Optimizing the detection of colorectal liver metastases within the Canadian health care system

BACKGROUND: Five to seven percent of patients with psoriasis suffer additionally from accompanying arthritis. AIM OF THE STUDY: In this article, we review the current knowledge on clinical, diagnostic and therapeutic aspects of the disease. PATIENTS AND RESULTS: Data are presented on the treatment of six patients with the immunosuppressant ciclosporin. Therapeutic results with this drug are superior to agents traditionally used for management of psoriatic arthritis. CONCLUSION: The therapeutic options have been enlarged by the introduction of new immunosuppressive drugs, particularly ciclosporin.     

Lack of effect of olanzapine on the pharmacokinetics of a single aminophylline dose in healthy men

STUDY OBJECTIVE: To test whether olanzapine, an atypical antipsychotic, is an inhibitor of cytochrome P450 (CYP) 1A2 activity, we conducted a drug interaction study with theophylline, a known CYP1A2 substrate. DESIGN: Two-way, randomized, crossover study. SETTING: Clinical research laboratory. SUBJECTS: Nineteen healthy males (16 smokers, 3 nonsmokers). INTERVENTIONS: Because the a priori expectation was no effect of olanzapine on theophylline pharmacokinetics, a parallel study using cimetidine was included as a positive control. In group 1, 12 healthy subjects received a 30-minute intravenous infusion of aminophylline 350 mg after 9 consecutive days of either olanzapine or placebo. In group 2, seven healthy subjects received a similar aminophylline infusion after 9 consecutive days of either cimetidine or placebo. MEASUREMENTS AND MAIN RESULTS: Concentrations of theophylline and its metabolites in serum and urine were measured for 24 and 72 hours, respectively. Plasma concentrations of olanzapine and its metabolites were measured for 24 hours after the next to last dose and 168 hours after the last olanzapine dose. Olanzapine did not affect theophylline pharmacokinetics. However, cimetidine significantly decreased theophylline clearance and the corresponding formation of its metabolites. Urinary excretion of theophylline and its metabolites was unaffected by olanzapine but was reduced significantly by cimetidine. Steady-state concentrations of olanzapine (15.3 ng/ml), 10-N-glucuronide (4.9 ng/ml), and 4'-N-desmethyl olanzapine (2.5 ng/ml) were observed after olanzapine 10 mg once/day and were unaffected by coadministration of theophylline. CONCLUSION: As predicted by in vitro studies, steady-state concentrations of olanzapine and its metabolites did not affect theophylline pharmacokinetics and should not affect the pharmacokinetics of other agents metabolized by the CYP1A2 isozyme.     

Margatoxin increases dopamine release in rat striatum via voltage-gated K+ channels

The distribution of iodinated margatoxin ([125I]margatoxin) binding sites in rat was investigated by autoradiography. Rat striatum expresses a high density of margatoxin binding sites and, therefore, the effects of margatoxin, charybdotoxin and iberiotoxin have been studied on [3H]dopamine release from rat striatal slices in vitro. Margatoxin (0.1-100 nM) and charybdotoxin (10-1000 nM), but not iberiotoxin increased the spontaneous and the electrically evoked [3H]dopamine release. [3H]dopamine release by margatoxin was inhibited by tetrodotoxin and omega-conotoxin GVIA, but not by atropine, naloxone, N(omega)-nitro-L-arginine and neurokinin or neurotensin receptor antagonists. In the buffer solution used for release experiments, [125I]margatoxin labels a maximum of 0.12 pmol of sites/mg protein in rat striatal membranes with a Kd of 5 pM. [125I]margatoxin binding was inhibited by margatoxin (Ki of 4 pM), charybdotoxin (Ki of 162 pM) but not by iberiotoxin. We conclude that inhibition of margatoxin-sensitive voltage-gated K+ channels increases [3H]dopamine release demonstrating their role in repolarization of nigrostriatal projections. In contrast, iberiotoxin-sensitive, high-conductance Ca2+-activated K+ channels are not involved in release of [3H]dopamine.     

Calcium regulation of nuclear pore permeability

The nuclear envelope is an integral part of the structural framework of the nucleus, and is involved in organizing intranuclear events. It serves as a selective barrier, actively transporting proteins required for normal nuclear function and exporting RNA. The movement of molecules across the nuclear envelope is critical for cellular homeostasis, and it allows cells to respond to external events. The only known pathway for direct communication between the cytoplasm and the nucleoplasm of a cell is through the nuclear pore complex. In the past decade, rapid advances have been made in elucidating the structure and function of the nuclear pore complex. Yet, researchers are just beginning to identify some of the regulatory mechanisms controlling transport through the pore complex. The nucleus is surrounded by a Ca2+ storage compartment, which sequesters and releases Ca2+ in response to intracellular second messengers, Recent evidence suggests that the nuclear Ca2+ store may indirectly regulate passive diffusion through the nuclear pore complex. The evidence for Ca2+ regulation of the nuclear pore complex will be discussed, along with the introduction of the simplest, testable model to describe the observations.     

