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.     

A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake

Previous work has reported that the 5-hydroxytryptamine (5-HT)_1A agonist, 8-hydroxy 2-(di-n-propylamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotransmission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol intake. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6–250 µg/kg) and by assessing concomitant changes in behaviour. Low doses of 8-OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Suppression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and non-fluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat depending on the dose used.     

Polymères thiocarboxyliques, 5. Synthèse de poly(oxyéthylène)s à fonction dithioester terminale. Application au traitement de cellules d'électrophorèse

Poly(oxyethylene)s with dithioster end groups were obtained from mono- and dihydroxyl terminated commercial polymers by reaction with dimethyl chloroacetamide, subsequent thionation of the amide group, and usual conversion of the thioamides into the dithioesters 14, 15 and 20, 21 . The best results were obtained in the syntheses of the S-carboxymethyl dithioesters ( 15 and 21 ). The resulting reactive poly(oxyethylene)s were grafted upon silica tubes and electrophoresis cells, previously activated by aminopropylsilanization. These graftings result in lowering of the surface potential of the tubes and in suppression of the electro-osmosis flow in an electrophoresis cell tested with a TiO₂ standard sample.     

Successful treatment of acute head and neck dog bite wounds without antibiotics

Dog bites continue to be the most common bite injury in the United States. We previously reported a series of 61 patients with 215 dog bite wounds. Of these, 55 patients had 188 dog bite wounds of the head and neck area which were treated with copious saline pressure irrigation, meticulous wound and wound edge debridement, repeated copious saline pressure irrigation, adequate antibiotic coverage, wound closure, and close postoperative monitoring. A wound infection rate of .53% and a patient infection rate of 1.8% were obtained using this protocol. Our present study uses the same protocol with the exclusion of antibiotic coverage. Our series of 49 patients with 145 head and neck wounds reveals a wound infection rate of 1.4% and a patient infection rate of 4%. This is not statistically significantly different from the outcome of the previous study.     

Implementation of a Patient Charting System: Challenges Encountered and Tactics Adopted in a Burn Center

The rapid movement of information technologies into health care organizations has raised managerial concern regarding the capability of today's institutions to satisfactorily manage their introduction. Indeed, several health care institutions have consumed huge amounts of money and frustrated countless people in wasted information systems implementation efforts. Unfortunately, there are no easy answers as to why so many health informatics projects are not more successful. In this light, the aim of this study is to provide a deeper understanding of how clinical information systems are being implemented by emphasizing research efforts on the dynamic nature of the process, that is, the “how” and “why” of what happened. Using a case study methodology, we examined the implementation of a patient charting system in the Burn Center of a large, not-for-profit, teaching hospital. Based on an in-depth examination of this implementation, several insights are offered to those who have responsibility for managing complex and risky clinical information system implementation projects.     

Staged bilateral thalamic electrode implantation utilizing frameless stereotactic guidance.

Deep brain stimulation (DBS) for medically intractable Parkinson's disease (PD) is well established, but carries the inconveniences of frame-based neurosurgery. Previous reports have demonstrated that ventricular shunt placement and some functional procedures can be accurately performed using frameless stereotaxy. We present a report indicating that staged deep brain electrode placement can be accurate and efficacious using a frameless skull-mounted guide.