The Traumatic Brain Injury Act Amendments of 2000.
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Brain Injuries↗
Biomedical subjects
J Bérubé
Publications and source records attributed to J Bérubé.
Hydrogen peroxide modifies the kinetics of HERG channel expressed in a mammalian cell line.
Reactive oxygen species such as H2O2 were shown to influence both electrical and contractile properties of the heart. H2O2 modulates action potential duration and leads to reperfusion-induced arrhythmias. As these effects could involve the modulation of repolarizing currents, we assessed effects of H2O2 on HERG (which encodes the cardiac potassium channel I(Kr)) expressed in Chinese hamster ovary cells. HERG currents were recorded using the whole-cell patch-clamp technique. HERG activation and deactivation were accelerated when cells were superfused with 30 microM, 100 microM, or 1 mM H2O2. For example, at 1 mM H2O2, tau(act) was decreased from 862 +/- 178 to 633 +/- 151 ms (P < 0.05; n = 6), and fast tau(deact) was reduced from 286 +/- 47 to 151 +/- 18 ms (P < 0.05; n = 6). A negative shift of V1/2 was also observed (from -1.9 to -13.7 mV with 30 microM H2O2; P < 0.05), reflecting the acceleration of the activating current. Effects of H2O2 superfusion were prevented by intracellular application of catalase but superoxide dismutase prevented only H2O2-induced acceleration of activation. This indicates that H2O2 diffuses intracellularly before acting on HERG and that its effects on activation but not deactivation are mediated by the superoxide anion. Moreover, tau(act) decrease preceded fast tau(deact) decrease by about 4 min, suggesting that these effects were not produced by the same intracellular pathway or at the same site on HERG protein. Acceleration of HERG activation kinetics leads to an increase of outward current during the plateau phase of the action potential. This could suggest a reason for H2O2-induced shortening of the action potential. The faster HERG deactivation could be involved in reperfusion-induced arrhythmias by reducing K+ conductance in the early diastole, thus increasing the risks of premature beats.
Animals↗
Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.
BACKGROUND-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L. Action potential duration increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current: activating current was 50% decreased at 100 mcmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I(K)-like current. CONCLUSIONS-Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.
Action Potentials↗
A short lived protein involved in the heat shock sensing mechanism responsible for stress-activated protein kinase 2 (SAPK2/p38) activation.
The stress-activated protein kinase 2 (SAPK2/p38) is activated by various environmental stresses and also by a vast array of agonists including growth factors and cytokines. This implies the existence of multiple proximal signaling pathways converging to the SAPK2/p38 activation cascade. Here, we show that there is a sensing mechanism highly specific to heat shock for activation of SAPK2/p38. After mild heat shock, cells became refractory to reinduction of the SAPK2/p38 pathway by a second heat shock. This was not the result of a toxic effect because the cells remained fully responsive to reinduction by other stresses, cytokines, or growth factors. Neither the activity of SAPK2/p38 itself nor the accumulation of the heat shock proteins was essential in the desensitization process. The cells were not desensitized to heat shock by other treatments that activated SAPK2/p38. Moreover, inhibiting SAPK2/p38 activity during heat shock did not block desensitization. Also, overexpression of HSP70, HSP27, or HSP90 by gene transfection did not cause desensitization, and inhibiting their synthesis after heat shock did not prevent desensitization. Desensitization rather appeared to be linked closely to the turnover of a putative upstream activator of SAPK2/p38. Cycloheximide induced a progressive and eventually complete desensitization. The effect was specific to heat shock and minimally affected activation by other stress inducers. Inhibiting protein degradation with MG132 caused the constitutive activation of SAPK2/p38, which was blocked by a pretreatment with either cycloheximide or heat shock. The results thus indicate that there is a sensing pathway highly specific to heat shock upstream of SAPK2/p38 activation. The pathway appears to involve a short lived protein that is the target of rapid successive up- and down-regulation by heat shock.
Amino Acid Sequence↗
Modulation of HERG potassium channel properties by external pH.
We expressed the human eag-related gene (HERG), known to encode for the cardiac potassium channel IKr, in Chinese hamster ovary (CHO) cells. This study investigated effects of external pH (pHo) on HERG current properties using the whole-cell patch-clamp technique. We observed that current amplitude was decreased and kinetics of activation and deactivation were faster when pHo was lowered from 7. 4 to 6.0, while activation was accelerated and V1/2 negatively shifted when pHo was changed from 7.4 to 8.0. These effects can be explained by surface charge screening, amino acid group titration and/or changes in ionic atmosphere. We conclude that alterations of HERG channel by pHo could have consequences for the onset of arrhythmias during cardiac ischemia.
