Behavior of nanoparticle clouds around a magnetized microsphere under magnetic and flow fields.

When a micron-sized magnetizable particle is introduced into a suspension of nanosized magnetic particles, the nanoparticles accumulate around the microparticle and form thick anisotropic clouds extended in the direction of the applied magnetic field. This phenomenon promotes colloidal stabilization of bimodal magnetic suspensions and allows efficient magnetic separation of nanoparticles used in bioanalysis and water purification. In the present work, the size and shape of nanoparticle clouds under the simultaneous action of an external uniform magnetic field and the flow have been studied in detail. In experiments, a dilute suspension of iron oxide nanoclusters (of a mean diameter of 60 nm) was pushed through a thin slit channel with the nickel microspheres (of a mean diameter of 50 µm) attached to the channel wall. The behavior of nanocluster clouds was observed in the steady state using an optical microscope. In the presence of strong enough flow, the size of the clouds monotonically decreases with increasing flow speed in both longitudinal and transverse magnetic fields. This is qualitatively explained by enhancement of hydrodynamic forces washing the nanoclusters away from the clouds. In the longitudinal field, the flow induces asymmetry of the front and the back clouds. To explain the flow and the field effects on the clouds, we have developed a simple model based on the balance of the stresses and particle fluxes on the cloud surface. This model, applied to the case of the magnetic field parallel to the flow, captures reasonably well the flow effect on the size and shape of the cloud and reveals that the only dimensionless parameter governing the cloud size is the ratio of hydrodynamic-to-magnetic forces-the Mason number. At strong magnetic interactions considered in the present work (dipolar coupling parameter α≥2), the Brownian motion seems not to affect the cloud behavior.

Recommendations for ICT use in Alzheimer's disease assessment: Monaco CTAD Expert Meeting.

Alzheimer disease (AD) and other related dementia represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments for assessing disease severity and disease progression to optimize patient's care and support to care providers, and also provide better tools for clinical research. In this area, Information and Communication Technologies (ICT) are of particular interest. Such techniques enable accurate and standardized assessments of patients' performance and actions in real time and real life situations. The aim of this article is to provide basic recommendation concerning the development and the use of ICT for Alzheimer's disease and related disorders. During he ICT and Mental Health workshop (CTAD meeting held in Monaco on the 30th October 2012) an expert panel was set up to prepare the first recommendations for the use of ICT in dementia research. The expert panel included geriatrician, epidemiologist, neurologist, psychiatrist, psychologist, ICT engineers, representatives from the industry and patient association. The recommendations are divided into three sections corresponding to 1/ the clinical targets of interest for the use of ICT, 2/ the conditions, the type of sensors and the outputs (scores) that could be used and obtained, 3/ finally the last section concerns specifically the use of ICT within clinical trials.

Ternary phase diagrams of a thermoreversible chelating non-ionic surfactant.

The behaviour of a di-block molecule associating a diamide group and a non-ionic surfactant (C(i)E(j)) is determined in a ternary surfactant/water/oil/system. Its properties are compared to the ones of a parent non-ionic surfactant C(i)E(j) through the limits of boundaries in the phase prisms. The existence of a stable microemulsion single phase in a defined temperature and concentration range is demonstrated. The extension of the microemulsion domain is limited by the presence of a gel, containing lyotropic liquid crystals as gelling agents. Temperature dependence is observed for the curvature below the temperature of zero spontaneous curvature, but the ternary system cannot produce reverse microemulsion as observed with classical C(i)E(j). The decrease of the mean curvature with temperature is inhibited by the presence of the diamide as a grafted complexing group. Liquid-liquid extraction processes with this type of surfactant are possible, but will require the presence of at least a fourth component to enlarge the water in an oil microemulsion domain.

The effect of bosentan on the pharmacokinetics of digoxin in healthy male subjects.

