Glucocorticoid hypersensitivity as a rare but potentially fatal side effect of paediatric asthma treatment: a case report

<p>Abstract</p> <p>Introduction</p> <p>Immediate-type hypersensitivity to glucocorticosteroids is rare but well known among allergists. Surprisingly, very few reports of glucocorticosteroid hypersensitivity in children exist although glucocorticosteroid treatment is particularly common in this age group.</p> <p>Case presentation</p> <p>We report the case of a 2-year-old boy who developed generalized urticaria, facial angio-oedema, nausea and severe dyspnoea after intravenous application of prednisolone-21-hydrogen succinate. Skin prick testing with prednisolone-21-hydrogen succinate elicited a positive result; no reactions were observed to prednisone, betamethasone or dexamethasone. While fluorescence enzyme immunoassay analysis revealed no specific IgE antibodies against prednisolone-21-hydrogen succinate, CD63-based basophil activation testing with the culprit drug prednisolone-21-hydrogen succinate was positive. In contrast, additional incubation of basophils with prednisone, betamethasone and dexamethasone did not elicit any significant response. Hence, we performed an oral provocation test with betamethasone and a titrated intravenous dexamethasone challenge. As both drugs were tolerated without any complications they were recommended for future treatment.</p> <p>Conclusion</p> <p>In a child with confirmed immediate-type hypersensitivity to glucocorticosteroids, it is still not possible to predict which glucocorticosteroid might be tolerated by solely relying on clinical history or results of skin and <it>in vitro </it>testing. Therefore, incremental glucocorticosteroid challenges under standardized clinical conditions remain necessary in order to facilitate a patient-tailored emergency treatment and to avoid severe reactions to glucocorticosteroids in these patients.</p

Hypoxia and adipose tissue function and dysfunction in obesity

The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signalling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors – the adipokines. Increases in the secretion of a number of adipokines occurs in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in pO2 is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of inflammation-related adipokines is up-regulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilisation is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at pO2 levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity

The brain's response to pleasant touch: an EEG investigation of tactile caressing

Somatosensation as a proximal sense can have a strong impact on our attitude toward physical objects and other human beings. However, relatively little is known about how hedonic valence of touch is processed at the cortical level. Here we investigated the electrophysiological correlates of affective tactile sensation during caressing of the right forearm with pleasant and unpleasant textile fabrics. We show dissociation between more physically driven differential brain responses to the different fabrics in early somatosensory cortex - the well-known mu-suppression (10-20 Hz) - and a beta-band response (25-30 Hz) in presumably higher-order somatosensory areas in the right hemisphere that correlated well with the subjective valence of tactile caressing. Importantly, when using single trial classification techniques, beta-power significantly distinguished between pleasant and unpleasant stimulation on a single trial basis with high accuracy. Our results therefore suggest a dissociation of the sensory and affective aspects of touch in the somatosensory system and may provide features that may be used for single trial decoding of affective mental states from simple electroencephalographic measurements

Oxygen-Independent Stabilization of Hypoxia Inducible Factor (HIF)-1 during RSV Infection

BACKGROUND: Hypoxia-inducible factor 1 (HIF)-1alpha is a transcription factor that functions as master regulator of mammalian oxygen homeostasis. In addition, recent studies identified a role for HIF-1alpha as transcriptional regulator during inflammation or infection. Based on studies showing that respiratory syncytial virus (RSV) is among the most potent biological stimuli to induce an inflammatory milieu, we hypothesized a role of HIF-1alpha as transcriptional regulator during infections with RSV. METHODOLOGY, PRINCIPAL FINDINGS: We gained first insight from immunohistocemical studies of RSV-infected human pulmonary epithelia that were stained for HIF-1alpha. These studies revealed that RSV-positive cells also stained for HIF-1alpha, suggesting concomitant HIF-activation during RSV infection. Similarly, Western blot analysis confirmed an approximately 8-fold increase in HIF-1alpha protein 24 h after RSV infection. In contrast, HIF-1alpha activation was abolished utilizing UV-treated RSV. Moreover, HIF-alpha-regulated genes (VEGF, CD73, FN-1, COX-2) were induced with RSV infection of wild-type cells. In contrast, HIF-1alpha dependent gene induction was abolished in pulmonary epithelia following siRNA mediated repression of HIF-1alpha. Measurements of the partial pressure of oxygen in the supernatants of RSV infected epithelia or controls revealed no differences in oxygen content, suggesting that HIF-1alpha activation is not caused by RSV associated hypoxia. Finally, studies of RSV pneumonitis in mice confirmed HIF-alpha-activation in a murine in vivo model. CONCLUSIONS/SIGNIFICANCE: Taking together, these studies suggest hypoxia-independent activation of HIF-1alpha during infection with RSV in vitro and in vivo