High temperature AFM study of CAP 30/45 pen grade bitumen

Bitumen is a complex mixture of hydrocarbons for which microstructural understanding is incomplete. In an effort to detail this microstructure, a asphalt cement sample (CAP 30/45) was analysed by thermal phase detection atomic force microscopy. Phase contrast and topography images showed that sample morphology is highly dependent on temperature. The ‘bee structure’ changed considerably at temperatures between 50°C and 56°C. A decrease of the oscillation amplitude was observed upon heating and the ‘bees’ completely disappeared at temperatures above 57°C. When the temperature was decreased after melting at 170°C, the ‘bees’ began to nucleate gradually at temperatures of 57°C and its evolution with time was followed. Changes in morphology were compared to thermal analysis results and a model for the ‘bee’ structure was proposed.     

Gridded Aclar: preparation methods and use for correlative light and electron microscopy of cell monolayers,by TEM and FIB–SEM

Aclar, a copolymer film with properties very similar to those of tissue culture plastic, is a versatile substrate to grow cells for light (including fluorescence) and electron microscopic applications in combination with both chemical fixation and cryoimmobilization. In this paper, we describe complete procedures to perform correlative light and electron microscopy using Aclar as substrate for the culture of cell monolayers to be finally embedded in plastic. First, we developed straightforward, efficient and flexible ways to mark the surface of the Aclar to create substrates to locate cells first at the light microscopy and then the electron microscopy level. All the methods enable the user to self‐design gridded Aclar pieces, according to the purpose of the experiments, and create a large number of substrates in a short time. Second, we confirmed that marked Aclar supports the normal growth and morphology of cells. Third, we validated the correlative light and electron microscopy procedure using Aclar. This validation was done for the high‐resolution analysis of endothelial cells using transmission electron microscopy and focused ion beam–scanning electron microscopy in combination with the use of fluorescence, phase contrast and/or bright field microscopy to map areas of interest at low resolution. The methods that we present are diverse, easy to implement and highly reproducible, and emphasize the versatility of Aclar as a cell growth substrate for diverse microscopic applications.     

3D crank-nicolson finite difference time domain method for dispersive media

The unconditionally stable Crank-Nicolson finite difference time domain (CN-FDTD) method is extended to incorporate frequency-dependent media in three dimensions. A Gaussian-elimination-based direct sparse solver is used to deal with the large sparse matrix system arising from the formulation. Numerical results validate and confirm that the scheme is unconditionally stable for time steps over the Courant-Friedrich-Lewy limit of classical FDTD.     

Wetting Behavior and Mechanical Properties of Sn-Zn and Sn-Pb Solder Alloys

A comparative experimental study of the main features of the eutectic Sn-Pb alloy and Sn-Zn alloys was carried out with a view to application of the latter alloys as alternative solder materials. The resulting microstructures, mechanical properties (ultimate tensile strength and elongation), and wettability behavior (spreading area and contact angle) of a hypoeutectic Sn-Zn (Sn-4wt.%Zn), a hypereutectic Sn-Zn (Sn-12wt.%Zn), and the eutectic Sn-9wt.%Zn alloy were examined and compared with the corresponding results of the conventional Sn-40wt.%Pb solder alloy. It was found that, of the Sn-Zn alloys examined, the eutectic Sn-9wt.%Zn alloy offers a compromise between lower wettability and higher mechanical strength.     

Dimming of High-Brightness LEDs by Means of Luminous Flux Thermal Estimation

Usually, pulsewidth modulation (PWM) operation is selected as the best dimming strategy to drive high-brightness LEDs. Nevertheless, to obtain an enhanced full linear dimming control of the device, the luminous flux should be measured. This paper proposes a control method based on an estimator of the luminous flux emitted by the LED. Based on the characterization of the LEDs, this estimator is defined. The estimator provides the flux value from only two temperature values (the case temperature and the ambient temperature). Once the estimator is validated, the electronic driver to supply the LEDs, as well as the digital control scheme, are presented. Such a control scheme is suitable for both AM and PWM dimming strategies. A prototype of the electronic driver has been built and tested, and experimental measurements of AM and PWM dimming are presented. It can be concluded that with the proposed estimator, the flux emitted by the LEDs can be accurately estimated. Thus, the output light control of the LEDs can be accomplished by sensing temperature rather than luminous flux. The final output characteristic of the system shows linearity between the output flux and the reference value, with AM as well as with PWM dimming of the LEDs.     

寓教于乐—乌干达的艾滋病孤儿学校

此项工程最初是由艾米·皮罗顿起的。艾米丽是H工程设计的创始人。同时在乌干迭西南部的Kutamba艾滋病孤儿学校做义务教员。