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1.
Ann Thorac Surg ; 113(3): 884-888, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33607054

RESUMO

BACKGROUND: Pulmonary artery sling (PAS) is usually associated with long-segment congenital tracheal stenosis (LSCTS). This combination of abnormalities can also be associated with lung hypoplasia abnormalities (hypoplasia, aplasia, or agenesis). This study analyzed the association of lung hypoplasia abnormalities with combined PAS and LSCTS and its influence on its surgical outcomes. METHODS: All patients (0 to 18 years) who underwent surgical procedures for both PAS and LSCTS from 1995 to 2019 were analyzed retrospectively for mortality, ventilation days, and intensive care unit days by dividing them into those with normal lungs (group 1) and hypoplastic lungs (group 2). RESULTS: Included were 75 patients (30 girls [40%]), who were a median age of 5.7 months (interquartile range [IQR], 2.9-13.3 months), median weight of 5.5 kg (IQR, 4.1-7.9 kg), and had a median follow-up of 99.8 months (IQR, 54.5-152.0 months); of these, 8 patients (10.7%) had hypoplastic right lung, comprising hypoplasia in 7 (87.5%), aplasia in 1 (12.5%), and agenesis in 0 (0%). There was a significant difference in mortality (group 1, 9.0%; group 2, 50%; P = .007) but no significant difference in median ventilation days (group 1, 9.0; group 2, 9.0; P = .89) or in median intensive care unit days (group 1, 14.0; group 2, 11.5; P = .44). CONCLUSIONS: Lung hypoplasia associated with PAS and LSCTS is usually right-sided. As a result of severe airway obstruction and single-lung physiology, there is a high requirement of preoperative cardiorespiratory support and a significant association with adverse surgical outcomes.


Assuntos
Anormalidades Múltiplas , Cardiopatias Congênitas , Pneumopatias , Anormalidades do Sistema Respiratório , Estenose Traqueal , Malformações Vasculares , Anormalidades Múltiplas/cirurgia , Constrição Patológica , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Pulmão/anormalidades , Pneumopatias/complicações , Artéria Pulmonar/cirurgia , Estudos Retrospectivos , Traqueia/anormalidades , Estenose Traqueal/congênito , Estenose Traqueal/cirurgia , Resultado do Tratamento , Malformações Vasculares/complicações
2.
Front Pediatr ; 8: 273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670994

RESUMO

Dieulafoy's disease is a rare vascular lesion characterized by presence of large aberrant arteries within the submucosa of gastrointestinal tract or respiratory tract with a potential to cause life-threatening hemorrhage. Treatment includes bronchoscopy ablation, angiographic embolization or surgery. We report management of 7-year old girl with Dieulafoy's disease in the airway who presented with recurrent hemoptysis. Bronchial angiography revealed multiple feeding vessels to the lesion. Considering the potential risk of recurrence with embolization, sleeve resection of bronchus offered complete resolution. This case demonstrates the usefulness of bronchial angiography as part of multi-faceted approach before surgery in the management of Dieulafoy's disease.

3.
Ann Thorac Surg ; 109(6): 1889-1896, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32119856

RESUMO

BACKGROUND: Comorbid long segment congenital tracheal stenosis and congenital cardiovascular abnormalities in children pose significant challenges with regard to repairing these abnormalities simultaneously or in stages. The aim of this study was to explore whether this combination of abnormalities needs a staged approach for surgical repairs. METHODS: All children who underwent both tracheal and cardiac surgical procedures at a tertiary hospital from 1995 to 2018 were analyzed retrospectively for mortality, ventilation days, postoperative intensive care unit days, mediastinitis, and unplanned reoperation by dividing them into simultaneous repairs (group 1), staged repairs within the same admission (group 2), and staged repairs during different admissions (group 3). RESULTS: Of 110 patients included in the study (group 1, 74; group 2. 10; and group 3, 26 patients), there was no significant difference in mortality (P = .85), median ventilation days (P = .99), median intensive care unit days (P = .23), unplanned airway reoperation (P = .36), and unplanned cardiac reoperation (P = .77). There was a significant difference in the rate of mediastinitis (group 1, 3%; group 2, 10%; and group 3, 19%; P = .02). There was no significant difference in 5-year survival (group 1, 86.2%; group 2, 77.8%; and group 3, 85.1%; P = .86). A higher STAT category was identified to be a risk factor for mortality in multivariate Cox regression analysis (relative risk, 5.45). CONCLUSIONS: Combined tracheal and cardiac abnormalities need a stratified approach to facilitate better clinical outcomes. Although the trajectory of care is often based on the clinical presentation, establishing a management protocol will be helpful, for which setting an international database will be useful.


