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Experimental assessment of electromigration properties of background electrolytes in capillary zone electrophoresis.

Electromigration dispersion (EMD) properties of background electrolytes (BGEs) used in capillary zone electrophoresis (CZE) are of key importance for the success of an analysis. The knowledge of these properties may serve well for the prediction of the asymmetry of peaks of analytes, for the prediction of unsafe regions where a strong interference of system zones may be expected, and for the selection of optimum conditions where the analytes of interest may give sharp and practically symmetric peaks. Present theories enable one to calculate and predict EMD properties of many BGEs but there is also a lot of BGEs that are beyond the present theoretical models as far as their composition and equilibria involved are considered. This contribution brings a method for assessment of EMD properties of any BGE from easily accessible experimental data. The method proposed is illustrated by model examples both for cationic and anionic separations. Imidazole acetate, histamine acetate, and histidine acetate served as model BGEs for cationic separations; as the model BGE for anionic separations, Tris-borate and sodium-borate BGEs have been selected since these buffers are frequently used and borate is well-known for its complexing equilibria in aqueous solutions.

Acetates↗

Pharmacokinetic applications of capillary electrophoresis: a review on recent progress.

This article covers recent publications from 2003 to 2005 on the subject of pharmacokinetic applications of CE. Many analytical methods were validated and more importantly, they were shown to have sufficient sensitivities to access pharmacokinetic data on different models. Because of unique advantages, such as simplified sample preparation methods, small sample amount required, high separation power, and speedy analysis, CE-based assays were found to gain popularity not only as a second method but also as a major method for many pharmacokinetic studies.

Animals↗

Twenty-first century learning in school systems: the case of the Metropolitan School District of Lawrence Township, Indianapolis, Indiana.

To empower students with skills such as information and technological literacy, global awareness and cultural competence, self-direction, and sound reasoning, teachers must master these skills themselves. This chapter examines how the Digital Age Literacy Initiative of the Metropolitan School District of Lawrence Township in Indianapolis, Indiana, which is funded by the Lilly Endowment, incorporated twenty-first century learning through a systemic approach involving teacher training and the use of data. The authors explain the district's content, process, and context goals toward accomplishing its mission of empowering students with the necessary twenty-first century skills to succeed in the digital age. The district places a strong emphasis on professional development for teachers. To support the necessary teacher learning and therefore sustain the work of the initiative, the district has adopted action research, self-assessment, and an online professional development network. To support teachers in implementing new strategies, master teachers serve as digital age literacy coaches. The chapter discusses the initiative's focus on evidence of progress. Through a partnership with the Metiri Group of California, the district has built a range of assessments including online inventories and twenty-first century skill rubrics. For example, the Mankato Survey collected teacher and student data around access, ability, and use of technology in the classroom in 2001 and then in 2004. This research showed significant gains in some technologies across all grade levels and consistent gains in nearly all technologies for middle and high school students. As it moves into the next phase of implementing the Digital Age Literacy Initiative, the district embraces the systemic shifts in school culture necessary to institutionalize twenty-first century learning.

Adolescent↗

Electron crystallographic analysis of a polysaccharide structure--direct phase determination and model refinement for mannan I.

Three-dimensional electron diffraction intensity data from the polysaccharide mannan I, previously published by H. Chanzy et al. (1987; Macromolecules 20, 2407-2413), were used for an ab initio structure determination. The space group is P2(1)2(1)2(1), with unit cell constants a = 8.92, b = 7.21, c = 10.27 A. After determination of crystallographic phases by evaluation of triplet and quartet structure invariants, 41 values were assigned to 58 unique reflections, 11 linked through a single algebraic unknown a. Two potential maps corresponding to two possible values of a were calculated by a Fourier transformation of the limited 3D data set, combining the phase terms with measured structure factor magnitudes. Either map allowed a monomer model, taken from the crystal structure of methyl alpha-D-mannopyranoside, to be fit very well in the xy plane, since 24 of 34 hk0 data are accessed by the direct phase determination. Although the limited goniometer tilt range is responsible for an incomplete sampling of the 3D reciprocal net, resulting in a series termination effect, a choice could be made between the two possible maps (permuting the unknown phase term a = +/- pi/2), since only one is a good envelope to the monomer structure in the chain direction. After optimizing linkage geometry, a structure that is very close to the initial determination was derived based on a conformational refinement.

