The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid dispersions of Itraconazole.

Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no Itraconazole peaks were visible; the polymer on the other hand appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly the physical mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.     

Radiation therapy of benign diseases. What's new eight years after?]

The authors present an update version of the indications for radiotherapy in the management of benign diseases. This is based on available randomized trials and recent international meetings. Validated indications remain the prevention of resected heterotopic bone ossifications, kelo?ds scars and pterygium and also treatment of arteriovenous malformations; the place of radiotherapy for malignant exophtalmia is more and more restricted. Randomized trials have demonstrated the efficacy of endobrachytherapy in the prevention of restenosis after angioplasty but the use of embedded stent has replaced this indication. Macular degeneration is no more an indication of radiotherapy. Quality requirements for radiotherapy are identical for benign or malignant indications.     

Comparison between ankle and toe index in patients with peripheral arterial disease

In contrast to the systolic blood pressure at the posterior tibial artery, the evaluation of pressure at the digital artery of the foot before and after exercise in patients with peripheral arterial disease is not well known. Twenty three patients with peripheral vascular disease were examined. The systolic pressure was measured by means of an ultrasound velocity detector at the brachial and posterior tibial artery. Digital artery pressure was determined with photoplethysmography. Pressures were measured before and within 5 and 10 minutes after a treadmill test. Ankle and toe index was calculated. At rest the toe index is lower than the ankle index and after a treadmill test the decrease in toe index occurs in parallel to the ankle index.     

Ultrastructure of aberrant serotonin-immunoreactive fibers in the caudate putamen complex of the aged rat

Degeneration of neurons in the central nervous system is associated with morphological changes. Previous observations made at the light microscopical level indicated degeneration of serotonin-immunoreactive (IR) fibers in the aged rat brain. In this study, a comparison at the ultrastructural level was made between serotonin-IR normal thin and aberrant swollen varicose fibers in the caudate-putamen complex of the aged rat. Ultrastructural features such as the size and content of the thin varicose fibers resembled those in the caudate-putamen complex of the young rat as reported by others. The aberrant profiles were swollen, reaching a size of 6 microns. Their vesicles varied in size and were no longer uniformly round. Moreover, distorted mitochondria and membrane-filled vacuolelike structures were a common feature of the aberrant profiles. These changes are indicative of a degenerative process and give further evidence that, whereas many serotonergic fibers are preserved at high age, other serotonergic fibers are degenerating in the caudate-putamen complex of the aged rat.     

VISUOMOTOR PERFORMANCE OF NORMAL AND CLUMSY CHILDREN. II: ARM-TRACKING WITH AND WITHOUT VISUAL FEEDBACK

Tracking performance was investigated in normal and clumsy children in two age-groups, six to seven and 10 to 11 years. Target signals moving unpredictably along a straight line had to be tracked, both with and without visual feedback. Performance was described in three ways: (1) performance in the low-frequency range (LF); (2) the delay between target signal and tracking movement (DL); and (3) a measure of tracking quality or over-all similarity in the shape of target signal and tracking movement (Q). Clumsy children in both age-groups had a lower tracking quality (Q) and longer delay (DL) than the normal children. Disturbances in the regulation of attention seemed to affect tracking performance, particularly of the six- to seven-year-old clumsy children. There was no significant difference between normal and clumsy children in the effect of visual feedback on tracking performance. This suggests that clumsiness is not linked to disturbance of integration of visual feedback information and motor processes.     

In vivo (31)P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice.

The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using (31)P magnetic resonance spectroscopy (MRS), fluorescence microscopy and two-dimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (P(i)/NTP) ratio increased rapidly as mean intervascular distances increased from 100 microm to 300 microm. Two morphometric parameters - the percentage of intervascular distances larger than 200 microm (ivd200) and the non-perfused area fraction at a distance larger than 100 microm from a nearest perfused vessel (area100), - were deduced from these experiments and related to the P(i)/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the P(i)/NTP ratio increased linearly with the percentage of ivd200 and the area100.     

Treatment of nasopharyngeal inlet stenosis following uvulopalatopharyngoplasty with the co2 laser

This report looks at outpatient treatment of nasopharyngeal inlet stenosis, a more commonly seen postoperative complication of uvulopalatopharyngoplasty (UPPP). It does not study the effectiveness of the UPPP for treatment of obstructive sleep apnea syndrome (OSAS). The authors evaluated six patients who had a UPPP for OSAS, all of whom developed stenosis in the nasopharyngeal inlet ranging from 14 mm to complete closure. Two patients had failed rotation flap repairs. The carbon dioxide laser was used to treat these patients in the office under a local anesthesia in a staged manner. We now have patients from 3 months to 12 months follow-up who have had stenosis treated successfully. We believe that the postoperative complication of nasopharyngeal inlet stenosis after UPPP can be treated in a safe and cost-effective manner in the office setting.