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1.
Scott Med J ; 69(1): 10-17, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050379

RESUMO

BACKGROUND: Poor mental health in medical students is a global concern. Effective interventions are required, which are tailored towards the training-related stressors medical students experience. The Reboot coaching programme is an online, tailored intervention based on cognitive-behavioural principles. AIMS: To evaluate whether the Reboot coaching programme tailored for medical students was feasible and associated with improvements in mental health outcome indicators. METHODS: Medical students participated in two group online workshops and a one-to-one coaching call with a Reboot-trained licensed psychological therapist. Participants provided data at: baseline (T1), post-workshops (T2), post-coaching call (T3) and 4-month follow-up (T4). Outcome measures included resilience, confidence, burnout and depression. Feedback was provided regarding the workshops at T2. RESULTS: 115 participants (93/80.9% women; mage = 23.9; SD = 2.8) were recruited, 83 (72.2%) completed all intervention elements and 82 (71.3%) provided T4 data, surpassing recruitment and retention targets. There were significant improvements following baseline in resilience (ps < .001), confidence (ps < .001), burnout (ps < .001) and depression (ps ≤ .001). Most participants agreed the workshops imparted useful skills (n = 92; 99%) and would recommend Reboot to others (n = 89; 95.6%). CONCLUSIONS: Existing interventions have produced mixed results regarding their effectiveness in improving medical students' mental health. Reboot is a feasible intervention in this group which is associated with improvements in resilience, confidence, burnout and depression. Further controlled studies of Reboot are now needed.


Assuntos
Tutoria , Resiliência Psicológica , Estudantes de Medicina , Humanos , Feminino , Masculino , Estudantes de Medicina/psicologia , Depressão , Esgotamento Psicológico
2.
J Clin Nurs ; 32(19-20): 7125-7134, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36823696

RESUMO

AIMS AND OBJECTIVES: The critical care nursing workforce is in crisis, with one-third of critical care nurses worldwide intending to leave their roles. This paper aimed to examine the problem from a wellbeing perspective, offering implications for research, and potential solutions for organisations. DESIGN: Discursive/Position paper. METHOD: The discussion is based on the nursing and wellbeing literature. It is guided by the authors' collaborative expertise as both clinicians and researchers. Data were drawn from nursing and wellbeing peer-reviewed literature, such as reviews and empirical studies, national surveys and government and thinktank publications/reports. RESULTS: Critical care nurses have been disproportionately affected by the COVID-19 pandemic with studies consistently showing critical care nurses to have the worst psychological outcomes on wellbeing measures, including depression, burnout and post-traumatic stress disorder (PTSD). These findings are not only concerning for the mental wellbeing of critical care nurses, they also raise significant issues for healthcare systems/organisations: poor wellbeing, increased burnout and PTSD are directly linked with critical care nurses intending to leave the profession. Thus, the wellbeing of critical care nurses must urgently be supported. Resilience has been identified as a protective mechanism against the development of PTSD and burnout, thus offering evidence-based interventions that address resilience and turnover have much to offer in tackling the workforce crisis. However, turnover data must be collected by studies evaluating resilience interventions, to further support their evidence base. Organisations cannot solely rely on the efficacy of these interventions to address their workforce crisis but must concomitantly engage in organisational change. CONCLUSIONS: We conclude that critical care nurses are in urgent need of preventative, evidence-based wellbeing interventions, and make suggestions for research and practice.


Assuntos
Esgotamento Profissional , COVID-19 , Enfermagem de Cuidados Críticos , Humanos , COVID-19/epidemiologia , Pandemias , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Recursos Humanos
3.
Sociology ; 57(2): 421-437, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37128258

RESUMO

This article contributes to sociologies of futures by arguing that quotidian imaginations, makings and experiences of futures are crucial to social life. We develop Sharma's concept of recalibration to understand ongoing and multiple adjustments of present-future relations, focusing on how these were articulated by Mass Observation writers in the UK during the early part of the COVID-19 pandemic. We identify three key modes of recalibration: fissure, where a break between the present and future means the future is difficult to imagine; standby, where the present is expanded but there is an alertness to the future, and; reset, where futures are modestly and radically recalibrated through a post-pandemic imaginary. We argue for sociologies of futures that can account for the diverse and contradictory ways in which futures emerge from and compose everyday life at different scales.

