To compare ondansetron (GR 38032F), a 5-hydroxytryptamine3-receptor antagonist, with metoclopramide in the prophylaxis of acute cisplatin-induced emesis, we conducted a double-blind crossover study in 97 patients scheduled to receive cisplatin (80 to 100 mg per square meter of body-surface area) for treatment of cancer. None had received chemotherapy before this trial. Among the 76 patients who satisfactorily completed both parts of the study, complete or nearly complete control of emesis (i.e., no episodes of emesis occurred, or only one or two) was achieved in 57 of 76 treatments (75 percent) with ondansetron and in 32 of 76 treatments (42 percent) with metoclopramide (P less than 0.001). Ondansetron was also more effective in controlling acute nausea, as assessed with a visual-analogue scale (P = 0.019) or a graded scale (P = 0.024). There was a significant preference among patients for ondansetron (55 vs. 26 percent; P = 0.006). Dystonic reactions were observed during three treatments with metoclopramide; both agents were otherwise well tolerated. We conclude that ondansetron is more effective than metoclopramide in the control of cisplatin-induced nausea and vomiting, and that this suggests that serotonin is an important mediator of this side effect.

We quantified the fate and transport of watershed-derived ammonium in a tidal freshwater marsh fringing the nutrientrich Scheldt River in a whole-ecosystem 15 N labeling experiment. 15 N-NH was added to the floodwater entering a 3,477 ϩ 4 m 2 tidal marsh area, and marsh ammonium processing and retention were traced in six subsequent tide cycles. We present data for the water phase components of the marsh system, in which changes in concentration and isotopic enrichment of NO , NO , N 2 O, N 2 , NH , and suspended particulate nitrogen (SPN) were measured in concert with a mass balancestudy. Simultaneous addition of a conservative tracer (NaBr) confirmed that tracer was evenly distributed, and the Br Ϫ budget was almost closed (115% recovery). All analyzed dissolved and suspended N pools were labeled, and 31% of added for 30% of 15 N-transformation. In situ whole-ecosystem nitrification rates were four to nine times higher than those in the water column alone, implying a crucial role for the large reactive marsh surface area in N-transformation. Under conditions of low oxygen concentrations and high ammonium availability, nitrifiers produced N 2 O. Our results show that tidal freshwater marshes function not only as nutrient sinks but also as nutrient transformers.

Nasal decongestants are recommended for the management of acute rhinosinusitis to reduce the consequences of often disabling nasal congestion. They are also recommended during rhinoscopic examination and for preparation of the nasal mucosa prior to endonasal surgery.

No abstract

In a rabbit model of Escherichia coli endocarditis, we studied the penetration into infected vegetations and the antibacterial effect of ceftriaxone. Ceftriaxone was given at different dosages, alone or with an interfering agent, diclofenac, a nonsteroidal anti-inflammatory drug, to determine the predictive value of the antibiotic levels in serum or infected vegetations on the antibacterial efficacy. Diclofenac increased the serum terminal half-life of ceftriaxone and increased its extravascular diffusion in tissue cage fluid, as well as in infected vegetations, allowing us to obtain various antibiotic concentrations in the infected site. Two hours after the fourth injection, around the time of peak level in serum, we observed a linear relationship between (i) serum and local antibiotic levels in vegetations, (ii) In severe infections, a bactericidal effect at the site of infection is essential for effective cure, as demonstrated by Scheld and Sande in experimental pneumococcal meningitis in rabbits (23) and by Decazes et al. in Escherichia coli meningitis (8). In the latter study, ceftriaxone levels in cerebrospinal fluid had to be at least 10 to 20 times higher than its MBC to obtain efficacy. The in vivo bactericidal effect depends on in vitro antibiotic activity and on the pharmacokinetic properties of the antibiotic molecule, which include the degree of diffusion at the infected site and consequently the local antibiotic concentration. In a previous study comparing the efficacy of cefotiam, cefmenoxime, and ceftriaxone in experimental E. coli endocarditis, we have shown that the antibiotic local level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed among these three drugs in vivo (19). We have also demonstrated that ceftriaxone was the most efficient of these three cephalosporins, even when given at relatively long dosing intervals, i.e., 24 h. Apart from the demonstration of this threshold of activity, the precise relationship between the range of concentrations and the antibacterial effect has not yet been determined.The purpose of this work was to assess the predictive value of serum antibiotic levels for the antibiotic concentrations in vegetations and for the local antibacterial effect. At the same time, we attempted to establish a correlation between the ceftriaxone levels in infected vegetations and * Corresponding author. the antibacterial effect. Because it is impossible to study these principles in humans, we used the experimental model of E. coli endocarditis that we have previously described (7). Although this type of infection is uncommon in humans, the model is reliable and the infection is easily reproducible. As it provides a rigourous test of in vivo antibiotic efficacy on a severe infection due to a gram-negative bacillus, the model appeared to be appropriate for studying the properties of ceftriaxone, a long-acting broad-spectrum cephalosporin. We administered different doses of ceftriaxone alone or com...