Improved behavior after adenotonsillectomy in children with higher and lower IQ.

OBJECTIVES: To examine whether high intellectual ability, in comparison to average or lower performance, reflects the consequences of sleep-disordered breathing and limits behavioral benefit observed 6 months after adenotonsillectomy. METHODS: Children aged 3-12 years (n=147) recruited from otolaryngology practices at two hospitals and assessed with Conners' Parent Rating Scales and an age range-appropriate intellectual measure, the Stanford-Binet Intelligence Scale at baseline and 6 months after clinically-indicated adenotonsillectomy. Subjects were classified as having high (IQ≥110), average (90≤IQ<110), or low (IQ<90) cognitive ability. RESULTS: After adenotonsillectomy, improvements in Conners' internalizing, externalizing, hyperactivity, and cognitive domains were observed across IQ groups (main effects for time, all p<0.01 or better), with no evidence for differential improvements among the groups (no significant time by IQ group interactions). The magnitude of behavioral improvement among children with high IQ resembled that observed among the other two groups. Changes in the Conners' domains were not significantly correlated with baseline IQ, age, socioeconomic status, body mass index z-score, or respiratory disturbance index. CONCLUSION: Behavioral function can improve after adenotonsillectomy even among children with relatively high intellectual ability at baseline. Diagnosis and treatment with expectation of neurobehavioral benefit should be considered among high-performing children as readily as it is more traditionally among their lower-performing peers.

Differences in Patterns of Preoperative Assessment Between High, Intermediate, and Low Volume Surgeons When Performing Hysterectomy for Uterovaginal Prolapse.

OBJECTIVE: The aim of the study was to determine whether surgeon case volume is associated with preoperative evaluation of pelvic organ prolapse before a hysterectomy for uterovaginal prolapse including a complete objective evaluation of prolapse (Baden-Walker or Pelvic Organ Prolapse Quantification), an offer of nonsurgical options for therapy (pessary), and a preoperative assessment of urinary incontinence METHODS: We performed a multicenter retrospective review of hysterectomies done for uterovaginal prolapse at 4 hospital systems between January 1, 2008 and December 31, 2011. The number of hysterectomies per surgeon for 4 years was evaluated to establish low-volume (≤10 cases), intermediate-volume (11-49 cases), and high-volume (≥50 cases) groups. Rates of preoperative standardized prolapse evaluations, offer of pessary, and evaluation of stress urinary incontinence were determined by chart review of 15% of the hysterectomy cases. Adjustment was made in a logistic regression model for age, race, insurance status, and prolapse size. RESULTS: Three hundred one surgeons performed 4238 hysterectomies for prolapse during the study period. Rates of preoperative assessment by standardized pelvic examination differed between high-, intermediate-, and low-volume surgeons (91.2% vs. 61.3% vs. 48.8%, respectively), as did offer of a pessary (86.5% vs. 71.9% vs. 69.9%, respectively) and preoperative stress test for urinary incontinence (93.5% vs. 72.8% vs. 63.5%, respectively). Regression analysis revealed that high-volume surgeons were more likely than intermediate- or low-volume surgeons to perform a standardized pelvic examination, offer a pessary, or perform preoperative evaluation for urinary incontinence. CONCLUSIONS: High-volume surgeons were more likely than low-volume surgeons to perform a standardized preoperative pelvic examination, offer a pessary, and evaluate stress urinary incontinence.

Analysis of High-, Intermediate-, and Low-Volume Surgeons When Performing Hysterectomy for Uterovaginal Prolapse.

