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1.
Cardiol Young ; 32(12): 1938-1943, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35287767

RESUMO

BACKGROUND: We aimed to assess the current nutritional practices in postoperative patients with Congenital Heart Disease. METHODS: Cross-sectional electronic survey was sent to members of The Pediatric Cardiac Intensive Care Society. MEASUREMENTS AND MAIN RESULTS: In Total, 52 members of the Pediatric Cardiac Intensive Care Society responded to the survey consisting of 14% paediatric intensivist, 53% paediatric cardiac intensivist, and 33% nurse/nurse practitioner with a median of 10 years of experience. There was an even distribution between intensivist (55%) and dietitian or nutritionist (45%) in nutrition management. Ninety-eight percent of respondents report that they would feed patients on inotropic or vasoactive support. Only 27% of respondents reported using indirect calorimetry in calculating resting energy expenditure which is the current gold standard. Academic hospitals compared to non-academic hospital were most likely to report feeding patients within 24 hours postoperative (p = 0.014). Having a feeding protocol was associated with feeding within 24 hours postoperative (p = 0.014) and associated with >50% goal intake by 48 hours postoperative (p = 0.025). CONCLUSIONS: Substantial variation in feeding practice still exists despite the American Society for Parenteral and Enteral Nutrition guidelines from 2017. Report of institutional established feeding protocol was associated with increased early feeding and reaching goal feeds by 48 hours postoperative. Very few centres reported use of indirect calorimetry in postoperative paediatric cardiac intensive care patients and many respondents lacked knowledge about applications in this population. Additional work to determine optimal feeding pathways and assessment of caloric needs in this population is needed.


Assuntos
Nutrição Enteral , Cardiopatias Congênitas , Humanos , Criança , Estudos Transversais , Nutrição Enteral/métodos , Nutrição Parenteral/métodos , Cardiopatias Congênitas/cirurgia , Período Pós-Operatório
2.
Neurocrit Care ; 28(3): 302-313, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29476389

RESUMO

BACKGROUND: Although small series have suggested that younger age is associated with less favorable outcome after severe traumatic brain injury (TBI), confounders and biases have limited our understanding of this relationship. We hypothesized that there would be an association between age and mortality in children within an ongoing observational, cohort study. METHODS: The first 200 subjects from the Approaches and Decisions for Acute Pediatric TBI trial were eligible for this analysis (inclusion criteria: severe TBI (Glasgow Coma Scale [GCS] score ≤ 8], age 18 years, and intracranial pressure (ICP) monitor placed; exclusion: pregnancy). Children with suspected abusive head trauma (AHT) were excluded to avoid bias related to the association between AHT and mortality. Demographics, and prehospital and resuscitation events were collected/analyzed, and children were stratified based on age at time of injury (< 5, 5-< 11, 11-18 years) and presented as mean ± standard error of the mean (SEM). Analyses of variance were used to test the equality of the means across the group for continuous variable, and Chi-square tests were used to compare percentages for discrete variables (post hoc comparisons were made using t test and Bonferroni corrections, as needed). Kaplan-Meier curves were generated for each age subgroup describing the time of death, and log-rank was used to compare the curves. Cox proportional hazards regression models were used to assess the effect of age on time to death while controlling for covariates. RESULTS: In the final cohort (n = 155, 45 excluded for AHT), overall age was 9.2 years ± 0.4 and GCS was 5.3 ± 0.1. Mortality was similar between strata (14.0, 20.0, 20.9%, respectively, p = 0.58). Motor vehicle accidents were the most common mechanism across all strata, while falls tended to be more common in the youngest stratum (p = 0.08). The youngest stratum demonstrated increased incidence of spontaneous hypothermia at presentation and decreased hemoglobin concentrations and coagulopathies, while the oldest demonstrated lower platelet counts. CONCLUSIONS: In contrast to previous reports, we failed to detect mortality differences across age strata in children with severe TBI. We have discerned novel associations between age and various markers of injury-unrelated to AHT-that may lead to testable hypotheses in the future.


