The effect of ranibizumab versus photodynamic therapy on DNA damage in patients with exudative macular degeneration

PURPOSE: To compare the effect of ranibizumab treatment versus photodynamic therapy (PDT) on single-stranded DNA damage in circulating leukocytes in patients with exudative age-related macular degeneration (AMD). METHODS: A comparative quantification of single-stranded DNA breaks was performed in circulating leukocytes of AMD patients before and 30 min, 45 min, 60 min, and 24 h after two different modes of therapy: a) PDT; and b) intravitreal ranibizumab injection. DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail. Damage of an individual cell was quantified as a comet tail moment. The proportion of non-zero values compared to the total number of observations was referred to as "amount of DNA damage" expressed in arbitrary units (AU). Comparisons between time points and study groups were assessed using a linear mixed-effect model. RESULTS: PDT induced an increase in the amount of single-stranded DNA damage in the circulating leukocytes from 0.2 AU (before treatment) to 0.53 AU (30 min after treatment). This increase was significant (p=0.004). In contrast, after ranibizumab treatment, the DNA damage in the circulating leukocytes remained unchanged. CONCLUSIONS: PDT purposely induces a local oxidative stress to damage the newly formed vessels. Our results indicate an additional systemic oxidative stress, apparent as amount of single-stranded DNA damage in the circulating leukocytes, for at least 30 min after treatment

The 2-global flash mfERG in glaucoma: attempting to increase sensitivity by reducing the focal flash luminance and changing filter settings

Purpose: To test a new 2-flash multifocal electroretinogram (mfERG) paradigm in glaucoma using a reduced light intensity of the m-frame flash as opposed to the global flash, as it has been suggested that this may increase the responses induced by the global flash, which has been the part of the mfERG response where most changes have been noted in glaucoma. Methods: A mfERG was recorded from one eye of 22 primary open angle glaucoma (POAG) patients [16 normal tension glaucoma (NTG), 6 high tension glaucoma (HTG)] and 20 control subjects. A binary m-sequence (2^13-1, L max 100cd/m2, L min <1cd/m2), followed by two global flashes (L max 200cd/m2) at an interval of 26ms (VERIS 6.0™, FMSIII), was used. The stimulus array consisted of 103 hexagons. Retinal signals were amplified (gain=50K) and bandpass filtered at 1-300Hz. For each focal response, the root mean square was calculated. We analyzed 5 larger response averages (central 15° and 4 adjoining quadrants) as well as 8 smaller response averages (central 10° and 7 surrounding response averages of approximately 7° radius each). Three epochs were analyzed: the direct component at 15-45ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75ms (IC-1) and at 75-105ms (IC-2). Statistical analysis was performed using linear mixed effects models adjusted for age. Results: Responses differed significantly between POAG patients and controls in all central response averages. This difference was larger for the central 10° than for the response average of the central 15°. While these observations held true for all response epochs analyzed, the DC differed least and the IC-1 most when POAG was compared to control. For POAG, the most sensitive differential measure was IC-1 of the central 10° with an area under the ROC curve of 0.78. With a cutoff value of 12.52nV/deg2, 80% of the POAG patients (100% HTG, 69% NTG) were correctly classified as abnormal, while 77% of the control subjects were correctly classified as normal. When the results of the mfERG were compared to the visual fields, there was a tendency for the mfERG to decrease as the mean defect increased. However, this correlation was only significant in the superior nasal quadrant when the IC-1 of the mfERG was compared to the corresponding area of the visual field. Conclusion: When compared to findings from previous studies, reducing the luminance of the m-frame flash in the 2-global flash paradigm did not increase the sensitivity and specificity of the mfERG to detect glaucoma furthe

hp-adaptive Galerkin Time Stepping Methods for Nonlinear Initial Value Problems

This work is concerned with the derivation of an a posteriori error estimator for Galerkin approximations to nonlinear initial value problems with an emphasis on finite-time existence in the context of blow-up. The structure of the derived estimator leads naturally to the development of both h and hp versions of an adaptive algorithm designed to approximate the blow-up time. The adaptive algorithms are then applied in a series of numerical experiments, and the rate of convergence to the blow-up time is investigated

