Early experience with a novel plaque excision system for the treatment of complex coronary lesions.

The use of directional coronary atherectomy (DCA) in current practice has been limited. The SilverHawk System is a newly developed plaque excision device that aims to overcome the drawbacks of prior DCA platforms. The device was evaluated in a porcine coronary model and in a series of patients. Procedural variables along with outcomes were reviewed. Quantitative angiography (QCA) was performed and excised tissue fragments were weighed and examined histologically. In porcine cases, pretreatment MLD increased from 0.51 +/- 0.26 to 2.36 +/- 0.59 mm postdebulking and 19.9 +/- 7.6 mg of tissue was retrieved. In human cases, pretreatment MLD increased from 0.8 +/- 0.4 to 2.2 +/- 0.5 mm postdebulking and 15.2 +/- 7.8 mg of tissue was retrieved without complications. These data show that the SilverHawk System may offer significant utility in treating a wide variety of complex coronary lesions.     

Is commercial alcohol availability related to adolescent alcohol sources and alcohol use? Findings from a multi-level study.

PURPOSE: To examine whether compliance with underage sales laws by licensed retail establishments is related to underage use of commercial and social alcohol sources, perceived ease of obtaining alcohol, and alcohol use. METHODS: In 2005, alcohol purchase surveys were conducted at 403 off-premise licensed retail establishments in 43 Oregon school districts. A survey also was administered to 3,332 11th graders in the districts. Multi-level logistic regression analyses were used to examine relationships between the school district-level alcohol sales rate and students' use of commercial and social alcohol sources, perceived ease of obtaining alcohol, past-30-day alcohol use, and heavy drinking. RESULTS: The school district-level alcohol sales rate was positively related to students' use of commercial alcohol sources and perceived alcohol availability, but was not directly associated with use of social alcohol sources and drinking behaviors. Additional analyses indicated stronger associations between drinking behaviors and use of social alcohol sources relative to other predictors. These analyses also provided support for an indirect association between the school district-level alcohol sales rate and alcohol use behaviors. CONCLUSIONS: Compliance with underage alcohol sales laws by licensed retail establishments may affect underage alcohol use indirectly, through its effect on underage use of commercial alcohol sources and perceived ease of obtaining alcohol. However, use of social alcohol sources is more strongly related to underage drinking than use of commercial alcohol sources and perceived ease of obtaining alcohol.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.