Fibrosis is a prevalent pathological condition arising from the chronic activation of fibroblasts. This activation results from the extensive intercellular crosstalk mediated by both soluble factors and direct cell-cell connections. Prominent among these are the interactions of fibroblasts with immune cells, in which the fibroblast-mast cell connection, although acknowledged, is relatively unexplored. We have used a Tg mouse model of skin fibrosis, based on expression of the transcription factor Snail in the epidermis, to probe the mechanisms regulating mast cell activity and the contribution of these cells to this pathology. We have discovered that Snail-expressing keratinocytes secrete plasminogen activator inhibitor type 1 (PAI1), which functions as a chemotactic factor to increase mast cell infiltration into the skin. Moreover, we have determined that PAI1 upregulates intercellular adhesion molecule type 1 (ICAM1) expression on dermal fibroblasts, rendering them competent to bind to mast cells. This heterotypic cell-cell adhesion, also observed in the skin fibrotic disorder scleroderma, culminates in the reciprocal activation of both mast cells and fibroblasts, leading to the cascade of events that promote fibrogenesis. Thus, we have identified roles for PAI1 in the multifactorial program of fibrogenesis that expand its functional repertoire beyond its canonical role in plasmin-dependent processes.
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Ophthalmoplegic migraine (OM) may be diagnosed after recurrent episodes of headache, followed by the paresis of one or more ocular cranial nerves (typically oculomotor 1 ). The diagnosis requires all other causes of focal intracranial neuropathy (i.e. vascular, inflammatory, tumor or infectious etiology), to be excluded. Contrast MR imaging typically reveals enhancement of the affected nerve at the site of its exit from the brainstem. 2 Ophthalmoplegic migraine is rare, with an annual incidence estimated at 0.7 per million. 3 However it does account for up to 7% of all isolated cases of childhood oculomotor nerve palsy. 4,5 ABSTRACT: Background: This critical review provides a summary of the clinical presentation, neuroimaging, treatment and prognosis in pediatric ophthalmoplegic migraine (OM). The features of OM are not in keeping with its classification as a migraine-variant. Method: We review 3 new and 37 reported pediatric OM cases. Results: Headache was an inconsistent feature, with 25% patients showing no evidence of pain at the initial OM episode. Patients demonstrated: 1) prolonged time for symptom resolution to occur (median time 3 weeks); 2) tendency for recurrent episodes to have more severe and persistent nerve involvement; 3) evidence of permanent neurological sequelae with recurrent episodes (30% of patients); 4) rapid improvement and shortened duration with corticosteroid therapy and; 5) transient, reversible MRI contrast enhancement of the affected cranial nerve (86% of patients). These features would not be expected in primary migraine headache. Conclusion: A detailed understanding of the natural history of OM is essential for the clinical. This review provides support that OM may result from cranial nerve inflammation with headache a secondary and later feature of this condition. RÉSUMÉ: La migraine ophtalmoplégique : s'agit-il d'une neuropathie inflammatoire avec migraine secondaire?Contexte : Cette revue présente un sommaire du tableau clinique, de la neuroimagerie, du traitement et du pronostic de la migraine ophtalmoplégique (MO) pédiatrique et une analyse critique ce ces données. Bien qu'on classifie la MO comme une forme variante de la migraine, ses manifestations ne cadrent pas avec cette classification. Méthode : Nous rapportons 3 nouvelles observations cliniques pédiatriques de MO et nous révisons 37 observations pédiatriques déjà rapportées. Résultats : La céphalée n'était pas toujours présente et 25% des patients n'avaient pas de douleur au moment du premier épisode de MO. À noter que : 1) les symptômes s'estompaient lentement (temps médian de 3 semaines) ; 2) au moment des rechutes, l'atteinte nerveuse avait tendance à être plus sévère et plus persistante ; 3) les patients ayant présenté plusieurs épisodes pouvaient avoir des signes de séquelles neurologiques permanentes (30% des patients) ; 4) la corticothérapie provoquait une amélioration rapide et des épisodes plus courts et 5) un rehaussement transitoire réversible du nerf crânien atteint était observé à l'IRM avec produit de co...
Preliminary experience suggests that intracameral injections of amphotericin B may have a role in the management of deep keratomycosis.
The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2 % and 94.9 ± 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP.
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