Prophylactic treatment of endotoxic shock with monophosphoryl lipid A in newborn rats.

Mortality due to gram-negative septic shock remains high despite advances in medical care. Induction of endotoxin tolerance might be a new treatment strategy to prevent septic shock in the newborn. The present study was performed to show that an injection in pregnant rats of monophosphoryl lipid A (MPL), a nontoxic derivative of lipopolysaccharide (LPS), induces tolerance to Salmonella enteritidis LPS and tumor necrosis factor alpha (TNF-alpha) in their offspring. MPL at a dose of 2 mg/kg was injected into pregnant rats on the 19th day of gestation. Their 0-day-old offspring later received an intraperitoneal injection of S. enteritidis LPS or TNF-alpha. Newborn rats of MPL-treated dams exhibited a higher survival rate, absence of lactacidemia and lower plasma TNF-alpha concentration in response to S. enteritidis LPS when compared to the newborn rats of saline-treated dams. Newborn rats of MPL-treated dams were more tolerant to TNF-alpha than those of saline-treated dams. MPL injection into pregnant rats did not increase plasma endotoxin concentration in the fetuses, suggesting no placental passage took place, but it did increase plasma TNF-alpha concentration. We concluded that an injection of MPL into pregnant rats induced tolerance to LPS in their offspring, which might be due to TNF-alpha-induced TNF-alpha tolerance.

Outcome of infants with a diagnosis of hydrops fetalis in the 1990s.

The diagnosis of Hydrops fetalis still carries a grave prognosis with reported mortality ranging from 50 to 100%. With the advent of more aggressive therapy, improvement of survival is undetermined. The study population of this outcome case series was gathered from all cases of hydrops fetalis admitted to our Loyola University Medical Center Neonatal Intensive Care Unit (NICU) from 1990 to 1997. Forty-one patients were eligible for inclusion. Only four had a diagnosis of immune hydrops fetalis, while the remainder had varied nonimmune causes. Models predicting survival were constructed with various neonatal and maternal factors as explanatory variables using Cox proportional Hazards technique. Kaplan-Meier estimates of median survival times for different stratifying variables were likewise computed. The overall mortality rate was 49% with an overall median survival time of 15 days (95% CI 8-38). Median survival time estimates differed significantly between patients who had (a) proven infection or not and (b) had less than or greater than two fluid-filled cavities. The use of steroids, surfactant, or high-frequency ventilation did not improve survival. Stratifying the study base into those treated in early or late 1990s likewise failed to show difference in survival times. Infection remains a significant problem (46%). In our series of 41 infants with hydrops fetalis, survival rates remain comparable to those reported in the literature, despite aggressive therapy. Although the use of surfactant, steroids, and high-frequency ventilation appear to prolong survival times, these treatments failed to alter overall survival outcome.