High carrier frequency of 21-hydroxylase deficiency in Cyprus.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder caused by mutations in the CYP21A2 gene. The carrier frequency of CYP21A2 mutations has been estimated to be 1:25 to 1:10 on the basis of newborn screening. The main objective of this study was to determine the carrier frequency in the Cypriot population of mutations in the CYP21A2 gene. Three hundred unrelated subjects (150 males and 150 females) from the general population of Cyprus were screened for mutations in the CYP21A2 gene and its promoter. The CYP21A2 genotype analysis identified six different mutants and revealed a carrier frequency of 9.83% with the mild p.Val281Leu being the most frequent (4.3%), followed by p.Qln318stop (2.5%), p.Pro453Ser (1.33%), p.Val304Met (0.83%), p.Pro482Ser (0.67%) and p.Met283Val (0.17%). The notable high CYP21A2 carrier frequency of the Cypriot population is one of the highest reported so far by genotype analysis. Knowledge of the mutational spectrum of CYP21A2 will enable to optimize mutation detection strategy for genetic diagnosis of 21-OHD not only in Cyprus, but also the greater Mediterranean region.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Development and application of a genotypic AZT resistance assay: quantitative assessment of the resistance profile of clinical samples and the relative predictive ability of a resistance index.

OBJECTIVES: To develop and validate a rapid, genotypic, quantitative AZT resistance assay, and to evaluate the predictive ability of a resistance index. METHODS: AZT resistance profiles of paired samples from HIV-infected patients were determined by a ligase chain reaction (LCR) assay. AZT resistance levels and surrogate markers of HIV disease progression (viral load and CD4 counts) were used to compare AZT-naive and AZT-experienced patients. The ability of a "mutant/wild-type HIV-1 quasi-species" index to predict viral load was assessed. RESULTS: AZT resistance, evident at baseline in both AZT-experienced and AZT-naive patients, increased over 6 months of treatment. The resistance profile of AZT-naive patients differed from that of AZT-experienced patients ( p <.05); viral load and CD4 counts were similar. The relative predictive ability (for subsequent viral load) of the resistance index was similar to or higher than that of baseline viral load or CD4 count. CONCLUSIONS: This assay used to detect AZT resistance could be adapted for use with other antiretrovirals. The predictive ability of the proposed resistance index was equal to or surpassed that of viral load and CD4 count, lending further support to the use of resistance assays in selecting drug regimens both before and during antiretroviral therapy.