Postcesarean pelvic floor dysfunction contributes to undisclosed psychosocial morbidity

OBJECTIVE: To estimate the prevalence and severity of postcesarean pelvic dysfunction. STUDY DESIGN: Using biopsychosocial interviewing at home, 184 postcesarean primiparas were compared to 100 vaginally delivered women regarding symptoms of stress incontinence, anal incontinence and dyspareunia. Delivery details were confirmed from medical records. RESULTS: Comparison of postcesarean vs. vaginally delivered women revealed stress incontinence in 33% vs. 54% and dyspareunia in 27% vs. 46%, both differences reaching statistical significance, unlike anal incontinence, which was manifest in 51% vs. 44%. When compared to emergency cesarean the relative risk of stress incontinence following an elective cesarean was 0.99 (0.71, 1.39), of dyspareunia 1.02 and of anal incontinence 1.05, indicating no statistically significant difference. Thirty (22%) stress incontinent and 4 (3%) fecally incontinent mothers used pads continuously, suggesting severe physical morbidity. Severe dysphoria (depression) was expressed by 41 (35%) stress incontinent mothers, 38 (30%) with dyspareunia and 34 (26%) with anal incontinence; the association of severe dysphoria with dyspareunia was statistically significant (OR = 2.504 [1.362, 4.602]). Few women came forward to seek help. CONCLUSION: Pelvic dysfunction was similar after elective or emergency cesarean. Compared to vaginal delivery, postcesarean stress incontinence and dyspareunia were less frequent but biopsychosocial morbidity could be severe.

Psychological therapies for chronic pelvic pain:systematic review of randomized controlled trials

Chronic pelvic pain (CPP), a common cause of disability in women, is a condition best viewed in the biopsychosocial framework. Psychological interventions are frequently considered alongside medical and surgical treatments. Our objective was to evaluate the effectiveness of psychological therapies for the treatment of CPP. Electronic literature searches were conducted in Medline, Embase, PsycInfo and DARE databases from database inception to April 2010. Reference lists of selected articles were searched for further articles. The studies selected were randomized controlled trials of psychological therapies in patients with CPP compared with no treatment, standard gynecological treatment or another form of psychological therapy. Two reviewers independently selected articles without language restrictions and extracted data covering study characteristics, study quality and results. Reduction in pain, measured using visual analog scales or other measurements, was the main outcome measure. Of the 107 citations identified, four studies satisfied the inclusion criteria. Compared with no psychological intervention, therapy produced a standardized mean pain score of -3.27 [95% confidence interval (CI) -4.52 to -2.02] and 1.11 (95% CI -0.05 to 2.27) at 3 months and -3.95 (95% CI -5.35 to -2.55) and 0.54 (95% CI -0.78 to 1.86) at 6 months and greater, based on a visual analog scale score of 0-10. The current evidence does not allow us to conclude whether psychological interventions have an effect on self-reported pain scores in women with CPP.

Does post-caesarean dyspareunia reflect sexual malfunction, pelvic floor and perineal dysfunction?

The aim was to define post-caesarean dyspareunia as a sexual and pelvic-perineal symptom. Post-caesarean (80 elective, 104 emergency) and 100 vaginally delivered primiparae had domiciliary interviews at 10 months postpartum. A total of 50 (28% and 27%) post-caesarean and 46 (46%) vaginally delivered, reported dyspareunia. Severely impaired general sexual health occurred in 82 (24% elective, 25% emergency, 35% vaginally delivered) as category 3 (dyspareunia with sexual symptoms) and 27 (10% elective, 7% emergency, 12% vaginally delivered) as category 4 (reduced frequency <6). The risk of dyspareunia (RR 1.14, CI 0.73, 1.77) or impaired general sexual health (RR 0.93, CI 0.32, 2.74) was similar among those with or without perineal trauma. Both caesarean and perineal scars were associated with sexual malfunction. Primiparae with new incontinence had a lower risk of dyspareunia than impaired general sexual health. Awareness of the associations of post-caesarean dyspareunia and impaired general sexual health with incontinence would facilitate appropriate obstetric decision-making. Further research is indicated. © 2011 Informa UK, Ltd.

