Language development at 3 years in pre-term children of birth weight below 1000 g

Language development at 3 years of pre-term children born below 1000 g birth weight was compared with full-term controls matched for social background. The pre-term group used less complex expressive language and showed lower receptive understanding, auditory memory and verbal reasoning. Language outcome was related to intraventricular haemorrhage but not to global indication of postnatal illness such as number of days on the ventilator. Average verbal intelligence in environmentally low risk, extremely low birth weight children is an insufficient indicator of complex language functioning.

Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Fetal and maternal leptin in pre-gestational diabetic pregnancy

Objective: To compare maternal and fetal leptin among women without diabetes, women with type 1 diabetes, and women with type 2 diabetes. 

Methods: In a prospective study at the National Maternity Hospital, Dublin, 40 women with type 1 diabetes, 10 with type 2 diabetes, and 30 without diabetes were enrolled between July 2006 and July 2008. Maternal (36-week) and cord blood leptin was measured by enzyme-linked immunoassay. 

Results: No difference was found in maternal leptin among the groups: without diabetes (mean, range): 325 pg/mL, 36-1492 pg/mL; type 1 diabetes: 343.2 pg/mL, 55.5-1108.2 pg/mL; type 2 diabetes: 2022 pg/mL, 35.1-1553.3 pg/mL (P>0.05). Leptin levels were higher among fetuses of women with type 1 (223 pg/mL, 25.7-810 pg/mL) and type 2 (447.2 pg/mL, 1363-679 pg/mL) diabetes than among women without diabetes (803 pg/mL, 273-623.1 pg/mL; P<0.05). The single significant predictor of fetal leptin for the whole cohort was maternal body mass index (BMI; r=039, P=0.01). Only third-trimester glycosylated hemoglobin (HbA1c) was significantly related to fetal leptin after controlling for maternal BMI among women with diabetes (r=028, P=0.04).

 Conclusion: Fetuses of women with diabetes might have some degree of leptin resistance. This might be important in appetite regulation in extrauterine life. (C) 2012 International Federation of Gynecology and Obstetrics. 

On thin ice: surface order and disorder during pre-melting

The effect of temperature on the structure of the ice Ih (0001) surface is considered through a series of molecular dynamics simulations on an ice slab. At relatively low temperatures (200K) a small fraction of surface self-interstitials (i.e. admolecules) appear that are formed exclusively from molecules leaving the outermost bilayer. At higher temperatures (ca. 250 K), vacancies start to appear in the inner part of the outermost bilayer exposing the underlying bilayer and providing sites with a high concentration of the dangling hydrogen bonds. Around 250-260 K aggregates of molecules formed on top of the outermost bilayer from self-interstitials become more mobile and have diffusivities approaching that of liquid water. At similar to 270-280 K the inner bilayer of one surface noticeably destructures and it appears that at above 285 K both surfaces are melting. The observed disparity in the onset of melting between the two sides of the slab is rationalised by considering the relationship between surface energy and the spatial distribution of protons at the surface; thermodynamic stability is conferred on the surface by maximising separations between dangling protons at the crystal exterior. Local hotspots associated with a high dangling proton density are suggested to be susceptible to pre-melting and may be more efficient at trapping species at the external surface than regions with low concentrations of protons thus potentially helping ice particles to catalyse reactions. A preliminary conclusion of this work is that only about 10-20 K below the melting temperature of the particular water potential employed is major disruption of the crystalline lattice noted which could be interpreted as being "liquid", the thickness of this film being about a nanometre.

Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation

Type II DNA topoisomerases catalyse DNA double-strand cleavage, passage and re-ligation to effect topological changes. There is considerable interest in elucidating topoisomerase II roles, particularly as these proteins are targets for anti-cancer drugs. Here we uncover a role for topoisomerase IIa in RNA polymerase I-directed ribosomal RNA gene transcription, which drives cell growth and proliferation and is upregulated in cancer cells. Our data suggest that topoisomerase IIa is a component of the initiation-competent RNA polymerase Iß complex and interacts directly with RNA polymerase I-associated transcription factor RRN3, which targets the polymerase to promoter-bound SL1 in pre-initiation complex formation. In cells, activation of rDNA transcription is reduced by inhibition or depletion of topoisomerase II, and this is accompanied by reduced transient double-strand DNA cleavage in the rDNA-promoter region and reduced pre-initiation complex formation. We propose that topoisomerase IIa functions in RNA polymerase I transcription to produce topological changes at the rDNA promoter that facilitate efficient de novo pre-initiation complex formation.

