Resident training to optimize patient-focused menopause management: a multispecialty menopause curriculum to enhance knowledge and preparedness.

OBJECTIVE: Surveys of residents in obstetrics and gynecology, internal medicine, and family medicine have demonstrated low levels of knowledge and comfort in treating patients with menopausal symptoms, suggesting a need for improved training during residency. To address this problem, we used a flipped classroom design to deliver a novel menopause curriculum for medical residents. The curriculum included six podcast episodes followed by an interactive case-based classroom session. We then assessed effects of the curriculum on the residents' knowledge and preparedness to manage menopause symptoms. METHODS: We targeted 200 residents (43 obstetrics and gynecology, 86 internal medicine, and 71 family medicine) from six residency programs from 2019 to 2020. Of these, 115 (58%) completed both pre- and postcurriculum assessments, including a 15-item knowledge test and self-ratings of their knowledge, comfort, and preparedness to manage menopause. RESULTS: Following the curriculum, the proportion of correctly answered knowledge questions rose from 60.8% to 79.1% (+18.3%; 95% confidence interval, 15.4-21.2; Cohen's d = 1.2). Improvement did not significantly differ by specialty or year of residency. There were higher gains for residents who listened to the entirety of all six podcast episodes ( b = 11.4, P < 0.001) and who attended the classroom session ( b = 11.6, P = 0.003). Residents' self-ratings of knowledge, comfort, and preparedness also improved following the curriculum across all medical specialties (Cohen's d = 0.47-1.2). Residents rated the podcast format as convenient (73%) and effective (65%) compared with an equivalent amount of reading. CONCLUSIONS: Pairing a podcast with a classroom discussion was found to be an effective combination for improving menopause knowledge.

Genitourinary Syndrome of Menopause: Pathophysiology, Clinical Presentation, and Differential Diagnosis.

Scientific information is incomplete regarding the genitourinary syndrome of menopause. Both the lower genital and urinary tracts are rich in receptors for reproductive hormones and are highly susceptible to waning ovarian hormones at menopause. Symptoms of dryness and pain emerge in late perimenopause, but they can also result earlier from cancer therapies or bilateral oophorectomy. Lower urinary tract symptoms rise in prevalence at midlife and increase further with advancing age. Because ovarian senescence is typically followed by years of aging, some postmenopausal complaints may be attributable to increasing longevity.

Treating where it hurts-a randomized comparative trial of vestibule estradiol for postmenopausal dyspareunia.

OBJECTIVE: To compare efficacies of two strengths of estradiol cream applied to the vulvar vestibule and use of silicone lubricant to reduce intercourse pain scores in postmenopausal women with moderate/severe dyspareunia. METHODS: This pilot randomized comparative trial assigned 50 women to nightly applications of estradiol cream, 50 or 100 µg, for 12 weeks. We asked women to have lubricated penetration twice weekly, with intercourse or performing a tampon test. Pain, recorded in dairies, was rated using the 0-10 Numerical Rating Scale. We assessed biopsychosocial outcomes, urinary symptoms, and measured serum estradiol levels and endometrial stripe thicknesses. We performed physical examinations to determine tenderness levels of the vestibule, vagina, pelvic floor muscles, bladder, uterus, and adnexa. Comparisons were made using two-sample t test, Wilcoxon rank-sum test, or χ2 /Fisher's exact test. RESULTS: Forty-seven women (94%), with a mean age of 59.7 years, completed the trial. The baseline median intercourse pain score was 8/10 (interquartile range, 6, 8). After 12 weeks, we measured no statistically significant difference between groups in the primary outcome, intercourse pain score, or any secondary outcome measure. For both groups together, the median intercourse pain score diminished by 50% after 4 weeks and 75% after 12 weeks ( P < 0.001). The most tender anatomic area, the vulvar vestibule, improved by 82% to 100% ( P < 0.001) with therapy. We did not measure a statistically significant difference in serum estradiol levels or endometrial stripe thickness between groups. CONCLUSION: Estradiol cream applied to the vulvar vestibule, paired with precoital silicone lubricant, is a promising alternative to vaginal therapy for dyspareunia.

