Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: <=90 (n=6264); <=85 (n=6264); <=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure<=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure <=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of <=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of <=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels <=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure <=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.

The influence of patient's consciousness regarding high blood pressure and patient's attitude in face of disease controlling medicine intake

OBJECTIVE: To assess the relation between blood pressure control and the following: the Morisky-Green test, the patient's consciousness regarding high blood pressure, the patient's attitude in face of medicine intake, the patient's attendance at medical consultations, and the subjective physician's judgment. METHODS: We studied 130 hypertensive patients with the following characteristics: 73% females, 60±11 years, 58% married, 70% white, 45% retired, 45% with incomplete elementary schooling, 64% had a familial income of 1 to 3 minimum wages, body mass index of 30±7 kg/m², consciousness regarding the disease for a mean period of 11±9.5 years, and mean treatment duration of 8 ±7 years. RESULTS: Only 35% of the hypertensive individuals had blood pressure under control and a longer duration of treatment (10±7 vs 7±6.5 years; P<0.05). The retiree predominated. The result of the Morisky-Green test did not relate to blood pressure control. In evaluating the attitude in face of medicine intake, the controlled patients achieved significantly higher scores than did the noncontrolled patients (8±1.9 vs 7 ±2, P<0.05). The hypertensive patients had higher levels of consciousness regarding their disease and its treatment, and most (70%) patients attended 3 or 4 medical consultations, which did not influence blood pressure control. The physicians attributed significantly higher scores regarding adherence to treatment to controlled patients (6±0.8 vs 5±1.2; P<0.05). CONCLUSION: Consciousness regarding the disease, the Morisky-Green test, and attendance to medical consultations did not influence blood pressure control.

Electrokinetic flow and transport in porous media : experimental methods, numerical analysis, and applications

Electrokinetic transport, electrochromatography, electroosmotic flow, electrophoresis, concentration polarization, fixed beds, monoliths, dynamic NMR microscopy, quantitative confocal laser scanning microscopy, mathematical modelling, numerical analysis

Malaria and Vascular Endothelium

Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease.

Elevated Blood Pressure and Obesity in Childhood: A Cross-Sectional Evaluation of 4,609 Schoolchildren

Background: The incidence of obesity in children is increasing worldwide, primarily in urbanized, high-income countries, and hypertension development is a detrimental effect of this phenomenon. Objective: In this cross-sectional study, we evaluated the prevalence of excess weight and its association with high blood pressure (BP) in schoolchildren. Methods: Here 4,609 male and female children, aged 6 to 11 years, from 24 public and private schools in Maringa, Brazil, were evaluated. Nutritional status was assessed by body mass index (BMI) according to cutoff points adjusted for sex and age. Blood pressure (BP) levels above 90th percentile for gender, age and height percentile were considered elevated. Results: The prevalence of excess weight among the schoolchildren was 24.5%; 16.9% were overweight, and 7.6% were obese. Sex and socioeconomic characteristics were not associated with elevated BP. In all age groups, systolic and diastolic BP correlated with BMI and waist and hip measurements, but not with waist-hip ratio. The prevalence of elevated BP was 11.2% in eutrophic children, 20.6% in overweight children [odds ratio (OR), 1.99; 95% confidence interval (CI), 1.61-2.45], and 39.7% in obese children (OR, 5.4; 95% CI, 4.23-6.89). Conclusion: Obese and overweight children had a higher prevalence of elevated BP than normal-weight children. Our data confirm that the growing worldwide epidemic of excess weight and elevated BP in schoolchildren may also be ongoing in Brazil.