Assuntos
Fatores Etários , Lesões Encefálicas Traumáticas/mortalidade , Índice de Gravidade de Doença , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Pesquisa Comparativa da Efetividade , Feminino , Humanos , Masculino
3.
Crit Care Med ; 45(8): 1398-1407, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28430697

RESUMO

OBJECTIVES: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. DESIGN: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative effectiveness study using an observational, cohort study design. SETTING: PICUs in tertiary children's hospitals in United States and abroad. PATIENTS: Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow Coma Scale ≤ 8; intracranial pressure monitoring). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, injury-related scores, prehospital, and resuscitation events were analyzed. Children were dichotomized based on likelihood of abusive head trauma. A total of 190 children were included (n = 35 with abusive head trauma). Abusive head trauma subjects were younger (1.87 ± 0.32 vs 9.23 ± 0.39 yr; p < 0.001) and a greater proportion were female (54.3% vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002), and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive head trauma had a higher prevalence of seizures during resuscitation (31.4 vs 9.7%; p = 0.002). After adjusting for covariates, there was no difference in mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma, 69.0%). CONCLUSIONS: In this large, multicenter series, children with abusive head trauma had differences in prehospital and in-hospital secondary injuries which could have therapeutic implications. Unlike other traumatic brain injury populations in children, female predominance was seen in abusive head trauma in our cohort. Similar mortality rates and refractory intracranial pressure deaths suggest that children with severe abusive head trauma may benefit from therapies including invasive monitoring and adherence to evidence-based guidelines.


Assuntos
Lesões Encefálicas Traumáticas/epidemiologia , Maus-Tratos Infantis/estatística & dados numéricos , Adolescente , Lesões Encefálicas Traumáticas/classificação , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Hospitais Pediátricos , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Fatores Socioeconômicos , Estados Unidos
4.
J Pediatr ; 166(2): 332-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25466680

RESUMO

OBJECTIVE: To determine the prevalence of and risk factors for extrathoracic upper-airway obstruction after pediatric cardiac surgery. STUDY DESIGN: A retrospective chart review was performed on 213 patients younger than 18 years of age who recovered from cardiac surgery in our multidisciplinary intensive care unit in 2012. Clinically significant upper-airway obstruction was defined as postextubation stridor with at least one of the following: receiving more than 2 corticosteroid doses, receiving helium-oxygen therapy, or reintubation. Multivariate logistic regression analysis was performed to determine independent risk factors for this complication. RESULTS: Thirty-five patients (16%) with extrathoracic upper-airway obstruction were identified. On bivariate analysis, patients with upper-airway obstruction had greater surgical complexity, greater vasoactive medication requirements, and longer postoperative durations of endotracheal intubation. They also were more difficult to calm while on mechanical ventilation, as indicated by greater infusion doses of narcotics and greater likelihood to receive dexmedetomidine or vecuronium. On multivariable analysis, adjunctive use of dexmedetomedine or vecuronium (OR 3.4, 95% CI 1.4-8) remained independently associated with upper-airway obstruction. CONCLUSION: Extrathoracic upper-airway obstruction is relatively common after pediatric cardiac surgery, especially in children who are difficult to calm during endotracheal intubation. Postoperative upper-airway obstruction could be an important outcome measure in future studies of sedation practices in this patient population.


Assuntos
Obstrução das Vias Respiratórias/epidemiologia , Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias/epidemiologia , Extubação , Feminino , Humanos , Lactente , Masculino , Prevalência , Estudos Retrospectivos , Fatores de Risco
5.
J Med Educ Curric Dev ; 11: 23821205241275357, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161643