Carbohydrate Conformation↗

Neurotropism and retrograde axonal transport of a canine adenoviral vector: a tool for targeting key structures undergoing neurodegenerative processes.

Viral tropism refers to the ability of a virus to selectively infect a given subset of cells. It relies on a variety of viral and host determinants that entail virus binding and entry into target cells, in addition to the presence of genetic elements that allow or enhance viral gene expression in a specific manner. Here we report the results of neuroanatomical studies in rat brains injected in different cerebral structures with vectors derived from the canine adenovirus type 2 (CAV2), whose natural target is the respiratory epithelium. Control animals injected with vectors derived from the human adenovirus type 5 (Ad5) displayed the previously documented pattern of gene transfer into both neurons and glial cells. Injection of CAV2 vectors resulted in selective transduction of neuronal cells. Cy3-labeled CAV2 particles allowed us to establish the high affinity of this vector for neuronal processes in vitro and their rapid uptake and retrograde axonal transport in vivo. After intrahippocampal injections, labeled particles were found, within 1 hour, closely associated to the nuclei of the neurons in layer II of the entorhinal cortex. Injections into the striatum resulted in a massive transduction of dopaminergic neurons in the substantia nigra compacta. The high efficiency with which CAV2 vectors are retrogradely transported opens the possibility of targeting a transgene to neuron populations remote from the injection site and difficult to access. Our data support the possibility to target key structures undergoing a degenerative process: the enthorhinal cortex, which is affected first in Alzheimer's disease; and the substantia nigra compacta, which undergoes degeneration in Parkinson's disease.

Adenoviridae↗

A knowledge-based alarm system for monitoring cardiac operated patients--technical construction and evaluation.

A knowledge-based alarm system for intensive care monitoring was designed, built, tested on-line, and evaluated. The system is a functional prototype of a highly specific patient monitor providing alarms on hypovolemia, hyperdynamic state, left ventricular failure and hypoventilation. These intelligent alarm functions aim to maintain the quality of patient monitoring even if nurses' attention is temporarily reduced or focused elsewhere. The alarm system has an electronic access to data available in a multichannel patient monitor and the patient data management system of the intensive care unit. Median filtering, trend estimation, and rule-based reasoning are applied when processing the measured variables and estimating the patient's state.

Artificial Intelligence↗

Computer-based inpatient medical record in colorectal surgery: pilot study.

PURPOSE: Clinical guidelines and care maps are important tools for improving quality of care and reducing costs. However, problems of quantity, quality, and accessibility of data recorded in the inpatient medical record have not been solved by the implementation of clinical pathways. Variance or "charting by exception" improves legibility, in part. The aim of the present study was to design a computer-based medical record on a database platform to provide legible notes within a clinical guideline and variance charting framework. METHODS: A computerized database program was written, integrating pre-established clinical guidelines into a user-friendly interface according to modification of the charting by exception principles. Patient care guidelines were provided for each postoperative day. After an initial debugging process by entering data from old charts of patients, the software was installed and its function was evaluated on selected patients. The charting time was compared with the standard charting method. Functionality and user friendliness were assessed. RESULTS: After a brief introduction of ten minutes, all users were able to use the software without difficulties. It was found to be functional and user friendly. The charting time was shorter for the computer-based inpatient medical record compared with the charting time of the standard charts. Because all daily notes were printed on standardized forms on a laser printer, legibility was excellent. CONCLUSIONS: The results of this pilot study suggest that the idea of computer-based inpatient medical record integrating an on-line inpatient medical record in a database platform is feasible. Further development and integration with other hospital information systems and the other health-care providers is required.

Colectomy↗

Renal transplantation: experience in Australia.

