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1.
ACS Sens ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32204587

RESUMO

A new fluorescence micromotors-based immunoassay (FMIm) has been developed for procalcitonin (PCT) determination as an early sepsis diagnostic analytical tool. The micromotors combine the high binding capacity of the specific antibod-ies onto their polymeric polypyrrol (PPy) outer layer, with their magnetic guidance (Ni layer) and self-propulsion by catalytic generation of oxygen bubbles (PtNPs inner layer), to actively recognize the PCT antigen. This FMIm allowed a sensitive (LOD = 0.07 ng mL-1) and direct PCT determination in clinical samples from very low birth weight infants (VLBWI) with sepsis suspicion, using small volumes of sample (25 µL) in a clinically relevant range of concentrations (0.5 - 150 ng mL-1). The good agreement between PCT levels obtained by our micromotor-based method and routine im-munofluorescence Hospital determination, demonstrates the feasibility for the analysis in VLBWI samples and its poten-tial as point-of-care diagnostic tool for sepsis.

2.
Nutrients ; 11(11)2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31717933

RESUMO

Postnatal steroids, often used to prevent and treat bronchopulmonary dysplasia, may influence the growth of preterm infants, although data are scarce in the literature. This is a multicenter cohort study including surviving preterm infants <32 weeks at birth (n = 17,621) from the Spanish Neonatal Network SEN1500 database, without major congenital malformations. Linear regression models were adjusted for postnatal steroids, respiratory severity course (invasive mechanical ventilation at 28 days), progression to moderate-severe bronchopulmonary dysplasia (O2 at 36 weeks), length of stay, sex, gestational age and z-scores at birth. A subgroup analysis depending on the timing of administration, ventilation status at 28 days and moderate-severe BPD diagnosis was also performed. Overall, systemic postnatal steroids were not independently associated with poorer weight gain (0.1; 95% CI: -0.05 to 0.2 g/kg/day), linear growth (0; 95% CI: -0.03 to 0.01 cm/week) or head circumference growth (-0.01; 95% CI: -0.02 to 0 cm/week). Patients who received steroids after 28 days or who were not O2 dependent at 36 weeks after having received steroids gained more weight (0.22; 95% CI: 0.04 to 0.4 and 0.2; 95% CI: 0.004 to 0.5 g/kg/day, respectively). Globally, systemic postnatal steroids had no significant adjusted effect on postnatal growth.

3.
ACS Sens ; 4(8): 2117-2123, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31305070

RESUMO

Early diagnosis of sepsis, combining blood cultures and inflammation biomarkers, continues to be a challenge, especially in very low birth weight (VLBW) infants because of limited availability of blood samples. Traditional diagnostic procedures are cumbersome, not fast enough, and require relatively large volumes of sample. Empiric use of antibiotics, before diagnostic confirmation, is required to decrease mortality, leading to potential antibiotic resistance and side effects in VLBW infants. To solve such a serious problem, a dual magnetoimmunosensor is proposed for simultaneous assessment of two of the most important sepsis biomarkers: procalcitonin (PCT for early phase) and C-reactive protein (CRP for late phase). This "sample-to-result" approach exhibited excellent sensitivity, selectivity, precision, and stability using low sample volumes (<30 µL) and under 20 min of total assay. The analytical usefulness of the approach was demonstrated by analyzing clinically relevant samples of preterm neonates with suspicion of sepsis.

4.
Acta Paediatr ; 108(10): 1793-1800, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31002411

RESUMO

AIM: We describe the postnatal weight gain, linear and head growth trends of surviving preterm infants from 2005 to 2017. METHODS: Multicentre cohort study, including surviving preterm infants <32 weeks (n = 21 084), from the Spanish Neonatal Network database, without major congenital malformations who were less than 50 weeks postmenstrual age at discharge. Outcomes were weight gain (g/kg/day), linear and head growth (cm/week) and changes in weight, length and head circumference z-scores from birth to discharge. The study period was divided into 2005-8, 2009-11, 2012-14 and 2015-17. RESULTS: Weight gain, linear growth and head growth were slightly higher in 2015-2017 than in 2005-2008: 12.2 ± 2.6 to 13.1 ± 2.5 g/kg/day, 0.98 ± 0.6 to 1.03 ± 0.6 cm/week and 0.76 ± 0.2 to 0.77 ± 0.3 cm/week, respectively. It was associated with a decreased fall in weigh, length and head circumference z-scores from birth to discharge (-1.32 ± 0.9 to -1.01 ± 0.84, -1.38 ± 1.2 to -1.18 ± 1.2 and -0.41 ± 1.2 to -0.33 ± 1.3, respectively). CONCLUSION: Postnatal growth restriction remained a common complication of prematurity despite some increment over the last years. Growth disproportionality seemed to be worsening as weight gain was increased more than linear growth.

