The effect of epigenetic therapy on congenital neurogenic bladders--a pilot study.
In this investigator-masked study, 48 patients with functioning filtering blebs requiring cataract surgery were randomised into six groups of eight patients. Groups 1, 2 and 3 received topical ofloxacin 0.3% (Ocuflox), ciprofloxacin 0.3% (Ciloxan) and levofloxacin (Quixin) respectively; Groups 4, 5 and 6 received the same treatment with the corresponding oral dose of ofloxacin 400 mg (Floxin), ciprofloxacin 400 mg (Cipro) and levofloxacin 250 mg (Levaquin). Aqueous antibiotic levels were determined by mass spectrometry of aqueous samples from each patient.
The mean aqueous level for topical levofloxacin was significantly higher than those achieved by topical ofloxacin or ciprofloxacin (p value = 0.02 and 0.01, respectively). The combination of topical and oral levofloxacin was significantly higher than topical levofloxacin alone (p = 0.05) and the ciprofloxacin combination (p = 0.003) but not significantly higher than the ofloxacin combination therapy.
Topical levofloxacin penetrates better than ofloxacin or ciprofloxacin into the aqueous of eyes with functioning filtering blebs. The combination of topical and oral levofloxacin may be preferable in the treatment of bleb-associated infections (NCT 00392275; Clinical trials.gov).
Signaling through vertebrate Hedgehog (Hh) proteins depends on the primary cilium. In response to Hh signals, the transcriptional activator of the pathway, Gli2, accumulates at the ciliary tip, raising the possibility that ciliary localization is important for Gli2 activation. To test this hypothesis, we used the Floxin system to create knock-in Gli2 alleles in embryonic stem cells (ESCs) to allow methodical testing of which domains and residues are essential for the ciliary localization of Gli2. The Gli2 zinc fingers, transcriptional activation domain, repressor domain, phosphorylation cluster and a Sufu binding motif were each dispensable for ciliary localization. Mutating residues that are required for Gli2 sumoylation and nuclear trafficking also did not abrogate ciliary localization. By contrast, several other domains restricted Gli2 nuclear localization, and a central region, distinct from previously characterized domains, was required for ciliary localization. In addition to an inability to localize to cilia, Gli2 lacking this central domain was unable to activate target genes. Thus, our systematic analysis in ESCs reveals that distinct regions of Gli2 regulate its nuclear and ciliary localization. The identification of a domain essential for both ciliary localization and transcriptional activity suggests that ciliary localization of Gli2 is required for its activation.
In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.
Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanostomy tube or tympanic membrane perforation. Many studies have demonstrated the ototoxicity of common otic preparations such as Cortisporin otic drops. Recent studies have suggested the use of fluoroquinolone antibiotic drops as an alternative owing to their excellent antimicrobial coverage and no ototoxic effect. The purpose of this study was to assess the relative ototoxicity of four common otic preparations by direct exposure to isolated cochlear outer hair cells (OHCs). OHCs from adult chinchilla cochlea were exposed to standard bathing solution (control), Cortisporin, Cipro HC, Ciloxan, and Floxin. The cells were observed using an inverted microscope, and the images recorded in digital still-frame and video, and analyzed on the Image Pro-Plus 3.0 program. As measured by time to cell death and change in morphology of OHCs, Cortisporin was most toxic to OHCs. Among the fluoroquinolone drops, Floxin was more toxic than Ciloxan or Cipro HC.
Fluoroquinolone antibiotics have rarely been associated with renal failure (1). However, temafloxacin, a member of this drug class, was voluntarily withdrawn from the U.S. market in 1992 after reports of renal failure and other adverse reactions (2). In this article, we report one of the first published cases of renal failure resulting from the administration of ofloxacin (Floxin, Ortho Pharmaceutical Corporation), one of the newest fluoroquinolone antibiotics.
This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE. RESEARCH DESIGN, PATIENTS, AND METHODS: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7-10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7-9), and test of cure (7-10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity.