Fabio Carmona

Late remote ischemic preconditioning in children undergoing cardiopulmonary bypass: a randomized controlled trial.

OBJECTIVE Cardiopulmonary bypass is associated with ischemia-reperfusion injury to multiple organs. We aimed to evaluate whether remote ischemic preconditioning performed the day before surgery for congenital heart disease with cardiopulmonary bypass attenuates the postoperative inflammatory response and myocardial dysfunction. METHODS This was a prospective, randomized, single-blind, controlled trial. Children allocated to remote ischemic preconditioning underwent 4 periods of 5 minutes of lower limb ischemia by a blood pressure cuff intercalated with 5 minutes of reperfusion. Blood samples were collected 4, 12, 24, and 48 hours after cardiopulmonary bypass to evaluate nuclear factor kappa B activation in leukocytes by quantification of mRNA of I kappa B alpha by real-time quantitative polymerase chain reaction and for interleukin-8 and 10 plasma concentration measurements by enzyme-linked immunosorbent assay. Myocardial dysfunction was assessed by N-terminal pro-B-type natriuretic peptide and cardiac troponin I plasma concentrations, measured by chemiluminescence, and clinical parameters of low cardiac output syndrome. RESULTS Twelve children were allocated to remote ischemic preconditioning, and 10 children were allocated to the control group. Demographic data and Risk Adjustment for Congenital Heart Surgery 1 classification were comparable in both groups. Remote ischemic preconditioning group had lower postoperative values of N-terminal pro-B-type natriuretic peptide, but cardiac troponin I levels were not significantly different between groups. Interleukin-8 and 10 concentrations and I kappa B alpha gene expression were similar in both groups. Postoperative morbidity was similar in both groups; there were no postoperative deaths in either group. CONCLUSIONS Late remote ischemic preconditioning did not provide clinically relevant cardioprotection to children undergoing cardiopulmonary bypass.

Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I.

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4h PO as independent predictors of LCOS, while cTnI 4h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB.

Effect of Oral Hygiene with 0.12% Chlorhexidine Gluconate on the Incidence of Nosocomial Pneumonia in Children Undergoing Cardiac Surgery

OBJECTIVE To evaluate the effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia and ventilator-associated pneumonia (VAP) in children undergoing cardiac surgery. DESIGN Prospective, randomized, double-blind, placebo-controlled trial. SETTING Pediatric intensive care unit (PICU) at a tertiary care hospital. PATIENTS One hundred sixty children undergoing surgery for congenital heart disease, randomized into 2 groups: chlorhexidine (n = 87) and control (n = 73). INTERVENTIONS Oral hygiene with 0.12% chlorhexidine gluconate or placebo preoperatively and twice a day postoperatively until PICU discharge or death. RESULTS Patients in experimental and control groups had similar ages (median, 12.2 vs 10.8 months; P = .72) and risk adjustment for congenital heart surgery 1 score distribution (66% in category 1 or 2 in both groups; P = .17). The incidence of nosocomial pneumonia was 29.8% versus 24.6% (P = .46) and the incidence of VAP was 18.3% versus 15% (P = .57) in the chlorhexidine and the control group, respectively. There was no difference in intubation time (P = .34), need for reintubation (P = .37), time interval between hospitalization and nosocomial pneumonia diagnosis (P = .63), time interval between surgery and nosocomial pneumonia diagnosis (P = .10), and time on antibiotics (P = .77) and vasoactive drugs (P = .16) between groups. Median length of PICU stay (3 vs 4 days; P = .53), median length of hospital stay (12 vs 11 days; P = .67), and 28-day mortality (5.7% vs 6.8%; P = .77) were also similar in the chlorhexidine and the control group. CONCLUSIONS Oral hygiene with 0.12% chlorhexidine gluconate did not reduce the incidence of nosocomial pneumonia and VAP in children undergoing cardiac surgery. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00829842 .

Evidence of Renal Infection in Fatal Cases of 2009 Pandemic Influenza A (H1N1).

The 2009 pandemic influenza A (H1N1) caused significant morbidity and mortality. Acute lung injury is the hallmark of the disease, but multiple organ system dysfunction can develop and lead to death. Therefore, we sought to investigate whether there was postmortem evidence of H1N1 presence and virus-induced organ injury in autopsy specimens. Five cases in which patients died of influenza A (H1N1) virus infection were studied. The lungs of all patients showed macroscopic and microscopic findings already described for H1N1 (consolidation, edema, hemorrhage, alveolar damage, hyaline membrane, and inflammation), and H1N1 viruses were present in alveolar cells in immunochemical studies. Acute tubular necrosis was present in all cases, but there was no evidence of direct virus-induced kidney injury. Nevertheless, H1N1 viruses were found in the cytoplasm of glomerular macrophages in the kidneys of 4 patients. Therefore, our data provide strong evidence that H1N1 presence is not restricted to the lungs.