Progression of Blood Pressure and Cardiovascular Outcomes in Hypertensive Patients in a Reference Center

Background: Hypertension is a public health problem, considering its high prevalence, low control rate and cardiovascular complications. Objective: Evaluate the control of blood pressure (BP) and cardiovascular outcomes in patients enrolled at the Reference Center for Hypertension and Diabetes, located in a medium-sized city in the Midwest Region of Brazil. Methods: Population-based study comparing patients enrolled in the service at the time of their admission and after an average follow-up of five years. Participants were aged ≥18 years and were regularly monitored at the Center up to 6 months before data collection. We assessed demographic variables, BP, body mass index, risk factors, and cardiovascular outcomes. Results: We studied 1,298 individuals, predominantly women (60.9%), and with mean age of 56.7±13.1 years. Over time, there was a significant increase in physical inactivity, alcohol consumption, diabetes, dyslipidemia, and excessive weight. As for cardiovascular outcomes, we observed an increase in stroke and myocardial revascularization, and a lower frequency of chronic renal failure. During follow-up, there was significant improvement in the rate of BP control (from 29.6% to 39.6%; p = 0.001) and 72 deaths, 91.7% of which were due to cardiovascular diseases. Conclusion: Despite considerable improvements in the rate of BP control during follow-up, risk factors worsened and cardiovascular outcomes increased.

Flow and transport in electrochromatography

Analyte retention, analyte transport, axial dispersion, adsorption, charge-selectivity, concentration polarization, confocal laser scanning microscopy, donnan-exclusion, electrical double layer; electrochromatography; electrohydrodynamics, electrokinetic instability, electroosmosis; electroosmotic flow; electroosmotic mobility, electroosmotic perfusion, electrophoresis, hierarchical porous media, hydrodynamic flow, induced-charge electroosmosis, ion-permselectivity, ion-permselective transport, monolith, nonequilibrium electrical double layer, nonequilibrium electrokinetic effects, nonlinear electroosmosis, plate height, plate number, porous media, pore-scale dispersion, refractive index matching, space charge effects, sphere packing, quantitative imaging, wall effect, zeta-potential

Granular flow and design studies in flighted rotating drums

Magdeburg, Univ., Fak. für Verfahrens- und Systemtechnik, Diss., 2013

Development of cell mediated immunity to flagellar antigens and acquired resistance to infection by Trypanosoma cruzi in mice

Modulation by BCG and/or cyclophosphamide of sensitization of mice with flagellar fraction (a tubulin-enriched fraction) prevented death of mice challenged with T. cruzi CL strain trypomastigotes recovered from Vero cells. A methodology was ceveloped to assay specific antigens and to determine optimal doses for sensitization and elicitation of DTH in mice. CL strain is predominantly myotropic strain which does not produce important parasitism of mononuclear phagocyte cells; these cells appear to control infection when activated in vivo. Maximum protection was seen in this study when BCG and cyclophosphamide were associated, but protection was observed also when cyclophosphamide, that prevents supressor T cells, was applied 2 days before flagellar fraction sensitization in normal mice. These experiments suggested that the macrophage may have an important role in the early phases of infection particularly when nonspecific stimulation is associated with specific sensitization. A correlation betwen delayed hypersensitivity to parasite antigens and protection was observed.

Female plumage spottiness and parasite resistance in the barn owl (Tyto alba)

The hypothesis that extravagant ornaments signal parasite resistance has received support in several species for ornamented males but more rarely for ornamented females. However, recent theories have proposed that females should often be under sexual selection, and therefore females may signal the heritable capacity to resist parasites. We investigated this hypothesis in the socially monogamous barn owl, Tyto alba, in which females exhibit on average more and larger black spots on the plumage than males, and in which males were suggested to choose a mate with respect to female plumage spottiness. We hypothesized that the proportion of the plumage surface covered by black spots signals parasite resistance. In line with this hypothesis, we found that the ectoparasitic fly, Carnus hemapterus, was less abundant on young raised by more heavily spotted females and those flies were less fecund. In an experiment, where entire clutches were cross-fostered between nests, we found that the fecundity of the flies collected on nestlings was negatively correlated with the genetic mother's plumage spottiness. These results suggest that the ability to resist parasites covaries with the extent of female plumage spottiness. Among females collected dead along roads, those with a lot of black spots had a small bursa of Fabricius. Given that parasites bigger the development of this immune organ, this observation further suggests that more spotted females are usually less parasitized. The same analyses performed on male plumage spottiness all provided non-significant results. To our knowledge, this study is the first one showing that a heritable secondary sexual characteristics displayed by females reflects parasite resistance.