4.
Hist Human Sci ; 36(2): 26-48, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37153714

RESUMO

The COVID-19 pandemic has foregrounded the significance of time to everyday life, as the routines, pace, and speed of social relations were widely reconfigured. This article uses rhythm as an object and tool of inquiry to make sense of spatio-temporal change. We analyse the Mass Observation (MO) directive we co-commissioned on 'COVID-19 and Time', where volunteer writers reflect on whether and how time was made, experienced, and imagined differently during the early stages of the pandemic in the UK. We draw on Henri Lefebvre and Catherine Régulier's 'rhythmanalysis', taking up their theorisation of rhythm as linear and cyclical and their concepts of arrhythmia (discordant rhythms) and eurhythmia (harmonious rhythms). Our analysis highlights how MO writers articulate (a) the ruptures to their everyday rhythms across time and space, (b) their experience of 'blurred' or 'merged' time as everyday rhythms are dissolved and the pace of time is intensified or slowed, and (c) the remaking of rhythms through new practices or devices and attunements to nature. We show how rhythm enables a consideration of the spatio-temporal textures of everyday life, including their unevenness, variation, and difference. The article thus contributes to and expands recent scholarship on the social life of time, rhythm and rhythmanalysis, everyday life, and MO.

5.
Clin Infect Dis ; 68(5): 865-872, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30202941

RESUMO

Clinical trials for Staphylococcus aureus bloodstream infections (SAB) are broadly grouped into 2 categories: registrational trials intended to support regulatory approval of antibiotics for the treatment of SAB and strategy trials intended to inform clinicians on the best treatment options for SAB among existing antibiotics. Both types of SAB trials are urgently needed but have been limited by cost, complexity, and regulatory uncertainty. Here, we review key SAB trial design considerations for investigators, sponsors, and regulators.


Assuntos
Antibacterianos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Projetos de Pesquisa/legislação & jurisprudência , Sepse/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Adulto , Humanos , Sepse/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
6.
Biomed Chromatogr ; 31(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28186342

RESUMO

Paralytic shellfish toxins (PSTs), including gonyautoxins and saxitoxins, are produced by multiple species of microalgae and dinoflagellates, and are bioaccumulated by shellfish and other animals. Human exposure to PSTs typically occurs through ingestion of recreationally harvested contaminated shellfish and results in nonspecific symptomology. Confirmation of exposure to PSTs has often relied on the measurement of saxitoxin, the most toxic congener; however, gonyautoxins (GTXs), the sulfated carbamate derivatives of saxitoxin, may be present in shellfish at higher concentrations. To improve identification of PST exposures, our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography method to identify GTX1-4 in human urine with tandem mass spectrometry. The reportable range varied for each analyte, with all falling within 0.899 and 250 ng/mL in urine with precision <15% and >85% accuracy as determined for all quality control samples. This new online method quantitates GTX1-4 following exposures to PSTs, supporting the work of public health authorities.


Assuntos
Cromatografia Líquida/métodos , Saxitoxina/análogos & derivados , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Ensaios de Triagem em Larga Escala/métodos , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Saxitoxina/química , Saxitoxina/isolamento & purificação , Saxitoxina/urina
7.
Anal Bioanal Chem ; 406(21): 5195-202, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24633507

RESUMO

Although nerve agent use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. Exposure can be detected through the analysis of hydrolysis products in urine as well as blood. An analytical method to detect exposure to five nerve agents, including VX, VR (Russian VX), GB (sarin), GD (soman), and GF (cyclosarin), through the analysis of the hydrolysis products, which are the primary metabolites, in serum has been developed and characterized. This method uses solid-phase extraction coupled with high-performance liquid chromatography for separation and isotopic dilution tandem mass spectrometry for detection. An uncommon buffer of ammonium fluoride was used to enhance ionization and improve sensitivity when coupled with hydrophilic interaction liquid chromatography resulting in detection limits from 0.3 to 0.5 ng/mL. The assessment of two quality control samples demonstrated high accuracy (101-105%) and high precision (5-8%) for the detection of these five nerve agent hydrolysis products in serum.


