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Biomedical subjects

F Lau

Publications and source records attributed to F Lau.

At least 19 recordsLinked to original sources

The School of Health Information Science at the University of Victoria: towards an intergrative model for health informatics education and research.

OBJECTIVES: There is an increasing need for well qualified health informatics practitioners and for educational programs that produce them. Since 1981, the School of Health Information Science at the University of Victoria has delivered a range of educational programs in health informatics. The School's objective has been to produce graduates who can assume a range of roles in health informatics, including managers, developers, researchers and evaluators of health care systems. METHODS: The approach taken by the School has been to provide an integrated 'holistic' approach to health informatics education that balances both theory and practice. The curriculum has emphasized interdisciplinary skills and has been based on a process of consultation with key stakeholders in both industry and academia. In addition, several new distance collaborative models for health informatics education (including a distributed MSc degree program) have been recently initiated through the University of Victoria with collaborating Canadian universities. RESULTS: To date, graduates of the programs offered have become highly sought after, with the demand for graduates of the programs continually exceeding the number of graduates. The core undergraduate curriculum has recently been undergone refinement to include training in new emerging areas of health informatics. In addition, a distributed MSc program has been successfully initiated by the School, currently with 23 students participating from dispersed geographical locations across Canada. CONCLUSIONS: The School of Health Information Science at the University of Victoria has been involved in providing unique interdisciplinary education in health informatics for over twenty years. The School continues to maintain its emphasis on integrated education, refining its curriculum and moving into new areas such as distance education and cross-Canadian collaborations.

Curriculum↗

The realities of synthesizing and disseminating research evidence.

This article describes the results of a 15-month pilot project to determine whether producers and users of organizations' research findings can synthesize and disseminate evidence collaboratively. The findings of the project suggest that the collaborative approach is a feasible but costly endeavor owing to differences in need, expertise, experience and context. Funding agencies should consider alternative ways to build sustainable partnerships and to address the cultural and political contexts of organizations involved with the synthesis and dissemination of evidence.

Cooperative Behavior↗

Fostering an Internet-based work group in community health through action research.

In this article, we describe an action research study to foster an Internet-based work group as part of a two-year community health research training program in Alberta, Canada. The objectives of our study were to incorporate Internet-based technology into the program, establish a distributed work group over time, and reflect on the lessons learned. The participants represented seventeen health regions. There were thirty-five instructors and expert resource persons (varied over time), two training coordinators, four support staff, a program coordinator, two action researchers, and two independent consultants. The data collected included program documents, phone interviews, online surveys, meeting notes, online discussions, computer usage log, site visits, keystroke entry logs, help desk logs, and program evaluation reports. Content analysis was conducted with NUD*IST to identify concepts and themes from the data. Our findings suggest that role clarification, facilitative support, network linkages, and workplace learning are important aspects of fostering Internet-based work groups in a health setting, where members strive to establish themselves, seek meaning in their work, support each other, and add value to their organizations.

Canada↗

Infection of CD4+ memory T cells by HIV-1 requires expression of phosphodiesterase 4.

Using PCR to monitor HIV-1 RNA genome reverse transcription and nuclear import of preintegration complexes, we found that memory, but not naive, CD4+ T cells could support transport of HIV-1 DNA to nuclei upon TCR/CD3 and IL-2 stimulation. Moreover, memory CD4+ T cells, unlike naive CD4+ T cells, express high levels of phosphodiesterase 4 (PDE4) constitutively. Selective blocking of PDE4 activity inhibited IL-2R expression and thereby led to abolishing HIV-1 DNA nuclear import in memory T cells; however, full-length viral DNA synthesis was not affected. Thus, blocking PDE4 prevents initiation of HIV-1 DNA circle formation in T cells. The fact that PDE4 is expressed constitutively at higher levels in memory vs naive CD4+ T cells may help HIV-1 readily infect memory T cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Replicability of SF-36 summary scores by the SF-12 in stroke patients.

