The Journal of infectious diseases
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Three Dutch marine battalions (n=2289) serving in Western Cambodia during 1992-1993 used mefloquine as weekly malaria chemoprophylaxis. One battalion started with a loading dose. Full compliance with prophylaxis was reported by 86.3%, and possible mefloquine-related adverse events were reported by 30.2%. ⋯ After return, there were 11 cases of falciparum malaria and 22 of vivax malaria, 16-72 days and 30-540 days, respectively, after stopping prophylaxis. Mefloquine-resistant parasites were isolated from 4 Dutch and 4 Khmer patients. Long-term mefloquine prophylaxis was well tolerated but not totally effective.
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Randomized Controlled Trial Clinical Trial
The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock.
Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinflammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-1 were significantly higher in nonsurvivors. ⋯ However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-alpha concentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher in nonsurvivors at a similar TNF-alpha concentration. Thus, an increased PAI-1 response to TNF-alpha may be associated with fatality, probably because of polymorphism of the PAI-1 gene.
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The role of macrophage inflammatory protein-2 (MIP-2) in bacterial pneumonia was characterized. Mice were challenged with Klebsiella pneumoniae intratracheally, and organs were harvested at 8, 24, and 48 h. Inoculation with K. pneumoniae resulted in the time-dependent expression of MIP-2 mRNA and protein within the lung, which was maximal 48 h after inoculation. ⋯ Finally, treatment with anti-MIP-2 serum decreased early (48-72 h) but not late (after 72 h) survival in animals with Klebsiella pneumonia. This study indicates that MIP-2 is produced during Klebsiella pneumonia and inhibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung bacterial clearance in murine Klebsiella pneumonia. MIP-2 is produced during Klebsiella pneumonia and inhibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung bacterial clearance in murine Klebsiella pneumonia.
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The in vivo efficacy of three cell wall-active antibiotics, imipenem, meropenem, and ceftazidime, was compared in mice rendered hypersusceptible to the pathophysiologic effects of lipopolysaccharide by treatment with D-galactosamine. When CF-1 mice were administered Escherichia coli, D-galactosamine, and saline intraperitoneally, an LD50 was achieved at an inoculum of approximately 2 x 10(4) cfu. ⋯ When the dose of antibiotic was decreased to 2 mg/kg, neither meropenem nor ceftazidime could provide measurable protection, whereas imipenem was almost fully protective (P < .002). These differences in protective efficacy were also noted with experimental Pseudomonas aeruginosa but not Staphylococcus aureus infection.
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Clostridium perfringens exotoxins have been implicated as major virulence factors responsible for shock and organ failure in gas gangrene, yet the mechanism(s) by which they mediate cardiovascular dysfunction remain enigmatic. Recombinant (r) phospholipase C (PLC), r theta-toxin, culture supernatant (crude toxin), or 0.9% NaCl was infused intravenously into awake rabbits. ⋯ Further, crude toxin and rPLC but not r theta-toxin inhibited cardiac contractility (dF/dt) in isolated rabbit atrial muscles. These results suggest that PLC-induced myocardial dysfunction contributes to shock in C. perfringens infection.