Cellular Imaging of Human Atherosclerotic Lesions by Intravascular Electric Impedance Spectroscopy

Background: Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) is able to provide information about the cellular composition of biological tissue. The present study was performed to determine the influence of inflammatory processes in type Va (lipid core, thick fibrous cap) and Vc (abundant fibrous connective tissue while lipid is minimal or even absent) human atherosclerotic lesions on the electrical impedance of these lesions measured by EIS. Methods and Results: EIS was performed on 1 aortic and 3 femoral human arteries at 25 spots with visually heavy plaque burden. Severely calcified lesions were excluded from analysis. A highly flexible micro-electrode mounted onto a balloon catheter was placed on marked regions to measure impedance values at 100 kHz. After paraffin embedding, visible marked cross sections (n = 21) were processed. Assessment of lesion types was performed by Movats staining. Immunostaining for CD31 (marker of neovascularisation), CD36 (scavenger cells) and MMP-3 (matrix metalloproteinase-3) was performed. The amount of positive cells was assessed semi-quantitatively. 15 type Va lesions and 6 type Vc lesions were identified. Lesions containing abundant CD36-, CD31- and MMP-3-positive staining revealed significantly higher impedance values compared to lesions with marginal or without positive staining (CD36+455650 V vs. CD36- 346653 V, p = 0.001; CD31+436643 V vs. CD31- 340655 V, p = 0.001; MMP-3+ 400668 V vs. MMP-3- 323633 V, p = 0.03)

Modulating Temporal and Spatial Oxygenation over Adherent Cellular Cultures

Oxygen is a key modulator of many cellular pathways, but current devices permitting in vitro oxygen modulation fail to meet the needs of biomedical research. A microfabricated insert for multiwell plates has been developed to more effectively control the temporal and spatial oxygen concentration to better model physiological phenomena found in vivo. The platform consists of a polydimethylsiloxane insert that nests into a standard multiwell plate and serves as a passive microfluidic gas network with a gas-permeable membrane aimed to modulate oxygen delivery to adherent cells. Equilibration time is on the order of minutes and a wide variety of oxygen profiles can be attained based on the device design, such as the cyclic profile achieved in this study, and even oxygen gradients to mimic those found in vivo. The proper biological consequences of the device's oxygen delivery were confirmed in cellular models via a proliferation assay and western analysis of the upregulation of hypoxia inducible transcription factor-1α. These experiments serve as a demonstration for the platform as a viable tool to increase experimental throughput and permit novel experimental possibilities in any biomedical research lab

Stationary Black Holes: Uniqueness and Beyond

The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.Comment: Major update of the original version by Markus Heusler from 1998. Piotr T. Chru\'sciel and Jo\~ao Lopes Costa succeeded to this review's authorship. Significantly restructured and updated all sections; changes are too numerous to be usefully described here. The number of references increased from 186 to 32

Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA damage inducing agents

10.1371/journal.pone.0010522PLoS ONE55

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial?

Background Low back pain (LBP) is common in the population and multifactorial in nature, often involving negative consequences. Reassuring information to improve coping is recommended for reducing the negative consequences of LBP. Adding a simple non-threatening explanation for the pain (temporary muscular dysfunction) has been successful at altering beliefs and behavior when delivered with other intervention elements. This study investigates the isolated effect of this specific information on future occupational behavior outcomes when delivered to the workforce. Design A cluster-randomized controlled trial. Methods Publically employed workers (n=505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non-threatening explanation for LBP - the ‘functional-disturbance’-model. Data collections took place monthly over a 1-year period using text message tracking (SMS). Primary outcomes were self-reported days of cutting down usual activities and work participation. Secondary outcomes were self-reported back beliefs, work ability, number of healthcare visits, bothersomeness, restricted activity, use of pain medication, and sadness/depression. Results There was no between-group difference in the development of LBP during follow-up. Cumulative logistic regression analyses showed no between-group difference on days of cutting down activities, but increased odds for more days of work participation in the intervention group (OR=1.83 95% CI: 1.08-3.12). Furthermore, the intervention group was more likely to report: higher work ability, reduced visits to healthcare professionals, lower bothersomeness, lower levels of sadness/depression, and positive back beliefs. Conclusion Reassuring information involving a simple non-threatening explanation for LBP significantly increased the odds for days of work participation and higher work ability among workers who went on to experience LBP during the 12-month follow-up. Our results confirm the potential for public-health education for LBP, and add to the discussion of simple versus multidisciplinary interventions