RESUMO

Objective: Physicians often use mobile apps for patient care, but few apps are dedicated to pediatric critical care medicine (PCCM). This study developed a mobile app specifically for Pediatric Critical Care Unit (PICU) residents to aid their onboarding process and aimed to assess whether it could enhance their confidence and comfort levels. Method: From March 2020 to April 2021, 90 residents participated and completed pre- and post-rotation quizzes with 20 questions each. Quiz score differences between the control and app groups were analyzed using t-tests. A survey was also administered at the end of the rotation to compare comfort level and confidence in PCCM knowledge pre- and post-rotation. Results: Enrollment included 50 residents in the control group and 40 in the app group. The participation rate was 100%, but not all participants completed both quizzes and survey. The app group showed a significantly greater improvement in quiz scores from pre- to post-rotation compared to the control group (increase of 0.23 questions vs 1.67, p = 0.045). However, the two groups had no significant differences in confidence in PCCM knowledge (p = 0.246) or comfort levels (p = 0.776) in the PICU. Conclusions: This study found no significant difference in confidence levels between the App and control groups at the end of the PICU rotation. However, the App group outperformed the control group in knowledge assessments. Frequent use of the app likely reinforced essential concepts and facilitated adaptation to the PICU service. Overall, the app's positive impact on knowledge and adaptation indicates it is a valuable tool for enhancing medical residents' educational experiences in busy clinical environments.

6.
Crit Care Med ; 41(7): 1733-44, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23660732

RESUMO

OBJECTIVE: Donation after cardiac death has been endorsed by professional organizations, including the American Academy of Pediatrics as a means of increasing the supply of transplantable organs. However, ethical concerns have been raised about donation after cardiac death, especially in children. This study explores the views of pediatric intensive care physicians on the ethics of pediatric donation after cardiac death. DESIGN: Internet survey. SUBJECTS: Physician members of the American Academy of Pediatrics Section of Critical Care. INTERVENTIONS: Physicians were emailed an anonymous survey consisting of four demographic items and 16 items designed to assess their views on the ethics of pediatric donation after cardiac death. Responses to ethics items were rated on a 5-point scale ranging from strongly disagree to strongly agree. Physicians were also given the opportunity to provide free-text comments regarding their views. MEASUREMENTS AND MAIN RESULTS: Of the 598 eligible physicians, 264 (44.1%) responded to the survey. Of these, 193 (73.4%) were practicing in a transplant center and 160 (60.6%) participated in at least one donation after cardiac death procedure at the time of survey completion. Two hundred twenty (83.4%) agreed or strongly agreed that regarding donation after cardiac death, parents should be able to make decisions based on the best interests of their child. Two hundred twenty-two (84.1%) agreed or strongly agreed that it is not acceptable to harvest organs from a child before the declaration of death, consistent with the Dead Donor Rule. However, only 155 (59.1%) agreed or strongly agreed that the time of death in donation after cardiac death can be conclusively determined. Twenty-nine (11.0%) agreed or strongly agreed that the pediatric donation after cardiac death donor may feel pain or suffering during the harvest procedure. CONCLUSIONS: Most pediatric intensive care physicians agree that the Dead Donor Rule should be applied for donation after cardiac death and that donation after cardiac death can be consistent with the best interest standard. However, concerns about the ability to determine time of death for the purpose of organ donation and the possibility of increasing donor pain and suffering exist.


Assuntos
Atitude do Pessoal de Saúde , Morte , Unidades de Terapia Intensiva Pediátrica , Médicos/psicologia , Obtenção de Tecidos e Órgãos/ética , Feminino , Humanos , Masculino
7.
Neurocrit Care ; 19(2): 192-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23896815

