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.

Endotoxemia following enteral refeeding in children.

Plasma endotoxin-like activity, tumor necrosis factor alpha (TNFalpha) concentrations, core body temperature, and liver functions were measured before and after enteral feeding in children who had been deprived of enteral feeding for 5 days because of their illness. Transient endotoxemia and elevations in plasma TNFalpha concentrations occurred. Core body temperature, aspartate aminotransferase, alamine aminotransferase, and bilirubin concentrations were normal in patients who had elevated plasma endotoxin-like activity. Transient endotoxemia following enteral feeding may be due to the translocation from the gastrointestinal (GI) tract as a result of increased mesenteric circulation and peristalsis. No clinical consequences were noted despite transient endotoxemia. The transient endotoxemia is not due to the immature GI tract; instead, it results from enteral feeding following the deprivation of enteral feeds.

A sublethal dose of LPS to pregnant rats induces TNF-alpha tolerance in their 0-day-old offspring.

The newborn has high mortality in septic shock. Induction of endotoxin tolerance may prevent endotoxic shock in the newborn. The present study showed that a small dose of Salmonella enteritidis lipopolysaccharide (S. ent. LPS), Rc mutant Escherichia coli lipopolysaccharide (J5 LPS), or tumor necrosis factor-alpha (TNF-alpha) given to pregnant rats on the 19th day of gestation induced endotoxin tolerance in their 0-day-old offspring. S. ent. LPS or J5 LPS injected into pregnant rats increased plasma endotoxin-like activity in dams, although not in their fetuses, and increased plasma TNF-alpha concentration in both dams and their fetuses. The endotoxin-tolerant newborn rats were also resistant to TNF-alpha. In those newborn rats, an LPS injection increased plasma TNF-alpha concentration and liver TNF-alpha mRNA abundance. These experiments showed that the endotoxin tolerance could be due to TNF-alpha tolerance. In conclusion, prenatal treatment of dams with a small dose of S. ent. LPS, J5 LPS, or TNF-alpha was beneficial in preventing endotoxic shock in the newborn.

Hadamard transforms of images by use of inexpensive liquid-crystal spatial light modulators.

Incoherent light imaging by Hadamard transformations by use of an inexpensive spatial light modulator from a liquid-crystal display television is demonstrated. The transforms are implemented by means of S matrices. Good-fidelity 31 x 33 pixel images are obtained. The image distortions caused by the limitations of the spatial light modulator are discussed.

Phase II trial of rhIL-6 (interleukin-6) prior to and concurrently with VAD (vincristine, doxorubicin and dexamethasone) chemotherapy for patients with multiple myeloma.

We examined the tolerability and safety of interleukin-6 (rhIL-6) when administered prior to and concurrent with vincristine, doxorubicin and dexamethasone (VAD) in patients with progressive multiple myeloma previously treated with VAD alone. Typical rhIL-6-related effects such as fever, chills, acute phase reactions and reversible abnormalities in liver function tests were observed. The study examined whether rhIL-6 predictably modulated indices of myeloma activity. No consistent, predictable change in myeloma-related parameters was documented upon rhIL-6 administration for either 8 days or 11 days prior to and concurrent with VAD. Two patients showed improved sensitivity to VAD chemotherapy when this was administered with rhIL-6. The overall response rate to rhIL-6 and VAD therapy in this study of relapsed and refractory patients was 50%, comparable to our previous experience with VAD alone in this cohort of patients.

LPS injected into the pregnant rat late in gestation does not induce fetal endotoxemia.

Endotoxin is abortifacient. Abortion may be due to maternal, fetal or combined endotoxemia. The present study was performed to evaluate if fetal rat endotoxemia was induced by maternal endotoxemia in late gestation. An intraperitoneal injection of smooth lipopolysaccharide (Escherichia coli LPS and Shigella flexneri LPS) or rough LPS (Rc mutant Escherichia coli LPS) induced Limulus activity in maternal plasma, but not fetal plasma. These results suggest that fetal rat endotoxemia is not induced during maternal endotoxemia. Thus, the abortion may not be due to fetal endotoxemia.