Glutaredoxin-1 up-regulation induces soluble vascular endothelial growth factor receptor 1, attenuating post-ischemia limb revascularization

Glutaredoxin-1 (Glrx) is a cytosolic enzyme that regulates diverse cellular function by removal of GSH adducts from S-glutathionylated proteins including signaling molecules and transcription factors. Glrx is up-regulated during inflammation and diabetes. Glrx overexpression inhibits VEGF-induced endothelial cell (EC) migration. The aim was to investigate the role of up-regulated Glrx in EC angiogenic capacities and in vivo revascularization in the setting of hind limb ischemia. Glrx overexpressing EC from Glrx transgenic mice (TG) showed impaired migration and network formation and secreted higher level of soluble VEGF receptor 1 (sFlt), an antagonizing factor to VEGF. After hind limb ischemia surgery Glrx TG mice demonstrated impaired blood flow recovery, associated with lower capillary density and poorer limb motor function compared to wild type littermates. There were also higher levels of anti-angiogenic sFlt expression in the muscle and plasma of Glrx TG mice after surgery. Non-canonical Wnt5a is known to induce sFlt. Wnt5a was highly expressed in ischemic muscles and EC from Glrx TG mice, and exogenous Wnt5a induced sFlt expression and inhibited network formation in human microvascular EC. Adenoviral Glrx-induced sFlt in EC was inhibited by a competitive Wnt5a inhibitor. Furthermore, Glrx overexpression removed GSH adducts on p65 in ischemic muscle and EC, and enhanced nuclear factor kappa B (NF-kB) activity which was responsible for Wnt5a-sFlt induction. Taken together, up-regulated Glrx induces sFlt in EC via NF-kB -dependent Wnt5a, resulting in attenuated revascularization in hind limb ischemia. The Glrx-induced sFlt may be a part of mechanism of redox regulated VEGF signaling.

Glutathione adducts induced by ischemia and deletion of glutaredoxin-1 stabilize HIF-1α and improve limb revascularization

Reactive oxygen species (ROS) are increased in ischemic tissues and necessary for revascularization; however, the mechanism remains unclear. Exposure of cysteine residues to ROS in the presence of glutathione (GSH) generates GSH-protein adducts that are specifically reversed by the cytosolic thioltransferase, glutaredoxin-1 (Glrx). Here, we show that a key angiogenic transcriptional factor hypoxia-inducible factor (HIF)-1α is stabilized by GSH adducts, and the genetic deletion of Glrx improves ischemic revascularization. In mouse muscle C2C12 cells, HIF-1α protein levels are increased by increasing GSH adducts with cell-permeable oxidized GSH (GSSG-ethyl ester) or 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanyl thiocarbonylamino) phenylthiocarbamoylsulfanyl] propionic acid (2-AAPA), an inhibitor of glutathione reductase. A biotin switch assay shows that GSSG-ester-induced HIF-1α contains reversibly modified thiols, and MS confirms GSH adducts on Cys520 (mouse Cys533). In addition, an HIF-1α Cys520 serine mutant is resistant to 2-AAPA–induced HIF-1α stabilization. Furthermore, Glrx overexpression prevents HIF-1α stabilization, whereas Glrx ablation by siRNA increases HIF-1α protein and expression of downstream angiogenic genes. Blood flow recovery after femoral artery ligation is significantly improved in Glrx KO mice, associated with increased levels of GSH-protein adducts, capillary density, vascular endothelial growth factor (VEGF)-A, and HIF-1α in the ischemic muscles. Therefore, Glrx ablation stabilizes HIF-1α by increasing GSH adducts on Cys520 promoting in vivo HIF-1α stabilization, VEGF-A production, and revascularization in the ischemic muscles

The role of supraspinal excitability in the development of healthy-limb deficits following anterior cruciate ligament injury

In the current study, we examined how supraspinal and spinal excitability were altered bilaterally after unilateral anterior cruciate ligament reconstruction (ACLr). 7 participants with ACLr and 7 healthy controls underwent transcranial magnetic stimulation (TMS) and electrical stimulation. To evaluate supraspinal excitability, resting motor thresholds (RMT) and motor evoked potential (MEP) stimulus response curves (SRC) were used. To measure spinal excitability, H-reflex SRC gain was assessed. Mixed factorial ANOVAs were used to compare measures between limbs and between groups. Cohen’s d was used to assess effect sizes between groups. Data indicated no significant differences between subject groups or between limbs. However, large effect sizes were found between limbs for H-reflex gain and RMTs suggesting that ACLr can have an effect on some of the variables examined. This study identified decreases in strength in the injured limbs and that subjects with an ACL injury exhibited decreases in spinal and supraspinal excitability of the quadriceps compared to Healthy controls.