Assuntos
Substâncias para a Guerra Química/análise , Compostos Organofosforados/sangue , Compostos Organotiofosforados/sangue , Sarina/sangue , Soman/sangue , Compostos de Amônio , Biotransformação , Soluções Tampão , Substâncias para a Guerra Química/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Fluoretos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Limite de Detecção , Compostos de Amônio Quaternário , Extração em Fase Sólida , Espectrometria de Massas em Tandem
8.
BJUI Compass ; 4(5): 533-542, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37636204

RESUMO

Background: Urology trainees experience high burnout, and there is an urgent need for acceptable and effective interventions. The current study evaluated Reboot coaching workshops (Reboot-C), a tailored intervention based on cognitive-behavioural principles, with urology trainees. Objective: Our primary objective was to evaluate the acceptability of Reboot-C among urology trainees. In addition, this study aimed to investigate whether there were changes in confidence, resilience, depression and burnout levels. Materials and method: A single-arm design was used, including pre- and post-online questionnaires and semi-structured interviews. Result: Twenty-one urology trainees replied to the survey, attended both Reboot-C workshops and responded to the post-intervention questionnaire. Thirteen of 21 (61%) urology trainees participated in the interview. Participating in Reboot-C was associated with significant improvements in resilience and confidence and a significant reduction in burnout. However, there was no significant reduction in depression. Qualitative data indicated that Reboot was acceptable and helped participants develop useful skills. Conclusion: These findings pave the way for more conclusive studies on the efficacy of Reboot-C for surgeons.

9.
J Anal Toxicol ; 46(3): 322-327, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33515246

RESUMO

Florida red tides have become more common and persistent in and around the Gulf of Mexico. When in bloom, red tides can produce brevetoxins in high concentrations, leading to human exposures primarily through contaminated food and ocean spray. The research described here includes adapting and validating a commercial brevetoxin water test kit for human plasma testing. Pooled plasma was fortified with a model brevetoxin, brevetoxin 3, at concentrations from 0.00500 to 3.00 ng/mL to generate calibration curves and quality control samples. The quantitative detection range was determined to be 0.0400-2.00 ng/mL brevetoxin 3 equivalents with inter- and intraday accuracies ranging from 94.0% to 109% and relative standard deviations <20%, which is within the US Food and Drug Administration guidelines for receptor-binding assays. Additionally, cross-reactivity was tested using 4 of the 10 known brevetoxins and 12 paralytic shellfish toxins. The cross-reactivity varied from 0.173% to 144% for the commercially available brevetoxin standards and 0% for the commercially available paralytic shellfish toxin standards. Fifty individual unexposed human plasma samples were measured to determine the limit of detection and endogenous interferences to the test. The validated method was used to test 31 plasma samples collected from humans potentially exposed to brevetoxins, detecting 11 positives. This method has been proven useful to measure human exposure to brevetoxins and can be applied to future exposure events.


Assuntos
Dinoflagellida , Bioensaio , Ensaio de Imunoadsorção Enzimática/métodos , Proliferação Nociva de Algas , Humanos , Toxinas Marinhas , Oxocinas , Estados Unidos
10.
Clin Toxicol (Phila) ; 60(2): 262-266, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33913398