AIMS: To investigate the effect of multiple oral dose treatment with the endothelin receptor antagonist bosentan on the pharmacokinetics of digoxin in healthy subjects. METHODS: This was an open-label, randomized, two-way crossover study in 18 evaluable young male subjects. They received, on two occasions which were separated by at least 2 weeks washout period, 0.375 mg digoxin once daily for 13 days following a loading dose of 0.375 mg given twice on the day before the once daily dosing regimen started. On one occasion treatment with 500 mg bosentan twice daily was started on the eighth day of digoxin treatment and continued for 1 week. Serum concentrations of digoxin were determined up to 24 h postdose on day 8 (first day of bosentan treatment) and day 14 (last day of bosentan treatment) of the digoxin treatment period. Plasma concentrations of bosentan were measured at two time points after the first bosentan dose and up to 12 h after the last morning dose of bosentan. Safety was assessed by adverse events, clinical laboratory tests, blood pressure and pulse rate measurements and ECG recordings. RESULTS: Steady-state of digoxin was always achieved after 7 days of treatment. Serum concentrations of digoxin were within the usual therapeutic range. Average steady-state Cmax and Ctr were 2-2.1 microg l-1 and 0.65-0.69 microg l-1, respectively, when given alone. Bosentan did not lead to statistically significant changes in Cmax and Ctr of digoxin. AUC (0,24h) of digoxin, however, was slightly reduced after 1 week of treatment with bosentan. The reduction was 12% on average with a narrow 95% confidence interval of 0-23%. Bosentan pharmacokinetic parameters after 1 week of treatment were as expected with a mean Cmax of 3260 microg l-1 and a mean AUC (0, 12h) of 12 600 microg l-1 h. CONCLUSIONS: Treatment with bosentan 500 mg twice daily for 1 week did not show clinically relevant effects on the pharmacokinetics of digoxin in healthy human subjects

Oral dolasetron mesylate for prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study. The Oral Dolasetron PONV Prevention Study Group.

STUDY OBJECTIVE: To examine the safety and effectiveness of a range of single oral doses of dolasetron mesylate for the prevention of postoperative nausea and vomiting. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 32 hospitals. PATIENTS: 789 female ASA physical status I, II, and III patients, ages 18 to 60 years, weighing between 45 and 100 kg, scheduled for major gynecologic surgery (including abdominal hysterectomy, gynecologic laparotomy, or vaginal hysterectomy) with general anesthesia. INTERVENTIONS: 25, 50, 100, or 200 mg oral doses of dolasetron mesylate or placebo were administered 1 to 2 hours before induction of anesthesia. Efficacy was assessed for 24 hours postrecovery by measuring complete response (no emetic episodes, no rescue medication), total response (complete response with no nausea), time to first emetic episode or rescue, and patient visual analog scale evaluations of nausea severity and satisfaction with antiemetic therapy. MEASUREMENTS AND MAIN RESULTS: Complete response rates for the 50, 100, and 200 mg dose groups were statistically greater than placebo (p < or = 0.018). Likewise, total response rates were statistically greater in the 50, 100, and 200 mg dose groups than in the placebo group (p = 0.012). Percentage of patients with no nausea and patient satisfaction scores were significantly higher for each dolasetron dose group than placebo (p < or = 0.047 and p < or = 0.004, respectively). Efficacy peaked at the 50 mg dose. The incidence of adverse events was similar in the placebo (30.1%) and dolasetron groups (29.4%). Headache was the most frequent treatment-related adverse event, with 2% to 5% incidence across groups. Incidence of adverse events did not increase with increasing dolasetron doses. Dose-related decreases in blood pressure at acute time points were not clinically significant. CONCLUSION: Single oral doses of dolasetron, administered 1 to 2 hours before induction of anesthesia, are safe and effective for preventing postoperative nausea and vomiting in this patient sample. Maximal antiemetic response was seen with the 50 mg oral dolasetron dose.

Intravenous dolasetron mesilate in the prevention of postoperative nausea and vomiting in females undergoing gynecological surgery.

