Assessment of false transmitters as treatments for nerve agent poisoning.

Nerve agents inhibit acetylcholinesterase (AChE), leading to a build-up of acetylcholine (ACh) and overstimulation at cholinergic synapses. Current post-exposure nerve agent treatment includes atropine to treat overstimulation at muscarinic synapses, a benzodiazepine anti-convulsant, and an oxime to restore the function of AChE. Aside from the oxime, the components do not act directly to reduce the overstimulation at nicotinic synapses. The false transmitters acetylmonoethylcholine (AMECh) and acetyldiethylcholine (ADECh) are analogs of ACh, synthesised similarly at synapses. AMECh and ADECh are partial agonists, with reduced activity compared to ACh, so it was hypothesised the false transmitters could reduce overstimulation. Synthetic routes to AMECh and ADECh, and their precursors, monoethylcholine (MECh) and diethylcholine (DECh), were devised, allowing them to be produced easily on a laboratory-scale. The mechanism of action of the false transmitters was investigated in vitro. AMECh acted as a partial agonist at human muscarinic (M1 and M3) and muscle-type nicotinic receptors, and ADECh was a partial agonist only at certain muscarinic subtypes. Their precursors acted as antagonists at muscle-type nicotinic, but not muscarinic receptors. Administration of MECh and DECh improved neuromuscular function in the soman-exposed guinea-pig hemi-diaphragm preparation. False transmitters may therefore help reduce nerve agent induced overstimulation at cholinergic synapses.

Incorporating children's and their parents' perspectives into condition-specific quality-of-life instruments for children with cerebral palsy: a qualitative study.

OBJECTIVES: This study investigated the extent of agreement between children with cerebral palsy (CP) and their parents concerning their views on what contributed to the children's quality of life. It also investigated how well an Australian condition-specific health-related quality of life self-report measure for children with CP, the Cerebral Palsy Quality of Life Questionnaire for Children (CP QOL-Child), mapped to the views of UK children and parents. METHODS: UK children with CP aged 8 to 13 years and their parents participated in qualitative interviews about their perspectives on the child's quality of life. RESULTS: The interviews with 28 children and 35 parents showed considerable overlap but also some divergence. For example, both parties considered social relationships to be important, but children described how they enjoyed being on their own at times whereas parents tended not to value time spent alone for children. The CP QOL-Child covered most themes considered to be important to the children's quality of life. Omissions included relationships with extended family members, restful recreational activities and associated possessions, relaxing, tiredness, negative emotions, and safety. CONCLUSIONS: Both children's and parents' views are required for the development of child health-related quality of life instruments. The CP QOL-Child has good coverage of many aspects discussed in the interviews. Cultural differences may account for its omission of some topics considered important by UK children and parents. Rewording of many of the CP QOL-Child's items and further work on item content would optimize its suitability for UK children and possibly for children elsewhere.

An assessment of vascularity and flow intensity of the placenta in normal pregnancy and pre-eclampsia using three-dimensional ultrasound.

OBJECTIVE: To test the hypothesis that parameters of vascularity and flow intensity of the placenta as determined by three-dimensional (3D) ultrasound, (1) are different in normal pregnancy compared to pre-eclampsia (2) decrease from the basal plate towards the chorionic plate. METHODS: Twenty women with normal pregnancy and 17 women with pre-eclampisa were studied. 3D power Doppler ultrasound was used to acquire individual placental volumes. Rotational measurements of placental volumes were acquired using virtual organ computer aided analysis (VOCAL). The power Doppler signals were then semi-quantified within 'histogram facility', which generates three vascularity and flow intensity parameters: flow index (FI), vascular index (VI) and vascularisation flow index (VFI). RESULTS: FI, VI and VFI were lower in pre-eclampsia compared to normal pregnancy in all regions of the placenta. This difference was statistically significant in most regions of the placenta after accounting for gestational age, body mass index and placental site. We were not able to demonstrate a decreasing gradient of these parameters from basal plate to chorionic plate. CONCLUSION: 3D ultrasound to assess placental vascularity and flow intensity appears to be an interesting research tool. However, other indices derived from Power Doppler may be more relevant to obstetric practice.