27†Chiasmal misrouting in infantile nystagmus syndrome (INS): phenotypes in patients with molecular diagnoses.

Chiasmal misrouting, once believed to be pathognomonic for albinism, has been reported in cases of INS, independent of melanin pathway disruption. The purpose of this study is to determine if there are clinical-electrophysiological parameters that correlate with particular genotypes in INS.A retrospective chart review at Moorfields Eye Hospital identified 71 patients with a molecular diagnosis relating to INS. Visual acuity; presence of nystagmus, signs of albinism and OCT foveal hypoplasia grade were recorded alongside flash and pattern VEP (Visual Evoked Potential) amplitude and peak time. VEP asymmetry was assessed using the Pearson Correlation Coefficient (r).Pathological variants in 8 genes (TYR, OCA2, HPS6, HPS3, HPS1, GPR143, FRMD7, SLC38A8, OCA1) were identified. Mean BCVA per group ranged from 0.38-0.74LogMAR F(0.72,3.5)=2.8; p=0.04 one-way ANOVA. All genotypes demonstrated foveal hypoplasia (mode grade 4) except FRMD7 (all grade 1). In this cohort, positive flash and pattern VEP amplitude/peak time asymmetry correlated with clinical signs of albinism (flash VEP, r=0.22(0-6yrs); pattern VEP, r=0.17(6-65yrs)). There was marked asymmetry in SLC38A8 patients (r = -0.85 to-0.93), a feature known to be associated with foveal hypoplasia 2.This study provides a detailed genotype-phenotype correlation of VEP findings in a molecularly characterised INS cohort - useful in selecting clinically guided genetic testing and counselling patients.

Determining health-related quality of life and health state utility values of recurrent urinary tract infections in women.

INTRODUCTION AND HYPOTHESIS: Health state utility values estimate an individual's valuation of their health-related quality of life. Despite prevalence of recurrent urinary tract infections (rUTIs), the health state utility value of rUTIs is unknown. The primary aim was to determine the utility value of rUTIs using the standard gamble (SG). The secondary aim was to compare the SG utility value with that derived from the EuroQol 5 dimensions (EQ-5D) and visual analog scale (VAS). We hypothesized that a utility value would be successfully derived from the SG and would differ from that derived using the EQ-5D and VAS. METHODS: Nonpregnant, adult English-speaking female patients with a diagnosis of rUTI were recruited and completed the EQ-5D, VAS, and SG (n = 25). Utility values were evaluated using Wilcoxon signed-rank tests and Spearman's rho correlation. RESULTS: Health state utility values varied depending on the assessment tool used: EQ-5D 0.76 (IQR 0.52), VAS 0.70 (IQR 0.30), and SG 0.85 (IQR 0.25). There were differences between VAS and the other two assessment methods (p<0.001), as well as between EQ-5D and SG (p=0.013). Spearman correlation demonstrated a moderately positive correlation between EQ-5D and VAS values (r(25) = 0.59, p=0.0019). CONCLUSIONS: Our data suggest that 0.85 reflects the true health state utility value of rUTIs among nonpregnant adult English-speaking women. The utility value for recurrent UTIs is worse (lower) than that previously published for nonrecurrent UTIs, reflecting the ability of the SG to convey the compounding impact of recurrent disease. In this study, neither the EQ-5D nor the VAS produced results consistent with those found using the SG, which suggests limited validity in this population.

Study on the use practices and knowledges of French practitioners about the use of intra-uterine devices in early post-partum contraception in France.