5.
Neonatology ; 115(4): 348-354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893696

RESUMO

BACKGROUND: Extrauterine growth restriction is common in the preterm infant, and it is associated with poor neurodevelopment. Nutrition plays an important role in postnatal growth, but growth is also influenced by other factors like co-morbidity, and, also, there might be sex differences. METHODS: This is a cohort study including preterm infants < 32 weeks at birth (n = 21,825) from the Spanish Neonatal Network database. The effect of sex and morbidity (patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing enterocolitis and late-onset sepsis) on weight gain as well as linear and head growth from birth to discharge/death was assessed with linear regression models adjusted by gestational age and Z-scores at birth. RESULTS: The 4 selected morbidities had an independent effect on all 6 growth parameters studied, which was greater in the case of necrotizing enterocolitis: changes in weight, length and head Z-scores were -0.60 (95% CI: -0.66 to -0.55), -0.62 (95% CI: -0.70 to -0.54) and -0.63 (95% CI: -0.71 to -0.56), respectively. Weight gain and linear growth were overall more affected than head growth. Girls lost slightly more weight Z-scores (-0.03; 95% CI: -0.06 to -0.002) than boys after adjustment by morbidity. There were no significant gender differences regarding linear and head growth velocity (cm/week), although girls lost more head Z-scores (-0.14; 95% CI: -0.18 to -0.10). CONCLUSIONS: Main co-morbidities associated with prematurity have an impact on postnatal growth. Head growth is less affected than length and weight. Girls are at slightly higher risk of postnatal weight and head restriction after adjustment by morbidity.


Assuntos
Estatura , Peso Corporal , Cabeça/fisiologia , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Doenças do Prematuro/epidemiologia , Caracteres Sexuais , Comorbidade , Bases de Dados Factuais , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Morbidade , Análise Multivariada , Estudos Retrospectivos , Espanha/epidemiologia
6.
PLoS One ; 14(3): e0213210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30840669

RESUMO

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in childhood, related to prematurity, and the most common cause of pulmonary hypertension (PH) secondary to pulmonary disease in children. Moderate and severe BPD have a worse outcome and relate more frequently with PH. The prediction of moderate or severe BPD development in extremely premature newborns is vital to implement preventive strategies. Starting with the hypothesis that molecular biomarkers were better than clinical and echocardiographic factors, this study aims to explore the ability of clinical, echocardiographic and analytical variables to predict moderate or severe BPD in a cohort of extremely preterm infants. PATIENTS AND METHODS: We designed a prospective longitudinal study, in which we followed a cohort of preterm newborns (gestational age <28 weeks and weight ≤ 1250 grams). In these newborns we recorded weekly clinical and echocardiographic variables as well as blood and tracheal aspirate samples, to analyze molecular biomarkers (IL-6, IL-1, IP10, uric acid, HGF, endothelin-1, VEGF, CCL5). Variables and samples were collected since birth up to week 36 (postmenstrual age), time-point at which the diagnosis of BPD is established. RESULTS: We included 50 patients with a median gestational age of 26 weeks (IQR 25-27) and weight of 871 g (SD 161,0) (range 590-1200g). Three patients were excluded due to an early death. Thirty-five patients (74.5%) developed BPD (mild n = 14, moderate n = 15, severe n = 6). We performed a logistic regression in order to identify risk factors for moderate or severe BPD. We compared two predictive models, one with two variables (mechanical ventilation and inter-ventricular septum flattening), and another-one with an additional molecular biomarker (ET-1). CONCLUSIONS: The combination of clinical and echocardiographic variables is a valuable tool for determining the risk of BPD. We find the two variable model (mechanical ventilation and echocardiographic signs of PH) more practical for clinical and research purposes. Future research on BPD prediction should be oriented to explore the potential role of ET-1.


