Browsing by Author "Koenig, Fatima"

We report a case of a 27-year-old female with thrombotic microangiopathy as an initial presentation of an unexpected disseminated gastric carcinoma. Based on clinical features and laboratory findings, thrombotic thrombocytopenic purpura (TTP) was diagnosed and plasma exchange started. However, she had responded poorly to plasmapheresis, developed multiorgan failure and died 72 h after admission. Autopsy revealed a disseminated gastric adenocarcinoma with metastatic infiltration of dura mater and disseminated tumor cell emboli in the microcirculation of the liver and lungs. Genetic analysis revealed amplification of KRAS oncogene and aberrations in DCC tumor suppressor gene, which can explain the young age and advanced disease at presentation. The role of plasmapheresis in cancer-associated TTP is uncertain. Plasmapheresis delivers fresh coagulation factors and may theoretically promote microthrombi formation and lead to worsening of the disease. Thrombotic thrombocytopenic purpura seems to be a late and prognostically poor manifestation of an underlying malignancy, with majority of patients dying soon after diagnosis. It is important to be aware of this possibility in thrombotic microangiopathy, especially with atypical features and poor response to standard treatment.

Impaired suppressive capacity of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) from peripheral blood of patients with multiple sclerosis (MS) has been reported by multiple laboratories. It is, however, currently unresolved whether Treg dysfunction in MS patients is limited to reduced control of peripheral T cell activation since most studies analyzed peripheral blood samples only. Here, we assessed early active MS lesions in brain biopsies obtained from 16 patients with MS by FOXP3 immunohistochemistry. In addition, we used six-color flow cytometry to determine numbers of Treg by analysis of FOXP3/CD127 expression in peripheral blood and cerebrospinal fluid (CSF) of 17 treatment-naive MS patients as well as quantities of apoptosis sensitive CD45RO(hi)CD95(hi) cells in circulating and CSF Treg subsets. Absolute numbers of FOXP3(+) and CD4(+) cells were rather low in MS brain lesions and Treg were not detectable in 30% of MS biopsies despite the presence of CD4(+) cell infiltrates. In contrast, Treg were detectable in all CSF samples and Treg with a CD45RO(hi)CD95(hi) phenotype previously shown to be highly apoptosis sensitive were found to be enriched in the CSF compared to peripheral blood of MS patients. We suggest a hypothetical model of intracerebral elimination of Treg by CD95L-mediated apoptosis within the MS lesion.

Objective: The aim of this rat study was to investigate the safety limits of extended transcranial direct current stimulation (tDCS). tDCS may be of therapeutic value in several neuro-psychiatric disorders. For its clinical applicability, however, more stable effects are required, which may be induced by intensified stimulations. Methods: Fifty-eight rats received single cathodal stimulations at 1-1000 mu A for up to 270 min through an epicranial electrode (3.5 mm(2)). Histological evaluation (H&E) was performed 48 h later. A threshold estimate was calculated from volumes of DC-induced lesions. Results: Brain lesions occurred at a current density of 142.9 A/m(2) for durations greater than 10 min. For current densities between 142.9 and 285.7 A/m(2), lesion size increased linearly with charge density; with a calculated zero lesion size intercept of 52400 C/m(2). Brains stimulated below either this Current density or charge density threshold, including stimulations over 5 consecutive days, were morphologically intact. Conclusion: The experimentally determined threshold estimate is two orders of magnitude higher than the charge density currently applied in humans (171-480 C/m(2)). In relation to transcranial DC Stimulation in humans the rat epicranial electrode montage may provide for an additional safety margin. Significance: Although these results cannot be directly transferred to humans, they encourage the development intensified tDCS protocols. Further animal studies are required, before such protocols can be applied in humans. (C) 2009 international Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.