Molecular analysis of CYP21A2 can optimize the follow-up of positive results in newborn screening for congenital adrenal hyperplasia

Neonatal screening for congenital adrenal hyperplasia (CAH) is useful in diagnosing salt wasting form (SW). However, there are difficulties in interpreting positive results in asymptomatic newborns. The main objective is to analyze genotyping as a confirmatory test in children with neonatal positive results. Patients comprised 23 CAH children and 19 asymptomatic infants with persistently elevated 17-hydroxyprogesterone (17OHP) levels. CYP21A2 gene was sequenced and genotypes were grouped according to the enzymatic activity of the less severe allele: A1 null, A2 < 2%, B 3-7%, C > 20%. Twenty-one children with neonatal symptoms and/or 17OHP levels > 80 ng/ml carried A genotypes, except two virilized girls (17OHP < 50 ng/ml) without CAH genotypes. Patients carrying SW genotypes (A1, A2) and low serum sodium levels presented with neonatal 17OHP > 200 ng/ml. Three asymptomatic boys carried simple virilizing genotypes (A2 and B): in two, the symptoms began at 18 months; another two asymptomatic boys had nonclassical genotypes (C). The remaining 14 patients did not present CAH genotypes, and their 17OHP levels were normalized by 14 months of age. Molecular analysis is useful as a confirmatory test of CAH, mainly in boys. It can predict clinical course, identify false-positives and help distinguish between clinical forms of CAH.

Home blood pressure monitoring in blood pressure control among haemodialysis patients: an open randomized clinical trial

Background. It is not known if the adjustment of antihypertensive therapy based on home blood pressure monitoring (HBPM) can improve blood pressure (BP) control among haemodialysis patients. Methods. This is an open randomized clinical trial. Hypertensive patients on haemodialysis were randomized to have the antihypertensive therapy adjusted based on predialysis BP measurements or HBPM. Before and after 6 months of follow-up, patients were submitted to ambulatory blood pressure monitoring (ABPM) for 24 h, HBPM during 1 week and echocardiogram. Results. A total of 34 and 31 patients completed the study in the HBPM and predialysis BP groups, respectively. At the end of study, the systolic (SBP) and diastolic (DBP) blood pressure during the interdialytic period measured by ABPM were significantly lower in the HBPM group in relation to the predialysis BP group (mean 24-h BP: 135 +/- 12 mmHg/76 +/- 7 mmHg versus 147 +/- 15 mmHg/79 +/- 8 mmHg; P < 0.05). In the HBPM analysis, the HBPM group showed a significant reduction only in SBP compared to the predialysis BP group (weekly mean: 144 +/- 21 mmHg versus 154 +/- 22 mmHg; P < 0.05). There were no differences between the HBPM and predialysis BP groups in relation to the left ventricular mass index at the end of the study (108 +/- 35 g/m(2) versus 110 +/- 33 g/m(2); P > 0.05). Conclusions. Decision making based on HBPM among haemodialysis patients has led to a better BP control during the interdialytic period in comparison with predialysis BP measurements. HBPM may be a useful adjuvant instrument for blood pressure control among haemodialysis patients.

Cardiac troponin T as a biochemical marker of cardiac dysfunction and ductus venosus Doppler velocimetry

Objectives: The aim of this study was to determine the correlation between ductus venosus (DV) Doppler velocimetry and fetal cardiac troponin T (cTnT). Study design: Between March 2007 and March 2008, 89 high-risk pregnancies were prospectively studied. All patients delivered by cesarean section and the Doppler exams were performed on the same day. Multiple regression included the following variables: maternial age, parity, hypertension, diabetes, gestational age at delivery, umbilical artery (UA) S/D ratio, diagnosis of absent or reversed end-diastolic flow velocity (AREDV) in the UA, middle cerebral artery (MCA) pulsatility index (131), and DV pulsatility index for veins (PIV). Immediately after delivery, UA blood samples were obtained for the measurement of pH and cTnT levels. Statistical analysis included the Kruskal-Wallis test and multiple regressions. Results: The results showed a cTnT concentration at birth >0.05 ng/ml in nine (81.8%) of AREDV cases, a proportion significantly higher than that observed in normal UA S/D ratio and UA S/D ratio >p95 with positive diastolic blood flow (7.7 and 23.1%, respectively, p < 0.001). A positive correlation Was found between abnormal DV-PIV and elevated cTnT levels in the UA. Multiple regression identified DV-PIV and a diagnosis of AREDV as independent factors associated with abnormal fetal cTnT levels (p < 0.0001, F(2.86) = 63.5, R = 0.7722). Conclusion: DV-PIV was significantly correlated with fetal cTnT concentrations at delivery. AREDV and abnormal DV flow represent severe cardiac compromise, with increased systemic venous pressure, and a rise in right ventricular afterload, demonstrated by myocardial damage and elevated fetal cTnT. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

