Intrauterine growth restriction, soluble fms-like tyrosine kinase-1 to placental growth factor ratio increase and preeclampsia.

BACKGROUND: Intrauterine growth restriction (IUGR) and preeclampsia (PE) share common features such as ischemic placental disease but also differ in their clinical expression regarding maternal diseases. The reason why IUGRremains isolated in some cases yet is followed by clinical manifestations of PE in other cases remains unexplained. CASE REPORT: A 40-year old woman, gravida two, para one, experienced early-onset IUGR with a significant increase in the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) but, surprisingly, without any maternal clinical manifestations of PE. CONCLUSION: IUGR and a significant increase in sFlt-1/PlGF ratio without PE raise the issue of a missing factor enabling IUGR, a significant increase in sFlt-1/PlGF ratio, and PE to be linked. TEACHING POINTS: (1) Early-onset IUGR and a significant increase in sFlt-1/PlGF ratio do not necessarily mean the onset of PE. (2) Combining early-onset IUGR and a significant increase in sFlt-1/PlGF ratio without PE raises the question of an additional factor responsible for the onset of PE.

Mechanical cell disruption of Parachlorella kessleri microalgae: Impact on lipid fraction composition.

Samples of nitrogen-starved Parachlorella kessleri containing intact cells (IC), cells ground by bead milling (BM), and cells subjected to high-pressure cell disruption (HPD), together with their supernatants after centrifugation, were compared for granulometry and lipid profiles. The effects of disruption on the lipid profile and organisation were evaluated. The quantity of lipids available for extraction increased with disruption, and up to 81% could be recovered in supernatants after centrifugation, but a marked reorganization occurred. The proportion of amphiphilic free fatty acids and lysophosphatidylcholine increased during disruption due to their release or owing to lipid degradation by enzymes or physical conditions. This effect was more marked in HPD than in BM. Lipids contained in the aqueous phase, after disruption and centrifugation, were enriched in unsaturated fatty acids, BM leading to larger droplets than HPD. The larger liquid lipid droplet would be easier to recover in the following downstream processing.

A damascene platform for controlled ultra-thin nanowire fabrication.

This paper presents a damascene process for the fabrication of titanium micro/nanostructures and nanowires with adjustable thickness down to 2 nm. Their depth is precisely controlled by chemical-mechanical planarization together with in-process electrical characterization. The latter, in combination with a model of the titanium resistivity versus thickness, allows control of the metal line depth in the nanometer range. In summary, we have developed a planarization end point detection method for metal nanostructures. In addition, the model adopted covers geometrical influences like oxidation and ageing. The fabricated titanium nanowire test structures have a thickness ranging from 2 to 25 nm and a width ranging between 15 and 230 nm.

Simulating STEM imaging of nanoparticles in micrometers-thick substrates.

Scanning transmission electron microscope (STEM) images of three-dimensional (3D) samples were simulated. The samples consisted of a micrometer(s)-thick substrate and gold nanoparticles at various vertical positions. The atomic number (Z) contrast as obtained via the annular dark-field detector was generated. The simulations were carried out using the Monte Carlo method in the CASINO software (freeware). The software was adapted to include the STEM imaging modality, including the noise characteristics of the electron source, the conical shape of the beam, and 3D scanning. Simulated STEM images of nanoparticles on a carbon substrate revealed the influence of the electron dose on the visibility of the nanoparticles. The 3D datasets obtained by simulating focal series showed the effect of beam broadening on the spatial resolution and on the signal-to-noise ratio. Monte Carlo simulations of STEM imaging of nanoparticles on a thick water layer were compared with experimental data by programming the exact sample geometry. The simulated image corresponded to the experimental image, and the signal-to-noise levels were similar. The Monte Carlo simulation strategy described here can be used to calculate STEM images of objects of an arbitrary geometry and amorphous sample composition. This information can then be used, for example, to optimize the microscope settings for imaging sessions where a low electron dose is crucial for the design of equipment, or for the analysis of the composition of a certain specimen.

Etazolate improves performance in a foraging and homing task in aged rats.