Transcameral suture to prevent tube-corneal touch after glaucoma drainage device implantation: a new surgical technique

PURPOSE: To report a new technique to correct tube position in anterior chamber after glaucoma drainage device implantation.

PATIENT AND METHODS: A patient who underwent a glaucoma drainage device implantation was noted to have the tube touching the corneal endothelium. A 10/0 polypropylene suture with double-armed 3-inch long straight needle was placed transcamerally from limbus to limbus, in the superior part of the eye, passing the needle in front of the tube.

RESULTS: The position of the tube in the anterior chamber was corrected with optimal distance from corneal endothelium and iris surface. The position remained satisfactory after 20 months of follow-up.

CONCLUSIONS: The placement of a transcameral suture offers a safe, quick, and minimal invasive intervention for the correction of the position of a glaucoma drainage device tube in the anterior chamber.

Simultaneous use of mitomycin-C with Baerveldt implantation

BACKGROUND AND OBJECTIVE: To evaluate the outcome of Baerveldt implantation with adjunctive mitomycin-C in cases of complicated glaucoma. PATIENTS AND METHODS: The authors reviewed the charts of all patients who had undergone Baerveldt implantation with mitomycin-C between January 1993 and March 1995. Success was defined before data collection as an intraocular pressure (IOP) between 5 and 21 mm Hg, with or without medications. The success rate was calculated using the Kaplan-Meier actuarial method. RESULTS: Twenty-nine patients were identified. The mean preoperative IOP was 33.6 mm Hg, with an average of 2.0 antiglaucoma medications. The probability of success at 6 and 12 months for patients who received mitomycin-C during Baerveldt implantation was 82.4% and 73.3%, respectively. Choroidal effusion with a flat anterior chamber (10.3%), corneal edema (6.8%), and conjunctival erosion (6.8%) were the most frequent complications. CONCLUSION: In this retrospective series of complicated glaucoma, the implantation of a Baerveldt drainage device with adjunctive mitomycin-C had a satisfactory outcome. The complications encountered and the clinical efficacy were comparable to those of previously reported series in which mitomycin-C was not used.

Pre-validation methods for developing a patient reported outcome instrument

BACKGROUND: Measures that reflect patients' assessment of their health are of increasing importance as outcome measures in randomised controlled trials. The methodological approach used in the pre-validation development of new instruments (item generation, item reduction and question formatting) should be robust and transparent. The totality of the content of existing PRO instruments for a specific condition provides a valuable resource (pool of items) that can be utilised to develop new instruments. Such 'top down' approaches are common, but the explicit pre-validation methods are often poorly reported. This paper presents a systematic and generalisable 5-step pre-validation PRO instrument methodology.

METHODS: The method is illustrated using the example of the Aberdeen Glaucoma Questionnaire (AGQ). The five steps are: 1) Generation of a pool of items; 2) Item de-duplication (three phases); 3) Item reduction (two phases); 4) Assessment of the remaining items' content coverage against a pre-existing theoretical framework appropriate to the objectives of the instrument and the target population (e.g. ICF); and 5) qualitative exploration of the target populations' views of the new instrument and the items it contains.

RESULTS: The AGQ 'item pool' contained 725 items. Three de-duplication phases resulted in reduction of 91, 225 and 48 items respectively. The item reduction phases discarded 70 items and 208 items respectively. The draft AGQ contained 83 items with good content coverage. The qualitative exploration ('think aloud' study) resulted in removal of a further 15 items and refinement to the wording of others. The resultant draft AGQ contained 68 items.

CONCLUSIONS: This study presents a novel methodology for developing a PRO instrument, based on three sources: literature reporting what is important to patient; theoretically coherent framework; and patients' experience of completing the instrument. By systematically accounting for all items dropped after the item generation phase, our method ensures that the AGQ is developed in a transparent, replicable manner and is fit for validation. We recommend this method to enhance the likelihood that new PRO instruments will be appropriate to the research context in which they are used, acceptable to research participants and likely to generate valid data.