RESUMO

BACKGROUND: As important mediators of solute transport at the blood-brain and blood-cerebrospinal fluid barriers, ATP-binding cassette (ABC) transporters (including ABCB1, ABCC1, and ABCC2), impact the bioavailability of drugs and endogenous substrates in the brain. While several ABCB1, ABCC1, and ABCC2 single nucleotide polymorphisms (SNPs) have been identified, their impact on outcome after traumatic brain injury (TBI) is unknown. HYPOTHESIS: ABCB1, ABCC1, and ABCC2 SNPs are associated with Glasgow Outcome Scale (GOS) score after TBI. METHODS: DNA samples from 305 adult patients with severe TBI (Glasgow Coma Scale, GCS score ≤ 8) were genotyped for tagging SNPs of ABCB1 (rs1045642; rs1128503), ABCC1 (rs212093; rs35621; rs4148382), and ABCC2 (rs2273697). For each SNP, patients were dichotomized based on presence of variant allele for multivariate analysis to determine associations with GOS assigned at 6 months adjusting for GCS, Injury Severity score, age, and patient sex. RESULTS: For ABCB1 rs1045642, patients homozygous for the T allele were less likely to be assigned poor outcome versus those possessing the C allele [CT/CC; odds of unfavorable GOS = 0.71(0.55-0.92)]. For ABCC1 rs4148382, patients homozygous for the G allele were less likely to be assigned poor outcome versus those possessing the A allele [AG/AA; odds of unfavorable GOS = 0.73(0.55-0.98)]. CONCLUSIONS: In this single-center study, patients homozygous for the T allele of ABCB1 rs1045642 or the G allele of ABCC1 rs4148382 were found to have better outcome after severe TBI. Further study is necessary to replicate these very preliminary findings and to determine whether these associations are due to central nervous system bioavailability of ABC transporter drug substrates commonly used in the management of TBI, brain efflux of endogenous solutes, or both.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Lesões Encefálicas/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adolescente , Adulto , Idoso , Barreira Hematoencefálica/fisiologia , Lesões Encefálicas/metabolismo , Feminino , Escala de Coma de Glasgow , Homozigoto , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Polimorfismo de Nucleotídeo Único , Recuperação de Função Fisiológica/genética , Adulto Jovem
8.
Pediatr Clin North Am ; 69(3): 415-424, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35667754

RESUMO

Brain injury in children is a major public health problem, causing substantial morbidity and mortality. Cause of pediatric brain injury varies widely and can be from a primary neurologic cause or as a sequela of multisystem illness. This review discusses the emerging field of pediatric neurocritical care (PNCC), including current techniques of imaging, treatment, and monitoring. Future directions of PNCC include further expansion of evidence-based practice guidelines and establishment of multidisciplinary PNCC services within institutions.


Assuntos
Lesões Encefálicas , Cuidados Críticos , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/terapia , Criança , Cuidados Críticos/métodos , Humanos
9.
JAMA Netw Open ; 5(3): e220891, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35267036

RESUMO

Importance: Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol. Objectives: To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP). Design, Setting, and Participants: In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021. Interventions: Boluses of HTS and mannitol were administered. Main Outcomes and Measures: Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments. Results: A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted ß, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted ß, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted ß, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted ß, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted ß, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis. Conclusions and Relevance: In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.


Assuntos
Lesões Encefálicas Traumáticas , Hipertensão Intracraniana , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Criança , Feminino , Humanos , Hipertensão Intracraniana/tratamento farmacológico , Hipertensão Intracraniana/etiologia , Pressão Intracraniana , Masculino , Manitol/uso terapêutico , Solução Salina Hipertônica/uso terapêutico
12.
Front Pediatr ; 4: 92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27626028

RESUMO

OBJECTIVE: To describe the utility of high frequency jet ventilation (HFJV) as a rescue therapy in patients with respiratory failure secondary to respiratory syncytial virus (RSV) that was refractory to conventional mechanical ventilation (CMV). DESIGN: Descriptive study by retrospective review. SETTING: Pediatric intensive care unit at a tertiary care children's hospital. PATIENTS: Infants on mechanical ventilation for respiratory failure due to RSV. INTERVENTIONS: Use of HFJV. MAIN RESULTS: Eleven patients were placed on HFJV. There was sustained improvement in ventilation on HFJV with a mean decrease in PCO2 of 9 mmHg at 24 h and 11 mmHg at 72 h. There were no significant changes in oxygenation by oxygenation index. No patients required extracorporeal support or suffered pneumothorax, pneumomediastinum, or subcutaneous emphysema. Ten out of 11 (91%) patients survived to discharge from the hospital. CONCLUSION: High frequency jet ventilation may represent an alternative therapy for RSV-induced respiratory failure that is refractory to CMV.

