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BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.

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Fibroblasts carrying an inducible ras oncogene acquire the transformed phenotype after oncogene induction. As a consequence, the transformed cells become sensitive to intercellular induction of apoptosis, a novel regulatory process directed by non-transformed fibroblasts against their transformed descendants. The causal relationship between oncogene expression and sensitivity to intercellular induction of apoptosis is based on extracellular superoxide anion production by oncogene-expressing cells. Superoxide anions (after dismutation to hydrogen peroxide) thereby foster HOCl synthesis and at the same time direct the selectivity of apoptosis induction through hydroxyl generation from HOCl. In parallel, ras expression enhances the sensitivity of fibroblasts for apoptosis-inducing stimuli like cycloheximide, ceramide and mitomycin C. This sensitization seems to be based on a decreased concentration of short lived endogenous apoptosis inhibitors. TGF-beta, like ras induction, decreases the concentration of endogenous apoptosis inhibitors, but does not induce the transformed phenotype. Therefore, TGF-beta treatment alone is not sufficient to render fibroblasts sensitive for intercellular induction of apoptosis, but TGF-beta treatment in parallel with ras activation enhances intercellular induction of apoptosis. Our findings demonstrate that Ras-mediated superoxide anion production determines sensitivity to intercellular induction of apoptosis, whereas the parallel decrease in endogenous apoptosis inhibitors modulates the kinetics of apoptosis induction.

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Inhibition of RNA or protein synthesis causes apoptosis in fibroblasts. This points to the constitutive expression of a long-lived apoptosis machinery which is controlled by shortlived negative regulatory proteins, termed endogenous survival factors. The length of time between addition of the inhibitor of macromolecular synthesis and the onset of apoptosis can be used as an estimation of the effective survival factor concentration. Transformation of rat fibroblasts by a constitutively expressed src oncogene or an inducible ras oncogene increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis, indicating that their endogenous survival factor pool has been decreased.

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Fibroblasts constitutively express a functional apoptosis machinery which is under negative control by operationally defined endogenous survival factors. Oncogenic transformation causes a marked downmodulation of endogenous survival factor concentration which renders transformed cells more sensitive to various apoptosis stimuli compared to their nontransformed counterparts. Endogenous survival factors can be inactivated by reactive oxygen species (ROS). Endogenous survival factors are the ultimate targets for apoptosis-inducing factors derived from TGF-beta-triggered nontransformed cells during intercellular induction of apoptosis. During this control step of oncogenesis, endogenous survival factors in transformed cells are inactivated by ROS and the apoptosis machinery is released from negative control. This mechanism leads to the specific elimination of transformed cells. Our data show that the transformed state causes both the ability of the cells to perceive the apoptosis-inducing signal and a decrease in the concentration of endogenous survival factors. These two mechanisms are of central importance for the regulation of intercellular induction of apoptosis.

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During intercellular induction of apoptosis, transformed fibroblasts are eliminated through the action of neighbouring nontransformed cells. TGF-beta thereby plays three distinct and central roles. a) TGF-beta released by transformed cells or added exogenously to the assay system triggers nontransformed cells to release a shortlived apoptosis inducing factor, which is specifically directed against transformed cells. b) TGF-beta is involved in the maintenance of the transformed state, which is required for expression of sensitivity for intercellular induction of apoptosis. c) TGF-beta further sensitizes transformed cells through downmodulation of their endogenous survival factors, which control a constitutively expressed apoptosis machinery. These data demonstrate that TGF-beta which is utilized by transformed fibroblasts for the maintenance of their transformed state, causes recognition of transformed cells by their nontransformed neighbours and triggers and enhances an apoptosis-inducing response which finally causes elimination of potential tumor cells.

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Two cases of retroperitoneal duodenum rupture following an upper abdominal blunt trauma are reported. Computed tomography (CT) demonstrates at best extraintestinal fluid and air in the retroperitoneum, especially if acquisition in right lateral decubitus is possible. Drawbacks of the method are also reviewed.

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Twelve cases have been reported in the literature to have developed acute, largely reversible, global amnesic syndromes some hours after ingesting substantial doses of clioquinol. Two of these cases presented again after asymptomatic intervals of some 12 years. Both had recently developed typical clinical and electroencephalographic evidence of partial epilepsy originating in a temporal lobe. The similarity of clinical events in these two subjects, the absence of any other known cause for their epilepsy and the fact that, in mice, acute clioquinol overdosage causes hippocampal and amygdaloid injury, suggest that the drug was responsible for both the acute encephalopathy and the epilepsy of delayed onset.

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