1,721,180 research outputs found
Characterization of immunologic mechanisms in rare childhood chronic inflammatory diseases: implication for specific therapeutic intervention
Full text linkA partire da osservazioni in clinica di pazienti con rare malattie genetiche della regolazione della risposta immune, in questo studio abbiamo analizzato le alterazioni delle vie coinvolte nei meccanismi di malattia con lo scopo di identificare target terapeutici specifici . In particolare lo studio si è focalizzato su due condizioni, l’una caratterizzata da un’anomalia nella risposta immune innata con flogosi cronica, l’altra caratterizzata da un’alterazione dei meccanismi di mantenimento della self tolerance:
i) Una rara malattia autosomica dominante chiamata sindrome PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, acne, OMIM 604410), che colpisce maggiormente le articolazioni e la pelle. La sindrome PAPA è classificata tra le malattie auto-infiammatorie croniche, caratterizzata da ricorrenti episodi infiammatori in assenza di un evento scatenante e in assenza di elevati livelli di auto-anticorpi o auto-antigeni. Questa malattia è causata da mutazioni del gene CD2BP1 (CD2 binding protein 1). Abbiamo studiato una famiglia affetta dalla sindrome PAPA e abbiamo osservato un’alterazione nella produzione delle citochine TNFtumor necrosis factor alfa) e IL-1 (interleuchina-1 beta). Questi risultati sperimentali hanno fornito il background per la somministrazione terapeutica di etanercept, un inibitore del TNF, con conseguente rapida remissione clinica del paziente.
ii) Una severa malattia autoimmune multiorgano la sindrome IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked OMIM 304790). Questa malattia è causata da mutazioni nel gene FOXP3 (transcription factor fork-head box protein 3) con conseguente alterazione e/o assenza della popolazione delle cellule T regolatorie (Treg). Abbiamo studiato due pazienti affetti da sindrome IPEX. Le mutazioni identificate non coinvolgono direttamente il dominio funzionale DNA-binding di FOXP3. La popolazione cellulare T CD4+CD25+ è stata isolata ed analizzata. È stata riscontrata un’alterazione del potenziale inibitorio delle cellule Treg. Recentemente è stato dimostrato che il trattamento di pazienti con la fotoferesi (ECP, “extracorporeal photopheresis”) aumenta i livelli circolanti di cellule Treg in vivo. Nonostante l’efficacia di tale trattamento debba essere ancora dimostrata in trials clinici controllati, la letteratura suggerisce che l’ECP rappresenti una valida alternativa alle convenzionali terapie immuno-soppressive. A scopo terapeutico, uno dei pazienti IPEX è stato sottoposto a trattamento con ECP. I nostri risultati dimostrano che il trattamento con ECP induce un significativo incremento della popolazione cellulare T CD4+CD25+ con proprietà inibitorie ed è associato ad un miglioramento clinico del paziente.The molecular defects recently identified in rare childhood immune-dysregulations outline critical steps in the pathways that contribute to the development of normal innate immune responses and the maintenance of self-tolerance. This project is based on the study of the mechanisms involved in the alteration of immune regulation, both in hereditary autoimmune diseases and in chronic inflammation, with the aim of developing a therapeutic target. Our attention has focused on:
i) A rare autosomic dominant inherited disorder of childhood named PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, acne, OMIM 604410), primarily affecting the joints and skin. This disease falls under the definition of chronic auto-inflammatory diseases, characterized by recurrent “unprovoked” inflammatory events which are not associated with high-titre of auto-antibodies or auto-antigen specific T cells. The disease has been associated with mutations in the CD2 binding protein 1 (CD2BP1) gene. We have observed a family affected with PAPA syndrome and identified an alteration in the tumor necrosis factor- α (TNFα) and early interluekine-1 (IL-1 production. This laboratory finding was associated with a valuable therapeutic goal represented by the administration of the TNF inhibitor etanercept which resulted in a rapid, sustained clinical remission.
ii) A sever multi-organ autoimmune disease, the IPEX syndrome (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked OMIM 304790). The disease is caused by mutations in the FOXP3 gene (transcription factor fork-head box protein 3) which results in absence/alteration of the regulatory T cells (Treg) population. We have studied two IPEX patients with a milder clinical phenotype and have identified their mutations which lay outside the FOXP3 functional DNA binding domain. The CD4+CD25+ T cell population was studied and analysed. A functional impairment in the suppressive properties of these cells was found. It has been recently demonstrated that extracorporeal photopheresis (ECP) treatment in humans increases the levels of circulating regulatory T cells in vivo. Although the efficacy of this treatment awaits definitive proof in controlled clinical trials, data in several published series suggest that ECP represents an alternative to standard immune-suppression. Based on these findings, with a therapeutic purpose, we tempted to modulate regulatory T cells in vivo in one of the IPEX patient. Our results show that treatment with ECP leads to a significant increase in CD4+CD25+ T cells with suppressive ability associated with a marked clinical response
Exploratory study describing 6 month outcomes for yaoung children with autism who receive treatment as usual in Italy
No full textBackground: In the last few years, the results of different studies have confirmed, in different ways, the importance of early intervention for autism. This study aims to evaluate the role of early "as usual" interventions in the outcome of toddlers diagnosed with autism spectrum disorder (ASD).