Assuntos
Anormalidades Múltiplas , Cardiopatias Congênitas/cirurgia , Procedimentos Cirúrgicos Torácicos/classificação , Estenose Traqueal/cirurgia , Procedimentos Cirúrgicos Cardíacos/classificação , Comorbidade , Feminino , Seguimentos , Cardiopatias Congênitas/epidemiologia , Humanos , Lactente , Masculino , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Estenose Traqueal/congênito , Estenose Traqueal/epidemiologia , Resultado do Tratamento
4.
Eur J Cardiothorac Surg ; 55(2): 300-303, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29878177

RESUMO

OBJECTIVES: Several procedures have been described to correct pectus excavatum and carinatum. We have used a modified Ravitch procedure (STRATOS titanium bars) for patients who were unsuitable for the minimally invasive Nuss procedure. The operation produced excellent cosmetic results, but we have noted several fractures and displacements of the STRATOS bars. METHODS: We reviewed all our STRATOS patients since first use in 2009 until 2014. We collated the following data of each patient: diagnosis, severity of pectus deformity, comorbidity, previous operations for pectus, age at bar implantation, the number of bars implanted and duration of implantation. Patients with severe comorbidity were excluded. RESULTS: Between 2009 and 2014, 39 patients were treated for pectus deformities using the STRATOS bars. Twelve of 39 patients (31%) were identified as having bar(s) broken before removal. There were no significant differences between patients with fractured bars and those without, except for the number of bars implanted (P = 0.016). CONCLUSIONS: This incidence of bar fracture is unexpectedly high, although the literature on this topic is sparse. The high fracture rate is alarming, because of its unpredictability and lack of clear aetiological factors. The operation is done (largely) for psychosocial and cosmetic reasons, and therefore, we must have complete confidence in the quality of the bars used in teenage pectus patients. We raise the issue to warn other units and encourage them to report bar fracture rates.


Assuntos
Tórax em Funil/cirurgia , Fixadores Internos/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/instrumentação , Parede Torácica/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Segurança do Paciente , Falha de Prótese , Estudos Retrospectivos , Adulto Jovem
6.
Early Hum Dev ; 91(2): 139-48, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25617864

RESUMO

BACKGROUND: The neuropathology of stillbirths has been widely studied but rarely on a population basis. Whether foetal apolipoprotein E (APOE) genotype exerts any influence has been little investigated, despite well known effects in adult brains. AIMS: To establish the neuropathology of a population cohort of stillbirths and compare with the APOE genotype. STUDY DESIGN AND SUBJECTS: The brains of 191 stillbirths (≥24weeks of gestation) were recruited from a Scottish population cohort and grouped by clinical history. APOE genotype was available for 97%. RESULTS AND CONCLUSIONS: One or more neuropathological features, most appearing relatively recent, were found in 54% of 157 antepartum singletons, 44% of 9 abruption-associated stillbirths, 85% of 13 in multiple pregnancies but in only 19% of 12 intrapartum stillbirths. White matter injury (WMI) occurred in 36% of preterm and 21% mature stillbirths. Fresh petechial haemorrhages were common in all groups (29%) but germinal matrix haemorrhage (GMH) (7%) and periventricular leucomalacia (1%) were confined to preterm. GMH was significantly associated with WMI (p=0.003). Placental inflammation was common in intrapartum stillbirths (50%), compared with antepartum (15%), multiple pregnancy (23%) and abruption (0%). ß-Amyloid precursor protein (ßAPP) positive axons (36% stillbirths overall) correlated closely with WMI (p<0.0001), justifying future routine inclusion in foetal neuropathological investigation. This study highlights the paucity of brain damage in intrapartum stillbirths. While APOE2 was significantly overrepresented in stillbirths, there was no correlation between APOE genotype and neuropathological findings. We conclude that APOE does not influence neuropathological outcomes in stillbirths.