OBJECTIVES: To determine if surgeon volume is associated with differences in the use of apical colpopexy and cystoscopy and in the rate of intraoperative complications during hysterectomy for prolapse. METHODS: We performed a multicenter retrospective review of hysterectomies done for uterovaginal prolapse at 4 hospital systems between January 1, 2008, and December 31, 2011. Low (≤10 cases)-, intermediate (11-49 cases)-, and high (≥50 cases)-volume surgeon groups for the 4-year period were established a priori. Rates of concomitant colpopexy, cystoscopy, and intraoperative complications were determined by chart review for 15% of the cases. Multivariate logistic regression models adjusted for site and other clinical and patient variables were used to estimate associations between surgeon case volume and the use of apical colpopexy and cystoscopy and the rate of intraoperative complications. RESULTS: Three hundred one surgeons performed 4238 hysterectomies for prolapse during the study period. Six hundred thirty-eight patients were selected for chart review. The rates among high-, intermediate-, and low-volume surgeons for performing colpopexy were 85.2% versus 77.8% versus 61.1% (P < 0.001) and for cystoscopy were 96.8% versus 78.3% versus 74.7% (P < 0.001), respectively. Rates of intraoperative complications among the 3 groups were 4.4%, 11.6%, and 6.3% (P = 0.011), respectively. With adjustment, high-volume surgeons were more likely to do a colpopexy than low-volume surgeons (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.1); however, the likelihood of colpopexy did not differ between high- and intermediate-volume surgeons (OR, 1.9; 95% CI, 0.84-4.3) or between intermediate- and low-volume surgeons (OR, 0.99; 95% CI, 0.50-2.0). High-volume surgeons were more likely than intermediate-volume (OR, 4.4; 95% CI, 1.7-11.0) and low-volume (OR, 4.5; 95% CI, 2.6-8.0) surgeons to do a cystoscopy. High-volume (OR, 0.42; 95% CI, 0.30-0.61) and low-volume (OR, 0.32; 95% CI, 0.15-0.66) surgeons were less likely than intermediate-volume surgeons to have intraoperative complications. The difference between high- and low-volume surgeons was not statistically significant (OR, 0.77; 95% CI, 0.5-1.2). CONCLUSIONS: Practice patterns with respect to hysterectomy for prolapse are complex when the use of colpopexy and cystoscopy and rates of intraoperative complications are analyzed by surgeon volume. The finding that intermediate-volume surgeons have the highest rates of intraoperative complications suggests a nonlinear relationship between surgeon volume and avoidance of injury.

Periodic leg movements during sleep in children scheduled for adenotonsillectomy: frequency, persistence, and impact.

OBJECTIVE: The aim of this study was to assess the frequency and potential clinical impact of periodic leg movements during sleep (PLMS), with or without arousals, as recorded incidentally from children before and after adenotonsillectomy (AT). METHODS: Children scheduled for AT for any clinical indications who participated in the Washtenaw County Adenotonsillectomy Cohort II were studied at enrollment and again 6 months thereafter. Assessments included laboratory-based polysomnography, a Multiple Sleep Latency Test (MSLT), parent-completed behavioral rating scales, neuropsychological testing, and psychiatric evaluation. RESULTS: Participants included 144 children (81 boys) aged 3-12 years. Children generally showed mild to moderate obstructive sleep apnea (median respiratory disturbance index 4.5 (Q1 = 2.0, Q3 = 9.5)) at baseline, and 15 subjects (10%) had at least five periodic leg movements per hour of sleep (PLMI ≥ 5). After surgery, 21 (15%) of n = 137 subjects who had follow-up studies showed PLMI ≥ 5 (p = 0.0067). Improvements were noted after surgery in the respiratory disturbance index; insomnia symptoms; sleepiness symptoms; mean sleep latencies; hyperactive behavior; memory, learning, attention, and executive functioning on NEPSY assessments; and frequency of attention-deficit/hyperactivity disorder (DSM-IV criteria). However, PLMI ≥ 5 failed to show associations with worse morbidity in these domains at baseline or follow-up. New appearance of PLMI ≥ 5 after surgery failed to predict worsening of these morbidities (all p > 0.05), with only one exception (NEPSY) where the magnitude of association was nonetheless negligible. Similar findings emerged for periodic leg movements with arousals (PLMAI ≥ 1). CONCLUSION: PLMS, with and without arousals, become more common after AT in children. However, results in this setting did not suggest substantial clinical impact.

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT00233194.

Soluble P-selectin for the diagnosis of lower extremity deep venous thrombosis.