OBJECTIVES: Intra-Uterine Device (IUD) insertion is possible in early postpartum. Although this contraception method is recognized and used in lots of country, it seems infrequent and poorly known in France. Our study aims to assess the barriers to the application of this method in France. METHODS: A questionnaire was sent to obstetricians-gynaecologist professionals and midwives in France, through the affiliation to CNGOF (French National College of Obstetricians and Gynecologists) and to CNSF (French National College of Midwives). Questions were focused on the practices and knowledge about the insertion of IUD in early postpartum. RESULTS: four hundred eight practitioners responded. Amongst them, 63% knew about the possibility to use IUDs after a vaginal delivery and 31% knew it could be inserted during cesarean section. Ten percent of them used this method. Most of these practitioners (80% of them) would like to discuss the insertion of an IUD in early postpartum with their patients and 71% would like to perform the insertion themselves after training. Besides, this study shows that contraception is rarely addressed by physicians during the follow-up of pregnancies. Less than 15% of respondents report discussing the topic systematically with the patient during the pregnancy follow during pregnancy follow. CONCLUSION: insertion of IUDs in early postpartum is uncommon in France. The main limitation seems to be a lack of knowledge, but practitioners seem to be interested in this practice. Training courses could be created in order to rase up the adoption of this practice.

[Treatment of synechiae related to infertility]. / Traitements des synéchies associées à une infertilité.

Synechiae are intrauterine adhesions that affect the fertility of women. They are most often of post-traumatic origin. The management of pregnancy abortions in the first trimester and post-delivery retention are the main contributing factors. Synechiae is responsible for cycle disorders and repeated pregnancy loss. Hysteroscopy is the reference method for its diagnosis and treatment. The surgical objective is the restoration of a normal sized cavity and a functional endometrium to allow fertilization and implantation. The use of small diameter (5mm) hysteroscopes and no energy or bipolar energy instruments are recommended. Echo guidance facilitates the treatment of severe synechiae and limits the risk of intraoperative perforation. The main risk of treatment is recurrence, particularly in severe cases where multiple operating times are sometimes necessary. An office hysteroscopy at 6 weeks is recommended to identify and treat these recurrences. Different physical, molecular or cellular methods are studied as primary and secondary prevention of postoperative synechiae. The objective of this review is to provide an update on the treatment of synechiae in the context of infertility.

Ovarian drilling in polycystic ovary syndrome: Long term pregnancy rate.

OBJECTIVE: To report long term pregnancy rate in polycystic ovary syndrome (PCOS) treated by ovarian drilling. To evaluate predictive factors of pregnancy and possibility of a second drilling. DESIGN: Retrospective, observational, multicenter study. SETTING: Gynecologic departments of two teaching's hospitals. PATIENTS: All infertile women with PCOS who were treated by ovarian drilling from 2004 to 2013. The Rotterdam criteria were applied to define PCOS. INTERVENTIONS: Surgical ovarian drilling by laparoscopy and trans vaginal hydro laparoscopy. MAIN OUTCOME MEASURES: The primary endpoint was pregnancy rate after ovarian drilling. The secondary endpoints were the predictive factors of pregnancy and the possibility of a second ovarian drilling. RESULTS: 289 women were included in the study. The mean follow-up period was 28.4 months (25.3-31.5). A pregnancy was obtained in at least 137 (47.4%) women after a drilling, and 71 (51.8%) of these pregnancies were spontaneous, 48 (16.6%) women achieved at least two pregnancies after drilling, and 27 (56.3%) of these were spontaneous. The predictive factors for effectiveness were a normal body mass index (BMI), an infertility period of less than three years, an AFC of less than 50, and an age of less than 35. Second drillings were performed on 33 women. Among them, 19 (57.6%) achieved at least one pregnancy, and 10 (52.6%) of these were spontaneous. It appeared that a second drilling was effective either when the first drilling had been successful (pregnancy achieved after drilling) or when it had failed in cases of high AFC (greater than 55). CONCLUSION: Ovarian drilling permitted to obtain spontaneous pregnancy for women with PCOS. This surgery could have durably effect permitted to obtain more than one pregnancy.

Hysteroscopic resection on virtual reality simulator: What do we measure?