OBJECTIVE: Outcome of renal transplantation in children under the age of 15 years, who received a renal allograft at The New Children's Hospital between January 1983 to June 1997 was studied. METHODS: Retrospective review of patients records and access to data collected from Renal Registry of the Hospital. 64 renal transplants were undertaken in 57 children during this period. Prednisone and Azathioprine were the mainstay of the immunosuppressive regimen up to 1983, then Cyclosporine A was introduced. Median age of first grafts was 10 years (range 1 month-14 years). There were 41 living related and 23 cadaveric grafts. 37 (64%) children had a congenital disorder as the cause of renal failure. Among them 14 (37%) had congenital renal dysplasia/hypoplasia, 20 (36%) had primary glomerular disorder as the cause of renal failure. RESULTS: Survival analysis at 12 month, 5 yr and 10 yr showed functioning grafts in 85%, 67% and 64% case respectively. Longest surviving transplant was 14 years. 6 children had died. Cumulative patient survival was 92.9% at 1 year, 90% at 5 year and 87% at 10 year. Sixteen primary grafts were lost with most common cause being chronic rejection accounting for 68% of all transplant lost. Recurrence of primary disease was the second most common cause of graft failure. There was one malignancy in this series. 25 of the 29 children of school age with functioning transplant attended school full time in a class appropriate for their age and nine of 13 years older patients were working full time, two worked part time. CONCLUSION: Renal transplantation is a successful treatment of end stage renal failure in children with high survival and normally functioning life. Chronic rejection remains a major cause of graft loss.

Adolescent↗

Network system: the integrated picture archiving and communication system with the hospital information system.

We describe the outline of Hokkaido University picture archiving and communication system (HU-PACS) and its network functions. HU-PACS processes 0.5 Gbytes of images daily through 10 acquisition devices. Functional integration of hospital information system (HIS) and PACS has been implemented. The HU-PACS can access common data base with HIS. Multi-image data-base systems provide fast throughput of image retrieval. The system is composed of 4 modules: (1) 2 image data-base systems (IDS), (2) 1 image management system (IMS), (3) image display terminals (IDT), and (4) 8 image acquisition nodes interfaced to 10 modalities and 1 film scanner. These 4 modules are connected by branch and loop type local area networks (LAN). HU-PACS has functions other than basic PACS functions. Images in optical disk library (ODL) are loaded onto magnetic disks (MD) in advance according to patient booking information, the images expected to be viewed are transferred to the local storage automatically, and the desired images can be pre-downloaded into local storage by instruction through HIS terminals.

Computer Communication Networks↗

Creation of a software application for the clinical radiologist.

PURPOSE: To create a software application that automates a significant portion of a clinical radiologist's work. METHODS: The daily workflow of clinical radiologists in a university-based department was analyzed, specifically looking for manual tasks that could be implemented in software. An application that a practicing radiologist would use in his daily work was created. RESULTS: By using speech recognition, reports could be created, edited, and verified immediately. Online medical reference information could be made instantly accessible. Billing data could be captured accurately and completely at report creation time. A radiologist could be alerted to important upcoming events by use of a reminder system. Reports could be delivered immediately to referring physicians using either the internet or telephone. CONCLUSIONS: It is possible to improve the productivity of busy practicing clinical radiologists by automating a large portion of their workflow and implementing it in an easily mastered software application.

Humans↗

[Statements of general practitioners on cooperation with specialists and a future health care system].

BACKGROUND AND PURPOSE: Ideas of general practitioners (GPs) could be of value for the restructuring of the German ambulant health care system. The way managed care is seen by GPs is of particular interest. The aim of this study was to record opinions of GPs, working in Berlin, in regard to several aspects of their daily work. METHODS: 14 female and 16 male GPs from Berlin participated in a qualitative survey. These 30 GPs were interviewed about their attitude toward cooperation with specialized colleagues and their opinions on a future medical care system. The interviews performed were summarized, structured and analyzed according to the qualitative content analysis by Mayring. RESULTS: From the GPs' point of view, ambulant cooperation is facilitated by knowing specialized colleagues, by staying in close contact to them via telephone and by being able to arrange short-term appointments with these specialists. A closer cooperation with specialists in a network as well as an advanced use of digital information systems for accessing patients' data were considered to be vital elements for a future health care system. CONCLUSION: An important reason for choosing the cooperation with specialists is to find quick comprehensive treatment strategies for patients. It may be concluded that ambulant managed care of patients could be optimized with the creation of medical networks.

