Biomedical subjects

Florian Frommlet

Publications and source records attributed to Florian Frommlet.

9 recordsLinked to original sources

PubMed2026

Longitudinal Prediction of Retinal Sensitivity Based on Disease Progression Quantified From Optical Coherence Tomography in Geographic Atrophy.

PURPOSE: The purpose of this study was to analyze the association between disease progression of geographic atrophy (GA) from optical coherence tomography (OCT) with retinal sensitivity (RS) in microperimetry (MP) over a 2-year follow-up period. METHODS: This is a longitudinal analysis of the OAKS Phase-III clinical trial. Both study and fellow eyes with GA that underwent imaging with the Spectralis OCT and consecutive MP examination were eligible. Pointwise quantification of ellipsoid zone (EZ) thickness, EZ and retinal pigment epithelium (RPE) loss from OCT volumes was correlated with localized RS. A longitudinal predictive model using a Markov Chain framework was implemented to predict RS change over time based on OCT biomarkers. The modeling of morphological and functional progression was based on the fellow-eye cohort. RESULTS: A total of 39,681 MP points from 406 patients were analyzed. In the fellow eye cohort, baseline (BSL) EZ thickness was positively associated with RS (0.3 decibel [dB]/µm, P < 0.001). Decrease in EZ thickness between visits during follow-up was significantly associated with decrease in RS (0.1 dB / 1 µm change). RS was significantly lower in MP points within EZ loss during follow-up compared with MP points within the retina with measurable EZ (P < 0.001). The largest functional decline was observed within RPE loss, also associated with the highest probability of absolute scotoma (P < 0.001). Morphological progression to EZ and RPE loss was influenced by EZ thickness and the morphology of adjacent MP points (P < 0.001). CONCLUSIONS: Two exploratory endpoints were developed, namely quantification of EZ thickness and loss, and localized RS within high-risk OCT areas. RS decline during follow-up is associated with automatically quantified disease progression in OCT.

Humans↗

PubMed2006

The end of submacular surgery for age-related macular degeneration? A meta-analysis.

BACKGROUND: The aim of this meta-analysis was to summarize and to discuss the results of the four main submacular surgical procedures for age-related macular degeneration (AMD) as reported in the literature through 2004 and to compare them to the Submacular Surgery Trials (SST) data. METHODS: The existing data in the literature on submacular surgery for AMD from 1992 to 2004 were evaluated. The main outcomes were proportion of patients with two or more lines of improvement in visual acuity (VA) and proportion with two or more lines of deterioration in VA after surgery. RESULTS: Eighty-eight studies including 1,915 cases met the inclusion criteria. Estimates for the treatment outcome within the four groups of treatment based on a logistic regression model gave comparable results for removal of choroidal neovascularization (CNV) (improvement of VA 28%, deterioration of VA 25%), macular translocation (improvement of VA 31%, deterioration of VA 27%), and for transplantation of pigment epithelium (improvement of VA 22%, deterioration of VA 21%). Estimates for removal of subretinal hemorrhage were significantly different (improvement of VA 62%, deterioration of VA 13%). CONCLUSIONS: Selected case series showed superior results of VA compared to the SST. The question of whether this is due to selection bias that seems inevitable when dealing with medium-sized nonrandomized case series or due to better results in single centers cannot be answered. In our opinion there still seem to be indications for submacular surgery such as in patients with AMD with low preoperative VA due to large hemorrhagic or fibrotic membranes or nonresponders to photodynamic therapy (PDT).

Humans↗

PubMed2006

On locating multiple interacting quantitative trait loci in intercross designs.

A modified version (mBIC) of the Bayesian Information Criterion (BIC) has been previously proposed for backcross designs to locate multiple interacting quantitative trait loci. In this article, we extend the method to intercross designs. We also propose two modifications of the mBIC. First we investigate a two-stage procedure in the spirit of empirical Bayes methods involving an adaptive (i.e., data-based) choice of the penalty. The purpose of the second modification is to increase the power of detecting epistasis effects at loci where main effects have already been detected. We investigate the proposed methods by computer simulations under a wide range of realistic genetic models, with nonequidistant marker spacings and missing data. In the case of large intermarker distances we use imputations according to Haley and Knott regression to reduce the distance between searched positions to not more than 10 cM. Haley and Knott regression is also used to handle missing data. The simulation study as well as real data analyses demonstrates good properties of the proposed method of QTL detection.