Assuntos
Apolipoproteína E2/genética , Encéfalo/patologia , Genótipo , Natimorto/genética , Precursor de Proteína beta-Amiloide/metabolismo , Apolipoproteína E2/metabolismo , Encéfalo/metabolismo , Feminino , Feto/metabolismo , Feto/patologia , Humanos , Gravidez , Escócia
7.
J Pediatr Endocrinol Metab ; 26(11-12): 1053-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23828491

RESUMO

BACKGROUND: Routine surveillance would be valuable for vitamin D deficiency as symptomatic vitamin D deficiency may be common in Scotland. AIM: To assess the effectiveness of an electronic surveillance system to determine the current incidence of hospital-based presentation of childhood vitamin D deficiency in Scotland. METHODS: Active surveillance was performed for 2 years as part of an electronic web-based surveillance programme by the Scottish Paediatric Surveillance Unit. Notifications were followed by completion of a questionnaire. To further examine the validity of the system, cases with severe vitamin D deficiency in Glasgow and Edinburgh were identified from the regional laboratory and their clinical details were checked against those identified through the surveillance system. RESULTS: Between September 2009 and August 2011, 109 cases of vitamin D deficiency were notified. The majority of cases (n=82) were reported in Glasgow with an annual incidence of 41 cases per year. Fourteen cases were reported in Edinburgh during the first year of the study and two cases during the second year. At the time of clinical diagnosis, the median age of the children was 2 years (range 3 months-16 years). Cross-validation of data showed that among symptomatic cases that had a measured serum vitamin D of <14 nmol/L, 89% of eligible cases had been reported in Glasgow and 33% of cases had been reported in Edinburgh. CONCLUSION: The incidence of vitamin D deficiency remains high in Scotland. An electronic surveillance system can provide data for studying the epidemiology of vitamin D deficiency but may underestimate the number of positive cases.


Assuntos
Vigilância da População , Deficiência de Vitamina D/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Escócia/epidemiologia
8.
Arch Dis Child ; 97(6): 502-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22493405

RESUMO

INTRODUCTION: The relative frequencies of the causes of hypernatraemia in children after the neonatal period are unknown. Salt poisoning and osmoregulatory dysfunction are extremely rare and potentially fatal. In this retrospective 10-year study, the incidence, causes and differential biochemistry of hypernatraemia in children is examined. METHODS: Children with hypernatraemia (sodium ≥ 150 mmol/litre) aged >2 weeks to 17 years were identified from laboratory data of two paediatric departments serving the Lothian region of Scotland. A review of patient notes established time of onset and cause. Denominator data were available from the Scottish Health Service. RESULTS: On admission to hospital, 1 in 2288 children (1:1535 admitted as an emergency) had hypernatraemia. This is 1 in 30 563 Lothian children <17 years. Overall 0.04% hospital stays had an episode of hypernatraemia. In 45 children admitted with 64 separate episodes (11 from a case of salt poisoning), the commonest cause was dehydration secondary to either gastroenteritis or systemic infection; 31% had an underlying chronic neurological disorder. A total of 177 further cases developed hypernatraemia after admission. The commonest causes were dehydration secondary to severe systemic infection and postoperative cardiac surgery. Urine sodium:creatinine ratio and fractional excretion of sodium were both much higher in the salt poisoning case than in a child with osmoregulatory dysfunction or children with simple dehydration. CONCLUSIONS: Hypernatraemia after 2 weeks of age is uncommon, and on admission is usually associated with dehydration. Salt poisoning and osmoregulatory dysfunction are rare but should be considered in cases of repeated hypernatraemia without obvious cause. Routine measurement of urea, creatinine and electrolytes on paired urine and plasma on admission will differentiate these rare causes.


