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.     

Assessment of alcohol and other drug use behaviors in health professions students.

Alcohol and other drug (AOD) use behaviors of health professions students (HPS) were assessed by surveying both university-based HPS and other nursing programs in a Midwestern state in 1999. Response was 2,646 (56.4%) of surveyed students. Family history of alcohol-related and drug-related problems were reported by 39.8% and 13.9%, respectively, with 42.6% of respondents reporting one or both. Among nursing respondents, 48.1%, 19.2% and 51.1%, respectively, reported family problems with alcohol, drugs, or one or both. Past-year alcohol use was comparable to undergraduate college students (UCS) nationally (83%); heavy drinking, tobacco and recreational drug use by HPS were lower. Past year drug use was highest among medical students. Marijuana was the predominant illicit drug; medical students and males most often reported use. Health professions educational systems should proactively address student AOD prevention, education and assistance needs.     

Standardized quick en bloc technique for procurement of cadaveric liver grafts for pediatric liver transplantation

This paper describes a quick procedure for cadaveric liver graft retrieval during multiple organ harvesting. The technique is based on minimal preliminary dissection, absence of in situ direct portal perfusion, and en bloc removal of the liver and pancreas, with an aortic patch encompassing the coeliac trunk and superior mesenteric artery. The results of 110 pediatric liver transplantations with 109 organs harvested using this technique are reported. There were no graft harvesting injuries. The liver graft primary nonfunction rate was 4.5% (5/110). The 3-month retransplantation rate was 10%. The actual patient survival rates were 93% at 3 months and 90% at 1 year; actual graft survival rates were 85.5% and 78%, respectively. The technique described was at least as safe as conventional procedures. A major advantage of the procedure is its flexibility, which allows for the easily combined procurement of other organs (whole pancreas and intestine).     

Neurotropic melanoma with prominent melanization

Neurotropic melanoma has generally been described in the context of desmoplastic melanoma. The vast majority of melanomas displaying neurotropism contain relatively little or no melanin. Herein, we report an unusual case of neurotropic melanoma with prominent melanin content. The patient developed a tumor notable For pagetoid (superficial spreading) melanoma with partial regression and a deep component characterized by perineurial aggregates of melanophages and intraneural infiltration by melanoma cells. This case serves to alert dermatopathologists to the fact that the spectrum of neurotropic melanoma includes tumors with perineurial aggregates of pigment-containing cells.     

A column study of the biological mobilization and speciation of cadmium in soil

An acid sandy loam soil was used in a column study to determine the effect of microorganisms on Cd mobilization in soil and its speciation in column leachates. Non-sterile and sterile (gamma-irradiated) soil columns were initially treated with 90 mg of Cd (NO₃)₂, and approximately 20 mg of added Cd was retained in the soil. Soil columns were subsequently eluted with a sterile nutrient medium for a period of up to 38 days. Non-sterile and sterile soil columns leached with sterile deionized water served as unsupplemented controls. During a leaching period of 38 days, about 36% of the sorbed Cd in soil was mobilized in the presence of microorganisms and nutrients, while less than 16% of the Cd was released from the sterile and unsupplemented soil controls. To characterize the chemical form of the microbially mobilized Cd, the leachates were analyzed by gel filtration chromatography. In this study, 86% to 93% of the mobilized Cd was associated with the low molecular weight inorganic and organic fraction, while the remainder was eluted in the high molecular weight range. The low molecular weight Cd fractions were further examined by solid phase extraction (C₁₈ Sep-Pak), and cation-exchange chromatography. From the various analyses, it was concluded that a significant amount of Cd existed as a hydrophilic organic complex, and the remainder as cationic Cd. Soil microorganisms were mostly responsible for the transformation of Cd in soil and its subsequent mobilization.     

Clinical pharmacokinetics of Neoral in pediatric recipients of primary liver transplants

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i. v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22 % and 21 % for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability. Received: 29 November 1996 Received after revision: 10 April 1997 Accepted: 15 May 1997     

BUILDING COMMUNITY: Developing Skills for Interprofessional Health Professions Education and Relationship-Centered Care

In 1995, the National League for Nursing commissioned a Panel on Interdisciplinary/Transdisciplinary Education. The focus of the Panel's work was to examine educational issues that transcend the health professions and to make recommendations for future implementation of an interdisciplinary approach to addressing them. This article is being simultaneously published by several professional journals. The goal is to seek as much feedback as possible.