Publications (17)45.88 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Purpose: To evaluate short-wavelength FAF as a parameter of retinal pigment epithelium function in eyes with acute symptomatic central serous chorioretinopathy after indocyanine green angiography-guided verteporfin photodynamic therapy with half-fluence rate. Methods: A retrospective review over a period of 1 year of short-wavelength FAF images of 15 consecutive patients treated with half-fluence rate (25 J/cm) indocyanine green angiography-guided verteporfin photodynamic therapy due to acute symptomatic central serous chorioretinopathy was performed. Short-wavelength (488 nm) FAF gray values were evaluated with a confocal scanning laser ophthalmoscope at a 350-μm diameter and a 1,200-μm diameter circle centered on the fovea. The change in short-wavelength (488 nm) FAF gray values for the 2 circles was evaluated by calculating the differences of respective values between the first month after treatment and the 3, 6, 9, and 12 months follow-up. Results: Mean differences (95% confidence interval) in short-wavelength (488 nm) FAF gray values of the 350-μm and 1,200-μm diameter circle between the 1-month and the 3-month (n = 15) follow-up were -0.03 (-0.11 to 0.05) (P = 0.46) and -0.03 (-0.17 to 0.10) (P = 0.6). Respective differences between the 1 month and the 6 (n = 15), 9 (n = 14), and 12 months (n = 13) of follow-up were -0.03 (-0.11 to 0.05) (P = 0.42) and -0.04 (-0.16 to 0.08) (P = 0.5); -0.05 (-0.12 to 0.03) (P = 0.23) and -0.06 (-0.18 to 0.07) (P = 0.33); -0.03 (-0.12 to 0.07) (P = 0.57) and -0.07 (-0.20 to 0.05) (P = 0.22). Conclusion: Half-fluence rate (25 J/cm) indocyanine green angiography-guided verteporfin photodynamic therapy did not significantly affect short-wavelength FAF at a 350-μm diameter and a 1,200-μm diameter circle in eyes with resolved acute symptomatic central serous chorioretinopathy throughout 12 months of follow-up.
- [Show abstract] [Hide abstract] ABSTRACT: Disease-specific categories of the International Classification of Functioning, Disability and Health have not yet been described for patients with chronic peripheral arterial obstructive disease (PAD). The authors examined the relationship between the categories of the Brief Core Sets for ischemic heart diseases with the Peripheral Artery Questionnaire and the ankle-brachial index to determine which International Classification of Functioning, Disability and Health categories are most relevant for patients with PAD. This is a retrospective cohort study including 77 patients with verified PAD. Statistical analyses of the relationship between International Classification of Functioning, Disability and Health categories as independent variables and the endpoints Peripheral Artery Questionnaire or ankle-brachial index were carried out by simple and stepwise linear regression models adjusting for age, sex, and leg (left vs. right). The stepwise linear regression model with the ankle-brachial index as dependent variable revealed a significant effect of the variables blood vessel functions and muscle endurance functions. Calculating a stepwise linear regression model with the Peripheral Artery Questionnaire as dependent variable, a significant effect of age, emotional functions, energy and drive functions, carrying out daily routine, as well as walking could be observed. This study identifies International Classification of Functioning, Disability and Health categories in the Brief Core Sets for ischemic heart diseases that show a significant effect on the ankle-brachial index and the Peripheral Artery Questionnaire score in patients with PAD. These categories provide fundamental information on functioning of patients with PAD and patient-centered outcomes for rehabilitation interventions.
- [Show abstract] [Hide abstract] ABSTRACT: Most of the publications on modern therapy of neovascular age-related macular degeneration focus on the effect of the treatment. The purpose of this study is to determine the frequency of non-responders to anti-vascular endothelial growth factor (anti-VEGF) treatment and find possible reasons for their failure to respond. The records of patients treated until the end of 2008 the first time with either bevacizumab or ranibizumab were reviewed. Based on the availability of measurable results and according to prior publications showing the effect of the therapy, loss of three lines of distance acuity, increase of retinal thickness or lesion size were identified as indicators of non-responders. Two of these three signs had to be present. 334 eyes of 283 patients were included; 74.55% received bevacizumab and 25.45% received ranibizumab. Overall 14.37% of the eyes were identified as non-responders (14.06% in the bevacizumab group and 15.29% in the ranibizumab group). Baseline distance acuity and vitreo-retinal adhesions were significantly correlated with non-responders. Correlations with age, gender, lesion type, other morphologic features, and the kind of anti-VEGF agent failed to be significant. 10.4% of the non-responders showed a delayed but good response to anti-VEGF treatment. About 15% did not sufficiently respond to anti-VEGF treatment. Vitreo-retinal adherences were the only ophthalmologic factor which could be identified to be significantly correlated with insufficient response.
