-The effects of mechanical perturbations (shear stress, pressure) on microvascular permeability primarily have been examined in micropipette-cannulated vessels or in endothelial monolayers in vitro. The objective of this study is to determine whether acute changes in blood flow shear stress might influence measurements of hydraulic conductivity (Lp) in autoperfused microvessels in vivo. Rat mesenteric microvessels were observed via intravital microscopy. Occlusion of a third-order arteriole with a micropipette was used to divert and increase flow through a nonoccluded capillary or fourth-order arteriolar branch. Using the micropipette occlusion technique in autoperfused rather than cannulated capillaries, Landis described how the fluid filtration rate was most rapid in the initial seconds following occlusion, becoming significantly slower in less than 1 min. This was attributed at least in part to the possibility that plasma oncotic pressure could increase with time in an occluded vessel as a result of greater efflux of water than of protein. However, another consideration is that the vessel occlusion includes an abrupt change in flow-induced shear stress and pressure, both of which could have a time-dependent effect on L p .As a microvessel is occluded, blood flow decreases from its basal value to essentially zero. Several studies have shown that transvascular exchange can be affected by a change in perfusion rate (14,17,19,32,33,43). A small-pore model has been proposed as a possible mechanism to account for flow-dependent transport of small solutes in cannulated vessels (32); moreover, there have been several recent studies of shearinduced increases in fluid filtration performed in vitro (3, 6, 37) and in vivo (27,40,41). The mechanism by which shear forces could increase L p appear to be dependent on nitric oxide (NO) (3,15,24). Therefore, when a capillary stops flowing, it might be expected that L p could decline in a matter of seconds as shear-induced production of NO is attenuated.Another mechanical factor associated with microvessel occlusion is the step increase in hydrostatic pressure. For example, when a capillary is occluded at its downstream end, pressure throughout the vessel increases to that of the feeding arteriole. Recent studies (7,38) indicate that a step increase in hydrostatic pressure causes a decrease in L p in what has been called a "sealing effect." However, the time courses of the changes in L p in these studies were over a period of minutes to hours.The effects of shear on L p have been examined previously in micropipette-cannulated vessels or in endothelial monolayers in vitro. The primary objective of the current study was to determine whether acute changes in blood flow shear might influence measurements of L p in autoperfused, rather than cannulated, microvessels. In addition, a role for NO in shearmediated changes in L p was investigated. MATERIALS AND METHODSAnimal preparation. Animal procedures were approved by an Institutional Animal Care And Use Committee. Male Wistar rats ϳ2...

PurposePhysician Orders for Life-Sustaining Treatment (POLST) form is a legal document for terminally ill patients to make medical decisions with physicians near the end-of-life. A multicenter prospective study was conducted to evaluate the feasibility of POLST administration in actual oncological practice.Materials and MethodsPatients with terminal cancer, age ≥ 20 years, and capable of communicating were eligible. The primary endpoint was the completion rate of POLST. Data about physicians’ or patients’ barriers were also collected.ResultsFrom June to December 2017, 336 patients from seven hospitals were eligible. Median patient age was 66 years (range, 20 to 94 years); 52.7% were male; and 60.4% had poor performance status. Primary cancer sites were hepato-pancreato-biliary (26.2%), lung (23.2%), and gastrointestinal (19.9%). Expected survival duration was 10.6±7.3 weeks, with 41.2% receiving hospice care, 37.9% showing progression after cancer treatment, and the remaining patients were under active treatment (15.8%) or initially diagnosed with terminal cancer (5.1%). POLST forms were introduced to 60.1% of patients, and 31.3% signed the form. Physicians’ barriers were reluctance of family (49.7%), lack of rapport (44.8%), patients’ denial of prognosis (34.3%), lack of time (22.7%), guilty feelings (21.5%), and uncertainty about either prognosis (21.0%) or the right time to discuss POLST (16.6%). The patients’ barriers were the lack of knowledge/understanding of POLST (65.1%), emotional discomfort (63.5%), difficulty in decision-making (66.7%), or denial of prognosis (14.3%).ConclusionOne-third of patients completed POLST forms, and various barriers were identified. To overcome such barriers, social engagement, education, and systematic support might be necessary.

