Prader-Willi syndrome in a large sample from Spain: general features, obesity and regular use of psychotropic medication.

BACKGROUND: Prader-Willi syndrome (PWS), a genetically determined disorder, the most frequent cause of early onset obesity, is associated with physical and cognitive dysfunctions and behavioural disturbances; these disturbances are frequently treated with psychotropic medication. The aim of this cross-sectional study was to describe the characteristics of the first large national sample of persons with PWS in Spain and analyse the relationships of those characteristics with key demographic and clinical factors, particularly with obesity and the regular use of psychotropic medication. METHODS: Participants were recruited among all members of the Spanish Prader-Willi Association who agreed to take part in the study and fulfilled its inclusion criteria. Family and patient demographic features, family size and birth order, intelligence quotient (IQ), anthropometric measures, lifestyle habits, behavioural disturbances (with the Aberrant Behavior Checklist) and clinical data, as well as use of psychotropic drugs and their side effects (with the UKU scale), were collected in genetically confirmed cases of PWS. Bivariate and logistic regression analyses were used for determining the associations of demographic and clinical factors with both obesity and the regular use of psychotropic medication. RESULTS: The cohort included 177 participants (aged 6-48 years), that is, 90 (50.8%) males and 87 (49.2%) females. Behavioural disturbances were present in a range of 75% to 93% of participants; psychotropic medication was prescribed to 81 (45.8%) of them. Number of siblings showed a direct correlation with IQ, especially among males, and inappropriate speech was more intense in only-child females. Obesity was, in parallel, strongly associated with ascending age and with not being currently under growth hormone (GH) treatment. Participants taking any psychotropic medication were characterised by more frequent age ≥30 years, high level of hyperactivity and a psychiatric diagnosis. CONCLUSIONS: Characterisation of persons with PWS in Spain confirms their physical and behavioural phenotype and supports the long-term application of GH therapy and the rational use of psychotropic medication.

Lack of reelin modifies the gene expression in the small intestine of mice.

We recently demonstrated that the mucosa of the small intestine of the rat expresses reelin and some components of its signaling system. The current study evaluates whether reelin affects the intestinal gene expression profile using microarray analysis and reeler mice, a natural mutant in which reelin is not expressed. The effect of the mutation on body weight and intestinal morphology is also evaluated. The mutation reduces body and intestinal weight during the first 2 months of age and modifies the morphology of the crypts and villi. For the microarray assays, total RNA was obtained from either isolated epithelial cells or intact small intestine. Of the 45,101 genes present in the microarray the mutation significantly alters the expression of 62 genes in the isolated epithelial cell samples and of 84 in the intact small intestine. The expression of 83% of the genes tested for validation was substantiated by reverse transcriptase polymerase chain reaction. The mutation notably up-regulates genes involved in intestinal metabolism, while it down-regulates genes related with immune response, inflammation, and tumor development. Genes involved in cell proliferation, differentiation, apoptosis, membrane transport and cytoskeleton are also differently expressed in the reeler mice as compared with the control. This is the first report showing that the lack of reelin modifies intestinal morphology and gene expression profile and suggests a role for reelin in intestinal epithelium homeostasis.

Na(+)/Cl(-)/creatine transporter activity and expression in rat brain synaptosomes.

Creatine is involved in brain ATP homeostasis and it may also act as neurotransmitter. Creatine transport was measured in synaptosomes obtained from the diencephalon and telencephalon of suckling and 2 month-old rats. Synaptosomes accumulate [(14)C]-creatine and this accumulation was Na(+)- and Cl(-)-dependent and inhibited by high external K(+). The latter suggests that the uptake process is electrogenic. The kinetic study revealed a K(m) for creatine of 8.7 microM. A 100-fold excess of either non-labelled creatine or guanidinopropionic acid abolished NaCl/creatine uptake, whereas GABA uptake was minimally modified, indicating a high substrate specificity of the creatine transporter. The levels of NaCl/creatine transporter (CRT) activity and those of the 4.2 kb CRT transcript (Northern's) were higher in the diencephalon than in the telencephalon, whereas the 2.7 kb transcript levels were similar in both brain regions and lower than those of the 4.2 kb. These observations suggest that the 4.2 kb transcript may code for the functional CRT. CRT activity and mRNA levels were similar in suckling and adult rats. To our knowledge the current results constitute the first description of the presence of a functional CRT in the axon terminal membrane that may serve to recapture the creatine released during the synapsis.

Whose health is it? The views of injecting drug users with HIV infection and their professional carers.

The views about autonomy in medical treatment of people with HIV infection (who had acquired it via the injection of drugs) and their professional carers were investigated using a standardized self-report instrument. Forty-two patients and 61 staff were entered in the study. Patients and staff reported strong endorsement of patient autonomy, but there were important differences between groups. Staff as a group reported higher preference for patients' involvement in decision-making than the patients themselves, while the opposite was true for information-seeking, where patients wanted more information than staff had anticipated. The practical implications of the findings are discussed.

Reliability and validity of an HIV-specific health-related quality-of-life measure for use with injecting drug users.

OBJECTIVE: To assess the reliability and validity of an HIV-specific quality of life (QoL) questionnaire for use with injecting drug users (IDU). METHOD: One hundred IDU with HIV infection (27 asymptomatic, 48 symptomatic, 25 with AIDS) completed the HIV adaptation of the Medical Outcomes Study questionnaire (MOS-HIV). Validity of the scale was assessed by comparing the scores on the MOS-HIV with measures of health and psychological status. Measures of health status used included Centers for Disease Control and Prevention (CDC) stage, CD4 cell count and number of HIV-related illnesses. Psychological status was assessed using the Hospital Anxiety and Depression Scale. Sociodemographic data and information on illegal drug consumption were also collected. RESULTS: The MOS-HIV showed a good internal reliability on all scales and the factor structure was comparable with that reported from previous studies. The psychological scales from the MOS-HIV showed good concurrent validity. For the physical aspects of QoL, however, some scales were poor at discriminating between different HIV disease stages. One reason for this may have been that factors associated with a history of injecting drug use had a significant negative impact on QoL, particularly for asymptomatic patients. It was notable that QoL in asymptomatic infection was found to be substantially lower than has been reported for gay/bisexual men using the same instruments and was more strongly associated with factors related to drug use rather than to HIV disease status. CONCLUSION: The MOS-HIV is a reliable and valid measure, but in patients with a history of injecting drug use some of the scales measuring the physical aspects of QoL may be relatively insensitive to changes in health.