[Canopy-enclosed bed for dementia patients with behavioural problems]. / Tentbed voor dementiepatiënten met gedragsproblemen.

Patients with dementia almost all have one or more symptoms of problem behaviour. This problem behaviour includes a wide range of symptoms including depression, anxiety and apathy, and behavioural problems such as aggression, general restlessness, compulsion to walk, disinhibition and calling, and psychotic disorders such as delusions and hallucinations. Due to the persistence and complexity of problem behaviour in patients with dementia, doctors often prescribe psychotropic drugs for long periods of time. In nursing homes there is a great need for non-pharmacological treatments for patients with psychological or psychiatric problems. The canopy-enclosed bed seems to meet this need and has positive effects. We observed that within a few weeks of patients getting a canopy-enclosed bed, psychotropic drugs could be reduced or even stopped. Using a canopy-enclosed bed is a measure of restraint. Therefore it remains important to carefully trade off its deployment with the intended goal.

Timing of the absence of FMR1 expression in full mutation chorionic villi.

Fragile X syndrome is caused by the expansion of the CGG repeat in the 5' untranslated region of the FMR1 gene. This expansion leads to methylation of the FMR1 promoter region thereby blocking FMR1 protein (FMRP) expression. Prenatal diagnosis can be performed on chorionic villi samples (CVS) by Southern blot analysis. Alternatively, for males, an immunohistochemical method has been introduced for CVS. In this study, we have used this immunocytochemical method for CVS in full mutation male fetuses at different times of gestational age, varying from 10.0-12.5 weeks, and in two cases of full mutation female fetuses (>13 weeks). FMRP expression studies in CVS from full mutation male fetuses (10.0-12.5 weeks) illustrate the timing of the disappearance of FMRP expression in these CVS. Until approximately 10 weeks of gestation, FMRP is expressed normally in full mutation male CVS, whereas FMRP is completely absent at 12.5 weeks of gestation. FMRP expression in full mutation female CVS (>13 weeks) is completely absent in a number of villi, whereas other villi show normal FMRP expression. Unlabelled villi can only be present in the absence of the expression of the full mutation FMR1 gene on one X-chromosome together with the X-inactivation of the normal X allele. FMRP positive villi can be explained by an active normal X allele. The presence of both positive and negative villi indicates that X-inactivation in human CVS is a random process. No villi are found with a mixture of both FMRP-expressing and non-FMRP-expressing cells. This indicates that X-inactivation occurs very early in development, before the villi start to proliferate, and that X-inactivation in villi is a clonal process. In addition, our results indicate that the timing of both X-inactivation and full mutation FMR1 allele inactivation is different, i.e. X-inactivation occurs earlier in development than inactivation of the full mutation.

Knockout mouse model for Fxr2: a model for mental retardation.

Fragile X syndrome is a common form of mental retardation caused by the absence of the FMR1 protein, FMRP. Fmr1 knockout mice exhibit a phenotype with some similarities to humans, such as macro-orchidism and behavioral abnormalities. Two homologs of FMRP have been identified, FXR1P and FXR2P. These proteins show high sequence similarity, including all functional domains identified in FMRP, such as RNA binding domains. They have an overlap in tissue distribution to that of FMRP. Interactions between the three FXR proteins have also been described. FXR2P shows high expression in brain and testis, like FMRP. To study the function of FXR2P, we generated an Fxr2 knockout mouse model. No pathological differences between knockout and wild-type mice were found in brain or testis. Given the behavioral phenotype in fragile X patients and the phenotype previously reported for the Fmr1 knockout mouse, we performed a thorough evaluation of the Fxr2 knockout phenotype using a behavioral test battery. Fxr2 knockout mice were hyperactive (i.e. traveled a greater distance, spent more time moving and moved faster) in the open-field test, impaired on the rotarod test, had reduced levels of prepulse inhibition, displayed less contextual conditioned fear, impaired at locating the hidden platform in the Morris water task and were less sensitive to a heat stimulus. Interestingly, there are some behavioral phenotypes in Fxr2 knockout mice which are similar to those observed in Fmr1 knockout mice, but there are also some different behavioral abnormalities that are only observed in the Fxr2 mutant mice. The findings implicate a role for Fxr2 in central nervous system function.