Assuntos
Biomarcadores/sangue , Displasia Broncopulmonar/diagnóstico , Ecocardiografia/métodos , Lactente Extremamente Prematuro/sangue , Recém-Nascido de Baixo Peso/sangue , Doenças do Prematuro/diagnóstico , Medição de Risco/métodos , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/metabolismo , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/metabolismo , Estudos Longitudinais , Masculino , Gravidez , Prognóstico , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia
7.
Neuropharmacology ; 146: 1-11, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468796

RESUMO

OBJECTIVE: Hypothermia, the gold standard after a hypoxic-ischemic insult, is not beneficial in all treated newborns. Cannabidiol is neuroprotective in animal models of newborn hypoxic-ischemic encephalopathy. This study compared the relative efficacies of cannabidiol and hypothermia in newborn hypoxic-ischemic piglets and assessed whether addition of cannabidiol augments hypothermic neuroprotection. METHODS: One day-old HI (carotid clamp and FiO2 10% for 20 min) piglets were randomized to vehicle or cannabidiol 1 mg/kg i.v. u.i.d. for three doses after being submitted to normothermia or 48 h-long hypothermia with a subsequent rewarming period of 6 h. Non-manipulated piglets (naïve) served as controls. Hemodynamic or respiratory parameters as well as brain activity (aEEG amplitude) were monitored throughout the experiment. Following termination, brains were obtained for histological (TUNEL staining, apoptosis; immunohistochemistry for Iba-1, microglia), biochemical (protein carbonylation, oxidative stress; and TNFα concentration, neuroinflammation) or proton magnetic resonance spectroscopy (Lac/NAA: metabolic derangement; Glu/NAA: excitotoxicity). RESULTS: HI led to sustained depressed brain activity and increased microglial activation, which was significantly improved by cannabidiol alone or with hypothermia but not by hypothermia alone. Hypoxic-ischemic-induced increases in Lac/NAA, Glu/NAA, TNFα or apoptosis were not reversed by either hypothermia or cannabidiol alone, but combination of the therapies did. No treatment modified the effects of HI on oxidative stress or astroglial activation. Cannabidiol treatment was well tolerated. CONCLUSIONS: cannabidiol administration after hypoxia-ischemia in piglets offers some neuroprotective effects but the combination of cannabidiol and hypothermia shows some additive effect leading to more complete neuroprotection than cannabidiol or hypothermia alone.


Assuntos
Canabidiol/farmacologia , Hipotermia/fisiopatologia , Hipóxia-Isquemia Encefálica/prevenção & controle , Hipóxia-Isquemia Encefálica/terapia , Fármacos Neuroprotetores/farmacocinética , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Asfixia/induzido quimicamente , Encéfalo/patologia , Lesões Encefálicas , Canabidiol/farmacocinética , Modelos Animais de Doenças , Quimioterapia Combinada , Hemodinâmica/efeitos dos fármacos , Hipotermia/induzido quimicamente , Hipotermia Induzida , Inflamação , Microglia/efeitos dos fármacos , Neuroproteção , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Suínos
8.
Pediatr Res ; 85(4): 432-441, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30464331

RESUMO

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in infants and presents as a consequence of preterm birth. Due to the lack of effective preventive and treatment strategies, BPD currently represents a major therapeutic challenge that requires continued research efforts at the basic, translational, and clinical levels. However, not all very low birth weight premature babies develop BPD, which suggests that in addition to known gestational age and intrauterine and extrauterine risk factors, other unknown factors must be involved in this disease's development. One of the main goals in BPD research is the early prediction of very low birth weight infants who are at risk of developing BPD in order to initiate the adequate preventive strategies. Other benefits of determining the risk of BPD include providing prognostic information and stratifying infants for clinical trial enrollment. In this article, we describe new opportunities to address BPD's complex pathophysiology by identifying prognostic biomarkers and develop novel, complex in vitro human lung models in order to develop effective therapies. These therapies for protecting the immature lung from injury can be developed by taking advantage of recent scientific progress in -omics, 3D organoids, and regenerative medicine.