A comparison of methods to identify open-lung PEEP

Purpose: Many methods exist in the literature for identifying PEEP to set in ARDS patients following a lung recruitment maneuver (RM). We compared ten published parameters for setting PEEP following a RM. Methods: Lung injury was induced by bilateral lung lavage in 14 female Dorset sheep, yielding a PaO(2) 100-150 mmHg at F(I)O(2) 1.0 and PEEP 5 cmH(2)O. A quasi-static P-V curve was then performed using the supersyringe method; PEEP was set to 20 cmH(2)O and a RM performed with pressure control ventilation (inspiratory pressure set to 40-50 cmH(2)O), until PaO(2) + PaCO(2) > 400 mmHg. Following the RM, a decremental PEEP trial was performed. The PEEP was decreased in 1 cmH(2)O steps every 5 min until 15 cmH(2)O was reached. Parameters measured during the decremental PEEP trial were compared with parameters obtained from the P-V curve. Results: For setting PEEP, maximum dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), and minimum shunt calculated during the decremental PEEP trial, and the lower Pflex and point of maximal compliance increase on the inflation limb of the P-V curve (Pmci,i) were statistically indistinguishable. The PEEP value obtained using the deflation upper Pflex and the point of maximal compliance decrease on the deflation limb were significantly higher, and the true inflection point on the inflation limb and minimum PaCO(2) were significantly lower than the other variables. Conclusion: In this animal model of ARDS, dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), minimum shunt, inflation lower Pflex and Pmci,i yield similar values for PEEP following a recruitment maneuver.

INTRACRANIAL PRESSURE MONITORING IN CHILDREN WITH FULMINANT HEPATIC FAILURE

Introduction. We describe a series of 10 children with intracranial hypertension complicating fulminant hepatic failure submitted to intracranial pressure (ICP) monitoring for intensive care an transplantation management. Patients and methods. Information from pediatrics patients acute liver failure admitted to our hospital was collected in a standard protocol form. We analyzed data from 10 patients, medium age 5.2 years old. In this period we studied aspects as ICP transducer used, number of days with ICP monitoring and complications of ICP monitoring. Results. Hepatitis A was diagnosed in five patients and hepatitis B in two cases. The initial ICP were 2 to 24 mmHg in transducer Seven patients died, four due to intracranial hypertension, included the patient operated for subdural hematoma, and three with transplantation failure. Only, a case of hematoma was verified. Conclusions. The application of ICP monitoring allows intensive care for aggressive ICP management. It can be used in children without adaptations. [REV NEUROL 2009: 48: 134-6]

Image reconstruction affects computer tomographic assessment of lung hyperinflation

