Antitumor activity and biodistribution of cisplatin nanocapsules in nude mice bearing human ovarian carcinoma xenografts

Cisplatin nanocapsules represent a novel lipid formulation of the anticancer drug cis-diamminedichloridoplatinum(II) (cisplatin), characterized by an unprecedented cisplatin-tolipid molar ratio, and exhibiting strongly increased in-vitro cytotoxicity compared with the free drug. In this study, antitumor efficacy and biodistribution of PEGylated cisplatin nanocapsules were compared with those of the free drug in a mouse tumor model. Nude mice bearing human ovarian carcinoma OVCAR-3 xenografts were treated twice with a 1-week interval by intravenous administration of cisplatin nanocapsules or cisplatin in solution, and the growth inhibitory effects were determined by measurement of tumor volumes. At a dose of 3mg cisplatin/kg, corresponding to the maximum tolerated dose of cisplatin nanocapsules, cisplatin nanocapsules and cisplatin in solution exhibited similar therapeutic effectiveness, reducing tumor growth by 90% at day 20 after first injection. The platinum biodistribution was assayed by analyzing plasma and tissues for total platinum content by nonflame atomic absorption spectroscopy. Plasma and tumor concentrations of platinum were similar for both formulations. During the first hour after injection of cisplatin nanocapsules, the platinum content of the kidney was 40% less than that after administering the free drug. Platinum from nanocapsules showed rapid and 4.5-fold higher accumulation in the liver compared with free cisplatin, and, at a slower rate, accumulation to a high concentration in the spleen. We conclude that the formulation of cisplatin nanocapsules inhibits the growth of OVCAR-3 xenografts in nude mice, albeit to a similar extent as free cisplatin. The results suggest that the antitumor efficacy of the nanocapsules could be improved by preventing rapid clearance from circulatio

Interactional implications of either/or-questions during telephone triage of callers with chest discomfort in out-of-hours primary care: A conversation analysis

Objective To explore the interactional implications of either/or-questions on the interaction between people who call out-of-hours services in primary care (OHS-PC) and triage nurses who use a decision support tool called the ‘Netherlands Triage Standard’ (NTS) during telephone triage. Methods A qualitative study of 68 triage conversations at six Dutch OHS-PC. Patients called the OHS-PC with symptoms, e.g. chest discomfort, suggestive of acute coronary syndrome. Using conversation analysis, we identified two categories of multiple-choice either/or-questions that indicated interactional difficulties, shown in hesitation markers within callers’ responses. Results Our analysis shows that interactional difficulties mainly arise when (i) questions are poorly designed by the triage nurse; or (ii) when the caller’s complaints are ambiguously presented reflecting patient’s difficulties to verbalize them (e.g. “not feeling well”). Conclusion The way NTS displays key diagnostic options encourages triage nurses to use multiple-choice either/or-questions. More awareness among triage nurses is needed on undesirable implications of either/or-questions on the interaction. Practice implications We recommend changing the NTS display of diagnostic options and to use questions with fewer options in order to decrease the chance of formulating ambiguous questions soliciting unclear responses. Furthermore, asking content questions when complaints are ambiguously formulated may specify the presentation of complaints

Interactional implications of either/or-questions during telephone triage of callers with chest discomfort in out-of-hours primary care: A conversation analysis

Objective To explore the interactional implications of either/or-questions on the interaction between people who call out-of-hours services in primary care (OHS-PC) and triage nurses who use a decision support tool called the ‘Netherlands Triage Standard’ (NTS) during telephone triage. Methods A qualitative study of 68 triage conversations at six Dutch OHS-PC. Patients called the OHS-PC with symptoms, e.g. chest discomfort, suggestive of acute coronary syndrome. Using conversation analysis, we identified two categories of multiple-choice either/or-questions that indicated interactional difficulties, shown in hesitation markers within callers’ responses. Results Our analysis shows that interactional difficulties mainly arise when (i) questions are poorly designed by the triage nurse; or (ii) when the caller’s complaints are ambiguously presented reflecting patient’s difficulties to verbalize them (e.g. “not feeling well”). Conclusion The way NTS displays key diagnostic options encourages triage nurses to use multiple-choice either/or-questions. More awareness among triage nurses is needed on undesirable implications of either/or-questions on the interaction. Practice implications We recommend changing the NTS display of diagnostic options and to use questions with fewer options in order to decrease the chance of formulating ambiguous questions soliciting unclear responses. Furthermore, asking content questions when complaints are ambiguously formulated may specify the presentation of complaints

Coordination of gaze and hand movements for tracking and tracing in 3D

Contains fulltext : 76777.pdf (publisher's version ) (Closed access)In this study we have investigated movements in three-dimensional space. Since most studies have investigated planar movements (like ellipses, cloverleaf shapes and “figure eights”) we have compared two generalizations of the two-thirds power law to three dimensions. In particular we have tested whether the two-thirds power law could be best described by tangential velocity and curvature in a plane (compatible with the idea of planar segmentation) or whether tangential velocity and curvature should be calculated in three dimensions. We defined total curvature in three dimensions as the square root of the sum of curvature squared and torsion squared. The results demonstrate that most of the variance is explained by tangential velocity and total curvature. This indicates that all three orthogonal components of movements in 3D are equally important and that movements are truly 3D and do not reflect a concatenation of 2D planar movement segments. In addition, we have studied the coordination of eye and hand movements in 3D by measuring binocular eye movements while subjects move the finger along a curved path. The results show that the directional component and finger position almost superimpose when subjects track a target moving in 3D. However, the vergence component of gaze leads finger position by about 250 msec. For drawing (tracing) the path of a visible 3D shape, the directional component of gaze leads finger position by about 225 msec, and the vergence component leads finger position by about 400 msec. These results are compatible with the idea that gaze leads hand position during drawing movement to assist prediction and planning of hand position in 3D space