- [Show abstract] [Hide abstract] ABSTRACT: To evaluate morphological changes due to uveitis-associated cystoid macular oedema (uvCME) and their impact on central retinal sensitivity (CRS) before and after intravitreal triamcinolone-acetonide (IVTA). 28 eyes with uvCME were examined with microperimetry and spectral-domain optical-coherence-tomography (SD-OCT) before and after IVTA. Microperimetry-maps were superimposed on SD-OCT and morphological-alterations were correlated point to point with CRS and followed-up for 3 months. The effects of morphological-alterations on CRS over time were evaluated with a linear mixed-model. Mean-CRS increased significantly after IVTA (p=0.009). Proportion of cysts correlated negatively with corresponding CRS (estimate/95% CI -3.8dB/-6.6 to -0.9, p=0.011). Proportion of diffuse macular-oedema (DifME) had no significant effect on mean-CRS (-0.76dB/-4.9 to 3.3, p=0.71). The proportion of serous retinal detachment (SRD) had a borderline significant effect on mean-CRS (-9.5dB/-19.1 to 0.1, p=0.052), however the initial presence of SRD at baseline had no significant negative effect on mean-CRS (-1.3dB/-4.9 to 2.3, p=0.46). Patients with epiretinal-membrane showed lower mean-CRS than patients without (-3.3dB/-6.5 to -0.008, p=0.05). The lowest percentage of morphological-alterations was achieved 30 days post IVTA concordant to best visual-acuity (logMAR 0.16±0.26), while best mean-CRS was achieved 90 days post IVTA (16.9±1.8dB). Fixation-stability showed no significant improvement. UvCME Morphological-alterations were associated with specific CRS-decreases. DifME showed no significant- and SRD only a borderline effect on mean-CRS, which implicates that their presence should be considered when interpreting SD-OCT and making treatment-decisions.
- [Show abstract] [Hide abstract] ABSTRACT: In-vitro endogenous colony (EEC) formation is a common finding in BCR-ABL negative myeloproliferative neoplasms. The aim of the present study was to determine the prevalence and the clinical significance of EEC growth in chronic myeloid leukemia (CML). Results of clonogeneic progenitor cell assays from 52 patients with newly diagnosed CML were correlated with disease characteristics at presentation and molecular response to imatinib. EECs (median 7 per dish, range 1-39) were detectable in 16 patients (=31%). The proportion of patients with a high risk Sokal score was lower in the EEC group (7% versus 30%, respectively). The cumulative incidence of achieving a major molecular response after 2 years of imatinib was similar for both groups. However, patients with EECs were less likely to achieve a more profound decline of BCR-ABL transcripts. After 6 years of imatinib, the cumulative probability [95% CI] of reaching a ≥4 log reduction of BCR-ABL was 48% [16%; 92%] for patients of the EEC group and 84% [63%; 97%] for patients of the No EEC group. The probability [95% CI] of achieving a >4.5 log reduction of BCR-ABL after 7 years was 13% [2%; 61%] for patients with and 52% [30%; 78%] for patients without EECs. In-vitro EECs disappeared after achievement of a major molecular response in all evaluable patients. The data indicate that EEC formation is a recurrent finding in patients with CML that deserves further attention as a possible biomarker predicting the degree of molecular response to imatinib.
- [Show abstract] [Hide abstract] ABSTRACT: Importance Given the high frequency of failure of first-line therapies, there is an urgent need for second-line treatment strategies for pediatric patients with multiple sclerosis (MS). Objective To report the use of natalizumab in pediatric MS. Natalizumab, a humanized monoclonal antibody targeting α4 integrin, is effective against active relapsing-remitting MS in adults. Design Retrospective study. Setting Eleven centers for neurology and pediatric neurology in Germany and Austria. Participants A total of 20 pediatric patients with MS who started treatment with natalizumab prior to 18 years of age. These patients underwent magnetic resonance imaging as clinically indicated, despite the fact that 19 of these 20 patients were undergoing first-line disease-modifying therapy. The mean (SD) age at initiation of natalizumab therapy was 16.7 (1.1) years, and the mean (SD) pretreatment period was 18 (10) months. Intervention Natalizumab, 300 mg every 4 weeks. Main Outcome Measures Annualized relapse rates, Expanded Disability Status Scale scores, number of new T2/fluid-attenuated inversion recovery lesions and contrast-enhancing lesions on magnetic resonance imaging, number of adverse events, the prevalence of neutralizing antibodies against natalizumab, and serum JC virus–antibody status. Results Treatment with natalizumab was associated with reductions in mean annualized relapse rates (3.7 without treatment vs 0.4 with treatment; P < .001), median Expanded Disability Status Scale scores (2 without treatment vs 1 with treatment; P < .02), and mean number of new T2/fluid-attenuated inversion recovery lesions per year (7.8 without treatment vs 0.5 with treatment; P < .001). Two patients developed high-titer neutralizing antibodies against natalizumab and had to stop therapy. Adverse events included headaches, asthenia, infections, and hypersensitivity. Abnormal laboratory results were found for 8 patients. JC virus antibodies were found in 5 of 13 patients. After the discontinuation of natalizumab therapy, relapse activity occurred in 6 of 8 patients within 6 months. Conclusions and Relevance Our data indicate that natalizumab may be safe and effective against MS in pediatric patients with breakthrough disease.
