Stevens-Johnson Syndrome Associated with Drugs and Vaccines in Children: A Case-Control Study

Objective

Stevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.

Methods

A multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child’s use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.

Results

Twenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1^st November 1999 and 31^st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0–6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4–86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5–7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8–9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5–6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3–2.8).

Discussion

Our study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.     

Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells

Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.     

SCLIP, a microtubule-destabilizing factor, interacts with RasGRF1 and inhibits its ability to promote Rac activation and neurite outgrowth

RasGRF1 is a neuron-specific guanine nucleotide exchange factor for the small GTPases Ras and Rac. It is implicated in the regulation of memory formation and in the development of tolerance to drug abuse, although the mechanisms have been elucidated only in part. Here we report the isolation, by the yeast two-hybrid screen, of the microtubule-destabilizing factor SCLIP (SCG10-like protein) as a novel RasGRF1-interacting protein. This interaction requires the region spanning the Dbl-homology domain of RasGRF1, endowed with catalytic activity on Rac. In search for a possible function we found by biochemical means that SCLIP influences the signaling properties of RasGRF1, greatly reducing its ability to activate the Rac/p38 MAPK pathway, while the Ras/Erk one remains unaffected. Moreover, a potential role is suggested by transfection studies in neuronal PC12 cells in which RasGRF1 induces neurite outgrowth, and coexpression of SCLIP counteracts this effect, causing a dramatic decrease in the percentage of cells bearing neurites, which also appear significantly shortened. This study unveils a physical and functional interaction between RasGRF1 and SCLIP. We suggest that this novel interplay may have possible implications in mechanisms that regulate neuronal morphology and structural plasticity.     

Development of antibodies to interferon beta in patients: technical and biological aspects.

There are now several papers describing the development of antibodies to interferons (IFN) in patients undergoing IFN therapy. Moreover, there is increasing evidence to indicate that the development of antibodies to IFN may be associated with a failure of the beneficial effects of the therapy. This paper will review and discuss what is currently known about the technical, and biological aspects of antibodies to IFN, with particular reference to antibodies to IFN beta that develop during therapy. Three main considerations arise from the data. Firstly, a standardized quantitative assay to detect antibody to IFN must be agreed upon. Only when results can be compared, both qualitatively and quantitatively, will it be possible to monitor fully the ability of antibodies to cause a relapse during treatment. Secondly, sufficient data are now available to provide a rationale for monitoring the presence of anti-IFN antibodies in patients treated with IFN. This approach may allow a better understanding of the disease reactivation state observed in numerous patients treated with IFN. Finally, approaches aimed at limiting the immunogenicity of IFN preparations and/or strategies designed to circumvent antibody-mediated resistance to IFN treatment are required.     

Neuronal and Glial Properties Coexist in a Novel Mouse CNS Immortalized Cell Line

A mes-c-myc A1 (A1) cell line was generated by retroviral infection of cultured embryonic mesencephalic cells and selected by neomycin resistance. A1 cells cease to divide and undergo morphological differentiation after serum withdrawal or addition of c-AMP. Proliferating or morphologically differentiated A1 cells are all positive for vimentin and nestin, a marker of neural precursor, and show neuronal markers such as microtubule-associated protein 1, neuron-specific enolase and peripherin, and the glial marker glial fibrillary acidic protein. Neuronal and glial markers coexist in single cells. Furthermore, A1 cells show presence of glutamic acid decarboxylase 67 mRNA and its embryonic form EP10 and accumulate the neurotransmitter GABA. Electrophysiological studies demonstrate that morphologically differentiated A1 cells display voltage-gated sodium and potassium channels in response to depolarizing stimuli. A1 cells thus represent a novel, bipotent neural cell line useful for studying CNS differentiation and plasticity, as well as the molecular mechanisms underlying development of GABAergic neurotransmission.     

Microarray analysis in Alzheimer's disease and normal aging

The purpose of this study was to investigate gene expression in Alzheimer's disease (AD), the most common form of senile dementia. We utilized the microarray technology to simultaneously compare the expression profile of 12,000 human genes in cerebral cortex of AD and normal aging. To identify gene expression related to neurodegeneration, beside the presence of amyloid deposition, we used control brains with abundant amyloid plaques, derived from cognitively normal elderly subjects. The microarray analysis indicated that 314 genes were differentially expressed in AD cerebral cortex, with differences greater than 5 folds in 25 genes. RT-PCR performed on a selected group of genes confirmed the increased expression of the interferon-induced protein 3 in AD brain. This protein, which is highly inducible by both type I and type II interferons, was not previously associated with the neurodegenerative disease.     

Distribution of surnames and identities in the Cimbro-Mòcheno communities of Italy

The surnames of populations of the municipalities with Cimbro and Mòcheno origins are compared with each other and with other municipalities of the neighbourhood. This study starts from the supposition that a community of surnames shares a common cultural origin, maintained by reciprocal mobility. The analysis has been carried out by using estimates of the similarities between populations, the topological representations obtained by them and the spatial autocorrelation. On the whole, this research shows no evidence of peculiar distinctions between the populations that share Cimbro and Mòcheno origins compared to the neighbouring ones. Moreover, there is not any evident process of undifferentiated diffusion along all the directions. On the contrary, it is emphasized that belonging to the same geographic region and to the same administrative subdivision mostly influences the similarity between populations. The exception is the Cimbro municipality of Luserna, which presents a peculiar structure of surnames different from other municipalities of the same territory.