Objectives: Lung hyperinflation may be assessed by computed tomography (CT). As shown for patients with emphysema, however, CT image reconstruction affects quantification of hyperinflation. We studied the impact of reconstruction parameters on hyperinflation measurements in mechanically ventilated (MV) patients. Design: Observational analysis. Setting: A University hospital-affiliated research Unit. Patients: The patients were MV patients with injured (n = 5) or normal lungs (n = 6), and spontaneously breathing patients (n = 5). Interventions: None. Measurements and results: Eight image series involving 3, 5, 7, and 10 mm slices and standard and sharp filters were reconstructed from identical CT raw data. Hyperinflated (V-hyper), normally (V-normal), poorly (V-poor), and nonaerated (V-non) volumes were calculated by densitometry as percentage of total lung volume (V-total). V-hyper obtained with the sharp filter systematically exceeded that with the standard filter showing a median (interquartile range) increment of 138 (62-272) ml corresponding to approximately 4% of V-total. In contrast, sharp filtering minimally affected the other subvolumes (V-normal, V-poor, V-non, and V-total). Decreasing slice thickness also increased V-hyper significantly. When changing from 10 to 3 mm thickness, V-hyper increased by a median value of 107 (49-252) ml in parallel with a small and inconsistent increment in V-non of 12 (7-16) ml. Conclusions: Reconstruction parameters significantly affect quantitative CT assessment of V-hyper in MV patients. Our observations suggest that sharp filters are inappropriate for this purpose. Thin slices combined with standard filters and more appropriate thresholds (e.g., -950 HU in normal lungs) might improve the detection of V-hyper. Different studies on V-hyper can only be compared if identical reconstruction parameters were used.

A synergistic relationship of elevated low-density lipoprotein cholesterol levels and systolic blood pressure with coronary artery calcification

We sought to evaluate this ""response-to-injury"" hypothesis of atherosclerosis by studying the interaction between systolic blood pressure (SBP) and LDL-cholesterol (LDL-C) in predicting the presence of coronary artery calcification (CAC) in asymptomatic men. We Studied 526 men (46 +/- 7 years of age) referred for electron-beam tomography (EBT) exam. The prevalence of CAC was determined across LDL-C tertiles (low: <115 mg/dl; middle: 115-139 mg/dl high: >= 140 mg/dl) within tertiles of SBP (low: <121 mmHg; middle: 121-130 mmHg; high: >= 131 mmHg). CAC was found in 220 (42%) men. There was no linear trend in the presence of CAC across LDL-C tertiles in the low (p = 0.6 for trend) and middle (p = 0.3 for trend) SBP tertile groups, respectively. In contrast, there was a significant trend for increasing CAC with increasing LDL-C (1st: 44%; 2nd: 49%; 3rd: 83%; p < 0.0001 for trend) in the high SBP tertile group. In multivariate logistic analyses (adjusting for age, smoking, triglyceride levels, HDL-cholesterol levels, body mass index, and fasting glucose levels), the odds ratio for any CAC associated with increasing LDL-C was significantly higher in those with highest SBP levels, whereas no such relationship was observed among men with SBP in the lower two tertiles. An interaction term (LDL-C x SBP) incorporated in the multivariate analyses was statistically significant (p = 0.038). The finding of an interaction between SBP and LDL-C relation to CAC in asymptomatic men support the response-to-injury model of atherogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction

Introduction: Quantitative computed tomography (qCT)-based assessment of total lung weight (M(lung)) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI. Methods: In this prospective observational study, M(lung) was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for M(lung) was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges. Results: The ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference M(lung) value was 885 (771 to 973) g, and the reference interval for M(lung) was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median M(lung) value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had M(lung) values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), Mlung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days. Conclusions: Atelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.

Extrapolation from ten sections can make CT-based quantification of lung aeration more practicable

Clinical applications of quantitative computed tomography (qCT) in patients with pulmonary opacifications are hindered by the radiation exposure and by the arduous manual image processing. We hypothesized that extrapolation from only ten thoracic CT sections will provide reliable information on the aeration of the entire lung. CTs of 72 patients with normal and 85 patients with opacified lungs were studied retrospectively. Volumes and masses of the lung and its differently aerated compartments were obtained from all CT sections. Then only the most cranial and caudal sections and a further eight evenly spaced sections between them were selected. The results from these ten sections were extrapolated to the entire lung. The agreement between both methods was assessed with Bland-Altman plots. Median (range) total lung volume and mass were 3,738 (1,311-6,768) ml and 957 (545-3,019) g, the corresponding bias (limits of agreement) were 26 (-42 to 95) ml and 8 (-21 to 38) g, respectively. The median volumes (range) of differently aerated compartments (percentage of total lung volume) were 1 (0-54)% for the nonaerated, 5 (1-44)% for the poorly aerated, 85 (28-98)% for the normally aerated, and 4 (0-48)% for the hyperaerated subvolume. The agreement between the extrapolated results and those from all CT sections was excellent. All bias values were below 1% of the total lung volume or mass, the limits of agreement never exceeded +/- 2%. The extrapolation method can reduce radiation exposure and shorten the time required for qCT analysis of lung aeration.