Algorithms↗

PubMed2005

Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers.

Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and ovarian cancer (OC). However, risk estimates vary depending on the study population and statistical methodology used, and there are indications that the birth cohort and location of the mutation influence cancer risk. We investigated the risks for BC and OC associated with BRCA1 mutations in a young cohort of female mutation carriers who were identified by molecular genetic testing and belonged to a genetically heterogeneous Central European population. The study included 106 healthy and 158 affected carriers identified at an Austrian risk evaluation center. Risk estimation employed the product limit method. The log rank test was used to compare different strata. The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 75-97%) and 53% for OC (95% CI 37-68%). Female mutation carriers born in 1958 or later were subject to a significantly higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to age 40) than those born earlier. Mutations in exon 11 were associated with lower BC risk than mutations in exons 1-10 (P=0.008) and exons 12-24 (P=0.0006). OC risk was not influenced by mutation location (P=0.86). We conclude that female BRCA1 mutation carriers should be counseled about their cohort-dependent cancer risk. Further research into variables that affect cancer risk and are amenable to modification (e.g., lifestyle-related factors) should be considered a priority.

Adult↗

PubMed2004

On the dependence structure of sequence alignment scores calculated with multiple scoring matrices.

A common practice in protein sequence alignment is to try several scoring matrices until "something interesting'' is found. This leads to a multiple testing problem making p- and E-values hard to interpret. We focus on local alignment and propose to use logistic copula functions to model explicitly the dependence structure of scores obtained using different scoring matrices. By doing this, we obtain p-value correction factors when using more than one scoring matrix on the same sequences. Furthermore the parameter of the logistic copula can be interpreted as measure of dependence, providing insight concerning the relatedness of the scores from different matrices.

Journal Article↗

PubMed2004

On the significance of sequence alignments when using multiple scoring matrices.

MOTIVATION: Pairwise local sequence alignment is commonly used to search data bases for sequences related to some query sequence. Alignments are obtained using a scoring matrix that takes into account the different frequencies of occurrence of the various types of amino acid substitutions. Software like BLAST provides the user with a set of scoring matrices available to choose from, and in the literature it is sometimes recommended to try several scoring matrices on the sequences of interest. The significance of an alignment is usually assessed by looking at E-values and p-values. While sequence lengths and data base sizes enter the standard calculations of significance, it is much less common to take the use of several scoring matrices on the same sequences into account. Altschul proposed corrections of the p-value that account for the simultaneous use of an infinite number of PAM matrices. Here we consider the more realistic situation where the user may choose from a finite set of popular PAM and BLOSUM matrices, in particular the ones available in BLAST. It turns out that the significance of a result can be considerably overestimated, if a set of substitution matrices is used in an alignment problem and the most significant alignment is then quoted. RESULTS: Based on extensive simulations, we study the multiple testing problem that occurs when several scoring matrices for local sequence alignment are used. We consider a simple Bonferroni correction of the p-values and investigate its accuracy. Finally, we propose a more accurate correction based on extreme value distributions fitted to the maximum of the normalized scores obtained from different scoring matrices. For various sets of matrices we provide correction factors which can be easily applied to adjust p- and E-values reported by software packages.

Data Interpretation, Statistical↗

PubMed2003

Motility-related protein-1/CD9 expression in head and neck squamous cell carcinoma.