A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma

ETHNOPHARMACOLOGICAL RELEVANCE Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses. AIMS OF THE STUDY To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma. MATERIALS AND METHODS Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500mgkg-1 concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed. RESULTS The concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250mgkg-1 of extract, which provided 0.745, 4.22 and 4.30mgkg-1day-1 of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced (P<0.05) respiratory resistance and elastance. Such effects were comparable with those produced by dexamethasone. The total number of inflammatory cells and eosinophils in the bronchoalveolar lavage and the concentrations of interleukin (IL)-4, IL-5 and IL-13 in lung homogenate were significantly reduced (P<0.05) by the methanol extract of E. prostrata. CONCLUSION The results presented herein demonstrate for the first time the anti-inflammatory activity of E. prostrata in a murine model of asthma, thereby supporting the ethnopharmacological uses of the plant.

Prevalence, risk factors and outcomes associated with pulmonary hemorrhage in newborns

Objectives to determine the prevalence of pulmonary hemorrhage in newborns and evaluate the associated risk factors and outcomes.OBJECTIVES to determine the prevalence of pulmonary hemorrhage in newborns and evaluate the associated risk factors and outcomes. METHODS this was a retrospective case-control study involving 67 newborns who met the criteria for pulmonary hemorrhage. A control was selected for each case: the next-born child of the same gender, similar weight (± 200g) and gestational age (± 1 week), with no previous pulmonary hemorrhage and no malformation diagnosis. Factors previous to pulmonary hemorrhage onset, as well as aspects associated to the condition, were assessed. RESULTS the prevalence was 6.7 for 1,000 live births, and the rates observed were: 8% among newborns <1,500g, and 11% among newborns <1,000g. Intubation in the delivery room (OR=7.16), SNAPPE II (OR=2.97), surfactant use (OR=3.7), and blood components used previously to pulmonary hemorrhage onset (OR=5.91) were associated with pulmonary hemorrhage. In the multivariate logistic regression model, only intubation in delivery room and previous use of blood components maintained the association. Children with pulmonary hemorrhage had higher mortality (OR=7.24). Among the survivors, the length of stay (p ≤ 0.01) and mechanical ventilation time were longer (OR=25.6), and oxygen use at 36 weeks of corrected age was higher (OR=7.67). CONCLUSIONS pulmonary hemorrhage is more prevalent in premature newborns, and is associated with intubation in the delivery room and previous use of blood components, leading to high mortality and worse clinical evolution.

Herbal medicines: old and new concepts, truths and misunderstandings

Men have been using herbal medicines for thousands of years. The advantages of this type of therapeutics include good availability, local cultural aspects, individual preferences, the increasing demand for natural and organic products, and the already validated synergistic effects of herbal medicines. However, ethically, the scope and limits of these drugs need to be established not only by ethnopharmacological evidences but also by scientific investigations, which confirm the therapeutic effects. With this study, we propose to discuss the possible advantages of using herbal medicines instead of purified compounds, the truth and myths about herbal medicines, drug discovery, and the implications for medical education and health care.

Chemical composition and therapeutic effects of Lippia alba (Mill.) N. E. Brown leaves hydro-alcoholic extract in patients with migraine☆

BACKGROUND There is no universally accepted and effective prophylaxis of migraine headache episodes. Thus we aimed to investigate the effects of Lippia alba (Mill.) N. E. Brown, an herb with many effects on central nervous system, on pain frequency and intensity of migraine patients. METHODS Patients were enrolled in a prospective, phase 2, non-controlled cohort study to orally receive hydro-alcoholic extract of L. alba leaves. Headache intensity and frequency of episodes were recorded before and after 30-60 days of treatment. We also studied the chemical composition of its essential oil by gas chromatography-mass spectrometry. RESULTS We described for the first time a particular L. alba chemotype with geranial and carvenone as major compounds. With treatment, both frequency and intensity of pain episodes significantly decreased from baseline to first reassessment date. More than 80% of patients experienced a minimum 50% reduction on pain intensity and frequency. No side effects were reported. CONCLUSIONS Treatment with a geranial plus carvenone chemotype of L. alba hydro-alcoholic extract is a cheap, widely available, highly effective therapy to reduce both the intensity and the frequency of headache episodes of migraine patients with no side effects.

Oxidative stress markers are not associated with outcomes after pediatric heart surgery.

To investigate whether perioperative serum levels of oxidative stress markers, thiobarbituric acid reactive substances (TBARS), and carbonyl moieties are associated with outcomes in children after heart surgery.

High-dose aprotinin does not affect troponin I, N-Terminal pro-B-type natriuretic peptid and renal function in children submitted to surgical correction with extracorporeal circulation

OBJECTIVE To evaluate if the use of hemostatic high-dose aprotinin seems influence to myocardial, renal and metabolic functions in children submitted to surgical correction with extracorporeal circulation (ECC). Material and Methods A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during ECC and the myocardial and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. RESULTS The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the pediatric postoperative intensive care unit (ICU) and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24h after surgery in the Control Group. Blood loss was similar for both groups. Cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), serum glutamic-oxaloacetic transaminase (SGOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) did not differ significantly between groups. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of aprotinin. CONCLUSION High-dose aprotinin did not significant influence in serum markers troponin I, NT-proBNP and renal function, but did associated with hemodilution, blood lactate concentration and metabolic acidosis more intense.