BACKGROUND AND PURPOSE: The replicability of the physical and mental component summary scores of the Short Form (SF)-36 has been established using the SF-12 in selected patient populations but has yet to be assessed in stroke patients. If the summary scores of the SF-12 are highly correlated with those of the SF-36, the benefits of using a shorter health-status measure may be realized without substantial loss of information or precision. Both self-reported and proxy assessments were evaluated for replicability. METHODS: Intraclass correlation coefficients (ICCs) and linear regression were used to assess the ability of the SF-12 physical component summary (PCS-12) scores to predict PCS-36 scores and the SF-12 mental component summary (MCS-12) scores to predict MCS-36 scores. Multivariate regression was used to explore the relationship between SF-12 and SF-36 scores. RESULTS: The MCS-12 and PCS-12 scores were strongly correlated with the corresponding SF-36 summary scores for surveys completed by proxy or self-report (ICCs ranged from 0.954 to 0.973). Regression analysis of the proxy assessments indicated that patient age was an important effect modifier in the relationship between MCS-12 and MCS-36 scores. CONCLUSIONS: The SF-12 reproduced SF-36 summary scores without substantial loss of information in stroke patients. Accordingly, the SF-12 can be used at the summary score level as a substitute for the SF-36 in stroke survivors capable of self-report. However, the mental health summary scores of proxy assessments are influenced by patient age, thereby limiting the replicability of the SF-36 by the SF-12 under these conditions.

Aged↗

Phenytoin-induced teratogenesis: a molecular basis for the observed developmental delay during neurulation.

PURPOSE: We wished to determine whether chronic phenytoin (PHT) exposure could impair neural development and if any morphological alterations could be linked to changes in gene expression. METHODS: Pregnant SWV mice were chronically administered PHT 40 mg/kg/day from gestational day (GD) 0:12 (day:h) until they were killed at various timepoints throughout neural tube closure (NTC). At each timepoint, embryos from both treated and control dams were collected and scored for their progression through NTC. The neural tubes were then isolated and subjected to in situ transcription (IST) and antisense RNA amplification procedures. Using these techniques, we examined the expression of 10 genes: N-cadherin (Ncad), collagen type IV (col-IV), bcl-2, c-jun, PAX-3, collular retinol binding protein-2 (CRBP-2), retinoic acid receptor alpha (RAR alpha), transforming growth factor(beta2) (TGF(beta2)), wee-1, and EMX-2. RESULTS: Chronic PHT exposure not only caused a delay in NTC whereby exposed embryos lagged behind the controls at each collection timepoint, but also significantly altered the expression of specific genes at distinct times during NTC. Early in NTC, PHT induced a significant reduction in the expression of N-cad, col-IV, and c-jun in exposed embryos as compared with controls. In contrast, during the midstages of NTC, the only significant molecular alterations observed in the PHT-exposed embryos was the continued decreased expression of col-IV and an increase in CRBP-2 expression. Finally, in the latter stages of NTC, PHT caused a significant reduction in the expression of bcl-2, RAR alpha, TGF(beta2), EMX-2, and PAX-3. CONCLUSIONS: These results show that although the effects of PHT are morphologically subtle, causing a delay in the development of the neural tube, this delay is accompanied by alterations in critical genes at crucial times of neural development that may account for the observed neurological deficits often associated with PHT exposure.

Abnormalities, Drug-Induced↗

Imaging inflammation with 99Tcm-labeled chemotactic peptides: analogues with reduced neutropenia.

Two 99Tcm-labelled analogues of the chemotactic peptide ForMLF were evaluated as potential agents for imaging inflammation and infection, in the hope that they would be simple to use and would give diagnostically useful images shortly after injection. The peptides differed in the chelation site for 99Tcm and the presence of a hydrophilic spacer. The sequences of RP050 and RP056 were ForNleLFNleYK(G)G-C(Acm)-GPic and ForNleLFNleYKK(DG)GC(Acm)SPic respectively, where Pic is picolinic acid. In in vitro tests of binding to the ForMLF receptor on polymorphonuclear neutrophils and potency for release of myeloperoxidase, RP056 was similar in potency to ForMLF, whereas RP050 was 10 times more potent. When administered in 5-nmol doses to rats, RP050 produced less extensive neutropenia than ForMLF, whereas RP056 produced very little neutropenia. Following labelling by ligand exchange from tartrate or glucoheptonate at 100 degrees C and purification using a C-18 solid-phase extraction cartridge, 4-MBq doses were administered to rats bearing infectious (Escherichia coli) or sterile (zymosan) inflammation sites in the thigh. The inflammation-to-normal muscle ratios at 30 min after injection were 3.9 +/- 0.4 for RP050 and 4.7 +/- 0.3 for RP056 (mean +/- S.E.M., n = 4), and the ratios were maintained for up to 3 h. These peptides are promising agents for imaging inflammation and infection.

