Characterising the Early Presentation of Motor Difficulties in Autistic Children

Journal of Autism and Developmental Disorders - This study aimed to explore the rates of motor difficulties in children from the Australian Autism Biobank, and how early motor concerns impacted on...     

Visual and auditory emotion recognition problems as familial cross-disorder phenomenon in ASD and ADHD

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently comorbid disorders. Emotion recognition problems are considered an important familial deficit in ASD, but this is unknown in ADHD. Very few studies have directly compared emotion recognition performance of youth with ASD and/or ADHD and of their unaffected siblings across age to quantify the contribution of emotion recognition problems to the ADHD phenotype. We therefore devised a study of 64 ASD+ADHD participants, 89 ASD-only participants, 111 ADHD-only participants, 122 unaffected ASD(+ADHD) siblings, 69 unaffected ADHD-only siblings and 220 controls aged 7–18 years, who had completed two tasks assessing auditory and visual emotion recognition. Factor analysis was used to detect underlying dimensions of emotion recognition capacity. Linear mixed models were used to compare performance across groups and to assess age effects. The factor-analysis revealed four factors separating speed and accuracy regarding visual and auditory emotion recognition. ASD+ADHD, ASD-only, and ADHD-only participants all performed worse than controls. ASD+ADHD, ASD-only, and ADHD-only participants did not differ in the severity of their emotion recognition problems. Both unaffected sibling groups performed intermediate between patients and controls. For ASD+ADHD and ADHD-only participants, group differences were more marked in adolescence than childhood, whereas in ASD participants this was not observed. We conclude that emotion recognition problems are a familial deficit in ADHD to a similar extent as in ASD. Emotion recognition problems specifically - and social cognition problems more generally - should be assessed in clinical practice for ADHD.     

Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions

Introduction: Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despite this, controversy remains as to how drugs interact with immune receptors to stimulate a T-cell response.

Areas covered: This article reviews the pathways of T-cell activation by drugs and how the ever increasing number of associations between expression of HLA alleles and susceptibility to hypersensitivity is impacting on our research effort to understanding this form of iatrogenic disease.

Expert opinion: For a drug to activate a T-cell, a complex is formed between HLA molecules, an HLA binding peptide, the drug and the T-cell receptor. T-cell responses can involve drugs and stable or reactive metabolites bound covalently or non-covalently to any component of this complex. Recent research has linked the HLA associations to the disease through the characterization of drug-specific T-cell responses restricted to specific alleles. However, there is now a need to identify the additional genetic or environment factors that determine susceptibility and use our increased knowledge to develop predictive immunogenicity tests that offer benefit to Pharma developing new drugs.     

Water-dispersible magnetic carbon nanotubes as T2-weighted MRI contrast agents

An efficient MRI T₂-weighted contrast agent incorporating a potential liver targeting functionality was synthesized via the combination of superparamagnetic iron oxide (SPIO) nanoparticles with multiwalled carbon nanotubes (MWCNTs). Poly(diallyldimethylammonium chloride) (PDDA) was coated on the surface of acid treated MWCNTs via electrostatic interactions and SPIO nanoparticles modified with a potential targeting agent, lactose–glycine adduct (Lac–Gly), were subsequently immobilized on the surface of the PDDA–MWCNTs. A narrow magnetic hysteresis loop indicated that the product displayed superparamagnetism at room temperature which was further confirmed by ZFC (zero field cooling)/FC (field cooling) curves measured by SQUID. The multifunctional MWCNT-based magnetic nanocomposites showed low cytotoxicity in vitro to HEK293 and Huh7 cell lines. Enhanced T₂ relaxivities were observed for the hybrid material (186 mm⁻¹ s⁻¹) in comparison with the pure magnetic nanoparticles (92 mm⁻¹ s⁻¹) due to the capacity of the MWCNTs to “carry” more nanoparticles as clusters. More importantly, after administration of the composite material to an in vivo liver cancer model in mice, a significant increase in tumor to liver contrast ratio (277%) was observed in T₂ weighted magnetic resonance images.     

Capacity building in health economics. Opportunities for training in developing countries

This paper provides an overview of the opportunities available for training in health economics in the regions of Africa, Asia and Latin America, following a WHO forum on Capacity Building in Health Economics held in Geneva in December 1995. It describes in brief the training opportunities available throughout Asia, Africa and Latin America. It then gives a detailed resume of courses available for students and professionals at Chulanlongkorn University, Thailand, the University of Cape Town, South Africa and the University of the West Indies, Trinidad. It also describes the international and regional networks which have developed and now provide further opportunities for training. The final section of this paper looks to the future and suggests that although continued financial and academic support will be needed from the countries of the North, the development of regional capacities in health economics should be as much as possible through regional resources, and regional strategies should be a priority.     

