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Background: The soluble isoform of FcɛRI, the high‐affinity IgE receptor (sFcεRI), is a protein of the IgE network with poorly defined functions. Objective: To define cellular sources and signals that result in the production of human sFcεRI and study its in vivo functions. Methods: FcεRI‐transfected human cell lines (MelJuso), human monocyte‐derived dendritic cells (moDCs), and murine bone marrow‐derived mast cells (MC) were stimulated by FcεRI cross‐linking and release of sFcεRI was analyzed (ELISA, Western Blot). Lysosomal‐associated membrane protein 1 degranulation assays and human basophil activation tests (BATs) were used to study IgE‐dependent activation. Recombinant sFcεRI (rsFcεRI) was used to assess its role in murine models of anaphylaxis with WT (wild‐type) and IgE−/− (IgE‐deficient) mice. Results: Antigen‐specific cross‐linking of IgE‐loaded FcɛRI on MelJuso cells that express the trimeric or tetrameric receptor isoform induced the production of sFcεRI. Using MCs and moDCs, we confirmed that IgE/FcɛRI activation induces sFcɛRI release. We demonstrated that generation of sFcɛRI requires Src phosphorylation and endo/lysosomal acidification. In experimental mouse models, sFcɛRI diminishes the severity of IgE‐mediated anaphylaxis. BATs confirmed that, comparable to the anti‐IgE monoclonal antibody omalizumab, sFcɛRI is an inhibitor of the human innate IgE effector axis, implying that sFcɛRI and omalizumab potentially inhibit each other in vivo. Conclusion: sFcɛRI is produced after antigen‐specific IgE/FcɛRI‐mediated activation signals and functions as an endogenous inhibitor of IgE loading to FcɛRI and IgE‐mediated activation. Our results imply, therefore, that sFcɛRI contributes to a negative regulatory feedback loop that aims at preventing overshooting responses after IgE‐mediated immune activation. The soluble isoform of FcεRI, sFcεRI is released after antigen‐specific cross‐linking on monocyte‐derived dendritic cells and murine bone marrow‐derived mast cells, where Src phosphorylation and endo/lysosomal acidification are key events. Comparable to omalizumab, sFcεRI prevents IgE binding and activation on human basophils in vitro. In experimental mouse models, sFcεRI diminishes severity of IgE‐mediated anaphylaxis and decreases surface IgE on basophils. [ABSTRACT FROM AUTHOR]

Aim: To develop and evaluate a classification system for magnetic resonance imaging (MRI) findings of children with cerebral palsy (CP) that can be used in CP registers.Method: The classification system was based on pathogenic patterns occurring in different periods of brain development. The MRI classification system (MRICS) consists of five main groups: maldevelopments, predominant white matter injury, predominant grey matter injury, miscellaneous, and normal findings. A detailed manual for the descriptions of these patterns was developed, including test cases (www.scpenetwork.eu/en/my-scpe/rtm/neuroimaging/cp-neuroimaging/). A literature review was performed and MRICS was compared with other classification systems. An exercise was carried out to check applicability and interrater reliability. Professionals working with children with CP or in CP registers were invited to participate in the exercise and chose to classify either 18 MRIs or MRI reports of children with CP.Results: Classification systems in the literature were compatible with MRICS and harmonization possible. Interrater reliability was found to be good overall (k=0.69; 0.54-0.82) among the 41 participants and very good (k=0.81; 0.74-0.92) using the classification based on imaging reports.Interpretation: Surveillance of Cerebral Palsy in Europe (SCPE) proposes the MRICS as a reliable tool. Together with its manual it is simple to apply for CP registers. [ABSTRACT FROM AUTHOR]