RESUMO

INTRODUCTION: Tetrodotoxin (TTX) is a potent sodium channel blocker, with significant neurotoxicity, found in marine animals like pufferfish and blue-ringed octopus. The severity of toxicity depends on the amount of toxin ingested and the outcome depends on the time-lapse to appropriate medical care. CASES REPORT: We report five patients who presented with tetrodotoxin poisoning after consuming fried internal organs of local pufferfish from the coast of Oman. The patients' clinical manifestations were consistent with the expected TTX toxidrome of perioral and generalized paresthesia, weakness of upper and lower extremities, gastrointestinal manifestations, dyspnea, dysarthria, ascending paralysis, hypotension, bradycardia and coma. The severity varied among the patients who recovered completely except one patient who developed a subarachnoid hemorrhage without underlying aneurysms on computed tomography-angiogram. This complication was potentially related to TTX poisoning and has not been previously reported. In addition to standard supportive management, patients with severe illness should potentially receive the intravenous acetylcholinesterase inhibitor neostigmine, and intermittent dialysis. Urine specimens were sent to CDC in Atlanta, where they were analyzed using online solid phase extraction (SPE) with LC-MS/MS and confirmed the diagnosis in all five cases. DISCUSSION: In general, the patients' clinical manifestations were consistent with the expected TTX toxidrome except patient 3 who developed a subarachnoid hemorrhage early during his clinical course. Two patients received neostigmine and underwent dialysis with complete recovery.


Assuntos
Acetilcolinesterase , Doenças Transmitidas por Alimentos , Tetrodotoxina , Animais , Inibidores da Colinesterase/uso terapêutico , Cromatografia Líquida , Doenças Transmitidas por Alimentos/diagnóstico , Doenças Transmitidas por Alimentos/etiologia , Doenças Transmitidas por Alimentos/terapia , Humanos , Omã/epidemiologia , Espectrometria de Massas em Tandem , Tetrodotoxina/análise , Tetrodotoxina/intoxicação
11.
Nurs Womens Health ; 25(1): 95-96, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33412109

RESUMO

A nurse recalls an important lesson she learned in her early days of maternity care nursing.


Assuntos
Enfermagem Obstétrica , Feminino , Humanos , Serviços de Saúde Materna , Gravidez
12.
Bioanalysis ; 10(4): 229-239, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29333869

RESUMO

AIM: An immunomagnetic capture protocol for use with LC-MS was developed for the quantitation of saxitoxin (STX) in human urine. MATERIALS & METHODS: This method uses monoclonal antibodies coupled to magnetic beads. STX was certified reference material grade from National Research Council, Canada. Analysis was carried out using LC-MS. RESULTS: With an extraction efficiency of 80%, accuracy and precision of 93.0-100.2% and 5.3-12.6%, respectively, and a dynamic range of 1.00-100 ng/ml, the method is well suited to quantify STX exposures based on previously reported cases. CONCLUSION: Compared with our previously published protocols, this method has improved selectivity, a fivefold increase in sensitivity and uses only a third of the sample volume. This method can diagnose future toxin exposures and may complement the shellfish monitoring programs worldwide.


Assuntos
Cromatografia Líquida/métodos , Testes Imunológicos , Saxitoxina/urina , Intoxicação por Frutos do Mar/urina , Espectrometria de Massas em Tandem/métodos , Anticorpos Monoclonais/imunologia , Calibragem , Humanos , Imãs , Microesferas , Padrões de Referência , Saxitoxina/química , Saxitoxina/normas , Intoxicação por Frutos do Mar/diagnóstico , Fatores de Tempo
13.
Anal Chim Acta ; 1033: 100-107, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30172315

RESUMO

A method was developed to detect and quantify organophosphate nerve agent (OPNA) metabolites in dried blood samples. Dried blood spots (DBS) and microsampling devices are alternatives to traditional blood draws, allowing for safe handling, extended stability, reduced shipping costs, and potential self-sampling. DBS and microsamplers were evaluated for precision, accuracy, sensitivity, matrix effects, and extraction recovery following collection of whole blood containing five OPNA metabolites. The metabolites of VX, Sarin (GB), Soman (GD), Cyclosarin (GF), and Russian VX (VR) were quantitated from 5.0 to 500 ng mL-1 with precision of ≤16% and accuracy between 93 and 108% for QC samples with controlled volumes. For unknown spot volumes, OPNA metabolite concentrations were normalized to total blood protein to improve interpretation of nerve agent exposures. This study provides data to support the use of DBS and microsamplers to collect critical exposure samples quickly, safely, and efficiently following large-scale chemical exposure events.


