N. González

Bio: N. González is an academic researcher from New York University. The author has contributed to research in topics: Risperidone & Autism. The author has an hindex of 18, co-authored 30 publications receiving 3536 citations. Previous affiliations of N. González include Kennedy Krieger Institute & University of Salamanca.

Risperidone in Children with Autism and Serious Behavioral Problems

Abstract: Background Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited. Methods We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions — Improvement (CGI-I) scale at eight weeks. Results A total of 101 children (82 boys and 19 girls; mean [±SD] age, 8.8±2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treat...

Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity

Abstract: CONTEXT Hyperactivity and inattention are common symptoms in children with autistic disorder and related pervasive developmental disorders, but studies of stimulants in these conditions have been inconclusive. OBJECTIVES To determine the efficacy and safety of methylphenidate hydrochloride in children with pervasive developmental disorders and hyperactivity. DESIGN Double-blind, placebo-controlled, crossover trial followed by open-label continuation. SETTING Five academic outpatient clinics. PARTICIPANTS Seventy-two drug-free children, aged 5 to 14 years, with pervasive developmental disorders accompanied by moderate to severe hyperactivity. INTERVENTIONS Prior to randomization, subjects entered a 1-week test-dose phase in which each subject received placebo for 1 day followed by increasing doses of methylphenidate (low, medium, and high doses) that were each given for 2 days. The low, medium, and high doses of methylphenidate hydrochloride were based on weight, and they ranged from 7.5 mg/d to 50.0 mg/d in divided doses. Subjects who tolerated the test dose (n = 66) were assigned to receive placebo for 1 week and then 3 methylphenidate doses in random order during a double-blind, crossover phase. Children responding to methylphenidate then entered 8 weeks of open-label treatment at the individually determined best dose. MAIN OUTCOME MEASURES The primary outcome measure was the teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist. Response was defined as \"much improved\" or \"very much improved\" on the Clinical Global Impressions Improvement item coupled with considerable reductions in the parent-rated and/or teacher-rated Aberrant Behavior Checklist hyperactivity subscale score. RESULTS Methylphenidate was superior to placebo on the primary outcome measure, with effect sizes ranging from 0.20 to 0.54 depending on dose and rater. Thirty-five (49%) of 72 enrolled subjects were classified as methylphenidate responders. Adverse effects led to the discontinuation of study medication in 13 (18%) of 72 subjects. CONCLUSIONS Methylphenidate was often efficacious in treating hyperactivity associated with pervasive developmental disorders, but the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder. Adverse effects were more frequent.

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

Abstract: OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children’s Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual rea...

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.

Abstract: Antigen-specific, CD8+, cytolytic T lymphocytes (CTLs) could potentially provide resistance to several infectious and malignant diseases. However, the cellular requirements for the generation of specific CTLs in human lymphocyte cultures are not well defined, and repetitive stimulation with antigen is often required. We find that strong CD8+ CTL responses to influenza virus can be generated from freshly isolated blood T cells, as long as dendritic cells are used as antigen presenting cells (APCs). Small numbers of dendritic cells (APC:T cell ratio of 1:50-1:100) induce these CTL responses from most donors in 7 d of culture, but monocytes are weak or inactive. Whereas both dendritic cells and monocytes are infected with influenza virus, the former serve as effective APCs for the induction of CD8+ T cells while the latter act as targets for the CTLs that are induced. The strong CD8+ response to influenza virus-infected dendritic cells is accompanied by extensive proliferation of the CD8+ T cells, but the response can develop in the apparent absence of CD4+ helpers or exogenous lymphokines. CD4+ influenza virus-specific CTLs can also be induced by dendritic cells, but the cultures initially must be depleted of CD8+ cells. These findings should make it possible to use dendritic cells to generate human, antigen-specific, CD8+ CTLs to other targets. The results illustrate the principle that efficient T cell-mediated responses develop in two stages: an afferent limb in which dendritic cells are specialized APCs and an efferent limb in which the primed T cells carry out an immune response to many types of presenting cells.