Aim: To monitor the trends in prevalence of cerebral palsy (CP) by birthweight in Europe, 1980 to 2003.Method: Data were collated from 20 population-based registers contributing to the Surveillance of Cerebral Palsy in Europe database. Trend analyses were conducted in four birthweight groups: <1000g (extremely low birthweight [ELBW]); 1000 to 1499g (very low birthweight [VLBW]); 1500 to 2499g (moderately low birthweight [MLBW]); and >2499g (normal birthweight [NBW]).Results: The overall prevalence of CP decreased from 1.90 to 1.77 per 1000 live births, p<0.001, with a mean annual fall of 0.7% (95% confidence interval [CI] -0.3% to -1.0%). Prevalence in NBW children showed a non-significant trend from 1.17 to 0.89 per 1000 live births (p=0.22). Prevalence in MLBW children decreased from 8.5 to 6.2 per 1000 live births (p<0.001), but not linearly. Prevalence in VLBW children also declined from 70.9 to 35.9 per 1000 live births (p<0.001) with a mean annual fall of 3.4% (95% CI -2.4% to -4.3%). Prevalence in ELBW children remained stable, at a mean rate of 42.4 per 1000 live births.Interpretation: The decline in prevalence of CP in children of VLBW continues, and confirms that previously reported. For the first time, there is also a significant decline among those of MLBW, resulting in a significant overall decrease in the prevalence of CP. [ABSTRACT FROM AUTHOR]

Background Drooling is common in children with disordered oral-motor control. There is little evidence about the comparative effectiveness of different interventions used to reduce the impact of drooling. Anecdotal reports suggest clinicians' management of drooling varies widely. The aims of this survey were to establish which drooling interventions are currently used, how their effectiveness is monitored and how frequently adverse effects are reported. Methods 151 UK paediatricians completed a questionnaire about their management of drooling. Results Paediatricians saw one new child with problematic drooling and three follow-up children per month. The most common prescribing pattern was hyoscine first line (84.7%) followed by glycopyrronium bromide second line. The reported rate of adverse effects of medications was lower than expected (median 10% for hyoscine). Very few paediatricians used standardized methods of measuring the medication's effectiveness or adverse effects. Conclusion Paediatricians regularly see small numbers of children with problematic drooling. Their clinical management of drooling varies; this is most likely because of a lack of evidence about the most effective approach. Comparative trials of interventions and the development of evidence-based clinical guidelines would improve the management of children's drooling. [ABSTRACT FROM AUTHOR]

The article discusses an investigation into the usefulness of the group interaction training programme It Takes Two to Talk (ITTT) for parents of children with motor disorders. The effects of the programme on parent-child interaction, therapists who provided the training, and the views of parents of young children with motor disorders on the programme's usefulness and acceptability were examined. The research methods used, the participants in the programme, an interview guide, the data collection and analysis, and parents' expectations of speech and language therapy are noted. It was found that the parents were enthusiastic about the outcomes of the ITTT programme for themselves and their children

Background Speech and language therapy for young children who have motor disorders targets both the children themselves and their parents. Therapy for parents often involves training about communication and how to foster children's development. It Takes Two to Talk – The Hanen Program® for Parents has become popular in the UK, but has not been specifically evaluated for this client group. This study, which was part of a larger investigation of the acceptability and potential effects of the programme on the communication patterns of mothers and their young children with motor disorders, investigated therapists' experiences of providing the training in the National Health Service (NHS) and their views on its effectiveness. Methods Four focus groups, which involved 16 speech and language therapists who provide It Takes Two to Talk in NHS Trusts in England, were analysed using qualitative methods. Results The themes indicated that therapists perceived the training programme to be effective in helping parents to develop a facilitative communication style. Therapists reported secondary outcomes of positive changes in parents' confidence and in relationships between parents and their children and between parents and therapists. Barriers to the provision and success of the programme were thought to relate to resources, parents' apprehensions about the programme's content and delivery and support from key stakeholders. Barriers were seen to be minimized in services where other members of the healthcare teams actively supported the training programme and where the intervention was integrated as part of a care pathway. Conclusions The information from this study may assist service providers in the marketing, planning and delivery of new intervention methods, to ensure that they are seen as valuable and acceptable by parents. [ABSTRACT FROM AUTHOR]

