The CRTH2 agonist Pyl A prevents lipopolysaccharide-induced fetal death but induces preterm labour.

We have previously demonstrated that the anti-inflammatory prostaglandin 15-deoxy-Δ 12,14-prostaglandin J(2) (15dPGJ(2)) delays inflammation-induced preterm labour in the mouse and improves pup survival through the inhibition of nuclear factor-κB (NF-κB) by a mechanism yet to be elucidated. 15dPGJ(2) is an agonist of the second prostaglandin D(2) receptor, chemoattractant receptor homologous to the T helper 2 cell (CRTH2). In human T helper cells CRTH2 agonists induce the production of the anti-inflammatory interleukins IL-10 and IL-4. We hypothesized that CRTH2 is involved in the protective effect of 15dPGJ(2) in inflammation-induced preterm labour in the murine model. We therefore studied the effects of a specific small molecule CRTH2 agonist on preterm labour and pup survival. An intrauterine injection of lipopolysaccharide (LPS) was administered to CD1 mice at embryonic day 16, ± CRTH2 agonist/vehicle controls. Mice were killed at 4.5 hr to assess fetal wellbeing and to harvest myometrium and pup brain for analysis of NF-κB, and T helper type 1/2 interleukins. To examine the effects of the CRTH2 agonist on LPS-induced preterm labour, mice were allowed to labour spontaneously. Direct effects of the CRTH2 agonist on uterine contractility were examined ex vivo on contracting myometrial strips. The CRTH2 agonist increased fetal survival from 20 to 100% in LPS-treated mice, and inhibited circular muscle contractility ex vivo. However, it augmented LPS-induced labour and significantly increased myometrial NF-κB, IL-1ß, KC-GRO, interferon-γ and tumour necrosis factor-α. This suggests that the action of 15dPGJ(2) is not via CRTH2 and therefore small molecule CRTH2 agonists are not likely to be beneficial for the prevention of inflammation-induced preterm labour.

Laparoscopic versus open colposuspension for urodynamic stress incontinence.

AIMS: Laparoscopic colposuspension aims to alleviate urodynamic stress incontinence whilst minimizing operative morbidity and mortality.The present study compared laparoscopic to open surgery with regards to short-term outcomes. METHODS: Meta-analysis of comparative studies published between 1995 and 2006 of laparoscopic versus open colposuspension was performed. End points evaluated were operative outcomes and subjective/objective cure. A random-effect model was used and sensitivity analysis performed to account for bias in patient selection. RESULTS: Sixteen studies matched the selection criteria, reporting on 1,807 patients, of whom 861 (47.6%) underwent laparoscopic and 946 (52.4%) underwent open colposuspension length of hospital stay (WMD = -1.52 days, CI = -2.08, -0.96 days) and return to normal life (WMD = -1.51 weeks, CI = -3.02, 0.01 weeks) were significantly reduced following laparoscopic surgery. These findings remained consistent on sensitivity analysis. Bladder injuries occurred more often in the laparoscopic group (OR = 2.23, CI = 1.11, 4.50), but only with marginal statistical significance. Comparable bladder injury rates were found when studies were matched for quality, year, and randomized trials. Cure rates were similar between the two procedures at 2 years follow-up. CONCLUSION: Laparoscopic colposuspension results in a significant reduction in hospital stay and earlier return to work, with a possible increased risk of bladder injury. When performed by appropriately experienced surgeons it may be a safe option with advantages for the patient, but further randomized controlled trials should be undertaken to evaluate continence in the longer term at 5 years.