[Rapidly lethal progression of a therapy-resistant status epilepticus]. / Refraktärer generalisiert konvulsiver Status epilepticus - Fallbericht eines rasch letalen Verlaufs.

We present a case of death after first manifestation of generalised convulsive status epilepticus in a young man. A previously healthy 23-year-old man was admitted to our emergency department by ambulance service with approximately 20 min of generalised convulsive seizures. First line treatment in the emergency ward with benzodiazepines failed. The patient was cardiopulmonary stable until, after more than 30 min of status epilepticus, he developed tachycardia and became bradypnoeic. Intubation and ventilation was performed and anticonvulsive treatment was escalated with thiopental. Fifteen minutes later he developed ventricular fibrillation. CPR was started. The patient became asystolic after 90 min CPR following the ILCOR (International Liaison Committee on Resuscitation) Instructions. CPR was continued for another 30 min without success. The patient died after 120 min of maximal efforts. Autopsy and toxicology were performed, neuropathologic examination showed general brain edema and neuronal cell loss in purkinje cell layers of the cerebellum and olive knots which may be the consequence of generalised convulsive status epilepticus. We conclude: status epilepticus becomes refractory in approximately 30 % of cases. Until now, there are no randomised trials on the optimal treatment of refractory status epilepticus. Better treatment algorithms are urgently needed.

Monocyte stimulation by reactive oxygen species: role of superoxide and intracellular Ca2+.

OBJECTIVE: Production of reactive oxygen species has generally been linked to inflammatory processes. Whether the presence of superoxide and hydrogen peroxide affects mononuclear cell function was investigated with an in vitro model using isolated human mononuclear cells. MATERIALS AND METHODS: Human mononuclear cells were isolated from buffy coat. Toxicity was measured with Trypan blue exclusion, secreted TNF-alpha was measured with an ELISA, reactive oxygen species within mononuclear cells were quantified with dichlorodihydrofluorescein diacetate fluorescence, intracellular TNF-alpha was measured with flow cytometry and fluorescence microscopy. RESULTS: The enzymatic production of superoxide caused a dose-dependent increase in TNF-alpha synthesis, whereas hydrogen peroxide was ineffective. Flow cytometric measurements and immunofluorescence microscopy demonstrated that monocytes were the main TNF-alpha producing population. This proinflammatory reaction was further characterized by pharmacologically investigating Ca2+ signalling pathways. Superoxide stimulated TNF-alpha secretion was inhibited by intracellular Ca2+-buffers (MAPT-AM and BAPT-AM) or VOC operating antagonists (diltiazem and verapamil) and only to a small extent by pharmacological inhibitors of ligand-gated pathways (TMB-8 and SKF 96368). CONCLUSION: We propose that superoxide activates human mononuclear cells in a Ca2+-dependent manner.

T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function.

T helper (Th) cells can be categorized according to their cytokine expression. The differential induction of Th cells expressing Th1 and/or Th2 cytokines is key to the regulation of both protective and pathological immune responses. Cytokines are expressed transiently and there is a lack of stably expressed surface molecules, significant for functionally different types of Th cells. Such molecules are of utmost importance for the analysis and selective functional modulation of Th subsets and will provide new therapeutic strategies for the treatment of allergic or autoimmune diseases. To this end, we have identified potential target genes preferentially expressed in Th2 cells, expressing interleukin (IL)-4, IL-5, and/or IL-10, but not interferon-gamma. One such gene, T1/ST2, is expressed stably on both Th2 clones and Th2-polarized cells activated in vivo or in vitro. T1/ST2 expression is independent of induction by IL-4, IL-5, or IL-10. T1/ST2 plays a critical role in Th2 effector function. Administration of either a mAb against T1/ST2 or recombinant T1/ST2 fusion protein attenuates eosinophilic inflammation of the airways and suppresses IL-4 and IL-5 production in vivo following adoptive transfer of Th2 cells.

Glycosylphosphatidylinositol (GPI)-anchored surface antigens in the allogeneic activation of T cells.

GPI-linked surface molecules have recently been described as structures with an activation potential for human T lymphocytes. To study the role of these molecules in T cell activation we analysed GPI-deficient or normal T cells from patients with paroxysmal nocturnal haemoglobinuria (PNH). On activation with allogeneic Epstein-Barr virus (EBV)-transformed B cell lines GPI-deficient freshly separated T cells or continuously growing T cell lines exhibited a significantly lower proliferation or cytokine production compared with their normal counterparts. In contrast, stimulation via the T cell receptor-associated CD3 structure resulted in a comparable response. There was no difference in activation of normal T lymphocytes when GPI-deficient B cells were used as stimulators compared with normal B cells obtained from the same PNH patient. We conclude from these data that GPI deficiency in PNH leads to a functional deficiency of GPI-deficient T cells. In contrast, no difference in activation of T lymphocytes for GPI-deficient cells on the stimulator cell level was observed.