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T-cells play an important role in the remission-maintenance in AML-patients (pts) after SCT, however the role of LAA- (WT1, PR1, PRAME) or minor-histocompatibility (mHag, HA1) antigen-specific CD4(+) and CD8(+)T-cells is not defined. A LAA/HA1-peptide/protein stimulation, cloning and monitoring strategy for specific CD8(+)/CD4(+)T-cells in AML-pts after SCT is given. Our results show that (1) LAA-peptide-specific CD8+T-cells are detectable in every AML-pt after SCT. CD8(+)T-cells, recognizing two different antigens detectable in 5 of 7 cases correlate with long-lasting remissions. Clonal TCR-Vβ-restriction exemplarily proven by spectratyping in PRAME-specific CD8(+)T-cells; high PRAME-peptide-reactivity was CD4(+)-associated, as shown by IFN-γ-release. (2) Two types of antigen-presenting cells (APCs) were tested for presentation of LAA/HA1-proteins to CD4(+)T-cells: miniEBV-transduced lymphoblastoid cells (B-cell-source) and CD4-depleted MNC (source for B-cell/monocyte/DC). We provide a refined cloning-system for proliferating, CD40L(+)CD4(+)T-cells after LAA/HA1-stimulation. CD4(+)T-cells produced cytokines (GM-CSF, IFN-γ) upon exposure to LAA/HA1-stimulation until after at least 7 restimulations and demonstrated cytotoxic activity against naive blasts, but not fibroblasts. Antileukemic activity of unstimulated, stimulated or cloned CD4(+)T-cells correlated with defined T-cell-subtypes and the clinical course of the disease. In conclusion we provide immunological tools to enrich and monitor LAA/HA1-CD4(+)- and CD8(+)T-cells in AML-pts after SCT and generate data with relevant prognostic value. We were able to demonstrate the presence of LAA-peptide-specific CD8(+)T-cell clones in AML-pts after SCT. In addition, we were also able to enrich specific antileukemic reactive CD4(+)T-cells without GvH-reactivity upon repeated LAA/HA1-protein stimulation and limiting dilution cloning., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Visual functions of patients with visual field defects after acquired brain injury affecting the primary visual pathway can be improved by means of vision restoration training. Since the extent of the restored visual field varies between patients, the prediction of treatment outcome and its visualization may help patients to decide for or against participating in therapies aimed at vision restoration. For this purpose, two treatment outcome prediction models were established based on either self-organizing maps (SOMs) or categorical regression (CR) to predict visual field change after intervention by several features that were hypothesized to be associated with vision restoration. Prediction was calculated for visual field changes recorded with High Resolution Perimetry (HRP). Both models revealed a similar predictive quality with the CR model being slightly more beneficial. Predictive quality of the SOM model improved when using only a small number of features that exhibited a higher association with treatment outcome than the remaining features, i.e. neighborhood activity and homogeneity within the surrounding 5° visual field of a given position, together with its residual function and distance to the scotoma border. Although both models serve their purpose, these were not able to outperform a primitive prediction rule that attests the importance of areas of residual vision, i.e. regions with partial visual field function, for vision restoration., (© 2013 Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: Traumatic optic neuropathy (TON) is an important cause of severe visual impairment following blunt or penetrating head trauma. Treatment options include steroids, decompression, or both. Studies have failed to show a clear benefit for either steroids or surgery or a combined therapy. This study describes the visual outcome in surgically managed patients with or without steroid treatment., Study Design: Retrospective analysis., Methods: In a retrospective chart review we included patients (n = 42) with TON who were managed with optic nerve decompression surgery with or without steroids. Comparison of initial and final visual acuity was the primary outcome parameter., Results: In 42 consecutive patients, steroids were used in 21 cases (50%). Ten patients received a high-dose systemic regimen of more than 500 mg methylprednisolone initial dose, and 11 patients were treated with a lower dose. The overall visual improvement rate was 33%, no change was noted in 50%, and no outcome data were available in 17%. The visual improvement rate of patients treated with decompression surgery and steroids was lower (29%, 6 of 21) than those treated with surgery alone (53%, 8 of 15). Comparing both groups, additional steroids had no beneficial effect on the visual outcome (P = .97). There was no case with a deterioration of visual function due to therapy., Conclusions: In patients with traumatic optic neuropathy who were treated with optic nerve decompression surgery, steroids had no beneficial effect on the visual outcome., Level of Evidence: 2c., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