Photodynamic therapy : a pathway for enhanced delivery of liposomal doxorubicin to tumors

Abstract Part I : Background : Isolated lung perfusion (ILP) was designed for the treatment of loco-regional malignancies of the lung. In contrast to intravenous (IV) drug application, ILP allows for a selective administration of cytostatic agents such as doxorubicin to the lung while sparing non-affected tissues. However, the clinical results with ILP were disappointing. Doxorubicinbased ILP on sarcoma rodent lungs suggested high overall doxorubicin concentrations within the perfused lung but a poor penetration of the cytostatic agent into tumors. The same holds true for liposomal-encapsulated macromolecular doxorubicin (LiporubicinTM) In specific conditions, low-dose photodynamic therapy (PDT) can enhance the distribution of macromolecules across the endothelial bamer in solid tumors. It was recently postulated that tumor neovessels were more responsive to PDT than the normal vasculature. We therefore hypothesized that Visudyne®-mediated PDT could selectively increase liposomal doxorubicin (LiporubicinTM) uptake in sarcoma tumors to rodent lungs during intravenous (IV) drug administration and isolated lung perfusion (ILP). Material and Methods : A sarcoma tumor was generated in the left lung of Fisher rats by subpleural injection of a sarcoma cell ,suspension via thoracotomy. Ten days later, LiporubicinTM is administered IV or by single pass antegrade ILP, with or without Visudyne® -mediated low-dose PDT pre-treatment of the sarcoma bearing lung. The drug concentration and distribution were assessed separately in tumors and lung tissues by high pressure liquid chromatography (HPLC) and fluorescence microscopy (FNI~, respectively. Results : PDT pretreatment before IV LiporubicinTM administration resulted in a significantly higher tumor drug uptake and tumor to lung drug ratio compared to IV drug injection alone without affecting the blood flow and drug distribution in the lung. PDT pre-treatment before LiporubicinTM-based ILP also resulted in a higher tumor drug uptake and a higher tumor to lung drug ratio compared to ILP alone, however, these differences were not significant due to a heterogeneous blood flow drug distribution during ILP which was further accentuated by PDT. Conclusions : Low-dose Visudyne®-mediated PDT pre-treatment has the potential to selectively enhance liposomal encapsulated doxorubicin uptake in tumors but not in normal lung tissue after IV drug application in a rat model of sarcoma tumors to the lung which opens new perspectives for the treatment of superficially spreading chemoresistant tumors of the chest cavity such as mesothelioma or malignant effusion. However, the impact of PDT on macromolecular drug uptake during ILP is limited since its therapeutic advantage is circumvented by ILP-induced heterogeneicity of blood flow and drug distribution Abstract Part II Background : 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. Material and Methods : Fluorescein isothiocyanate dextran (FITC-D, 2000kDa), a macromolecular agent, was intravenously injected 10 minutes before (LKO group, n=14) or 2 hours (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 2500 seconds 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. Results : 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 LKO group had significantly less FITC-D extravasation than those from the LK2 group (p = 0.0002). In the LKO group FITC-D leakage correlated significantly with the inflammation (p < 0.001). Conclusions: 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. Résumé : La perfusion cytostatique isolée du poumon permet une administration sélective des agents cytostatiques sans implication de la circulation systémique avec une forte accumulation au niveau du poumon mais une faible pénétration dans les tumeurs. La thérapie photodynamique (PDT) qui consiste en l'application d'un sensibilisateur activé par lumière laser non- thermique d'une longueur d'onde définie permet dans certaines conditions, une augmentation de la pénétration des agents cytostatiques macromoléculaires à travers la barrière endothéliale tumorale. Nous avons exploré cet avantage thérapeutique de la PDT dans un modèle expérimental afin d'augmenter d'une manière sélective la pénétration tumorale de la doxorubicin pegylée, liposomal- encapsulée macromoléculaire (Liporubicin). Une tumeur sarcomateuse a été générée au niveau du poumon de rongeur suivie d'administration de Liporubicin, soit par voie intraveineuse soit par perfusion isolée du poumon (ILP). Une partie des animaux ont reçus un prétraitement de la tumeur et du poumon sous jacent par PDT avec Visudyne comme photosensibilisateur. Les résultats ont démontrés que la PDT permet, sous certaines conditions, une augmentation sélective de Liporubicin dans les tumeurs mais pas dans le parenchyme pulmonaire sous jacent. Après administration intraveineuse de Liporubicin et prétraitement par PDT, l'accumulation dans les tumeurs était significative par rapport au poumon, et aux tumeurs sans PDT. Le même phénomène est observé après ILP du poumon. Cependant, les différences avec ou sans PDT n'étaient pas significatives lié à und distribution hétérogène de Liporubicin dans le poumon perfusé après ILP. Dans une deuxième partie de l'expérimentation, nous avons exploré la microscopie intra-vitale pour déterminer l'extravasion des substances macromoléculaires (FITS) à travers la barrière endothéliale avec ou sans Visudyne-PDT au niveau des chambres dorsales des souris nues. Les résultats montrent qu'après PDT, l'extravasion de FITS a été augmentée de manière significative par rapport au tissu non traité. L'intensité de l'extravasion de FITS dépendait également de l'intervalle entre PDT et injection de FITS. En conclusion, les expérimentations montrent que la PDT est capable, sous certaines conditions, d'augmenter de manière significative l'extravasion des macromolécules à travers la barrière endothéliale et leur accumulation dans des tumeurs mais pas dans le parenchyme pulmonaire. Ces résultats permettent une nouvelle perspective de traitement pour des tumeurs superficielles intrathoraciques chimio-résistent comme l'épanchement pleural malin ou le mésothéliome pleural.