Etazolate is a phosphodiesterase 4 (PDE4) inhibitor and GABAA receptor modulator that also stimulates alpha-secretase activity and neurotrophic soluble amyloid precursor protein (sAPPalpha) production, currently developed as a possible Alzheimer's disease therapeutic. In this study two doses of etazolate were tested for cognitive effects in normally aged rats, using a complex spatial learning and memory task that emphasized two naturally occurring behaviors in rodents, foraging for food and returning large pieces of found food to a safe home location. Both etazolate doses completely prevented both (1) a foraging deficit that developed in untreated aged rats over the course of the test, as well as (2) a trial-specific deficit in memory for previously visited food locations that also developed over the course of the test in untreated aged rats. Both doses also significantly reduced a separate memory deficit for changing locations of the animals' home box, plus completely prevented a significant tendency for untreated aged animals to attempt entry into similar-appearing but incorrect home boxes. The combined behavioral data demonstrate positive effects of etazolate on separate age-related cognitive deficits, using a complex task based on naturally occurring rodent behaviors.

[Knowledge transfer and implementation of clinical practice guidelines. Experience of the Canadian Hypertension Education Program]. / Le transfert des connaissances et la mise en oeuvre de lignes directrices de pratique Expérience du Programme d'Education Canadien sur l'Hypertension.

For the last 10 years, the update of guidelines for the treatment of hypertension in Canada is part of an annual process. This national strategy called the Canadian Hypertension Education Program (CHEP) has an organizational structure which allows not only to revise guidelines using an evidence-based scientific process but also to facilitate the implementation and the dissemination of the recommendations to the various healthcare professionals (doctors, pharmacists, nurses, etc.). As part of this process, the CHEP is also measuring different outcomes which could estimate the impact of its interventions. Recent data clearly show an improvement of the screening of hypertension as well as the quality of antihypertensive treatment (increase in the number of new prescriptions and of the percentage of subjects treated with 2 antihypertensive agents or more) in Canada. Finally, recent Canadian data showing a reduction of the cardiovascular complications attributable to hypertension suggest a possible link of causality with the implementation of the CHEP. This article will describe the functioning of the CHEP with its various strategies aiming at a better management of hypertension in Canada.

The effect of fast secondary electrons on x-ray microanalysis in the scanning electron microscope.

In this paper, the effect of fast secondary electrons (FSE), which result from inelastic scattering of incident electrons, on the characterization of materials in the scanning electron microscope are investigated with the aid of Monte Carlo simulations. The effect of FSE on x-ray microanalysis of light elements is investigated. A full description of the Monte Carlo simulations of FSE in solids is given.

Cutaneously applied 4-hydroxytamoxifen is not carcinogenic in female rats.

Tamoxifen is widely used to treat oestrogen-dependent carcinoma of the breast. Previous long-term studies have shown that oral administration of tamoxifen induces hepatoproliferative lesions and hepatocellular tumours in rats. 4-hydroxytamoxifen is an active metabolite of tamoxifen undergoing clinical evaluation for the treatment of various non-malignant breast diseases by topical application. In the present study, 4-hydroxytamoxifen was administered daily by cutaneous application for 101 weeks to groups of 50 female Sprague-Dawley rats at 20, 140 or 1000 microg/kg/day. The product was applied with no occlusive bandage and oral ingestion was avoided by application of an Elizabethan collar for 6 h after administration. Treatment with 4-hydroxytamoxifen was clinically well tolerated and induced changes such as decreased food consumption and body weight gain, uterine and ovarian atrophy, mucification of vaginal epithelium and reduced mammary development, all of which were attributed to its pharmacological action. Mortality was significantly lower in the treated animals. The number of animals with palpable masses was similarly reduced. The incidence of mammary tumours and hypophyseal tumours was markedly lower in 4-hydroxytamoxifen-treated animals. The incidence of chronic tubulo-interstitial nephropathies, a common cause of mortality, was also lowered. There was no evidence of a carcinogenic action of 4-hydroxytamoxifen on the liver, genital organs or skin. Plasma levels of 4-hydroxytamoxifen were stable over the duration of the study and were proportional to the administered dose, exceeding clinical plasma levels by 60-fold at the high dose-level. In conclusion, 4-hydroxytamoxifen is not carcinogenic in the rat and reduces the incidence of spontaneous mammary and hypophyseal tumours.