OBJECTIVE: Although duplex ultrasound is the standard for the diagnosis of lower extremity deep venous thrombosis (LE-DVT), imaging is not always available. The use of D-dimer can exclude (high-sensitivity), but not rule in (low-specificity) LE-DVT. Previously, we demonstrated that soluble P-selectin (sP-sel) in combination with the Wells score, establishes the diagnosis of LE-DVT with a specificity of 96% and a positive predictive value of 100%. In order to validate our previous results, we applied the model to a separate but similar patient cohort. Additionally, we analyzed the role of biomarkers for diagnosing upper extremity DVT (UE-DVT). METHODS: Between April 2009 and March 2012, all patients presenting for a duplex ultrasound exam with concern of DVT were screened. Demographics, clinical data, D-dimer, sP-sel, C-reactive protein, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, and von Willebrand factor levels were prospectively collected in 279 patients (234 LE-DVT, 45 UE-DVT). Continuous and categorical variables among patients with DVT were compared with patients without DVT. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were then calculated using our previously derived cut points to rule in or exclude DVT. RESULTS: Among 234 patients evaluated for LE-DVT, 112 (48%) patients had a confirmed LE-DVT with significant differences in all biomarkers. When Wells score ≥2, sP-sel could rule in LE-DVT with a specificity of 97.5% and a positive predictive value of 91%, which was more accurate than Wells score ≥2 and D-dimer (specificity, 65%; positive predictive value, 69%). When Wells score was <2, D-dimer was superior to sP-sel for excluding the diagnosis of LE-DVT (sensitivity, 98%; negative predictive value, 95% vs sensitivity, 91%; negative predictive value, 79%). The use of additional biomarkers did not increase accuracy. Had imaging not been available, we could have correctly ruled in or ruled out LE-DVT in 29% (67/234) of patients. The use of sP-sel in UE-DVT was nondiagnostic. CONCLUSIONS: We demonstrate that when Wells score ≥2, sP-sel is an excellent biomarker to rule in LE-DVT. Different from our previous study, D-dimer and a Wells score <2 was most sensitive at excluding a diagnosis of LE-DVT. Combined, Wells score, sP-sel, and D-dimer can both rule in and exclude LE-DVT in approximately one-third of patients.

Prothrombotic effects of thrombolytic therapy in a rat (Rattus norvegicus) model of venous thrombolysis.

The use of thrombolytic agents has greatly improved patient outcomes, but the prothrombotic response to these drugs in vivo is unknown. Approximately 24 h after we induced thrombosis in male Sprague-Dawley rats, we placed an infusion line in the inferior vena cava and administered either saline or a thrombolytic agent (tissue plasminogen activator [tPA] or plasmin) for 30 min. Blood was drawn immediately after infusion; rats were euthanized 24 h after infusion for collection of blood and tissue (inferior vena cava and thrombus). Thrombus size was decreased in the tPA-treated rats but not in those that received saline or plasmin; this change correlated with the significant rise in D-dimer levels noted immediately after infusion in the tPA-treated rats. Plasma soluble P-selectin, a prothrombotic marker, was elevated at 24 h in the plasmin group compared with the other treatment groups. There were no significant differences in plasma C3a, C5a, or C5b9 levels or in thrombus C3 levels between groups. According to ultrastructural analysis, thrombus structure and vein wall effects did not differ between groups. Local tPA did not induce a prothrombotic state during acute DVT or after thrombolytic therapy in a rodent model of venous thrombolysis. Conversely, levels of the prothrombotic marker plasma soluble P-selectin increased when plasmin was administered.

Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

OBJECTIVES: One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. DESIGN: Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. RESULTS: Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. CONCLUSIONS: These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Is cervical elongation associated with pelvic organ prolapse?

