Sexual health at 5 years after diagnosis of head and neck cancer.

PURPOSE: Sexual health (SH) is an emerging concern in the assessment of quality of life in patients surviving head and neck cancer (HNC). Using data from the French National Prospective VICAN Survey, this study aimed to assess SH deterioration five years after HNC diagnosis and related factors. METHODS: Using univariate and multivariate analyses were performed in the 241 HNC survivors. We studied the factors associated between the sexuality and intimate life of these patients with demographic and medical data from the national epidemiological survey VICAN 5. RESULTS: Sexuality and body image were altered in 78.8% for men and 79.2% for women. This alteration in sexual quality of life affects both men and women. Dissatisfaction with the frequency of sexual intercourse was associated with being treated with radiotherapy (p=0.024), as well as decrease of sexual desire in patients treated with chemotherapy (p=0.044). Fatigue (p=0.002), impaired physical health (p=0.049), and high disease stage (p=0.001) remained significantly associated, after multivariate analysis, with decreased sexual desire. Among these 3 factors negatively influencing sexual quality of life, two are treatable with appropriate management. CONCLUSION: Five years after the diagnosis of HNC, a decrease in sexuality and body image are frequent and significantly impact the quality of life of survivors. These observations imply an adaptation of the management of the professionals involved.

Accurate determination of the scattering length of metastable helium atoms using dark resonances between atoms and exotic molecules.

We present a new measurement of the s-wave scattering length a of spin-polarized helium atoms in the 2(3)S1 metastable state. Using two-photon photoassociation spectroscopy and dark resonances, we measure the energy E(nu)=14= -91.35+/- 0.06 MHz of the least-bound state nu = 14 in the interaction potential of the two atoms. We deduce a value of a=7.512+/-0.005 nm, which is at least 100 times more precise than the best previous determinations and is in disagreement with some of them. This experiment also demonstrates the possibility to create exotic molecules binding two metastable atoms with a lifetime of the order of 1 micros.

In vitro and in vivo evaluation of carbamazepine-PEG 6000 solid dispersions.

The present work extended previous physico-chemical investigations on the effects of solid dispersion on the solubility, the dissolution rate and the pharmacokinetic profile of carbamazepine. Solubility studies showed a linear increase in carbamazepine solubility with the increase of PEG 6000 concentration. There is no marked difference between physical mixtures and solid dispersions for the enhancement of carbamazepine solubility by PEG 6000. Less than 60% of pure carbamazepine was dissolved in 90 min. Physical mixtures (carbamazepine phase III) and solid dispersions (carbamazepine phase II) dissolution rates were higher in comparison of the parent drug. The dissolution of carbamazepine phase III was more pronounced than that evoked by the phase II. The dissolution profiles indicated that the percentage of the drug dissolved was dependent on the proportion of PEG 6000. In solid dispersions there was a remarkable enhancement in the dissolution rates of the drug in the vicinity of the eutectic composition as compared with those of corresponding physical mixtures. Hence, the optimum value for the solid dispersion was 80.5+/-1.7% of carbamazepine having dissolved within the first 10 min compared to 40+/-1% for the corresponding physical mixtures of the same composition. Statistical analysis of pharmacokinetic parameters confirmed that the carbamazepine:PEG 6000 binary systems displayed higher bioavailability of the drug than the pure carbamazepine. The area under the curve (AUC) values highlighted the evidence that only slight differences in the bioavailability of the drug occur between physical mixtures and solid dispersions prepared at the 80:20 and 50:50 drug:carrier compositions. However, the mean normalized plasma concentrations showed that standard error deviations are rather wide intervals for pure drug and physical mixtures in comparison to solid dispersions. One additional interesting point to consider is the disappearance of the multiple peaks on the individual kinetic curves of the 50:50 solid dispersion composition. Furthermore, our investigations have highlighted the interest of solid dispersions prepared at <>-eutectic composition as our preliminary data show that the plasma concentration (C(5h)) of the drug for the 15:85 dispersed sample containing 150 mg of carbamazepine is not significantly different from that obtained for the 50:50 dispersed sample containing 300 mg of the drug.

Polymorphism of sulfanilamide: (II) Stability hierarchy of alpha-, beta-, and gamma-forms from energy calculations by the atom-atom potential method and from the construction of the p, T phase diagram.

PURPOSE: Sulfanilamide trimorphism was chosen as a model system for comparison between stability hierarchies obtained from lattice-energy calculations with those deduced from the relative locations of the sublimation curves of polymorphs in the sulfanilamide p, T diagram. METHODS: The atom-atom potential (AAP) method was used for lattice-energy calculations. The p, T diagram was constructed by using crystallographic and thermodynamic data for alpha-, beta-, and gamma-forms, and by assigning the temperatures of the experimentally observed phase transitions to triple points involving the vapour phase. RESULTS: The hierarchy obtained with the AAP method (E alpha > or = E gamma > > E beta) differs only slightly from that deduced from the positions of the sublimation curves (p gamma > p alpha > p beta) in the p, T diagram at room temperature. No stable phase region was found for form alpha. Thus it is really monotropic. CONCLUSIONS: Provided enthalpy and volume changes at the transitions are accurate enough, it is possible to draw a p, T diagram that accounts for the stability hierarchy of polymorphs.

Thermodynamic study of sulfanilamide polymorphism: (I). Monotropy of the alpha-variety.

PURPOSE: Sulfanilamide was chosen as a model compound in order to gain insights on the stability hierarchy of drug polymorphs from structural and thermodynamic criteria. Despite numerous studies, disagreements remained on the reported enthalpies associated with the mutual interconvertions of the alpha-, beta-, and gamma-forms of sulfanilamide. Therefore, the unambiguous determination of these enthalpies was the purpose of this work. METHODS: Samples, free of solvent inclusions and made of only one form, were prepared, and analyzed combining X-ray powder diffraction and Differential Scanning Calorimetry (DSC). RESULTS: The enthalpy values associated with the alpha- to gamma- and beta- to gamma-transitions were found to be + 10.2 and + 10.9 J g-1, respectively. The calculated enthalpy of the beta- to alpha-transition is consistent with the experimental one (+ 1 J g-1). CONCLUSIONS: The monotropy of the alpha-form was ascertained over the explored temperature range at ordinary pressure.

Polymorphism of carbamazepine: solid-state studies on carbamazepine dihydrate.

Carbamazepine dihydrate (CBZ.2H2O) crystallizes in the orthorhombic system, space group Cmca or C2ca. The unit-cell constants are: a = 19.834(7), b = 4.945(1), c = 28.826(9) A. M = 272.27, V = 2827(2) A3, Z = 8, D = 1.280 g.cm-3. Indexed X-ray powerder diffraction pattern is given. Dehydration process was studied by means of thermogravimetry and differential thermal analysis: the enthalpy of dehydration was found at 51 kJ per H2O mole. Thermal dehydration leads to an (anhydrous) gamma-form of CBZ when processed in dry atmosphere. The presence of water vapour induces the formation of the beta-form of CBZ as well as the grinding of CBZ.2H2O at room temperature.