Use of pulse pressure variation to estimate changes in preload during experimental acute normovolemic hemodilution

Background. Acute normovolemic hemodilution (ANH) is an alternative to blood transfusion in surgeries involving blood loss. This experimental study was designed to evaluate whether pulse pressure variation (PPV) would be an adequate tool for monitoring changes in preload during ANH, as assessed by transesophageal echocardiography. Methods. Twenty-one anesthetized and mechanically ventilated pigs were randomized into three groups: CTL (control), HES (hemodilution with 6% hydroxyethyl starch at a 1:1 ratio) or NS (hemodilution with saline 0.9% at a 3:1 ratio). Hemodilution was performed in animals of groups NS and HES in two stages, with target hematocrits 22% and 15%, achieved at 30-minute intervals. After two hours, 50% of the blood volume withdrawn was transfused and animals were monitored for another hour. Statistical analysis was based on ANOVA for repeated measures followed by multiple comparison test (P<0.05). Pearson's correlations were performed between changes in left ventricular end-diastolic volume (LVEDV) and PPV, central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP). Results. Group NS received a significantly greater amount of fluids during ANH (NS, 900 +/- 168 mL vs. HES, 200 +/- 50 mL, P<0.05) and presented greater urine output (NS, 2643 +/- 1097mL vs. HES, 641 +/- 338mL, P<0.001). Significant decreases in LVEDV were observed in group NS from completion of ANH until transfusion. In group HES, only increases in LVEDV were observed, at the end of ANH and at transfusion. Such changes in LVEDV (Delta LVEDV) were better reflected by changes in PPV (Delta PPV, R=-0.62) than changes in CVP (Delta CVP R=0.32) or in PAOP (Delta PAOP, R=0.42, respectively). Conclusion. Changes in preload during ANH were detected by changes in PPV. Delta PPV was superior to Delta PAOP and Delta CVP to this end. (Minerva Anestesiol 2012;78:426-33)

How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography

Introduction: The benefits of higher positive end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) have been modest, but few studies have fully tested the "open-lung hypothesis". This hypothesis states that most of the collapsed lung tissue observed in ARDS can be reversed at an acceptable clinical cost, potentially resulting in better lung protection, but requiring more intensive maneuvers. The short-/middle-term efficacy of a maximum recruitment strategy (MRS) was recently described in a small physiological study. The present study extends those results, describing a case-series of non-selected patients with early, severe ARDS submitted to MRS and followed until hospital discharge or death. Methods: MRS guided by thoracic computed tomography (CT) included two parts: a recruitment phase to calculate opening pressures (incremental steps under pressure-controlled ventilation up to maximum inspiratory pressures of 60 cmH(2)O, at constant driving-pressures of 15 cmH(2)O); and a PEEP titration phase (decremental PEEP steps from 25 to 10 cmH2O) used to estimate the minimum PEEP to keep lungs open. During all steps, we calculated the size of the non-aerated (-100 to +100 HU) compartment and the recruitability of the lungs (the percent mass of collapsed tissue re-aerated from baseline to maximum PEEP). Results: A total of 51 severe ARDS patients, with a mean age of 50.7 years (84% primary ARDS) was studied. The opening plateau-pressure was 59.6 (+/- 5.9 cmH(2)O), and the mean PEEP titrated after MRS was 24.6 (+/- 2.9 cmH(2)O). Mean PaO2/FiO(2) ratio increased from 125 (+/- 43) to 300 (+/- 103; P < 0.0001) after MRS and was sustained above 300 throughout seven days. Non-aerated parenchyma decreased significantly from 53.6% (interquartile range (IQR): 42.5 to 62.4) to 12.7% (IQR: 4.9 to 24.2) (P < 0.0001) after MRS. The potentially recruitable lung was estimated at 45% (IQR: 25 to 53). We did not observe major barotrauma or significant clinical complications associated with the maneuver. Conclusions: MRS could efficiently reverse hypoxemia and most of the collapsed lung tissue during the course of ARDS, compatible with a high lung recruitability in non-selected patients with early, severe ARDS. This strategy should be tested in a prospective randomized clinical trial.

Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

A snapshot of suspended sediment and fluid mud occurrence in a mixed-energy embayment, Tijucas Bay, Brazil

Along the southern Brazilian coast, Tijucas Bay is known for its unique muddy tidal flats associated with chenier plains. Previous field observations pointed to very high suspended sediment concentrations (SSCs) in the inner parts of the bay, and in the estuary of the Tijucas River, suggesting the presence of fluid mud. In this study, the occurrences of suspended sediments and fluid mud were examined during a larger-scale, high-resolution 2-day field campaign on 1-2 May 2007, encompassing survey lines spanning nearly 80 km, 75 water sampling stations for near-bottom density estimates, and ten sediment sampling stations. Wave refraction modeling provided qualitative wave energy estimates as a function of different incidence directions. The results show that SSC increases toward the inner bay near the water surface, but seaward near the bottom. This suggests that suspended sediment is supplied by the local rivers, in particular the Tijucas. Near-surface SSCs were of the order of 50 mg l(-1) close to the shore, but exceeded 100 mg l(-1) near the bottom in the deeper parts of the bay. Fluid mud thickness and location given by densimetry and echo-sounding agreed in some places, although being mostly discordant. The best agreement was observed where wave energy was high during the campaign. The discrepancy between the two methods may be an indication for the existence of fluid mud, which is recorded by one method but not the other. Agreement is considered to be an indication of fluidization, whereas disagreement indicates more consolidation. Wave modeling suggests that waves from the ENE and SE are the most effective in supplying energy to the inner bay, which may induce the liquefaction of mud deposits to form fluid mud. Nearshore mud resuspension and weak horizontal currents result in sediment-laden offshore flow, which explains the higher SSCs measured in the deeper parts of the bay, besides providing a mechanism for fine-sediment export to the inner shelf.

Effects of Matrix Metalloproteinase (MMP)-2 Polymorphisms on Responsiveness to Antihypertensive Therapy of Women with Hypertensive Disorders of Pregnancy

Imbalanced matrix metalloproteinase (MMP) expression, including MMP-2, has been demonstrated in pre-eclampsia. However, little is known about the effect of polymorphisms in MMP-2 gene on hypertensive disorders of pregnancy. We examined whether two functional MMP-2 polymorphisms (g.-1306C>T and g.-735C>T) are associated with pre-eclampsia and/or gestational hypertension and whether these polymorphisms affect therapeutic responses in women with these conditions. We studied 216 healthy pregnant women (HP), 185 patients with gestational hypertension (GH) and 216 patients with pre-eclampsia (PE). They were stratified as responsive or non-responsive to antihypertensive therapy according to clinical and laboratorial parameters of therapeutic responsiveness. Genomic DNA was extracted from whole blood and genotypes for g-1306C>T and g.-735C>T polymorphisms were determined by real-time PCR using Taqman allele discrimination assays. Haplotype frequencies were inferred using the PHASE 2.1 program. The distributions of MMP-2 genotypes and haplotypes were similar in HP, GH and PE patients (p > 0.05). In addition, we found no significant differences in MMP-2 genotype or haplotype frequencies when GH or PE patients were classified as responsive or non-responsive to antihypertensive therapy (p > 0.05). Our results suggest that MMP-2 polymorphisms do not affect the susceptibility to hypertensive disorders of pregnancy. In parallel, MMP-2 polymorphisms apparently do not affect the responsiveness to antihypertensive therapy of women with these hypertensive disorders of pregnancy.

Fluid intake patterns: an epidemiological study among children and adolescents in Brazil

Background: Energy from liquids is one of the most important factors that could impact on the high prevalence of children and adolescents obesity around the world. There are few data on the liquid consumption in Brazil. The aim of this study is to evaluate the volume and quality of liquids consumed by Brazilian children and adolescents and to determine the proportion of their daily energy intake composed of liquids. Methods: A multicenter study was conducted in five Brazilian cities; the study included 831 participants between 3 and 17 years of age. A four-day dietary record specific to fluids was completed for each individual, and the volume of and Kcal from liquid intake were evaluated. The average number of Kcal in each beverage was determined based on label information, and the daily energy intake data from liquids were compared with the recommendations of the National Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria-ANVISA), the Brazilian food regulation authority, according to each subject's age. Results: As the children aged, the volume of carbonated beverages that they consumed increased significantly, and their milk intake decreased significantly. For children between the ages of 3 and 10, milk and dairy products contributed the greatest daily number of Kcal from liquids. Sugar sweetened beverages which included carbonated beverages, nectars and artificial beverages, accounted for 37% and 45% of the total Kcal from liquid intake in the 3-to 6-year-old and 7- to 10-year-old groups, respectively. Among adolescents (participants 11- to 17-years old), most of the energy intake from liquids came from carbonated beverages, which accounted for an average of 207 kcal/day in this group (42% of their total energy intake from liquids). Health professionals should be attentive to the excessive consumption of sugar sweetened beverages in children and adolescents. The movement toward healthier dietary patterns at the individual and population levels may help to improve programs for preventing overweight and obesity in children and adolescents. Conclusion: From childhood to adolescence the daily volume of liquid ingested increased reaching a total of 2.0 liters on average. Of this volume, the daily volume of milk ingested decreased while the carbonated drinks, sweetened, nectars and artificial beverages increased significantly. The proportion of water remained constant in about 1/3 of the total volume. From 3 to 17 years of age the energy intake from carbonated beverages increased by about 20%. The carbonated drinks on average corresponded to a tenth of the daily requirements of energy of adolescents.