Assuntos
Teste em Amostras de Sangue Seco , Agentes Neurotóxicos/análise , Compostos Organofosforados/sangue , Compostos Organotiofosforados/sangue , Sarina/sangue , Soman/sangue , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Agentes Neurotóxicos/metabolismo , Compostos Organofosforados/metabolismo , Compostos Organotiofosforados/metabolismo , Sarina/metabolismo , Soman/metabolismo , Espectrometria de Massas em Tandem
14.
Toxicon ; 119: 64-71, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27212629

RESUMO

Tetrodotoxin (TTX) is an extremely potent paralytic toxin responsible for yearly illness and death around the world. A clinical measurement is necessary to confirm exposure because symptoms of TTX intoxication cannot be distinguished from other paralytic toxins. Our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography (HILIC) method for the analysis of TTX in human urine with tandem mass spectrometry. The reportable range for the method was 2.80 - 249 ng/mL in urine with precision and accuracy within 15% as determined for all quality control samples. No isotopically-labeled internal standard is available for TTX; thus a surrogate internal standard, voglibose, was investigated to compensate for matrix effects and ionization suppression. However, upon evaluation, voglibose was ineffective for this purpose. This new online method rapidly identifies TTX, facilitating the work of public health authorities and providing support to monitoring programs worldwide.


Assuntos
Cromatografia Líquida/métodos , Ensaios de Triagem em Larga Escala , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Tetrodotoxina/urina , Calibragem , Humanos , Limite de Detecção , Padrões de Referência
15.
Proc SPIE Int Soc Opt Eng ; 98630: 98630P-98630P9, 2016 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-27942095

RESUMO

Public health response to large scale chemical emergencies presents logistical challenges for sample collection, transport, and analysis. Diagnostic methods used to identify and determine exposure to chemical warfare agents, toxins, and poisons traditionally involve blood collection by phlebotomists, cold transport of biomedical samples, and costly sample preparation techniques. Use of dried blood spots, which consist of dried blood on an FDA-approved substrate, can increase analyte stability, decrease infection hazard for those handling samples, greatly reduce the cost of shipping/storing samples by removing the need for refrigeration and cold chain transportation, and be self-prepared by potentially exposed individuals using a simple finger prick and blood spot compatible paper. Our laboratory has developed clinical assays to detect human exposures to nerve agents through the analysis of specific protein adducts and metabolites, for which a simple extraction from a dried blood spot is sufficient for removing matrix interferents and attaining sensitivities on par with traditional sampling methods. The use of dried blood spots can bridge the gap between the laboratory and the field allowing for large scale sample collection with minimal impact on hospital resources while maintaining sensitivity, specificity, traceability, and quality requirements for both clinical and forensic applications.

16.
J Am Board Fam Med ; 29(2): 263-75, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26957384

RESUMO

The incidence of obstructive sleep apnea (OSA) has reached epidemic proportions, and it is an often unrecognized cause of perioperative morbidity and mortality. Profound hypoxic injury from apnea during the postoperative period is often misdiagnosed as cardiac arrest due to other causes. Almost a quarter of patients entering a hospital for elective surgery have OSA, and >80% of these cases are undiagnosed at the time of surgery. The perioperative period puts patients at high risk of apneic episodes because of drug effects from sedatives, narcotics, and general anesthesia, as well as from the effects of postoperative rapid eye movement sleep changes and postoperative positioning in the hospital bed. For adults, preoperative screening using the STOP or STOP-Bang questionnaires can help to identify adult patients at increased risk of OSA. In the pediatric setting, a question about snoring should be part of every preoperative examination. For patients with known OSA, continuous positive airway pressure should be continued postoperatively. Continuous pulse oximetry monitoring with an alarm system can help to prevent apneic catastrophes caused by OSA in the postoperative period.