STUDY OBJECTIVE: To evaluate a range of doses of intravenous (i.v.) dolasetron mesilate, in preventing postoperative nausea and vomiting (PONV). DESIGN: Double-blind, placebo-controlled, randomized, multicenter trial. SETTING: Ten hospitals and/or surgical centers. PATIENTS: 281 women undergoing gynecologic surgery with general anesthesia. INTERVENTIONS: Patients received one of four single, i.v. doses of dolasetron mesilate (12.5 mg, 25 mg, 50 mg, and 100 mg) or placebo administered following cessation of anesthesia. MEASUREMENTS AND MAIN RESULTS: Patients were monitored for 24 hours following study drug administration. The antiemetic efficacy of each dolasetron mesilate dose was evaluated by recording the number and timing of emetic episodes, and the effects on nausea were assessed by use of visual analog scales (VAS). Safety was assessed by adverse event reports, clinical laboratory tests, electrocardiographic (ECG) measurements, and monitoring vital signs. Complete responses (patients with no emetic episodes and no escape antiemetic medication requirements in 24 hours) were achieved by 54% in the 12.5-mg, 67% in the 25-mg, and 59% in both the 50-mg and 100-mg dolasetron mesilate dose groups, and by 43% in the placebo group. Nausea VAS assessments demonstrated that dolasetron-treated patients were significantly (p = 0.048) more likely to report no nausea (VAS score < 5 mm) than those in the placebo group. Adverse events reported generally were mild in intensity, and there were no clinically significant changes in laboratory tests, vital signs, or ECG parameters. CONCLUSIONS: Dolasetron was effective and well tolerated for the prevention of PONV in female patients undergoing gynecologic surgery with general anesthesia.

Intravenous dolasetron and ondansetron in prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study.

BACKGROUND: Intravenous dolasetron mesilate has shown efficacy in the prevention of postoperative nausea and vomiting (PONV) when administered as a single dose prior to emergence from anesthesia. This trial compared intravenous dolasetron and ondansetron for the prevention of PONV when administered at induction of anesthesia. METHODS: This double-blind, placebo-controlled, multicenter trial randomized patients to one of four single IV treatments placebo, 25 or 50 mg dolasetron, or 4 mg ondansetron. Efficacy was measured by complete response (0 emetic episodes and no rescue medication), nausea severity and patient satisfaction as measured on a visual analog scale (VAS), investigator's rating, of nausea severity, and total response (complete response with no nausea [< or = 5 mm VAS]). RESULTS: 514 patients at 24 sites were evaluated for efficacy. The 50 mg dolasetron and 4 mg ondansetron doses were statistically equivalent, and superior to placebo, for all efficacy measures. Complete response rates were 49%, 51%, 71% and 64% for placebo, 25 and 50 mg dolasetron, and ondansetron, respectively. Dolasetron 50 mg was statistically superior to 25 mg dolasetron for complete response, total response, VAS maximum nausea, time to first emetic episode, and patient satisfaction. The majority of adverse events were of mild-to-moderate intensity. Headache was the most frequently reported treatment-related adverse event with a 3%-5% incidence across treatments. CONCLUSION: When given at induction of anesthesia, 50 mg intravenous dolasetron is equivalent to 4 mg ondansetron and superior to 25 mg dolasetron and placebo for the prevention of PONV. All treatments were safely administered and well tolerated.

Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting.

PURPOSE: To compare the efficacy, safety, and tolerability of dolasetron mesilate with placebo for the treatment of postoperative nausea and vomiting (PONV). METHODS: In a randomized, multicentre, double-blind, placebo-controlled study 337 adult patients undergoing surgery with general anaesthesia received one of four single, doses of dolasetron mesilate iv (12.5, 25, 50, or 100 mg) or placebo. Study medication was administered postoperatively when the patient reported nausea lasting 10 min or when one emetic episode occurred within two hours of the patient's arrival in the recovery room. Efficacy was assessed by the investigators over the 24-hr study period by recording the number and timing of emetic episodes, the severity of nausea, the timing of administration of escape antiemetic medications, and patients' and investigators' satisfaction with antiemetic therapy. RESULTS: The study sample was predominately women, and the surgical procedures were primarily gynaecological. All dolasetron mesilate doses produced higher complete response rates than placebo (P < 0.05). Only approximately one-third of dolasetron patients required escape antiemetic medication compared with more than 50% of patients in the placebo group. Both patient and physician satisfaction with dolasetron treatment was high. The most common adverse event was mild or moderate headache for both placebo-treated patients and dolasetron-treated patients. Clinical laboratory results were unremarkable. CONCLUSION: Single doses of dolasetron mesilate iv, given after the first episode of PONV, were both effective and safe in this adult patient population.