Method: Seventy children with ASD aged between 24 and 48 months were recruited at different centers in Italy. They were evaluated by blind researchers at baseline and after 6 months of using Autism Diagnostic Observation Schedule-Generic (ADOS-G), Griffiths Mental Developmental Scales, and Vineland Adaptive Behavior scales. Parents filled out the MacArthur Inventory, Social Communication Questionnaire, and Child Behavior Check List. All children were referred to community providers for available interventions.
Results: At the endpoint, most of the children were still classified as having an ADOS-G classification of ASD. However, 21 (34.2%) passed from autism to autism spectrum, and 3 (4.2%) passed from autism spectrum to no spectrum. Treatment effects were obtained for cognitive functioning, language, adaptive behavior, and child behavior without differences between development-oriented and behavior-oriented interventions. Parent involvement was a mediator for the best clinical outcome. Baseline low impairments of communication, language comprehension, and gesture were predictors of positive outcome.
Conclusion: Treatment as usual, composed of individual therapy plus school-supported inclusion, may be an effective intervention in ASD. Better initial levels of communication in child and parent involvement during treatment have an important role for a positive outcome. Keywords: autism, preschoolers, treatment as usual, early interventio
George Frankl: an undervalued voice in the history of autism
Full text linkThis paper aims to propose that the psychiatrist George Frankl had more than a marginal role in the early history of autism. Frankl’s conception of autism as characterized by a lack of affective language has influenced both Asperger and Kanner. First, this proposal is historically supported; second it is corroborated by Frankl’s unpublished manuscript on Autism. We found that Frankl’s perspective about autism was, and still can be, considered innovative for multiple reasons. Specifically, Frankl proposed that autism could cover a spectrum of conditions; that it is a state of mind that is not necessarily abnormal; and that it is a neurobiological condition, which primarily needs to be understood by others. Finally, Frankl’s concepts of affective contact and affective language are reconsidered with reference to contemporary neuropsychology from which autism emerges not as a higher-order cognitive deficit, but as a result of an impairment of primordial ability to process low level sensory, motor and perceptual information gained through experiencing other persons
Disturbi del neurosviluppo e autismo: possibile integrazione tra approccio dimensionale e categoriale
No full textIn recent years clinical and neuroscience studies have highlighted some weaknesses of the current psychopathological categories included in neurodevelopmental disorders, both from a diagnostic and therapeutic point of view. In this context, the present work analyzes the dimensional and categorical aspects of Autism Spectrum Disorders (ASD) within the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). If on the one hand the DSM-5 introduced the dimensional concept of "spectrum", on the other, the presence of "specifiers" makes it possible to categorize the variegated group of ASDs into more homogeneous subgroups. In fact, the specifiers, in addition to describing the phenotypic expression of the disorder and being predictive indices of the clinical evolution of the autistic person in terms of autonomy and quality of life, will be able to help in the identification of patients who share a common neural substrate, potential target of future therapeutic interventions. It is therefore hoped to be able to expand the number of specifiers, in order to better characterize patients and reduce the heterogeneity that has so far prevented the development of both diagnostic and prognostic biomarkers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The communicative use of pointing in autism: developmental profile and factors related to change
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Outcomes and moderators of Early Start Denver Model intervention in young children with autism spectrum disorder delivered in a mixed individual and group setting
Full text linkSeveral studies have shown the efficacy and effectiveness of the Early Start Denver Model, both in university and in community-based settings. However, a limited number of studies have investigated predictors of outcomes. In this study, we examined outcomes in 32 children diagnosed with autism spectrum disorder after 1 year of community-based Early Start Denver Model intervention, with the aim to identify predictors of treatment objectives acquisition, as measured by the Early Start Denver Model Curriculum Checklist. At a group level, the participants demonstrated improvement in their communication as well as adaptive functioning skills, while they showed a decrease in symptom severity. The large heterogeneity in outcomes identified was related to the pre-treatment non-verbal abilities, symptom severity, action and gesture repertoire, and lexical comprehension. We discussed our results in terms of implications for developing “personalized” interventions for children with autism spectrum disorder
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