Tranexamic acid pharmacokinetics are influenced by CPB. Our TA pharmacokinetic model does not provide support for the wide range of TA dosing techniques that have been reported. Variation in TA efficacy from study to study and confusion about the optimal duration of TA treatment may be the result of dosing techniques that do not maintain stable, therapeutic TA concentrations.

A promising approach to improving outcomes in patients with cryptococcal meningitis is to use adjunctive passive immunotherapy with a monoclonal antibody (MAb) directed against the capsular polysaccharide of Cryptococcus neoformans. This is the first application of MAb therapy for the treatment of a fungal disease in humans. We determined the safety and maximum tolerated dose of the murine anticryptococcal MAb 18B7 in a phase I dose-escalation study. The subjects were human immunodeficiency virus-infected patients who had been successfully treated for cryptococcal meningitis. Six dosing cohorts received MAb 18B7 at 0.01 to 2 mg/kg of body weight as a single infusion. Three patients each received 0.01, 0.05, 0.2, and 0.5 mg of MAb 18B7 per kg without significant adverse events. Four of the subjects who received the 1-mg/kg dose had mild study drugassociated toxicity, including transient nausea, vomiting, back pain, and urticarial rash. Two of the subjects who received 2 mg/kg developed drug-associated mild to moderate nausea, vomiting, chills, and myalgias. One of the subjects who received 2 mg/kg developed intracranial hypertension 10 weeks after MAb 18B7 administration. Serum cryptococcal antigen titers in the cohorts receiving doses of 1 and 2 mg/kg declined by a median of twofold at 1 week and a median of threefold at 2 weeks postinfusion, but the titers subsequently returned toward the baseline values by week 12. The half-life of MAb 18B7 in serum was approximately 53 h, while the MAb was undetectable in the cerebrospinal fluid of all patients. These data support the continued investigation of MAb 18B7 at a maximum single dose of 1.0 mg/kg.

There were consistent differences among the local anesthetics, the sum of which suggests that larger doses and blood concentrations of ropivacaine (ROP) and lidocaine will be tolerated as compared with bupivacaine (BUP) and levobupivacaine (LBUP). Lidocaine intoxication results in myocardial depression from which resuscitation is consistently successful but will require continuing drug support. After BUP, LBUP, or ROP, resuscitation is not always successful, and the administration of epinephrine may lead to severe arrhythmias. The unbound plasma concentrations at collapse were larger for ROP compared with BUP, whereas the concentrations of LBUP and BUP were not significantly different from each other. Furthermore, larger plasma concentrations of ROP than BUP are present after resuscitation, suggesting a wider margin of safety when large volumes and large concentrations are used to establish upper or lower extremity nerve blocks for surgical anesthesia and during long-term infusions for pain management.

The results of this pilot study suggest that liarozole 75 mg twice daily is an effective and well-tolerated therapy for PPP. In addition, the pharmacokinetics of liarozole may help to circumvent side-effects associated with synthetic retinoids and allow its use in premenopausal women.

In Experiment 1, participants were presented with pairs of stimuli (one visual and the other tactile) from the left and/or right of fixation at varying stimulus onset asynchronies and were required to make unspeeded temporal order judgments (TOJs) regarding which modality was presented first. When the participants adopted an uncrossed-hands posture, just noticeable differences (JNDs) were lower (i.e., multisensory TOJs were more precise) when stimuli were presented from different positions, rather than from the same position. This spatial redundancy benefit was reduced when the participants adopted a crossed-hands posture, suggesting a failure to remap visuotactile space appropriately. In Experiment 2, JNDs were also lower when pairs of auditory and visual stimuli were presented from different positions, rather than from the same position. Taken together, these results demonstrate that people can use redundant spatial cues to facilitate their performance on multisensory TOJ tasks and suggest that previous studies may have systematically overestimated the precision with which people can make such judgments. These results highlight the intimate link between spatial and temporal factors in determining our perception of the multimodal objects and events in the world around us.

Because no completely effective antiemetic exists for the prevention of postoperative nausea and vomiting (PONV), we hypothesize that a multimodal approach to management of PONV may reduce both vomiting and the need for rescue antiemetics in high-risk patients. After IRB approval, women undergoing outpatient laparoscopy were randomized to one of three groups. Group I (n = 60) was managed by using a predefined multimodal clinical care algorithm. Patients undergoing the same surgical procedure who received a standard balanced outpatient anesthetic with ondansetron 4 mg (Group II, n = 42) or placebo (Group III, n = 37) prophylaxis were chosen to establish baseline incidence of nausea and vomiting. None of the Group I patients vomited before discharge, compared with 7% in Group II (P = 0.07) and 22% in Group III (P = 0.0003). However, one patient (2%) in Group I required treatment for symptoms in the postanesthesia care unit, compared with 24% in Group II (P<0.0001) and 41% in Group III (P< 0.0001). Time to discharge-ready was significantly shorter in Group I (128, 118-139 min; mean, 95% confidence interval) versus Group II (162, 145-181 min; P = 0.0015) and Group III (192, 166-222 min; P = 0.0001). Patient satisfaction with control of PONV was not different between Group I and Group II. Return to normal daily activity and overall satisfaction were not different among groups. Multimodal management resulted in a 98% complete response rate and a 0% incidence of vomiting before discharge; however, this improvement did not result in an increased level of patient satisfaction when compared with routine monotherapy prophylaxis. We conclude that both multimodal management and routine monotherapy antiemetic prophylaxis resulted in an increased level of patient satisfaction than symptomatic treatment in this high-risk population.

Administration of calf lung surfactant extract, calfactant, appears to be safe and is associated with rapid improvement in oxygenation, earlier extubation, and decreased requirement for intensive care in children with acute hypoxemic respiratory failure. Further study is needed, however, before widespread use in pediatric respiratory failure can be recommended.

Glucosinolates contained in members of the Brassicaceae release isothiocyanates potentially useful in controlling Fusarium oxysporum pathogens in conifer seedling nursery soils. Our objective was to determine the toxicity of individual isothiocyanates to different growth stages of the fungus. Bioassays with four F. oxysporum isolates were conducted using sealed containers in which 0.3 μl of 2-propenyl, ethyl, buty, phenylethyl, benzyl, or phenyl isothiocyanate was allowed to volatilize. Propenyl and ethyl isothiocyanates were the most fungistatic of those compounds tested. The same concentrations of propenyl and ethyl isothiocyanates that inhibited mycelial growth completely suppressed conidial and chlamydospore germination of all isolates. Other isothiocyanates including ethyl, benzyl, and phenethyl were also fungitoxic to F. oxysporum conidia and chlamydospores. Reduction in pathogen populations resulting from a green-manure crop are likely achievable since chlamydospores are sensitive to isothiocyanate. Pathogenic F. oxysporum isolates infesting nursery soils would likely be most suppressed by species of plants such as Brassica carinata, B. nigra, and B. juncea, which contain glucosi-nolates that release high concentrations of propenyl isothiocyanate.