9.
Am J Perinatol ; 36(9): 943-948, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30414597

RESUMO

OBJECTIVE: To evaluate the initial doses of surfactant administered to preterm infants with respiratory distress syndrome. STUDY DESIGN: This is a retrospective cohort study of 206 preterm infants admitted in four level III neonatal intensive care units of acute tertiary care hospitals in Spain between 2013 and 2015. RESULTS: The mean initial dose of surfactant was 173.9 (37.3) mg/kg, and 47.5% of infants received a dose of 200 mg/kg ± 10% (180-220 mg/kg), 47% less than 180 mg/kg (-10%), and 5.4% more than 220 mg/kg (+10%). Very preterm infants (<28 weeks) received higher initial doses than more mature infants, but in all cases, the mean doses were below the recommended 200 mg/kg (by 9.2% in gestational age 23-28 weeks, by 15.9% in 29-32 weeks, and by 24.3% in >32 weeks). CONCLUSION: Administration of surfactant below the prescribed dose is a frequent error in clinical practice. Inadvertently rounding down doses seems a plausible explanation.

10.
Cytotherapy ; 20(11): 1337-1344, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30327248

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most prevalent sequelae of premature birth, for which therapeutic options are currently limited. Mesenchymal stromal cells (MSCs) are a potential therapy for prevention or reversal of BPD. SERIES OF CASES: We report on two infants with severe BPD in whom off-label treatment with repeated intravenous doses of allogeneic bone marrow-derived MSCs were administered. We analyzed the temporal profile of serum and tracheal cytokines and growth factors as well as safety, tolerability and clinical response. The administration of repeated intravenous doses of MSCs in two human babies with severe and advanced BPD was feasible and safe and was associated with a decrease of pro-inflammatory molecules and lung injury biomarkers. Both patients were at very advanced stages of BPD with very severe lung fibrosis and did not survive the disease. CONCLUSIONS: MSCs are a promising therapy for BPD, but they should be administered in early stages of the disease.


Assuntos
Displasia Broncopulmonar/terapia , Pulmão/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Administração Intravenosa , Biomarcadores/sangue , Displasia Broncopulmonar/diagnóstico por imagem , Citocinas/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais , Traqueia/metabolismo
11.
Arch Dis Child Fetal Neonatal Ed ; 103(3): F233-F237, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28667190

RESUMO

OBJECTIVES: Current neonatal resuscitation guidelines suggest the use of ECG in the delivery room (DR) to assess heart rate (HR). However, reliability of ECG compared with pulse oximetry (PO) in a situation of bradycardia has not been specifically investigated. The objective of the present study was to compare HR monitoring using ECG or PO in a situation of bradycardia (HR <100 beats per minute (bpm)) during preterm stabilisation in the DR. STUDY DESIGN: Video recordings of resuscitations of infants <32 weeks of gestation were reviewed. HR readings in a situation of bradycardia (<100 bpm) at any moment during stabilisation were registered with both devices every 5 s from birth. RESULTS: A total of 29 episodes of bradycardia registered by the ECG in 39 video recordings were included in the analysis (n=29). PO did not detect the start of these events in 20 cases (69%). PO detected the start and the end of bradycardia later than the ECG (median (IQR): 5 s (0-10) and 5 s (0-7.5), respectively). A decline in PO accuracy was observed as bradycardia progressed so that by the end of the episode PO offered significantly lower HR readings than ECG. CONCLUSIONS: PO detects the start and recovery of bradycardia events slower and less accurately than ECG during stabilisation at birth of very preterm infants. ECG use in this scenario may contribute to an earlier initiation of resuscitation manoeuvres and to avoid unnecessary prolongation of resuscitation efforts after recovery.


