The Journal of laboratory and clinical medicine
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The vasoconstriction induced by hemoglobin-based oxygen carriers (HBOCs), mainly a result of nitric oxide (NO) scavenging, until now has limited the application of HBOCs as resuscitation fluids. In this study, we tested the hypothesis that the new modified recombinant-hemoglobin solution rHb2.0, with a 20 to 30 times lesser NO-scavenging rate, would minimize vasoconstriction without adverse effects on microvascular oxygenation. Responses were compared with those to rHb1.1, a recombinant-hemoglobin solution with a wild-type NO-scavenging rate, as well as an oncotically matched albumin solution. ⋯ Intestinal microvascular Po2 , determined on the basis of oxygen-dependent quenching of palladium-porphyrin phosphorescence, revealed no difference between rHb2.0 and rHb1.1. The findings of this study confirm that the well-known pressure effect of HBOCs is caused by their effect on the NO-scavenging rate; recombinant modification of this rate did not increase MAP during resuscitation compared with baseline values. Although systemic vasoconstriction was absent, intestinal vasoconstriction almost negligible, and Do2int greater after resuscitation with rHb2.0, the effect of rHb2.0 on pH, base-excess and microvascular Po2 levels after resuscitation were comparable to those achieved with the use of the albumin solution.
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Energy-metabolism disturbances during sepsis are characterized by enhanced glycolytic fluxes and reduced mitochondrial respiration. However, it is not known whether these abnormalities are the result of a specific mitochondrial alteration, decreased pyruvate dehydrogenase (PDH) complex activity, depletion of ubiquinone (CoQ(10); electron donor for the mitochondrial complex III), or all 3. In this study we sought to specify metabolism disturbances in a murine model of sepsis, using either a PDH-activator infusion (dichloroacetate, DCA) or CoQ(10) supplementation. ⋯ Increased muscle glycolysis fluxes were observed after 4 hours in the control group, but to a slighter degree in both the DCA and CoQ(10) groups. Only DCA restored a normal temperature sensitivity in the hyperthermia range, but we noted no differences in survival time. In conclusion, only DCA infusion restores normal glycolysis function.
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Streptococcus pneumoniae remains the most common bacterial cause of community-acquired pneumonia, and these infections are associated with significant morbidity and mortality worldwide. A major concern is the increasing incidence of antibiotic resistance among pneumococcal isolates, which, in the case of certain of the antibiotic classes, has been associated with treatment failure. Yet despite multiple reports of infections with penicillin-resistant pneumococcal isolates, no cases of bacteriologic failure have been documented with the use of penicillin or ampicillin in the treatment of pneumonia caused by penicillin-resistant pneumococci. ⋯ However, several cases of macrolide/azalide treatment failure have been documented, and many clinicians recommend that these agents not be used on their own in areas with a high prevalence and levels of macrolide/azalide resistance. However, evidence is emerging to show beneficial effects on outcome with combination therapy, especially that of a beta-lactam agent and a macrolide given together to sicker, hospitalized patients with pneumococcal pneumonia. In an attempt to prevent the emergence of resistance, it has been recommended by some that the new fluoroquinolones not be used routinely as first-line agents in the treatment of community-acquired pneumonia; instead, they say, these agents should be reserved for patients who are allergic to the commonly used beta-lactam agents, for infections known to be or suspected of being caused by highly resistant strains, and for patients in whom initial therapy has failed.
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Biography Historical Article
250 years of controlled clinical trials: where it all began.