INTRODUCTION AND HYPOTHESIS: It is commonly believed that pelvic organ prolapse (POP) is associated with cervical elongation. However, cervical lengths have not been formally compared between women with prolapse and those with normal support. METHODS: Cervix and uterine corpus lengths were measured on magnetic resonance images in a case-control study of 51 women with prolapse and 46 women with normal support determined by the Pelvic Organ Prolapse Quantification (POP-Q) examination. Group matching ensured similar demographics in both groups. Ranges for normal cervical lengths were determined from the values in the control group in order to evaluate for cervical elongation amongst women with prolapse. RESULTS: The cervix is 36.4 % (8.6 mm) longer in women with prolapse than in women with normal pelvic support (p < 0.001). Linear regression modeling suggests the feature most highly associated with cervical length is the degree of uterine descent (POP-Q point C). Approximately 40 % of women with prolapse have cervical elongation; 57 % of cervical elongation in prolapse can be explained by a logistic regression-based model including POP-Q point C, body mass index, and menopausal status. CONCLUSIONS: Cervical elongation is found in one third of women with POP, with the extent of elongation increasing with greater degrees of uterine descent.

Esophageal pressures, polysomnography, and neurobehavioral outcomes of adenotonsillectomy in children.

BACKGROUND: Esophageal pressure monitoring during polysomnography in children offers a gold-standard, "preferred" assessment for work of breathing, but is not commonly used in part because prospective data on incremental clinical utility are scarce. We compared a standard pediatric apnea/hypopnea index to quantitative esophageal pressures as predictors of apnea-related neurobehavioral morbidity and treatment response. METHODS: Eighty-one children aged 7.8 ± 2.8 (SD) years, including 44 boys, had traditional laboratory-based pediatric polysomnography, esophageal pressure monitoring, multiple sleep latency tests, psychiatric evaluations, parental behavior rating scales, and cognitive testing, all just before clinically indicated adenotonsillectomy, and again 7.2 ± 0.8 months later. Esophageal pressures were used, along with nasal pressure monitoring and oronasal thermocouples, not only to identify respiratory events but also more quantitatively to determine the most negative esophageal pressure recorded and the percentage of sleep time spent with pressures lower than -10 cm H(2)O. RESULTS: Both sleep-disordered breathing and neurobehavioral measures improved after surgery. At baseline, one or both quantitative esophageal pressure measures predicted a disruptive behavior disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined attention-deficit/hyperactivity disorder, conduct disorder, or oppositional defiant disorder) and more sleepiness and their future improvement after adenotonsillectomy (each P < .05). The pediatric apnea/hypopnea index did not predict these morbidities or treatment outcomes (each P > .10). The addition of respiratory effort-related arousals to the apnea/hypopnea index did not improve its predictive value. Neither the preoperative apnea/hypopnea index nor esophageal pressures predicted baseline hyperactive behavior, cognitive performance, or their improvement after surgery. CONCLUSIONS: Quantitative esophageal pressure monitoring may add predictive value for some, if not all, neurobehavioral outcomes of sleep-disordered breathing.

Changes in neuropsychological and behavioral functioning in children with and without obstructive sleep apnea following Tonsillectomy.

The most common treatment for sleep disordered breathing (SDB) is adenotonsillectomy (AT). Following AT, SDB resolves in most cases, and gains in cognitive and behavior scores are consistently reported, although persistent neuropsychological deficits or further declines also have been noted. This study presents results of the comprehensive 1-year follow-up neuropsychological examinations for children in the Washtenaw County Adenotonsillectomy Cohort I (95% return rate). After adjusting for normal developmental and practice-effect related changes in control children, significant improvements 1 year following AT were noted in polysomnography and sleepiness, as well as parental reports of behavior, although cognitive outcomes were mixed. Children undergoing AT with and without polysomnography-confirmed obstructive sleep apnea improved across a range of academic achievement measures, a measure of delayed visual recall, short-term attention/working memory, and executive functioning, along with parental ratings of behavior. On the other hand, measures of verbal abstraction ability, arithmetic calculations, visual and verbal learning, verbal delayed recall, sustained attention, and another measure of visual delayed recall demonstrated declines in ability, while other measures did not improve over time. These findings call into question the expectation that AT resolves most or all behavioral and cognitive difficulties in children with clinical, office-based diagnoses of SDB.

3D analysis of cystoceles using magnetic resonance imaging assessing midline, paravaginal, and apical defects.