Scope and significance of non-uniform classification practices in breast cancer with non-inflammatory skin involvement: a clinicopathologic study and an international survey

Background: The study evaluates the scope of non-uniform classification practices concerning breast carcinomas with non-inflammatory skin involvement. Patients and methods: We compared the clinical course of patients with histologically proven non-inflammatory skin involvement: 119 (65.4%) with clinically obvious ‘classical' skin changes (Group A) and 63 (34.6%) with no or only discreet changes (Group B). A questionnaire was circulated to pathology departments in 24 countries to assess the practice concerning the placement of skin- involved breast carcinomas in the TNM classification. Results: Patients in Group B showed a significantly better disease specific survival (P = 0.0002). Eighty-six respondents (70.5%) of the survey preferred the ‘histological view' and classified tumors with only histological proven skin involvement as T4b/stage IIIB. The opposing classification principle (‘clinical view'), which dictates that T4b breast cancer is a clinical diagnosis and the classical signs must be present, was supported by 31 respondents (25.4%). Conclusions: A large number of breast cancer patients with non-inflammatory skin involvement are only histologically proven and show, compared with cases exhibiting the classical clinical signs, significant differences in clinical course and prognosis. In general, both subsets were aggregated in one T category/stage (T4b/IIIB). This results in a considerable distortion of the reported statistical dat

Comparison of Two Different OCT Systems: Retina Layer Segmentation and Impact on Structure-Function Analysis in Glaucoma

Purpose. To compare two different spectral-domain optical coherence tomography (OCT) systems in regard to full macular thickness (MT) and ganglion cell layer-inner plexiform layer (GCIPL) measures and in regard to structure-function correlation when compared to standard automated perimetry (SAP). Methods. Seventeen primary open angle glaucoma patients and 16 controls (one eye per subject) were enrolled. MT and GCIPL thicknesses were measured by Cirrus and Spectralis OCTs. Octopus Perimeter 101 (G2 protocol) reports sensitivity in mean defect (dB). Differences between measurements were assessed with Student’s t-test and Bland Altman. Diagnostic performance was also compared between each parameter calculating the areas under the operator receiver (ROC). Linear models were used to investigate structure-function association between OCT and SAP. Results. Disagreement between OCTs in both MT and GCIPL values was significant. Spectralis values were thicker than Cirrus. Average difference between OCTs was 21.64 μm (SD 4.5) for MT and 9.8 μm (SD 5.4) for GCIPL (p<0.001). Patients differed significantly from controls in both OCTs, in both measurements. MT and GCIPL were negatively associated with MD (p<0.001). Conclusions. Although OCT values were not interchangeable, both machines differentiated patients from controls with statistical significance. Structure-function analysis results were comparable, when either OCT was compared to SAP

Plane wave discontinuous Galerkin methods: exponential convergence of the hp-version

We consider the two-dimensional Helmholtz equation with constant coefficients on a domain with piecewise analytic boundary, modelling the scattering of acoustic waves at a sound-soft obstacle. Our discretisation relies on the Trefftz-discontinuous Galerkin approach with plane wave basis functions on meshes with very general element shapes, geometrically graded towards domain corners. We prove exponential convergence of the discrete solution in terms of number of unknowns

Target and reality of adjuvant endocrine therapy in postmenopausal patients with invasive breast cancer

Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15–50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.8%) showed non-adherence to therapy. Patients who had follow-up with a general practitioner, rather than in an oncologic unit, were more likely to be non-adherent (P=0.0088). Of 25 patients who changed medication due to therapy-related adverse effects, 20 (80%) patients fully completed the therapy after drug change. In adjuvant endocrine therapy, a lowering of the non-adherence rate to 10.8%, the lowest reported in the literature, is realistic when patients are cared for by a specialised oncologic unit focusing on the individual needs of the patients