Antibacterial activity of bovine lactoferrin-derived peptides

Several peptides sharing high sequence homology with lactoferricin B (Lf-cin B) were generated from bovine lactoferrin (Lf) with recombinant chymosin. Two peptides were copurified. one identical to Lf-cin B and another differing from Lf-cin B by the inclusion of a C-terminal alanine (lactoferricin). Two other peptides were copurified from chymosin-hydrolyzed Lf. one differing from Lf-cin B by the inclusion of C-terminal alanyl-leucine and the other being a heterodimer linked by a disulfide bond, These peptides were isolated in a single step from chymosin-hydrolyzed Lf by membrane ton-exchange chromatography and were purified by reverse-phase high-pressure liquid chromatography (HPLC), They were characterized by. N-terminal Edman sequencing, mass spectrometry, and antibacterial activity determination, Pure lactoferricin, prepared from pepsin-hydrolyzed Lf, was purified by standard chromatography techniques, This peptide was analyzed against a number of gram-positive and gram-negative bacteria before and after reduction of its disulfide bond or cleavage after its single methionine residue and was found to inhibit the growth of all the test bacteria at a concentration of 8 mu M or less, Subfragments of lactoferricin were isolated from reduced and cleaved peptide by reverse-phase HPLC, Subfragment 1 (residues I to 10) was active against most of the test microorganisms at concentrations of 10 to 50 mu M. Subfragment 2 (residues 11 to 26) was active against only a few microorganisms at concentrations up to 100 mu M. These antibacterial studies indicate that the activity of lactoferricin Is mainly, but not wholly, due to its N-terminal region.

Negative Pressure Therapy for Complex Wounds in Patients with Sickle-Cell Disease: A Case Study

Sickle-cell disease is the most prevalent genetic disease in the Brazilian population. Lower limb ulcers are the most frequent cutaneous complications, affecting 8% to 10% of the patients. These ulcers are usually deep and may take many years to heal. Evidence about the effectiveness of systemic or topical treatment of these wounds is limited, apart from stabilization of the anemia. A 28-year old woman with sickle-cell disease was admitted for treatment of three deep chronic lower leg ulcers. All wounds had tendon exposure and contained firmly adherent fibrin slough. Following surgical debridement and before grafting, the wounds were managed with three different dressings: a rayon and normal saline solution dressing, a calcium alginate dressing covered with gauze, and negative pressure therapy. All three wounds healed successfully and their grafts showed complete integration; only the rayon-dressed wound required a second debridement. The alginate and rayon-dressed wounds recurred after 9 months and required additional skin grafts. Helpful research on managing ulcers in patients with sickle-cell disease is minimal, but the results of this case study suggest that topical treatment modalities may affect outcomes. Research to explore the safety and effectiveness of NPT in patients with sickle-cell wounds is warranted.

A Comparison Between Pulse Pressure Variation and Right End Diastolic Volume Index as Guides to Resuscitation in a Model of Hemorrhagic Shock in Pigs

Background: Different hemodynamic parameters including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally induced hemorrhagic shock. Methods: Twenty-six anesthetized and mechanically ventilated pigs were allocated into control (group I), PPV (group II), or RVEDVI (group III) group. Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40 mm Hg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, 60 minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), 1 hour and 2 hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on analysis of variance for repeated measures followed by the Bonferroni test (p < 0.05). Results: Volume and time to resuscitation were higher in group III than in group II (group III = 1,305 +/- 331 mL and group II = 965 +/- 245 mL, p < 0.05; and group III = 24.8 +/- 4.7 minutes and group II = 8.8 +/- 1.3 minutes, p < 0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. Conclusion: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.