Mutant Mouse Models: Genotype-Phenotype Relationships to Negative Symptoms in Schizophrenia

Negative symptoms encompass diminution in emotional expression and motivation, some of which relate to human attributes that may not be accessible readily in animals. Additionally, their refractoriness to treatment precludes therapeutic validation of putative models. This review considers critically the application of mutant mouse models to the study of the pathobiology of negative symptoms. It focuses on 4 main approaches: genes related to the pathobiology of schizophrenia, genes associated with risk for schizophrenia, neurodevelopmental-synaptic genes, and variant approaches from other areas of neurobiology. Despite rapid advances over the past several years, it is clear that we continue to face substantive challenges in applying mutant models to better understand the pathobiology of negative symptoms: the majority of evidence relates to impairments in social behavior, with only limited data relating to anhedonia and negligible data concerning avolition and other features; even for the most widely examined feature, social behavior, studies have used diverse assessments thereof; modelling must proceed in cognizance of increasing evidence that genes and pathobiologies implicated in schizophrenia overlap with other psychotic disorders, particularly bipolar disorder. Despite the caveats and challenges, several mutant lines evidence a phenotype for at least one index of social behavior. Though this may suggest superficially some shared relationship to negative symptoms, it is not yet possible to specify either the scope or the pathobiology of that relationship for any given gene. The breadth and depth of ongoing studies in mutants hold the prospect of addressing these shortcomings.     

Phenotypic,ethologically based resolution of spontaneous and D(2)-like vs D(1)-like agonist-induced behavioural topography in mice with congenic D(3) dopamine receptor "knockout"

Uncertainty as to the functional role of the D(3) dopamine receptor, due primarily to a paucity of selective agonists or antagonists, is being addressed in mice with targeted gene deletion ("knockout") thereof. This study describes, for the first time, the phenotype of congenic D(3)-null mice. Initially, 129/Sv x C57BL/6 D(3)-null mice were backcrossed 14 times onto C57BL/6; they were then assessed using an ethologically based approach which resolves all topographies of behaviour within the mouse repertoire. The ethogram of D(3)-null mice, on comparison with wildtypes, was characterised by no alteration in any topography of behaviour over an initial period of exploration; subsequent assessment over several hours revealed only increased rearing among females due to delayed habituation. Low doses of the selective D(2)-like agonist RU 24213 (0.016-0.25 mg/kg) inhibited topographies of exploratory behaviour; this effect was diminished in D(3)-null mice only when investigated following prolonged habituation, and then only for certain topographies of behaviour, primarily sniffing and rearing. High doses of RU 24213 (0.1-12.5 mg/kg) induced stereotyped sniffing and "ponderous" locomotion, while the selective D(1)-like agonist SK&F 83959 (0.016-2.0 mg/kg) promoted characteristic grooming syntax; these effects did not differ materially between the genotypes. When examined topographically on an essentially congenic C57BL/6 background (<0.005% 129/Sv), the resultant phenotype indicated essential conservation of the mouse ethogram, high-dose D(2)-like stimulatory effects, and D(1)-like stimulatory effects in the absence of D(3) receptors. A role for D(3) receptors in inhibitory processes appeared topographically circumscribed and only when baseline levels of behaviour were low.     

Early complication of pediatric central venous cannulation

We describe a case of hemothorax following central venous catheter (CVC) insertion in an infant. Presumably injury occurred as a result of perforation with the dilator. Strategies to reduce the risk of complications and possible factors influencing the unsatisfactory delay in diagnosis, including the role of 'Fixation Error', are discussed.     

Long-term thalidomide use in refractory cutaneous lesions of lupus erythematosus: a 65 series of Brazilian patients

Thalidomide has been reported as efficacious in refractory cutaneous lupus erythematosus (LE). The most fearful side-effects are teratogenicity and neuropathy. We reported clinical efficacy of long-term low-dose use of thalidomide in 65 patients with LE, emphasizing the prevalence of adverse effects, especially of neuropathy and its related factors. Data obtained from medical records included age, sex, disease duration, and the presence of diagnostic criteria for systemic lupus erythematosus (SLE), the extent and activity of cutaneous lesions and previous treatments. Sixty-three patients (98.9%) presented complete or partial improvement with thalidomide therapy. Drowsiness occurred in 50 patients (77%). Twenty-eight patients (43.2%) presented neuropathy symptoms. Nerve conduction studies were done in 21 (75%) of them and were abnormal in 12 (57%). With the interruption of thalidomide, 24 (82.5%) had complete or partial improvement of neuropathy symptoms and 23 (82%) of them had cutaneous relapse. There were no significant differences between those who developed or not neuropathy in treatment duration, age, total dose and systemic versus cutaneous LE. In conclusion, thalidomide can be used in refractory cutaneous LE with great efficacy and relative security. Controlled studies with schemes with lower doses or intermittent usage or alternative drugs are wanted to reduce the burden of cutaneous morbidity of lupus erythematosus.