Where does postmenopausal dyspareunia hurt? A cross-sectional report.

OBJECTIVE: A common symptom of genitourinary syndrome of menopause (GSM) is dyspareunia, attributed to vulvovaginal atrophy. Our objective was to systematically describe the pain characteristics and anatomic locations of tenderness in a cohort with moderate/severe dyspareunia likely due to GSM. METHODS: This cross-sectional study reports the baseline data of postmenopausal women with dyspareunia screened for an intervention trial of topical estrogen. Postmenopausal women not using hormone therapy who had moderate or severe dyspareunia were eligible if estrogen was not contraindicated. Biopsychosocial assessments were performed using the Vulvar Pain Assessment Questionnaire, and participants underwent a systematic vulvovaginal examination that included a visual assessment and cotton swab testing for tenderness rated using the Numerical Rating Scale (0-10). Vaginal pH and mucosal sensitivity were assessed; pelvic floor muscles and pelvic viscera were palpated for tenderness. RESULTS: Fifty-five eligible women were examined between July 2017 and August 2019. Mean age was 59.5 ±â€Š6.8 years, and duration of dyspareunia was 6.2 ±â€Š4.3 years. The mean intercourse pain score was 7.3 ±â€Š1.8, most often described as "burning" and "raw." Ninety-eight percent had physical findings of vulvovaginal atrophy. Median pain scores from swab touch at the vulvar vestibule (just outside the hymen) were 4 to 5/10, and topical lidocaine extinguished pain. Median vaginal mucosal pain was zero. CONCLUSIONS: Participants described their pain as "burning" and "dry." Tenderness was most severe and most consistently located at the vulvar vestibule. Correlating the symptom of dyspareunia with genital examination findings may further our understanding of treatment outcomes for GSM.

Video Summary:http://links.lww.com/MENO/A916 .

Improving management of the genitourinary syndrome of menopause: evaluation of a health system-based, cluster-randomized intervention.

BACKGROUND: Genitourinary symptoms are common in postmenopausal women and adversely affect the quality of life. National surveys and data collected from our healthcare system indicate that postmenopausal women with the genitourinary syndrome of menopause often fail to receive appropriate diagnosis or treatment. OBJECTIVE: To promote greater detection and treatment of the genitourinary syndrome of menopause, we created and tested a clinician-focused health system intervention that included clinician education sessions and a suite of evidence-based electronic health record tools. STUDY DESIGN: Using a cluster-randomized design, we allocated primary care (16) and gynecology (6) clinics to the intervention or control group. From September to November 2014, we provided training about the diagnosis and treatment of genitourinary syndrome of menopause in face-to-face presentations at each intervention clinic and in an online video. We developed clinical decision support tools in the electronic health record that contained an evidence-based, point-of-care knowledge resource, a standardized order set, and a checklist of patient education materials for the patient's after visit summary. The tools aimed to facilitate accurate diagnostic coding and prescribing (SmartSet, SmartRx) along with relevant patient information (SmartText). Clinicians who only performed visits at control clinics received no training or notification about the tools. Our primary outcome was vulvovaginal diagnoses made at well visits for women at the age of 55 years and older from November 15, 2014 to November 15, 2015. We also assessed urinary diagnoses, vaginal estrogen prescriptions, and use of the electronic tools. There was departmental support for the intervention but no prioritization within the healthcare system to incentivize change. RESULTS: In the 1-year period, 386 clinicians performed 14,921 well visits for women at the age of 55 years and older. Among the 190 clinicians who performed well visits in the intervention clinics, 109 (57.4%) completed either in-person or online educational training. The proportion of visits that included a vulvovaginal (7.2% vs 5.8%; odds ratio, 1.27; 95% confidence interval, 0.65-2.51) or urinary diagnosis (2.5% vs 3.1%; odds ratio, 0.79; 95% confidence interval, 0.55-1.13) or vaginal estrogen prescription (4.5% vs 3.7%; odds ratio, 1.24; 95% confidence interval, 0.63-2.46) did not differ between study arms. There was a significant interaction for primary care and gynecology, which revealed more vulvovaginal diagnoses by gynecology but not primary care intervention clinics (odds ratio, 1.63; 95% confidence interval, 1.15-2.31), but there was no significant interaction for prescriptions. Clinicians in the intervention clinics were more likely to use decision support tools than those in control clinics-SmartSet (22.2% vs 1.5%; odds ratio, 18.8; 95% confidence interval, 5.5-63.8) and SmartText for patient information (38.0% vs 24.4%; odds ratio, 1.91; 95% confidence interval, 1.10-3.34). A per-protocol analysis revealed similar findings. CONCLUSION: Overall, the intervention did not lead to more diagnoses or prescription therapy for postmenopausal genitourinary symptoms but did result in greater distribution of patient information. Gynecology clinicians were more likely to address genitourinary symptoms generally and were more likely to make a vulvovaginal diagnosis after the intervention. Further efforts for improving care should consider ongoing clinician education beginning with enhanced menopause curricula in residency training. Additional interventions to consider include greater access for postmenopausal women to gynecologic care, addressing treatment barriers, and development of national performance metrics.