13.
Front Pediatr ; 3: 100, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26636051

RESUMO

The lifesaving processes of organ donation and transplantation in neonatology and pediatrics carry important ethical considerations. The medical community must balance the principles of autonomy, non-maleficence, beneficence, and justice to ensure the best interest of the potential donor and to provide equitable benefit to society. Accordingly, the US Organ Procurement and Transplantation Network (OPTN) has established procedures for the ethical allocation of organs depending on several donor-specific and recipient-specific factors. To maximize the availability of transplantable organs and opportunities for dying patients and families to donate, the US government has mandated that hospitals refer potential donors in a timely manner. Expedient investigation and diagnosis of brain death where applicable are also crucial, especially in neonates. Empowering trained individuals from organ procurement organizations to discuss organ donation with families has also increased rates of consent. Other efforts to increase organ supply include recovery from donors who die by circulatory criteria (DCDD) in addition to donation after brain death (DBD), and from neonates born with immediately lethal conditions such as anencephaly. Ethical considerations in DCDD compared to DBD include a potential conflict of interest between the dying patient and others who may benefit from the organs, and the precision of the declaration of death of the donor. Most clinicians and ethicists believe in the appropriateness of the Dead Donor Rule, which states that vital organs should only be recovered from people who have died. The medical community can maximize the interests of organ donors and recipients by observing the Dead Donor Rule and acknowledging the ethical considerations in organ donation.

15.
Pediatrics ; 132(5): e1418-23, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24167177

RESUMO

Pertussis is an illness that causes significant morbidity and mortality, especially in infants younger than 3 months old. In the most severe cases, it can cause pneumonia, respiratory failure, acute respiratory distress syndrome, pulmonary hypertension, and death. There are reports of using rescue extracorporeal membrane oxygenation (ECMO) as a rescue therapy. However, the mortality of ECMO with pertussis is higher than with other causes of pediatric respiratory failure. We report here the case of a 2-month-old boy with severe respiratory failure and pulmonary hypertension who satisfied ECMO criteria but was successfully treated with repeated bronchoscopy with instillation of N-acetylcysteine. Our patient's respiratory failure was refractory to multiple therapies that have shown benefit in pediatric hypoxemic respiratory failure, including open lung strategies, prone positioning, intratracheal surfactant, and inhaled nitric oxide. Although pulmonary hypertension is a key factor in most cases of fatal pertussis, the adverse effects of hyperinflation and air leaks were more important in this patient's clinical course. Because bronchiolar obstruction from inflammatory, mucous, and airway epithelial debris can be seen in severe pertussis, a regimen of repeated therapeutic bronchoscopy was initiated, and thick, inspissated secretions were retrieved. The patient's airway obstruction gradually resolved, and he eventually recovered with minimal sequelae.


Assuntos
Acetilcisteína/administração & dosagem , Broncoscopia/métodos , Infecções Respiratórias/terapia , Índice de Gravidade de Doença , Coqueluche/terapia , Humanos , Lactente , Masculino , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Irrigação Terapêutica/métodos , Coqueluche/complicações , Coqueluche/diagnóstico
17.
J Neurotrauma ; 27(3): 465-71, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19925161

