Amphiphilic association systems for Amphotericin B delivery

The present study describes the production and characterization of amphiphilic association systems for Amphotericin B (AMB). In particular, three different classes of microemulsions and different monoglyceride–water systems were produced. Formulations were characterized for macroscopic aspect, pH, rheology, mean size and size distribution, both in the absence and in the presence of AMB.

AMB solubility was investigated in the different formulations by HPLC studies. The formulations increased AMB solubility up to 20-fold with respect to the single oil and aqueous phases employed for microemulsion production.

AMB diffusion studies from two microemulsions taken as models were performed in a Franz cell system using a nylon membrane.

The physical and chemical stability of AMB-containing amphiphilic association systems were investigated for three months after production. For physical stability studies both the macroscopic aspect, droplet mean size and dimensional distribution were analysed. For chemical stability studies, the AMB content of the formulations was quantified by HPLC analysis. Microemulsions and monoglyceride–water systems were free from phase separation for up to three months and in some cases the AMB content was unchanged even after three months.     

Effects of High Hydrostatic Pressure on Several Sensitive Therapeutic Molecules and a Soft Nanodispersed Drug Delivery System

PURPOSE: According to the development in the last decade of industrial processes using high hydrostatic pressure (HHP) for preservation of several commercial food products, novel sterilization or decontamination processes for pharmaceutical products could be conceivable. The aim of this work is to evaluate the effects of HHP on the integrity of insulin and heparin solutions, suspension of monoclonal antibodies and Spherulites. METHODS: High performance liquid chromatography, thin layer chromatography, capillary electrophoresis assays, ELISA tests, laser granulometry and spectrophotometry analyses have been performed to compare HHP treated drugs (in a domain of pressure and temperature ranging respectively from 20 up to 500 MPa and from 20 degrees C up to 37 degrees C) vs. untreated ones. RESULTS: No difference has been detected except for monoclonal antibodies that are altered above 500 MPa. CONCLUSIONS: The structure integrity of sensitive molecule due to the small energy involved by HHP and the development of industrial plants (intended for the decontamination of food products) confer to this technology the potential of a new method for sterilization of fragile drugs and an original alternative to aseptic processes and sterilizing filtration.     

Critical care outreach services and early warning scoring systems: a review of the literature

AIM: The aim of this paper is to explore the literature relating to critical care outreach services and the use of early warning scoring systems to detect developing critical illness. BACKGROUND: Several studies have identified how suboptimal care may contribute to physiological deterioration of patients with major consequences on morbidity, mortality and requirement for intensive care. In a review of adult critical care services, the Department of Health (DOH) (England) recommended in 2000 that outreach services be established to avert admissions to Intensive Care, to enable discharges and to share critical care skills. METHODS: A literature search was carried out of the BIOMED and NESLI databases using the key words "outreach", "early warning signs/systems" and "suboptimal care". The literature review was limited to the past 10 years, and primary research articles of particular relevance were included in the review. The literature is examined within the context of recent findings relating to the provision of suboptimal care within general wards prior to cardiac arrest and/or admission to Intensive Care Units (ICU), and subsequent government initiatives. Discussion. The discussion explores the potential contribution of critical care outreach services and early warning scoring systems to the care of patients in acute general wards, including the role that education can have in developing the knowledge base and assessment skills of ward nurses. CONCLUSION: The paper concludes that further study is required to evaluate the effectiveness of critical care outreach services and early warning scoring systems, and that ward staff need to be educated to identify those patients at risk of developing critical illness. Finally, it is suggested that nurses' decision-making in relation to calling the outreach team requires further investigation.     

Intra-operative tachycardia and peri-operative outcome

Background Intra-operative tachycardia is a common adverse event, often recorded as an indicator for process quality in quality assurance projects in anaesthesia.Methods This retrospective study is based on data sets of 28,065 patients recorded with a computerised anaesthesia record-keeping system from 23 February 1999 to 31 December 2000 at a tertiary care university hospital. Cases were defined as patients with intra-operative tachycardia; references were automatically selected according to matching variables (high-risk surgery, severe congestive heart failure, severe coronary artery disease, significant carotid artery stenosis and/or history of stroke, renal failure, diabetes mellitus and urgency of surgery) in a stepwise fashion. Main outcome measures were hospital mortality, admission to the intensive care unit (ICU) and prolonged hospital stay. Differences in outcome measures between the matched pairs were assessed by univariate analysis. Stepwise regression models were developed to predict the impact of intra-operative tachycardia on the different outcome measures.Results In our study 474 patients (1.7%) were found to have had intra-operative tachycardia. Matching was successful for 99.4% of the cases, leading to 471 cases and references. The crude mortality rates for the cases and matched references were 5.5% and 2.5%, respectively (P=0.020). Of all case patients, 22.3% were treated in an ICU, compared to 11.0% of the matched references (P=0.001). Hospital stay was prolonged in 25.1% of the patients with tachycardia compared to 15.1% of the matched references (P=0.001).Conclusions In this study, patients with intra-operative tachycardia who were undergoing non-cardiac surgery had a greater peri-operative risk, leading to increased mortality, greater frequency of admission to an ICU and prolonged hospital stay.Financial support for this study was provided in part by a grant from IMESO GmbH, Hüttenberg, Germany. The founding agreement ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the reportM. B. is a partner of the IMESO GmbH (Hüttenberg, Germany) and employee of the University Hospital of Giessen. None of the other authors or participants has any financial interest in the subject matter, materials, or equipment discussed, or in competing materialsA part of the results has been presented as a lecture at the 50th German Congress of Anaesthesiology (DAC 2003, 9–12 April) in Munich     