Complex Female Pelvic Pain: A Case Series From a Multidisciplinary Clinic in Urogynecology and Physiatry.

OBJECTIVE: The internal pelvic floor muscles that support the pelvic viscera lie within the external pelvic structures, which support posture and locomotion. The presence of pain in the hip, groin, leg, abdomen, and/or back in patients with pelvic pain suggests that external pelvic sites may act as pain generators that contribute to chronic pelvic pain (CPP). The aim of this study was to report musculoskeletal diagnoses resulting from including a physiatry evaluation as part of a Multidisciplinary Pelvic Pain Clinic for women with complex chronic pain. METHODS: This retrospective case series was conducted by chart review of all women attending the clinic from February 2016 through March 2018. Variable definitions were created for each demographic and clinical characteristic and used to guide a structured review of the chart. Descriptive statistical analysis was performed. RESULTS: Ninety-six percent of the 68 women (mean age, 51 years) had CPP of 6 months' duration or longer. Levator ani tenderness was present in 81% and obturator internus tenderness in 81%. Seventy-one percent of women had failed pelvic physical therapy. Musculoskeletal diagnoses included osteoarthritis, tendinopathies, enthesopathies, osteitis pubis, ischiofemoral impingement, Paget disease, and other systemic conditions. CONCLUSIONS: Musculoskeletal abnormalities were common in this highly selected cohort of complex CPP cases with external pelvic symptoms. The imaging findings and specific diagnoses allowed targeted therapy beyond generalized physical therapy for CPP. The expertise of urogynecologists and physical therapists who evaluate the internal pelvic muscles and viscera combined with the physiatrist's expertise in musculoskeletal assessment and imaging provides an expanded, collaborative approach for managing these patients.

Clinician knowledge, attitudes, and barriers to management of vulvovaginal atrophy: variations in primary care and gynecology.

OBJECTIVE: Vulvovaginal atrophy is a common, but under-recognized condition affecting postmenopausal women. To guide development of an intervention to boost its detection and treatment, we surveyed primary care and gynecology clinicians practicing in an integrated healthcare system. METHODS: We constructed a three-part survey that contained (1) eight multiple-choice knowledge questions; (2) three Likert-scale questions regarding clinicians' likelihood of assessing for vulvovaginal atrophy symptoms at a routine (well) visit, confidence in advising patients about symptoms and counseling about therapy; and (3) a 12-item check list of potential barriers to diagnosis and treatment. Analyses were performed using multiple regression. RESULTS: Of the 360 clinicians who were sent an e-mail request, 119 (90 primary care, 29 gynecology) completed the survey (33%). Responders and nonresponders did not differ by age, specialty, or clinician type. The proportion with correct responses to knowledge questions differed between primary care (63%) and gynecology (77%) (adjusted mean difference [AMD] =16, 95% CI [10-22]). Primary care clinicians were less likely than gynecology clinicians to assess for symptoms (AMD = 1.04, 95% CI [0.55-1.52]), and were less confident about their ability to advise on symptoms (AMD = 0.66, 95% CI [0.33-0.99]) and to counsel patients about treatment (AMD = 0.76, 95% CI [0.42-1.10]). Lack of time (71%) and educational materials (44%) were the most common barriers to diagnosis and treatment. CONCLUSIONS: Primary care and gynecology clinicians differ in their knowledge and confidence in managing vulvovaginal atrophy but report similar practice barriers. Addressing identified knowledge deficits and practice barriers may lead to improved management of vulvovaginal atrophy.