Hypercholesterolemia is associated with an attenuation of endothelium-dependent dilation in arterioles and an increase in leukocyte and platelet adhesion in venules. The proximity of closely paired arterioles and venules is thought to facilitate heat and mass transport between the two and could be involved in transport of inflammatory and/or vasoactive mediators from venule to arteriole. In the current study, we tested the hypothesis that the impaired arteriolar dilation associated with hypercholesterolemia might be dependent on P-selectin-dependent blood cell adhesion in the closely paired venules. Leukocyte and platelet recruitment in venules and the endothelium-dependent response to bradykinin in second-order arterioles were observed in the mouse intestinal submucosa using intravital microscopy. Four weeks of a high-cholesterol diet decreased bradykinin-induced arteriolar dilation more dramatically in closely paired arterioles than in distantly paired arterioles. The dysfunctional arteriolar dilation of closely paired arterioles in hypercholesterolemic mice was significantly improved when the experiments were repeated in P-selectin-deficient mice (given the high-cholesterol diet) or in hypercholesterolemic mice injected with a P-selectin monoclonal antibody. A similar improvement in dilation of closely paired arterioles was attained in hypercholesterolemic mice given the superoxide dismutase mimetic Tempol. These findings indicate that hypercholesterolemia-induced increases in venular leukocyte and platelet adhesion might contribute to the impaired endothelium-dependent dilation of closely paired arterioles via a mechanism that is distance limited and dependent on P-selectin and superoxide.

The present study addresses the effect of a sustained change in pressure on microvascular permeability assessed by hydraulic conductivity (Lp) measurements from microvessels of the rat mesentery. With a microperfusion technique, transvascular filtration (normalized to surface area; Jv/S) and Lp were measured in small arterioles (baseline Lp= 0.26 x 10(-7) cm.s(-1).cmH2O(-1)) and venules (baseline Lp= 2.88 x 10(-7) cm.s(-1).cmH2O(-1)). The main finding of this study is that step increases in microvascular pressure led to time-dependent alterations of L(p). Immediately after a twofold step increase in pressure, Jv/S increased in proportion to the pressure change. This observation is consistent with Starling's law that predicts filtration proportional to the overall pressure gradient when Lp is constant. However, when Jv/S measurements continued for 60-90 min past the step in pressure, there was an initial decrease in Jv/S for 30 min ("sealing effect") followed by a substantial increase in Jv/S out to 90 min. The sustained increase in Jv/S suggests an increase in Lp of 36 +/- 7% for small arterioles and 42 +/- 5% for small venules (P < 0.05 for both). In addition, the increase in Lp in response to an increase in pressure was attenuated significantly by nitric oxide synthase inhibition. These results indicate that a pressure-induced mechanical stimulus (possibly Jv) activates a NO-dependent biochemical response that leads to an increase in hydraulic conductivity.

We examined the effect of long-term changes in environmental factors on the prevalence of allergic diseases in elementary school students in Ulsan, Korea. This longitudinal study was conducted among 390 students who were enrolled from three elementary schools in Ulsan in both the first (2009–2010) and second survey (2013–2014). The International Study of Asthma and Allergies in Childhood questionnaire was used to determine the prevalence of allergic diseases and hazardous environmental factors. Generalized estimating equations (GEE) were used to investigate the impact of environmental factors on the change in the prevalence of allergic diseases. The survey revealed that an increased risk of allergic rhinitis was associated with exposure to secondhand smoke, the remodeling of a room, the replacement of wallpaper or flooring, the use of a humidifier, and irritation symptoms of air pollution. Atopic dermatitis was associated with the relocation to or repairs of a new house, and allergic conjunctivitis was associated with low levels of weekly physical activity, the use of insecticides, and irritation symptoms of air pollution. The results indicate that (1) allergic rhinitis and atopic dermatitis are associated with indoor pollution, (2) allergic conjunctivitis is associated with exposure to indoor chemical compounds and low levels of weekly physical activity. This study suggested that the proper evaluation and decrease in the number of environmental risk factors could effectively manage allergic diseases.