Assuntos
Bradicardia/diagnóstico , Eletrocardiografia/métodos , Oximetria/métodos , Frequência Cardíaca/fisiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico , Monitorização Fisiológica/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Ressuscitação/métodos , Sensibilidade e Especificidade
12.
Eur J Pediatr ; 176(12): 1587-1593, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28889192

RESUMO

Bronchopulmonary dysplasia (BPD) is one of the most serious chronic lung diseases in infancy and one of the most important sequels of premature birth (prevalence of 15-50%). Our objective was to estimate the cost of BPD of one preterm baby, with no other major prematurity-related complications, during the first 2 years of life in Spain. Data from the Spanish Ministry of Health regarding costs of diagnosis-related group of preterm birth, hospital admissions and visits, palivizumab administration, and oxygen therapy in the year 2013 were analyzed. In 2013, 2628 preterm babies were born with a weight under 1500 g; 50.9% were males. The need for respiratory support was 2.5% needed only oxygen therapy, 39.5% required conventional mechanical ventilation, and 14.9% required high-frequency ventilation. The incidence of BPD was of 34.9%. The cost of the first 2 years of life of a preterm baby with BPD and no other major prematurity-related complications ranged between 45,049.81 € and 118,760.43 €, in Spain, depending on birth weight and gestational age. If the baby required home oxygen therapy or developed pulmonary hypertension, this cost could add up to 181,742.43 €. CONCLUSION: Prematurity and BPD have an elevated cost, even for public health care systems. This cost will probably increase in the coming years if the incidence and survival of preterm babies keeps rising. The development of new therapies and preventive strategies to decrease the incidence of BPD and other morbidities associated with prematurity should be a priority. What is known: • Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease related with premature birth. • BPD is an increasing disease due to the up-rise in the number of premature births. What is new: • The economic cost of preterm birth and BPD has never before been estimated in Spain nor published with European data. • Preterm babies with BPD and a good clinical outcome carry also an important economic and social burden.


Assuntos
Displasia Broncopulmonar/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/terapia , Pré-Escolar , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Espanha/epidemiologia
13.
Pediatr Res ; 82(1): 79-86, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28388598

RESUMO

BackgroundBrain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.MethodsNewborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT1A receptor antagonist) after HI brain damage (carotid flow interruption and FiO2 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (OI), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1ß concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF).ResultsCBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW.ConclusionsCBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.


Assuntos
Canabidiol/farmacologia , Hipóxia-Isquemia Encefálica/patologia , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Hemodinâmica , Hipóxia/metabolismo , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Pulmão/fisiopatologia , Masculino , Estresse Oxidativo , Oxigênio/metabolismo , Suínos
14.
Indian Pediatr ; 53(4): 349-50, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27156554

RESUMO

BACKGROUND: Severe pulmonary hypertension may following ibuprofen administration for ductal closure. CASE CHARACTERISTICS: An extremely preterm infant who developed severe pulmonary hypertension unresponsive to inhaled nitric oxide after ibuprofen administration. OUTCOME: Pulmonary hypertension reversed after the administration of oral sildenafil, but the infant died due to complications related to bronchopulmonary dysplasia. MESSAGE: Sildenafil may have a role in treatment of severe pulmonary hypertension after ibuprofen treatment for ductal closure.


Assuntos
Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Ibuprofeno/efeitos adversos , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico , Humanos , Recém-Nascido , Masculino
15.
Arch Dis Child ; 101(4): 371-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26819267

RESUMO

AIM: To investigate the frequency and characteristics of adverse drug reactions (ADRs) in hospitalised neonates to obtain a better understanding of and improvement in neonatal healthcare. METHODOLOGY: A prospective cohort study. Data were collected on 313 neonates and 2166 drug prescriptions. Clinical characteristics of patients, drugs administered and ADRs were prospectively recorded and analysed. Informed consent was obtained in all cases. RESULTS: 116 different ADRs were detected. 17% of the neonates experienced at least one of these ADRs. Systemic antimicrobials and caffeine citrate were the drugs that most commonly caused ADRs. According to the ADR Severity Assessment Scale, 41% were mild, 42% were moderate and 17% were severe. Of the ADRs identified, 11% were classified as 'certain' by the Naranjo method and 20% were classified as 'defined' by the Karch and Lasagna modified algorithm. Most of the ADRs detected were related to feed intolerance, phlebitis and tachycardia. Most were acute (73%) and lasted between 1 and 7 days (39%). After the occurrence of an ADR, it was necessary to initiate specific treatment in 44 cases, discontinue the drugs involved in 30 cases, and reduce the drug dose in another 30 cases. An association was shown between the number of drugs prescribed and ADR onset. CONCLUSIONS: There is a high incidence of ADRs in hospitalised newborns, which increases with the number of prescriptions.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos , Estudos de Coortes , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Recém-Nascido , Masculino , Estudos Prospectivos
16.
Pediatr Res ; 79(3): 401-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25950454