Neutrophil Gelatinase-Associated Lipocalin Biomarker and Urinary Tract Infections: A Diagnostic Case-Control Study (NUTI Study).

OBJECTIVES: Acute uncomplicated urinary tract infection (UTI) in women is often treated based on symptoms alone. Urinary tract infection symptoms are highly sensitive but lack specificity and result in overuse of antibiotics. We sought to determine if urine neutrophil gelatinase-associated lipocalin (uNGAL) levels in urine can accurately discriminate between UTI and healthy women. METHODS: We recruited adult women aged 18 to 85 years presenting in the ambulatory setting from November 2014 to January 2016. Cases were defined as women with Centers for Disease Control and Prevention-defined UTI symptoms and a positive urine culture of more than 10 organisms/mL on a midstream clean-catch specimen. Women without UTI symptoms were matched by age and menopausal status as control subjects. Exclusion criteria were no UTIs within 8 weeks, urinary tract anomalies, renal disease, pregnancy, or diabetes. Clean-catch urine samples were obtained for measuring uNGAL, prior to antibiotic treatment of cases. We used Mann-Whitney U test to compare the 2 groups. Receiver operating characteristic curves were plotted to compare the performance of uNGAL to established urinary markers. RESULTS: We enrolled 50 UTI cases and 50 control subjects. Urine NGAL levels were higher in the UTI group than in the control subjects (P < 0.0001). Using a cutoff of 23.9 ng/mL, NGAL achieved 98% sensitivity and 100% specificity. The receiver operating characteristic curve had an area under the curve of 0.97 (95% confidence interval, 0.93-1.00), which was significantly high and showed that uNGAL can identify UTI. CONCLUSIONS: Urine NGAL has the potential as a biomarker for diagnosing UTIs in adult women.

miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy.

Noncoding RNAs have emerged as important modulators in cardiac development and pathological remodeling. Recently, we demonstrated that regulation of the Gtl2-Dio3 noncoding RNA locus is dependent on the MEF2 transcription factor in cardiac muscle, and that two of its encoded miRNAs, miR-410 and miR-495, induce robust cardiomyocyte proliferation. Given the possibility of manipulating the expression of these miRNAs to repair the damaged heart by stimulating cardiomyocyte proliferation, it is important to determine whether the Gtl2-Dio3 noncoding RNAs are regulated in cardiac disease and whether they function downstream of pathological cardiac stress signaling. Therefore, we examined expression of the above miRNAs processed from the Gtl2-Dio3 locus in various cardiomyopathies. These noncoding RNAs were upregulated in all cardiac disease models examined including myocardial infarction (MI) and chronic angiotensin II (Ang II) stimulation, and in the cardiomyopathies associated with muscular dystrophies. Consistent with these observations, we show that the Gtl2-Dio3 proximal promoter is activated by stress stimuli in cardiomyocytes and requires MEF2 for its induction. Furthermore, inhibiting miR-410 or miR-495 in stressed cardiomyocytes attenuated the hypertrophic response. Thus, the Gtl2-Dio3 noncoding RNA locus is a novel marker of cardiac disease and modulating the activity of its encoded miRNAs may mitigate pathological cardiac remodeling in these diseases.