An interactive workshop: An effective means of integrating the Canadian Cardiovascular Society clinical practice guidelines on congestive heart failure into Canadian family physicians' practice.

OBJECTIVE: To use an interactive workship as a means of integrating clinical practice guidelines on congestive heart failure into Canadian family physicians' practice. SETTING: Interested practitioners from the Association des Médecins Omnipraticiens de Québec, the Centre de Santé Publique de Québec and the continuing medical education (CME) department, Merck Frosst Canada, Montreal, formed the initial task force. Train-the-trainer sessions took place in many provinces in a variety of CME settings. DESIGN: The interactive, problem-based workshop was facilitated by local interested general practitioners, while local experts served as consultants to reinforce key messages from clinical practice guidelines and to guide participants through the learning process. MAIN RESULTS: By December 31, 1996, 187 family practitioners and 81 specialists had been trained in train-the-trainer sessions across the country. A total of 1698 general practitioners had participated in over 52 workshops during the same time. Pre- and postworkshop testing indicate that the workshops improved knowledge, and that the knowledge gained during the workshop was retained at three- and six-months' follow-up. Separate chart evaluations conducted before and after the workshop showed that participants provided more complete chart information related to congestive heart failure and that they significantly increased their use of angiotensin-converting enzyme inhibitor therapy after the workshop. Participant evaluation of the workshop also indicates a high index of satisfaction with the presentation and the content of the workshop as being relevant to clinical practice. CONCLUSION: An interactive, problem-based, small group workshop developed by a core group of interested practitioners and guided by local trained facilitators and experts is an effective teaching tool through which clinical practice guidelines can be successfully transferred into clinical practice in a timely and meaningful way.

Leisure activities and service knowledge and use among the rural elderly.

This exploratory study uses Andersen's service utilization model to examine the relationship between the leisure activity patterns of older people and their knowledge and use of health and social services. Hierarchical stepwise multiple regression analyses of data from 418 people ages 65 and older in rural Qu/ebec revealed that leisure activity patterns may explain a greater amount of variation in service knowledge and use than conventional need characteristics such as physical and psychological health. Various activity patterns were significantly related to knowledge and use of services even after controlling for variables such as age and health status. Although some types of leisure activities appeared to augment knowledge and use of services, others seemed to deter it. Future explanatory models of service utilization among the elderly should be expanded to include leisure activity patterns.

Pilocarpine hydrochloride liposomes: characterization in vitro and preliminary evaluation in vivo in rabbit eye.

Liposomes containing either pilocarpine hydrochloride or pilocarpine free base were prepared by the sonication method. This manufacturing process yielded after removal of non-encapsulated solute, small multilamellar vesicles (MLV) as was confirmed by electron microscopy examinations. For an identical liposomal composition, the encapsulation capacity and the drug content of the liposomes were drastically higher for pilocarpine hydrochloride than for pilocarpine free base. Investigation of the preparative parameters revealed that increasing the initial amount of drug decreased the drug content and the encapsulation efficiency of the liposomes formed. Since fixed amounts of lipids were used, the volume sequestration rate decrease was attributed to a moderate viscosity increase of the dispersion medium. Increase of phospholipid concentration at a constant ratio of cholesterol and dicetylphosphate to phosphatidylcholine reduced the aqueous volume entrapped per mg of lipid and subsequently the pilocarpine content in the liposomes. Negatively charged liposomes gave larger rates of pilocarpine hydrochloride and aqueous volume encapsulation than neutral liposomes but, on the contrary, positively charged liposomes gave the lowest rates of pilocarpine hydrochloride and aqueous volume encapsulation. Thus, for drug carrying the same net charge as the phospholipids an increase in the surface charge density of the liposome was not only ineffective, but actually resulted in a lower drug encapsulation due to electrostatic repulsion. Preliminary in vivo results on rabbit eyes suggested that the liposomal vehicle was probably unable to improve sufficiently the corneal penetration of pilocarpine to reach satisfactory therapeutic levels when administered at lower concentrations than commonly used.