Structural properties of magnesium stearate pseudopolymorphs: effect of temperature

A thorough review of the relevant literature reveals that the interaction between water vapour and magnesium stearate, in contrast to many other metal soaps, is not properly understood. The structural modifications associated with the up-take or loss of water of vegetable-derived commercial magnesium stearate powders exposed to humid air or vacuum at room temperature are investigated using standard powder X-ray diffractometry. It is found that in such conditions magnesium stearate reacts reversibly with the vapour phase with structural consequences very similar to the high temperature transition between the crystalline and rotator phases of other anhydrous metal soaps. When temperature is increased under dry nitrogen the diffraction band characteristic of the rotator phase shifts towards higher angle values and the corresponding lattice spacing increases at the rate of 6.9x10(-4)C(-1). Melting takes place gradually above 100 degrees C as revealed by the collapse of the diffraction band and the growth of the broader diffusion band characteristic of the liquid state. Full clarification of the structure of the hydrated and dried phases proves impossible based on powder diffraction spectra obtained with conventional high resolution X-ray diffraction equipment.     

The transferrin receptor: a potential molecular imaging marker for human cancer

Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR) has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI) probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.     

Which medico-economic approaches must be taken to evaluate the impact of costly molecules in oncology? The model of Herceptin in the breast metastatic cancer

In an era where health care expenditure control is a necessity, weighing a new treatment's cost against its added benefits is of crucial importance. These medico-economic analyses may be planned for the evaluation of new molecules in their daily use. Different methods may be used. The medico-economic evaluation of a drug can be performed with the use of clinical studies or modelization techniques. "Clinical studies" include the following methods: randomized trials, so-called "experimental", non-randomized studies, and observational studies. This classification follows a downward evolution of both the investigator's intervention power and the level of proof. Finally, modelization is becoming a commonly used tool. Randomized trials are the "gold standard" but the other, more pragmatic study types, providing a lesser degree of proof can complete the evaluation of a new molecule. One must find the best compromise between the study's objectives and the study type.     

CT dacryography without selective lacrimal duct catheterization: review of 39 patients

OBJECTIVES: Dacryographies and CT dacryographies are usually performed after catheterization of a lacrimal canaliculus. We evaluated the quality of opacification on CT scan after simple instillation of contrast medium, without any catheterization. PATIENTS AND METHODS: 39 patients (78 nasolacrimal ducts) were examined for lacrimal pathways obstruction by CT scan after instillation of diluted contrast medium. Additional CT scan imaging was performed after catheterization when the first study did not provide adequate opacification. RESULTS: CT dacryography after instillation is a well tolerated technique. In our study, it allowed detection of all pathologic lacrimal ducts; 7 normal lacrimal pathways (after catheterization) were not opacified after instillation (false positives). The sensitivity of the method was 100%, its specificity 84%. CONCLUSION: CT dacryography after instillation is a physiologic, simple and sensitive method to evaluate lacrimal obstruction. We propose it as a first step, catheterization being used only in the absence of opacification after instillation.     

Sequence dependent instability of mononucleotide microsatellites in cultured mismatch repair proficient and deficient mammalian cells

We have measured the mutation rates of G(17) and A(17) repeat sequences in cultured mammalian cells with and without mismatch repair and have compared these rates to those of a (CA)(17) repeat sequence. Plasmids containing microsatellites that disrupt the reading frame of a downstream neomycin-resistance gene were introduced into the cells by transfection and revertants were selected using the neomycin analog G418. Comparison of mutation rates within cell lines showed that the mutation rates of A(17) and (CA)(17) sequences were similar in the mismatch repair proficient cells, but the mutation rate of G(17) was significantly higher than that of either A(17) or (CA)(17). In the mismatch repair deficient cells, the G(17) and (CA)(17) mutation rates were similar and were significantly higher than the A(17) rate. PCR analysis of the mutants showed that 1 bp insertions predominated in both mononucleotide repeats in the mismatch repair proficient cells; in mismatch repair deficient cells, 2 bp deletions were the most common mutation in the A(17) sequence, but 1 bp insertions and 2 bp deletions were equally represented in the G(17) sequence. These results indicate that a G(17) repeat is less stable than an A(17) repeat in both mismatch repair proficient and mismatch repair deficient mammalian cells. This observation implies that the replication fidelity is lower in G(17) repeats.     