MicroRNAs in the Myocyte Enhancer Factor 2 (MEF2)-regulated Gtl2-Dio3 Noncoding RNA Locus Promote Cardiomyocyte Proliferation by Targeting the Transcriptional Coactivator Cited2.

Understanding cell cycle regulation in postmitotic cardiomyocytes may lead to new therapeutic approaches to regenerate damaged cardiac tissue. We have demonstrated previously that microRNAs encoded by the Gtl2-Dio3 noncoding RNA locus function downstream of the MEF2A transcription factor in skeletal muscle regeneration. We have also reported expression of these miRNAs in the heart. Here we investigated the role of two Gtl2-Dio3 miRNAs, miR-410 and miR-495, in cardiac muscle. Overexpression of miR-410 and miR-495 robustly stimulated cardiomyocyte DNA synthesis and proliferation. Interestingly, unlike our findings in skeletal muscle, these miRNAs did not modulate the activity of the WNT signaling pathway. Instead, these miRNAs targeted Cited2, a coactivator required for proper cardiac development. Consistent with miR-410 and miR-495 overexpression, siRNA knockdown of Cited2 in neonatal cardiomyocytes resulted in robust proliferation. This phenotype was associated with reduced expression of Cdkn1c/p57/Kip2, a cell cycle inhibitor, and increased expression of VEGFA, a growth factor with proliferation-promoting effects. Therefore, miR-410 and miR-495 are among a growing number of miRNAs that have the ability to potently stimulate neonatal cardiomyocyte proliferation.

MEF2D deficiency in neonatal cardiomyocytes triggers cell cycle re-entry and programmed cell death in vitro.

The cardiomyocyte cell cycle is a poorly understood process. Mammalian cardiomyocytes permanently withdraw from the cell cycle shortly after birth but can re-enter the cell cycle and proliferate when subjected to injury within a brief temporal window in the neonatal period. Thus, investigating the mechanisms of cell cycle regulation in neonatal cardiomyocytes may provide critical insight into the molecular events that prevent adult myocytes from proliferating in response to injury or stress. MEF2D is a key transcriptional mediator of pathological remodeling in the adult heart downstream of various stress-promoting insults. However, the specific gene programs regulated by MEF2D in cardiomyocytes are unknown. By performing genome-wide transcriptome analysis using MEF2D-depleted neonatal cardiomyocytes, we found a significant impairment in the cell cycle, characterized by the up-regulation of numerous positive cell cycle regulators. Expression of Pten, the primary negative regulator of PI3K/Akt, was significantly reduced in MEF2D-deficient cardiomyocytes and found to be a direct target gene of MEF2D. Consistent with these findings mutant cardiomyocytes showed activation of the PI3K/Akt survival pathway. Paradoxically, prolonged deficiency of MEF2D in neonatal cardiomyocytes did not trigger proliferation but instead resulted in programmed cell death, which is likely mediated by the E2F transcription factor. These results demonstrate a critical role for MEF2D in cell cycle regulation of post-mitotic, neonatal cardiomyocytes in vitro.

MEF2 transcription factors regulate distinct gene programs in mammalian skeletal muscle differentiation.

Skeletal muscle differentiation requires precisely coordinated transcriptional regulation of diverse gene programs that ultimately give rise to the specialized properties of this cell type. In Drosophila, this process is controlled, in part, by MEF2, the sole member of an evolutionarily conserved transcription factor family. By contrast, vertebrate MEF2 is encoded by four distinct genes, Mef2a, -b, -c, and -d, making it far more challenging to link this transcription factor to the regulation of specific muscle gene programs. Here, we have taken the first step in molecularly dissecting vertebrate MEF2 transcriptional function in skeletal muscle differentiation by depleting individual MEF2 proteins in myoblasts. Whereas MEF2A is absolutely required for proper myoblast differentiation, MEF2B, -C, and -D were found to be dispensable for this process. Furthermore, despite the extensive redundancy, we show that mammalian MEF2 proteins regulate a significant subset of nonoverlapping gene programs. These results suggest that individual MEF2 family members are able to recognize specific targets among the entire cohort of MEF2-regulated genes in the muscle genome. These findings provide opportunities to modulate the activity of MEF2 isoforms and their respective gene programs in skeletal muscle homeostasis and disease.