- [Show abstract] [Hide abstract] ABSTRACT: The whole blood lysis method has become a standard procedure to remove red cells prior to immunophenotypic analysis of leukocytes. In the present study we investigated the influence of four different lysis protocols on the flow cytometric recovery of leukemic blasts. 32 blast cell containing blood samples were stained with anti-CD45 and anti-CD34 monoclonal antibody combinations. Red cell lysis was performed with FACS Lysing Solution and BD PharmLyse™ (Becton Dickinson and Company BD Biosciences, San Jose, CA; n=32) as well as Optilyse C and IOTest 3 (Immunotech SAS, Marseille; n=15 out of 32). Flow cytometric enumeration of blasts was performed on a FACS-Canto flow cytometer. The percentage of blasts after treatment with FACS Lyse was significantly smaller than after PharmLyse™ (p<0.0001), Optilyse C (p<0.0001), or IOTest 3 (p<0.0001), respectively. The difference between PharmLyse™ and Optilyse C (p=0.93), PharmLyse™ and IOTest 3 (p=0.31), and Optilyse C and IOTest 3 (p=0.34) was not significant. These results emphasize the importance of harmonization of red cell lysis protocols for the application of flow cytometry in hematological neoplasms.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: The aim of this study was to analyze several factors regarding their possible influence on neurosensory disturbance (NSD) of the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy (BSSO). Study design: We investigated the possible influence of sex, age at the time of surgery, total operating time, intraoperative nerve encounter, advancement versus setback, fixation method, additional genioplasty, side, and region (lower lip vs. chin) on subjective neurosensory outcome a half-year after surgery. Results of a battery of neurosensory testing methods are also presented; 103 out of the initial 128 patients were available for further follow-up 1 year after surgery. Results: Normal subjective sensibility was found in 74.6% and 77.2% of the regions after 6 and 12 months, respectively. Multiple regression models revealed significant effects of age, region, and total operating time after 6 months, and significant effects of age, region, and sex after 12 months. Conclusions: NSD of the IAN after BSSO is influenced by age, total operating time (at 6 months), and sex (at 12 months). Significantly higher rates of NSD were found in the chin region.
- [Show abstract] [Hide abstract] ABSTRACT: DNA methylation is part of the epigenetic gene regulation complex which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stage I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis (MeDIP-chip). Overall, we identified 2414 genomic positions differentially methylated between tumor and non-malignant lung tissue samples. Ninety-seven % of them were found to be tumor-specifically methylated. Annotation of these genomic positions resulted in the identification of 477 tumor-specifically methylated genes of which many are involved in regulation of gene transcription and cell adhesion. Tumor-specific methylation was confirmed by a gene specific approach. In the majority of tumors methylation of certain genes was associated with loss of their protein expression determined by immunohistochemistry. Treatment of NSCLC cells with epigenetically active drugs resulted in upregulated expression of many tumor-specifically methylated genes analysed by gene expression microarrays suggesting that about one third of these genes are transcriptionally regulated by methylation. Moreover, comparison of methylation results with certain clinico-pathological characteristics of the patients suggests that methylation of HOXA2 and HOXA10 may be of prognostic relevance in squamous cell carcinoma (SCC) patients.In conclusion, we identified a large number of tumor-specifically methylated genes in NSCLC patients. Expression of many of them is regulated by methylation. Moreover, HOXA2 and HOXA10 methylation may serve as prognostic parameters in SCC patients. Overall, our findings emphasize the impact of methylation on the pathogenesis of NSCLCs.
Dataset: Supplementary Table 2[Show abstract] [Hide abstract] ABSTRACT: Ingenuity pathway analysis lists p53 and STAT3 among the most affected transcription regulators.
Dataset: Supplementary Table 3[Show abstract] [Hide abstract] ABSTRACT: After preselection of 725 genes that are described in Gius  and Carén  85 genes were deregulated in our dataset. After multiple testing correction seven of these were found in our top 31 differentially regulated genes. Intensity1 and Intensity2: KARPAS-299+ PBS, Intensity3 and Intensity4: KARPAS-299+ 1 μM 5-aza-CdR.