RESUMO

BACKGROUND: We aimed to investigate whether neonatal hypoxic-ischemic (HI) brain injury induces inflammatory lung damage. METHODS: Thus, hypoxic (HYP, FiO2 10% for 30 min), ischemic (ISC, bilateral carotid flow interruption for 30 min), or HI event was performed in 1-2-d-old piglets. Dynamic compliance (Cdyn), oxygenation index (OI), and extravascular lung water (EVLW) were monitored for 6 h. Then, histologic damage was assessed in brain and lung (lung injury severity score). Total protein content (TPC) was determined in broncoalveolar lavage fluid (BALF), and IL-1ß concentration was measured in lung and brain tissues and blood. RESULTS: Piglets without hypoxia or ischemia served as controls (SHM). HI-induced brain damage was associated with decreased Cdyn, increased OI and EVLW, and histologic lung damage (interstitial leukocyte infiltration, congestive hyperemia, and interstitial edema). BALF TPC was increased, suggesting inflammatory damage. In agreement, tissue IL-1ß concentration increased in the brain and lung, in correspondence with increased IL-1ß serum concentration. Neither HYP nor ISC alone led to brain or lung damage. CONCLUSION: HI brain damage in newborn piglets led to inflammatory lung damage, suggesting an additional mechanism accounting for the development of lung dysfunction after neonatal HI encephalopathy.


Assuntos
Encéfalo/patologia , Hipóxia-Isquemia Encefálica/patologia , Inflamação , Lesão Pulmonar/patologia , Pulmão/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Hipóxia , Interleucina-1beta/metabolismo , Pulmão/fisiopatologia , Masculino , Suínos
17.
Fetal Pediatr Pathol ; 34(2): 117-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25394297

RESUMO

Angiotensin II receptor blockers (ARBs) are potent antihypertensive agents that block the renin angiotensin aldosterone system (RAS). Their use in pregnancy may cause malformations, oligoanuria, hypotension, and death. Hypotension is observed up to 15% of cases and is described as refractory to volume and inotropic support, although its pathophysiology is unknown. We present a case of prenatal exposure to ARBs in order to characterize the hemodynamic compromise in the newborn, help in decision-making, and guide the therapeutic approach to these patients.


Assuntos
Bloqueadores do Receptor Tipo 2 de Angiotensina II/farmacologia , Hemodinâmica/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Hipertensão/fisiopatologia , Recém-Nascido , Gravidez , Resultado da Gravidez
18.
Childs Nerv Syst ; 30(5): 967-70, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24193149

RESUMO

BACKGROUND: Intracranial traumatic pseudoaneurysms are rare in children. If left untreated, mortality rate can be as high as 50% due to delayed rupture and disastrous bleeding. Endovascular embolization is considered the preferred treatment option because of its minimal invasiveness and negligible mortality. However, exclusion of the pseudoaneurysm with preservation of the parental vessel is not always possible. In comparison with peripheral aneurysms, intracavernous internal carotid artery lesions are technically more challenging with both open surgery and endovascular techniques. CASE REPORT: We report the case of a successful two-stage coil embolization of a traumatic intracavernous carotid artery pseudoaneurysm with preservation of parental vessel in a 6-year-old boy. CONCLUSION: Endovascular embolization with parental vessel preservation should be considered the first treatment option for traumatic intracavernous internal carotid artery pseudoaneurysms in children. Although treatment of pseudoaneurysms in this location may be technically difficult, it is feasible in experienced hands.


