Pseudophakic accommodation? A study of the stability of capsular bag supported,one piece,rigid tripod,or soft flexible implants.

A group of pseudophakic patients was investigated to determine whether their implants shift along an anteroposterior axis under different conditions of ciliary muscle stimulation. There was no statistically significant change in refraction after either pilocarpine or cyclopentolate administration. A change in anterior chamber depth between the position after pilocarpine and that after cyclopentolate was found. It appears that rigid posterior chamber implants do move backwards on ciliary muscle relaxation, but by a maximum 0.25 mm. This is not thought to represent a mechanical threat to ocular health. It is also not enough to account for the apparent accommodative ability of some pseudophakic patients. The possible causes for this phenomenon are discussed.     

Antitumor activity of combretastatin-A4 phosphate, a natural product tubulin inhibitor

Summary The tubulin-binding natural product combretastatin A-4 (CA-4) was tested for antitumor activity against fresh human tumors in vitro and 2 mouse tumors, both in vitro and in vivo. In colony forming assays using 10% fetal bovine serum, CA-4 was inhibitory in 27/40 human ovary cancers with a mean IC₅₀ of 3.18 g/mL for a 1-hour exposure (n = 35 specimens) and 0.27 g/mL for a continuous exposure to CA-4 for 11–14 days (n = 5 specimens). Murine B-16 melanoma and P-388 leukemia were also highly sensitive to CA-4 in vitro with an identical IC₅₀ value of 0.0007 g/mL for continuous drug exposure for 8 days. Comparable in vitro cell culture studies performed in serum concentrations higher than 10%, revealed a significant loss of cytotoxic potency. Using the same reversed-phase HPLC technique as developed for paclitaxel, CA-4 was shown to bind to serum proteins (30,000 mw) > 99% and to albumin approximately 70%. CA-4 was only marginally active (25% increased lifespan) in DBA/2 mice bearing P-388 leukemia who were given doses of 100 mg/kg IP on either days, 1, 5 and 9 (p = 0.075 by Wilcoxon analysis) or on consecutive days 1–9 (p = 0.19 compared to control). A higher IP dose of 150 mg/kg on days 1, 5 and 9 did not delay subcutaneous B-16 melanoma tumor growth in C57/Bl mice. These findings demonstrate a substantial loss of antitumor efficacy for CA-4 in physiologic serum concentrations in vitro. No consistent antitumor activity was observed in two murine tumor models in vivo.     

Ocular therapy with silicone oils

It has been 30 years since the first reported use of intraocular liquid silicones for retinal reattachment. During this time, there have been many notable advances in surgical techniques and instrumentation together with an improved understanding of the pathogenic mechanisms of complex retinal detachment associated with proliferative vitreoretinopathy. More recent attention has also been focused on improving the quality of the previously used commercial silicone oils. Enhanced surgical results combined with refined high-viscosity oils have led to a dramatic decrease in complications previously associated with and ascribed to the use of liquid silicone. This article reviews the literature regarding ocular use of silicone oils as an instrument and as a tamponade.     

Evaluation of inter‐observer variability in the grading of oral dysplasia using two different grading systems

Objectives. To compare the inter‐observer variability in grading of oral dysplasia between two consultant pathologists specialising in head and neck cancer, and one non‐specialist, using both the WHO classification 2005 and the Binary Grading system (proposed by Kujan et al. 2005). Methods. Eighty archived oral biopsy slides consisting of cases with different grades of dysplasia treated and followed up in a tertiary regional centre, were reviewed by three pathologists, blinded to the initial diagnosis and the clinical outcome. The H&E slides were graded according to the criteria of both systems. Inter‐observer reliability and variation were computed with kappa coefficient analysis. Results. The overall inter‐observer kappa agreement for the WHO grading system was κ = 0.21(95% CI: 0.10–0.34) and for the binary system was κ = 0.55(95% CI: 0.42–0.71). There was closer correlation in grading of the lesions between the two experts (WHO κ = 0.40, 95% CI: 0.28–0.53 and Binary κ = 0.59, 95% CI: 0.34–0.80), when compared to that between an expert and the non‐expert (WHO κ = 0.18 95% CI: 0.05–0.30 and Binary κ = 0.32 95% CI: 0.15–0.50) Kappa agreements between the three observers on individual architectural and cytological features of the binary system showed great variability, the highest agreement being in increased mitotic figures (κ = 0.49,95% CI: 0.25–0.72) and the lowest on atypical mitotic figures (κ = 0.15,95% CI: 0.01–0.32). Conclusions. There was closer agreement between all three pathologists when using the binary system in comparison to the WHO system, but both systems showed at best only moderate agreement. Improved agreement of scoring of individual features of the binary system should improve overall agreement of this system.     

Gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence

γ-Hydroxybutyric Acid (GHB) is thought to be a weak partial agonist at the γ-aminobutyric acid_B Receptor (GABA_BR), but the precise relationship of the GHB receptor (GHBR) to the GABA_BR remains unclear. In order to test the hypothesis that the GHBR is not identical to the GABA_BR, we conducted two groups of experiments. First, GABA_BR subtype 1 (R1) and/or subtype 2 (R2) were over expressed in HEK 293 cells and membrane binding studies on the transfected cells done using [³H]GHB and [³H] (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([³H]NCS-382). The latter is a specific antagonist at the GHB binding site. Second, [³H]GHB and [³H]NCS-382 autoradiographic binding studies were done on the brains of mice in which the gene for GABA_BR1a was deleted. Such mice do not have a functioning GABA_BR. There was no detectable specific [³H]GHB or [³H]NCS-382 binding in HEK 293 cells transfected with GABA_BR1, R2, or R1/R2. Binding to [³H]CGP54626A, a high affinity GABA_BR antagonist, was absent in GABA_BR1a^−/− mice. There was no difference in [³H]NCS-382 binding observed in the brains of GABA_BR1a^−/−, GABA_BR1a^+/− or GABA_BR1a^+/+ mice. Specific [³H]GHB binding was observed in the brain of GABA_BR1a^−/− mice but was significantly lower than in wild type mice. These data support the hypothesis that the GHB binding site is separate and distinct from the GABA_BR.     

Spatially filtered magnetoencephalography compared with electrocorticography to identify intrinsically epileptogenic focal cortical dysplasia

This study was carried out to evaluate Synthetic Aperture Magnetometry-kurtosis (SAM(g(2))), a spatially filtered source localization technique in magnetoencephalography (MEG), for identification of epileptogenic areas of focal cortical dysplasia (FCD). Three children with FCD were investigated to localize the ictal onset zone (IOZ). All patients subsequently had extraoperative electrocorticography (ECoG) for intractable epilepsy and surgical resection. SAM(g(2)) analysis showed overlapping of interictal MEG spike sources with the IOZ on ECoG in all children. We recommend MEG-SAM(g(2)) and MEG interictal spike source localization in patients with epileptogenic FCD.     

Optimal methods for collecting and storing vaginal specimens for prostate-specific antigen testing in research studies

BackgroundProstate-specific antigen (PSA) detected in vaginal fluid can be used in studies of HIV/sexually transmitted infection (STI) and pregnancy prevention as an alternative to relying on participant reports of exposure to semen. Optimal methods for collecting and storing specimens for this testing have not been determined.Study DesignWe conducted a controlled, in vitro experiment of 550 specimens spiked with semen to determine the effects of swab type (five types), storage conditions of the swabs (room temperature with or without desiccant or at ? 80°C without desiccant) and time from collection to testing (seven intervals over the course of 12 months) on the identification of PSA. We performed factorial analysis of variance to identify factors influencing PSA detection.ResultsConcentrations of PSA detected in the swabs declined with time of storage over the 1-year experiment (p<.01). The 1-mL, rayon-tipped swab stored immediately at ? 80°C following collection performed best.ConclusionsIf immediate testing or freezer storage is not feasible, investigators should use a swab with 1-mL capacity with processing and testing as soon as possible after specimen collection.     

Identification of the protein kinase A regulatory RIalpha-catalytic subunit interface by amide H/2H exchange and protein docking

An important goal after structural genomics is to build up the structures of higher-order protein-protein complexes from structures of the individual subunits. Often structures of higher order complexes are difficult to obtain by crystallography. We have used an alternative approach in which the structures of the individual catalytic (C) subunit and RIalpha regulatory (R) subunit of PKA were first subjected to computational docking, and the top 100,000 solutions were subsequently filtered based on amide hydrogen/deuterium (H/2H) exchange interface protection data. The resulting set of filtered solutions forms an ensemble of structures in which, besides the inhibitor peptide binding site, a flat interface between the C-terminal lobe of the C-subunit and the A- and B-helices of RIalpha is uniquely identified. This holoenzyme structure satisfies all previous experimental data on the complex and allows prediction of new contacts between the two subunits.