The incidence of contralateral iliac venous thrombosis after stenting across the iliocaval confluence in patients with acute or chronic venous outflow obstruction.

OBJECTIVE: Percutaneous transluminal angioplasty with stenting of the iliac veins is the method of choice to treat patients with symptomatic lower extremity venous outflow obstruction. The optimal method of performing this technique remains to be solved, however. One question in particular is that when braided stainless steel stents (Wallstents; Boston Scientific, Natick, Mass) are used, should these venous stents extend into the vena cava or should they stop short of this for fear of causing thrombosis of the patient's normal contralateral iliofemoral vein? It has been our practice to extend our venous stents significantly into the vena cava to coapt with the inferior vena cava (IVC) wall in the majority of patients with disease of the common iliac vein at the iliocaval junction. The aim of this study was to assess whether this placement led to thrombosis of a normal contralateral common iliac vein. METHODS: We retrospectively reviewed prospectively collected data from 2008 to 2012 in patients with symptomatic acute or chronic iliocaval venous obstruction who underwent percutaneous angioplasty and stenting at our institution. Data were collected by use of the American Venous Forum venous stent database variables. Stent patency rates and the incidence of contralateral iliac vein thrombosis were analyzed. RESULTS: In 65 patients (median age, 48 years; range, 15-80 years), 200 iliocaval stents were placed. Of these patients, 41 received ipsilateral stents that extended into the IVC and completely across the contralateral common iliac vein orifice; 39 (95%) of these had venous outflow obstruction as a result of thrombotic disease. In 22 patients (54%), post-thrombotic disease involved the IVC. All patients had stents that extended into the IVC, crossing the normal contralateral iliac vein orifice completely. Most patients (97.5%) were maintained by full anticoagulation with warfarin or low-molecular-weight heparin. Four patients (9.7%) suffered new thrombosis of the nonstented contralateral iliofemoral vein; two patients had initial involvement of the IVC, and three were totally noncompliant with their postoperative anticoagulation. Thus, 2.4% of compliant patients had new contralateral thrombosis after stenting across a normal contralateral common iliac vein and into the vena caval wall. In this select patient population, univariate analysis of patient compliance with the postoperative anticoagulation strategy showed a strong correlation with postoperative contralateral iliofemoral venous thrombosis (P = .0004). CONCLUSIONS: From these data, it appears that stenting across the iliocaval confluence can be done safely in the majority of patients maintained with therapeutic anticoagulation. In post-thrombotic patients, however, stenting across the iliocaval confluence can result in a small number of new contralateral thromboses, more often if the patients are noncompliant with anticoagulation after stenting. Current stent technology limits the ability of practitioners to treat common femoral venous obstruction precisely. Future stent development is likely to eliminate the need to cross the iliocaval confluence and risk contralateral venous thromboses.

Concentric Needle Quantitative EMG of Pubovisceralis Muscle Group: Normative Data from Asymptomatic Nulliparous Women.

OBJECTIVES: The muscles of the pelvic floor closest to the vaginal opening are subject to the greatest degree of stretch during vaginal childbirth. We aim to define normative quantitative EMG (QEMG) parameters for the pubovisceralis (PV) muscle in nulliparous women, and compare them to the external anal sphincter (EAS). METHODS: In 31 asymptomatic nulliparous women, concentric Needle EMG of the PV and the EAS was performed. Multi-motor unit action potential (Multi-MUAP) and interference pattern (IP) algorithms were utilized to obtain QEMG parameters. We used paired t-tests to compare PV and EAS parameters. RESULTS: The motor units for the PV were of greater duration (p < 0.002) and had more turns (p = 0.03) than the paired motor units in the EAS. The EAS demonstrated more turns/second (p = 0.02), greater activity (p = 0.01), and more short segments (p = 0.009) than the PV. CONCLUSIONS: The PV has longer and more complex motor units than the EAS. This knowledge continues to improve our ability to detect neuropathic changes in this vulnerable muscle area following childbirth or in women with pelvic floor dysfunction. In addition, the PV muscle group appears less responsive to requests for increased neuromuscular activity than the EAS. This needs to be further evaluated, as it may be associated with understanding which portion of the muscle functionally shortens to maintain the closure of the levator hiatus.