Functional in vivo characterization of human monoclonal anti-D in NOD-scid mice

The prophylaxis of the hemolytic disease of the newborn requires significant amounts of plasma-derived polyclonal human anti-D. Because of procurement problems, there is a growing interest in replacing plasma-derived anti-D by in vitro-produced human monoclonal anti-D. Hundreds of monoclonal anti-D have been prepared, but the selection of the most potent for in vivo use is difficult because it cannot be predicted by in vitro characterization. This study evaluated the possibility of using nonobese diabetic/severe combined immunodeficient (NOD-scid) mice for the in vivo evaluation of human monoclonal anti-D. Human red blood cells (RBCs) were found to circulate normally in the blood of NOD-scid mice previously injected with a physiologic amount of human immunoglobulin G (10 mg). The addition of a small amount of anti-D (1 to 5 microg) resulted in the clearance of Rh D(+) RBCs within 4 hours. The comparative testing of 8 monoclonal anti-Ds showed a wide range of potency (15% to 87%) relative to plasma-derived polyclonal anti-D. There was no strong correlation between the in vivo potency index and the immunoglobulin G isotype, affinity, or fine specificity of the antibodies. These results show the usefulness of NOD-scid mice for the initial in vivo screening of human monoclonal anti-D before testing the most active antibodies in clinical trials done in human volunteers.     

An evaluation of psychometric properties of the client's questionnaire of the Wisconsin Quality of Life Index-Canadian version (CaW-QLI)

Psychometric properties of Client's questionnaire from the Canadian version of the Wisconsin Quality of Life-Index (CaW-QLI) were assessed with two groups, 89 English (E) and 94 French (F) individuals with schizophrenia or schizoaffective disorder. Sub-samples of 40E and 36F were re-interviewed within a 2-week period. Spearman correlations-SC between each domain and CaW-QLI global Score ranged from 0.39 to 0.76, while inter-domain correlations were low, confirming the multidimensional properties of the scale. Cronbach's (internal consistency) were 0.78(E) and 0.70(F) for the CaW-QLI global scores and, from 0.45 to 0.88 among seven of eight domains. Test–retest (Concordance Correlation Coefficient-CCC) ranged from 0.36 to 0.80 among the domains, and from 0.80(E) and 0.85(F) between CaW-QLI global scores. Regarding convergent validity, SC between CaW-QLI global score and Spitzer's QOL-Index were 0.72(E) and 0.58(F). As hypothesized, there were higher correlations between CaW-QLI global scores (E and F) and SF-36 scales related to mental health than those related to physical health. Minor changes in the scoring are proposed to enhance face and content validity.     

Clinical implementation of wedge filter optimization in three-dimensional radiotherapy treatment planning.

BACKGROUND AND PURPOSE: To describe a wedge filter optimization technique which automatically chooses the beam weights and wedge filters and to demonstrate the implementation of the algorithm in clinical three-dimensional (3D) radiotherapy treatment planning. MATERIAL AND METHODS: Given the incident directions and beam energies of J beams, the dose distribution is a function of the beam weights, wedge angles, and wedge orientations. Instead of decomposing an incident field into a superposition of an open and two nominal wedged fields and then optimizing their weights, the algorithm optimizes the objective function with respect to the beam weights, wedge angles and wedge orientations directly. A salient feature of the algorithm is that no planner intervention was required in the selection of wedge filters during the optimization process. A dose-based objective function which incorporated the relative importance of structures was adopted in this work. The objective function was minimized by the method of simulated annealing. The technique was demonstrated by using a phantom study and two clinical cases. RESULTS: For the phantom case, the classical wedge pair result was obtained, providing a useful test of the algorithm. Dose distributions and dose volume histograms for the target and surrounding organs were presented for the two clinical cases. It was also shown that dose homogeneity to the target could be compromised by increasing the relative importance factors to the surrounding organs. CONCLUSIONS: A 3D wedge filter optimization algorithm has been developed. The technique has the potential to fully automate the 3D radiotherapy treatment planning process. In addition, treatment planning time and efforts were significantly reduced.