OBJECTIVE: The objective was to compare results of two groups of population (novices and experts) on a virtual reality simulator of hysteroscopy resection for different metrics and for a multimetric score to assess its construct validity. MATERIALS AND METHODS: Nineteen gynecologist who had at least 5 years of experience with hysteroscopy and self-evaluated their expertise at 4/5 or 5/5 were included as expert population. Twenty first-year gynecology residents in Paris were included as novice population. A standardized set of 4 hysteroscopy resection cases (polypectomy, myomectomy, roller ball endometrial ablation and septum resection) was performed on a virtual reality simulator (HystSim™) by the group of novices and experts. Results obtained on the simulator for overall score and for the parameters were compared by applying the Mann-Whitney test. RESULTS: Overall score of novices and experts were significantly different for three resection cases (polypectomy P<0.001, myomectomy P<0.001, roller ball endometrial ablation <0.001). The overall score was not different in the septum resection (P=0.456). For the four cases, the economy score (included cumulative path length, procedure time and camera alignment) were statistically different between novices and experts (polypectomy P<0.001, myomectomy P=0.001, roller ball endometrial ablation P<0.001, septum resection P<0.001). CONCLUSION: The overall score on HystSim™ was able to discriminate novices between experts on polypectomy, myomectomy and roller ball endometrial ablation cases but not on septum resection. The economy score was the more reliable to reflect the surgeon experience. It could be used to evaluate and to train students on hysteroscopic resection on a virtual reality simulator.

Assessing technical competence in laparoscopic surgery in France: Ratification of the GOALS rating scale.

BACKGROUND: The question of assessing surgical competence is the focus of mainly Anglo-Saxon studies. The GOALS questionnaire (Global Operative Assessment of Laparoscopic Skills) specific to laparoscopic surgery assessment has been developed since 2005. The aim of the study was to assess the metrological qualities of the GOALS questionnaire after ratification in French language. METHODS: To produce a French version of the GOALS surgical competence assessing tool according to an established method (translation - backward translation - retranslation) and to check the metrological qualities (user satisfaction, acceptability, reliability and validity) of this questionnaire through observing residents while in training program on 22 residents in Gynaecology Obstetrics during the laparoscopy training, with the performance of a nephrectomy on a porcine model. RESULTS: The discrepancies in the initial translations were mainly due literal translations. Only synonymous differences were observed in the two backward translations. Comparison with original version led to 8 minor changes. No changes occurred between the 2 French versions. Satisfaction surveys when using the GOALS questionnaire by both examiners and students are similar. Face and content validity seemed good and there is no significant discrepancy between the examiners and the students (11.5 [9-15]; 12.4 [9-15]; P=0.40). Assessment by examiners showed an median value of 17.8 [9-26] with good correlation (α=0.80). By contrast, self-assessment, although there is no significant discrepancy, showed heterogeneity. GOALS French version was able to prove a significant progression both in self-assessment and external evaluation between the act performed on the first nephrectomy on the first day of the first session of the training and the fourth nephrectomy performed on the first day of the second session of the training. CONCLUSION: Our work allowed obtaining a GOALS French version with acceptable validity, good consistency between the assessments and ability to measure progress.

Ordinary stoichiometry of extraordinary microorganisms.

All life on Earth seems to be made of the same chemical elements in relatively conserved proportions (stoichiometry). Whether this stoichiometry is conserved in settings that differ radically in physicochemical conditions (extreme environments) from those commonly encountered elsewhere on the planet provides insight into possible stoichiometries for putative life beyond Earth. Here, we report measurements of elemental stoichiometry for extremophile microbes from hot springs of Yellowstone National Park (YNP). Phototrophic and chemotrophic microbes were collected in locations spanning large ranges of temperature (24 °C to boiling), pH (1.6-9.6), redox (0.1-7.2 mg L(-1) dissolved oxygen), and nutrient concentrations (0.01-0.25 mg L(-1) NO2-, 0.7-12.9 mg L(-1) NO3-, 0.01-42 mg L(-1) NH4 (+), 0.003-1.1 mg L(-1) P mostly as phosphate). Despite these extreme conditions, the microbial cells sampled had a major and trace element stoichiometry within the ranges commonly encountered for microbes living in the more moderate environments of lakes and surface oceans. The cells did have somewhat high C:P and N:P ratios that are consistent with phosphorus (P) limitation. Furthermore, chemotrophs and phototrophs had similar compositions with the exception of Mo content, which was enriched in cells derived from chemotrophic sites. Thus, despite the extraordinary physicochemical and biological diversity of YNP environments, life in these settings, in a stoichiometric sense, remains much the same as we know it elsewhere.