Assuntos
Desidratação/complicações , Hidratação/efeitos adversos , Hipernatremia/epidemiologia , Sódio/sangue , Adolescente , Criança , Pré-Escolar , Desidratação/epidemiologia , Feminino , Hospitalização , Humanos , Hipernatremia/etiologia , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Escócia/epidemiologia , Equilíbrio Hidroeletrolítico
10.
Ann Clin Biochem ; 47(Pt 4): 331-5, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20592332

RESUMO

BACKGROUND: Substance P (SP) and neurokinin A (NKA) are neuropeptides that have been researched as pain markers in adults, as they are involved in transmission and modulation of pain signals. There is a potential role for them as neurochemical markers of pain in neonates, but this has never previously been investigated. AIM: To establish normative values of SP and NKA in neonates. METHODS: Longitudinal once-daily morning blood samples were collected over two weeks from 142 neonates, gestation 23-40 weeks. Peptides were extracted, and then quantified using an in-house radioimmunoassay. Infants with presumed painful conditions were excluded. RESULTS: SP concentrations ranged from <0.98 to 11.2 pmol/L (median 1.7 pmol/L) and NKA concentrations from <1.95 to 74.6 pmol/L (median 6.0 pmol/L). Gestation and birth weight had no significant correlation with peptide concentrations. Postnatally, there was a gradual rise in median SP during the first three days, which decreased again by day 14. Median NKA showed a similar rise, but was not statistically significant. This postnatal rise and fall were more apparent in preterm infants < or = 32 weeks gestation. CONCLUSIONS: This is the first description of normative values of SP and NKA in neonates. SP and NKA show changes with postnatal age, which are more marked in preterm infants.


Assuntos
Neurocinina A/normas , Substância P/normas , Fatores Etários , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Neurocinina A/sangue , Dor/sangue , Gravidez , Nascimento Prematuro/sangue , Valores de Referência , Substância P/sangue
11.
IEEE Trans Pattern Anal Mach Intell ; 31(9): 1537-51, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19574617

RESUMO

Condition monitoring often involves the analysis of systems with hidden factors that switch between different modes of operation in some way. Given a sequence of observations, the task is to infer the filtering distribution of the switch setting at each time step. In this paper, we present factorial switching linear dynamical systems as a general framework for handling such problems. We show how domain knowledge and learning can be successfully combined in this framework, and introduce a new factor (the "X-factor") for dealing with unmodeled variation. We demonstrate the flexibility of this type of model by applying it to the problem of monitoring the condition of a premature baby receiving intensive care. The state of health of a baby cannot be observed directly, but different underlying factors are associated with particular patterns of physiological measurements and artifacts. We have explicit knowledge of common factors and use the X-factor to model novel patterns which are clinically significant but have unknown cause. Experimental results are given which show the developed methods to be effective on typical intensive care unit monitoring data.


Assuntos
Algoritmos , Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Diagnóstico por Computador/métodos , Terapia Intensiva Neonatal/métodos , Monitorização Fisiológica/métodos , Reconhecimento Automatizado de Padrão/métodos , Análise Fatorial , Humanos , Recém-Nascido , Modelos Lineares
12.
Pediatrics ; 123(5): 1301-5, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19403495

RESUMO

BACKGROUND: Valid consent for research requires comprehensive and understandable information to be disclosed to participants. The way that information is shared varies, but regulatory bodies usually determine style. Some reports have suggested that although information may be all-inclusive, it does little to support understanding. OBJECTIVE: To explore the impact of various information-sharing approaches on parents' understanding of a research study and the validity of their consent. METHODS: This was a randomized, controlled trial. Parents of immature but well infants admitted to a large tertiary NICU in Edinburgh, Scotland, were randomly assigned within 72 hours of their infant's admission to receive 1 of 2 information leaflets, with or without a standardized verbal explanation, for a hypothetical intensive care research study. The leaflets differed in length and in the amount of detail in which the study process, risks, benefits, and patient rights were described. A questionnaire was used to elicit understanding about the purpose of the research, design of the study, procedures involved, and the consent process. RESULTS: Forty-one parents participated in the study. Those who received the longer leaflet without verbal explanation gained only limited understanding of the purpose of the research. The procedures involved in the study were understood better by those who received the shorter leaflet. Issues relating to consent and study design were readily understood in all groups. Irrespective of documentation style, verbal explanation significantly improved understanding. Differences in understanding had little effect on whether a parent would enroll his or her infant into the study. CONCLUSIONS: Verbal explanation significantly enhances understanding of the research process for participants regardless of the style of written documentation. However, shorter written information may lead to better understanding than lengthy, more complex documentation.