INTRODUCTION: Motility-related protein (MRP)-1/CD9 is implicated in cell adhesion and motility and was shown to be clearly involved in tumor prognosis and angiogenesis. Elevated MRP-1/CD9 expression on tumor cells has been linked to a favorable prognosis in breast cancer, colon cancer, lung cancer, and HNSCC. Because MRP-1/CD9 is associated with angiogenesis, it might play a role in tumor angiogenesis as well. METHODS: We analyzed MRP-1/CD9 expression in HNSCC specimens and cell lines by real-time RT-PCR and in HNSCC biopsy specimens and stromal vessels by immunohistochemistry. Kruskal Wallis and Chi2 test, univariate and multivariate Cox regression, and Kaplan-Meier methods were used for statistical analysis. RESULTS: Real-time and PCR RT showed elevated expression of MRP-1/CD9 in one (SCC25) of four HNSCC cell lines and two of six HNSCC patients, whereas two cell lines (SCC9 and JPPA) and one HNSCC patient had lower MRP-1/CD9 levels compared with other specimens. Immunohistochemistry demonstrated strong MRP-1/CD9 IR expression on tumor cells in 13 patients (39%), whereas 21 patients (61%) had less to medium MRP-1/CD9 IR expression. Increased MRP-1/CD9 expression on tumor cells was correlated with prolonged patient survival (p =.02) and a longer disease-free interval (p =.004), a diminished recurrence rate (p =.02), and lower stages of neck lymph nodes (p =.04). MRP-1/CD9 IR was also found in a subpopulation of vessels that seem to be less in tumor specimens than in normal mucosa (p <.0001). MRP-1/CD9+ vessels are podoplanin+ and are therefore regarded as lymphatic vessels. CONCLUSIONS: Our results revealed that elevated MRP-1/CD9 expression on HNSCC is linked to a favorable clinical outcome and confirmed reports of MRP-1/CD9 expression in other carcinomas. MRP-1/CD9+ vessels were found to be lymphatic in nature. The number and staining intensity of these vessels is decreased in tumor tissue, which suggests a stabilizing role for this protein in lymphangiogenesis.

Adult↗

PubMed2003

Platelets are mitogenic for periosteum-derived cells.

The early stages of bone regeneration are associated with a high mitogenic activity of periosteal cells. Here we addressed the question of whether platelets that accumulate within the developing haematoma can account for this tissue response. Addition of platelets, platelet-released supernatants, platelet membranes, and microparticles to bovine periosteum-derived cells resulted in an increase in 3H-thymidine incorporation; lipid extracts had no effect. Platelet-released supernatants retained their activity after incubation at 56 degrees C, but not at 100 degrees C. Gel chromatographic analysis revealed the highest mitogenic activity at approximately 35 kD. Of the factors released from activated platelets, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) increased 3H-thymidine incorporation. The mitogenic activity of platelet-released supernatants was decreased by anti-PDGF, and anti-bFGF antibodies. Platelet-released supernatants increased the number of proliferating periosteum-derived cells as determined by the expression pattern of Ki67. Platelet-released supernatants also resulted in a stimulation of cell proliferation in periosteal explants. These results suggest that platelets have the potential to stimulate the mitogenic response of the periosteum during bone repair.

Animals↗

PubMedDate not supplied

Effects of mydriatics on intraocular pressure and pupil size in the normal feline eye.

OBJECTIVE: To determine the effect of various mydriatics (1% atropine, 1% cyclopentolate, 0.5% tropicamide, 10% phenylephrine) on intraocular pressure (IOP) and pupil size (PS) in normal cats. ANIMALS STUDIED: The mydriatics were tested in 10 adult ophthalmoscopically normal European Domestic Short-haired cats. Procedure Single-dose drug studies were divided into placebo (vehicle of phenylephrine), 10% phenylephrine, 0.5% tropicamide, 1% cyclopentolate and 1% atropine. After measurement of IOP and pupil size (PS) at 8 a.m. on the first day, one drop of the tested drug was applied to one randomly selected eye. The IOP and PS were measured for a minimum of 36 h until the pupil returned to pretest size. RESULTS: Ten per cent phenylephrine had no significant effect on IOP, and the effect on the pupil size was minimal (<or= 1 mm difference). One per cent atropine showed a maximal mean difference of 4.3 mmHg +/- 4.1 mmHg in IOP compared to the untreated eye. These differences were statistically significant at 1, 3, 6, 12 and 16 h post-treatment. At 1, 1.5 and 2 h after unilateral application of 1% cyclopentolate, the IOP in the treated eye was significantly higher than the IOP in the untreated eye with a maximal mean difference of 4.1 mmHg +/- 4.5 mmHg. With 0.5% tropicamide, IOP of the treated eye was significantly higher than IOP of the untreated eye at 1 and 1.5 h after treatment with a maximal mean difference of 3.5 mmHg +/- 3.3 mmHg. One per cent atropine caused the greatest increase in IOP, followed by 1% cyclopentolate and 0.5% tropicamide. The dilating effect of atropine, cyclopentolate and tropicamide lasted longer than the effect on intraocular pressure. CONCLUSIONS: The parasympatholytics 1% atropine, 1% cyclopentolate and 0.5% tropicamide caused a statistically significant elevation of IOP and produced mydriasis in the treated eye in normal cats, while the sympathomimetic 10% phenylephrine had no significant effect on IOP or pupil size.

Administration, Topical↗