Information Technology in Emergency Medicine Residency–Affiliated Emergency Departments

OBJECTIVES: To describe acquisition and implementation of information technology (IT) in U.S. emergency medicine (EM) residency-affiliated emergency departments (EDs), including automatic medication error checking. METHODS: This was a survey of all U.S. EM residencies active in September 2000. Respondents specified whether specific IT tools had been "acquired" and "implemented fully." EDs were categorized according to primary versus affiliated training site, trauma level, and census. Numbers of "yes" responses were compared according to ED type (Kruskal-Wallis test, p < or = 0.05 significant). RESULTS: Of 121 residency programs, data were obtained from 93 (77%) for a total of 149 EDs. The percentages of EDs that reported full implementation for each technology are as follows: medication error checking, 7%; medication order entry, 18%; nonmedication orders, 7%; clinical documentation, 21%; old electrocardiograms, 62%; laboratory results, 84%; radiography order entry, 62%; image retrieval, 29%; radiologists' interpretations, 67%; cardiology reports, 62%; pathology reports, 70%; surgical reports/dictations, 60%; triage, 34%; tracking, 46%; electronic reference materials, 56%; registration, 84%; accounts, 72%; patient management software package, 20%; voice recognition, 7%. Trauma centers reported more IT tools than nontrauma centers (p = 0.01), and primary training sites reported fewer IT tools than affiliated EDs (p = 0.027). CONCLUSIONS: Incorporation of IT is not uniform in EDs where EM residents train. Acquisition of effective IT tools varies, and implementation lags behind acquisition. Fully implemented IT for medication error checking was reported in 7% of EDs; an additional 12% had acquired IT without implementing it fully.     

Working more productively: tools for administrative data

OBJECTIVE: This paper describes a web-based resource (http://www.umanitoba.ca/centres/mchp/concept/) that contains a series of tools for working with administrative data. This work in knowledge management represents an effort to document, find, and transfer concepts and techniques, both within the local research group and to a more broadly defined user community. Concepts and associated computer programs are made as "modular" as possible to facilitate easy transfer from one project to another. STUDY SETTING/DATA SOURCES: Tools to work with a registry, longitudinal administrative data, and special files (survey and clinical) from the Province of Manitoba, Canada in the 1990-2003 period. DATA COLLECTION: Literature review and analyses of web site utilization were used to generate the findings. PRINCIPAL FINDINGS: The Internet-based Concept Dictionary and SAS macros developed in Manitoba are being used in a growing number of research centers. Nearly 32,000 hits from more than 10,200 hosts in a recent month demonstrate broad interest in the Concept Dictionary. CONCLUSIONS: The tools, taken together, make up a knowledge repository and research production system that aid local work and have great potential internationally. Modular software provides considerable efficiency. The merging of documentation and researcher-to-researcher dissemination keeps costs manageable.     

CDKN2A/p16 in ependymomas

Sixteen cases of ependymoma were studied for CDKN2A/p16 inactivation by immunohistochemistry using a p16 monoclonal antibody, by homozygous deletion (HD) assay and 5CpG promoter methylation assay (methylation-specific PCR). Three out of 16 cases were p16 immuno-negative: two corresponded to grade II ependymomas and one to grade III. The latter ependymoma, characterized by a high Ki-67/MIB-1 LI, was the only one of the whole series to show CDKN2A HD. No promoter methylation was found in the two immuno-negative cases without CDKN2A HD. Alternative mechanisms, such as point mutations or alterations in p16 post-translational regulation, may be responsible for p16 inactivation. Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas.Amplification of CCND1 and CDK4, p27/Kip1 degradation and TP53 mutations were previously studied by other authors and were demonstrated not to correlate with anaplasia. Up to date, molecular genetic studies have not been useful in recognizing the anaplastic variant in ependymomas.     

Skin occlusion and irritant and allergic contact dermatitis: an overview

Occlusion, widely used to enhance percutaneous absorption of drugs, also increases penetration of other chemicals and antigens, and hence may exacerbate irritant and allergic contact dermatitis. This overview summarizes the adverse effects of occlusion.     

Current status of positron emission tomography in oncology

Positron emission tomography (PET) has emerged as a powerful diagnostic tool in oncology patients. There is evidence of the superior utility over conventional imaging methods of the principal PET tracer 18F-fluoro-2-deoxy-glucose in the staging of a range of cancers and monitoring disease recurrence, as well as changing patient management to more appropriate therapy. The methods for evaluating the evidence for PET remain complex, particularly as the standard evidence-based approach of randomized controlled trials is not generally applicable to imaging technologies. PET has the potential to dramatically improve our ability to manage patients with cancer and is also making major contributions to the development of new therapies.