Adult↗

Personal digital assistants.

Personal digital assistant sales are growing exponentially, and as medical technology advances the amount of information available becomes staggering, making a handheld device, with the ability to store a great amount of information, progressively more valuable to health care providers. Mobile computing allows for a great deal of knowledge in a small package, creating a "walking library" with a mobile collection of data always accessible. There are many diverse types of PDAs, and this article discusses the history of PDAs, general purchasing issues, general PDA features, and the most significant differences between the Palm and the Windows CE operating systems.

Computer Communication Networks↗

Important preoperative prognostic factors for extracapsular extension, seminal vesicle invasion and lymph node involvement in cases with radical retropubic prostatectomy.

INTRODUCTION: Initial diagnostic evaluation may provide information about the extent of disease after radical retropubic prostatectomy (RRP). The aim of this study was to investigate the predictive value of preoperative serum prostate specific antigen (PSA) level, local disease extension identified by transrectal ultrasound (TRUS), total number of positive biopsies and percentage of positive cores for cancer, as well as TRUS Biopsy Gleason score in determining the extent of disease in radical retropubic prostatectomy specimens. MATERIALS AND METHODS: A retrospective analysis was performed on 171 patients who underwent RRP from March 1993 to February 2003 for organ confined prostate cancer and whose follow-up data was accessible. The correlation of preoperative serum PSA level, local disease extension in TRUS, the total number of positive sextant biopsies and the percent of cores positive for cancer and Gleason score at TRUS biopsy specimen with the extent of disease at final pathology (Extra-capsular extension (ECE), seminal vesicle invasion (SVI), lymph node involvement (LNI) and surgical margin (SM) status on RRP specimens) were analyzed. RESULTS: The median age of the patients was 65 years. The mean preoperative serum PSA level of all patients was 11.6+/-1.2 (median 8.6) ng/ml. Histopathological evaluation of RRP specimens revealed 60 (35%) patients with ECE, 38 (22.2%) with SVI, 7 (0.04%) with LNI, and 58 (33.9%) had positive SM. Comparing the preoperative TRUS findings and postoperative evaluation of RRP specimens, the sensitivity of TRUS in predicting the ECE was 11.8% and specificity was 96%. Sensitivity of TRUS in predicting SVI was 9.8% and its specificity was 99%. With univariate analysis (sample t-test), Gleason score, percent of cores positive for cancer, and DRE were found to be predictive factors for extra-prostatic disease in RRP specimens. But with multivariate analysis (logistic regression test) Gleason score appears to be the most important and independent predictive factor for extra-prostatic disease in RRP specimens. Serum PSA levels and percentages of cores positive for cancer were also significant predictors of non organ-confined disease found at final pathology. CONCLUSION: Gleason score is the most important and independent predictive factor for extra-prostatic disease. Serum PSA levels and percentages of cores positive for cancer are the other important but non-independent predictive factors.

Aged↗

Conflicts of interest in drug development: the practices of Merck & Co., Inc.

Conflicts of interest are common and exist in academia, government, and many industries, including pharmaceutical development. Medical journal editors and others have recently criticized "the pharmaceutical industry," citing concerns over investigator access to data, approaches to analysis of clinical trial data, and publication practices. Merck & Co., Inc. is a global, research-driven pharmaceutical company that discovers, develops, manufactures, and markets a broad range of human and animal health products, directly and through its joint ventures. Although part of its mission is to provide a superior rate of return to its investors, Merck does not believe this creates an irreconcilable conflict of interest, particularly in activities concerning clinical drug development. We employ rigorous scientific methods to design, conduct, analyze, and report results of clinical trials in the development of innovative drugs and vaccines, with a focus on meeting unmet medical needs and with an ethic that puts the interests of the patient first. This article describes Merck's approaches to potential conflicts of interest in drug development, particularly with regard to clinical trials. We believe that proprietary interests of the Company can be respected while observing objectivity and transparency in communicating clinical research results. The standards for the review of manuscripts reporting such trials for peer-reviewed publication should be the same, whether they are from Merck or elsewhere.