Animals↗
Can a patient smart card improve decision making in a clinical setting?.
In the health field, clinical information is the raw material for the clinician delivering health services. Therefore, the clinical information available to the physician is often incomplete or even non¿existent upon consultation. Furthermore, the reconstruction of the medical history, which is the most important source of data for the clinician to establish a diagnosis and initiate a treatment, suffers from many constraints. The smart card, like the one used in Quebec's project, could ease the physician's decision-making by allowing fast access to accurate and pertinent data. The smart card is a major asset in the present health system.
Decision Making, Computer-Assisted↗
A microprocessor card software server to support the Quebec health microprocessor card project.
The Quebec Health Smart Card Project is advocating the use of a memory card software server[1] (SCAM) to implement a portable medical record (PMR) on a smart card. The PMR is viewed as an object that can be manipulated by SCAM's services. In fact, we can talk about a pseudo-object-oriented approach. This software architecture provides a flexible and evolutive way to manage and optimize the PMR. SCAM is a generic software server; it can manage smart cards as well as optical (laser) cards or other types of memory cards. But, in the specific case of the Quebec Health Card Project, SCAM is used to provide services between physicians' or pharmacists' software and IBM smart card technology. We propose to expose the concepts and techniques used to provide a generic environment to deal with smart cards (and more generally with memory cards), to obtain a dynamic an evolutive PMR, to raise the system global security level and the data integrity, to optimize significantly the management of the PMR, and to provide statistic information about the use of the PMR.
Computer Security↗
Médicarte software developed for the Quebec microprocessor health card project.
The Quebec Patient Smart Card Project is a Provincial Government initiative under the responsibility of the Rgie de l'assurance-maladie du Québec (Quebec Health Insurance Board). Development, implementation, and assessment duties were assigned to a team from Université Laval, which in turn joined a group from the Direction de la santé publique du Bas-St-Laurent in Rimouski, where the experiment is taking place. The pilot project seeks to evaluate the use and acceptance of a microprocessor card as a way to improve the exchange of clinical information between card users and various health professionals. The card can be best described as a résumé containing information pertinent to an individual's health history. It is not a complete medical file; rather, it is a summary to be used as a starting point for a discussion between health professionals and patients. The target population is composed of persons 60 years and over, pregnant women, infants under 18 months, and the residents of a small town located in the target area, St-Fabien, regardless of age. The health professionals involved are general practitioners, specialists, pharmacists, nurses, and ambulance personnel. Participation in the project is on a voluntary basis. Each health care provider participating in the project has a personal identification number (PIN) and must use both an access card and a user card to access information. This prevents unauthorized access to a patient's card and allows the staff to sign and date information entered onto the patient card. To test the microprocessor card, we developed software based on a problem-oriented approach integrating diagnosis, investigations, treatments, and referrals. This software is not an expert system that constrains the clinician to a particular decisional algorithm. Instead, the software supports the physician in decision making. The software was developed with a graphical interface (Windows 3.1) to maximize its user friendliness. A version of the software was developed for each of the four groups of health care providers involved. In addition we designed an application to interface with existing pharmaceutical software. For practical reasons and to make it possible to differentiate between the different access profiles, the information stored on the card is divided in several blocks: Identification, Emergency, History (personal and family), Screening Tests, Vaccinations, Drug Profile, General follow-up, and some Specific follow-ups (Pregnancy, Ophthalmology, Kidney failure, Cardiology, Pediatrics, Diabetes, Pneumology, Specific parameters). Over 14,000 diagnoses and symptoms are classified with four levels of precision, the codification being based on the ICPC (International Classification for Primary Care). The software contains different applications to assist the clinician in decision making. A "Drug Advisor" helps the prescriber by detecting possible interactions between drugs, giving indications (doses) and contraindications, cautions, potential side-effects and therapeutic alternatives. There is also a prevention module providing recommendations for vaccination and periodic examinations based on the patient's age and sex. The pharmaceutical, vaccination, and screening tests data banks are updated every six months. These sections of the software are accessible to access card holders at any times, even without a patient card, and constitute in themselves an interesting clinical tool. We developed a software server (SCAM) allowing the different applications to access the data in a memory card regardless of the type of memory card used. Using a single high level command language, this server provides a standardized utilization of memory cards from various manufacturers. It ensures the compatibility of the applications using the card as a storage medium. (abstract truncated)
Aged↗