Identifying the neural correlates of executive functions in early cerebral microangiopathy: a combined VBM and DTI study.

Cerebral microangiopathy (CMA) has been associated with executive dysfunction and fronto-parietal neural network disruption. Advances in magnetic resonance imaging allow more detailed analyses of gray (e.g., voxel-based morphometry-VBM) and white matter (e.g., diffusion tensor imaging-DTI) than traditional visual rating scales. The current study investigated patients with early CMA and healthy control subjects with all three approaches. Neuropsychological assessment focused on executive functions, the cognitive domain most discussed in CMA. The DTI and age-related white matter changes rating scales revealed convergent results showing widespread white matter changes in early CMA. Correlations were found in frontal and parietal areas exclusively with speeded, but not with speed-corrected executive measures. The VBM analyses showed reduced gray matter in frontal areas. All three approaches confirmed the hypothesized fronto-parietal network disruption in early CMA. Innovative methods (DTI) converged with results from conventional methods (visual rating) while allowing greater spatial and tissue accuracy. They are thus valid additions to the analysis of neural correlates of cognitive dysfunction. We found a clear distinction between speeded and nonspeeded executive measures in relationship to imaging parameters. Cognitive slowing is related to disease severity in early CMA and therefore important for early diagnostics.

Consequences of smoking for body weight, body fat distribution, and insulin resistance

Our aim was to critically evaluate the relations among smoking, body weight, body fat distribution, and insulin resistance as reported in the literature. In the short term, nicotine increases energy expenditure and could reduce appetite, which may explain why smokers tend to have lower body weight than do nonsmokers and why smoking cessation is frequently followed by weight gain. In contrast, heavy smokers tend to have greater body weight than do light smokers or nonsmokers, which likely reflects a clustering of risky behaviors (eg, low degree of physical activity, poor diet, and smoking) that is conducive to weight gain. Other factors, such as weight cycling, could also be involved. In addition, smoking increases insulin resistance and is associated with central fat accumulation. As a result, smoking increases the risk of metabolic syndrome and diabetes, and these factors increase risk of cardiovascular disease. In the context of the worldwide obesity epidemic and a high prevalence of smoking, the greater risk of (central) obesity and insulin resistance among smokers is a matter of major concern