Using the Brink score to predict postpartum anal incontinence.

OBJECTIVE: To evaluate whether antepartum pelvic floor muscle strength, as measured by the Brink scale, predicts postpartum anal incontinence. STUDY DESIGN: This prospective cohort study of primigravid women used validated questionnaires and standardized pelvic examinations to evaluate subjects during the third trimester and at 2 postpartum time points. RESULTS: Of the initial 129 subjects, 102 and 81 completed 2 week and 6 month postpartum visits. 35% had cesarean deliveries. The antepartum prevalence of fecal incontinence (14%) did not differ significantly from the postpartum (17% at 2 weeks, 11% at 6 months). However, the prevalence of flatal incontinence fell from antepartum (65%) to postpartum (47% at 2 weeks, P = .001; 49% at 6 months, P = .012). Mean Brink score decreased postpartum; no correlations were found between Brink score and questionnaire scores. CONCLUSION: Anal incontinence symptoms are common in the third trimester of a first pregnancy and may regress or resolve after delivery. Brink score did not predict postpartum anal incontinence.

Effect of unsaturation in fatty acids on the binding and oxidation by myeloperoxidase: ramifications for the initiation of atherosclerosis.

Oxidation of low density lipoproteins (LDL) in the presence of myeloperoxidase and subsequent uptake of the oxidized LDL by specialized receptors on macrophages has been suggested as an initiating event of atherosclerosis. Oxidized fatty acid chains within the glycerophospholipids of LDL have been implicated as the recognition feature by the receptors. The ability of three fatty acids (oleic, linoleic, and arachidonic acids) typically contained in the lipid portion of the glycerophospholipids to bind and be oxidized by myeloperoxidase was measured by spectroscopically observing interactions of the lipids with the heme prosthetic group of the enzyme. As unsaturation increases in the lipid chain, myeloperoxidase binds and oxidizes the fatty acid more readily, as measured by K(D), K(M), and k(cat). A possible mechanism of the free radical oxidation by myeloperoxidase is discussed.

Reference lines in dynamic magnetic resonance imaging of the pelvic floor.

OBJECTIVE: : To compare the variability in two commonly used reference lines in pelvic magnetic resonance imaging (MRI), the pubococcygeal line (PCL) and the sacrococcygeal to inferior pubis (SCIPP) line, with respect to their distance from pelvic floor points of interest. METHODS: : We obtained pelvic MR images of 20 asymptomatic nulliparous women who are part of an ongoing pelvic floor nerve injury postpartum study. The subjects underwent a high-resolution two-dimensional, T2-weighted sagittal pelvic MRI in the supine position using a GE Signa scanner with a body phased-array coil. We also obtained dynamic T2-weighted sagittal MR images in supine position during Kegel and Valsalva maneuvers. Using the midsagittal image, we measured the length of two reference lines: the PCL and the more cephalad SCIPP line. From each line, we then measured the perpendicular distance to the bladder neck and to the posterior margin of the anorectal angle (M-line). We compared the mean values of all measurements between the two reference lines with paired Student t tests. RESULT: : The SCIPP line (mean [SD], 11.60 [0.91] cm) is longer than the PCL (mean [SD], 10.54 [0.85] cm) at rest (P < 0.001). There is no significant change in length from resting to Kegel maneuver or from resting to Valsalva maneuver in either reference line. Only the resting to Valsalva maneuver for the M-line was significantly different between the 2 reference lines (P = 0.02). The resting to Kegel for the perpendicular distance to the bladder neck and the M-line was not significantly different between the two lines. CONCLUSIONS: : Both reference lines remain stable during pelvic floor maneuvers.