Multi-centre variability of ISCEV standard ERGs in two normal adults.

BACKGROUND: The reproducibility of an individual's full-field ERG between centres has not previously been investigated. METHODS: ERGs were recorded using both silver thread and skin electrodes from the same two normal adult subjects at 15 UK centres using routine, local protocols and a highly standardised, 'ISCEV-specified' protocol matching the values specified in the ISCEV standard; where the ISCEV standard allows options, a single value was chosen. RESULTS: Inter-ocular differences were small, and amplitudes were smaller for skin than silver thread electrodes. No centre produced outlying data points, and ERGs across all 15 centres were remarkably similar. Amplitude variability was less for local protocols (using LED flashes) than for the ISCEV-specified protocol using xenon flashes (22 vs. 24 %, p = 0.01), but peak time variability was less for the ISCEV-specified protocol (6.1 vs. 7.4 %, p = 0.001). Only the DA 0.01 ERG correlated with photometric variability. The bifidity of the DA 3 a-wave doubled its peak time variability compared with the DA 10 a-wave. CONCLUSIONS: Inter-centre amplitude variability was typically within clinically significant thresholds, suggesting that inter-centre variability with suitable standardisation may not add more to total variability than inter-subject variability. Variability improvements gained by the tighter specifications of the ISCEV-specified protocol were possibly more than lost due to imprecisions of xenon flashtubes. Peak time variability was far lower than amplitude variability, corresponding with acceptable variability of biochemical assays. These results represent a vindication of the existence of an ERG standard and suggest that further standardisation would lend itself to greater reproducibility of ERGs worldwide.

Dynamic contrast-enhanced MRI in mouse tumors at 11.7 T: comparison of three contrast agents with different molecular weights to assess the early effects of combretastatin A4.

Dynamic contrast-enhanced (DCE)-MRI is useful to assess the early effects of drugs acting on tumor vasculature, namely anti-angiogenic and vascular disrupting agents. Ultra-high-field MRI allows higher-resolution scanning for DCE-MRI while maintaining an adequate signal-to-noise ratio. However, increases in susceptibility effects, combined with decreases in longitudinal relaxivity of gadolinium-based contrast agents (GdCAs), make DCE-MRI more challenging at high field. The aim of this work was to explore the feasibility of using DCE-MRI at 11.7 T to assess the tumor hemodynamics of mice. Three GdCAs possessing different molecular weights (gadoterate: 560 Da, 0.29 mmol Gd/kg; p846: 3.5 kDa, 0.10 mmol Gd/kg; and p792: 6.47 kDa, 0.15 mmol Gd/kg) were compared to see the influence of the molecular weight in the highlight of the biologic effects induced by combretastatin A4 (CA4). Mice bearing transplantable liver tumor (TLT) hepatocarcinoma were divided into two groups (n = 5-6 per group and per GdCA): a treated group receiving 100 mg/kg CA4, and a control group receiving vehicle. The mice were imaged at 11.7 T with a T1 -weighted FLASH sequence 2 h after the treatment. Individual arterial input functions (AIFs) were computed using phase imaging. These AIFs were used in the Extended Tofts Model to determine K(trans) and vp values. A separate immunohistochemistry study was performed to assess the vascular perfusion and the vascular density. Phase imaging was used successfully to measure the AIF for the three GdCAs. In control groups, an inverse relationship between the molecular weight of the GdCA and K(trans) and vp values was observed. K(trans) was significantly decreased in the treated group compared with the control group for each GdCA. DCE-MRI at 11.7 T is feasible to assess tumor hemodynamics in mice. With K(trans) , the three GdCAs were able to track the early vascular effects induced by CA4 treatment.

SU-E-I-32: Sterile Radiation Reduction Gloves May Be Contraindicated in Fluoroscopically Guided Interventions.

