Aims: To examine the effect of a single dose of human synthetic secretin (HSS) on behaviour and communication in children with autism spectrum disorder (ASD) using an objective measure of communication and social reciprocity and standardised rating scales. Methods: Randomised, crossover, double blind, and placebo controlled trial of a single intravenous dose of human synthetic secretin (HSS) 2 CU/kg. The 62 subjects (3-8 years) were assigned to group 1 (saline placebo/HSS) or group 2 (HSS/saline placebo). Diagnosis was confirmed by ADI-R (Autism Diagnostic Interview-Revised) algorithm. Severity of symptoms was rated using the CARS (Childhood Autism Rating Scale). Outcome measures included Communication and Symbolic Behavior Scale (CSBS), Ritvo Real-life Rating Scale, weekly Global Rating Scale (GBRS) by parents and teachers, and daily log of gastrointestinal symptoms. The communication subscale of the CSBS, specifying communication function, reciprocity, and social-affective signalling was videotaped and scored by a blinded, trained observer. Results: Sixty one children completed the study. After randomisation, there were no significant differences in gender, race, age, and parent and teacher GBRS and Ritvo Scale between the two groups. Compared with placebo, secretin treatment was not associated with significant improvement of CSBS standard scores from baseline to 2 or 4 weeks post-infusion. Five children showed clinical improvement in standard scores: two after HSS and three after placebo. There were no significant changes in gastrointestinal symptoms after HSS or saline placebo. Conclusions: A single dose of intravenous human secretin is not effective in changing behaviour and communication in children with ASD when compared to placebo.A utistic spectrum disorders (ASD) are heterogeneous, complex disorders with deficits in core symptoms of social interaction, communication, and behaviour. Estimates of prevalence rates range from 1 in 1000 to 1 in 160; with most authorities accepting 1 in 500.1 The disorders included in the spectrum (autism, Rett's disorder, childhood disintegrative disorder, Asperger's disorder, and pervasive developmental disorder (PDD), not otherwise specified) 2 represent a range of severity and underlying aetiologies. Recent research reports implicate a strong genetic predisposition.3 A number of neuropathological abnormalities of prenatal origin have been reported. 4 The rate of causally associated medical disorders ranges from 5% to 37%.5 6 In the majority of patients a specific underlying aetiology is not identified. Many untested theories have emerged that purport to explain the core symptoms and associated medical conditions, spawning a range of novel treatments.Current accepted treatments for children with ASD involve intensive, coordinated programmes of educational, language, developmental, and behavioural intervention. Evidence gathered over the past 10 years shows that intensive early intervention in optimal educational settings results in improved outcomes in most young children...

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ABSTRACT. Objectives. To compare language development in infants and young children with human immunodeficiency virus (HIV) infection to language development in children who had been exposed to HIV but were uninfected, and (among subjects with HIV infection) to compare language development with cognitive and neurologic status.Design. Prospective evaluation of language development in infected and in exposed but uninfected infants and young children.Setting. Pediatric Infectious Disease Clinic, State University of New York-Health Science Center at Syracuse.Subjects. Nine infants and young children infected with HIV and 69 seropositive but uninfected infants and children, age 6 weeks to 45 months.Results. Mean Early Language Milestone Scale, 2nd edition (ELM-2) Global Language scores were significantly lower for subjects with HIV infection, compared with uninfected subjects (89.3 vs 96.2, Mann-Whitney U test). The proportion of subjects scoring >2 SD below the mean on the ELM-2 on at least one occasion also was significantly greater for subjects with HIV infection, compared with uninfected subjects (4 of 9 infected subjects, but only 5 of 69 uninfected subjects; Fisher's exact test). Seven of the 9 subjects with HIV infection manifested deterioration of language function. Four manifested unremitting deterioration; only 1 of these 4 demonstrated unequivocal abnormality on neurologic examination. Three subjects with HIV infection and language deterioration showed improvement in language almost immediately after the initiation of antiretroviral drug treatment. Magnetic resonance imaging or computed tomography of the brain were performed in 6 of 7 infected subjects with language deterioration, and findings were normal in all 6. ELM-2 Global Language scaled scores showed good agreement with the Bayley Mental Developmental Index or the McCarthy Global Cognitive Index (r ‫؍‬ 0.70). Language deterioration, or improvement in language after initiation of drug therapy, coincided with or preceded changes in global cognitive function, at times by intervals of up to 12 months.Conclusions. Language deterioration occurs commonly in infants and young children with HIV infection, is seen frequently in the absence of abnormalities on neurologic examination or central nervous system imag-

Two brothers, with dissimilar clinical features, were each found to have different abnormalities of chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since chromosome 20 is a metacentric chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal chromosome 20 homologues, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially-available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, ~900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, ~1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e. between RP11-93B14 and proximal BAC RP11-765G16).

These data provide preliminary validation of a statistical model for clinical outcome of ASD on the basis of 3 parameters: age, degree of atypicality, and level of intelligence. This model, if replicated in a prospective, population-based sample that is controlled for treatment modalities, will enhance our ability to offer a prognosis for the child with ASD and will provide a benchmark against which to judge the putative benefits of various treatments for ASD. Our model may also be useful in etiologic and epidemiologic studies of ASD, because different causes of ASD are likely to follow different developmental trajectories along these 3 parameters.