Alexandra Goll

Biological Variation of the Platelet Proteome in the Elderly Population and Its Implication for Biomarker Research

Knowledge about the extent of total variation experienced between samples from different individuals is of great importance for the design of not only proteomics but every clinical study. This variation defines the smallest statistically significant detectable signal difference when comparing two groups of individuals. We isolated platelets from 20 healthy human volunteers aged 56–100 years because this age group is most commonly encountered in the clinics. We determined the technical and total variation experienced in a proteome analysis using two-dimensional DIGE with IPGs in the pI ranges 4–7 and 6–9. Only spots that were reproducibly detectable in at least 90% of all gels (n = 908) were included in the study. All spots had a similar technical variation with a median coefficient of variation (cv) of about 7%. In contrast, spots showed a more diverse total variation between individuals with a surprisingly low median cv of only 18%. Because most known biomarkers show an effect size in a 1–2-fold range of their cv, any future clinical proteomics study with platelets will require an analytical method that is able to detect such small quantitative differences. In addition, we calculated the minimal number of samples (sample size) needed to detect given protein expression differences with statistical significance.

Two-stage designs applying methods differing in costs

MOTIVATION Two-stage pilot and integrated designs are powerful tools for investigating large numbers of hypotheses. Asymptotically, optimal two-stage designs controlling the familywise error or false discovery rate are considered when costs and effect sizes per measurement differ between stages and total costs are constrained. RESULTS Depending on the cost and effect size ratios between the measurements, it is generally more powerful to apply two-stage procedures using one measurement method at both stages. For the practically relevant case that the same method is applied at both stages but designing the second-stage measurements raises extra costs, two-stage designs are more powerful than the single-stage design even for large costs ratios. The power of the optimal pilot and integrated two-stage designs generally are similar, however, the integrated approach is less sensitive even to severe design misspecifications in the planning phase. AVAILABILITY R-programs (R, 2005) to calculate asymptotically optimal designs are available on: http://statistics.msi.meduniwien.ac.at/index.php?page=ao2stage

Subretinal surgery and transplantation of autologous pigment epithelial cells in retinal angiomatous proliferation

Purpose:  The aim of this study was to examine whether the presence of retinal angiomatous proliferation (RAP) is a prognostic factor in subretinal surgery with transplantation of a suspension of autologous retinal pigment epithelial (RPE) cells.

Die Wiener PDT-Studie

ZusammenfassungEinleitungZiel der Studie war es, einen Zusammenhang zwischen den funktioneilen Ergebnissen nach photodynamischer Therapie (PDT) und der Fähigkeit unserer Patienten, sich im täglichen Leben zurechtzufinden, herzustellen. Vier Wiener Spitäler (Hanuschkrankenhaus, Krankenanstalt Rudolfstiftung, Krankenhaus Lainz und Sozialmedizinisches Zentrum Ost) beteiligten sich an dieser Studie. Die Ergebnisse nach 1 Jahr werden präsentiert.Patienten und MethodeAugen mit vorwiegend klassischer choroidaler Neovaskularisation (CNV) bei Altersbedingter Makuladegeneration (AMD) und mit CNV bei hoher Myopie oder multifokaler Choroiditis, die mit PDT behandelt wurden, wurden rekrutiert. Die Patienten wurden vor der PDT und dann im Abstand von 3 Monaten untersucht, wobei Fernvisus mit ETDRS-Charts, Nahvisus mit Radner-Tafeln, Kontrastsehen mit Pelli-Robson-Charts und eine Fluoreszenzangiographie durchgeführt wurden. 1 Jahr nach der 1. PDT erhielten die Patienten einen für die Studie modifizierte VF-14-Fragebogen. Eine neuerliche Befragung nach 24 Monaten ist vorgesehen.Ergebnisse71 Augen von 67 Patienten wurden rekrutiert, 49 (53 Augen) Patienten waren weiblich, 18 Patienten (18 Augen) waren männlich. Das Durchschnittsalter betrug 72,5 Jahre. 57 Augen mit CNV bei AMD und 14 Augen mit CNV bei hoher Myopie oder multifokaler Choroiditis wurden eingeschlossen.Der Fernvisus verschlechterte sich im Mittel von 68 Buchstaben vor der 1. PDT auf 57 Buchstaben bei der Jahreskontrolle. Die Mittelwerte des logRAD verschlechterte sich von 0,83 auf 0,99 im selben Zeitraum. Die Kontrastempfindlichkeit betrug 1,0 vor der 1. PDT und 0,94 12 Monate danach. Der mittlere Index aus den Fragebögen betrug 2,73 (von 1: keine Schwierigkeit, bis 5: Tätigkeit nicht möglich).SchlussfolgerungDie Durchschnittswerte der 3 gemessenen Funktionen verschlechterten sich im Beobachtungszeitraum. 44% der Augen zeigten eine Verschlechterung des Fernvisus von mehr als 3 ETDRS-Zeilen, 49% eine Verschlechterung des Nahvisus und 29% des Kontrastsehens. 75% der Patienten, bei denen das funktioneil bessere Auge behandelt wurde, hatten deutlich Schwierigkeiten im Alltag trotz funktioneller Stabilisierung.SummaryIntroductionThe aim of this study was to examine correlations between functional results after Photodynamic therapy and the ability of the patients to perform their daily tasks. Four Viennese hospitals participated in this multicentre study. The 1 year results are presented.Patients and methodsEyes with predominantly classic choroidal neovascularization in age related macular degeneration, pathologic myopia, and multifocal choroiditis treated with PDT were included. Following examinations were performed in a three month interval: Distance acuity with ETDRS Charts, reading acuity with Radner Charts, contrast sensitivity with Pelli Robson Charts, Fluorescein angiography. At the month 12 and month 24 examinations the patients were asked to answer the VF-14 questionnaire.Results71 eyes of 67 patients were included, 49 patients (53 eyes) were female, 18 patients (18 eyes) were male. The mean age was 72.5 years. 57 eyes with age related macular degeneration and 14 eyes with pathologic myopia or multifocal choroiditis were included.The mean letter score decreased from 68 letters at base-line to 57 letters at the one year control examination. In the same interval the log RAD value increased (decrease of reading acuity) from 0.83 to 0.99, and the contrast sensitivity decreased from 1.0 to 0.94. The mean value of the score of the questionnaire was 2.73 (ranging from 1–5).ConclusionThere was a decrease of distance acuity of more than 3 ETDRS lines in 44%, a decrease of reading acuity in 49% and a decrease of contrast sensitivity in 29%. The scores of the questionnaire significantly correlated with the functional tests. 75% of the patients who were stabilized had difficulties to perform their daily tasks if the better eye was treated.