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1.  A Randomized Controlled Trial of Interleukin-1 Receptor Antagonist in a Rabbit Model of Ascending Infection in Pregnancy 
Objective: To determinewhether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-α) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy.
Methods: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 106–106 cfu Escherichia coli . Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1 – 2 h after inoculation. Blood was drawn fromthe does for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and at necropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays of TNF-α, prostaglandin E2 (PGE2) and IL1-ra.
Results: Serum IL1-ra concentrations rose to a mean of 2 mg/ml at mid-infusion and fell markedly after the infusion to concentrations barely detectable at necropsy. Between the two groups, there were no significant differences in the rates of fever or positive cultures or in amniotic fluid concentrations of PGE2 or TNF-α.One unique finding was the demonstration that administration of human IL1-ra to the does resulted inmeasurable concentrationsof human IL1-ra in the amniotic fluid.
Conclusions: Treatment with an intravenous infusion of human IL1-ra after cervical inoculation with E. coli did not affect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-α or PGE2. This experiment provides the first demonstration of passageof human IL1-ra from the maternal bloodstreamto the amniotic fluid.
doi:10.1155/S1064744901000382
PMCID: PMC1784656  PMID: 11916181
2.  Compliance With a Risk-Factor-Based Guideline for the Prevention of Neonatal Group B Streptococcal Sepsis 
Objective: The purpose of this study was to determine the compliance rate with a maternal risk-factor-based guideline for the prevention of neonatal group B streptococcal (GBS) sepsis.
Methods: In August 1994, a risk-factor-based guideline for selective intrapartum prophylaxis against neonatal GBS was adopted by a group model health maintenance organization. This guideline identified the following maternal risk factors for neonatal GBS sepsis: preterm delivery, rupture of membranes for >18 h, fever/chorioamnionitis, and history of a previous GBS-affected child. Patients with one or more risk factors were to receive intrapartum antibiotic prophylaxis consisting of either ampicillin, erythromycin, or clindamycin. We conducted a retrospective chart review to record risk factors and use of antibiotics. We hypothesized that >90% of patients with risk factors would receive intrapartum chemoprophylaxis.
Results: A total of 805 maternal charts were reviewed. Of these, 105 (13%) were candidates for intrapartum prophylaxis. We found an overall compliance rate of 65%. Compliance rates by risk factor were preterm delivery (51%), prolonged rupture of membranes (73%), fever/chorioamnionitis (87%), and previous affected child (100%).
Conclusions: Our results show unexpectedly low compliance rates with a risk-factor-based guideline for the prevention of neonatal GBS sepsis. Only 65% of women with any risk factor for neonatal GBS sepsis received intrapartum antibiotic prophylaxis appropriately. Educational efforts to improve compliance with a risk-factor-based guideline should specifically address mothers delivering at 34–36 weeks gestation and mothers with prolonged rupture of membranes.
doi:10.1155/S1064744997000604
PMCID: PMC2364582  PMID: 18476183
3.  Randomized, Placebo-Controlled Trial of Transplacental Antibiotic Prophylaxis of Neonatal Group B Streptococcal Colonization and Bacteremia in Rabbits 
Objective: We evaluated the effect of maternal administration of ampicillin/sulbactam on colonization and bacteremia in newborn rabbits after intracervical inoculation of mothers with group B streptococci (GBS).
Methods: New Zealand white rabbits on day 30 of a 31-day gestation were inoculated intracervically with 104−105 colony forming units (cfu) GBS. Two hours after inoculation mothers received ampicillin/sulbactam (50 mg/kg) or saline (control) intramuscularly as a single dose, in a randomized double-blinded manner. We induced labor 4 h later with intramuscular oxytocin. At delivery, cultures for GBS were taken from neonatal oropharynx. Thereafter, cultures were taken from neonatal oropharynx and anorectum daily and from neonatal heart at death or after 96 h. Sample size analysis showed a need for 17 pups in each group.
Results: In the control group, induction failed in one animal that was excluded from analysis. At birth, 0 of 39 pups of treated does had positive oropharyngeal cultures compared to 26 of 27 (96%) pups of saline-treated does (P < 0.0001). Pups treated with antibiotic in utero were also significantly less likely to have positive oropharyngeal cultures at 24, 48, and 72 h after birth compared to controls (24 h, 0% vs. 100%, P < 0.0001; 48 h, 8% vs. 100%, P < 0.0001; 72 h, 16% vs. 100%, P < 0.0001). Treated pups were significantly less likely to have positive anorectal cultures at 24, 48, and 72 h after birth compared to control animals (24 h, 0% vs. 100%, P < 0.0001; 48 h, 0% vs. 95%, P < 0.0001; 72 h, 0% vs. 92%, P < 0.0001). Treated pups were significantly less likely to have positive heart cultures at 72 h after birth compared to controls (11% vs. 92%, P < 0.0002). Cumulative neonatal survival was higher in treated pups compared to controls at 72 and 96 h after birth (72 h, 32% vs. 0%, P = 0.0003; 96 h, 26% vs. 0%, P = 0.015).
Conclusions: Single dose transplacental prophylaxis given 4 h before delivery resulted in decreased neonatal GBS colonization and bacteremia and improved neonatal survival in rabbits.
doi:10.1155/S1064744997000628
PMCID: PMC2364579  PMID: 18476185
4.  Animal Models of Ascending Genital-Tract Infection in Pregnancy 
This article reviews animal models currently used for investigation of ascending genital-tract infection in pregnancy. The specific models reviewed are those in the rabbit, monkey, and mouse. These models investigate both the direct effects of bacteria in the setting of ascending infection and the role of cytokines produced by the immune system. For each model, experiments that delineate the pathophysiology of ascending genital-tract infection in pregnancy are described. Intervention experiments, including the use of antibiotics, anti-inflammatory agents, immunotherapy, and anti-cytokine therapy, are described. Comparison of these models is made with respect to pathogenesis in humans, reproducibility, anatomy, and cost.
doi:10.1155/S1064744994000414
PMCID: PMC2364364  PMID: 18475368

Results 1-4 (4)