INTRODUCTION AND HYPOTHESIS: This study assesses relative contributions of "midline defects" (widening of the vagina) and "paravaginal defects" (separation of the lateral vagina from the pelvic sidewall). METHODS: Ten women with anterior predominant prolapse and ten with normal support underwent pelvic MR imaging. 3-D models of the anterior vaginal wall (AVW) were generated to determine locations of the lateral AVW margin, vaginal width, and apical position. RESULTS: The lateral AVW margin was farther from its normal position in cases than controls throughout most of the vaginal length, most pronounced midvagina (effect sizes, 2.2-2.8). Vaginal widths differed in the midvagina with an effect size of 1.0. Strong correlations between apical and paravaginal support were evident in mid- and upper vagina (r = 0.77-0.93). CONCLUSIONS: Changes in lateral AVW location were considerably greater than changes in vaginal width in cases vs controls, both in number of sites affected and effect sizes. These "paravaginal defects" are highly correlated with apical descent.

Aggressive behavior, bullying, snoring, and sleepiness in schoolchildren.

BACKGROUND: To assess whether urban schoolchildren with aggressive behavior are more likely than peers to have symptoms suggestive of sleep-disordered breathing. METHODS: Cross-sectional survey of sleep and behavior in schoolchildren. Validated screening assessments for conduct problems (Connor's rating scale), bullying behavior, and sleep-disordered breathing (pediatric sleep questionnaire) were completed by parents. Teachers completed Connor's teacher rating scale. RESULTS: Among 341 subjects (51% female), 110 (32%) were rated by a parent or teacher as having a conduct problem (T-score ⩾65) and 78 (23%) had symptoms suggestive of sleep-disordered breathing. Children with conduct problems, bullying, or discipline referrals, in comparison to non-aggressive peers, more often had symptoms suggestive of sleep-disordered breathing (each p<0.05). Children with vs. without conduct problems were more likely to snore habitually (p<0.5). However, a sleepiness subscale alone, and not a snoring subscale, predicted conduct problems after accounting for age, gender, a measure of socioeconomic status, and stimulant use. CONCLUSIONS: Urban schoolchildren with aggressive behaviors may have symptoms of sleep-disordered breathing with disproportionate frequency. Sleepiness may impair emotional regulation necessary to control aggression.

Evaluation of soluble P-selectin as a marker for the diagnosis of deep venous thrombosis.

OBJECTIVE: The combination of D-dimer and Wells score can exclude, but not confirm, the diagnosis of deep venous thrombosis (DVT). Since thrombosis and inflammation are interrelated, we evaluated the combination of soluble P-selectin (sPsel) with other inflammatory biomarkers for the diagnosis of DVT. METHODS: Sixty-two positive and one hundred and sixteen patients with negative DVT, by duplex scan, were prospectively evaluated for sPsel, D-dimer, C-reactive protein (CRP), microparticles (MPs; total, leukocyte, and platelet-derived and tissue factor positive microparticles), and clinical Wells score. RESULTS: Biomarkers and clinical scores that differentiated DVT positives from negatives were sPsel (87.3 vs 53.4 ng/mL, P < .0001), D-dimer (5.8 vs 2.1 mg/ L, P < .0001), CRP (2.1 vs 0.8 µg/mL, P < .0005), and Wells score (3.2 vs 2.0, P < .0001). For MP analysis, platelet-derived MPs were found to differentiate DVT from negatives. Using multivariable logistic regression, a combination of sPsel and Wells score could establish the diagnosis of DVT (cut point ≥ 90 ng/mL + Wells ≥ 2), with a specificity of 96% and positive predictive value (PPV) of 100%, and could exclude DVT diagnosis (cut point ≤ 60 ng/mL and Wells <2) with a sensitivity of 99%, a specificity of 33%, and a negative predictive value (NPV) of 96%. CONCLUSION: This study establishes a biomarker and clinical profile combination that can both confirm and exclude the diagnosis of DVT.

Metabolic consequences of sepsis-induced acute lung injury revealed by plasma ¹H-nuclear magnetic resonance quantitative metabolomics and computational analysis.