PURPOSE: Sterile radiation reduction gloves have been widely used in the past decade to provide modest decreases in operator hand dose when the hands are placed in the field of view (FOV). While multiple publications have quantified the potential dose reduction from the use of such gloves, possible effects on the patient have not yet been assessed. The aim of this study was to determine if radiation reduction gloves can Result in a significant increase in patient dose and increased risk of radiation induced skin injury when used in interventional radiology. METHODS: The effect of radiation reduction gloves when used in the FOV was determined by measurement of patient entrance exposure rate (EER) for a variety of patient sizes and varying operating and magnification modes. EERs were measured with no glove in the FOV, with one glove and, to replicate the actions of many dose-conscious radiologists, with double gloves in the FOV. RESULTS: Compared to an ungloved hand, the use of a single radiation reduction glove near the center of the FOV results in a 2-fold average increase in patient EER. The use of double radiation reduction gloves results in a 3-fold average increase in EER. In both cases, this increase was only weakly dependent on the size of the patient and on the operating and magnification modes used. In fact, patient thicknesses ranging from 6-14 inches and operating modes ranging from low-dose fluoroscopy to DSA produced less than a 20% deviation from the increases in EER quoted above. CONCLUSIONS: When used in the FOV, radiation reduction gloves can substantially increase patient EER. This increase in patient dose, when compared with the relatively small published reduction in extremity dose provided to the operator, may make their use contraindicated in cases where radiation induced skin injury is a possible risk.

[Delivery in lateral position. Comparative study in low risk pregnancy between lateral and dorsal position for the delivery in eutocic vaginal birth]. / Accouchement sur le côté. Étude comparative chez les grossesses à bas risque entre décubitus latéral et dorsal lors de la phase expulsive des accouchements eutociques.

OBJECTIVE: For several years in French labour wards, delivery in the lateral decubitus position (LP) has raised great interest. We wanted to assess perineal outcomes and neonatal morbidity following delivery in the lateral LP compared to the dorsal decubitus position (DP). PATIENTS AND METHODS: Two teams of midwives, in a private and in a public hospital, performed a total of 6800 deliveries in the area of Tours following a training session on the techniques of delivery in the lateral decubitus position. The design was a retrospective case-control study including patients with low obstetrical risks and normal vaginal delivery. We included 645 patients who gave birth from May 1st to September 30th, 2007. RESULTS: We showed a significant difference in perineum outcomes, with a lower episiotomy rate (56.7% in LP/40.7% in DP, P=0.0001), a higher rate of intact perineum (56.7% in LP/40.7% in DP, P=0.0001) and no differences with respect to perineal laceration. These differences were significant in primiparous (intact perineum: 46.8% in LP/20.2% in DP, P=0.004; episiotomy: 17% en DL/44.7% en DD, P=0.006) and secondiparous patients (episiotomy: 8.6% in LP/30.7% in DP, P=0.0001). We showed significant differences in fetal heart abnormalities during labour in favour of the lateral decubitus position (no anomaly, P=0.00004; separated decrease, P=0.04; bradycardia, P=0.0009; early decrease, P=0.04). DISCUSSION AND CONCLUSION: The neonatal mortality and morbidity did not differ between delivery positions. The lateral position seems to be protective for the perineum without affecting neonatal outcome. Incorporating lateral decubitus deliver into daily practice is possible in large groups of midwives after appropriate training.

Chiasm formation in man is fundamentally different from that in the mouse.

