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Objectives: The aim of this survey was to compare stressful life events, social support and sense of coherence (sac) between frequent attenders (FAs) and normal attenders (controls) in primary health care. Study design: A cross-sectional study was conducted in a primary healthcare centre in the south-west of Sweden. Methods: A postal questionnaire was sent to 263 frequent attenders and 703 normal attenders. The questionnaire comprised sociodemographic variables and scales of stressful life events, social support and SOC. The results from the questionnaire were compared between the groups, and the significance of the variables in terms of attendance was tested in a multiple regression analysis. Results: More of the FAs were secondarily single, they had more chronic diseases and were more often living on a sickness/disablement pension than the controls. FAs did not report more stressful life events than the controls nor was their experience of events more negative. Social support was as strong among FAs as among controls, and it had no significant effect on their frequent attendance. FAs had a significantly weaker SOC compared with controls. The variables that significantly influenced frequent attendance were high age [odds ratio (OR)=1.02], chronic disease (OR= 3.08), sickness/disablement pension (OR=2.46) and sac (OR=0.97). Conclusions: SOC had a significant influence on frequent attendance in primary health care, but stressful life events and social support did not. FAs did not report more stressful life events. However, due to an inadequate coping strategy, indicated by a weak SOC, the life events probably caused them more symptoms and diseases, and thereby a higher consulting frequency. [ABSTRACT FROM AUTHOR]

Abstract: Photodynamic therapy (PDT) with Visudyne® acts by direct cellular phototoxicity and/or by an indirect vascular-mediated effect. Here, we demonstrate that the vessel integrity interruption by PDT can promote the extravasation of a macromolecular agent in normal tissue. To obtain extravasation in normal tissue PDT conditions were one order of magnitude more intensive than the ones in tissue containing neovessels reported in the literature. Fluorescein isothiocyanate dextran (FITC-D, 2000kDa), a macromolecular agent, was intravenously injected 10min before (LK0 group, n =14) or 2h (LK2 group, n =16) after Visudyne®-mediated PDT in nude mice bearing a dorsal skin fold chamber. Control animals had no PDT (CTRL group, n =8). The extravasation of FITC-D from blood vessels in striated muscle tissue was observed in both groups in real-time for up to 2500s after injection. We also monitored PDT-induced leukocyte rolling in vivo and assessed, by histology, the corresponding inflammatory reaction score in the dorsal skin fold chambers. In all animals, at the applied PDT conditions, FITC-D extravasation was significantly enhanced in the PDT-treated areas as compared to the surrounding non-treated areas (p <0.0001). There was no FITC-D leakage in the control animals. Animals from the LK0 group had significantly less FITC-D extravasation than those from the LK2 group (p =0.0002). In the LK0 group FITC-D leakage correlated significantly with the inflammation (p <0.001). At the selected conditions, Visudyne®-mediated PDT promotes vascular leakage and FITC-D extravasation into the interstitial space of normal tissue. The intensity of vascular leakage depends on the time interval between PDT and FITC-D injection. This concept could be used to locally modulate the delivery of macromolecules in vivo. [Copyright &y& Elsevier]

Abstract: In photodynamic therapy (PDT), excitation of a drug by light leads to a cascade of biochemical processes that can cause closure of blood vessels. It has been observed clinically that significant short-term leakage from the irradiated vasculature can occur prior to vessel closure and blood flow stasis. In this paper we demonstrate in a chicken embryo model that this leakage can be significantly enhanced by the presence of the cyclo-oxygenase inhibitor, aspirin. We also observe that following this aspirin-enhanced leakage, blood vessels close as effectively as after PDT in the absence of aspirin. Consequently we propose that this PDT-induced aspirin-enhanced leakage can be used to locally deliver a drug for combination therapy. This is then demonstrated in the chicken embryo using Visudyne® as a PDT agent in combination with aspirin and fluorescein isothiocyanate dextran 10 kDa as leakage indicator. The latter represents a hypothetical drug to be delivered in various kinds of combination therapy. Two examples of this procedure would be the photodynamic treatment of choroidal neovasculature associated with exudative age-related macular degeneracy (AMD) where local delivery of an anti-angiogenic or an anti-inflammatory drug has been shown to be effective, or PDT of cancer where local dosing of a chemotherapeutic drug may well increase the treatment efficacy. [Copyright &y& Elsevier]