Risperidone Treatment of Autistic Disorder: Longer-Term Benefits and Blinded Discontinuation After 6 Months

Abstract: OBJECTIVE Risperidone is effective for short-term treatment of aggression, temper outbursts, and self-injurious behavior in children with autism. Because these behaviors may be chronic, there is a need to establish the efficacy and safety of longer-term treatment with this agent. METHOD The authors conducted a multisite, two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums, aggression, and/or self-injurious behavior who showed a positive response in an earlier 8-week trial. Part I consisted of 4-month open-label treatment with risperidone, starting at the established optimal dose; part II was an 8-week randomized, double-blind, placebo-substitution study of risperidone withdrawal. Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale. RESULTS Part I included 63 children. The mean risperidone dose was 1.96 mg/day at entry and remained stable over 16 weeks of open treatment. The change on the Aberrant Behavior Checklist irritability subscale was small and clinically insignificant. Reasons for discontinuation of part I included loss of efficacy (N=5) and adverse effects (N=1). The subjects gained an average of 5.1 kg. Part II included 32 patients. The relapse rates were 62.5% for gradual placebo substitution and 12.5% for continued risperidone; this difference was statistically significant. CONCLUSIONS Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums, aggression, and/or self-injurious behavior. Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects.

Dendritic cells and the control of immunity

Abstract: B and T lymphocytes are the mediators of immunity, but their function is under the control of dendritic cells. Dendritic cells in the periphery capture and process antigens, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. They not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions. Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis. With knowledge comes the realization that these cells are a powerful tool for manipulating the immune system.

Immunobiology of Dendritic Cells

Abstract: Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.

Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample

Abstract: Objective Autism spectrum disorders are now recognized to occur in up to 1% of the population and to be a major public health concern because of their early onset, lifelong persistence, and high levels of associated impairment. Little is known about the associated psychiatric disorders that may contribute to impairment. We identify the rates and type of psychiatric comorbidity associated with ASDs and explore the associations with variables identified as risk factors for child psychiatric disorders. Method A subgroup of 112 ten- to 14-year old children from a population-derived cohort was assessed for other child psychiatric disorders (3 months' prevalence) through parent interview using the Child and Adolescent Psychiatric Assessment. DSM-IV diagnoses for childhood anxiety disorders, depressive disorders, oppositional defiant and conduct disorders, attention-deficit/hyperactivity disorder, tic disorders, trichotillomania, enuresis, and encopresis were identified. Results Seventy percent of participants had at least one comorbid disorder and 41% had two or more. The most common diagnoses were social anxiety disorder (29.2%, 95% confidence interval [Cl)] 13.2-45.1), attention-deficit/hyperactivity disorder (28.2%, 95% Cl 13.3-43.0), and oppositional defiant disorder (28.1 %, 95% Cl 13.9-42.2). Of those with attention-deficit/hyperactivity disorder, 84% received a second comorbid diagnosis. There were few associations between putative risk factors and psychiatric disorder. Conclusions Psychiatric disorders are common and frequently multiple in children with autism spectrum disorders. They may provide targets for intervention and should be routinely evaluated in the clinical assessment of this group. J. Am. Acad. Child Adolesc. Psychiatry , 2008;47(8):921-929.

Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs

Abstract: CD8+ cytotoxic T lymphocytes (CTLs) mediate resistance to infectious agents and tumours. Classically, CTLs recognize antigens that are localized in the cytoplasm of target cells, processed and presented as peptide complexes with class I molecules of the major histocompatibility complex (MHC). However, there is evidence for an exogenous pathway whereby antigens that are not expected to gain access to the cytoplasm are presented on MHC class I molecules. The most dramatic example is the in vivo phenomenon of cross-priming: antigens from donor cells are acquired by bone-marrow-derived host antigen-presenting cells (APCs) and presented on MHC class I molecules. Two unanswered questions concern the identity of this bone-marrow-derived cell and how such antigens are acquired. Here we show that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs. Our findings suggest a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of CTLs.

Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells.

Abstract: Inadequate presentation of tumor antigens by host professional antigen-presenting cells (APCs), including dendritic cells (DCs), is one potential mechanism for the escape of tumors from the host immune system. Here, we show that human cancer cell lines release a soluble factor or factors that dramatically affect DC maturation from precursors without affecting the function of relatively mature DCs. One factor responsible for these effects was identified as vascular endothelial growth factor (VEGF). Thus, VEGF may play a broader role in the pathogenesis of cancer than was previously thought, and therapeutic blockade of VEGF action may improve prospects for immunotherapy as well as inhibit tumor neovasculature.