Low Hematocrit Levels Increase Intracranial Pressure in an Animal Model of Cryogenic Brain Injury

Background: Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over optimal fluid management for these patients. This study aimed to investigate the effects of acute hemodilution with hydroxyethyl starch (HES) or lactated Ringer`s solution (LR) in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in dogs submitted to a cryogenic brain injury model. Methods: Design-Prospective laboratory animal study. Setting-Research laboratory in a teaching hospital. Subjects-Thirty-five male mongrel dogs. Interventions-Animals were enrolled to five groups: control, hemodilution with LR or HES 6% to an hematocrit target of 27% or 35%. Results: ICP and CPP levels were measured after cryogenic brain injury. Hemodilution promotes an increment of ICP levels, which decreases CPP when hematocrit target was estimated in 27.% after hemodilution. However, no differences were observed regarding crystalloid or colloid solution used for hemodilution in ICP and CPP levels. Conclusions: Hemodilution to a low hematocrit level increases ICP and decreases CPP scores in dogs submitted to a cryogenic brain injury. These results suggest that excessive hemodilution to a hematocrit below 30% should be avoided in traumatic brain injury patients.

Measurements of adipocity and high blood pressure among children and adolescents living in Belo Horizonte

Objective: To verify an association, if it exists, between obesity and blood pressure raised beyond the 90th percentile in children and adolescents, and to determine the measure of adiposity that best correlates with blood pressure in these subjects. Design: Cross-sectional study. Setting: A school-based study in Belo Horizonte, Brazil. Participants: We selected randomly 1,403 students, aged from 6 to 18 years, from 545,046 students attending 521 public and private schools. Those selected completed the study. Main measures of outcome: We recorded the weight, height, skin fold in the triceps, subscapular, and suprailiac areas, waist and hip circumference, body-mass index, and resting systolic and diastolic blood pressures using a mercury sphygmomanometer. Results: In univariate analyses, body mass index greater or lesser than 85th percentile, measurements of skin thickness in the subscapular and suprailiac areas, and the sum of all measurements of skinfold thickness, were associated with both systolic and diastolic measurements of blood pressure. After multivariate analyses that adjusted for all measurements of adiposity except itself, and age, race, and socioeconomic state, we found that the increased body mass index was associated with a 3.6-fold increased frequency of elevated systolic measurements of blood pressure, with 9596 confidence intervals from 2.2 to 5.8, and a 2.7-fold increased frequency of elevated measurements of diastolic blood pressure, with 95% confidence intervals from 1.9 to 4.0. Conclusions: Body-mass index serves as a better predictor of elevated blood pressure among children than do local measurements of adiposity.

The association between air pollution and blood pressure in traffic controllers in Santo Andre, Sao Paulo, Brazil

Background: Urban air pollutants are associated with cardiovascular events. Traffic controllers are at high risk for pollution exposure during outdoor work shifts. Objective: The purpose of this study was to evaluate the relationship between air pollution and systemic blood pressure in traffic controllers during their work shifts. Methods: This cross-sectional study enrolled 19 male traffic controllers from Santo Andre city (Sao Paulo, Brazil) who were 30-60 years old and exposed to ambient air during outdoor work shifts. Systolic and diastolic blood pressure readings were measured every 15 min by an Ambulatory Arterial Blood Pressure Monitoring device. Hourly measurements (lags of 0-5 h) and the moving averages (2-5 h) of particulate matter (PM(10)), ozone (O(3)) ambient concentrations and the acquired daily minimum temperature and humidity means from the Sao Paulo State Environmental Agency were correlated with both systolic and diastolic blood pressures. Statistical methods included descriptive analysis and linear mixed effect models adjusted for temperature, humidity, work periods and time of day. Results: Interquartile increases of PM(10) (33 mu g/m(3)) and O(3) (49 mu g/m(3)) levels were associated with increases in all arterial pressure parameters, ranging from 1.06 to 2.53 mmHg. PM(10) concentration was associated with early effects (lag 0), mainly on systolic blood pressure. However, O(3) was weakly associated most consistently with diastolic blood pressure and with late cumulative effects. Conclusions: Santo Andre traffic controllers presented higher blood pressure readings while working their outdoor shifts during periods of exposure to ambient pollutant fluctuations. However, PM(10) and O(3) induced cardiovascular effects demonstrated different time courses and end-point behaviors and probably acted through different mechanisms. (C) 2011 Elsevier Inc. All rights reserved.