Once daily triamcinolone acetonide nasal spray is effective for the treatment of perennial allergic rhinitis

A randomized, double-blind, placebo-controlled, parallel group study was conducted in 11 centers to evaluate the safety and efficacy of a once-a-day regimen of 110 micrograms, 220 micrograms; and 440 micrograms of triamcinolone acetonide intranasal aerosol versus placebo in relieving the symptoms of rhinitis in 305 adult and older pediatric patients with perennial allergic rhinitis. Nasal stuffiness, nasal discharge, sneezing, nasal itching and the nasal index (the sum of the mean scores of the first three symptoms) averaged over the first 6 weeks and second 6 weeks of the study were significantly reduced in patients who received the 220 micrograms/day and the 440 micrograms/day dosages. The 110 micrograms/day group had a reduction in these nasal symptoms, but only the sneezing and nasal index were significantly (P less than .05) better than placebo. During the last 6 weeks of the study, patients were allowed to take oral back-up medication for their nasal symptoms; all three groups receiving triamcinolone nasal aerosol took less back-up medication than did the placebo group. There were no significant adverse effects or laboratory abnormalities noted during this study. Intranasal triamcinolone acetonide 220 micrograms and 440 micrograms, used once-a-day for 12 weeks is clinically and statistically superior to placebo for the treatment of perennial allergic rhinitis.     

CDKN2A variants in a population-based sample of Queensland families with melanoma

BACKGROUND: Mutations in the CDKN2A gene confer susceptibility to cutaneous malignant melanoma (CMM); however, the population incidence of such mutations is unknown. Polymorphisms in CDKN2A have also been described, but it is not known whether they influence melanoma risk. We investigated the association of CDKN2A mutations and polymorphisms with melanoma risk in a population-based sample of families ascertained through probands with melanoma. METHODS: The 482 Queensland, Australia, families in our sample were characterized previously as having high, intermediate, or low family risk of CMM. Unrelated individuals (n = 200 families/individuals) drawn from the Australian Twin Registry served as control subjects. For individuals in the high-risk group, the entire CDKN2A gene coding region was screened for mutations by use of the polymerase chain reaction, agarose gel electrophoresis, allele-specific oligonucleotide (ASO) hybridization, and single-strand conformation polymorphism analysis. The intermediate- and low-risk families and control subjects were analyzed by ASO hybridization for a total of six recurring mutations as well as for polymorphisms at nucleotides (Nts) 442, 500, and 540. RESULTS: CDKN2A mutations were found only in the high-risk families (nine [10.3%] of 87). The prevalence of the Nt500G (guanosine) polymorphism increased linearly with increasing familial risk (two-sided P = .02) and was highest in the nine (primarily Celtic) families with CDKN2A mutations. After adjustment for ethnic origin, the relationship between risk group and the frequency of the Nt500G allele was weakened (P = .25); however, there was no relationship between ethnic origin and Nt500-polymorphism frequency among the control subjects. CONCLUSIONS: CDKN2A mutations are rare in this population (approximately 0.2% of all melanoma cases in Queensland) and appear to be associated with melanoma in only the most affected families. The Nt500G allele appears to be associated with familial risk, but this association probably reflects Celtic ancestry.     

Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1.

Tumor metastasis is one of the most important clinical aspects of neoplastic disease because patient mortality is frequently attributable to disseminated rather than primary tumors. However, it still is not possible to definitively distinguish those individuals at high risk for disseminated disease, who would benefit from aggressive adjuvant therapy, from the low-risk patients who might be spared the side effects of additional anticancer therapy. To identify factors that predispose toward metastatic disease, we have used a genetic approach. Using a highly metastatic model of mammary cancer, we identified previously inbred mouse strains (DBA/2J, NZB/B1NJ, and I/LnJ) that harbor genetic factors that significantly suppress metastatic efficiency. In this study, we report the results of four experiments to localize the genetic map locations of the metastasis efficiency modifier genes. One statistically significant locus was identified on proximal Chr 19 designated Mtes1. Secondary candidate intervals were detected on Chrs 6, 9, 13, and 17. Interestingly, Mtes1 colocalizes with the murine orthologue of the human breast cancer metastasis suppressor gene Brms1, suggesting that allelic variants of Brms1 might be responsible for the metastasis suppression observed.