Assuntos
Comunicação , Consentimento Livre e Esclarecido/psicologia , Pais/psicologia , Pesquisa/legislação & jurisprudência , Adulto , Feminino , Humanos , Recém-Nascido , Consentimento Livre e Esclarecido/normas , Unidades de Terapia Intensiva Neonatal , Masculino , Escócia , Inquéritos e Questionários
13.
Steroids ; 74(8): 666-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19463688

RESUMO

BACKGROUND: The use of saliva for measurement of cortisol permits non-invasive study of adrenal function, but collection can be technically difficult, particularly in small infants. Saliva collection can be assisted by citric acid to increase saliva flow, or by the use of cotton or polyester swabs in the mouth. AIM: To determine whether different methods of saliva collection affect cortisol radioimmunoassay (RIA) performance. EXPERIMENTAL: Cortisol was measured in saliva collected from 16 adults using intra-oral cotton swabs or polyester swabs, compared with saliva dribbled directly into a pot either alone (plain saliva) or after citric acid had been placed on the tongue. An in-house RIA, without prior extraction, was used to measure cortisol with an encapsulated sheep antibody. RESULTS: Mean (median) salivary cortisol was 10.9 (10.5) nmol L(-1) in plain saliva, 10.4 (8.4) nmol L(-1) in citric acid stimulated saliva; 25.3 (25.1) nmol L(-1) in saliva collected on cotton swabs, and 27.9 (27.3) nmol L(-1) collected on polyester swabs. Cortisol in saliva collected using citric acid was not significantly different from plain saliva (p=0.997), but cortisol in saliva collected using cotton and polyester swabs was significantly higher than that of plain saliva (p<0.01). CONCLUSION: The use of cotton or polyester swabs for collection of saliva can result in spuriously high levels of cortisol when measured by RIA.


Assuntos
Artefatos , Hidrocortisona/análise , Saliva , Manejo de Espécimes/métodos , Adulto , Feminino , Humanos , Imunoensaio , Masculino , Risco , Saliva/química , Manejo de Espécimes/normas
14.
Br J Gen Pract ; 58(557): 877-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19068161

RESUMO

The frequency of oronasal haemorrhage in infancy was estimated from two national GP research databases (6% UK population). When a case was identified, other presentations in the child over the first year were available from one dataset. In the first year haemoptysis is rare. In contrast, epistaxis (7-20 cases of per 10,000 infants) was 10 times more common, and 14.3% of these infants had an injury at some other point in infancy, (four times greater than the general population). In general practice epistaxis may herald other trauma presentations, implying that such infants may be part of a high-risk group for injury.


Assuntos
Maus-Tratos Infantis/diagnóstico , Epistaxe/etiologia , Hemoptise/etiologia , Maus-Tratos Infantis/prevenção & controle , Pré-Escolar , Epistaxe/epidemiologia , Medicina de Família e Comunidade , Hemoptise/epidemiologia , Humanos , Incidência , Lactente , Fatores de Risco , Reino Unido/epidemiologia
15.
AMIA Annu Symp Proc ; : 323-7, 2008 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-18998961

RESUMO

It has been shown that summarizing complex multi-channel physiological and discrete data in natural language (text) can lead to better decision-making in the intensive care unit (ICU). As part of the BabyTalk project, we describe a prototype system (BT-45) which can generate such textual summaries automatically. Although these summaries are not yet as good as those generated by human experts, we have demonstrated experimentally that they lead to as good decision-making as can be achieved through presenting the same data graphically.


