A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

OBJECTIVES: We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. PATIENTS AND METHODS: We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. RESULTS: We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. CONCLUSIONS: The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin.

Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene in sporadic renal cell carcinoma.

PURPOSE: Somatic mutations of the von Hippel-Lindau tumor suppressor gene VHL and loss of heterozygosity of 3p25 to 26 have been well analyzed in renal cell carcinoma but it is not yet clear how often complete biallelic inactivation of VHL occurs in sporadic renal cell carcinoma. We improved the estimation of loss of heterozygosity of VHL and examined 2-hit inactivation of VHL based on loss of heterozygosity, mutation and methylation of sporadic renal cell carcinoma. MATERIALS AND METHODS: DNA extracted from 59 Japanese sporadic renal cell carcinoma samples containing clear cells was examined for loss of heterozygosity of 4 intragenic markers of single nucleotide polymorphism and 2 extragenic microsatellite markers. Mutation was analyzed by sequencing amplified VHL DNA and methylation was analyzed by methylation specific polymerase chain reaction. RESULTS: Four intragenic markers showed loss of heterozygosity in 13 of 22 samples (59.1%), whereas the 2 extragenic markers D3S1560 and D3S1317 showed loss of heterozygosity in 15 of 46 (32.6%) and 11 of 49 (22.4%), respectively. Considering loss of heterozygosity in 14 renal cell carcinomas informative at all 3 loci the incidence of loss of heterozygosity of VHL in renal cell carcinoma was estimated to be 73.5% or 25 of 34 cases. Mutations in VHL were found in 25 of 59 renal cell carcinomas (42.4%) and frame shift mutations in 68% of all mutations often occurred at nucleotide repeat sequences. Of the 34 loss of heterozygosity informative renal cell carcinoma 15 (44.1%) had 2-hit inactivation of VHL and 11 (32.4%) had 1-hit inactivation. CONCLUSIONS: The frequency of biallelic inactivation of VHL in sporadic renal cell carcinomas was unexpectedly low. According to the 2-hit theory of tumor suppressor genes another hit in VHL that to our knowledge remains unknown to date is thought to be involved in the development of renal cell carcinoma.