Endoscopic and endoscope-assisted resections of inverted sinonasal papillomas.

OBJECTIVE: To evaluate the success of endoscopic and endoscope-assisted resection of inverted sinonasal papillomas and to assess the indications for adjunctive external procedures. STUDY DESIGN: Retrospective chart review. RESULTS: Fifty patients were treated surgically during the 10-year study period and had greater than 1 year of follow-up care. These patients had a recurrence rate of 14% (7/50) with a mean follow-up of 31.1 months. Of these 7 patients with recurrences, 3 were treated primarily at this institution, and 4 had been treated prior to referral. Recurrence was 11% (3/27) for primary resections and 17% (4/23) for secondary resections. Average time to recurrence was 11.7 months. Of the patients, 38% (19/50) had adjunctive external procedures either during the initial resection or for the management of recurrent disease. CONCLUSIONS: Endoscopic and endoscope-assisted resections of inverted papilloma are effective techniques for managing inverted papilloma. The intraoperative findings, most importantly the site(s) of tumor attachment, dictate whether an endoscopic procedure is sufficient to complete resect the inverted papilloma or whether an adjunctive external procedure is required. Appropriate patient selection and an aggressive surgical approach are necessary for the management of these neoplasms.     

Sinonasal surfactant protein A1, A2, and D gene expression in cystic fibrosis: a preliminary report.

OBJECTIVE: To measure alterations in SPA1, A2, and D gene expression in various forms of inflammatory chronic rhinosinusitis (CRS). STUDY DESIGN AND SETTING: Sinus mucosal biopsies were performed in patients with allergic fungal rhinosinusitis (AFS), CRS with nasal polyposis, cystic fibrosis (CF), and controls. SP mRNA was measured with quantitative polymerase chain reaction. RESULTS: Patients with CF (n = 4) showed significantly increased SPA1 (82-fold), SPA2 (100-fold), and SPD (47-fold) mRNA (P < 0.05) when compared with controls (n = 5). Patients with CRS with nasal polyposis (n = 5) also demonstrated elevated SPA1 (27-fold), SPA2 (13-fold), and SPD (13-fold). Patients with AFS (n = 7) had increased SPA1 (5-fold), SPA2 (9-fold), and SPD (17-fold), but were not statistically significant. CONCLUSION: SPA1, A2, and D are upregulated in various forms of CRS, but are significantly elevated in cystic fibrosis CRS. SIGNIFICANCE: Understanding the role of SPs in CRS will help develop novel treatment approaches for sinonasal pathoses.     

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.      

Five novel mutations in the L1CAM gene in families with X linked hydrocephalus.

Five novel mutations have been identified in the gene encoding L1CAM, a neural cell adhesion protein, in families with X linked hydrocephalus (XHC). Interestingly, all five mutations are in the evolutionarily highly conserved Ig-like domains of the protein. The two frameshift mutations (52insC and 955delG) and the nonsense mutation (Trp276Ter) most probably result in functional null alleles and complete absence of L1CAM at the cell surface. The two missense mutations (Tyr194Cys and Pro240Leu) may considerably alter the structure of the L1CAM protein. These data provide convincing evidence that XHC is genetically extremely heterogeneous.