Metabolomics is an emerging component of systems biology that may be a viable strategy for the identification and validation of physiologically relevant biomarkers. Nuclear magnetic resonance (NMR) spectroscopy allows for establishing quantitative data sets for multiple endogenous metabolites without preconception. Sepsis-induced acute lung injury (ALI) is a complex and serious illness associated with high morbidity and mortality for which there is presently no effective pharmacotherapy. The goal of this study was to apply ¹H-NMR based quantitative metabolomics with subsequent computational analysis to begin working towards elucidating the plasma metabolic changes associated with sepsis-induced ALI. To this end, this pilot study generated quantitative data sets that revealed differences between patients with ALI and healthy subjects in the level of the following metabolites: total glutathione, adenosine, phosphatidylserine, and sphingomyelin. Moreover, myoinositol levels were associated with acute physiology scores (APS) (ρ = -0.53, P = 0.05, q = 0.25) and ventilator-free days (ρ = -0.73, P = 0.005, q = 0.01). There was also an association between total glutathione and APS (ρ = 0.56, P = 0.04, q = 0.25). Computational network analysis revealed a distinct metabolic pathway for each metabolite. In summary, this pilot study demonstrated the feasibility of plasma ¹H-NMR quantitative metabolomics because it yielded a physiologically relevant metabolite data set that distinguished sepsis-induced ALI from health. In addition, it justifies the continued study of this approach to determine whether sepsis-induced ALI has a distinct metabolic phenotype and whether there are predictive biomarkers of severity and outcome in these patients.

Proteomics of microparticles after deep venous thrombosis.

BACKGROUND: Microparticles (MP) are submicron size membrane vesicles released from activated cells that are associated with thrombosis and inflammation. MP present diverse biological expressions that may be linked to a unique subset of proteins derived from their origin cells. METHODS: To identify these proteins, plasma samples were taken from 9 patients with deep venous thrombosis (DVT) documented by duplex ultrasound, 9 with leg pain but negative for DVT by duplex, and 6 healthy controls without a history of thrombosis, for fold variation. MP were extracted from platelet-poor plasma, digested separately with trypsin and tagged using iTRAQ reagents. The digests were subjected to 2-D LC separation followed by MALDI tandem mass spectrometry. Peak lists were generated and searched against all human sequences. For protein identification, a minimum of two peptides at 95% confidence was required. Later, iTRAQ ratios were generated comparing relative protein levels of DVT patients to baseline. The proteomic analysis was performed twice for each blood sample. Proteins were considered elevated or depressed if the iTRAQ ratio (R) deviated by 20% change from normal and a p-value less than 0.05. RESULTS: Two proteins (Galectin-3 Binding Protein, [Gal3BP], R=1.76 and Alpha-2 macroglobulin [A2M] R=1.57) were differentially expressed on DVT patients. Nine proteins were depleted including fibrinogen beta and gamma chain precursors (R=0.65). CONCLUSIONS: These proteins influence thrombosis through inflammation, cell shedding, inhibition of fibrinolysis and hemostatic plug formation. Further studies are needed to confirm the mechanistic role of these proteins in the pathogenesis of venous thrombosis in humans.

Levator ani defect status and lower urinary tract symptoms in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Among women with pelvic organ prolapse, compare rates of lower urinary tract symptoms by levator ani defect (LAD) status. METHODS: Urinary incontinence and obstructive voiding are analyzed among 151 women with prolapse whose LAD status was determined with magnetic resonance imaging. RESULTS: Women with major LAD are less likely to experience stress incontinence when "coughing, laughing, or sneezing" (odds ratio (OR) 0.27) and when "twisting, reaching, lifting, or bending over" (OR 0.26) than women with normal muscles. They are less likely to have obstructive symptoms characterized by assuming an "unusual toileting position" or "changing positions...to start or complete urination" (OR 0.27). Women with minor LAD are more likely to experience stress incontinence with exercise (OR 3.1) and urge incontinence (OR 4.0) than those with normal muscles. CONCLUSIONS: Lower urinary tract symptoms are less common among women with prolapse and major levator ani defects and more common among those with minor defects.

Racial differences in bother for women with urinary incontinence in the Establishing the Prevalence of Incontinence (EPI) study.