Assuntos
Lesões das Artérias Carótidas/cirurgia , Traumatismos Craniocerebrais/cirurgia , Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Lesões das Artérias Carótidas/etiologia , Artéria Carótida Interna , Angiografia Cerebral , Criança , Traumatismos Craniocerebrais/complicações , Humanos , Masculino
19.
Life Sci ; 91(7-8): 264-70, 2012 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-22884805

RESUMO

AIMS: The purpose of this study is to investigate circulating endothelial progenitor cells (EPCs) and the signaling pathways involved in their recruitment in the ischemic retina of the 50/10 rat model of oxygen-induced retinopathy (OIR). MAIN METHODS: Within 12h after birth, litters of Sprague-Dawley rats and their mothers were exposed to alternating oxygen concentrations, followed by a room air exposition, to induce OIR. Retinopathy was quantified by ADPase stain in flat-mounted retinas and pre-ILM nuclei count in retinal sections. Semiquantitative real-time PCR and immunofluorescence were assessed in retinas to study stromal cell-derived factor 1 (SDF-1), its receptor CXCR4 and vascular endothelial growth factor (VEGF) expression. Circulating EPCs were evaluated by flow cytometry in peripheral blood. KEY FINDINGS: Our results showed increased immunolabelling of SDF-1 in endothelial cells and strong expression of CXCR4 in Müller cells in OIR retinas as compared to control retinas. We found increased levels of CXCR4 and VEGF mRNA in OIR retinas, especially during the vascular attenuation stage. The number of circulating EPCs was decreased in OIR rats as compared to control rats. SIGNIFICANCE: The decrease in circulating EPCs could be implied in vessel growth arrest during normal retinal development in OIR rats, while pro-angionenic signals released by Müller cells in the hypoxic retina could drive pathological neovascularization in the ischemic retina. These data warrant further studies to investigate new therapeutic approaches for ROP.


Assuntos
Quimiocina CXCL12/fisiologia , Células Endoteliais/citologia , Neovascularização Patológica , Oxigênio/administração & dosagem , Receptores CXCR4/fisiologia , Doenças Retinianas/etiologia , Vasos Retinianos/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Animais , Células da Medula Óssea/patologia , Quimiocina CXCL12/genética , Citometria de Fluxo , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Oxigênio/efeitos adversos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptores CXCR4/genética , Doenças Retinianas/metabolismo , Doenças Retinianas/fisiopatologia , Vasos Retinianos/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
20.
Pediatrics ; 124(3): e439-49, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19661049

RESUMO

OBJECTIVE: The goal was to reduce adverse pulmonary adverse outcomes, oxidative stress, and inflammation in neonates of 24 to 28 weeks of gestation initially resuscitated with fractions of inspired oxygen of 30% or 90%. METHODS: Randomized assignment to receive 30% (N = 37) or 90% (N = 41) oxygen was performed. Targeted oxygen saturation values were 75% at 5 minutes and 85% at 10 minutes. Blood oxidized glutathione (GSSG)/reduced glutathione ratio and urinary o-tyrosine, 8-oxo-dihydroxyguanosine, and isoprostane levels, isofuran elimination, and plasma interleukin 8 and tumor necrosis factor alpha levels were determined. RESULTS: The low-oxygen group needed fewer days of oxygen supplementation (6 vs 22 days; P < .01) and fewer days of mechanical ventilation (13 vs 27 days; P < .01) and had a lower incidence of bronchopulmonary dysplasia at discharge (15.4% vs 31.7%; P < .05). GSSG/reduced glutathione x 100 ratios at day 1 and 3 were significantly higher in the high-oxygen group (day 1: high-oxygen group: 13.36 +/- 5.25; low-oxygen group: 8.46 +/- 3.87; P < .01; day 3: high-oxygen group: 8.87 +/- 4.40; low-oxygen group: 6.97 +/- 3.11; P < .05). Urinary markers of oxidative stress were increased significantly in the high-oxygen group, compared with the low-oxygen group, in the first week after birth. GSSG levels on day 3 and urinary isofuran, o-tyrosine, and 8-hydroxy-2'-deoxyguanosine levels on day 7 were correlated significantly with development of chronic lung disease. CONCLUSIONS: Resuscitation of preterm neonates with 30% oxygen causes less oxidative stress, inflammation, need for oxygen, and risk of bronchopulmonary dysplasia.


Assuntos
Displasia Broncopulmonar/prevenção & controle , Doenças do Prematuro/prevenção & controle , Inflamação/prevenção & controle , Estresse Oxidativo , Oxigenoterapia , Oxigênio/administração & dosagem , Ressuscitação/métodos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Prospectivos
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