Amino Acid Sequence↗

Bradykinin potentiates acetylcholine induced responses in native endothelial cells from rabbit aorta.

Membrane potential and intracellular [Ca2+] were measured in freshly isolated rabbit aortic endothelial cells. Acetylcholine (10 microM) induced transient membrane hyperpolarization and increased [Ca2+]i. Bradykinin (4 microM) had no direct effect on membrane potential or [Ca2+]i on its own, but potentiated the subsequent ACh response. It changed the usual transient ACh response to a maintained hyperpolarization. The maintained hyperpolarization was blocked by NiCl2 and TEA, indicating an involvement of receptor-operated-Ca2+ channel and Ca2+ -dependent K+ -channel activity. This potentiating effect on bradykinin in isolated cells was confirmed in organ bath studies using isolated aortic rings.

Acetylcholine↗

Acetylcholine-sensitive intracellular Ca2+ store in fresh endothelial cells and evidence for ryanodine receptors.

In a freshly isolated endothelial cell preparation from rabbit aorta, the regulation of the acetylcholine (ACh)-sensitive intracellular Ca2+ store and the effects of the Ca(2+)-induced Ca2+ release agonists ryanodine and caffeine were studied using fura 2 imaging fluorescence microscopy. ACh (10 mumol/L) caused a transient release of Ca2+ from an intracellular store, presumably via an inositol tris-phosphate-sensitive mechanism. This ACh response could be repeated in the presence of extracellular Ca2+ but was obtained only once in Ca(2+)-free bathing solution, which shows that a depleted intracellular Ca2+ store can be rapidly refilled from the extracellular space. Refilling can be prevented by the endoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (10 mumol/L), implying that Ca2+ enters the cytoplasm before accumulation in the endoplasmic reticulum. Ionomycin (10 mumol/L) caused a large Ca2+ release even after the ACh-releasable store had been emptied, indicating the existence of other ACh-insensitive stores, perhaps including the mitochondria. In one third of the cells studied, ACh induced oscillations in [Ca2+]i that were dependent on extracellular Ca2+. Also investigated were the effects of caffeine and ryanodine. In this cell preparation neither caffeine nor ryanodine induced a Ca2+ transient but instead slowly increased [Ca2+]i. It was observed that both caffeine and ryanodine were able to slowly deplete the ACh-sensitive store. These results indicate the presence of functional ryanodine receptors in native endothelial cells and demonstrate overlap between the caffeine and agonist-sensitive Ca2+ stores. We also found that caffeine was able to directly inhibit the process of ACh-induced Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

A knowledge-based care protocol system for ICU.

There is a growing interest in using care maps in ICU. So far, the emphasis has been on developing the critical path, problem/outcome, and variance reporting for specific diagnoses. This paper presents a conceptual knowledge-based care protocol system design for the ICU. It is based on the manual care map currently in use for managing myocardial infarction in the ICU of the Sturgeon General Hospital in Alberta. The proposed design uses expert rules, object schemas, case-based reasoning, and quantitative models as sources of its knowledge. Also being developed is a decision model with explicit linkages for outcome-process-measure from the care map. The resulting system is intended as a bedside charting and decision-support tool for caregivers. Proposed usage includes charting by acknowledgment, generation of alerts, and critiques on variances/events recorded, recommendations for planned interventions, and comparison with historical cases. Currently, a prototype is being developed on a PC-based network with Visual Basic, Level-Expert Object, and xBase. A clinical trial is also planned to evaluate whether this knowledge-based care protocol can reduce the length of stay of patients with myocardial infarction in the ICU.

Alberta↗

A clinical decision support system prototype for cardiovascular intensive care.

