Challenges and Prospects of Adoptive Immunotherapy in Prevention and Treatment of Opportunistic Mycoses in Hematologic Transplant Recipients

Invasive fungal infections remain a serious and life-threatening complication in patients undergoing hematopoietic stem cell transplantation. Since it became clear that lymphocytes, in particular lymphocytes from the T helper 1 (T_H1) subset, play a critical secondary defense against fungal pathogens, the adoptive transfer of functionally active antifungal T_H1 cells might be an attractive option to restore adaptive antifungal immune effector mechanisms. Major advances have been made in the generation and characterization of antifungal T cells, which are active against medical important fungi such as Aspergillus spp and Candida spp. However, given the paucity of large homogenous patient populations, major challenges remain in evaluating the clinical usefulness of adoptive antifungal immunotherapy, which should be performed in international collaborative trials.     

Neurodegeneration in autoimmune demyelination: recent mechanistic insights reveal novel therapeutic targets

Multiple sclerosis (MS) is the most common chronic demyelinating disease of the central nervous system (CNS) and the major cause of neurological disability in young adults in Western countries. In spite of intensive research efforts, treatment options established to date do not sufficiently prevent the accumulation of tissue damage and clinical disability in patients with MS. We here describe recently identified molecules responsible for the inflammatory and the neurodegenerative processes in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), and review new treatment options targeting both aspects of this disease.     

Mouse model mimics multiple sclerosis in the clinico-radiological paradox

The value of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, in deriving novel diagnostic and therapeutic input has been subject to recent debate. This study is the first to report a disseminated distribution of plaques including cranial nerves, prior to or at early stages of disease in murine adoptive transfer EAE, irrespective of the development of clinical symptoms. We induced EAE by adoptive proteolipid protein-specific T-cell transfer in 26 female SJL/J mice, and applied high-field-strength magnetic resonance imaging (MRI) scans longitudinally, assessing blood-brain barrier (BBB) disruption by gadopentate dimeglumine enhancement. We visualized inflammatory nerve injury by gadofluorine M accumulation, and phagocytic cells in inflamed tissue by very small anionic iron oxide particles (VSOP-C184). MRI was correlated with immunohistological sections. In this study, we discovered very early BBB breakdown of white and grey brain matter in 25 mice; one mouse developed exclusively spinal cord inflammation. Widely disseminated contrast-enhancing lesions preceded the onset of disease in 10 animals. Such lesions were present despite the absence of any clinical disease formation in four mice, and coincided with the first detectable symptoms in others. Cranial nerves, predominantly the optic and trigeminal nerves, showed signal intensity changes in nuclei and fascicles of 14 mice. At all sites of MRI lesions we detected cellular infiltrates on corresponding histological sections. The discrepancy between the disease burden visualized by MRI and the extent of disability indeed mimics the human clinico-radiological paradox. MRI should therefore be implemented into evaluational in vivo routines of future therapeutic EAE studies.     

An infection with linezolid-resistant S. aureus in a patient with left ventricular assist system

We report an infection with a linezolid-resistant S. aureus in a patient with a left ventricular assist system. Linezolid should be used with caution when invasive devices or foreign materials are in place or therapeutic courses last longer than 14 d. Previous cases of linezolid-resistant S. aureus are summarized.     

Flat-panel-detector-based volumetric CT: performance evaluation of imaging for skeletal structures of small animals in comparison to multislice CT

OBJECTIVES: The aim of this study was to compare the image performance of silicon-based flat-panel-detector-based volumetric computed tomography (fpVCT) to multislice spiral computed tomography (MSCT) for the visualization and detail detectability of skeletal structures in rodents of different development stages. MATERIALS AND METHODS: Rodents of different development stages were imaged with fpVCT (GE prototype with circular gantry with two 1024 x 1024, 200-microm pixel size, amorphous silicon/Cesium lodid (Csl) flat-panel detector) and eight-slice MSCT (LightSpeed Ultra). Imaging parameters (80 kVp, 100 mA) and the position of the rodents were identical in both techniques. Image quality, detail detectability, and contour of skeletal structures were judged by two observers in consensus using a 4-point scale (1 = unsatisfactory...4 = good). Findings were displayed and evaluated in axial slices, multiplanar reconstructions (MPR), maximum intensity projections (MIP) and volume rendering technique (VRT) in both modalities. Mean and standard of error of mean were calculated. RESULTS: In axial slices, visualization and detail detectability of very subtle skeletal structures, e.g., the basis of the skull was better in fpVCT than in MSCT (4 vs. 2 points). The MPRs of fpVCT showed less artifacts and more details than those of the MSCT. The MIPs and VRTs of the fpVCT demonstrated best image quality in all rodents of different development stages, whereas MSCT showed significant artifacts. CONCLUSION: fpVCT outperformed MSCT in imaging of small rodents. Due to the truly isotropic volume data set with high spatial resolution, fpVCT is a powerful tool in evaluating detailed skeletal structures.     

Early detection of psychosis - establishing a service for persons at risk

PURPOSE: The establishment phase of an early detection centre for prodromal psychosis is introduced and characterised, along with its detaining and promoting factors within a universal multi-payer health care system. METHOD: Across the first six years (1998-2003), users' characteristics are compared between different diagnostic groups and to the local population statistics; and, for an exemplary 12-months period (3-1-2002 to 2-28-2003), the characteristics of telephone contacts with the service are studied. RESULTS: Rising steadily in number across the first three years, 872 persons, predominantly of German citizenship and higher education, consulted the service until 2003, 326 with first-episode psychosis and 144 not fulfilling criteria for a current or beginning psychosis. Of the 402 putatively prodromal patients, 94% reported predictive basic symptoms, 68.9% attenuated and 20.6% transient psychotic symptoms. Most contacts by persons meeting any prodromal criterion were initiated by mental health professionals (psychiatrists or psychologists) and counselling services. CONCLUSION: Supported by public awareness campaigns, an early detection service is well received by its users and private practitioners as reflected by the large proportion of referrals from the latter. However, persons of non-German background as well as of lower education were underrepresented indicating that these sub-groups should be approached by tailored programmes.