The objective of this work was to develop an easily applicable technique and a standardized protocol for high-quality post-mortem angiography. This protocol should (1) increase the radiological interpretation by decreasing artifacts due to the perfusion and by reaching a complete filling of the vascular system and (2) ease and standardize the execution of the examination. To this aim, 45 human corpses were investigated by post-mortem computed tomography (CT) angiography using different perfusion protocols, a modified heart-lung machine and a new contrast agent mixture, specifically developed for post-mortem investigations. The quality of the CT angiographies was evaluated radiologically by observing the filling of the vascular system and assessing the interpretability of the resulting images and by comparing radiological diagnoses to conventional autopsy conclusions. Post-mortem angiography yielded satisfactory results provided that the volumes of the injected contrast agent mixture were high enough to completely fill the vascular system. In order to avoid artifacts due to the post-mortem perfusion, a minimum of three angiographic phases and one native scan had to be performed. These findings were taken into account to develop a protocol for quality post-mortem CT angiography that minimizes the risk of radiological misinterpretation. The proposed protocol is easy applicable in a standardized way and yields high-quality radiologically interpretable visualization of the vascular system in post-mortem investigations.

Objective: Controllable lifestyle has become an important factor influencing career decision-making among physicians. In academic medicine, doctors are required to combine both patient care and research in their daily routine. Insufficient release of clinicians for research during contracted work hours may lead to increased weekly working hours in academic medical centers and deter medical graduates from academia. We tested for an association between numbers of scientific publications and an increased hourly workload among physicians., Methods: This was a cross-sectional online survey among all salaried physicians working in the university hospitals of Innsbruck and Salzburg, Austria. The main outcome measures were the self-reported total number of scientific papers published in peer-reviewed medical journals over the past two years and self-reported working hours., Results: Of 590 returned surveys, 393 were fully completed and included in the study. The sample was stratified into three groups according to scientific output in the past two years: Group A, >/= 6 publications; Group B, 1-5 publications; Group C, no publications. Men were more likely than women to have a scientific publication: in Group A there was a male predominance of 75%, whereas in Group C only 48% were men (P = 0.0034). A total of 59% (n = 232) of all participants had not published a scientific article in the past two years (Group C) and worked a mean of 58.3 +/- 12 h/week. Physicians in Group B (n = 113) had published 2.4 +/- 1.4 papers and worked 62.8 +/- 12.9 h/week; those in Group A (n = 48) had published 11.5 +/- 6.6 papers and worked 73 +/- 13.1 h/week (P < 0.0001). In Group A, research accounted for only 13.3% of total work time but for 60% of overtime hours, reflecting the fact that research was mainly performed during overtime., Conclusion: Research activity among clinicians in academic medical centers is associated with significantly increased overtime hours. Measures need to be taken to allow medical graduates an academic career at reasonable impairment of personal lifestyle.

After eradication of variola virus the worldwide vaccination program was stopped to avoid the severe complications observed in a small fraction of vaccinees. Hence, there is at least one non-vaccinated generation in the human population that is immunologically naive with respect to variola virus infections. The possibility of a deliberate release of variola virus by bioterrorist attacks has led to the resumption of vaccination of hospital employees and military personnel with vaccinia virus in certain parts of the world. However, the appearance of a single confirmed smallpox case worldwide would result in vaccination of possible contact persons with vaccinia virus. Therefore, reliable confirmation of vaccinia virus in patients presenting with smallpox-like syndromes is required. A vaccinia virus-specific single nucleotide polymorphism was identified in the gene B8R coding for a vaccinia virus IFNgamma receptor. Based on this polymorphism, the LightCycler real-time PCR assay detects vaccinia virus DNA in a linear range from 10(6) to 10 genome equivalents and discriminates vaccinia virus from other orthopoxviruses by fluorescence melting curve analysis (DeltaT = 9 degrees C). While the assay amplifies generically DNA of all orthopoxviruses tested, amplification curves are only displayed for vaccinia virus strains including strains formerly used for vaccination. In addition, an internal amplification control is described that allows reliable interpretation of results.