Mitomycin-C supplemented trabeculectomy, phacoemulsification, and foldable lens implantation

Purpose: To evaluate the outcome of combined mitomycin-C filtering surgery, phacoemulsification, and foldable intraocular lens (IOL) implantation. Setting: Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Methods: This retrospective study evaluated 182 eyes of 174 patients who had combined mitomycin-C trabeculectomy, phacoemulsification, and insertion of a foldable IOL through a 3.5 mm incision. Success of the combined procedure was defined as intraocular pressure (IOP) below 21 mm Hg, with or without medications, and no serious complication. Success rates were calculated using the Kaplan-Meier actuarial method. Results: Mean follow-up was 16.7 months ± 5.4 (SD). The probability of success at 6, 12, 18, and 24 months was 98.3, 95.6, 90.6, and 88.0%, respectively. When compared with preoperativety, visual acuity improved one or more lines in 148 eyes (81.3%) and worsened one or more lines in 15 (8.2%); 111 eyes (61.0%) achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsule opacification requiring capsulotomy, which occurred in 22 cases (12.0%). Conclusion: The 1 year and 2 year IOP control rate of combined mitomycin-C filtering procedures and phacoemulsification in glaucoma patients was high.

Efficacy and safety of adjunctive mitomycin C during Ahmed Glaucoma Valve implantation:A prospective randomized clinical trial

Purpose To evaluate the efficacy and safety of intraoperative mitomycin C (MMC) in eyes undergoing Ahmed Glaucoma Valve implantation. Design Randomized controlled clinical trial. Participants Sixty patients with refractory glaucoma. Intervention Sixty eyes of 60 patients with refractory glaucoma were randomized to receive intraoperative MMC (0.5 mg/ml for 5 minutes) (n = 34) or balanced salt solution (n = 26) during Ahmed Glaucoma Valve implantation. Main outcome measures Surgical success was defined according to 2 different criteria: (1) postoperative intraocular pressure (IOP) between 6 and 21 mmHg, with or without antiglaucoma medications, and (2) IOP reduction of at least 30% relative to preoperative values. Eyes requiring additional glaucoma surgery, developing phthisis, or showing loss of light perception were classified as failures. Success rates in both groups were compared using Kaplan-Meier survival curves and the log rank test. Other outcome measures were mean IOP, number of glaucoma medications, and complications. Results After a mean follow-up of 12.3 months, Kaplan-Meier survival analysis showed a probability of success of 59% at 18 months for the MMC group and 61% for the control group when the first criterion for success was used (IOP between 6 and 21 mmHg). When an IOP reduction of at least 30% was used as the criterion to define success, the Kaplan-Meier survival analysis demonstrated a probability of success at 18 months of 62% for the MMC group and 67% for the control group. There were no significant differences in survival rates between the 2 groups with either criterion (P = 0.75 and P = 0.37, respectively). After 15 days postoperatively, the mean IOP did not significantly differ for both MMC and control eyes. Mean numbers of postoperative antiglaucoma medications were similar in MMC-treated eyes and controls. There was no significant difference between the incidences of postoperative complications in both groups. Conclusion Mitomycin C did not increase the short- or intermediate-term success rates of Ahmed Glaucoma Valve implantation. © 2004 by the American Academy of Ophthalmology.

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): Study protocol for a randomized controlled trial

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care.EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care.

METHODS/DESIGN: EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible.The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events.A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate.

TRIAL REGISTRATION: ISRCTN44464607.

Cataract extraction and intraocular lens implantation in anterior megalophthalmos

This report describes the implantation of a standard posterior chamber intraocular lens (IOL) in a patient with bilateral cataract and anterior megalophthalmos. After extracapsular cataract extraction, the IOL was sutured to the posterior surface of the iris and anterior capsule. Different types of IOLs were used in each eye, and the surgical technique was adapted to the characteristics of the IOL. No complications were noted. Visual rehabilitation was successful. Extracapsular cataract extraction with a posterior chamber IOL sutured to the posterior surface of the iris and anterior capsule is a useful option in patients with anterior megalophthalmos and cataract.