Morbidity and mortality following pelvic rami fractures in an elderly Newfoundland population

Introduction: Pelvic rami fractures in the elderly are associated with significant morbidity and mortality. Despite our rapidly aging population there is a paucity of literature dealing with fractures of the pelvic rami in this age group. The purpose of this study is report mortality rates following these injuries in the Eastern region of Newfoundland. Additionally, we aim to describe and quantify the important resultant morbidity in this vulnerable elderly population . Methods: A retrospective chart review was performed of all the pelvic fractures in individuals over the age of 60 between 2000 and 2005 in the Eastern Health region of Newfoundland and Labrador. From these patients, only those with the radiographic parameters consistent with low energy pattern pelvic ring injuries were included. Excluded from the study were those with concurrent fractures of the femur. Survival data, comorbidities, injury characteristics, hospital stay, ambulatory status, and place of residence were recorded from the chart. A surrogate control group was formulated from Statistics Canada survival data for use as a survival comparison group. Results: There were 80 fractures of the pelvis identified in patients over 60 years old from 2000-2005. Of these, 43 met our inclusion/exclusion criteria and were used in our analysis. The one and five year mortalities of these patients were 16.3% (95% CI; 7.80% to 30.3%) and 58.1% (95% CI; 43.3% to 71.6%), respectively. These were both significantly different from the point estimates from our constructed age and gender matched control group from the Statistics Canada data of 6.58% (one year mortality) and 31.3% (five year mortality). Morbidity was quantified by change in ambulatory status (independent, walker/cane assisted, wheelchair) and change in residential independence (independent, assisted living, nursing home). Post fracture, 36% of patients permanently required increased ambulatory aids and 21% of patients required a permanent increase in everyday level of care. Conclusion: This study suggests that there may be significantly increased mortality and morbidity following low energy pattern pelvic rami fractures in an elderly population compared to age and gender matched controls. In contrast to previous studies describing these injuries, there is greater homogeneity in this population with respect to age and mechanism of injury. This study generates several important hypotheses for future research and in particular highlights the need for larger prospective studies to identify factors predicting the highest risk for poor outcomes in this population.

Constructs of health belief and disabling distal upper limb pain

Peer reviewed

Chronic pelvic pain in women of reproductive and post-reproductive age : a population-based study

Abimbola Ayorinde’s PhD funded by the Medical Research Council. This study was funded by the British Pain Society (Mildred Clulow Award) and preparatory work by National Health Service Grampian.

Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study) : study protocol for a randomised controlled trial

The VUE study is funded by the National Institute for Health Research Health Technology Assessment programme (project number 11/129/183).

Application of a new method in the study of pelvic floor muscle passive properties in continent women

The aim of this study was to present a new methodology for evaluating the pelvic floor muscle (PFM) passive properties. The properties were assessed in 13 continent women using an intra-vaginal dynamometric speculum and EMG (to ensure the subjects were relaxed) in four different conditions: (1) forces recorded at minimal aperture (initial passive resistance); (2) passive resistance at maximal aperture; (3) forces and passive elastic stiffness (PES) evaluated during five lengthening and shortening cycles; and (4) percentage loss of resistance after 1 min of sustained stretch. The PFMs and surrounding tissues were stretched, at constant speed, by increasing the vaginal antero-posterior diameter; different apertures were considered. Hysteresis was also calculated. The procedure was deemed acceptable by all participants. The median passive forces recorded ranged from 0.54 N (interquartile range 1.52) for minimal aperture to 8.45 N (interquartile range 7.10) for maximal aperture while the corresponding median PES values were 0.17 N/mm (interquartile range 0.28) and 0.67 N/mm (interquartile range 0.60). Median hysteresis was 17.24 N∗mm (interquartile range 35.60) and the median percentage of force losses was 11.17% (interquartile range 13.33). This original approach to evaluating the PFM passive properties is very promising for providing better insight into the patho-physiology of stress urinary incontinence and pinpointing conservative treatment mechanisms.