Minimal residual disease in cerebrospinal fluid at diagnosis: a more intensive treatment protocol was able to eliminate the adverse prognosis in children with acute lymphoblastic leukemia

We analyzed cerebrospinal fluid (CSF) samples from 65 consecutive children with acute lymphoblastic leukemia (ALL) treated according to two different treatment protocols (GBTLI-ALL-93 and -99) with no puncture accident for minimal residual disease (MRD) in the central nervous system (CNS). Minimal residual disease was detected by polymerase chain reaction (PCR) with homo/heteroduplex analysis using consensus primers to IgH and TCR genes. MRD in the CSF at diagnosis was detected by PCR in 46.8% of children with no puncture accident or morphological involvement. In patients treated with GBTLI-ALL-93 a significantly lower 5-year event-free survival (EFS) was demonstrated for those with CSF involvement, in univariate (p = 0.01) and multivariate (p = 0.04) analysis. This observation was not true for patients treated with the more intensive protocol GBTLI-ALL-99 (p = 0.81). These findings suggest that MRD detection in the CSF is a common event in children with ALL. Treatment intensification provided by the GBTLI-ALL-99 apparently overcomes the detrimental effect of CNS minimal residual disease at diagnosis.

Quantitation of malondialdehyde in gingival crevicular fluid by a high-performance liquid chromatography-based method

Lipid peroxidation (LPO) has been associated with periodontal disease, and the evaluation of malondialdehyde (MDA) in the gingival crevicular fluid (GCF), an inflammatory exudate from the surrounding tissue of the periodontium, may be useful to clarify the role of LPO in the pathogenesis of periodontal disease. We describe the validation of a method to measure MDA in the GCF using high-performance liquid chromatography. MDA calibration curves were prepared with phosphate-buffered solution spiked with increasing known concentrations of MDA. Healthy and diseased GCF samples were collected from the same patient to avoid interindividual variability. MDA response was linear in the range measured, and excellent agreement was observed between added and detected concentrations of MDA. Samples' intra- and interday coefficients of variation were below 6.3% and 12.4%, respectively. The limit of quantitation (signal/noise = 5) was 0.03 mu M. When the validated method was applied to the GCF, excellent agreement was observed in the MDA quantitation from healthy and diseased sites, and diseased sites presented more MDA than healthy sites (P < 0.05). In this study, a validated method for MDA quantitation in GCF was established with satisfactory sensitivity, precision, and accuracy. (C) 2012 Elsevier Inc. All rights reserved.

Metabolic Disorders and Adipose Tissue Insulin Responsiveness in Neonatally STZ-Induced Diabetic Rats Are Improved by Long-Term Melatonin Treatment

Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin can improve insulin resistance and other metabolic disorders in these animals. At the fourth week of age, diabetic animals started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking water at night. Animals were then killing, and the sc, epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Blood samples were collected for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by constant glucose disappearance rate and homeostasis model of assessment-insulin resistance. However, melatonin treatment was unable to recover body weight deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin, whereas neither plasma insulin level nor insulin secretion capacity was improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development, leaving genital structures smaller than those of nontreated diabetic animals. Melatonin treatment improved the responsiveness of adipocytes to insulin in diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose oxidation, and incorporation of glucose into lipids (EP and RP), an effect that seems partially related to an increased expression of insulin receptor substrate 1, acetyl-coenzyme A carboxylase and fatty acid synthase. In conclusion, melatonin treatment was capable of ameliorating the metabolic abnormalities in this particular diabetes model, including insulin resistance and promoting a better long-term glycemic control. (Endocrinology 153: 2178-2188, 2012)

Evaluation of Distinct Freezing Methods and Cryoprotectants for Human Amniotic Fluid Stem Cells Cryopreservation

Amniotic fluid (AF) was described as a potential source of mesenchymal stem cells (MSCs) for biomedicine purposes. Therefore, evaluation of alternative cryoprotectants and freezing protocols capable to maintain the viability and stemness of these cells after cooling is still needed. AF stem cells (AFSCs) were tested for different freezing methods and cryoprotectants. Cell viability, gene expression, surface markers, and plasticity were evaluated after thawing. AFSCs expressed undifferentiated genes Oct4 and Nanog; presented typical markers (CD29, CD44, CD90, and CD105) and were able to differentiate into mesenchymal lineages. All tested cryoprotectants preserved the features of AFSCs however, variations in cell viability were observed. In this concern, dimethyl sulfoxide (Me2SO) showed the best results. The freezing protocols tested did not promote significant changes in the AFSCs viability. Time programmed and nonprogrammed freezing methods could be used for successful AFSCs cryopreservation for 6 months. Although tested cryoprotectants maintained undifferentiated gene expression, typical markers, and plasticity of AFSCs, only Me2SO and glycerol presented workable viability ratios.