RESUMO

Poly(ADP-ribose) polymerase-1 (PARP-1) plays an important role in the cellular response to stress and DNA damage. However, excessive activity of PARP-1 exacerbates brain injury via NAD+ depletion and energy failure. The purpose of this study was to determine if tagging single nucleotide polymorphisms (tSNPs) covering multiple regions of the PARP-1 gene are related to outcome after traumatic brain injury (TBI) in humans. DNA from 191 adult patients with severe TBI was assayed for four tSNPs corresponding to haplotype blocks spanning the PARP-1 gene. Categorization as favorable or poor outcome was based on Glasgow Outcome Scale (GOS) score assigned at 6 months. PARP-1 enzyme activity was indirectly evaluated by quantifying poly-ADP-ribose (PAR)-modified proteins in cerebrospinal fluid (CSF) using an enzyme-linked immunosorbent assay. In multiple logistic regression analysis controlling for age, initial Glasgow Coma Scale score, and gender, the AA genotype of SNP rs3219119 was an independent predictor of favorable neurologic outcome. This SNP tags a haplotype block spanning the automodification and catalytic domains of the PARP-1 gene. SNP rs2271347 correlated with CSF PAR-modified protein level. This SNP, which did not correlate with outcome, tags a haplotype block spanning the promoter region of the PARP-1 gene. We conclude that after severe TBI in humans, a PARP-1 polymorphism within the automodification-catalytic domain is associated with neurological outcome, while a polymorphism within the promoter region was associated with CSF PAR-modified protein level. These findings must be replicated in a prospective study before the relevance of PARP-1 polymorphisms after TBI can be established.


Assuntos
Lesões Encefálicas/genética , Predisposição Genética para Doença/genética , Poli(ADP-Ribose) Polimerases/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Idoso , Química Encefálica/genética , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , Análise Mutacional de DNA , Feminino , Testes Genéticos , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Poli(ADP-Ribose) Polimerase-1 , Valor Preditivo dos Testes , Prognóstico , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
18.
J Cereb Blood Flow Metab ; 28(9): 1523-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18506195

RESUMO

Poly-ADP-ribosylation (PAR) of proteins by poly(ADP-ribose) polymerases (PARP) occurs after experimental traumatic brain injury (TBI) and modulates neurologic outcome. Several promising pharmacological PARP inhibitors have been developed for use in humans, but there is currently no clinically relevant means of monitoring treatment effects. We therefore used an enzyme-linked immunosorbent assay to measure PAR-modified proteins in cerebrospinal fluid (CSF). Cerebrospinal fluid samples from 17 pediatric TBI patients and 15 controls were plated overnight and then incubated with polyclonal antibody against PAR. Histone-1, a PARP substrate, was incubated with active PARP, NAD, and nicked DNA, and served as the standard. Both peak and mean CSF PAR-modified proteins were increased in TBI patients versus controls. Peak CSF PAR-modified protein levels occurred on day 1 and levels remained increased on day 2 after TBI. Increases in peak CSF PAR-modified protein concentrations were independently associated with age and male sex, but not initial Glasgow Coma Scale score, Glasgow outcome score, or mechanism of injury. The increase in PAR-modified proteins in CSF after TBI may be because of increased PARP activation, decreased PAR degradation, or both. As PAR-modified protein concentration correlated with age and male sex, developmental and sex-dependent roles for PARP after TBI are implicated.


Assuntos
Lesões Encefálicas/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Fatores Etários , Lesões Encefálicas/etiologia , Estudos de Casos e Controles , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Processamento de Proteína Pós-Traducional , Fatores Sexuais
19.
Indian J Pediatr ; 72(4): 339-42, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15876764

RESUMO

Application of traditional ethical principles in developing countries may not, indeed should not, conform to the western philosophy and ideology. The principle of distributive justice is of utmost importance when critical resources are scarce. There is no ethical imperative, nor is one followed even in the most advanced countries, that every citizen is entitled to the very best available care. However, a society must establish a uniform code of ethics that can be applied nationally, whereby all citizens are eligible for a minimum acceptable level of care. The traditional principles of autonomy, beneficence, nonmaleficence and justice are still applicable in structuring an ethical framework that is most suited for the country's needs and resources.


Assuntos
Cuidados Críticos/ética , Unidades de Terapia Intensiva Pediátrica/ética , Atitude Frente a Morte , Criança , Características Culturais , Diversidade Cultural , Países em Desenvolvimento , Eutanásia , Humanos , Índia , Recém-Nascido , Ciência de Laboratório Médico , Princípios Morais , Filosofia , Relações Médico-Paciente , Qualidade de Vida , Justiça Social
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