OBJECTIVE: The purpose of this study was to compare differences in degree of bother in black and white women with urinary incontinence (UI). STUDY DESIGN: A population-based study was conducted in black and white women in Michigan. Participants completed an interview and the Incontinence Impact Questionnaire short form (IIQ-7). Statistical analysis included 2-way analysis of variance for post hoc comparisons of IIQ-7 scores between races at different frequencies, amounts, and types of UI. RESULTS: Black women with moderate UI had significantly higher IIQ-7 scores than white women (31.4 +/- 3.5 vs 23.7 +/- 1.9; P = .03). Overall, black women with urge incontinence had higher scores than white women (30.5 +/- 4.0 vs 21.0 +/- 3.0; P = .05). After adjustment for severity, black women with urge and mixed incontinence tended to be more bothered (P = .06). CONCLUSION: With moderate UI (not mild or severe), black women are more bothered than white women. At this discriminatory level of UI severity, racial differences are important, because they may dictate care-seeking behavior.

Contrasting the use of 2 vision-specific quality of life questionnaires in subjects with open-angle glaucoma.

PURPOSE: To compare 2 vision-specific functional status measures to each other and to clinical parameters in the Collaborative Initial Glaucoma Treatment Study (CIGTS). METHODS: CIGTS participants completed the Visual Activities Questionnaire (VAQ) and the National Eye Institute-Visual Function Questionnaire (NEI-VFQ) and were tested for visual field (VF) and visual acuity (VA). In all, 426 subjects contributed the VAQ and NEI-VFQ scores at 54 months. Pearson correlations were used to assess associations. RESULTS: The VAQ subscales (range, 0 to 100) that assessed light-dark adaptation (mean=66.1), glare disability (66.4), and acuity/spatial vision (67.7) indicated vision-related functions that CIGTS participants found most difficult. On the NEI-VFQ, subjects reported high levels of visual functioning, with mean >/=90 (out of 100) on the total score and in 9 of 12 subscales. General vision (mean=82.6) received the lowest subscale score. Two subscales common to both questionnaires were highly correlated: VA (r=0.68) and peripheral vision (r=0.77) (both P<0.0001). Correlations between participants' perceptions and clinical measures of visual function were in the expected direction, but weaker. Stronger associations were found between clinical measures and the NEI-VFQ than the VAQ. Better eye VF and worse eye VA had the highest number of significant correlations with subjects' perceptions of their visual function. Increasing VF loss was associated with a significant decrease in the overall and peripheral vision subscale scores from both questionnaires, and also several other subscales. CONCLUSIONS: CIGTS patients reported excellent visual function on both the NEI-VFQ and VAQ. These findings will help researchers interested in assessing patients' perceptions of their visual function make an informed selection when choosing between the VAQ and the NEI-VFQ.

Urethral sphincter morphology and function with and without stress incontinence.

PURPOSE: Using magnetic resonance images we analyzed the relationship between urethral sphincter anatomy, urethral function and pelvic floor function. MATERIALS AND METHODS: A total of 103 women with stress incontinence and 108 asymptomatic continent controls underwent urethral profilometry, urethral axis measurement with a cotton swab, vaginal closure force measurement with an instrumented speculum and magnetic resonance imaging. Striated urogenital sphincter length was determined and its thickness was measured in the proximal sphincter, where its circular shape enables estimation of striated urogenital sphincter area. A length-area index was calculated as a proxy for volume. RESULTS: The striated urogenital sphincter in women with stress incontinence was 12.5% smaller than that in asymptomatic continent women (mean +/- SD length-area index 766.4 +/- 294.3 vs 876.2 +/- 407.3 mm(3), p = 0.04). The groups did not differ significantly in striated urogenital sphincter length (13.2 +/- 3.4 vs 13.7 +/- 3.9 mm, p = 0.40), thickness (2.83 +/- 0.8 vs 3.11 +/- 1.4 mm, p = 0.09) or area (59.1 +/- 18.4 vs 62.9 +/- 24.7 mm(2), p = 0.24). Striated urogenital sphincter length and area, and the length-area index were associated during voluntary pelvic muscle contraction with more urethral axis elevation and increased vaginal closure force augmentation. CONCLUSIONS: A smaller striated urogenital sphincter is associated with stress incontinence and poorer pelvic floor muscle function.