Correlates of nonparticipation in an HIV prevention program for MSM.

Providing HIV prevention services to high-risk individuals remains challenging. We assessed factors associated with nonparticipation among high-risk, sexually active MSM found eligible to participate in a brief, telephone-delivered HIV prevention trial designed to evaluate the efficacy of motivational enhancement therapy (the Sex Check). Two levels of nonparticipation are evaluated: eligible participants who did versus those who did not complete their baseline/enrollment interview, and enrolled participants who did versus those who did not attend any of their counseling sessions. Nonenrollers were younger, less educated, more closeted, and were more likely to report sex with an injection drug using partner. Enrolled participants who did not engage in their counseling session(s) were less educated, reported greater use of alcohol and drugs during sex and use of injection drugs. Innovative methods to reduce barriers to engaging high-risk, sexually active MSM in risk reduction counseling are needed.     

Normalized protein catabolic rate versus serum albumin as a nutrition status marker in pediatric patients receiving hemodialysis.

BACKGROUND: Protein-energy malnutrition occurs commonly in patients receiving hemodialysis (HD). Although serum albumin (sAlb) is recommended to monitor nutrition status in patients receiving HD, many processes unrelated to nutrition status can affect albumin concentrations. METHODS: We previously showed normalized protein catabolic rate (nPCR) to be superior to sAlb to reflect improvement in nutrition status in pediatric patients receiving maintenance HD after treatment with intradialytic parenteral nutrition for severe protein-energy malnutrition. We now compare nPCR and sAlb as nutrition status markers for pediatric patients on HD irrespective of current nutrition status. RESULTS: Forty-four patients comprising 840 months of HD provision were assessed. nPCR was higher for younger patients. Mean nPCR values were significantly lower for adolescent patients with persistent weight loss of at least 2% for at least 3 consecutive months versus patients without persistent weight loss (1.03 +/- 0.29 g/kg/d vs. 1.15 +/- 0.27 g/kg/d, P < .002), and the odds for developing persistent weight loss were four times greater for adolescent patients with nPCR less than 1 g/kg/d. No association between nPCR and weight loss was observed for younger patients. Mean sAlb levels were greater than 4 g/dL for all patient age groups and did not demonstrate a clinically significant difference between patients with or without weight loss. CONCLUSION: We suggest that nPCR may be useful for monthly nutrition status in adolescent patients receiving maintenance HD and that adolescents with nPCR less than 1 g/kg/d may be at increased risk for subsequent weight loss.     

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.      

Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA

We have used a mouse model to study the ability of human CFTR to correct the defect in mice deficient of the endogenous protein. In this model, expression of the endogenous Cftr gene was disrupted and replaced with a human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for the gene replacement failed to show neither improved intestinal pathology nor survival when compared to mice completely lacking CFTR. RNA analyses showed that the human CFTR sequence was transcribed from the targeted allele in the respiratory and intestinal epithelial cells. Furthermore, in vivo potential difference measurements showed that basal CFTR chloride channel activity was present in the apical membranes of both nasal and rectal epithelial cells in all homozygous knock-in animals examined. Ussing chamber studies showed, however, that the cAMP-mediated chloride channel function was impaired in the intestinal tract among the majority of homozygous knock-in animals. Hence, failure to correct the intestinal pathology associated with loss of endogenous CFTR was related to inefficient functional expression of the human protein in mice. These results emphasize the need to understand the tissue- specific expression and regulation of CFTR function when animal models are used in gene therapy studies.