Assuntos
Cuidados Pós-Operatórios , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Insuficiência Respiratória/prevenção & controle , Apneia Obstrutiva do Sono/diagnóstico , Tonsila Faríngea/patologia , Adulto , Anestesia Geral/efeitos adversos , Criança , Humanos , Hipertrofia/complicações , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/uso terapêutico , Entorpecentes/efeitos adversos , Entorpecentes/uso terapêutico , Oximetria , Tonsila Palatina/patologia , Posicionamento do Paciente/efeitos adversos , Complicações Pós-Operatórias/etiologia , Guias de Prática Clínica como Assunto , Insuficiência Respiratória/etiologia , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/etiologia , Ronco/diagnóstico , Ronco/fisiopatologia , Inquéritos e Questionários
17.
Toxicon ; 99: 118-24, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25817003

RESUMO

Saxitoxin (STX) and neosaxitoxin (NEO) are potent neurotoxins that cause paralytic shellfish poisoning (PSP). PSP typically occurs through the ingestion of bivalve shellfish that have consumed toxin producing dinoflagellates. Due to initial presentation of symptoms being nonspecific, a clinical measurement is needed to confirm exposure to these toxins. Our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography (HILIC) method for the analysis of STX and NEO in human urine with tandem mass spectrometry. A unique feature of this online method is the incorporation of a new synthetic (15)N4-STX labeled internal standard used for quantitation. Manual sample preparation time was reduced by approximately 70% for 98 urine samples as compared to a previously reported method. The lowest reportable limit for STX was improved from 5.0 ng/mL to 1.01 ng/mL and from 10.0 ng/mL to 2.62 ng/mL for NEO. Three analysts validated the method with 20 calibration curves total over 30 days with precision and accuracy within ±15% for all QCs. This new online method rapidly identifies STX and NEO exposure with improved sensitivity, which can facilitate the work of public health authorities to confirm the cases of PSP, complementing the many shellfish monitoring programs worldwide.


Assuntos
Neurotoxinas/urina , Saxitoxina/análogos & derivados , Saxitoxina/urina , Intoxicação por Frutos do Mar/urina , Métodos Analíticos de Preparação de Amostras , Automação Laboratorial , Calibragem , Cromatografia Líquida de Alta Pressão , Humanos , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Neurotoxinas/química , Neurotoxinas/toxicidade , Isótopos de Nitrogênio , Reprodutibilidade dos Testes , Saxitoxina/química , Saxitoxina/toxicidade , Sensibilidade e Especificidade , Intoxicação por Frutos do Mar/diagnóstico , Intoxicação por Frutos do Mar/etiologia , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Toxicocinética
19.
Pediatr Res ; 64(1): 50-5, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18344903

RESUMO

Oxygen fluctuation patterns in preterm infants who develop retinopathy of prematurity (ROP) are varied and poorly represented in animal models. We examined the hypothesis that clustered (CL) episodes of hypoxia during hyperoxia results in a more severe form of oxygen-induced retinopathy (OIR) than dispersed episodes. Rat pups were exposed to alternating cycles of 1) 50% O2 with three CL episodes of 12% O2 every 6 h; or 2) 50% O2 with one episode of 12% O2 every 2 h, for 7 (P7) or 14 (P14) days postnatal age. Pups were killed after hyperoxia, or placed in room air (RA) until P21. RA littermates were killed at P7, P14, and P21. Systemic and ocular vascular endothelial growth factor (VEGF), soluble VEGFR-1 (sVEGFR-1), insulin-like growth factor I (IGF-I), and growth hormone were examined. All hyperoxia-exposed retinas had evidence of neovascularization. Animals in the CL group had a more severe form of OIR at P21 evidenced by vascular tufts, leaky vessels, retinal hemorrhage, and vascular overgrowth. These characteristics were associated with low body weight; high systemic and ocular VEGF; and low systemic and high ocular sVEGFR-1 and IGF-I. These data suggest that preterm infants who experience CL fluctuations in Pao2 during supplemental O2 therapy are at a higher risk for severe ROP.


Assuntos
Hiperóxia/complicações , Hipóxia/complicações , Fator de Crescimento Insulin-Like I/metabolismo , Retina/metabolismo , Retinopatia da Prematuridade/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Peso Corporal , Modelos Animais de Doenças , Idade Gestacional , Hormônio do Crescimento/metabolismo , Humanos , Hiperóxia/metabolismo , Hiperóxia/patologia , Hipóxia/metabolismo , Hipóxia/patologia , Recém-Nascido , Ratos , Ratos Sprague-Dawley , Retina/patologia , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/metabolismo , Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/patologia , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
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