Abstract: The objective of this study was to evaluate the ability of meso-tetra(hydroxyphenyl)chlorin (m-THPC) encapsulated into liposomal formulations to occlude neovascularization. Two m-THPC formulations including conventional or plain liposomes (Foslip) based on dipalmitoylphosphatidylcholine (DPPC) and the corresponding long-circulating poly(ethylene glycol) (PEG)-modified liposomes (PEGylated liposomes: Fospeg) were evaluated as delivery systems. Using the chick chorioallantoic membrane (CAM) as in vivo model, the fluorescence pharmacokinetic behaviour of encapsulated m-THPC reflecting the rate of the extravasation of the dye from the CAM vasculature and its photothrombic effectiveness were determined. This study was focused on the influence of the drug and/or light doses on the mean retention time of m-THPC within the CAM blood vessels after intravenous injection, and its photothrombic efficacy. Irrespective of the formulations tested and the drug doses injected, similar fluorescence pharmacokinetic profiles were obtained. The fluorescence contrast reached a steady state 30s after injection. Constant positive values of the fluorescence contrast suggest that m-THPC is confined into the intravascular compartment during the experimental time (500s). However, the photodynamic therapy assays showed that Foslip appears to be less potent than Fospeg in terms of photothrombic activities on the CAM model. For instance, the light dose necessary to induce the desired vascular damage with Foslip was twice (100J/cm2) higher than with Fospeg (50J/cm2). It can be inferred that this pre-clinical study showed that the formulation based on PEGylated liposomes technology offers a suitable delivery system for the treatment of choroidal neovascularization associated with age-related macular degeneration. [Copyright &y& Elsevier]

The Grenoble metropolitan area, located in the French Alps, regularly has periods of high ozone concentrations during the summertime. Grenoble is located in a Y shaped convergence of three deep valleys, some 3000 m above sea level, with typical wind pattern. During the summer of 1999, a major field campaign GRENOble PHOTochemistry (GRENOPHOT) was held in order to obtain measurements necessary for air quality model validation. The air quality model METeorological PHOtochemistry MODel (METPHOMOD) is used to investigate the dynamic characteristics of air pollution in the Grenoble area during the GRENOPHOT field campaign. The meteorological and atmospheric chemistry simulations were validated using both ground and vertical profile measurements (e.g. lidar) performed during the observation period (25–27 July) when the measured ozone concentrations reached 95 ppb. Both the spatial as well as the temporal variability of the simulated ozone concentrations were in good agreement with the measured values. The highest ozone values were found, in the southern zone, some 20 km downwind of the city center. It was found that about 32 ppb of fresh ozone are generated in the Grenoble plume. For developing ozone abatement strategies it is important to know whether in a specific area the ozone production is limited by VOC or NOx. Several indicators were proposed for distinguishing between VOC and NOx limitation. The morning Θ=τHOVOC/τHONOx (the ratio of the lifetimes of OH against losses by reacting with VOC and NOx) was applied and the afternoon indicator was κ=[H2O2]/[HNO3]. The Θ indicator gives information about the effect of changes in the emissions on the ozone formation in the air parcel which passes there, whereas κ provides information about the sensitivity of ozone formation in the aging plume. A combination of both indicators can be used to obtain a comprehensive view of the ozone formation in the Grenoble area. These results are confirmed by the investigation of the air mass regime with the time evolution of the ozone isopleths at the maximums locations (south and north west valleys). [Copyright &y& Elsevier]

An episode selection procedure was developed and applied to select sets of days representing characteristic meteorological conditions leading to high ozone episodes over the Swiss Plateau. The selection procedure was applied to data extending from January 1991 through December 1998, and is comprised of two steps: First, days were classified according to observed air quality and meteorological characteristics using classification and regression trees analysis (CART). Second, the CART results were used in conjunction with observed air quality data to identify sets of days characteristic of those leading to elevated ozone. These sets of days were selected to optimise how well a limited number of days represented seasonal air quality, and that formed longer episodes for use in the air quality modelling. CART analysis was performed for three zones of the Swiss Plateau that have different air quality and meteorological characteristics. The results for two zones were used together in the episode selection procedure in order to identify days representative for the whole Plateau. Meteorological analysis for a third zone suggested that it would be strongly impacted by pollutants transported in from outside the country. One thousand and eight hundred optimisation runs were performed to minimise the likelihood that the set of days was a local optimum, increasing the robustness for use in air quality modelling analysis. Fifteen days, grouped in four episodes ranging from 3 to 5 days were selected along with their calculated representativeness (or weight) to recreate a seasonal metric. The variety of local as well as regional meteorological characteristics showed that the episode selection procedure chose days representing a diverse set of meteorological situations which are associated with elevated ozone. This set of episodes can now be used to test air quality strategies. [Copyright &y& Elsevier]