Assuntos
Cuidados Críticos/métodos , Apresentação de Dados , Diagnóstico por Computador/métodos , Disseminação de Informação/métodos , Monitorização Fisiológica/métodos , Processamento de Linguagem Natural , Interface Usuário-Computador , Sistemas de Apoio a Decisões Administrativas/organização & administração
16.
AMIA Annu Symp Proc ; : 1225, 2008 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-18998986

RESUMO

As ICUs generate increasing amounts of information, writing medical reports involves complex time-consuming reasoning to build a coherent text which will be meaningful to those who will use it for decision making (e.g.: for nurse handover). Moreover, it has been shown that summarizing complex multi-channel physiological and discrete data in natural language (text) can lead to better decision-making in the intensive care unit (ICU). To facilitate this summarisation, as part of the BabyTalk project, we have developed a system called BT-45 that automatically generates textual summaries from periods of continuous and discrete data in a neonatal ICU. The demonstration will show the system running on real data and will detail the steps in the construction of the final text. Although these summaries are not yet as good as those generated by human experts, we have demonstrated experimentally that they lead to as good decision-making as can be achieved through presenting the same data graphically.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Unidades de Terapia Intensiva Neonatal , Anamnese/métodos , Registro Médico Coordenado , Sistemas Computadorizados de Registros Médicos , Monitorização Fisiológica/métodos , Processamento de Linguagem Natural , Algoritmos , Inteligência Artificial , Armazenamento e Recuperação da Informação/métodos , Reino Unido
17.
Neonatology ; 93(4): 316-23, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18525216

RESUMO

Newborn babies, even if extremely preterm, show responses to pain. The major stress responses seen with surgical pain are associated with serious adverse medical outcomes. There is an ethical imperative to consider pain relief in babies, despite the fact that they cannot verbalise their experience. Ventilator support, and accompanying treatments are described as distressing in adults, and are associated with an endocrine stress response in babies. Opiates have been shown to reduce physiological instability in sick newborn babies. Despite this, they have not been shown to reduce morbidity when given by infusion in ventilated infants, and in view of their serious side effects probably should not be used routinely in this way. It is logical and may be appropriate to give opiates peri-operatively and in babies likely to have severe pain (either from an underlying disease process such as necrotising enterocolitis, or during certain procedures). It is now accepted practice to use a potent analgesic/sedative for elective intubation and as cover for the treatment of retinopathy of prematurity. Topical anaesthetic creams reduce the pain response when used in anticipation of phlebotomy or vascular cannulation. Intra-oral sucrose is effective cover for procedures associated with mild to moderate distress, but its role in preterm infants is uncertain. Nursing interventions to reduce environmental stress, although commonly used, have not consistently been shown to be of benefit.


Assuntos
Analgesia , Recém-Nascido Prematuro , Terapia Intensiva Neonatal/métodos , Dor/prevenção & controle , Respiração Artificial/efeitos adversos , Analgésicos Opioides/uso terapêutico , Benzodiazepinas/uso terapêutico , Sedação Consciente , Humanos , Hipnóticos e Sedativos/uso terapêutico , Recém-Nascido , Dor/etiologia , Dor/fisiopatologia , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/etiologia
18.
Neonatology ; 94(2): 113-22, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18332640

RESUMO

BACKGROUND: Preterm infants receiving supplemental oxygen therapy experience frequent fluctuations in their blood oxygen levels, the magnitude of which has been associated with the incidence and severity of retinopathy of prematurity in such infants. OBJECTIVE: Our objective was to investigate in a relevant animal model whether the immature brain with its poorly vascularised white matter might also be susceptible to injury when exposed to such fluctuations in blood oxygen. METHODS: Newborn rats were reared in an atmosphere in which a computer reproduced the oxygen fluctuations derived from the transcutaneous oxygen levels of a 24-week preterm infant who had developed severe retinopathy. Following 14 days of exposure, we measured the expression of active caspase-3, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the brains comparing with rat pups raised in room air. RESULTS: Compared to room air controls, at day 14, the expression of active caspase-3 was increased by up to 162% (significant increase in 7 of 9 regions), MBP decreased by up to 70% (significant in the hypothalamus only) and GFAP increased by up to 103% (significant in 6 of 7 regions. On day 21, following 7 days of reparative recovery, GFAP levels in most areas of oxygen-exposed brains had returned to near control levels. There were no longer significant differences in caspase-3 levels apart from the cerebral cortex, cerebellum and striatum. In contrast, MBP expression was now much higher in most regions of the treated brains compared to controls. CONCLUSION: We conclude that fluctuations in blood oxygen, observed in preterm survivors, may constitute a source of injury to the white matter and corpus striatum of the developing brain and contribute to the neurological sequelae in extremely premature infants.