This paper describes the development and validation of a decision-support system prototype that can help manage hypovolemic hypotension in the Cardiovascular Intensive Care Unit (CVICU). The prototype uses physiologic pattern-matching, therapeutic protocols, computational drug-dosage response modeling and expert reasoning heuristics in its selection of intervention strategies and choices. As part of model testing, the prototype simulated real-time operation by processing historical physiologic and intervention data on a patient sequentially, generating alerts on questionable data, critiques of interventions instituted and recommendations on preferred interventions. Bench-testing with 399 interventions from 13 historical cases showed therapies for bleeding and fluid replacement proposed by the prototype were significantly more consistent (p < 0.0001) than those instituted by the staff when compared against expert critiques (80% versus 44%). This study has demonstrated the feasibility of formalizing hemodynamic management of CVICU patients in a manner that may be implemented and evaluated in a clinical setting.

Alberta↗

Modularity of protein function: chimeric interleukin 1 beta s containing specific protease inhibitor loops retain function of both molecules.

Although it is widely recognized that many proteins contain discrete functional domains, it is less certain whether smaller, less obviously discrete, units of structure will retain their specific function when transplanted into a different context. The observation that the potent inflammatory cytokine human interleukin 1 beta has the same overall structure as soybean trypsin inhibitor (STI) (Kunitz) prompted us to replace a tight turn in the cytokine sequence with the large loop in soybean trypsin inhibitor that binds to the active site of trypsin. Wild-type interleukin 1 beta (IL-1 beta) is highly resistant to proteolysis, but the chimeric STI/IL is specifically cleaved by trypsin, apparently in the inserted loop. Other chimeric interleukins have also been constructed, by replacing the same tight turn with inhibitory loops from other protein protease inhibitors: turkey ovomucoid inhibitor (TOI), a chymotrypsin inhibitor, and alpha 1-antitrypsin (AT), an elastase inhibitor. Although these loops come from proteins not related structurally to interleukin 1, they confer specific protease sensitivity or inhibition on the chimeric cytokine. The cytokine properties of these chimeric interleukins have also been evaluated. The chimeras formed from human IL-1 beta and all inhibitory loops tested bind to the interleukin 1 receptor with reasonable affinity. The typical cellular effects of IL-1, however, are not observed with all the recombinant proteins, thus confirming that receptor binding and signal transduction can be uncoupled. When these results are taken together with the results of site-directed mutagenesis of IL-1, reported in this paper and elsewhere, they allow the receptor and intracellular transduction sites on the protein to be mapped in detail.

Amino Acid Sequence↗

Formalized decision support for cardiovascular intensive care.

The massive volume of hemodynamic data routinely available within the Cardiovascular Intensive Care Unit (CVICU) can adversely affect the quality, relevance, and timing of hemodynamic management decisions on patients after cardiac surgery. Yet, at the same time, the lack of appropriate treatment-outcome data and access to prior CV case histories deprives the clinician of any opportunity to improve personal decision-making skill and assess the effectiveness of various treatment methods. This paper presents a formalized decision-support model for CVICU that incorporates expert and quantitative knowledge, as well as prior outcome and case experience to augment the clinician's decision-making capability. This includes the use of optimal hemodynamic patterns derived from outcome analysis as therapy goals, expert rules and trend analysis to interpret incoming data, standardized protocols based on predefined hemodynamic patterns from clinical cases, and access to the database for similar case comparison. Most importantly, the model suggests an integrated approach where the clinical database not only is a documentation source for the patient, but also can serve as an outcome research database where clinical experience can be formalized and combined with expert knowledge to influence future therapy decisions. At present, a prototype is being developed at the CVICU of the University of Alberta Hospitals on a Unix platform using ART-IM, C and Ingres. Once implemented, the prototype will be evaluated on a small group of CV patients for its effectiveness and acceptability to clinicians.

Artificial Intelligence↗

Some computer-based decision support tools for the rehabilitation manager.