Effects of pelvic floor muscle rehabilitation on PFM function and morphology in older women

Aims The purpose of this study was to examine the effect of a pelvic floor muscle (PFM) rehabilitation program on incontinence symptoms, PFM function, and morphology in older women with SUI. Methods Women 60 years old and older with at least weekly episodes of SUI were recruited. Participants were evaluated before and after a 12-week group PFM rehabilitation intervention. The evaluations included 3-day bladder diaries, symptom, and quality of life questionnaires, PFM function testing with dynamometry (force) and electromyography (activation) during seven tasks: rest, PFM maximum voluntary contraction (MVC), straining, rapid-repeated PFM contractions, a 60 sec sustained PFM contraction, a single cough and three repeated coughs, and sagittal MRI recorded at rest, during PFM MVCs and during straining to assess PFM morphology. Results Seventeen women (68.9 ± 5.5 years) participated. Following the intervention the frequency of urine leakage decreased and disease-specific quality of life improved significantly. PFM function improved significantly: the participants were able to perform more rapid-repeated PFM contractions; they activated their PFMs sooner when coughing and they were better able to maintain a PFM contraction between repeated coughs. Pelvic organ support improved significantly: the anorectal angle was decreased and the urethrovescial junction was higher at rest, during contraction and while straining. Conclusions This study indicated that improvements in urine leakage were produced along with improvements in PFM co-ordination (demonstrated by the increased number of rapid PFM contractions and the earlier PFM activation when coughing), motor-control, pelvic organ support.

Postnatal pelvic floor muscle training for preventing and treating urinary incontinence : where do we stand?

Purpose of review: Postnatal pelvic floor muscle training aims to rehabilitate the pelvic floor muscles. To be effective, a certain exercise dosage must be respected. Recent trials evaluated the effect of different programs on prevention/treatment of urinary incontinence immediately after delivery and in treatment of persistent incontinence. Recent findings: Only three systematic reviews, six trials, and four follow-up studies have been published in the past two decades. High heterogeneity in postnatal pelvic floor muscle training programs is observed throughout the literature, making comparisons difficult. In the prevention/treatment of postnatal urinary incontinence immediately after delivery and in persistent incontinence, supervised intensive programs prove more effective than standard postnatal care. Longer-term results have yet to show advantages for postnatal training programs. Summary: Although a certain exercise dosage must be respected for a postnatal pelvic floor muscle training program to be effective, a few randomized controlled trials present such dosage. Randomized controlled trials should study the effect of supervised, intensive training protocols with adherence aids. As standard care does not seem to reduce the prevalence of postnatal urinary incontinence, obstetrics services must address delivery of postnatal pelvic floor muscle training.

Descending Control of Limb Movements in Drosophila melanogaster

Because the interactions between feedforward influences are inextricably linked during many motor outputs (including but not limited to walking), the contribution of descending inputs to the generation of movements is difficult to study. Here we take advantage of the relatively small number of descending neurons (DNs) in the Drosophila melanogaster model system. We first characterize the number and distribution of the DN populations, then present a novel load free preparation, which enables the study of descending control on limb movements in a context where sensory feedback can be is reduced while leaving the nervous system, musculature, and cuticle of the animal relatively intact. Lastly we use in-vivo whole cell patch clamp electrophysiology to characterize the role of individual DNs in response to specific sensory stimuli and in relationship to movement. We find that there are approximately 1100 DNs in Drosophila that are distributed across six clusters. Input from these DNs is not necessary for coordinated motor activity, which can be generated by the thoracic ganglion, but is necessary for the specific combinations of joint movements typically observed in walking. Lastly, we identify a particular cluster of DNs that are tuned to sensory stimuli and innervate the leg neuromeres. We propose that a multi-layered interaction between these DNs, other DNs, and motor circuits in the thoracic ganglia enable the diverse but well-coordinated range of motor outputs an animal might exhibit.