Short Report: Identification of Oropouche Orthobunyavirus in the Cerebrospinal Fluid of Three Patients in the Amazonas, Brazil

Oropouche fever is the second most frequent arboviral infection in Brazil, surpassed only by dengue. Oropouche virus (OROV) causes large and explosive outbreaks of acute febrile illness in cities and villages in the Amazon and Central-Plateau regions. Cerebrospinal fluid (CSF) samples from 110 meningoencephalitis patients were analyzed. The RNA extracted from fluid was submitted to reverse transcription-polymerase chain reaction and sequencing to identify OROV. Three CSF samples showed the presence of OROV causing infection in the central nervous system (CNS). These patients are adults. Two of the patients had other diseases affecting CNS and immune systems: neurocysticercosis and acquired immunodeficiency syndrome, respectively. Nucleotide sequence analysis showed that the OROV from the CSF of these patients belonged to genotype I. We show here that severe Oropouche disease is occurring during outbreaks of this virus in Brazil

Analysis of energy dissipation in stirred suspension polymerisation reactors using computational fluid dynamics

This work evaluates the spatial distribution of normalised rates of droplet breakage and droplet coalescence in liquidliquid dispersions maintained in agitated tanks at operation conditions normally used to perform suspension polymerisation reactions. Particularly, simulations are performed with multiphase computational fluid dynamics (CFD) models to represent the flow field in liquidliquid styrene suspension polymerisation reactors for the first time. CFD tools are used first to compute the spatial distribution of the turbulent energy dissipation rates (e) inside the reaction vessel; afterwards, normalised rates of droplet breakage and particle coalescence are computed as functions of e. Surprisingly, multiphase simulations showed that the rates of energy dissipation can be very high near the free vortex surfaces, which has been completely neglected in previous works. The obtained results indicate the existence of extremely large energy dissipation gradients inside the vessel, so that particle breakage occurs primarily in very small regions that surround the impeller and the free vortex surface, while particle coalescence takes place in the liquid bulk. As a consequence, particle breakage should be regarded as an independent source term or a boundary phenomenon. Based on the obtained results, it can be very difficult to justify the use of isotropic assumptions to formulate particle population balances in similar systems, even when multiple compartment models are used to describe the fluid dynamic behaviour of the agitated vessel. (C) 2011 Canadian Society for Chemical Engineering

Positive fluid balance is associated with reduced survival in critically ill patients with cancer

Background There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. Method One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, MannWhitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. Results The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675?ml/24?h (4712921) vs. 887?ml/24?h (104557), P?=?0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100?ml/24?h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.051.26), P?=?0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.293.87), P?=?0.004] and a positive fluid balance higher than 1100?ml/24?h at ICU [OR 5.14; 95% CI (1.4518.24), P?=?0.011]. Conclusion A cumulative positive fluid balance higher than 1100?ml/24?h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring

Aims: The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Main methods: Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.1 6%NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. Key findings: TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA. ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. Significance: High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. (C) 2012 Elsevier Inc. All rights reserved.

Cytotoxicity evaluation of Curcuma zedoaria (Christm.) Roscoe fluid extract used in oral hygiene products

Objective. This in vitro study evaluated the cytotoxic effects of the Curcuma zedoaria (Christm.) Roscoe (popular name: zedoary) fluid extract, as used in preparations for oral hygiene, mostly for anti-septic purposes. Materials and methods. The cell viability and cell growth were assessed by Trypan blue dye exclusion assay using the LMF cell line derived from oral mucosa. Cell viability (short-term assay) was measured 0, 6, 12 and 24 h after contact with the fluid extract. Cell growth (long-term assay) was analyzed in 1, 3, 5 and 7 days. The experimental groups were those testing the fluid extract obtained from the zedoary rhizome and the extractor liquid (ethanol 70 degrees GL) in the concentrations of 0.01-0.0001% v/v. Fresh DMEM were used in the control cultures. Results. Short-term assay-all studied cultures maintained stable cell viability; Long-term assay-there was progressive cell growth in all studied cultures. Conclusion. According to the results, the zedoary fluid extract presents low cytotoxicity and probably can be used in the oral hygiene products.