The recent introduction of the Management Information System (MIS) guidelines has sparked much interest among health care institutions across Canada regarding proper approaches to the recording and interpretation of various financial and workload indicators. While the benefits of the MIS guidelines are widely acknowledged, much less attention has been directed to how departmental managers can analyze and make use of the vast amount of information generated. In this paper we attempt to review some of the computer-based decision-support tools that may be useful to the manager of the rehabilitation services department in analyzing the various MIS data that are collected. The data are assumed to be available through a computerized rehabilitation information system which includes workload measures. The quantitative models reviewed in this paper include basic descriptive statistics, deviation, trend and what-if-analysis and graph-plotting. Although the use of such tools can assist the rehabilitation manager in the routine decision-making process, it is very important that we ask the right questions and employ the proper model to make the most rational and best decision. In this respect, ongoing training in general problem-solving skills, decision-making processes, and use of computer-based decision-support tools may be very beneficial.

Canada↗

Formalized decision-support for cardiovascular intensive care.

The massive volume of hemodynamic data routinely available within the Cardiovascular Intensive Care Unit (CVICU) can adversely affect the quality, relevance and timing of hemodynamic management decisions on patients after cardiac surgery. Yet, at the same time, the lack of appropriate treatment-outcome data and access to prior CV case histories deprives the clinician of any opportunity to improve personal decision-making skill and assess the effectiveness of various treatment methods. This paper presents a formalized decision-support model for CVICU that incorporates expert and quantitative knowledge, as well as prior outcome and case experience to augment the clinician's decision-making capability. This includes the proposed use of optimal hemodynamic patterns derived from outcome analysis as therapy goals, expert rules and trend analysis to interpret incoming data, standardized protocols based on predefined hemodynamic patterns from clinical cases, and access to the database for similar case comparison. Most importantly, the model suggests an integrated approach where the clinical database is not only a documentation source for the patient, but can also serve as an outcome research database where clinical experience can be formalized and combined with expert knowledge to influence future therapy decisions. At present, a prototype is being developed at the CVICU of the University of Alberta Hospitals on a Unix platform using ART-IM, C and Ingres. Once implemented, the prototype will be evaluated on a small group of CV patients for its effectiveness and acceptability to clinicians.

Cardiovascular Diseases↗

Designing an outcome-oriented computer decision-support system for cardiovascular ICU--a preliminary report.

This paper describes the conceptual framework and preliminary results of an outcome-oriented decision-support system prototype for the cardiovascular intensive care unit (CVICU). The major characteristics of this design include: (1) its problem-based approach to solving clinical problems; (2) an integrated structure with the hospital information system in terms of its data, model and knowledge bases; (3) proposed alternative modes of interaction that include monitoring and critiquing; (4) and research modules that design, manage, and analyze outcome-based clinical studies. At present, an initial prototype has been implemented on a PC as a set of modules accessible from a main menu. The structural framework of the overall system is fairly well defined but only limited quantitative, statistical and expert knowledge has been captured. The second phase of the project involves porting the prototype to a Unix workstation environment, refining and adding models to the model base, expanding its knowledge bases, reasoning capability, and testing the prototype with actual clinical cases in a real-time fashion.

Alberta↗

In search of the perfect laboratory computer system.

Some personal views on the selection of an ideal laboratory computer system are presented in this paper. Topics discussed include a review of some of the essential requirements for the ideal system; a survey of some of the commercial turn-key laboratory computer systems that are available; typical future trends that should be noted; and lastly, some criteria that may be used in the evaluation and selection of the ultimate system.

Canada↗

R--pulse wave timing: a technique for continuous cardiovascular monitoring in obstetrics--preliminary report.

A simple, noninvasive technique for continuous cardiovascular monitoring in obstetrics using R--pulse wave timing is described. This preliminary study suggests that different maternal heart rate/R pulse patterns are found in different clinical circumstances. A significant decrease in the R pulse interval occurred in the third trimester in both normal and diabetic women in the left lateral position when compared to the supine position. The R pulse intervals were all prolonged in the standing position in both gravid and nongravid women. During labor R pulse interval usually shortened during uterine contraction. Prolongation of R pulse interval was observed during thiopental injection, hypotension, and excessive bleeding at cesarean section. Exercise testing in healthy male subjects suggested that the change in R pulse interval becomes constant when the oxygen consumption rate reaches a plateau at 100% maximal work load. Further extensive clinical study appears worthwhile since it may add another dimension to cardiovascular monitoring and give an early indication of cardiovascular reserve.

Anesthesia, Obstetrical↗