Children with cerebral palsy and severe speech disorders have been described as passive communicators, whose conversation partners control and dominate interaction. This paper studies the effects of speech intelligibility on interaction between mothers and their children with cerebral palsy to examine if similar patterns of child passivity and adult domination are also observed in dyads in which children are physically dependent but naturally intelligible to their parents. Two groups, each of 20 children who had four-limb cerebral palsy and who differed in their speech intelligibility, participated in the study. Children in Group 1 (whose interaction has been previously reported) were unintelligible to their parents out of context. Children in Group 2 had speech that was understood without situational cues. Children and their mothers were videotaped playing with a set of toys that had been shown to elicit from non-disabled children a full range of the conversational moves and speech acts targeted in the study. Videotaped interaction was transcribed and coded at three levels to show conversation structure, the pragmatic functions expressed and the method of communication used. Percentage distribution of coding categories was compared across groups using coda. Results showed that verbally intelligible children initiated more conversations and used their communication for a wider range of functions than did non-speaking children, for whom more restricted patterns of conversation were noted. Unexpectedly, few differences were observed between the two groups of mothers, who initiated and closed most exchanges. Implications for intervention are discussed. [ABSTRACT FROM AUTHOR]

This paper presents an in-depth analysis of the interaction between mothers and their severely physically disabled children who have motor speech disorders. The study was designed to partially replicate previous investigations, most notably those undertaken by Light et al., to examine if the patterns of conversation previously described were observed in interaction involving children of a wide age range. Twenty children who had four-limb cerebral palsy, with no diagnosed learning difficulties or sensory impairments, and who were between 2 and 10 years of age inclusive participated in the research with their mothers. Children's speech was unintelligible to their parents out of context and most had been provided with aided communication systems. Other carers were excluded from the research due to possible differences in interaction style. Conversation between mothers and children was videotaped in a standard play situation. The toys used to stimulate interaction had been shown to elicit the full range of communication skills targeted in the present study from nondisabled children. Videotaped interaction was coded to show the structure of conversation and the functions used. The mode of communication used by the children was also recorded. In addition, communicative functions were elicited from the children in a semi-scripted conversation with a clinician developed from that used by Light et al. Structural moves and communicative functions used by mothers and children were examined using mean proportions. Sequential analysis of mother-child interaction was also undertaken at both levels to investigate the patterns that recurred in conversation. Results support those obtained in previous studies, showing restricted conversation patterns and high levels of maternal directiveness. Mothers initiated most communicative exchanges, asking many questions and issuing many requests for attention, objects or activities. Children across the age range produced more response moves than any other move type. Their responses contained yes/no answers and acknowledgements, and to a lesser extent provisions of information. When children did produce communicative functions other than simple confirmation, denials and acknowledgements, they were often not fully understood and were followed by requests for clarification by the mothers. Children produced a wider range of communicative functions in the semi-scripted elicitation conversation with the clinician than in conversation with their mothers (z=3.52, p=0.0002). The results obtained support those of previous research and suggest that interaction for children with severe motor and speech impairments becomes 'fossilized', changing little throughout childhood. Findings support the two-pronged approach to intervention for children using augmentative communication systems that is now developing. Intervention should focus not only on the children, teaching them how to use their augmentative systems and to produce a full range of conversation skills, but also should focus on their carers. Training for carers aims to increase their interaction skills, teaching them how to facilitate and expand children's communication skills. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including the large-scale study of early childhood intervention programs in the U.S. and behavioral support package for children with disabilities age 2.5-3.3 years.

The effect of the diltiazem-cyclosporine interaction on cyclosporine pharmacokinetics, pharmacodynamics, and pharmacoeconomics was studied in 10 recipients of renal allografts. Each subject was studied while receiving diltiazem 60 mg twice/day and while not taking the drug. After achieving steady-state conditions, cyclosporine and metabolite concentrations were determined in whole blood from samples drawn after the morning cyclosporine dose. After pharmacokinetic analysis, all patients were followed for 6 months during treatment with cyclosporine plus diltiazem or cyclosporine alone. Cyclosporine blood clearance decreased significantly after treatment with diltiazem (18.0-11.0 ml/min.kg; p = 0.008). The apparent volume of cyclosporine distribution also decreased significantly (4.26-2.62 L/kg; p < 0.05). After 6 months, diltiazem had no effect on renal function indexes, and no apparent effect on immunosuppression. Alterations in cyclosporine clearance and apparent volume of distribution secondary to diltiazem result in dosage reduction and potential cost savings in transplant pharmacotherapy. The mean decrease in cyclosporine dosage requirements would produce a cost saving of $1520 or 28% per patient per year.