At the optic chiasm axons make a key binary decision either to cross the chiasmal midline to innervate the contralateral optic tract or to remain uncrossed and innervate the ipsilateral optic tract. In rodents, midline interactions between axons from the two eyes are critical for normal chiasm development. When one eye is removed early in development the hemispheric projections from the remaining eye are disrupted, increasing the crossed projection at the expense of the uncrossed. This is similar to the abnormal decussation pattern seen in albinos. The decussation pattern in marsupials, however, is markedly different. Early eye removal in the marsupial has no impact on projections from the remaining eye. These differences are related to the location of the uncrossed projection through the chiasm. In rodents, axons that will form the uncrossed projection approach the chiasmal midline, while in marsupials they remain segregated laterally through the chiasm. Histological analysis of the optic chiasm in man provides anatomical evidence to suggest that, unlike in rodents, uncrossed axons are confined laterally from the optic nerve through to the optic tract and do not mix in each hemi-chiasm. This is a pattern similar to that found in marsupials. Electrophysiological evidence in human anophthalmics shows that the failure of one eye to develop in man has no impact on the hemispheric projections from the remaining eye. This strongly suggests that the mechanisms regulating chiasmal development in man differ from those in rodents, but may be similar to marsupials. This implies that optic chiasm formation in rodents and ferrets is not common to placental mammals in general.

The clinical features of albinism and their correlation with visual evoked potentials.

AIM: To investigate the relation between the clinical and electrophysiological abnormalities of patients undergoing visual evoked potential investigation for albinism. METHODS: 40 subjects with a probable or possible clinical diagnosis of albinism underwent pattern appearance and/or flash visual evoked potential (VEP) examination. The VEP findings are correlated with the clinical features of albinism determined by clinical examination and orthoptic assessment. RESULTS: The majority of patients with clinical evidence of albinism showed a contralateral predominance in the VEPs. There was close correlation between the clinical signs of albinism and the degree of contralateral VEP predominance. This manifested as an interhemispheric latency asymmetry to monocular pattern appearance stimulation but amplitude asymmetry to flash stimulation. The strongest correlation for pattern appearance interhemispheric latency difference was with foveal hypoplasia (rho = 0.58; p = 0.0003) followed by nystagmus (rho = 0.48; p = 0.0027) and iris transillumination (rho = 0.33; p = 0.039). The VEP abnormalities were of greater magnitude in those patients with most features of albinism. Several patients with apparently mild disorders of ocular pigmentation had small but significantly abnormal VEP latency asymmetries. CONCLUSION: There is a strong association between the magnitude of the interhemispheric latency asymmetry of the pattern appearance VEP, and of amplitude asymmetry of the flash VEP, with the clinical signs of albinism. The data are consistent with a spectrum of abnormalities in albinism involving both clinical expression and electrophysiological misrouting, which is wider than previously recognised.

Abnormal visual projection in a human albino studied with functional magnetic resonance imaging and visual evoked potentials.

The albino visual pathway is abnormal in that many fibres from the temporal retina project to the contralateral visual cortex. The visual projections in a human albino and a control have been investigated with fMRI and VEP during independent visual stimulation of both hemifields. Activity in the occipital cortex in the normal was contralateral to the stimulated visual field, whereas it was contralateral to the stimulated eye in the albino, independent of the stimulated visual field. Thus, the albino visual cortex is activated not only by stimulation in the contralateral visual field, but also by abnormal input representing the ipsilateral visual field. These novel findings help elucidate the nature of albino misrouting.

Increased binocular enhancement of contrast sensitivity and reduced stereoacuity in Duane syndrome.

PURPOSE: To compare the binocular enhancement of contrast sensitivity and stereoacuity in patients with Duane syndrome and normal subjects. METHODS: Monocular and binocular contrast sensitivity functions were determined using a two-alternative, forced-choice method in 14 patients with Duane syndrome and 14 normal subjects. Monocular and binocular log minimum angle of resolution (logMAR) acuities were measured, and stereoacuity was determined using the Titmus and TNO stereotests. RESULTS: In the patients with Duane syndrome, the binocular enhancement of contrast sensitivity was increased across all spatial frequencies, although stereoacuity was reduced compared to that of the normal subjects. The increased enhancement was caused by a reduction in monocular contrast sensitivity rather than an increase in binocular contrast sensitivity. The patients with Duane syndrome also showed a generalized reduction of contrast sensitivity at high spatial frequencies. CONCLUSIONS: It is suggested that the combination of reduced stereoacuity and increased binocular enhancement of contrast sensitivity seen in Duane syndrome can be explained by a partial loss of binocular cortical cells, caused by intermittent misalignment of the eyes during early visual development.