Dataset: Supplementary Table 1[Show abstract] [Hide abstract] ABSTRACT: The 31 top differentially expressed genes after taking a multiple testing correction cut-off include nine cancer testis antigens (CXCL11, CT45A6, DAZL, DAZ1, CTCFL/BORIS, MAGE2B, DAZ2, RHOXF2B, MAEL). Eight of the 31 genes are involved in cell migration and adhesion (RAB13, MMP13, DYSFIP1, CETP, CNP2, SPARC, EMP2, SLC16A2), five genes are associated with immune responses (GBP5, LBP, SSX1, PNMA5, TNFAIP2) and four genes with cell migration and adhesion and immune responses (TGFB1, ITGBP4, LGAL3BP, SPP1). Intensity1 and Intensity2: KARPAS-299+ PBS, Intensity3 and Intensity4: KARPAS-299+ 1 μM 5-aza-CdR.
- [Show abstract] [Hide abstract] ABSTRACT: Objectives Melatonin is a hormone, which is involved in the control of the circadian rhythm, but also acts as an antioxidant and immune modulator. Previous studies reported decreased salivary and serum melatonin levels in periodontitis. This prospective cohort trial assessed the effect of non-surgical periodontal therapy on melatonin levels. Methods Salivary and serum samples of 60 participants (30 patients suffering from a severe generalized form of periodontitis, 30 healthy controls) were collected at baseline and 19 samples of periodontitis patients after treatment. Salivary and serum melatonin levels were determined by a commercially available ELISA kit and serum C-reactive protein (CRP) by a routine laboratory test. Results At baseline, periodontitis patients showed significantly increased serum CRP values and significantly decreased salivary melatonin levels compared to the control group. Clinical periodontal parameters significantly correlated with salivary melatonin levels and serum CRP. Periodontal therapy resulted in a recovery of the decreased salivary melatonin levels and a negative correlation was detected for the changes of salivary melatonin and the inflammatory parameter bleeding on probing. Serum melatonin levels showed no significant differences. Conclusions Salivary melatonin levels recovered after periodontal therapy and correlated with a decrease of local periodontal inflammation. This may imply the local involvement of melatonin in the pathogenesis of periodontitis due to its antioxidant abilities. However, the exact role of melatonin in periodontal disease remains to be investigated in future trials. Clinical relevance The present results suggest salivary melatonin as a risk indicator for the severity of periodontal disease.
- [Show abstract] [Hide abstract] ABSTRACT: DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16(INK4A) after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use.
- [Show abstract] [Hide abstract] ABSTRACT: Combining tramadol with paracetamol is an established analgesic treatment strategy. However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined. After Ethics Committee approval, 32 volunteers have been included in this 2 phased, double blinded, placebo controlled, cross-over study. A defined small skin area was irradiated with a UVB source inducing hyperalgesia. Twenty-four hours after irradiation, heat pain-, cold pain threshold (HPPT, CPPT), mechanical pain sensitivity to pin prick (MPS) in the area of pin prick hyperalgesia (AsH) and MPS in the sunburn were determined. In phase I, measurements have been repeated 30 min after receiving cumulative 0.3, 0.6 and 1 mg/kg of intravenous (i.v.) tramadol or active placebo. Only at 1 mg/kg tramadol and solely for MPS in the sunburn a reduction to placebo could be demonstrated (p = 0.024). Accordingly in phase II, the trial has been repeated using 1 mg/kg tramadol and paracetamol or placebo in a cumulative i.v. dose of 330, 660 and 990 mg. Now the addition of 330 mg paracetamol to tramadol reduced thermal hyperalgesia by 1.15 °C (CI 0.55; 1.76). This effect, however, did not increase with higher doses. Tramadol showed week anti-hyperalgesia reducing CPPT, MPS and AsH compared to baseline measurements (p < 0.05). Paracetamol also reduced secondary hyperalgesia, but no combination effect with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol alone exerts only weak anti-hyperalgesia. Even adding a small dose paracetamol enhances thermal anti-hyperalgesia.
- [Show abstract] [Hide abstract] ABSTRACT: Recent data obtained in mouse models have initiated a controversy whether basophils are the key antigen-presenting cells (APCs) in allergy. Here, we investigate whether basophils are of importance for the presentation of allergen and the induction of T cell proliferation in allergic patients. T cells, basophils, and APCs depleted of basophils were purified from allergic patients. Co-culture systems based on purified major allergens were established to study allergen-specific T cell responses using proliferation assays. Only co-cultures of T cells with APCs depleted of basophils but not with basophils proliferated in response to allergen. Even addition of IL-3 to T cell-basophil co-cultures failed to induce allergen-specific T cell proliferation. Our data demonstrate by classical in vitro proliferation assays that basophils are not key antigen-presenting cells that promote T cell proliferation in secondary immune responses to allergen in allergic patients.