To determine whether treatment with recombinant human tissue factor pathway inhibitor (TFPI), an inhibitor of the extrinsic coagulation pathway, can improve survival in a clinically relevant model of gram-negative sepsis, rabbits were given an intraperitoneal inoculation of a suspension containing hemoglobin (40 microg/mL), porcine mucin (150 microg/mL), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Treatment with gentamicin (5 mg/kg every 12 h for five doses) was instituted 4 h after induction of peritonitis. At the same time point, rabbits were randomized to receive a 24-h infusion of vehicle or one of three different doses of TFPI. Treatment groups, 7-day survival rates, and significance versus control were as follows: control, 1 of 20; TFPI(LOW DOSE) (0.1 mg/kg, then 1 microg/kg/min), 3 of 12 (P = .14); TFPI(MID DOSE), (0.5 mg/kg, then 5 microg/kg/min), 7 of 12 (P = .002); TFPI(HIGH DOSE) (10 mg/kg, then 10 microg/kg/min), 4 of 13 (P = .04). Thus, delayed treatment with TFPI improves survival in septic rabbits.
External hydrocephalus appears to be a benign form of infantile macrocephaly which typically resolves in the second year of life. Macrocephaly may persist into adulthood and is closely associated with benign familial macrocephaly. 1 The CT findings include a prominent and widened interhemispheric fissure, enlargement of the subarachnoid space over the frontal convexities, and prominent basal cisternae.2 Although obstruction of the arachnoid villae has been proposed, the etiology of the accumulation of this extra-axial fluid is unknown.3 The following case study of dizygotic triplets with idiopathic external hydrocephalus highlights the hereditary basis of the condition.
Polymyxin B (PMB) is an amphipathic nephrotoxic antibiotic, which has been shown to neutralize the effects of endotoxin both in vitro and in vivo. PMB-D70 (PMX-622), a covalent conjugate of PMB with dextran 70 (D70), is less nephrotoxic than the parent compound. We sought to determine whether therapy with PMB-D70, in addition to conventional antimicrobial chemotherapy, could improve survival in a model of Gram-negative peritonitis. At T = 0 h, New Zealand white rabbits were implanted intraperitoneally with 10 ml of a suspension containing hemoglobin (40 μg/ml), mucin (150 μg/ml), and 1.0 ± 0.2 x 104 cfu/kg of viable Escherichia coli (O18:K1). Beginning at T = 4 h, the rabbits were treated with gentamicin (5 mg/kg every 12 h) for five doses or until death, and infused for 24 h or until death with either D70 or PMB-D70. Two pairs of groups were studied (doses indicate cumulative amounts infused over 24 h). The PMB-D70 (low dose) group received PMB-D70 (5 mg/kg of the PMB component) and the D70 (low dose) group received an equivalent dose of D70. The PMB-D70 (high dose) group received PMB-D70 (10 mg/kg of the PMB component) and the D70 (high dose) group received an equivalent dose of D70. Results for the two PMB-D70 groups, on the one hand, and the two D70 group, on the other hand, were statistically indistiguishable and, accordingly, were pooled for all analyses. Survival at 7 days was 11/25 (44%) for rabbits treated with PMB-D70 as compared to 2/23 (9%) for animals treated with D70 ( P = 0.007). We conclude that adjuvant treatment with PMB-D70 improves survival in a clinically relevant model of Gram-negative sepsis.
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