback to medical therapy, in addition to side effects, is that the benefit lasts only while the patient takes the medication. Surgical options have concentrated mainly on endometrial ablation and hysterectomy, and it is unclear whether one is superior to the other in terms of long-term outcome and patient satisfaction. Newer and less invasive ablation techniques, such as thermal balloon ablation, offer more treatment alternatives.
View details for Web of Science ID 000077010900004
View details for PubMedID 9830356