Assuntos
Encéfalo/efeitos dos fármacos , Hiperóxia/metabolismo , Proteína Básica da Mielina/metabolismo , Oxigênio/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Caspase 3/metabolismo , Contagem de Células , Modelos Animais de Doenças , Técnica Direta de Fluorescência para Anticorpo , Proteína Glial Fibrilar Ácida/metabolismo , Hiperóxia/induzido quimicamente , Hiperóxia/patologia , Técnicas Imunoenzimáticas , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley
19.
Early Hum Dev ; 84(2): 83-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18234458

RESUMO

Retinopathy of Prematurity (ROP) occurs when premature birth interrupts normal retinal vascular development. Postnatal tissue oxygen levels are significantly higher than those present in utero. Oxygen therapy further increases oxygen levels in the developing retina. Hypoxia driven, VEGF mediated, retinal endothelial cell proliferation is reduced. Low IGF-1 levels may also contribute to delayed retinal vascular development. The neural structures of the peripheral avascular retina continue to develop, and become more metabolically active. Complex, as yet poorly understood abnormalities of structural and molecular interactions between immature endothelial cells and immature astrocytes at the anterior "leading edge" of retinal vascular development leads to the development of an ROP ridge. VEGF produced by the hypoxic peripheral retina, along with structural abnormalities of cell relationships within, and at the vitreoretinal interface of the ROP ridge, results in extraretinal angiogenesis - stage 3 ROP. Stage 3 ROP may resolve spontaneously, or may progress to traction retinal detachment and blindness.


Assuntos
Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/prevenção & controle , Animais , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Neovascularização Patológica/patologia , Neovascularização Patológica/prevenção & controle , Oxigênio/efeitos adversos , Oxigênio/uso terapêutico , Ratos , Retinopatia da Prematuridade/patologia
20.
Early Hum Dev ; 84(8): 549-54, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18280677

RESUMO

BACKGROUND: Specific genetic polymorphisms have been shown to be more common in unexplained infant death. The APOE genotype exhibits opposite effects at the extremes of age with protective effects of e4 on perinatal mortality but detrimental effects as age progresses. OBJECTIVE: To determine whether the APOE e4 allele is associated with early childhood (1 week-2 years) unexplained death ('sudden infant death syndrome', SIDS) or with recognised causes (non-SIDS) and to compare these cohorts with published perinatal and adult data. METHODS: DNA was extracted from spleen tissue of children dying in South East Scotland between 1990 and 2002. APOE alleles (e2, e3, e4) were determined using PCR. Comparisons of allele frequencies between groups were made. RESULTS: There were 167 SIDS cases and 117 non-SIDS cases. Allele distributions of SIDS cases were similar to healthy newborns. Allele distributions of non-SIDS cases were more similar to adults than to healthy newborns. The percentage of children with at least one e4 allele was significantly lower in non-SIDS compared to SIDS (p = 0.016). Non-SIDS cases had a higher frequency of e3 compared to SIDS cases (p = 0.01) and to healthy newborns (0.005). CONCLUSIONS: Children dying from identified causes have different APOE allele distributions from SIDS cases, but are similar to adults. Children dying from SIDS have an allele distribution comparable to healthy newborns. The prevalence of e4 in SIDS is not of an order to contribute significantly to the age-related decline in e4.


Assuntos
Alelos , Apolipoproteína E4/genética , Morte Súbita do Lactente/genética , Adulto , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Morte Súbita do Lactente/epidemiologia
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