Chemistry, Pharmaceutical↗

A portable ergonomic observation method (PEO) for computerized on-line recording of postures and manual handling.

A new portable ergonomic observation method (PEO) is presented. It is applicable to most professions and work tasks and requires only moderate human resources for data collection and analysis. Observations are made in real time directly at the workplace using a portable personal or hand-held computer, and data are accessible for immediate analysis and presentation. Duration and number of events are calculated for postures at four body regions (arms, neck, trunk and knee) as well as for manual handling. An evaluation of the PEO method, assessing some important aspects of internal validity as well as intra- and inter-observer reliability, was carried out using video recordings. It showed acceptable validity for some types of physical exposure, and high intra- and inter-observer reliability. Practical experiences from using the PEO method in a field study and further improvements of the method are discussed.

Journal Article↗

Accessibility of cell surface thiols in human lymphocytes is altered by ionophores or OKT-3 antibody.

The accessibility of cell surface sulfhydryl groups in human peripheral lymphocytes was investigated with 5,5'-dithiobis-(2-nitrobenzoic acid) in the presence and absence of ionophore antibiotics and the monoclonal antibody, OKT-3. Only a few accessible protein thiols have been found on the cells as demonstrated by labeling with a fluorescent non-penetrating thiol-marker, monobromotrimethyl-ammoniobimane and the subsequent gel electrophoretic analysis of the protein pattern. Difference spectrophotometric measurement of thiol-DTNB reaction revealed that ionophores altering the transmembrane potential induced an enhanced cell surface thiol-exposure on the minute time scale. The effect showed a dependence on the external concentration of the cations. The binding of monoclonal antibody, OKT-3, directed against T3 complexes, resulted in a similar, concentration-dependent increase of thiol-accessibility. These data are interpreted as early membrane-effects of ionophores and the specific antibody including changes in the conformational equilibrium or vertical displacements of certain membrane proteins. These events are likely to be coupled to the changes in the transmembrane potential of the lymphocytes.

Anti-Bacterial Agents↗

Study of the heteromeric structure of the untransformed glucocorticoid receptor using chemical cross-linking and monoclonal antibodies against the 90K heat-shock protein.

The untransformed rat glucocorticoid receptor is assumed to be a hetero-oligomeric complex, containing a non-steroid binding component, the 90K heat-shock protein (HSP 90). Direct measurement of its molecular weight by chemical cross-linking provides new evidence for a trimeric structure with a Mr of ca. 270,000. Resorting to an anti HSP 90 probe (AC 88), we show that the native dimeric HSP 90 possess two accessible epitopes for this monoclonal antibody, while when bound to the steroid-binding subunit, only one epitope remains accessible. These data clearly suggest that the untransformed rat glucocorticoid receptor is an asymmetrical hetero-oligomeric complex.

Animals↗

Integrating non-proprietary workstations into proprietary systems.

'Clinical workstations', increasingly described as pivotal components of information systems for patient care, can be characterized as providing several major functions: access to data, presentation of data, computation (including medical decision logic), entry of data, and combinations of the above, integrated appropriately for various clinical situations. Because workstation technology is developing rapidly on many fronts and the demands on health-care organizations are growing, it is increasingly unlikely that any single total-system solution can effectively meet the needs. This paper discusses some of the issues pertinent to the integration of non-proprietary workstations with proprietary hospital systems. The approach of a particular vendor, the role of a meta-database, user interface design standards, and some problems consequent to the new technologies are discussed.

Computer Security↗