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Background To study the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy and to compare the rates of persistence, progression and regression of CIN by colposcopically guided biopsy (CGB) during pregnancy with outcome in non-pregnant-women. Methods A retrospective analysis of all pregnant women diagnosed with CIN at our outpatient clinic between 2005 and 2010 was performed. A CGB for histo-pathological analysis was obtained in all participants and observational management was performed. The histo-pathologic findings of initial and postpartum visits were collected. Rates of persistence, progression and regression of CIN were assessed. Results were compared to a matched control group of non-pregnant women where observational management was performed for at least three months. In addition a review of the literature and pooled analysis of published data was performed. Results A total of 51 pregnant women with CIN were included into analysis. CIN 1, 2, and 3 was diagnosed by CGB in 33.3, 13.7 and 52.9 % of all pregnant women, respectively. The postpartum histo-pathologic evaluation of the pregnant cohort revealed a significantly higher tendency to spontaneous regression (56.9 versus 31.4 %, p = 0.010) and a considerably, but not significantly higher complete remission rate (41.2 versus 27.5 %, p = 0.144) when compared to the non-pregnant cohort. In addition, we observed a significantly lower CIN persistence rate than in the non-pregnant cohort (39.2 versus 58.8 %, p = 0.048). The progression rate was notably low in the pregnant cohort (3.9 %) and no progression to invasive cancer was observed. Conclusions CIN lesions show considerably high spontaneous regression rates postpartum. Once presence of invasive cancer is ruled out definitive treatment can be deferred to the postpartum period.

Introduction: This study aims to explore the efficacy of the topical application of 10% benzocaine for treating pruritus and pain as compared to vehicle ointment. Methods: Twenty male subjects were treated in a randomized double-blind fashion with the investigational medicinal product (IMPD) and vehicle. Immediately after the injection of 100 µg histamine on both arms, subjects received topical treatment and pruritus was subsequently assessed with visual analogue scale (VASpruritus) and Eppendorfer questionnaire. Ultraviolet B radiation (UVB) was administered on the back to induce slight sunburn. Twelve hours after UVB application again the IMPD was applied on the right or left upper back and vehicle on the other side and pain related to sunburn was measured with VASpain and pressure algometry. Results: A trend towards better reduction of pruritus was shown for benzocaine in VASpruritus. For the VASpain significant differences in group comparison (p = 0.02) were observed. Algometer measurements showed onset of pain reduction in the verum group after 20 min whereas in the vehicle-treated area pain relief occurred only after 60 min after application. Conclusions: The topically administered ointment containing 10% benzocaine was found superior over vehicle for treating pain, but not pruritus.

AP301 is an activator of ENaC-mediated Na+ uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this “first-in-man” study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled by healthy male subjects. In a double-blind, placebo-controlled study, 48 healthy male subjects were randomized to 6 ascending dose groups (single doses up to 120 mg) of 8 subjects each (3:1 randomization of AP301: placebo). Serial assessments included spirometry, exhaled nitric oxide (eNO), vital signs, ECG, safety laboratory, adverse events (AE), and blood samples for the quantification of AP301 in plasma. Descriptive statistics was applied. All 48 subjects received treatment, and completed the study as per protocol. No serious, local (e.g., hoarseness, cough, bronchospasm), or dose-limiting AEs were noted. None of the assessments indicated notable dose or time-related alterations of safety outcomes. Observed AP301 systemic exposure levels were very low, with mean Cmax values of

Linezolid is considered for treatment of central nervous system (CNS) infections caused by multidrug-resistant Gram-positive bacteria. Therefore, the influence of cerebrospinal fluid (CSF) on the antimicrobial activity of linezolid was evaluated in vitro. Time-kill curves were conducted in CSF and Mueller-Hinton broth (MHB) using Staphylococcus aureus (ATCC 29213) and Staphylococcus epidermidis (ATCC 12228) strains. In CSF lower linezolid concentrations were needed against S. aureus (1× MIC) and S. epidermidis (0.5× MIC) to achieve bacteriostasis than in MHB (4× MIC for both strains). Good activity of linezolid in CSF supports performance of clinical trials evaluating its potential for treatment of CNS infections.

Objectives: Though used for infections of the central nervous system, the pharmacodynamics of antimicrobial agents is commonly evaluated only in commercially available bacterial growth media. In the present study, the effects of cerebrospinal fluid (CSF) on bacterial killing by cefepime and rifampicin were investigated. Methods: CSF was collected from patients who did not receive antibiotics. Time‐kill curves were performed over 24 h using drug concentrations of 0.25-, 0.5-, 1-, 2-, 4- and 8-fold the respective MIC for the Staphylococcus aureus test strain. Killing curves were performed in Mueller‐Hinton broth (MHB), in CSF incubated in ambient air (CSFAIR) and in CSF in air with 5% CO2 (CSFCO2 ). CO2 served to adjust the pH of CSF to physiological values. Results: Sustained bacterial killing was achieved by cefepime at lower drug concentrations in CSFCO2 than in MHB. In contrast, rifampicin concentrations above the MIC were required to exert sustained killing in CSFCO2 . Both drugs were least effective in CSFAIR. Conclusions: Standard susceptibility tests may lead to over- or underestimation of the activity of distinct antibiotics in CSF. Evaluation of the antimicrobial activity in pH-adjusted CSF can provide useful information on drugs considered for the treatment of bacterial infections residing in CSF.

e16524 Background: Gamma-glutamyltransferase (GGT) – a membrane bound enzyme crucially involved in the cell’s detoxification pathway and apoptotic balance – is involved in tumor development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. Methods: In this multi-center study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n = 567) and borderline tumor of the ovary (BTO, n = 67). GGT serum levels were associated with clinico-pathological parameters and uni- and multivariate survival analyses were performed.Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels. Results: Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 [38.24] U/L) than in patients with BTO (20.01 [12.78] U/L, p = 0.01). High GGT serum levels were associated with advanced FIGO stage (p

Methods Time-kill curves of daptomycin, doripenem, linezolid, moxifloxacin, and tigecycline were determined for Staphylococcus aureus ATCC 29213 and of colistin, doripenem and moxifloxacin for a clinical isolate of Pseudomonas aeruginosa at concentrations above or equal to the respective MICs. All experiments were performed over 24 h in Mueller-Hinton broth (MHB) and in MHB enriched with porcine surfactant at a concentration of 1 mg/mL (MHBsurf).