Transfusion-related sepsis due to Serratia liquefaciens in the United States.

BACKGROUND: Severe, often fatal, transfusion reactions due to bacterial contamination of blood components continue to occur. Serratia liquefaciens, an unusual human pathogen, is a recently recognized potential cause of transfusion-related sepsis. CASE REPORTS: Five episodes of transfusion-related sepsis and endotoxic shock due to S. liquefaciens were reported to the CDC from July 1992 through January 1999. One episode has been described. The remaining four, all fatal, are described here: three associated with RBC transfusion and one associated with transfusion of platelets. In each instance, the source of contamination could not be found. The implicated units tended to be older (mean RBC age 28 days), and visual discoloration was noted in each RBC unit, although usually in retrospect. CONCLUSION: S. liquefaciens is an increasingly recognized cause of transfusion-related sepsis and is associated with a high mortality rate. S. liquefaciens can contaminate both RBCs and platelets, but the mechanism(s) of contamination remain unknown. Increased attention to pretransfusion visual inspection may avert the transfusion of some S. liquefaciens-contaminated RBC units. However, more sensitive rapid diagnostic tests are needed to further reduce the risk of transfusion-related sepsis and endotoxic shock.

Cocaine and cocaethylene: effects on extracellular dopamine in the primate.

Cocaine and cocaethylene (a psychoactive metabolite of concurrent cocaine and ethanol consumption) were studied in the anesthetized vervet monkey. The ability of each to elevate extracellular DA in the caudate nucleus was assessed using microdialysis probes acutely lowered through chronic guide cannulae. Blood samples were also collected to determine plasma levels of the two drugs. Doses of 1.5 mumol/kg cocaine (equivalent to 0.5 mg/kg cocaine-HCl) and cocaethylene were administered intravenously. Microdialysis and blood samples were collected at 5-min intervals immediately following drug administration. Both drugs caused a maximal four-fold increase in extracellular DA during the 5- to 10-min period following drug administration. This is the first report of cocaine (and cocaethylene) induced alterations in extracellular DA in primates. The abilities of cocaine and cocaethylene to produce euphoria are being compared in ongoing clinical research studies. The potential use of these results for interpreting the neurochemical basis of any differences in those studies is discussed.

Differences in bioavailability between cocaine and cocaethylene and their implications for drug-reward studies.

Cocaethylene, a psychoactive metabolite resulting from combined ethanol/cocaine consumption, is of interest because its psychostimulant properties may partially underlie combined cocaine/ethanol use, and because it has the potential for use as a probe of drug reward mechanisms due to its enhanced selectivity at monoamine uptake sites compared to cocaine. To determine the relative systemic bioavailabilities of cocaine and cocaethylene, sequential plasma samples were obtained from awake rats following drug administration. Following intravenous administration of 3 mumol/kg (molar equivalent of 1 mg/kg cocaine-HCl), both drugs achieved similar time courses and areas under the plasma concentration versus time curve. In contrast, intraperitoneal administration of 44 mumol/kg (molar equivalent of 15 mg/kg cocaine HCl) showed peak plasma levels, and the area under the plasma concentration vs time curve for cocaine to be approximately twice that for cocaethylene. Comparison of dose corrected areas under the curve of the two routes of administration for each drug indicated that relative systemic bioavailability of cocaethylene following intraperitoneal administration is only 58% that of cocaine. In addition, the elimination of both cocaine and cocaethylene was found to be slower following intraperitoneal administration compared to the intravenous route. The implications of these results are discussed with respect to the relative potency of these two compounds, as inferred from behavioral, drug reward, and lethality studies. Also, the differences noted will need to be taken into account when making mechanistic interpretations from comparative drug reward studies.

Cocaine and cocaethylene: microdialysis comparison of brain drug levels and effects on dopamine and serotonin.

Cocaethylene is a pharmacologically active metabolite resulting from concurrent cocaine and ethanol consumption. The effects of cocaine and cocaethylene on extracellular levels of dopamine in the nucleus accumbens, and serotonin in the striatum were characterized in vivo in the anesthetized rat. Both intravenous (3 mumol/kg) and intraperitoneal (44 mumol/kg) routes of administration were used. In addition to monitoring neurotransmitter levels, microdialysate levels of cocaine and cocaethylene were determined at 4-min intervals after intravenous administration, and at 20-min intervals after intraperitoneal administration. Extracellular levels of dopamine in the nucleus accumbens were increased to approximately 400% of preinjection value by both cocaine and cocaethylene when administered intravenously. Cocaine caused a significant increase of striatal serotonin to 200% preinjection value, whereas cocaethylene had no effect. Brain levels of cocaine and cocaethylene after intravenous administration did not differ. After intraperitoneal administration, extracellular levels of dopamine in the nucleus accumbens were increased to 400% of preinjection levels by cocaine, but were only increased to 200% of preinjection levels by cocaethylene, the difference being statistically significant. Serotonin levels were increased to 360% of preinjection levels by cocaine, but only to 175% of preinjection value by cocaethylene. Levels of cocaine attained in brain were significantly higher than those for cocaethylene, suggesting pharmacokinetic differences with the intraperitoneal route. These results confirm in vivo that cocaethylene is more selective in its actions than cocaine with respect to dopamine and serotonin uptake. In addition, route-dependent differences in attainment of brain drug levels have been observed that may impact on interpretations of the relative potency of the reinforcement value of these compounds.

An inhibitor of T lymphocyte blastogenesis derived from the unfertilized ova of Shad (Alosa sapidissima).

Unfertilized ova from Shad, a North Atlantic herring, contains a cytostatic inhibitor of T lymphocyte blastogenesis. The inhibitor has an estimated molecular weight of 10,000-30,000 Da, is heat stable, non dialyzable, and resistant to protease digestion and periodate oxidation. Although the inhibitor functions at an early metabolic event in T lymphocyte mitogenesis, it does not appear to interfere with thymidine transport, antagonize lectin binding to lymphocyte surface receptors, or interfere with the function of an essential serum component in the cell culture media.

Effect of 6-hydroxydopamine on bovine adrenal chromaffin cells in culture.

The effect of 6-hydroxydopamine on the catecholamine content and cell morphology of bovine adrenal chromaffin cells in culture was investigated. 6-Hydroxydopamine markedly reduced the catecholamine content of the cultured chromaffin cells after 6 and 24 h exposure. The effect was dose-related, with half-maximal depletion occurring at 2.4 X 10(-5) M. Cells exposed to 6-hydroxydopamine for 3 h and then to normal medium without the drug for 3 h more showed the same degree of toxicity as cells exposed to the drug for the entire 6 h. Ascorbate at high concentrations also exhibited toxicity toward chromaffin cells between 6 and 24 h of exposure. 6-Hydroxydopamine produced marked changes in cell morphology. At 1 h the cells appeared normal, at 3 h the processes were markedly shortened, and at 6 h they were completely retracted. On exposure for 24 h there were gross morphological changes and most cells were detached and free-floating in the medium. The toxicity of 6-hydroxydopamine in bovine adrenal chromaffin cells is discussed.