Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial.

CONTEXT AND OBJECTIVE: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy. DESIGN: This was a phase 3, prospective, open-label study. SETTING AND PARTICIPANTS: Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase. OUTCOME MEASURES: Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up. RESULTS: Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy. CONCLUSIONS: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP.

Bacterial communication ("quorum sensing") via ligands and receptors: a novel pharmacologic target for the design of antibiotic drugs.

The purpose of the present Perspectives is to present a synopsis of the literature on bacterial "quorum sensing" as a background for the proposal that interference with this communication system offers potential targets for the design of novel antibiotic drugs. Quorum sensing is the recently discovered chemical communication system among bacteria (both Gram-positive and -negative). It is vital for intra- and interbacterial gene regulation and for keeping bacterial colonies ("biofilms") intact, allowing resident bacteria to assume specialized roles that contribute to enhanced survival of the group. There are several processes involved in quorum sensing that are familiar to pharmacologists; i.e., specific signaling molecules bind to and activate receptors that transduce the quorum-sensing signal into intracellular second messenger responses. We highlight herein the similarity between quorum-sensing communication to ligand-receptor interactions, suggesting that inhibitor drugs could be designed using current standard pharmacologic principles. Such drugs would have novel mechanisms of action and might therefore be more effective against antibiotic-resistant strains of bacteria.